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The scientific evidence on the causes for sick leave attributed to back and neck disorders was review ed . Categories were established for acute , recurring , and chronic problems based on the duration of the sick leave period . Forty-eight articles were found to be relevant , whereof two were of high quality and 26 were of medium or low quality . Quality was assessed exclusively in relation to the aim of this systematic review . The results reveal limited published research on causes for sick leave from back and neck disorders . The generalisability of the findings is also limited since most of the subjects were men and employees in manufacturing industries . Women , white-collar workers , employees in the public sector ( care , social services , schools , etc ) were underrepresented in the studies . Hence , these groups and areas should be studied further to verify conclusions and enhance knowledge about the causes for sick leave from back and neck disorders . The following factors were found to have consistent , but limited , support as regards their influence on the risk for sick leave due to back and neck disorders : ( a ) heavy physical workload , bent or twisted working position , and low work satisfaction increases the risk for short-term and long-term sick leave ; ( b ) specific back diagnoses and previous sick leave due to back disorders increases the risk for short-term and long-term sick leave ; ( c ) female gender , smoking , exposure to vibration , and deficient social support were not found to significantly increase the risk for short-term and long-term sick leave ; ( d ) self-reported pain and functional impairments were associated with a high risk for long-term sick leave ; ( e ) longer employment periods reduced the risk for short-term sick leave ; ( f ) perceived dem and s at work did not influence short-term sick leave ; ( g ) female gender and higher age increases the risk for disability pension
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"Study Design . A prospect i ve cohort study including patients with nonspecific spinal pain was performed . Objectives . To investigate whether the use of expert judgment in routine practice can provide a basis for reliable decision making concerning the need for intervention in patients with spinal pain and their ability to benefit from treatment . Summary of Background Data . A wide range of instruments and techniques are used to assess and treat patients with spinal pain . Many instruments are used without being clinimetrically tested . Methods . A question naire concerning the patients ’ need of treatment and their potential to assimilate it was sent to experts in the health care arena : physicians , physical therapists , social insurance officers . The experts included were those connected with patients participating in a larger outcome study . Two cohorts of patients ( sample 1 , n = 217 ; sample 2 , n = 257 ) were followed for 6 and 12 months , during which time the patients ’ health and work status were mapped . Results . No acceptable agreement was found between any of the experts ’ ratings of patients ’ needs and potential for rehabilitation . Logistic regression showed that the experts ’ judgments were based almost solely on the age of the patient . The prediction analyses showed that the most consistent predictor of the patients ’ status at the 6-month follow-up assessment was the patients ’ own belief in the existence of effective treatments and their perceived ability for learning to cope with the condition . Conclusions . Expert judgment as exercised in routine practice can not be used as basis for reliable decision making concerning the need of the patient with spinal pain for intervention and the patient ’s ability to benefit from treatment",
"Study Design . A prospect i ve cross-sectional study was conducted . Objective . To determine the relation between degeneration of all the joints in the cervical spine , and to identify the effects of litigation on pain and disability levels in trauma and nontrauma patients . Summary of Background Data . The link between spinal degeneration and patient symptoms remains controversial . Two recent similar studies present conflicting results concerning the association between spinal degeneration and symptomatology . These two studies , performed in different countries , did not consider the impact of impending litigation on self-reported pain and disability levels . The role of the uncovertebral and facet articulations has hitherto not been investigated . Methods . Radiographic and question naire data from 180 consecutive patients with neck pain were collected . Neck pain severity was measured using two time-dependent scales . All patients completed the Neck Disability Index ( NDI ) and questions about chronicity , etiology , and associated litigation . The radiographs were evaluated for the number of levels of degeneration and the severity of degeneration in the discs as well as the uncovertebral and facet articulations . Results . In this study , 71 patients ( 40.57 % ) reported neck pain as a result of injury . However , only 5.1 % had associated litigation . There was no statistically significant difference in pain severity or disability levels between the patients with and those without cervical degeneration . According to the findings , the number of levels of cervical degeneration and the severity of degeneration in the discs , facets , and uncovertebral joints are not related to the levels of pain and disability . Patients reporting neck pain caused by injury had a tendency ( P = 0.055 ) to more pain during the preceding week and significantly more disability ( P pain intensity ( P reading ( P headaches ( P ability to drive ( P concentration ( P pain ( P disability ( P degeneration in any of the joints . Conclusions . In patients with neck pain , there is no difference in reported pain and disability levels between those with and those without evidence of cervical spine degeneration . Patients whose neck pain is the result of trauma report significantly more pain and disability than nontrauma patients . This is not because of more spinal degeneration or overriding litigation issues",
"The authors prospect ively evaluated 3020 volunteers of the Boeing-Everett plant to assess risk factors that predispose workers to file industrial back injury cl aims . During four years of follow-up observation , more than 279 subjects reported acute back problems . The effect of the only predictive physical variable was explainable by a history of medical treatment . The most predictive individual factors were ( 1 ) job task dissatisfaction and ( 2 ) distress as reported on Scale 3 of the Minnesota Multiphasic Personality Inventory ( MMPI ) . This data perhaps explains why the focus on purely physical and injury-related factors has met with little success in dealing with what has become the most expensive orthopedic problem . Clinical ly , nonphysical factors that significantly impact the reporting of back injuries may also affect patients ' responses to medical treatment",
"Study Design . R and omized controlled trial . Objectives . To investigate the effectiveness and costs of a mini-intervention , provided in addition to the usual care , and the incremental effect of a work site visit for patients with subacute disabling low back pain . Summary of Background Data . There is lack of data on cost-effectiveness of brief interventions for patients with prolonged low back pain . Methods . A total of 164 patients with subacute low back pain were r and omized to a mini-intervention group ( A ) , a work site visit group ( B ) , or a usual care group ( C ) . Groups A ( n = 56 ) and B ( n = 51 ) underwent one assessment by a physician plus a physiotherapist . Group B received a work site visit in addition . Group C served as controls ( n = 57 ) and was treated in municipal primary health care . All patients received a leaflet on back pain . Pain , disability , specific and generic health-related quality of life , satisfaction with care , days on sick leave , and use and costs of health care consumption were measured at 3- , 6- , and 12-month follow-ups . Results . During follow-up , fewer subjects had daily pain in Groups A and B than in Group C ( Group A vs. Group C , P = 0.002 ; Group B vs. Group C , P = 0.030 ) . In Group A , pain was less bothersome ( Group A vs. Group C , P = 0.032 ) and interfered less with daily life ( Group A vs. Group C , P = 0.040 ) than among controls . Average days on sick leave were 19 in Group A , 28 in Group B , and 41 in Group C ( Group A vs. Group C , P = 0.019 ) . Treatment satisfaction was better in the intervention groups than among the controls , and costs were lowest in the mini-intervention group . Conclusions . Mini-intervention reduced daily back pain symptoms and sickness absence , improved adaptation to pain and patient satisfaction among patients with subacute low back pain , without increasing health care costs . A work site visit did not increase effectiveness",
"Objective : To determine whether physical and psychosocial load at work influence sickness absence due to low back pain . Methods : The research was a part of the study on musculoskeletal disorders , absenteeism , stress , and health ( SMASH ) , a 3 year prospect i ve cohort study on risk factors for musculoskeletal disorders . Workers from 21 companies located throughout The Netherl and s participated in the part of this study on sickness absence due to low back pain . The study population consisted of 732 workers with no sickness absences of 3 days or longer due to low back pain in the 3 months before the baseline survey and complete data on the reasons for absences during the follow up period . The mean ( range ) period of follow up in this group was 37 ( 7–44 ) months . Physical load at work was assessed by analyses of video recordings . Baseline information on psychosocial work characteristics was obtained by a question naire . Data on sickness absence were collected from company records . The main outcome measure was the rate of sickness absences of 3 days or longer due to low back pain during the follow up period . Results : After adjustment of the work related physical and psychosocial factors for each other and for other potential determinants , significant rate ratios ranging from 2.0 to 3.2 were found for trunk flexion , trunk rotation , lifting , and low job satisfaction . A dose-response relation was found for trunk flexion , but not for trunk rotation or lifting . Non-significant rate ratios of about 1.4 were found for low supervisor support and low coworker support . Quantitative job dem and s , conflicting dem and s , decision authority , and skill discretion showed no relation with sickness absence due to low back pain . Conclusions : Flexion and rotation of the trunk , lifting , and low job satisfaction are risk factors for sickness absence due to low back pain . Some indications of a relation between low social support , either from supervisors or coworkers , and sickness absence due to low back pain are also present",
"Study Design . Population ‐based r and omized clinical trial . Objectives . To develop and test a model of management of subacute back pain , to prevent prolonged disability . Summary of Background Data . The present management of back pain seems inadequate , and development of innovative models has been urged . Methods . A model for the treatment of subacute work‐related back pain has been developed and evaluated in a population ‐based r and omized clinical trial . Workers ( n = 130 ) from eligible workplaces in the Sherbrooke area ( N = 31 ) , who had been absent from work for more than 4 weeks for back pain , were r and omized , based on their workplace , in one of four treatment groups : usual care , clinical intervention , occupational intervention , and full intervention ( a combination of the last two ) . The duration of absence from regular work and from any work was evaluated using survival analysis . Functional status and pain were compared at study entry and after 1 year of follow‐up . Results . The full intervention group returned to regular work 2.41 times faster than the usual care intervention group ( 95 % confidence interval 1.19‐4.89 ; P = 0.01 ) . The specific effect of the occupational intervention accounted for the most important part of this result , with a rate ratio of return to regular work of 1.91 ( 95 % confidence interval = 1.18‐3.10 ; P demonstrated either a statistically significant reduction or a trend toward reduction in the three intervention groups , compared with the trend in the usual care intervention group . Conclusions . Close association of occupational intervention with clinical care is of primary importance in impeding progression toward chronicity of low back pain",
"The aim of this study was to determine whether grade d activity restored occupational function in industrial blue-collar workers who were sick-listed for 8 weeks because of subacute , nonspecific , mechanical low back pain ( LBP ) . Patients with LBP , who had been examined by an orthopedic surgeon and a social worker , were r and omly assigned to either an activity group ( n = 51 ) or a control group ( n = 52 ) . Patients with defined orthopedic , medical , or psychiatric diagnoses were excluded before r and omization . The grade d activity program consisted of four parts : ( 1 ) measurements of functional capacity ; ( 2 ) a work-place visit ; ( 3 ) back school education ; and ( 4 ) an individual , submaximal , gradually increased exercise program , with an operant-conditioning behavioral approach , based on the results of the tests and the dem and s of the patient 's work . Records of the amount of sick leave taken over a 3-year period ( ie , the 1-year periods before , during , and after intervention ) were obtained from each patient 's Social Insurance Office . The patients in the activity group returned to work significantly earlier than did the patients in the control group . The median number of physical therapist appointments before return to work was 5 , and the average number of appointments was 10.7 ( SD = 12.3 ) . The average duration of sick leave attributable to LBP during the second follow-up year was 12.1 weeks ( SD = 18.4 ) in the activity group and 19.6 weeks ( SD = 20.7 ) in the control group . Four patients in the control group and 1 patient in the activity group received permanent disability pensions . The grade d activity program made the patients occupationally functional again , as measured by return to work and significantly reduced long-term sick leave",
"Study Design . Population ‐based , cross‐sectional mailed survey . Objective . To determine the lifetime , period , and point prevalence of neck pain and its related disability among Saskatchewan adults and investigate the presence and strength of nonresponse bias . Summary of Background Data . In Europe , the life‐time and point prevalence of neck pain is almost as high as the prevalence of low back pain . Similarly , chronic neck pain is highly prevalent and a common source of disability in the working‐age population . However , no studies specifically have documented the prevalence of neck pain and its related disability in North America . Methods . The Saskatchewan Health and Back Pain Survey was mailed to 2184 r and omly selected Saskatchewan adults aged 20‐69 years . Fifty‐five percent of the study population participated . The presence of nonresponse bias was investigated through logistic regression and wave analysis . The Chronic Pain Question naire was used to classify the severity of chronic neck pain . Results . The age‐st and ardized lifetime prevalence of neck pain is 66.7 % ( 95 % confidence interval , 63.8‐69.5 ) , and the point prevalence is 22.2 % ( 95 % confidence interval , 19.7‐24.7 ) . The age‐st and ardized 6‐month prevalence of low‐intensity and low‐disability neck pain is 39.7 % ( 95 % confidence interval , 36.7‐42.7 ) , whereas it is 10.1 % ( 95 % confidence interval , 8.2‐11.9 ) for high‐intensity and low‐disability neck pain and 4.6 % ( 95 % confidence interval , 3.3‐5.8 ) for significantly disabling neck pain . The prevalence of low‐intensity and low‐disability neck pain decreases with age . More women experience high‐disability neck pain than men . Wave analysis suggests that the point prevalence and 6‐month prevalence of high‐intensity and low‐disability neck pain are overestimated in this survey . Conclusion . This cross‐sectional study shows that neck pain is highly prevalent in Saskatchewan and that it significantly disables 4.6 % ( 95 % confidence interval , 3.3‐5.8 ) of the adult population",
"OBJECTIVES The incidence of upper-limb , neck-shoulder , and low-back disorders and their induction times were investigated among new workers in tasks with various physical workloads . METHODS New trailer assemblers ( N=364 ) were followed prospect ively for 45 months -- the workers ' health status via medical records and exposure to physical workload factors via job titles , walk-throughs , task descriptions , and some direct measurements . The incidence rate of first sick leave due to such disorders was calculated for different workload groups . The proportion of workers surviving without musculoskeletal disorders was estimated by the Kaplan-Maier product-limit estimator , and the effect of the exposure on the risk of incident disorders was estimated with the Cox proportional hazards model . RESULTS The highest annual incidences were observed for strenuous tasks , the incidence rate for men being 16.8 per 100 person-years [ 95 % confidence interval ( 95 % CI ) 8.0 - 30.9 ] for upper-limb disorders in strenuous tasks and 6.1 ( 95 % CI 2.0 - 14.1 ) in nonstrenuous tasks and that for women being 32.0 ( 95 % CI 11.7 - 69.7 ) and 9.9 ( 95 % CI 0.2 - 54.9 ) , respectively . The men 's risk of contracting an upper-limb or neck-shoulder disorder in strenuous tasks was about threefold [ hazard ratio ( HR ) 3.2 ( 95 % CI 1.1 - 9.4 ) for upper-limb disorders and 2.7 ( 95 % CI 0.9 - 8.1 ) for neck-shoulder disorders ] that of nonstrenuous tasks , whereas workload seemed not to affect low-back disorders . The workers first sought medical advice for their disorders typically some months after employment began . CONCLUSIONS Newly employed workers in h and -intensive tasks have a high risk of upper-limb and neck-shoulder disorders . An etiologic role for activities involving high force dem and s in upper-limb and neck-shoulder disorders is possible",
"Study Design This was a prospect i ve community-based , observational design . Objective To describe the epidemiology and risk/prognostic factors for back pain episodes of care in a population representing the nonelderly in the United States . Summary of Background Data Previous United States studies of the epidemiology of back pain care have used defined industrial population s or have relied on the patient 's recall of symptoms and care . Methods Cl aims forms from the R AND Health insurance Experiment , a r and omized controlled trial of the use of health services , were analyzed . Cl aims forms were selected if one of the patient- design ated reasons for the visit was back pain . Visits were grouped into episodes of care . Descriptive statistics were calculated for episodes . Multivariate logistic regression was used to calculate adjusted odds ratios for independent explanatory sociodemographic and health status variables associated with back pain episodes of care . Results The 3105 adults in the Health Insurance Experiment had a combined 11 , 171 person-years of exposure . Six-hundred-eighty-six persons ( 22 % ) had a total 1020 episodes of back pain care , representing 8825 visits . Seventy-one percent of persons had a single episode during the Health Insurance Experiment , and 40 % of these episodes consisted of a single visit . There were 9.1 episodes per 100 person-years . Insurance status , geographic site , white race , lesser education , poorer physical functioning , and greater pain at baseline all were independently associated with having a back pain episode of care . Conclusions Back pain episodes of care occur commonly in the adult U.S. population , but usually are brief and recur infrequently",
"The results of a prospect i ve study of 134 patients with lower back pain suggest that nonorganic factors are better predictors of return of work than organic findings . Patients who returned to work had fewer job , personal , or family rotated problems . There were no significant differences between patients who returned to work and those who did not when comparing myelograms , computed tomographic scans , or roentgenographs . The only significant difference in physical organic findings was for muscle atrophy . Patients who did not return to work had a statistically higher incidence rate of muscle atrophy . Length of time off from work was significantly related to outcome , but when patients were categorized according to time off the job , different factors predicted failure to return for patients , off work for less than 6 months and patients off for more than 6 months . For patients off for less than 6 months , important predictors were a high Oswestry score , history of leg pain , family relocation , short tenure on the job , verbal magnification of pain , reports of moderate to severe pain an superficial palpation , and positive reaction to a “ sham ” sciatic tension test . None of these was a significant predictor for the group off for more than 6 months . For the group off work for more than 6 month , previous injuries , and stability of family living arrangements were among the significant predictors not significant for the group off less than 6 months . Using 21 factors selected from a larger group of 92 factors , three statistically significant ( P ≤ 0.001 ) predictive measures were developed . These measures predicted return to work for the total sample , and for the two subgroups ( off more than , or less than 6 months ) more accurately than did the total set of 90 factors",
"Study Design . A controlled r and omized clinical trial was performed . Objective . To investigate the effect of a light mobilization program on the duration of sick leave for patients with subacute low back pain . Summary of Background Data . Early intervention with information , diagnostics , and light mobilization may be a cost-effective method for returning patients quickly to normal activity . In this experiment , patients were referred to a low back pain clinic and given this simple and systematic program as an outpatient treatment . Methods . In this study , 457 patients sick-listed 8 to 12 weeks for low back pain , as recorded by the National Insurance Offices , were r and omized into two groups : an intervention group ( n = 237 ) and a control group ( n = 220 ) . The intervention group was examined at a spine clinic and given information and advice to stay active . The control group was not examined at the clinic , but was treated with conventional primary health care . Results . At 12-month follow-up assessment , 68.4 % in the intervention group had returned to full-duty work , as compared with 56.4 % in the control group . Conclusions . Early intervention with examination , information , and recommendations to stay active showed significant effects in reducing sick leave for patients with low back pain",
"Objective - To investigate whether physical examination findings can be used in predicting recovery from back pain and new episodes of sick leave . Design - One-year prospect i ve study of a single cohort . Setting s - Semi-rural Swedish county . Population - A cross-section of a general population with back pain ( 207 women , 176 men ) between 20 and 59 years of age . Main outcome measures - Cumulative incidence of sick leave due to back pain , cumulative incidence of sick leave due to back pain > 30 days , incidence of recovery from back pain . Results - For recovery from pain , the absence of tenderness in the trapezius muscle ( OR 0.33 ; CI 0.1 - 0.5 ) was predictive . New sick leave was predicted by tenderness in the trapezius muscle ( OR 2.67 ; CI 1.5?4.9 ) , and had a tendency to be associated with a flattened lumbar lordosis and a restricted cervical range of motion . For long-term sick leave , the same findings and also observation of scoliosis ( OR 3.44 ; CI 1.1?10.5 ) were predictive . Conclusion ? There are subgroups with back pain predisposed to development of more persistent symptoms and a higher risk for sick-listing",
"Study Design . A prospect i ve cohort study with identical question naires and inclusion criteria was performed . Objectives . To compare in six different countries the frequencies and effects of the common medical interventions used for patients with low back pain who are work incapacitated . Summary of Background Data . Low back pain is a huge problem with increasing costs for health care , industry , and society . Methods . Cohorts of employed men and women ages 18 to 59 years who had been sick-listed ( 100 % ) for a minimum of 90 days because of low back pain were recruited in Denmark , Germany , Israel , Sweden , the Netherl and s , and the United States . The subjects received three separate question naires with identical questions after 90 days , 1 year , and 2 years . The question naires included separate questions about background factors , treatment , and the like , as well as vali date d scales such as the Hannover Activities of Daily Living , von Korff pain score , Short Form-36 , and Karasek-Theorell . Working status was obtained from registers . Main outcome measures were working/not working , back function , and pain . Results . All three question naires were completed by 2080 subjects in the six countries . With few exceptions , there were great similarities in the appointments , examinations , and treatments in the different countries . Considerable differences were found between the back surgery rates , which ranged from 6 % in Sweden to 32 % in the United States during the first 90 days of the study . Very few of the interventions had any noticeable positive effects on work resumption , pain , or back function . Back surgery in Sweden was a striking exception , positively affecting all three outcome measures . The frequencies of work resumption within the first year ranged from 73 % in the Netherl and s to 32 % in Denmark . Conclusions . Almost none of the commonly occurring and frequently practice d medical interventions for patients who are sick-listed because of low back pain had any positive effects on either the recorded health measures or work resumption",
"& NA ; The purpose of this Dutch prospect i ve population ‐based study was to identify prognostic factors for return‐to‐work of employees with 3–4 months sick leave due to low back pain ( LBP ) . A cohort of 328 employees was formed and baseline data were collected . One year after the first day of the sick leave , 91 % of the original cohort participated in a second interview ( n=298 ) . During the baseline measurement , information was collected about health status , history of LBP , occupational variables , job characteristics and social economic variables . At the second interview , 66 % of the employees had returned to work ( n=198 ) . Return‐to‐work was independently predicted by having a better general health status ( OR 1.53 ; 95 % CI 1.30–1.80 ) , having better job satisfaction ( OR 1.26 ; 95 % CI 1.11–1.44 ) , being a bread winner ( OR 2.46 ; 95 % CI 1.37–4.40 ) , having a lower age ( OR 0.70 ; 95 % CI 0.52–0.93 ) and reporting less pain ( OR 0.85 ; 95 % CI 0.73–0.99 ) all measured at cohort entry . This study shows that psycho‐social aspects of health and work in combination with economic aspects have a significantly larger impact on return‐to‐work when compared to relatively more physical aspects of disability and physical requirements of the job . This suggests that interventions aim ed at return‐to‐work of employees sicklisted with LBP should predominantly be focused on these psycho‐social aspects such as health behavior and job satisfaction , and on the ( lack of ) economic incentives for return‐to‐work ",
"Abstract A functional restoration ( FR ) program , dealing with a combination of intensive physical and ergonomic training , psychological pain management , and patient education , was tested in two r and omized , parallel group studies . In one of these patients following the FR program were compared with a non-treated control group ( project A ) , and in the other with patients on two less intensive treatment programs ( project B ) . A total of 238 chronic low back pain patients participated in the two studies , 106 entering project A and 132 project B. Patients from the two projects were comparable except that the patients in project A were recruited from all over the country , whereas patients in project B all were living in and around Copenhagen . Thirteen patients never started any treatment , and 20 patients ( 9 % ) dropped out during the treatment period . Of the 207 who completed treatment , 89 % returned a mailed question naire 5 years later . This was the case for 55 % of the drop-outs . The questions referred to work situation , pain level , activities of daily living , days of sick leave , contact with health care professionals , physical activity , use of medication , and a subjective overall assessment . The results show that in project A the treated group reported significantly fewer contacts with the health care system and significantly fewer days of sick leave over the 5-year follow-up period compared to the control group . In all other parameters , including work ability , there was no statistically significant difference between the two groups . In project B , patients treated in the FR program did significantly better in most measured parameters , except in leg pain , use of pain medication and sport activity , where no significant differences were found between groups . The overall result shows a positive long-term effect of the FR program , but it also shows the necessity of testing a given treatment in different projects and design s , among other things due to statistical variations",
"Clinical practice guidelines recommend a conservative approach to management of acute low back pain ( LBP ) . The present study sought to determine whether health care utilization and the physician ’s initial management of work-related LBP were associated with disability duration . Clinical management information was obtained for 98 r and omly selected , workers ’ compensation cl aim ants with acute , uncomplicated , disabling work-related LBP . Length of disability was based on indemnity ( wage replacement ) payments . Disability was significantly associated with increased utilization of specialty referrals ( P = 0.013 ) and provider visits ( P magnetic resonance imaging ( P = 0.003 ) , and use of opioids for more than 7 days ( P = 0.013 ) . Effects of early diagnostic imaging ( first 30 days of care ) on length of disability were observed ( P = 0.001 ) . Patients whose treatment course did not involve extended opioid use and early diagnostic testing were 3.78 times more likely ( 95 % confidence interval , 1.6 to 8.9 ) to have gone off disability status by the end of the study . The nature of the association between these initial clinical management aspects and LBP disability duration merits further exploration",
"OBJECTIVES Because musculoskeletal pain is the second most frequent reason for seeking health care , the aims of this study were to determine the value of psychosocial variables in evaluating risk for developing chronic back pain problems and to develop a screening methodology to identify patients likely to have a poor prognosis . STUDY DESIGN A prospect i ve study was conducted on consecutive patients with acute or subacute back pain , in which patients completed a screening question naire and were then followed up for 6 months to determine outcome . The primary outcome variable was accumulated sick leave . METHODS One hundred forty-two consecutive patients were asked to complete a question naire design ed for this study . This question naire contained 24 items concerning psychosocial aspects of the problem . Six months later , patients were contacted to complete outcome questions about accumulated sick leave . RESULTS A total of 97 % of the patients completed both question naires . Although patients , on average , improved greatly , 18 % had 1 - 30 days and 20 % had fewer than 30 days of sick leave during the follow-up period . Five variables were found to be the strongest predictors of sick leave outcome ( fear-avoidance work beliefs , perceived improvement , problems with work function , stress , and previous sick leave ) , correctly classifying 73 % of the patients as opposed to a chance rate of 33 % . A total score was evaluated as a means of judging risk and found to be strongly related to outcome . CONCLUSION Potent psychosocial risk factors associated with future sick absenteeism were identified . Because the total score was related to outcome , the instrument may have use in screening patients with acute or subacute spinal pain in clinical situations",
"To study the natural history of acute sciatica , 208 patients with obvious symptoms and signs of a lumbar radiculopathy ( L5 and S1 ) were examined within 14 days of onset . A concomitant double-blind investigation of the effect of the nonsteroidal anti-inflammatory drug piroxicam was performed . The results measured by visual analog scale and Rol and 's functional tests showed a satisfactory improvement throughout the 4 weeks of observation . The piroxicam-treated group had same results as the control group . Based on question naires at months 3 and 12 approximately 30 % of the patients still complained about back trouble and 19.5 % were out of work after 1 year . Four patients underwent surgery during this period",
"Objective . This r and omized clinical trial was design ed to determine the effect of treating low back pain as a benign , self limiting condition by light normal activity . Methods . Patients on sickness leave from work for more than 8 weeks were r and omized into two groups : intervention ( n = 463 ) and control ( n = 512 ) . Those in the intervention group were examined , provided information , and given instruction . Outcome was measured by return or failure to return to work ( still on sickness leave ) . Results . Survival analysis showed a highly significant ( P = 0.000 ) reduction in sickness leave in the intervention group as compared with the control group . At 200 days 60 % were still on sickness leave in the control group vs. 30 % in the intervention group . A multivariate analysis with age , sex , and treatment as cofactors showed that sex had no effect on length of sickness leave and that treatment retained its effect when adjusting for differences in age composition . Conclusion . This study indicates that low back pain treated as a benign , self limiting condition recommended to light mobilization gives superior results as compared to treatment within a conventional medical system",
"BACKGROUND Bed rest and back-extension exercises are often prescribed for patients with acute low back pain , but the effectiveness of these two competing treatments remains controversial . METHODS We conducted a controlled trial among employees of the city of Helsinki , Finl and , who presented to an occupational health care center with acute , nonspecific low back pain . The patients were r and omly assigned to one of three treatments : bed rest for two days ( 67 patients ) , back-mobilizing exercises ( 52 patients ) , or the continuation of ordinary activities as tolerated ( the control group ; 67 patients ) . Outcomes and costs were assessed after 3 and 12 weeks . RESULTS After 3 and 12 weeks , the patients in the control group had better recovery than those prescribed either bed rest or exercises . There were statistically significant differences favoring the control group in the duration of pain , pain intensity , lumbar flexion , ability to work as measured subjectively , the Oswestry back-disability index , and number of days absent from work . Recovery was slowest among the patients assigned to bed rest . The overall costs of care did not differ significantly among the three groups . CONCLUSIONS Among patients with acute low back pain , continuing ordinary activities within the limits permitted by the pain leads to more rapid recovery than either bed rest or back-mobilizing exercises",
"Study Design . A prospect i ve cohort study was conducted on workers cl aim ing earnings-related compensation for low back pain . Information obtained at the time of the initial cl aim was linked to compensation status ( still cl aim ing or not cl aim ing ) 3 months later . Objective . To identify individual , psychosocial , and workplace risk factors associated with the transition from acute to chronic occupational back pain . Summary of Background Data . Despite the magnitude of the economic and social costs associated with chronic occupational back pain , few prospect i ve studies have investigated risk factors identifiable in the acute stage . Methods . At the time of the initial compensation cl aim , a self-administered question naire was used to gather information on a wide range of risk factors . Then 3 months later , chronicity was determined from cl aim ants ’ computerized records . Results . The findings showed that 3 months after the initial assessment , 204 of the recruited 854 cl aim ants ( 23.9 % ) still were receiving compensation payments . A combined multiple regression model of individual , psychosocial , and workplace risk factors demonstrated that severe leg pain ( odds ratio [ OR ] , 1.9 ) , obesity ( OR , 1.7 ) , all three Oswestry Disability Index categories above minimal disability ( OR , 3.1–4 ) , a General Health Question naire score of at least 6 ( OR , 1.9 ) , unavailability of light duties on return to work ( OR , 1.7 ) , and a job requirement of lifting for three fourths of the day or more all were significant , independent determinants of chronicity ( P < 0.05 ) . Conclusions . Simple self-report measures of individual , psychosocial , and workplace factors administered when earnings-related compensation for back pain is cl aim ed initially can identify individuals with increased odds for development of chronic occupational disability",
" A cohort of3,342 cases constituting a r and om sample of all occupational back injuries compensated in Quebec ( Canada ) during 1981 was observed prospect ively for 3 years to study associations between cumulative duration of absence from work and sex , age , site of symptoms ( cervical , thoracic , and lumbar ) , and occupation . Of the cohort members , 287 ( 9.7 % ) cumulated 6 months of absence or more . A logistic regression model showed age and site of symptoms to be the two most important risk factors associated with absences of 6 months or more . No association was found with sex or occupation . The results showed discrepancies between measures of frequency distribution of back injuries and duration of absence from work , an important finding in terms of identifying health priorities",
"Objectives . This pilot study explored a broad range of work-related outcomes for occupational low back injuries . Methods . A model of occupational outcomes and a survey instrument were developed on the basis of interviews , expert opinion , and literature review s. New Hampshire workers who had an occupational back injury a year before the study were sample d from first reports of injury and sent a mailed survey about their postinjury experiences and related factors . Results . Of 251 r and omly selected cases , a valid address could be identified for 121 , and 99 patients responded . Almost 60 % of the respondents had lost 1 week of work or more . At 1 year after injury , half of the respondents had returned to their preinjury job and employer , and 20 % were unemployed , half of them because of the injury . Most working respondents reported no decrease in their work capacity . However , 68 % still had pain exacerbated by work , and 47 % worried that their condition would worsen with continued work . Reinjury occurred in 42 % of the respondents . The work-related outcome measures were largely independent of each other . Exploratory multivariate analyses demonstrated unique patterns of factors associated with each outcome . Reinjury risk was significantly greater in respondents whose employers offered accommodations or whose postinjury jobs had greater ergonomic risk . The small sample size limited the ability to achieve statistically significant results in multivariate analyses . Conclusions . Simply measuring return to work did not appear to capture the full range of job-related consequences from occupational back injuries in this pilot evaluation . Timing of return to work , occupational ergonomic risks , and appropriate job modifications appeared to be particularly important in a safe return to the job after an occupational low back injury . Results suggest opportunities to address risk factors that may improve work outcomes",
"Study Design The incidence of two common discharge recommendations , return to work unrestricted ( RTWU ) and restricted ( RTWR ) suggested that most restrictions were applied on the basis of patients ' subjective reports of pain or therapist 's unfounded fears that return to full duty would result in physical harm . Objectives This prospect i ve study compares the therapist 's return to work recommendation to the patient 's actual work status and analyzes the effect of that recommendation on outcome . Methods There were 1438 consecutive patients review ed by structured telephone interviews during the two halves of the study : the control group when pain was accepted as a reason for restriction and the study group when it was not . Summary of Background Data In the control group , 44 % of the patients were recommended to RTWU ; for the study group , 81 % received this recommendation . Compliance was 84 % for the control subjects and 78 % for the study group . Results The absolute number of patients who returned to unrestricted work doubled in the study group . Conclusions The probability of a successful return to normal duty increased with a recommendation of RTWU ( P = 0.0001 ) , whereas the probability of failure increased when restrictions were imposed ( P = 0.0001 )",
"OBJECTIVES This study investigates the relationship between physical and psychosocial load at work and sickness absence due to neck pain . METHODS A prospect i ve cohort study with a follow-up period of 3 years ( 1994 - 1998 ) was performed among a working population . At the beginning of the study , physical load at work was quantified by means of video recordings . Work-related psychosocial variables were measured by means of the Job Content Question naire . The frequency of sickness absence due to neck pain with a minimal duration of 3 days was assessed on the basis of company registration s during the follow-up period . Altogether 758 workers were included in the analyses . Possible confounding by individual characteristics , physical load , and psychosocial load was studied . RESULTS Work-related neck flexion and neck rotation , low decision authority , and medium skill discretion showed statistically significant increased risks for sickness absence due to neck pain ( adjusted rate ratios ranging from 1.6 to 4.2 ) . High quantitative job dem and s , low skill discretion , and low job security showed nonsignificant increased risks for sickness absence due to neck pain ( adjusted rate ratios of 2.0 , 1.6 and 1.7 , respectively ) . Work-related sitting , conflicting job dem and s , supervisor support , and co-worker support did not increase sickness absence due to neck pain . CONCLUSION Work-related neck flexion , neck rotation , low decision authority , and medium skill discretion are risk factors for sickness absence due to neck pain . There are indications that high job dem and s , low skill discretion , and low job security are also risk factors for sickness absence due to neck pain",
"& NA ; This prospect i ve study identifies physical , behavioral , and psychosocial correlates of subsequent employment status in a sample of low back pain patients . The sample of 150 subjects was drawn from 2 population s of persons with chronic low back pain : 87 individuals who were receiving care at a university low back pain clinic , and 63 individuals who had applied for ( but not yet received ) Social Security compensation on the basis of low back pain . All subjects had worked at least 3 months prior to their latest unemployment period and were currently out of work . Initial assessment included a medical history , physical examination , biomechanical testing , psychiatric interview , and MMPI testing . All subjects were followed up 6 months later to determine whether they had returned to work . Cross‐sectional group comparisons at the time of initial assessment showed that , after controlling for the effects of age , the two sample s differed on several physical and biomechanical measures , the Social Security group reflecting a more chronic picture . Group differences on physical variables were found , but most significant differences disappeared when adjusted for length of time out‐of‐work . Longitudinal analyses showed that few objective physical or biomechanical measures were associated with return‐to‐work at 6 months , while a number of psychosocial variables were significant predictors of 6‐month work status . The data suggest that exclusive reliance on the physical examination to determine level of disability , without consideration of psychosocial conditions , and without adjusting for the confounding effects of age and length of time out‐of‐work , is not empirically justified . Logistic regression analysis was used to ascertain the relative contribution of each predictor to outcome and to illustrate the hypothetical effects of changes in the levels of selected risk factors on the likelihood of return‐to‐work . Implication s for interventions with low back pain patients are discussed and future research directions suggested",
"OBJECTIVES To test the hypotheses that : ( 1 ) Lumbar spine radiography in primary care patients with low back pain is not associated with improved patient outcomes , including pain , disability , health status , sickness absence , reassurance , and patient satisfaction or belief in the value of radiography . ( 2 ) Lumbar spine radiography in primary care patients with low back pain is not associated with changes in patient management , including medication use , and the use of primary and secondary care services , physical therapies and complementary therapies . ( 3 ) Participants choosing their treatment group ( i.e. radiography or no radiography ) do not have better outcomes than those r and omised to a treatment group . ( 4 ) Lumbar spine radiography is not cost-effective compared with usual care without lumbar spine radiography . DESIGN A r and omised unblinded controlled trial . SETTING Seventy-three general practice s in Nottingham , North Nottinghamshire , Southern Derbyshire , North Lincolnshire and North Leicestershire . Fifty-two practice s recruited participants to the trial . SUBJECTS R and omised arm : 421 participants with low back pain , with median duration of 10 weeks . Patient preference arm : 55 participants with low back pain , with median duration of 11 weeks . INTERVENTION Lumbar spine radiography and usual care versus usual care without radiography . MAIN OUTCOME MEASURES Rol and adaptation of the Sickness Impact Profile , visual analogue pain scale , health status scale , EuroQol , use of primary and secondary care services , and physical and complementary therapies , sickness absence , medication use , patient satisfaction , reassurance and belief in value of radiography at 3 and 9 months post-r and omisation . RESULTS Participants r and omised to receive an X-ray were more likely to report low back pain at 3 months ( odds ratio ( OR ) = 1.56 ; 95 % confidence interval ( CI ) , 1.02 to 2.40 ) and had a lower overall health status score ( p = 0.02 ) . There were no differences in health or functional status at 9 months . A higher proportion of participants consulted the general practitioner ( GP ) in the 3 months following an X-ray ( OR = 2.72 ; 95 % CI , 1.80 to 4.10 ) . There were no differences in use of any other services , medication use or sickness absence at 3 or 9 months . No serious spinal pathology was identified in either group . The commonest X-ray reports were of discovertebral degeneration and normal findings . Many patients did not perceive their information needs were met within the consultation . Satisfaction with care was greater in the group receiving radiography at 9 months . Participants r and omised to receive an X-ray were not less worried , or more reassured about serious disease causing their low back pain . Satisfaction was associated with meeting participants ' information needs and reduced belief in the necessity for investigations for low back pain , including X-rays and blood tests . In both groups , at 3 and 9 months 80 % of participants would choose to have an X-ray if the choice was available . Participants in the patient preference group achieved marginally better outcomes than those r and omised to a treatment group , but the clinical significance of these differences is unclear . Lumbar spine radiography was associated with a net economic loss at 3 and 9 months . CONCLUSIONS Lumbar spine radiography in primary care patients with low back pain of at least 6 weeks duration is not associated with improved functioning , severity of pain or overall health status , and is associated with an increase in GP workload . Participants receiving X-rays are more satisfied with their care , but are not less worried or more reassured about serious disease causing their low back pain . CONCLUSIONS - RECOMMENDATIONS FOR FURTHER RESEARCH : Further work is required to develop and test an educational package that educates patients and GPs about the utility of radiography and provides strategies for identifying and meeting the information needs of patients , and the needs of patients and GPs to be reassured about missing serious disease . Guidelines on the management of low back pain in primary care should be consistent about not recommending lumbar spine radiography in patients with low back pain in the absence of red flags for serious spinal pathology , even if the pain has persisted for at least 6 weeks",
"Study Design . A prospect i ve observational study with an 11-year follow-up period was performed . Objective . To investigate the influence of education and socioeconomic position on the incidence of permanent disability retirement from back pain . Summary of Background Data . Early retirement because of back pain is the extreme end point of a disabling process that is a great burden to the individual and costly for the society . Groups of employees at particular risk for permanent back pain disability need to be identified . Methods . All employed men and women in Norway between the ages of 20 and 53 years in 1980 were included ( n = 1,333,556 ) . Outcome measures were disability retirement from inflammatory back pain ( ICD-9 code 720 ) and noninflammatory back pain ( ICD-9 codes 721 to 724 ) . Results . The 11-year cumulative incidence was 0.15 % ( n = 1990 ) for disability retirement from inflammatory back pain and 1.64 % ( n = 21,829 ) for noninflammatory back pain and was somewhat higher in women than in men . Each year of formal education was independently associated with decreased risk for disability retirement from noninflammatory back pain ( odds ratio [ OR ] = 0.78 ; 95 % confidence interval [ CI ] = 0.77–0.79 ) and from inflammatory back pain ( OR = 0.83 ; 95 % CI = 0.81–0.86 ) . Whereas disability from inflammatory back pain was moderately associated with socioeconomic status , there was a consistent upward trend in the association between disability retirement from noninflammatory back pain and lower socioeconomic position . The OR for unskilled workers was 3.1 ( 95 % CI = 2.6–3.7 ) for men and 2.1 ( 95 % CI = 1.7–2.5 ) for women , as compared with that of higher professionals . Stepwise analyses suggest that the effect of education is not mediated by socioeconomic status . Conclusions . The consistent upward trend in the relation of disability retirement to lower levels of education and socioeconomic position , even for inflammatory back pain , shows that factors related to the occupational and social environment play an important role in the disabling process . The stepwise , monotonic relation between socioeconomic position and disability retirement from back pain , even at the higher end of the socioeconomic scale , suggests that the relation between social class and back pain disability can not be explained solely in terms of manual versus nonmanual jobs",
"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",
"A population -based survey of approximately 4000 adults in Belgium , a bi-cultural country with a uniform health care system , explored the relationships of socio-cultural and employment factors to the reported experience of low back pain ( LBP ) . Predictors of 1 ) history of LBP , 2 ) first LBP , and 3 ) daily LBP were examined by multiple logistic regression analysis . Thirty-three percent of the population had current LBP , including 5 % experiencing their first episode ; 26 % had past but not current LBP , and 41 % had never had LBP . Increasing age ( OR > 2.0 , P = .000 ) and female gender ( OR 2.16 , P = .000 ) were associated with history of LBP ; only gender ( OR 1.40 , P = .02 ) was associated with first episode ; neither was associated with daily LBP . Language was associated with history ( OR 1.80 , P = .000 ) and first occurrence ( OR 1.77 , P = .000 ) but not daily LBP . Among those employed , work dissatisfaction was associated with history of LBP ( OR > 2.4 , P = .02 ) and daily LBP ( OR 3.85 , P = .02 ) , but not with first episode . The results suggest that sociocultural factors influence the expression of LBP , but not the risk of chronicity once LBP is reported , and that work satisfaction may not be causally related to LBP , but may intervene along with type of occupation in the possibility of continuing employment once LBP is present . Prospect i ve studies are needed to confirm these results and eluci date causal relationships"
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41186fd0-06ff-11f0-808a-c43d1ab1c353
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Objective : To gain an insight into the daily physical activity levels of patients with chronic pain or fatigue compared with asymptomatic controls . Data sources : MEDLINE , EMBASE , PsycINFO , Picarta , Cochrane Data base of Systematic Review s , reference tracking and a manual search of relevant journals . Review methods : A systematic , computerized data base search of the medical data bases up to September 2006 was performed . In addition , a h and search of relevant journals was carried out . Appropriate studies reported on the daily physical activities of adult patients with chronic pain or fatigue and included an asymptomatic control group . Two review ers independently carried out method ological quality assessment and data extraction . A qualitative analysis was performed . Results : Twelve studies were included , involving five different syndromes . Results show large heterogeneity in methods used and syndromes investigated , which limited evidence . Eleven different methods were used to assess daily physical activities result ing in 16 different outcome parameters . There seem to be differences between the different syndromes , but results are not conclusive . Eight studies reported a lower physical activity level in patients compared with controls . There seems to be a difference in results between studies using objective versus those using subjective methods . Conclusions : Results reported in the literature with respect to the activity level of patients with chronic pain or fatigue compared with controls were too heterogeneous to give sufficient evidence and were not conclusive
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"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 Recent guidelines for those with acute low back pain have advocated early resumption of normal activity and increased physical activity . Little is known about the relationship between low back pain and physical activity , and on the impact of that relationship on the promotion of increased levels of physical activity within a general practice population . OBJECTIVES We aim ed to explore associations between factors that influence changes in physical activity and the way individuals perceive and behave with their low back pain , and the impact of those perceptions and behaviour on physical activity . METHODS Twenty-seven informants were chosen using a purposive sample from a larger group of individuals who , because of their low back trouble , had been referred by their GPs to a community-based , single-blind , r and omized controlled trial ( RCT ) at the University of York , which is evaluating the effectiveness and cost-effectiveness of a progressive exercise programme . Fifty-four interviews were conducted with this subgroup of the RCT ; four informants were interviewed once , 19 twice and four of them three times . Interviews were transcribed and analysed using manual and computer-aided approaches . RESULTS Physical activity was perceived as ( i ) activities of daily living , ( ii ) activities causing breathlessness that they went out of the way to do and ( iii ) more competitive-type activity . The avoidance of physical activity and fear of pain returning were the two main factors directly associated with informants ' backs and changes in physical activity . These two factors hindered increases in physical activity , even though the majority of informants believed strongly that being physically active helped ease their low back pain . CONCLUSIONS When advocating that individuals with acute low back pain return to or increase physical activity , it is important that clinicians identify avoidance of physical activity and /or fear of pain at the earliest stage in order to tailor advice and reassurance appropriately . If avoidance of activity and fear of pain is identified and clinicians want to encourage patients to take up and sustain increased physical activity , they should explore issues of fear of pain , and avoidance of and confidence to do physical activities , in addition to other factors influencing physical activity",
"The reliability of the doubly labeled water method for measuring total daily energy expenditure ( TDEE ) was measured in six adult women at a 6-mo interval . The contribution of r and om error to reliability was assessed by repeating each isotopic analysis . Physiologic variation was calculated from the difference between the total variance and the analytic variance . In addition , postabsorptive resting metabolic rate and thermic effect of a meal were measured to partition the physiologic variation in TDEE into its three components . No seasonal effect ( summer-winter ) in TDEE was detected in these six subjects . The within-subject coefficient of variation for TDEE was 7.8 % , of which physiologic variation was 6.4 % . Within-subject variation in physical activity was the major source of variation in TDEE . Review of the 16 published studies , in which at least two measurements of TDEE by doubly labeled water were performed in each subject , indicated that the reliability of the method is 7.8 % , except under conditions of high water flux . Care , however , must be taken to ensure that the analytic contribution does not inflate this figure in any given laboratory",
"OBJECTIVE To examine the reliability , validity , and responsiveness of a continuous ambulatory activity monitor in patients with rheumatoid arthritis ( RA ) . METHODS Forty-one patients with RA , participating in a r and omized controlled trial examining the effect of an intensive exercise program , were assessed by means of the Dynaport ADL ( activities of daily living ) monitor ( AM ) . The time spent on activities ( locomotion , st and ing , and active sitting ) during 24 hours and the intensity of trunk movement during these activities were recorded . To determine test-retest reliability 20 patients were reassessed with the AM one week after the first assessment . Construct validity of the AM was determined by comparing the AM results with physical fitness measures ( muscle strength , endurance , joint mobility ) , disease activity , and functional status . As well , 37 patients were assessed 18 months after the first assessment to determine responsiveness . RESULTS All AM measurements showed satisfactory test-retest reliability ( ICC 0.63 - 0.76 ) . AM measures were significantly associated with physical fitness , functional status , and disease activity , indicating construct validity of the AM . The AM could discriminate between patients with improvement and deterioration in physical fitness , indicating sufficient responsiveness of AM variables . CONCLUSION This study shows the value of an ambulatory activity monitor to quantify both the amount and intensity of physical activity of patients with RA during a day in their own environment . The ambulatory activity monitor seems to be a promising instrument for research into rehabilitation of patients with RA",
"OBJECTIVE Changes in physical activity are thought to play an important role in maintaining symptoms in chronic fatigue syndrome ( CFS ) . The aim of this study was to describe intraindividual physical activity patterns in more detail and to identify pervasively passive patients . METHODS With help of a movement-sensing device , physical activity levels were registered continuously over a 12-day period in 277 CFS patients . Within this registration period , the 10 largest activity peaks were computed . The intensity and duration of these activity peaks and their subsequent rest periods were described and compared to those of 47 healthy controls . In addition , the patients ' 12 daily activity scores were used to identify patients who were characterised by low levels of physical activity throughout the registration period . RESULTS The CFS sample had less intense and shorter activity peaks , while the average rest periods that followed these peaks lasted longer . Approximately one-fourth of the CFS sample differed distinctly from the control group and was labelled as pervasively passive . CONCLUSION The measurements and classification of actual physical activity levels were found to reduce heterogeneity in the CFS population and therefore could provide the opportunity to optimise behavioural intervention protocol s for CFS",
"INTRODUCTION During the last 20 years a great number of studies have emphasized the potential role of psychological factors as relevant predictors for the first onset of back pain as well as for the development of chronic pain . The formulation of a biopsychosocial perspective of the etiology and chronicity of back pain was a natural consequence . Actual questions concern the relative impact of psychological risk factors in the process of chronicity of back pain compared to biomedical , social and occupational factors . METHODS Whereas several review articles regarding the role of psychological risk factors are available up to now , a recently published review conducted by Steven Linton was the first systematic analysis of well controlled prospect i ve studies published since 1967 . Using a grading system similar to that recommended for guidelines the author defined a level A evidence when at least two good- quality prospect i ve studies supported the prospect i ve power of a variable . Level B evidence had support from one prospect i ve study . Level C represented inconclusive data and level D indicated that no studies met the criteria . Based on a literature search of more than 900 studies , 37 good- quality prospect i ve studies were analysed in detail . RESULTS The results indicated level A evidence for the following interrelations : ( 1 ) Psychosocial variables , especially chronic distress in daily life , depression and work dissatisfaction were clearly associated with the onset of back and neck pain ( 2 ) . Psychological variables , especially chronic stress in daily life , work dissatisfaction , depression and pain-related cognitions and coping behaviour were clearly linked to the transition from acute to chronic pain and disability ( 3 ) . Psychological variables generally had more prospect i ve power than biomedical , social or objective occupational variables . Among the pain-related cognitions , catastrophizing and fear-avoidance-beliefs yielded the most empirical support . Among coping behaviour passive coping stretegies such as avoiding behaviour was most important . At least level B evidence has been shown for the counterpart of an extreme suppressive coping behaviour . Patients who tended to suppress or ignore pain in order to finish all activities they started , who were unable to integrate phases of passive relaxation into the daily routine displayed a high risk of chronicity of pain 6 months after an acute phase of pain . One international and two German good- quality prospect i ve studies have shown the predictive power of a maladaptive suppressive behaviour pattern . Based on the avoidance-endurance-model of pain chronification , both extreme and one-sided passive pain coping as well as one-sided suppressive coping modes were conceptualized as maladaptive due to the process of chronicity . We assume that extreme passive behaviour will lead to immobility and muscular atrophy . Neurophysiological processes of sensitization will further lead to the development of chronic pain . On the other h and , extreme suppressive behaviour will lead to an overuse of muscles and joints with a repetitive combination of muscular hyperactivity and pain . These repetitive pain experiences will also elicit neurophysiological processes of sensitization . ( 4 ) Psychosocial variables displayed more predictive power than biomedical or biomechanical factors . ( 5 ) Psychosocial factors may be used as predictors of the risk for developing long-term pain and disability . Mixed empirical evidence has been shown for the role of personality factors ( level C evidence ) and no support has been found for the idea of a \" pain prone \" personality disorder or for the role of sexual and physical abuse . DISCUSSION 20 years of research , several qualitative review s and a recently published systematic review of 37 good- quality prospect i ve studies regarding the role of psychological , biomedical , social and objective occupational factors in the process of chronicity of back pain revealed that psychological factors are significantly related to the onset of back pain as well as to the development of chronic pain . Furthermore , the psychological factors displayed more predictive power than biomedical or biomechanical variables . As a consequence for clinical practice , these psychological risk factors have to be considered as \" yellow flags \" if a back pain problem wo n't respond to medical treatment for more than four weeks . As a further consequence , special risk factor - based psychosocial interventions should be offered in addition to the medical treatment to patients with high psychological risk factors for the development of chronic pain . The efficacy of such an interdisciplinary care in the very early phases of back pain in order to prevent chronicity of pain and disability has been published recently by our group",
"This paper describes the assessment of physical activity in chronic fatigue syndrome ( CFS ) and investigated the following questions : Do patients with CFS have low levels of physical activity ; is there a relationship between actual level of physical activity and fatigue ; can self-report measures adequately assess actual level of physical activity ; what is the role of cognitions with respect to physical activity ; and are results with respect to physical activity specific to CFS ? Three different types of activity measures were used : self-report question naires , a 12-day self-observation list , and a motion-sensing device ( Actometer ) which was used as a reference for actual activity level . Fifty-one patients with CFS , 50 fatigued patients with multiple sclerosis ( MS ) , and 53 healthy subjects participated in this study . Although none of the self-report question naires showed high correlations with the Actometer , question naires that require simple ratings of specified activities were related to the Actometer and can be used as acceptable substitutes , in contrast to instruments that require general subjective interpretations of activity that had low or non-significant correlations with the Actometer . Actometer results showed that CFS patients and MS patients had similar activity levels and both groups were significantly less active than healthy subjects . Compared to MS patients , CFS patients were more likely to indicate that they had been less active than other persons they knew . Activities which patients expected to result in higher fatigue levels were less frequently performed . Patients with CFS had significantly higher scores on this measure than MS patients and healthy subjects . Low levels of physical activity were related to severe fatigue in CFS but not in MS . In conclusion , although CFS patients have similar low activity levels than MS patients , there are also important differences between both groups : in CFS cognitive factors are more prominently involved in producing the low activity levels than in MS and in CFS patients activity level is related to fatigue but not in MS",
"OBJECTIVE A variety of instruments have been applied to the measurement of activity , yet few , if any , have been vali date d specifically for older people with chronic pain . This study has sought to examine the utility of the Human Activity Profile ( HAP ) for describing activity in a sample drawn from a pain clinic for older people . DESIGN The HAP was administered to 193 older pain clinic patients , 72 of whom completed the profile on a second occasion . A further 55 responses were collected from a group of community-dwelling volunteers . The factor structure of the HAP was tested using these 320 responses . The factors subsequently derived were compared with the Sickness Impact Profile ( SIP ) and the Barthel Index ( BI ) . The discriminant validity of the HAP was examined by comparing factor scores for groups determined by gender , diagnosis , and status in the pain clinic . RESULTS The 94 items of the HAP loaded onto 10 factors , which explained 63.7 % of the variance . These factors demonstrated moderate associations with the BI and the subscales of the SIP . The factors discriminated between men and women ( F[12.180 ] = 9.85 . p subjects with a musculoskeletal pain problem , postherpetic neuralgia , and pain-free volunteers ( F[24.340 ] = 4.7 . p Factor scores increased between pre- and postclinic assessment s ( F[12.60 ] = 4.79 . p HAP has demonstrated qualities which favor its adoption as an activity measure for older pain clinic patients"
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4118700c-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND More than 180 different types of therapy have been used in the treatment and management of painful bladder syndrome/interstitial cystitis ( PBS/IC ) , yet evidence from clinical trials remains inconclusive . This study aim ed to evaluate the efficacy of pharmacologic approaches to PBS/IC , to quantify the effect size from r and omized controlled trials , and to begin to inform a clinical consensus of treatment efficacy for PBS/IC . METHODS We identified r and omized controlled trials for the pharmacologic treatment of patients with PBS/IC diagnosed on the basis of National Institute of Diabetes and Digestive and Kidney Diseases or operational criteria . Study limitations include considerable patient heterogeneity as well as variability in the definition of symptoms and in outcome assessment . RESULTS We included a total of 1470 adult patients from 21 r and omized controlled trials . Only trials for pentosan polysulfate sodium had sufficient numbers to allow a pooled analysis of effect . According to a r and om-effects model , the pooled estimate of the effect of pentosan polysulfate therapy suggested benefit , with a relative risk of 1.78 for patient-reported improvement in symptoms ( 95 % confidence interval , 1.34 - 2.35 ) . This result was not heterogeneous ( P = .47 ) and was without evidence of publication bias ( P = .18 ) . Current evidence also suggests the efficacy of dimethyl sulfoxide and amitryptyline therapy . Hydroxyzine , intravesical bacille Calmette-Guérin , and resiniferatoxin therapy failed to demonstrate efficacy , but evidence was inconclusive owing to method ological limitations . CONCLUSIONS Pentosan polysulfate may be modestly beneficial for symptoms of PBS/IC . There is insufficient evidence for other pharmacologic treatments . A consensus on st and ardized outcome measures is urgently needed
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[
"PURPOSE In a previous retrospective analysis , cyclosporine A ( CyA ) was highly efficient in treating patients with interstitial cystitis . A prospect i ve r and omized study with this immunosuppressive agent was warranted . We compared CyA to pentosan polysulfate sodium ( PPS ) in patients with interstitial cystitis . MATERIAL S AND METHODS A total of 64 patients with interstitial cystitis meeting the National Institute of Diabetes and Digestive and Kidney Diseases criteria were enrolled in a r and omized prospect i ve study . Patients were r and omized in a 1:1 ratio to 1.5 mg/kg CyA twice daily ( 27 women , 5 men ) or 100 mg PPS 3 times daily ( 26 women , 6 men ) for a period of 6 months . The primary end point was daily micturition frequency , and secondary end points were mean and maximal voided volume , number of nocturia episodes , O'Leary-Sant symptom and problem indexes , visual analogue scale for pain , and subjective global response assessment . RESULTS CyA was superior to PPS in all clinical outcome parameters measured at 6 months . Micturition frequency in 24 hours was significantly reduced in the CyA arm compared to the PPS arm ( -6.7 + /- 4.7 vs -2.0 + /- 5.1 times ) . The clinical response rate ( according to global response assessment ) was 75 % for CyA compared to 19 % for PPS ( p adverse events in the CyA arm than in the PPS arm , 29 patients completed the 6-month followup in both groups . CONCLUSIONS CyA is more effective than PPS in interstitial cystitis",
"Sodium pentosanpolysulfate ( Elmiron ) is a synthetic , sulfated polysaccharide available in an oral form that is excreted into the urine . This drug was used in a double-blind fashion to evaluate its efficacy in the management of symptoms of interstitial cystitis . A dose of 100 mg . 3 times daily was used for a minimum of 4 months and was continued for longer than 18 months in some individuals . A total of 62 patients was evaluated from 2 different medical centers . Subjective improvements were greater in all parameters when the drug was compared to placebo therapy , with significant improvement in pain , urgency , frequency and nocturia . Objective improvement in average voided volumes was greater with the drug than with placebo ( p equals 0.009 ) . No significant difference was found between drug and placebo groups in the average number of daily voiding episodes",
"The O'Leary-Sant Interstitial Cystitis Symptom Index ( ICSI ) has been proposed as a treatment outcome measure in interstitial cystitis ( IC ) . The psychometric properties of the ICSI were assessed for reliability and validity in a r and omized , double-blind clinical study of 300 , 600 , and 900 mg daily dose of pentosan polysulfate sodium ( PPS ) in patients with IC . The ICSI contains 4 items that measure urgency and frequency of urination , nighttime urination , and pain or burning . The ICSI index score is the sum of the item scores ( range : 0 - 20 ) . ICSI scores were obtained at baseline , 4 , 8 , 12 , 16 , 24 , and 32 weeks of treatment . Patients ' overall ratings of improvement of symptoms ( PORIS ) scores evaluating improvements in pain , urgency , and overall IC symptoms were also collected except at baseline . A total of 376 patients were included in the analysis . Psychometric properties evaluated included variability ( range ) , test-retest reliability ( intraclass correlation coefficient [ ICC ] ) , internal consistency ( the Cronbach alpha ) , construct validity ( convergent , discriminant ) , responsiveness , and clinical ly meaningful change . The ICSI items and index score had good variability and test-retest reliability . The ICSI demonstrated internal consistency reliability and was responsive to change . Participants indicating a 75 % improvement in PORIS had a 48 % mean reduction in the ICSI score , while participants reporting 100 % improvement in PORIS had a 77 % mean reduction in the ICSI score . The ICSI is a valid , reliable , and responsive measure of change in IC symptoms . This outcome measure should be utilized in future treatment outcomes studies in IC",
"PURPOSE This pilot study was design ed to evaluate the feasibility of a multicenter , r and omized , clinical trial in interstitial cystitis ( IC ) . Secondary objectives were to evaluate the safety and efficacy of oral pentosan polysulfate sodium ( PPS ) , hydroxyzine , and the combination to consider their use in a larger r and omized clinical trial . MATERIAL S AND METHODS A 2 x 2 factorial study design was used to evaluate PPS and hydroxyzine . Participants met the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC and reported at least moderate pain and frequency for a minimum of 6 months before study entry . The primary end point was a patient reported global response assessment . Secondary end points included vali date d symptom indexes and patient reports of pain , urgency and frequency . The target sample size was 136 participants recruited during 10 months . RESULTS A total of 121 ( 89 % of goal ) participants were r and omized over 18 months and 79 % provided complete followup data . The response rate for hydroxyzine was 31 % for those treated and 20 % for those not treated ( p = 0.26 ) . A nonsignificant trend was seen in the PPS treatment groups ( 34 % ) as compared to no PPS ( 18 % , p = 0.064 ) . There were no treatment differences for any of the secondary end points . Adverse events were mostly minor and similar to those in previous reports . CONCLUSIONS The low global response rates for PPS and hydroxyzine suggest that neither provided benefit for the majority of patients with IC . This trial demonstrated the feasibility of conducting a multicenter r and omized clinical trial in IC using uniform procedures and outcomes . However , slow recruitment underscored the difficulties of evaluating commonly available IC drugs",
"PURPOSE We test the hypothesis that women without chronic pelvic pain or irritative voiding symptoms do not demonstrate petechial hemorrhages known as glomerulations that are characteristic of patients with interstitial cystitis . MATERIAL S AND METHODS A prospect i ve cohort design was used for examination with cystoscopy and bladder distention of 20 asymptomatic women undergoing tubal ligation . Cystoscopy with the patient under general anesthesia was performed to inspect the bladder mucosa before and after distention at 70 cm . of water pressure for 2 or 6 minutes . Photographs of the right , posterior and left of the bladder surfaces taken before and after the distention were scored on a scale of 1 to 5 using a panel of st and ards . Five urologists blinded to the source of individual photographs independently evaluated 120 research images interspersed with 46 other pictures from a library containing images from 19 symptomatic patients with and without interstitial cystitis . RESULTS A total of 20 normal women with a mean age plus or minus st and ard deviation of 29+/-6 years consented to participate in this trial during laparoscopic tubal ligation . Photographs of bladder sites before and after distention with 890+/-140 ml . were scored as 1.4+/-0.3 ( before distention ) and 3.1+/-1.1 ( after distention ) on the scale of 1 to 5 . The increase in scores following distention in normal subjects was seen to the same degree and in the same proportion as in patients with symptoms of interstitial cystitis ( 8 of 19 symptomatic patients in this series met current diagnostic criteria for interstitial cystitis ) . Slight but significant differences were seen among sites in the bladder but not between 2 and 6-minute distention duration s. CONCLUSIONS Bladder mucosal lesions characteristically associated with irritative voiding symptoms and pelvic pain in patients diagnosed with interstitial cystitis were observed in asymptomatic women",
"A r and omized , prospect i ve , double-blind , placebo-controlled study was conducted at 7 clinical centers on 148 patients . Patients received orally either 100 mg . pentosanpolysulfate ( a synthetic polysaccharide ) 3 times per day or a placebo . Of the patients on drug therapy 32 % showed significant improvement compared to 16 % of those on placebo ( p = 0.01 ) . This study provides a model to assess this disease quantitatively in a prospect i ve manner using a method whereby the patients globally assess their symptoms as either worse or improved by 0 , 25 , 50 , 75 or 100 % . Patients on drug therapy also experienced a significant decrease in pain and urgency ( p = 0.04 and 0.01 ) on analogue scales when compared to placebo and also more drug patients showed an average increase of more than 20 ml . in voided volume than did placebo patients ( p = 0.02 ) . All adverse effects were minor , with 7 in the drug group and 10 in the placebo group . The results support the concept that some patients with the interstitial cystitis syndrome may have abnormal bladder surface glycosaminoglycans",
"PURPOSE We conducted a double-blind , sham controlled study to evaluate the safety , efficacy and feasibility of hyperbaric oxygenation for interstitial cystitis . MATERIAL S AND METHODS A total of 21 patients with interstitial cystitis were r and omized to 90 minutes treatment in a hyperbaric chamber pressurized with 100 % O2 to 2.4 atmosphere absolute for 30 treatments sessions or 1.3 atmosphere absolute , breathing normal air in the control group . Moderate or marked improvement in a global response assessment question naire was defined as treatment response ( primary outcomes ) . Secondary measurements included changes of pain and urgency evaluated by visual analog scales , functional bladder capacity and frequency . Changes in the O'Leary-Sant Interstitial Cystitis Index and rating of overall satisfaction with the therapeutic outcome were also reported . RESULTS There were 3 of 14 patients on verum and no control patients who were identified as responders ( p oxygenation result ed in a decrease of baseline urgency intensity from 60.2 + /- 15.0 to 49.9 + /- 35.2 mm at 3 months and decrease of pain intensity from 43.1 + /- 20.5 to 31.2 + /- 19.8 mm , respectively ( p Interstitial Cystitis Symptom Index score sum decreased from 25.7 to 19.9 points in patients on verum . Sham treatment did not result in improvement of the baseline parameters . CONCLUSIONS A total of 30 treatment sessions of hyperbaric oxygenation appear to be a safe , effective and feasible therapeutic approach to interstitial cystitis . In the treatment responders application of hyperbaric oxygenation result ed in a sustained decrease of interstitial cystitis symptoms with a discordant profile regarding the peak amelioration of the various interstitial cystitis symptoms compared with a normobaric , normoxic sham treatment",
"OBJECTIVE To evaluate the therapeutic efficacy of intravesical pentosanpolysulphate ( PPS ) compared with placebo in patients with interstitial cystitis ( IC ) . PATIENTS AND METHODS Twenty patients who fulfilled the diagnostic criteria for IC participated in a double-blind placebo-controlled study ; 10 received intravesical PPS ( 300 mg in 50 mL of 0.9 % sodium chloride ) applied twice a week for 3 months and the other 10 received a placebo . Symptomatic relief and objective variables ( bladder capacity voiding volumes and urinary frequency ) were assessed after 3 months and the long-term outcome of those continuing treatment was determined . RESULTS Of the patients treated with PPS , four gained significant symptomatic relief compared with only two receiving placebo . Only the urodynamic bladder capacity showed a statistically significant increase in patients treated with PPS ( P = 0.047 ) . At 18 months from the start of the study , the symptoms were relieved in eight patients while still receiving PPS instillations and in four without treatment . CONCLUSIONS These results suggest that intravesical PPS is an effective option for the treatment of IC and shows that the intravesical application of PPS is a safe treatment with no important side-effects",
"Pentosan polysulfate sodium ( PPS ) was compared with placebo for the symptomatic therapy of interstitial cystitis in a double-blind , multicenter study . A total of 110 patients were enrolled and treated for three months . In this study , overall improvement of greater than 25 percent was reported by 28 percent of the PPS-treated patients and by 13 percent of the placebo-treated patients ( p = 0.03 ) . The investigators ' overall evaluation provided similar results , 26 percent vs 11 percent in favor of PPS ( p = 0.04 ) . Improvement in pain and pressure to urinate also favored PPS over placebo and approached statistical significance ( p = 0.07 and 0.08 ) . The incidence of adverse reactions was 6 percent in the PPS-treated group and 13 percent in the placebo-treated group . All adverse reactions were minor , and treatment was discontinued by 1 patient in the PPS group and 2 in the placebo group . In this study , PPS was found to be significantly more effective than , and equally as safe as , placebo",
"PURPOSE Present therapeutic approaches to control hypersensitive disorder of the lower urinary tract and bladder pain are clinical ly and scientifically unsatisfactory . We performed a r and omized placebo controlled study with followup after 1 and 3 months using intravesical resiniferatoxin to treat hypersensitive disorder and bladder pain . MATERIAL S AND METHODS We prospect ively r and omized 18 patients into 2 groups to receive a single dose of 10 nM. resiniferatoxin intravesically ( group 1 ) or a placebo saline solution only ( group 2 ) . All patients had at least a 6-month history of frequency , nocturia , urgency and symptoms of pelvic pain as well as no urinary tract infection within the last 3 months , functional disorders of the lower urinary tract , or other vesical or urethral pathology . Pretreatment voiding pattern and pain score were recorded . Patients were evaluated after 30 days ( primary end point ) and 3 months ( secondary end point ) . RESULTS The 2 groups were adequately homogeneous in regard to patient age , sex ratio , disease duration , voiding pattern and pain score . At the primary end point mean frequency plus or minus st and ard error of mean was decreased from 12 . 444 + /- 0.70 voids to 7.111 + /- 0.67 and nocturia from 3.777 + /- 0 . 27 to 1.666 + /- 0.16 ( p mean frequency in group 1 at the secondary end point to 10.444 + /- 0.94 voids ( p placebo . Mean pain score significantly decreased in group 1 at the primary end point from 5.555 + /- 0.29 to 2.666 + /- 0.23 ( p 0.05 ) . No statistically significant improvement in mean pain score was observed in placebo group 2 . During resiniferatoxin infusion 4 group 1 patients noticed a light warm or burning sensation at the suprapubic and /or urethral level . CONCLUSIONS Intravesical resiniferatoxin may significantly improve the voiding pattern and pain score in patients with hypersensitive disorder and bladder pain . Because resiniferatoxin did not cause a significant warm or burning sensation at the suprapubic and /or urethral level , it may be considered a new strategy for treating hypersensitive disorder and bladder pain . However , further studies are necessary to confirm our results and define the resiniferatoxin mechanism of action , dose and necessary treatment schedule",
"Objectives To determine , in a double‐blind placebo‐controlled crossover study , whether l‐arginine improves the symptoms of interstitial cystitis ( IC ) , a chronic condition in which nitric oxide ( NO ) may be important , as previous open pilot studies suggested that l‐arginine reduced the pain and frequency associated with IC",
"PURPOSE We compared intravesical bacillus Calmette-Guerin ( BCG ) to placebo instillations in patients with treatment refractory interstitial cystitis ( IC ) . MATERIAL S AND METHODS Subjects who met the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC , and reported at least moderate pain and frequency for a minimum of 6 months before study entry , were r and omized to 6 weekly double-blinded intravesical instillations of either BCG or placebo , and then followed for a total of 34 weeks . The primary outcome was a patient reported global response assessment at week 34 , supplemented with medications for IC during weeks 31 to 34 . Secondary outcomes included a 24-hour voiding diary , pain , urgency , vali date d IC symptom indexes and adverse events . The target sample size was 260 participants , design ed to detect a difference in response rates between placebo and BCG of 30 % and 50 % , respectively . RESULTS A total of 265 participants were r and omized and 17 ( 6 % ) patients withdrew from study . The response rates for the primary outcome were 12 % for placebo and 21 % for BCG ( p = 0.062 ) . Small improvements were observed for all secondary outcomes , some more so with BCG , but these differences were of borderline statistical significance . Although a large number of adverse events were reported in the BCG arm , there was no statistically significant difference between the treatment arms in overall adverse event rates . CONCLUSIONS Although the BCG safety profile was acceptable , the response rate for the primary outcome was low . Effective medical treatment for patients with moderate to severe interstitial cystitis remains elusive",
"Painful bladder disease , sensory bladder disease , chronic abacterial cystitis and interstitial cystitis are ill-defined conditions of unknown etiology and pathogenesis , and , therefore , they are without any rational therapy . Pathogenetic theories concerning defects in the epithelium and /or mucous surface coat ( including glycosaminoglycans ) of the bladder , and theories concerning immunological disturbances predominate . Sodium pentosanpolysulfate ( Elmiron ) acts by substituting a defective glycosaminoglycan layer and inhibits complement reactions in inflammatory processes . We compared sodium pentosanpolysulfate versus placebo in a prospect i ve double-blind , clinical ly controlled multicenter trial of 115 patients with painful bladder disease . Two protocol s were used . Protocol A included 43 patients with clinical ly and pathologically anatomically verified interstitial cystitis ( 28 or more mast cells per mm.2 ) , and protocol B included 72 patients with a painful bladder and unspecific histological findings . The patients were r and omized to receive either sodium pentosanpolysulfate ( 200 mg . twice daily ) or placebo capsules for 4 months . Before and after the trial the patients were evaluated with symptom grading , urodynamics and cystoscopy with distension and deep bladder biopsies . The results showed no difference between the pre-trial and post-trial values in the sodium pentosanpolysulfate and placebo groups in both protocol s in regard to symptoms , urodynamic parameters , cystoscopic appearance and mast cell counts . A significant increase in the cystoscopically determined bladder capacity in the sodium pentosanpolysulfate group in protocol A was found . We conclude that no statistically or clinical ly significant effect of sodium pentosanpolysulfate was found compared to placebo in patients with painful bladder disease",
"PURPOSE We present baseline characteristics and longitudinal profiles of symptoms in the Interstitial Cystitis Data Base study , a prospect i ve cohort study of patients with interstitial cystitis . MATERIAL S AND METHODS A total of 637 eligible patients were entered into the study and followed for symptoms of pain , urgency and urinary frequency . Median followup was 31 months . RESULTS More than 90 % of patients were white women with a median age of 43 years . Using the overall pain-urgency-frequency score 7 % of participants presented with mild , 44 % with moderate and 49 % with severe symptoms . Severe urgency in 41 % of cases and severe 24-hour frequency in 41 % were more common than severe pain in 29 % . Of the patients 51 % reported nighttime frequency of 2 or more voids . Median duration of interstitial cystitis symptoms was 8 years and 68 % of participants were previously diagnosed with the condition . The 36 % of patients who withdrew from study or were lost to followup were more likely to have had more severe symptoms at baseline . Patterns of change with time suggest initial symptom improvement due to regression to the mean , and an intervention effect associated with the increased followup and care of cohort participants . Although all symptoms fluctuated , there was no evidence of significant long-term change in overall disease severity . CONCLUSIONS Our observations support the clinical observation that interstitial cystitis is a chronic disease and no current treatments have a significant impact on symptoms with time . These results provide a foundation for the design and performance of future clinical trials in interstitial cystitis using these end points in a similar patient population",
"OBJECTIVES To compare the current recommended dose of pentosan polysulfate sodium ( PPS ) with doses two to three times higher . METHODS We evaluated three dosages ( 300 , 600 , and 900 mg ) of PPS in a r and omized , double-blind , double-dummy , parallel-group , multicenter , 32-week study . Adults ( n = 380 ) with a diagnosis of interstitial cystitis ( IC ) as determined by a positive cystoscopic examination combined with bladder pain and urgency or a history of IC symptoms for at least 6 months were enrolled . Participants completed the Patient 's Overall Rating of Symptom Index ( PORIS ) and the O'Leary-Sant Interstitial Cystitis Symptom Index ( ICSI ) at baseline ( ICSI only ) and during follow-up visits at 4 , 8 , 12 , 16 , 24 , and 32 weeks . RESULTS Mean ICSI scores improved significantly during the 32 weeks for all dosages ( baseline 11.2 , 11.9 , and 11.9 to endpoint 8.2 , 8.1 , 8.6 for 300 , 600 , and 900 mg , respectively ; P mild , moderate , and severe symptoms , respectively , as assessed by the ICSI . At study end , 27.5 % , 56.9 % , and 15.7 % reported mild , moderate , and severe symptoms , respectively . The PORIS scores improved within 4 weeks with 15.8 % to 21.1 % of all patients classified as responders ( 50 % or greater improvement on PORIS ) . At 32 weeks , 49.6 % , 49.6 % , and 45.2 % of all patients were responders at a dose of 300 , 600 , and 900 mg , respectively . Most adverse events were mild and resolved without intervention . CONCLUSIONS For all three dosages of PPS , a clinical ly significant but similar response was demonstrated . The duration of therapy appears to be more important than the dosage",
"PURPOSE Interstitial cystitis ( IC ) is a clinical condition occurring predominantly in women that is characterized by irritative voiding symptoms , including urinary frequency , urgency and pain . To our knowledge its etiology is unknown and little is known about its occurrence . We evaluated the prevalence of IC in women in Finl and . MATERIAL S AND METHODS A total of 2,000 participants were r and omly selected from the Finnish population register . Urinary symptoms were evaluated using the vali date d O'Leary-Sant IC symptom and problem index question naire . Women with moderate or severe symptom scores ( 7 or higher ) without any urinary tract infection during the last month were invited to undergo clinical examination . RESULTS Of the 1,331 respondents 32 had moderate or severe symptoms involving a suspicion of IC , of whom 21 underwent clinical evaluation . Three women were found to have probable IC and 4 had possible IC . Thus , the prevalence of clinical ly confirmed probable IC in women was 230/100.000 ( 95 % CI 100 to 360 ) and that of possible/probable IC was 530/100.000 ( 95 % CI 140 to 910 ) . Considering the lack of information on 8 patients with urinary symptoms the corrected estimates were 300/100,000 ( 95 % CI 120 to 770 ) and 680/100,000 women ( 95 % CI 360 to 1,300 ) , respectively . CONCLUSIONS Our results based on a large and representative population , and clinical ly confirmed diagnoses indicate that IC is substantially more common than previously thought",
"PURPOSE Interstitial cystitis is a debilitating bladder disease of unknown etiology with no cure . A recent report suggested that bacillus Calmette-Guerin ( BCG ) may be effective in the treatment of interstitial cystitis . A r and omized , prospect i ve , double-blind , placebo controlled trial to evaluate the safety and efficacy of intravesical BCG in treating interstitial cystitis was done . MATERIAL S AND METHODS Patients meeting the National Institute of Arthritis , Diabetes and Digestive and Kidney Diseases criteria for interstitial cystitis received 6 weekly instillations of Tice strain BCG or placebo . Periodic question naires , voiding diaries and cystometrograms were obtained . A total of 30 evaluable subjects was enrolled in the study with a mean followup of 8 months ( range 6 to 13 ) . Based on an exit question naire a responder was defined as one who rated the interstitial cystitis symptoms as moderately improved or better . RESULTS A 60 % BCG response rate was noted , compared to a 27 % placebo response rate . Minimum voided volume and quality of life improved in the BCG group compared to placebo . Adverse events were similar in each group , mostly irritative in nature , and no significant systemic events were noted . CONCLUSIONS Intravesical Tice strain BCG appears to be safe and efficacious in the treatment of interstitial cystitis . Additional studies must be performed to confirm the results of this pilot study",
"OBJECTIVES The aims of this study were to ( 1 ) identify trends and risk factors for mycobacterial disease and ( 2 ) determine the effect of exp and ed access to isoniazid chemoprophylaxis on tuberculosis incidence . METHODS A prospect i ve observational cohort study was conducted among community-based injecting drug users ( IDUs ) ; 2960 IDUs ( 942 human immunodeficiency virus [ HIV ] seropositive ) were followed up from January 1988 to June 1994 . Directly observed chemoprophylaxis with twice-weekly isoniazid ( 10 to 15 mg/kg ) was offered to purified protein derivative ( PPD ) tuberculin-positive ( > or = 5-mm in duration diameter in HIV-seropositive subjects and > or = 10-mm diameter in HIV-seronegative subjects ) individuals but not to those with cutaneous anergy . Overall and annual incidence rates of disease due Mycobacterium tuberculosis , Mycobacterium avium complex , and other atypical mycobacteria were estimated using Poisson regression . RESULTS HIV seropositivity was the strongest risk factor for tuberculosis , M avium complex , and other mycobacterial disease ( relative risk [ RR ] , 3.8 , 17.2 , and 6.9 , respectively ) . Median CD4 lymphocyte cell counts for the three groups of mycobacterial disease were 0.17 , 0.03 , and 0.02 x 10(9)/L ( 167/microL , 30/microL , 18/microL ) within 6 months of diagnosis ( before or after ) . Overall incidence rates of tuberculosis , M avium complex disease , and other mycobacterial disease were 1.9 , 8.8 , and 2.7 per 1000 person-years , respectively . Tuberculosis incidence peaked in 1991 at six per 1000 person-years . However , after access to directly observed preventive therapy was exp and ed for tuberculin-positive subjects , incidence fell to only one case in 1992 and zero cases for 24 months from mid-1992 to mid-1994 . During this period the number of PPD-positive patients who completed at least 26 weeks of therapy ( or were still receiving isoniazid ) more than tripled ( from 21 to 70 ) . None of the 12 patients with tuberculosis diagnosed during follow-up had received any preventive therapy . In addition , no tuberculosis developed among participants with cutaneous anergy . Calendar trends in risk for M avium complex and tuberculosis diverged after exp and ed access to isoniazid prophylaxis . Compared with 1988 - 1989 , risk of M avium complex increased sevenfold . Tuberculosis risk fell 83 % from the peak risk in 1990 - 1991 . CONCLUSIONS Exp and ed access to directly observed isonazid therapy for tuberculin-positive IDUs with and without HIV infection was associated with an 83 % drop in tuberculosis incidence , while in the same period M avium complex incidence significantly increased . These population -based data are consistent with those obtained from clinical trials of isoniazid prophylaxis and were obtained without offering chemoprophylaxis to HIV-infected patients with cutaneous energy",
"Health status measures are being used with increasing frequency in clinical research . Up to now the emphasis has been on the reliability and validity of these measures . Less attention has been given to the sensitivity of these measures for detecting clinical change . As health status measures are applied more frequently in the clinical setting , we need a useful way to estimate and communicate whether particular changes in health status are clinical ly relevant . This report considers effect sizes as a useful way to interpret changes in health status . Effect sizes are defined as the mean change found in a variable divided by the st and ard deviation of that variable . Effect sizes are used to translate “ the before and after changes ” in a “ one group ” situation into a st and ard unit of measurement that will provide a clearer underst and ing of health status results . The utility of effect sizes is demonstrated from four different perspectives using three health status data sets derived from arthritis population s administered the Arthritis Impact Measurement Scales ( AIMS ) . The first perspective shows how general and instrument-specific benchmarks can be developed and how they can be used to translate the meaning of clinical change . The second perspective shows how effect sizes can be used to compare traditional clinical measures with health status measures in a st and ard clinical drug trial . The third application demonstrates the use of effect sizes when comparing two drugs tested in separate drug trials and shows how they can facilitate this type of comparison . Finally , our health status results show how effect sizes can supplement st and ard statistical testing to give a more complete and clinical ly relevant picture of health status change . We conclude that effect sizes are an important tool that will facilitate the use and interpretation of health status measures in clinical research in arthritis and other chronic diseases",
"RATIONALE Rifabutin was recommended in place of rifampin during treatment of HIV-related tuberculosis ( TB ) to facilitate concomitant potent antiretroviral therapy , but this approach has not been evaluated in a prospect i ve study . OBJECTIVE To evaluate the activity of intermittent rifabutin-based therapy . METHODS Patients with culture-confirmed TB were treated under direct supervision with 2 mo of rifabutin , isoniazid , pyrazinamide , and ethambutol ( given daily , thrice-weekly , or twice-weekly per the local tuberculosis control program ) , followed by 4 mo of twice-weekly rifabutin plus isoniazid . MEASUREMENTS Culture-positive treatment failure or relapse . MAIN RESULTS A total of 169 eligible patients were enrolled . Most had advanced HIV disease ; the median CD4 cell count and HIV-RNA level were 90 cells/mm3 ( interquartile range , 35 - 175 ) and 5.3 log10 copies/ml ( interquartile range , 4.8 - 5.7 ) , respectively . Nine ( 5.3 % ) patients had culture-positive treatment failure ( n = 3 ) or relapse ( n = 6 ) . Eight of these nine ( 89 % ) cases had isolates with acquired rifamycin resistance . Treatment failure or relapse was associated with baseline CD4 lymphocyte count , being 12.3 % ( 9/73 ; 95 % confidence interval , 6.5 - 22.0 % ) among patients with CD4 One hundred thirty-seven ( 81 % ) patients received antiretroviral therapy during TB treatment . Adverse events were common , but only two patients ( 1 % ) permanently discontinued study drugs . CONCLUSIONS Intermittent rifabutin-based therapy for HIV-related TB was well tolerated , but there was a high risk of treatment failure or relapse with acquired rifamycin resistance among patients with low CD4 lymphocyte counts ",
"PURPOSE We conducted a prospect i ve , double-blind study with a crossover design of intravesical bacillus Calmette-Guerin ( BCG ) and dimethyl sulfoxide to determine whether patients with classic and nonulcer interstitial cystitis , respectively , might benefit from either regimen . MATERIAL S AND METHODS A total of 21 patients , including 11 with classic and 10 with nonulcer interstitial cystitis , r and omly underwent treatments with intravesical BCG or dimethyl sulfoxide and , if not improved , were treated with the other substance after a washout period . All 21 patients were evaluated with symptom question naires , including a visual analog pain scale and voiding diaries . RESULTS Regardless of regimen , there was no improvement in maximal functional capacity . There was a reduction in urinary frequency following dimethyl sulfoxide treatment but only in the classic subtype ( p pain decrease was noted in classic ( p maximal functional capacity but result ed in a significant reduction in pain and urinary frequency , although only in patients with classic interstitial cystitis",
"PURPOSE Interstitial cystitis is a chronic disease of unknown etiology characterized by bladder pain , urgency and frequency . Although a single microbe has not been implicated as a cause of interstitial cystitis , several groups noted various organisms in the urine of some women with interstitial cystitis and some patients reported that antibiotics decrease symptoms . Consequently we performed a prospect i ve , r and omized , double-blinded , placebo controlled pilot study of sequential oral antibiotics . MATERIAL S AND METHODS We r and omized 50 patients with interstitial cystitis to receive 18 weeks of placebo or antibiotics , including rifampin plus a sequence of doxycycline , erythromycin , metronidazole , clindamycin , amoxicillin and ciprofloxacin for 3 weeks each . RESULTS Intent to treat analysis demonstrated that 12 of 25 patients ( 48 % ) in the antibiotic and 6 of 25 ( 24 % ) in the placebo group reported overall improvement ( p = 0.14 ) , while 10 and 5 , respectively , noticed improvement in pain and urgency ( p = 0.22 ) . In the antibiotic group 20 participants ( 80 % ) had adverse effects compared with 10 ( 40 % ) in the placebo group ( p = 0.009 ) . CONCLUSIONS Our findings suggest that these antibiotics alone or in combination may sometimes be associated with decreased symptoms in some patients but they do not represent a major advance in therapy for interstitial cystitis",
"PURPOSE We assess the efficacy of intravesical administration of oxybutynin chloride in patients with interstitial cystitis . MATERIAL S AND METHODS The study included 36 women with a mean age of 45 years with a diagnosis of interstitial cystitis . Patients were treated with gradual intravesical instillation of saline oxybutynin solution ( oxybutynin group ) or gradual filling of simple saline ( control group ) . Evaluation parameters consisted of symptom problem index , voids per day , volume per void , functional bladder capacity , volume at first sensation , cystometric bladder capacity and cystometric volume at first sensation . RESULTS Statistically significant improvement of all evaluated parameters was found in both groups . When comparing the outcomes statistically significant improvement of parameters favored the oxybutynin group . CONCLUSIONS Bladder training alone produces a satisfactory result by gradually exp and ing the bladder , and an additional statistically significant improvement is evident with intravesical oxybutynin",
"Objective To evaluate the efficacy of oral cimetidine as a treatment for painful bladder disease ( PBD , variously described as a ‘ symptom complex ’ of suprapubic pain , frequency , dysuria and nocturia in the absence of overt urine infection ) by assessing symptom relief and histological changes in the bladder wall tissue components , compared with placebo",
"PURPOSE Nitric oxide synthase activity is decreased in the urine of patients with interstitial cystitis compared to the urine of controls . In a preliminary trial oral L-arginine , the substrate for nitric oxide synthase , increased urinary nitric oxide synthase activity and improved interstitial cystitis symptoms . This r and omized , double-blind , placebo controlled study further investigates the efficacy of L-arginine treatment for interstitial cystitis . MATERIAL S AND METHODS A total of 53 interstitial cystitis patients were assigned to receive daily 1,500 mg . L-arginine or placebo orally for 3 months . Interstitial cystitis symptoms were assessed by interviews at 2 weeks , and 1 , 2 and 3 months . RESULTS The trial was completed by 21 of 27 patients in the L-arginine group and 25 of 26 in the placebo group . Using per protocol analysis 29 % ( 6 of 21 patients ) in the L-arginine group and 8 % ( 2 of 25 ) in the placebo group were clinical ly improved by the end of the trial ( p = 0.07 ) . A Likert scale showed greater global improvement in the L-arginine group ( 48 % , 10 of 21 ) compared to the placebo group ( 24 % , 6 of 25 ) at 3 months ( p = 0.05 ) with a decrease in pain intensity ( p = 0.04 ) , and tendency toward improvement in urgency ( p = 0.06 ) and frequency of pain ( p = 0.09 ) . Using an intention to treat approach to analysis there were no differences between groups . CONCLUSIONS Oral L-arginine ( 1,500 mg . daily ) may decrease pain and urgency in a subset of interstitial cystitis patients",
"To evaluate the effectiveness of dimethyl sulfoxide in the treatment of patients with biopsies suggestive of interstitial cystitis , 33 patients underwent a controlled crossover trial . Patients were allocated r and omly to receive 50 per cent dimethyl sulfoxide or placebo ( saline ) . The medication was administered intravesically every 2 weeks for 2 sessions of 4 treatments each . Response was assessed urodynamically and symptomatically . Thirty women and 3 men ( mean age 48 years and mean duration of symptoms 5.5 years ) were entered into the study . No significant side effects to dimethyl sulfoxide were noted . When assessed subjectively , 53 per cent of dimethyl sulfoxide treated patients were markedly improved compared to 18 per cent of the placebo treated patients . Of the dimethyl sulfoxide group 93 per cent had objective improvement versus 35 per cent of the placebo group . Thus , dimethyl sulfoxide proved to be superior to placebo in the objective and subjective improvement of patients with interstitial cystitis"
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41187048-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND Opioid substitution treatment ( OST ) can increase quality of life ( WHOQOL-BREF ) and reduce addiction severity index ( ASI ) scores among participants over time . OST program participants have noted that improvement in quality of life is one of the most important variables to their reduction in drug use . However , there is little systematic underst and ing of WHOQOL-BREF and ASI domain changes among OST participants in low and middle-income countries ( LMIC ) . METHODS Utilizing PRISMA guidelines we conducted a systematic literature search to identify OST program studies documenting changes in WHOQOL-BREF or ASI domains for participants in buprenorphine or methadone programs in LMIC . St and ardized mean differences for baseline and follow-up domain scores were compared along with relationships between domain scores , OST dosage , and length of follow-up . RESULTS There were 13 OST program studies with 1801 participants from five countries eligible for inclusion in the review . Overall , statistically significant changes were noted in all four WHOQOL-BREF domain and four of the seven ASI domain scores ( drug , psychological , legal , and family ) documented in studies . Dosage of pharmacologic medication and length of follow-up did not affect changes in domain scores . CONCLUSION WHOQOL-BREF and ASI domain scoring is a useful tool in measuring overall quality of life and levels of addiction among OST participants . Coupled with measurements of blood-borne infection , drug use , relapse , and overdose , WHOQOL-BREF and ASI represent equally important tools for evaluating the effects of OST over time and should be further developed as integrated tools in the evaluation of participants in LMIC
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"AIMS AND OBJECTIVES This study aim ed to examine the effects of nurse-delivered home visits combined with telephone intervention on medication adherence , and quality of life in HIV-infected heroin users . BACKGROUND Drug use is consistently reported as a risk factor for medication non-adherence in HIV-infected people . DESIGN An experimental , pretests and post-tests , design was used : baseline and at eight months . METHODS A sample of 116 participants was recruited from three antiretroviral treatment sites , and 98 participants completed the study . They were r and omly assigned to two groups : 58 in the experimental group and 58 in the control group . The experimental group received nurse-delivered home visits combined with telephone intervention over eight months , while the control group only received routine care . The question naire of Community Programs for Clinical Research on AIDS ( CPCRA ) Antiretroviral Medication Self-Report was used to assess levels of adherence , while quality of life and depression were evaluated using Chinese versions of World Health Organization Quality of Life Instrument-Abbreviated version ( WHOQOL-BREF ) and Self-rating Depression Scale , respectively . Data were obtained at baseline and eight months . RESULTS At the end of eight months , participants in the experimental group were more likely to report taking 100 % of pills ( Fisher 's exact = 14.3 , p = 0.0001 ) and taking pills on time ( Fisher 's exact = 18.64 , p = 0.0001 ) than those in the control group . There were significant effects of intervention in physical ( F = 10.47 , p = 0.002 ) , psychological ( F = 9.41 , p = 0.003 ) , social ( F = 4.09 , p = 0.046 ) and environmental ( F = 4.80 , p = 0.031 ) domains of WHOQOL and depression ( F = 5.58 , p = 0.02 ) . CONCLUSIONS Home visits and telephone calls are effective in promoting adherence to antiretroviral treatment and in improving the participants ' quality of life and depressive symptoms in HIV-infected heroin users . RELEVANCE TO CLINICAL PRACTICE It is important for nurses to recognise the issues of non-adherence to antiretroviral treatment in heroin users . Besides st and ard care , nurses should consider conducting home visits and telephone calls to ensure better health outcome of antiretroviral treatment in this population",
"BACKGROUND The partial opiate-receptor agonist buprenorphine has been suggested for treatment of heroin dependence , but there are few long-term and placebo-controlled studies of its effectiveness . We aim ed to assess the 1-year efficacy of buprenorphine in combination with intensive psychosocial therapy for treatment of heroin dependence . METHODS 40 individuals aged older than 20 years , who met DSM-IV criteria for opiate dependence for at least 1 year , but did not fulfil Swedish legal criteria for methadone maintenance treatment were r and omly allocated either to daily buprenorphine ( fixed dose 16 mg sublingually for 12 months ; supervised daily administration for a least 6 months , possible take-home doses thereafter ) or a tapered 6 day regimen of buprenorphine , thereafter followed by placebo . All patients participated in cognitive-behavioural group therapy to prevent relapse , received weekly individual counselling sessions , and su bmi tted thrice weekly supervised urine sample s for analysis to detect illicit drug use . Our primary endpoint was 1-year retention in treatment and analysis was by intention to treat . FINDINGS 1-year retention in treatment was 75 % and 0 % in the buprenorphine and placebo groups , respectively ( p=0.0001 ; risk ratio 58.7 [ 95 % CI 7.4 - 467.4 ] ) . Urine screens were about 75 % negative for illicit opiates , central stimulants , cannabinoids , and benzodiazepines in the patients remaining in treatment . INTERPRETATION The combination of buprenorphine and intensive psychosocial treatment is safe and highly efficacious , and should be added to the treatment options available for individuals who are dependent on heroin",
"Background : Opioid dependence and HIV infection are associated with poor health-related quality of life ( HRQOL ) . Buprenorphine/naloxone ( bup/nx ) provided in HIV care setting s may improve HRQOL . Methods : We surveyed 289 HIV-infected opioid-dependent persons treated with clinic-based bup/nx about HRQOL using the Short Form Health Survey ( SF-12 ) administered at baseline , 3 , 6 , 9 , and 12 months . We used normalized SF-12 scores , which correspond to a mean HRQOL of 50 for the general US population ( SD 10 , possible range 0 - 100 ) . We compared mean normalized mental and physical composite and component scores in quarters 1 , 2 , 3 , and 4 with baseline scores using generalized estimating equation models . We assessed the effect of clinic-based bup/nx prescription on HRQOL composite scores using mixed effects regression with site as r and om effect and time as repeated effect . Results : Baseline normalized SF-12 scores were lower than the general US population for all HRQOL domains . Average composite mental HRQOL improved from 38.3 ( SE 12.5 ) to 43.4 ( SE 13.2 ) [ β 1.13 ( 95 % CI : 0.72 to 1.54 ) ] and composite physical HRQOL remained unchanged [ β 0.21 ( 95 % CI : −0.16 to 0.57 ) ] over 12 months follow-up . Continued bup/nx treatment across all 4 quarters was associated with improvements in both physical [ β 2.38 ( 95 % CI : 0.63 to 4.12 ) ] and mental [ β 2.51 ( 95 % CI : 0.42 to 4.60 ) ] HRQOL after adjusting for other contributors to HRQOL . Conclusions : Clinic-based bup/nx maintenance therapy is potentially effective in ameliorating some of the adverse effects of opioid dependence on HRQOL for HIV-infected population ",
"AIMS To compare the effectiveness and cost-effectiveness of unobserved versus observed dosing of patients seeking treatment of heroin dependence . DESIGN R and omized controlled trial and cost-effectiveness analysis . Setting Specialist out-patient drug treatment centres in Australia . PARTICIPANTS Heroin users seeking maintenance treatment . INTERVENTION Participants were allocated r and omly to observed or unobserved dosing for 3 months . All subjects received buprenorphine-naloxone and weekly clinical review s. MEASUREMENTS Primary end-points were retention in treatment and heroin use at 3 months . Costs of treatment were measured ( in Australian dollars , AU$ ) and cost-effectiveness compared . Secondary outcomes included quality of life , psychological symptoms and use of non-opioid drugs . FINDINGS A total of 119 subjects were r and omized and analysed . At 3 months , 33/58 ( 57 % ) r and omized to unobserved treatment , and 37/61 ( 61 % ) observed were retained ( log-rank chi2 = 0.04 , df = 1 , P = 0.84 ) . On an intention-to-treat analysis , reductions in days of heroin use in the preceding month , from baseline to 3 months , did not differ significantly ; 18.5 days ( 95 % CI : 21.8 - 15.3 ) and 22.0 days ( 95 % CI : 24.3 - 19.7 ) , respectively ( Mann-Whitney U = 807.5 , P = 0.13 ) . The mean cost for the unobserved group was AU$1,663 ( 95 % CI 1308 - 2017 ) per treatment episode , significantly less than the mean cost for the observed group at AU$2,138 ( 95 % CI 1713 - 2562 ) . CONCLUSIONS Retention and heroin use was not significantly different between observed and unobserved dosing groups . Attendance for observed dosing was not associated with worse retention . Treatment with close clinical monitoring , but no observation of dosing , was significantly cheaper and therefore significantly more cost-effective",
"A study was made of the effect of staff commitment to abstinence-oriented policies on retention of patients in methadone maintenance . Staff working in six public methadone programs in Sydney , Australia , were surveyed in 1989 and 1992 using the Abstinence Orientation Scale . The association of the clinics ' median Abstinence Orientation scores with the time in treatment of a r and om sample of their 1988 - 1989 admissions was summarised using Cox regression . Patients ' risk of discharge increased by a factor of three with every one unit increase in the clinics ' median Abstinence Orientation scores , ( RR 3.4 , 95 % CI 2.3 - 5.0 ) . Abstinence-oriented policies were shown to disadvantage ex-prisoners",
"Predictors of methadone maintenance treatment outcome have not been extensively studied as they relate to variations in program philosophy , nor have such predictors received much examination among recently treated , older cohorts of opioid addicts for whom drug use patterns have changed . Predictors of outcome were examined at 18 months post-treatment entry for 353 admissions to methadone maintenance who received r and om assignment to one of three counseling conditions : ( 1 ) medication only , ( 2 ) st and ard counseling and ( 3 ) enhanced services ; and one of two contingency conditions : ( 1 ) no contingencies , and ( 2 ) contingency contracting in a six-cell 3 x 2 design . Subjects in contingency contracting conditions were placed on contingency contracts for positive urine toxicology results and ultimately discharged for unremitting drug use . All subjects completed the Addiction Severity Index ( ASI ) and provided weekly urine specimens . Predictors of urinalysis results and treatment retention were determined using bivariate and multivariate techniques . Interactions between subject characteristics by experimental condition assignment were also examined as predictors . Higher rates of total positive urine specimens were predicted by younger age , greater pre-treatment frequency of smoking cocaine , lower ASI psychiatric composite scores , and higher ASI legal composite scores . Higher rates of opiate positive specimens were predicted by younger age , lower pre-treatment frequency of alcohol intoxication , higher ASI legal and lower ASI employment and psychiatric composite scores , and assignment to medication only/no contingencies condition . Higher rates of cocaine positives were predicted by younger age , black race , lower ASI psychiatric composite score , greater pre-treatment frequency of intravenous and smoked cocaine use , less pre-treatment frequency of marijuana use , and lower methadone dose level . Assignment to enhanced/contingency contracting predicted lower rates of cocaine positives . Treatment retention was predicted by older age , non-black race , lower ASI legal composite score , higher methadone dose level and assignment to non-contingent conditions . While subject variables over which treatment providers have little control were , thus , related to outcome , type of treatment provided and methadone dose also influenced outcome",
"The final development of the Sickness Impact Profile ( SIP ) , a behaviorally based measure of health status , is presented . A large field trial on a r and om sample of prepaid group practice enrollees and smaller trials on sample s of patients with hyperthyroidism , rheumatoid arthritis and hip replacements were undertaken to assess reliability and validity of the SIP and provide data for category and item analyses . Test-retest reliability ( r = 0.92 ) and internal consistency ( r = 0.94 ) were high . Convergent and discriminant validity was evaluated using the multitrait – multi method technique . Clinical validity was assessed by determining the relationship between clinical measures of disease and the SIP scores . The relationship between the SIP and criterion measures were moderate to high and in the direction hypotheszed . A technique for describing and assessing similarities and differences among groups was developed using profile and pattern analysis . The final SIP contains 136 items in 12 categories . Overall , category , and dimension scores may be calculated",
"AIMS Methadone maintenance treatment has been made available in China in response to the rapid spread of human immunodeficiency virus ( HIV ) , but high rates of dropout and relapse are problematic . The aim of this study was to apply and test if a contingency management ( or motivational incentives ) intervention can improve treatment retention and reduce drug use . DESIGN R and om assignment to usual care with ( n = 160 ) or without ( n = 159 ) incentives during a 12-week trial . Incentives participants earned draws for a chance to win prizes on two separate tracks targeting opiate-negative urine sample or consecutive attendance ; the number of draws increased with continuous abstinence or attendance . SETTING Community-based methadone maintenance clinics in Shanghai and Kunming . PARTICIPANTS The sample was 23.8 % female , mean age was 38 , mean years of drug use was 9.4 and 57.8 % had injected drugs in the past 30 days . MEASUREMENTS Treatment retention and negative drug urine . FINDINGS Relative to the treatment-as-usual ( control ) group , better retention was observed among the incentive group in Kunming ( 75 % versus 44 % ) , but no difference was found in Shanghai ( 90 % versus 86 % ) . Su bmi ssion of negative urine sample s was more common among the incentive group than the usual care ( 74 % versus 68 % in Shanghai , 27 % versus 18 % in Kunming ) , as was the longest duration of sustained abstinence ( 7.7 weeks versus 6.5 in Shanghai , 2.5 versus 1.6 in Kunming ) . The average total prize amount was 371 Yuan ( or $ 55 ) per participant ( 527 for Shanghai versus 216 in Kunming ) . CONCLUSIONS Contingency management improves treatment retention and drug abstinence in methadone maintenance treatment clinics in China , although there can be considerable site differences in magnitude of effects",
" This article reports results for patients who completed the 16-week maintenance phase of a double-blind clinical trial comparing buprenorphine ( N = 43 ; average dose = 9.0 mg/day sublingually ) with methadone ( N = 43 ; average dose = 54 mg/day orally ) in the outpatient treatment of opioid dependence . In addition to pharmacotherapy , treatment during the clinical trial included individual counseling , weekly group therapy , and on-site medical services . Patients in both medication groups showed significant and substantial improvements over time in areas of psychosocial functioning , as assessed by the Addiction Severity Index , rates of urinalysis tests positive for opioids , and self-reports of opioid withdrawal symptoms , illicit opioid use , and cocaine use . Buprenorphine and methadone produced very similar outcomes on the wide array of outcome measures assessed , and improvements for both groups were large and occurred rapidly after treatment entry . A trend toward continued improvement in opioid-positive urines over time was noted for the buprenorphine but not the methadone group . These results provide further evidence of the efficacy of buprenorphine in the treatment of opioid dependence and provide a characterization of the time course of effects for buprenorphine and methadone . In addition , these results demonstrate the benefits of drug abuse treatment , both for drug and alcohol use and in other areas of psychosocial functioning",
"This study was conducted to compare long-term outcome effects on the quality of life ( QOL ) of oral methadone with sublingual buprenorphine maintenance treatment . The QOL status of opioid-dependent patients was assessed using the German version ( “ Berlin Quality of Life Profile ” ) of the Lancashire Quality of Life Profile . Physical symptoms were measured using the Opiate Withdrawal Scale ( OWS ) . Urine tests were carried out r and omly to detect additional consumption . In the first study period , 53 opioid-dependent subjects were enrolled and 25 could be reached after 3 years . The retention rate was 50 % for methadone and 45 % for buprenorphine ( p = 0.786 ) . Baseline values of the total sample ( completers and noncompleters ) QOL and somatic complaints did not show significant differences between the two treatment groups . QOL characteristics at 6 months of treatment of the buprenorphine completer and noncompleter groups differed significantly regarding job ( p = 0.013 ) , family , and total score of physical symptoms ( p = 0.002 ) , in which the completer group showed the more favorable values . Concerning physical symptoms at 36 months , logistic regression revealed significantly less stomach cramps ( p = 0.037 ) and fatigue and tiredness ( p = 0.034 ) in buprenorphine compared to the methadone . Moreover , the buprenorphine-maintained group showed significantly less additional consumption of benzodiazepines ( p = 0.015 ) compared with methadone participants . It is concluded that opioid addicts improved their QOL and health status when treated with methadone or buprenorphine . In summary , regarding QOL and health status , the present data indicate that buprenorphine is also a useful long-term alternative for maintenance treatment of opioid-dependent patients",
"This paper review s the evidence for the effectiveness of methadone maintenance as used in the treatment of opioid dependence . Findings from r and omized controlled trials and observational studies suggest that methadone maintenance reduces heroin use , crime , injection-related risk behaviours and premature mortality among people dependent on opioids . The research further suggests that two aspects of treatment are important in ensuring this effectiveness . Methadone treatment is more effective when higher doses ( > 50 mg ) are employed and , overall , the evidence suggests that a treatment goal of successful maintenance on methadone rather than total abstinence is appropriate . The importance of ancillary services in treatment outcome is less clear and is the subject of current research and debate"
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41187084-06ff-11f0-808a-c43d1ab1c353
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CONTEXT Two often cited assumptions for treating children with GH are that short stature ( SS ) , as an isolated physical characteristic , is associated with psychosocial morbidity and that GH treatment may increase height and improve psychological adjustment . Findings across studies regarding the psychological consequences associated with GH management of children with SS are variable and frequently contradictory . The purpose of this systematic review is to evaluate the degree to which any conclusions about the relative risks or benefits of GH treatment on psychological outcomes can be made based on the published literature . EVIDENCE ACQUISITION Electronic data bases were search ed for r and omized clinical trials and nonr and omized studies , published between 1958 - 2014 , in which GH was administered for management of children with SS and psychosocial , cognitive , academic , or health-related quality of life outcomes were assessed . Method ological quality of each study was assessed using the Cochrane Collaboration 's tool for assessing risk of bias . EVIDENCE SYNTHESIS Eighty studies were evaluated . No studies were rated as having a low risk of bias , the risk of bias was unclear in seven study outcome areas , and the remaining studies were judged as having a high risk of bias . CONCLUSIONS The high risk of bias present in the majority of the literature on GH treatment effects on psychological outcomes ( in particular , lack of blinding ) substantially weakens confidence in their results . This may serve to explain the variability of findings for these outcomes across studies
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"Early puberty is frequently observed in adopted children . This r and omized trial treated 30 adopted children with early puberty and short stature with either gonadotropin‐releasing hormone agonist ( GnRHa ) alone or in combination with growth hormone ( GH ) for 3 y. Before the start of treatment ( T1 ) in the trial and at discontinuation ( T2 ) the children and their parents underwent a psychological evaluation . At the start of treatment the children did not have increased levels of behavioural or emotional problems as assessed by the Child Behaviour Checklist ( CBCL ) . During treatment the CBCL scores did not increase . Self‐perception of the children appeared to be normal , and after 3 y a significantly higher score for acceptance by peers was observed . At T1 , an overestimation of future height was present in 80 % of the children and 17 % of the parents . Lower family stress was observed at T1 and T2 compared with reference values . Intelligence quotient levels decreased significantly during treatment . The findings are discussed with reference to the reported levels of behavioural and emotional problems in adopted children and the psychosocial effects of precocious puberty",
"CONTEXT Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions . OBJECTIVE To explore whether the association between funding and conclusions in r and omized drug trials reflects treatment effects or adverse events . DESIGN Observational study of 370 r and omized drug trials included in meta-analyses from Cochrane review s selected from the Cochrane Library , May 2001 . From a r and om sample of 167 Cochrane review s , 25 contained eligible meta-analyses ( assessed a binary outcome ; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment ) . The primary binary outcome from each meta- analysis was considered the primary outcome for all trials included in each meta- analysis . The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect , adverse events , and additional confounding factors ( method ological quality , control intervention , sample size , publication year , and place of publication ) . MAIN OUTCOME MEASURE Conclusions in trials , classified into whether the experimental drug was recommended as the treatment of choice or not . RESULTS The experimental drug was recommended as treatment of choice in 16 % of trials funded by nonprofit organizations , 30 % of trials not reporting funding , 35 % of trials funded by both nonprofit and for-profit organizations , and 51 % of trials funded by for-profit organizations ( P funding , treatment effect , and double blinding were the only significant predictors of conclusions . Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice ( odds ratio , 5.3 ; 95 % confidence interval , 2.0 - 14.4 ) compared with trials funded by nonprofit organizations . This association did not appear to reflect treatment effect or adverse events . CONCLUSIONS Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results . Readers should carefully evaluate whether conclusions in r and omized trials are supported by data",
"The imminent commercial availability of synthetic growth hormone ( GH ) and the potential for large scale and possibly indiscriminant use m and ate a critical examination of possible adverse effects . This doubleblind study examined the effects of human GH on attention . Treatment of eight GH-deficient children , aged 8.7 to 14.1 years , was suspended to establish base lines . Injections with GH ( 0.1 units/kg ) and placebo followed in counterbalanced 2-week periods . At the end of each period , GH levels were assayed , and attention was tested . Scores earned under the GH condition did not differ from base line and placebo values . However , patients displaying high levels ( 14 ± 2.12 ng/ml ) of exogenous GH 12 hours after injection generally surpassed norms and patients with low levels ( 3.5 ± 1.12 ng/ml ) of GH under all conditions of the experiment . If 12-hour levels in this study are indicative of the fate of GH received during therapy , prolonged use of GH may bring benefits to attention that vary directly with half-life",
"GH production rates markedly increase during human puberty , mostly as an amplitude-modulated phenomenon . However , GH-deficient children have been dosed on a st and ard per kg BW basis similar to prepubertal children . This r and omized study was design ed to compare the efficacy and safety of st and ard recombinant human GH ( rhGH ) therapy ( group I , 0.3 mg/kg x week ) vs. high dose therapy ( group II , 0.7 mg/kg x week ) in GH-deficient adolescents previously treated with rhGH for at least 6 months . Ninety-seven children with documented evidence of GH deficiency ( peak GH in response to stimuli , , st and ardized height ( group I , -1.4+/-1.1 ; group II , -1.2+/-1.1 ) , bone age ( group I , 13.1+/-1.3 yr ; group II , 13.1+/-1.3 ) etiology , maximum stimulated GH , previous growth rate , and midparental target height . All subjects were in puberty ( Tanner stage 2 - 5 ) at study entry . Of the 97 subjects enrolled , 45 were treated for 3 yr or more ; 48 completed the study . Of the subjects who discontinued the study , the most common reason was satisfaction with their height , although others discontinued for adverse events or personal reasons . The frequency of patients who discontinued was the same in both groups . The primary efficacy analysis was the difference between dose groups for near-adult height , defined as the height attained at a bone age of 16 yr or more in males and 14 yr or more in girls ; all subjects who qualified were included in the analysis . This difference was statistically significant at 4.6 cm by analysis of covariance ( ANCOVA ; P rhGH treatment , the difference between dose groups at that time point was 5.7 cm ( by ANCOVA , P = 0.024 ; n = 20 ) . The mean height SD score at near-adult height was -0.7+/-0.9 in the st and ard dose group and 0.0+/-1.2 in the high dose group . At 36 months the cumulative change in height ( centimeters ) was 21.5+/-5.3 cm ( group I ) vs. 25.1+/-4.9 ( group II ; P change in Bayley-Pinneau predicted adult height was 4.8+/-4.2 cm ( group I ) vs. 8.4+/-5.7 ( group II ; P = 0.032 ) . Median plasma IGF-I concentrations at baseline were 427 microg/L ( range , 204 - 649 ) in group I and 435 microg/L ( range , 104 - 837 ) in group II ; at 36 months they were 651 microg/L ( range , 139 - 1079 ) in group I vs. 910 microg/L ( range , 251 - 1843 ) in group II ( P = NS ) . No difference in change in bone age was detected between groups at any interval . High dose rhGH was well tolerated , with a similar safety profile as st and ard dose treatment and no difference in hemoglobin A1c or glucose concentrations between groups . In summary , compared to conventional treatment , high dose rhGH therapy in adolescents 1 ) increased near-adult height and height SD scores significantly , 2 ) did not increase the rate of skeletal maturation , and 3 ) appears to be well tolerated and safe . In conclusion , high dose rhGH therapy may have a beneficial effect in adolescent GH-deficient patients , particularly those who are most growth retarded at the start of puberty",
"Aim : To examine psychosocial functioning of medically referred adolescents with idiopathic short stature ( ISS ) or persistent short stature born small for gestational age ( SGA ) during 3 years of combined growth hormone ( GH ) and gonadotropin-releasing hormone agonist ( GnRHa ) treatment . Methods : Thirty-eight adolescents participated in a controlled trial with GH/GnRHa treatment or no intervention . Each year the adolescents and their parents completed question naires and structured interviews . Multilevel analysis was used to analyze data . Results : The adolescents of the treatment group showed a worse outcome than the adolescents of the control group on 3 of 16 variables : perceived competence of scholastic ( p athletic ability ( p trait anxiety ( p current height ( p self- appraisal of physical appearance ( p combined GH/GnRHa treatment in adolescents with ISS or SGA . It is uncertain whether the hypothesized positive effects of the expected gain in final height by adulthood can sufficiently counterbalance possible short-term negative effects",
"It is common practice in the case of Turner syndrome ( TS ) to treat short stature with GH treatment and to induce puberty with estrogens at an age as close to normal puberty as possible . This approach in most cases leads to a height in the normal range in childhood , adolescence , and adulthood in TS . Little data is available , however , on its effect on psychosocial functioning . In the present study , we evaluated psychosocial functioning in a group of 50 women with TS , after reaching final height in two multicenter GH trials . Thirty-six girls participated in a r and omized dose-response study from mean ( SEM ) age 6.8 ( 0.4 ) years , and 14 girls participated in a frequency-response study from age 13.2 ( 0.4 ) years . After discontinuation of long-term GH treatment , these 50 girls were evaluated for psychosocial functioning at a mean age of 18.8 ( 0.3 ) years . GH was given in a dosage of 4 IU/m2/day ( ∼0.045 mg/kg/day ) , 6 IU/m2/day , or 8 IU/m2/day . After a mean GH treatment duration of 7.1 ( 0.4 ) years , mean final height ( ref . normal girls ) was FH1.2 ( 0.2 ) SD score . Behavioral problem scores ( Achenbach ) of the TS women were comparable to normal Dutch peers . Although self-perception ( Harter total scale : p and bodily attitude ( Baardman : p no evidence of depression . TS women rated their family functioning higher than their Dutch peers ( p still experience psychosocial problems . It is likely , however , that GH and estrogen treatment improved psychosocial functioning . Long-term follow-up of these GH-treated patients will allow an evaluation of their life achievements ",
"Traditionally , it has been assumed that intellectual development in children with growth hormone deficiency ( GHD ) is distributed between ranges of a normal population based on the observation that it does not differ substantially from that of children of the same age . Nevertheless , few studies have investigated this assumption . This Spanish Collaborative study was prospect ively planned with two main purpose s : to study a possible influence of GHD on intelligence quotient ( IQ ) , personality traits and adaptative capacity and to study the evolution of these parameters during substitution therapy with growth hormone ( GH ) . Although the overall intellectual ability of children with GHD is comparable to that of a normal reference population , some areas such the motor-component scale ( evaluated by McCarthy test ) and performance IQ ( evaluated by WISC-R ) were below the mean at the beginning of the study , showing significant improvement during therapy . Emotional adjustment ( normal at study start ) also improved significantly during treatment . Females showed better adjustment capacity before and during GH therapy . Longer studies with an increased number of cases are needed to confirm these effects of GHD and its treatment in children",
"The aim of the study was to evaluate whether treatment with recombinant human growth hormone ( rhGH ) affects the quality of life of young adults who were diagnosed as idiopathic short stature ( ISS ) during childhood , and whether their quality of life and aspects of the personality are different from normal . Experiences and expectations concerning rhGH treatment of the subjects and their parents were also investigated . Eighty‐nine subjects were included into the study : 24 subjects ( 16 M , 8F ) were treated with rhGH from childhood , whereas 65 subjects ( 40 M , 25F ) were never treated . At the time of the interview all subjects had attained final height [ mean ( SD ) ‐2.3 ( 0.9 ) SDS for Dutch references ] , and the age of the treated subjects was 20.5 (1.0)y , and 25.7 (3.5)y of the control subjects ( p The level of education was similar , but the treated subjects had less often a partner compared to the control subjects ( adjusted for age and gender , p The Nottingham Health Profile and Short Form 36 Health Survey showed no difference in general health state between treated and control subjects , and the healthy Dutch age‐specific references ( norm group ) . Although 74 % of the subjects reported one or more negative events related to their height , and 61 % would like to be taller , only 22 % and 11 % were willing to trade‐off at Time Trade‐Off and St and ard Gamble , respectively . The personality of the subjects , which was measured by the Minnesota Multiphasic Personality Inventory , was not different from the norm group . The satisfaction with the rhGH treatment was high , as it had caused 12 ( 8) cm and 13 ( 7 ) cm gain in final height according to the subjects and parents , respectively . Based on initial predicted adult height ( Bayley & Pinneau ) , this gain was only 3.3(5.6 ) cm . We concluded that although the treated subjects had a partner less often when compared to the control subjects , the quality of life of subjects with ISS at adult age is normal and appears not to be affected by rhGH therapy , The treated subjects were very satisfied with the treatment , probably by overestimation of the final height gain",
"The influence of short stature on psychological adaptation in childhood and adolescence is controversial . GH is currently used to treat children with idiopathic short stature ( ISS , also known as non-GH-deficient short stature ) . This study represents the first double-blind , placebo-controlled trial of the effects of GH on the psychological adaptation of children and adolescents with ISS , treated with GH until adult height was attained . Sixty-eight children ( 53 males , 15 females ) , 9 - 16 yr old , with marked ISS ( measured height or predicted adult height -2.5 sd or less ) received either GH 0.074 mg/kg or placebo sc three times per week until height velocity decreased to less than 1.5 cm/yr . Parents completed the Child Behavior Checklist ( CBCL ) and children the Self-Perception Profile ( SPP ) and Silhouette Apperception Technique at baseline and annually thereafter . Baseline behavioral/emotional adjustment ( CBCL ) and self-concept ( SPP ) scores for children with ISS were within the normative range . The two study groups exhibited similar behavioral and self-concept profiles ( CBCL ) during the first 2 yr of the study . However , CBCL behavior problems ( internalizing , externalizing , and total problems ) appeared to decline , in yr 3 and 4 , in the GH-treated group relative to the placebo-treated group . Group differences in CBCL competency domains and the SPP were not observed at any point during the study . Short stature among children with ISS enrolled in this long-term , placebo-controlled study was not associated with problems in psychological adaptation or self-concept with the psychological instruments employed . GH treatment was associated with a trend toward improvement in problem behaviors , as measured by question naires ( CBCL ) completed by study participants ' parents . It remains to be determined whether GH treatment significantly impacts adaptation , psychosocial function , or quality of life in children with ISS"
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411870c0-06ff-11f0-808a-c43d1ab1c353
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Background Allergic rhinitis ( AR ) is a disease of respiratory allergy , and probiotics can provide a potential strategy for its management . The purpose of this study was to carry out a systematic review to investigate the role of probiotics in the prevention and treatment of AR . Methods We search ed for r and omized controlled trials ( RCTs ) of the use of probiotics for the prevention and treatment of AR in the major electronic data bases up to March 2014 . The quality of the included RCTs was evaluated , and the data were independently extracted by two assessors . Meta-analyses were performed . Continuous data were expressed as the mean difference ( MD ) or st and ardized MD with 95 % confidence interval ( CI ) . Dichotomous data were expressed as odds ratio with the 95 % CI . A p value Results A total of 11 RCTs were included in the analysis . Probiotic intake was associated with a significant overall improvement of the quality of life scores and nasal symptom scores of patients with AR ( MD −2.97 [ 95 % CI , −4.77 to −1.16 ) ] ; p = 0.001 ) . No improvements with regard to prevention or immunologic parameters were noted in the patients with AR . Conclusions The current evidence is not sufficiently strong to verify a preventive role of probiotics in AR , but probiotics may improve the overall quality of life and nasal symptom scores . Because the available data were generated from only a few trials with a high degree of heterogeneity , routine use of probiotics for prevention and treatment in patients with AR can not be recommended
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"ABSTRACT : Human Lactobacillus sp strain GG ( Lactobacillus GG ) administered during acute rotavirus diarrhea has been shown to promote clinical recovery . To eluci date the immune mechanisms behind such a favorable outcome , the ELISPOT ( solid phase enzyme-linked immunospot ) assay of Ig- and specific antibody-secreting cells among circulating lymphocytes was used , giving indirect evidence of the immunologic events in the gut . After rehydration , 39 children with acute rotavirus diarrhea , mean age 16 ( SD 6 ) mo , r and omly received either a Lactobacillus GG fermented milk product ( study group ) or a pasteurized yogurt ( placebo group ) . The duration of diarrhea was significantly shorter in the study group than in the placebo group [ mean 1.1 ( SD 0.6 ) versus 2.5 ( SD 1.4 ) d , p = 0.001 ] . Lactobacillus GG therapy was associated with a significantly enhanced nonspecific humoral response during the acute phase of the infection , reflected in the IgG , IgA , and IgM Ig-secreting cell numbers . At convalescence , 90 % of the study group versus 46 % of the placebo group had developed an IgA specific antibody-secreting cell response to rotavirus ( p = 0.006 ) . The results indicate that Lactobacillus GG promotes recovery from rotavirus diarrhea via augmentation of the local immune defense . Furthermore , specific IgA response to rotavirus is endorsed , which is possibly relevant in protection against reinfections",
"Background : Oral probiotic bacteriotherapy with Lactobacillus rhamnosus has given promising results in small children with food allergy . We studied the effects of similar therapy in teenagers and young adults , who were allergic to birch pollen and apple food and had intermittent symptoms of atopic allergy and /or mild asthma",
"Perinatal administration of the probiotic Lactobacillus rhamnosus strain GG ( ATCC 53103 ) , reduces incidence of atopic eczema in at-risk children during the first 2 years of life ( infancy ) . We have therefore assessed persistence of the potential to prevent atopic eczema at 4 years . Atopic disease was diagnosed on the basis of a question naire and a clinical examination . 14 of 53 children receiving lactobacillus had developed atopic eczema , compared with 25 of 54 receiving placebo ( relative risk 0.57 , 95 % CI 0.33 - 0.97 ) . Skin prick test reactivity was the same in both groups : ten of 50 children previously given lactobacillus compared with nine of 50 given placebo tested positive . Our results suggest that the preventive effect of lactobacillus GG on atopic eczema extends beyond infancy",
"A placebo-controlled , single-blind study was conducted to evaluate the effects of Lactobacillus acidophilus strain L-92 ( L-92 ) on the symptoms of Japanese cedar-pollen allergy . This study was carried out during the 2002 and 2003 seasons of Japanese cedar pollination . Twenty-three in-house volunteers were asked to drink 100 ml of heat-treated milk fermented with L-92 containing 5 × 1010 of the bacteria , twice a day , for 6 consecutive weeks . A similar study was carried out during the 2003 season for 10 weeks , but the daily dose of bacteria was 2 × 1010 . A significant improvement of the ocular symptom-medication score ( SMS ) was observed in 2002 and of the score of distress of life in 2003 . These data show that a daily oral intake of not less than 2 × 1010 heat-treated L-92 cells improved the symptoms of Japanese cedar pollinosis , thereby contributing to reduce the dose of concomitant medications . However , no blood parameter was significantly affected in these trials",
"The effect of dietary therapy with a human Lactobacillus strain GG ( ATCC 53103 ) , bovine colostrum , or bovine immune colostrum with specific antibodies against anaerobic intestinal bacteria on gut defence mechanisms were studied in juvenile chronic arthritis . Thirty patients with juvenile chronic arthritis were r and omly allocated to receive a freeze-dried powder of Lactobacillus GG , or bovine colostrum , or bovine immune colostrum , for a two-week period . Immunologic and non-immunologic gut defence mechanisms were indirectly investigated in blood and faecal sample s. In patients receiving Lactobacillus GG , the median ( interquartile range ) frequency of immunoglobulin-secreting cells , determined by enzyme-linked immunospot assay , increased in the IgA class from 1840 ( 690–2530 ) to 3480 ( 1030–13 170)/106 cells ; p=0.02 . Likewise the median ( interquartile range ) frequency of specific antibody-secreting cells against dietary antigens increased during the Lactobacillus GG therapy in the IgM class from 3.8 ( 1.4–5.0 ) to 11.2 (5.0–30.0)/106 cells ; p=0.02 . In addition , Lactobacillus GG therapy decreased the median ( interquartile range ) activity of faecal urease , which has been associated with mucosal tissue damage , from 40.3 ( 21.7–54.3 ) to 28.6 ( 24.5–49.4 ) nmol . min−1 ( mg protein)−1 ; p=0.10 , while , in patients receiving bovine colostrum , faecal urease activity increased ( from 42.2 to 80.6 ; p=0.04 ) . All findings were transient . We suggest that gut defence mechanisms are disturbed in juvenile chronic arthritis and we further suggest that orally administered Lactobacillus GG has a potential to reinforce the mucosal barrier mechanisms in juvenile chronic arthritis",
"Live Lactobacillus paracasi 33 ( LP33 ) may effectively improve the quality of life for patients with perennial allergic rhinitis . It has been demonstrated that heat-killed lactic acid bacteria ( LAB ) suppress specific immunoglobulin E synthesis and stimulate interleukin-12 production in animals . The aim of this study was , therefore , to evaluate the efficacy of heat-killed LP33 in the treatment of allergic rhinitis induced by house-dust-mite in human subjects . A total of 90 patients were enrolled in a r and omized , double blind , placebo-controlled trial and assigned to three treatment groups . Patients in groups A and B received two capsules per day of live or heat-killed LAB ( 5 x 10(9 ) colony-forming units/capsule ) , respectively , over a period of 30 days while those in Group C received placebo capsules . A modified question naire on pediatric rhinoconjunctivitis-related quality of life was administered to all subjects or their parents during each clinical visit . The overall quality of life score decreased for groups A and B , as compared with the placebo group , in terms of both frequency ( 9.47 + /- 2.89 , 6.30 + /- 2.19 , vs. -3.47 + /- 1.53 , respectively ; p efficacy of the heat-killed LP33 was not inferior to the live variant . No obvious side effects were reported for either active treatment group during the study period . Our results suggest that heat-killed LP33 can effectively improve the overall quality of life for patients with allergic rhinitis , and that it may be efficacious as an alternative treatment",
"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 study , we examined the effect of Lactobacillus salivarius on the clinical symptoms and medication use among children with established allergic rhinitis ( AR ) . Design Double blind , r and omized , controlled trial . Setting Hualien Tzu-Chi General Hospital . Methods Atopic children with current allergic rhinitis received 4 × 109 colony forming units/g of Lactobacillus salivarius ( n=99 ) or placebo ( n=100 ) daily as a powder mixed with food or water for 12 weeks . The SCORing Allergic rhinitis index ( specific symptoms scores [ SSS ] and symptom medication scores [ SMS ] ) , which measures the extent and severity of AR , was assessed in each subject at each of the visits — 2 weeks prior to treatment initiation ( visit 0 ) , at the beginning of the treatment ( visit 1 ) , then at 4 ( visit 2 ) , 8 ( visit 3 ) and 12 weeks ( visit 4 ) after starting treatment . The WBC , RBC , platelet and , eosinophil counts as well as the IgE antibody levels of the individuals were evaluated before and after 3 months of treatment . Results The major outcome , indicating the efficacy of Lactobacillus salivarius treatment , was the reduction in rhinitis symptoms and drug scores . No significant statistical differences were found between baseline or 12 weeks in the probiotic and placebo groups for any immunological or blood cell variables . Conclusions Our study demonstrates that Lactobacillus salivarius treatment reduces rhinitis symptoms and drug usage in children with allergic rhinitis",
"We conducted two r and omized , placebo-controlled , double-blind studies of Lactobacillus plantarum No. 14 ( LP14 ) in female students with seasonal allergic diseases . We also examined the mitogenic activity and cytokine inducibility of LP14 using Peyer ’s patch cells and mesenteric lymph node cells of swine . For subjects who took 8.7 × 108 of LP14 , a significant improvement in ocular symptom-medication score was observed . In the placebo group , the T helper type 1 (Th1)/T helper type 2 ( Th2 ) ratio tended to decrease after a 6-week intake period , while in the LP14 group , the percentage of Th1 cells significantly increased . Post-intake eosinophil counts significantly increased in comparison to those at intake cessation in the placebo group , but it appeared to be suppressed in the LP14 group . There were no changes in fecal microflora . LP14 strongly induced the gene expression of Th1-type cytokines . This study indicates the clinical effects of LP14 on seasonal allergic diseases",
"Studies in animals have suggested that lactic acid bacteria alleviate allergic diseases , however , little information is available on their clinical effect on allergy in humans . Thus , we examined the efficacy of orally administered Lactobacillus acidophilus strain L-92 ( L-92 ) on perennial allergic rhinitis . In a r and omized , double-blind , placebo-controlled clinical trial , 49 patients with perennial allergic rhinitis were r and omized to receive either 100 mL of heat-treated fermented milk containing L-92 ( n = 25 ) or acidified milk without lactic acid bacteria ( placebo ; n = 24 ) for 8 wk . The severity of symptoms was evaluated based on the changes in the scores of clinical symptoms . Oral administration of milk fermented with L-92 result ed in a statistically significant improvement of nasal symptom-medication scores . Ocular symptom-medication scores of patients in the L-92 intervention group tended to improve compared with those in the placebo group . In addition , clear decreases of the scores of swelling and color of the nasal mucosa were observed in the L-92 intervention group at 6 and 8 wk after the start of ingestion of fermented milk . There were no significant differences in serum antihouse dust mite immunoglobulin E levels nor in T helper type 1/T helper type 2 ratio between the 2 groups . These results suggest that oral administration of L-92 can alleviate the symptoms of perennial allergic rhinitis , however , statistically significant changes were not shown in blood parameters",
"Previous studies have suggested that probiotic administration may have therapeutic and /or preventive effects on atopic dermatitis in infants ; however , its role in allergic airway diseases remains controversial . To determine whether daily supplementation with specific Lactobacillus gasseri A5 for 8 weeks can improve the clinical symptoms and immunoregulatory changes in school children suffering from asthma and allergic rhinitis ( AR ) . We conducted a r and omized , double-blind , placebo-controlled study on school children ( age , 6 - 12 years ) with asthma and AR . The eligible study subjects received either L. gasseri A5 ( n = 49 ) or a placebo ( n = 56 ) daily for 2 months . Pulmonary function tests were performed , and the clinical severity of asthma and AR was evaluated by the attending physicians in the study period . Diary cards with records of the day- and nighttime peak expiratory flow rates ( PEFR ) , symptoms of asthma , and AR scores of the patients were used for measuring the outcome of the treatment . Immunological parameters such as the total IgE and cytokine production by the peripheral blood mononuclear cells ( P BMC s ) were determined before and after the probiotic treatments . Our results showed the pulmonary function and PEFR increased significantly , and the clinical symptom scores for asthma and AR decreased in the probiotic-treated patients as compared to the controls . Further , there was a significant reduction in the TNF-α , IFN-γ , IL-12 , and IL-13 production by the P BMC s following the probiotic treatment . In conclusion , probiotic supplementation may have clinical benefits for school children suffering from allergic airway diseases such as asthma and AR",
"Probiotic microorganisms have been shown to be effective in the treatment of allergic inflammation and food allergy , but their efficacy remains controversial . This study tested the effect of a yogurt supplemented with a probiotic strain Bifidobacterium longum BB536 in the treatment of Japanese cedar pollinosis ( JCPsis ) . Forty subjects with a clinical history of JCPsis were given yoghurt either containing BB536 ( BB536 yoghurt ) or without BB536 ( placebo yoghurt ) at 2 X 100 g per day for 14 weeks , in a r and omized , double-blind , placebo-controlled trial . Subjective symptoms and self-care measures were recorded daily and blood sample s were taken before and during the intervention ( at weeks 4 , 9 , and 14 ) to measure the blood parameter levels related to JCPsis . Yoghurt supplemented with BB536 significantly alleviated eye symptoms compared with placebo yoghurt ( odds ratio 0.31 ; 95 % confidence interval 0.10 - 0.97 ; p = 0.044 ) . Although no statistically significant differences were detected , nasal symptoms such as itching , rhinorrhea , and blockage , as well as throat symptoms tended to be relieved with the BB536 yoghurt . BB536 tended to suppress the decreasing blood levels of interferon-gamma ( IFN-y ) and the increasing blood eosinophil rates ; a significantly higher IFN-gamma level was observed for the difference from baseline at week 4 . A decreased trend in the difference from baseline levels of JCP-specific IgE levels was also observed at week 4 in the BB536 group compared with the placebo group . In conclusion , these results suggest that intake of BB536-supplemented yoghurt may relieve JCPsis symptoms , probably through a modulating effect on Th balance",
"AIM To investigate whether birch pollen allergy symptoms are linked with gut microbiota changes and whether probiotics have an effect on these . METHODS Forty seven children with confirmed birch pollen allergy were r and omized to receive either a probiotic combination of Lactobacillus acidophilus ( L. acidophilus ) NCFM ( ATCC 700396 ) and Bifidobacterium lactis ( B. lactis ) Bl-04 ( ATCC SD5219 ) or placebo in a double-blind manner for 4 mo , starting prior to onset of the birch pollen season . Symptoms were recorded in a diary . Blood sample s were taken for analysis of cytokines and eosinophils . Fecal sample s were analysed for microbiota components , calprotectin and IgA. Nasal swabs were taken for analysis of eosinophils . RESULTS The pollen season induced a reduction in Bifidobacterium , Clostridium and Bacteroides which could not be prevented by the probiotic intervention . During the intervention , significantly higher numbers of B. lactis 11.2 x 10(7 ) + /- 4.2 x 10(7 ) vs 0.1 x 10(7 ) + /- 0.1 x 10(7 ) bacteria/g feces ( P runny nose , while during June , fewer subjects , 11.1 % vs 33.3 % , reported nasal blocking in the probiotics group ( P = 0.101 ) . Concomitantly , fewer subjects in the probiotic group had infiltration of eosinophils in the nasal mucosa compared to the placebo group , 57.1 % vs 95 % ( P = 0.013 ) . Eye symptoms tended to be slightly more frequent in the probiotic group , 12.5 d [ interquartile range ( IQR ) 6 - 18 ] vs 7.5 d ( IQR 0 - 11.5 ) ( P = 0.066 ) during May. Fecal IgA was increased in the placebo group during the pollen season ; this increase was prevented by the probiotics ( P = 0.028 ) . CONCLUSION Birch pollen allergy was shown to be associated with changes in fecal microbiota composition . The specific combination of probiotics used was shown to prevent the pollen-induced infiltration of eosinophils into the nasal mucosa , and indicated a trend for reduced nasal symptoms",
"Background / Objectives : Probiotics are defined as ‘ living micro-organisms that when administered in adequate amounts confer a health benefit to the host ’ . Different probiotic strains have been investigated for beneficial effects on allergic disorders . The purpose of the current study was to evaluate the effect of orally administering the probiotic Nestlé culture collection (NCC)2818 Bifidobacterium lactis strain on immune parameters and nasal symptom scores in subjects suffering from seasonal allergic rhinitis (SAR).Subjects/ Methods : The study was a double-blinded , parallel , r and omized placebo-controlled trial conducted during the peak of the pollen season . Adult subjects with clinical history of SAR and positive skin prick test to grass pollen were recruited . The subjects received B. lactis NCC2818 or placebo for 8 weeks and completed symptom question naires every week . Whole blood was collected at baseline ( V1 ) , 4 weeks ( V2 ) and 8 weeks ( V3 ) to measure immune parameters . Results : Concentrations of Th-2 cytokines , secreted by stimulated blood lymphocytes , were significantly lower in the probiotic group compared with the placebo group at V3 ( interleukin (IL)-5 , P=0.016 ; IL-13 , P=0.005 ) . Total nasal symptom scores were significantly lower in the second month of the study ( weeks 5–8 ) in the probiotic group compared with the placebo group ( P=0.03 ) . Also , percentages of activated CD63 expressing basophils were significantly lower in the probiotic group at V2 ( P=0.02 ) . Conclusions : Oral administration of the probiotic NCC2818 mitigates immune parameters and allergic symptoms during seasonal exposure . These promising results warrant that B. lactis NCC2818 be investigated further in large-scale trials for management of respiratory allergy",
"A r and omized , double-blind , placebo-controlled clinical trial was conducted to determine whether oral administration of heat-killed Lactobacillus gasseri OLL2809 would affect the immune response and reduce the symptoms of Japanese cedar pollinosis ( JCP ) in subjects with JCP . Following a 1-week pre-observation period , the subjects were r and omly divided into two groups and were orally administered a placebo or tablets containing 100 mg of L. gasseri OLL2809 per d for 8 weeks during the pollen season in 2007 . The results showed no obvious differences between the groups . Supplementary subgroup analysis revealed that the OLL2809 subgroups with CAP-RAST scores of 4 or 5 exhibited improvement in nasal symptoms scores and serum allergy-related items , including Japanese cedar pollen-specific IgE levels . L. gasseri OLL2809 was found to be effective in reducing symptoms in subjects with a high predisposition to allergies by modulating systemic immune systems",
"Allergic rhinitis is characterized by T-helper (Th)2 polarization as elevated levels of Th2-derived cytokines , including interleukin (IL)-4 , IL-5 and IL-13 , have been evidence d at nasal level in allergic rhinitics ( 1 ) . Th2 cytokines play a pathogenic role as they induce IgE synthesis and eosinophil infiltration . Th2 polarization in allergic subjects may occur as consequence of reduced pressure of microbial agents in the gut : the so-called Hygiene Hypothesis ( 2 ) . Probiotics may stimulate immune system at all mucosal surfaces and exert a primary prevention of atopic diseases and reduce allergic symptoms and inflammatory parameters ( 3 ) . We previously found out that Bacillus clausii was capable of modulating cytokine pattern at nasal level in allergic children with recurrent respiratory infections ( 4 ) . Particularly , B. clausii restored physiological Th1 polarization and induced T-regulatory cell response , as documented by increased levels of IL-10 and tumor growth factor (TGF)b after treatment ( 4 ) . Therefore , we conducted a pilot study to investigate the potential effects exerted by B. clausii on nasal symptoms , eosinophils , and symptomatic use of antihistamines in children with allergic rhinitis . Twenty allergic children , 13 males and seven females , with an average age of 13.4 years ( range 12–15 ) were consecutively evaluated . A detailed clinical history and a complete physical examination , including allergy evaluation , were carried out for each patient . The diagnosis of allergic rhinitis due to pollen sensitization was made according to vali date d criteria ( 5 ) . The study was blinded both to the investigator who performed the nasal eosinophil assessment and the investigator who carried out statistical analysis . Symptomatic use of levocetirizine ( 5 mg tablets ) was prescribed for all children . Ten of them were r and omly treated with oral B. clausii ( EnterogerAL LERGY 2 0 0 5 : 6 0 : 7 0 2 – 7 1 0 • COPYRIGHT a 2005 BLACKWELL MUNKSGAARD • ALL R IGHTS RESERVED • CONTRIBUT IONS TO THIS SECT ION WILL NOT UNDERGO PEER REV IEW , BUT WILL BE REV IEWED BY THE ASSOCIATE ED ITORS",
"Probiotics are perceived to exert beneficial effects in the prevention and treatment of allergic diseases via modifying the gut ecosystem . The aim of this study was to assess whether ingestion of fermented milk containing Lactobacillus paracasei-33 ( LP-33 ) , a strain newly isolated from the human intestinal tract , can improve the quality of life of patients with perennial allergic rhinitis . In a r and omized , double-blind , placebo-controlled trial , we gave patients fermented milk with ( n = 60 ) or without ( n = 20 ) the addition of LP-33 ( 2 x 10(9 ) colony-forming units per bottle ) for 30 days . A modified question naire concerning pediatric rhinoconjunctivitis quality of life was administered to all subjects or their parents at each clinical visit . Scores for the overall quality of life significantly decreased in the LP-33 group as compared with the placebo group , in both frequency ( -16.02 + /- 2.14 vs. -7.27 + /- 3.55 , respectively ; p = 0.037 ) and level of bother ( -16.35 + /- 2.33 vs. -6.20 + /- 3.13 , respectively ; p = 0.022 ) after the 30-day treatment . Subjects reported no severe adverse effects such as fever , abdominal pain , or diarrhea . The results suggest that ingestion of LP-33-fortified fermented milk for 30 days can effectively and safely improve the quality of life of patients with allergic rhinitis , and may serve as an alternative treatment for allergic rhinitis",
"Early treatment of new-born high-risk children with certain probiotic strains has reduced the risk of atopic eczema . Whether probiotics reduce risk for airway inflammation in long term is not known . We aim ed at study ing the effect of probiotic treatment during the six first months of life on airway inflammation at age 5 yr . In a r and omized double-blind allergy prevention trial between 2000 and 2007 in Helsinki , Finl and , we gave a probiotic combination , plus pre-biotics , or placebo , to 1018 children during 6 months from birth . At age 5 , we measured exhaled nitric oxide ( FE(NO ) ) in a r and omized sub- population of 160 children . Allergic diseases and IgE-sensitization were assessed in all infants . FE(NO ) did not differ between probiotic and placebo groups , median ( interquartile range , IQR ) 5.45 ( 4.3 - 7.3 ) vs. 5.70 ( 3.9 - 6.8 ) ppb , p = 0.22 . FE(NO ) was elevated among those suffering from asthma during the first 5 yr than in healthy non-sensitized children ( p = 0.009 ) . FE(NO ) correlated positively with serum total and allergen-specific IgE concentrations . Early intervention with probiotics and pre-biotics does not affect airway inflammation later in childhood",
"BACKGROUND Less microbial exposure in early childhood is associated with more allergic disease later . Allergic children have a different fecal microflora , with less lactobacilli and bifidobacteria . Beneficial effects regarding the development of allergy have been suggested to come through probiotic supplementation . OBJECTIVE We sought to study the effect of probiotic and prebiotic supplementation in preventing allergies . METHODS In a double-blinded , placebo-controlled study we r and omized 1223 mothers with infants at high risk for allergy to receive a probiotic mixture ( 2 lactobacilli , bifidobacteria , and propionibacteria ) or placebo during the last month of pregnancy and their infants to receive it from birth until age 6 months . Infants also received a prebiotic galacto-oligosaccharide or placebo . At 5 years , we evaluated the cumulative incidence of allergic diseases ( eczema , food allergy , allergic rhinitis , and asthma ) and IgE sensitization . RESULTS Of the 1018 intent-to-treat infants , 891 ( 88 % ) attended the 5-year visit . Frequencies of allergic and IgE-associated allergic disease and sensitization in the probiotic and placebo groups were similar : 52.6 % versus 54.9 % and 29.5 % versus 26.6 % , respectively , and 41.3 % in both . No significant difference appeared in frequencies of eczema ( 39.3 % vs 43.3 % ) , atopic eczema ( 24.0 % vs 25.1 % ) , allergic rhinitis ( 20.7 % vs 19.1 % ) , or asthma ( 13.0 % vs 14.1 % ) between groups . However , less IgE-associated allergic disease occurred in cesarean-delivered children receiving probiotics ( 24.3 % vs 40.5 % ; odds ratio , 0.47 ; 95 % CI , 0.23 % to 0.96 % ; P = .035 ) . CONCLUSIONS No allergy-preventive effect that extended to age 5 years was achieved with perinatal supplementation of probiotic bacteria to high-risk mothers and children . It conferred protection only to cesarean-delivered children"
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BACKGROUND The Six-Minute Walk Test ( 6MWT ) is increasingly being used as a functional outcome measure for chronic pediatric conditions . Knowledge about its measurement properties is needed to determine whether it is an appropriate test to use . PURPOSE The purpose of this study was to systematic ally review all published clinimetric studies on the 6MWT in chronic pediatric conditions . DATA SOURCES The data bases MEDLINE , EMBASE , CINAHL , PEDro , and SPORTD iscus were search ed up to February 2012 . STUDY SELECTION Studies design ed to evaluate measurement properties of the 6MWT in a chronic pediatric condition were included in the systematic review . DATA EXTRACTION The method ological quality of the included studies and the measurement properties of the 6MWT were examined . DATA SYNTHESIS A best evidence synthesis was performed on 15 studies , including 9 different chronic pediatric conditions . Limited evidence to strong evidence was found for reliability in various chronic conditions . Strong evidence was found for positive criterion validity of the 6MWT with peak oxygen uptake in some population s , but negative criterion validity was found in other population s. Construct validity remained unclear in most patient groups because of method ological flaws . Little evidence was available for responsiveness and measurement error . Studies showed large variability in test procedures despite existing guidelines for the performance of the 6MWT . LIMITATIONS Unavailability of a specific checklist to evaluate the method ological quality of clinimetric studies on performance measures was a limitation of the study . CONCLUSIONS Evidence for measurement properties of the 6MWT varies largely among chronic pediatric conditions . Further research is needed in all patient groups to explore the ability of the 6MWT to measure significant and clinical ly important changes . Until then , changes measured with the 6MWT should be interpreted with caution . Future studies or consensus regarding modified test procedures in the pediatric population is recommended
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"OBJECTIVE To confirm the efficacy and safety of recombinant human alpha-L-iduronidase ( laronidase ) in patients with mucopolysaccharidosis I ( MPS I ) . STUDY DESIGN This was a r and omized , double-blinded , multinational study of 45 patients with MPS I administered 100 U/kg ( 0.58 mg/kg ) laronidase , or placebo intravenously weekly for 26 weeks . The co primary efficacy end points compared the median change from baseline to week 26 between groups in percentage of predicted normal forced vital capacity ( FVC ) and in 6-minute walk test ( 6MWT ) distance through the use of the Wilcoxon rank sum test . RESULTS The laronidase ( n=22 ) and placebo ( n=23 ) groups had similar baseline characteristics . After 26 weeks , patients receiving laronidase compared with placebo showed mean improvements of 5.6 percentage points in percent of predicted normal FVC ( median , 3.0 ; P=.009 ) and 38.1 meters in 6MWT distance ( median , 38.5 ; P=.066 ; P=.039 , analysis of covariance ) . Laronidase also significantly reduced hepatomegaly and urinary glycosaminoglycans , and , in more severely affected patients , improved sleep apnea/hypopnea and shoulder flexion . Laronidase was well-tolerated . Nearly all patients receiving enzyme had development of IgG antibodies , without apparent clinical effects . CONCLUSIONS In patients with MPS I , laronidase significantly improves respiratory function and physical capacity , reduces glycosaminoglycan storage , and has a favorable safety profile",
"Study Design . Clinical prospect i ve , r and om study . Objective . Analyze the results of the six-minute walk test ( 6MWT ) in patients with adolescent idiopathic scoliosis . Summary of Background Data . Although it is widely believed that Adolescent Idiopathic Scoliosis ( AIS ) causes cardiorespiratory dysfunctions , there is no report in literature of objective measurements of this restriction in the ventilatory performance during physical exertion . Methods . One hundred twenty-six adolescents matched by gender and age were prospect ively studied at a tertiary teaching institution : 40 patients without spine deformities ( group I – controls ) , and 86 patients with AIS with a spine curve ranging from 45 ° to 138 ° ( group II ) . All patients underwent radiographic evaluations and the 6MWT . Results . Normal controls presented significantly lower mean heart rate and Borg scores , as well as higher oxygen saturation and walked longer distances on the 6MWT . Conclusion . The 6MWT effectively demonstrated the cardiorespiratory restrictions presented by patients with AIS",
"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",
"PURPOSE We assessed the exercise tolerance and cardiorespiratory responses during 2-month weight-loss programmes using the 6-minute walking test ( 6MWT ) in obese children . METHODS Twenty-eight male obese children were r and omly assigned to either a control group ( C ) , an energy restriction group ( R ) , an exercise training at maximum lipid-oxidation ( LIPOXmax ) group ( E ) , or an energy restriction/training group ( RE ) . The body composition , the submaximal incremental cycling exercise , and the 6MWT were performed before and after the 2-month programme . RESULTS . After the programme , RE group showed a significant improvement of body composition ( body weight reduced by 6.3 ± 1.5 kg , p increase of 6-minute walking distance ( 6MWD ) ( + 13.7 % , p Similarly , maximum oxygen uptake calculated according to the American College of Science Medicine guideline ( VO(2max ) ACSM ) and VO(2max ) predicted from 6MWD were respectively higher ( + 12.9 % and + 10.0 % , p Bl and -Altman analysis highlighted an agreement of these two methods of VO(2max ) measurement . Moreover , in all participants the 6MWD was significantly correlated with VO(2max ) ACSM and LIPOXmax ( r = 0.77 , p improved body composition and cardiorespiratory tolerance in obese children . Furthermore , the 6MWT could be considered as a useful and reliable tool for the assessment and the follow-up of cardiorespiratory responses during weight-loss programme in obese children",
"BACKGROUND Local intramuscular administration of the antisense oligonucleotide PRO051 in patients with Duchenne 's muscular dystrophy with relevant mutations was previously reported to induce the skipping of exon 51 during pre-messenger RNA splicing of the dystrophin gene and to facilitate new dystrophin expression in muscle-fiber membranes . The present phase 1 - 2a study aim ed to assess the safety , pharmacokinetics , and molecular and clinical effects of systemically administered PRO051 . METHODS We administered weekly abdominal subcutaneous injections of PRO051 for 5 weeks in 12 patients , with each of four possible doses ( 0.5 , 2.0 , 4.0 , and 6.0 mg per kilogram of body weight ) given to 3 patients . Changes in RNA splicing and protein levels in the tibialis anterior muscle were assessed at two time points . All patients subsequently entered a 12-week open-label extension phase , during which they all received PRO051 at a dose of 6.0 mg per kilogram per week . Safety , pharmacokinetics , serum creatine kinase levels , and muscle strength and function were assessed . RESULTS The most common adverse events were irritation at the administration site and , during the extension phase , mild and variable proteinuria and increased urinary α(1)-microglobulin levels ; there were no serious adverse events . The mean terminal half-life of PRO051 in the circulation was 29 days . PRO051 induced detectable , specific exon-51 skipping at doses of 2.0 mg or more per kilogram . New dystrophin expression was observed between approximately 60 % and 100 % of muscle fibers in 10 of the 12 patients , as measured on post-treatment biopsy , which increased in a dose-dependent manner to up to 15.6 % of the expression in healthy muscle . After the 12-week extension phase , there was a mean ( ±SD ) improvement of 35.2±28.7 m ( from the baseline of 384±121 m ) on the 6-minute walk test . CONCLUSIONS Systemically administered PRO051 showed dose-dependent molecular efficacy in patients with Duchenne 's muscular dystrophy , with a modest improvement in the 6-minute walk test after 12 weeks of extended treatment . ( Funded by Prosensa Therapeutics ; Netherl and s National Trial Register number , NTR1241 . )",
"OBJECTIVE To estimate the minimal clinical ly important difference ( MCID ) for the 6-minute walk test ( 6MWT ) and the 200-m fast-walk test ( FWT ) in patients with coronary artery disease ( CAD ) during a cardiac rehabilitation program . DESIGN Prospect i ve study using distribution- and anchor-based methods . SETTING Out patients from a cardiac rehabilitation unit . PARTICIPANTS Stable patients with CAD ( N=81 ; 77 men ; mean±SD age , 58.1±8.7y ) enrolled 31±12.1 days after an acute coronary syndrome ( ACS ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES 6MWT and 200-m FWT results before and after an 8-week cardiac rehabilitation program and at the 6th and 12th sessions . Patients and physiotherapists who supervised the training were asked to provide a global rating of perceived change in walking ability while blinded to changes in walk test performances . RESULTS Mean change in 6MWT distance ( 6MWD ) in patients who reported no change was -6.5 m versus 23.3 m in those who believed their performance had improved ( P the MCID determined by using the distribution method ( 23 m ) . Considering a 25-m cutoff , positive and negative predictive values were 0.9 and .63 , respectively . Conversely , there was no difference in 200-m FWT performance between these 2 groups ( 0.1 vs -1.4s , respectively ) . There was poor agreement with the physiotherapist 's perceived change . CONCLUSIONS The MCID for 6MWD in patients with CAD after ACS was 25 m . This result will help physicians interpret 6MWD change and help research ers estimate sample sizes in further studies using 6MWD as an endpoint",
"OBJECTIVE To investigate the feasibility and effects of a physical exercise programme on functioning and health-related quality of life in adults with myotonic dystrophy type 1 . DESIGN A r and omized controlled trial . SUBJECTS Thirty-five adults with myotonic dystrophy type 1 . METHODS After stratification for level of functioning , study participants were assigned by lot to either a training group or a control group . Training-group participants attended a 60-minute comprehensive group-training programme , Friskis&Svettis ® Open Doors , twice a week for 14 weeks . The six-minute walk test was the primary outcome measure and the timed-st and s test , the timed up- and -go test , the Epworth sleepiness scale and the Short Form-36 health survey were secondary outcome measures . RESULTS Intention-to-treat analyses revealed no significant differences in any outcome measures , except for an increased between-group difference after intervention in the Short Form-36 mental health subscale and a decrease in the vitality subscale for the control group . The programme was well tolerated and many training-group participants perceived subjective changes for the better . No negative effects were reported . CONCLUSION The Friskis&Svettis ® Open Doors programme was feasible for adults with myotonic dystrophy type 1 who had been screened for cardiac involvement , had distal or mild-to-moderate proximal muscle impairment , and no severe cognitive impairments . No beneficial or detrimental effects were evident",
"Objectives For the measurement of patient-reported outcomes , such as ( health-related ) quality of life , often many measurement instruments exist that intend to measure the same construct . To facilitate instrument selection , our aim was to develop a highly sensitive search filter for finding studies on measurement properties of measurement instruments in PubMed and a more precise search filter that needs less abstract s to be screened , but at a higher risk of missing relevant studies . Methods A r and om sample of 10,000 PubMed records ( 01 - 01 - 1990 to 31 - 12 - 2006 ) was used as a gold st and ard . Studies on measurement properties were identified using an exclusion filter and h and search ing . Search terms were selected from the relevant records in the gold st and ard as well as from 100 systematic review s of measurement properties and combined based on sensitivity and precision . The performance of the filters was tested in the gold st and ard as well as in two validation sets , by calculating sensitivity , precision , specificity , and number needed to read . Results We identified 116 studies on measurement properties in the gold st and ard . The sensitive search filter was able to retrieve 113 of these 116 studies ( sensitivity 97.4 % , precision 4.4 % ) . The precise search filter had a sensitivity of 93.1 % and a precision of 9.4 % . Both filters performed very well in the validation sets . Conclusion The use of these search filters will contribute to evidence -based selection of measurement instruments in all medical fields",
"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",
"This study assessed the exercise tolerance and the cardiorespiratory responses to a training program by the six-minute walk test ( 6'WT ) in children with congenital heart disease ( CHD ) . Seventeen cardiac and 14 healthy children performed maximal cardiopulmonary exercise test ( CPET ) and 6'WT . Reliability of 6'WT was assessed in all subjects ( test-retest ) by Bl and -Altman plots . Cardiac subjects were r and omly divided in training ( T-CHD ) and control groups ( C-CHD ) . T-CHD underwent an individualized training exercise at the ventilatory threshold ( VT ) intensity during 12 weeks . We found that the 6'WT is a reliable and reproducible test . CHD children walked a lower distance than healthy children before training ( 472.5 + /- 18.1 vs. 548.8 + /- 7.7 m , respectively , p power output , oxygen uptake ( V.O ( 2 ) ) , and heart rate ( HR ) at the maximum and the VT levels , were significantly lower in patients ( p walking distance ( WD ) was shown in T-CHD ( 529.6 + /- 15.3 vs. 467.7 + /- 17.1 m , p power output , VO2 , HR , and V.E increased slightly ( 6 to 10 % , p > 0.05 ) at peak exercise and significantly at ventilatory threshold level ( p WD and VO2max as well as VO2 at VT were founded ( p < 0.05 ) . We concluded that the 6'WT is a useful and reliable tool in the assessment and follow-up of functional capacity during rehabilitation program in children with CHD",
"Background With emerging interest in exercise and lifestyle interventions for children and adolescents with spina bifida , there is a need for appropriate measurements in exercise testing . Objective The purpose of this study was to assess both reliability and agreement of maximal and submaximal exercise measures in “ normal ambulatory ” and “ community ambulatory ” children and adolescents with spina bifida . Design This was a reproducibility study . Methods Twenty-three children and adolescents with spina bifida ( 10 normal ambulatory and 13 community ambulatory ) participated in the study . Maximal exercise outcomes were measured using a grade d treadmill test . Peak measures ( peak oxygen uptake [ V̇o2peak ] , peak heart rate [ HRpeak ] , heart rate response [ HRR ] , and oxygen pulse ) were recorded . For submaximal measures , heart rate ( HR ) and oxygen uptake ( V̇o2 ) at the ventilatory threshold and oxygen uptake efficiency slope ( OUES ) were derived from the maximal measures . Functional performance was measured as the 6-minute walking distance and the maximal speed during the treadmill test . After checking for normality and heteroscedasticity , paired t tests , intraclass correlation coefficients ( ICCs ) , and the smallest detectable difference ( SDD ) or the coefficient of variation ( CV ) were calculated . Results Performance measures showed good reliability and agreement . For maximal measures , acceptable ICCs were found for all measures . For submaximal measures , only HR at the ventilatory threshold showed an ICC of less than .80 . Agreement showed a CV of less than 10 % for all measures , except for V̇o2 at the ventilatory threshold , HRR , and OUES . Limitations Limitations of the study include missing data due to equipment failure . Furthermore , the outcomes were limited to normal ambulatory and community ambulatory children and adolescents with spina bifida . Conclusions Both maximal and submaximal measures of exercise testing can be used for discriminative purpose s in ambulatory children and adolescents with spina bifida . For evaluative purpose s , HR measures are superior to V̇o2 measures , while taking into account the individual variation of 5 % to 8 % . The SDD was 0.5 km/h for peak speed and 36.3 m for 6-minute walking distance . Heart rate response , oxygen pulse , and OUES are not recommended in the evaluation of exercise testing in this population",
"Exercise tolerance may be reduced in patients with cystic fibrosis , but it is not always possible to predict this from st and ard lung function measurements . Formal exercise testing may , therefore , be necessary , and the test should be simple and readily available . We have developed a \" 3-minute step test \" and compared it with the st and ard 6-minute walking test . Subjects stepped up and down a 15-cm-high single step at a rate of 30 steps per minute for 3 minutes . The effect of the step test on spirometry was tested first in 31 children with CF ( mean age , 12.0 years ) , who had a mean ( range ) baseline forced expired volume in 1 second ( FEV1 ) of 64 % ( 18 - 94 % ) of predicted values . The step test was then compared with the st and ard 6-minute walk in a further 54 patients with cystic fibrosis ( mean age , 12.5 years ) , with mean ( range ) baseline FEV1 of 61 % ( 14 - 103 % ) of predicted values . Outcome measures were minimum arterial oxygen saturation ( SaO2 ) , maximum pulse rate , and the modified Borg dyspnea score . Post-step test spirometry showed mean ( 95 % CI ) changes of -1.1 % ( -6.0 + 3.9 % ) for forced vital capacity , of -1.6 % ( -4.2 + 1.1 % ) for FEV1 , and + 0.25 % ( -2.8 + 3.3 % ) for peak expiratory flow , although 5/31 children showed > 15 % drop in one or more parameters . The step and walk tests both produced significant changes ( P minimum SaO2 of 92 % ( 75 - 98 % ) versus 92 % ( 75 - 97 % ) , a maximum pulse rate of 145 b.p.m . ( 116 - 189 ) versus 132 ( 100 - 161 ) , and a Borg score of 2.5 ( 0 - 9 ) versus 1.0 ( 0 - 5 ) , respectively . Comparison of the two tests showed that the step test increased breathlessness ( mean change Borg score , 2.3 vs. 0.8 ; P pulse rate ( mean change , 38 % vs. 24 % , P SaO2 was similar ( mean change , -2.9 % vs. -2.6 % ; P = 0.12 ) . Some patients with a significant drop in SaO2 ( > 4 % ) would not have the decrease predicted from their baseline lung function . Reproducibility for the two tests was similar . The step test is quick , simple and portable , and is not dependent on patient motivation . Although the step test is more tiring , its effect on SaO2 is similar to the 6-minute walking test . It is a safe test that may prove to be a valuable measure of exercise tolerance in children with pulmonary disease , although longitudinal studies are now needed"
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41187142-06ff-11f0-808a-c43d1ab1c353
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Objective To perform a systematic review of the published literature to evaluate how functional capacity , as measured by the University of California at San Diego ( UCSD ) Performance-based Skills Assessment ( UPSA ) , relates to other functional measures and real-world outcomes among individuals with schizophrenia . Methods The MEDLINE ® and Embase ® data bases were search ed to identify joint evaluations with UPSA and key functional outcomes ( functional scale measures ; generic or disease-specific , health-related quality of life [ HRQoL ] ; or real-world outcomes [ residential status ; employment status ] ) in patients with schizophrenia . Pearson correlations were estimated between UPSA scores , HRQoL , other functional scale measures , and real-world outcomes , for outcomes described in at least six studies . Results The synthesis included 76 studies that provided 73 unique data sets . Quantitative assessment between the Specific Level of Function ( SLOF ) ( n=18 ) scores and UPSA scores demonstrated a moderate borderline-significant correlation ( 0.45 , p=0.06 ) . Quantitative analysis of the relationship between the Global Assessment of Functioning ( GAF ) ( n=11 ) and the Multidimensional Scale of Independent Functioning ( MSIF ) ( n=6 ) scales revealed moderate and small nonsignificant Pearson correlations of -0.34 ( p=0.31 ) and 0.12 ( p=0.83 ) , respectively . There was a small borderline-significant correlation between UPSA score and residential status ( n=36 ; 0.31 ; p=0.08 ) , while no correlation was found between UPSA score and employment status ( n=19 ; 0.04 ; p=0.88 ) . Conclusion The SLOF was the most often used functional measure and had the strongest observed correlation with the UPSA . Although knowledge gaps remain , evidence from this review indicates that there is a quantitative relationship between functional capacity and real-world outcomes in individuals with schizophrenia
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[
"OBJECTIVE The authors sought to compare the effects of olanzapine , quetiapine , and risperidone on neurocognitive function in patients with early psychosis . METHOD In a 52-week double-blind , multicenter study , 400 patients early in the course of psychotic illness ( were r and omly assigned to treatment with olanzapine ( 2.5 - 20 mg/day ) , quetiapine ( 100 - 800 mg/day ) , or risperidone ( 0.5 - 4 mg/day ) . The mean modal daily dose was 11.7 mg ( SD=5.3 ) for olanzapine , 506 mg ( SD=215 ) for quetiapine , and 2.4 mg ( SD=1.0 ) for risperidone . A total of 224 patients completed neurocognitive assessment s at baseline and at 12 weeks , and 81 patients also completed them at 52 weeks . Neurocognitive composite scores were calculated from the neurocognitive battery used in the Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) and from the Brief Assessment of Cognition in Schizophrenia . RESULTS At week 12 , there was significant improvement in neurocognition for each treatment ( p Composite z score improvements on the CATIE neurocognitive battery were 0.17 for olanzapine , 0.33 for quetiapine , and 0.32 for risperidone . Composite z score improvements on the Brief Assessment of Cognition in Schizophrenia were 0.19 for olanzapine , 0.34 for quetiapine , and 0.22 for risperidone . Statistically significant relationships between improvements in neurocognition and functional outcome were observed at weeks 12 and 52 . CONCLUSIONS Olanzapine , quetiapine , and risperidone all produced significant improvements in neurocognition in early-psychosis patients . Although cognitive improvements were modest , their clinical importance was suggested by relationships with improvements in functional outcome",
"Purpose : The aim of this study was to compare the effects of risperidone long-acting injection ( RLAI ) and paliperidone palmitate ( PP ) on non-acute-phase social functioning in patients with schizophrenia . Patients and Methods : In this 6-month pilot , open-label , r and omized controlled study , 30 patients with schizophrenia who had been treated with RLAI were r and omly allocated to the RLAI continuation group or switched to the PP group . Patients were evaluated at baseline and 6 months with the Social Functioning Scale ( SFS ) as the primary outcome variable and University of California San Diego Performance-Based Skills Assessment Brief ( UPSA-B ) , Social Emotional Cognition Task ( SECT ) , Positive and Negative Syndrome Scale ( PANSS ) , and Drug-Induced Extrapyramidal Symptoms Scale ( DIEPSS ) scores as secondary outcomes . Results : At baseline , the two groups did not significantly differ in demographic or clinical features . The two groups did not differ in total score changes for the UPSA-B , the SECT , the PANSS , and the DIEPSS . However , the total scores and the two subscales of the SFS , i.e. independence-competence and independence-performance , were more improved in the PP group compared to the RLAI group ( total scores , p = 0.038 ; competence , p = 0.001 , and performance , p = 0.007 , respectively ) . Conclusion : These results suggest that PP may improve the total social functioning , independent life competence , and performance as compared to the RLAI group . However , these results are preliminary and need independent replication in larger sample s before any definitive statement can be made",
"Enhancing cognitive performance to improve functioning in schizophrenia is a fundamental research priority . Previous investigations have demonstrated that various types of cognitive training ( CT ) can improve neuropsychological performance , psychosocial functioning , and psychiatric symptom severity . However , there is limited information about individual differences that may predict CT response and adherence to treatment . The purpose of this study was to identify who is likely to drop out of this type of study as well as this type of intervention and to explore individual factors predicting treatment outcome . Participants included 89 out patients diagnosed with a primary psychotic disorder who enrolled in a r and omized controlled trial of compensatory CT and were assessed at baseline , 3 months ( posttest ) , and 6 months ( follow-up ) . Study completers had more formal education and lower daily doses of antipsychotic medications than did dropouts with no CT exposure , but the groups did not otherwise differ . There were no significant differences between participants who completed CT and those who began CT but later dropped out . CT-associated improvement was correlated with worse baseline scores on measures of cognitive performance , symptom severity , functional capacity , and self-rated quality of life , cognitive problems , and strategy use . These results suggest that those with lower baseline functioning may have more room to improve following CT . The pattern of correlations in this sample indicated that many types of individuals can improve with CT treatment , including older patients",
"OBJECTIVE Treatments for the cognitive impairments of schizophrenia are urgently needed . We developed and tested a 12-week , group-based , manualized , compensatory cognitive training intervention targeting prospect i ve memory , attention , learning/memory , and executive functioning . The intervention focused on compensatory strategies , such as calendar use , self-talk , note taking , and a 6-step problem-solving method , and did not require computers . METHOD In a r and omized controlled trial , 69 out patients with DSM-IV primary psychotic disorders were assigned to receive st and ard pharmacotherapy alone or compensatory cognitive training + st and ard pharmacotherapy for 12 weeks . Assessment s of neuropsychological performance and functional capacity ( primary outcomes ) and psychiatric symptom severity , quality of life , social skills performance , cognitive insight , and self-reported everyday functioning ( secondary outcomes ) were administered at baseline , posttreatment , and 3-month follow-up . Data were collected between September 2003 and August 2009 . RESULTS Hierarchical linear modeling analyses demonstrated significant compensatory cognitive training-associated effects on attention at follow-up ( P = .049 ) , verbal memory at posttreatment and follow-up ( P values ≤ .039 ) , and functional capacity ( University of California , San Diego Performance-based Skills Assessment ) at follow-up ( P = .004 ) . The compensatory cognitive training group also differentially improved in negative symptom severity at posttreatment and follow-up ( P values ≤ .025 ) and subjective quality of life at follow-up ( P = .002 ) . CONCLUSIONS Compensatory cognitive training , a low-tech , brief intervention , has the potential to improve not only cognitive performance but also functional skills , negative symptoms , and self-rated quality of life in people with psychosis . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01521026",
"A recent single-site study ( Fisher et al. , 2009 . Am J Psychiatry . 166 ( 7 ) 805 - 11 ) showed that repeated training with the Brain Fitness Program ( BFP ) improved performance on a battery of neuropsychological tasks . If replicated these data suggest an important non-pharmacological method for ameliorating cognitive impairment in schizophrenia . Our study evaluated the BFP training effects in an open-label , multi-site , multinational clinical trial . Fifty-five stable adult patients with schizophrenia on regular antipsychotic medication completed ≥ 32 BFP training sessions over 8 - 10 weeks . Training effects on cognitive performance and functional capacity outcome measures were measured using CogState ® schizophrenia battery , UCSD Performance based Skills Assessment ( UPSA-2 ) and Cognitive Assessment Interview ( CAI ) . BFP training showed a large and significant treatment effect on a training exercise task ( auditory processing speed ) , however this effect did not generalize to improved performance on independent CogState ® assessment . There were no significant effects on UPSA-2 or CAI scores . Our study demonstrated the feasibility of implementing BFP training in a multi-site study . However , BFP training did not show significant treatment effects on cognitive performance or functional capacity outcome measures despite showing large and significant effects on a training exercise",
"The early course of neuropsychological dysfunction in schizophrenia and the impact of treatment on these deficits need to be better specified . A sample of 45 patients with schizophrenia underwent five neuropsychological evaluations from prior to treatment with antipsychotic treatment through a 2-year follow-up period . A comparison sample of 33 matched healthy individuals underwent neuropsychological evaluations at similar time points . At baseline , a generalized deficit across cognitive domains was evident for the schizophrenia sample . After 6 weeks of treatment , patients showed modest improvements in visual memory and visual perception , but a decline in verbal memory . Verbal memory performance returned to baseline levels by the 6-month follow-up while deficits in other neuropsychological domains persisted throughout the 2-year period . Relatively static and generalized neuropsychological dysfunction , evident from illness onset , is consistent with neurodevelopmental rather than neurodegenerative models of schizophrenia",
"OBJECTIVE Supported employment is the evidence -based treatment of choice for assisting individuals with severe mental illness to achieve competitive employment , but few supported employment programs specifically target older clients with psychiatric illness . The purpose of this study was to evaluate the efficacy of supported employment for middle-aged or older people with schizophrenia . METHOD Participants included 58 out patients with schizophrenia or schizoaffective disorder aged 45 or older who were recruited from a community mental health clinic . Participants were r and omly assigned to receive Individual Placement and Support ( IPS ; the manualized version of supported employment ) or conventional vocational rehabilitation ( CVR ) for one year , and completed assessment s at baseline , six months , and twelve months . RESULTS IPS was superior to CVR on nearly all work outcome measures , including attainment of competitive employment , weeks worked , and wages earned . Fifty-seven percent of IPS participants worked competitively , compared with 29 % of CVR participants ; 70 % of IPS participants obtained any paid work , compared with 36 % of CVR participants . Within the IPS group , better baseline functional capacity ( as measured by the UCSD Performance Based Skills Assessment ) and more recent employment were modestly associated with better work outcomes . CONCLUSIONS Middle-aged and older adults with schizophrenia are good c and i date s for supported employment services"
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4118717e-06ff-11f0-808a-c43d1ab1c353
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Aims /hypothesisDietary non-oil-seed pulses ( chickpeas , beans , peas , lentils , etc . ) are a good source of slowly digestible carbohydrate , fibre and vegetable protein and a valuable means of lowering the glycaemic-index ( GI ) of the diet . To assess the evidence that dietary pulses may benefit glycaemic control , we conducted a systematic review and meta- analysis of r and omised controlled experimental trials investigating the effect of pulses , alone or as part of low-GI or high-fibre diets , on markers of glycaemic control in people with and without diabetes . Methods We search ed MEDLINE , EMBASE , CINAHL , and the Cochrane Library for relevant controlled trials of ≥7 days . Two independent review ers ( A. Esfahani and J. M. W. Wong ) extracted information on study design , participants , treatments and outcomes . Data were pooled using the generic inverse variance method and expressed as st and ardised mean differences ( SMD ) with 95 % CIs . Heterogeneity was assessed by χ2 and quantified by I2 . Meta-regression models identified independent predictors of effects . Results A total of 41 trials ( 39 reports ) were included . Pulses alone ( 11 trials ) lowered fasting blood glucose ( FBG ) ( −0.82 , 95 % CI −1.36 to −0.27 ) and insulin ( −0.49 , 95 % CI −0.93 to −0.04 ) . Pulses in low-GI diets ( 19 trials ) lowered glycosylated blood proteins ( GP ) , measured as HbA1c or fructosamine ( −0.28 , 95 % CI −0.42 to −0.14 ) . Finally , pulses in high-fibre diets ( 11 trials ) lowered FBG ( −0.32 , 95 % CI −0.49 to −0.15 ) and GP ( −0.27 , 95 % CI −0.45 to −0.09 ) . Inter- study heterogeneity was high and unexplained for most outcomes , with benefits modified or predicted by diabetes status , pulse type , dose , physical form , duration of follow-up , study quality , macronutrient profile of background diets , feeding control and design . Conclusions /interpretationPooled analyses demonstrated that pulses , alone or in low-GI or high-fibre diets , improve markers of longer term glycaemic control in humans , with the extent of the improvements subject to significant inter- study heterogeneity . There is a need for further large , well- design ed trials
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"The study was carried out in 10 females with type 2 diabetes aged 32 - 60 yrs . All of them were receiving weight-maintaining diets composed of 12 per cent protein , 30 per cent fat and 58 per cent carbohydrate . The only difference among all study -diets was the types of complex carbohydrate used . High-glycemic diet ( HG ) or low glycemic diet ( LG ) consisted mainly of glutinous rice or mungbean noodles and the intermediate-glycemic diet ( DM ) was solely white rice . After the metabolic evaluation of the baseline diet ( BL ) , each subject was placed on DM and followed r and omly by HG and LG or vice versa for 4 weeks each . The diurnal plasma glucose levels tended to be lowest after LG . The integrated plasma glucose levels among all diets were not different . The integrated insulin levels after DM and LG did not differ but they were lower than HG and BL . Long-term ingestion of all test-diets spilt less urinary glucose than BL , the lowest was LG . HbA1 levels and nitrogen balance after all diets were better than BL , the best was LG . It was concluded that in addition to strict dietary control , ingestion of mungbean noodles ( a low glycemic diet ) without increasing fiber intake , can improve diabetic control and protein conservation in type 2 diabetes",
"Our objective was to evaluate whether isocaloric replacement of refined rice with whole grains and other plant products as a form of powder reduces coronary artery disease ( CAD ) risk factors , such as insulin dem and and lipid peroxidation in CAD patients . Seventy-six male patients with CAD were r and omly assigned to either a group ingesting a whole-grain meal daily or a control group for 16 weeks . In the whole-grain group , serum concentrations of glucose and insulin decreased by 24 % and 14 % , respectively , without altering body weight and energy intake , whereas daily intakes of fiber and vitamin E increased by 25 % and 41 % , respectively . Consumption of whole grains and legume powder in CAD patients without diabetes decreased fasting levels of glucose and insulin . The areas under the curve for insulin and glucose during the oral glucose tolerance test were also decreased . CAD patients with diabetes in the whole-grain group also showed reductions in fasting glucose and in the area under the curve for glucose . In the whole-grain group , plasma malondialdehyde and homocysteine and urinary 8-epi-prostagl and in F2&agr ; concentrations decreased by ≈28 % . Also , lipid-corrected concentrations of & agr;-carotene , retinol , tocopherols , and lycopene increased by 11 % to 40 % , and the percentage composition of n-6 fatty acids of serum phospholipid increased by 14 % in the whole-grain group . The replacement of refined rice with whole grain and legume powder as a source of carbohydrate in a meal showed significant beneficial effects on glucose , insulin , and homocysteine concentrations and lipid peroxidation in CAD patients . These effects are likely to substantially reduce the risk factors for CAD and diabetes",
"Abstract Objective : To examine the effect of a diet containing a novel legume food ingredient , Australian sweet lupin ( Lupinus angustifolius ) kernel fibre ( LKFibre ) , compared to a control diet without the addition of LKFibre , on serum lipids in men . Design : R and omized crossover dietary intervention study . Setting : Melbourne , Australia — Free-living men . Subjects : A total of 38 healthy males between the ages of 24 and 64 y completed the intervention . Intervention : Subjects consumed an LKFibre and a control diet for 1 month each . Both diets had the same background menus with seven additional experimental foods that either contained LKFibre or did not . Depending on energy intake , the LKFibre diet was design ed to contain an additional 17 to 30 g/day fibre beyond that of the control diet . Results : Compared to the control diet , the LKFibre diet reduced total cholesterol ( TC ) ( mean±s.e.m . ; 4.5±1.7 % ; P=0.001 ) , low-density lipoprotein cholesterol ( LDL-C ) ( 5.4±2.2 % ; P=0.001 ) , TC : high-density lipoprotein cholesterol ( HDL-C ) ( 3.0±2.0 % ; P=0.006 ) and LDL-C : HDL-C ( 3.8±2.6 % ; P=0.003 ) . No effects on HDL-C , triacylglycerols , glucose or insulin were observed . Conclusions : Addition of LKFibre to the diet provided favourable changes to some serum lipid measures in men , which , combined with its high palatability , suggest this novel ingredient may be useful in the dietary reduction of coronary heart disease risk . Sponsorship : Grains Research and Development Corporation , Australian Research Council and the Department of Agriculture Western Australia",
"Breakfasts of lentils or wholemeal bread of identical carbohydrate content were taken by seven healthy volunteers . The lentils produced a significant 71 % ( p less than 0.001 ) reduction in the blood glucose area and flattened the plasma insulin and gastric inhibitory polypeptide responses by comparison with the bread . In addition , the lentil breakfast was followed by a significantly flatter blood glucose response to the st and ard bread lunch which followed 4 h later ( by 38 % , p less than 0.01 ) . The blood glucose pattern was mimicked by feeding the bread breakfast slowly over the 4 h before lunch . Giving a bread breakfast containing a quarter of the carbohydrate reduced the breakfast glucose profile but result ed in a significantly impaired blood glucose response to lunch ( 168 % of control , p less than 0.01 ) . These results , together with breath hydrogen studies , performed on a separate group of four volunteers , indicate that the flattened response to lentils is not due to carbohydrate malabsorption . Slow release or \" lente \" carbohydrate foods such as lentils may form a useful part of the diets of those with impaired carbohydrate tolerance",
"This study examined the hypocholesterolemic effect and hormonal changes result ing from 30 d of supplementation with Vicia faba L. ( field bean ) flour of diets of young men ( aged 18 - 21 y ; n = 40 ) with borderline-high or high serum cholesterol values . All subjects ( groups A-D ) consumed the same basic diet . Additionally , volunteers in the control group ( A ) consumed 90 g control flour/d whereas those in the three bean groups received either 90 g cooked field bean flour ( groups B and C ) or 90 g raw field bean flour ( group D ) daily . Groups A and B included volunteers with borderline-high cholesterol values [ 5.2 - 6.2 mmol total cholesterol/L and 3.4 - 4.1 mmol low-density-lipoprotein ( LDL ) cholesterol/L ] . Subjects in groups C and D had high serum cholesterol concentrations ( total cholesterol > 6.2 mmol/L and LDL cholesterol > 4.1 mmol/L ) . After 30 d , serum glucose , insulin , triacylglycerol , total , LDL-cholesterol , and very-low-density-lipoprotein (VLDL)-cholesterol values were significantly lower than initial values in all subjects who consumed diets containing field bean flour ( P LDL-cholesterol concentrations in group C , for which P glucagon and high-density-lipoprotein cholesterol . Neither cortisol nor thyroid hormone values changed significantly . The results suggest that the hypocholesterolemic effect of field bean intake depends at least partly on a concomitant increase in glucagon and decrease in insulin values . The more marked reduction in triacylglycerol and VLDL-cholesterol concentrations in subjects who consumed raw field beans indicates a coparticipation of their thermolabile components",
"BACKGROUND Legumes are recommended for better glucose control in persons with diabetes . Whether subjects with normal insulin sensitivity would also benefit from legume consumption is not clear . OBJECTIVE Our goal was to compare the effects on insulin sensitivity of chickpea-based and wheat-based foods when eaten as single meals or over 6 wk . DESIGN Acute and long-term studies were conducted in healthy middle-aged men and women . In the acute study ( n = 19 ) , plasma glucose , insulin , and calculated homeostasis model assessment ( HOMA ; an index of insulin sensitivity ) were measured on 3 separated days over 3 h after the subjects consumed 50-g available carbohydrate loads from either chickpeas , wheat-based foods , or white bread . The long-term comparison ( n = 20 ) was a r and omized , crossover study in which chickpea-based and wheat-based foods were eaten for 6 wk each . Plasma glucose , insulin , and HOMA were measured in the fasting state and 2 h after a 75-g glucose load . RESULTS After single meals , plasma glucose was substantially lower 30 and 60 min after the chickpea meal than after the other 2 meals ( P plasma insulin and HOMA were lower at 120 min ( P plasma glucose , insulin , or HOMA either in the fasting state or after a glucose load . CONCLUSION Compared with a wheat-based meal , a single chickpea-based meal led to a lesser response in plasma glucose and insulin concentrations , but this was not translated into long-term improvement in insulin sensitivity over 6 wk , at least in healthy subjects",
"Reliable tables of glycemic index ( GI ) compiled from the scientific literature are instrumental in improving the quality of research examining the relation between GI , glycemic load , and health . The GI has proven to be a more useful nutritional concept than is the chemical classification of carbohydrate ( as simple or complex , as sugars or starches , or as available or unavailable ) , permitting new insights into the relation between the physiologic effects of carbohydrate-rich foods and health . Several prospect i ve observational studies have shown that the chronic consumption of a diet with a high glycemic load ( GI x dietary carbohydrate content ) is independently associated with an increased risk of developing type 2 diabetes , cardiovascular disease , and certain cancers . This revised table contains almost 3 times the number of foods listed in the original table ( first published in this Journal in 1995 ) and contains nearly 1300 data entries derived from published and unpublished verified sources , representing > 750 different types of foods tested with the use of st and ard methods . The revised table also lists the glycemic load associated with the consumption of specified serving sizes of different foods",
"The objective of this study was to evaluate the effects of repeated consumption of two high-fiber diets on postpr and ial glucose and insulin responses . Two mixed-food breakfast meals composed predominantly of either red kidney beans or bran cereal were fed to six healthy young men . The meals provided equivalent levels of digestible carbohydrate , protein , fat , and fiber . Insulin responses measured after breakfast were lower with the bean diet than with the bran cereal diet but higher when measured after a st and ard lunch . No significant interactions were found between the diets and the length of the time the subjects were on the diets ( days 1 vs 7 ) . In comparison to the postpr and ial responses on day 1 of the diet periods , postpr and ial responses on day 7 showed reduced glucose and insulin responses to breakfast and reduced insulin responses to lunch . Responses to an oral glucose tolerance test were not affected by repeated consumption of these diets",
"Eight patients with noninsulin-dependent diabetes underwent two 2-wk study periods in r and om order during which they were provided with carbohydrate foods with either a high or low glycemic index ( GI ) . Over both high-GI and low-GI periods there were significant reductions in body weight , serum fructosamine , and cholesterol . Reductions in fasting blood glucose , HbA1c , and urinary c-peptide-to-creatinine ratio were significant only over the low-GI period despite a smaller mean weight loss . Reductions in triglyceride were significant only over the high-GI diet . Inclusion of low-GI foods into diets of patients with diabetes may be an additional measure that favorably influences carbohydrate metabolism without increasing insulin dem and",
"BACKGROUND The optimal source and amount of dietary carbohydrate for managing type 2 diabetes ( T2DM ) are unknown . OBJECTIVE We aim ed to compare the effects of altering the glycemic index or the amount of carbohydrate on glycated hemoglobin ( HbA1c ) , plasma glucose , lipids , and C-reactive protein ( CRP ) in T2DM patients . DESIGN Subjects with T2DM managed by diet alone ( n=162 ) were r and omly assigned to receive high-carbohydrate , high-glycemic-index ( high-GI ) , high-carbohydrate , low-glycemic-index ( low-GI ) , or low-carbohydrate , high-monounsaturated-fat ( low-CHO ) diets for 1 y. RESULTS The high-GI , low-GI , and low-CHO diets contained , respectively , 47 % , 52 % , and 39 % of energy as carbohydrate and 31 % , 27 % , and 40 % of energy as fat ; they had GIs of 63 , 55 , and 59 , respectively . Body weight and HbA1c did not differ significantly between diets . Fasting glucose was higher ( P=0.041 ) , but 2-h postload glucose was lower ( P=0.010 ) after 12 mo of the low-GI diet . With the low-GI diet , overall mean triacylglycerol was 12 % higher and HDL cholesterol 4 % lower than with the low-CHO diet ( P ratio of total to HDL cholesterol disappeared by 6 mo ( time x diet interaction , P=0.044 ) . Overall mean CRP with the low-GI diet , 1.95 mg/L , was 30 % less than that with the high-GI diet , 2.75 mg/L ( P=0.0078 ) ; the concentration with the low-CHO diet , 2.35 mg/L , was intermediate . CONCLUSIONS In subjects with T2DM managed by diet alone with optimal glycemic control , long-term HbA1c was not affected by altering the GI or the amount of dietary carbohydrate . Differences in total : HDL cholesterol among diets had disappeared by 6 mo . However , because of sustained reductions in postpr and ial glucose and CRP , a low-GI diet may be preferred for the dietary management of T2DM",
"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",
"Carbohydrate portions ( 2 g ) of lentils , soya beans , and wholemeal bread were incubated for three hours with human digestive juices and the effect of digestibility on blood glucose examined . Lentils and soya beans released only 39 % and 8 % respectively of the sugars and oligosaccharides liberated from bread . In healthy volunteers 50 g carbohydrate portions of cooked lentils and soya beans raised blood glucose concentrations by only 42 % ( p blood glucose concentration after a meal and that supplementing chemical analysis with in-vitro and in-vivo food testing might permit identification of especially useful foods for diabetics",
"OBJECTIVE To determine the long-term effect of low glycemic index dietary advice on metabolic control and quality of life in children with type 1 diabetes . RESEARCH DESIGN AND METHODS Children with type 1 diabetes ( n = 104 ) were recruited to a prospect i ve , stratified , r and omized , parallel study to examine the effects of a measured carbohydrate exchange ( CHOx ) diet versus a more flexible low-glycemic index ( GI ) dietary regimen on HbA(1c ) levels , incidence of hypo- and hyperglycemia , insulin dose , dietary intake , and measures of quality of life over 12 months . RESULTS At 12 months , children in the low-GI group had significantly better HbA(1c ) levels than those in the CHOx group ( 8.05 + /- 0.95 vs. 8.61 + /- 1.37 % , P = 0.05 ) . Rates of excessive hyperglycemia ( > 15 episodes per month ) were significantly lower in the low-GI group ( 35 vs. 66 % , P = 0.006 ) . There were no differences in insulin dose , hypoglycemic episodes , or dietary composition . The low-GI dietary regimen was associated with better quality of life for both children and parents . CONCLUSIONS Flexible dietary instruction based on the food pyramid with an emphasis of low-GI foods improves HbA(1c ) levels without increasing the risk of hypoglycemia and enhances the quality of life in children with diabetes",
"OBJECTIVE To evaluate in type 1 diabetic patients 1 ) the long-term feasibility of a high-fiber ( HF ) diet composed exclusively of natural foodstuffs and 2 ) the efficacy of this diet in relation to blood glucose control and incidence of hypoglycemic episodes . RESEARCH DESIGN AND METHODS The study was r and omized with parallel groups . Participants were part of a larger multicenter study on the effects of acarbose on glucose control in diabetes . A total of 63 type 1 diabetic patients , age 28 + /- 9 years , BMI 24 + /- 0.6 kg/m2 , after a 4-week run-in period on their habitual diet , were r and omized to either an HF ( n = 32 ) or a low-fiber ( LF ) diet ( n = 31 ) for 24 weeks . The two diets , composed exclusively of natural foodstuffs , were weight-maintaining and , aside from their fiber content , were similar for all nutrients . At the end of the run-in period and the dietary treatment , fasting blood sample s for the measurement of plasma cholesterol , HDL cholesterol , triglyceride , and HbA(1c ) were collected . A daily glycemic profile was performed on a day in which the participants had consumed a st and ard menu representative of their treatment diet ( HF or LF ) . RESULTS Of the 63 study subjects , 29 in the HF group ( 91 % ) and 25 in the LF group ( 81 % ) completed the study Compared with the LF diet , the HF diet after 24 weeks decreased both mean daily blood glucose concentrations ( P number of hypoglycemic events ( P mean daily blood glucose concentrations ( P HbA(1c ) ( P number of hypoglycemic events ( P type 1 diabetic patients , an HF diet is feasible in the long term and , compared with an LF diet , improves glycemic control and reduces the number of hypoglycemic events",
"BACKGROUND The worldwide increase in type 2 diabetes mellitus is becoming a major health concern . We aim ed to assess the effect of acarbose in preventing or delaying conversion of impaired glucose tolerance to type 2 diabetes . METHODS In a multicentre , placebo-controlled r and omised trial , we r and omly allocated patients with impaired glucose tolerance to 100 mg acarbose or placebo three times daily . The primary endpoint was development of diabetes on the basis of a yearly oral glucose tolerance test ( OGTT ) . Analyses were by intention to treat . FINDINGS We r and omly allocated 714 patients with impaired glucose tolerance to acarbose and 715 to placebo . We excluded 61 ( 4 % ) patients because they did not have impaired glucose tolerance or had no postr and omisation data . 211 ( 31 % ) of 682 patients in the acarbose group and 130 ( 19 % ) of 686 on placebo discontinued treatment early . 221 ( 32 % ) patients r and omised to acarbose and 285 ( 42 % ) r and omised to placebo developed diabetes ( relative hazard 0.75 [ 95 % CI 0.63 - 0.90 ] ; p=0.0015 ) . Furthermore , acarbose significantly increased reversion of impaired glucose tolerance to normal glucose tolerance ( p placebo for 3 months was associated with an increase in conversion of impaired glucose tolerance to diabetes . The most frequent side-effects to acarbose treatment were flatulence and diarrhoea . INTERPRETATION Acarbose could be used , either as an alternative or in addition to changes in lifestyle , to delay development of type 2 diabetes in patients with impaired glucose tolerance",
"Low glycaemic index foods produce low blood glucose and insulin responses in normal subjects , and improve blood glucose control in Type 1 and well‐controlled Type 2 diabetic patients . We studied the effects of a low glycaemic index diet in 15 Type 2 diabetic patients with a mean fasting blood glucose of 9.5 mmol I−1 using a r and omized , crossover design . Patients were given pre‐weighed diets ( 59 % energy as carbohydrate , 21 % fat , and 24 g 1000‐kcal−1 dietary fibre ) for two 2‐week periods , with a diet glycaemic index of 60 during one period and 87 during the other . On the low glycaemic index diet , the blood glucose response after a representative breakfast was 29 % less than on the high glycaemic index diet ( 874 ± 108 ( ± SE ) vs ± 204 ± 112 mmol min I−1 ; p index diet , fasting serum fructosamine and cholesterol levels were significantly less than after the high glycaemic index diet ( 3.17 ± 0.12 vs 3.28 ± 0.16 mmol I−1 p mmol I−1 , p , as an index of insulin secretion , was 30 % lower on the low than the high glycaemic index diet ( 2.05 ± 0.30 vs 2.93 ± 0.49 nmol mmol‐creatinine−1 ; p urea was reduced by 19 % ( 347 ± 27 vs 402 ± 39 mmol 24‐h−1 ; p that low glycaemic index starchy foods may be beneficial in the treatment of Type 2 diabetes",
"OBJECTIVE We compared the effects of a low glycemic index ( GI ) diet with the American Diabetes Association ( ADA ) diet on glycosylated hemoglobin ( HbA1c ) among individuals with type 2 diabetes . METHODS Forty individuals with poorly controlled type 2 diabetes were r and omized to a low-GI or an ADA diet . The intervention , consisting of eight educational sessions ( monthly for the first 6 mo and then at months 8 and 10 ) , focused on a low-GI or an ADA diet . Data on demographics , diet , physical activity , psychosocial factors , and diabetes medication use were assessed at baseline and 6 and 12 mo . Generalized linear mixed models were used to compare the two groups on HbA1c , diabetic medication use , blood lipids , weight , diet , and physical activity . RESULTS Participants ( 53 % female , mean age 53.5 y ) were predominantly white with a mean body mass index of 35.8 kg/m(2 ) . Although both interventions achieved similar reductions in mean HbA1c at 6 mo and 12 mo , the low-GI diet group was less likely to add or increase dosage of diabetic medications ( odds ratio 0.26 , P = 0.01 ) . Improvements in high-density lipoprotein cholesterol , triacylglycerols , and weight loss were similar between groups . CONCLUSION Compared with the ADA diet , the low-GI diet achieved equivalent control of HbA1c using less diabetic medication . Despite its limited size , this trial suggests that a low-GI diet is a viable alternative to the ADA diet . Findings should be evaluated in a larger r and omized controlled trial",
"BACKGROUND Despite the popularity of low-glycemic index ( GI ) and high-protein diets , to our knowledge no r and omized , controlled trials have systematic ally compared their relative effects on weight loss and cardiovascular risk . METHODS A total of 129 overweight or obese young adults ( body mass index , > or = 25 [ calculated as weight in kilograms divided by the square of height in meters ] ) were assigned to 1 of 4 reduced-fat , high-fiber diets for 12 weeks . Diets 1 and 2 were high carbohydrate ( 55 % of total energy intake ) , with high and low GIs , respectively ; diets 3 and 4 were high protein ( 25 % of total energy intake ) , with high and low GIs , respectively . The glycemic load was highest in diet 1 and lowest in diet 4 . Changes in weight , body composition , and blood chemistry profile were studied . RESULTS While all groups lost a similar mean + /- SE percentage of weight ( diet 1 , -4.2 % + /- 0.6 % ; diet 2 , -5.5 % + /- 0.5 % ; diet 3 , -6.2 % + /- 0.4 % ; and diet 4 , -4.8 % + /- 0.7 % ; P = .09 ) , the proportion of subjects in each group who lost 5 % or more of body weight varied significantly by diet ( diet 1 , 31 % ; diet 2 , 56 % ; diet 3 , 66 % ; and diet 4 , 33 % ; P = .01 ) . Women on diets 2 and 3 lost approximately 80 % more fat mass ( -4.5 + /- 0.5 [ mean + /- SE ] kg and -4.6 + /- 0.5 kg ) than those on diet 1 ( -2.5 + /- 0.5 kg ; P = .007 ) . Mean + /- SE low-density-lipoprotein cholesterol levels declined significantly in the diet 2 group ( -6.6 + /- 3.9 mg/dL [ -0.17 + /- 0.10 mmol/L ] ) but increased in the diet 3 group ( + 10.0 + /- 3.9 mg/dL [ + 0.26 + /- 0.10 mmol/L ] ; P = .02 ) . Goals for energy distribution were not achieved exactly : both carbohydrate groups ate less fat , and the diet 2 group ate more fiber . CONCLUSION Both high-protein and low-GI regimens increase body fat loss , but cardiovascular risk reduction is optimized by a high-carbohydrate , low-GI diet",
"OBJECTIVE To evaluate whether a 5-week low-glycemic index ( LGI ) diet versus a high-glycemic index ( HGI ) diet can modify glucose and lipid metabolism as well as total fat mass in nondiabetic men . RESEARCH DESIGN AND METHODS In this study , 11 healthy men were r and omly allocated to 5 weeks of an LGI or HGI diet separated by a 5-week washout interval in a crossover design . RESULTS The LGI diet result ed in lower postpr and ial plasma glucose and insulin profiles and areas under the curve ( AUCs ) than the HGI diet . A 5-week period of the LGI diet lowered plasma triacylglycerol excursion after lunch ( AUC , P total fat mass by approximately 700 g ( P lean body mass ( P body weight . This decrease in fat mass was accompanied by a decrease in leptin , lipoprotein lipase , and hormone-sensitive lipase RNAm quantities in the subcutaneous abdominal adipose tissue ( P LGI diet ameliorates some plasma lipid parameters , decreases total fat mass , and tends to increase lean body mass without changing body weight . These changes were accompanied by a decrease in the expression of some genes implicated in lipid metabolism . Such a diet could be of benefit to healthy , slightly overweight subjects and might play a role in the prevention of metabolic diseases and their cardiovascular complications",
"Objective : Recent epidemiological and prospect i ve trial evidence suggests that consumption of a low glycaemic index ( LGI ) diet will reduce coronary risk . We hypothesise that introduction of an LGI diet will improve the metabolic profile of patients who have undergone coronary artery bypass grafting . Design : We conducted a r and omised parallel group trial comparing a control group ( n=29 , age 61.8±9 y ) , who received currently advocated healthy eating dietary advice only , to an intervention group , who received healthy eating advice emphasising LGI carbohydrates ( n=26 , age 63.6±9.4 y ) over a 12-week period in free-living patients with coronary heart disease . Outcome measures included fasting glucose , insulin , total cholesterol , high-density lipoprotein cholesterol , very low-density lipoprotein cholesterol , low density lipoprotein cholesterol and triglycerides . Results : A significant lower dietary glycaemic index was achieved in the group assigned to an LGI diet compared to the healthy eating control group ( 71±1 vs 81±1 ) ; fibre intake was also higher in the LGI group ( 20±1 vs 15±1 g ) . All biochemical markers of glucose and lipid metabolism measured were similar after 12 weeks of the LGI diet or control diet . Discussion : The LGI group achieved a significant LGI and a higher dietary fibre intake . However , there was no measurable significant effect of either the LGI diet or the health eating diet on lipid levels ; this may have been hidden by concurrent drug therapy",
"Oat or bean products , rich in water-soluble fiber , have distinct hypocholesterolemic effects in humans . After a control diet , 20 hypercholesterolemic men were r and omly allocated to oat-bran or bean supplemented diets for 21 days on a metabolic ward . Control and test diets provided equivalent energy , fat , and cholesterol but test diets had twice more total and 3-fold more soluble fiber . Oat-bran diets decreased serum cholesterol concentrations by 19 % ( p less than 0.0005 ) and calculated low-density lipoprotein cholesterol by 23 % ( p less than 0.0025 ) . Bean diets decreased serum cholesterol concentrations by 19 % ( p less than 0.0005 ) and low-density lipoprotein cholesterol by 24 % ( p less than 0.0005 ) . Oat-bran increased fecal weight by 43 % but beans did not . While oat-bran increased fecal bile acid excretion , beans had the opposite effect . Oat-bran or bean supplements may have an important role in nutritional management of selected hypercholesterolemic patients",
"OBJECTIVE To determine whether a chronic low-glycemic index ( LGI ) diet , compared with a high-glycemic index ( HGI ) diet , has beneficial effects on plasma glucose control , lipid metabolism , total fat mass , and insulin resistance in type 2 diabetic patients . RESEARCH DESIGN AND METHODS Twelve type 2 diabetic men were r and omly allocated to two periods of 4 weeks of an LGI or HGI carbohydrate diet separated by a 4-week washout interval , in a crossover design . RESULTS The LGI diet induced lower postpr and ial plasma glucose and insulin profiles and areas under the curve than after the HGI diet . At the end of the two dietary periods , the 7-day dietary records demonstrated equal daily total energy and macronutrient intake . Body weight and total fat mass were comparable . Four-week LGI versus HGI diet induced improvement of fasting plasma glucose ( P HbA(1c ) ( P whole-body glucose utilization measured by the euglycemic-hyperinsulinemic clamp ( P fasting plasma total and LDL cholesterol ( Delta changes LGI vs. HGI , P free fatty acids ( P CONCLUSIONS Only 4 weeks of an LGI diet was able to improve glycemic control , glucose utilization , some lipid profiles , and the capacity for fibrinolysis in type 2 diabetes . Even if changes in glycemic control were modest during the 4-week period , the use of an LGI diet in a longer-term manner might play an important role in the treatment and prevention of diabetes and related disorders",
"Objective : To compare the effect of a diet supplemented with chickpeas to a wheat-based diet of similar fibre content on serum lipids , glucose tolerance , satiety and bowel function . A third , lower-fibre wheat diet provided further information on dietary fibre quantity and bowel function and satiety . Method : Twenty-seven free-living adults followed two r and omized , crossover dietary interventions each of five weeks duration . The chickpea diet included canned drained chickpeas , bread and shortbread biscuits containing 30 % chickpea flour . The wheat diet included high-fibre wheat breakfast cereals and wholemeal bread . The diets were isoenergetic to the participants ’ usual diet , matched for macronutrient content and controlled for dietary fibre . Following on from the second r and omised intervention , a sub-group of 18 participants underwent a third , isoenergetic lower-fibre wheat diet that included low-fibre breakfast cereals and bread . Results : Repeated measures ANOVA revealed reductions in serum TC of 0.25 mmol/L ( p LDL-C of 0.20 mmol/L ( p = 0.02 ) following the chickpea diet compared to the wheat . An unintended significant increase in PUFA and corresponding decrease in MUFA consumption occurred during the chickpea diet and statistical adjustment for this reduced but did not eliminate the effect on serum lipids . There was no significant difference in glucose tolerance . Perceived general bowel health improved significantly during the chickpea diet although there was considerable individual variation . Some participants reported greater satiety during the chickpea diet . Conclusions : The small but significant decrease in serum TC and LDL-C during the chickpea diet compared to the equivalent fibre wheat diet was partly due to unintentional changes in macronutrient intake occurring because of chickpea ingestion . If dietary energy and macronutrients were not controlled , chickpea consumption might result in greater benefits via influence on these factors",
"In a r and omised cross-over study 18 nondependent ( NIDDM ) and 9 insulin-dependent ( IDDM ) diabetics were put on to a high carbohydrate diet containing leguminous fibre ( HL ) for 6 weeks , and also a st and ard low carbohydrate diet ( LC ) for 6 weeks . During two identical 24 h metabolic profiles mean prepr and ial and mean 2 hour postpr and ial blood glucoses were significantly lower on HL in both groups , as were also several overall measures of diabetic control , including the degree of glycosuria . Total cholesterol was reduced significantly on HL in both groups , and the HDL/LDL cholesterol ratio increased significantly on HL in the NIDDM group . A diet high in complex carbohydrate and leguminous fibre improves all aspects of diabetic control , and continued use of a low carbohydrate diet no longer appears justified",
"BACKGROUND The effect of increasing the intake of dietary fiber on glycemic control in patients with type 2 diabetes mellitus is controversial . METHODS In a r and omized , crossover study , we assigned 13 patients with type 2 diabetes mellitus to follow two diets , each for six weeks : a diet containing moderate amounts of fiber ( total , 24 g ; 8 g of soluble fiber and 16 g of insoluble fiber ) , as recommended by the American Diabetes Association ( ADA ) , and a high-fiber diet ( total , 50 g ; 25 g of soluble fiber and 25 g of insoluble fiber ) , containing foods not fortified with fiber ( unfortified foods ) . Both diets , prepared in a research kitchen , had the same macronutrient and energy content . We compared the effects of the two diets on glycemic control and plasma lipid concentrations . RESULTS Compliance with the diets was excellent . During the sixth week , the high-fiber diet , as compared with the the sixth week of the ADA diet , mean daily prepr and ial plasma glucose concentrations were 13 mg per deciliter [ 0.7 mmol per liter ] lower ( 95 percent confidence interval , 1 to 24 mg per deciliter [ 0.1 to 1.3 mmol per liter ] ; P=0.04 ) and mean median difference , daily urinary glucose excretion 1.3 g ( 0.23 ; 95 percent confidence interval , 0.03 to 1.83 g ; P= 0.008 ) . The high-fiber diet also lowered the area under the curve for 24-hour plasma glucose and insulin concentrations , which were measured every two hours , by 10 percent ( P=0.02 ) and 12 percent ( P=0.05 ) , respectively . The high-fiber diet reduced plasma total cholesterol concentrations by 6.7 percent ( P=0.02 ) , triglyceride concentrations by 10.2 percent ( P=0.02 ) , and very-low-density lipoprotein cholesterol concentrations by 12.5 percent ( P=0.01 ) . CONCLUSIONS A high intake of dietary fiber , particularly of the soluble type , above the level recommended by the ADA , improves glycemic control , decreases hyperinsulinemia , and lowers plasma lipid concentrations in patients with type 2 diabetes",
"Objective : To determine effects of daily intake of 1/2 cup pinto beans , black-eyed peas or carrots ( placebo ) on risk factors for coronary heart disease ( CHD ) and diabetes mellitus ( DM ) in free-living , mildly insulin resistant adults over an 8 week period . Methods : R and omized , crossover 3 × 3 block design . Sixteen participants ( 7 men , 9 women ) received each treatment for eight-weeks with two-week washouts . Fasting blood sample s collected at beginning and end of periods were analyzed for total cholesterol ( TC ) , low density lipoprotein cholesterol ( LDL-C ) , high density lipoprotein cholesterol , triacylglycerols , high-sensitivity C-reactive protein , insulin , glucose , and hemoglobin A1c . Results : A significant treatment-by-time effect impacted serum TC ( p = 0.026 ) and LDL ( p = 0.033 ) after eight weeks . Paired t-tests indicated that pinto beans were responsible for this effect ( p = 0.003 ; p = 0.008 ) . Mean change of serum TC for pinto bean , black-eyed pea and placebo were −19 ± 5 , 2.5 ± 6 , and 1 ± 5 mg/dL , respectively ( p = 0.011 ) . Mean change of serum LDL-C for pinto bean , black-eyed pea and placebo were −14 ± 4 , 4 ± 5 , and 1 ± 4 mg/dL , in that order ( p = 0.013 ) . Pinto beans differed significantly from placebo ( p = 0.021 ) . No significant differences were seen with other blood concentrations across the 3 treatment periods . Conclusions : Pinto bean intake should be encouraged to lower serum TC and LDL-C , thereby reducing risk for CHD",
"Objectives To determine whether low-glycemic index ( GI ) diets have clinical utility in overweight patients with non-insulin-dependent diabetes mellitus ( NIDDM ) . Research Design and Methods Six patients with NIDDM were studied on both high- and low-GI diets of 6-wk duration with metabolic diets with a r and omized crossover design . Both diets were of similar composition ( 57 % carbohydrate , 23 % fat , and 34 g/day dietary fiber ) , but the low-GI diet had a GI of 58 compared with 86 for the high-GI diet . Results Small and similar amounts of weight were lost on both diets : 2.5 kg on high-GI diet and 1.8 kg on low-GI diet . On the low-GI diet , the mean level of serum fructosamine , as an index of overall blood glucose control , was lower than on the high-GI diet by 8 % ( P total serum cholesterol was lower by 7 % ( P overweight patients with NIDDM , reducing diet GI improves overall blood glucose and lipid control",
"The plasma cholesterol lowering potential of canned baked beans was examined in a cross-over comparison with canned spaghetti . The difference in total dietary non-starch polysaccharide ( NSP ) of 12 g daily ( 6.6 g difference in soluble NSP ) , was insufficient to alter the plasma cholesterol , HDL cholesterol , triglyceride and glucose concentrations in 20 mildly hyper-cholesterolaemic men . Thus , eating an average of six 440 g cans of this source of baked beans per week , large servings , does not lower the plasma cholesterol when dietary fat is not displaced",
"OBJECTIVE Several methods have been proposed to evaluate insulin sensitivity from the data obtained from the oral glucose tolerance test ( OGTT ) . However , the validity of these indices has not been rigorously evaluated by comparing them with the direct measurement of insulin sensitivity obtained with the euglycemic insulin clamp technique . In this study , we compare various insulin sensitivity indices derived from the OGTT with whole-body insulin sensitivity measured by the euglycemic insulin clamp technique . RESEARCH DESIGN AND METHODS In this study , 153 subjects ( 66 men and 87 women , aged 18 - 71 years , BMI 20 - 65 kg/m2 ) with varying degrees of glucose tolerance ( 62 subjects with normal glucose tolerance , 31 subjects with impaired glucose tolerance , and 60 subjects with type 2 diabetes ) were studied . After a 10-h overnight fast , all subjects underwent , in r and om order , a 75-g OGTT and a euglycemic insulin clamp , which was performed with the infusion of [3 - 3H]glucose . The indices of insulin sensitivity derived from OGTT data and the euglycemic insulin clamp were compared by correlation analysis . RESULTS The mean plasma glucose concentration divided by the mean plasma insulin concentration during the OGTT displayed no correlation with the rate of whole-body glucose disposal during the euglycemic insulin clamp ( r = -0.02 , NS ) . From the OGTT , we developed an index of whole-body insulin sensitivity ( 10,000/square root of [ fasting glucose x fasting insulin ] x [ mean glucose x mean insulin during OGTT ] ) , which is highly correlated ( r = 0.73 , P glucose disposal during the euglycemic insulin clamp . CONCLUSIONS Previous methods used to derive an index of insulin sensitivity from the OGTT have relied on the ratio of plasma glucose to insulin concentration during the OGTT . Our results demonstrate the limitations of such an approach . We have derived a novel estimate of insulin sensitivity that is simple to calculate and provides a reasonable approximation of whole-body insulin sensitivity from the OGTT",
"In prescribing a diabetic diet more attention has traditionally been paid to the amount of dietary carbohydrate than to its type or structure . We have compared the effect on blood glucose of substituting unrefined , whole foods for refined , processed foods in liberal carbohydrate diets ( 50 - 55 % of dietary energy ) eaten by 10 diabetic children in a r and omised crossover study . All measurements were made at home . The unrefined diet used whole foods ( including ) dried beans ) supplying 60 g/day of dietary fibre . The refined diet used processed foods supplying 20 g/day of dietary fibre . Diets were isocaloric for carbohydrate , fat , and protein . Glycaemic control was assessed by daily urine analysis for glucose , home blood glucose measurements , glycosylated haemoglobin , and by a 24-hour profile of blood and urinary glucose carried out at home after 6 weeks on each diet . Glycaemic control was significantly better on the unrefined diet . On profile days mean blood glucose levels on the unrefined and refined diets respectively were : prepr and ial : 5.5 and 8.4 mmol/l ; postpr and ial 8.5 and 12.2 mmol/l . The mean 24-hour urinary glucose excretion on the unrefined diet was 9.3 g and on the refined diet was 38.0 g. Six months after the study the children were eating appreciably more dietary fibre than before ( mean increase 13.6 g/day ) . Attention to food type and structure can improve blood glucose control in diabetic children and should provide an acceptable and more rational basis for dietary prescription than one based on carbohydrate quantity alone",
"BACKGROUND Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes . We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors . METHODS In this r and omized study , 10,251 patients ( mean age , 62.2 years ) with a median glycated hemoglobin level of 8.1 % were assigned to receive intensive therapy ( targeting a glycated hemoglobin level below 6.0 % ) or st and ard therapy ( targeting a level from 7.0 to 7.9 % ) . Of these patients , 38 % were women , and 35 % had had a previous cardiovascular event . The primary outcome was a composite of nonfatal myocardial infa rct ion , nonfatal stroke , or death from cardiovascular causes . The finding of higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up . RESULTS At 1 year , stable median glycated hemoglobin levels of 6.4 % and 7.5 % were achieved in the intensive-therapy group and the st and ard-therapy group , respectively . During follow-up , the primary outcome occurred in 352 patients in the intensive-therapy group , as compared with 371 in the st and ard-therapy group ( hazard ratio , 0.90 ; 95 % confidence interval [ CI ] , 0.78 to 1.04 ; P=0.16 ) . At the same time , 257 patients in the intensive-therapy group died , as compared with 203 patients in the st and ard-therapy group ( hazard ratio , 1.22 ; 95 % CI , 1.01 to 1.46 ; P=0.04 ) . Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group ( P st and ard therapy , the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events . These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes . ( Clinical Trials.gov number , NCT00000620 .",
"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 ."
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A systematic review and meta- analysis identified 42 r and omised control trials comparing a nurse-led intervention with ' usual care ' to quantify their effect on glycated haemoglobin ( HbA1c ) and major cardiovascular risk factors in diabetes patients . All relevant data bases were systematic ally search ed for publications to February 2016 : MEDLINE , Cochrane Central Register of Controlled Trials , EMBASE and Cumulative Index to Nursing & Allied Health Literature ( CINAHL ) . The 42 trials recruited 9955 diabetes patients ( 5022 r and omised to intervention and 4933 to ' usual care ' ) . For patients receiving the nurse-led intervention , compared with ' usual care ' , there were small but significant mean reductions for HbA1c [ -0.28 % ; 95 % CI -0.38 % , -0.18 % ; p-value and serum triglyceride levels [ -0.27mmol/L ; 95 % CI -0.49 , -0.06 ; p=0.01 , n=1169 ] , and a greater proportion of patients stopped smoking [ risk ratio=2.70 ; 95 % CI 1.35 , 5.43 ; p=0.005 , n=1890 patients ] . Mean reductions for systolic [ -1.84mmHg ; 95 % CI -3.97 , -0.10 ; p=0.06 , 4241 patients ] and diastolic [ -0.95mmHg ; 95 % CI -2.15 , -0.25 ; p=0.12 , 3811 patients ] blood pressures trended towards significance . There were no significant mean reductions for body mass index or serum cholesterol . Nurse-led interventions produced greater improvements than ' usual care ' for HbA1c , serum triglyceride and smoking cessation and support an increased independent role for nurses in diabetes management
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"The authors examined whether tailored self-management support ( SMS ) strategies reach patients in a safety net system and explored variation by language , literacy , and insurance . English- , Spanish- , and Cantonese-speaking diabetes patients were r and omized to weekly automated telephone disease management ( ATDM ) or monthly group medical visits . The SMS programs employ distinct communication methods but share common objectives , including behavioral “ action plans . ” Reach was measured using three complementary dimensions : ( a ) participation among clinics , clinicians , and patients ; ( b ) patient representativeness ; and ( c ) patient engagement with SMS . Participation rates were high across all levels and preferentially attracted Spanish- language speakers , uninsured , and Medicaid recipients . Although both programs engaged a significant proportion in action planning , ATDM yielded higher engagement , especially among those with limited English proficiency and limited literacy . These results provide important insights for health communication and translational research with respect to realizing the public health benefits of SMS and can inform system-level planning to reduce health disparities",
"BACKGROUND Diabetic patients taking insulin often have suboptimal glucose control , and st and ard methods of health care delivery are ineffective in improving such control . This study was undertaken to determine if insulin adjustment according to advice provided by telephone by a diabetes nurse educator could lead to better glucose control , as indicated by level of glycated hemoglobin ( HbA1c ) . METHODS The authors conducted a prospect i ve r and omized trial involving 46 insulin-requiring diabetic patients who had poor glucose control ( HbA1c of 0.085 or more ) . Eligible patients were those already taking insulin and receiving endocrinologist-directed care through a diabetes centre and whose most recent HbA1c level was 0.085 or higher . The patients were r and omly assigned to receive st and ard care or to have regular telephone contact with a diabetes nurse educator for advice about adjustment of insulin therapy . RESULTS At baseline there was no statistically significant difference between the 2 groups in terms of HbA1c level ( mean [ and st and ard deviation ] for st and ard-care group 0.094 [ 0.008 ] and for intervention group 0.096 [ 0.010 ] ) , age , sex , type or duration of diabetes , duration of insulin therapy or complications . After 6 months , the mean HbA1c level in the st and ard-care group was 0.089 ( 0.010 ) , which was not significantly different from the mean level at baseline . However , the mean HbA1c level in the intervention group had fallen to 0.078 ( 0.008 ) , which was significantly lower than both the level at baseline for that group ( p Insulin adjustment according to advice from a diabetes nurse educator is an effective method of improving glucose control in insulin-requiring diabetic patients",
"BACKGROUND Cardiovascular disease ( CVD ) and diabetes account for one-third of the mortality difference between African American and white patients . We evaluated the effect of a CVD risk reduction intervention in African Americans with diabetes . METHODS We r and omized 359 African Americans with type 2 diabetes to receive usual care or a nurse telephone intervention . The 12-month intervention provided monthly self-management support and quarterly medication management facilitation . Co primary outcomes were changes in systolic blood pressure ( SBP ) , hemoglobin A1c ( HbA1c ) , and low-density lipoprotein cholesterol ( LDL-C ) over 12 months . We estimated between-intervention group differences over time using linear mixed-effects models . The secondary outcome was self-reported medication adherence . RESULTS The sample was 72 % female ; 49 % had low health literacy , and 37 % had annual income Model-based estimates for mean baseline SBP , HbA1c , and LDL-C were 136.8 mm Hg ( 95 % CI 135.0 - 138.6 ) , 8.0 % ( 95 % CI 7.8 - 8.2 ) , and 99.1 mg/dL ( 95 % CI 94.7 - 103.5 ) , respectively . Intervention patients received 9.9 ( SD 3.0 ) intervention calls on average . Primary providers replied to 76 % of nurse medication management facilitation contacts , 18 % of these result ed in medication changes . There were no between-group differences over time for SBP ( P = .11 ) , HbA1c ( P = .66 ) , or LDL-C ( P = .79 ) . Intervention patients were more likely than those receiving usual care to report improved medication adherence ( odds ratio 4.4 , 95 % CI 1.8 - 10.6 , P = .0008 ) , but adherent patients did not exhibit relative improvement in primary outcomes . CONCLUSIONS This intervention improved self-reported medication adherence but not CVD risk factor control among African Americans with diabetes . Further research is needed to determine how to maximally impact CVD risk factors in African American patients",
"Abstract OBJECTIVE : To examine the impact of a nurse-coordinated intervention delivered to patients with non-insulin-dependent diabetes mellitus between office visits to primary care physicians . DESIGN : R and omized , controlled trial . SETTING : Veterans Affairs general medical clinic . PATIENTS : 275 veterans who had NIDDM and were receiving primary care from general internists . INTERVENTION : Nurse-initiated contacts were made by telephone at least monthly to provide patient education ( with special emphasis on regimens and significant signs and symptoms of hyperglycemia and hypoglycemia ) , reinforce compliance with regimens , monitor patients ’ health status , facilitate resolution of identified problems , and facilitate access to primary care . MEASUREMENTS : Glycemic control was assessed using glycosylated hemoglobin ( GHb ) and fasting blood sugar ( FBS ) levels . Health-related quality of life ( HRQOL ) was measured with the Medical Outcomes Study SF-36 , and diabetes-related symptoms were assessed using patients ’ self-reports of signs and symptoms of hyper- and hypoglycemia during the previous month . MAIN RESULTS : At one year , between-group differences favored intervention patients for FBS ( 174.1 mg/dL vs 193.1 mg/dL , p=0.011 ) and GHb ( 10.5 % vs 11.1 % , p=0.046 ) . Statistically significant differences were not observed for either SF-36 scores ( p=0.66 ) or diabetes-related symptoms ( p=0.23 ) . CONCLUSIONS : The intervention , design ed to be a pragmatic , low-intensity adjunct to care delivered by physicians , modestly improved glycemic control but not HRQOL or diabetes-related symptoms ",
"OBJECTIVE To investigate whether monitoring and discussing psychological well-being in out patients with diabetes improves mood , glycemic control , and the patient 's evaluation of the quality of diabetes care . RESEARCH DESIGN AND METHODS This study was a r and omized controlled trial of 461 out patients with diabetes who were r and omly assigned to st and ard care or to the monitoring condition . In the latter group , the diabetes nurse specialist assessed and discussed psychological well-being with the patient ( with an interval of 6 months ) in addition to st and ard care . The computerized Well-being Question naire was used for this purpose . Primary outcomes were mood , HbA(1c ) , and the patient 's evaluation of the quality of diabetes care at 1-year follow-up . The number of referrals to the psychologist was analyzed as a secondary outcome . Intention-to-treat analysis was used . RESULTS The monitoring group reported better mood compared with the st and ard care group , as indicated by significantly lower negative well-being and significantly higher levels of energy , higher general well-being , better mental health , and a more positive evaluation of the quality of the emotional support received from the diabetes nurse . The two groups did not differ for HbA(1c ) or in their overall evaluation of the quality of diabetes care . In the monitoring condition , significantly more subjects were referred to the psychologist . CONCLUSIONS Monitoring and discussing psychological well-being as part of routine diabetes outpatient care had favorable effects on the mood of patients but did not affect their HbA(1c ) . Our results support the recommendation to monitor psychological well-being in patients with diabetes",
"Abstract Objective . To study the effectiveness of a comprehensive diabetes programme in general practice that integrates patient-centred lifestyle counselling into structured diabetes care . Design and setting . Cluster r and omised trial in general practice s. Intervention . Nurse-led structured diabetes care with a protocol , record keeping , reminders , and feedback , plus training in motivational interviewing and agenda setting . Subjects . Primary care nurses in 58 general practice s and their 940 type 2 diabetes patients with an HbA1c concentration above 7 % , and a body mass index ( BMI ) above 25 kg/m2 . Main outcome measures . HbA1c , diet , and physical activity ( medical records and patient question naires ) . Results . Multilevel linear and logistic regression analyses adjusted for baseline outcomes showed that despite active nurse participation in the intervention , the comprehensive programme was no more effective than usual care after 14 months , as shown by HbA1c levels ( difference between groups = 0.13 ; CI 20.8–0.35 ) and diet ( fat ( difference between groups = 0.19 ; CI 20.82–1.21 ) ; vegetables ( difference between groups = 0.10 ; CI-0.21–0.41 ) ; fruit ( difference between groups = 20.02 ; CI 20.26–0.22 ) ) , and physical activity ( difference between groups = 21.15 ; CI 212.26–9.97 ) , or any of the other measures of clinical parameters , patient 's readiness to change , or quality of life . Conclusion . A comprehensive programme that integrated lifestyle counselling based on motivational interviewing principles integrated into structured diabetes care did not alter HbA1c or the lifestyle related to diet and physical activity . We thus question the impact of motivational interviewing in terms of its ability to improve routine diabetes care in general practice",
"Background Type 2 diabetes mellitus is a chronic condition that requires ongoing , life-long care in order to be controlled . Objectives The aims of the study were to assess the effect of nursing case management on glycated hemoglobin ( HbA1c ) levels compared to usual care in people with type 2 diabetes mellitus and to determine if effects of nursing case management varied by gender , age , duration of disease , education , and income . Methods This is a pragmatic clinical trial , conducted in the municipality of B and eirantes , Paraná , Brazil , in 2011 and 2012 . Eighty individuals were recruited and r and omized equally to receive nursing case management or usual care . Covariates were sociodemographic and clinical factors . The outcome was HbA1c measured at baseline , 6 months , and 12 months . Results The sample consisted predominately of women ; most had been diagnosed with type 2 diabetes mellitus within the previous 5 years . Mean age was 50.14 ( SD = 7.00 ) , with 5.27 ( SD = 4.39 ) years of schooling and an average HbA1c of 9.90 % ( SD = 2.49 ) . Hemoglobin A1c was reduced from an average of 10.33 % to 9.0 % ( p nursing case management group and from 9.57 % to 8.93 % ( p = .05 ) in the usual care group ; the group by time effect was not significant . Case management effects varied by younger age ( p = .05 ) , duration of type 2 diabetes less than 5 years ( p = .03 ) , up to 4 years of schooling ( p = .04 ) , and being in the lowest-income stratum ( p = .02 ) . Discussion Both groups showed a statistically significant reduction of HbA1c at 6 and 12 months following baseline . The difference in proportional reduction of HbA1c between groups was not statistically significant",
"BACKGROUND Improved blood-glucose control decreases the progression of diabetic microvascular disease , but the effect on macrovascular complications is unknown . There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation . We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a r and omised controlled trial . METHODS 3867 newly diagnosed patients with type 2 diabetes , median age 54 years ( IQR 48 - 60 years ) , who after 3 months ' diet treatment had a mean of two fasting plasma glucose ( FPG ) concentrations of 6.1 - 15.0 mmol/L were r and omly assigned intensive policy with a sulphonylurea ( chlorpropamide , glibenclamide , or glipizide ) or with insulin , or conventional policy with diet . The aim in the intensive group was FPG less than 6 mmol/L. In the conventional group , the aim was the best achievable FPG with diet alone ; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment : any diabetes-related endpoint ( sudden death , death from hyperglycaemia or hypoglycaemia , fatal or non-fatal myocardial infa rct ion , angina , heart failure , stroke , renal failure , amputation [ of at least one digit ] , vitreous haemorrhage , retinopathy requiring photocoagulation , blindness in one eye , or cataract extraction ) ; diabetes-related death ( death from myocardial infa rct ion , stroke , peripheral vascular disease , renal disease , hyperglycaemia or hypoglycaemia , and sudden death ) ; all-cause mortality . Single clinical endpoints and surrogate sub clinical endpoints were also assessed . All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy . FINDINGS Over 10 years , haemoglobin A1c ( HbA1c ) was 7.0 % ( 6.2 - 8.2 ) in the intensive group compared with 7.9 % ( 6.9 - 8.8 ) in the conventional group -- an 11 % reduction . There was no difference in HbA1c among agents in the intensive group . Compared with the conventional group , the risk in the intensive group was 12 % lower ( 95 % CI 1 - 21 , p=0.029 ) for any diabetes-related endpoint ; 10 % lower ( -11 to 27 , p=0.34 ) for any diabetes-related death ; and 6 % lower ( -10 to 20 , p=0.44 ) for all-cause mortality . Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25 % risk reduction ( 7 - 40 , p=0.0099 ) in microvascular endpoints , including the need for retinal photocoagulation . There was no difference for any of the three aggregate endpoints between the three intensive agents ( chlorpropamide , glibenclamide , or insulin ) . Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis ( both p rates of major hypoglycaemic episodes per year were 0.7 % with conventional treatment , 1.0 % with chlorpropamide , 1.4 % with glibenclamide , and 1.8 % with insulin . Weight gain was significantly higher in the intensive group ( mean 2.9 kg ) than in the conventional group ( p insulin had a greater gain in weight ( 4.0 kg ) than those assigned chlorpropamide ( 2.6 kg ) or glibenclamide ( 1.7 kg ) . INTERPRETATION Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications , but not macrovascular disease , in patients with type 2 diabetes . ( ABSTRACT TRUNCATED",
"BACKGROUND There is a need for r and omized , prospect i ve trials of case management interventions with re source utilization analyses . OBJECTIVES To determine whether algorithm-driven telephone care by nurses improves lipid control in patients with diabetes . DESIGN Prospect i ve , r and omized , controlled trial . PARTICIPANTS Adults with diabetes at a federally funded community health center were r and omly assigned to intervention ( n = 381 ) or usual-care ( n = 381 ) groups . INTERVENTIONS Nurses independently initiated and titrated lipid therapy and promoted behavioral change through motivational interviewing and self-management techniques . Other parameters of diabetes care were addressed based on time constraints . MAIN MEASURES The primary outcome was the proportion of patients with a low-density lipoprotein ( LDL ) less than 100 mg/dL. Secondary outcomes included the number of hospital admissions , total hospital charges per patient , and the proportion of patients meeting other lipid , glycemic , and blood pressure guidelines . KEY RESULTS The percent of patients with an LDL increased from 52.0 % to 58.5 % in the intervention group and decreased from 55.6 % to 46.7 % in the control group ( P Average cost per patient to the healthcare system was less for the intervention group ( $ 6600 vs $ 9033 , P = .03 ) . Intervention patients trended toward fewer hospital admissions ( P = .06 ) . The intervention did not affect glycemic and blood pressure outcomes . CONCLUSIONS Nurses can improve lipid control in patients with diabetes in a primarily indigent population through telephone care using moderately complex algorithms , but a more targeted approach is warranted . Telephone-based outreach may decrease re source utilization , but more study is needed",
"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 To investigate the effectiveness of a nurse short message service ( SMS ) by cellular phone and wire Internet on plasma glucose levels in people with diabetes for six months . BACKGROUND Blood glucose management system using telemedicine approaches may maintain the appropriate blood glucose levels in type-2 diabetic patients . DESIGN A control group pre-test-post-test design was used to assess the effectiveness of nurse 's education . METHODS Twenty-five patients were r and omly assigned to an intervention group and 26 to a control group . The intervention was applied for six months . The goal of the intervention was to keep blood glucose concentrations close to the normal range . Participants were requested to input their blood glucose level , diet and exercise diary everyday in the website by cellular phone or wire Internet . The research er sends optimal recommendations to each patient using SMS by cellular phone and wire Internet weekly . RESULTS Glycosylated hemoglobin ( HbA(1)c ) decreased 1.15 % points at three months and 1.05 % points at six months compared with baseline in the intervention group . Patients in the intervention group had a decrease of two hours post meal glucose ( 2HPMG ) of 85.1 mg/dl at three months and 63.1 mg/dl at six months compared with baseline . CONCLUSION This web-based intervention using SMS of cellular phone improved HbA(1)c and 2HPMG for six months in type-2 diabetic patients . RELEVANCE TO CLINICAL PRACTICE An SMS of cellular phone intervention by a nurse can reduce HbA(1)c and 2HPMG for six months in type-2 diabetic patients",
"OBJECTIVE Despite the importance of self-management support ( SMS ) , few studies have compared SMS interventions , involved diverse population s , or entailed implementation in safety net setting s. We examined the effects of two SMS strategies across outcomes corresponding to the Chronic Care Model . RESEARCH DESIGN AND METHODS A total of 339 out patients with poorly controlled diabetes from county-run clinics were enrolled in a three-arm trial . Participants , more than half of whom spoke limited English , were uninsured , and /or had less than a high school education , were r and omly assigned to usual care , interactive weekly automated telephone self-management support with nurse follow-up ( ATSM ) , or monthly group medical visits with physician and health educator facilitation ( GMV ) . We measured 1-year changes in structure ( Patient Assessment of Chronic Illness Care [ PACIC ] ) , communication processes ( Interpersonal Processes of Care [ IPC ] ) , and outcomes ( behavioral , functional , and metabolic ) . RESULTS Compared with the usual care group , the ATSM and GMV groups showed improvements in PACIC , with effect sizes of 0.48 and 0.50 , respectively ( P improvements in IPC ( effect sizes 0.40 vs. usual care and 0.25 vs. GMV , P improvements in self-management behavior versus the usual care arm ( P fewer bed days per month than the usual care group ( −1.7 days , P = 0.05 ) and the GMV group ( −2.3 days , P less interference with daily activities than the usual care group ( odds ratio 0.37 , P = 0.02 ) . We observed no differences in A1C change . CONCLUSIONS Patient-centered SMS improves certain aspects of diabetes care and positively influences self-management behavior . ATSM seems to be a more effective communication vehicle than GMV in improving behavior and quality of life",
"This meta- analysis assessed how successfully Diabetes Self-Management Education ( DSME ) interventions help people with type 2 diabetes achieve and maintain healthy blood glucose levels . We included 52 DSME programs with 9,631 participants that reported post-intervention A1c levels in r and omized controlled trials . The training conditions result ed in significant reductions in A1c levels compared to control conditions . However , the impact of intervention was modest shifting of only 7.23 % more participants from diabetic to pre-diabetic or normal status , relative to the control condition . Most intervention participants did not achieve healthy A1c levels . Further , few DSME studies assessed long-term maintenance of A1c gains . Past trends suggest that gains are difficult to sustain over time . Our results suggested that interventions delivered by nurses were more successful than those delivered by non-nursing personnel . We suggest that DSME programs might do better by going beyond procedural interventions . Most DSME programs relied heavily on rules and procedures to guide decisions about diet , exercise , and weight loss . Future DSME may need to include cognitive self-monitoring , diagnosis , and planning skills to help patients detect anomalies , identify possible causes , generate corrective action , and avoid future barriers to maintaining healthy A1c levels . Finally , comprehensive descriptions of DSME programs would advance future efforts",
"OBJECTIVE To test whether the implementation of elements of the Chronic Care Model ( CCM ) via a specially trained practice nurse leads to an improved cardiovascular risk profile among type 2 diabetes patients . RESEARCH DESIGN AND METHODS This cluster r and omized controlled trial with primary care physicians as the unit of r and omization was conducted in the German part of Switzerl and . Three hundred twenty-six type 2 diabetes patients ( age > 18 years ; at least one glycosylated hemoglobin [ HbA1c ] level of ≥7.0 % [ 53 mmol/mol ] in the preceding year ) from 30 primary care practice s participated . The intervention included implementation of CCM elements and involvement of practice nurses in the care of type 2 diabetes patients . Primary outcome was HbA1c levels . The secondary outcomes were blood pressure ( BP ) , LDL cholesterol , accordance with CCM ( assessed by Patient Assessment of Chronic Illness Care [ PACIC ] question naire ) , and quality of life ( assessed by the 36-item short-form health survey [ SF-36 ] ) . RESULTS After 1 year , HbA1c levels decreased significantly in both groups with no significant difference between groups ( −0.05 % [ −0.60 mmol/mol ] ; P = 0.708 ) . Among intervention group patients , systolic BP ( −3.63 ; P = 0.050 ) , diastolic BP ( −4.01 ; P ) , LDL cholesterol ( −0.21 ; P = 0.033 ) , and PACIC subscores ( P improved the cardiovascular risk profile and is experienced by patients as a better structured care . Our study showed that care according to the CCM can be implemented even in small primary care practice s , which still represent the usual structure in most European health care systems",
"OBJECTIVE We evaluated automated telephone disease management ( ATDM ) with telephone nurse follow-up as a strategy for improving diabetes treatment processes and outcomes in Department of Veterans Affairs ( VA ) clinics . We also compared the results with those of a prior ATDM trial conducted in a county health care system . RESEARCH DESIGN AND METHODS A total of 272 VA patients with diabetes using hypoglycemic medications were r and omized . During the 1-year study period , intervention patients received biweekly ATDM health assessment and self-care education calls , and a nurse educator followed up with patients based on their ATDM assessment reports . Telephone surveys were used to measure patients ' self-care , symptoms , and satisfaction with care . Outpatient service use was evaluated using electronic data bases and self-reports , and glycemic control was measured by HbA1c and serum glucose testing . RESULTS At 12 months , intervention patients reported more frequent glucose self-monitoring and foot inspections than patients receiving usual care and were more likely to be seen in podiatry and diabetes specialty clinics . Intervention patients also were more likely than control patients to have had a cholesterol test . Among patients with baseline HbA1c levels > or = 8 % , mean end-point values were lower among intervention patients than control patients ( 8.7 vs. 9.2 % , respectively ; P = 0.04 ) . Among intervention and control patients with baseline values > or = 9 % , mean end-point values were 9.1 and 10.2 % , respectively ( P = 0.04 ) . At follow-up , intervention patients reported fewer symptoms of poor glycemic control than control patients and greater satisfaction with their health care . CONCLUSIONS This intervention improved the quality of VA diabetes care . Intervention effects for most end points replicated findings from the prior county clinic trial , although intervention-control differences in the current study were smaller because of the relatively good self-care and health status among the current study 's enrollees",
"BACKGROUND The effects of intensive glucose control on cardiovascular events in patients with long-st and ing type 2 diabetes mellitus remain uncertain . METHODS We r and omly assigned 1791 military veterans ( mean age , 60.4 years ) who had a suboptimal response to therapy for type 2 diabetes to receive either intensive or st and ard glucose control . Other cardiovascular risk factors were treated uniformly . The mean number of years since the diagnosis of diabetes was 11.5 , and 40 % of the patients had already had a cardiovascular event . The goal in the intensive-therapy group was an absolute reduction of 1.5 percentage points in the glycated hemoglobin level , as compared with the st and ard-therapy group . The primary outcome was the time from r and omization to the first occurrence of a major cardiovascular event , a composite of myocardial infa rct ion , stroke , death from cardiovascular causes , congestive heart failure , surgery for vascular disease , inoperable coronary disease , and amputation for ischemic gangrene . RESULTS The median follow-up was 5.6 years . Median glycated hemoglobin levels were 8.4 % in the st and ard-therapy group and 6.9 % in the intensive-therapy group . The primary outcome occurred in 264 patients in the st and ard-therapy group and 235 patients in the intensive-therapy group ( hazard ratio in the intensive-therapy group , 0.88 ; 95 % confidence interval [ CI ] , 0.74 to 1.05 ; P=0.14 ) . There was no significant difference between the two groups in any component of the primary outcome or in the rate of death from any cause ( hazard ratio , 1.07 ; 95 % CI , 0.81 to 1.42 ; P=0.62 ) . No differences between the two groups were observed for microvascular complications . The rates of adverse events , predominantly hypoglycemia , were 17.6 % in the st and ard-therapy group and 24.1 % in the intensive-therapy group . CONCLUSIONS Intensive glucose control in patients with poorly controlled type 2 diabetes had no significant effect on the rates of major cardiovascular events , death , or microvascular complications with the exception of progression of albuminuria ( P = 0.01 ) [ added ] . ( Clinical Trials.gov number , NCT00032487 .",
"CONTEXT Telemedicine is a promising but largely unproven technology for providing case management services to patients with chronic conditions and lower access to care . OBJECTIVES To examine the effectiveness of a telemedicine intervention to achieve clinical management goals in older , ethnically diverse , medically underserved patients with diabetes . DESIGN , Setting , and Patients A r and omized controlled trial was conducted , comparing telemedicine case management to usual care , with blinded outcome evaluation , in 1,665 Medicare recipients with diabetes , aged > /= 55 years , residing in federally design ated medically underserved areas of New York State . Interventions Home telemedicine unit with nurse case management versus usual care . Main Outcome Measures The primary endpoints assessed over 5 years of follow-up were hemoglobin A1c ( HgbA1c ) , low density lipoprotein ( LDL ) cholesterol , and blood pressure levels . RESULTS Intention-to-treat mixed models showed that telemedicine achieved net overall reductions over five years of follow-up in the primary endpoints ( HgbA1c , p = 0.001 ; LDL , p systolic and diastolic blood pressure , p = 0.024 ; p HgbA1c , 3.84 ( -0.08 , 7.77 ) mg/dL for LDL cholesterol , and 4.32 ( 1.93 , 6.72 ) mm Hg for systolic and 2.64 ( 1.53 , 3.74 ) mm Hg for diastolic blood pressure . There were 176 deaths in the intervention group and 169 in the usual care group ( hazard ratio 1.01 [ 0.82 , 1.24 ] ) . CONCLUSIONS Telemedicine case management result ed in net improvements in HgbA1c , LDL-cholesterol and blood pressure levels over 5 years in medically underserved Medicare beneficiaries . Mortality was not different between the groups , although power was limited . Trial Registration http:// clinical trials.gov Identifier : NCT00271739",
"OBJECTIVE To evaluate the effectiveness of a culturally adapted , primary care – based nurse – community health worker ( CHW ) team intervention to support diabetes self-management on diabetes control and other biologic measures . RESEARCH DESIGN AND METHODS Two hundred sixty-eight Samoan participants with type 2 diabetes were recruited from a community health center in American Samoa and were r and omly assigned by village clusters to the nurse-CHW team intervention or to a wait-list control group that received usual care . RESULTS Participants had a mean age of 55 years , 62 % were female , mean years of education were 12.5 years , 41 % were employed , and mean HbA1c was 9.8 % at baseline . At 12 months , mean HbA1c was significantly lower among CHW participants , compared with usual care , after adjusting for confounders ( b = −0.53 ; SE = 0.21 ; P = 0.03 ) . The odds of making a clinical ly significant improvement in HbA1c of at least 0.5 % in the CHW group was twice the odds in the usual care group after controlling for confounders ( P = 0.05 ) . There were no significant differences in blood pressure , weight , or waist circumference at 12 months between groups . CONCLUSIONS A culturally adapted nurse-CHW team intervention was able to significantly improve diabetes control in the U.S. Territory of American Samoa . This represents an important translation of an evidence -based model to a high-risk population and a re source -poor setting",
"AIMS AND OBJECTIVES To determine whether the management of type 2 diabetes mellitus in a primary care setting can be safely transferred to practice nurses . BACKGROUND Because of the increasing prevalence of type 2 diabetes mellitus and the burden of caring for individual patients , the dem and type 2 diabetes mellitus patients place on primary health care re sources has become overwhelming . DESIGN R and omised controlled trial . METHODS The patients in the intervention group were cared for by practice nurses who treated glucose levels , blood pressure and lipid profile according to a specified protocol . The control group received conventional care from a general practitioner . The primary outcome measure was the mean decrease seen in glycated haemoglobin ( HbA1c ) levels at the end of the follow-up period ( 14 months ) . RESULTS A total of 230 patients was r and omised with 206 completing the study . The between-group differences with respect to reduction in HbA1c , blood pressure and lipid profile were not significant . Blood pressure decreased significantly in both groups ; 7.4/3.2 mm Hg in the intervention group and 5.6/1.0 mm Hg in the control group . In both groups , more patients met the target values goals for lipid profile compared to baseline . In the intervention group , there was some deterioration in the health-related quality of life and an increase in diabetes-related symptoms . Patients being treated by a practice nurse were more satisfied with their treatment than those being treated by a general practitioner . CONCLUSION Practice nurses achieved results , which were comparable to those achieved by a general practitioner with respect to clinical parameters with better patient satisfaction . RELEVANCE TO CLINICAL PRACTICE This study shows that diabetes management in primary care can be safely transferred to practice nurses",
"OBJECTIVE The aim of this study was to determine the effect of regular st and ardized telephone contact by a diabetes nurse educator ( DNE ) on metabolic control , treatment compliance , and quality of life in adolescents with poorly controlled type 1 diabetes . METHODS A single-blinded 6-month r and omized controlled trial was used . Participants included 46 of 49 eligible adolescents ( 13 - 17 yr ) with type 1 diabetes > 1-yr duration and hemoglobin A1c ( HbA1c ) > 8.5 % for the previous 6 months . Subjects were r and omly assigned to 6 months of st and ard diabetes management or st and ard care plus weekly telephone contact by a DNE . Telephone conversations included review of events in the adolescents ' lives and diabetes education , but the primary focus was on blood glucose results and insulin-dose adjustments . HbA1c , compliance with glucose monitoring , quality of life [ Diabetes Quality of Life Scale for Youth ( DQOLY ) ] , and family functioning [ Family Environment Scale ( FES ) ] were assessed at baseline , and at 3 and 6 months . Posthoc , HbA1c levels were assessed 6 months following study completion . RESULTS Six months of regular telephone contact by a DNE had no immediate effect on any of the outcome measures . However , posthoc 6 months , HbA1c levels decreased ( 1 % change compared to baseline ) in 6/21 of the study group and 0/18 of the control group , while HbA1c increased in 4/21 of study subjects compared to 8/18 of control subjects ( p = 0.015 ) . CONCLUSIONS In contrast to adult studies , regular telephone contact did not lead to immediate improvements in metabolic control in adolescents with poorly controlled type 1 diabetes . However , knowledge and skills gained during the intervention may have had a delayed beneficial effect in these high-risk adolescents",
"Objective To evaluate the effectiveness of goal focused telephone coaching by practice nurses in improving glycaemic control in patients with type 2 diabetes in Australia . Design Prospect i ve , cluster r and omised controlled trial , with general practice s as the unit of r and omisation . Setting General practice s in Victoria , Australia . Participants 59 of 69 general practice s that agreed to participate recruited sufficient patients and were r and omised . Of 829 patients with type 2 diabetes ( glycated haemoglobin ( HbA1c ) > 7.5 % in the past 12 months ) who were assessed for eligibility , 473 ( 236 from 30 intervention practice s and 237 from 29 control practice s ) agreed to participate . Intervention Practice nurses from intervention practice s received two days of training in a telephone coaching programme , which aim ed to deliver eight telephone and one face to face coaching episodes per patient . Main outcome measures The primary end point was mean absolute change in HbA1c between baseline and 18 months in the intervention group compared with the control group . Results The intervention and control patients were similar at baseline . None of the practice s dropped out over the study period ; however , patient attrition rates were 5 % in each group ( 11/236 and 11/237 in the intervention and control group , respectively ) . The median number of coaching sessions received by the 236 intervention patients was 3 ( interquartile range 1 - 5 ) , of which 25 % ( 58/236 ) did not receive any coaching sessions . At 18 months ’ follow-up the effect on glycaemic control did not differ significantly ( mean difference 0.02 , 95 % confidence interval −0.20 to 0.24 , P=0.84 ) between the intervention and control groups , adjusted for HbA1c measured at baseline and the clustering . Other biochemical and clinical outcomes were similar in both groups . Conclusions A practice nurse led telephone coaching intervention implemented in the real world primary care setting produced comparable outcomes to usual primary care in Australia . The addition of a goal focused coaching role onto the ongoing generalist role of a practice nurse without prescribing rights was found to be ineffective . Trial registration Current Controlled Trials IS RCT N50662837",
"We studied the impact of nurse case management ( NCM ) on blood pressure ( BP ) , hemoglobin A1C , lipids , and diabetes complication screening . A 1-year r and omized-controlled trial was conducted in two primary care clinics of the Penn State Hershey Medical Center . Diabetes patients were r and omized to control group ( CG ) ( n=182 ) who received usual care by their primary care provider and intervention group ( IG ) ( n=150 ) who received additional NCM care , including self-management education , and implementation of diabetes guidelines . Primary outcomes included BP , A1C , lipid , process measures , and secondary outcome was diabetes-related emotional distress as assessed by Problem Areas in Diabetes ( PAID ) . BP significantly decreased from 137/77 to 129/72 in IG as compared to an increase from 136/77 to 138/79 in CG after 1 year . PAID scores improved significantly in IG ( from 23 to 10 ) due to reduced emotional stress . A1C ( 7.4 ) and LDL ( 105 ) were unaffected . Complications screening significantly improved in IG compared to CG : opthalmologic exam 26 to 68 % , foot exam 47 to 64 % , and nephropathy screening 34 to 72 % . NCM improved BP , diabetes-related emotional distress , and process measures in primary care . Unchanged A1C and lipids might be due to a threshold effect . Intervention based upon initial risk assessment may prove more cost-effective ",
"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",
"OBJECTIVE To evaluate the effectiveness of a nurse-managed smoking cessation intervention in diabetic patients . RESEARCH DESIGN AND METHODS This r and omized controlled clinical trial involved 280 diabetic smokers ( age range 17 - 84 years ) who were r and omized either into control ( n = 133 ) or intervention ( n = 147 ) groups at 12 primary care centers and 2 hospitals located in Navarre , Spain . The intervention consisted of a 40-min nurse visit that included counseling , education , and contracting information ( a negotiated cessation date ) . The follow-up consisted of telephone calls , letters , and visits . The control group received the usual care for diabetic smokers . Baseline and 6-month follow-up measurements included smoking status ( self-reported cessation was verified by urine cotinine concentrations ) , mean number of cigarettes smoked per day , and stage of change . RESULTS At the 6-month follow-up , the smoking cessation incidence was 17.0 % in the intervention group compared with 2.3 % in the usual care group , which was a 14.7 % difference ( 95 % CI 8.2 - 21.3 % ) . Among participants who continued smoking , a significant reduction was evident in the average cigarette consumption at the 6-month follow-up . The mean number of cigarettes per day decreased from 20.0 at baseline to 15.5 at 6 months for the experimental group versus from 19.7 to 18.1 for the control group ( P structured intervention managed by a single nurse was shown to be effective in changing the smoking behavior of diabetic patients",
"The purpose of this study was to evaluate the effrcacy of using a telecommunication system to assist in the outpatient management of pediatric patients with insulin- dependent diabetes . Metabolic control , patients ' psychosocial status , family functioning , perceived quality of life , patterns of parental/child responsibility for daily diabetes maintenance , and nursing time-on-task were evaluated . One hundred six pediatric patients ( mean age= 13.3 years ) were r and omly assigned to an experimental or control outpatient clinic for 1 year . Experimental subjects transmitted self-monitoring blood glucose data by modem to the hospital every 2 weeks . Transmitted data were review ed by nurse practitioners who telephoned subjects to discuss regimen adjustments . Control subjects received st and ard care with regimen adjustments made by physicians . There were no significant between-group differences for metabolic control , rates of hospitalization or emergency-room visits , psychological status , general family functioning , quality of life , or parent-child responsibility . A significant decrease was noted in nursing time-on-task for experimental subjects",
"BACKGROUND The aim of the present study was to determine whether the addition of nurse case managers ( NCMs ) trained in motivational interviewing ( MI ) to usual care would result in improved outcomes in high-risk type 2 diabetes patients . METHODS A 2-year r and omized controlled pragmatic trial r and omized 545 patients to usual care control ( n=313 ) or those who received the intervention ( n=232 ) with additional practice -embedded NCM care , including MI-guided behavior change counseling . The NCMs received intensive MI training with ongoing fidelity assessment . RESULTS Systolic blood pressure ( SBP ) was better in the intervention than usual care group ( 131 ± 15 vs. 135 ± 18 mmHg , respectively ; P terms of HbA1c ( from 9.1 % to 8.0 % and from 8.8 % to 7.8 % , respectively ) , low-density lipoprotein ( LDL ; from 127 to 100 mg/dL and from 128 to 102 mg/dL , respectively ) , and diastolic blood pressure ( from 78 to 74 mmHg and from 80 to 74 mmHg , respectively ) . Depression symptom scores were better in the intervention group . The reduction in diabetes-related distress approached statistical significance . CONCLUSIONS The NCMs and MI improved SBP and complications screening . The large decrease in HbA1C and LDL in the control group may have obscured any further intervention effect . Although nurses prompted providers for medication titration , strategies to reduce provider clinical inertia may also be needed",
"AIM This paper reports a study comparing the outcomes of diabetic patients undergoing either early discharge or routine care . BACKGROUND The hospital is not the best place to monitor the glycaemic control of patients with diabetes with no other morbidity or complications . It is an unnatural environment in which diet is planned and the activity level is low . The hospital is also an expensive place in which to treat patients . METHODS This r and omized controlled trial was conducted in the medical department of a regional hospital in Hong Kong . A total of 101 patients who needed glycaemic monitoring , but who were otherwise fit for discharge , were recruited . The control group continued to receive routine hospital care . The study group was discharged early and received a follow-up programme which included a weekly or biweekly telephone call from a nurse . FINDINGS When compared with the control group , the study group had a greater decrease in HbA1c at 24 weeks , although the statistical difference was marginal ( 7.6 vs. 8.1 , P = 0.06 ) , a higher blood monitoring adherence score at both 12 weeks ( 5.4 vs. 3.6 , P higher exercise adherence score at 12 weeks ( 5.3 vs. 3.4 , P = 0.001 ) and 24 weeks ( 5.5 vs. 3.2 , P shorter hospital stay ( 2.2 vs. 5.9 , P savings were HK$11,888 per patient . CONCLUSION It is feasible to integrate treatment into the real life environments of patients with diabetes , and nurse-led transitional care is a practical and cost-effective model . Nurse follow-up is effective in maintaining optimal glycaemic control and enhancing adherence to health behaviours . Management of glycaemic control is better done in the community than in the hospital",
"This study investigated the effects of a nurse-coordinated intervention on patients with type 2 diabetes in Korea . Fifteen patients were r and omly assigned to an intervention group and 10 to a control group . The intervention was implemented for 12 weeks by telephone . Patients in the intervention group had a mean decrease of 1.2 % in glycosylated hemoglobin ( HbA1c ) levels and those in the control group had a mean increase of 0.5 % . Patients ' satisfaction with care was higher in the intervention group than in the control group after the intervention . These findings indicated that the nurse-coordinated intervention could improve HbA1c levels and satisfaction with care in patients with type 2 diabetes in Korea",
"BACKGROUND Disease management programs that include ongoing telephone support for patients with diabetes have shown promise , but published studies have enrolled few socially and economically disadvantaged patients . METHODS We conducted a r and omized controlled trial with 201 patients with poorly controlled type 2 diabetes mellitus ( 72 % African American or Latino ; 74 % with incomes of ≤$15,000 ) . Participants were r and omized to an intervention package consisting of a 24-minute video behavior support intervention with a workbook and 5 sessions of telephone coaching by a trained diabetes nurse or a 20-page brochure developed by the National Diabetes Education Program . Study measures were completed at baseline , 1 month , and 6 months . Participants ' review of the intervention material s was assessed at 1 month . The primary trial end point was hemoglobin A(1c ) value . Secondary end points included lipid levels , blood pressure , diabetes knowledge , and self-care behaviors . Data were analyzed with repeated measures analysis of variance . RESULTS Most participants in both groups ( 94 % ) review ed the intervention provided , and 73 % of participants assigned to the experimental group completed 5 sessions of telephone coaching . There was a significant overall reduction in mean ( SD ) hemoglobin A(1c ) value from baseline ( 9.6 % [ 2.0 % ] ) to 6 months ( 9.1 % [ 1.9 % ] ) ( P on other clinical measures ( lipid levels and blood pressure ) and measures of diabetes knowledge and self-care behaviors were also nonsignificant . CONCLUSIONS There was no significant effect of the experimental intervention compared with the control condition . The dose of intervention provided was less than in previously published studies . More intensive interventions may be necessary for the most disadvantaged patients . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00668590",
"AIMS To study the effect of a target-driven telecoaching intervention on HbA1c and other modifiable risk factors in people with Type 2 diabetes . METHODS We conducted a r and omized controlled trial in patients receiving hypoglycaemic agents . The primary outcome was HbA1c level at 6 months in the entire sample and in a subgroup with HbA1c levels ≥ 53 mmol/mol ( 7 % ) at baseline . Secondary outcomes were HbA1c at 18 months ; total cholesterol , LDL , HDL , triglycerides , blood pressure , BMI and proportion of people who had achieved guideline -recommended targets at 6 and 18 months . RESULTS A total of 287 participants were r and omized to telecoaching and 287 to usual care . The mean ( sd ) baseline HbA1c level was 53 ( 11 ) mmol/mol [ 7.0 (1.0)% ] overall and 63 ( 10 ) mmol/mol [ 7.9 (0.9)% ] in the elevated HbA1c subgroup . At 6 months , the between-group differences in favour of telecoaching were : HbA1c -2 ( 95 % CI -4 ; -1 ) mmol/mol [ -0.2 ( 95 % CI -0.3;-0.1)% ; P=0.003 ] overall and -4 ( 95 % CI -7 ; -2 ) mmol/mol [ -0.4 ( 95 % CI -0.7 ; -0.2)% ; P=0.001 ] in the elevated HbA1c subgroup ; BMI -0.4 kg/m(2 ) ( 95 % CI -0.6 ; -0.1 ; P=0.003 ) ; total cholesterol -6 mg/dl ( 95 % CI -11 ; -1 , P=0.012 ) . The proportion of participants on target for the composite of HbA1c , LDL and blood pressure increased by 8.9 % in the intervention group and decreased by 1.3 % in the control group ( P=0.011 ) . At 18 months , the difference in HbA1c was : -2 ( 95 % CI -3;-0 ) mmol/mol [ -0.2 ( 95 % CI -0.3 ; -0.0)% ; P=0.046 ] overall and -4 ( -7 ; -1 ) mmol/mol [ -0.4 ( 95 % CI -0.7 ; -0.1)% ; P=0.023 ] in the elevated HbA1c subgroup . CONCLUSION Nurse-led telecoaching improved glycaemic control , total cholesterol levels and BMI in people with Type 2 diabetes . Twelve months after the intervention completion , there were sustained improvements in glycaemic control",
"The purpose of this study was to evaluate the efficacy and feasibility of a newly developed diabetes patient education program consisting of a three-day hospitalization and a six-month follow-up by telephone counseling for patients with mild type 2 diabetes or impaired glucose tolerance ( IGT ) by a r and omized controlled trial ( RCT ) method . Fifty-two patients with mild type 2 diabetes or IGT ( HbAlc were r and omly assigned to either an intervention group or a control group . The current care was continued for the control group and the new education program was provided in addition to the current care for the intervention group . Changes in weight , blood glucose in a 75g-oral glucose tolerance test ( 75g-OGTT ) , and HbAlc were measured in June 1997 as baseline data and again in Dec. 1997 . Scores for knowledge of diabetes , dietary habits , physical activity , health practice index , diabetes quality of life ( DQOL ) , and self-efficacy were also obtained . After six months , the intervention group showed a statistically significant weight loss and blood glucose reduction in the 75g-OGTT test , but the control group did not . A significant improvement in lifestyle was observed in the intervention group , especially in terms of dietary habits and physical activity . The knowledge test scores increased in both groups . There were no significant differences in HbAlc , DQOL , or self-efficacy between the two groups . The results of this study show that the combination of a three-day hospitalization and a six-month follow-up by telephone counseling is effective in metabolic control and improvement of lifestyle for patients with mild type 2 diabetes or IGT . The reasons for the effectiveness were considered to be that l)changes in lifestyle were based on autonomous decision-making ; 2)regular , consistent counseling was provided by the nurse in charge of each patient ; 3)extended follow-up is more effective than initial education in preventing a rebound of weight or metabolic control",
"AIM To determine whether a nurse telephone follow-up service could improve the level of adherence to a diabetes therapeutic regimen for patients with type 2 diabetes . METHODS A total of 61 patients attended a 3 day diabetes self-care program at the Iranian Diabetes Society . They were r and omly assigned to one of the experimental or control groups . A telephone follow-up program was applied to the experimental group for 3 months , twice per week for the first month and weekly for the second and third months . The data - collection instruments included a data sheet to record the glycosylated hemoglobin ( HbA1c ) level and a question naire . The data were collected at baseline and after 12 weeks . RESULTS There were significant differences between the control and the experimental groups in their adherence to a diabetic diet , exercise , foot care , blood glucose monitoring , and medication-taking . Also , the HbA1c levels differed significantly between the two groups after 3 months . CONCLUSION A nurse-led telephone follow-up was effective in enhancing the level of adherence to a diabetes therapeutic regimen , such that the HbA1c level decreased",
"AIMS The aim of this study was to examine whether a nurse-administered minimal psychological intervention for depressive symptoms improves diabetes-specific quality of life and glycaemic control in older persons with diabetes . BACKGROUND Depression is common among persons with diabetes and may have a negative impact on diabetes . Interventions aim ed at reducing depressive symptoms may positively influence diabetes-specific quality of life as well . METHODS A pragmatic , r and omized controlled trial was carried out comparing the intervention with usual care among 208 Dutch primary care patients of ≥60 years with type 2 diabetes and co-occurring minor to moderate depression . Data on symptom distress and emotional distress were collected during 2003 - 2006 , and haemoglobin A1c levels were obtained from general practice s. Data were analysed using mixed model , repeated measures ANCOVAS . Hba1c was collected retrospectively from general practice s between December 2006-February 2007 . In July 2007 we retrieved some additional HbA1c data from the medical records of the university hospital . RESULTS Only in higher-educated persons did the intervention have statistically significant effect on both emotional distress and symptom distress ( DSC-R total score at 9 months P=0.001 ; PAID , 9 months P=0.03 ) . Furthermore , we found an effect on symptom distress in men ( 9 months P=0.01 ) , and on emotional distress in persons with a shorter diabetes duration ( for haemoglobin A1c was found in favour of the intervention , with a statistically significant difference between groups after 9 months ( P=0.02 ) . CONCLUSION The nurse-administered intervention had limited effects on diabetes-specific quality of life . As only certain subgroups benefited , ways of increasing effectiveness in other groups should be explored . The potentially beneficial effect on glycaemic control is encouraging and needs further research because of small numbers in the analysis",
"OBJECTIVE This study evaluated the efficacy of a nurse-care management system design ed to improve outcomes in patients with complicated diabetes . RESEARCH DESIGN AND METHODS In this r and omized controlled trial that took place at Kaiser Permanente Medical Center in Santa Clara , CA , 169 patients with longst and ing diabetes , one or more major medical comorbid conditions , and HbA(lc ) > 10 % received a special intervention ( n = 84 ) or usual medical care ( n = 85 ) for 1 year . Patients met with a nurse-care manager to establish individual outcome goals , attended group sessions once a week for up to 4 weeks , and received telephone calls to manage medications and self-care activities . HbA(lc ) , LDL , HDL , and total cholesterol , triglycerides , fasting glucose , systolic and diastolic blood pressure , BMI , and psychosocial factors were measured at baseline and 1 year later . Annualized physician visits were determined for the year before and during the study . RESULTS At 1 year , the mean reductions in HbA(lc ) , total cholesterol , and LDL cholesterol were significantly greater for the intervention group compared with the usual care group . Significantly more patients in the intervention group met the goals for HbA(1c ) ( psychosocial variables or in physician visits . CONCLUSIONS A nurse-care management program can significantly improve some medical outcomes in patients with complicated diabetes without increasing physician visits",
"BACKGROUND Most patient chronic disease self-management interventions target single-disease outcomes . We evaluated the effect of a tailored hypertension self-management intervention on the unintended targets of glycosylated hemoglobin ( HbA1c ) and low-density lipoprotein cholesterol ( LDL-C ) . METHODS We evaluated patients from the Veterans Study to Improve the Control of Hypertension , a 2-year r and omized controlled trial . Patients received either a hypertension self-management intervention delivered by a nurse over the telephone or usual care . Although the study focused on hypertension self-management , we compared changes in HbA1c among a subgroup of 216 patients with diabetes and LDL-C among 528 patients with measurements during the study period . Changes in these laboratory values over time were compared between the 2 treatment groups using linear mixed-effects models . RESULTS For the patients with diabetes , the hypertension self-management intervention result ed in a 0.46 % reduction in HbA1c over 2 years compared with usual care ( 95 % confidence interval , 0.04%-0.89 % ; P = .03 ) . For LDL-C , there was a minimal 0.9 mg/dL between-group difference that was not statistically significant ( 95 % confidence interval , -7.3 - 5.6 mg/dL ; P = .79 ) . CONCLUSIONS There was a significant effect of the self-management intervention on the unintended target of HbA1c , but not LDL-C. Chronic disease self-management interventions might have \" spill-over \" effects on patients ' comorbid chronic conditions",
"OBJECTIVES To determine whether ( i ) motivational enhancement therapy ( MET ) + cognitive behaviour therapy ( CBT ) compared with usual care , ( ii ) MET compared with usual care , ( iii ) or MET + CBT compared with MET was more effective in improving glycaemic control when delivered by general nurses with additional training in these techniques . DESIGN A three-arm parallel r and omised controlled trial as the gold st and ard design to test the effectiveness of psychological treatments . SETTING The recruiting centres were diabetes clinics in seven acute trusts in south-east London and Greater Manchester . PARTICIPANTS Adults ( 18 - 65 years ) with a confirmed diagnosis of type 1 diabetes for a minimum duration of 2 years and a current glycated ( or glycosylated ) haemoglobin ( HbA1c ) value between 8.2 % and 15.0 % . INTERVENTIONS The control arm consisted of usual diabetes care which varied between the hospitals , but constituted at least three monthly appointments to diabetes clinic . The two treatments arms consisted of usual care with MET and usual care with MET + CBT . MAIN OUTCOME MEASURES The primary outcome was HbA1c at 12 months from r and omisation . Secondary outcome measures were 1-year costs measured by the Client Service Receipt Inventory at baseline , 6 months and 12 months ; quality of life-years [ quality -adjusted life-years ( QALYs ) ] measured by the SF-36 ( Short Form-36 Health Survey Question naire ) and EQ-5D ( European Quality of Life-5 Dimensions ) at baseline and 12 months . RESULTS One thous and six hundred and fifty-nine people with type 1 diabetes were screened and 344 were r and omised to MET + CBT ( n = 106 ) , MET ( n = 117 ) and to usual care ( n = 121 ) . The 12-month follow-up rate for HbA1c was 88 % ( n = 305 ) . The adjusted mean 12-month HbA1c was 0.45 % lower in those treated with MET + CBT [ 95 % confidence interval ( CI ) 0.16 % to 0.79 % , p = 0.008 ] than for usual care ; 0.16 % lower in those treated with MET ( 95 % CI 0.20 % to 0.51 % , p = 0.38 ) than for usual care ; and 0.30 % lower with MET + CBT than with MET ( 95 % CI -0.07 % to 0.66 % , p = 0.11 ) . The higher the HbA1c , and the younger the participant at baseline , the greater was the reduction in HbA1c . The interventions had no effect on secondary outcomes such as depression and quality of life . The economic evaluation was inconclusive . Both interventions were associated with increased health care costs than for usual care alone . There was no significant difference in social costs . Cost effectiveness ratios , up to one year , varied considerably according to whether QALY estimates were based on EQ-5D or SF-36 and whether imputed or complete data were used in the analyses . CONCLUSIONS A combination of MET and CBT may be useful for patients with persistent sub-optimal diabetic control . MET alone appears less effective than usual care . Economic evaluation was inconclusive . TRIAL REGISTRATION Current Controlled Trials IS RCT N77044517",
"OBJECTIVE To examine whether a telephone-delivered intervention ( TDI ) , design ed to improve glycemie control in patients with non-insulin-dependent diabetes mellitus ( N1DDM ) , improved coronary risk factors in high-risk patients . RESEARCH DESIGN AND METHODS This r and omized controlled trial involved 275 veterans with N1DDM followed in a general medical clinic . Intervention ( TDI ) patients were telephoned at least monthly by a nurse . Calls emphasized compliance with the medical regimen ( diet , medications , and exercise ) , encouraged behavioral changes , and facilitated referrals to a dietitian or smoking cessation clinic . Control patients received no such calls . Baseline and 12-month follow-up measurements included fasting lipid profiles , weight , smoking status ( self-reported ; cessation verified by measurement of exhaled CO ) , adherence to diet and exercise ( self-reported ) , appointments , and medications ( hospital computerized data base ) . RESULTS After 12 months , equal numbers of obese patients in the two groups reported adhering to a diabetic diet and exercising , although more obese TDI patients had seen a dietitian ( 30 vs. 7 % , P = 0.003 ) . Weight loss was not seen in either group ( —0.9 ± 5.3 vs. —0.1 ± 3.6 kg , P = 0.202 ) . Hyperlipidemic TDI patients were more likely to see a dietitian ( 31 vs. 6 % , P = 0.003 ) and receive lipid-lowering medications ( 22 vs. 9 % , P = 0.096 ) , but serum cholesterol reduction was similar between groups ( –11.7 ± 33.4 vs. –4.3 ± 32.7 mg/dl , P = 0.270 ) ; comparable results were seen for high-density lipoprotein , low-density lipoprotein , and triglyceride levels . More TDI group smokers reported quitting ( 26 vs. 0 % , P = 0.033 ) , but the difference was not significant for CO-verified abstention ( 10 vs. 0 % , P = 0.231 ) . CONCLUSIONS The TDI improved self-reported adherence to regimens that might reduce coronary risk , but had little effect on objective measures of risk",
"PURPOSE The purpose of this pilot study was to determine the efficacy of a 6-month nurse-coaching intervention that was provided after diabetes education for women with type 2 diabetes . METHODS In this pilot study , 53 women were r and omized to the nurse-coaching intervention or a st and ard care control condition . The nurse-coaching intervention consisted of 5 individualized sessions and 2 follow-up phone calls over 6 months . The nurse-coaching sessions included educational , behavioral , and affective strategies . Data were collected on physiologic adaptation ( hemoglobin A1c [ A1C ] and body mass index [ BMI ] ) , self-management ( dietary and exercise ) , psychosocial adaptation ( diabetes-related distress and integration ) , and treatment satisfaction at baseline , 3 months , and 6 months . RESULTS Women in the treatment group demonstrated better diet self-management , less diabetes-related distress , better integration , and more satisfaction with care , and had trends of better exercise self-management and BMI . The A1C levels improved in both groups at 3 months , yet the difference between the groups was not significant . Attendance at nurse-coaching sessions was 96 % . CONCLUSIONS This nurse-coaching intervention demonstrates promise as a means of improving self-management and psychosocial outcomes in women with type 2 diabetes",
"AIMS The study tested the hypothesis that a theory driven Diabetes Self-Management ( DSM ) intervention delivered by trained nurses would result in a clinical ly significant improvement in glycaemic control . METHODS Patients with an HbA1c > 7.5 % ( 58mmol/mol ) and free of diabetes complications were enrolled into a r and omized controlled trial ( n=85 ) . Intervention consisted of four sessions and monthly follow up for 6 months . Biochemical tests , and diet and physical activity assessment s were done in both groups . Analysis of covariance was used to test the effectiveness of the intervention . RESULTS At 6 months , there was a significant difference ( P=0.001 ) in HbA1c between the groups controlling for baseline values and other variables . Based on the primary outcome , 28 % in the intervention group achieved the target value of 6.5 % HbA1c , compared to 8 % in the \" usual care \" group ( P The reduction in total energy intake and increase in physical activity was significant in the intervention group between baseline and follow up . CONCLUSIONS The DSM intervention has result ed in a clinical ly significant impact on glycaemia , change in diet and physical activity , and has demonstrated the feasibility of using it within existing care arrangements in a developing country setting",
"AIMS To estimate the efficacy of a self-monitoring-based disease management strategy in patients with Type 2 diabetes treated with oral agent monotherapy . METHODS This was an open-label , r and omized , pilot study , primarily led by diabetes nurses . Patients were r and omly allocated to either a self-monitoring-based disease management strategy or usual care ( ratio 3:1 ) and followed up for 6 months . Education was centred on how to modify lifestyle according self-monitoring readings . Self-monitoring of blood glucose results were discussed during monthly telephone contact . The primary endpoint was mean change in HbA(1c ) levels , estimated with an ANOVA for repeated measures . All analyses were intention to treat . RESULTS Three diabetic clinics recruited 62 patients , of whom five were lost to follow-up . At baseline , both groups had a mean HbA(1c ) value of 7.9 % ± 0.6 % ( 63 ± 6 mmol/mol ) . After 6 months , mean HbA(1c ) reduction was 1.2 ± 0.1 % ( -13 ± 1 mmol/mol ) in the intervention group and 0.7 ± 0.2 (-8 ± 2 mmol/mol ) in the control group , with an absolute mean difference between groups of -0.5 % ( 95 % CI -0.9 to -0.0 % ; P = 0.04 ) ( -5 mmol/mol , 95 % CI -10 to 0 ) . At study end , 61.9 % of patients in the intervention group and 20.0 % in the control group reached the target level of HbA(1c ) ( P = 0.005 ) . Body weight reduction was significantly greater in the intervention group than in the control group ( between-group absolute mean difference : -3.99 kg ; 95 % CI -7.26 to -0.73 ; P = 0.02 ) . Therapy changes were more frequent in the control group . CONCLUSIONS A self-monitoring disease management strategy , primarily led by diabetes nurses and allowing a timely and efficient use of self-monitoring readings , is able to improve metabolic control , primarily through lifestyle modifications leading to weight loss",
"The purpose of the study was to compare three nursing interventions and their impact on glycemic control among children with type I diabetes . The 75 subjects ' mean + /- SD age was 12.5 + /- 3.4 years , 55 % were boys , and 55 % were White . Subjects were r and omly assigned to a st and ard care ( SC ) , an education ( ED ) , or an education and telephone case management ( ED + TCM ) group . The primary outcome measure was glycemic control ( hemoglobin A1c , or HbA1c ) . Secondary outcome measures were diabetes knowledge ( KNOW ) , parent-child teamwork ( TEAM ) , and adherence ( ADH ) . After 6 months of follow-up , results demonstrated no significant differences among groups in HbA1c . KNOW and TEAM scores improved slightly in the ED and ED + TCM groups , but no statistically significant differences were found among the three groups . Significant improvement in ADH scores among ED + TCM groups was reported when compared with the ED and SC groups . This change may represent a move toward improved adherence to diabetes care and subsequent improvement in diabetes control . The challenges of recruitment and retention of subjects in this study will also be discussed",
"OBJECTIVES To evaluate the uptake and effectiveness of tailored smoking cessation support , provided primarily by the practice nurse ( PN ) , and compare this to other forms of cessation support . METHODS Three arm cluster r and omized controlled trial conducted in 101 general practice s in Sydney and Melbourne involving 2390 smokers . The Quit with PN intervention was compared to Quitline referral and a usual care control group . Smoking cessation pharmacotherapy was recommended to all groups . Outcomes were assessed by self-report at 3- and 12-month follow-up . Uptake of the interventions is also reported . RESULTS The three groups were similar at baseline . Follow-up at 12 months was 82 % . The sustained and point prevalence abstinence rates , respectively , at 3 months by group were : PN intervention 13.1 % and 16.3 % ; Quitline referral 10.8 % and 14.2 % ; Usual GP care 11.4 % and 15.0 % . At 12 months , the rates were : PN intervention 5.4 % and 17.1 % ; Quitline referral 4.4 % and 18.8 % ; Usual GP care 2.9 % and 16.4 % . Only 43 % of patients in the PN intervention group attended to see the nurse . Multilevel regression analysis showed no effect of the intervention overall , but patients who received partial or complete PN support were more likely to report sustained abstinence [ partial support odds ratio ( OR ) 2.27 ; complete support OR 5.34 ] . CONCLUSION The results show no difference by group on intention to treat analysis . Those patients who received more intensive PN intervention were more likely to quit . This may have been related to patient motivation or an effect of PN led cessation support",
"OBJECTIVE To test trial design issues related to measuring the effectiveness of a peer telephone intervention to enhance self-efficacy in type 2 diabetes ; evaluate the impact on self-efficacy and clinical outcome ; and describe patient and peer experience . METHODS Eligible patients had raised HbA1c ( initial threshold > 8 % , reduced to > 7.4 % mid-way through trial ) . Patients were recruited from 40 general practice s and r and omised ( 40:40:20 ratio ) to receive routine care alone or , in addition , motivational telephone support from a peer supporter or a diabetes specialist nurse ( 9 peers and 12 DSNs ) for a period of up to 6 months . The primary outcome measure was self-efficacy score , and secondary outcome measures included HbA1c . Patient and telecare supporter satisfaction and experience were evaluated . RESULTS In all , 231 patients participated . At 6 months there were no statistically significant differences in self-efficacy scores ( p=0.68 ) , HbA1c ( p=0.87 ) or other secondary outcome measures . There was evidence of a high level of acceptability , but peer telecare support was less highly valued than that from a DSN . Some patients stated that they would have valued more information and advice . CONCLUSIONS Further consideration needs to be given to the targeting of the telecare peer support , its intensity , the training and ongoing supervision of peer supporters , and the extent to which information and advice should be incorporated . PRACTICE IMPLICATION S While some patients with poorly controlled type 2 diabetes value peer telephone support , this approach appears not to suit all patients . Further intervention development and evaluation is required before widespread adoption can be recommended"
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Obesity is one of the main causes of inflammation . Previous studies have reported inconclusive results regarding the effect of bariatric surgery on inflammatory markers . This systematic review and meta- analysis is aim ed at describing the effect of bariatric surgery on C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , tumor necrosis factor-α ( TNF-α ) . PubMed / Medline and Scopus were systematic ally search ed for all eligible studies from inception to June 2018 . Results are expressed as weighted mean difference ( MD ) with 95 % confidence intervals ( CI ) using a r and om effects model . Overall , 116 studies which evaluated serum CRP , IL-6 , and TNF-α after bariatric surgery were included . Pooled effect size showed significant reduction in serum CRP ( − 5.30 mg/l , 95 % CI − 5.46 , − 5.15 , P ( − 0.58 pg/ml , 95 % CI − 0.64 , − 0.53 , P , and TNF-α ( − 0.20 pg/ml , 95 % CI − 0.39 , − 0.02 , P = 0.031 ) with significant heterogeneity across studies ( > 95 % for all factors ) . Bariatric surgery significantly lowered inflammatory factors ; however , baseline BMI , follow-up duration and type of surgery could impact the extent of observed effects
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"Objective : To assess different factors influencing adiponectinemia in obese and normal-weight women ; to identify factors associated with the variation ( Δ ) in adiponectinemia in obese women following a 6-month weight loss program , according to surgical/non-surgical interventions . Methods : We studied 100 normal-weight women and 112 obese premenopausal women ; none of them was on any medical treatment . Women were characterized for anthropometrics , daily macronutrient intake , smoking status , contraceptives use , adiponectin as well as IL-6 and TNF-α serum concentrations . Results : Adiponectinemia was lower in obese women ( p Normal-weight women presented lower adiponectinemia among smokers ( p = 0.041 ) ; body fat , waist-to-hip ratio , TNF-α levels , carbohydrate intake , and smoking all influence adiponectinemia ( r2 = 0.436 ) . After weight loss interventions , a significant modification in macronutrient intake occurs followed by anthropometrics decrease ( chiefly after bariatric procedures ) and adiponectinemia increase ( similar after surgical and non-surgical interventions ) . After bariatric intervention , Δ adiponectinemia was inversely correlated to Δ waist circumference and Δ carbohydrate intake ( r2 = 0.706 ) . Conclusion : Anthropometrics , diet , smoking , and TNF-α levels all influence adiponectinemia in normal-weight women , although explaining less than 50 % of it . In obese women , anthropometrics modestly explain adiponectinemia . Opposite to non-surgical interventions , after bariatric surgery adiponectinemia increase is largely explained by diet composition and anthropometric changes",
"Abstract A definitive relationship between adiposity and MP production is yet to be demonstrated . The aim of our study was to prospect ively evaluate the levels of microparticles ( MP ) in a group of 20 III degree obese patients before and after weight loss . Plasma levels of annexin V-MP , endothelial-derived MP , platelet-derived MP ( CD61 + and P-Selectin+ ) , leukocyte-derived MP , tissue factor-bearing ( TF+ ) and CD36+MP were prospect ively measured in 20 patients with III degree obesity ( BMI ≥ 40 kg/m2 ) before ( T0 ) and 3 ( T3 ) and 12 ( T12 ) months after sleeve gastrectomy ( SLG ) . Obese patients had lost 18 % of their body weight at T3 and 41 % at T12 . We find that considering all MP , except for endothelial-derived MP , which had significantly decreased at T3 , all MP subtypes had significantly decreased at T12 . At T12 , subjects showed a higher median level of all types of MP , except endothelial-derived MP , compared to T3 , but without a statistically significant difference . The percentages of reduction of all the MP were significantly correlated with the percentage of reduction of BMI . The reductions of leukocyte-derived , TF+ and CD36+MP were significantly correlated with the reduction of leptin . Moreover , the reductions of leukocyte-derived and CD36+MP were significantly correlated with hs-CRP decrease . The decrease of BMI post-SLG in morbid obesity was matched with a decrease of circulating MP of endothelial , platelet , leukocyte origin , TF+ and CD36 + . A trend of slight increase in all MP subtypes , except endothelial-derived , was detected 12 months after gastrectomy , indicating a possible underlying slow low- grade inflammatory/hypercoagulability state from adipose tissue before the potential overt weight gain",
"BACKGROUND Circulating pentraxin 3 ( PTX3 ) , the main regulator of the inflammatory response , rapidly increases following cardiovascular events , and low PTX3 is associated with high body mass index . METHODS AND RESULTS We conducted a 12-month longitudinal study , to test the hypothesis that laparoscopic adjustable gastric b and ing (LAGB)-induced weight loss was associated with changes in platelet activation markers and PTX3 . Twelve obese patients , scheduled to undergo LAGB , were enrolled at the University Obesity Center . Urinary 11-dehydro-thromboxane (Tx)B2excretion rate was measured on radioimmunoassay , and PTX3 and CD40L were determined on immunoassay . Plasma PTX3 increased by 178.8 and 214.9 % ( P High-sensitivity CRP decreased by 24 and 29.7 % ( P CD40L decreased by 64.3 and 58.6 % ( P=0.002 ) , respectively . Urinary 11-dehydro-TxB2decreased from 1,443 to 715 and 564 pg/mg creatinine , respectively 6 months and 12 months after LAGB ( P PTX3 was inversely related to platelet activation markers , 11-dehydro-TxB2 and CD40L . Moreover , multiple regression analysis on pooled data showed that plasma PTX3 was an independent predictor of urinary 11-dehydro-TxB2 . CONCLUSIONS There is an association between inflammation , platelet activation and metabolic dysfunction in obesity , and PTX3 is a key player within these circuits",
"Background : Many foods and nutrients have been suggested to influence life expectancy . However , previous studies have not examined the relationship between dietary patterns and cause-specific mortality . Our study prospect ively examines the relationship of dietary patterns with total mortality and cause-specific mortality in a population -based cohort study of Chinese women . Methods : The Shanghai Women 's Health Study is a population -based cohort study of 74,942 women age 40 to 70 years at the time of recruitment ( September 1996 to May 2000 ) . Detailed dietary information was collected using a vali date d , quantitative food frequency question naire . The cohort has been followed using a combination of in-person interviews and record linkage with various registries . Dietary patterns , derived from principal component analysis , were examined for their relation to total mortality and cause-specific mortality using Cox regression models . Results : After an average of 5.7 years of follow-up ( 423,717 person-years of observation ) , there were 1565 deaths . We derived 3 major dietary patterns ( vegetable-rich , fruit-rich , and meat-rich ) . The adjusted hazard ratios for the fruit-rich diet were 0.94 ( 95 % CI = 0.89–0.98 ) for all causes of death and 0.89 ( 0.81–0.99 ) , 0.79 ( 0.69–0.91 ) , and 0.51 ( 0.39–0.65 ) for death caused by cardiovascular disease , stroke , and diabetes , respectively . The meat-rich diet was associated with increased risk of diabetes ( HR = 1.18 ; 95 % CI = 0.98–1.42 ) and a slightly elevated risk of total mortality . Conclusion : In general , a fruit-rich diet was related to lower mortality , whereas a meat-rich diet appeared to increase the probability of death",
"Background Obesity is considered a low- grade chronic inflammatory condition as reflected by increased C-reactive protein ( CRP ) levels . Inflammation is emerging as a predictor of cardiovascular disease and it may be a precursor of the metabolic syndrome . Bariatric surgery is commonly performed as a treatment for morbid obesity offering significant reductions in premature myocardial infa rct ion . Laparoscopic sleeve gastrectomy ( LSG ) is a relatively new bariatric procedure that is currently used as a definitive procedure for weight loss . The aim of this study is to assess the impact of sleeve gastrectomy on CRP levels . Methods This study is part of an ongoing , prospect i ve , cohort study to evaluate LSG impact on iron indices . CRP levels were compared preoperatively and 6 months after surgery . Similarly , demographics including body mass index and excess weight were also compared at these same study points . Data were analyzed using Student paired t test and Pearson product moment correlation analysis . Results Twenty-nine morbidly obese patients were included . There was significant decrease in body mass index ( BMI ) between the preoperative and 6-month period ( 50.9 ± 13.2 and 35.1 ± 6.85 , respectively ; P 0.001 ) . Also CRP levels were statistically significantly lower at 6 months after surgery ( preoperative 12.3 ± 7.53 mg/L and postoperative 5.6 ± 4.2 mg/L. P . The significant weight loss as reflected by change in BMI was correlated with the difference between preoperative and postoperative CRP levels . Conclusions Massive weight loss in morbidly obese patients induced by LSG causes a significant decrease in CRP levels , which could reduce the risk of cardiovascular diseases in these patients",
"Background Obesity has been widely recognized as a chronic inflammatory condition and associated with elevated inflammatory indicators including C-reactive protein ( CRP ) and white blood cell count ( WBC ) . Recent studies have shown elevated CRP or WBC is a significant risk factor for cardiac events and stroke but the clinical significance of CRP and WBC has not been clearly studied in morbidly obese patients . This study is aim ed at the clinical significance of WBC and CRP in morbidly obese patients and the change after bariatric surgery . Methods The study was a prospect ively controlled clinical study . From December 1 , 2001 to January 31 , 2006 , of 640 ( 442 females and 198 males ) consecutive morbid obese patients enrolled in a surgically supervised weight loss program with at least 1 year ’s follow-up were examined . Results Of the patients , 476 ( 74.4 % ) had elevated CRP and 100 ( 15.6 % ) had elevated WBC at preoperative study . CRP and WBC were significantly related and both increased with increasing body mass index ( BMI ) . CRP is also increased with increasing waist , glucose level , hemoglobin , albumin , Ca , insulin , C-peptide , and metabolic syndrome while WBC is increased with metabolic syndrome but decreased with increasing age . Multivariate analysis confirmed fasting glucose level and hemoglobin are independent predictors of the elevation of CRP while age is the only independent predictor for elevated WBC . Both WBC and CRP levels decreased rapidly after obesity surgery . These improvements result ed in a 69.8 % reduction of CRP and 26.4 % reduction of WBC 1 year after surgery . Although individuals who underwent laparoscopic gastric bypass lost significantly more weight ( 36.8 ± 11.7 kg vs. 17.3 ± 10.8 kg ; p = 0.000 ) and achieved a lower BMI ( 27.8 ± 4.6 vs. 35.0 ± 5.5 ; p = 0.000 ) than individuals who underwent laparoscopic gastric b and ing , there was no difference in the resolution of elevated CRP 1 year after surgery ( 95.9 % vs. 84.5 % ; p = 0.169 ) and WBC ( 99.4 % vs. 98.3 % ; p = 0.323 ) . Conclusions Both baseline WBC and CRP are elevated in morbid obese patients but CRP has a better clinical significance . Significant weight reduction 1 year after surgery markedly reduced CRP and WBC with a resolution rate of 93.9 % and 98.2 % separately . Obesity surgery performed by laparoscopic surgery is recommended for obese patients with elevated CRP or WBC",
"Objectives To examine the effects of Roux-en-Y gastric bypass ( RYGB ) surgery with and without laparoscopic removal of omental fat ( omentectomy ) on the temporal gene expression profiles of skeletal muscle . Design Previously reported were the whole-body metabolic effects of a r and omized , single-blinded study in patients receiving RYGB surgery stratified to receive or not receive omentectomy . In this follow up study we report on changes in skeletal muscle gene expression in a subset of 21 patients , for whom biopsies were collected preoperatively and at either 6 months or 12 months postoperatively . Methodology /Principal Findings RNA isolated from skeletal muscle biopsies of 21 subjects ( 8 without omentectomy and 13 with omentectomy ) taken before RYGB or at 6 and 12 months postoperatively were subjected to gene expression profiling via Exon 1.0 S/T Array and Taqman Low Density Array . Robust Multichip Analysis and gene enrichment data analysis revealed 84 genes with at least a 4-fold expression difference after surgery . At 6 and 12 months the RYGB with omentectomy group displayed a greater reduction in the expression of genes associated with skeletal muscle inflammation ( ANKRD1 , CDR1 , CH25H , CXCL2 , CX3CR1 , IL8 , LBP , NFIL3 , SELE , SOCS3 , TNFAIP3 , and ZFP36 ) relative to the RYGB non-omentectomy group . Expressions of IL6 and CCL2 were decreased at all postoperative time points . There was differential expression of genes driving protein turnover ( IGFN1 , FBXW10 ) in both groups over time and increased expression of PAAF1 in the non-omentectomy group at 12 months . Evidence for the activation of skeletal muscle satellite cells was inferred from the up-regulation of HOXC10 . The elevated post-operative expression of 22 small nucleolar RNAs and the decreased expression of the transcription factors JUNB , FOS , FOSB , ATF3 MYC , EGR1 as well as the orphan nuclear receptors NR4A1 , NR4A2 , NR4A3 suggest dramatic reorganizations at both the cellular and genetic levels . Conclusions / Significance These data indicate that RYGB reduces skeletal muscle inflammation , and removal of omental fat further amplifies this response . Trial Registration Clinical Trials.gov",
"The aim of this study was to investigate the potential role of adipose cytokines in the obesity-associated insulin resistance . To that end , we compared : 1 ) serum concentrations of interleukin 6 ( IL-6 ) , tumor necrosis factor alpha ( TNFalpha ) , and leptin in eight healthy lean control females and in and roid obese female without ( n = 14 ) and with ( n = 7 ) type 2 diabetes ; and 2 ) the levels of these cytokines both in serum and in sc adipose tissue in the 14 obese nondiabetic women before and after 3 weeks of a very low-calorie diet ( VLCD ) . As compared with lean controls , obese nondiabetic and diabetic patients were more insulin resistant and presented increased values for leptin , IL-6 , TNFalpha , and C-reactive protein . In the whole group , IL-6 values were more closely related to the parameters evaluating insulin resistance than leptin or TNFalpha values . VLCD result ed in weight loss and decreased body fat mass ( approximately 3 kg ) . Insulin sensitivity was improved with no significant change in both serum and adipose tissue TNFalpha levels . In contrast , VLCD induced significant decreases in IL-6 and leptin levels in both adipose tissue and serum . These results suggest that , as for leptin , circulating IL-6 concentrations reflect , at least in part , adipose tissue production . The reduced production and serum concentrations after weight loss could play a role in the improved sensitivity to insulin observed in these patients",
"Background Obesity is associated with a chronic low- grade inflammatory state , insulin resistance , and endothelial dysfunction , all of which contribute to increased risk of cardiovascular disease . We hypothesized that gastric bypass would produce rapid improvements in endothelial function , reduce inflammation , and lead to a decrease in cardiovascular risk . Methods We performed a prospect i ve study of morbidly obese patients who underwent laparoscopic Roux-en-Y gastric bypass ( RYGB ) . Clinical data , biochemical markers of inflammation , and parameters indicative of cardiovascular risk were collected preoperatively and at 3 and 6 months postoperatively . Metabolic and inflammatory mediators that were quantified included C-reactive protein , fibrinogen , PAI-1 , IL-6 , IL-10 , IL-1Ra , adiponectin , leptin , triglycerides , total cholesterol , HDL , LDL , glucose , insulin , and HbA1c . Brachial artery reactivity testing ( BART ) was performed to assess peripheral arterial endothelial function , and Framingham cardiovascular risk score ( FRS ) was calculated on all study participants pre- and postoperatively . Results Fifteen patients ( 11 female ) were enrolled ( age = 49.2 ± 10.4 years ; BMI = 48.1 ± 5.3 kg/m2 ) . Six months post RYGB , mean BMI decreased to 35.4 ± 4.5 , corresponding to 51.7 % excess weight loss ( P 0.001 ) . Mean waist circumference decreased significantly from 132 cm at baseline to 110 cm at 3 months ( P = 0.003 ) and 107 cm at 6 months ( P weight loss led to significant improvements in clinical parameters indicative of cardiovascular disease or risk , including brachial artery diameter , endothelial independent vasodilation , and FRS . Favorable improvements in the proinflammatory markers CRP ( P = 0.01 ) and leptin ( P = 0.005 ) , the anti-inflammatory mediator adiponectin ( P = 0.002 ) , and insulin sensitivity ( HOMA-IR , P = 0.007 ) were evident at 3 months . At 6 months , improvements in CRP , leptin , and fasting insulin were maintained and fibrinogen levels also decreased ( P = 0.047 ) . Adiponectin continued to increase at 6 months ( P = 0.004 ) . Conclusion Gastric bypass is associated with early reversal of endothelial dysfunction , a more favorable inflammatory milieu , and , most importantly , a reduction in cardiovascular risk",
"In a prospect i ve study , indices of glucose homeostasis , lipid profile , and systemic inflammation were monitored after an aesthetic abdominoplasty , aim ing to scrutinize the possible metabolic benefits for abdominal fat removal . Premenopausal females with substantial weight loss ( N = 40 ) undergoing circumferential abdominoplasty ( index group , n = 20 ) or augmentation mammoplasty with mastopexy ( controls , n = 20 ) were recruited . All of them originally underwent Roux-en-Y gastric bypass . Variables included BMI , white blood cell count , C-reactive protein , hemoglobin , total cholesterol and fractions , triglycerides , glucose , and HbA1c . Follow-up reached 20.3 ± 13.6 months for index cases and 29.5 ± 17.4 months for controls . The metabolic and inflammatory indices improved after the bariatric surgery . Subsequent monitoring indicated a stable body weight and biochemical profile in both groups . The exceptions were HDL cholesterol and C-reactive protein , which respectively increased and diminished after the abdominoplasty , consistent with an inflammatory and metabolic advantage for this operation . This is the first long-term study in a weight-stable population to point out such a pattern after abdominoplasty",
"Studies have shown that mortality was reduced by 31.6 % in patients that underwent bariatric surgery compared with the non-operative control group . However , in most surgical series the majority of patients were women , and men had higher post-operative mortality rates and a higher postoperative morbidity , regardless of weight . Our primary end point was to study gender effects on vascular inflammation following bariatric surgery for weight loss . Methods . A prospect i ve study evaluated vascular inflammation in obese patients before and three months after bariatric surgery . Markers of vascular inflammation were measured - before surgery and three months afterwards . Results . One hundred and two patients ( 73 women and 29 men , 40.5 ± 12.3 years old ) underwent bariatric surgery . Correlation was found between BMI change and waist circumference change ( r = 0.658 , P , BMI was significantly decreased ( p 8.82 ) , waist circumference was reduced ( p 17.33 cm ) . ICAM-1 levels and hs-CRP levels were decreased ( both P = 0.0001 ) . Gender differences seem to be borderline significant with respect to the prevalence of type II diabetes mellitus ( men > women ; P = 0.05 ) and hypertension ( men > women ; P = 0.06 ) . In women , following bariatric surgery , BMI was decreased ( p 9.25 ) , waist circumference was reduced ( p 18.8 cm ) . ICAM-1 levels were decreased ( p = 0.002 ) and hs-CRP levels were also decreased ( P = 0.0001 ) . In men , following bariatric surgery , BMI was decreased ( p = 0.001 ) ( a decrease of 8.1 ) , waist circumference was reduced ( p although ICAM-1 levels and hs-CRP levels were decreased the decreases were non-significant ( both P = 0.09 ) . Discussion . Our study examined gender effects of bariatric surgery on vascular inflammation . Bariatric surgery had no significant effect on biochemical inflammatory markers in male patients , while females undergoing the same kind of bariatric surgery for weight loss showed a significant decrease in these markers of inflammation . These results may explain the epidemiological data that described higher morbidity and mortality among obese men undergoing bariatric operation for weight loss . This is the first study that has demonstrated a gender difference in the inflammatory responses that may affect clinical outcome , and cardiovascular morbidity and mortality",
"Purpose Bariatric surgery ( BS ) promotes carotid intima-media thickness ( C-IMT ) regression as early as 6 months post-surgery . To verify whether C-IMT regression occurs even earlier , we aim ed at the effect of Roux-en-Y gastric bypass ( RYGBP ) and biliopancreatic diversion ( BPD ) on C-IMT 1–2 months and 12 months post-surgery . Subjects/ Methods Prospect i ve trial . BS was performed on 109 patients either with ( RYGBP = 42 ; BDP = 40 ) or without type 2 diabetes ( RYGBP = 27 ) . Healthy volunteers served as control group . Follow-up : baseline , 1–2 months , 12 months post-surgery . Endpoints : changes ( ∆ ) in C-IMT , weight , body mass index , fat mass , waist and neck circumferences , blood pressure , HbA1c , glucose , insulin , insulin sensitivity [ HOMA-IR ; OGIS , from meal tolerance test ] , lipids , C-reactive protein , leptin , adiponectin , MCP-1 . Results All surgery subgroups had similar levels of ∆-C-IMT . C-IMT in the pooled surgery group reduced from [ mean ( 95 % confidence interval ) ] 0.81 ( 0.77–0.84 ) mm to 0.66 ( 0.63–0.69 ) mm , p . ∆-C-IMT 1–2 months and 12 months post-surgery correlated to baseline C-IMT , and with ∆-leptin at 1–2 months , but not at 12 months post-surgery . In linear regression analysis , ∆-leptin and baseline C-IMT were predictors of ∆-C-IMT 1–2 months post-surgery . Conclusions A remarkable C-IMT regression occurred as early as 1–2 months after BS in obese patients either with or without type 2 diabetes , which was associated to the early reduction in leptin , ( at least partially ) independent of weight loss . Whether this is a causative or correlative association needs further investigation",
"Introduction Hypoglycemia is a known adverse event following gastric bypass . The incidence of hypoglycemia after laparoscopic sleeve gastrectomy ( LSG ) is still under investigation . The aim of our study was to verify the presence of oral glucose tolerance test (OGTT)-related hypoglycemia after LSG and to identify any baseline predictors of its occurrence . Methods We analyzed 197 consecutive non-diabetic morbid obese patients that underwent LSG . All patients were studied before and 12 months after LSG . Evaluation included anthropometric parameters , 3-h OGTT for blood glucose ( BG ) , insulin and c-peptide , lipid profile , interleukin-6 ( IL-6 ) , tumor necrosis factor alpha ( TNF-α ) , highly sensitive C-reactive protein ( hsCRP ) , and leptin . Hypoglycemia was defined as BG ≤ 2.7 mmol/l . Results After surgery , 180 patients completed the OGTT . Eleven patients did not complete the test for gastric intolerance , and in six patients , the test was stopped earlier for the onset of severe symptomatic hypoglycemia . Of the patients , 61/186 ( 32.8 % ) had at least one OGTT-related hypoglycemia . The highest frequency of hypoglycemic events occurred 150′ after glucose load ( 20.2 % ) . At baseline , patients with hypoglycemic events after surgery ( Hypo ) were younger ( 40 ± 11 vs 46 ± 10 years ; p ± 5.7 vs 48.4 ± 7.9 kg/m2 ; p worse lipid profile as compared to patients without hypoglycemic events ( N-Hypo ) . Moreover , after LSG , Hypo patients compared with N-Hypo presented a higher weight loss ( % E BMI L 80 ± 20 vs 62 ± 21 % ; p age , low fasting glucose , and high triglyceride levels before LSG were independent predictors of hypoglycemia development after surgery ( r2 = 0.131 ) . Conclusion These findings confirm the high incidence of post-pr and ial hypoglycemia 1 year after LSG . Hypoglycemia is more frequent in younger patients with lower fasting glucose and higher triglyceride levels before surgery",
"Background Epidemiological studies have identified obesity as a major risk factor for cancer in humans , and trials have demonstrated a significant reduction in the incidence of cancer after bariatric surgery . The rapidity of weight loss after bariatric surgery provides an opportunity to identify the molecular changes associated with effective obesity treatment . Indirectly , this may provide some insights into the mechanisms that drive the association between obesity and cancer . We sought to measure circulating cancer-associated proteins before and after laparoscopic sleeve gastrectomy ( LSG ) . Methods We prospect ively enrolled 15 patients undergoing LSG . Thirty-four plasma protein biomarkers thought to be associated with cancer processes were analyzed at baseline and following successful weight loss at 12 weeks using a multiplex bead-based assay . Results Mean excess body weight loss was 44 % at 12-week follow-up . After LSG , a significant reduction in circulating plasma levels was observed for half ( 17/34 ) of the proteins assessed : VEGF-A , VEGF-C , VEGF-D , endoglin , PLGF , sFASL , IGFBP-1 , IL-18 , prolactin , EGF , TGFα , sCD40L , IL-18 , TNFα , IL-6 , HB-EGF , and PAI-1 . Nonsignificant decreases were found for the remaining proteins . Conclusions Circulating cancer-related biomarker levels were reduced by surgical weight loss , and this benefit was achieved as early as 3 months after operation . The observed reduction in cancer biomarkers may be related to the reported decrease in cancer incidence following bariatric surgery",
"Excess adiposity is associated with low- grade inflammation and decreased iron status . Iron depletion in obesity is thought to be mediated by an inflammation-induced increase in the body 's main regulator of iron homeostasis , hepcidin . Elevated hepcidin can result in iron depletion as it prevents the release of dietary iron absorbed into the enterocytes , limiting replenishment of body iron losses . Weight reduction is associated with decreased inflammation ; however , the impact of reduced inflammation on iron status and systemic hepcidin in obese individuals remains unknown . We determined prospect ively the impact of weight loss on iron status parameters , serum hepcidin , inflammation , and dietary iron in 20 obese premenopausal females 6 months after restrictive bariatric surgery . At baseline , the presence of iron depletion was high with 45 % of the women having serum transferrin receptor ( sTfR ) > 28.1 nmol/l . Differences between baseline and 6 months after surgery for BMI ( 47.56 vs. 39.55 kg/m(2 ) ; P ) ( 10.83 vs. 5.71 mg/l ; P ) , sTfR ( 29.97 vs. 23.08 nmol/l ; P = 0.001 ) , and serum hepcidin ( 111.25 vs. 31.35 ng/ml ; P whereas hemoglobin ( Hb ) ( 12.10 vs. 13.30 g/dl ; P and hematocrit ( Hct ) ( 36.58 vs. 38.78 % ; P = 0.001 ) were significantly higher . Ferritin and transferrin saturation ( Tsat ) showed minimal improvement at follow-up . At baseline , hepcidin was not correlated with sTfR ( r = 0.02 ) ; however , at follow-up , significant correlations were found ( r = -0.58 ) . Change in interleukin-6 ( IL-6 ) from baseline was marginally associated with decreased log serum hepcidin ( Δ IL-6 : β = -0.22 ; P = 0.15 ) , whereas change in BMI or weight was not . No significant difference in dietary iron was noted after surgery . Weight loss in obese premenopausal women is associated with reduced serum hepcidin and inflammation . Reduction in inflammation and hepcidin likely allow for enhanced dietary iron absorption result ing in an improved functional iron profile",
"BACKGROUND Morbidly obese patients are at risk of developing insulin resistance and cardiovascular disease . Low- grade systemic inflammation is an important factor for this development . We evaluated the effect of bariatric surgery on markers of inflammation , coagulation and glucose metabolism . METHODS Ninety-seven morbidly obese patients and 17 lean subjects ( control group ) participated . Anthropometric measurements as well as fasting blood sample s were obtained at first admission , prior to surgery , and 1 year after surgery . RESULTS At admission , the morbidly obese group had significantly elevated levels of the complement components C3 and C4 compared to the lean control group ( P . Levels of C3 and C4 dropped significantly in the morbidly obese group over time ( P for markers of inflammation ( high-sensitivity C-reactive protein , tumor necrosis factor-α , interferon-γ , interleukin-1 receptor antagonist , IL-6 , and IL-13 ) , coagulation ( fibrinogen and plasminogen activator inhibitor-1 ) , and glucose metabolism ( leptin and insulin ) . There was a positive correlation between changes in C3 and body mass index , weight , coagulation parameters , inflammatory parameters , and leptin , respectively . CONCLUSIONS Bariatric surgery in morbidly obese patients reduced weight effectively . Even more importantly , the increased levels of several risk factors associated with diabetes and cardiovascular co-morbidity normalized 1 year after surgery",
"Background Increased visceral adipose tissue is a risk factor for the metabolic complications associated with obesity and promotes a low- grade chronic inflammatory process . Resection of the great omentum in patients su bmi tted to a bariatric procedure has been proposed for the amelioration of metabolic alterations and the maximization of weight loss . The aim of the present study was to investigate the impact of omentectomy performed in patients with morbid obesity undergoing sleeve gastrectomy ( SG ) on metabolic profile , adipokine secretion , inflammatory status , and weight loss . Methods Thirty-one obese patients were r and omized into two groups : SG alone or with omentectomy . Adiponectin , omentin , interleukin-6 ( IL-6 ) , tumor necrosis factor-α ( TNF-α ) , high-sensitivity C-reactive protein ( hs-CRP ) , blood lipids , fasting glucose , insulin , and insulin resistance were measured before surgery and at 7 days , and 1 , 3 and 12 months after surgery . Results During the 1-year follow-up , body mass index ( BMI ) decreased markedly and comparably in both groups ( p Insulin , IL-6 , and hs-CRP levels decreased significantly compared to baseline ( p groups . Adiponectin and high-density lipoprotein cholesterol levels were significantly and similarly increased compared to baseline ( p groups . Omentin levels increased significantly ( p in TNF-α levels in either group . Conclusions The theoretical advantages of omentectomy in regard to weight loss and obesity-related abnormalities are not confirmed in this prospect i ve study . Furthermore , omentectomy does not induce important changes in the inflammatory status in patients undergoing SG",
"Abstract Objective . Exogenous bile acid ( BA ) administration is associated with beneficial metabolic effects very similar to those seen after Roux-en-Y gastric bypass ( RYGB ) surgery . Re-routing of bile into a biliopancreatic limb with simultaneous exclusion of food occurs after RYGB , with subsequent increased fasting plasma BAs . The study assessed fasting and post-pr and ial plasma BA response before and 15 months after RYGB . Material and methods . The prospect i ve study recruited 63 obese individuals ( 43 females ) , aged 43 ( 36–56 ) [ median ( IQR ) ] years . Blood sample s were collected before and every 30 min for 120 min after a st and ard 400 kcal meal . Fasting and post-pr and ial plasma BAs , glucagons like peptide-1 ( GLP-1 ) , –tyrosine ( PYY ) , fasting C-reactive protein ( CRP ) , glucose and insulin were measured and homeostasis model assessment -insulin resistance ( HOMA-IR ) was calculated . Results . Following RYGB , body mass index , CRP , fasting glucose and HOMA-IR decreased ; 43.7 ( 39.3–49.2 ) kg/m2 to 29.2 ( 25.1–35.0 ) kg/m2 , 7.9 ( 4.1–11.9 ) mg/L to 0.4 ( 0.2–1.0 ) mg/L , 5.5 ( 5.0–6.0 ) mmol/L to 4.6 ( 4.3–4.9 ) mmol/L and 5.9 ( 3.5–9.2 ) to 1.7 ( 1.1–2.2 ) , respectively , all P 0.001 . Fasting total BAs , GLP-1 and PYY increased after RYGB ; 1.69 ( 0.70–2.56 ) µmol/L to 2.43 ( 1.23–3.82 ) µmol/L ( P = 0.02 ) , 6.8 ( 1.5–15.3 ) pmol/L to 17.1 ( 12.6–23.9 ) pmol/L ( P post-pr and ial total BAs , total glycine-conjugated BAs , GLP-1 and PYY were greater after RYGB ; 486 ( 312–732 ) µmol/L/min versus 1012 ( 684–1921 ) µmol/L/min , 315 ( 221–466 ) µmol/L/min versus 686 ( 424–877 ) µmol/L/min , 3679 ( 3162–4537 ) pmol/L/min versus 5347 ( 4727–5781 ) pmol/L/min and 1887 ( 1423–2092 ) pmol/L/min versus 3296 ( 2534–3834 ) pmol/L/min , respectively , all P in post-pr and ial plasma BA response due to larger amounts of glycine-conjugated BAs . This suggests up regulation of BA production and conjugation after RYGB",
"BACKGROUND Obesity is a risk factor for self-reported asthma and makes asthma management more difficult . The effects of bariatric surgery on asthma in severely obese subjects remain to be documented . METHODS In this prospect i ve study , 12 asthmatic patients with severe obesity were evaluated before , 6 and 12 months after bariatric surgery . Each had methacholine inhalation tests , measures of expiratory flows and lung volumes , measurements of C-reactive protein and question naires on asthma medication , asthma symptoms and co-morbid conditions . Eleven severely obese patients with asthma ( considered as controls ) underwent the same evaluations . Primary endpoint was airway responsiveness to methacholine and secondary endpoints were lung volumes and markers of systemic inflammation . RESULTS Mean body mass index decreased from 51.2 to 34.4 kg/m(2 ) twelve months post-surgery . Mean PC(20 ) methacholine improved from 0.84 to 6.2 mg/ml ( P 0.001 ) ; FEV(1 ) , FVC , FRC , FRC/TLC and ERV all improved ( P ≤ 0.006 ) . C-reactive protein decreased from 8.6 to 1.7 mg/L ( P 0.001 ) Asthma symptoms total score was significantly reduced ( P = 0.03 ) and asthma medication needs decreased , ten patients being able to stop all asthma drugs . No significant changes of these parameters from baseline were observed in asthmatic controls . Improvements in airway responsiveness and lung volumes happened in parallel and correlated with reductions of body mass index ( r = 0.58 , P = 0.049 ) , C-reactive protein levels ( r = -0.74 , P = 0.004 ) . CONCLUSION Airway responsiveness , lung volumes and asthma severity/control markedly improved with weight loss following bariatric surgery in severely obese patients",
"High blood pressure ( HBP ) has been associated with elevated C-reactive protein ( CRP ) , a marker of chronic mild inflammation . However , the association between HBP and other inflammatory markers , particularly interleukin 6 ( IL-6 ) and tumour necrosis alpha ( TNF-α ) , has not been evaluated in well-controlled studies . We examined the cross-sectional relationship between IL-6 , TNF-α , and CRP and HBP in a r and om sample of 196 healthy subjects . All markers were measured in duplicate with high-sensitivity ELISA tests . Three blood pressure ( BP ) measurments were averaged for the analysis , and subjects with systolic BP ⩾140 and /or diastolic BP ⩾90 mmHg were considered hypertensive . Log binomial regression was used to estimate multivariate-adjusted prevalence ratios ( PR ) of HBP . Of the subjects , 40 % ( 79 ) were hypertensive ( mean age : 44 years ; range 30–64 ) . After adjustment for age , sex , body mass index , family history of HBP , and the level of the other inflammatory markers , subjects in the second ( PR : 3.10 , P=0.003 ) , third ( PR : 2.32 ; P=0.031 ) , and fourth quartiles ( PR : 2.30 ; P=0.036 ) of IL-6 were more than twice as likely to be hypertensive than those in the first quartile . Corresponding PR estimates for TNF-α levels were 1.41 ( P=0.014 ) for the second ; 1.59 ( P=0.001 ) for the third ; and 1.61 ( P=0.025 ) for the fourth quartile . The CRP – HBP association was not statistically significant . Our results suggest that TNF-α and IL-6 could be independent risk factors for HBP in apparently healthy subjects . Nevertheless , the temporal relationship between elevated inflammation markers and HBP should be ascertained in prospect i ve cohort studies",
"The aim of this study was to describe the effect of surgically induced weight loss on vascular function measured by flow-mediated dilatation ( FMD ) in hypertensive obese patients . This prospect i ve study included 33 patients ( 78 % females , mean age 53 ( 9 ) years ) undergoing bariatric surgery ( BS ) . Before and 12 months postoperatively , the BMI , 24-h ambulatory BP , high-sensitivity C-reactive protein ( hs-CRP ) , leptin , homeostasis model assessment ( HOMA IR ) , and abdominal fat were measured . Endothelial function was assessed by FMD . After BS , the excess body weight loss was 71 % ; the 24-h [ systolic 18(11)//diastolic 7(7 ) mmHg ] BP values , hs-CRP , leptin , HOMA , and abdominal fat significantly decreased , with no changes in endothelial function . Weight loss achieved by BS was associated with a significant improvement in BP and metabolic and inflammation parameters , but FMD did not improve",
"AIM The aim this study was to evaluate the influence of gastric bypass surgery ( GBS ) on periodontal disease and quantify the periodontopathogenic bacteria in patients undergoing this surgery . MATERIAL AND METHODS This prospect i ve study was composed of 50 patients who underwent bariatric surgery and the data collection was performed in three periods pre-operative , 6 ( 6 M ) and 12 months ( 12 M ) postoperative . The oral clinical examination to assess periodontal disease ; gingival fluid sample collection for quantification of the periodontopathogenic bacteria Porphyromonas gingivalis , Tannerella forsythia , Treponema denticola , and Prevotella intermedia using q-PCR ; body mass index ( BMI ) and for collection of the individual 's health-related data from medical files . RESULTS There was a significant reduction in serum C-reactive protein ( CRP ) and glucose levels after surgery . The mean probing pocket depth ( PPD ) and clinical attachment level ( CAL ) increased significantly in the postoperative period of 6 months ( p = 0.001 ) . In the same period , the amount of P. gingivalis increased ( p = 0.028 ) and the other bacteria decreased slightly ( p > 0.050 ) . In the presence of P. gingivalis , T. forsythia , T. denticola and P. intermedia , a poor periodontal condition was observed . CONCLUSION The periodontal disease increased in severity and P. gingivalis increased after GBS . A systemic inflammation resolution due to bariatric surgery in obese subjects does not seem to affect the course of periodontal disease",
"BACKGROUND Excess visceral adipose tissue predicts for incipient diabetes mellitus and cardiovascular disease . Human data are mixed regarding the benefits of selective visceral adipose tissue reduction . We investigated the effects of omentectomy added to laparoscopic Roux-en-Y gastric bypass on glucose homeostasis and lipids , inflammatory markers , and adipokines 90 days postoperatively in nondiabetic patients at the Legacy Good Samaritan Hospital and Oregon Health and Science University ( Portl and , OR ) . METHODS A single-blind , r and omized study of laparoscopic Roux-en-Y gastric bypass plus omentectomy versus laparoscopic Roux-en-Y gastric bypass alone in 28 subjects ( 7 men and 21 women ) . The groups were matched at baseline for gender , age , and body mass index ( BMI ) . The eligibility criteria included age ≥18 years , BMI ≥40 and The primary outcome measures were changes in the fasting plasma glucose , insulin , and homostatic model assessment of insulin resistance . The secondary measures were BMI and the high-sensitivity C-reactive protein , tumor necrosis factor-α , interleukin , total and high-molecular-weight adiponectin , fibrinogen , and plasminogen activator inhibitor-1 levels . RESULTS After surgery , the BMI decreased significantly in both groups and was not different at the follow-up point . Although many outcome parameters improved with weight loss in both groups postoperatively , only the omentectomy group experienced statistically significant decreases in fasting glucose ( P ) , total ( P = .004 ) and very-low-density lipoprotein ( P = .001 ) cholesterol , and an increase in the high-molecular-weight/total adiponectin ratio ( P = .013 ) . CONCLUSIONS Omentectomy added to laparoscopic Roux-en-Y gastric bypass results in favorable changes in glucose homeostasis , lipid levels , and adipokine profile at 90 days postoperatively . These data support the hypothesis that selective ablation of visceral adipose tissue conveys metabolic benefits in nondiabetic humans",
"Background Increased visceral adipose tissue ( VAT ) is thought to be a risk factor for cardiovascular and metabolic diseases . There are only limited data on whether VAT loss after laparoscopic gastric b and ing surgery ( LGBS ) is related to risk factor reduction . This study determined whether improvements in risk markers , in particular insulin resistance , were related to VAT reduction at 6 months after LGBS ( T2 ) . Methods Thirty-four LGBS patients and 17 normal weight controls underwent initial and T2 testing . Fasting venous blood sample s were taken to evaluate glucose , insulin , hemoglobin A1c , lipids , C-reactive protein ( CRP ) , and hormone profiles . Insulin resistance was estimated using the homeostasis model assessment ( HOMA ) index . VAT was measured using CT techniques . Data were analyzed using repeated measures ANOVA and regression analysis . Results Results at T2 showed that patients had significant improvements in body composition , HOMA , and hemoglobin A1c . There were also reductions in plasma renin activity and leptin , and increases in ghrelin and GLP-1 . Reductions in VAT were significantly correlated with reductions in insulin , HOMA , and glucose . While high density lipoprotein cholesterol , triglycerides , CRP , and the apolipoprotein A1/B ratio were also improved , VAT reduction was significantly correlated only with an increased apolipoprotein A1/B ratio . Conclusion These data indicate that 6 months after LGBS there were significant improvements in many cardiovascular and metabolic risk markers . However , VAT reduction was most strongly associated with reductions in insulin resistance . Body weight loss was not associated with markers of improved insulin sensitivity",
" Bariatric surgery has been suggested to improve arterial hypertension and renal function . This prospect i ve controlled observational study aim ed to investigate changes in renal inflammation , renal function and arterial blood pressure before and after bariatric surgery",
"Background C-Reactive protein ( CRP ) has been associated with the macro- and microvascular effects of hypertension and diabetes mellitus . Referring to serum cortisol , it has been proposed to contribute to the pathogenesis of metabolic syndrome , and it has been demonstrated that weight loss normalizes cortisol levels and improves insulin resistance . The aims of this study were to analyze CRP and cortisol levels pre- and postoperatively in morbidly obese patients undergoing a laparoscopic sleeve gastrectomy and to correlate them with weight loss and parameters associated with cardiovascular risk . Methods A prospect i ve study of all the morbidly obese patients undergoing laparoscopic sleeve gastrectomy as bariatric procedure between October 2007 and May 2011 was performed . Results A total of 40 patients were included in the study . CRP levels decreased significantly 12 months after surgery ( median reduction of 8.9 mg/l ; p = 0.001 ) . Serum cortisol levels decreased significantly 6 months after surgery ( median reduction of 34.9 μg/dl ; p = 0.001 ) . CRP values reached the normal range ( cardiovascular risk predictor ( triglyceride/high-density lipoprotein cholesterol ratio ) from the 6th month after surgery onward ( Pearson correlation coefficient , 0.559 ; p = 0.008 ) . Conclusion CRP levels are increased preoperatively and in the postoperative course up to 1 year after surgery . Serum cortisol levels remain elevated until the 6th month after surgery . From this moment onward , serum cortisol is associated with the cardiovascular risk predictor reflecting the cardiovascular risk decreasement during the weight loss",
"Background Osteopontin ( OPN ) is a multifunctional matrix glycoprotein associated with bone metabolism and has been linked to chronic inflammation , insulin resistance , and atherosclerosis . Diet-induced weight loss decreases elevated OPN concentrations in obese patients . The aim of the current study was to investigate the role of OPN after bariatric surgery , where not only improvements of chronic inflammation , insulin resistance and comorbidities , but also malabsorption and altered bone metabolism have been reported . Methods OPN plasma concentrations were determined in 31 morbidly obese patients ( 5 men , 26 women , BMI 46.2 ± 7.1 kg/m2 , age 41 ± 11 years ; mean ± SD ) before and 18 months after bariatric surgery , together with parameters of bone metabolism and inflammation . Results OPN concentrations increased by + 20.3 ± 26.6 ng/ml ( mean ± SD , p weight loss of −38 ± 22 kg , and a decrease in BMI by −13.1 ± 7.7 kg/m2 ( both p improved from 5.2 ± 3.4 to 1.5 ± 1.0 ( p , and phosphate increased ( −0.06 ± 0.13 mmol/l and + 0.08 ± 0.16 mmol/l , respectively ; both p while 25-OH-VitaminD3 remained unchanged and PTH tended to increase ( + 5.1 ± 14.0 pg/ml , p = 0.054 ) . Monocyte chemoattractant protein 1 and interleukin 18 were significantly decreased and associated with HOMA both before and after bariatric surgery . ΔOPN was correlated with ΔPTH , but not with other parameters . Conclusions OPN plasma concentrations increased concomitant to weight loss after bariatric surgery , which was independent from an improvement of insulin sensitivity and a decrease of inflammatory markers . Further studies are needed to differentiate whether these changes in bone metabolism after bariatric surgery are secondary to calcium deficiency or an adaptation to weight loss",
"BACKGROUND Bariatric surgery is an effective treatment for morbid obesity . Obesity and type 2 diabetes are associated with chronic inflammation . There is lack of data examining the effects of sleeve gastrectomy ( SG ) on inflammatory biomarkers . Our aim was to study the effects of SG on specific cytokines associated with obesity including interleukin-6 ( IL-6 ) , interleukin-10 ( IL-10 ) , leptin , adiponectin , and C-reactive protein ( CRP ) preoperatively , 1 and 6 months after surgery . METHODS A nonr and omized prospect i ve study comprising of 22 participants with impaired glucose homeostasis and type 2 diabetes undergoing SG ( body mass index 50.1 kg/m(2 ) , glycated hemoglobin [ HbA1c ] 53 mmol/mol ) . Serial measurements of IL-6 , IL-10 , leptin , adiponectin , and CRP were performed during oral glucose tolerance testing preoperatively , 1 and 6 months postoperatively . RESULTS We observed significant improvements at 1 and 6 months in leptin ( P≤.001 ) and CRP ( P = .003 ) after SG . We also observed a significant reduction in IL-6 at 6 months ( P = .001 ) . No statistically significant differences were observed for adiponectin and IL-10 . CONCLUSION This study is the first to examine the detailed changes in the inflammatory cytokines after SG . Our study shows significant improvements in the inflammatory biomarkers after SG in patients with impaired glucose homeostasis and type 2 diabetes",
"Background Laparoscopic sleeve gastrectomy ( LSG ) has been recently introduced as a st and -alone , restrictive bariatric surgery . Theoretically , LSG attenuates micronutrients deficiencies and associated complications that typically observed following malabsorptive procedures . The aim of this study was to assess iron indices and the 1-year incidence of iron deficiency in patients undergoing LSG . Methods This was a prospect i ve , cohort study ; patients who underwent LSG from June 2007 to April 2008 at our institution were screened for inclusion . Preoperative hemoglobin and iron indices including serum iron , transferrin saturation , ferritin , and soluble transferrin receptor were compared to their levels at 6 and 12 months after surgery . Similarly , vitamin B12 and red blood cell ( RBC ) folate were analyzed as secondary end points . Weight parameters and C-reactive protein ( CRP ) levels were compared before surgery and 1 year postoperatively . Results A total of 61 patients were included in the study . One year after surgery , there was a significant decrease in the mean body mass index from 47.5 ± 9.6 to 30.5 ± 6.5 ( P incidence of iron deficiency was 4.9 % at both follow-up time points . Anemia was evident in 4.9 % of patients 1 year postoperatively . Significant decrease in the means of the natural logarithm of vitamin B12 and RBC folate were observed as early as 6 months after surgery ( P = 0.014 ; P decrease in mean CRP level 12 months postoperatively was statistically significant compared to its preoperative value ( P Conclusion LSG is an effective procedure for the treatment of morbid obesity and its associated inflammatory state . One year after surgery , development of iron deficiency was insignificant",
"BACKGROUND We investigated the biochemical and inflammatory parameters as well as biomarkers of oxidative stress in morbidly obese patients before and after bariatric surgery and clinical treatment . METHODS This study was conducted using 60 individuals ( 10 men and 50 women ) distributed into 3 groups : the control group , 20 non-diabetic obese patients given clinical treatment , the bariatric group , 20 non-diabetic obese patients given a Roux-en-Y bypass gastroplasty , and the bariatric diabetic group , 20 diabetic obese patients given a Roux-en-Y bypass gastroplasty . Measurements were made before and 1 , 3 , 6 , and 12months after surgery and clinical treatment . RESULTS We showed a significant decrease in body weight , body mass index ( BMI ) and waist circumference , accompanied by a decrease in the lipid profile and glucose and glycated hemoglobin concentrations in the groups that received bariatric surgery . The concentrations of lipid peroxidation , carbonyl protein and NPSH , as well as superoxide dismutase ( SOD ) and catalase ( CAT ) activity , significantly decreased in both groups after surgery . The concentrations of inteleukin-6 , inteleukin-1 , TNF-α and resistin were also significantly lower , while adiponectin concentrations significantly increased 12months after bariatric surgery . No significant alterations were observed in the biochemical , inflammatory or oxidative parameters of the control group . CONCLUSIONS Our findings demonstrate a decrease in body mass and a subsequent improvement in biochemical , metabolic and anthropometric parameters in patients given bariatric surgery . This may contribute to the reduction of oxidative damage in these patients and consequently a reduction in the risk of the development and progression of multiple co-morbidities associated with obesity",
"Background The effects of surgical weight loss ( WL ) on inflammatory biomarkers associated with sleep apnea remain unknown . We sought to determine if any biomarkers can predict amelioration of sleep apnea achieved by bariatric surgery . We hypothesized that surgical WL would substantially reduce severity of sleep apnea and levels of proinflammatory cytokines . Methods Twenty-three morbidly obese adults underwent anthropometric measurements , polysomnography , and serum biomarker profiling prior to and 1 year following bariatric surgery . We examined the effect of WL and amelioration of sleep apnea on metabolic and inflammatory markers . Results Surgical WL result ed in significant decreases in BMI ( 16.7 ± 5.97 kg/m2/median 365 days ) , apnea – hypopnea index ( AHI ) , CRP , IL-6 , sTNFαR1 , sTNFαR2 , and leptin levels , while ghrelin , adiponectin , and soluble leptin receptor concentrations increased significantly . Utilizing an AHI cutoff of 15 events/h , we found significantly elevated levels of baseline sTNFαR2 and greater post-WL sTNFαR2 decreases in subjects with baseline AHI ≥15 events/h compared to those with AHI decreases in AHI were an independent predictor of the decreases in sTNFαR2 and altogether accounted for 46 % of the variance of ΔsTNFαR2 ( P = 0.011 ) in the entire cohort . Conclusions Of all the biomarkers , the decrease in sTNFαR2 was independently determined by the amelioration of sleep apnea achieved by bariatric surgery . The results suggest that sTNFαR2 may be a specific sleep apnea biomarker across a wide range of body weight",
"Background : Leptin is a hormone that regulates food intake ; its concentrations are elevated in the majority of obese individuals . During inflammation , plasma leptin is usually increased and may contribute to the anorexia and cachexia of infection . The purpose of this study was to characterize the dynamics of circulating leptin in the early postoperative period in relation to the acute phase response in extremely obese patients undergoing laparoscopic non-adjustable gastric b and ing ( LNAGB ) . We compared plasma leptin changes with 4 proinflammatory cytokines and BMI . Methods : The prospect i ve study was performed on 18 patients with 3rd degree obesity . Plasma concentration of leptin , tumor necrosis factor-α ( TNF-α ) , interleukin (IL)-1 , soluble IL-2 receptor ( sIL-2R ) , and IL-6 were estimated before operation and 24 , 48 , and 72 h after NALGB . Results : We demonstrate statistically significant elevation of plasma leptin concentration ( 32.2±10.2 µg/l ) 24 h after operation compared with preoperative status ( 18.4±5.2 µg/l , p of plasma leptin and BMI in this period . Leptin levels + 48 and + 72 h after b and ing quickly returned to preoperative levels . The regression coefficient was the highest for leptin and TNFalpha 24 h after surgery ( r = 0.40 , p leptin and IL-6 24 h after surgery ( r = 0.29 , p between leptin and IL-1 and between leptin and sIL-2R respectively . Conclusions : During the non-infectious stress response ( as with abdominal surgery ) , leptin shows itself as an acute phase reactant . Proinflammatory cytokines can be the main regulatory factors of leptin in this period . Significant correlation between leptin and TNF-alpha ( similarly demonstrated by other authors in models of bacterial inflammation ) indicates that TNF-alpha can be a crucial regulator of leptin generation in the early postoperative period",
"BACKGROUND Increased adipokine production and hyperfiltration may explain the links between obesity and chronic kidney disease . Indeed , hyperfiltration may precede a subsequent accelerated decline of kidney function in these patients . Glomerular filtration rate decreases after bariatric surgery in young obese patients with hyperfiltration . OBJECTIVE Our aim was to identify the factors associated with this decrease 1 year after bariatric surgery . SETTING We used data from a prospect i ve cohort of severely obese patients who underwent bariatric surgery in Nice University Hospital . METHODS We analyzed 175 patients before and 1 year after bariatric surgery . Low- grade inflammation was evaluated by serum C-reactive protein levels . Lean body mass and fat body mass were estimated by bioelectric impedance analysis . Body surface area was assessed by the Du Bois formula . Serum creatinine levels were used to estimate glomerular filtration rate by the chronic kidney disease-epidemiology collaboration ( CKD-EPI ) equation . Glomerular filtration rate was de-adjusted from st and ard body surface area and then divided by lean body mass to calculate the decrease in hyperfiltration and to separate the patients into 2 groups : above or below the median decrease of hyperfiltration after bariatric surgery . RESULTS The factors associated with a large correction of hyperfiltration were baseline C-reactive protein levels ( 10.0 ± 5.8 mg/L versus 12.7 ± 7.4 mg/L , P = .01 ) and brachial circumference ( 41 ± 4 cm versus 44 ± 5 cm , P = .006 ) . A high fat mass reduction rate was significantly associated with a substantial hyperfiltration reduction after bariatric surgery ( P after bariatric surgery but may be limited by low- grade inflammation ",
"Background This study examined the effect of weight loss on energy intake , vitamin C , E , β-carotene ( diet/blood ) , reduced glutathione ( GSH ) , C-reactive protein ( CRP ) , thiobarbituric acid reactive substances ( TBARS ) , catalase , and myeloperoxidase , in patients with Roux-en-Y bypass gastroplasty . Methods Prospect i ve clinical study with control ( C ) and bariatric ( B ) groups ( n = 20 each ) . Age was 38.8 ± 11.1 ( C ) and 37.8 ± 11.2 years ( B ) , and body mass indices ( BMI ) were 22.4 ± 2.4 and 48.1 ± 8.7 kg/m2 , respectively . Group C was assessed on a single occasion and B at three time points ( basal period and 3 and 6 months after gastroplasty ) . Results BMI was decreased at three ( 38.3 ± 1.7 , P = 0.018 ) and 6 months after surgery ( 34.9 ± 1.7 , P 0.001 ) . Mean weight loss was 20.53 ± 1.1 after three and 27.96 ± 1.3 kg after 6 months . Serum vitamin C and β-carotene ( P basal . Basal serum vitamin C ( P = 0.001 ) and β-carotene ( P controls . Serum vitamin E corrected for cholesterol and triglycerides was higher in group B at three ( P = 0.01 ) and 6 months ( P = 0.001 ) and lower at basal ( P controls . GSH was higher in controls ( P basal . Catalase ( P = 0.01 ) and TBARS ( P 6 months . TBARS were higher ( P controls . Myeloperoxidase and CRP decreased in group B after three ( P = 0.028 , P = 0.010 ) and 6 months ( P Conclusions Roux-en-Y bypass gastroplasty led to decreased proinflammatory parameters together with increased nutritional antioxidants , catalase , and TBARS , and decreased GSH 6 months after surgery",
"BACKGROUND & AIMS Roux-en-Y gastric bypass ( RYGB ) is associated with an increased risk for micronutrient deficiencies . This study aim ed to assess total ( dietary and supplement ) intake and association with iron ( including hepcidin ) , vitamin B12 , vitamin C and zinc status markers before and after Roux-en-Y gastric bypass ( RYGB ) . METHODS This prospect i ve study included patients with a planned RYGB in University Hospitals Leuven , Belgium ; who were followed until 12 months post-RYGB . Patients completed an estimated dietary record of two non-consecutive days before and 1 , 3 , 6 and 12 months post-RYGB and supplement/drug use was registered . Associations between total micronutrient intake and status markers were analyzed . RESULTS Fifty-four patients ( 21 males ; mean age : 48.0 [ 95%CI 46.6 ; 49.3 ] years ; mean preoperative BMI : 40.4 [ 95%CI 39.4 ; 41.4 ] kg/m2 ) were included . One month post-RYGB , usual dietary intake of the studied micronutrients was significantly decreased compared to pre-RYGB , but gradually increased until 12 months post-RYGB , remaining below baseline values . By including micronutrient supplement intake , 12 months post-RYGB values were higher than baseline , except for zinc . Hemoglobin , ferritin , vitamin B12 and C-reactive protein serum concentrations were significantly decreased and transferrin saturation and mean corpuscular volume were significantly increased 12 months post-RYGB . Serum hepcidin concentration was significantly decreased 6 months post-RYGB . CONCLUSIONS Medical nutritional therapy is essential following RYGB as dietary intake of iron , vitamin B12 , vitamin C , copper and zinc was markedly decreased postoperatively and some patients still had an inadequate total intake one year post-RYGB",
"INTRODUCTION Weight loss interventions such as Roux-en-Y gastric bypass ( RYGB ) and very low calorie diets ( VLCD ) lead to improvement of glucose metabolism in obese individuals with type-2 diabetes . Weight loss can also positively influence the unfavorable inflammatory profile associated with obesity . However , a direct comparison of the effect of VLCD and RYGB on systemic inflammation is lacking . METHODS Systemic inflammation was investigated in age- and BMI -matched morbidly obese T2DM women by determining the number and activation- or memory status of peripheral blood leukocytes by flow cytometry , in addition to measuring circulating levels of cytokines and CRP . Systemic inflammation was assessed one month before and three months after RYGB ( n=15 ) or VLCD ( n=12 ) . An age matched group of lean women ( n=12 ) was studied as control group . RESULTS Three months after the intervention , CRP and leptin levels were reduced whereas adiponectin levels were increased both by RYGB and VLCD . TNF-α levels were increased by RYGB , but reduced by VLCD . IL-2 and IL-6 levels were reduced and IL-4 levels were increased by VLCD but not affected by RYGB . The number of activated peripheral cytotoxic T ( CD8+CD25 + ) and B ( CD19+CD38 + ) cells was significantly higher after RYGB than after VLCD . CONCLUSION In conclusion , RYGB and VLCD have differential effects on the activation status of peripheral leukocytes and levels of cytokines in obese women with T2DM , despite comparable weight loss three months after the intervention . VLCD seems to have more favorable effects on the inflammatory profile as compared to RYGB",
"OBJECTIVE Obesity and weight loss influence thyroid hormone physiology . The effects of weight loss by calorie restriction vs Roux-en-Y gastric bypass ( RYGB ) in obese subjects have not been studied in parallel . We hypothesized that differences in transient systemic inflammation and catabolic state between the intervention types could lead to differential effects on thyroid hormone physiology . DESIGN AND METHODS We recruited 12 lean and 27 obese females with normal fasting glucose ( normal glucose tolerant ( NGT ) ) and 27 obese females with type 2 diabetes mellitus ( T2DM ) for this study . Weight loss was achieved by restrictive treatment ( gastric b and ing or high-protein-low-calorie diet ) or by RYGB . Fasting serum leptin , TSH , triiodothyronine ( T₃ ) , reverse T₃ ( rT₃ ) , and free thyroxine ( fT₄ ) concentrations were measured at baseline and 3 weeks and 3 months after the start of the interventions . RESULTS Obesity was associated with higher TSH , T₃ , and rT₃ levels and normal fT₄ levels in all the subjects when compared with the controls . After 3 weeks , calorie restriction and RYGB induced a decline in TSH levels and a rise in rT₃ and fT₄ levels . The increase in rT₃ levels correlated with serum interleukin 8 ( IL8 ) and IL6 levels . After 3 months , fT₄ and rT₃ levels returned to baseline levels , whereas TSH and T₃ levels were persistently decreased when compared with baseline levels . No differences in the effects on thyroid hormone parameters between the interventions or between NGT and T2DM subjects were observed at any time point . CONCLUSIONS In summary , weight loss directly influences thyroid hormone regulation , independently of the weight loss strategy used . The effects may be explained by a combination of decreased leptin levels and transient changes in peripheral thyroid hormone metabolism",
"OBJECTIVE To evaluate the behavior of acute phase proteins and lipid profile in patients undergoing Roux-en-Y gastric bypass . METHODS We conducted a prospect i ve study , consisting of three moments : M1 - preoperative ( 24 hours before surgery ) ; M2 - 30 days after surgery ; and M3 - 180 days after surgery . We carried measured height and BMI , as well as determined the concentrations of acute phase proteins ( C-reactive protein ( CRP ) , albumin and Alpha-1-acid glycoprotein ) and total cholesterol , LDL-c , HDL-c and triacylglycerol . RESULTS participants comprised 25 individuals , with a mean age of 39.28 ± 8.07 , 72 % female . At all times of the study there was statistically significant difference as for weight loss and BMI . We found a significant decrease in CRP concentrations between the moments M1 and M3 ( p = 0.041 ) and between M2 and M3 ( p = 0.018 ) . There was decrease in Alpha-1-GA concentrations between M1 and M2 ( p = 0.023 ) and between M1 and M3 ( p = 0.028 ) . The albumin values increased , but did not differ between times . Total cholesterol and triacylglycerol decreased significantly ay all times . LDL-c concentrations decreased and differed between M1 and M2 ( p = 0.001 ) and between M1 and M3 ( p = 0.001 ) . HDL-c values increased , however only differing between M1 and M2 ( p = 0.050 ) . CONCLUSION Roux-en-Y gastric bypass promoted a decrease in plasma concentrations of CRP and Alpha-1-acid glycoprotein , improving lipid and inflammatory profiles",
"Background Obesity causes renal problems including albuminuria . Bariatric surgery ( BS ) improves albuminuria . We investigated whether albuminuria is reduced by weight loss per se or by improved systemic inflammation induced by weight loss after BS . Methods Patients older than 18 years who received BS in Soonchunhyang University Hospital from 01 January 2011 to 31 December 2011 were included . Other inclusion criteria included body mass index ( BMI ) ≥ 30 kg/m2 , creatinine level ≤ 1.0 mg/dL , and no overt proteinuria ( trace amount or undetectable by dipstick ) . The patients were followed at 1 and 6 months after BS . Results Forty-three patients were analyzed . Three patients were men , 10 patients had diabetes , and 12 patients had hypertension . All patients had normal renal function ( creatinine ≤ 1.0 mg/dL ) , and estimated glomerular filtration rate was 115.7 ± 16.5 mL/min/1.73 m2 . There were significant reductions in body weight , BMI , high-sensitivity C-reactive protein ( hs-CRP ) , and urine albumin-to-creatinine ratio ( ACR ) . There were positive correlations between delta hs-CRP and delta body weight ( r = 0.349 , p = 0.043 ) or delta body mass index ( BMI , r = 0.362 , p = 0.035 ) ; between hs-CRP and body weight ( r = 0.374 , p = 0.001 ) , BMI ( r = 0.431 , p suggests that BS can reduce albuminuria in patients with severe obesity and normal kidney function by reducing systemic inflammation"
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The purpose of this research was to up date the series of articles on evidence -based treatment for children and adolescents with attention deficit/hyperactivity disorder that have appeared in this journal ( Evans , Owens & Bunford , 2014 ; Pelham & Fabiano , 2008 ; Pelham , Wheeler , & Chronis , 1998 ) . We completed a systematic review of the literature published between 2012 and 2016 to establish levels of evidence for psychosocial treatments for these youth . We identified articles using criteria established by the Society of Clinical Child and Adolescent Psychology using keyword search es of abstract s and titles . Articles were classified according to a modified version of the Division 12 task force guidelines that was used in other review s in this series . The results revealed that findings are becoming increasingly nuanced with variations in levels of evidence related to ages of the children and characteristics of the specific treatment . In addition , we focused our critique on generalization of treatment effects across setting s and time and on sample diversity ( with regard to ethnicity and levels of parent education ) in relation to the population . Children of parents with higher levels of education than average appear to be overrepresented in the literature . Implication s for future treatment development and evaluation and for dissemination research are discussed
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"OBJECTIVE Impairments associated with attention-deficit/hyperactivity disorder ( ADHD ) and noncompliance are prevalent in children with autism spectrum disorder ( ASD ) . However , ADHD response to stimulants is well below rates in typically developing children , with frequent side effects . Group studies of treatments for noncompliance are rare in ASD . We examined individual and combined-effectiveness of atomoxetine ( ATX ) and parent training ( PT ) for ADHD symptoms and noncompliance . METHOD In a 3-site , 10-week , double-blind , 2 × 2 trial of ATX and PT , 128 children ( ages 5 - 14 years ) with ASD and ADHD symptoms were r and omized to ATX , ATX+PT , placebo+PT , or placebo . ATX was adjusted to optimal dose ( capped at 1.8 mg/kg/day ) over 6 weeks and maintained for 4 additional weeks . Nine PT sessions were provided . Primary outcome measures were the parent-rated DSM ADHD symptoms on the Swanson , Nolan and Pelham ( SNAP ) scale and Home Situations Question naire ( HSQ ) . RESULTS On the SNAP , ATX , ATX+PT and placebo+PT were each superior to placebo ( effect sizes 0.57 - 0.98 ; p values of .0005 , .0004 , and .025 , respectively ) . For noncompliance , ATX and ATX+PT were superior to placebo ( effect sizes 0.47 - 0.64 ; p values .03 and .0028 , respectively ) . ATX was associated with decreased appetite but was otherwise well tolerated . CONCLUSION Both ATX and PT result ed in significant improvement on ADHD symptoms , whereas ATX ( both alone and combined with PT ) was associated with significant decreases on measures of noncompliance . ATX appears to have a better side effects profile than psychostimulants in the population with ASD . CLINICAL TRIAL REGISTRATION INFORMATION Atomoxetine , Placebo and Parent Management Training in Autism ; http:// clinical trials.gov/ ; NCT00844753",
"Fathers , in general , have been underrepresented in studies of parent training outcome for children with attention deficit hyperactivity disorder ( ADHD ) , and the present study aim ed to investigate the efficacy of a behavioral parent training program developed expressly for fathers . The present investigation r and omly assigned 55 fathers of children ages 6 to 12 with ADHD to the Coaching Our Acting-out Children : Heightening Essential Skills ( COACHES ) program or a waitlist control group . Outcomes for the study included objective observations of parent behaviors and parent ratings of child behavior . Results indicated that fathers in the COACHES group reduced their rates of negative talk and increased rates of praise as measured in parent – child observations , and father ratings of the intensity of problem behaviors were reduced , relative to the waitlist condition . Groups did not differ on observations of use of comm and s or father ratings of child behavior problems . Untreated mothers did not significantly improve on observational measures or behavioral ratings . This study provides preliminary evidence for the efficacy of the COACHES parenting program for fathers of children with ADHD . Results are cast in light of the larger literature on behavioral parent training for ADHD as well as how to best work with fathers of children with ADHD in treatment context",
"This study examined the individual and combined effects of two nonpharmacological treatments for attention deficit/hyperactivity disorder ( ADHD ) : Cogmed working memory training ( CWMT ) for adolescents and behavioral parent training ( BPT ) for mothers . Ninety-one adolescents ( ages 11–15 ) and their mothers were r and omized to one of four CWMT and BPT treatment and active control ( placebo ) group combinations of 5-week interventions . At pre- and posttest , mothers and teachers completed rating forms , and adolescents completed neuropsychological measures of working memory ( WM ) . Individual intervention effects showed that treatment CWMT significantly improved WM spans , whereas there were no significant differences for treatment or control BPT on reports of parent-related outcomes . Combined treatment effects indicated an overall pattern of greatest improvements for the control CWMT/treatment BPT group , as compared to the other three groups , on adolescent WM deficit , behavioral regulation problems , and global executive deficit . Most significant effects for outcomes were main effects of improvements over time . A combination of CWMT and BPT did not result in increased treatment gains . However , potential effects of combined treatment may have been masked by greater perceived benefits arising from lack of struggle in the nonadaptive , CWMT active control condition . Future combined intervention research should focus on specific , theoretically driven WM deficits among individuals with ADHD , should include possible adaptations to the st and ard CWMT program , should examine effectiveness of cognitive treatments combined with context ual interventions and should utilize appropriate control groups to fully underst and the unique and combined effects of interventions",
"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 )",
"We investigated whether parenting and child behavior improve following psychosocial treatment for Attention-Deficit/Hyperactivity Disorder , Predominantly Inattentive Presentation ( ADHD-I ) and whether parenting improvements mediate child outcomes . We analyzed data from a r and omized clinical trial investigating the efficacy of a multicomponent psychosocial intervention ( Child Life and Attention Skills , CLAS , n = 74 ) in comparison to Parent-Focused Treatment ( PFT , n = 74 ) and treatment as usual ( TAU , n = 51 ) for youth with ADHD-I ( average child age = 8.6 years , range 7–11 years , 58 % boys ) . Child and parent/family functioning were assessed prior to treatment , immediately following treatment , and at follow-up into the subsequent school year using parent and teacher reports of inattention , organization , social skills , academic competency ( teachers only ) , parenting daily hassles , and positive and negative parenting behaviors ( parents only ) . Both treatment groups improved on negative parenting and home impairment , but only CLAS families also improved on positive parenting as well as academic impairment . Improvements in positive and negative parenting mediated treatment effects on child impairment independent of improvements in child inattention , implicating parenting as an important mechanism of change in psychosocial treatment for ADHD-I. Further , whereas parent-focused training produces improvements in negative parenting and impairment at home for children with ADHD-I , a multicomponent approach ( incorporating child skills training and teacher consultation ) more consistently produces improvements at school and in positive parenting , which may contribute to improvements in social skills into the next school year",
"OBJECTIVE In the intent-to-treat analysis of the Multimodal Treatment Study of Children With ADHD ( MTA ) , the effects of medication management ( MedMgt ) , behavior therapy ( Beh ) , their combination ( Comb ) , and usual community care ( CC ) differed at 14 and 24 months due to superiority of treatments that used the MTA medication algorithm ( Comb+MedMgt ) over those that did not ( Beh+CC ) . This report examines 36-month outcomes , 2 years after treatment by the study ended . METHOD For primary outcome measures ( attention-deficit/hyperactivity disorder [ ADHD ] and oppositional defiant disorder [ ODD ] symptoms , social skills , reading scores , impairment , and diagnostic status ) , mixed-effects regression models and orthogonal contrasts examined 36-month outcomes . RESULTS At 3 years , 485 of the original 579 subjects ( 83.8 % ) participated in the follow-up , now at ages 10 to 13 years , ( mean 11.9 years ) . In contrast to the significant advantage of MedMgt+Comb over Beh+CC for ADHD symptoms at 14 and 24 months , treatment groups did not differ significantly on any measure at 36 months . The percentage of children taking medication > 50 % of the time changed between 14 and 36 months across the initial treatment groups : Beh significantly increased ( 14 % to 45 % ) , MedMed+Comb significantly decreased ( 91 % to 71 % ) , and CC remained constant ( 60%-62 % ) . Regardless of their treatment use changes , all of the groups showed symptom improvement over baseline . Notably , initial symptom severity , sex ( male ) , comorbidity , public assistance , and parental psychopathology ( ADHD ) did not moderate children 's 36-month treatment responses , but these factors predicted worse outcomes over 36 months , regardless of original treatment assignment . CONCLUSIONS By 36 months , the earlier advantage of having had 14 months of the medication algorithm was no longer apparent , possibly due to age-related decline in ADHD symptoms , changes in medication management intensity , starting or stopping medications altogether , or other factors not yet evaluated",
"Behavioral parent training is an efficacious treatment for attention-deficit/hyperactivity disorder ( ADHD ) . However , single-mother households are at high risk for poor outcomes during and following behavioral parent training . This study r and omly assigned cohorts of 120 single mothers of children ( ages 5–12 years ) with ADHD to a waitlist control group , a traditional behavioral parent training program , or an enhanced behavioral parent training program — the Strategies to Enhance Positive Parenting ( STEPP ) program . Intent-to-treat analysis demonstrated benefits of participating in behavioral parent training , in general , and the STEPP program more specifically at immediate posttreatment on child and parental functioning . Moreover , the STEPP program result ed in increased engagement to treatment . However , results indicated that behavioral parent training does not normalize behavior for most children and treatment gains are not maintained",
"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",
"Abstract During a 3-month intervention program , 43 hyperactive children and their families were assessed and followed . Families were r and omly assigned to one of three groups : parent training in behavior modification while the child was administered a placebo ; parent training plus methylpheni date ; and methylpheni date only . All groups showed improved home and school behavior . However , only with medication were there also gains on measures of attention and impulse control . The results also revealed greater improvement in the area of academic achievement and classroom behavior in the medication groups as compared with children on placebo . There was no evidence of significant benefit from the addition of parent training to the administration of medication",
"There are no empirically supported psychosocial treatments for adolescents with attention-deficit hyperactivity disorder ( ADHD ) . This study examined the treatment benefits of the Challenging Horizons Program ( CHP ) , a psychosocial treatment program design ed to address the impairment and symptoms associated with this disorder in young adolescents . In addition to evaluating social and academic functioning outcomes , two critical questions from previous studies pertaining to the timing , duration , and family involvement in treatment were addressed . Forty-nine students recruited in two cohorts were r and omly assigned to receive either the CHP or a community care condition . Outcomes suggested that students who received the CHP improved compared to students in the control condition on measures of symptoms and impairment . Implication s related to timing , duration , and family involvement are reported , as well as recommendations for future studies",
"OBJECTIVE More than 50 % of mothers of children with attention-deficit/hyperactivity disorder ( ADHD ) have a lifetime history of major depressive disorder ( MDD ) . Maternal depressive symptoms are associated with impaired parenting and predict adverse developmental and treatment outcomes for children with ADHD . For these reasons , we developed and examined the preliminary efficacy of an integrated treatment targeting parenting and depressive symptoms for mothers of children with ADHD . This integrated intervention incorporated elements of 2 evidence -based treatments : behavioral parent training ( BPT ) and cognitive behavioral depression treatment . METHOD Ninety-eight mothers with at least mild depressive symptoms were r and omized to receive either st and ard BPT ( n = 51 ) or the integrated parenting intervention for ADHD ( IPI-A ; n = 47 ) . Participants were assessed at baseline , posttreatment , and 3- to 6-month follow-up on measures of ( a ) self-reported maternal depressive symptoms , ( b ) observed positive and negative parenting , and ( c ) observed and mother-reported child disruptive behavior and mother-reported child and family impairment . RESULTS The IPI-A produced effects of small to moderate magnitude relative to BPT on maternal depressive symptoms , observed negative parenting , observed child deviance , and child impairment at posttreatment and on maternal depressive symptoms , child disruptive behavior , child impairment and family functioning at follow-up . Contrary to expectations , the BPT group demonstrated moderate to large effects relative to IPI-A on observed positive parenting at follow-up . CONCLUSIONS This treatment development study provides encouraging preliminary support for the integrated intervention targeting parenting and depressive symptoms in mothers of children with ADHD . Future studies should examine whether this integrated intervention improves long-term developmental outcomes for children with ADHD . ( PsycINFO Data base Record ( c ) 2013 APA , all rights reserved )",
"BACKGROUND The ' New Forest Parenting Package ' ( NFPP ) , an 8-week home-based intervention for parents of preschoolers with attention-deficit/hyperactivity disorder ( ADHD ) , fosters constructive parenting to target ADHD-related dysfunctions in attention and impulse control . Although NFPP has improved parent and laboratory measures of ADHD in community sample s of children with ADHD-like problems , its efficacy in a clinical sample , and relative to an active treatment comparator , is unknown . The aims are to evaluate the short- and long-term efficacy and generalization effects of NFPP compared to an established clinic-based parenting intervention for treating noncompliant behavior [ ' Helping the Noncompliant Child ' ( HNC ) ] in young children with ADHD . METHODS A r and omized controlled trial with three parallel arms was the design for this study . A total of 164 3 - 4-year-olds , 73.8 % male , meeting DSM-IV ADHD diagnostic criteria were r and omized to NFPP ( N = 67 ) , HNC ( N = 63 ) , or wait-list control ( WL , N = 34 ) . All participants were assessed at post-treatment . NFPP and HNC participants were assessed at follow-up in the next school year . Primary outcomes were ADHD ratings by teachers blind to and uninvolved in treatment , and by parents . Secondary ADHD outcomes included clinician assessment s , and laboratory measures of on-task behavior and delay of gratification . Other outcomes included parent and teacher ratings of oppositional behavior , and parenting measures . ( Trial name : Home-Based Parent Training in ADHD Preschoolers ; Registry : Clinical Trials.gov Identifier : NCT01320098 ; URL : http://www/ clinical trials.gov/ct2/show/NCT01320098 ) . RESULTS In both treatment groups , children 's ADHD and ODD behaviors , as well as aspects of parenting , were rated improved by parents at the end of treatment compared to controls . Most of these gains in the children 's behavior and in some parenting practice s were sustained at follow-up . However , these parent-reported improvements were not corroborated by teacher ratings or objective observations . NFPP was not significantly better , and on a few outcomes significantly less effective , than HNC . CONCLUSIONS The results do not support the cl aim that NFPP addresses putative dysfunctions underlying ADHD , bringing about generalized change in ADHD , and its underpinning self-regulatory processes . The findings support documented difficulties in achieving generalization across nontargeted setting s , and the importance of using blinded measures to provide meaningful assessment s of treatment effects",
"Two family therapies were compared using teens with attention-deficit/hyperactivity disorder . Ninety-seven families were assigned to either 18 sessions of problem-solving communication training ( PSCT ) alone or behavior management training ( BMT ) for 9 sessions followed by PSCT for 9 sessions ( BMT/PSCT ) . Both treatments demonstrated significant improvement in ratings of parent-teen conflicts at the midpoint but did not differ . By posttreatment , both produced improvement on ratings and observations but did not differ . Significantly more families dropped out of PSCT alone than out of BMT/PSCT . At most , 23 % of families showed reliable change either by midpoint or by posttreatment , with no differences between therapies . Yet 31%-70 % of families were normalized . Group-level change and normalization rates support treatment efficacy , whereas indices of reliable change are less impressive",
"The goal of this study was to compare the effects of before school physical activity ( PA ) and sedentary classroom-based ( SC ) interventions on the symptoms , behavior , moodiness , and peer functioning of young children ( Mage = 6.83 ) at risk for attention-deficit/hyperactivity disorder ( ADHD-risk ; n = 94 ) and typically developing children ( TD ; n = 108 ) . Children were r and omly assigned to either PA or SC and participated in the assigned intervention 31 min per day , each school day , over the course of 12 weeks . Parent and teacher ratings of ADHD symptoms ( inattention , hyperactivity/impulsivity ) , oppositional behavior , moodiness , behavior toward peers , and reputation with peers , were used as dependent variables . Primary analyses indicate that the PA intervention was more effective than the SC intervention at reducing inattention and moodiness in the home context . Less conservative follow-up analyses within ADHD status and intervention groups suggest that a PA intervention may reduce impairment associated with ADHD-risk in both home and school domains ; interpretive caution is warranted , however , given the liberal approach to these analyses . Unexpectedly , these findings also indicate the potential utility of a before school SC intervention as a tool for managing ADHD symptoms . Inclusion of a no treatment control group in future studies will enable further underst and ing of PA as an alternative management strategy for ADHD symptoms",
"Sixty-one 12- to 18-year-olds were r and omized to 8 - 10 sessions of behavior management training ( n = 20 ) , problem-solving and communication training ( n = 21 ) , or structural family therapy ( n = 20 ) . Families were assessed at pre- and posttreatment and 3-month follow-up . All treatments result ed in significant reductions in negative communication , conflicts , and anger during conflicts and improved ratings of school adjustment , reduced internalizing and externalizing symptoms , and decreased maternal depressive symptoms . Most outcomes remained stable between posttreatment and follow-up , and some continued to improve over this time . Despite group improvements , analyses of clinical ly significant change and clinical recovery within Ss showed that only 5 - 30 % reliably improved from treatment and only 5 - 20 % recovered following treatment . The three treatments did not differ in these rates",
"The efficacy of the Incredible Years parent and child training programs is established in children diagnosed with oppositional defiant disorder but not among young children whose primary diagnosis is attention-deficit/hyperactivity disorder ( ADHD ) . We conducted a r and omized control trial evaluating the combined parent and child program interventions among 99 children diagnosed with ADHD ( ages 4–6 ) . Mother reported significant treatment effects for appropriate and harsh discipline , use of physical punishment , and monitoring , whereas fathers reported no significant parenting changes . Independent observations revealed treatment effects for mothers ' praise and coaching , mothers ' critical statements , and child total deviant behaviors . Both mothers and fathers reported treatment effects for children 's externalizing , hyperactivity , inattentive and oppositional behaviors , and emotion regulation and social competence . There were also significant treatment effects for children 's emotion vocabulary and problem-solving ability . At school teachers reported treatment effects for externalizing behaviors and peer observations indicated improvements in treated children 's social competence",
"A pilot r and omized clinical trial was conducted to examine the initial efficacy of Pay Attention ! , an intervention training sustained , selective , alternating , and divided attention , in children diagnosed with Attention-Deficit/Hyperactivity Disorder ( ADHD ) . After a diagnostic and baseline evaluation , school-aged children with ADHD were r and omized to receive 16 bi-weekly sessions of Pay Attention ! ( n=54 ) or to a waitlist control group ( n=51 ) . Participants completed an outcome evaluation approximately 12 weeks after their baseline evaluation . Results showed significant treatment effects for parent and clinician ratings of ADHD symptoms , child self-report of ability to focus , and parent ratings of executive functioning . Child performance on neuropsychological tests showed significant treatment-related improvement on strategic planning efficiency , but no treatment effects were observed on other neuropsychological outcomes . Treatment effects were also not observed for teacher ratings of ADHD . These data add to a growing body of literature supporting effects of cognitive training on attention and behavior , however , additional research is warranted",
"Few behavioral parent training ( BPT ) treatment studies for attention-deficit/hyperactivity disorder ( ADHD ) have included and measured outcomes with fathers . In this study , fathers were r and omly assigned to attend a st and ard BPT program or the Coaching Our Acting-Out Children : Heightening Essential Skills ( COACHES ) program . The COACHES program included BPT plus sports skills training for the children and parent-child interactions in the context of a soccer game . Groups did not differ at baseline , and father ratings of treatment outcome indicated improvement at posttreatment for both groups on measures of child behavior . There was no significant difference between groups on ADHD-related measures of child outcome . However , at posttreatment , fathers who participated in the COACHES program rated children as more improved , and they were significantly more engaged in the treatment process ( e.g. , greater attendance and arrival on time at sessions , more homework completion , greater consumer satisfaction ) . The implication s for these findings and father-related treatment efforts are discussed",
"Objective : To examine the efficacy of a Cognitive-Functional ( Cog-Fun ) intervention for children with ADHD . Method : R and om allocation of 107 children to study or control groups preceded 10 parent – child weekly Cog-Fun sessions emphasizing executive strategy training in games and daily activities . Controls received treatment after crossover . Study participants were followed up 3 months post-treatment . Outcomes included parent/teacher ratings of executive functions , ADHD symptoms , and parent ratings of quality of life . Results : Eight children withdrew prior to treatment . All children in both groups who began treatment completed it . Mixed effects ANOVA revealed significant Time × Group interaction effects on all parent-reported outcomes . Treatment effects were moderate to large , replicated after crossover in the control group and not moderated by medication . Parent-reported treatment gains in the study group were maintained at follow-up . No significant Time × Group interaction effects were found on teacher outcomes . Conclusion : Cog-Fun occupational therapy ( OT ) intervention shows positive context -specific effects on parent , but not teacher , ratings",
"OBJECTIVE To determine the efficacy of group cognitive-behavioral therapy ( CBT ) on adolescents with attention-deficit/hyperactivity disorder ( ADHD ) who were in pharmacological treatment but still had persistent symptoms . METHOD We conducted a multicenter , r and omized , rater-blinded , controlled trial between April 2012 and May 2014 in a cohort of 119 adolescents ( 15 - 21 years of age ) . Participants were r and omly assigned to 12 manualized group CBT sessions ( n = 45 ) or a waiting list control group ( n = 44 ) . Primary outcomes were assessed by a blinded evaluator ( ADHD Rating Scale [ ADHD-RS ] , Clinical Global Impression Scale for Severity [ CGI-S ] , Global Assessment of Functioning [ GAF ] ) before and after treatment , as well as by self-report and parent informant ratings . RESULTS Of the initial 119 participants enrolled , 89 completed treatment . A mixed-effects model analysis revealed that participants who were assigned to the group CBT sessions experienced significantly reduced ADHD symptoms compared to the control group ( ADHD-RS Adolescent : -7.46 , 95 % CI = -9.56 to -5.36 , p CGI-S Self-Report : -0.68 , 95 % CI = -0.98 to -0.39 , p Clinician : -0.79 , 95 % CI = -0.95 to -0.62 , p 7.71 ) . Functional impairment decreased significantly in the CBT group according to parents ( Weiss Functional Impairment Scale -4.02 , 95 % CI = -7.76 to -0.29 , p Group CBT associated with pharmacological treatment is an efficacious intervention for reducing ADHD symptoms and functional impairment in adolescents . Clinical trial registration information-CBT Group for Adolescents With ADHD : a R and omized Controlled Trial ; http:// clinical trials.gov/ ; NCT02172183",
"BACKGROUND Until now , working memory training has not reached sufficient evidence as effective treatment for ADHD core symptoms in children with ADHD ; for young children with ADHD , no studies are available . To this end , a triple-blind , r and omized , placebo-controlled study was design ed to assess the efficacy of Cogmed Working Memory Training ( CWMT ) in young children with ADHD . METHODS Fifty-one children ( 5 - 7 years ) with a DSM-IV-TR diagnosis of ADHD ( without current psychotropic medication ) were r and omly assigned to the active ( adaptive ) or placebo ( nonadaptive ) training condition for 25 sessions during 5 weeks . The compliance criterion ( > 20 sessions ) was met for 47 children . The primary outcome measure concerned the core behavioural symptoms of ADHD , measured with the ADHD Rating Scale IV ( ADHD-RS ) . Secondary outcome measures were neurocognitive functioning , daily executive functioning , and global clinical functioning . The influence of the increase in difficulty level ( Index-Improvement ) for the treatment group was also analysed . Clinical trial registration information - ' Working Memory Training in Young ADHD Children ' ; www . clinical trials.gov ; NCT00819611 . RESULTS A significant improvement in favour of the active condition was found on a verbal working memory task ( p = .041 ; adapted Digit Span WISC-III , backward condition ) . However , it did not survive correction for multiple testing . No significant treatment effect on any of the primary or other secondary outcome measurements was found . The Index-Improvement significantly contributed to ADHD-RS and the Behavior Rating Inventory of Executive Function , both rated by the teacher , but revealed no significant group difference . CONCLUSIONS This study failed to find robust evidence for benefits of CMWT over the placebo training on behavioural symptoms , neurocognitive , daily executive , and global clinical functioning in young children with ADHD",
"Behavioral and pharmacological treatments for children with attention deficit/hyperactivity disorder ( ADHD ) were evaluated to address whether endpoint outcomes are better depending on which treatment is initiated first and , in case of insufficient response to initial treatment , whether increasing dose of initial treatment or adding the other treatment modality is superior . Children with ADHD ( ages 5–12 , N = 146 , 76 % male ) were treated for 1 school year . Children were r and omized to initiate treatment with low doses of either ( a ) behavioral parent training ( 8 group sessions ) and brief teacher consultation to establish a Daily Report Card or ( b ) extended-release methylpheni date ( equivalent to .15 mg/kg/dose bid ) . After 8 weeks or at later monthly intervals as necessary , insufficient responders were rer and omized to secondary interventions that either increased the dose/intensity of the initial treatment or added the other treatment modality , with adaptive adjustments monthly as needed to these secondary treatments . The group beginning with behavioral treatment displayed significantly lower rates of observed classroom rule violations ( the primary outcome ) at study endpoint and tended to have fewer out-of-class disciplinary events . Further , adding medication secondary to initial behavior modification result ed in better outcomes on the primary outcomes and parent/teacher ratings of oppositional behavior than adding behavior modification to initial medication . Normalization rates on teacher and parent ratings were generally high . Parents who began treatment with behavioral parent training had substantially better attendance than those assigned to receive training following medication . Beginning treatment with behavioral intervention produced better outcomes overall than beginning treatment with medication",
"BACKGROUND Cogmed Working Memory Training ( CWMT ) has received considerable attention as a promising intervention for the treatment of Attention-Deficit/Hyperactivity Disorder ( ADHD ) in children . At the same time , method ological weaknesses in previous clinical trials call into question reported efficacy of CWMT . In particular , lack of equivalence in key aspects of CWMT ( i.e. , contingent reinforcement , time-on-task with computer training , parent-child interactions , supportive coaching ) between CWMT and placebo versions of CWMT used in previous trials may account for the beneficial outcomes favoring CWMT . METHODS Eighty-five 7- to 11-year old school-age children with ADHD ( 66 male ; 78 % ) were r and omized to either st and ard CWMT ( CWMT Active ) or a well-controlled CWMT placebo condition ( CWMT Placebo ) and evaluated before and 3 weeks after treatment . Dependent measures included parent and teacher ratings of ADHD symptoms ; objective measures of attention , activity level , and impulsivity ; and psychometric indices of working memory and academic achievement ( Clinical trial title : Combined cognitive remediation and behavioral intervention for the treatment of Attention-Deficit/Hyperactivity Disorder ; http:// clinical trials.gov/ct2/show/NCT01137318 ) . RESULTS CWMT Active participants demonstrated significantly greater improvements in verbal and nonverbal working memory storage , but evidence d no discernible gains in working memory storage plus processing/manipulation . In addition , no treatment group differences were observed for any other outcome measures . CONCLUSIONS When a more rigorous comparison condition is utilized , CWMT demonstrates effects on certain aspects of working memory in children with ADHD ; however , CWMT does not appear to foster treatment generalization to other domains of functioning . As such , CWMT should not be considered a viable treatment for children with ADHD",
"OBJECTIVE To test cognitive behavioral therapy ( CBT ) for persistent attention-deficit hyperactivity disorder ( ADHD ) symptoms in a sample of medication-treated adolescents . METHODS Forty-six adolescents ( ages 14 - 18 ) , with clinical ly significant ADHD symptoms despite stable medication treatment were r and omly assigned to receive CBT for ADHD or wait list control in a cross-over design . Twenty-four were r and omized to CBT , 22 to wait list , and 15 crossed-over from wait list to CBT . A blind independent evaluator ( IE ) rated symptom severity on the ADHD Current Symptom Scale , by adolescent and parent report , and rated each subject using the Clinical Global Impression Severity Scale ( CGI ) , a global measure of distress and impairment . These assessment s were performed at baseline , 4-months ( post-CBT or post wait list ) , and 8-months ( post-treatment for those originally assigned to the wait list condition and 4-month follow-up for those originally assigned to CBT ) . TRIAL REGISTRATION http:// clinical trials.gov/show/NCT01019252 . RESULTS Using all available data , mixed effects modeling , and pooling for the wait list cross-over , participants who received CBT received a mean score 10.93 lower on the IE-rated parent assessment of symptom severity ( 95 % CI : -12.93 , -8.93 ; p IE-rated adolescent assessment of symptom severity ( 95 % CI : -7.21 , -3.28 ; p CGI ( 95 % CI : -1.39 , -.94 ; p CBT by parent ( 50 % vs. 18 % , p = .00 ) and adolescent ( 58 % vs. 18 % p = .02 ) report . CONCLUSIONS This study demonstrates initial efficacy of CBT for adolescents with ADHD who continued to exhibit persistent symptoms despite medications",
"Background The need for accessible and motivating treatment approaches within mental health has led to the development of an Internet-based serious game intervention ( called “ Plan-It Comm and er ” ) as an adjunct to treatment as usual for children with attention-deficit/hyperactivity disorder ( ADHD ) . Objective The aim was to determine the effects of Plan-It Comm and er on daily life skills of children with ADHD in a multisite r and omized controlled crossover open-label trial . Methods Participants ( N=170 ) in this 20-week trial had a diagnosis of ADHD and ranged in age from 8 to 12 years ( male : 80.6 % , 137/170 ; female : 19.4 % , 33/170 ) . They were r and omized to a serious game intervention group ( group 1 ; n=88 ) or a treatment-as-usual crossover group ( group 2 ; n=82 ) . Participants r and omized to group 1 received a serious game intervention in addition to treatment as usual for the first 10 weeks and then received treatment as usual for the next 10 weeks . Participants r and omized to group 2 received treatment as usual for the first 10 weeks and crossed over to the serious game intervention in addition to treatment as usual for the subsequent 10 weeks . Primary ( parent report ) and secondary ( parent , teacher , and child self-report ) outcome measures were administered at baseline , 10 weeks , and 10-week follow-up . Results After 10 weeks , participants in group 1 compared to group 2 achieved significantly greater improvements on the primary outcome of time management skills ( parent-reported ; P=.004 ) and on secondary outcomes of the social skill of responsibility ( parent-reported ; P=.04 ) , and working memory ( parent-reported ; P=.02 ) . Parents and teachers reported that total social skills improved over time within groups , whereas effects on total social skills and teacher-reported planning/organizing skills were nonsignificant between groups . Within group 1 , positive effects were maintained or further improved in the last 10 weeks of the study . Participants in group 2 , who played the serious game during the second period of the study ( weeks 10 to 20 ) , improved on comparable domains of daily life functioning over time . Conclusions Plan-It Comm and er offers an effective therapeutic approach as an adjunct intervention to traditional therapeutic ADHD approaches that improve functional outcomes in daily life . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 62056259 ; http://www.controlled-trials.com/IS RCT N62056259 ( Archived by WebCite at http://www.webcitation.org/6eNsiTDJV )",
"OBJECTIVE This study evaluates a parent-teen skills-based therapy for attention deficit/hyperactivity disorder ( ADHD ) blended with motivational interviewing ( MI ) to enhance family engagement . Supporting Teens ' Autonomy Daily ( ST AND ) is an adolescent-specific treatment for ADHD that targets empirically identified adolescent ( i.e. , organization , time management , and planning , or OTP skills ) and parent-based ( i.e. , monitoring and contingency management ) mechanisms of long-term outcome through individual parent-teen sessions . METHOD The current r and omized trial ( N = 128 ) evaluates efficacy at posttreatment and 6-month follow-up . Participants were ethnically diverse teens ( 7.7 % non-Hispanic White , 10.8 % African American , 78.5 % Hispanic , 3.0 % other ) r and omly assigned to ST AND or Treatment As Usual ( TAU ) . RESULTS Primary findings were that ( 1 ) ST AND was delivered in an MI-adherent fashion and most families fully engaged in treatment ( 85 % completed ) ; ( 2 ) ST AND produced a range of significant acute effects on ADHD symptoms , OTP skills , homework behavior , parent-teen contracting , implementation of home privileges , parenting stress , and daily homework recording ; and ( 3 ) 6 months after treatment ceased , effects on ADHD symptom severity , OTP skills , and parenting stress maintained , while parent use of contracting and privilege implementation strategies , as well as teen daily homework recording and homework behavior gains , were not maintained . CONCLUSION Skills-based behavior therapy blended with MI is an acutely efficacious treatment for adolescents with ADHD although more work is needed to establish the nature of long-term effects . ( PsycINFO Data base",
"BACKGROUND An abnormality in long chain-polyunsaturated fatty acid ( LC-PUFA ) levels has been implicated in attention-deficit/hyperactivity disorder ( ADHD ) . Studies evaluating LC-PUFA supplementation for therapeutic efficacy in ADHD have shown mixed and , therefore , inconclusive results . METHODS Seventy-six male adolescents ( age 12 - 16 years , mean = 13.7 ) with ADHD were assessed for the effects of 12 weeks omega-3 and omega-6 supplements on biochemical and psychological outcomes in a r and omized , placebo-controlled , clinical trial . The primary outcome measure was change in the Conners ' Teacher Rating Scales ( CTRS ) following 12 weeks of supplementation of LC-PUFA or placebo . At baseline , the placebo and treatment groups had comparable levels of LC-PUFA as measured by red blood cell phosphatidylcholine . In the treatment group , supplementation enhanced eicosapentaenoic acid ( EPA ) , docosahexaenoic acid ( DHA ) , and total omega-3 fatty acid levels . RESULTS No superiority of LC-PUFAs to placebo was observed on the primary outcome . Further , there were no reliable treatment effects on aggression , impulsivity , depression , and anxiety . CONCLUSIONS Future studies should use larger sample sizes and longer supplementation period to detect small-modest effects for clinical recommendations in ADHD",
"Objective : Evidence indicates that children with Attention Deficit Hyperactivity Disorder ( ADHD ) experience acute and prolonged academic impairment and underachievement including marked difficulty with completing homework . This study is the first to examine the effects of behavioral , psychostimulant , and combined treatments on homework problems , which have been shown to predict academic performance longitudinally . Method : Children with ADHD ( ages 5–12 , N = 75 , 71 % male , 83 % Hispanic/Latino ) and their families were r and omly assigned to either behavioral treatment ( homework-focused parent training and a daily report card ; BPT + DRC ) or a waitlist control group . Children also participated in a concurrent psychostimulant crossover trial conducted in a summer treatment program . Children ’s objective homework completion and accuracy were measured as well as parent-reported child homework behaviors and parenting skills . Results : BPT + DRC had large effects on objective measures of homework completion and accuracy ( Cohen ’s ds from 1.40 to 2.21 , ps children ’s homework completion and accuracy ( the difference between passing and failing , on average ) , whereas long-acting stimulant medication result ed in limited and largely nonsignificant acute effects on homework performance",
"Decreased success at work and educational attainment by adulthood are of concern for children with ADHD given their widely documented academic difficulties ; however there are few studies that have examined this empirically and even fewer that have studied predictors and individual variability of these outcomes . The current study compares young adults with and without a childhood diagnosis of ADHD on educational and occupational outcomes and the predictors of these outcomes . Participants were from the Pittsburgh ADHD Longitudinal Study ( PALS ) , a prospect i ve study with yearly data collection . Significant group differences were found for nearly all variables such that educational and occupational attainment was lower for adults with compared to adults without histories of childhood ADHD . Despite the mean difference , educational functioning was wide-ranging . High school academic achievement significantly predicted enrollment in post-high school education and academic and disciplinary problems mediated the relationship between childhood ADHD and post-high school education . Interestingly , ADHD diagnosis and disciplinary problems negatively predicted occupational status while enrollment in post-high school education was a positive predictor . Job loss was positively predicted by a higher rate of academic problems and diagnosis of ADHD . This study supports the need for interventions that target the child and adolescent predictors of later educational and occupational outcomes in addition to continuing treatment of ADHD in young adulthood targeting developmentally appropriate milestones , such as completing post-high school education and gaining and maintaining stable employment",
"Introduction Executive functions ( EFs ) training interventions aim ed at ADHD-symptom reduction have yielded mixed results . Generally , these interventions focus on training a single cognitive domain ( e.g. , working memory [ WM ] , inhibition , or cognitive-flexibility ) . However , evidence suggests that most children with ADHD show deficits on multiple EFs , and that these EFs are largely related to different brain regions . Therefore , training multiple EFs might be a potentially more effective strategy to reduce EF-related ADHD symptoms . Methods Eighty-nine children with a clinical diagnosis of ADHD ( aged 8–12 ) were r and omized to either a full-active-condition where visuospatial WM , inhibition and cognitive-flexibility were trained , a partially-active-condition where inhibition and cognitive-flexibility were trained and the WM-training task was presented in placebo-mode , or to a full placebo-condition . Short-term and long-term ( 3-months ) effects of this gamified , 25-session , home-based computer-training were evaluated on multiple outcome domains . Results During training compliance was high ( only 3 % failed to meet compliance criteria ) . After training , only children in the full-active condition showed improvement on measures of visuospatial short-term-memory ( STM ) and WM . Inhibitory performance and interference control only improved in the full-active- and the partially-active condition . No Treatment-condition x Time interactions were found for cognitive-flexibility , verbal WM , complex-reasoning , nor for any parent- , teacher- , or child-rated ADHD behaviors , EF-behaviors , motivational behaviors , or general problem behaviors . Nonetheless , almost all measures showed main Time-effects , including the teacher-ratings . Conclusions Improvements on inhibition and visuospatial STM and WM were specifically related to the type of treatment received . However , transfer to untrained EFs and behaviors was mostly nonspecific ( i.e. , only interference control improved exclusively in the two EF training conditions ) . As such , in this multiple EF-training , mainly nonspecific treatment factors – as opposed to the specific effects of training EFs — seem related to far transfer effects found on EF and behavior . Trial Registration trialregister.nl NTR2728 . Registry name : improving executive functioning in children with ADHD : training executive functions within the context of a computer game ; registry number : NTR2728",
"The revised new forest parenting programme ( NFPP ) is an 8-week psychological intervention design ed to treat ADHD in preschool children by targeting , amongst other things , both underlying impairments in self-regulation and the quality of mother – child interactions . Forty-one children were r and omized to either the revised NFPP or treatment as usual conditions . Outcomes were ADHD and ODD symptoms measured using question naires and direct observation , mothers ’ mental health and the quality of mother – child interactions . Effects of the revised NFPP on ADHD symptoms were large ( effect size > 1 ) and significant and effects persisted for 9 weeks post-intervention . Effects on ODD symptoms were less marked . There were no improvements in maternal mental health or parenting behavior during mother – child interaction although there was a drop in mothers ’ negative and an increase in their positive comments during a 5-min speech sample . The small-scale trial , although limited in power and generalizability , provides support for the efficacy of the revised NFPP . The findings need to be replicated in a larger more diverse sample",
"OBJECTIVE This study evaluated the efficacy of the Child Life and Attention Skills ( CLAS ) program , a behavioral psychosocial treatment integrated across home and school , for youth with attention-deficit/hyperactivity disorder-inattentive type ( ADHD-I ) . METHOD In a 2-site r and omized controlled trial , 199 children ( ages 7 - 11 years ) were r and omized to CLAS ( N = 74 ) , parent-focused treatment ( PFT , N = 74 ) , or treatment as usual ( TAU , N = 51 ) . We compared groups on parent and teacher ratings of inattention symptoms , organizational skills , social skills , and global improvement at posttreatment and also at follow-up during the subsequent school year . RESULTS CLAS result ed in greater improvements in teacher-reported inattention , organizational skills , social skills , and global functioning relative to both PFT and TAU at posttreatment . Parents of children in CLAS reported greater improvement in organizational skills than PFT and greater improvements on all outcomes relative to TAU at posttreatment . Differences between CLAS and TAU were maintained at follow-up for most parent-reported measures but were not significant for teacher-reported outcomes . CONCLUSIONS These findings extend support for CLAS across 2 study sites , revealing that integrating parent , teacher , and child treatment components , specifically adapted for ADHD-I , is superior to parent training alone and to usual care . Direct involvement of teachers and children in CLAS appears to amplify effects at school and home and underscores the importance of coordinating parent , teacher , and child treatment components for cross- setting effects on symptoms and impairment associated with",
"OBJECTIVE Many geographic locations are without services and staff available to provide treatment for children with attention deficit hyperactivity disorder ( ADHD ) . This is a r and omized controlled trial to evaluate the effectiveness of group parent training on ADHD treatment delivered via videoconferencing . SUBJECTS AND METHODS Twenty-two subjects were enrolled in the study , with 9 subjects in the videoconference session ( treatment group ) and 13 in the face-to-face session ( control group ) . The parent child relationship question naire for child and adolescents ( PCQ-CA ) , V and erbilt assessment scales ( parent and teacher versions ) , children global assessment scale , clinical global impression-severity score , clinical global impression-improvement score , and social skills rating system assessed the effectiveness of the treatment . A Likert scale evaluated parents ' acceptance of the training modality . Our results showed that the parent training program significantly improved parents ' disciplinary practice s based on the PRQ-CA , parent ratings of ADHD , oppositional defiant disorder , and conduct disorder symptoms , and the children 's global functioning . RESULTS The treatment effects did not differ between the videoconference and face-to-face groups ; however , the videoconference group evidence d statistically greater improvement on the hyperactive symptoms of V and erbilt assessment scales . Our findings suggest that parent training through a videoconferencing modality may be as effective as face-to-face training and is well accepted by parents . CONCLUSIONS Parent training via videoconferencing may be an important tool for addressing ADHD in geographic locations that do not have access to appropriate treatment providers",
"OBJECTIVE The study compared the efficacy of 2 behavioral interventions to ameliorate organization , time management , and planning ( OTMP ) difficulties in 3rd- to 5th- grade children with attention-deficit/hyperactivity disorder ( ADHD ) . METHOD In a dual-site r and omized controlled trial , 158 children were assigned to organizational skills training ( OST ; N = 64 ) ; PATHKO , a performance-based intervention that precluded skills training ( N = 61 ) ; or a wait-list control ( WL , N = 33 ) . Treatments were 20 individual clinic-based sessions over 10 - 12 weeks . OST involved skills building provided primarily to the child . PATHKO trained parents and teachers to reinforce children contingently for meeting end-point target goals . Primary outcomes were the Children 's Organizational Skills Scales ( COSS-Parent , COSS-Teacher ) . Other relevant functional outcomes were assessed . Percentage of participants no longer meeting inclusion criteria for OTMP impairments informed on clinical significance . Assessment s occurred at post-treatment , 1-month post-treatment , and twice in the following school year . RESULTS OST was superior to WL on the COSS-P ( Cohen 's d = 2.77 ; p COSS-T ( d = 1.18 ; p ) , children 's COSS self-ratings , academic performance and proficiency , homework , and family functioning . OST was significantly better than PATHKO only on the COSS-P ( d = 0.63 ; p academic proficiency . Sixty percent of OST and PATHKO participants versus 3 % of controls no longer met OTMP inclusion criteria . Significant maintenance effects were found for both treatments . CONCLUSIONS Two distinct treatments targeting OTMP problems in children with ADHD generated robust , sustained functional improvements . The interventions show promise of clinical utility in children with ADHD and organizational deficits",
"OBJECTIVE Nonepisodic irritability is a common and impairing problem , leading to the development of the diagnoses severe mood dysregulation ( SMD ) and disruptive mood dysregulation disorder ( DMDD ) . No psychosocial therapies have been formally evaluated for either , with medication being the most common treatment . This study examined the feasibility and efficacy of a joint parent-child intervention for SMD . METHOD A total of 68 participants aged 7 to 12 years with attention-deficit/hyperactivity disorder ( ADHD ) and SMD were r and omly assigned to the 11-week therapy or community-based psychosocial treatment . All participants were first stabilized on psychostimulant medication by study physicians . Of the participants , 56 still manifested impairing SMD symptoms and entered the therapy phase . Masked evaluators assessed participants at baseline , midpoint , and endpoint , with therapy participants reassessed 6 weeks later . RESULTS All but 2 therapy participants attended the majority of sessions ( n = 29 ) , with families reporting high levels of satisfaction . The primary outcome of change in mood symptoms using the Mood Severity Index ( MSI ) did not reach significance except in the subset attending the majority of sessions ( effect size = 0.53 ) . Therapy was associated with significantly greater improvement in parent-rated irritability ( effect size = 0.63 ) . Treatment effects for irritability but not MSI diminished after therapy stopped . Little impact on ADHD symptoms was seen . Results may not be generalizable to youth with SMD and comorbidities different from those seen in this sample of children with ADHD , and are limited by the lack of a gold st and ard for measuring change in SMD symptoms . CONCLUSION While failing to significantly improve mood symptoms versus community treatment , the integrative therapy was found to be a feasible and efficacious treatment for irritability in participants with SMD and ADHD . CLINICAL TRIAL REGISTRATION INFORMATION Group-Based Behavioral Therapy Combined With Stimulant Medication for Treating Children With Attention Deficit Hyperactivity Disorder and Impaired Mood ; http:// clinical trials.gov/ ; NCT00632619",
"Adolescents with ADHD have planning problems , often affecting school- and social functioning . Evidence -based treatments for adolescents with ADHD are scarce and treatment drop-out rates are substantial . The effectiveness of two new , individual , short-term cognitive behavioral therapies ( CBT ) was investigated : One with an aim on improving planning skills and one solution-focused treatment ( SFT ) without such an aim . Motivational Interviewing elements were added to both treatments to enhance treatment compliance . In a multi-center r and omized clinical trial , 159 adolescents ( 12–17 years ) with ADHD were r and omly assigned to one of both treatments . Pre- , post- and 3-month follow-up data were gathered on five domains : Parent-rated ADHD , planning problems and executive functioning ( primary outcomes ) , neuropsychological measures of planning , comorbid symptoms , general functioning , and teacher measures . Attrition was low in both treatments ( 5 % ) . Adolescents improved significantly between pre- and post-test with large effect sizes on all domains . Improvements remained stable or continued to improve from post-test to follow-up , also when controlling for medication use . Marginally significant differences were found in favor of the planning-focused treatment : parents and therapists evaluated this treatment more positively than SFT and the planning-focused treatment showed more reduction of parent-rated planning problems . Two new CBTs with integrated motivational components were feasible and attrition was low . ADHD symptoms and co-existing problems of the adolescents improved from pre-test to 3 months after treatment . As the planning-focused treatment was evaluated more positive and had marginal additional beneficial effects to SFT , especially planning-focused CBT seems promising to fill the gap in available treatments for adolescents with ADHD",
"PURPOSE To evaluate the efficacy of combined methylpheni date and EEG feedback treatment for children with ADHD . METHODS Forty patients with ADHD were r and omly assigned to the combination group ( methylpheni date therapy and EEG feedback training ) or control group ( methylpheni date therapy and non-feedback attention training ) in a 1:1 ratio using the double-blind method . These patients , who met the DSM-IV diagnostic criteria and were aged between 7 and 16 years , had obtained optimal therapeutic effects by titrating the methylpheni date dose prior to the trial . The patients were assessed using multiple parameters at baseline , after 20 treatment sessions , after 40 treatment sessions , and in 6-month follow-up studies . RESULTS Compared to the control group , patients in the combination group had reduced ADHD symptoms and improved in related behavioural and brain functions . CONCLUSION The combination of EEG feedback and methylpheni date treatment is more effective than methylpheni date alone . The combined therapy is especially suitable for children and adolescents with ADHD who insufficiently respond to single drug treatment or experience drug side effects",
"In a r and omized controlled trial , neurofeedback ( NF ) training was found to be superior to a computerised attention skills training concerning the reduction of ADHD symptomatology ( Gevensleben et al. , 2009 ) . The aims of this investigation were to assess the impact of different NF protocol s ( theta/beta training and training of slow cortical potentials , SCPs ) on the resting EEG and the association between distinct EEG measures and behavioral improvements . In 72 ( of initially 102 ) children with ADHD , aged 8 - 12 , EEG changes after either a NF training ( n=46 ) or the control training ( n=26 ) could be studied . The combined NF training consisted of one block of theta/beta training and one block of SCP training , each block comprising 18 units of 50 minutes ( balanced order ) . Spontaneous EEG was recorded in a two-minute resting condition before the start of the training , between the two training blocks and after the end of the training . Activity in the different EEG frequency b and s was analyzed . In contrast to the control condition , the combined NF training was accompanied by a reduction of theta activity . Protocol -specific EEG changes ( theta/beta training : decrease of posterior-midline theta activity ; SCP training : increase of central -midline alpha activity ) were associated with improvements in the German ADHD rating scale . Related EEG-based predictors were obtained . Thus , differential EEG patterns for theta/beta and SCP training provide further evidence that distinct neuronal mechanisms may contribute to similar behavioral improvements in children with ADHD",
"OBJECTIVE Most children with mental health disorders do not receive timely care because of access barriers . These initial trials aim ed to determine whether distance interventions provided by nonprofessionals could significantly decrease the proportion of children diagnosed with disruptive behavior or anxiety disorders compared with usual care . METHOD In three practical r and omized controlled trials , 243 children ( 80 with oppositional-defiant , 72 with attention-deficit/hyperactivity , and 91 with anxiety disorders ) were stratified by DSM-IV diagnoses and r and omized to receive the Strongest Families intervention ( treatment ) or usual care ( control ) . Assessment s were blindly conducted and evaluated at 120 , 240 , and 365 days after r and omization . The intervention consisted of evidence -based participant material s ( h and books and videos ) and weekly telephone coach sessions . The main outcome was mental health diagnosis change . RESULTS Intention-to-treat analysis showed that for each diagnosis significant treatment effects were found at 240 and 365 days after r and omization . Moreover , in the overall analysis significantly more children were not diagnosed as having disruptive behavior or anxiety disorders in the treatment group than the control group ( 120 days : χ(2)(1 ) = 13.05 , p with usual care , telephone-based treatments result ed in significant diagnosis decreases among children with disruptive behavior or anxiety . These interventions hold promise to increase access to mental health services . CLINICAL TRIAL REGISTRATION INFORMATION Strongest Families : Pediatric Disruptive Behaviour Disorder , http://www . clinical trials.gov , NCT00267579 ; Strongest Families : Pediatric Attention-Deficit/Hyperactivity Disorder , http://www . clinical trials.gov , NCT00267605 ; and Strongest Families : Pediatric Anxiety , http://www . clinical trials.gov , NCT00267566",
"Objective : This pilot study tested the short- and long-term efficacy ( 9 weeks follow-up ) of an executive functioning ( EF ) remediation training with game elements for children with ADHD in an outpatient clinical setting , using a r and omized controlled wait-list design . Furthermore , in a sub sample , that is , those treated with methylpheni date , additive effects of the EF training were assessed . Method : A total of 40 children ( aged 8 - 12 years ) were r and omized to the EF training or wait-list . The training consisted of a 25-session training of inhibition , cognitive flexibility , and working memory . Treatment outcome was assessed by parent- and teacher-rated EF , ADHD , oppositional deviant disorder , and conduct disorder symptoms . Results : Children in the EF training showed significantly more improvement than those in the wait-list condition on parent-rated EF and ADHD behavior in the total sample and in the sub sample treated with methylpheni date . Effects were maintained at follow-up . Conclusion : This pilot study shows promising evidence for the efficacy of an EF training with game elements",
"The Strategies to Enhance Positive Parenting ( STEPP ) program , an enhanced behavioral parent training ( BPT ) intervention , was developed to improve engagement in and outcomes following treatment for single-mother families of school-age youth with attention-deficit/hyperactivity disorder ( ADHD ) . A previous r and omized clinical trial of the STEPP program demonstrated that the intervention result ed in statistically significant improvements at the group-level in child oppositional behavior , various areas of child impairment , parental stress , and parenting behavior , relative to a wait-list control condition and a traditional BPT group . Despite benefits at the group-level , little is known about outcomes at the individual-level of enhanced BPT relative to traditional BPT for various child- and parent-level outcomes . The current study compares the extent to which traditional BPT and the STEPP program result in reliable change and recovery across various child- and parent-level outcomes in a sample of 80 , 5–12 year old youth with ADHD ( 70 % male ) . Analyses demonstrated the benefit of participating in either BPT treatment ; and participation in the STEPP program compared to traditional BPT was associated with only minimal incremental clinical benefit . Results , as well as clinical and research implication s for assessment and treatment of high-risk families of youth with ADHD enrolled in BPT are discussed"
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In an early view issue of this journal , Yu and co-workers ( 1 ) published a systematic review and meta- analysis about the mutual relationship between obesity and intelligence quotient ( IQ ) . The authors observed that a lower IQ score in childhood was associated with obesity in later adulthood . Although it is not possible to definitively rule out reverse causation in the IQ – obesity relationship , two main mechanisms have been put forward by the authors that could explain why a low IQ has been found to be a predictor of obesity . First , higher intelligence may reduce the risk of obesity by promoting more healthful behaviours . For example , data from a cohort study showed that children with higher mental ability scores reported significantly more frequent consumption of fruit and vegetables and more high-intensity physical activity participation in adulthood ( 2 ) . Second , higher childhood IQ may predict favourable socioeconomic positions later in life . The authors even suggested in this case increasing educational levels as a means of reducing obesity . Beyond this interpretation , our physiological vision and experience in the field leads us to extend and /or propose another explanation . Recent data from our research group support the relevance of considering mental work and its related cognitive effort as a potential mediator of the relationship . Indeed , we have recently reported results from two experimental studies showing that mental work up-regulates appetite-stimulating hormones and promotes overconsumption of food ( 3,4 ) . Furthermore , a careful examination of our data revealed that when the subjects were categorized on the basis of the mental workload intensity , those for whom the intensity of the mental effort was greater significantly increased their spontaneous food intake as compared with those characterized by a less strenuous cognitive effort . In other words , the harder we think the more we eat . This hyperphagic effect of intense thinking was also accompanied by more plasma glucose instabilities ( 5 ) . The fluctuations in plasma glucose levels that were observed are in agreement with the literature showing that a period of intense cognitive processing leads to a measurable decrease in levels of blood glucose ( 6 ) , a fall that has also been associated with feeling less energetic ( 7 ) . Accordingly , food intake might be perceived as a strategy for allowing the individual to recover optimal body functioning . These observations are also relevant for students having hard times to learn at school and for whom study ing is arduous and mentally challenging . On the basis of our observations , we find it realistic to postulate that those susceptible to commit more cognitive effort to take in charge st and ard mental tasks are more likely to over-eat and gain weight compared with those for whom the accomplishment of mental tasks at the same level of performance is elementary or more natural . Along the same lines , it would not be surprising to find a higher dropout rate for those ‘ mentally stressed ’ students . In a system where academic performance continues to rank as high priority in public schools , it seems obvious that some students are genetically more gifted and likely to perform at a higher level ( 8) . As previously shown , better cognitive abilities are predictive of more important life achievements such as earning a doctorate , securing a patent , or publishing a novel or major literary work ( 9 ) . It may be somewhat paradoxical that the amount of knowledge-based work is more important in the higher socioeconomic groups whereas population data show a higher prevalence of obesity for the socioeconomically disadvantaged . However , we need to look at the obesity epidemic in a broader context if we want to underst and its aetiology . Obesity is a very complex condition with numerous determinants interacting together and showing large inter-individual variations . Thus , individuals highly involved in mental work are not all likely to over-eat and other healthy behaviours such as regular physical activity may counterbalance the net impact on energy balance . With the advent of computers and new technologies , the pendulum has swung far in the direction of excessive mental activities , as opposed to excessive physical activities . A careful examination of computer-related activities reveals that they represent a particular type of sedentary activities ; they are stressful and biologically dem and ing for the body and deserve to be counterbalanced by an adequate physical activity regimen ( 10 ) . The low IQ – obesity relationship is a timely and meaningful research topic in a context of economic competitiveness and globalization . As mentioned in the paper by Yu and co-workers ( 1 ) , educational attainment seems to be an important mediator of this relationship . However , the orexigenic effects of thinking too hard must be further obesity review s doi : 10.1111/j.1467 -
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"A series of three studies examined the influence of glucose drinks and increasing blood glucose levels on mood . Experiment one considered the short-term effect of a glucose containing drink on mood in young adults : a glucose drink in the morning and higher blood glucose levels were both associated with feeling less tense . Higher blood glucose was also correlated with greater self-reported energy . In the second experiment high blood glucose levels were sustained for 2 hr by repeatedly taking a glucose containing drink . Again higher blood glucose levels were associated with reports of less tension . In a final study subjects were placed in a frustrating situation . The consumption of a glucose drink result ed in fewer negative responses , following a negative statement from the experimenter , in subjects who had fasted over-night . It was concluded that higher blood glucose levels are associated with feeling less tense",
"Previous studies have found a small association between the level of blood glucose and subjective reports of energy in those sitting quietly . Given reports that both memory and attention are influenced by the level of blood glucose it was hypothesised that under conditions of cognitive dem and there would be a stronger association between mood and blood glucose levels . In three studies , with three cognitive tasks , the Stroop Task , Rapid Information Processing Task , and a difficult test of h and -eye coordination , falling blood glucose was associated with feeling less energetic "
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Parental iron is used to optimize hemoglobin and enhance erythropoiesis in end-stage renal disease along with erythropoietin-stimulating agents . Safety of iron has been debated extensively and there is no definite evidence whether parenteral iron increases the risk of infections and mortality . We performed this meta- analysis to evaluate the incidence of infectious complications , hospitalizations and mortality with use of parenteral iron . Medical electronic data bases [ PubMed , EMBASE , Scopus , Web of Science , and cochrane central register for controlled clinical trials ( CENTRAL ) ] were queried for studies that investigated the association between intravenous iron administration and infection in hemodialysis patients . 24 studies ( 8 R and omized control trials ( RCTs ) and 16 observational studies ) were considered for qualitative and quantitative analysis . All-cause mortality Data from 6 RCTs show that high-dose IV iron conferred 17 % less all-cause mortality compared to controls ; however , this outcome was not statistically significant ( OR = 0.83 , CI [ 0.7 , 1.01 ] , p = 0.07 ) . Nine observational studies were pooled under the r and om effects model due to significant heterogeneity ( I2 = 83 % , p increased risk of all-cause mortality in the high-dose group but was statistically non-significant ( HR = 1.1 , CI [ 1 , 1.22 ] , p = 0.06 ) . Infections Four RCTs with no heterogeneity among their data ( I2 = 0 % , p = 0.61 ) . Under the fixed effect model , there was no difference in the infection rate between high-dose iron and control group ( OR = 0.97 , CI [ 0.82 , 1.16 ] , p = 0.77 ) ; eight observational studies with significant heterogeneity and utilizing r and om effects model . Summary HR showed increased yet non-significant risk of infection in the high-dose group ( HR = 1.13 , CI [ 0.99 , 1.28 ] , p = 0.07 ) Hospitalization 1 RCT and six observational studies provided data for the rate of all-cause hospitalization . There was marked heterogeneity among observational studies . RCT showed no significant difference between high-dose iron and controls in the rate of hospitalization ( OR = 1.03 , CI [ 0.87 , 1.23 ] , p = 0.71 ) . Summary HR for observational data showed increased rate of hospitalization in the high-dose group ; however , this effect was not statistically significant ( HR = 1.11 , CI [ 0.99 , 1.24 ] , p = 0.07 ) . Cardiovascular events One RCT compared the rate of adverse cardiovascular events between high-dose and low-dose iron . No significant difference was observed between the two groups ( 22.3 % vs 25.6 % , p = 0.12 ) . Six heterogeneous observational studies ( I2 = 65 % , p the rate of cardiovascular events . No significant difference was observed between high-dose iron and controls ( HR = 1.18 , CI [ 0.89 , 1.57 ] , p = 0.24 ) . High-dose parenteral iron does not seem to be associated with higher risk of infection , all-cause mortality , increased hospitalization or increased cardiovascular events on analysis of RCTs . Observational studies show increased risk for all-cause mortality , infections and hospitalizations that were not statistically significant and were associated with significant heterogeneity
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" Background Administration of ferric pyrophosphate citrate ( FPC , Triferic ™ ) via hemodialysate may allow replacement of ongoing uremic and hemodialysis-related iron losses . FPC donates iron directly to transferrin , bypassing the reticuloendothelial system and avoiding iron sequestration . Methods Two identical Phase 3 , r and omized , placebo-controlled trials ( CRUISE 1 and 2 ) were conducted in 599 iron-replete chronic hemodialysis patients . Patients were dialyzed with dialysate containing 2 µM FPC-iron or st and ard dialysate ( placebo ) for up to 48 weeks . Oral or intravenous iron supplementation was prohibited , and doses of erythropoiesis-stimulating agents were held constant . The primary efficacy end point was the change in hemoglobin ( Hgb ) concentration from baseline to end of treatment ( EoT ) . Secondary end points included reticulocyte hemoglobin content ( CHr ) and serum ferritin . Results In both trials , Hgb concentration was maintained from baseline to EoT in the FPC group but decreased by 0.4 g/dL in the placebo group ( P 0.2–0.6 ) . Placebo treatment result ed in significantly larger mean decreases from baseline in CHr ( −0.9 pg versus −0.4 pg , P ) and serum ferritin ( −133.1 µg/L versus −69.7 µg/L , P than FPC treatment . The proportions of patients with adverse and serious adverse events were similar in both treatment groups . Conclusions FPC delivered via dialysate during hemodialysis replaces iron losses , maintains Hgb concentrations , does not increase iron stores and exhibits a safety profile similar to placebo . FPC administered by hemodialysis via dialysate represents a paradigm shift in delivering maintenance iron therapy to hemodialysis patients",
"Although iron therapy is essential to optimize use of erythropoiesis-stimulating agents ( ESA ) , r and omized , controlled trials have heretofore been unavailable to evaluate reliably the efficacy of intravenous iron as an adjuvant to ESA treatment in peritoneal dialysis ( PD ) patients . In a multicenter trial , patients who had anemia , PD-dependent chronic kidney disease , stable ESA therapy , and a broad range of iron status ( ferritin were r and omly assigned to receive either 1 g of iron sucrose intravenously in three divided doses ( 300 mg over 1.5 h on days 1 and 15 , 400 mg over 2.5 h on day 29 ) or no supplemental iron . No serious adverse drug events occurred after intravenous iron administration . The primary end point , peak hemoglobin increase , was higher ( 1.3 + /- 1.1 versus 0.7 + /- 1.1 , mean + /- SD ; P = 0.0028 ) , and anemia intervention ( transfusion , increase in ESA dose , or intravenous iron therapy not called for in protocol ) occurred later ( P = 0.0137 ) and less often in intravenous iron-treated patients compared with untreated control subjects ( one of 66 [ 1.3 % ] versus five of 30 [ 16.7 % ] ) . Among patients who did not require intervention , iron-treated patients showed a calculated net ESA dose decrease compared with untreated control subjects . Baseline iron status did not predict responsiveness to intravenous iron therapy . Intravenous iron sucrose is an effective adjunct to ESA therapy in anemic patients with PD-dependent chronic kidney disease and is administered safely as 300 mg over 1.5 h or 400 mg over 2.5 h. Evidence of iron deficiency at baseline is not required to demonstrate intravenous iron efficacy",
"Although functional iron deficiency ( FID ) may be present in hemodialysis ( HD ) patients with high serum ferritin levels ( > 800 ng/mL ) , current protocol s often preclude the use of intravenous ( IV ) iron in these patients . However , it has not been demonstrated that iron supplementation during erythropoietin therapy is ineffective or unsafe in increasing hemoglobin ( Hb ) levels in patients with high serum ferritin . This report describes the hematologic efficacy and safety of ferric gluconate ( FG ) therapy in patients with serum ferritin > 800 ng/mL. A retrospective analysis was performed on HD patients at a single California dialysis center from January 1 to December 31 , 2003 . Patients classified as having high ferritin levels ( serum ferritin > 800 ng/mL on at least 66 % of routine monthly measurements and transferrin saturation [ TSAT ] were stratified as follows : patients in Group I were suspected of having FID and received FG ≥250 mg IV over a 3‐month period when Hb was received st and ard recombinant human erythropoietin therapy as per the unit 's protocol . Of 496 patients , 95 exhibited high ferritin and of these , 39 patients had sufficient data for analysis . Group I patients ( n=14 ) showed a significant increase in Hb levels compared with Group II ( n=25 ) . There was no increase in ferritin levels in response to iron administration . No significant differences in hospitalizations or infections were observed between groups . Hemodialysis patients with high ferritin levels may have FID , and IV iron therapy safely improves FID in some patients . A larger r and omized trial examining the optimal management of iron administration in HD patients with high ferritin levels is warranted",
"Background Anemia management protocol s in hemodialysis ( HD ) units differ conspicuously regarding optimal intravenous ( IV ) iron dosing ; consequently , patients receive markedly different cumulative exposures to IV iron and erythropoiesis-stimulating agents ( ESAs ) . Complementary to IV iron safety studies , our goal was to gain insight into optimal IV iron dosing by estimating the effects of IV iron doses on Hgb , TSAT , ferritin , and ESA dose in common clinical practice . Methods 9,471 HD patients ( 11 countries , 2009 - 2011 ) in the DOPPS , a prospect i ve cohort study , were analyzed . Associations of IV iron dose ( 3-month average , categorized as 0 , 3-month change in Hgb , TSAT , ferritin , and ESA dose were evaluated using adjusted GEE models . Results Relative change : Monotonically positive associations between IV iron dose and Hgb , TSAT , and ferritin change , and inverse associations with ESA dose change , were observed across multiple strata of prior Hgb , TSAT , and ferritin levels . Absolute change : TSAT , ferritin , and ESA dose changes were nearest zero with IV iron that IV iron dosing IV iron doses ( 300 - 400 mg/month ) often given in many European and North American hemodialysis clinics . Alongside studies supporting the safety of IV iron in 100 - 200 mg/month dose range , these findings help guide the rational dosing of IV iron in anemia management protocol s for everyday hemodialysis practice",
"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",
"BACKGROUND Correction of iron deficiency is critical in chronic hemodialysis patients , and intravenous administration is superior to the oral route in this goal . Recently , concern was raised that intravenous iron administration might promote infection in dialysis patients . METHODS We review ed the data from a recent prospect i ve study of 985 patients in which no link between iron therapy and bacteremia had been found . We tested the potential role of the administration route of the iron ( intravenous vs. oral ) , the weekly amount of iron administered and the administration rate on the risk for bacteremia in these patients . RESULTS were 4-fold : in multivariate analysis , neither intravenous iron administration in the whole population nor the weekly amount of iron in the subgroup of i.v . iron-treated patients were significant risk factors for bacteremia ; iron was not given more frequently intravenously in bacteremic than in non-bacteremic patients ; among patients treated with intravenous iron , the frequency and the amount of iron administered were significantly higher in those who developed bacteremia than in those who did not ; and in patients receiving i.v . iron , there was an increased risk of bacteremia associated with concurrent administration of erythropoietin , which was not observed in patients receiving iron orally . CONCLUSION This study failed to demonstrate a significant association between intravenous iron administration and the risk of bacteremia in dialysis patients . However , there might be a slightly increased risk of bacteremia in patients given high-frequency , high-dose intravenous iron",
"Background In patients treated by maintenance hemodialysis the relationship to survival of hemoglobin level and administered epoetin-alfa and intravenous iron is controversial . The study aim was to determine effects on patient survival of administered epoetin-alfa and intravenous iron , and of hemoglobin and variables related to iron status . Methods The patients were 1774 treated by maintenance hemodialysis in 3 dialysis units in New York , NY from January 1998 to June , 2007 . A patient-centered , coded , electronic patient record used in patient care enabled retrospective analysis of data collected prospect ively . For survival analysis , patients were censored when transplanted , transferred to hemodialysis at home or elsewhere , peritoneal dialysis . Univariate Kaplan-Meier analysis was followed by multivariate analysis with Cox 's regression , using as variables age , race , gender , major co-morbid conditions , epoetin-alfa and intravenous iron administered , and 15 laboratory tests . Results Median age was 59 years , epoetin-alfa ( interquartile range ) 18,162 ( 12,099 , 27,741 ) units/week , intravenous iron 301 ( 202 , 455 ) mg/month , survival 789 ( 354 , 1489 ) days . Median hemoglobin was 116 ( 110 , 120)g/L , transferrin saturation 29.7 ( 24.9 , 35.1)% , serum ferritin 526 ( 247 , 833 ) μg/L , serum albumin 39.0 ( 36.3 , 41.5 ) g/L. Survival was better the higher the hemoglobin , best with > 120 g/L. Epoetin-alfa effect on survival was weak but had statistically significant interaction with intravenous iron . For intravenous iron , survival was best with 1–202 mg/month , slightly worse with 202–455 mg/month ; it was worst with no intravenous iron , only slightly better with > 455 mg/month . Survival was worst with transferrin saturation ≤ 16 % , serum ferritin ≤ 100 μg/L , best with transferrin saturation > 25 % , serum ferritin > 600 μg/L The effects of each of hemoglobin , intravenous iron , transferrin saturation , and serum ferritin on survival were independently significant and not mediated by other predictors in the model . Conclusion Long term survival of maintenance hemodialysis patients was favorably affected by a relatively high hemoglobin level , by moderate intravenous iron administration , and by indicators of iron sufficiency . It was unfavorably influenced by a low hemoglobin level , and by indicators of iron deficiency",
" Ferric pyrophosphate citrate ( FPC ) is a water-soluble iron salt administered via dialysate to supply iron directly to transferrin . The PRIME study tested whether treatment with FPC could reduce prescribed erythropoiesis-stimulating agent ( ESA ) use and maintain hemoglobin in hemodialysis patients . This 9-month , r and omized , placebo-controlled , double-blind , multicenter clinical study included 103 patients undergoing hemodialysis 3–4 times weekly . The FPC group received dialysate containing 2 μmol/l of iron . The placebo group received st and ard dialysate . A blinded central anemia management group facilitated ESA dose adjustments . Intravenous iron was administered according to the approved indication when ferritin levels fell below 200 μg/l . The primary end point was the percentage change from baseline in prescribed ESA dose at end of treatment . Secondary end points included intravenous iron use and safety . At the end of treatment , there was a significant 35 % reduction in prescribed ESA dose in FPC-treated patients compared with placebo . The FPC patients used 51 % less intravenous iron than placebo . Adverse and serious adverse events were similar in both groups . Thus , FPC delivered via dialysate significantly reduces the prescribed ESA dose and the amount of intravenous iron needed to maintain hemoglobin in chronic hemodialysis patients",
"Iron deficiency limits the efficacy of recombinant human erythropoietin ( rhEPO ) therapy in end-stage renal disease ( ESRD ) patients . Functional iron deficiency occurs with serum ferritin > 500 ng/ml and /or transferrin saturation ( TSAT ) of 20 to 30 % . This study examines the effects of a maintenance intravenous iron dextran ( ivID ) protocol that increased TSAT in ESRD hemodialysis patients from conventional levels of 20 to 30 % ( control group ) to those of 30 to 50 % ( study group ) for a period of 6 mo . Forty-two patients receiving chronic hemodialysis completed a 16- to 20-wk run-in period , during which maintenance ivID and rhEPO were administered in amounts to achieve average TSAT of 20 to 30 % and baseline levels of hemoglobin of 9.5 to 12.0 g/dl . After the run-in period , 19 patients r and omized to the control group received ivID doses of 25 to 150 mg/wk for 6 mo . Twenty-three patients r and omized to the study group received four to six loading doses of ivID , 100 mg each , over a 2-wk period to achieve a TSAT > 30 % followed by 25 to 150 mg weekly to maintain TSAT between 30 and 50 % for 6 mo . Both regimens were effective in maintaining targeted hemoglobin levels . Fifteen patients in the control group and 17 patients in the study group finished the study in which the primary outcome parameter by intention to treat analysis was the rhEPO dose needed to maintain pre study hemoglobin levels . Maintenance ivID requirements in the study group increased from 176 to 501 mg/mo and were associated with a progressive increase in serum ferritin to 658 ng/ml . Epoetin dose requirements for the study group decreased by the third month and remained 40 % lower than for the control group , result ing in an overall cost savings in managing the anemia . Secondary indicators of iron-deficient erythropoiesis were also assessed . Zinc protoporphyrin did not change in either group . Reticulocyte hemoglobin content increased only in the study group from 28.5 to 30.1 pg . It is concluded that maintenance of TSAT between 30 and 50 % reduces rhEPO requirements significantly over a 6-mo period",
"Ferric citrate ( FC ) is a phosphate binder with shown efficacy and additional effects on iron stores and use of intravenous ( iv ) iron and erythropoiesis-stimulating agents ( ESAs ) . We provide detailed analyses of changes in iron/hematologic parameters and iv iron/ESA use at time points throughout the active control period of a phase 3 international r and omized clinical trial . In all , 441 subjects were r and omized ( 292 to FC and 149 to sevelamer carbonate and /or calcium acetate [ active control ( AC ) ] ) and followed for 52 weeks . Subjects on FC had increased ferritin and transferrin saturation ( TSAT ) levels compared with subjects on AC by week 12 ( change in ferritin , 114.1±29.35 ng/ml ; P ) . Change in TSAT plateaued at this point , whereas change in ferritin increased through week 24 , remaining relatively stable thereafter . Subjects on FC needed less iv iron compared with subjects on AC over 52 weeks ( median [ interquartile range ] dose=12.9 [ 1.0 - 28.9 ] versus 26.8 [ 13.4 - 47.6 ] mg/wk ; P requiring iv iron was higher with FC ( P over 52 weeks was lower with FC than AC ( median [ interquartile range ] dose=5303 [ 2023 - 9695 ] versus 6954 [ 2664 - 12,375 ] units/wk ; P=0.04 ) . Overall , 90.3 % of subjects on FC and 89.3 % of subjects on AC experienced adverse events . In conclusion , treatment with FC as a phosphate binder results in increased iron parameters apparent after 12 weeks and reduces iv iron and ESA use while maintaining hemoglobin over 52 weeks , with a safety profile similar to that of available binders",
"BACKGROUND AND OBJECTIVES Clinical trials assessing effects of larger cumulative iron exposure with outcomes are lacking , and observational studies have been limited by assessment of short-term exposure only and /or failure to assess cause-specific mortality . The associations between short- and long-term iron exposure on all-cause and cause-specific mortality were examined . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS The study included 14,078 United States patients on dialysis initiating dialysis between 2003 and 2008 . Intravenous iron dose accumulations over 1- , 3- , and 6-month rolling windows were related to all-cause , cardiovascular , and infection-related mortality in Cox proportional hazards models that used marginal structural modeling to control for time-dependent confounding . RESULTS Patients in the 1-month model cohort ( n=14,078 ) were followed a median of 19 months , during which there were 27.6 % all-cause deaths , 13.5 % cardiovascular deaths , and 3 % infection-related deaths . A reduced risk of all-cause mortality with receipt of > 150 - 350 ( hazard ratio , 0.78 ; 95 % confidence interval , 0.64 to 0.95 ) or > 350 mg ( hazard ratio , 0.79 ; 95 % confidence interval , 0.62 to 0.99 ) intravenous iron compared with > 0 - 150 mg over 1 month was observed . There was no relation of 1-month intravenous iron dose with cardiovascular or infection-related mortality and no relation of 3- or 6-month cumulative intravenous iron dose with all-cause or cardiovascular mortality . There was a nonstatistically significant increase in infection-related mortality with receipt of > 1050 mg intravenous iron in 3 months ( hazard ratio , 1.69 ; 95 % confidence interval , 0.87 to 3.28 ) and > 2100 mg in 6 months ( hazard ratio , 1.59 ; 95 % confidence interval , 0.73 to 3.46 ) . CONCLUSIONS Among patients on incident dialysis , receipt of ≤ 1050 mg intravenous iron in 3 months or 2100 mg in 6 months was not associated with all-cause , cardiovascular , or infection-related mortality . However , nonstatistically significant findings suggested the possibility of infection-related mortality with receipt of > 1050 mg in 3 months or > 2100 mg in 6 months . R and omized clinical trials are needed to assess the safety of exposure to greater cumulative intravenous iron doses",
"BACKGROUND AND OBJECTIVES Intravenous iron is a key component of anemia management for chronic kidney disease ( CKD ) . Ferumoxytol is a unique intravenous iron product that can be administered as a rapid injection in doses up to 510 mg . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This was a r and omized , open-label , controlled , multicenter Phase 3 trial to evaluate the safety and efficacy of intravenous ferumoxytol compared with oral iron . Anemic patients with CKD stage 5D on hemodialysis and on a stable erythropoiesis-stimulating agent regimen received either two injections of 510 mg of ferumoxytol within 7 d ( n = 114 ) or 200 mg elemental oral iron daily for 21 d ( n = 116 ) . The primary efficacy endpoint was the change in hemoglobin from baseline to day 35 . Safety was closely monitored . RESULTS Ferumoxytol result ed in a mean increase in hemoglobin of 1.02 + /- 1.13 g/dl at day 35 compared with 0.46 + /- 1.06 g/dl with oral iron ( P = 0.0002 ) . Twice as many ferumoxytol-treated patients than oral iron-treated patients achieved a > or = 1 g/dl hemoglobin increase at day 35 ( P = 0.0002 ) . There was a greater mean increase in transferrin saturation ( TSAT ) with ferumoxytol compared with oral iron at day 35 ( P hemoglobin increase after ferumoxytol compared with oral iron at day 35 persisted after adjustment for baseline hemoglobin , TSAT , and serum ferritin . Overall adverse event rates were comparable between groups . CONCLUSIONS In patients on hemodialysis , rapid intravenous injection of 510 mg of ferumoxytol led to significantly greater hemoglobin increases compared with oral iron , with comparable tolerability",
"In recent times , therapy for renal anemia has changed dramatically in that iron administration has increased and doses of erythropoiesis-stimulating agents ( ESAs ) have decreased . Here we used a prospect i ve , observational , multicenter design and measured the serum ferritin and hemoglobin levels every 3 months for 2 years in 1086 patients on maintenance hemodialysis therapy . The associations of adverse events with fluctuations in ferritin and hemoglobin levels and ESA and iron doses were measured using a Cox proportional hazards model for time-dependent variables . The risks of cerebrovascular and cardiovascular disease ( CCVD ) , infection , and hospitalization were higher among patients who failed to maintain a target-range hemoglobin level and who exhibited high-amplitude fluctuations in hemoglobin compared with patients who maintained a target-range hemoglobin level . Patients with a higher compared with a lower ferritin level had an elevated risk of CCVD and infectious disease . Moreover , the risk of death was significantly higher among patients with high-amplitude ferritin fluctuations compared with those with a low ferritin level . The risks of CCVD , infection , and hospitalization were significantly higher among patients who were treated with high weekly doses of intravenous iron compared with no intravenous iron . Thus , there is a high risk of death and /or adverse events in patients with hemoglobin levels outside the target range , in those with high-amplitude hemoglobin fluctuations , in those with consistently high serum ferritin levels , and in those with high-amplitude ferritin fluctuations",
"The independent association between the indices of iron stores or administered intravenous iron , both of which vary over time , and survival in patients who are on maintenance hemodialysis ( MHD ) is not clear . It was hypothesized that the observed associations between moderately high levels of three iron markers ( serum ferritin , iron , and iron saturation ratio ) or administered intravenous iron and all-cause and cardiovascular death is due to the time-varying confounding effect of malnutrition-inflammation-cachexia syndrome ( MICS ) . Time-dependent Cox regression models were examined using prospect ively collected data of the 2-yr ( July 2001 to June 2003 ) historical cohort of 58,058 MHD patients from virtually all DaVita dialysis clinics in the United States . After time-dependent and multivariate adjustment for case mix , administered intravenous iron and erythropoietin doses , and available surrogates of MICS , serum ferritin levels between 200 and 1200 ng/ml ( reference 100 to 199 ng/ml ) , serum iron levels between 60 and 120 microg/ml ( reference 50 to 59 microg/ml ) , and iron saturation ratio between 30 and 50 % ( reference 45 to 50 % ) were associated with the lowest all-cause and cardiovascular death risks . Compared with those who did not receive intravenous iron , administered intravenous iron up to 400 mg/mo was associated with improved survival , whereas doses > 400 mg/mo tended to be associated with higher death rates . The association between serum ferritin levels > 800 ng/ml and mortality in MHD patients seems to be due mostly to the confounding effects of MICS . For ascertaining whether the observed associations between moderate doses of administered intravenous iron and improved survival are causal or due to selection bias by indication , clinical trials are warranted",
"Few data exist to guide treatment of anemic hemodialysis patients with high ferritin and low transferrin saturation ( TSAT ) . The Dialysis Patients ' Response to IV Iron with Elevated Ferritin ( DRIVE ) trial was design ed to evaluate the efficacy of intravenous ferric gluconate in such patients . Inclusion criteria were hemoglobin epoetin dosage > or=225 IU/kg per wk or > or=22,500 IU/wk . Patients with known infections or recent significant blood loss were excluded . Participants ( n=134 ) were r and omly assigned to no iron ( control ) or to ferric gluconate 125 mg intravenously with eight consecutive hemodialysis sessions ( intravenous iron ) . At r and omization , epoetin was increased 25 % in both groups ; further dosage changes were prohibited . At 6 wk , hemoglobin increased significantly more ( P=0.028 ) in the intravenous iron group ( 1.6 + /- 1.3 g/dl ) than in the control group ( 1.1 + /- 1.4 g/dl ) . Hemoglobin response occurred faster ( P=0.035 ) and more patients responded after intravenous iron than in the control group ( P=0.041 ) . Ferritin or > 800 ng/ml had no relationship to the magnitude or likelihood of responsiveness to intravenous iron relative to the control group . Similarly , the superiority of intravenous iron compared with no iron was similar whether baseline TSAT was above or below the study median of 19 % . Ferritin decreased in control subjects ( -174 + /- 225 ng/ml ) and increased after intravenous iron ( 173 + /- 272 ng/ml ; P iron result ed in a greater increase in TSAT than in control subjects ( 7.5 + /- 7.4 versus 1.8 + /- 5.2 % ; P Reticulocyte hemoglobin content fell only in control subjects , suggesting worsening iron deficiency . Administration of ferric gluconate ( 125 mg for eight treatments ) is superior to no iron therapy in anemic dialysis patients receiving adequate epoetin dosages and have a ferritin 500 to 1200 ng/ml and TSAT < or=25 %",
"Patients on dialysis require phosphorus binders to prevent hyperphosphatemia and are iron deficient . We studied ferric citrate as a phosphorus binder and iron source . In this sequential , r and omized trial , 441 subjects on dialysis were r and omized to ferric citrate or active control in a 52-week active control period followed by a 4-week placebo control period , in which subjects on ferric citrate who completed the active control period were rer and omized to ferric citrate or placebo . The primary analysis compared the mean change in phosphorus between ferric citrate and placebo during the placebo control period . A sequential gatekeeping strategy controlled study -wise type 1 error for serum ferritin , transferrin saturation , and intravenous iron and erythropoietin-stimulating agent usage as prespecified secondary outcomes in the active control period . Ferric citrate controlled phosphorus compared with placebo , with a mean treatment difference of -2.2±0.2 mg/dl ( mean±SEM ) ( P comparable safety profiles . Subjects on ferric citrate achieved higher mean iron parameters ( ferritin=899±488 ng/ml [ mean±SD ] ; transferrin saturation=39%±17 % ) versus subjects on active control ( ferritin=628±367 ng/ml [ mean±SD ] ; transferrin saturation=30%±12 % ; P less intravenous elemental iron ( median=12.95 mg/wk ferric citrate ; 26.88 mg/wk active control ; P and less erythropoietin-stimulating agent ( median epoetin-equivalent units per week : 5306 units/wk ferric citrate ; 6951 units/wk active control ; P=0.04 ) . Hemoglobin levels were statistically higher on ferric citrate . Thus , ferric citrate is an efficacious and safe phosphate binder that increases iron stores and reduces intravenous iron and erythropoietin-stimulating agent use while maintaining hemoglobin",
"This prospect i ve study was design ed to evaluate the eventual correction of anemia and iron status in 39 iron-deficient uremics starting hemodialysis . Nine patients ( control group ) had no iron supplementation , 10 had oral ferrous iron , and 20 were treated with intravenous iron gluconate . Follow-up periods were 12 months for the control group and 26 months for patients treated with oral or intravenous iron . No patient was treated with erythropoietin . At zero time , all patients were anemic ( Hb severe iron deficiency , diagnosed on the basis of depleted bone marrow iron stores , reduced hemoglobin iron , and transferrin saturation hemoglobin levels , observed in patients of the control and the oral iron groups at the end of the follow-up periods , were not significantly different from those detected at zero time . In contradistinction , patients treated with intravenous iron showed after 26 months of follow-up a significant increase of blood hemoglobin values , reaching a mean value of 126 g/l . So far , this evidence supports both the concept that iron absorption is compromised in chronic uremics and that the parenteral way is the more effective route for iron replacement in this specific group of patients"
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411872e6-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND despite availability of effective treatments for osteoporosis , impact on fracture rates may be suboptimal because of failure to adhere to recommended anti-resorptive therapy . OBJECTIVE to identify r and omized controlled trials ( RCTs ) evaluating interventions intended to improve persistence with anti-resorptive therapy for treating women with osteoporosis or osteopenia . The design of the study is a systematic review and meta- analysis of RCTs . METHODS included trials were those reporting interventions to improve persistence with or adherence to anti-resorptive treatment compared to a control medication or usual care . A search of MEDLINE , EMBASE , CINAHL and the Cochrane Library was supplemented by review of cited literature . Reports were review ed and data pooled where appropriate . The primary outcome was duration of persistence with medication . RESULTS six trials met inclusion criteria , including four reporting persistence as an outcome measure indicating a relative reduction in non-persistence of 22 % ( pooled relative risk : 0.78 , 95 % confidence interval 0.65 - 0.95 ) for active compared to control interventions . Heterogeneity between the trial effects was present but not significant ( I(2 ) = 47 % , P = 0.11 ) . Interventions were varied in design , and some measurements of adherence were subject to self-report bias . Two trials included the majority of participants ( 3386/3497 ) , accounting for > 90 % of the weight in the pooled estimate . CONCLUSIONS trials to date suggest potential for improving persistence with medication taking thus improving treatment outcomes and reducing fracture risk . More precise measurement of medication taking and promoting fidelity to a precisely defined intervention protocol may lead to better assessment of impact on clinical ly important outcomes
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"Introduction Adherence to treatment in osteoporosis remains poor . The aim of this study was to evaluate the effects of an educational leaflet on adherence to medication and to assess the association between adherence and health-related quality of life ( HRQOL ) . Methods A naturalistic , observational , multi-center , prospect i ve study of 12 months ’ follow-up was performed . Consecutive post-menopausal women aged 50 years to 86 years starting treatment with raloxifene according to daily practice were enrolled from 126 primary care offices in Spain . The women were assigned to two study groups . Group A received an educational leaflet with general information about osteoporosis ; group B followed current practice . To assess adherence to medication and HRQOL , the Morisky test and the EuroQoL question naire were administered . A total of 745 post-menopausal women ( group A , n=366 ; group B n=379 ) , with a mean age of 62 years , were included . Results Most patients in both study groups showed high adherence to raloxifene at the 3-month visit : 56.3 % vs 62.7 % for groups A and B , respectively ; this proportion at the 12-month visit was 47.4 % ( P=0.15 ) and 52.5 % ( P=0.02 ) , respectively . At baseline , “ pain/discomfort ” was the dimension showing the highest percentage of women reporting problems : 86.4 % vs 83.2 % in groups A and B , respectively ( P=0.22 ) . HRQOL improved in both groups throughout the study , with an overall mean increment in the EuroQoL visual analog scale ( EQ VAS ) of 9.2 at 12 months ( P adherence and HRQOL were weak . After receiving an educational leaflet , young post-menopausal women suffering osteoporosis did not show improvement in adherence to therapy . HRQOL improved at 12-month follow-up under treatment . Conclusion No consistent correlation between adherence and HRQOL was found",
"Osteoporosis is a common and debilitating condition associated with significant morbidity and mortality . The efficacy and safety of oral bisphosphonates for the treatment of osteoporosis are well established . However , patient adherence and persistence on treatment are suboptimal . This r and omised open-label multi-centre study of 6-months ’ duration compared persistence on treatment in postmenopausal women with osteoporosis receiving either once-monthly ib and ronate plus a patient support programme ( PSP ) , or once-weekly alendronate . To avoid falsely elevated persistence rates often associated with clinical trials , the study was design ed to reflect everyday clinical practice in the UK and follow-up visits were limited to be consistent with the primary care setting . Analysis of the primary endpoint showed that persistence was significantly higher in the ib and ronate/PSP group compared with the alendronate group ( p proportion of patients persisting with treatment at 6 months was 56.6 % ( 306/541 ) and 38.6 % ( 198/513 ) in the ib and ronate/PSP and alendronate groups , respectively . Therefore , compared with alendronate , there was a 47 % relative improvement in the proportion of patients persisting with treatment in the ib and ronate/PSP group . Secondary endpoint measurements of adherence ( e.g. proportion of patients remaining on treatment at study end ; proportion of patients discontinuing from the study ) were also significantly different in favour of ib and ronate plus patient support . In summary , the PERSIST study demonstrated that persistence on treatment was increased in patients receiving once-monthly ib and ronate plus patient support compared with once-weekly alendronate . Increased persistence on bisphosphonate treatment is expected to improve patient outcomes and decrease the social and economic burden of osteoporosis",
"CONTEXT Persistence with osteoporosis treatment is poor but is important for maximum benefit . OBJECTIVE The objective of the study was to assess the impact of physician reinforcement using bone turnover markers ( BTMs ) on persistence with risedronate treatment . DESIGN AND SETTING This was a 1-yr multinational prospect i ve , open-label , blinded study in 171 osteoporosis centers in 21 countries . PATIENTS A total of 2382 postmenopausal women ( 65 - 80 yr old ) with spine/hip T-score -2.5 or less or T-score -1.0 or less with a low-trauma fracture . INTERVENTION Intervention included calcium 500 mg/d , vitamin D 400 IU/d , and risedronate 5 mg/d for 1 yr . Centers were r and omized to reinforcement ( RE+ ) or no reinforcement ( RE- ) . At 13 and 25 wk , reinforcement based on urinary N-telopeptide of type I collagen change from baseline was provided to the RE+ patients using the following response categories : good ( > 30 % decrease ) , stable ( -30 % to + 30 % change ) , or poor ( > 30 % increase ) . MAIN OUTCOME MEASURES Persistence assessed with electronic drug monitors was measured . RESULTS In the overall efficacy population ( n=2302 ) , persistence was unexpectedly high and was similar for both groups ( RE- , 77 % ; RE+ , 80 % ; P=0.160 ) . A significant relationship between the type of message and persistence was observed ( P=0.017 ) . Compared with RE- , intervention based on a good BTM response was associated with a significant improvement in persistence [ hazard ratio ( HR ) 0.71 ; 95 % confidence interval ( CI ) 0.53 - 0.95 ] . Persistence was unchanged ( HR 1.02 ; 95 % CI 0.74 - 1.40 ) or lower ( HR 2.22 ; 95 % CI 1.27 - 3.89 ) when reinforcement was based on a stable or poor BTM response , respectively . Reinforcement was associated with a lower incidence of new radiologically determined vertebral fractures ( odds ratio 0.4 ; 95 % CI , 0.2 - 1.0 ) . CONCLUSIONS Reinforcement using BTMs influences persistence with treatment in postmenopausal women with osteoporosis , depending on the BTM response observed",
"Clinical studies were performed to examine the oral bioavailability of alendronate ( 4‐amino‐1‐hydroxybutylidene‐1,1‐bisphosphonate monosodium ) . All studies , with the exception of one performed in men , involved postmenopausal women . Short‐term ( 24 to 36 hours ) urinary recovery of alendronate after an intravenous dose of 125 to 250 μg averaged about 40 % in both men and women . In women , oral bioavailability of alendronate was independent of dose ( 5 to 80 mg ) and averaged ( 90 % confidence interval ) 0.76 % ( 0.58 , 0.98 ) when taken with water in the fasting state , followed by a meal 2 hours later . Bioavailability was similar in men [ 0.59 % , ( 0.43 , 0.81 ) ] . Taking alendronate either 60 or 30 minutes before a st and ardized breakfast reduced bioavailability by 40 % relative to the 2‐hour wait . Taking alendronate either concurrently with or 2 hours after breakfast drastically ( > 85 % ) impaired availability . Black coffee or orange juice alone , when taken with the drug , also reduced bioavailability ( approximately 60 % ) . Increasing gastric pH , by infusion of ranitidine , was associated with a doubling of alendronate bioavailability . A practical dosing recommendation , derived from these findings and reflective of the long‐term nature of therapy for a disease such as osteoporosis , is that patients take the drug with water after an overnight fast and at least 30 minutes before any other food or beverage",
"Long-term adherence and persistence with any therapy are very poor ( approximately 50 % ) . Adherence to therapy is defined as the percentage of prescribed medication taken , and persistence is defined as continuing to take prescribed medication . We examined whether monitoring by nursing staff could enhance adherence and persistence with antiresorptive therapy and whether presenting information on response to therapy provided additional benefit . In addition we evaluated the impact of monitoring on treatment efficacy . Seventy-five postmenopausal women with osteopenia were r and omized to 1 ) no monitoring , 2 ) nurse-monitoring , or 3 ) marker-monitoring . All subjects were prescribed raloxifene . At 12 , 24 , and 36 wk , the nursing staff review ed subjects in the monitored ( nurse-monitoring or marker-monitoring ) groups using a predefined protocol . The marker-monitored group were also presented a graph of response to therapy using percentage change in urinary N-telopeptide of type I collagen ( uNTX ) , a bone resorption marker , at each visit . Biological response to therapy at 1 yr was determined using the percent change in bone mineral density ( BMD ) and uNTX . Treatment adherence and persistence were assessed using electronic monitoring devices . Survival analysis showed that the monitored group increased cumulative adherence to therapy by 57 % compared with no monitoring ( P = 0.04 ) . There was a trend for the monitored group to persist with therapy for 25 % longer compared with no monitoring ( P = 0.07 ) . Marker measurements did not improve adherence or persistence to therapy compared with nurse-monitoring alone . Adherence at 1 yr was correlated with percent change in hip ( BMD ) ( r = 0.28 ; P = 0.01 ) and percent change in uNTX ( r = -0.36 ; P = 0.002 ) . In conclusion , monitoring of patients increased adherence to therapy by 57 % at 1 yr . Increased adherence to therapy increased the effectiveness of raloxifene therapy determined using surrogate end points",
"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"
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Introduction The purpose of this systematic literature review is to review published studies on foot care knowledge and foot care practice interventions as part of diabetic foot care self-management interventions . Methods Medline , CINAHL , CENTRAL , and Cochrane Central Register of Controlled Trials data bases were search ed . References from the included studies were review ed to identify any missing studies that could be included . Only foot care knowledge and foot care practice intervention studies that focused on the person living with type 2 diabetes were included in this review . Author , study design , sample , intervention , and results were extracted . Results Thirty studies met the inclusion criteria and were classified according to r and omized controlled trial ( n=9 ) , survey design ( n=13 ) , cohort studies ( n=4 ) , cross-sectional studies ( n=2 ) , qualitative studies ( n=2 ) , and case series ( n=1 ) . Improving lower extremity complications associated with type 2 diabetes can be done through effective foot care interventions that include foot care knowledge and foot care practice s. Conclusion Preventing these complications , underst and ing the risk factors , and having the ability to manage complications outside of the clinical encounter is an important part of a diabetes foot self-care management program . Interventions and research studies that aim to reduce lower extremity complications are still lacking . Further research is needed to test foot care interventions across multiple population s and geographic locations
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"Purpose The purpose s of this study were to assess the level of foot self-care performed in a rural , multiethnic population of older adults and to identify factors associated with foot self-care . Methods The Evaluating Long-term Diabetes Self-management Among Elder Rural Adults study included a r and om sample of 701 African American , Native American , and white adults from 2 rural North Carolina counties . Participants completed in-home interviews , 5 foot selfcare practice s from the Summary of Diabetes Self-Care Activities ( SDSCA ) , functional status measures , and measures of education and support for foot care . Results Foot care practice s/behaviors reported at least 6 days/week ranged from 35.6 % for inspecting shoes to 79.2 % for not soaking feet . Four independent predictors of the SDSCA summary foot care index score were observed : having been shown how to care for feet ( P doctor check nerves in feet in past year ( P= .02 ) , and not receiving support caring for feet ( P = .0425 ) . Conclusions These findings indicate that educating patients about foot self-care may encourage routine foot care but that those dependent on either formal or informal support to perform foot care do so less frequently than those who perform it independently",
"PURPOSE The purpose of this study was to evaluate an intensive diabetes foot education program for veterans at high risk for foot ulcer . METHODS We invited 100 consecutive patients with diabetes from a Department of Veterans Affairs Medical Center clinic who were insensate to the Semmes-Weinstein 5.07 monofilament to participate in a foot care education program . Two sessions were conducted by a nurse diabetes educator 3 months apart . Multiple educational approaches were used to teach patients foot self-examination , foot washing , proper footwear , and encouragement in enlisting proper physician foot care . Knowledge and satisfaction with care was measured before and after each visit . RESULTS The 34 patients who attended both education sessions improved their foot care knowledge over the course of the program . After the second session , the mean improvement over baseline was 14 % . These patients also reported improved satisfaction with foot care ; mean improvement was 33 % . CONCLUSIONS An intensive education program improved the foot care knowledge and behavior of high-risk patients . Those who adhered to a foot care education program were more satisfied with their foot care than prior to the program . Ways to improve accessibility of education sessions must be explored",
"Although many studies have shown strong associations between certain causal factors and patients with foot ulcers , it is unclear how many of these factors interact . A model that could help identify unique causal pathways and pivotal factors associated with the development of foot ulcers may lead to earlier intervention as well as less frequent and less severe complications . Therefore , the purpose of this study was to identify the responsible causal pathways associated with foot ulcers in persons with diabetes , to determine the frequency of components of the pathway and to identify pivotal events of the pathway . Eighty-seven patients with 103 existing or recently healed ulcers were prospect ively evaluated . The data used in the pathway analysis reflected seven variables that have been associated with the development of foot ulcers . The data were interpreted to assess which component causes and pivotal events were responsible for the present ulcer . A cluster analysis was used to confirm findings from the descriptive analysis . Twenty-four pathways were identified . The seven most common unique pathways accounted for 64.1 % of the cases . The results of the cluster analysis showed four consistent , dominant clusters : ( i ) neuropathy , deformity , callus and elevated peak pressure ; ( ii ) peripheral vascular disease ; ( iii ) penetrating trauma and ( iv ) Ill-fitting shoe gear . These results suggest that there is a finite number of key factors that , if identified and addressed with appropriate intervention strategies , may reduce the risk for the cascade of events towards ulceration and subsequent amputation",
"This prospect i ve r and omized study evaluated the influence of a simple education program on the incidence of lower extremity amputation in diabetic patients . Two hundred three patients were r and omized into two groups : Group 1 , education ( 103 patients , 203 limbs ) and Group 2 , no education ( 100 patients , 193 limbs ) . There were no significant differences in medical management or clinical risk factors between the two groups . The amputation rate was three times higher in Group 2 ( 21 of 177 limbs versus 7 of 177 limbs ; p less than or equal to 0.025 ) , the ulceration rate was three times higher in Group 2 ( 26 of 177 limbs versus 8 of 177 limbs ; p less than or equal to 0.005 ) , and there was no difference in the overall incidence of infection ( 2 of 177 limbs ) . Overall success in Group 1 was highly significantly different from Group 2 ( 160 of 177 limbs versus 128 of 177 limbs ; p less than or equal to 0.0005 ) . This study demonstrated that a simple education program significantly reduced the incidence of ulcer or foot and limb amputation in diabetic patients",
"Participants who received Pies Sanos , a 15-min intervention design ed to improve diabetes self-efficacy and foot self-care behaviors in adult patients with type 2 diabetes who lived in a predominantly Mexican American community , performed more-complete foot self-care 1 month later in their homes . Recruited when they presented for nonurgent care to the emergency department in two community hospitals near the U.S .— Mexico border , participants were r and omized into one of three groups . At follow-up , there was a significant difference in observed foot self-care behaviors between groups , F(2 , 135 ) = 2.99 , p follow-up self-reported foot self-care behaviors . Baseline diabetes self-efficacy was significantly and positively correlated with both baseline ( r = .335 , p .05 ) foot self-care behaviors ",
"This quasi-experimental pilot study used a convenience sample of 23 adult men and women with either Type 1 or Type 2 diabetes who received hemodialysis three times a week . The experimental group received a four-part intervention that included individual and group foot care education , foot assessment , and special shoes . Pre- and posttesting of foot care knowledge was done using the Siriraj question naire . Out of a possible score of 20 , those in the experimental group had a mean score of 15.3 versus 14.33 in the control group on the posttest . The nephrology nurse has the opportunity to play a role in early detection and intervention in clients with ESRD",
"Despite the established role of foot care education in diabetes management , reports evaluating such interventions are rare . The effectiveness of an intensive foot care intervention programme and a conventional one were therefore compared in Type 2 diabetes . The intensive group showed significantly greater improvements than the conventional group in foot care knowledge ( p less than 0.001 ) , compliance with the recommended foot care routine ( p = 0.012 ) , and compliance with the initial advice to consult a podiatrist ( other than the project podiatrist ) for further treatment ( p = 0.008 ) . At the first follow-up visit the intensive group also showed a significantly greater reduction in the number of foot problems requiring treatment than the conventional group",
"PURPOSE the purpose of this study was to test the effectiveness of an educational intervention to improve patients ' foot care knowledge , self-efficacy , and self-care practice s. METHODS A prospect i ve , r and omized , single center , 2-group design was used with a convenience sample of 40 home care patients from a Medicare-certified home health agency . Baseline measures of foot care knowledge , self-efficacy , and reported self-care practice s were obtained at study entry and 6 weeks later to control for foot care interventions provided during routine home care services . After obtaining the 6-week baseline measures , patients who were r and omized to the intervention group received individualized education about proper foot care . All patients were interviewed a third time 3 months after study entry to determine the effectiveness of the intervention . RESULTS The educational intervention improved patients ' knowledge , confidence , and reported foot care behaviors . CONCLUSIONS A brief , individualized educational intervention about st and ard foot care topics improved patients ' foot care knowledge and self-efficacy as well as reported self-care practice s. Incorporating such interventions into routine home care services may enhance the quality of care and decrease the incidence of lower-extremity complications",
"Associations between specific foot-care behaviors and foot lesions in patients with non-insulin-dependent diabetes mellitus were prospect ively investigated . Data from a r and omized controlled trial for preventing diabetic foot lesions were analyzed as a prospect i ve cohort using logistic regression . Independent variables included foot-care behaviors , patient self-foot examination , going barefoot , availability of foot-care assistance , and visits to health-care providers . The dependent variable was a foot wound on each foot at follow-up . In the final multivariate model , patients who rarely lubricated their feet had an increased risk of foot lesions . Increasing patient use of emollients may be key to preventing foot lesions",
"A cohort of Medicare beneficiaries with diabetes was identified from inpatient and outpatient cl aims data and their risk for foot complications was estimated based on cl aims reflecting services for recent foot problems . A telephone survey of a r and om sample from this cohort was conducted to assess their foot care practice s , barriers , and perceptions of risk . Eight percent of respondents reported a history of foot ulcers and 7 % a history of lower extremity amputation . Based on cl aims data , 30 % of respondents were at high risk for future foot complications . Compared to those at low risk , those at high risk were more likely to report having an annual foot exam , using protective footwear , and perceiving themselves to be high risk for future foot complications . However , 50 % of those with cl aims indicating a high risk perceived themselves to be at low risk for future foot complications . Overall , 20 % of respondents seldom checked their feet daily for sores or irritations . Among this group , 60 % felt that it was unimportant and 9 % reported they were limited by poor vision or physical problems . Our findings suggest that strategies are needed to improve the delivery of preventive foot care services to older persons with diabetes . Additionally , emphasis is needed to help individuals underst and their risk and seek and perform appropriate preventive foot care",
"This study investigated the effectiveness of a \" h and s-on \" foot care teaching/learning approach for adults with diabetes . By r and om assignment , the control group received a lecture presentation on foot care , while the experimental group participated in a h and s-on session on foot care in addition to the lecture presentation . Data concerning the subjects ' foot care knowledge and skills , the condition of their feet , and their level of HbA1c were gathered prior to and six months after the foot care educational sessions . No significant increases in knowledge about foot care were observed in the experimental group . The experimental group reported improvements in inspecting and washing their feet on a daily basis , and in care of the toenails . No significant differences were observed in the status of the subjects ' feet . The HbAlc readings were significantly improved for both the experimental ( t=4.10 , df=10 , p=0.002 ) and control ( t=2.25 , df=9 , p=0.051 ) groups . A h and s-on educational session may improve foot care practice s temporarily . However , long term effects need to be studied to discern overall improvement of foot care practice s and physical status of the feet",
"Given that 14 million Americans have diabetes [ 1 ] , the common complications of this disorder , such as foot ulcers and lower extremity amputations , are of major concern to the medical community . Approximately 20 % of all diabetic patients hospitalized in the United States are admitted because of foot complications [ 2 , 3 ] . Furthermore , about 50 % of all nontraumatic amputations in the United States are done in patients with diabetes [ 1 , 4 ] . This proportion equates to about 55 000 amputations a year [ 1 ] or 59.7 amputations for every 10 000 persons with diabetes [ 5 ] . Patients who undergo an amputation are at greater risk for a second similar procedure on either the same or the other leg [ 6 , 7 ] . Yet , it has been estimated that about one half of the amputations in patients with diabetes , or about one fourth of the total amputations done in the United States , are preventable [ 1 , 4 ] . Recently , the focus has been on preventive strategies that minimize foot damage in diabetic patients and thereby reduce the rates of ulcers and amputations . These preventive strategies are based on two observations : first , that simple efforts on the part of the health care provider or patient can reduce the likelihood of subsequent amputation due to diabetes-associated foot disease [ 8 ] ; and second , that many of these simple procedures are not being systematic ally applied by health care providers or patients [ 9 ] . For example , studies indicate that physicians infrequently examine the feet of patients with diabetes [ 9 , 10 ] . Also , most patients with diabetes do not engage in simple foot-care assessment s to identify lesions requiring early treatment [ 11 ] . Preventive strategies are not systematic ally applied for several reasons : First , patients may not be aware of foot-care procedures or how to do them , or they may not believe that such procedures can make a difference ; second , podiatry and orthopedics services that could assist in foot salvage in diabetic patients may not be available ; and , finally , the health care system may make it difficult for patients or health care providers to examine the feet of patients with diabetes [ 10 ] . Several uncontrolled studies found that implementation of improved foot-care programs can significantly reduce lower extremity complications in patients with diabetes ; these studies showed a 44 % to 85 % reduction in the rate of lower extremity amputations [ 4 , 12 - 14 ] . A recent casecontrol study also supports the implementation of preventive strategies , such as foot care , use of protective footwear , and aggressive treatment of foot infection by patients or health care providers , to decrease the risk for lower extremity amputation [ 15 ] . The intervention in our study was design ed to reduce the prevalence of risk factors for lower extremity amputations in patients with noninsulin-dependent diabetes and involved the three major elements of a prevention program : the patient , health care providers , and the health care system . Specifically , we did a r and omized , controlled trial to determine whether a comprehensive foot-care intervention could improve patients ' knowledge and performance of appropriate foot care ; increase the number of referrals to specialty clinics such as the podiatry clinic ; increase the frequency of foot examinations by health care providers and the documentation of risk factors in the medical record ; and improve short-term patient outcomes such as skin and nail conditions known to be risk factors for ulcers and amputations . Methods Setting Our study , the design of which is summarized in Figure 1 , was done from April 1989 to March 1991 in the academic general medicine practice of the Regenstrief Health Center in Indianapolis , Indiana [ 16 ] . The practice is subdivided into four primary care teams ( labeled A , B , C , and D ) , each with its own nursing and clerical staff . Each team sees patients for eight half-day sessions per week , with each session staffed by one or two faculty internists and two to four housestaff . Teams A and C were r and omly assigned to the intervention group ; teams B and D were assigned to the control group . Previous studies in which this method of r and omization was used have shown no baseline interteam differences in patient characteristics and physician practice behavior and no effect of the team on the study outcome [ 16 - 19 ] . Figure 1 . Summary of the study design . Patient Identification and Recruitment The computerized Regenstrief Medical Record System [ 20 ] was used to identify approximately 3000 patients with noninsulin-dependent diabetes , as well as the date and time of their next appointment . Only patients with noninsulin-dependent diabetes who were seen at least two times in the preceding year by the same provider were included in the study . Additional criteria for inclusion were as follows : an age greater than 40 years ; a diagnosis of diabetes after 30 years of age ; a diagnosis of diabetes based on National Diabetes Data Group criteria [ 21 ] or the presence of disease requiring medication for the control of hyperglycemia ; an intention to obtain care at the general medicine practice for the next 2 years ; and a body weight that was either ideal or heavier than ideal . Exclusion criteria included pregnancy ; major psychiatric illness , including dementia ; terminal illness likely to cause death within 1 year ; renal failure ( serum creatinine > 440 mol/L ) ; previous bilateral amputations above or below the knee ; or an inability to provide any self-care . Patients of investigators involved in the protocol were also excluded from the study . Of the 728 eligible patients , 244 refused to participate , 89 enrolled in the study but failed to keep their appointments for assessment , and 395 were assessed by trained nurse-clinicians . Of the 395 patients assessed , 352 ( 89 % ) completed the study ; 43 patients ( 11 % ) did not complete the study for the following reasons : death ( 11 patients ) ; change of residence ( 15 patients ) ; illness ( 6 patients ) ; transportation problems ( 3 patients ) ; and miscellaneous reasons ( 8 patients ) . Patient Assessment Sample s for determining fasting plasma glucose , cholesterol , triglyceride , high-density lipoprotein , hemoglobin A1C , and C-peptide levels were obtained from enrolled patients and immediately transported to a certified laboratory for analysis . Patients gave a history and had a physical examination at study entry and approximately 1 year later ( mean , 11.8 1.5 months ) . These examinations focused on risk factors for amputation and were administered by two trained nurse-clinicians who were blinded to the patients ' experimental conditions . Foot-related data derived from the history and physical examination included the patient 's self-reported foot-care behaviors ; the quality of the patient 's examination of his or her feet ; the severity of any foot lesions ; and the presence of musculoskeletal abnormalities , dermatologic conditions , peripheral vascular disease , and peripheral neuropathy ( the neuropathy assessment included quantitative measures of pressure and temperature sensation ) . Patients were question ed about their regular foot-care routine and were asked to show how they examined their feet . During this self-examination , nurse-clinicians observed whether patients ' scrutinized the toenails , the soles of the feet , and the area between toes . Musculoskeletal and dermatologic abnormalities were assessed using st and ard definitions of findings such as callus , hammer toe , and Charcot foot [ 3 , 22 ] . The nurse-clinicians palpated the dorsalis pedis , posterior tibial , and femoral pulses bilaterally in their assessment for peripheral vascular disease . If a pulse was absent at any one of the six sites palpated , the assessment was considered abnormal . Foot lesions were rated for severity using the Seattle Wound Classification System [ 23 ] , which ranges from a grade of 1.1 ( absence of lesions ) to a grade of 10 ( entire foot or leg is gangrenous ) . In our study , a foot lesion was defined as any wound , with or without functional interruption of the protective cutaneous barrier , ranging from a superficial scratch to an ulcer involving the epidermis . A serious foot lesion was defined by a severity grade of at least 1.3 , which indicates a minor , nonulcerated lesion with clinical evidence of healing sufficient to close previous interruption of the cutaneous barrier [ 23 ] or a blister . Pressure and temperature sensations were measured using the 5.07-log ( 0.1 mg)-force Semmes-Weinstein monofilament and the thermal sensitivity testing apparatus , according to st and ard techniques [ 24 - 26 ] . Thermal sensitivity was considered abnormal if the patient had a value greater than 2 st and ard deviations from the mean value for a group of healthy persons without diabetes ( warm > 2.04 C ; cool > 1.58 C ) . Practice Patterns of Health Care Providers Immediately after each scheduled visit , study patients had a structured interview [ 10 ] with a research assistant , who asked about foot self-examination and foot-care education given by health care providers ( the primary care physician or nursing personnel ) . In addition , a chart audit was conducted by a nurse-clinician who was blinded to the patients ' experimental condition . Information abstract ed from the medical record included the physician 's documentation of the findings from the history and physical examination ; any referral to podiatry , orthopedics , or vascular surgery clinics ; and diagnostic-test ordering related to the evaluation and treatment of diabetes-associated foot problems . Intervention The intervention cohort was exposed to several risk-reduction strategies . The nurse-clinicians conducted the patient education session with one to four patients , covering appropriate foot-care behaviors and footwear , using a commercially available slide and audiotape presentation [ 27 ] and pamphlets [ 28 ] . Behavioral contracts regarding desired foot-care behaviors were negotiated with each patient . Follow-up was done by telephone 2 weeks after the education sessions to remind patients"
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41187368-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND Cardiovascular disease ( CVD ) is the leading cause of death and disability worldwide , yet CVD risk factor control and secondary prevention rates remain low . A fixed-dose combination of blood pressure and cholesterol lowering and antiplatelet treatments into a single pill , or polypill , has been proposed as one strategy to reduce the global burden of CVD by up to 80 % given its potential for better adherence and lower costs . OBJECTIVES To determine the effectiveness of fixed-dose combination therapy on reducing fatal and non-fatal CVD events and on improving blood pressure and lipid CVD risk factors for both primary and secondary prevention of CVD . We also aim ed to determine discontinuation rates , adverse events , health-related quality of life , and costs of fixed-dose combination therapy . SEARCH METHODS We search ed the Cochrane Central Register of Controlled Trials ( CENTRAL ) in The Cochrane Library ( 2013 , Issue 6 ) , MEDLINE Ovid ( 1946 to week 2 July 2013 ) , EMBASE Ovid ( 1980 to Week 28 2013 ) , ISI Web of Science ( 1970 to 19 July 2013 ) , and the Data base of Abstract s of Review s of Effects ( DARE ) , Health Technology Assessment Data base ( HTA ) , and Health Economics Evaluations Data base ( HEED ) ( 2011 , Issue 4 ) in The Cochrane Library . We used no language restrictions . SELECTION CRITERIA We included r and omised controlled trials of a fixed-dose combination therapy including at least one blood pressure lowering and one lipid lowering component versus usual care , placebo , or a single drug active component for any treatment duration in adults ≥ 18 years old with no restrictions on presence or absence of pre-existing cardiovascular disease . DATA COLLECTION AND ANALYSIS Three review authors independently selected studies for inclusion and extracted the data . We evaluated risk of bias using the Cochrane risk of bias assessment tool . We sought to include outcome data on all-cause mortality , fatal and non-fatal CVD events , adverse events , changes in systolic and diastolic blood pressure , total and low density lipoprotein ( LDL ) cholesterol concentrations , discontinuation rates , quality of life , and costs . We calculated risk ratios ( RR ) for dichotomous data and weighted mean differences ( MD ) for continuous data with 95 % confidence intervals ( CI ) using fixed-effect models when heterogeneity was low ( I(2 ) 50 % ) . MAIN RESULTS We found nine r and omised controlled trials with a total of 7047 participants . Seven of the nine trials evaluated the effects of fixed-dose combination therapy on primary CVD prevention , and the trial length ranged from six weeks to 15 months . We found a moderate to high risk of bias in the domains of selection , performance , detection , attrition , and other types of bias in five of the nine trials . Compared with the comparator groups , the effects of the fixed-dose combination treatment on mortality ( 1.2 % versus 1.0 % , RR 1.26 , 95 % CI 0.67 to 2.38 , N = 3465 ) and cardiovascular events ( 4.0 % versus 2.9 % , RR 1.38 , 95 % CI 0.91 to 2.10 , N = 2479 ) were uncertain ( low quality evidence ) . The low event rates for these outcomes , limited availability of data as only two out of nine trials reported on these outcomes , and a high risk of bias in at least one domain suggest that these results should not be viewed with confidence . Adverse events were common in both the intervention ( 30 % ) and comparator ( 24 % ) groups , with participants r and omised to fixed-dose combination therapy being 20 % ( 95 % CI 9 % to 30 % ) more likely to report an adverse event . Notably , no serious adverse events were reported . Compared with placebo , the rate of discontinuation among participants r and omised to fixed-dose combination was higher ( 14 % versus 11 % , RR 1.26 95 % CI 1.02 to 1.55 ) . The weighted mean differences in systolic and diastolic blood pressure between the intervention and control arms were -7.05 mmHg ( 95 % CI -10.18 to -3.87 ) and -3.65 mmHg ( 95 % CI -5.44 to -1.85 ) , respectively . The weighted mean differences ( 95 % CI ) in total and LDL cholesterol between the intervention and control arms were -0.75 mmol/L ( 95 % CI -1.05 to -0.46 ) and -0.81 mmol/L ( 95 % CI -1.09 to -0.53 ) , respectively . There was a high degree of statistical heterogeneity in comparisons of blood pressure and lipids ( I(2 ) ≥ 70 % for all ) that could not be explained , so these results should be viewed with caution . Fixed-dose combination therapy improved adherence to a multi-drug strategy by 33 % ( 26 % to 41 % ) compared with usual care , but this comparison was reported in only one study . The effects of fixed-dose combination therapy on quality of life are uncertain , though these results were reported in only one trial . No trials reported costs . AUTHORS ' CONCLUSIONS Compared with placebo , single drug active component , or usual care , the effects of fixed-dose combination therapy on all-cause mortality or CVD events are uncertain ; only few trials report these outcomes and the included trials were primarily design ed to observe changes in CVD risk factor levels rather than clinical events . Reductions in blood pressure and lipid parameters are generally lower than those previously projected , though substantial heterogeneity of results exists . Fixed-dose combination therapy is associated with modest increases in adverse events compared with placebo , single drug active component , or usual care but may be associated with improved adherence to a multidrug regimen . Ongoing trials of fixed-dose combination therapy will likely inform key outcomes
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"BACKGROUND Patients with grade 2 or 3 hypertension may require high-dose combination therapy to achieve blood pressure ( BP ) targets in a timely manner . OBJECTIVES This study compared the effectiveness and tolerability of a single-pill combination ( SPC ) of telmisartan/hydrochlorothiazide 80/25 mg ( T80/H25 ) with T80 monotherapy . METHODS In a Phase IV , multinational , r and omized , double-blind , double-dummy , active-controlled , parallel-group trial , 894 patients with mean seated trough cuff systolic BP [ SBP ] ≥160 mm Hg and diastolic BP [ DBP ] ≥100 mm Hg were r and omly assigned in a 2:1 ratio to receive T40/H12.5 SPC or telmisartan 40 mg monotherapy for 1 week before the dose was uptitrated to T80/H25 SPC or T80 , respectively , administered for 6 weeks . The primary efficacy measure was the change from baseline in mean seated cuff trough SBP . Adverse events ( AEs ) were recorded . RESULTS A total of 888 patients received treatment ( 294 and 594 patients in the T80/H25 and T80 groups , respectively ) ( mean age , 57.0 years ; age ≥65 years , 25.7 % ; male , 53.8 % ; white , 68.0 % ) ; 61 patients prematurely discontinued . Mean baseline SBP/DBP values were 172.3/104.3 mm Hg ( T80/H25 ) and 173.3/104.5 mm Hg ( T80 ) . After 7 weeks , SBP was changed by -37.0 and -28.5 mm Hg in the T80/H25 and T80 groups ( P was changed by -18.6 and -15.4 mm Hg respectively ( P ( P BP target ( SBP/DBP ) . T80/H25 SPC and T80 had a similar frequency of overall AEs ( 16.0 % vs 17.0 % ) . The prevalences of treatment-related AEs with T80/H25 SPC and T80 were low ( 4.6 % and 2.8 % ) , as were the rates of AEs that led to discontinuation ( 1.0 % and 2.8 % ) . CONCLUSIONS In these patients with grade 2 or 3 hypertension , initial therapy with T80/H25 was associated with a significantly greater reduction in mean seated cuff trough SBP compared with T80 alone , as well as with improved hypertension goal attainment rates . Both treatments appeared to be well tolerated",
"Background The Kanyini Guidelines Adherence with the Polypill ( Kanyini-GAP ) Study aims to examine whether a polypill-based strategy ( using a single capsule containing aspirin , a statin and two blood pressure-lowering agents ) amongst Indigenous and non-Indigenous people at high risk of experiencing a cardiovascular event will improve adherence to guideline -indicated therapies , and lower blood pressure and cholesterol levels . Methods / Design The study is an open , r and omised , controlled , multi-centre trial involving 1000 participants at high risk of cardiovascular events recruited from mainstream general practice s and Aboriginal Medical Services , followed for an average of 18 months . The participants will be r and omised to one of two versions of the polypill , the version chosen by the treating health professional according to clinical features of the patient , or to usual care . The primary study outcomes will be changes , from baseline measures , in serum cholesterol and systolic blood pressure and self-reported current use of aspirin , a statin and at least two blood pressure lowering agents . Secondary study outcomes include cardiovascular events , renal outcomes , self-reported barriers to indicated therapy , prescription of indicated therapy , occurrence of serious adverse events and changes in quality -of-life . The trial will be supplemented by formal economic and process evaluations . Discussion The Kanyini-GAP trial will provide new evidence as to whether or not a polypill-based strategy improves adherence to effective cardiovascular medications amongst individuals in whom these treatments are indicated . Trial Registration This trial is registered with the Australian New Zeal and Clinical Trial Registry ACTRN126080005833347",
"Background There has been widespread interest in the potential of combination cardiovascular medications containing aspirin and agents to lower blood pressure and cholesterol ( ‘ polypills ’ ) to reduce cardiovascular disease . However , no reliable placebo-controlled data are available on both efficacy and tolerability . Methods We conducted a r and omised , double-blind placebo-controlled trial of a polypill ( containing aspirin 75 mg , lisinopril 10 mg , hydrochlorothiazide 12.5 mg and simvastatin 20 mg ) in 378 individuals without an indication for any component of the polypill , but who had an estimated 5-year cardiovascular disease risk over 7.5 % . The primary outcomes were systolic blood pressure ( SBP ) , LDL-cholesterol and tolerability ( proportion discontinued r and omised therapy ) at 12 weeks follow-up . Findings At baseline , mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 mmol/L. Over 12 weeks , polypill treatment reduced SBP by 9.9 ( 95 % CI : 7.7 to 12.1 ) mmHg and LDL-cholesterol by 0.8 ( 95 % CI 0.6 to 0.9 ) mmol/L. The discontinuation rates in the polypill group compared to placebo were 23 % vs 18 % ( RR 1.33 , 95 % CI 0.89 to 2.00 , p = 0.2 ) . There was an excess of side effects known to the component medicines ( 58 % vs 42 % , p = 0.001 ) , which was mostly apparent within a few weeks , and usually did not warrant cessation of trial treatment . Conclusions This polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6 people . The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate is moderately higher . Nonetheless , substantial net benefits would be expected among patients at high risk . Trial Registration Australian New Zeal and Clinical Trials Registry",
"Background — A daily single capsule ( polycap ) of 3 blood pressure ( BP ) lowering drugs ( hydrochlorthiazide , 12.5 mg ; atenolol , 50 mg ; ramipril , 5 mg ) at low doses , simvastatin ( 20 mg ) , and aspirin ( 100 mg ) has been demonstrated to be well tolerated and to reduce BP and low-density lipoprotein cholesterol . We examined the incremental effects of 2 ( full dose ) plus K+ supplementation versus single polycap ( low dose ) on risk factors and tolerability . Methods and Results — After a run-in period , 518 individuals with previous vascular disease or diabetes mellitus from 27 centers in India were r and omly assigned to a single-dose polycap or to 2 capsules of the polycap plus K+ supplementation for 8 weeks . The effects on BP , heart rate ( HR ) , serum lipids , serum and urinary K+ , and tolerability were assessed using an intention-to-treat analysis . The full-dose polycap ( plus K+ supplementation ) reduced BP by a further 2.8 mm Hg systolic and 1.7 mm Hg diastolic , compared with that observed with the low-dose polycap ( P=0.003 ; P=0.001 ) , but there were no differences in HR ( 0.1 bpm ) . The differences in total and low-density lipoprotein cholesterol between the full-dose and low-dose polycap was 7.2 mg/dL ( P=0.014 ) and 6.6 mg/dL ( P=0.006 ) , respectively , but there were no differences in high-density lipoprotein cholesterol or triglycerides . The rates of discontinuation of the study drug after r and omization were similar in the 2 groups ( 6.9 % low dose versus 7.8 % full dose ) . Conclusions — The full-dose polycap ( plus K+ supplementation ) reduces BP and low-density lipoprotein cholesterol to a greater extent compared with the low dose , with similar tolerability . Therefore , the full-dose polycap should potentially lead to larger benefits . Clinical Trial Registration — URL : http://www.ctri.nic.in . Unique identifier : CTRI/2010/091/000054",
"IMPORTANCE Most patients with cardiovascular disease ( CVD ) do not take recommended medications long-term . The use of fixed-dose combinations ( FDCs ) improves adherence in several clinical areas . Previous trials of cardiovascular FDCs have assessed short-term effects compared with placebo or no treatment . OBJECTIVE To assess whether FDC delivery of aspirin , statin , and 2 blood pressure-lowering agents vs usual care improves long-term adherence to indicated therapy and 2 major CVD risk factors , systolic blood pressure ( SBP ) and low-density lipoprotein cholesterol ( LDL-C ) . DESIGN , SETTING , AND PARTICIPANTS The UMPIRE trial , a r and omized , open-label , blinded-end-point trial among 2004 participants with established CVD or at risk of CVD enrolled July 2010-July 2011 in India and Europe . The trial follow-up concluded in July 2012 . INTERVENTIONS Participants were r and omly assigned ( 1:1 ) to an FDC-based strategy ( n=1002 ) containing either ( 1 ) 75 mg aspirin , 40 mg simvastatin , 10 mg lisinopril , and 50 mg atenolol or ( 2 ) 75 mg aspirin , 40 mg simvastatin , 10 mg lisinopril , and 12.5 mg hydrochlorothiazide or to usual care ( n=1002 ) . MAIN OUTCOMES AND MEASURES Adherence to medication ( defined as self-reported use of antiplatelet , statin , and ≥2 BP-lowering medications ) and changes in SBP and LDL-C from baseline . RESULTS At baseline , mean BP was 137/78 mm Hg , LDL-C was 91.5 mg/dL , and 1233 ( 61.5 % ) of 2004 participants reported use of antiplatelet , statin , and 2 or more BP-lowering medications . Median follow-up was 15 months ( interquartile range , 12 - 18 months ) . The FDC group had improved adherence vs usual care ( 86 % vs 65 % ; relative risk [ RR ] of being adherent , 1.33 ; 95 % CI , 1.26 - 1.41 ; P reductions in SBP ( -2.6 mm Hg ; 95 % CI , -4.0 to -1.1 mm Hg ; P .001 ) and LDL-C ( -4.2 mg/dL ; 95 % CI , -6.6 to -1.9 mg/dL ; P 727 participants ( 36 % ) , adherence at the end of study was 77 % vs 23 % ( RR , 3.35 ; 95 % CI , 2.74 - 4.09 ; P .001 for interaction ) , SBP was reduced by 4.9 mm Hg ( 95 % CI 7.3 - 2.6 mm Hg ; P = .01 for interaction ) , and LDL-C was reduced by 6.7 mg/dL ( 95 % CI , 10.5 - 2.8 mg/dL ; P = .11 for interaction ) . There were no significant differences in serious adverse events or cardiovascular events ( 50 [ 5 % ] in the FDC group and 35 [ 3.5 % ] in the usual care group ; RR , 1.45 ; 95 % CI , 0.94 - 2.24 ; P=.09 ) between the groups . CONCLUSIONS AND RELEVANCE Among patients with or at high risk of CVD , use of an FDC strategy for blood pressure , cholesterol , and platelet control vs usual care result ed in significantly improved medication adherence at 15 months and statistically significant but small improvements in SBP and LDL-C. TRIAL REGISTRATION clinical trials.gov Identifier : NCT01057537",
"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 19342 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 , 10305 with non-fasting 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",
"Abstract Background : In many countries , combination therapy with amlodipine and atorvastatin is indicated for the treatment of patients with hypertension and hypercholesterolemia . The aim of this study was to investigate the impact of this combination therapy on plasma adiponectin levels . Hypothesis : Combination therapy with amlodipine and atorvastatin would increase plasma adiponectin levels . Methods : A total of 25 patients with coronary artery disease and concomitant hypertension and hypercholesterolemia were evaluated . The combination of amlodipine and atorvastatin in 8 different dosage strengths were flexibly titrated over a period of 14 weeks . Lipid profile and plasma adiponectin were measured . Brachial flow-mediated dilation ( FMD ) was determined by vascular ultrasound . Results : As compared with baseline , combination therapy with amlodipine and atorvastatin significantly reduced systolic and diastolic blood pressure , total cholesterol , and low-density lipoprotein cholesterol ( all P in adiponectin levels ( mean [ 95 % confidence interval ( CI ) ] , 12.1 [ 10.7 - 13.7 ] vs 8.1 [ 6.5 - 10.0 ] μg/mL ; P and brachial FMD ( 4.4 ± 0.6 % vs 5.6 ± 0.5 % ; P = 0.046 ) over 14 weeks of treatment . The change in adiponectin levels correlated significantly with the changes in diastolic blood pressure ( r = −0.49 ; P = 0.014 ) and FMD ( r = 0.55 ; P = 0.007 ) . Conclusion : The results of this study indicate that along with its antihypertensive and cholesterol-lowering effects , combination therapy with amlodipine and atorvastatin appears to increase plasma adiponectin levels and improve endothelial function",
"In spite of advances in prevention and treatment , the burden of cardiovascular diseases is increasing . A fixed-dose combination ( FDC ) pill , or \" polypill , \" composed of evidence -based drugs has been proposed as a means of improving cardiovascular prevention by reducing cost and increasing patient adherence to treatment . The aim of the FOCUS project , funded by the 7th Framework Programme of the European Commission , is to characterize the factors that underlie inadequate secondary prevention and to test a new FDC . To achieve these goals , a 9-member consortium has been constituted , including institutions from Argentina , France , Italy , Spain , and Switzerl and . FOCUS Phase-1 will examine factors potentially related to lack of adequate secondary prevention in 4,000 post-myocardial infa rct ion ( MI ) patients and analyze the relationship between these factors and patient treatment adherence . Primary end points will be ( 1 ) the percentage of patients receiving aspirin , angiotensin-converting enzyme inhibitors , and statins and ( 2 ) adherence to treatment measured by the Morisky-Green test . FOCUS Phase-2 is a r and omized trial that will compare adherence to treatment in 1,340 post-myocardial infa rct ion patients either receiving an FDC comprising aspirin ( 100 mg ) , ramipril ( 2.5 , 5 , or 10 mg ) , and simvastatin ( 40 mg ) or receiving the same 3 drugs separately ",
"Background The feasibility of conducting a large-scale Polypill clinical trial in developing countries remains unclear . More information is needed regarding the efficacy in reducing the risk factors of cardiovascular disease ( CVD ) , side effects , improvement in adherence and physician/patient \" acceptability \" of the Polypill . Methods We conducted an open-label , parallel-group , r and omized clinical trial involving three sites in Sri Lanka that enrolled a total of 216 patients without established CVD . The trial compared a Polypill ( 75 mg aspirin , 20 mg simvastatin , 10 mg lisinopril and 12.5 mg hydrochlorothiazide ) to St and ard Practice . After r and omization , patients were followed monthly for three months . Pre-specified primary outcomes included reduction in systolic blood pressure , total cholesterol and estimated 10-year CVD risk . We also evaluated the recruitment process and acceptability of the Polypill by both physicians and patients . Results Patients were recruited in a six-month period as planned . Two hundred three patients ( 94.0 % ) completed the treatment program and returned for their three-month follow-up visits . No safety concerns were reported . These findings suggest a high rate of patient acceptability , a finding that is bolstered by the majority of patients completing the trial ( 90 % ) indicating that they would take the Polypill \" for life \" if proven to be effective in reducing CVD risk . Approximately 86 % of the physicians surveyed agreed with and supported use of the Polypill for primary prevention and 93 % for secondary prevention of CVD . Both the Polypill and St and ard Practice result ed in marked reductions in systolic blood pressure , total cholesterol and 10-year risk of CVD . However , the differences between the treatment groups were not statistically significant . Conclusions We successfully completed a Polypill feasibility trial in Sri Lanka . We were able to document high acceptability of the Polypill to patients and physicians . We were unable to estimate the risk factor reductions on the Polypill because the control group received similar treatment with individual drugs . The Polypill was however simpler and achieved comparable risk factor reductions , highlighting its potential usefulness in the prevention of CVD.Trial registration number Clinical trials.gov :",
"Background A Polypill is proposed for the primary prevention of cardiovascular disease in people judged to be at risk on account of their age alone . Its efficacy in reducing cholesterol and blood pressure is uncertain . Methods We conducted a r and omized double-blind placebo-controlled crossover trial of a Polypill among individuals aged 50 + without a history of cardiovascular disease and compared the reductions with those predicted from published estimates of the effects of the individual drugs . Participants took the Polypill ( amlodipine 2.5 mg , losartan 25 mg , hydrochlorothiazide 12.5 mg and simvastatin 40 mg ) each evening for 12 weeks and a placebo each evening for 12 weeks in r and om sequence . The mean within-person differences in blood pressure and low density lipoprotein ( LDL ) cholesterol at the end of each 12 week period were determined . Results 84 out of 86 participants completed both treatment periods . The mean systolic blood pressure was reduced by 17.9 mmHg ( 95 % CI , 15.7–20.1 ) on the Polypill , diastolic blood pressure by 9.8 mmHg ( 8.1–11.5 ) , and LDL cholesterol by 1.4 mmol/L ( 1.2–1.6 ) , reductions of 12 % , 11 % , and 39 % respectively . The results were almost identical to those predicted ; 18.4 mmHg , 9.7 mmHg , and 1.4 mmol/L respectively . Conclusion The Polypill result ed in the predicted reductions in blood pressure and LDL cholesterol . Long term reductions of this magnitude would have a substantial effect in preventing heart attacks and strokes . Trial Registration Controlled-Trials.com IS RCT",
"Objective To compare the effects of two antihypertensive treatment strategies for the prevention of coronary heart disease and other cardiovascular events in the large sub population ( n = 5137 ) with diabetes mellitus in the blood pressure-lowering arm of the Anglo-Sc and inavian Cardiac Outcomes Trial . Methods Patients had either untreated hypertension or treated hypertension . For those with type II diabetes mellitus , inclusion criteria required at least two additional risk factors . Patients were r and omized to amlodipine with addition of perindopril as required ( amlodipine-based ) or atenolol with addition of thiazide as required ( atenolol-based ) . Therapy was titrated to achieve a target blood pressure of less than 130/80 mmHg . Results The trial was terminated early due to significant benefits on mortality and stroke associated with the amlodipine-based regimen . In patients with diabetes mellitus , the amlodipine-based treatment reduced the incidence of the composite endpoint – total cardiovascular events and procedures – compared with the atenolol-based regimen ( hazard ratio 0.86 , confidence interval 0.76–0.98 , P = 0.026 ) . Fatal and nonfatal strokes were reduced by 25 % ( P = 0.017 ) , peripheral arterial disease by 48 % ( P = 0.004 ) and noncoronary revascularization procedures by 57 % ( P coronary heart disease deaths and nonfatal myocardial infa rct ions ( the primary endpoint ) , which were reduced nonsignificantly by 8 % ( hazard ratio 0.92 , confidence interval 0.74–1.15 ) . Conclusion In the large diabetic subgroup in the blood pressure-lowering arm of the Anglo-Sc and inavian Cardiac Outcomes Trial , the benefits of amlodipine-based treatment , compared with atenolol-based treatment , on the incidence of total cardiovascular events and procedures was significant ( 14 % reduction ) and similar to that observed in the total trial population ( 16 % reduction )",
"BACKGROUND The Valsartan Antihypertensive Long-term Use Evaluation ( VALUE ) trial was design ed to test the hypothesis that for the same blood-pressure control , valsartan would reduce cardiac morbidity and mortality more than amlodipine in hypertensive patients at high cardiovascular risk . METHODS 15?245 patients , aged 50 years or older with treated or untreated hypertension and high risk of cardiac events participated in a r and omised , double-blind , parallel-group comparison of therapy based on valsartan or amlodipine . Duration of treatment was event-driven and the trial lasted until at least 1450 patients had reached a primary endpoint , defined as a composite of cardiac mortality and morbidity . Patients from 31 countries were followed up for a mean of 4.2 years . FINDINGS Blood pressure was reduced by both treatments , but the effects of the amlodipine-based regimen were more pronounced , especially in the early period ( blood pressure 4.0/2.1 mm Hg lower in amlodipine than valsartan group after 1 month ; 1.5/1.3 mm Hg after 1 year ; p valsartan group ( 10.6 % , 25.5 per 1000 patient-years ) and 789 in the amlodipine group ( 10.4 % , 24.7 per 1000 patient-years ; hazard ratio 1.04 , 95 % CI 0.94 - 1.15 , p=0.49 ) . INTERPRETATION The main outcome of cardiac disease did not differ between the treatment groups . Unequal reductions in blood pressure might account for differences between the groups in cause-specific outcomes . The findings emphasise the importance of prompt blood-pressure control in hypertensive patients at high cardiovascular risk",
"BACKGROUND A combination of medications that simultaneously reduce several cardiovascular risk factors in people above a specified age , without selection based on risk factor measurement , has been proposed as a simple strategy for reducing the risk of cardiovascular disease and shown to be effective in r and omized trials ( the Polypill approach ) . AIMS To assess acceptance of the Polypill approach and adherence to preventive treatment among individuals taking part in a cardiovascular disease prevention service . METHODS Daily treatment with simvastatin ( 40 mg ) , amlodipine ( 2.5 mg ) , bendroflumethiazide ( 1.25 mg ) , lisinopril ( 5 mg ) [ or c and esartan ( 4 mg ) if cough was reported ] and folic acid ( 0.8 mg ) was offered , as separate components , to people ≥ 55 years with no history of cardiovascular , renal or liver disease . An audit of adverse effects , adherence and requests for blood pressure and cholesterol measurement was determined by telephone consultation . RESULTS Between 2006 and 2010 , 269 participants started treatment with the Polypill components . Follow-up ranged from 3 to 48 months ( mean 20 ) . A total of 222 participants ( 83 % ) adhered to treatment , including 30 ( 11 % ) who switched from the angiotensin-converting enzyme inhibitor ( lisinopril ) to the angiotensin receptor blocker ( c and esartan ) because of cough . Ten participants ( 4 % ) continued to take treatment but stopped taking one or more drugs because of other symptoms , and 37 ( 14 % ) stopped all treatment , eight because of adverse effects and 29 for non-medical reasons . No one requested a blood pressure or cholesterol measurement . CONCLUSION This is the first demonstration of the application of the Polypill approach in practice . The method was accepted and the Polypill components were well tolerated , with good adherence and no dem and for information about risk factors",
"BACKGROUND Although most cardiovascular disease occurs in low-income and middle-income countries , little is known about the use of effective secondary prevention medications in these communities . We aim ed to assess use of proven effective secondary preventive drugs ( antiplatelet drugs , β blockers , angiotensin-converting-enzyme [ ACE ] inhibitors or angiotensin-receptor blockers [ ARBs ] , and statins ) in individuals with a history of coronary heart disease or stroke . METHODS In the Prospect i ve Urban Rural Epidemiological ( PURE ) study , we recruited individuals aged 35 - 70 years from rural and urban communities in countries at various stages of economic development . We assessed rates of previous cardiovascular disease ( coronary heart disease or stroke ) and use of proven effective secondary preventive drugs and blood-pressure-lowering drugs with st and ardised question naires , which were completed by telephone interviews , household visits , or on patient 's presentation to clinics . We report estimates of drug use at national , community , and individual levels . FINDINGS We enrolled 153,996 adults from 628 urban and rural communities in countries with incomes classified as high ( three countries ) , upper-middle ( seven ) , lower-middle ( three ) , or low ( four ) between January , 2003 , and December , 2009 . 5650 participants had a self-reported coronary heart disease event ( median 5·0 years previously [ IQR 2·0 - 10·0 ] ) and 2292 had stroke ( 4·0 years previously [ 2·0 - 8·0 ] ) . Overall , few individuals with cardiovascular disease took antiplatelet drugs ( 25·3 % ) , β blockers ( 17·4 % ) , ACE inhibitors or ARBs ( 19·5 % ) , or statins ( 14·6 % ) . Use was highest in high-income countries ( antiplatelet drugs 62·0 % , β blockers 40·0 % , ACE inhibitors or ARBs 49·8 % , and statins 66·5 % ) , lowest in low-income countries ( 8·8 % , 9·7 % , 5·2 % , and 3·3 % , respectively ) , and decreased in line with reduction of country economic status ( p(trend) received no drugs in high-income countries ( 11·2 % ) , compared with 45·1 % in upper middle-income countries , 69·3 % in lower middle-income countries , and 80·2 % in low-income countries . Drug use was higher in urban than rural areas ( antiplatelet drugs 28·7 % urban vs 21·3 % rural , β blockers 23·5%vs 15·6 % , ACE inhibitors or ARBs 22·8%vs 15·5 % , and statins 19·9%vs 11·6 % ; all p affected rates of drug use more than did individual-level factors ( eg , age , sex , education , smoking status , body-mass index , and hypertension and diabetes statuses ) . INTERPRETATION Because use of secondary prevention medications is low worldwide-especially in low-income countries and rural areas - systematic approaches are needed to improve the long-term use of basic , inexpensive , and effective drugs . FUNDING Full funding sources listed at end of paper ( see Acknowledgments )",
"Poor control of hypertension or dyslipidemia may at least in part be due to these risk factors being treated in isolation . The Caduet in Untreated Subjects Population ( CUSP ) trial was an 8-week , r and omized , double-blind , placebo-controlled trial evaluating the efficacy/safety of the combination of a calcium channel blocker ( amlodipine besylate ) and a statin ( atorvastatin calcium ) in a single-pill form ( 5/20 mg ) plus therapeutic lifestyle changes ( TLC ) compared with placebo plus TLC in patients with comorbid hypertension and dyslipidemia without evidence of cardiovascular disease . At week 4 , additional antihypertensive/lipid-lowering medication was permitted . The primary end point was the proportion of patients in whom the dual goal of blood pressure ( low-density lipoprotein cholesterol control ( dual goal attainment was significantly greater with amlodipine/atorvastatin plus TLC compared with placebo plus TLC at week 4 ( 47.6 % vs 1.7 % ; P adverse events were mild to moderate . Therapy with single-pill amlodipine/atorvastatin plus TLC in these patients significantly increased dual blood pressure/low-density lipoprotein cholesterol goal attainment compared with placebo plus TLC",
"AIM Our objective was to investigate the effects and tolerability of fixed-dose combination therapy on blood pressure and LDL in adults without elevated blood pressure or lipid levels . METHODS This was a double-blind r and omised placebo-controlled trial in residents of Kalaleh , Golestan , Iran . Following an 8-week placebo run-in period , 475 participants , aged 50 to 79 years , without cardiovascular disease , hypertension or hyperlipidaemia were r and omised to fixed-dose combination therapy with aspirin 81 mg , enalapril 2.5 mg , atorvastatin 20 mg and hydrochlorothiazide 12.5 mg ( polypill ) or placebo for a period of 12 months . The primary outcomes were changes in LDL-cholesterol , systolic and diastolic blood pressure and adverse reactions . Analysis was by intention-to-treat basis . RESULTS At baseline , there were differences in systolic blood pressure ( 6 mmHg ) . Taking account of baseline differences , at 12 months , polypill was associated with statistically significant reductions in blood pressure ( 4.5/1.6 mmHg ) and LDL-cholesterol ( 0.46 mmol/l ) . The study drug was well tolerated , but result ed in the modest reductions in blood pressure and lipid levels . CONCLUSION The effects of the polypill on blood pressure and lipid levels were less than anticipated , raising questions about the reliability of the reported compliance . There is a case for a fully powered trial of a polypill for the prevention of cardiovascular disease",
"Background Single-pill amlodipine/atorvastatin targets the two most common modifiable cardiovascular risk factors , hypertension and dyslipidaemia . We evaluated the clinical utility of this single pill to help patients across Europe and Canada achieve country-specific targets for blood pressure ( BP ) and low-density lipoprotein cholesterol ( LDL-C ) . Design Two 16-week , open-label studies conducted in 122 study centres across the United Kingdom and Canada ( JEWEL 1 ) and 113 centres across 11 European countries ( JEWEL 2 ) . Methods Patients with uncontrolled BP and controlled/uncontrolled LDL-C qualifying for treatment according to local governing guidelines were administered single-pill amlodipine/atorvastatin with appropriate lifestyle modification . Eight dosages of amlodipine/atorvastatin ( 5/10–10/80 mg ) were titrated to achieve country-specific BP and LDL-C targets . The primary outcome was the percentage of patients reaching country-specific BP and LDL-C targets in 16 weeks . Results Among 2245 patients enrolled in the studies ( JEWEL 1 , n = 1138 ; JEWEL 2 , n = 1107 ) , 62.9 % in JEWEL 1 and 50.6 % in JEWEL 2 achieved both country-specific BP and LDL-C goals . BP was reduced by 20.4/10.7 and 21.8/12.6 mmHg in JEWEL 1 and JEWEL 2 , respectively , and reductions in LDL-C were 0.90 mmol/l ( 34.8 mg/dl ) and 1.09 mmol/l ( 42.2 mg/dl ) , respectively . The most common adverse events were peripheral oedema ( 11.0 % ) , joint swelling ( 2.9 % ) and headache ( 2.9 % ) , of which , only oedema was linked to study treatment . Conclusion Single-pill amlodipine/atorvastatin is an effective and well-tolerated treatment , which in a real-world setting helped more than half of the patients achieve both BP and LDL-C targets as recommended by local guidelines . Although fewer patients met their goals in JEWEL 2 than JEWEL 1 , reductions in BP and LDL-C were slightly greater in JEWEL 2 , suggesting that the observed differences are likely because of more stringent targets in Europe than in the UK/Canada",
"BACKGROUND Chlorthalidone has proven efficacy to reduce cardiovascular morbidity and mortality , yet it is infrequently used in practice . This study provides a direct comparison of chlorthalidone with hydrochlorothiazide , each combined with the angiotensin receptor blocker azilsartan medoxomil , on blood pressure reduction and control rates . METHODS This is a r and omized , double-blind , titrate-to-target blood pressure trial comparing the single-pill combination of azilsartan medoxomil and chlorthalidone versus co-administration of azilsartan medoxomil and hydrochlorothiazide in participants with stage 2 primary hypertension . After 2 weeks of treatment with azilsartan medoxomil 40 mg alone , all participants also received 12.5 mg of diuretic for 4 weeks ( up to week 6 ) and were titrated to 25 mg for another 4 weeks ( up to week 10 ) if they failed to achieve target blood pressure . The primary end point was change in clinic systolic blood pressure . Target blood pressure was defined as clinic blood pressure participants without diabetes or chronic kidney disease or participants with diabetes or chronic kidney disease . RESULTS The mean age of the 609 participants was 56.4 years , and the mean baseline clinic blood pressure was 164.6/95.4 mm Hg . The primary end point analysis at week 6 demonstrated a greater reduction of clinic systolic blood pressure for the chlorthalidone ( -35.1 mm Hg ) versus hydrochlorothiazide combination ( -29.5 mm Hg ) ( mean difference , -5.6 mm Hg ; 95 % confidence interval , -8.3 to -2.9 ; P 24-hour ambulatory systolic blood pressure at week 6 was -5.8 mm Hg ( 95 % confidence interval , -8.4 to -3.2 ; P azilsartan medoxomil/chlorthalidone group . The percentage of participants achieving target clinic blood pressure at week 6 was greater for the chlorthalidone versus hydrochlorothiazide combination ( 64.1 % vs 45.9 % , P Drug discontinuations due to adverse events were not statistically significantly different between groups ( 9.3 % vs 7.3 % , P = .38 ) , and hypokalemia was uncommon in both groups . CONCLUSIONS Chlorthalidone combined with azilsartan medoxomil provides better blood pressure reduction and a higher likelihood of achieving blood pressure control than hydrochlorothiazide combined with azilsartan medoxomil . This benefit occurred without a difference in safety measurements",
"Abstract Objective : To investigate whether a proactive multifactorial risk factor intervention strategy using single-pill amlodipine/atorvastatin ( 5/10 , 10/10 mg ) in addition to other antihypertensive and lipid-lowering therapy , as required , result ed in greater reduction in calculated Framingham 10-year coronary heart disease ( CHD ) risk compared with usual care ( UC ) after 52-weeks treatment . Research design and methods : Prospect i ve , multinational , open-label , cluster r and omized trial , with the investigator as the unit of r and omization . Eligible hypertensive patients were 35–79 years of age , with ≥3 additional cardiovascular risk factors , but no history of CHD and baseline total cholesterol ( TC ) ≤6.5 mmol/l . Clinical trial registration : Trial registration : Clinical Trials.gov identifier : NCT00407537 . Main outcome measure : The primary endpoint was calculated Framingham 10-year CHD risk at 52 weeks . Results : Of the 140 r and omized sites , 136 sites contributed 1461 patients . Mean baseline age and low-density lipoprotein cholesterol ( LDL-C ) were comparable between treatment arms . Mean baseline BP ( 150.3/89.7 vs. 144.3/86.5 mmHg ) and Framingham CHD risk ( 20.0 vs. 18.1 % ) were higher in the proactive intervention versus the UC arm ( p 52 , mean CHD risk was 12.5 % in the proactive intervention arm and 16.3 % in the UC arm ( p differences in systolic BP and in TC between the two arms . Overall , adverse events ( AEs ) were reported in 48.8 % and 44.0 % of patients in the proactive intervention and the UC arm , respectively . Although there were differences in the incidence of AEs between the treatment arms , the AE profile in the proactive intervention arm was consistent with previous safety experience for this medication . Conclusions : A proactive multifactorial risk factor intervention strategy that simultaneously treated both BP and cholesterol regardless of individual risk factors per se , is more effective in reducing calculated Framingham 10-year CHD risk than UC in patients with hypertension and additional risk factors",
"BACKGROUND In previous clinical trials in high-risk hypertensive patients , paradoxically higher cardiovascular event rates have been reported in patients of normal weight compared with obese individuals . As a prespecified analysis of the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension ( ACCOMPLISH ) trial , we aim ed to investigate whether the type of hypertension treatment affects patients ' cardiovascular outcomes according to their body size . METHODS On the basis of body-mass index ( BMI ) , we divided the full ACCOMPLISH cohort into obese ( BMI ≥30 , n=5709 ) , overweight ( ≥25 to The ACCOMPLISH cohort had already been r and omised to treatment with single-pill combinations of either benazepril and hydrochlorothiazide or benazepril and amlodipine . We compared event rates ( adjusted for age , sex , diabetes , previous cardiovascular events , stroke , or chronic kidney disease ) for the primary endpoint of cardiovascular death or non-fatal myocardial infa rct ion or stroke . The analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00170950 . FINDINGS In patients allocated benazepril and hydrochlorothiazide , the primary endpoint ( per 1000 patient-years ) was 30·7 in normal weight , 21·9 in overweight , and 18·2 in obese patients ( overall p=0·0034 ) . However , in those allocated benazepril and amlodipine , the primary endpoint did not differ between the three BMI groups ( 18·2 , 16·9 , and 16·5 , respectively ; overall p=0·9721 ) . In obese individuals , primary event rates were similar with both benazepril and hydrochlorothiazide and benazepril and amlodipine , but rates were significantly lower with benazepril and amlodipine in overweight patients ( hazard ratio 0·76 , 95 % CI 0·59 - 0·94 ; p=0·0369 ) and those of normal weight ( 0·57 , 0·39 - 0·84 ; p=0·0037 ) . INTERPRETATION Hypertension in normal weight and obese patients might be mediated by different mechanisms . Thiazide-based treatment gives less cardiovascular protection in normal weight than obese patients , but amlodipine-based therapy is equally effective across BMI subgroups and thus offers superior cardiovascular protection in non-obese hypertension . FUNDING Novartis Pharmaceuticals",
"The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) consisted of 42,418 participants r and omized to one of four antihypertensive treatment groups : chlorthalidone , amlodipine , lisinopril , or doxazosin . A subset of these participants with fasting low-density lipoprotein cholesterol levels 100 - 189 mg/dL were r and omized into a lipid-lowering component : 5170 to receive pravastatin ( 40 mg daily ) and 5185 to receive usual care . This report describes the characteristics and lipid distribution of these participants . There were no important differences between the r and omized treatment groups . Women had higher total cholesterol , low-density lipoprotein cholesterol , and high-density lipoprotein cholesterol than men . There was a similar finding for black participants compared with whites , except blacks had lower triglycerides . Diabetics had lower high-density lipoprotein cholesterol and higher triglycerides than nondiabetics , and patients with body mass index higher high-density lipoprotein cholesterol but lower low-density lipoprotein cholesterol and triglycerides than patients with higher body mass index . The success of the r and omization of this large , diverse population and the differences in the lipid distributions among its subgroups will allow further underst and ing of optimal lipid-lowering treatment",
"TOGETHER investigated whether targeting multiple cardiovascular ( CV ) risk factors using single-pill amlodipine/atorvastatin ( AML/ATO ) and therapeutic lifestyle changes ( TLC ) results in greater blood pressure (BP)/lipid control and additional reduction in estimated cardiovascular disease ( CVD ) risk compared with blood pressure intervention only using amlodipine ( AML ) + TLC . TOGETHER was a 6-week , r and omized , double-blind , double-dummy trial using hypertensive participants with additional CV risk factors without CVD/diabetes . Participants were r and omized to either AML/ATO ( 5 to 10/20 mg ) + TLC or AML ( 5 to 10 mg ) + TLC . The primary end point was the difference in proportion of participants attaining both BP ( ( goals at week 6 . At week 6 , 67.8 % of participants receiving AML/ATO + TLC attained the combined BP/LDL-C goal versus 9.6 % with AML + TLC ( RD [ A – B ] : 58.2 ; 95 % CI [ 48.1 to 68.4 ] P in LDL-C , total cholesterol and triglycerides and estimated 10-year Framingham risk were also observed . Treatment with AML/ATO was well tolerated . In conclusion , a multifactorial CV management approach is more effective in achieving combined BP/LDL-C targets as well as CV risk reduction compared with BP intervention only in this patient population",
"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",
"This 8-week , r and omized , double-blind , controlled study compared efficacy and tolerability of telmisartan/amlodipine ( T/A ) single-pill combination ( SPC ) vs the respective monotherapies in 858 patients with severe hypertension ( systolic/diastolic blood pressure [ SBP/DBP ] ≥180/95 mm Hg ) . At 8 weeks , T/A provided significantly greater reductions from baseline in seated trough cuff SBP/DBP ( -47.5 mm Hg/-18.7 mm Hg ) vs T ( P weeks . Blood pressure ( BP ) goal and response rates were consistently higher with T/A vs T or A. T/A was well tolerated , with less frequent treatment-related adverse events vs A ( 12.6 % vs 16.4 % ) and a numerically lower incidence of peripheral edema and treatment discontinuation . In conclusion , treatment of patients with substantially elevated BP with T/A SPCs result ed in high and significantly greater BP reductions and higher BP goal and response rates than the respective monotherapies . T/A SPCs were well tolerated ",
"BACKGROUND Type 2 diabetes is associated with a substantially increased risk of cardiovascular disease , but the role of lipid-lowering therapy with statins for the primary prevention of cardiovascular disease in diabetes is inadequately defined . We aim ed to assess the effectiveness of atorvastatin 10 mg daily for primary prevention of major cardiovascular events in patients with type 2 diabetes without high concentrations of LDL-cholesterol . METHODS 2838 patients aged 40 - 75 years in 132 centres in the UK and Irel and were r and omised to placebo ( n=1410 ) or atorvastatin 10 mg daily ( n=1428 ) . Study entrants had no documented previous history of cardiovascular disease , an LDL-cholesterol concentration of 4.14 mmol/L or lower , a fasting triglyceride amount of 6.78 mmol/L or less , and at least one of the following : retinopathy , albuminuria , current smoking , or hypertension . The primary endpoint was time to first occurrence of the following : acute coronary heart disease events , coronary revascularisation , or stroke . Analysis was by intention to treat . FINDINGS The trial was terminated 2 years earlier than expected because the prespecified early stopping rule for efficacy had been met . Median duration of follow-up was 3.9 years ( IQR 3.0 - 4.7 ) . 127 patients allocated placebo ( 2.46 per 100 person-years at risk ) and 83 allocated atorvastatin ( 1.54 per 100 person-years at risk ) had at least one major cardiovascular event ( rate reduction 37 % [ 95 % CI -52 to -17 ] , p=0.001 ) . Treatment would be expected to prevent at least 37 major vascular events per 1000 such people treated for 4 years . Assessed separately , acute coronary heart disease events were reduced by 36 % ( -55 to -9 ) , coronary revascularisations by 31 % ( -59 to 16 ) , and rate of stroke by 48 % ( -69 to -11 ) . Atorvastatin reduced the death rate by 27 % ( -48 to 1 , p=0.059 ) . No excess of adverse events was noted in the atorvastatin group . INTERPRETATION Atorvastatin 10 mg daily is safe and efficacious in reducing the risk of first cardiovascular disease events , including stroke , in patients with type 2 diabetes without high LDL-cholesterol . No justification is available for having a particular threshold level of LDL-cholesterol as the sole arbiter of which patients with type 2 diabetes should receive statins . The debate about whether all people with this disorder warrant statin treatment should now focus on whether any patients are at sufficiently low risk for this treatment to be withheld",
"Guidelines stress the importance of the simultaneous management of multiple cardiovascular risk factors . This can in part be achieved by coadministration of lipid-lowering and antihypertensive treatments . Potential pharmacodynamic interaction between drugs should be investigated as part of developing single-pill combinations . The Respond trial assessed whether combining amlodipine to treat hypertension and atorvastatin to treat dyslipidemia affected the action of either monotherapy . A total of 1660 hypertensive patients with dyslipidemia received 1 of 15 combinations of amlodipine ( placebo , 5 , or 10 mg ) and atorvastatin ( placebo , 10 , 20 , 40 , or 80 mg ) in a 3 x 5 factorial r and omized , placebo-controlled design . At 8 weeks , combination-treated patients experienced dose-related and statistically significant reductions in systolic blood pressure , low-density lipoprotein cholesterol , and Framingham risk score . Overall , coadministered atorvastatin and amlodipine was well tolerated and without adverse pharmacodynamic interaction ; combination treatment did not affect the low-density lipoprotein cholesterol-lowering efficacy and safety of atorvastatin , or the systolic blood pressure-lowering efficacy and safety of amlodipine",
"BACKGROUND Around 80 % of all cardiovascular deaths occur in developing countries . Assessment of those patients at high risk is an important strategy for prevention . Since developing countries have limited re sources for prevention strategies that require laboratory testing , we assessed if a risk prediction method that did not require any laboratory tests could be as accurate as one requiring laboratory information . METHODS The National Health and Nutrition Examination Survey ( NHANES ) was a prospect i ve cohort study of 14 407 US participants aged between 25 - 74 years at the time they were first examined ( between 1971 and 1975 ) . Our follow-up study population included participants with complete information on these surveys who did not report a history of cardiovascular disease ( myocardial infa rct ion , heart failure , stroke , angina ) or cancer , yielding an analysis data set N=6186 . We compared how well either method could predict first-time fatal and non-fatal cardiovascular disease events in this cohort . For the laboratory-based model , which required blood testing , we used st and ard risk factors to assess risk of cardiovascular disease : age , systolic blood pressure , smoking status , total cholesterol , reported diabetes status , and current treatment for hypertension . For the non-laboratory-based model , we substituted body-mass index for cholesterol . FINDINGS In the cohort of 6186 , there were 1529 first-time cardiovascular events and 578 ( 38 % ) deaths due to cardiovascular disease over 21 years . In women , the laboratory-based model was useful for predicting events , with a c statistic of 0.829 . The c statistic of the non-laboratory-based model was 0.831 . In men , the results were similar ( 0.784 for the laboratory-based model and 0.783 for the non-laboratory-based model ) . Results were similar between the laboratory-based and non-laboratory-based models in both men and women when restricted to fatal events only . INTERPRETATION A method that uses non-laboratory-based risk factors predicted cardiovascular events as accurately as one that relied on laboratory-based values . This approach could simplify risk assessment in situations where laboratory testing is inconvenient or unavailable",
"Background The Polycap ™ ( polypill ; aspirin [ acetylsalicylic acid ] , ramipril , simvastatin , atenolol , and hydrochlorothiazide ) was found to be safe and effective for reducing multiple cardiovascular risk factors in The Indian Polycap ™ Study ( TIPS ) . Objective We evaluated the bioavailability of each ingredient of the Polycap ™ and determined any drug-drug interactions relative to single component reference preparations . Methods The bioavailability of the ingredients of the Polycap ™ ( T ; test ) when formulated as a single capsule was compared with that of identical capsules with each of its ingredients administered separately ( R ; reference ) in a five-arm , r and omized , single-dose , two-period , two-treatment , two-sequence , crossover trial with at least a 2-week washout period in a total of 195 healthy volunteers . Plasma concentrations of each drug and , where applicable , its active metabolite were measured using vali date d liquid chromatographyt and em mass spectrometry and ultra-performance liquid chromatography . Mean pharmacokinetic parameters and their st and ard deviations were computed for each analyte . Results Comparative bioavailability was computed and no drug-drug interactions and no difference in comparative bioavailability were concluded for each ingredient based on point estimates of the T/R ratio of the geometric means falling within 80–125 % for peak plasma concentration ( Cmax ) , area under the plasma concentration-time curve from time zero to the last measurable concentration ( AUCt ) , and AUC from time zero to infinity ( AUC∞ ) . The T/R ratio for Cmax , AUCt and AUC∞ was within 80–125 % for atenolol , hydrochlorothiazide , ramipril , ramiprilat and dose-normalized salicylic acid . However , for simvastatin , the T/R point estimates for Cmax , AUCt and AUC∞ for Ln-transformed data were significantly lower ( ∼3–4 % ) than the lower bound of 80 % . For its active metabolite , simvastatin acid , these estimates were significantly higher ( ∼25–35 % ) than the higher bound of 125 % . Thus , the increased bioavailability of active simvastatin acid appeared to compensate for the loss of bioavailability of simvastatin . Conclusion The Polycap ™ was found to be effective and safe in the previously published TIPS trial . The present study in healthy volunteers establishes that Polycap ™ is safe ( no serious adverse events ) and well tolerated , and that there is no indication of pharmacokinetic drug-drug interactions for any of the ingredients , with their bioavailabilities being well preserved",
"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",
"BACKGROUND Cardiovascular disease ( CVD ) is the leading cause of death , and principal reason for the large difference in life expectancy between indigenous Māori and the non-indigenous population in New Zeal and . CVD guidelines recommend that people who are at high risk or who have had previous CVD should be offered aspirin , blood pressure lowering and lipid lowering therapies . However , prescribing and adherence rates are low and CVD events remain high . AIM To assess whether a medication strategy using a fixed dose combination pill ( ' polypill ' ) could improve prescribing and adherence to recommended medications , lower blood pressure and improve lipids compared with current care over 12 months . METHODS IMProving Adherence using Combination Therapy ( IMPACT ) is an open-label r and omised controlled trial comparing a once-daily polypill containing four preventive medications with usual care . Six hundred participants who have had previous CVD events or are at high risk of CVD will be enrolled , including 300 Māori . Participants are identified , enrolled and prescribed either the polypill or current medications at their usual primary health care practice , with medications ( including the polypill ) dispensed through local community pharmacies . The polypill contains 75 mg aspirin , 40 mg simvastatin , 10 mg lisinopril and either 12.5 mg hydrochlorothiazide or 50 mg atenolol . Primary outcomes are adherence to guidelines -recommended medications and changes in systolic blood pressure and low density lipoprotein at 12 months . Secondary outcomes include other lipids , medication dispensing , barriers to adherence , CVD and other serious adverse events , quality of life and prescriber acceptability . The trial is registered with the Australian New Zeal and Clinical Trial Registry ( ACTRN12606000067572 )",
"The Gemini Study was a 14-week , open-label , non-comparative , office-based , multicenter trial to evaluate single-pill therapy in the treatment of concomitant hypertension and dyslipidemia . In addition to recommending lifestyle modifications , eight dosage strengths of amlodipine/atorvastatin single pill ( 5/10 , 5/20 , 5/40 , 5/80 , 10/10 , 10/20 , 10/40 , and 10/80 mg ) were electively titrated to improve blood pressure and lipid control . A total of 1220 patients with uncontrolled hypertension at baseline received study medication . At baseline , mean blood pressure was 146.6/87.9 mm Hg and mean low-density lipoprotein cholesterol concentration was 152.9 mg/dL. At study end , 57.7 % of patients had achieved both their blood pressure and low-density lipoprotein cholesterol goals ( 51.9 % of patients with uncontrolled low-density lipoprotein cholesterol at baseline ) . The mean dose of study medication at end point was amlodipine component 7.1 mg and atorvastatin component 26.2 mg . Fifty-eight patients ( 4.8 % ) discontinued therapy due to adverse events . Single-pill therapy is effective in reducing both blood pressure and lipid levels and in helping patients achieve goals for both hypertension and dyslipidemia",
"To assess the combined influence of blood pressure ( BP ) , serum cholesterol level , and cigarette smoking on death from coronary heart disease ( CHD ) and to describe how these associations vary with age , data on those factors and on mortality for 316,099 men screened for the Multiple Risk Factor Intervention Trial ( MRFIT ) were examined . Vital status of participants has been determined after an average follow-up of 12 years ; 6327 deaths from CHD have been identified . Strong grade d relationships between serum cholesterol levels above 4.65 mmol/L ( 180 mg/dL ) , systolic BP above 110 mm Hg , and diastolic BP above 70 mm Hg and mortality due to CHD were evident . Smokers with serum cholesterol and systolic BP levels in the highest quintiles had CHD death rates that were approximately 20 times greater than nonsmoking men with systolic BP and cholesterol levels in the lowest quintile . Systolic and diastolic BP , serum cholesterol level , and cigarettes per day were significant predictors of death due to CHD in all age groups . Systolic BP was a stronger predictor than diastolic BP . These results , together with the findings of clinical trials , offer strong support for intensified preventive efforts in all age groups",
"BACKGROUND Cardiovascular morbidity is a major burden in patients with type 2 diabetes . In the Steno-2 Study , we compared the effect of a targeted , intensified , multifactorial intervention with that of conventional treatment on modifiable risk factors for cardiovascular disease in patients with type 2 diabetes and microalbuminuria . METHODS The primary end point of this open , parallel trial was a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , nonfatal stroke , revascularization , and amputation . Eighty patients were r and omly assigned to receive conventional treatment in accordance with national guidelines and 80 to receive intensive treatment , with a stepwise implementation of behavior modification and pharmacologic therapy that targeted hyperglycemia , hypertension , dyslipidemia , and microalbuminuria , along with secondary prevention of cardiovascular disease with aspirin . RESULTS The mean age of the patients was 55.1 years , and the mean follow-up was 7.8 years . The decline in glycosylated hemoglobin values , systolic and diastolic blood pressure , serum cholesterol and triglyceride levels measured after an overnight fast , and urinary albumin excretion rate were all significantly greater in the intensive-therapy group than in the conventional-therapy group . Patients receiving intensive therapy also had a significantly lower risk of cardiovascular disease ( hazard ratio , 0.47 ; 95 percent confidence interval , 0.24 to 0.73 ) , nephropathy ( hazard ratio , 0.39 ; 95 percent confidence interval , 0.17 to 0.87 ) , retinopathy ( hazard ratio , 0.42 ; 95 percent confidence interval , 0.21 to 0.86 ) , and autonomic neuropathy ( hazard ratio , 0.37 ; 95 percent confidence interval , 0.18 to 0.79 ) . CONCLUSIONS A target-driven , long-term , intensified intervention aim ed at multiple risk factors in patients with type 2 diabetes and microalbuminuria reduces the risk of cardiovascular and microvascular events by about 50 percent",
"The AVALON study was a r and omized , multicenter trial to assess the efficacy and safety of coadministered amlodipine and atorvastatin in patients with hypertension and dyslipidemia . Phase one was an 8-week , double-blind , double-dummy , placebo-controlled period whereby patients received amlodipine 5 mg , atorvastatin 10 mg , amlodipine 5 mg and atorvastatin 10 mg , or placebo . Thereafter , all patients received single-blind amlodipine 5 mg and atorvastatin 10 mg for 8-weeks , followed by 12 weeks of open-label treatment where doses could be titrated to improve low-density lipoprotein cholesterol and blood pressure control . A total of 847 patients entered the double-blind phase . At Week 8 , 45 % of the patients receiving amlodipine 5 mg and atorvastatin 10 mg reached both their blood pressure and low-density lipoprotein cholesterol goals , compared with 8.3 % with amlodipine ( p atorvastatin ( p placebo . At 28 weeks , 67.1 % of patients coadministered amlodipine and atorvastatin ( mean doses , 7.6 mg and 28.4 mg , respectively ) achieved both targets . Framingham estimated 10-year risk of coronary heart disease declined from baseline levels of 15.1 % to 6.9 % at Week 28 . Following coadministered treatment , the adverse events reported were similar to either agent alone . Concomitant administration of amlodipine and atorvastatin is an effective and well tolerated treatment for coexisting hypertension and dyslipidemia",
"The Gemini-AALA ( Australia , Asia , Latin America , Africa/Middle East ) study evaluated the efficacy and safety of single-pill amlodipine/atorvastatin ( Caduet ) for the treatment of patients of diverse ethnicity with concomitant hypertension and dyslipidaemia . This was a 14-week , open-label study including patients from 27 countries across the Middle East , Asia-Pacific , Africa and Latin America . Eight dosage strengths of single-pill amlodipine/atorvastatin ( 5/10 , 10/10 , 5/20 , 10/20 , 5/40 , 10/40 , 5/80 and 10/80 mg ) were titrated to improve blood pressure and lipid control . Blood pressure and lipid goals were determined according to the Seventh Report of the Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC 7 ) and National Cholesterol Education Program Expert Panel on Detection , Evaluation , and Treatment of High Blood Cholesterol in Adults ( NCEP ATP III ) guidelines , respectively ( blood pressure , Overall , 1649 patients received study medication . Most patients ( 91.4 % ) had ⩾1 cardiovascular risk factor ( as defined by NCEP ATP III guidelines ) in addition to hypertension/dyslipidaemia , and 61.7 % had coronary heart disease/risk equivalent . At baseline , mean blood pressure was 146.6/88.3 mm Hg and LDL-C was 3.4 mmol l−1 ( 130.2 mgdl−1 ) . At week 14 , 55.2 % of patients reached both blood pressure and lipid goals , 61.3 % reached blood pressure goal and 87.1 % reached lipid goal ( 34.0 % were at lipid goal at baseline ) . Mean blood pressure reduction was 20.2/11.4 mm Hg . For patients who were lipid-lowering drug naive at baseline , mean reduction in LDL-C was 41.0 % . Treatment-related adverse events led to the discontinuation of 3.6 % of patients . Single-pill amlodipine/atorvastatin therapy was well tolerated and effective for the reduction of blood pressure and lipids to recommended goals in patients from diverse ethnic background",
"OBJECTIVE To investigate the efficacy and safety of single-pill amlodipine/atorvastatin therapy for the simultaneous treatment of hypertension ( HTN ) and dyslipidemia in African Americans . PATIENTS AND METHODS Conducted between July 19 , 2004 , and August 9 , 2005 , the Clinical Utility of Caduet in Simultaneously Achieving Blood Pressure and Lipid End Points trial was a 20-week , open-label , noncomparative , multicenter trial of the efficacy and safety of single-pill amlodipine/atorvastatin in controlling elevated blood pressure ( BP ) and low-density lipoprotein cholesterol ( LDL-C ) in African Americans with concomitant HTN and dyslipidemia and either no additional risk factors , 1 or more cardiovascular risk factors , or coronary heart disease or a risk equivalent . Eight dosage strengths of single-pill amlodipine/atorvastatin were flexibly titrated . The primary efficacy assessment of the main trial was the percentage of patients who attained the LDL-C treatment goals of both the Seventh Report of the Joint National Committee on the Prevention , Detection , Evaluation , and Treatment of High Blood Pressure and the National Cholesterol Education Program Adult Treatment Panel III . RESULTS Of the 1170 African American patients screened , 501 were enrolled in the study and 499 received drug therapy . At end point , 236 ( 48.3 % ) of 489 patients reached both their BP and LDLC goals ( vs 4 [ 0.8 % ] of 484 at baseline ) ; 280 ( 56.8 % ) of 493 reached BP goals ( vs 7 [ 1.4 % ] of 494 at baseline ) ; and 361 ( 73.7 % ) of 490 reached LDL-C goals ( vs 138 [ 28.5 % ] of 484 at baseline ) . Among the 499 patients receiving drug therapy , common treatment-related adverse events were peripheral edema ( 17 patients [ 3.4 % ] ) , headache ( 11 [ 2.2 % ] ) , myalgia ( 11 [ 2.2 % ] ) , and constipation ( 10 [ 2.0 % ] ) . CONCLUSION Single-pill amlodipine/atorvastatin therapy was well tolerated and effectively targeted HTN and dyslipidemia in this population of African Americans who were at risk of cardiovascular disease",
"CONTEXT Blood homocysteine levels are positively associated with cardiovascular disease , but it is uncertain whether the association is causal . OBJECTIVE To assess the effects of reducing homocysteine levels with folic acid and vitamin B(12 ) on vascular and nonvascular outcomes . DESIGN , SETTING , AND PATIENTS Double-blind r and omized controlled trial of 12,064 survivors of myocardial infa rct ion in secondary care hospitals in the United Kingdom between 1998 and 2008 . INTERVENTIONS 2 mg folic acid plus 1 mg vitamin B(12 ) daily vs matching placebo . MAIN OUTCOME MEASURES First major vascular event , defined as major coronary event ( coronary death , myocardial infa rct ion , or coronary revascularization ) , fatal or nonfatal stroke , or noncoronary revascularization . RESULTS Allocation to the study vitamins reduced homocysteine by a mean of 3.8 micromol/L ( 28 % ) . During 6.7 years of follow-up , major vascular events occurred in 1537 of 6033 participants ( 25.5 % ) allocated folic acid plus vitamin B(12 ) vs 1493 of 6031 participants ( 24.8 % ) allocated placebo ( risk ratio [ RR ] , 1.04 ; 95 % confidence interval [ CI ] , 0.97 - 1.12 ; P = .28 ) . There were no apparent effects on major coronary events ( vitamins , 1229 [ 20.4 % ] , vs placebo , 1185 [ 19.6 % ] ; RR , 1.05 ; 95 % CI , 0.97 - 1.13 ) , stroke ( vitamins , 269 [ 4.5 % ] , vs placebo , 265 [ 4.4 % ] ; RR , 1.02 ; 95 % CI , 0.86 - 1.21 ) , or noncoronary revascularizations ( vitamins , 178 [ 3.0 % ] , vs placebo , 152 [ 2.5 % ] ; RR , 1.18 ; 95 % CI , 0.95 - 1.46 ) . Nor were there significant differences in the numbers of deaths attributed to vascular causes ( vitamins , 578 [ 9.6 % ] , vs placebo , 559 [ 9.3 % ] ) or nonvascular causes ( vitamins , 405 [ 6.7 % ] , vs placebo , 392 [ 6.5 % ] ) or in the incidence of any cancer ( vitamins , 678 [ 11.2 % ] , vs placebo , 639 [ 10.6 % ] ) . CONCLUSION Substantial long-term reductions in blood homocysteine levels with folic acid and vitamin B(12 ) supplementation did not have beneficial effects on vascular outcomes but were also not associated with adverse effects on cancer incidence . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N74348595",
"BACKGROUND The combination of three blood-pressure-lowering drugs at low doses , with a statin , aspirin , and folic acid ( the polypill ) , could reduce cardiovascular events by more than 80 % in healthy individuals . We examined the effect of the Polycap on blood pressure , lipids , heart rate , and urinary thromboxane B2 , and assessed its tolerability . METHODS In a double-blind trial in 50 centres in India , 2053 individuals without cardiovascular disease , aged 45 - 80 years , and with one risk factor were r and omly assigned , by a central secure website , to the Polycap ( n=412 ) consisting of low doses of thiazide ( 12.5 mg ) , atenolol ( 50 mg ) , ramipril ( 5 mg ) , simvastatin ( 20 mg ) , and aspirin ( 100 mg ) per day , or to eight other groups , each with about 200 individuals , of aspirin alone , simvastatin alone , hydrochlorthiazide alone , three combinations of the two blood-pressure-lowering drugs , three blood-pressure-lowering drugs alone , or three blood-pressure-lowering drugs plus aspirin . The primary outcomes were LDL for the effect of lipids , blood pressure for antihypertensive drugs , heart rate for the effects of atenolol , urinary 11-dehydrothromboxane B2 for the antiplatelet effects of aspirin , and rates of discontinuation of drugs for safety . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00443794 . FINDINGS Compared with groups not receiving blood-pressure-lowering drugs , the Polycap reduced systolic blood pressure by 7.4 mm Hg ( 95 % CI 6.1 - 8.1 ) and diastolic blood pressure by 5.6 mm Hg ( 4.7 - 6.4 ) , which was similar when three blood-pressure-lowering drugs were used , with or without aspirin . Reductions in blood pressure increased with the number of drugs used ( 2.2/1.3 mm Hg with one drug , 4.7/3.6 mm Hg with two drugs , and 6.3/4.5 mm Hg with three drugs ) . Polycap reduced LDL cholesterol by 0.70 mmol/L ( 95 % CI 0.62 - 0.78 ) , which was less than that with simvastatin alone ( 0.83 mmol/L , 0.72 - 0.93 ; p=0.04 ) ; both reductions were greater than for groups without simvastatin ( p reductions in heart rate with Polycap and other groups using atenolol were similar ( 7.0 beats per min ) , and both were significantly greater than that in groups without atenolol ( p reductions in 11-dehydrothromboxane B2 were similar with the Polycap ( 283.1 ng/mmol creatinine , 95 % CI 229.1 - 337.0 ) compared with the three blood-pressure-lowering drugs plus aspirin ( 350.0 ng/mmol creatinine , 294.6 - 404.0 ) , and aspirin alone ( 348.8 ng/mmol creatinine , 277.6 - 419.9 ) compared with groups without aspirin . Tolerability of the Polycap was similar to that of other treatments , with no evidence of increasing intolerability with increasing number of active components in one pill . INTERPRETATION This Polycap formulation could be conveniently used to reduce multiple risk factors and cardiovascular risk",
"The purpose of this study was to evaluate a fixed olmesartan/amlodipine combination on blood pressure control , lipid profile , insulin sensitivity , and some inflammatory markers compared with single-drug monotherapy . A total of 276 hypertensive patients were r and omly assigned to olmesartan 20 mg , amlodipine 10 mg , or a single pill containing olmesartan/amlodipine combination 20/5 mg for 12 months . We evaluated the following at baseline and after 6 and 12 months : body weight , body mass index , systolic ( SBP ) and diastolic blood pressures ( DBP ) , fasting plasma glucose ( FPG ) , fasting plasma insulin ( FPI ) , lipid profile , tumor necrosis factor-α ( TNF-α ) , retinol binding protein-4 ( RBP-4 ) , and interleukins 6 and 7 ( IL-6 and IL-7 ) . At baseline , and after 6 and 12 months , patients underwent an euglycemic , hyperinsulinemic clamp . The olmesartan/amlodipine combination provided a greater decrease of SBP and DPB compared with amlodipine and olmesartan monotherapies . The olmesartan/amlodipine combination decreased FPG after 12 months compared with amlodipine monotherapy . The combination decreased FPI and homeostasis model assessment index and increased M value both compared with baseline and with olmesartan and amlodipine monotherapies . Olmesartan/amlodipine decreased IL-7 , but not IL-6 , compared with single drug components . The olmesartan/amlodipine combination is effective and safe in reducing blood pressure and has some additive effects not shown by single drugs , such as an improvement of IL-7",
"BACKGROUND Two 8-week , r and omized , double-blind , controlled studies previously evaluated the efficacy and tolerability of single-pill combinations of telmisartan 40 - 80 mg/amlodipine 5 - 10 mg ( T40 - 80/A5 - 10 ) in patients with hypertension not at diastolic blood pressure ( DBP ) goal ( DBP amlodipine 5 mg monotherapy ( A5 ) ( TEAMSTA-5 ) or amlodipine 10 mg monotherapy ( A10 ) ( TEAMSTA-10 ) . The long-term ( ≥6 months ) tolerability and efficacy of single-pill combinations of T40-T80/A5-A10 have now been evaluated in 2 open-label studies in patients who had successfully completed either TEAMSTA-5 or TEAMSTA-10 ( TEAMSTA-5 and TEAMSTA-10 Follow-Ups ) . METHODS In the TEAMSTA-5 Follow-Up , 976 patients whose blood pressure was not initially controlled by taking A5 received T40/A5 for 4 or 8 weeks , with consecutive uptitration to T80/A5 if DBP was ≥90 mm Hg . In TEAMSTA-10 Follow-Up , 838 patients not initially achieving blood pressure control using A10 received T40/A10 for 4 weeks before r and omization to T40/A10 or T80/A10 ; after 4 weeks , patients r and omized to T40/A10 with DBP ≥90 mm Hg were uptitrated to T80/A10 . In both studies , add-on antihypertensive medication was allowed if DBP was not at goal . RESULTS Treatment compliance in both follow-up studies was ≥98.4 % . Single-pill combinations of T40-T80/A5-A10 result ed in additional clinical ly relevant blood pressure reductions and 67 % to 93 % of patients achieved DBP goal ( achieved DBP goal . Long-term treatment with T40-T80/A5-A10 was well tolerated , with comparable adverse event profiles for all telmisartan/amlodipine combinations . The most common drug-related adverse events were peripheral edema ( 1.9%-3.9 % ) and dizziness ( 1.5 % in the T80/A5 group only ) ; these were consistent with the known tolerability profiles of telmisartan/amlodipine combinations . Overall treatment discontinuation rates due to adverse events were low ( 0.7%-1.5 % ) . CONCLUSIONS In patients not achieving DBP goal with either A5 or A10 monotherapy , the vast majority achieved DBP goal with single-pill combinations of T40-T80/A5-A10 . Long-term treatment was well tolerated with high compliance , promoting treatment adherence regardless of telmisartan/amlodipine dose . Clinical Trials.gov identifiers : NCT00614380 ( TEAMSTA-5 Follow-up ) and NCT00624052 ( TEAMSTA-10 Follow-up )"
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The effects of propranolol in the treatment of anxiety disorders have not been systematic ally evaluated previously . The aim was to conduct a systematic review and meta- analysis of r and omised controlled trials , addressing the efficacy of oral propranolol versus placebo or other medication as a treatment for alleviating either state or trait anxiety in patients suffering from anxiety disorders . Eight studies met the inclusion criteria . These studies concerned panic disorder with or without agoraphobia ( four studies , total n = 130 ) , specific phobia ( two studies , total n = 37 ) , social phobia ( one study , n = 16 ) , and posttraumatic stress disorder ( PTSD ) ( one study , n = 19 ) . Three out of four panic disorder trials qualified for pooled analyses . These meta-analyses found no statistically significant differences between the efficacy of propranolol and benzodiazepines regarding the short-term treatment of panic disorder with or without agoraphobia . Also , no evidence was found for effects of propranolol on PTSD symptom severity through inhibition of memory reconsolidation . In conclusion , the quality of evidence for the efficacy of propranolol at present is insufficient to support the routine use of propranolol in the treatment of any of the anxiety disorders
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"14 phobic subjects were given propranolol ( Inderal ) , atenolol ( Tenormin ) and placebo in a double-blind fashion according to a repeated measurement design . Subjects were exposed to their source of fear while their anxiety and cardiovascular responses ( heart rate , blood pressure and peripheral temperature ) were recorded . In accordance with the Three-Systems Model of fear and phobias , the subjects were divided into two groups of high and low physiological reactors , operationalized by the cardiovascular items in their anxiety pattern from a revised version of the Autonomic Perception Question naire ( APQ ) . It was found that beta-blockade had the predicted effect on heart rate and peripheral temperature while diastolic blood pressure was unaffected . The systolic blood pressure finally was lowered for the low cardiovascular reactors . The subjectively rated anxiety rose consistently during exposure . There was no general effect of the beta-blocking drugs on subjective anxiety . For the high cardiovascular reactors propranolol was associated with a higher anxiety level",
"The efficacy and safety of propranolol in the treatment of anxiety was compared with those of chlordiazepoxide and placebo in a 3-week , double-blind study of 212 patients . After a 1-week , single-blind placebo-washout period , patients were r and omized to receive either propranolol ( 80 , 160 , or 320 mg/day ) , chlordiazepoxide ( 30 , 45 , or 75 mg/day ) , or placebo . Patients were evaluated by three physician-rated scales -- Hamilton Rating Scale for Anxiety ( HAM-A ) , Covi Anxiety Scale ( CAS ) , and Clinical Global Impressions scale-- and two patient-rated scales -- Symptoms Checklist 90 and Profile of Mood States . Patients in all groups demonstrated significant improvement in their level of anxiety at all time points compared with their baseline level . At Week 1 propranolol and chlordiazepoxide patients were significantly better than placebo patients , as measured by the HAM-A and CAS . At Week 2 only propranolol was superior to placebo , based on HAM-A and CAS scores . Fifteen patients prematurely terminated because of adverse reactions ( 4 taking propranolol , 4 taking placebo , and 7 taking chlordiazepoxide ) . The incidence of side effects was similar for the two active drugs ; fatigue , drowsiness , and change in libido were significantly more frequent with chlordiazepoxide and drowsiness and indigestion were more frequent with propranolol compared with placebo",
"The effect of propranolol was studied on 23 dental phobics in a double-blind , placebo-controlled clinical trial involving actual dental treatment . The subjects were selected because they showed high physiological reactivity in the dental situation . Twelve subjects received the test drug and 11 subjects received the placebo at individualized doses of either 80 or 120 mg . A significant difference in self-reported anxiety at the injection phase of treatment and less overall pain intensity and aversiveness were observed for the propranolol as compared with the placebo group . No differences were detected for behavior ratings . Beta-adrenergic blocking agents may have utility for reducing anxiety in individuals fearful of dental treatment",
"The trial showed propranolol to be as effective as chlordiazepoxide overall in the treatment of these cases of anxiety states , but in depression and sleep disturbance chlordiazepoxide was better . Nevertheless , the new drug may have some part to play in the treatment of anxiety as an alternative to tranquillizers , and it may be possible in future to define more precise indications for its use",
"Simple tests of verbal reasoning and mental arithmetic , taken under mildly stressful conditions , have been shown to give a reproducible test of intellectual function within groups of normal subjects . Using these tests , in two separate examinations , a double-blind cross-over study was performed on 35 medical students to assess the effects of acute beta-adrenoceptor blockade with propranolol on intellectual function . With placebo treatment , students recorded an average total score of 231.3 marks , with average scores of 108.9 marks on the mental arithmetic paper and 122.4 marks on the verbal reasoning paper . Treatment with propranolol was associated with an improvement in total score of 9.2 + /- 3.9 marks ( P less than 0.05 ) , an improvement in mental arithmetic score of 5.6 + /- 2.3 marks ( P less than 0.05 ) and an improvement in verbal reasoning score of 3.6 + /- 2.4 marks ( NS ) . Eighteen out of the 35 students said that they were mildly anxious before one examination and 13 students said they were anxious before both examinations . Those students who admitted anxiety seemed to benefit the most , in terms of improved examination performance , from treatment with propranolol",
"OBJECTIVE Performance anxiety in musicians may be severe enough to require intervention but has been the subject of relatively little clinical research . The authors ' objectives were to describe the results of a comprehensive clinical and laboratory assessment and to perform a double-blind , placebo-controlled study comparing buspirone , cognitive-behavior therapy , and the combination of these treatments for performance anxiety . METHOD Ninety-four subjects were recruited by mass media announcements and were seen in a university-based outpatient psychiatric clinic . Assessment s were 1 ) question naires for all 94 subjects , 2 ) diagnostic interview of 50 subjects , and 3 ) laboratory performance of 34 subjects . Treatment conditions were 1 ) 6 weeks of buspirone , 2 ) 6 weeks of placebo , 3 ) a five-session , group cognitive-behavior therapy program with buspirone , or 4 ) the cognitive-behavior therapy program with placebo . Treatment outcome measures included subjective anxiety ratings and heart rate measures during a laboratory performance , a question naire measure of performance confidence , and a blind rating of musical performance quality . RESULTS All subjects fulfilled criteria for DSM-III-R social phobia . Of the 15 full-time professional musicians , ten had tried propranolol and three had stopped performing . Most of the subjects had substantial anxiety and heart rate increases during laboratory speech and musical performances . Cognitive-behavior therapy result ed in statistically significant reductions in subjective anxiety , improved quality of musical performance , and improved performance confidence . Buspirone was not an effective treatment . CONCLUSIONS Cognitive-behavior therapy is a viable treatment approach for performance anxiety in musicians",
"BACKGROUND Although serotonin reuptake inhibitors are effective in panic disorder , questions concerning whether doses associated with antidepressant efficacy are also effective for panic disorder remain . AIMS To assess the efficacy of the usual antidepressant dose of fluoxetine in treating full panic attacks . METHOD Patients with panic disorder were r and omised to placebo or to fluoxetine initiated at 10 mg daily for 1 week and then increased to 20 mg daily . The trial lasted 12 weeks , but after 6 weeks patients who had failed to achieve a satisfactory response were eligible for dose escalation to a maximum of 60 mg of fluoxetine daily . RESULTS Fluoxetine was associated with a statistically significantly greater proportion of panic-free patients compared with placebo after 6 weeks and at end-point . CONCLUSIONS Fluoxetine at a dose of 20 mg daily is safe and efficacious in reducing symptoms of panic disorder . Patients who fail to obtain a satisfactory response at 20 mg daily may benefit from further dose increases",
"We studied the efficacy of propranolol ( Inderal ) compared to alprazolam ( Xanax ) in 29 patients with a diagnosis of agoraphobia with panic disorder or panic disorder with or without limited phobic avoidance in a 6-week double-blind controlled experiment . Alprazolam is effective in those syndromes , whereas to date only negative or ambiguous results had been reported for propranolol . Fourteen patients received a mean daily dose of 5.0 + /- 2.3 mg of alprazolam and 15 patients received 182.0 + /- 60.5 mg mean daily dose of propranolol . We found both drugs to be effective to suppress panic attacks and reduce avoidance behavior . The only significant between-drug difference was a more rapid onset of alprazolam 's panicolytic effect . Propranolol merits further study . We suggest patients worthy of a clinical trial",
"OBJECTIVE To find out if propranolol , a non-cardioselective beta-blocker , can reduce the anxiety associated with day case surgery . DESIGN Prospect i ve r and omized double blind trial . SETTING University hospital , Irel and . SUBJECTS An unselected group of 53 patients undergoing day case surgery . INTERVENTION Subjects r and omised to receive either propranolol ( 10 mg ) or placebo on the morning of operation . MAIN OUTCOME MEASURES Blood pressure ; pulse , anxiety , pain score and patient satisfaction . RESULTS Mean ( SD ) Hospital Anxiety and Depression score was significantly lower in the propranolol group than in the control group ( 2.5 ( 0.7 ) compared with 4.6 ( 0.7 ) , p propranolol given on the morning of day case surgery significantly reduced patients ' anxiety",
"Sixteen socially phobic out patients underwent a 4-week course of social skills training that attempted to maximize rehearsal in real-life setting s. The therapy was largely conducted by nonprofessional volunteers after a 2-hour training workshop . It consisted of multiple role-played practice in the clinic , followed immediately by rehearsal in a real-life setting in the company of a nonprofessional therapist and a fellow patient . Subsequently , patients were r and omly paired to perform further rehearsals between sessions . Drug therapy was controlled by double blind assignment to propranolol or inert placebo throughout the course of treatment . Measures of specific fears , generalized social anxiety , self-image , and global tension and anxiety were administered 1 month before treatment , immediately before and after treatment , and at 6 months follow-up . During a 4-week drug-free period prior to active treatment no improvement was noted on any measures . After the 4-week treatment period significant improvement had occurred on all outcome measures . Propranolol and placebo subgroups showed very similar results . Treatment gains were sustained at follow-up . It was concluded that repeated behavior rehearsal , both in the clinic and in real life is a cost-effective treatment procedure for many social phobias . The approach is straightforward and can be applied by nonprofessionals , including the patients themselves , after limited training and with minimal supervision",
"The effectiveness of propranolol , a nonsedating anxiolytic premedication , was studied by monitoring preoperative anxiety and postoperative recovery of cognitive function in 92 healthy ASA physical status 1 females aged 15–42 yr undergoing outpatient dilatation and curretage (D&C)for therapeutic abortion . In a r and omized double-blind design , patients received one of the following oral medications 1–1.5 hr preoperatively : ( 1 ) diazepam 10 mg ( n = 31 ) ; ( 2 ) propranolol 80 mg ( n = 31 ) ; ( 3 ) placebo ( n = 30 ) . Anxiety throughout the hospital stay was monitored using the State-Trait Anxiety Inventory ( STAI ) . Postoperative cognitive recovery was assessed using the digit span and Trieger tests . STAI anxiety levels were recorded on admission to hospital , immediately before entering the operating room , and two hours postoperatively . There was no difference among the anxiolytic properties of the three medications and all three patient groups showed a significant decrease in anxiety levels after administration of the medication . Tests of cognitive function after anaesthesia showed the fastest return to baseline status in patients receiving propranolol , possibly because beta adrenergic blockade blunted the autonomic signs of light anaesthesia and less anaesthetic was administered . None of the study premedications was demonstrated to have an anxiolytic advantage , but propranolol did offer a faster return of cognitive function in the postoperative period . RésuméNous avons voulu évaluer l’efficacité du propranolol à litre de prémédication anxiolytique non-sédative en mesurant le degré d’anxiété préopératoire et la rapidité de la récupération postopératoire des fonctions cognitives . Quatre-vingt douze femmes de 15 à 42 ans de classe ASA I , c and i date s à une dilatation cervicale et curetage pour avortement en externe , se sont prêtées à notre étude . Après r and omisation à double-insu , elles prenaient par la bouche soit 10 mg de diazépam ( n = 31 ) , soit 80 mg de propranolol ( n = 31 ) , soit un placebo ( n = 30 ) et ce , de 60 à 90 minutes avant l’intervention . Nous mesurions le niveau d’anxiété à l’admission , juste avant d’entrer en salle d’opération et deux heures après l’intervention en utilisant le « State-Trait Anxiety Inventory ( STAI ) » . Le « digit span » , test mnémonique numérique et le test de Trieger nous servaient à mesurer les fonctions cognitives avant et après l’opération . Les trois médications utilisés n’ont pas démontré de propriétés anxiolytiques différentes , les niveaux d’anxiété allant décroissant dans les trois groupes à partir de l’admission à l’hôpital . Par contre , après l’opération , les fonctions cognitives retournaient plus vite à la normale chez les patientes du groupe propranolol , peut-être parce que le blocage β-adrénergique avait permis de surestimer la profondeur de l’anesthésie pendant l’intervention entraînant l’utilisation de moindres doses d’anesthésique",
"PURPOSE To determine whether propranolol can decrease surgical tremor and anxiety in residents performing ocular microsurgery without impairing patient or physician safety . METHODS In this r and omized , double-masked , crossover study , 5 third-year ophthalmology residents ingested a capsule containing either propranolol , 40 mg , or placebo 1 hour prior to performing ophthalmic microsurgery . All residents were healthy men under age 30 years . Prior to commencement of the study , all participants had successfully been administered a test dose of propranolol without side effects . The study took place over a 10-week period . At the conclusion of each case , both the resident and attending surgeon observer independently completed a form grading , on a sliding scale : ( 1 ) amount of overall tremor ; ( 2 ) amount of tremor during placement of the first 3 sutures after lens or nucleus extraction ; ( 3 ) anticipated difficulty of the case ; ( 4 ) actual difficulty with the case ; and ( 5 ) anxiety ( surgeon only ) . In addition , the type of procedure performed , complications encountered , and surgeon side effects were recorded . The data were analyzed with a 2-way analysis of variance for unbalanced data . RESULTS A total of 73 surgical cases were performed ; the surgeons were administered propranolol for 40 cases and placebo for 33 . As judged by the resident surgeon , there was a highly significant effect of propranolol in decreasing anxiety ( P = .0058 ) , reducing surgical tremor overall ( P tremor while placing the first 3 sutures following lens extraction ( P Complications and difficulty of the case , as judged by both the resident and attending surgeons , were not significantly different in the propranolol versus placebo groups ( P > .05 ) . There were no side effects reported or observed in any of the surgeons . CONCLUSIONS Propranolol , 40 mg , administered 1 hour prior to surgery , significantly decreases tremor and anxiety in the surgeon without untoward effects to the surgeon and the patient . However , it is unknown whether decreased tremor and anxiety improved surgical outcome",
"In a double-blind crossover study the beta-adrenergic blocking drug propranolol hydrochloride reduced symptoms in 17 of 26 patients with chronic anxiety disorders . Both somatic and psychic symptoms improved as judged by patient and observer ratings . The most frequent side effects ( dizziness , fatigue , and insomnia ) were difficult to distinguish from anxiety symptoms and were , for the most part , mild . The therapeutic and side effects observed suggested CNS activity of the drug . Although propranolol is of benefit to patients with anxiety , its efficacy , compared with that of other antianxiety drugs , has not been established",
" Abstract Thirty-eight patients agreed to participate in a preliminary crossover trial comparing imipramine to propranolol for the treatment of panic disorder and agoraphobia with panic attacks . An independent blind assessor was used as well as several st and ard rating scales . There was no placebo group . Twenty-three patients completed a trial of both drugs . Approximately half of the patients lost their panic attacks completely , both on imipramine and propranolol . Other patients were partially , but not completely improved . The implication s and limitations of this finding and others are discussed",
" Fifty-five patients completed a 5-week double-blind study comparing alprazolam , propranolol , and placebo in the treatment of panic disorder and agoraphobia with panic attacks . There was no concomitant behavioral treatment . Patient and therapist rating scales included Sheehan 's Panic and Anxiety Attack Scales , the Marks-Sheehan Phobia Scale , the Hamilton Anxiety Scale , the Hamilton Depression Scale , and the Side Effects Checklist . The results generally support the efficacy of alprazolam , but not propranolol , in the treatment of panic disorder and agoraphobia with panic attacks . The significance of the results are discussed , as well as a number of the unique aspects of our procedures and patient population",
"The purpose of the present study was to compare the effects of oral premedication with ketohemidone 5 mg , lorazepam 1 mg , propranolol 40 mg or placebo , given about an hour prior to anaesthesia , in a prospect i ve r and omized double‐blind fashion . One hundred and twenty ASA I female patients scheduled for elective laparos‐copy were r and omly prescribed one of the study drugs . Patient evaluation of anxiety , nurse evaluation of premedication , induction and postoperative course were studied . Ninety‐three of the 120 patients ( 78 % ) experienced no change or a decrease in anxiety , regardless of type of active drug or placebo administered . Eighty‐eight of the patients ( 73 % ) were considered adequately premedicated by the nurse observer , with no differences between the groups . Pre induction pulse rate , blood pressure and amount of induction agent needed was also similar between the four groups of patients . No major differences could be seen during the postoperative course . We found no major effects of any of the active drugs studied compared to placebo . Routine use of small doses of oral premedication one hour before elective surgery among low anxiety patients could probably be omitted",
"The efficacy of oxprenolol ( Trasicor ) and propranolol in controlling anxiety was compared in a double-blind study of patients with anxiety and tension . Efficacy was assessed by the investigator with the aid of a psychiatric rating scale consisting of 19 items , bythe patients using visual analogue scales , and by the investigator 's and the patients ' over-all assessment s. Tolerance to the drugs was evaluated by over-all assessment and by means of a checklist of signs and symptoms which emerged during treatment . Little difference in the efficacy of the two drugs was observed . Both were effective in the treatment of anxiety and tension . In general , oxprenolol was significantly better tolerated than propranolol . Evidence of the intrinsic sympathomimetic activity of oxprenolol emerged during the course of the study or , alternatively , evidence that propranolol had a greater cardiac-depressant effect",
"The beta-adrenergic blocker propranolol given within hours of a psychologically traumatic event reduces physiologic responses during subsequent mental imagery of the event . Here we tested the effect of propranolol given after the retrieval of memories of past traumatic events . Subjects with chronic post-traumatic stress disorder described their traumatic event during a script preparation session and then received a one-day dose of propranolol ( n=9 ) or placebo ( n=10 ) , r and omized and double-blind . A week later , they engaged in script-driven mental imagery of their traumatic event while heart rate , skin conductance , and left corrugator electromyogram were measured . Physiologic responses were significantly smaller in the subjects who had received post-reactivation propranolol a week earlier . Propranolol given after reactivation of the memory of a past traumatic event reduces physiologic responding during subsequent mental imagery of the event in a similar manner to propranolol given shortly after the occurrence of a traumatic event",
"To determine which symptoms characterized isoproterenol-induced panic attacks , we analyzed the presence of panic attacks in 54 panic disorder patients who panicked , 24 patients who did not panic , and 37 controls who did not panic during isoproterenol infusions . The increases over the baseline of the symptoms shortness of breath and fear of going crazy were highly associated with panicking patients when compared to nonpanicking patients and nonpanicking controls . The increases of the symptoms trembling and shaking , generally nervous , and fear of going crazy were highly associated with patients when compared to controls . The possibility of a cognitive theory of panic attacks is discussed",
"Abstract Propranolol , a β-adrenergic blocking agent , is useful in the treatment of heroin addiction . It prevents the euphoric effects of heroin ; in addicts from whom heroin is withdrawn it eliminates , or much reduces , the distressing and enduring residual craving for the narcotic ; and it is a non-narcotic , non-addicting , and relatively safe drug that is effective when given orally in small doses . Propranolol taken in the usual amounts does not help in the management of the acute physical withdrawal symptoms . Two cases are described in which heroin , self-administered after the use of propranolol , actually precipitated , without accompanying euphoric effects , major symptoms of withdrawal . In one case the symptoms occurred after a single oral dose of propranolol 10 mg . given for the first time in the course of a double-blind trial of this medication , and persisted for twenty-four hours despite further use of heroin . In the other case , they were subsequently reactivated for twenty-four hours by further medications with propranolol ; the adverse reaction led to a request for continued treatment with propranolol as a prophylactic against recurrent use of heroin",
"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",
"BACKGROUND This study compared the efficacy and tolerability of paroxetine with placebo in the treatment of panic disorder . METHOD After three weeks of placebo , patients received 12 weeks of treatment with paroxetine ( 20 , 40 , or 60 mg ) or placebo , and finally two weeks of placebo . Dosages were adjusted according to efficacy and tolerability . St and ardised cognitive therapy was given to all patients . The primary measure of outcome was reduction in the number of panic attacks . RESULTS Analysis of the results showed statistically significant differences in favour of paroxetine between the two treatment groups in two out of the three primary measures of outcome , i.e. 50 % reduction in total number of panic attacks and number of panic attacks reduced to one or zero over the study period . For the third measure of outcome , the mean change in the total number of attacks from baseline , there was a positive trend in favour of paroxetine . The results of the primary measures of outcome were strongly supported by the results of the secondary efficacy measures of outcome . In addition , paroxetine , at all doses , was very well tolerated . CONCLUSION Paroxetine plus cognitive therapy was significantly more effective than placebo plus cognitive therapy in the treatment of panic disorder"
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411873e0-06ff-11f0-808a-c43d1ab1c353
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Atrial fibrillation is the most common type of arrhythmia in adults , accounting for about one third of hospitalizations for arrhythmia ( 1 ) . The prevalence increases from less than 1 % in persons younger than 60 years of age to more than 8 % in those older than 80 years of age ( 2 - 6 ) . The incidence ranges from 0.2 % per year for men 30 to 39 years of age to 2.3 % per year in men 80 to 89 years of age ( 7 , 8) . The age-adjusted incidence for women is about half that of men ( 9 ) . The cardiac conditions most commonly associated with atrial fibrillation are rheumatic mitral valve disease , coronary artery disease , congestive heart failure , and hypertension ( 8 , 10 ) . Noncardiac causes include hyperthyroidism , hypoxic conditions , surgery , and alcohol intoxication . A predisposing condition exists in more than 90 % of cases ( 5 , 11 , 12 ) ; the remaining cases have what is called lone atrial fibrillation . Patients with atrial fibrillation frequently have symptoms of hemodynamic compromise , ranging from irregular palpitations to the more insidious feeling of malaise . They also have an increased risk for thromboembolism . Comparing with age-matched controls , the relative risk for stroke is increased 2- to 7-fold in patients with nonrheumatic atrial fibrillation ( 3 , 8 , 13 ) , and the absolute risk for stroke is between 1 % and 5 % per year , depending on clinical characteristics ( 3 , 12 , 14 - 16 ) . Quality of life is an important consideration for patients . Paroxysmal atrial fibrillation disrupts the lives of patients ( 17 ) , but this perception may not be associated with frequency or duration of symptoms . Warfarin therapy affects quality of life because of frequent blood testing and recommendations for limiting some activities . Gage and colleagues ( 18 ) found that atrial fibrillation decreases utility , a quantitative assessment of quality of life used in decision analysis , by 1.3 % . Protheroe and associates ( 19 ) found that only 61 % of patients would prefer anticoagulation to no treatment , considerably fewer than those for whom guidelines would recommend treatment . Little is known about the direct effects of antiarrhythmic therapy and rate-control therapy on quality of life . The American College of Cardiology/American Heart Association/European Society of Cardiology Task Force on Clinical Guidelines for the Management of Atrial Fibrillation classified atrial fibrillation into 4 types ( 20 ) : first detected episode , paroxysmal ( terminates spontaneously ) , persistent ( electrical or pharmacologic termination necessary ) , and permanent ( resistant to electrical or pharmacologic conversion or accepted by the physician ) . The purpose of this review was to summarize the evidence that was available during formulation of the guidelines developed by the American College of Physicians ( ACP ) and the American Academy of Family Physicians ( AAFP ) for management of adult patients with nonpostoperative atrial fibrillation . The foundation of this background paper was a systematic review of the pharmacologic management of atrial fibrillation that examined the efficacy of medications used for stroke prevention , ventricular rate control , acute conversion , and maintenance of sinus rhythm , as well as the role of echocardiography in guiding pharmacologic therapy ( 21 ) . For this up date d version of the systematic review , we considered observational data , consensus statements , decision analyses , and relevant guidelines . This review focused on the evaluation and pharmacologic management of adult patients with nonpostoperative atrial fibrillation . The rapidly advancing field of nonpharmacologic management of atrial fibrillation is outside the scope of this paper . Methods A full description of the methods used in the systematic review can be found in a detailed evidence report ( 21 ) . A brief description of these methods and additional methods specific to this article are given below . Literature Identification Whenever possible , we focused our search es for relevant evidence on the strongest study design : r and omized , controlled trials ( RCTs ) . For our previous systematic review , we identified controlled trials in the CENTRAL data base produced by the Cochrane Collaboration 's international efforts , search ed MEDLINE from 1966 to 1998 for citations tagged as r and omized , controlled trial or controlled clinical trial , search ed the PubMed Related Articles feature , review ed h and search es su bmi tted to the Baltimore Cochrane Center , scanned the reference lists in relevant publications , and scanned the table of contents of relevant journals . For the current review , we also search ed MEDLINE from May 1998 through September 2001 ( using the same search terms as in the original review plus terms to identify meta-analyses and decision analyses ) . For topics without sufficient RCTs , we used observational data , consensus statements , review articles , and decision analyses obtained from our search of MEDLINE from 1966 through September 2001 . Although we had to use September 2001 as a cutoff for the systematic search ing of the literature in order to generate a report for the ACPAAFP Guideline group , we included selected studies published after September 2001 on the basis of input from the group . Article Review Process Studies were eligible for review if they were r and omized trials of adult patients that addressed the management of nonpostoperative atrial fibrillation . In the previous systematic review , 521 citations were identified and 179 articles were eligible for detailed review . The up date d search yielded 29 additional articles that met our inclusion criteria . Statistical Analysis For the quantitative analysis , we stratified the data to obtain an effect measure for each drug . We used Stata , version 7.0 ( Stata Corp. , College Station , Texas ) to calculate the odds ratio ( OR ) of success of the drug compared with placebo . Respective 95 % CIs and P values were also calculated . We used ORs because they provide less heterogeneity of study results than relative risk ratio . Estimates of the relative rates of the outcomes of interest were pooled by using st and ard methods for combining the OR for the outcomes of conversion to sinus rhythm , maintenance of sinus rhythm , stroke , peripheral embolism , major bleeding , minor bleeding , and death ( 21 ) . Studies were weighted on the basis of the precision of the estimate within each study . When no heterogeneity was found , meta-analyses used the fixed-effects model ( MantelHaenszel method for pooling ) ( 22 ) . When heterogeneity was found , the r and om-effects model was used ( DerSimonian and Laird method of pooling ) ( 23 ) . An OR was considered significantly different from 1 if the P value was less than 0.05 . Statistical strength of evidence was categorized as strong ( P 0.01 ) , moderate ( 0.01 0.2 ) . Role of the Funding Sources The initial systematic review was funded through a contract with the Agency for Healthcare Research and Quality ( 21 ) . Subsequent work was supported by the American College of Physicians . Drafts of the manuscript were review ed by members of the ACP/AAFP guidelines committee for management of atrial fibrillation . Data Synthesis Does Aggressive Rhythm Control Improve Mortality and Morbidity Compared with Rate Control ? Although the relative benefits and risks of rate versus rhythm control are of paramount importance in the management of atrial fibrillation , studies directly addressed this issue only recently . By far the largest , the Atrial Fibrillation Follow-up Investigation of Rhythm Management ( AFFIRM ) trial was a multicenter RCT that enrolled 4060 patients from more than 200 sites in Canada and the United States ( 24 ) . Eligibility criteria included documented atrial fibrillation lasting at least 6 hours and at least 1 risk factor for stroke ( age > 65 years , hypertension , diabetes mellitus , previous stroke , and poor ventricular function ) . Average age was 70 years . Sixty-one percent of patients were men , 89 % were white , 71 % had hypertension , 38 % had coronary artery disease , and 18 % had had failure of antiarrhythmic therapy . After patients were r and omly assigned to the rhythm-control or rate-control group , physicians could choose from a list of pharmacologic and nonpharmacologic therapies . Although anticoagulation was continued indefinitely for the rate-control group , discontinuation of anticoagulation was permitted at 1 month or later following conversion in the rhythm-control arm . The mortality rate at 5 years was 23.8 % in the rhythm-control group and 21.3 % in the rate-control group ( hazard ratio , 1.15 [ 95 % CI , 0.99 to 1.34 ] ; P = 0.08 ) . Combined central nervous system ischemic strokes and hemorrhagic events occurred in 8.9 % of patients in the rhythm-control group and 7.4 % of patients in the rate-control group ( P > 0.2 ) . Eighty-five patients in the rhythm-control group and 79 in the rate-control group had strokes ( P > 0.2 ) . Of note , more than 70 % of the strokes in both groups occurred in patients who had stopped taking anticoagulant therapy or who had an international normalized ratio less than 2.0 . Preliminary analyses of other secondary end points , including quality of life and functional capacity , did not show statistical difference between treatment groups . However , more hospitalizations occurred in the rhythm-control group . A smaller study conducted in the Netherl and s , the RAte Control versus Electrical cardioversion for persistent atrial fibrillation ( RACE ) study ( 25 ) , r and omly assigned 522 patients to aggressive rhythm control or rate control only . Mean age was 68 years . Sixty-four percent were men , 49 % had hypertension , and 27 % had coronary artery disease . The primary composite end point of cardiovascular mortality , heart failure , thromboembolic complications , bleeding , pacemaker implantation , and severe side effects of antiarrhythmic drugs occurred in 17.2 % of patients in the rate-control group and in 22.6 % of patients in the rhythm-control group over a mean of 2.3 years . Thus , rate control was not
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[
"OBJECTIVES The purpose of this study was to investigate the efficacy and safety of amiodarone and propafenone in the conversion of chronic atrial fibrillation in a prospect i ve , r and omized , placebo-controlled study . BACKGROUND The effectiveness of amiodarone and propafenone in the treatment of patients with chronic atrial fibrillation has not been adequately studied . METHODS One hundred one patients ( 48 men , mean age 64 + /- 9 years ) with atrial fibrillation lasting > 3 weeks participated in the study . Thirty-four patients received amiodarone ( 300 mg intravenously over 1 h , followed by 20 mg/kg over the next 24 h plus 600 mg orally , in three doses , for 1 week , then 400 mg/day orally , for three weeks ) , 32 received propafenone ( 2 mg/kg intravenously over 15 min , followed by 10 mg/kg over 24 h and then 450 mg/day orally , for one month ) and the remaining 35 served as control subjects . All patients received digoxin and anticoagulant treatment as indicated ( International Normalized Ratio 2 to 3 ) . RESULTS Conversion to sinus rhythm was achieved in 16 ( 47.05 % ) patients who received amiodarone , in 13 ( 40.62 % ) who received propafenone and in none of the control subjects ( p smaller atria than those who did not and atrial fibrillation of shorter duration in both the amiodarone and propafenone groups . Treatment was discontinued in one patient of the propafenone group because of significant QRS widening . CONCLUSIONS Amiodarone and propafenone appear to be safe and equally effective in the termination of chronic atrial fibrillation . Left atrial diameter and arrhythmia duration are independent predictors of conversion",
"Background Delivery of shocks within the right atrium has been reported to be more effective than conventional external shocks in converting atrial fibrillation ( AF ) , but these two cardioversion techniques have never been compared prospect ively . The purpose of this study was to compare the efficacies of external and internal cardioversion in patients with chronic AF unresponsive to prior attempts at electrical and /or pharmacological cardioversion . Low-dose amiodarone was used in all patients after cardioversion to suppress recurrences of AF . Methods and Results One hundred twelve patients with AF of at least 1 month in duration were r and omly assigned to undergo external cardioversion with 300–360-J shocks or internal cardioversion with 200–300-J shocks delivered through a st and ard electrode catheter within the right atrium . The patients were treated with amiodarone ( 200 mg/day 5–7 days/week ) for 1 month before electrical cardioversion and afterward if the cardioversion was successful . The patients were-evaluated at regular intervals during 1 year of follow-up . The efficacy of internal cardioversion was significantly greater than that of external cardioversion ( 91 % versus 67 % , p = 0.002 ) . The only variable that was associated with the outcome of cardioversion was body weight . Among patients in whom sinus rhythm was restored , AF recurred as often after internal and external cardioversion ; at 1 year of follow-up , 37 % of patients in whom external or internal cardioversion had been effective were still in sinus rhythm . Patients who had undergone an attempt at electrical cardioversion before entry into this study were less likely to remain in sinus rhythm after cardioversion . The only complications of cardioversion were one instance of cerebral thromboembolism after external cardioversion and one instance of transient pulmonary edema after internal cardioversion . Therapy with amiodarone was discontinued because of an adverse drug effect in only three patients . Conclusions Internal cardioversion is more effective than external cardioversion in restoring sinus rhythm and is as safe as external cardioversion in patients with chronic AF . The recurrence rate of AF is the same after both types of cardioversion . If conventional electrical cardioversion is ineffective , internal cardioversion should be attempted . The combination of low-dose amiodarone and external or internal cardioversion may result in maintaining sinus rhythm long-term in patients with refractory AF",
"BACKGROUND Atrial fibrillation can not always be converted to sinus rhythm by transthoracic electrical cardioversion . We examined the effect of ibutilide , a class III antiarrhythmic agent , on the energy requirement for atrial defibrillation and assessed the value of this agent in facilitating cardioversion in patients with atrial fibrillation that is resistant to conventional transthoracic cardioversion . METHODS One hundred patients who had had atrial fibrillation for a mean ( + /-SD ) of 117+/-201 days were r and omly assigned to undergo transthoracic cardioversion with or without pretreatment with 1 mg of ibutilide . We design ed a step-up protocol in which shocks at 50 , 100 , 200 , 300 , and 360 J were used for transthoracic cardioversion . If transthoracic cardioversion was unsuccessful in a patient who had not received ibutilide pretreatment , ibutilide was administered and transthoracic cardioversion attempted again . RESULTS Conversion to sinus rhythm occurred in 36 of 50 patients who had not received ibutilide ( 72 percent ) and in all 50 patients who had received ibutilide ( 100 percent , P sinus rhythm was restored when cardioversion was attempted again after the administration of ibutilide . Pretreatment with ibutilide was associated with a reduction in the mean energy required for defibrillation ( 166+/-80 J , as compared with 228+/-93 J without pretreatment ; P Sustained polymorphic ventricular tachycardia occurred in 2 of the 64 patients who received ibutilide ( 3 percent ) , both of whom had an ejection fraction of 0.20 or less . The rates of freedom from atrial fibrillation after six months of follow-up were similar in the two r and omized groups . CONCLUSIONS The efficacy of transthoracic cardioversion for converting atrial fibrillation to sinus rhythm was enhanced by pretreatment with ibutilide . However , use of this drug should be avoided in patients with very low ejection fractions ",
"OBJECTIVE To determine whether clonidine can slow ventricular rate in patients with rapid atrial fibrillation . DESIGN R and omized , controlled trial , with a 4-hour follow-up period . SETTING Emergency room of a university hospital . PATIENTS A consecutive sample of 18 hemodynamically stable patients who were evaluated or treated for rapid atrial fibrillation . Exclusion criteria included acute or terminal illness ; current use of antiarrhythmic agents , calcium-channel blockers , or beta-blockers ; excessive hypertension ; pulmonary , valvular , or pericardial disease ; and electrolyte imbalance . INTERVENTIONS Patients were r and omly assigned to receive either \" no treatment \" ( control group ) or clonidine , 0.075 mg orally , at baseline and after 2 hours if heart rate did not decrease by at least 20 % . MEASUREMENTS Blood pressure was measured by the same nurse in the same arm for 4 consecutive hours , and a full 12-lead electrocardiographic evaluation was done . MAIN RESULTS Heart rate decreased to below 100 beats/min in eight of nine patients receiving clonidine compared with two of nine patients in the control group . The difference in the mean decreases in heart rate was 38 beats/min ( 95 % CI , 20 to 56 beats/min ) . Six patients who were treated with clonidine and one patient in the control group reverted to normal sinus rhythm . Systolic blood pressure decreased slightly in both groups , without significant differences . Clinical follow-up was uneventful . CONCLUSION Low-dose clonidine was an easy , efficient , and effective treatment for patients with rapid atrial fibrillation who were hemodynamically stable",
"This study evaluates the effectiveness and safety of intravenous diltiazem for the treatment of atrial fibrillation and atrial flutter . A double-blind , parallel , r and omized , placebo-controlled protocol was used , and 6 large , urban hospitals , both university-affiliated and private , participated . The study involved 113 patients with atrial fibrillation or flutter , a ventricular rate greater than or equal to 120 beats/min and systolic blood pressure greater than or equal to 90 mm Hg without severe heart failure . The dose of intravenous diltiazem ( or identical placebo ) was 0.25 mg/kg/2 minutes followed 15 minutes later by 0.35 mg/kg/2 minutes if the first dose was tolerated but ineffective . If a patient did not respond , the code was broken and the patient was allowed to receive open-label diltiazem if placebo had been given . Of 56 patients , 42 ( 75 % ) r and omized to receive diltiazem responded to 0.25 mg/kg and 10 of 14 responded to 0.35 mg/kg , for a total response rate of 52 of 56 patients ( 93 % ) , whereas 7 of 57 patients ( 12 % ) responded to placebo ( p less than 0.001 ) . After the double-blind protocol , 49 of the 57 patients who received placebo were then given diltiazem ; 47 of 49 responded , for an overall response rate of 99 of 105 patients ( 94 % ) with diltiazem . The median time from the start of drug infusion to the maximal decrease in heart rate was 4.3 minutes . Side effects occurred in 14 patients , 7 of whom had asymptomatic hypotension not requiring intervention . Thus , intravenous diltiazem was rapidly effective for slowing the ventricular response in most patients with atrial fibrillation or atrial flutter . Blood pressure decreased slightly . Side effects were mild",
"Dofetilide may be advantageous in terminating atrial fibrillation/atrial flutter ( AFl ) when there are contraindications for class I drugs ( left ventricular dysfunction and /or manifest myocardial ischemia ) and beta blockers . In particular , its successful outcome in usually drug-resistant AFl is promising and underscores the importance of selective class III action for terminating AFl",
"OBJECTIVE This study was performed to characterize the risk of stroke in elderly patients with recurrent intermittent atrial fibrillation ( AF ) . BACKGROUND Although intermittent AF is common , relatively little is known about the attendant risk of stroke . METHODS A longitudinal cohort study was performed comparing 460 participants with intermittent AF with 1,552 with sustained AF treated with aspirin in the Stroke Prevention in Atrial Fibrillation studies and followed for a mean of two years . Independent risk factors for ischemic stroke were identified by multivariate analysis . RESULTS Patients with intermittent AF were , on average , younger ( 66 vs. 70 years , p women ( 37 % vs. 26 % p heart failure ( 11 % vs. 21 % , p annualized rate of ischemic stroke was similar for those with intermittent ( 3.2 % ) and sustained AF ( 3.3 % ) . In patients with intermittent AF , independent predictors of ischemic stroke were advancing age ( relative risk [ RR ] = 2.1 per decade , p hypertension ( RR = 3.4 , p = 0.003 ) and prior stroke ( RR = 4.1 , p = 0.01 ) . Of those with intermittent AF predicted to be high risk ( 24 % ) , the observed stroke rate was 7.8 % per year ( 95 % confidence interval 4.5 to 14 ) . CONCLUSIONS In this large cohort of AF patients given aspirin , those with intermittent AF had stroke rates similar to patients with sustained AF and similar stroke risk factors . Many elderly patients with recurrent intermittent AF have substantial rates of stroke and likely benefit from anticoagulation . High-risk patients with intermittent AF can be identified using the same clinical criteria that apply to patients with sustained AF",
"The aim of the study was to compare the effects of atenolol ( 50 mg b.i.d . ) , verapamil ( 80 mg b.i.d . ) , xamoterol ( 200 mg b.i.d . ) , and matching placebo on heart rate ( HR ) and exercise tolerance in digitalised patients with chronic atrial fibrillation . Each treatment was taken for 4 weeks , and digoxin was continued throughout the study . During treatment with placebo ( digoxin alone ) , the mean postexercise heart rate was 164 beats/min , and four subjects had rates of greater than or equal to 170 beats/min . Atenolol , verapamil , and xamoterol achieved significantly better control of exercise-induced tachycardia , mean postexercise heart rates being reduced to 120 , 131 , and 130 beats/min , respectively ( p less than 0.01 for each ) . However , minimum HRs less than or equal to 45 beats/min occurred during treatment with placebo , atenolol , and verapamil , whereas treatment with xamoterol was associated with a minimum heart rate of 56 beats/min . Treatment with atenolol was associated with a marked reduction in maximum treadmill walking distance ( mean 356 m ) as compared both with placebo ( mean 421 m , p less than 0.01 ) and verapamil ( mean 439 m , p less than 0.01 ) . Xamoterol reduced maximum walking distances as compared with verapamil ( 402 vs. 439 m ; p less than 0.05 ) but not placebo ( 402 vs. 421 m ; NSS ) . Thus , atenolol , verapamil , and xamoterol achieved better control of exercise-induced tachycardia than digoxin , but atenolol clearly impaired exercise tolerance whereas verapamil did not . Xamoterol achieved more even control of ventricular response rates and prevented the resting bradycardias that occurred with the other treatments . However , walking distances were significantly lower than those noted during treatment with verapamil ",
"BACKGROUND The combination therapy of low-dose diltiazem or bexatolol with digoxin can be a useful adjunct for achieving heart rate control with minimal side effects . But there has not been a study including patients with impaired left ventricular function and evaluating whether the beneficial effects of medication will be maintained during a follow-up period . OBJECTIVES The purpose of this study was three-fold : ( 1 ) to compare the efficacy of digoxin with low-dose diltiazem and digoxin with low-dose betaxolol on r and omized crossover study ; ( 2 ) to evaluate whether the beneficial effects of medication will be maintained after 7 months ; ( 3 ) to evaluate the safety of the combination therapy in patients with impaired left ventricular function . METHODS We did a prospect i ve r and omized crossover study in 35 patients with chronic atrial fibrillation ( AF ) including 15 patients with left ventricular dysfunction . After enrollment , each patient was evaluated for heart rate , blood pressure , rate-pressure products , maximal exercise tolerance at rest and during symptom-limited treadmill test before medication , at 4 weeks after medication of digoxin ( 0.125 - 0.5 mg daily ) with diltiazem ( 90 mg twice daily ) , and at 4 weeks after digoxin with betaxolol ( 20 mg once daily ) . We performed 24-h ambulatory electrocardiogram ( ECG ) in 15 patients at the end of each phase of treatment . We repeated symptom-limited treadmill test like above method in 15 patients at 7 months of medication . RESULTS ( 1 ) Ventricular rates were significantly reduced in digoxin with low-dose betaxolol therapy at rest and during exercise ( 67 + /- 3 , 135 + /- 5 ( mean + /- S.E.M. ) beats/min , respectively ) in comparison to digoxin with low-dose diltiazem therapy ( 80 + /- 7 , 154 + /- 5 ) ( P Rate-pressure products were significantly less in digoxin with low-dose betaxolol at rest and during exercise ( 85 + /- 4 , 213 + /- 12 x 10(2 ) mmHg/min ) than in digoxin with low-dose diltiazem therapy ( 105 + /- 6 , 269 + /- 12 ) ( P Exercise capacity was significantly improved in digoxin with low-dose betaxolol ( 9.3 + /- 0.5 METS ) or digoxin with low-dose diltiazem ( 9.7 + /- 0.5 ) in comparison to control state ( 8.3 + /- 0.5 ) ( P 24-h ambulatory ECG showed the same findings as on treadmill test . ( 6 ) Although side effects occurred more frequently in digoxin with low-dose betaxolol therapy , they were minimal and no patient had to withdraw medication . Worsening of left ventricular dysfunction was not observed . CONCLUSION Our study suggested that ( 1 ) combination therapy of low-dose betaxolol with digoxin was more superior to low-dose diltiazem with digoxin in controlling ventricular rate and reducing rate-pressure products ; ( 2 ) the effects controlling ventricular rate , reducing rate-pressure products and improving exercise capacity have been well maintained even after 7 months of medication with each combination therapy",
"The heart rate increase induced by dynamic exercise in patients with chronic atrial fibrillation is competitively attenuated by beta-blockade . The influence of oral celiprolol on exercise induced tachycardia was evaluated in 23 patients with chronic stable atrial fibrillation in a dose-titration study . This was succeeded by a placebo-controlled double-blind , crossover multi-center trial . During the dose-titration phase each patient underwent a single-blind three week dose escalation period-taking celiprolol 200 mg once daily for one week , celiprolol 400 mg once daily for the third week . After a one week placebo washout , patients then entered a double-blind crossover phase , consisting of one week each of placebo or celiprolol according to a pre-determined r and omization . After one week of placebo washout , each patient was crossed-over . In 21 patients celiprolol reduces exercise-induced increased heart rate by approximately 35 % when compared with placebo . These results indicate that celiprolol should be effective in controlling the exercise-induced increase in heart rate in patients with chronic atrial fibrillation . In addition , results of 24 h ambulatory ECG monitoring ( Holtor monitoring ) indicate that celiprolol reduces the ventricular premature contractions",
"Atrial fibrillation ( AF ) is one of the most common cardiac arrhythmias in the adult population . Propafenone is a class 1c antiarrhythmic agent that has an electrophysiologic profile suggesting that it might be potentially effective in recent-onset AF . The present study was undertaken , therefore , to examine the time course as well as the frequency of successful conversion in patients with recent-onset AF treated with propafenone administered orally . Fifty patients with recent-onset AF were recruited into 2 groups : 25 patients were given propafenone , 150 mg every 4 h , and 25 patients served as a control group and received verapamil ( a drug known to slow the ventricular response but not to restore sinus rhythm ) 40 mg , every 4 h and up to 48 h or until conversion to sinus rhythm occurred . Of the 50 patients , 2 refused to continue the study and another 2 were excluded because of left heart failure . Conversion to sinus rhythm occurred in 21 of 24 patients ( 87 percent ) in the propafenone group as compared with 9 of 22 ( 41 percent ) in the verapamil group ( p propafenone group , conversion occurred within 12 h , within 24 h in another 9 patients , and between 24 and 48 h in the remaining 2 patients . There was no correlation between the duration of AF prior to entry into the study and the subsequent incidence of and time to conversion with propafenone . With respect to cause of AF , all groups showed a high incidence of conversion . Two patients developed heart failure during treatment and one patient ( in the verapamil group ) developed embolic stroke while still having atrial fibrillation . We conclude that in patients with AF , the prognosis for conversion to sinus rhythm within 48 h , with propafenone , is excellent ( 87 percent ) and safe",
"Abstract Objective : To investigate the effectiveness of aspirin and coumarin in preventing thromboembolism in patients with non-rheumatic atrial fibrillation in general practice . Design : R and omised controlled trial . Participants : 729 patients aged ≥60 years with atrial fibrillation , recruited in general practice , who had no established indication for coumarin . Mean age was 75 years and mean follow up 2.7 years . Setting : Primary care in the Netherl and s. Interventions : Patients eligible for st and ard intensity coumarin ( international normalised ratio 2.5 - 3.5 ) were r and omly assigned to st and ard anticoagulation , very low intensity coumarin ( international normalised ratio 1.1 - 1.6 ) , or aspirin ( 150 mg/day ) ( stratum 1 ) . Patients ineligible for st and ard anticoagulation were r and omly assigned to low anticoagulation or aspirin ( stratum 2 ) . Main outcome measures : Stroke , systemic embolism , major haemorrhage , and vascular death . Results : 108 primary events occurred ( annual event rate 5.5 % ) , including 13 major haemorrhages ( 0.7 % a year ) . The hazard ratio was 0.91 ( 0.61 to 1.36 ) for low anticoagulation versus aspirin and 0.78 ( 0.34 to 1.81 ) for st and ard anticoagulation versus aspirin . Non-vascular death was less common in the low anticoagulation group than in the aspirin group ( 0.41 , 0.20 to 0.82 ) . There was no significant difference between the treatment groups in bleeding incidence . High systolic and low diastolic blood pressure and age were independent prognostic factors . Conclusion : In a general practice population ( without established indications for coumarin ) neither low nor st and ard intensity anticoagulation is better than aspirin in preventing primary outcome events . Aspirin may therefore be the first choice in patients with atrial fibrillation in general practice . Key messages Studies have shown that patients with non-rheumatic atrial fibrillation may benefit from anticoagulation This study in a general practice population found no benefit of st and ard or low dose anticoagulation on risk of stroke , systemic embolism , major haemorrhage , or vascular death when compared with aspirin Hypertension and age were prognostic factors for event occurrence Aspirin is the treatment of choice for preventing thromboembolism in primary care patients at low",
"AIM Low-energy ( 1 to 15 J ) , catheter-based intracardiac cardioversion was compared with transthoracic external cardioversion ( 360 J ) in a prospect i ve , cross-over clinical trial . METHODS AND RESULTS In 187 consecutive patients with chronic atrial fibrillation , over a period of a mean of 10.0 + /- 7.3 ( SD ) months , 217 cardioversion attempts were made . Intracardiac shocks were r and omly applied between two 6-F catheters located in either the right atrium and coronary sinus or between the right atrium and left pulmonary artery . When a cardioversion attempt with one method failed , the other method was implemented . After cardioversion , all patients were treated orally with sotalol with a mean daily dose of 174 + /- 54 mg . Internal cardioversion was more effective than external cardioversion ( 65/70 = 93 % vs 92/117 = 79 % , P mean energy for successful cardioversion was 5.8 + /- 3.2 J for the internal and 313 + /- 71 J for the external cardioversion group . At a mean follow-up of 12.5 + /- 6.4 months , 48 % ( 38 % ) of the patients treated with internal ( external ) cardioversion were in sinus rhythm ( P external cardioversion failed , sinus rhythm was restored with internal cardioversion at a mean energy of 6.5 + /- 3.0 J. Overweight patients had twice the risk of unsuccessful external cardioversion . CONCLUSIONS Internal cardioversion is effective in restoring sinus rhythm . It might be indicated in patients in whom external cardioversion had failed or in whom external cardioversion is assumed to be difficult or even contraindicated",
"The safety and efficacy of a 10- to 15-mg/h continuous infusion of intravenous diltiazem were evaluated in 47 patients with atrial fibrillation or flutter who first responded to 20 mg or 20 mg followed by one or more 25-mg bolus doses of open label intravenous diltiazem . Of the 47 patients , 44 responded to the bolus injection and were r and omized under double-blind conditions to receive either a continuous infusion of intravenous diltiazem ( 10 to 15 mg/h ) ( 23 patients ) or placebo ( 21 patients ) for up to 24 h. Seventeen ( 74 % ) of the 23 patients receiving diltiazem infusion and none of the 21 with placebo infusion maintained a therapeutic response for 24 h ( p less than 0.001 ) . Over 24 h , patients receiving diltiazem infusion lost response significantly more slowly than did those receiving placebo infusion ( p less than 0.001 ) . Nonresponders to the double-blind infusion were given an additional bolus injection of open label intravenous diltiazem and administered an open label 24-h intravenous diltiazem infusion . The overall proportion of patients maintaining a response to a 24-h infusion of intravenous diltiazem under double-blind or open label conditions combined was 83 % ( 34 of 41 ) . Efficacy of the 24-h infusion of intravenous diltiazem was similar in elderly versus young patients , those who did versus those who did not receive digoxin and those weighing less than 84 versus greater than or equal to 84 kg . However , intravenous diltiazem appeared to be more effective in atrial fibrillation than in atrial flutter . No significant untoward effects were noted . ( ABSTRACT TRUNCATED AT 250 WORDS",
"Summary The effectiveness of intravenous propafenone for conversion to sinus rhythm ( SR ) of paroxysmal atrial fibrillation ( AF ) , lasting less than 7 days , was evaluated with a single-blind , r and omized , placebo-controlled study , given the possible spontaneous conversion of this arrhythmia . Group 1 ( 98 patients ) received intravenous propafenone ( 2 mg/kg iv over 10 minutes followed by 0.007 mg/kg/min ) ; and group 2 ( 84 patients ) received intravenous placebo ( 0.9 % saline solution ) . The infusion was continued until restoration of SR but no longer than 24 hours . Eight-nine patients ( 90.8 % ) received propafenone and 27 patients ( 32 % ) receiving placebo were converted to SR ( p The mean conversion time was 2.46±2.59 hours in group 1 and 17.15±5.78 hours in group 2 ( p treated with propafenone , conversion of SR mostly occurred in the first 4 hours ( 86.5 % ) , considered to be the optimal infusion time in our experience . In both groups , the left atrial size was significantly larger in nonconverted than in converted patients . Similarly , the duration of the arrhythmia was significantly longer in nonconverted patients . In nonconverted patients , the mean ventricular rate decreased from 143±beats/min to 101±18 beats/min after propafenone and from 135±19 beats/min to 199 ±16 beats/min after placebo ( group 1 vs. group 2 : p of sinus st and still ( 3.4 and 3.8 , seconds , respectively ) occurred at SR restoration obtained with propafenone . Intravenous propafenone is an effective , safe , and usually rapid drug for AF treatment . Moreover , it produces a real and significant reduction in the mean ventricular rate in nonconverted patients",
"Background This double-blind , multicenter , placebo-controlled study determined the efficacy and safety of dofetilide in converting atrial fibrillation ( AF ) or atrial flutter ( AFl ) to sinus rhythm ( SR ) and maintaining SR for 1 year . Methods and Results Patients with AF or AFl ( n=325 ) were r and omized to 125 , 250 , or 500 & mgr;g dofetilide or placebo twice daily . Dosages were adjusted for QTc response and , after 105 patients were enrolled , for calculated creatinine clearance ( ClCr ) . Pharmacological cardioversion rates for 125 , 250 , and 500 & mgr;g dofetilide were 6.1 % , 9.8 % , and 29.9 % , respectively , versus 1.2 % for placebo ( 250 and 500 & mgr;g versus placebo;P = 0.015 and P pharmacological cardioversions with dofetilide were achieved in 24 hours and 91 % in 36 hours . For the 250 patients who successfully cardioverted pharmacologically or electrically , the probability of remaining in SR at 1 year was 0.40 , 0.37 , 0.58 for 125 , 250 , and 500 & mgr;g dofetilide , respectively , and 0.25 for placebo ( 500 & mgr;g versus placebo , P = 0.001 ) . Two cases of torsade de pointes occurred , 1 on day 2 and the other on day 3 ( 0.8 % of all patients given active drug ) ; 1 sudden cardiac death , classified as proarrhythmic , occurred on day 8 ( 0.4 % of all patients given active drug ) . Conclusions Dofetilide , a new class III antiarrhythmic agent , is moderately effective in cardioverting AF or AFl to SR and significantly effective in maintaining SR for 1 year . In-hospital initiation and dosage adjustment based on QTc and ClCr are necessary to minimize a small but nonnegligible proarrhythmic risk",
"BACKGROUND In a multicenter , double-blind , placebo-controlled study , the long-term effects of amiodarone on morbidity and mortality in patients with congestive heart failure ( CHF ) and atrial fibrillation ( AF ) were evaluated during a 4-year period . METHODS AND RESULTS Of 667 patients with CHF , 103 ( 15 % ) had AF at baseline . Of these , 51 were r and omized to amiodarone and 52 to placebo . The group with sinus rhythm and the group in AF were comparable except for a higher proportion of AF in patients with nonischemic versus ischemic cardiomyopathy ( 41 % versus 27 % , P mean ventricular response ( VR ) during AF over 24 hours was reduced by amiodarone at 2 weeks ( 20 % , P=0.001 ) , at 6 months ( 18 % , P=0.001 ) , and at 12 months ( 16 % , P=0.006 ) . Maximal VR was reduced 22 % ( P=0.001 ) at 2 weeks , 19 % ( P=0.001 ) at 6 months , and 14 % ( P=0.001 ) at 12 months . Sixteen of 51 patients on amiodarone and 4 of 52 on placebo converted to sinus rhythm during the study ( chi2=9.23 , P=0.002 ) . During follow-up , 11 of 268 patients in sinus rhythm on amiodarone at baseline and 22 of the 263 in sinus rhythm on placebo developed AF ; the difference was significant ( chi2=12.88 , P=0.005 ) . Analysis of total mortality during follow-up showed a significantly lower mortality rate ( P=0 . 04 ) in patients in AF at baseline who subsequently converted to sinus rhythm on amiodarone than in those who did not convert to sinus rhythm on the drug . CONCLUSIONS In patients with CHF , amiodarone has a significant potential to spontaneously convert patients in AF to sinus rhythm , with patients who convert having a lower mortality rate than those who do not . The drug prevented the development of new-onset AF and significantly reduced the VR in those with persistent AF",
"OBJECTIVES This study evaluated the role of various clinical and echocardiographic parameters , including the left atrial appendage ( LAA ) antero grade flow velocity , for prediction of the long-term preservation of sinus rhythm ( SR ) in patients with successful cardioversion ( CV ) of nonvalvular atrial fibrillation ( AF ) . BACKGROUND Echocardiographic parameters for assessing long-term SR maintenance after successful CV of nonvalvular AF are not accurately defined . METHODS Clinical , transthoracic echocardiographic and transesophageal echocardiographic ( TEE ) data --measured in AF lasting > 48 h -- of 186 consecutive patients ( 116 men , mean age : 65 + /- 9 years ) with successful CV ( electrical or pharmacologic ) were analyzed for assessment of one-year maintenance of SR . RESULTS At one-year follow-up , 91 of 186 ( 49 % ) patients who underwent successful CV continued to have SR . Mean LAA peak emptying flow velocity was higher in patients remaining in SR for one year than in those with AF relapse ( 41.7 + /- 20.2 cm/s vs. 27.7 + /- 17.0 cm/s ; p mean LAA peak emptying velocity > 40 cm/s ( p = 0.0001 ; chi(2 ) : 23.9 , odds ratio [ OR ] = 5.2 , confidence interval [ CI ] 95 % = 2.7 to 10.1 ) and the use of preventive antiarrhythmic drug treatment ( p = 0.0398 ; chi(2 ) : 4.2 ; OR = 2.0 , CI 95 % = 1.0 to 3.8 ) predicted the continuous preservation of SR during one year , outperforming other univariate predictors such as absence of left atrial spontaneous echocardiographic contrast during TEE , the left atrial parasternal diameter ventricular ejection fraction > 46 % and AF duration mean LAA peak emptying velocity > 40 cm/s for assessing preservation of SR were 66 % ( CI 95 % = 56.9 to 74.2 ) and 73 % ( CI 95 % = 62.4 to 83.3 ) , respectively . CONCLUSIONS In TEE-guided management of nonvalvular AF , high LAA flow velocity identifies patients with greater likelihood to remain in SR for one year after successful CV . Low LAA velocity is of limited value in identifying patients who will relapse into AF",
"Objective Evaluation of efficacy of intravenous flecainide to revert supraventricular arrhythmias to sinus rhythm in patients with respiratory insufficiency . Design Comparative r and omized prospect i ve trial . Setting ICU in a University Hospital Patients 30 patients with acute respiratory insufficiency or acute exscerbation of chronic respiratory insufficiency and supraventricular arrhythmias . Intravenous flecainide was administered to 15 patients ( Group A ) ( 2 mg/kg for 10 min and continuous perfusion of 1.5 mg/kg for 1 h ) . Intravenous verapamil was administered to 15 patients ( Group B ) ( 0.15 mg/kg for 5 min and continuous perfusion of 0.005 mg/kg/min for 1 h ) . Measurements and results The categories of patients ' arrhythmias were : Group A — atrial fibrillation ( AF ) in 5 cases , atrial flutter ( AFl ) in 2 , multifocal atrial tachycardia ( MAT ) in 4 and other supraventricular tachycardia ( SVT ) in 4 . Group B — AF in 6 cases , AFL in 2 , MAT in 2 and SVT in 5 cases . Flecainide reverted arrhythmias to sinus rhythm in 12 out of 15 cases ( 80 % ) ; of these 12 , 11 reverted with the initial bolus . Verapamil reverted 5 out of 12 cases ( 33.3%,p secondary adverse effects were detected . Conclusion Intravenous flecainide is an effective antiarrhythmic drug to treat acute supraventricular arrhythmias in patients with respiratory insufficiency",
"In order to compare the efficacy and long-term tolerability of flecainide acetate versus quinidine , 239 patients with paroxysmal atrial fibrillation were prospect ively treated with flecainide ( n = 122 ) or quinidine ( n = 117 ) in an open-label , r and omized trial . All patients were followed for 1 year after initiation of therapy unless their antiarrhythmic drug was discontinued due to an inadequate therapeutic response or intolerable side effects . Although both drugs were equally effective in adequately controlling recurrences of atrial fibrillation ( difference , p = 0.282 ; not significant ) , fewer flecainide patients had to have their therapy discontinued due to adverse experiences ( p = 0.012 ) . Based on both endpoints ( efficacy and tolerability ) , an estimated 70.5 % of flecainide versus 55.4 % of quinidine patients would remain effectively treated at the end of 1 year on therapy ( p flecainide and quinidine are equally effective in the acceptable suppression of symptomatic paroxysmal atrial fibrillation ; ( 2 ) flecainide is better tolerated than quinidine and is less likely to be discontinued due to adverse effects ; and ( 3 ) given the overall endpoint of efficacy and tolerability , more patients are likely to continue long-term therapy with flecainide than with quinidine",
"OBJECTIVES This multicenter study compared the efficacy and safety of ibutilide versus procainamide for conversion of recent-onset atrial flutter or fibrillation . BACKGROUND Ibutilide fumarate is an intravenous ( IV ) class III antiarrhythmic agent that has been shown to be significantly more effective than placebo in the pharmacologic conversion of atrial flutter and fibrillation to sinus rhythm . Procainamide is commonly used for conversion of recent-onset atrial fibrillation to normal sinus rhythm . METHODS One hundred twenty-seven patients ( age range 22 to 92 years ) with atrial flutter or fibrillation of 3 h to 90 days ' ( mean 21 days ) duration were r and omized to receive either two 10-min IV infusions of 1 mg of ibutilide fumarate , separated by a 10-min infusion of 5 % dextrose in sterile water , or three successive 10-min IV infusions of 400 mg of procainamide hydrochloride . RESULTS Of the 127 patients , 120 were evaluated for efficacy : 35 ( 58.3 % ) of 60 in the ibutilide group compared with 11 ( 18.3 % ) of 60 in the procainamide group had successful termination within 1.5 h of treatment ( p patients with atrial flutter , ibutilide had a significantly higher success rate than procainamide ( 76 % [ 13 of 17 ] vs. 14 % [ 3 of 22 ] , p=0.001 ) . Similarly , in the atrial fibrillation group , ibutilide had a significantly higher success rate than procainamide ( 51 % [ 22 of 43 ] vs. 21 % [ 8 of 38 ] , p=0.005 ) . One patient who received ibutilide , which was found to be a protocol violation , had sustained polymorphic ventricular tachycardia requiring direct current cardioversion . Seven patients who received procainamide became hypotensive . CONCLUSIONS This study establishes the superior efficacy of ibutilide over procainamide when administered to patients to convert either atrial fibrillation or atrial flutter to sinus rhythm . Hypotension was the major adverse effect seen with procainamide . A low incidence of serious proarrhythmia was seen with the administration of ibutilide occurring at the end of infusion",
"BACKGROUND AND PURPOSE The optimal intensity of warfarin therapy for secondary prevention of stroke in nonvalvular atrial fibrillation ( NVAF ) remains unclear . We studied the efficacy and safety of conventional- and low-intensity warfarin therapy in a prospect i ve , r and omized , multicenter trial . METHODS The study population consisted of patients with NVAF ( The patients were r and omly allocated into a conventional-intensity group ( international normalized ratio [ INR ] 2.2 to 3.5 ) and a low-intensity group ( INR 1.5 to 2.1 ) . They were carefully monitored , and the annual rate of recurrent ischemic stroke and major hemorrhagic complications were compared between the groups . RESULTS We enrolled 115 patients ( mean age 66.7+/-6.5 years ) into the study . Fifty-five and 60 patients were allocated into the conventional- and low-intensity groups , respectively . The trial was stopped after a follow-up of 658+/-423 days , when major hemorrhagic complications occurred in 6 patients of the conventional-intensity group and the frequency ( 6.6 % per year ) was significantly higher than that in the low-intensity group ( 0 % per year , P=0.01 , Fisher 's exact test ) . All of the 6 patients with major bleeding were elderly ( mean age 74 years ) , and their mean INR before the major hemorrhage was 2.8 . The annual rate of ischemic stroke was low in both groups ( 1.1 % per year in the conventional-intensity group and 1.7 % per year in the low-intensity groups ) and did not differ significantly . CONCLUSIONS For secondary prevention of stroke in persons with NVAF , especially in old patients , the low-intensity warfarin ( INR 1.5 to 2 . 1 ) treatment seems to be safer than the conventional-intensity ( INR 2.2 to 3.5 ) treatment",
"BACKGROUND Because atrial thrombi are poorly detected by conventional noninvasive techniques such as transthoracic echocardiography , patients with prolonged atrial fibrillation usually receive several weeks of oral anticoagulation therapy before cardioversion is attempted . We wondered whether transesophageal echocardiography , an accurate method of detecting atrial thrombi , would allow early cardioversion to be performed safely if no thrombi were identified . METHODS A total of 669 consecutive patients admitted with the diagnosis of atrial fibrillation were screened . Patients were excluded if they were receiving long-term anticoagulation , if the duration of atrial fibrillation was two days or less , if they were not c and i date s for cardioversion , or if transesophageal echocardiography was contraindicated . Of 119 qualifying patients , 94 agreed to participate ; the average duration of atrial fibrillation was 4.5 weeks . Participating patients underwent transthoracic echocardiography and transesophageal echocardiography followed by cardioversion if no thrombi were seen . Short-term anticoagulation with heparin was used in 80 patients before cardioversion , and 60 patients received warfarin for one month after cardioversion . RESULTS Fourteen atrial thrombi were identified in 12 patients ( 13 percent ) , and 12 of the 14 thrombi were visualized only on transesophageal echocardiography . Cardioversion was deferred in all 12 patients . Two of these 12 patients died suddenly ; 4 of the 10 surviving patients underwent uneventful cardioversion after prolonged oral anticoagulation . Seventy-eight of the 82 patients without thrombi underwent successful cardioversion to sinus rhythm ( 47 by means of antiarrhythmic drugs and 31 by electrical cardioversion ) , all without long-term oral anticoagulation . None of these patients ( 95 percent confidence interval , 0 to 4.6 percent ) had an embolic event . CONCLUSIONS In patients with atrial fibrillation of unknown or prolonged duration who are not receiving long-term anticoagulation , atrial thrombi are detected by transesophageal echocardiography in only a small minority ( 13 percent in our study ) . Our preliminary data suggest that if transesophageal echocardiography excludes the presence of thrombi , early cardioversion can be performed safely without the need for prolonged oral anticoagulation before the procedure",
"The objective of this multicenter , r and omized , double-blind , placebo-controlled study was to determine the safety and efficacy of intravenous diltiazem in the treatment of 37 patients with rapid ( ventricular rate , mean + /- SD 142 + /- 17 beats/min ) atrial fibrillation or flutter and moderate to severe congestive heart failure ( ejection fraction , mean + /- SD 36 + /- 14 % ; New York Heart Association class III [ 23 patients ] , class IV [ 14 patients ] ) . During the double-blind portion of the study , patients received either intravenous diltiazem , 0.25 mg/kg over 2 minutes , or placebo followed 15 minutes later by diltiazem or placebo , 0.35 mg/kg over 2 minutes , if the first dose was tolerated but ineffective . Placebo nonresponders were given open-label intravenous diltiazem in a similar fashion as in the double-blind portion of the study . In the double-blind part of the study , 21 ( 18 with 0.25 mg/kg , 3 with an additional 0.35 mg/kg ) of the 22 patients ( 95 % ) responded to diltiazem , and 0 of 15 patients ( 0 % ) responded to placebo ( p placebo during the double-blind period had a therapeutic response to diltiazem during open-label therapy . Overall , 36 of 37 patients ( 97 % ) had a therapeutic response to intravenous diltiazem . Heart rate response to diltiazem after the 2-minute bolus infusions consisted of a > or = 20 % decrease in heart rate from baseline in 36 patients ; in addition , 17 patients also had heart rates decreased to < 100 beats/min , whereas no patient had conversion to sinus rhythm . ( ABSTRACT TRUNCATED AT 250 WORDS",
"Objective : We sought to assess the efficacy and safety of amiodarone for restoration and maintenance of sinus rhythm in patients with chronic atrial fibrillation in a prospect i ve , r and omized , double blind trial . Background : Restoration and preservation of sinus rhythm is difficult in patients with chronic atrial fibrillation . The efficacy of oral amiodarone has not been conclusively established . Methods : Ninety-five patients with chronic atrial fibrillation , lasting an average of 35.6 months , were r and omized to either amiodarone ( 600 mg/d ) ( 47 patients ) or placebo ( 48 patients ) during four weeks . Nonresponders underwent electric cardioversion , and those who reverted continued with amiodarone ( 200 mg/d ) or placebo . End-points were successful cardioversion and sinus rhythm maintenance . Results : Sixteen patients ( 34.04 % ) in the amiodarone group reverted within 27.28 ± 8.85 days in comparison with 0 % in the placebo group ( P 0.000009 ) . The conversion rate rose to 51.72 % in patients with chronic atrial fibrillation lasting less than 12 months . Twenty-eight patients in the amiodarone group and 39 in the placebo group underwent electric cardioversion , which was successful in 19 patients ( 67.8 % ) of the amiodarone group and in 15 ( 38.46 % ) of the placebo group ( P = 0.017 ) . Altogether , conversion was obtained in 79.54 % of the amiodarone group patients and in 38.46 % of the placebo group patients ( P , atrial fibrillation relapsed in 13 ( 37.14 % ) of 35 patients of the amiodarone group within 8.84 + 8.57 months and in 12 ( 80 % ; P = 0.009 ) of 15 patients of the placebo group within 2.74 ± 3.41 months . Conclusions : Oral amiodarone restored sinus rhythm in one third of patients with chronic atrial fibrillation , increased the success rate of electric cardioversion , decreased the number of relapses and delayed their occurrence",
"OBJECTIVES This study sought to determine the safety and efficacy of a single bolus of intravenous dofetilide , a pure class III antiarrhythmic agent , for the termination of sustained atrial fibrillation or flutter . BACKGROUND Dofetilide is a highly selective blocker of the rapid component of the delayed rectifier current causing action potential prolongation . These effects , and preliminary clinical data , suggest that it may be effective in the treatment of atrial fibrillation and flutter . METHODS Ninety-one patients with sustained atrial fibrillation ( 75 patients ) or flutter ( 16 patients ) were entered into a double-blind , r and omized multicenter study of one of two doses of dofetilide ( 4 or 8 micrograms/kg body weight ) or placebo . RESULTS Dofetilide effectively terminated the arrhythmia in 31 % of patients receiving 8 micrograms/kg , a statistically significant difference from those receiving 4 micrograms/kg ( conversion rate 12.5 % , p placebo ( no conversion , p Patients with atrial flutter had a greater response to dofetilide ( 54 % conversion rate ) than those with atrial fibrillation ( 14.5 % conversion rate , p dofetilide can convert sustained atrial fibrillation or flutter to sinus rhythm . However , its efficacy is greater in flutter -- a response that contrasts with the poorer response seen with class I agents . This finding potentially represents an important advance in the pharmacologic termination of atrial flutter",
"In a placebo-controlled study the effects on ventricular rate regulation and exercise performance of xamoterol , 100 mg two times a day and 200 mg two times a day , and slow-release verapamil , 240 mg once a day , were assessed in 21 patients with chronic atrial fibrillation . The mean ventricular rate from noon to 6:00 PM was 101 + /- 20 beats/min with placebo , 95 + /- 17 beats/min with xamoterol 100 mg two times a day ( not significant ) , 90 + /- 16 beats/min with xamoterol 200 mg two times a day ( p less than 0.001 vs placebo ) and 78 + /- 19 beats/min with verapamil ( p less than 0.001 vs each other treatment ) . The mean ventricular rate from midnight to 6:00 AM was 69 + /- 16 beats/min with placebo , increased with xamoterol 100 mg two times a day and 200 mg two times a day to 75 + /- 15 beats/min and 74 + /- 16 beats/min , respectively ( p less than 0.001 vs placebo ) , but decreased with verapamil to 62 + /- 15 beats/min ( p less than 0.001 vs each other treatment ) . The number of ventricular pauses greater than 2.0 seconds was increased by verapamil ( p less than 0.05 ) . All active treatments reduced exercise ventricular rates ( p less than 0.001 ) , but the decrease was more pronounced with verapamil . The anaerobic threshold was reached significantly earlier with verapamil than with placebo ( 72 + /- 32 W vs 79 + /- 37 W ; p less than 0.01 ) . Xamoterol is preferable to verapamil for treatment of patients with chronic atrial fibrillation who exhibit both bradycardia at rest and excessive tachycardia during exercise . ( ABSTRACT TRUNCATED AT 250 WORDS",
"Background Atrial fibrillation in the absence of rheumatic valvular disease is associated with a fivefold to sevenfold increased risk of ischemic stroke . Methods and Main Results . The Stroke Prevention in Atrial Fibrillation Study , a multicenter , r and omized trial , compared 325 mg/day aspirin ( double-blind ) or warfarin with placebo for prevention of ischemic stroke and systemic embolism ( primary events ) , and included 1,330 in patients and out patients with constant or intermittent atrial fibrillation . During a mean follow-up of 1.3 years , the rate of primary events in patients assigned to placebo was 6.3 % per year and was reduced by 42 % in those assigned to aspirin ( 3.6 % per year , p = 0.02 ; 95 % confidence interval , 9–63 % ) . In the subgroup of warfarin-eligible patients ( most less than 76 years old ) , warfarin dose-adjusted to prolong prothrombin time to 1.3-fold to 1.8-fold that of control reduced the risk of primary events by 67 % ( warfarin versus placebo , 2.3 % versus 7.4 % per year , p = 0.01 ; 95 % confidence interval , 27–85 % ) . Primary events or death were reduced 58 % ( p = 0.01 ) by warfarin and 32 % ( p = 0.02 ) by aspirin . The risk of significant bleeding was 1.5 % , 1.4 % , and 1.6%o per year in patients assigned to warfarin , aspirin , and placebo , respectively . Conclusions Aspirin and warfarin are both effective in reducing ischemic stroke and systemic embolism in patients with atrial fibrillation . Because warfarin-eligible patients composed a subset of all aspirin-eligible patients , the magnitude of reduction in events by warfarin versus aspirin can not be compared . Too few events occurred in warfarin-eligible patients to directly assess the relative benefit of aspirin compared with warfarin , and the trial is continuing to address this issue . Patients with nonrheumatic atrial fibrillation who can safely take either aspirin or warfarin should receive prophylactic antithrombotic therapy to reduce the risk of stroke",
"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",
"The antiarrhythmic effect of timolol was investigated in 160 subjects with supraventricular arrhythmias . In our double‐blind , r and omized , parallel , multiclinic study , subjects received timolol , 1 mg iv , or matching placebo as a starting dose , followed by a second and third dose of 1 mg each ( or matching placebo ) at 20‐min intervals if the arrhythmia did not convert to sinus rhythm . Subjects in whom the sinus rhythm returned or the ventricular rate decreased to timolol in 10‐mg tablets twice a day by mouth , 1 hr after the last intravenous dose . Data indicated that the mean decrease in heart rate was 44 bpm after timolol and 7 bpm after placebo . The overall proportion of responders ( either conversion to sinus rhythm or a decrease in ventricular rate to ) was 68 % after timolol and 7 % after placebo . The proportions of responders after timolol were significantly higher than the proportions after placebo for paroxysmal supraventricular tachycardia ( 26 of 32 subjects and two of 38 subjects ) , atrial fibrillation ( 17 of 29 subjects and three of 32 subjects ) , and atrial flutter ( seven of 11 subjects and one of nine subjects ) . The most common adverse effects were bradycardia and hypotension ",
"We evaluated the effectiveness of oral verapamil therapy for control of ventricular rate in digitalized patients with atrial fibrillation ( AF ) with three clinical problems : chronic AF with rapid rate at rest ( four patients ) , chronic AF with accelerated rate during modest exercise ( five patients ) , and rapid rates during paroxysmal AF ( four patients ) . Patients in the first two categories were evaluated both by open-label dosage titration and by a r and omized , double-blind , cross-over protocol . In chronic AF with rapid rate of rest , there was a significant reduction in resting heart rate ( from 125 + /- 7 to 87 + /- 14 , P less than 0.01 ) and in peak exercise heart rate ( from 162 + /- 33 to 126 + /- 25 , P less than 0.01 ) . In chronic AF with rapid rate during exercise , there was also a significant decrease in resting heart rate ( from 90 + /- 7 to 66 + /- 4 , P less than 0.01 ) and in peak exercise heart rate ( from 126 + /- 19 to 101 + /- 15 , P less than 0.01 ) . These effects continued during longterm follow-up of one to 12 months ( mean seven months ) . In patients with paroxysmal AF , verapamil slowed the ventricular response from 16- + /- 24 to 72 + /- 4 P less than 0.01 ) with only some amelioration of symptoms . Therapy was well tolerated despite a high prevalence ( seven of 13 patients ) of radiographic cardiomegaly ( cardiothoracic ratio greater than 0.55 ) . We conclude that verapamil is a safe and useful drug for control of ventricular rate in digitalized patients with chronic and paroxysmal AF",
"Summary This open , parallel-group , multicenter study was conducted to compare the efficacy and safety of sotalol with that of quinidine for the prevention of atrial fibrillation relapse following DC conversion 183 . DC-converted 183 patients with a 1- to 12-month history of atrial fibrillation were r and omized to sotalol or quinidine after 2 hours of sinus rhythm following the conversion and followed on treatment for 6 months . The efficacy of sotalol and quinidine for the prevention of atrial fibrillation relapse during a 6-month period following DC conversion was similar . However , sotalol was better tolerated than quinidine",
"Patients with atrial fibrillation frequently show a wide variation in heart rate with digoxin therapy . We have compared the effect on heart rate variability , of doubling the digoxin dosage or adding verapamil 120 mg daily in a r and omized cross-over study in 14 patients . Twenty-four hour ambulatory electrocardiographic recordings , six minute walking tests and palpitation and breathlessness scores were obtained on each regime . All patients exhibited a diurnal pattern in heart rate variability . Both treatments significantly lowered heart rate but high dose digoxin lowered minimum heart rate significantly more than digoxin and verapamil , causing more night time bradycardia . Overall , digoxin with verapamil produced significantly less heart rate variability than digoxin alone . Day time but not night time pauses were prolonged by digoxin and verapamil but were prolonged more by high dose digoxin . Five ( 36 % ) patients had serum digoxin levels in the toxic range when taking high dose digoxin . Palpitations were significantly reduced by both treatments but most improvement occurred with digoxin and verapamil . No significant effect was found on six minute walking distances or breathlessness scores . In conclusion , the addition of verapamil to digoxin was superior to increasing the dose of digoxin alone , producing significantly better control of heart rate variability with less night time bradycardia",
"In a single-blind r and omized study , the efficacy of intravenous flecainide ( 2 mg/kg/10 minutes ) versus verapamil ( 10 mg/1 minute ) was assessed in 40 patients with paroxysmal atrial fibrillation ( AF ) or atrial flutter ( AFI ) . The treatment was considered successful if sinus rhythm occurred within 1 hour . Of 20 patients receiving flecainide , 14 of 17 ( 82 % ) with AF converted to sinus rhythm , but in 3 patients with AFI flecainide failed . All patients treated with verapamil ( 17 AF , 3 AFI ) showed lower ventricular rates after 1 hour ; however , only 1 ( 6 % ) with AF converted to sinus rhythm and 1 ( 6 % ) converted to AFI . Patients who did not convert to sinus rhythm after treatment with verapamil were treated with flecainide and observed for another hour . After the change to flecainide , 9 of 15 patients ( 60 % ) with AF still converted . Thus , 23 of 32 patients ( 72 % ) with AF and none of 7 with AFI converted to sinus rhythm after treatment with flecainide . Conversion to sinus rhythm was achieved in 19 of 22 patients ( 86 % ) when AF lasted less than 24 hours and in 4 of 10 ( 40 % ) when the arrhythmia lasted greater than 24 hours . Transient adverse effects were noted in 10 patients ( 26 % ) after flecainide . In summary , flecainide is an effective and safe drug for conversion of paroxysmal AF to sinus rhythm , but ineffective for AFI . Verapamil appears to be of no use for conversion of AF or AFI to sinus rhythm",
"The risk for ischemic stroke in patients with atrial fibrillation is related to underlying structural heart disease [ 1 - 3 ] . Although most strokes are believed to arise from embolism of left atrial thrombi [ 4 , 5 ] , other mechanisms may contribute . Transesophageal echocardiography ( TEE ) provides a unique diagnostic window for evaluating the left atrium , left atrial appendage , and thoracic aorta , but the manner in which specific TEE findings in patients with atrial fibrillation correlate with thromboembolic risk and response to therapy has not been fully established [ 6 - 13 ] . We performed TEE in patients with nonvalvular atrial fibrillation who were at high intrinsic risk for thromboembolism and were participating in the Stroke Prevention in Atrial Fibrillation ( SPAF-III ) study , a r and omized clinical trial . In that study , adjusted-dose warfarin ( target international normalized ratio [ INR ] , 2 to 3 ) was compared with combination therapy consisting of low-intensity warfarin ( INR , 1.2 to 1.5 ) plus aspirin , 325 mg/d . The trial was stopped after an interim analysis indicated that the efficacy of adjusted-dose warfarin therapy was superior to that of combination therapy . Low anticoagulation intensity in the combination therapy group yielded high stroke rates that were similar to those expected during treatment with aspirin alone [ 14 , 15 ] . In the current analysis , we 1 ) correlate TEE observations among patients with atrial fibrillation at high risk for thromboembolism with rate of subsequent stroke and 2 ) compare treatment responses . Methods Patients Patients were recruited from the SPAF-III multicenter trial , which was design ed to compare two antithrombotic medication regimens for prevention of ischemic stroke and systemic embolism ( primary events ) . The study , whose design is described else-where in detail [ 14 ] , involved patients with nonvalvular atrial fibrillation who were stratified for risk on the basis of clinical and transthoracic echocardiographic criteria derived from previous analyses [ 15 ] . Women older than 75 years of age and patients of any age and either sex with systolic hypertension ( systolic blood pressure > 160 mm Hg ) , previous thromboembolism , or impaired left ventricular function ( M-mode echocardiographic fractional shortening of 0.25 or recent clinical congestive heart failure ) were r and omly assigned to receive adjusted-dose warfarin ( target INR , 2.0 to 3.0 ) or a combination of low-intensity warfarin ( 0.5 to 3.0 mg/d ; dose was initially adjusted to cause deviation of the INR to 1.2 to 1.5 and was then fixed ) and aspirin . Seventy-three percent of the patients were receiving warfarin at various dose intensities before trial entry ; these patients were equally distributed between assigned treatment groups . Antithrombotic treatment was assigned before performance of TEE and was not influenced by TEE findings . Patients were followed monthly by telephone and in clinic every 3 months , and a st and ard question naire on stroke symptoms was administered annually . All patients whose responses to the question naire suggested the occurrence of stroke were referred for clinical examination by a local affiliated neurologist who was blinded to treatment , and all events were adjudicated by a blinded event verification committee [ 14 ] . This project was design ed to supplement the SPAF-III clinical trial on the basis of the hypothesis that spontaneous echocardiographic contrast detected by TEE identifies patients at high risk for thromboembolism for whom adjusted-dose warfarin would prove superior to combination therapy . All participants in the parent study were encouraged , but not required , to provide separate , written informed consent for TEE after r and om assignment to antithrombotic treatment . This was done to prevent the results of TEE from influencing recruitment of patients into the trial or from altering treatment . The intended sample size of 412 TEE examinations was selected to detect an absolute difference in event rates of 3.9 % per year ( based on projected event rates of 5.4 % per year in patients with spontaneous echocardiographic contrast and 1.5 % per year in patients without contrast ) over a mean observation period of 2.5 years . Secondary objectives were to correlate clinical thromboembolic events with function of the left atrial appendage , thrombus of the left atrium and left atrial appendage , and atherosclerotic lesions in the thoracic aorta imaged by TEE . Transesophageal Echocardiography Transesophageal echocardiography was performed within 3 months of enrollment with patients under light sedation and topical anesthesia , according to specific protocol s for acquisition and interpretation [ 16 ] . Commercially available ultrasonography equipment incorporated biplane or multiplane transducers with at least 48 crystals operating at a st and ard frequency of 5 MHz with gray-scale imaging . Signal processing , log compression , and persistence values were established for each manufacturer . Images were interpreted locally , and data were entered into st and ardized forms by echocardiographers who were blinded to antithrombotic treatment assignment but not to patient demographic or clinical features . Original videotaped recordings were collected in a central echocardiographic registry for validation and quality control . To assure generalizability of the results to laboratories used in clinical practice , the analyses reported here are based on image interpretation at the local laboratories . The following features were specifically assessed : left atrial appendage size , peak ante grade ( emptying ) velocity of blood flow in the left atrial appendage , spontaneous echocardiographic contrast in the left atrium or left atrial appendage , thrombus of the left atrium or left atrial appendage , and atherosclerotic disease of the thoracic aorta . Spontaneous echocardiographic contrast was defined as a pattern of slowly swirling intracavitary echodensities imaged with gain setting s adjusted to distinguish background noise . Contrast was classified as faint when visualized intermittently during the cardiac cycle or when enhanced gain setting s were required for detection and was classified as dense when continuously present at st and ard gain . Aortic plaque was classified by location and as either simple or complex according to mobility , ulceration , pedunculation , or thickness greater than 4 mm [ 16 ] . We postulated that reduced emptying velocity from the left atrial appendage , which reflects stasis , would be associated with dense spontaneous echocardiographic contrast and thrombus formation , whereas complex aortic plaque would be a consequence of atherosclerotic vascular abnormality . We also postulated that these findings would predispose patients to ischemic stroke through separate pathogenic mechanisms . Statistical Analysis The analyses reported here were limited to variables accessible only by TEE and were hypothesized a priori to have potential predictive relations to clinical thromboembolism . Baseline comparisons between groups were done by using the chi-square test for categorical data and the Student t-test for continuous variables . The Cox proportional-hazards regression model was used to estimate the univariate relative risk associated with TEE characteristics . The primary analysis compared rates of cerebral ischemic events and systemic embolism among patients who had dense spontaneous echocardiographic contrast detected in the left atrium or left atrial appendage with rates in patients who did not have dense contrast ; the log-rank statistic was used to compare the times to events between these groups . Secondary analyses , conducted similarly , compared event rates in groups that were identified by left atrial appendage size , flow velocity , thrombus , and aortic plaque . For these comparisons , the area of the left atrial appendage was dichotomized at the upper quartile ; flow velocity was dichotomized at the lower quartile . When interaction was seen between treatment and TEE characteristics , analysis of the relation of TEE findings to events was confined to the combination therapy group and treatment effect was described separately ; when no interaction was seen , the analysis was stratified by therapy . The relative reduction in event rate associated with adjusted-dose warfarin therapy was computed as the difference between unity and the rate ratio determined by a Poisson regression model [ 17 ] . A Cox proportional-hazards regression model was fit to confirm the independence of TEE characteristics identified as univariate thromboembolic risk factors . Confidence intervals for event rates were calculated by using a Poisson regression model ; tests of significance were two-sided and were not adjusted for multiple comparisons . All analyses were done according to the intention-to-treat principle . Results Of 1044 high-risk patients with atrial fibrillation enrolled in the r and omized trial , 382 ( 37 % ) volunteered for TEE ( range , 10 % to 80 % of SPAF-III participants recruited at 18 clinical centers offering TEE ) . Salient features of these 382 patients were similar to those of the 662 participants who did not undergo transesophageal imaging ( Table 1 ) . The mean patient age was 71 years , 36 % of patients had clinical ischemic heart disease , and almost half had a history of congestive heart failure . Balanced proportions of patients were assigned to therapy with adjusted-dose warfarin ( n = 190 ) or fixed-dose warfarin and aspirin ( n = 192 ) . Time from r and om assignment of treatment to TEE was similar in the two groups ( mean , 23 days ) . The trial was stopped after a mean observation period of 1.1 years because an interim analysis indicated the lack of efficacy of the combination regimen [ 18 ] . Up to that point , 23 primary events ( all of which were ischemic strokes ) occurred in the subset of participants who had undergone TEE ( event rate , 3.1 % per year in patients assigned to adjusted-dose warfarin compared with 7.8 % per year in those assigned to combination therapy ; P = 0.04 ) .",
"BACKGROUND AND PURPOSE The results of a large prospect i ve r and omized trial have shown the efficacy of oral anticoagulation in the secondary prevention of major vascular events in patients with nonrheumatic atrial fibrillation ( NRAF ) ; less well established is the role of antiplatelet agents . The present study compared the effects of indobufen , a reversible inhibitor of platelet cyclooxygenase , with those of warfarin in this setting . METHODS A total of 916 patients with NRAF and a recent ( , during which they were treated with either indobufen ( 100 or 200 mg BID ) or warfarin ( to obtain an international normalized ratio of 2.0 to 3.5 ) for 12 months . The two groups ( 462 on indobufen and 454 on warfarin ) were well balanced in terms of their main baseline characteristics . The primary outcome of the study was the combined incidence of nonfatal stroke ( including intracerebral bleeding ) , pulmonary or systemic embolism , nonfatal myocardial infa rct ion , and vascular death . RESULTS At the end of follow-up , the incidence of primary outcome events was 10.6 % in the indobufen group ( 95 % confidence interval , 7.7 % to 13.5 % ) and 9.0 % in the warfarin group ( 95 % confidence interval , 6.3 % to 11.8 % ) , with no statistically significant difference between treatments . The frequency of noncerebral major bleeding complications was low : only four cases ( 0.9 % ) of gastrointestinal bleeding were observed , all of them in the warfarin group . CONCLUSIONS We conclude that , within the limitations of its design , this study may help the medical community in devising appropriate antithrombotic strategies for NRAF patients for whom oral anticoagulants are contraindicated or do not represent a feasible approach to treatment",
"One hundred patients were subjected to a controlled study of the effectiveness of quinidine treatment upon the maintenance of sinus rhythm after electroconversion . The quinidine series was treated with a long-acting preparation of quinidine sulphate , which was given in a dosage to achieve serum levels between 4 and 6 mg/l . The control series received no quinidine . The maintenance rate did not differ significantly in the two series during the first three months , but for the remaining observation time until I2 months a sigmficant difference in favour of quinidine was present . Identical results were found in a cross-over experiment , in which 24 patients served as their own controls . Further analysis broughtforward that quinidine was effective only if the atrial fibrillation had lasted for less than one year before electroconversion . Complications due to",
"STUDY OBJECTIVES To investigate the efficacy and safety of amiodarone administered as the drug of first choice in the conversion of atrial fibrillation , regardless of its duration . DESIGN : Prospect i ve , r and omized , controlled clinical study . SETTING : Tertiary cardiac referral center . PATIENTS Two-hundred eight consecutive patients ( 102 men ; mean [ + /- SD ] age , 65 + /- 10 years ) with atrial fibrillation . INTERVENTIONS One-hundred eight patients received amiodarone , and 100 patients received placebo treatment . Patients r and omized to amiodarone received 300 mg IV for 1 h , and then 20 mg/kg for 24 h. They were also given 600 mg/d orally , divided into three doses , for 1 week , and thereafter 400 mg/d for 3 weeks . Patients r and omized to placebo treatment received an identical amount of saline solution IV over 24 h , and oral placebo treatment for 1 month . MEASUREMENTS AND RESULTS Baseline clinical characteristics were similar in the two groups . Conversion to sinus rhythm was achieved in 87 of 108 patients ( 80.05 % ) who received amiodarone , and in 40 of 100 patients ( 40 % ) in the placebo group ( p duration of the arrhythmia and the size of the left atrium affected both the likelihood of conversion to sinus rhythm and the time to conversion in both groups . No side effects requiring discontinuation of treatment were observed in either group . CONCLUSIONS Amiodarone appears to be safe and effective in the termination of atrial fibrillation . However , extreme cases with a large left atrium and long-lasting arrhythmia need long-term therapy",
"Ninety-two patients were entered in a double-blind controlled trial of long-acting quinidine bisulphate for the maintenance of sinus rhythm following DC reversion of atrial fibrillation . By r and om selection two statistically comparable groups of patients were obtained , a control group being given a placebo and a treated group quinidine bisulphate 1.5 g. per day in two 12-hourly doses . Thirty-seven patients were followed up in the control group and twenty-eight patients in the treated group . The maintenance of sinus rhythm in the treated group was significantly longer than in the control group , especially during the first three months . The mean serum quinidine level in the treated group was 2.2+/-0.3 ( SEM ) mg . per litre . There was one death among the patients treated with quinidine , which may have been due to quinidine toxicity caused by a high serum quinidine level",
"In 39 patients undergoing electrical cardioversion for atrial fibrillation ( AF ) , we examined the effect of total electrical energy used for cardioversion on postcardioversion peak left atrial ( LA ) rapid filling velocity ( A ) and the atrial emptying fraction , and recovery of LA effective mechanical atrial function ( defined as peak A velocity > or = 0.50 m/s ) , as assessed by transthoracic echocardiography . In a subset of 27 patients who underwent pre- and postcardioversion transesophageal echocardiography , we assessed the relation between total electrical energy and LA appendage filling and emptying velocities and spontaneous echo contrast . Patients were r and omized to receive an initial shock of 1.5 J/kg based on body weight , or 2.5 , 3.5 , 5 J/kg , or 360 J , followed sequentially by higher shock intensities until sinus rhythm was achieved . Patients were classified into 4 groups based on quartiles of total energy delivered for cardioversion . Conversion to sinus rhythm was associated with a significant decrease in the LA appendage filling velocities ( 0.42 + /- 0.20 m/s vs 0.29 + /- 0.14 m/s ; p = 0.002 ) and LA appendage emptying velocities ( 0.40 + /- 0.22 m/s vs 0.29 + /- 0.18 m/s ; p = 0.03 ) , but no change in the incidence of spontaneous echo contrast ( 61 % vs 70 % , p = 0.08 ) . The 4 groups of patients did not differ with respect to postcardioversion LA appendage filling velocities , LA appendage emptying velocities , incidence of spontaneous echo contrast , or worsening of spontaneous echo contrast . Similarly , the change in LA appendage filling and emptying velocities associated with cardioversion was not different between the groups . Furthermore , postcardioversion peak A velocity and atrial emptying fraction and recovery of effective mechanical atrial function were similar between the 4 groups . These results suggest that in patients undergoing electrical cardioversion for AF , the total electrical energy used for cardioversion has no effect on the mechanical function of the left atrium or LA appendage following cardioversion",
"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",
"OBJECTIVE To investigate whether an oral loading dose of flecainide is as safe and effective as intravenous flecainide for the cardioversion of acute atrial fibrillation . DESIGN Prospect i ve , r and omised , double blind , double placebo study . SETTING Cardiac care unit of a large district general hospital in the UK . PATIENTS AND METHODS 79 patients presenting with symptomatic acute atrial fibrillation : patients were given either intravenous flecainide ( n = 39 ) or a solution of oral flecainide ( n = 40 ) , with appropriate placebos . All patients were heparinised during the study . PRIMARY OUTCOME MEASURES Safety ; mean time to cardioversion ; proportion of patients restored to sinus rhythm at two hours and eight hours after treatment . Analysis was by intention to treat . RESULTS There were no differences in baseline characteristics between the oral and intravenous groups . Both forms of flecainide were well tolerated , with no adverse clinical events during the study . The mean time to cardioversion was 110 minutes in the oral group and 52 minutes in the intravenous group ( p = 0.002 ) . Two hours after treatment , 27 of the 40 patients in the oral group ( 68 % ) and 25 of the 39 in the intravenous group ( 64 % ) had reverted to sinus rhythm ( p = 0.74 ) . Eight hours after treatment , 30 patients in the oral group ( 75 % ) and 28 in the intravenous group ( 72 % ) had reverted to sinus rhythm ( p = 0.76 ) . CONCLUSIONS Intravenous flecainide restored sinus rhythm more rapidly than oral flecainide , but at two hours and eight hours after treatment there was no difference in the proportion of patients cardioverted by the two approaches . These results suggest a role for oral loading doses of flecainide in the treatment of acute or symptomatic paroxysmal atrial fibrillation",
"AIMS This study compared the efficacy and safety of intravenous dofetilide with amiodarone and placebo in converting atrial fibrillation or flutter to sinus rhythm . METHODS AND RESULTS One hundred and fifty patients with atrial fibrillation or flutter ( duration range 2 h-6 months ) were given 15-min intravenous infusions of 8 microg . kg(-1)of dofetilide ( n=48 ) , 5 mg . kg(-1)of amiodarone ( n=50 ) , or placebo ( n=52 ) and monitored continuously for 3 h. Sinus rhythm was restored in 35 % , 4 % , and 4 % of patients , respectively ( P dofetilide vs placebo;P = ns , amiodarone versus placebo ) . Dofetilide was more effective in atrial flutter than in atrial fibrillation ( cardioversion rates 75 % and 22 % , respectively;P=0.004 ) . The mean time to conversion with dofetilide was 55+/-15 min . Dofetilide prolonged the QTc interval ( + 16 % at 20 min ) . Amiodarone substantially decreased the ventricular rate in non-converters ( -18 beats . min(-1)at 30 min ) . Two patients given dofetilide ( 4 % ) had non-sustained ventricular tachycardias , and four ( 8 % ) had torsade de pointes , in one case requiring electrical cardioversion . CONCLUSION Intravenous dofetilide is significantly more effective than amiodarone or placebo in restoring sinus rhythm in patients with atrial fibrillation or flutter . However , when infused intravenously at this dose and rate , dofetilide causes a significant incidence of torsade de pointes",
"BACKGROUND Clinical studies have shown that biphasic shocks are more effective than monophasic shocks for ventricular defibrillation . The purpose of this study was to compare the efficacy of a rectilinear biphasic waveform with a st and ard damped sine wave monophasic waveform for the transthoracic cardioversion of atrial fibrillation . METHODS AND RESULTS In this prospect i ve , r and omized , multicenter trial , patients undergoing transthoracic cardioversion of atrial fibrillation were r and omized to receive either damped sine wave monophasic or rectilinear biphasic shocks . Patients r and omized to the monophasic protocol ( n=77 ) received sequential shocks of 100 , 200 , 300 , and 360 J. Patients r and omized to the biphasic protocol ( n=88 ) received sequential shocks of 70 , 120 , 150 , and 170 J. First-shock efficacy with the 70-J biphasic waveform ( 60 of 88 patients , 68 % ) was significantly greater than that with the 100-J monophasic waveform ( 16 of 77 patients , 21 % , P cumulative efficacy with the biphasic waveform ( 83 of 88 patients , 94 % ) was significantly greater than that with the monophasic waveform ( 61 of 77 patients , 79 % ; P=0.005 ) . The following 3 variables were independently associated with successful cardioversion : use of a biphasic waveform ( relative risk , 4.2 ; 95 % confidence intervals , 1.3 to 13.9 ; P=0.02 ) , transthoracic impedance ( relative risk , 0.64 per 10-Omega increase in impedance ; 95 % confidence intervals , 0.46 to 0.90 ; P=0.005 ) , and duration of atrial fibrillation ( relative risk , 0.97 per 30 days of atrial fibrillation ; 95 % confidence intervals , 0.96 to 0.99 ; P=0.02 ) . CONCLUSIONS For transthoracic cardioversion of atrial fibrillation , rectilinear biphasic shocks have greater efficacy ( and require less energy ) than damped sine wave monophasic shocks",
"UNLABELLED This r and omized study compared the efficacy and safety of amiodarone , propafenone and sotalol in the prevention of atrial fibrillation . METHODS The population consisted of 214 consecutive patients ( mean age 64 + /- 8 years , 106 men ) with recurrent symptomatic atrial fibrillation . After restoration of sinus rhythm , patients were r and omized to amiodarone ( 200 mg/day ) , propafenone ( 450 mg/day ) or sotalol ( 320 + /- 20 mg/day ) . Follow-up evaluations were conducted at 1 , 2 , 4 and 6 months , and at 3-month intervals thereafter . The proportion of patients developing recurrent atrial fibrillation and /or experiencing unacceptable adverse effects was measured in the three groups by the Kaplan-Meier method . RESULTS Recurrent atrial fibrillation occurred in 25 of the 75 patients treated with amiodarone compared to 51 of the 75 patients treated with sotalol and 24 of the 64 patients treated with propafenone . Fourteen patients treated with amiodarone , five with sotalol , and one with propafenone experienced adverse effects while in sinus rhythm , necessitating discontinuation of treatment ( P amiodarone and propafenone vs sotalol ) . The difference between amiodarone and propafenone was statistically nonsignificant when all events were included in the analysis . However , if the analysis was limited to recurrent atrial fibrillation events , amiodarone was more effective than propafenone ( P Amiodarone and propafenone were superior to sotalol in maintaining long-term normal sinus rhythm in patients with atrial fibrillation . Amiodarone tended to be superior to propafenone , though its long-term efficacy was limited by adverse side effects",
"The safety and efficacy of oral verapamil to control exercise tachycardia in 27 patients with atrial fibrillation and 3 with atrial flutter receiving digitalis was evaluated in a double-blind , r and omized , crossover study . The heart rate in patients who received verapamil compared with placebo group was lower at rest ( mean 69 + /- 13 versus 87 + /- 20 beats/min , p less than 0.01 ) , as was the degree of tachycardia at the end of 3 minutes of a st and ardized exercise test ( 104 + /- 14 versus 136 + /- 23 beats/min , p less than 0.01 ) . Doses of verapamil required to achieve suppression of tachycardia were 240 mg/day in 18 patients , 320 mg/day in 6 patients , and 480 mg/day in 3 patients . Only 3 patients complained of adverse effects from verapamil during the double-blind phase of the study . Two patients were discontinued from the study because of adverse reactions . No clinical ly significant changes during verapamil therapy were observed on the electrocardiogram , chest roentgenogram , echocardiogram or in the laboratory evaluation . Digoxin blood levels were higher in patients who received concomitant verapamil compared with placebo ( 1.23 + /- 0.59 versus 0.85 + /- 0.46 ng/ml , p less than 0.01 ) , but no patient had signs or symptoms of digitalis toxicity . Thus , oral verapamil given in addition to digitalis is a safe and effective agent in the treatment of patients with chronic atrial fibrillation or flutter to decrease exercise-induced tachycardia",
"BACKGROUND Few antiarrhythmic agents have been shown in r and omized controlled trials to be effective and well tolerated in the prophylaxis of paroxysmal supraventricular tachycardia or paroxysmal atrial fibrillation . Propafenone , a class IC anti-arrhythmic agent with weak beta-adrenoceptor antagonist properties , has shown promise in preliminary clinical studies . METHODS AND RESULTS A double-blind , placebo-controlled trial of the efficacy and tolerability of propafenone was undertaken in 100 patients with paroxysmal supraventricular tachycardia ( [ PSVT ] n = 52 ) or atrial fibrillation/flutter ( [ PAF ] n = 48 ) who had recorded two or more symptomatic arrhythmia recurrences by transtelephonic ECG monitoring during a 3-month drug-free observation period . Patients were r and omized into two consecutive crossover periods of propafenone ( 300 mg BID ) versus placebo followed by 300 mg TID propafenone versus placebo . Analysis was based on the time to treatment failure , defined as the interval from treatment onset to the occurrence of either ECG-documented arrhythmia or an intolerable adverse event . With a proportional-hazards model , we determined the relative risk ( 95 % confidence interval ) of treatment failure after the achievement of steady-state drug levels for placebo compared with propafenone 300 mg BID to be 6.8 ( 2.2 to 21.2 , P placebo rather than propafenone 300 TID were only 2.2 ( 0.9 to 5.3 , P = .1 , n = 34 ) for PSVT and 1.9 ( 0.7 to 4.7 , P = .2 , n = 25 ) for PAF . However , if adverse events were excluded in the high-dose comparison , relative risks for arrhythmia recurrence were 15.0 ( 2.0 to 113 , P = .009 ) for PSVT and incalculable ( no preferences for placebo , P = .0002 ) for PAF . One episode of wide-complex tachycardia was documented during propafenone therapy . CONCLUSIONS Propafenone is of value in the prophylaxis of both PSVT and PAF . A dose of 300 mg BID is effective and well tolerated . A larger dose of 300 mg TID causes more adverse effects but may be more effective in those who can tolerate it",
"BACKGROUND Despite the efficacy of warfarin sodium therapy for stroke prevention in atrial fibrillation , many physicians hesitate to prescribe it to elderly patients because of the risk for bleeding complications and because of inconvenience for the patients . METHODS The Second Copenhagen Atrial Fibrillation , Aspirin , and Anticoagulation Study was a r and omized , controlled trial examining the following therapies : warfarin sodium , 1.25 mg/d ; warfarin sodium , 1.25 mg/d , plus aspirin , 300 mg/d ; and aspirin , 300 mg/d . These were compared with adjusted-dose warfarin therapy ( international normalized ratio of prothrombin time [ INR ] , 2.0 - 3.0 ) . Stroke or a systemic thromboembolic event was the primary outcome event . Transient ischemic attack , acute myocardial infa rct ion , and death were secondary events . Data were h and led as survival data , and risk factors were identified using the Cox proportional hazards model . The trial was scheduled for 6 years from May 1 , 1993 , but due to scientific evidence of inefficiency of low-intensity warfarin plus aspirin therapy from another study , our trial was prematurely terminated on October 2 , 1996 . RESULTS We included 677 patients ( median age , 74 years ) . The cumulative primary event rate after 1 year was 5.8 % in patients receiving minidose warfarin ; 7.2 % , warfarin plus aspirin ; 3.6 % , aspirin ; and 2.8 % , adjusted-dose warfarin ( P = .67 ) . After 3 years , no difference among the groups was seen . Major bleeding events were rare . CONCLUSIONS Although the difference was insignificant , adjusted-dose warfarin seemed superior to minidose warfarin and to warfarin plus aspirin after 1 year of treatment . The results do not justify a change in the current recommendation of adjusted-dose warfarin ( INR , 2.0 - 3.0 ) for stroke prevention in atrial fibrillation",
"Six patients with chronic atrial fibrillation ( AF ) took single doses of digoxin , verapamil and diltiazem , alone and in combination . Three hours after dosing , resting and post-exercise heart rate , exercise tolerance and resting and post-exercise cardiac output were measured . Post-exercise heart rates ranged from 167 bpm ( after placebo ) to 122 bpm ( after digoxin plus diltiazem ) ( P less than 0.05 ) . However , the lower ventricular rates seen after treatment with the calcium antagonists were not associated with improved exercise tolerance , which did not differ significantly between the various treatments . Reduction of the ventricular rate was associated with a small increase in stroke volume but the benefits of this were offset by a rate related reduction in cardiac output . Further reduction of the rapid ventricular rates seen in digitalized patients with AF does not appear to be of benefit in terms of improving either exercise tolerance or cardiac output",
"OBJECTIVES This study was design ed to determine the efficacy of intravenous amiodarone in the management of recent-onset atrial fibrillation . BACKGROUND The optimal approach for acute atrial fibrillation has not been established . Amiodarone is a unique antiarrhythmic agent with activity in both supraventricular and ventricular tachyarrhythmias , but its value for the restoration of sinus rhythm in patients with recent-onset atrial fibrillation has not been demonstrated . METHODS Sample size was calculated to detect a 25 % increase in reversion rate with amiodarone with a statistical power of 80 % . One hundred consecutive patients with recent-onset ( to receive either intravenous amiodarone , 5 mg/kg body weight in 30 min followed by 1,200 mg over 24 h , or an identical amount of saline . Both groups received intravenous digoxin , 0.5 mg initially , followed by 0.25 mg at 2 h and 0.25 mg every 6 h thereafter , to complete 24 h while the ventricular rate was > 100 beats/min . Amiodarone and digoxin blood levels were determined . Both groups were homogeneous regarding underlying heart disease , time from onset to treatment , initial ventricular rate and left atrial size . RESULTS By the end of the 24-h treatment period , 34 patients ( 68 % , 95 % confidence interval [ CI ] 53 % to 80 % ) in the amiodarone group and 30 ( 60 % , 95 % CI 45 % to 74 % ) in the control group had returned to sinus rhythm ( p = 0.532 ) . Mean times ( + /-SD ) of conversion were 328 + /- 335 and 332 + /- 359 min , respectively ( p = 0.957 ) . Among patients who did not convert to sinus rhythm , treatment with amiodarone was associated with a slower ventricular rate ( 82 + /- 15 beats/min in the amiodarone group vs. 91 + /- 23 beats/min in the control group , p = 0.022 ) . After restoration of sinus rhythm , atrial fibrillation recurred during a 15-day follow-up period in 4 ( 12 % ) of 34 patients ( 95 % CI 3 % to 27 % ) in the amiodarone group and in 3 ( 10 % ) of 30 ( 95 % CI 2 % to 26 % ) in the control group ( p = 0.861 ) . CONCLUSIONS Intravenous amiodarone , at the doses used in this study , produces a modest but not significant benefit in converting acute atrial fibrillation to sinus rhythm",
"STUDY OBJECTIVES The objectives of this study were to assess the efficacy of parenteral magnesium sulfate ( MgSO4 ) , digoxin , and combined MgSO4-digoxin therapies in acutely lowering ventricular rates in patients with newly recognized atrial fibrillation . DESIGN A r and omized , double-blinded , placebo-controlled clinical study . SETTING US Army tertiary care facility . PARTICIPANTS Fifteen adults ( mean age , 62 + /- 19 years ) presenting with newly recognized atrial fibrillation and rapid ventricular rate ( more than 99 ) . INTERVENTIONS Patients were given an initial parenteral MgSO4 bolus with continuous infusion or placebo . After 30 minutes , all patients were given 0.5 mg IV digoxin and followed for 3.5 hours . MEASUREMENTS AND MAIN RESULTS Ventricular rates were obtained at baseline , every 5 minutes for the first 30 minutes , and then every 30 minutes for 3.5 hours . At 5 minutes , ventricular rates decreased 16 + /- 7 % ( P ; this was comparable with rate control with digoxin ( 18 + /- 9 % ) at 4 hours . Rate control tended ( 26 + /- 7 % ) to improve with combined therapy . CONCLUSION Parenteral MgSO4 may be useful in the acute management of rapid ventricular rates in patients with atrial fibrillation",
"BACKGROUND Atrial fibrillation ( AF ) is associated with impaired exercise capacity . Oxygen uptake ( VO2 ) kinetics determines cardiopulmonary performance during submaximal exercise , which may be impaired in patients with AF . AIM To study oxygen kinetics and cardiopulmonary performance in patients with AF without structural heart disease and the effects of oral sotalol on these parameters . PATIENTS AND METHODS Twenty consecutive patients ( mean age , 56+/-8 years ) with chronic AF were recruited . The protocol design was a r and omized , single-blinded , and placebo-controlled trial . Patients received either sotalol or placebo for an 8-week study period , and the alternative treatment in the subsequent period . Cardiopulmonary function tests using constant workload and incremental workload protocol s were performed at the end of each phase . Sixteen age-matched normal subjects were included as control subjects . RESULTS During constant submaximal exercise , patients with AF had a larger oxygen deficit ( 425+/-140 mL vs 289+/-80 mL in normal subjects ; p time for achieving 63 % of VO2 ( mean response time ) was also delayed ( 46+/-15 s vs 33+/-10 s ; p patients with chronic AF had a higher maximal exercise heart rate ( 180+/-34 beats/min vs 153+/-22 beats/min ; p maximal VO2 ( 20+/-4 mL/kg/min vs 26+/-6 mL/kg/min ; p resting ( 72+/-15 beats/min vs 93+/-22 beats/min ; p exercise heart rate compared with placebo ( 125+/-27 beats/min vs 180+/-34 beats/min ; p normalized oxygen pulse and the heart rate to minute ventilation ratio during maximal exercise . There was no significant difference between those receiving sotalol and those receiving placebo in oxygen deficit ( 502+/-150 mL vs 425+/-140 mL ; p=0.38 ) , maximal VO2 ( 17.2+/-4.9 mL/kg/min vs 20.4+/-4.7 mL/kg/min ; p=0.17 ) , and other gas exchange variables . In patients with AF , oxygen deficit has a fair correlation with VO2 at the anaerobic threshold ( r2=0.43 ; p , patients with chronic AF without significant structural heart disease had impaired submaximal exercise performance as assessed by VO2 kinetics . These parameters were not significantly affected by sotalol used for rate control",
"Efficacy and safety of intravenous flecainide ( 2 mg/kg body weight in 10 minutes ) , verapamil ( 10 mg in 1 minute ) , and propafenone ( 2 mg/kg body weight in 10 minutes ) were investigated in 90 consecutive patients with atrial fibrillation ( AF ) or flutter ( AFL ) . In the first 40 patients , flecainide and verapamil were evaluated ; in the second 50 patients , flecainide and propafenone were compared , both in a single-blind r and omized study design . The primary end point was sinus rhythm occurring within 1 hour after start of infusion . Sinus rhythm was attained in 32 of 37 patients ( 86 % ) with AF treated with flecainide and in 11 of 20 patients ( 55 % ) with AF treated with propafenone . In recent onset AF ( less than or equal to 24 hours ) conversion rates were 24 of 25 patients ( 96 % ) in the flecainide group and 8 of 14 patients ( 57 % ) in the propafenone group ( p less than 0.05 ) . Conversion of AFL occurred in only 1 of 8 patients ( 13 % ) in the flecainide-treated patients and in 2 of 5 patients ( 40 % ) treated with propafenone ( difference not significant ) . Verapamil was almost ineffective , since only 1 of 20 patients ( 5 % ) responded within 1 hour . Time to conversion was 21 + /- 17 minutes in the flecainide group and 16 + /- 10 minutes in the propafenone group . QRS widening occurred in flecainide-treated patients ( 83 + /- 15 to 99 + /- 20 msec ; p less than 0.001 ) , but not after propafenone ( 83 + /- 11 to 86 + /- 12 msec ) . Significantly higher plasma levels were found in patients with conversion within 1 hour using propafenone . ( ABSTRACT TRUNCATED AT 250 WORDS",
"UNLABELLED The aim of the study was to investigate the efficacy of diltiazem bolus intravenous administration , compared to disopyramide , in the treatment of various types of paroxysmal supraventricular tachyarrhythmias . METHOD Fifty patients ( 23 males , 27 females , mean age 47.7 + /- 15.2 years ) with paroxysmal supraventricular tachyarrhythmia ( 20 with paroxysmal atrial tachycardia , 23 with paroxysmal atrial fibrillation and rapid ventricular response and 7 with atrial fluttering ) were studied . Diltiazem at a dose of 0.25 - 0.30 mg/kg BW or disopyramide at a dose of 50 mg were given bolus IV . If conversion of the arrhythmia to sinus rhythm could not be achieved with the initial drug , the alternate was given . The order of administration of the drugs was r and om , independent of the type of the arrhythmia . Before and during drug administration detailed clinical examination and frequent blood pressure ( BP ) measurements were performed . Twenty-four hour Holter monitoring was done in all patients , starting with the administration of the antiarrhythmic drug . RESULTS 1 ) Paroxysmal atrial tachycardia : diltiazem administration converted the arrhythmia to sinus rhythm in all patients while disopyramide in only 1 of 9 patients who received this drug . 2 ) Paroxysmal atrial fibrillation : disopyramide converted the arrhythmia in 5 patients without significant change in ventricular response in the others . Diltiazem did not convert the arrhythmia though it caused significant decrease in ventricular response ( bradycardia ( 45 bpm ) . 3 ) Atrial fluttering : disopyramide converted the arrhythmia to sinus rhythm in 1 patient without significant change in the ventricular response in the others . Diltiazem caused significant decrease in the ventricular response without conversion to sinus rhythm . During conversion to sinus rhythm an AV junctional rhythm of short duration ( premature contraction in the remaining 21 . Disopyramide administration was not associated with side effects . Diltiazem administration cause small ( decrease of BP without symptoms with the exception of the patient with bradycardia in whom the BP decrease was significant ( 90/60 from 160/80 mm Hg ) followed by intense symptoms which lasted for six hours . CONCLUSIONS Diltiazem administration is extremely effective in conversion of paroxysmal atrial tachycardia to sinus rhythm . In addition it retards ventricular response in patients with atrial fibrillation and fluttering . Compared to disopyramide these effects of diltiazem are more pronounced and clinical ly pertinent",
"A 24 h intravenous dosing regimen of amiodarone was design ed to reach a peak plasma concentration at 1 h and to maintain the concentration above a certain level during the infusion period . A r and omized , open-label , digoxin-controlled study was undertaken to observe the efficacy and safety of the dosing regimen of amiodarone in treating recent-onset , persistent , atrial fibrillation and flutter with ventricular rates above 130 beats.min-1 . Fifty patients with a mean age of 70 + /- 7 ( SD ) years were enrolled and r and omly assigned to receive either amiodarone intravenously ( n = 26 ) or digoxin ( n = 24 ) . Amiodarone HCl was infused over 24 h according to the following regimen : 5 mg.min-1 , 3 mg.min-1 , 1 mg.min-1 and 0.5 mg.min-1 for 1 , 3 , 6 and 14 h , respectively , for a 70-kg subject . Digoxin ( 0.013 mg.kg-1 ) was infused in three divided doses , each dose 2 h apart and infused over 30 min . The mean heart rates in the amiodarone group decreased significantly from 157 + /- 20 beats.min-1 to 122 + /- 25 beats.min-1 after 1 h ( P digoxin group had fewer dramatic alterations in heart rates , compared to the amiodarone group , in the first 8 h ( P amiodarone infusion was prematurely aborted in two patients due to severe bradycardia and death after conversion in one patient and aggravation of heart failure in the other . ( ABSTRACT TRUNCATED AT 250 WORDS",
"STUDY OBJECTIVE to determine whether digoxin is effective in converting atrial fibrillation of recent onset to normal sinus rhythm . DESIGN r and omized , double-blinded , placebo-controlled trial with a maximum 18-hour treatment period . SETTING emergency room and medical floors of a non-referral city hospital . PATIENTS consecutive sample of 36 patients with atrial fibrillation of 7 days ' duration or less , not on digitalis glycoside or anti-arrhythmic agents , with ventricular rate between 85 to 175 beats/min , without evidence of heart failure , acute myocardial infa rct ion , unstable angina , preexcitation syndrome , thyrotoxicosis , hypokalemia , renal impairment , or severe metabolic disturbances . INTERVENTIONS digoxin solution in capsules or identical placebo , given in doses of 0.6 , 0.4 , 0.2 , and 0.2 mg , at 0 , 4 , 8 , and 14 hours , respectively , or until conversion to sinus rhythm , whichever occurred first . Continuous electrocardiographic recording by Holter monitor . MEASUREMENTS AND MAIN RESULTS nine of eighteen patients receiving digoxin and 8 of 18 receiving placebo had a return to sinus rhythm within 18 hours of study entry ( 95 % confidence interval for the difference in proportions , -11 % to 22 % ) . Mean time to conversion was 5.1 hours in the digoxin group and 3.3 in the placebo group ( 95 % Cl , -3.6 to 7.0 hours ) . CONCLUSIONS spontaneous reversion to sinus rhythm is common in patients with atrial fibrillation of recent onset . Digitalization was not shown to affect the likelihood of reversion to sinus rhythm , and thus can not be recommended for this purpose in patients with atrial fibrillation",
"BACKGROUND This study was design ed to assess the efficacy and safety of intravenous dofetilide in acute termination of atrial fibrillation ( AF ) and flutter ( AFL ) . Dofetilide , an investigational class III antiarrhythmic agent , selectively inhibits the rapid component of the delayed rectifier potassium current , thus prolonging the effective refractory period and duration of the action potential . Dofetilide can be administered intravenously and has a rapid onset of electrophysiologic action . METHODS AND RESULTS Ninety-six patients with AF ( n = 79 ) or AFL ( n = 17 ) with a median arrhythmia duration of 62 days ( range 1 to 180 ) were r and omized to placebo ( n = 30 ) or 8 micrograms/kg IV dofetilide ( n = 66 ) over 30 minutes . Conversion was defined as termination of the atrial arrhythmia within 3 hours from the start of infusion . The conversion rate was 30.3 % after dofetilide and 3.3 % after placebo ( P Conversion rate was higher in AFL than in AF : 64 % versus 24 % ( P = . 012 ) . In nonconverters , there was no statistically significant difference between the change in heart rate among the dofetilide-treated compared with the placebo-treated patients ( P = . 42 ) . Torsade de pointes ventricular tachycardia developed in 2 patients ( 3 % ) . In both patients , drug infusion was discontinued before the event because of prolongation of the QT interval . CONCLUSIONS Intravenous dofetilide is effective in acute termination of AF and AFL of medium duration , with a particularly high efficacy rate in AFL . A small but serious risk of proarrhythmia must be anticipated",
"To compare the safety and efficacy of amiodarone and sotalol in the treatment of patients with recurrent symptomatic atrial fibrillation ( AF ) , 70 patients were entered into a r and omized , double-blind study . Of these , 35 received amiodarone and 35 sotalol . There were no significant differences in baseline clinical characteristics between groups . Patients with ejection fraction Patients r and omized to amiodarone began with 800 to 1,600 mg/day for 7 to 14 days orally . After the initial loading phase , the drug dose was tapered to maintenance levels over 7 to 12 days ; thereafter , therapy was generally maintained at a dosage of 200 mg/day . The sotalol dosage was 80 to 360 mg twice daily , as tolerated . Follow-up clinical evaluations were conducted at 1 , 2 , 4 , 6 , 9 , and 12 months . The proportion of patients remaining in sinus rhythm on each agent was calculated for the 2 groups using the Kaplan-Meier method . Ten of the 35 patients who were taking amiodarone developed AF during the 12-month observation period , compared with 21 of the 35 who were taking sotalol ( p = 0.008 ) . No significant effect of sex , age , left atrial size , or type of AF could be detected that increased the risk of development of AF . We conclude that both amiodarone and sotalol can be used for the maintenance of normal sinus rhythm in patients with recurrent symptomatic AF but that amiodarone is the more effective of the 2 drugs for this purpose",
"OBJECTIVES This study compared a biphasic waveform with a conventional monophasic waveform for cardioversion of atrial fibrillation ( AF ) . BACKGROUND Biphasic shock waveforms have been demonstrated to be superior to monophasic shocks for termination of ventricular fibrillation , but data regarding biphasic shocks for conversion of AF are still emerging . METHODS In an international , multicenter , r and omized , double-blind clinical trial , we compared the effectiveness of damped sine wave monophasic versus impedance-compensated truncated exponential biphasic shocks for the cardioversion of AF . Patients received up to five shocks , as necessary for conversion : 100 J , 150 J , 200 J , a fourth shock at maximum output for the initial waveform ( 200 J biphasic , 360 J monophasic ) and a final cross-over shock at maximum output of the alternate waveform . RESULTS Analysis included 107 monophasic and 96 biphasic patients . The success rate was higher for biphasic than for monophasic shocks at each of the three shared energy levels ( 100 J : 60 % vs. 22 % , p monophasic performance at 360 J ( 91 % vs. 85 % , p = 0.29 ) . Biphasic patients required fewer shocks ( 1.7 + /- 1.0 vs. 2.8 + /- 1.2 , p total energy delivered ( 217 + /- 176 J vs. 548 + /- 331 J , p lower frequency of dermal injury ( 17 % vs. 41 % , p biphasic shock waveform has greater efficacy , requires fewer shocks and lower delivered energy , and results in less dermal injury than a monophasic shock waveform",
"Oral verapamil has previously been shown to reduce heart rate at rest and during mild exercise in chronic atrial fibrillation . Its efficacy in improving cardiovascular performance at higher levels of exercise and its safety were investigated in a prospect i ve , r and omized , placebo controlled double-blind study preceded by an open label titration phase in 20 digitalized patients with chronic atrial fibrillation . Maximal exercise capacity was improved ( from 522 + /- 257 to 806 + /- 348 work units , p less than 0.0005 ) when tested by a st and ardized multistage ergometry exercise test . Heart rate was also reduced at rest , at the end of 3 minutes of 300 KPM exercise , and at the point of maximal exercise . Blood pressure and double product were also reduced . Its efficacy and safety may make verapamil the treatment of choice in chronic atrial fibrillation",
"Currently d , l-sotalol is widely used to prevent recurrence of atrial fibrillation and /or atrial flutter , although a r and omized dose-response study has not previously been conducted to guide therapy for this indication . This study summarizes findings of a double-blind , placebo-controlled , multicenter , r and omized trial evaluating the efficacy , safety , and dose-response relation of 3 fixed doses of d , l-sotalol ( 80 , 120 , and 160 mg twice daily ) for the maintenance of sinus rhythm in 253 patients with atrial fibrillation and /or atrial flutter . All patients were in sinus rhythm at r and omization . Treatment ( 69 patients on placebo , 59 on 80 mg , 63 on 120 mg , and 62 on 160 mg given twice daily ) was continued for 12 months or until documented recurrence of symptomatic atrial fibrillation and /or flutter . Transtelephonic electrocardiographic monitoring was used to detect symptomatic recurrences . Demographic characteristics were not different in the 4 groups . Structural heart disease was present in 57 % of patients . Patients with a history of heart failure were excluded . The time from r and omization to symptomatic arrhythmia recurrence was significantly longer in the 2 higher d , l-sotalol dose groups than in the placebo group . The median times to recurrence were 27 , 106 , 229 , and 175 days for the placebo , 80 , 120 , and 160 mg groups , respectively . There were no deaths or cases of torsade de pointes , sustained ventricular tachycardia , or ventricular fibrillation reported . Thus , d , l-sotalol appeared to be both safe and effective in maintaining sinus rhythm in patients with symptomatic atrial fibrillation and /or flutter . Further , the 120-mg twice daily dose appeared to provide the most favorable benefit and /or risk",
"STUDY OBJECTIVE To compare the effects of i.v . diltiazem and i.v . digoxin on ventricular rate control in the emergency treatment of acute atrial fibrillation and flutter ( AFF ) . METHODS This prospect i ve , r and omized , open-label trial involved 30 consecutive patients who presented with acute AFF to the emergency department of an urban , 420-bed community teaching hospital from April 1993 through March 1994 . Exclusion criteria included systolic blood pressure lower than 100 mm Hg , treatment with calcium-channel blockers other than diltiazem , lack of informed consent , and objection of the private physician . Patients were r and omly assigned to receive either i.v . diltiazem alone , i.v . digoxin alone , or both . Heart rate control was defined as a ventricular rate of less than 100 beats/minute . I.v . digoxin , 25 mg , was given as a bolus at time 0 and at time 30 minutes . An initial dose of .25 mg/kg diltiazem was given intravenously over the first 2 minutes , followed by a dose of .35 mg/kg at time 15 minutes and then a titratable i.v . infusion at a rate of 10 to 20 mg/hour to maintain heart rate control . The dosing regimens were the same whether the drugs were given alone or in combination . Heart rhythm , heart rate , and blood pressure were measured at time 0 , 5 , 10 , 15 , 30 , 60 , 120 , and 180 minutes . Statistical significance was assessed with the use of Student 's t test and ANOVA methodology . RESULTS At time 0 , the heart rate ( mean + /- SD ) was 150 + /- 19 beats/minute in the diltiazem group and 144 + /- 12 in the digoxin group ( difference not significant , P = .432 ) . The decrease in heart rate from time 0 reached statistical significance at time 5 minutes in the diltiazem group ( P = .0006 ) ; the mean rates at time 5 minutes were 111 + /- 26 beats/minute for diltiazem and 144 + /- 13 for digoxin . The decrease in heart rate achieved with digoxin did not reach statistical significance until time 180 minutes ( P = .0099 ) , at which time the rates were 90 + /- 13 for diltiazem and 117 + /- 22 for digoxin . CONCLUSION Treatment of acute AFF with i.v . diltiazem decreases ventricular heart rate significantly within 5 minutes , compared with 3 hours for treatment with i.v . digoxin . No advantage was noted within 3 hours for i.v . treatment with a combination of diltiazem and digoxin . I.v . diltiazem is superior to i.v . digoxin in the emergency control of ventricular rate in acute AFF and should be considered as a drug of choice for this condition . This study was not large enough to adequately assess adverse effects , and further studies may be warranted for clinical validation",
"The results of the long-term follow-up of 119 patients who had DC cardioversion performed are described . All patients had had corrective cardiac surgery for chronic rheumatic valvar heart disease . The poor prognosis for maintenance of sinus rhythm in this type of patient is emphasized . Of the total patients , 83 per cent were converted to sinus rhythm , but relapses were common in those who had atrial fibrillation before operation . Only 40 per cent of such patients maintained sinus rhythm for 2 months , 15 per cent for 1 year , and 9 per cent for 2 years . By contrast , when atrial fibrillation occurred for the first time in the post-operative period , 82 per cent maintained sinus rhythm for 2 years after conversion . Post-operative DC cardioversion is in general not recommended for patients with rheumatic heart disease and atrial fibrillation unless atrial fibrillation occurs for the first time in the post-operative period . A controlled trial of prophylactic quinidine is reported and shows no significant increase in the number of patients remaining in sinus rhythm as compared with a control group not receiving quinidine",
"In some patients with chronic atrial fibrillation , treatment with digitalis alone may fail to produce a satisfactory decrease in heart rate at rest or during exercise or emotional stress . Findings of a few clinical studies suggest that beta blockade in combination with digitalis therapy may be of benefit in these patients . In a r and omized , double-blind , placebo-controlled , parallel-group , 8-week study of 32 patients with chronic atrial fibrillation , the effects of digoxin therapy alone were compared with a combination of digoxin and nadolol . Criteria for entry into the study included ventricular rate at rest greater than or equal to 80/min or greater than or equal to 120/min with exercise , and serum digoxin levels within the therapeutic range . After digoxin dose titration to produce therapeutic levels , digoxin dosage remained constant throughout the balance of the study . After a 2-week , single-blind placebo lead-in period , patients were r and omized to receive either digoxin plus placebo or a combination of digoxin and nadolol . The dose of nadolol/placebo was titrated from 20 to 120 mg daily as tolerated . Twenty-four hour ambulatory electrocardiographic ( Holter ) recordings , symptom-limited exercise treadmill tests and serum digoxin and nadolol levels were obtained at the end of the single and double-blind treatment periods . Comparing endpoint with baseline , results from Holter recordings showed that patients treated with a combination of digoxin and nadolol had significant ( p less than 0.001 ) decreases in 24 hour average ( 78 + /- 4 to 63 + /- 3 ) . ( ABSTRACT TRUNCATED AT 250 WORDS",
"1 . The ideal drug treatment for atrial fibrillation will control resting heart rate , blunt exercise induced tachycardia whilst not exacerbating nocturnal bradycardia . Monotherapy with digoxin may not be ideal . We have compared the effect of combining digoxin ( 0.25 mg daily ) with atenolol 50 mg and 100 mg or pindolol 5 mg twice daily and 15 mg twice daily in a cross-over r and omised single-blind trial in eight symptomatic patients ( six male ; mean age 62 years ) with poorly controlled atrial fibrillation . 2 . Heart rate control was measured by 24 h ECG at baseline on digoxin therapy and after 2 weeks with each treatment . Symptom scores for breathlessness and palpitation were measured using visual analogue scales . 3 . The addition of both beta-adrenoceptor blockers significantly reduced mean diurnal maximum heart rate from baseline ( all P Atenolol at both doses caused a greater reduction than either dose of pindolol ( P Nocturnal maximum heart rate was not significantly reduced from baseline by either beta-adrenoceptor blocker , but both doses of pindolol caused increases in nocturnal maximum heart rate compared with atenolol ( P Atenolol caused a reduction in diurnal minimum heart rate compared with baseline and caused a reduction in nocturnal minimum heart rate whereas pindolol caused an increase ( P Atenolol 100 mg caused longer nocturnal pauses compared with baseline but pindolol 15 mg twice daily reduced the number of nocturnal pauses > 1.5 s ( P = 0.05 ) . ( ABSTRACT TRUNCATED AT 250 WORDS",
"Nine male patients ( mean age 65 yr ) with chronic atrial fibrillation underwent maximal exercise testing during placebo , beta-adrenergic ( celiprolol , 600 mg ) , or calcium ( diltiazem , 30 or 60 mg four times daily ) channel blockade . The results were analyzed to determine which factors most closely related to ratings of perceived exertion ( RPE ) during exercise . Heart rate ( HR ) , blood pressure ( BP ) , oxygen uptake ( VO2 ) , minute ventilation ( VE ) , and carbon dioxide production ( VCO2 ) were evaluated at rest , 3.0 mph/0 % grade , the gas exchange anaerobic threshold ( ATge ) , 80 % of placebo maximal O2 uptake , and maximal exercise . Both beta-adrenergic and calcium channel blockade significantly reduced heart rate and systolic blood pressure relative to placebo ; these effects were more profound during beta-adrenergic blockade and as exercise progressed . Correlation coefficients and estimates of slope were derived for changes in RPE during exercise vs. changes in HR , VO2 , VE , and VCO2 during the three treatments ( r = 0.76 to 0.92 , P less than 0.001 ) . Although RPE was significantly correlated with HR during placebo and diltiazem therapy ( r = 0.45 , P less than 0.01 ) , this was not the case during beta-adrenergic blockade ( r = 0.31 , NS ) . Slope of the regression lines between RPE and VO2 , VE , and VCO2 did not differ between the three treatments . Slope of the regression lines between RPE and HR differed only during calcium channel blockade . Because the presence of atrial fibrillation and beta-adrenergic blockade altered the associations between RPE , VO2 , and HR , these results suggest that VE is more closely related to RPE than the other parameters",
"Sotalol is an antiarrhythmic agent with combined beta-blocking and class III antiarrhythmic properties . This study was design ed to assess the safety and efficacy of sotalol in terminating supraventricular tachycardia ( SVT ) , atrial fibrillation ( AFib ) , and atrial flutter ( AFl ) . Ninety-three patients with spontaneous or induced SVT ( n = 45 ) or AF ( AFib or AFl ; n = 48 ) with a ventricular rate of > or = 120 beats/min were studied . In the first phase , the double-blind phase , patients were r and omly assigned to receive placebo or intravenous ( i.v . ) sotalol , 1.0 or 1.5 mg/kg . If SVT or AF did not convert to sinus rhythm or if the ventricular rate did not slow to conversion to sinus rhythm occurred in 2 ( 14 % ) of 14 of patients who received placebo , 10 ( 67 % ) of 15 who received sotalol , 1.0 mg/kg ( p conversion to sinus rhythm occurred in 2 ( 14 % ) of 14 of patients who received placebo , 2 ( 11 % ) of 18 who received 1.0 mg/kg sotalol ( p not significant [ NS ] vs placebo ) , and 2 ( 13 % ) of 16 who received 1.5 mg/kg sotalol ( p = NS vs placebo ) ; in these groups , a > 20 % reduction of ventricular rate without conversion to sinus rhythm occurred in 0 ( 0 % ) of 14 , 13 ( 72 % ) of 18 ( p adverse events were hypotension and dyspnea . During the double-blind phase they occurred in 10 % of patients who received placebo , 9 % of those who received 1.0 mg/kg i.v . sotalol ( p = NS vs placebo ) , and 10 % of those who received 1.5 mg/kg i.v . sotalol ( p = NS vs placebo ) . Most of these events were mild to moderate , but all were transient and clinical ly manageable . ( ABSTRACT TRUNCATED AT 400 WORDS",
"UNLABELLED Eighty-seven patients with recent onset atrial fibrillation ( were r and omly allocated to one of the following treatments : ( i ) oral propafenone ( 600 mg as a loading dose followed after 8 h by 300 mg t.i.d . ) ; ( ii ) intravenous digoxin as acute scheme ( up to 1.125 mg/24 h ) followed after 6 h by hydroquinidine chlorhydrate ( total dose , 1350 mg ) ; or ( iii ) placebo . The patients were su bmi tted to Holter monitoring for 48 h. RESULTS propafenone achieved higher successful conversion rates at 6 , 12 and 24 h compared either with placebo ( 62 % vs. 17 % , 83 % vs. 34 % ; 86 % vs. 55 % ; P digoxin at 6 h ( 62 % vs. 38 % ; P digoxin plus quinidine at 12 h ( 83 % vs. 48 % ; P placebo conversion rate of 76 % was observed with consequent lack of any significant difference with the active treatments . Mean conversion times within 48 h were 267 + /- 238 min for propafenone , 648 + /- 631 min for digoxin plus quinidine ( P propafenone ) and 893 + /- 622 min for placebo ( P ) . Propafenone and digoxin plasma levels were within the therapeutic range . Asymptomatic phases of atrial flutter with > or = 2:1 atrio-ventricular conduction ratio were observed during Holter monitoring , before conversion to sinus rhythm , in four patients treated with propafenone , in one patient taking digoxin plus quinidine and in four patients with placebo . ( ABSTRACT TRUNCATED AT 250 WORDS",
"BACKGROUND Spontaneous conversion of recent onset paroxysmal atrial fibrillation to normal sinus rhythm occurs commonly and is not affected by low-dose amiodarone treatment . METHODS In a r and omized , placebo-controlled trial of 100 patients with paroxysmal atrial fibrillation of recent onset ( we compared the effects of treatment with continuous intravenous amiodarone 125 mg per hour ( total 3 g ) and intravenous placebo . Patients in the placebo group who did not convert to normal sinus rhythm within 24 h were started on amiodarone therapy . RESULTS Conversion to normal sinus rhythm occurred within 24 h in 32 of 50 patients ( 64 % ) in the placebo group , most of whom converted within 8 h. Lower conversion rates were observed in patients with hypertension , ischaemic heart disease or congestive heart failure and in patients with echocardiographic findings of left atrial diameter above 45 mm , ejection fraction below 45 % or significant mitral regurgitation . However , in most patients these clinical or echocardiographic risk factors of decreases in conversion rate were not present . In such patients the spontaneous conversion rate was approximately 90 % . The conversion rate during 24 h of treatment in the amiodarone group was 92 % ( P=0.0017 , compared to the placebo group ) . In this group , the conversion rate was largely unaffected by baseline characteristics . Of the 18 patients who did not convert with placebo , 15 ( 85 % ) converted after being crossed over to amiodarone . All patients not responding to high-dose amiodarone were in chronic atrial fibrillation within 1 month . In patients still in atrial fibrillation after 8 h of treatment , the pulse rate decreased significantly more in the amiodarone as compared to the placebo group ( 83+/-15 vs 114+/-20 beats . min(-1 ) , P=0.0014 ) . CONCLUSION The spontaneous conversion of recent onset paroxysmal atrial fibrillation is high and approaches 90 % in specific clinical and echocardiographically defined subgroups . Intravenous high-dose amiodarone safely facilitates conversion of paroxysmal atrial fibrillation . However , such treatment should be reserved for patients with unfavourable risk factor profiles , not converting during 8 h of observation or requiring rate control",
"To compare the efficacy and safety of sotalol and quinidine after conversion of atrial fibrillation ( AF ) of , a prospect i ve multicenter trial enrolled 121 patients who were r and omized to receive dl-sotalol ( 160 to 320 mg/day , 58 patients ) or quinidine sulfate ( 600 to 800 mg/day , 63 patients ) . Patients with left ventricular ejection fraction of 5.2 cm were excluded . After 6 months of follow-up , using the Kaplan-Meier method , the probabilities of success were comparable between sotalol ( 74 % ) and quinidine ( 68 % ) , but recurrences occurred later with sotalol than with quinidine ( 69 vs 10 days , p proarrhythmic events , 3 ( 5 % ) with sotalol and 1 ( 2 % ) with quinidine , which were all associated with diuretic therapy . In patients converted from recent-onset AF ( quinidine ( 93 % vs 64 % , p = 0.01 ) , whereas in chronic AF ( > 72 hours ) , quinidine was more effective than sotalol ( 68 % vs 33 % , p ventricular rate was significantly reduced in patients taking sotalol ( 98 to 82 beats/min , p therapeutic success were recent-onset AF in the sotalol group ( p sotalol and quinidine have comparable efficacy and safety for the maintenance of sinus rhythm in the overall group . In recent-onset AF , sotalol was more effective , whereas in chronic AF , quinidine had a better result . Recurrences occurred later with sotalol when compared with quinidine . Because of proarrhythmia , these drugs should be used judiciously in patients on diuretic therapy ",
"In patients with chronic nonrheumatic atrial fibrillation , prophylaxis of peripheral arterial embolism is strongly indicated . LMWHs may be an alternative regimen if contraindications for oral anticoagulants are present . In the present study the effect of LMWH on the incidence of embolism in atrial fibrillation has been studied in 75 consecutive patients in comparison to no specific treatment . Patients received one daily injection of the LMWH CY 216 ( n = 35 ) subcutaneously over a period of 6 months . Patients of the control group ( n = 40 ) were observed over the same period of time . In the group treated with CY 216 , three embolic events ( 8.6 % ) occurred , of which two were localized in the cerebrum . One of these two cerebral embolic events was fatal . In the control group , eight embolic events ( 20 % ) occurred , six of these were intracerebral and , of these , five were fatal . An even more pronounced difference between the groups was observed on evaluation of the patients with preceding cerebral embolism . Of 15 patients treated with LMWH , one extracerebral nonfatal embolism occurred . In the control group three of the seven patients ( 43 % ) experienced fatal reembolism . The results show that in patients with atrial fibrillation one daily subcutaneous injection of LMWH reduces the incidence of arterial embolism to about one third . No adverse effects were observed during the 6-month treatment period with LMWH",
"OBJECTIVE The main aim of the study was to evaluate the safety and efficacy of propafenone versus quinidine as an initial choice in treatment of symptomatic paroxysmal atrial fibrillation . DESIGN The study consisted of a 3-month treatment with oral propafenone hydrochloride or quinidine sulphate in patients with paroxysmal symptomatic atrial fibrillation , according to a double-blind r and omized system . SETTING The study was performed in the out-patient clinic of university hospital . MAIN OUTCOME MEASURES The effects of the two drugs on attack frequency , ventricular rate and symptoms of symptomatic paroxysmal atrial fibrillation . RESULTS In the oral propafenone group ( n = 48 ) , two patients ( 4 % ) discontinued the treatment because of dizziness . In the 46 patients who continued the treatment , the attack frequency decreased from 11 + /- 3 times per week at baseline to 1 + /- 1 times per week after treatment ( P propafenone ( more than 75 % reduction of symptomatic arrhythmic attacks ) on a mean dose of 615 + /- 10 mg day-1 ; the decrease in attack frequency was from 10 + /- 3 to 1 + /- 1 times per week . Twenty-three ( 50 % ) patients were free from recurrence of symptomatic paroxysmal atrial fibrillation . Comparisons of symptom scores for patients ( n = 23 ) with attacks of paroxysmal atrial fibrillation after oral propafenone treatment showed that there was a significantly lower symptom score of palpitation , asthenia , effort dyspnea , dizziness , rest dyspnea and chest oppression in attacks of paroxysmal atrial fibrillation after propafenone treatment ( 11.05 + /- 3.78 versus 7.60 + /- 3.46 , P gastrointestinal discomfort . In the 46 patients who continued the treatment , the attack frequency decreased from 11 + /- 4 times per week at baseline to 3 + /- 2 times per week after treatment ( P quinidine on a mean dose of 1067 + /- 462 mg day-1 , with a decrease in attack frequency from 12 + /- 3 to 1 + /- 1 times per week . Only 10 ( 22 % ) patients were free from recurrence of paroxysmal atrial fibrillation . Comparisons of symptom scores for patients ( n = 36 ) with attacks of paroxysmal atrial fibrillation after quinidine treatment showed that there was no significant decrease of symptom score in attacks of atrial fibrillation ( 10.65 + /- 3.92 versus 10.20 + /- 3.80 , P = 0.57 ) . Furthermore , the percentage decrease of ventricular rate during atrial fibrillation was significantly greater in patients with propafenone ( -25 + /- 4 % versus -8 + /- 3 % , P propafenone appeared to be more effective than quinidine in suppressing attacks and alleviating symptoms of paroxysmal atrial fibrillation ",
"Abstract Amiodarone and verapamil are well-known antiarrhythmic drugs used for treatment of ventricular and supraventricular arrhythmias . Although verapamil is the drug of choice for control of the atrioventricular node , it has also been reported to terminate atrial fibrillation . 1–3 Amiodarone has been used extensively for drug-refractory ventricular tachycardia but seldom for termination of paroxysmal atrial fibrillation . 4–6 To our knowledge , no comparative study with amiodarone and verapamil has been reported . Because of this , we compared the efficacy of intravenous amiodarone versus verapamil for conversion of paroxysmal atrial fibrillation to sinus rhythm in a single-blind r and omized study",
"STUDY OBJECTIVE A prospect i ve , r and omized controlled trial of new-onset atrial fibrillation was conducted to compare the efficacy and safety of sotalol and amiodarone ( active treatment ) with rate control by digoxin alone for successful reversion to sinus rhythm at 48 hours . METHODS We prospect ively r and omly assigned 120 patients with atrial fibrillation of less than 24 hours ' duration to treatment with sotalol , amiodarone , or digoxin using a single intravenous dose followed by 48 hours of oral treatment . Patients had ECG monitoring for 48 hours , and time of reversion , adequacy of rate control , and numbers of adverse events were compared . After 48 hours , those still in atrial fibrillation underwent cardioversion according to a st and ardized protocol . After 48 hours of therapy and attempted cardioversion , the number of patients whose rhythms had successfully reverted were compared . RESULTS There was a significant reduction in the time to reversion with both sotalol ( 13 . 0+/-2.5 hours , P amiodarone ( 18.1+/-2.9 hours , P digoxin only ( 26.9+/-3.4 hours ) . By 48 hours , the active treatment group was significantly more likely to have reverted to sinus rhythm than the rate control group ( 95 % versus 78 % , P ventricular rate control in the sotalol group at both 24 and 48 hours compared with those who received either amiodarone or digoxin . There were also fewer adverse events in the active treatment group compared with the rate control group . CONCLUSION Immediate pharmacologic therapy for new-onset atrial fibrillation with class III antiarrhythmic drugs ( sotalol or amiodarone ) improves complication-free 48-hour reversion rates compared with rate control with digoxin",
"OBJECTIVES Currently available antiarrhythmic drugs have limited efficacy for short-term , rapid termination of atrial fibrillation and atrial flutter . BACKGROUND Ibutilide fumarate is an investigational class III antiarrhythmic agent that prolongs repolarization by increasing the slow inward sodium current and by blocking the delayed rectifier current . It can be administered intravenously and has a rapid onset of electrophysiologic effects . METHODS The efficacy and safety of ibutilide were studied in 200 patients with atrial flutter > 3 h in duration or atrial fibrillation 3 h to 90 days in duration . Patients were r and omized to receive a single intravenous dose of placebo or an infusion of ibutilide fumarate at 0.005 , 0.010 , 0.015 or 0.025 mg/kg body weight over 10 min . Conversion was defined as termination of the atrial arrhythmia during or within 60 min after infusion . Forty-one patients received placebo and 159 received ibutilide ( 0.005 mg/kg [ n = 41 ] , 0.010 mg/kg [ n = 40 ] , 0.015 mg/kg [ n = 38 ] or 0.025 mg/kg [ n = 40 ] ) . RESULTS The arrhythmia terminated in 34 % of drug-treated patients . The rates of successful arrhythmia termination were 3 % for placebo and 12 % , 33 % , 45 % and 46 % , respectively , for 0.005- , 0.010- , 0.015- and 0.025-mg/kg ibutilide . The placebo and 0.005-mg/kg ibutilide groups had lower success rates than all other dose groups ( p mean time to termination of the arrhythmia was 19 min ( range 3 to 70 ) from the start of infusion . Successful arrhythmia termination was not affected by enlarged left atrial diameter , decreased ejection fraction , presence of valvular heart disease or the use of concomitant medications ( beta-adrenergic blocking agents , calcium channel blocking agents or digoxin ) . Arrhythmia termination was not predicted by the magnitude of corrected QT interval prolongation but was associated with a shorter duration of atrial arrhythmia . The most frequent adverse events in ibutilide-treated patients were sustained and nonsustained polymorphic ventricular tachycardia ( 3.6 % ) . All patients with sustained polymorphic ventricular tachycardia were successfully treated with direct current cardioversion and had no recurrence . The occurrence of proarrhythmia did not correlate with ibutilide plasma concentration . CONCLUSIONS These data demonstrate that ibutilide is able to rapidly terminate atrial fibrillation and atrial flutter",
"OBJECTIVE To analyze the efficacy of an IV combination of diltiazem and digoxin vs IV diltiazem alone for acute ventricular rate control in patients with atrial fibrillation . DESIGN Prospect i ve , r and omized , open-label study . PATIENTS AND METHODS Fifty-two patients with atrial fibrillation and uncontrolled ventricular rates were r and omized to receive either an IV combination of diltiazem and digoxin or IV diltiazem alone and were observed for 12 h. The successful rate control was defined as a ventricular rate beats per minute ( bpm ) persisting for 1 h or conversion to sinus rhythm . The loss of rate control was defined as an increase in the ventricular rate to > 100 bpm persistently for > 30 min or rebound to atrial fibrillation . RESULTS In both treatment arms ( n = 26 each ) , all patients achieved successful and comparable ventricular rate control at 12 h. The mean ( + /- SD ) time taken to achieve successful rate control was shorter in the combination arm ( 15 + /- 16 vs. 22 + /- 22 min ) . Six patients in the combination arm and 11 in the diltiazem-alone arm experienced episodes of loss of rate control . This loss in the combination arm was less than that in the diltiazem-alone arm ( 14 vs 39 episodes ; p = 0.05 ) . The loss of rate control per patient in the combination arm was also less than that in the diltiazem-alone arm ( 2.0 + /- 1.0 vs. 3.5 + /- 1.9 episodes per patient ; p = 0.04 ) . CONCLUSIONS This study demonstrates that in patients with atrial fibrillation who have a rapid ventricular response , the IV combination of diltiazem and digoxin results in a more efficacious ventricular rate control with fewer fluctuations than that achieved by therapy with IV diltiazem alone ",
"Atrial fibrillation ( AF ) is one of the most frequent dysrhythmias in patients coming to emergency departments ( EDs ) , and pharmacological treatment is frequently performed . The aim of this r and omized placebo-controlled multicenter trial was to compare propafenone ( a class 1C antidysrhythmic agent ) , administered i.v . in the ED , with placebo in the treatment of recent-onset AF ( . We r and omly allocated 156 patients ( 88 males ; 68 females ) from 18 to 80 years old , with recent-onset AF , to receive i.v . propafenone ( 2 mg/kg for 10 min ) or the matching placebo . The patients were followed for 2 h. Exclusion criteria were the presence of one of the following : lack of informed consent , clinical evidence of heart failure , clinical hyperthyroidism , recent acute myocardial infa rct ion , atrioventricular block , cardiac valve dysfunction , a history of bronchial asthma , and current treatment with antidysrhythmic agents including digitalis . The two groups did not differ significantly in terms of sex , age , body weight , or estimated time elapsed since the beginning of atrial fibrillation . Conversion to sinus rhythm occurred in 13 of the 75 patients who received the placebo ( 17.3 % ) and in 57 of the 81 patients who were given propafenone ( 70.3 % ) . In conclusion , intravenous propafenone administration in the ED can be considered a safe and effective approach for converting AF to sinus rhythm",
"OBJECTIVES We compared the effects of five pharmacologic regimens on the circadian rhythm and exercise-induced changes of ventricular rate ( VR ) in patients with chronic atrial fibrillation ( CAF ) . BACKGROUND Systematic comparison of st and ardized drug regimens on 24 h VR control in CAF have not been reported . METHODS In 12 patients ( 11 male , 69+/-6 yr ) with CAF , the effects on VR by 5 st and ardized daily regimens : 1 ) 0.25 mg digoxin , 2 ) 240 mg diltiazem-CD , 3 ) 50 mg atenolol , 4 ) 0.25 mg digoxin + 240 mg diltiazem-CD , and 5 ) 0.25 mg digoxin + 50 mg atenolol ; were studied after 2 week treatment assigned in r and om order . The VR data were analyzed by ANOVA with repeated measures . The circadian phase differences were evaluated by cosinor analysis . RESULTS The 24-h mean ( + /-SD ) values of VR ( bpm ) were - digoxin : 78.9 + /- 16.3 , diltiazem : 80.0+/-15.5 , atenolol : 75.9+/-11.7 , digoxin + diltiazem : 67.3+/-14.1 and digoxin + atenolol : 65.0+/-9.4 . Circadian patterns were significant in each treatment group ( p VR on digoxin + atenolol was significantly lower than that on digoxin ( p diltiazem ( p atenolol ( p time of peak VR on Holter was significantly delayed with regimens 3 and 5 which included atenolol ( p digoxin and digoxin + atenolol treatments result ed in the highest and lowest mean VR respectively . The exercise Time-VR plots of all groups were nearly parallel ( p = ns ) . The exercise duration was similar in all treatment groups ( p = ns ) . CONCLUSIONS This study indicates that digoxin and diltiazem , as single agents at the doses tested , are least effective for controlling ventricular rate in atrial fibrillation during daily activity . Digoxin + atenolol produced the most effective rate control reflecting a synergistic effect on the AV node . The data provides a basis for testing the effects of chronic suppression of diurnal fluctuations of VR on left atrial and ventricular function in CAF",
"Background : Pharmacological conversion of paroxysmal atrial fibrillation is frequently necessary . The aim of this study was to compare intravenous propafenone , a class Ic antiar‐rhythmic agent , with placebo in paroxysmal atrial fibrillation ( AF ) of recent onset ( < 72 h )",
"AIMS To evaluate the efficacy and safety of a single loading oral dose of propafenone in the interruption of recent-onset atrial fibrillation . METHODS After a complete medical history , physical examination , 12-lead ECG , chest X-ray , and routine biochemical laboratory testing , 55 consecutive patients with recent-onset atrial fibrillation were r and omized double-blind in the emergency department for the administration of either a single oral dose ( 450 to 750 mg ) of propafenone ( 29 cases ) or a placebo ( 26 cases ) . After the 24-h observation period , comprehensive echocardiographic examination was performed . RESULTS The groups were homogeneous as regards biological , clinical and echocardiographic characteristics . Two hours after treatment , 12 patients ( 41 % ) on propafenone but only two ( 8 % ) on placebo had converted to sinus rhythm ( P = 0.005 ) . This striking difference was maintained 6 h after treatment ( 65 vs 31 % ; P = 0.015 ) but lessened at 12 h ( 69 % vs 42 % ; P = 0.060 ) and was insignificant at the end of the 24-h treatment period ( 79 % , vs 73 % ; P = 0.752 ) . Apart from hypotension , transient in three cases and sustained in one whose later echocardiographic examination demonstrated left systolic ventricular dysfunction , propafenone was well tolerated . CONCLUSION Although there is no significant difference in the rates of conversion 24 h after treatment , propafenone works faster than placebo in achieving sinus rhythm . This rapid action of oral propafenone can be useful to solve quickly the clinical problems of a high proportion of patients arriving at the emergency department with acute atrial fibrillation",
"Atrial fibrillation ( AF ) is a common arrhythmia in elderly persons and a common cause of embolic stroke . Most studies of the prevalence and correlates of AF have used selected , hospital-based population s. The Cardiovascular Health Study is a population -based , longitudinal study of risk factors for coronary artery disease and stroke in 5,201 men and women aged > or = 65 years . AF was diagnosed in 4.8 % of women and in 6.2 % of men at the baseline examination , and prevalence was strongly associated with advanced age in women . Prevalence of AF was 9.1 % in men and women with clinical cardiovascular disease , 4.6 % in patients with evidence of sub clinical but no clinical cardiovascular disease , and only 1.6 % in subjects with neither clinical nor sub clinical cardiovascular disease . A history of congestive heart failure , valvular heart disease and stroke , echocardiographic evidence of enlarged left atrial dimension , abnormal mitral or aortic valve function , treated systemic hypertension , and advanced age were independently associated with the prevalence of AF . The low prevalence of AF in the absence of clinical and sub clinical cardiovascular disease calls into question the existence and clinical usefulness of the concept of so-called \" lone atrial fibrillation \" in the elderly",
"This study was conducted to evaluate the clinical efficacy of intravenous ( i.v . ) magnesium sulphate 2 gm bolus in sustained supraventricular tachycardia ( SVT ) and atrial flutter-fibrillation with fast ventricular rate of more than 160/min ( AF-FVR ) and to compare it with i.v . verapamil 5 mg . In this r and omised controlled trial , 68 cases of SVT and 86 cases of AF-FVR were studied . Patients with evidence of renal dysfunction and systolic blood pressure less then 90 mm Hg were excluded . Response was considered when the heart rate fell to less than 100/min . In SVT , 33.3 % ( 11 out of 33 ) responded to magnesium sulphate which was significantly less than verapamil ( 23 out of 35 , 65.7 % ) p = 0.007 . Similarly , in AF-FVR , response was more with verapamil ( 25 out of 45 , 55.6 % ) than magnesium sulphate ( 8 out of 41 , 19.5 % ) p magnesium sulphate was better in patients with IHD . There were no significant side effects , except flushing and sense of warmth with i.v . magnesium sulphate . Serum magnesium rose significantly after i.v . magnesium bolus . Though magnesium sulphate is a weaker antiarrhythmic drug than verapamil , further studies are needed to identify subgroups of supraventricular tachyarrhythmias which would respond to magnesium sulphate",
"STUDY OBJECTIVE To compare placebo vs two different regimens of propafenone administration -- intravenous administration or short-term oral loading -- in converting recent-onset atrial fibrillation to sinus rhythm . DESIGN Single-blind placebo-controlled study . PATIENTS Eighty-seven patients with atrial fibrillation of recent onset ( The patients were assigned r and omly to treatment with intravenous propafenone ( 29 patients ) , oral propafenone ( 29 patients ) , or placebo ( 29 patients ) . INTERVENTIONS Administration of propafenone intravenously ( 2-mg/kg bolus followed by 0.0078 mg/kg/min ) or as short-term oral loading ( 600 mg orally single dose ) . Patients were su bmi tted to Holter monitoring and conversion to sinus rhythm was evaluated at 1 , 3 , and 8 h. RESULTS Conversion to sinus rhythm was obtained within 1 h in 28 % with intravenous propafenone , in 3 % with oral propafenone , and in 3 % with placebo . At 3 h , the efficacy of intravenous propafenone ( 41 % ) and of oral propafenone ( 55 % ) were statistically superior to placebo ( 10 % of conversions ) and at 8 h either intravenous or oral propafenone were effective in almost two thirds of the patients with a statistical difference vs placebo , whose efficacy was 24 % . No major side effects were observed . CONCLUSIONS Propafenone as an oral loading dose is an efficacious and fast way of treating atrial fibrillation of recent onset and due to its simplicity of administration and safety can be preferred to the intravenous route",
"AIMS A r and omized , double-blind study with a high dose of digoxin administered intravenously for conversion of atrial fibrillation ( not due to haemodynamic alternations ) to sinus rhythm , and for rate control in converters and non-converters was set up . Outcome measures were conversion within 12 h ; time to conversion ; early rate control ; and stable slowing within 12 h. METHODS We studied 40 patients with recent onset ( saline intravenously , the other patients digoxin 1.25 mg . RESULTS One patient converted before digoxin administration . Conversion occurred in 9/19 patients on digoxin and in 8/20 on placebo ( ns ) . The mean time to conversion tended to be shorter only for digoxin . Two late conversions on placebo were observed within 24 h. Heart rate during atrial fibrillation decreased after 30 min for converters and non-converters ( P digoxin , heart rate after 30 min was lower compared to baseline ( P placebo ( P Persistent , stable slowing occurred only in 3/10 non-converters on digoxin ( P bradyarrhythmias . QTc was shortened immediately after conversion in all patients . Converters had baseline characteristics similar to those of non-converters . CONCLUSIONS Intravenous digoxin offers no substantial advantages over placebo in recent onset atrial fibrillation with respect to conversion , and provides weak rate control",
" Thirty-nine patients with paroxysmal atrial fibrillation or supraventricular tachycardia r and omly received amiodarone or propafenone intravenously at home . Fifteen patients received amiodarone and 24 received propafenone ; 87.5 % of the patients who received propafenone and 40 % of the patients who received amiodarone were converted at home to sinus rhythm ( P less than .005 ) . The median time of conversion was 10 minutes ( range 5 to 35 ) for propafenone and 60 minutes ( range 20 to 130 ) for amiodarone ( P less than 0.005 ) . When either drug failed to terminate atrial tachydysrhythmias at home , the same drug always restored sinus rhythm with subsequent oral treatment during hospitalization . No major side effects were observed after the infusion of either drug . The incidence of minor side effects was not significantly different between the two drugs . Both the drugs are efficacious and safe in the acute management of primary supraventricular tachydysrhythmias . Propafenone showed a greater rapidity of action",
"The Canadian Atrial Fibrillation Anticoagulation Study was a r and omized double-blind placebo-controlled trial to assess the potential of warfarin to reduce systemic thromboembolism and its inherent risk of hemorrhage . As a result of the publication of two other \" positive \" studies of similar design and objective , this study was stopped early before completion of its planned recruitment of 630 patients . There were 187 patients r and omized to warfarin and 191 to placebo . Permanent discontinuation of study medication occurred in 26 % of warfarin-treated and 23 % of placebo-treated patients . The target range of the international normalized ratio was 2 to 3 . For the warfarin-treated patients , the international normalized ratio was in the target range 43.7 % of the study days , above it 16.6 % of the study days and below it 39.6 % of the study days . Fatal or major bleeding occurred at annual rates of 2.5 % in warfarin-treated and 0.5 % in placebo-treated patients . Minor bleeding occurred in 16 % of patients receiving warfarin and 9 % receiving placebo . The primary outcome event cluster was nonlacunar stroke , non central nervous systemic embolism and fatal or intracranial hemorrhage . Events were included in the primary analysis of efficacy if they occurred within 28 days of permanent discontinuation of the study medication . The annual rates of the primary outcome event cluster were 3.5 % in warfarin-treated and 5.2 % in placebo-treated patients , with a relative risk reduction of 37 % ( 95 % confidence limits , -63.5 % , 75.5 % , p = 0.17 ) . ( ABSTRACT TRUNCATED AT 250 WORDS",
"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",
"Transesophageal echocardiography visualizes the left atrium and its appendage and is more sensitive than transthoracic echocardiography for diagnosing thrombi of the left atrium and the left atrial appendage and spontaneous echocardiographic contrast of the left atrium [ 1 - 3 ] . The left atrium and especially the left atrial appendage are the presumed sites of thrombus formation and sources of arterial emboli in patients with atrial fibrillation [ 4 ] . Patients with atrial fibrillation and a history of stroke or embolism were shown to have a higher prevalence of thrombi of the left atrium or the left atrial appendage , a higher prevalence of spontaneous echocardiographic contrast , and a larger left atrial appendage than patients with no history of stroke or embolism [ 2 , 5 , 6 ] . However , whether these abnormalities are predictors for stroke or embolism remains controversial [ 7 , 8 ] . Furthermore , no studies have determined whether transesophageal echocardiography helps to assess risk for stroke or embolism in out patients with atrial fibrillation who have no history of stroke or embolism or whether transesophageal echocardiography is useful in the decision to initiate anticoagulation . We therefore performed a prospect i ve , multicenter study of out patients with atrial fibrillation who had not recently had stroke . We sought to determine whether thrombi of the left atrium or the left atrial appendage , spontaneous echocardiographic contrast , and size of the left atrial appendage are associated with stroke or embolism . Our hypothesis was that patients with thrombi of the left atrium or the left atrial appendage , spontaneous echocardiographic contrast , and enlargement of the left atrial appendage have a higher rate of stroke or embolism than do patients without these abnormalities . The baseline clinical and echocardiographic characteristics of our study sample have been reported elsewhere [ 9 ] . Methods Patient Recruitment Our study was conducted in Austria and Slovakia . At the beginning of the study , general practitioners and internists from surrounding participating centers were informed about the study and were asked to refer patients who had constant or intermittent atrial fibrillation . At each patient 's first visit , a cardiologist recorded baseline data , associated illnesses , clinical characteristics ( definitions of which are listed in Appendix 2 ) , and the cause of atrial fibrillation . A 12-lead electrocardiogram was recorded on 2 separate days . We excluded patients with prosthetic valves and those who were already receiving anticoagulation . Current therapy with aspirin was not an exclusion criterion . Patients who had mitral valve stenosis or had recently had stroke were excluded because anticoagulation was indicated for such conditions . For the definition of recent stroke , we chose a cutoff value of 1 year because a previous study reported that the risk for recurrent stroke was increased in patients who had had an ischemic event in the previous year [ 10 ] . Echocardiography For transthoracic echocardiography , 2.5- or 3.5-MHz probes were used . For M-mode measurements , we applied the recommendations of the American Society of Echocardiography [ 11 ] . M-mode measurements were performed on-line and were documented on printouts . Regional wall-motion and valvular abnormalities were recorded . In patients without regional wall-motion abnormalities , left ventricular systolic function was assessed by calculation of left ventricular fractional shortening . For transesophageal echocardiography , biplane 5-MHz probes were used in 64 % of the patients and monoplane 5-MHz probes were used in 36 % . After local anesthesia with lidocaine spray was administered , the probe was introduced into the nonse date d patients , who lay on their left side . The entire study was recorded on S-VHS videotapes . The cardiac chambers and valves were investigated by using all obtainable views [ 12 , 13 ] . Special care was taken to visualize the whole cavity of the left atrium and its appendage from different planes , with the tip of the probe slightly flexed . The size of the left atrial appendage was measured off-line . A frame that best visualized the left atrial appendage with respect to its orifice , extension , and delineation of borders was selected just before the QRS complex . The length of the left atrial appendage was defined as the distance between the limbus of the left superior pulmonary vein and the apex of the left atrial appendage ; the width of the left atrial appendage was defined as the longest distance between the lateral and ventricular left atrial appendage wall , measured in a line perpendicular to the course of the left atrial appendage curvature ; and the left atrial appendage area was defined as described elsewhere [ 14 ] . For the assessment of intra- and interobserver deviations , left atrial appendage size was measured 1 year after the initial measurement in 20 r and omly selected video recordings by the same observer and in 60 r and omly selected video recordings by three observers from different centers . A thrombus of the left atrium or left atrial appendage was considered definite if at least three of the following five criteria were present : clear borders , echogenicity different from that of surrounding structures , independent mobility , longest diameter greater than 15 mm , and evidence of thrombus in more than one imaging plane [ 15 ] . A second observer from a different center review ed video recordings to confirm diagnosis of thrombus of the left atrium or left atrial appendage . A thrombus was considered probable if only two criteria were present or if the observers disagreed . Spontaneous echocardiographic contrast was diagnosed in the presence of dynamic smoke-like echoes within the left atrium or left atrial appendage with a characteristic swirling motion that was distinct from white noise artifact [ 16 ] . When spontaneous echocardiographic contrast was suspected , the gain setting s were decreased in a stepwise manner to exclude artifact caused by excessive gain . The compression and gain controls were then adjusted to ensure the best possible visualization . Spontaneous echocardiographic contrast was not quantified . A second observer from a different center checked the diagnosis of spontaneous echocardiographic contrast by review ing all video recordings . When the observers disagreed about the presence or absence of spontaneous echocardiographic contrast , the decision made at the time of examination was chosen . This was done because spontaneous echocardiographic contrast was not always visible on review of the video recordings . Outcome Events Primary events were stroke and embolism that extended to viscera or extremities . Stroke was defined as acute onset of a focal neurologic deficit that lasted more than 24 hours and was consistent with a vascular event . Severity and subtypes of stroke were assessed according to established criteria [ 17 ] . Embolism extending to viscera or extremities was defined as a sudden onset of pain that was associated with typical findings on Doppler ultrasonography , angiography , surgery , or autopsy . Secondary events were the need for anticoagulation during follow-up in patients who were primarily receiving aspirin and death not caused by stroke or embolism . Death not caused by stroke or embolism was classified as cardiac or noncardiac on the basis of information from the treating physician and the patient 's family . Follow-up Visits took place 3 , 6 , 12 , 18 , and 24 months after study entry . After a follow-up period of at least 2 years ( ending in February 1994 ) , it was evident that the number of primary outcome events was low . We therefore prolonged the follow-up period and planned further visits , one to be held in 1994 and one to be held in 1995 . Patients who were unwilling or unable to attend the visits were contacted by telephone . Medical records were obtained for patients who had been admitted to a hospital . If a patient had died , an autopsy report or death certificate was obtained . Treatment and Ethical Considerations Although our study was design ed to be observational , we recommended antithrombotic treatment to the patients because of ethical considerations . Because patients with thrombi of the left atrium or left atrial appendage are considered to have a high risk for embolism , we recommended that they receive anticoagulation . The target range for the international normalized ratio was 2.0 to 3.0 , and the treating physicians monitored the ratio [ 5 , 18 ] . We recommended that the remaining patients receive aspirin , 160 mg/d , because preliminary data indicated that aspirin reduces the risk for stroke or embolism in patients with atrial fibrillation [ 19 ] . The institutional review board of the participating centers approved the study . Patients were informed about the background and the procedures of the trial , and informed consent was obtained according to the rules of each center . Statistical Analysis For baseline data , group comparisons were done by analysis of variance for normally distributed data and by the nonparametric Kruskal-Wallis test for data that were not normally distributed . If appropriate , we used the Scheffe post hoc test . The Wilk-Shapiro test was used to check for normality . Contingency table methods , including the chi-square test and the Fisher exact test , were used to analyze categorical data . We used the Cox proportional-hazards model to obtain estimates of relative risk and 95 % CIs for all univariate and multivariate analyses of time-to-event data . All tests were two-sided . The level of significance assumed was an level of 0.05 . We used SAS software ( SAS Institute , Cary , North Carolina ) for analyses . Role of Funding Sources The funding sources had no role in the collection , analysis , or interpretation of the data ; did not review the manuscript at any time ; and were not involved in su bmi tting the paper for publication . Results Patients Patients were recruited between January 1990 and February 1992 . Of the 474",
"Estimates of the risk of stroke for men with non-rheumatic atrial fibrillation were obtained from two large cohort studies --the Whitehall Study of London Civil Servants and the British Regional Heart Study . The first cohort provided an estimated relative risk of stroke of 6.9 compared with controls . This increased risk confirms that of the other prospect i ve estimate , 5.6 , found in the Framingham study . In the second cohort only one of the men at risk had a stroke , and the risk estimate did not differ significantly from unity . The absolute rates of stroke in both cohorts were lower than those reported in the Framingham study , implying a lesser potential benefit from preventive measures . These lower rates should be considered in the planning of trials . The risk of stroke was significantly associated with raised systolic or diastolic blood pressure but not with age or coronary heart disease",
"We r and omized 61 patients with paroxysmal atrial fibrillation ( AF ) ( sotalol or quinidine treatment . Conversion of rhythm was recorded by Holter monitoring . The starting 80 mg dose of sotalol was repeated at 2 , 6 , and 10 hours if AF persisted ( heart rate > 80 beats/min ) , and if systolic blood was > or = 120 mm Hg . In the quinidine group , if heart rate > 100 beats/min , it was decreased with intravenous digoxin , whereafter 200 mg of oral quinidine sulfate was given maximally 3 times , each dose 2 hours apart . Conversion of AF to sinus rhythm occurred in 17 or 33 patients ( 52 % ) taking sotalol , and in 24 of 28 patients ( 86 % ) taking quinidine ( p Electric cardioversion was necessary in 39 % of the former and in 14 % of the latter group . The mean delay from first trial drug to sinus rhythm with the trial medication was 10.2 + /- 7.6 hours in the sotalol group and 4.0 + /- 2.9 hours in the quinidine group ( p sotalol ( 48 % ) because of asymptomatic bradycardia or hypotension , and in 20 taking quinidine ( 71 % ) because of rhythm conversion . Asymptomatic wide complex tachycardia ( QRS > 0.12 second ) was found in 13 % and 27 % of patients taking sotalol and quinidine , respectively . The longest RR intervals were 6.4 and 3.8 seconds in the sotalol and quinidine groups , respectively . Oral sotalol did not appear as effective as quinidine sulfate treatment in conversion of paroxysmal AF . ( ABSTRACT TRUNCATED AT 250 WORDS",
"Summary Using available data on time-concentration and time-effect relationships in normal persons the results of infusion of digoxin in various time periods were simulated and compared with administration of digoxin by bolus injections , using a three-compartment pharmacokinetic model to which a separate small side-effect compartment was subsequently added . The validity of the simulations was tested in 11 patients with rapid atrial fibrillation . Serum digoxin concentrations , ventricular rate and side effects were monitored in a double-blind study comparing an infusion of 1.5 mg digoxin over 6 h with administration of three bolus injections of 0.5 mg digoxin 8 h apart . In agreement with the predictions of the model , the maximal fall in ventricular rate was reached after 8–9 h in the infusion group and after 19–20 h in the bolus injection group , without any detectable difference in side effects . There were certain discrepancies between the results of the clinical study and the predictions of the model , e.g. in serum digoxin concentrations , perhaps due to impaired clearance in the patients .However , it is concluded that the tested model is valid in elderly patients with rapid atrial fibrillation",
"BACKGROUND Atrial fibrillation is the most commonly encountered sustained cardiac arrhythmia . Restoration and maintenance of sinus rhythm is believed by many physicians to be superior to rate control only . However , there are no prospect i ve data that compare both therapeutic strategies . METHODS The Pharmacological Intervention in Atrial Fibrillation ( PIAF ) trial was a r and omised trial in 252 patients with atrial fibrillation of between 7 days and 360 days duration , which compared rate ( group A , 125 patients ) with rhythm control ( group B , 127 patients ) . In group A , diltiazem was used as first-line therapy and amiodarone was used in group B. The primary study endpoint was improvement in symptoms related to atrial fibrillation . FINDINGS Over the entire observation period of 1 year , a similar proportion of patients reported improvement in symptoms in both groups ( 76 responders at 12 months in group A vs 70 responders in group B , p=0.317 ) . Amiodarone administration result ed in pharmacological restoration of sinus rhythm in 23 % of patients . Walking distance in a 6 min walk test was better in group B compared with group A , but assessment of quality of life showed no differences between groups . The incidence of hospital admission was higher in group B ( 87 [ 69 % ] out of 127 vs 30 [ 24 % ] out of 125 in group A , p=0.001 ) . Adverse drug effects more frequently led to a change in therapy in group B ( 31 [ 25 % ] patients compared with 17 [ 14 % ] in group A , p=0.036 ) . INTERPRETATION With respect to symptomatic improvement in patients with atrial fibrillation , the therapeutic strategies of rate versus rhythm control yielded similar clinical results overall . However , exercise tolerance is better with rhythm control , although hospital admission is more frequent . These data may serve as a basis to select therapy in individual patients",
"The safety and efficacy of the intravenous ( IV ) calcium channel blocker , verapamil , in controlling the ventricular response or converting to sinus rhythm patients with atrial flutter or atrial fibrillation were assessed . Seventeen patients ( nine with atrial flutter and eight with atrial fibrillation ) with these arrhythmias that were difficult to control pharmacologically were chosen for the study . All patients at the time of study were receiving digoxin . Either verapamil or placebo was chosen r and omly and a bolus of 0.075 mg/kg ( up to 5 mg ) was administered . Twelve patients had a marked reduction in their ventricular response after IV administration of verapamil ( seven with atrial flutter and five with atrial fibrillation ) . None of these 12 patients converted ( nonconverters ) . The average reduction in heart rate was from 120 + /- 6 beats per minute to a minimum of 83 + /- 13 beats per minute within 20 minutes after drug administration . Verapamil was found to convert five patients with atrial arrhythmias to sinus rhythm ( two with atrial flutter and three with atrial fibrillation ) ( converters ) . In addition , three patients with atrial arrhythmias of less than one month who did not convert with parenteral drug therapy converted within 24 hours while receiving the oral drug . Converters had their supraventricular arrhythmias of significantly shorter duration ( median , three hours v 30 days ) and tended to have smaller left atrial size ( 3.8 + /- 0.7 cm v 4.3 + /- 1.3 cm ) compared with the nonconverters . We conclude that verapamil is safe and effective when administered IV to patients with atrial flutter and fibrillation for control of ventricular response . In short duration atrial arrhythmias , conversion to sinus rhythm is likely once the ventricular response is controlled",
"The efficacy of amiodarone has been proved in long-term maintenance of sinus rhythm ( SR ) in patients with paroxysmal atrial fibrillation ( AF ) . The present study evaluates the efficacy and safety of a single oral dose of amiodarone in patients with recent-onset AF ( amiodarone or placebo . Conversion to SR was verified by 24-hour Holter monitoring . Ten patients were excluded because of SR in the beginning of monitoring or technical failure during Holter monitoring . The remaining study groups were comparable ( n = 31 for each ) , except that in the placebo group beta blockers were more common . The patients receiving amiodarone converted to SR more effectively than those receiving placebo ( p amiodarone group and 20 % in the placebo group ( Holter successful ) had converted to SR , whereas after 24 hours the corresponding figures were 87 % and 35 % , respectively . The median time for conversion ( 8.7 hours for amiodarone and 7.9 hours for placebo ) did not differ in the groups . Amiodarone was hemodynamically well tolerated , and the number of adverse events in the study groups was similar . Amiodarone as a single oral dose of 30 mg/kg appears to be effective and safe in patients with recent-onset AF",
"The optimal way to convert recent-onset atrial fibrillation to sinus rhythm is a subject of much debate . The effectiveness of intravenous propafenone has been shown [ 1 - 3 ] , but the full antiarrhythmic effect of this regimen depends not only on the parent compound but on its 5-hydroxylated metabolite [ 4 , 5 ] . This dependence provides a strong rationale for the use of oral loading regimens [ 3 ] . Results of previous controlled studies have shown that oral loading of propafenone is highly effective in converting recent-onset atrial fibrillation to sinus rhythm [ 6 , 7 ] . Safety is a major concern with antiarrhythmic therapy . One of the primary proarrhythmic risks of propafenone and flecainide is the transformation of atrial fibrillation to flutter with 1:1 atrioventricular conduction and hemodynamic impairment [ 8 - 10 ] . We sought to determine whether the effectiveness and safety of propafenone differ in patients who have structural heart disease and patients who do not . Methods From June 1990 to June 1994 , consecutive patients with recent-onset atrial fibrillation ( 7 days ) who presented to one of three centers were considered for enrollment . Onset of arrhythmia was documented by electrocardiography or by an abrupt onset of palpitations with subsequent evidence of atrial fibrillation on electrocardiography . Patients were excluded for any of the following reasons : age greater than 80 years , heart failure greater than NYHA ( New York Heart Association ) class II , mean ventricular rate during atrial fibrillation less than 70 beats/min , recent myocardial infa rct ion ( within bifascicular block , the sick sinus syndrome , hypokalemia ( potassium level renal or hepatic failure with severe hypoxia ( Pao 2 metabolic disturbances , or known thyroid dysfunction . Patients who were receiving long-term digoxin therapy or antiarrhythmic drugs or had received such treatments within 8 hours before study entry were also excluded . Patients who had atrial fibrillation that lasted 72 hours or longer were enrolled only if they were receiving long-term warfarin therapy for anticoagulation . Patients provided informed consent . Eligible patients had a 24-hour Holter monitor applied ; after 1 to 2 hours of observation to assess the stability of atrial fibrillation , they were r and omly assigned by center in a single-blind manner to receive propafenone ( 300 mg in two tablets as a single oral dose ) or placebo . All patients received intravenous saline throughout the study period . The electrocardiogram was monitored by telemetry , blood pressure was measured every 2 hours , and 12-lead electrocardiography was done every hour for the first 4 hours and then every 2 hours for the next 4 hours . When patients converted to sinus rhythm , 12-lead electrocardiography was done immediately . Conversion was defined as a stable sinus rhythm that lasted for at least 1 hour . Eight hours after the study drug was administered , physicians could continue treatment with the study drug or switch to a different therapeutic option . Holter monitor tapes were analyzed by two blinded observers using computer scanning systems ( Marquette 8000 , Milwaukee , Wisconsin , and Del Mar Avionics , Irvine , California ) to determine the time of conversion to sinus rhythm and whether an abnormal rhythm was present . Within 24 hours after enrollment , echocardiography was done for each patient and left atrial diameter was measured in the left parasternal long-axis view . On the basis of clinical history and the results of physical examination , echocardiography , and chest radiography , patients were classified as having structural heart disease ( defined as the presence of cardiac abnormalities other than atrial fibrillation ) , hypertension without structural heart disease ( defined as previously recognized systemic hypertension according to the criteria of the World Health Organization ) , or neither . Continuous outcomes and baseline characteristics of the patients were compared by using the chi-square statistic and t-test as appropriate . The rates of conversion to sinus rhythm were assessed at 3 and 8 hours . Odds ratios and corresponding CIs were calculated according to the methods of Gardner and Altman [ 11 ] . We did logistic regression analysis to describe how the interaction of treatment with the presence or absence of heart disease and hypertension affected the probability of conversion to sinus rhythm . Analyses were done using SPS software , version 6.1.3 ( SPS , Inc. , Chicago , Illinois ) . Results Patients During the study period , 407 patients presented to the three centers and were screened for eligibility . Two hundred forty-three patients were eligible , and 240 gave consent . A total of 164 patients were excluded for one or more of the following reasons : age greater than 80 years ( n = 10 ) , heart failure greater than NYHA class II ( n = 33 ) , recent myocardial infa rct ion ( n = 20 ) , bundle-branch block ( n = 24 ) , the sick sinus syndrome ( n = 6 ) , severe hypoxia ( n = 13 ) , thyroid dysfunction ( n = 12 ) , and previous antiarrhythmic treatment ( n = 63 ) . Two hundred forty patients were r and omly assigned to receive propafenone ( n = 119 ) or placebo ( n = 121 ) . The two groups were similar with regard to age , sex , cause of atrial fibrillation , NYHA class , left atrial dimension ( measured by echocardiography ) , structural heart disease , and hypertension ( Table 1 ) . The duration of atrial fibrillation before r and omization ranged from 2.5 to 120 hours and did not differ significantly between the treatment groups . Table 1 . Patient Characteristics Conversion to Sinus Rhythm and Presence of Heart Disease The probability of conversion to sinus rhythm was greater after propafenone than after placebo at 3 and 8 hours ( P Conversion to sinus rhythm within 8 hours in patients receiving propafenone or placebo . At 8 hours , the probability of conversion to sinus rhythm was significantly higher in the propafenone group than in the placebo group for patients who had heart disease ( odds ratio , 21.7 [ CI , 5.9 to 80.1 ] ; P Conversion rates at 8 hours for patients receiving propafenone were similar among the three heart disease subgroups , but conversion rates for patients receiving placebo differed significantly ( 56 % for patients without structural heart disease , 27 % for patients with hypertension , and 17 % patients with structural heart disease [ P = 0.009 by logistic regression model ] ) . At 3 hours , the probability of conversion to sinus rhythm was higher in the propafenone group than in the placebo group for patients who did not have heart disease ( 48 % for propafenone compared with 26 % for placebo ; odds ratio , 2.6 [ CI , 1.2 to 6.0 ] ; P = 0.02 ) , patients who had hypertension ( 41 % for propafenone compared with 16 % for placebo ; odds ratio , 3.5 [ CI , 1.2 to 10.5 ] ; P = 0.02 ) , and patients who had structural heart disease ( 47 % for propafenone compared with 7 % for placebo ; odds ratio , 12.3 [ CI , 2.5 to 60.5 ] ; P Mean time SD for conversion to sinus rhythm within 8 hours was 181 118 minutes for propafenone and 181 112 minutes for placebo ( P > 0.2 ) . Adverse Effects Sustained atrial flutter or tachycardia ( lasting 1 min ) occurred in eight patients ( 7 % ) receiving propafenone and seven patients ( 6 % ) receiving placebo ( P > 0.2 ) , regardless of heart disease status . Among these patients , atrioventricular conduction was 2:1 in two patients receiving propafenone ( heart rate , 115 to 140 beats/min ) and three patients receiving placebo ( heart rate , 120 to 150 beats/min ) , 3:1 in six patients receiving propafenone ( heart rate , 60 to 95 beats/min ) and three patients receiving placebo ( heart rate , 60 to 100 beats/min ) , and 1:1 in one patient receiving placebo ( heart rate , 240 beats/min ) . This patient developed atrial flutter and collapsed . Pauses in ventricular rate lasting longer than 2 seconds were seen in one patient ( 1 % ) receiving propafenone and three patients ( 2 % ) receiving placebo ( P > 0.2 ) . Among patients receiving propafenone , nine ( 8 % ) had the following adverse effects : QRS complexes of the electrocardiogram greater than 120 ms ( n = 3 ) , hypotension ( n = 2 ) , slight hypotension and bradycardia at conversion ( n = 3 ) , and phases of junctional rhythm after conversion ( n = 1 ) . No ventricular proarrhythmic effects occurred . Discussion Oral loading of propafenone was effective for conversion to sinus rhythm in our study , as it has been in smaller studies [ 3 , 6 , 7 , 12 , 13 ] . The recent findings of Wijffels and colleagues [ 14 ] in a model of chronic atrial fibrillation in animals indicate that electrophysiologic remodeling occurs within a few hours of persistent atrial fibrillation and results primarily from changes in atrial refractoriness that enhance the persistence of atrial fibrillation . This observation provides a strong rationale for prompt conversion to sinus rhythm . Therefore , oral loading of propafenone ( which has an effectiveness similar to that of intravenous propafenone [ 3 ] ) offers many advantages over such regimens as oral quinidine and intravenous amiodarone , which require titration of dose or a longer period of time to achieve an effect [ 6 , 13 , 15 ] . In controlled trials , propafenone was shown to be more effective and to take effect more quickly than amiodarone [ 13 ] or digoxin plus quinidine [ 6 ] . Intravenous amiodarone was no more effective than placebo ",
"In recent-onset atrial fibrillation , intravenous propafenone has been shown to effectively restore sinus rhythm , whereas the efficacy of intravenous digoxin has been question ed . We directly compared these 2 drugs and placebo in acute atrial fibrillation . One hundred twenty-three patients with atrial fibrillation lasting were r and omized to a 10-minute intravenous infusion of either propafenone ( 2 mg/kg , 41 patients ) or digoxin ( 0.007 mg/kg , 40 patients ) or placebo ( 42 patients ) . After 1 hour , nonconverted propafenone or digoxin patients were switched to the alternative drug , while nonconverted placebo patients were r and omized to either propafenone or digoxin . The observation time ended 1 hour later . By 1 hour , conversion rates were 49 % in the propafenone group , 32 % in the digoxin group ( p = 0.12 ) , and 14 % in placebo group ( p propafenone , p = 0.08 vs digoxin ) . After crossover , digoxin converted 5 % of propafenone patients , while propafenone converted 48 % of digoxin patients ( p 36 nonconverted placebo patients , sinus rhythm was obtained in 53 % of cases with propafenone , and in 5 % with digoxin ( p 116 patients who received a drug as first treatment , 30 of 60 patients ( 50 % ) were converted by propafenone versus 14 of 56 ( 25 % ) by digoxin ( p ventricular rate reduction was faster ( 15 vs 45 minutes ) and more prominent ( -24 % vs -14 % ) with propafenone than with digoxin . In conclusion , intravenous propafenone terminates atrial fibrillation more effectively than either placebo or intravenous digoxin . In addition , in nonconverted patients , it obtains a more rapid and marked control of the ventricular rate",
"The main goal of this study is to evaluate the safety and efficacy of propafenone versus sotalol as an initial choice of treatment in patients with symptomatic paroxysmal atrial fibrillation ( AF ) , according to a double-blind r and omized system . In the oral propafenone group ( n = 41 ) , 2 patients ( 5 % ) discontinued therapy because of gastrointestinal discomfort in 1 and dizziness in the other . Thirty-one ( 79 % ) of the 39 patients who continued the treatment had effective response to oral propafenone ( > 75 % reduction of symptomatic arrhythmic attacks ) on a mean dose of 663 + /- 99 mg/day with a decrease in attack frequency from 10 + /- 3 to 2 + /- 1 times per week . In the oral sotalol group ( n = 38 ) , 4 patients ( 11 % ) discontinued treatment because of dizziness in 2 and symptomatic bradycardia in 2 . Twenty-six of the 34 patients ( 76 % ) who continued the treatment had effective response to oral sotalol on a mean dose of 200 + /- 57 mg/day with a decrease in attack frequency from 11 + /- 3 to 2 + /- 1 times per week . Comparisons of the results between propafenone and sotalol groups showed a similar incidence of intolerable ( 2 of 41 vs 4 of 38 , p = 0.42 ) and tolerable side effects ( 10 of 39 vs 8 of 34 , p = 1.0 ) . The attack frequency at baseline ( 11 + /- 3 vs 10 + /- 4 times per week , p = 0.23 ) and after treatment ( 3 + /- 1 vs 3 + /- 2 times per week , p = 0.85 ) did not differ significantly between the 2 groups . The incidence of effective response to drugs was also similar ( 31 of 39 vs 26 of 34 , p = 0.78 ) . Furthermore , the decrease of symptom scores ( -32 + /- 8 % vs -29 + /- 7 % , p = 0.18 ) and percentage decrease of ventricular rate ( -15 + /- 4 % vs -18 + /- 4 % , p = 0.10 ) during AF were also similar between the 2 groups . In conclusion , oral propafenone and sotalol are equally effective and safe in preventing attacks and alleviating symptoms of paroxysmal AF",
"Summary Safety and efficacy of propafenone and disopyramide for long-term maintenance of sinus rhythm after electrical cardioversion was studied in 56 patients with chronic altrial fibrillation ( median arrhythmia duration , 5 months ) . After cardioversion , patients were r and omly assigned to receive double-blind propafenone 300 mg tid ( 25 patients ) or disopyramide 250 mg tid ( 31 patients ) . Downward dose adjustment was allowed in case of intolerable side effects . The endpoints were arrhythmia recurrence ; and side effects not amenable to dose reduction . For patients r and omized to propafenone ( mean dose , 878±65 mg/day ) , 66 % [ 95 % confidence interval [ ( CI ) 46–85 % ] and 55 % ( 95 % CI , 34–76 % ) remained in sinus rhythm at 3 and 6 months , respectively ( Kaplan-Meier method ) . Similar figures were found with disopyramide ( mean dose , 704±81 mg/day ) : 71 % ( 95 % CI , 54–87 % ) and 67 % ( 95 % CI , 50–84 % ) at 3 and 6 months , respectively ( p = NS ) . In the patients with a relapse of atrial fibrillation , the ventricular rate while still using the prophylactic agents did not increase significantly compared with precardioversion . However , one patient on disopyramide had an excessively high relapse heart rate ( 170 vs. 100 beats/min ) . Side effects were more frequent on disopyramide . Side effects necessitating drug discontinuation occurred in 12 patients : 4 patients ( 16 % ) on propafenone and 8 ( 26 % ) on disopyramide . Severe adverse effects occurred in two patients , who developed heart failure while on disopyramide . There were no proarrhythmic events or deaths . Thus , propafenone and disopyramide are equally effective for maintaining sinus rhythm after cardioversion of atrial fibrillation . Propafenone is , however , better tolerated than disopyramide , which may cause heart failure ",
"This study sought to compare the efficacy and safety of intravenous flecainide and sotalol for immediate cardioversion of atrial fibrillation . We performed a prospect i ve , r and omized , single-blind , multicenter trial , including 106 hemodynamically stable patients with atrial fibrillation , stratified according to duration of the arrhythmia . Exclusion criteria included severely reduced left ventricular systolic function , recent antiarrhythmic therapy , and hypokalemia . Patients were r and omly assigned to receive either intravenous flecainide or intravenous sotalol . Trial medication was given at a dose of 1.5 mg/kg body weight ( maximum 150 mg ) . Overall , 28 of 54 patients ( 52 % ) given flecainide and 12 of 52 patients ( 23 % ) given sotalol converted to sinus rhythm during the first 2 hours after start of the infusion ( p = 0.003 ) . Multivariate analysis confirmed that treatment allocation to flecainide , an arrhythmia duration of plasma magnesium level at baseline , higher age for men , and lower age for women independently increases the probability of conversion . The frequency of adverse effects was not significantly different in the 2 treatment groups",
"BACKGROUND Because most strokes cause neurological impairment rather than death , stroke prophylaxis may improve quality of life more than length of life . Thus , an underst and ing of how stroke and stroke prophylaxis affect quality of life is central to clinical decision making for many patients . METHODS We elicited quality -of-life estimates , known as utilities , for 3 degrees of severity of anticipated stroke-mild , moderate , and major- and for stroke prophylaxis with either warfarin sodium or aspirin therapy . We used the time tradeoff and st and ard gamble methods to elicit these utilities from 83 patients who had atrial fibrillation . RESULTS Seventy patients completed the interview successfully . Their utilities for stroke ranged from worse than death ( current health ( 1.0 ) . The median utilities for mild , moderate , and major stroke were 0.94 , 0.07 , and 0.0 , respectively . Although the median utilities decreased with increasing severity of stroke ( P stroke utilities , the median utilities for warfarin and aspirin therapy were high-0.997 and 1.0 , respectively . However , the interpatient variability for warfarin therapy was also important : 11 patients ( 16 % ) with atrial fibrillation rated the utility of warfarin therapy so low that their quality -adjusted life expectancy would be greater with aspirin . CONCLUSION Patients ' utilities for stroke prophylaxis and anticipated stroke vary substantially . Many patients view the quality of life with major stroke as tantamount to or worse than death . These findings highlight the relevance of incorporating patient preferences when choosing stroke prophylaxis",
"BACKGROUND A study was conducted to determine the efficacy and safety of ibutilide fumarate versus placebo in the acute termination of atrial flutter and fibrillation . METHODS AND RESULTS Two hundred sixty-two patients aged 28 to 88 years with atrial flutter or fibrillation duration of 3 hours to 90 days were r and omly assigned in a 5:1 ratio ( ibutilide : placebo ) to receive two 10-minute infusions , 10 minutes apart , of ibutilide ( 1 mg ) or placebo . Patients were hospitalized and monitored by telemetry for 24 hours , with follow-up 72 hours later . Seventy-three ( 34.9 % ) of 209 evaluable ibutilide recipients had termination of atrial flutter or fibrillation within 1.5 hours compared with 0 ( 0 % ) of 41 placebo recipients . Those with atrial flutter had a higher success rate . At hour 24 , 86.3 % remained in normal or alternative sinus rhythm . Of the patients who received ibutilide , 2.3 % experienced drug-related sustained polymorphic or monomorphic ventricular tachycardia and recovered after intervention . Additionally , 7.3 % experienced nonsustained polymorphic or monomorphic ventricular tachycardia . Other frequent medical events in ibutilide recipients were generally also noted in the placebo group . CONCLUSIONS Ibutilide is effective and safe for acute termination of atrial fibrillation or atrial flutter ",
"Abstract In new-onset atrial fibrillation ( AF ) , digoxin has a limited ability to control ventricular response , is no better than placebo for facilitating conversion to sinus rhythm , and has a slow onset of action with a narrow toxic-therapeutic ratio . 1,2 Magnesium ( Mg ) has been shown to slow and sometimes normalize the heart rhythm in supraventricular tachyarrhythmias . 3,4 A r and omized trial found Mg prevents AF in patients after cardiac surgery.5 Because of these factors , we conducted a prospect i ve , r and omized , double-blind , placebo-controlled study addressing whether Mg and digoxin were superior to digoxin alone in controlling the ventricular response of AE",
" Thirteen patients in chronic atrial fibrillation with a normal resting heart rate but with exercise tachycardia and episodes of bradycardia were r and omised to treatment periods of two weeks on xamoterol ( 200 mg twice daily ) , low dose digoxin , or placebo , in a blind crossover study . The results ( mean SEM ) of symptom scores , a treadmill exercise test , and 24 hour ambulatory electrocardiographic monitoring were obtained . Xamoterol improved symptom scores and controlled exercise heart rate better than digoxin . Xamoterol was better than digoxin or placebo in reducing the heart rate response to exercise and tended to improve exercise duration . Xamoterol , by reducing the daytime maximum hourly heart rate and increasing the night time minimum hourly heart rate , significantly reduced the difference between the two compared with placebo . In contrast , digoxin tended to reduce both the maximum and minimum hourly heart rates through day and night . Both the frequency and duration of ventricular pauses were reduced by xamoterol but tended to increase with digoxin . Xamoterol reduced both the circadian variation in ventricular response to atrial fibrillation and exercise tachycardia by modulating the heart rate according to the prevailing level of sympathetic activity . These changes were translated into symptomatic benefit for the patients studied",
"The effect and choice of a drug to control heart rate for symptomatic improvement in patients with isolated mitral stenosis with normal sinus rhythm ( n = 10 ) or atrial fibrillation ( n = 10 ) were studied . Digoxin ( 0.25 - 0.5 mg daily ) , metoprolol ( 50 - 100 mg twice a day ) and verapamil ( 40 - 80 mg three times a day ) were evaluated for this purpose . An open r and omised cross-over design was followed . The efficacy of a drug was evaluated by : ( 1 ) subjective improvement on a visual analog scale , and ( 2 ) objective improvement on repeated multi-stage symptom-limited treadmill exercise . In patients with sinus rhythm greater than or equal to 50 % subjective improvement was seen in 90 % , 40 % and nil with metoprolol , verapamil and digoxin , respectively . The total work done by these patients was 1008 + /- 541 kpm ( control ) , 2869 + /- 1418 kpm on metoprolol , 2369 + /- 884 kpm on verapamil and 1654 + /- 918 kpm on digoxin . In patients with atrial fibrillation greater than or equal to 50 % subjective improvement was seen in 80 % , 40 % and 30 % with verapamil , metoprolol and digoxin , respectively . The total work done by these patients was 555 + /- 232 kpm ( control ) , 1379 + /- 553 kpm on verapamil , 1251 + /- 575 kpm on metoprolol and 716 + /- 340 kpm on digoxin . The degree of improvement on a drug appeared to be a function of its ability to control resting and exercise heart rates in two different rhythms in these patients . ( ABSTRACT TRUNCATED AT 250 WORDS",
"In patients with recent-onset atrial fibrillation ( AF ) , restoration of sinus rhythm is considered to be the first-line therapeutic option . Although this conversion might be obtained by direct-current shock or intravenous antiarrhythmic drugs , administration of an oral loading dose of class I or III antiarrhythmic drugs is more simple and convenient . This prospect i ve , r and omized , multicenter study compares the time to conversion to sinus rhythm obtained with an oral loading dose of propafenone or amiodarone . Patients with recent-onset AF ( , were r and omly assigned to be treated with propafenone ( 600 mg for the first 24 hours and if necessary a repeated dose of 300 mg for 24 hours ) or amiodarone ( 30 mg/kg for the first 24 hours and if necessary a repeated dose of 15 mg/kg for 24 hours ) . Exact conversion time during the first 24 hours was determined by Holter monitoring . In each treatment group 43 patients with the same baseline characteristics were included . The median time for restoration of sinus rhythm was shorter ( p = 0.05 ) in the propafenone ( 2.4 hours ) than in the amiodarone ( 6.9 hours ) group . After 24 hours ( 56 % in the propofenone and 47 % in the amiodarone group ) and 48 hours , the same proportion of patients in the 2 groups recovered sinus rhythm ( no serious adverse events were noticed ) . Thus , oral loading dose of propafenone or amiodarone was safe with a similar conversion rate of recent-onset AF . Propafenone had a faster action",
"The safety of a method of outpatient antiarrhythmic drug loading utilizing a continuous loop event recorder was evaluated . The findings suggest that the st and ard 2-day hospital admission for drug loading is not necessary in all patients and a method of outpatient loading may be equally safe",
"OBJECTIVES Our aim was to evaluate the benefits and risks of administering propafenone before electrical defibrillation for chronic atrial fibrillation . BACKGROUND In this context , an antiarrhythmic drug-although potentially useful in preventing early recurrence of arrhythmia-could adversely affect the defibrillation threshold and reduce the cardioversion success rate . METHODS We r and omly assigned 100 patients with chronic atrial fibrillation to oral treatment with either placebo ( 51 patients ) or 750 mg/day of propafenone ( 49 patients ) for 48 h before administration of direct current shock . After successful cardioversion , all patients received propafenone therapy and were followed up for 48 h. RESULTS Before defibrillation , three patients in the propafenone group ( 6.1 % ) had reversion to sinus rhythm and one had sustained ventricular tachycardia . Shock efficacy ( 82.4 % vs. 84.4 % ) and the cumulative effective energy ( 395 + /- 258 vs. 421 + /- 236 J ) were not different between the placebo and propafenone groups . In the propafenone group , 11 patients had their arrhythmia transformed into atrial flutter and required a lower energy level for arrhythmia conversion than did the other patients with continued atrial fibrillation ( 245 + /- 197 vs. 493 + /- 215 J , p energy requirements than that of patients who received placebo . The incidence of asymptomatic bradyarrhythmias was higher in the propafenone group ( 28.9 % vs. 7.1 % , p placebo had early recurrence of atrial fibrillation ( 16.7 % vs. 0 % , p propafenone ( 73.5 % vs. 52.9 % , p sinus rhythm . During the in-hospital stay , propafenone was withdrawn from six patients ( 6.6 % ) because of side effects . CONCLUSIONS Propafenone , given before electrical cardioversion for chronic atrial fibrillation does not affect the mean defibrillation threshold or the rate of successful arrhythmia conversion . It decreases the recurrence of atrial fibrillation early after shock , thus allowing more patients to be discharged from the hospital with sinus rhythm",
"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",
"BACKGROUND Clinical features that consistently predict ischemic stroke in patients with nonvalvular atrial fibrillation have been identified , while echocardiographic risk factors are less well defined . OBJECTIVE To determine whether the results of transthoracic echocardiography add independent information to the clinical risk factors for stroke in patients with atrial fibrillation . METHODS Transthoracic echocardiographic findings and clinical features from 1066 patients with atrial fibrillation assigned to placebo or control in 3 r and omized trials ( Boston Area Anticoagulation Trial for Atrial Fibrillation , Stroke Prevention in Atrial Fibrillation I Study , and Veterans Affairs Prevention in Atrial Fibrillation Study ) were correlated with subsequent ischemic stroke by multivariate analysis . RESULTS The mean + SD age of patients was 67 + /- 10 years , 78 % were men , 55 % had a history of hypertension , 19 % had a history of diabetes , 7 % had a previous transient ischemic attack or stroke , and 27 % had a history of heart failure . During a mean follow-up of 1.6 years , 78 ischemic strokes occurred ( annual rate , 4.7 % ) . Moderate to severe left ventricular systolic dysfunction shown via 2-dimensional echocardiography was a strong independent predictor of stroke ( relative risk , 2.5 ; P stroke ( relative risk , 1.02/mm ; P = .10 ) . Of 163 patients categorized as low risk based on clinical features ( annual stroke rate , 0.8 % ; 95 % confidence interval , 0.2%-3.0 % ) , 10 had moderate to severe left ventricular dysfunction shown via 2-dimensional echocardiography and a 9.3 % per year risk of stroke ( 95 % confidence interval , 1.3%-66 % ) . Conversely , 728 of the 847 patients at high risk for stroke based on clinical criteria had normal or mildly abnormal left ventricular function ; their stroke rate was 4.4 % ( 95 % confidence interval , 3.4%-5.8 % ) . CONCLUSIONS Left ventricular systolic dysfunction shown via 2-dimensional transthoracic echocardiography independently predicts risk of stroke in patients with atrial fibrillation . Echocardiography may prove most useful in a small group of patients who have a low risk of stroke according to clinical factors",
"Nadolol , a long-acting beta-adrenergic-blocking agent , was evaluated in 20 patients with chronic atrial fibrillation by means of a r and omized , double-blind , crossover study . Patients were required either to demonstrate resting heart rates in excess of 80 bpm or to show a rate of 120 bpm or an increment of greater than 50 bpm during mild treadmill exercise provocation ( 3 minutes , 1.75 mph , 10 % grade ) . With placebo the group averaged a heart rate of 92 + /- 19 bpm , determined by 24 hours of ambulatory ECG recordings ; this rate was significantly reduced to 73 + /- 16 bpm ( p less than 0.001 ) with nadolol ( mean dosage , 87 + /- 43 mg/day ) . During st and ardized exercise testing , heart rates increased to 153 + /- 26 bpm with placebo and to 111 + /- 24 bpm with nadolol ( p less than 0.001 ) , representing 65 % and 52 % increments , respectively . Digoxin blood levels averaged 0.8 + /- 0.5 ng/ml with placebo and were similar with nadolol ( 0.9 + /- 0.4 ; p = NS ) . Total exercise time on a modified Bruce treadmill protocol was 466 + /- 143 seconds with placebo and was significantly decreased by nadolol ( 380 + /- 143 ; p less than 0.01 ) . During initial dose titration with nadolol , one patient was dropped from study for intolerable fatigue and one for worsened claudication . No patients were dropped from the double-blind treatment periods , although two patients receiving nadolol and one patient receiving placebo complained of moderate fatigue . We conclude that nadolol is a safe and effective agent for the control of spontaneous and exercise-provoked heart rates in patients with chronic atrial fibrillation who were already receiving digoxin treatment",
"Background : The management of permanent atrial fibrillation ( PAF ) consists primarily of long‐term anticoagulation with either aspirin or warfarin to prevent systemic embolization , and modulation of ventricular rate ( VR ) to improve cardiac function by prolonging the ventricular diastolic filling time",
"OBJECTIVES This study was design ed to test the hypothesis that conversion of atrial flutter in humans by ibutilide , a new class III antiarrhythmic agent , is characterized by an increase in atrial cycle length variability . BACKGROUND Conversion of tachyarrhythmias has been associated with increased oscillations of cycle length . METHODS Electrograms and monophasic action potentials from the right atrium in 35 patients with spontaneous , sustained atrial flutter were recorded before , during and after intravenous ibutilide ( 0.005 to 0.025 mg/kg body weight , n = 25 ) or placebo ( n = 10 ) . Atrial cycle length , cycle length variability ( coefficient of variation ) , diastolic interval and diastolic interval variability were measured from 10 consecutive cycles at baseline and 3 min before , 1 min before , 30 s before and immediately before conversion . Similar measurements were made in patients who received ibutilide or placebo but did not convert . RESULTS Ibutilide converted atrial flutter in 14 of 25 patients 25 + /- 16 min ( mean + /- SD ) after initiation of the infusion , whereas placebo converted no patients . Atrial cycle length was prolonged to the same extent in ibutilide converters and nonconverters ( 36 + /- 19 vs. 38 + /- 21 ms , p = NS ) and was not affected by placebo . Beat-to-beat variability in atrial cycle length ( baseline 1.2 + /- 0.7 vs. preconversion 7.3 + /- 4.9 , p diastolic interval ( baseline 11 + /- 8 vs. preconversion 33 + /- 23 , p ibutilide nonconverters and placebo group patients . CONCLUSIONS Ibutilide prolongs atrial cycle length , but conversion of atrial flutter by ibutilide is characterized by increased variability in atrial cycle length and diastolic interval",
"The effects of two calcium channel blockers , diltiazem ( 270 mg/day ) and verapamil ( 240 mg/day ) , were studied in 18 patients with chronic atrial fibrillation . During 24 h Holter electrocardiographic monitoring , mean ventricular rate ( beats/min ) decreased from 88 + /- 14 with placebo to 76 + /- 13 ( p less than 0.001 ) with diltiazem and 80 + /- 11 ( p less than 0.01 ) with verapamil . Maximal symptom-limited exercise tolerance ( W ) increased from 127 + /- 39 during the placebo period to 136 + /- 42 ( p less than 0.01 ) with diltiazem and 137 + /- 39 ( p less than 0.01 ) with verapamil . Ventricular rate and rate-pressure product were lower at rest and during exercise with diltiazem and verapamil than with placebo ( p less than 0.001 ) , with the drugs being similarly effective . Ventricular rate at maximal exercise ( beats/min ) was 179 + /- 13 with placebo compared with 159 + /- 21 with diltiazem and 158 + /- 23 with verapamil . Maximal oxygen uptake ( ml/kg per min ) was 22.3 + /- 4.5 with placebo , 23.7 + /- 4.9 ( p less than 0.05 ) with diltiazem and 22.9 + /- 4.5 with verapamil ( p = NS ) . Respiratory gas exchange anaerobic threshold was reached at a work load ( W ) of 76 + /- 21 with placebo , 84 + /- 27 ( p less than 0.05 ) with diltiazem and 85 + /- 23 ( p less than 0.01 ) with verapamil . In conclusion , patients with chronic atrial fibrillation have modestly improved exercise tolerance with calcium channel blockade therapy . The dromotropic responses and the effects on physical performance are of similar magnitude for diltiazem and verapamil",
"Beta-adrenergic blocking agents are useful in controlling excessive ventricular rate in chronic atrial fibrillation ( AF ) but often reduce exercise capacity . To investigate the advantage of labetalol -- a unique beta blocker with alpha-blocking property -- in chronic AF , 10 patients without underlying structural heart disease were studied with treadmill test , 12-minute walk and 24-hour ambulatory electrocardiographic monitoring . Patients were r and omized and crossed over to receive 4 phases of treatment ( placebo , digoxin , digoxin with half-dose labetalol , and full-dose labetalol ) . Exercise duration s were 14.1 + /- 1.5 , 14.2 + /- 1.5 , 16.1 + /- 1.1 and 15.6 + /- 1.1 minutes , respectively , indicating that labetalol did not reduce exercise tolerance . Although digoxin had no advantage over placebo in controlling maximal heart rate ( 177 + /- 2 vs 175 + /- 3 beats/min ) , labetalol , both as monotherapy or as an adjunct to digoxin , was advantageous ( 156 + /- 4 vs 177 + /- 2 beats/min , p less than 0.01 , and 154 + /- 4 vs 177 + /- 2 beats/min , p less than 0.01 , respectively ) . The rate-pressure product was consistently lowered by labetalol at rest and during exercise . At peak exercise , the addition of labetalol to digoxin reduced the maximal rate-pressure product achieved from 30,900 + /- 1300 to 24,100 + /- 2,000 mm Hg/min ( p less than 0.01 ) and the maximal rate-pressure product was lowest with full-dose labetalol ( 22,300 + /- 1,600 mm Hg/min ) . During submaximal exercise on treadmill or during the 12-minute walk , the combination of labetalol and digoxin produced the best heart rate control , whereas labetalol monotherapy was comparable to digoxin therapy . ( ABSTRACT TRUNCATED AT 250 WORDS",
"Magnesium has previously been used in the treatment of various arrhythmias , but few r and omized and prospect i ve studies are available . In a single‐blind study , the efficacy and safety of intravenous magnesium sulfate ( bolus doses of 5 + 5 mmol followed by infusion of 0.04 mmol/min ) versus verapamil ( 5 + 5 mg followed by 0.1 mg/min ) was evaluated in 57 patients with supraventricular arrhythmias ( supraventricular tachycardia , atrial fibrillation , and atrial flutter ) of recent onset ( less than 1 week ) . Fifteen ( 58 % ) of the patients receiving magnesium ( n = 26 ) converted to sinus rhythm within 4 h , and 16 ( 62 % ) within 24 h. Verapamil caused a lower ventricular rate , but only six ( 19 % ) of the patients ( n = 31 ) converted to sinus rhythm within 4 h ( p No side effects were observed during magnesium infusion , whereas six patients receiving verapamil had to be withdrawn from further study medication due to symptomatic side effects ( hypotension in three , cardiac failure in three ) . Magnesium appears to be an effective and safe drug for the treatment of supraventricular arrhythmias . The overall efficacy for conversion to sinus rhythm is at least as effective as with verapamil , and its action is more rapid",
"In a r and omized , double-blind , controlled study of 98 patients with atrial fibrillation ( AF ) ( present for > or = 30 minutes , or = 100 beats/min ) , intravenous flecainide ( 2 mg/kg , maximum 150 mg ) was compared with intravenous amiodarone ( 7 mg/kg ) and placebo . Exclusion criteria included significant left ventricular dysfunction , inotrope dependence , recent antiarrhythmic therapy , hypokalemia , and pacemaker dependence . Reversion to stable sinus rhythm within 2 hours of starting medication was considered likely to be due to drug effect . Twenty of 34 patients ( 59 % ) given flecainide , 11 of 32 ( 34 % ) given amiodarone , and 7 of 32 ( 22 % ) given placebo reverted to stable sinus rhythm in stable rhythm with flecainide than with placebo ( p = 0.005 ; odds ratio 5.1 , 95 % confidence interval 1.54 to 17.5 ) . There was no significant difference between amiodarone and placebo or between flecainide and amiodarone . However , after 8 hours there were no significant differences in reversion between the treatment groups : flecainide ( n = 23 , 68 % ) , amiodarone ( n = 19 , 59 % ) , and placebo ( n = 18 , 56 % ) . Amiodarone promptly reduced the ventricular rate , and this effect was maintained for 8 hours in those whose reversion to stable sinus rhythm was unsuccessful : flecainide was no more effective than placebo in controlling ventricular rate . Adverse effects were not significantly different in the 3 groups . Thus , intravenous flecainide results in earlier reversion of AF than does intravenous amiodarone or placebo . Amiodarone , although less effective in reverting AF , slows the rapid ventricular response . ( ABSTRACT TRUNCATED AT 250 WORDS",
"In a prospect i ve , single-blind trial , we r and omized 150 consecutive symptomatic patients with acute ( flecainide , propafenone , or amiodarone . Flecainide and propafenone were administered as a bolus dose of 2 mg/kg in 20 minutes . A second bolus dose of 1 mg/kg in 20 minutes was administered if conversion to sinus rhythm was not achieved after 8 hours . Amiodarone was administered as a bolus of 5 mg/kg in 20 minutes followed by a continuous infusion of 50 mg/hour . By the end of a 12-hour observation period , conversion to sinus rhythm was achieved in 45 patients ( 90 % ) in the flecainide group , 36 ( 72 % ) in the propafenone group , and 32 ( 64 % ) in the amiodarone group ( p = 0.008 for the overall comparison , p = 0.002 for flecainide vs amiodarone , p = 0.022 for flecainide vs propafenone , and p = 0.39 for propafenone vs amiodarone ) . When compared with amiodarone , this higher reversion rate with flecainide was present from the first hour of the study period . However , only after administering the second bolus was there a significant difference between flecainide and propafenone . Median time to conversion to sinus rhythm was different among groups ( p flecainide ( 25 minutes ; range 4 to 660 ) and propafenone ( 30 minutes ; range 10 to 660 ) groups than in the amiodarone group ( 333 minutes ; range 15 to 710 ; p Flecainide , at the doses administered in this study , is more effective than propafenone and amiodarone for conversion of acute atrial fibrillation to sinus rhythm . Propafenone and amiodarone have similar conversion rates , although propafenone was faster in achieving the conversion to sinus rhythm",
"A population of 105 patients with recent onset ( was r and omly treated with propafenone as a single oral loading dose of 450 mg ( Regimen A ) or 600 mg ( Regimen B ) or with placebo . A 24-h Holter was performed . Criteria of efficacy were conversion to sinus rhythm at 2 , 4 and 8 h compared to placebo and also significant reduction of mean ventricular rate in persistent atrial fibrillation . After 2 h , regimen B was more effective than either regimen A ( 43 % vs. 8 % ; p = 0.001 ) or placebo ( 11 % ; p = 0.004 ) . At 4 h , both the active treatments were more effective than placebo ( 17 % vs. 46 % regimen A and 57 % vs. regimen B ; p Sinus rhythm resumed within 24 h in 71 % , 80 % and 69 % of the patients with regimen A , B and placebo , respectively ( p = not significant ) . The mean ventricular rate reduction after 1 h was 8 % , 11 % and 4 % for regimen A , B and placebo , respectively ( p major adverse effect occurred . Atrial flutter with 1:1 atrioventricular conduction only in one case who received placebo . Propafenone acute oral administration is more effective than placebo in rapidly converting recent-onset atrial fibrillation to sinus rhythm and may be the treatment of choice in this setting limiting hospitalization and contributing to improved quality of life",
"Fifty-three patients with chronic atrial fibrillation participated in a r and omized cross-over trial in order to compare the ability of two drug regimens to establish and maintain sinus rhythm . The patients were given orally either sustained release quinidine 0.4 g twice day or verapamil 80 mg three times a day . Thirty-one patients tried both regimens . Quinidine was found to have a greater ability to induce conversion to sinus rhythm by drug alone ( p less than 0.05 ) and also a greater ability to maintain sinus rhythm after conversion ( after 3 months p less than 0.05 ) . There was , however , also a significantly larger proportion of patients on quinidine who were withdrawn from the study due to side effects and two patients on quinidine died outside hospital . The study indicate that quinidine is somewhat superior to verapamil both in the establishing and preserving of sinus rhythm in subjects who are able to tolerate the drug",
"To assess the cardiac and extracardiac safety and efficacy of flecainide versus propafenone in patients suffering from episodes of paroxysmal atrial fibrillation ( AF ) or atrial flutter , 97 patients were enrolled in a r and omized , open-label , long-term , parallel , comparative multicenter study . The diagnosis of paroxysmal AF or atrial flutter had to be fully documented prior to inclusion in the study . Of the 97 patients enrolled in the study , 48 patients ( 25 men , 23 women , mean age 62.4 + /- 12.3 years ) received flecainide ; 49 patients ( 26 men , 23 women , mean age 63.6 + /- 12.2 years ) received propafenone . The initial dose of flecainide was 50 mg twice daily , and this could be increased in steps of 50 mg twice daily every 4 days to a maximum of 300 mg/day . The initial dose of propafenone was 300 mg twice daily and this could be increased in steps of 300 mg every 4 days to a maximum of 1200 mg/day . At each visit , medical events , vital sign measurements ( blood pressure , pulse rate ) , concomitant medications , adverse experiences , and study drug dosage changes were evaluated . Routine clinical laboratory tests were evaluated at the month 6 visit , and a 24-hr Holter recording was obtained at the month 1 visit . Almost half ( 45 ) of the patients were discontinued from the study before completing 1 year of therapy . The probability of successful treatment versus time -- i.e . , the proportion of patients who remained on therapy over the course of 1 year therapy -- was 0.619 for the flecainide group and 0.469 for the propafenone group ( p = 0.079 ; difference not significant ) . The difference is largely attributed to the higher proportion of patients in the propafenone group ( 9 ) than in the flecainide group ( 2 ) who experienced side effects important enough to stop the treatment . ( The incidence of side effects was not statistically different between treatment groups , although it was higher in the propafenone group . ) The proportion of patients who discontinued treatment due to inadequate response was similar in the 2 groups : 11 patients ( 22.9 % ) in the flecainide group and 12 patients ( 24.4 % ) in the propafenone group withdrew from the study , primarily because of an inadequate response , i.e. , they experienced an increase in duration , frequency , and severity of attacks of AF or atrial flutter . Neurologic signs , central and peripheral , were mostly encountered in the flecainide group ( 8.5 % ) , and , gastrointestinal effects were more often reported in the propafenone group ( 16.7 % ) . In paroxysmal AF and paroxysmal atrial flutter , flecainide and propafenone are equally effective . However , in this study the probability of a patient 's staying on flecainide after 1 year had a tendency to be higher than the probability of staying on propafenone , due to a greater proportion of secondary effects with propafenone",
"To evaluate the efficacy of propafenone in converting recent‐onset atrial fibrillation ( AF ) lasting propafenone ( Group 1 , n = 98 ) and with placebo 0.9 % saline solution ( Group 2 , n = 84 ) in a double blind study . The treatment was continued until sinus rhythm ( SR ) was restored , but for no more than 24 h. Eighty‐nine patients treated with propafenone ( 90.8 % ) and 27 patients treated with placebo ( 32.1 % ) responded to the treatment and SR was restored ( p The mean time for SR restoration was 2.51± 2.77 h in Group 1 , and 17.15± 7.8 h in Group 2 ( p larger left atrial size and longer duration of AF than responders at the onset of the arrhythmia . Nonresponders in Group 1 showed a decrease in mean ventricular rate ( MVR ) from 143± 16 to 101± 18 ( p no reduction of MVR was observed . Two patients whose SR was restored with propafenone had sinus st and still lasting 3.4 and 3.8 s , respectively . Propafenone used intravenously is an effective , quick , and safe drug for treating AF . Moreover , it significantly reduces MVR in nonresponders",
"In a single-blind r and omized study , the efficacy and safety of intravenous propafenone ( 2 mg/kg body weight per 10 min ) versus flecainide ( 2 mg/kg per 10 min ) were assessed in 50 patients with atrial fibrillation or flutter . Treatment was considered successful if sinus rhythm occurred within 1 h. Conversion to sinus was achieved in 11 ( 55 % ) of 20 patients with atrial fibrillation treated with propafenone and in 18 ( 90 % ) of 20 with atrial fibrillation treated with flecainide ( p less than 0.02 ) . If atrial fibrillation was present less than or equal to 24 h , conversion to sinus rhythm was achieved in 8 ( 57 % ) of 14 patients in the propafenone group and 13 ( 93 % ) of 14 in the flecainide group ( p less than 0.05 ) . Atrial flutter was converted in two ( 40 % ) of five patients treated with propafenone and in one ( 20 % ) of five with flecainide ( p = NS ) . Mean time to conversion was 16 + /- 10 min in the propafenone group versus 18 + /- 13 min in the flecainide group ( p = NS ) . QRS lengthening ( 83 + /- 15 to 99 + /- 20 ms ) was observed only in the patients treated with flecainide ( p less than 0.001 ) . Patients successfully treated with propafenone showed significantly higher plasma levels than those whose arrhythmia did not convert to sinus rhythm . Transient adverse effects were more frequent in the flecainide group ( 40 % ) than in the propafenone group ( 8 % ) ( p less than 0.01 ) . In conclusion , at a dose of 2 mg/kg in 10 min , flecainide is more effective than propafenone for conversion of paroxysmal atrial fibrillation to sinus rhythm . However , considering the propafenone plasma levels and very few adverse effects , the dose or infusion rate , or both , used in the propafenone group may not have been sufficient to achieve an optimal effect . Neither drug seems very effective in patients with atrial flutter",
"The efficacy and safety of flecainide were studied in the maintenance of sinus rhythm after electrical cardioversion for chronic atrial fibrillation or atrial flutter . Eighty-one patients were r and omized to flecainide treatment or no treatment . Baseline characteristics of both groups were comparable . Compared to previous studies , patients could be classified as difficult-to-treat patients . Multiple regression analysis showed New York Heart Association class I for exercise tolerance ( p = 0.0004 ) and flecainide treatment ( p = 0.01 ) to be the main factors increasing the arrhythmia-free episode . However , Mantel-Cox lifetable analysis did not reveal significant differences between arrhythmia-free survival curves of both treatment groups . In the flecainide-treated group , 9 % of patients experienced side effects , mostly related to negative dromotropic effects . The incidence of ventricular proarrhythmia in this group of patients was low . Thus , flecainide may be effective in postponing arrhythmia recurrence , even in difficult-to-treat patients . Caution should be excercised in treating patients with underlying conduction disturbances , sick sinus syndrome or characteristics favoring development of ventricular proarrhythmia",
"Summary : Thirty-four patients with atrial fibrillation complicating suspected acute myocardial infa rct ion were r and omised to treatment with intravenous amiodarone ( n = 18 ) or intravenous digoxin ( n = 16 ) . After 24 h , similar proportions of patients in each group had reverted to sinus rhythm . However , there was a tendency towards earlier reversion with amiodarone . At 4 h , 72 % of the amiodarone group had reverted to sinus rhythm , compared with 31 % of the digoxin group ( p amiodarone 75 % reversion , digoxin 10 % reversion ) . Neither drug had a significant effect on blood pressure . Atrial fibrillation may cause serious haemodynamic deterioration in acute myocardial infa rct ion . In comparison with digoxin , amiodarone offers more rapid control of the ventricular response rate and may , in addition , restore sinus rhythm more rapidly",
"The effect of the combined treatment with propranolol 20 mg tid and diltiazem 60 mg tid in patients with chronic atrial fibrillation treated with digoxin was evaluated . Thirteen patients entered a double‐blind , three‐phase crossover study . Heart rate was significantly reduced during rest and at maximal exercise ( p in maximal work load , exercise time , systolic blood pressure at maximal work load , or subjective sensation of well‐being could be demonstrated during combined drug treatment . The RR distribution pattern was unaffected by the addition of propranolol , diltiazem , or their combination to the chronic digoxin treatment . It is concluded that the combination of diltiazem and propranolol has no advantages over any of these drugs singly , in the moderation of heart rate in patients with atrial fibrillation even combined with basic digitalis treatment , and that the intrinsic AV nodal function is unaffected by these drugs or their combination",
"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",
"UNLABELLED The efficacy and safety of intravenous propafenone , amiodarone , or placebo were compared in the treatment of atrial fibrillation ( AF ) of recent onset ( duration METHODS 143 patients ( 77 men , mean age 63 + /- 12 years ) were studied , of whom 46 received propafenone ( 2 mg/kg over 15 minutes followed by 10 mg/kg over the next 24 hours ) , 48 received amiodarone ( 300 mg intravenously over 1 hour , followed by 20 mg/kg over the next 24 hours , plus 1,800 mg/day orally , in 3 divided doses ) , and 49 received placebo ( the equivalent amount of saline i.v . over 24 hours ) . Digoxin was administered to all patients who had not previously received it . RESULTS Conversion to normal sinus rhythm occurred in 36 of 46 patients ( 78.2 % ) receiving propafenone , in 40 of 48 patients ( 83.3 % ) receiving amiodarone , and in 27 of the 49 ( 55.10 % ) controls ( P placebo , between drugs NS ) . The mean time to conversion was 2 + /- 3 hours for propafenone , 7 + /- 5 hours for amiodarone , and 13 + /- 9 for placebo ( P smaller atria than those who did not ( diameter : 42.7 + /- 5 vs 47.2 + /- 7 mm , P amiodarone group because of an allergic reaction and in two patients in the propafenone group because of excessive QRS widening . No side effects were observed in the placebo group . CONCLUSIONS Both drugs tested intravenously were equally effective and safe for the rapid conversion of recent-onset atrial fibrillation to sinus rhythm . However , propafenone offered the advantage of more rapid conversion than amiodarone",
"Fourteen patients ( four females ) with chronic atrial fibrillation were entered into a r and omized , double-blind crossover study to compare the effects of treatment with diltiazem alone , digoxin alone , and a combination of diltiazem plus digoxin . The dose of digoxin was adjusted so as to achieve serum concentrations within the range 1.3 - 2.6 nmol l-1 between six and eight hours after dosing . Four patients were withdrawn from the study ; three patients experienced side effects while taking diltiazem and one reverted to sinus rhythm while taking digoxin . Among the remaining 10 patients , mean heart rates were significantly lower during treatment with the combination of digoxin and diltiazem than with digoxin alone both at rest , after exercise and during ambulatory ECG monitoring . Post-exercise heart rates were reduced by 15 % with combination therapy when compared with digoxin alone ( 151.9 vs. 128.1 bpm ) , but there was no evidence that this reduction in ventricular rate was associated with improved exercise tolerance . The results suggest that further reduction of the rapid ventricular rates seen in digitalized patients with AF by the use of diltiazem does not appear to be of benefit in the majority of patients",
"Sixty-two patients with recent-onset ( less than or equal to 1 week ) atrial fibrillation ( New York Heart Association functional class 1 and 2 ) were r and omized in a single-blind study to 1 of the following treatment groups : ( 1 ) flecainide ( 300 mg ) as a single oral loading dose ; or ( 2 ) amiodarone ( 5 mg/kg ) as an intravenous bolus , followed by 1.8 g/day ; or ( 3 ) placebo for the first 8 hours . Twenty-four-hour Holter recording was performed , and conversion to sinus rhythm at 3 , 8 , 12 and 24 hours was considered as the criterion of efficacy . Conversion to sinus rhythm was achieved within 8 hours ( placebo-controlled period ) in 20 of 22 patients ( 91 % ) treated with flecainide , 7 of 19 ( 37 % ) treated with amiodarone ( p less than 0.001 vs flecainide ) , and 10 of 21 ( 48 % ) treated with placebo ( p less than 0.01 vs flecainide ) . Resumption of sinus rhythm within 24 hours occurred in 21 of 22 patients ( 95 % ) with flecainide and in 17 of 19 ( 89 % ) with amiodarone ( p = not significant ) . Mean conversion times were shorter for flecainide ( 190 + /- 147 minutes ) than for amiodarone ( 705 + /- 418 ; p less than 0.001 ) . No major side effects occurred . At Holter monitoring , a pause of 9.3 seconds was observed in 1 asymptomatic patient treated with flecainide . Phases of atrial flutter with a ventricular rate less than or equal to 150 beats/min were detected before sinus conversion in 1 patient receiving placebo and in 2 receiving flecainide . ( ABSTRACT TRUNCATED AT 250 WORDS",
"Warfarin is an established treatment for prevention of ischaemic stroke in patients with atrial fibrillation , but the value of this agent relative to aspirin in unclear . In the first Stroke Prevention in Atrial Fibrillation ( SPAF-I ) study , direct comparison of warfarin with aspirin was limited by the small number of thromboembolic events . SPAF-II aims to address this issue and also to assess the differential effects of the two treatments according to age . We compared warfarin ( prothrombin time ratio 1.3 - 1.8 , international normalised ratio 2.0 - 4.5 ) with aspirin 325 mg daily for prevention of ischaemic stroke and systemic embolism ( primary events ) in two parallel r and omised trials involving 715 patients aged 75 years or less and 385 patients older than 75 ; we sought reductions in the absolute rate of primary events by warfarin compared with aspirin of 2 % per year and 4 % per year , respectively . In the younger patients , warfarin decreased the absolute rate of primary events by 0.7 % per year ( 95 % CI-0.4 to 1.7 ) . The primary event rate per year was 1.3 % with warfarin and 1.9 % with aspirin ( relative risk [ RR ] 0.67 , p = 0.24 ) . The absolute rate of primary events in low-risk younger patients ( without hypertension , recent heart failure , or previous thromboembolism ) on aspirin was 0.5 % per year ( 95 % CI 0.1 to 1.9 ) . Among older patients , warfarin decreased the absolute rate of primary events by 1.2 % per year ( 95 % CI-1.7 to 4.1 ) . The primary event rate per year was 3.6 % with warfarin and 4.8 % with aspirin ( RR 0.73 , p = 0.39 ) . In this older group , the rate of all stroke with residual deficit ( ischaemic or haemorrhagic ) was 4.3 % per year with aspirin and 4.6 % per year with warfarin ( RR 1.1 ) . Warfarin may be more effective than aspirin for prevention of ischaemic stroke in patients with atrial fibrillation , but the absolute reduction in stroke rate by warfarin is small . Younger patients without risk factors had a low rate of stroke when treated with aspirin . In older patients the rate of stroke ( ischaemic and haemorrhagic ) was substantial , irrespective of which agent was given . Patient age and the inherent risk of thromboembolism should be considered in the choice of antithrombotic prophylaxis for patients with atrial fibrillation ",
"Twenty digitalized elderly patients with chronic atrial fibrillation were r and omized into a double-blind cross-over study . None was in overt heart failure and all were taking They received xamoterol 200 mg b.d . for 2 months with their usual dose of digoxin for 1 month and placebo digoxin for the other month . Twenty-four-hour heart rate analysis was done at baseline and at the end of each treatment period . Compared with baseline digoxin , xamoterol alone significantly increased nocturnal minimum heart rate [ 85 + /- 17 vs. 62 + /- 9 ( mean + /- SD ) , p daytime maximum heart rate ( 132 + /- 18 vs. 122 + /- 20 , p = NS ) . Compared with baseline digoxin , xamoterol plus digoxin significantly increased nocturnal minimum heart rate ( 68 + /- 8 , p daytime heart rate ( 114 + /- 17 , p mean number of pauses > 1.5 s was significantly reduced by xamoterol alone . Walking distance in 6 minutes was 406.1 + /- 27.1 m ( mean + /- SE ) at baseline and improved significantly on both treatments ( 450.3 + /- 19.8 on xamoterol ; p digoxin ; p measurements of palpitations , breathlessness and well-being using visual analogue scales . Xamoterol combined with digoxin improves effort tolerance and heart-rate control by reducing diurnal tachycardia and nocturnal bradycardia and pauses",
"OBJECTIVES The primary objective was to evaluate the usefulness of transesophageal echocardiography (TEE)-guided cardioversion to prevent thromboembolic complications in patients with atrial fibrillation ( AF ) and effective anticoagulation ( International Normalized Ratio of 2 or 3 ) at least three weeks before cardioversion . BACKGROUND Transesophageal echocardiography has been proposed as a method of screening patients for left atrial thrombi before direct-current cardioversion of AF . The usefulness of TEE as a screening tool has always been evaluated in patients without long-term anticoagulation before cardioversion . METHODS This prospect i ve , single-center , observational study , performed on an intention-to-cardiovert basis , comprised 1,076 consecutive , unselected patients with AF . The initial two years were design ed to be the control phase , during which the conventional approach was used . After that , cardioversion guided by TEE was performed in consecutive patients . RESULTS The prevalence of left atrial thrombi was 7.7 % in patients with persistent AF and effective anticoagulation . During the first four weeks after electrical cardioversion , six thromboembolic complications were observed in patients in whom the TEE-guided approach was employed ( 6 [ 0.8 % ] of 719 patients ) , compared with three thromboembolic complications in patients in whom the conventional approach was used ( 3 [ 0.8 % ] of 357 patients ) . None of the patients in whom electrical cardioversion was not performed experienced an embolic event . CONCLUSIONS There were no differences in the rate of embolic events between the two treatment groups . In patients with AF and effective anticoagulation , TEE-guided electrical cardioversion does not reduce the embolic risk . However , TEE revealed left atrial thrombi in 7.7 % of patients with AF and effective anticoagulation , before direct-current cardioversion",
"BACKGROUND The clinical presentation and causes of atrial fibrillation ( AF ) in the 1990s may differ from AF seen 2 to 3 decades ago . It was the objective of this prospect i ve study to characterize various clinical presentations and underlying conditions of patients with AF observed in general practice in France . METHODS AND RESULTS The study population comprised 756 patients ( 19 to 95 years of age ) with electrocardiographically documented AF subdivided into paroxysmal ( chronic ( last episode > 1 month ) and recent onset AF(persistent > 7 days and Symptoms were present in 670 patients ( 88.6 % ) . The relative prevalences of paroxysmal , chronic , and recent onset AF were 22.1 % , 51.4 % , and 26.4 % , respectively . Cardiac disorders , present in 534 patients ( 70.6 % ) , included hypertension ( 39.4 % ) , coronary artery disease ( 16.6 % ) , and myocardial diseases ( 15.3 % ) as the most common . Rheumatic valvular disease represented a common cause in women ( 25 . 0 % ) but not in men ( 8.0 % ) . The paroxysmal group differed by a high percentage of palpitations ( 79.0 % ) and a low percentage of underlying heart disease ( 53.9 % ) . With a mean follow-up of 8.6+/-3.7 months , 28 patients ( 3.7 % ) died , including 6 fatal cerebrovascular accidents . Among the 728 patients who survived , congestive heart failure occurred in 30 patients ( 4.1 % ) , and embolic complications occurred in 13 patients ( 1.8 % ) . In the paroxysmal AF group , 13 patients ( 8.0 % ) developed chronic AF and 51 ( 31.3 % ) had AF recurrences . At the time of follow-up , 53 patients ( 14.3 % ) from the chronic AF group and 108 patients ( 55.7 % ) from the recent onset AF group were in sinus rhythm . CONCLUSIONS This large-scale study establishes the current demographic profile of out-of-hospital patients with AF and highlights some of the changes that have occurred in the past decades , including a particular shift in cardiac causes toward nonrheumatic AF . This study also demonstrates significant differences between various subsets of AF",
"OBJECTIVES This study compared the efficacy and safety of sotalol and quinidine for conversion and prevention of recurrent atrial fibrillation . BACKGROUND Atrial fibrillation is the most common arrhythmia . Pharmacologic therapy has been advocated for both immediate restoration of sinus rhythm and prevention of recurrent atrial fibrillation . Quinidine is the therapeutic mainstay for both purpose s , but its safety has recently been question ed . Although sotalol has been used successfully to maintain sinus rhythm after direct current cardioversion , its efficacy in pharmacologically reverting atrial fibrillation has not been examined . METHODS Fifty consecutive patients with persistent atrial fibrillation were r and omized to receive quinidine or sotalol for up to 7 days to restore sinus rhythm . Patients were followed up for 6 months . RESULTS Quinidine was more effective than sotalol in terminating atrial fibrillation ( 60 % vs. 20 % , p = 0.009 ) . When nonresponders to drug therapy underwent subsequent direct current cardioversion , total conversion rates in the quinidine and sotalol groups were comparable ( 88 % vs. 68 % , p = 0.17 ) , as was the efficacy of the two drugs in preventing recurrent atrial fibrillation . Side effects necessitating drug discontinuation were more often observed with quinidine . No patient receiving sotalol but four patients receiving quinidine had drug-associated arrhythmia ( torsade de pointes in three patients , sustained ventricular tachycardia in one patient ) . Precordial QT dispersion determined on the surface electrocardiogram ( ECG ) increased with quinidine ( mean + /- SD 34 + /- 9 vs. 44 + /- 16 ms , p = 0.02 ) , indicating enhanced inhomogeneity in ventricular repolarization . There was no change in QT dispersion in patients receiving sotalol ( 36 + /- 18 vs. 40 + /- 17 ms , p = 0.44 ) . CONCLUSIONS Quinidine is more effective than sotalol in terminating atrial fibrillation but is associated with more side effects . The proarrhythmic risk may be related to quinidine 's propensity to increase disparity in ventricular repolarization . This risk warrants careful ECG monitoring during the 1st 4 to 7 days of therapy . Because most proarrhythmic effects occurred shortly after restoration of sinus rhythm , observation should continue > or = 2 to 3 days after sinus rhythm is reestablished",
"Pharmacologic therapy is widely used for restoration of sinus rhythm and prevention of recurrences of atrial fibrillation . Because concerns have been raised about their potential proarrhythmic effects , therapeutic regimens should be evaluated by placebo-controlled studies to determine their efficacy and safety . One hundred thirty-six patients with persistent atrial fibrillation were r and omized to receive propafenone 2 mg/kg over 30 minutes , followed by oral propafenone 150 mg 3 times daily or matching placebo . Nonresponders to intravenous therapy underwent direct-current cardioversion . Both responders to intravenous therapy and converters to sinus rhythm after direct-current cardioversion were followed for 6 months in a double-blind oral treatment period of propafenone 150 mg 3 times daily or matching placebo . Pharmacologic conversion to sinus rhythm was achieved in 29 % of the patients taking propafenone and in 17 % of patients taking placebo ( p > or = 0.10 ) . Subsequent direct-current cardioversion in nonresponders was equally successful ( 70 % ) in both groups ( p > or = 0.10 ) . The proportion of patients free from recurrent symptomatic arrhythmia at 6 months was 67 % for the propafenone and 35 % for the placebo group ( p Time to atrial fibrillation relapse was more favorable with propafenone than with placebo ( p incidence of drug-related side effects was 10 % in the propafenone group and 14 % in the placebo group . Thus , \" slow \" infusion of propafenone seems to be of limited value for terminating atrial fibrillation . Oral propafenone at a low dosage 150 mg 3 times daily is well tolerated and effective in maintaining sinus rhythm for 6 months after pharmacologic or electrical restoration of sinus rhythm",
"Abstract Objective : To investigate the impact of patients ' preferences for the treatment of atrial fibrillation , by using individualised decision analysis combining probability and utility assessment s into a decision tree . Design : Observational study based on interviews with patients . Setting : Eight general practice s in Avon . Participants : 260 r and omly selected patients aged 70–85 years with atrial fibrillation . Main outcome measures : Patients ' treatment preferences regarding anticoagulation treatment ( warfarin ) after individualised decision analysis ; comparison of these preferences with treatment guidelines on the basis of comorbidity and absolute risk and compared with current prescription . Results : Of 195 eligible patients , 97 participated in decision making using decision analysis . Among these 97 , the decision analysis indicated that 59 ( 61 % ; 95 % confidence interval 50 % to 71 % ) would prefer anticoagulation treatment — considerably fewer than those who would be recommended treatment according to guidelines . There was marked disagreement between the decision analysis and guideline recommendations ( kappa = 0.25 or less ) . Of 38 patients whose decision analysis indicated a preference for anticoagulation , 17 ( 45 % ) were being prescribed warfarin ; on the other h and , 28 ( 47 % ) of 59 patients were not being prescribed warfarin although the results of their decision analysis suggested they wanted to be . Conclusions : In the context of shared decision making , individualised decision analysis is valuable in a sizeable proportion of elderly patients with atrial fibrillation . Taking account of patients ' preferences would lead to fewer prescriptions for warfarin than under published guideline recommendations . Decision analysis as a shared decision making tool should be evaluated in a r and omised controlled trial",
" 1 . The efficacy of verapamil alone , or in combination with digoxin , was compared with digoxin alone in eight patients with chronic atrial fibrillation in this double-blind placebo-controlled study . 2 . After 2 weeks on each treatment regimen , heart rate at rest and during progressive load treadmill exercise , left ventricular function at rest and nocturnal heart rate were measured . 3 . Oral verapamil alone at a dose of 80 mg three times daily , or 40 mg of verapamil three times daily in combination with 0.25 mg of digoxin daily , was superior to digoxin alone in doses associated with high serum digoxin concentrations ( mean + /- SEM 1.6 + /- 0.3 micrograms/l ) . This superiority manifested as greater control of heart rate during work rates equivalent to regular daily activities , and was not associated with deterioration in left ventricular function or worsening nocturnal bradycardia . 4 . We conclude that the treatment of choice in patients with chronic atrial fibrillation is either 80 mg of verapamil three times daily or 40 mg of verapamil three times daily in combination with digoxin",
"OBJECTIVES This study examined the influence of left atrial spontaneous echo contrast on the subsequent stroke or embolic event rate and on survival in patients with nonvalvular atrial fibrillation . BACKGROUND Left atrial spontaneous echo contrast is associated with atrial fibrillation and a history of previous stroke or other embolic events . However , the prognostic implication s of spontaneous contrast in patients with nonvalvular atrial fibrillation are unknown . METHOD The study group comprised 272 consecutive patients with nonvalvular atrial fibrillation undergoing transesophageal echocardiography . Clinical and echocardiographic data were collected at baseline , and patients were prospect ively followed up , and all strokes , other embolic events and deaths were documented . The relation between spontaneous contrast at baseline and subsequent stroke , other embolic events and survival was analyzed . RESULTS Left atrial spontaneous echo contrast was detected at baseline in 161 patients ( 59 % ) . The mean follow-up was 17.5 months . The stroke or other embolic event rate was 12%/year ( 15 strokes , 3 transient ischemic attacks , 2 peripheral embolisms ) in patients with , compared with 3%/year ( 5 strokes ) in patients without , baseline spontaneous contrast ( p = 0.002 ) . In 149 patients without previous thromboembolism , the event rate was 9.5%/year in patients with and 2.2%/year in patients without spontaneous contrast ( p = 0.003 ) . There were 25 deaths in patients with and 11 deaths in patients without spontaneous contrast . Patients with spontaneous contrast had significantly reduced survival ( p = 0.025 ) . On multivariate analysis , spontaneous contrast was the only positive predictor ( odds ratio 3.5 , p = 0.03 ) and warfarin therapy on follow-up the only negative predictor ( odds ratio 0.23 , p = 0.02 ) of subsequent stroke or other embolic events . CONCLUSIONS Transesophageal echocardiography can risk stratify patients with nonvalvular atrial fibrillation by identifying left atrial spontaneous echo contrast . These patients have both a significantly higher risk of developing stroke or other embolic events and a reduced survival , and they may represent a subgroup in whom the risk/benefit ratio of anticoagulation may be most favorable",
"BACKGROUND Adjusted-dose warfarin is highly efficacious for prevention of ischaemic stroke in patients with atrial fibrillation ( AF ) . However , this treatment carries a risk of bleeding and the need for frequent medical monitoring . We sought an alternative that would be safer and easier to administer to patients with AF who are at high-risk of thromboembolism . METHODS 1044 patients with AF and with at least one thromboembolic risk factor ( congestive heart failure or left ventricular fractional shortening were r and omly assigned either a combination of low-intensity , fixed-dose warfarin ( international normalised ratio [ INR ] 1.2 - 1.5 for initial dose adjustment ) and aspirin ( 325 mg/day ) or adjusted-dose warfarin ( INR 2.0 - 3.0 ) . Drugs were given open-labelled . FINDINGS The mean INR during follow-up of patients taking combination therapy ( n = 521 ) was 1.3 , compared with 2.4 for those taking adjusted-dose warfarin ( n = 523 ) . During follow-up , 54 % of INRs in patients taking combination therapy were 1.2 - 1.5 and 34 % were less than 1.2 . The trial was stopped after a mean , follow-up of 1.1 years when the rate of ischaemic stroke and systemic embolism ( primary events ) in patients given combination therapy ( 7.9 % per year ) was significantly higher than in those given adjusted-dose warfarin ( 1.9 % per year ) at an interim analysis ( p warfarin . The annual rates of disabling stroke ( 5.6 % vs 1.7 % , p = 0.0007 ) and of primary event or vascular death ( 11.8 % vs 6.4 % , p = 0.002 ) , were also higher with combination therapy . The rates of major bleeding were similar in both treatment groups . INTERPRETATION Low-intensity , fixed-dose warfarin plus aspirin in this regimen is insufficient for stroke prevention in patients with non-valvular AF at high-risk for thromboembolism ; adjusted-dose warfarin ( target INR 2.0 - 3.0 ) importantly reduces stroke for high-risk patients",
"In this prospect i ve , controlled and r and omized cross-over study we tried to establish the efficiency and safety of flecainide vs procainamide for the treatment of acute atrial fibrillation . Eighty patients ( 30 females , 50 males , mean age : 55 + /- 14 years ) were included . Patients entered into the study if they had atrial fibrillation of recent onset ( 100 beats.min-1 at rest and were R and omly 40 patients received flecainide and 40 procainamide as the first treatment . There were no significant clinical difference between the two groups . Procainamide ws given at a dose of 1 g infused over 30 min , and followed by an infusion of 2 mg.min-1 over 1 h. Flecainide was given at a dose of 1.5 mg.kg-1 over 15 min followed by an infusion of 1.5 mg.kg-1 over 1 h. Drug infusion was continued until maximal dose , intolerance or reversion to sinus rhythm . After 1 h of wash out , patients remaining in atrial fibrillation were started on the second drug . Left atrial size was measured by echo . Serum levels of drug and atrial size did not differ between patients who returned to sinus rhythm and those who remained in atrial fibrillation . Conversion to sinus rhythm was achieved in 37 ( 92 % ) of the 40 patients treated with flecainide and 25 ( 65 % ) of those treated with procainamide ( P < 0.001 ) . The time required for reversion to sinus rhythm was similar between the two groups . ( ABSTRACT TRUNCATED AT 250 WORDS",
"Adjusted-dose warfarin is effective for stroke prevention in patients with nonrheumatic atrial fibrillation ( AF ) , but the risk of bleeding is high , especially among the elderly . Fixed minidose warfarin is effective in preventing venous thromboembolism with low risk of bleeding and no need for frequent clinical monitoring . Patients > 60 years with nonrheumatic AF were r and omized in an open-labeled trial to receive fixed minidose warfarin ( 1.25 mg/day ) or st and ard adjusted-dose warfarin ( International Normalized Ratio [ INR ] between 2.0 and 3.0 ) . Primary outcome events were ischemic stroke , peripheral or visceral embolism , cerebral or fatal bleeding , and vascular death . Secondary end points were major bleeding , myocardial infa rct ion , and death . This study was discontinued before completion in light of publication of the Stroke Prevention in Atrial Fibrillation III trial , which indicated that low-intensity fixed-dose warfarin treatment ( i.e. , INR patients with nonrheumatic AF . From a total of 1,209 considered patients , 303 were r and omized to be studied ( 150 in the minidose group and 153 in the adjusted-dose group ) . Mean follow-up was 14.5 months . The rate of cumulative primary events was 11.1 % ( 95 % confidence intervals [ CI ] 4.0 to 18.2 ) in the fixed minidose group and 6.1 % ( 95 % CI 1.1 to 11.1 ) in the adjusted-dose group ( p = 0.29 ) . The rate of ischemic stroke was significantly higher in the minidose group ( 3.7 % vs 0 % per year , p = 0.025 ) . Major bleedings were more frequent in st and ard treatment group ( 2.6 % vs 1 % per year , p = 0.19 ) . Most thromboembolic complications occurred at INRs hemorrhages occurred at INRs > 3.0 . No significant difference in primary outcome events was observed in the abbreviated study . However , the significantly increased occurrence of ischemic stroke in the fixed minidose warfarin group suggests that this regimen does not protect patients with nonrheumatic AF",
"AIMS The DAAF Trial was design ed to investigate whether digoxin , within 16 h of its use , increases the rate of conversion to sinus rhythm in patients with acute atrial fibrillation . METHODS AND RESULTS In a r and omized , double-blind multicentre trial the effects of intravenous digoxin and placebo , ( mean dose 0.88 + /- 0.35 mg and 0.96 + /- 0.37 mg ) were compared in 239 patients with a mean age of 66.2 + /- 13.0 years and atrial fibrillation of , at most , 7 days ' duration . The mean arrhythmia duration was 21.7 + /- 30.4 h and baseline heart rate 122.0 + /- 23.0 beats.min-1 . At 16 h , 46 % of the placebo group and 51 % of the digoxin group had converted to sinus rhythm , ( ns ) . Time to sinus rhythm was shorter in the digoxin group , but the difference was not significant . Digoxin had a pronounced and rapid effect on heart rate , which was already significant at 2 h ; 104.6 + /- 20.9 beats.min-1 vs 116.8 + /- 22.5 beats.min-1 ( P = 0.0001 ) . CONCLUSION Acute intravenous treatment with digoxin does not increase the rate of conversion to sinus rhythm , but has a fast acting and clinical ly significant effect on heart rate and should remain an alternative in haemodynamically stable patients",
"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",
"Transesophageal echocardiography ( TEE ) has emerged as an efficient method for detecting left atrial ( LA ) thrombi in recent years , but its accuracy has not been fully evaluated . A prospect i ve clinicopathologic study in 213 consecutive patients with chronic rheumatic mitral valve disease over a period of 39 months was undertaken . All patients underwent open heart surgery within 3 days after the TEE study . The presence or absence of LA thrombi was confirmed at surgery by direct inspection of the left atrium and proven by histopathologic examination . Of the 213 patients , 147 had predominant mitral stenosis , and the remaining 66 patients had significant mitral regurgitation . Twenty-eight patients had LA thrombi by TEE criteria . These findings were all confirmed at surgicopathologic studies ( specificity 100 % ) . However , in 2 patients , LA thrombi were present but could not be detected by TEE ( sensitivity 93.3 % ) . Therefore , the positive predictive value was 100 % , the negative predictive value was 98.9 % and the diagnostic accuracy was 99.1 % . No thrombi were found in patients with significant mitral regurgitation . The frequency of LA thrombi in patients with predominant mitral stenosis was 20 % ( 30 of 147 ) , and most of these patients had chronic atrial fibrillation ( 28 of 30 , 93 % ) . Only 16 patients ( 16 of 30 , 53 % ) were found to have LA thrombi by transthoracic echocardiography . Furthermore , our data showed poor correlation between the echogenicity of LA thrombi and the degree of thrombus organization . Thus , TEE is excellent for detecting LA thrombi in patients with rheumatic heart disease severe enough to warrant mitral valve operations",
"Objective To compare the efficacy and safety of a single dose of ibutilide , a new class III antiarrhythmic drug , with that of dl-sotalol in terminating chronic atrial fibrillation or flutter in haemodynamically stable patients . Design Double blind , r and omised study . Setting 43 European hospitals . Patients 308 patients ( mean age 60 years , 70 % men , 48 % with heart disease ) with sustained atrial fibrillation ( n = 251 ) or atrial flutter ( n = 57 ) ( duration three hours to 45 days ) were r and omised to three groups to receive a 10 minute infusion of 1 mg ibutilide ( n = 99 ) , 2 mg ibutilide ( n = 106 ) , or 1.5 mg/kg dl-sotalol ( n = 103 ) . Infusion was discontinued at termination of the arrhythmia . Main outcome measure Successful conversion of atrial fibrillation or flutter , defined as termination of arrhythmia within one hour of treatment . Results Both drugs were more effective against atrial flutter than against atrial fibrillation . Ibutilide was superior to dl-sotalol for treating atrial flutter ( 70 % and 56%v 19 % ) , while the high dose of ibutilide was more effective for treating atrial fibrillation than dl-sotalol ( 44 % v 11 % ) and the lower dose of ibutilide ( 44%v 20 % , p mean ( SD ) time to arrhythmia termination was 13 ( 7 ) minutes with 2 mg ibutilide , 19 ( 15 ) minutes with 1 mg ibutilide , and 25 ( 17 ) minutes with dl-sotalol . In all patients , the duration of arrhythmia before treatment was a predictor of arrhythmia termination , although this was less obvious in the group that received 2 mg ibutilide . This dose converted almost 48 % of atrial fibrillation that was present for more than 30 days . Concomitant use of digitalis or nifedipine and prolongation of the QTc interval were not predictive of arrhythmia termination . Bradycardia ( 6.5 % ) and hypotension ( 3.7 % ) were more common side effects withdl-sotalol . Of 211 patients given ibutilide , two ( 0.9 % ) who received the higher dose developed polymorphic ventricular tachycardia , one of whom required direct current cardioversion . Conclusion Ibutilide ( given in 1 or 2 mg doses over 10 minutes ) is highly effective for rapidly terminating persistent atrial fibrillation or atrial flutter . This new class III drug , under monitored conditions , is a potential alternative to currently available cardioversion options",
"This study was performed to evaluate , using a r and omized double-blind , placebo-controlled protocol , the long-term efficacy and safety of propafenone and sotalol in maintaining sinus rhythm after conversion of recurrent symptomatic atrial fibrillation ( AF ) . The maintenance of sinus rhythm in patients with recurrent AF has several potential benefits , the most important being a reduced risk of thromboembolic events . Three hundred patients with recurrent AF ( > or = 4 episodes in the last year ) and AF at enrollment lasting to receive either propafenone ( mean daily dose 13 + /- 1.5 mg/kg ; 102 patients ) , sotalol ( mean daily dose 3 + /- 0.4 mg/kg ; 106 patients ) , or placebo ( 92 patients ) . After 1-year follow-up , Kaplan-Meier estimates of the proportion of patients remaining in sinus rhythm were comparable between propafenone ( 63 % ) and sotalol ( 73 % ) and superior to placebo ( 35 % ; p = 0.001 vs both drugs ) . Symptomatic recurrences occurred later with propafenone and sotalol than with placebo . Nine patients ( 9 % ) in the propafenone group , 11 ( 10 % ) in the sotalol group , and 3 ( 3 % ) in the placebo group discontinued therapy due to adverse effects . Malignant nonfatal arrhythmias due to proarrhythmic effects were documented with sotalol only , and occurred ventricular rate was significantly reduced in patients taking propafenone and sotalol ( p = 0.001 for both drugs vs placebo ) . The likelihood of remaining in sinus rhythm during follow-up was higher in younger patients with smaller left atrial size and without concomitant heart disease . In patients with recurrent symptomatic AF , propafenone and sotalol are not significantly different from each other and are superior to placebo in maintaining sinus rhythm at 1 year . Recurrences occur later and tend to be less symptomatic with propafenone and sotalol compared with placebo",
"Abstract Among 437 patients in whom electrical conversion of atrial arrhythmia was attempted 228 were on long-term anticoagulant therapy and 209 were not given anticoagulants . Thirteen ( 3 per cent ) had an embolic episode , 2 of the 186 patients in the anticoagulant group and 11 of the 162 patients in the comparative group whose arrhythmias were converted . This difference is statistically significant at the 5 per cent level ( p = 0.012 ) . Three of 11 patients with a history of embolic episodes , whose arrhythmia was converted without anticoagulants , had a new episode after conversion , compared to none of the 55 patients with previous episodes who were receiving anticoagulant therapy . We attach importance to the significant difference in embolic episodes between the two groups even if the patients were not allocated at r and om , perhaps even greater importance , because the difference in composition of the two groups produced a bias against the anticoagulant group . For example , patients with a history of previous embolic episodes and those with rheumatic valvular disease were considerably over-represented in this group . In both of these categories an increased risk of embolism is present . Our results lead to the conclusion that prophylactic anticoagulant therapy is clearly indicated before and after attempts to convert atrial fibrillation in patients with a history of previous embolic episodes . In our opinion such prophylaxis should preferably be given in connection with attempts at conversion in all cases",
"OBJECTIVES The purpose of this study was to assess the effectiveness of azimilide , a class III antiarrhythmic drug , in reducing the frequency of symptomatic arrhythmia recurrences in patients with atrial fibrillation , atrial flutter or both . BACKGROUND Atrial fibrillation is an increasingly common disorder of the heart rhythm , and most patients with this problem are identified because they have symptoms associated with their arrhythmia . New antiarrhythmic therapies are needed to treat patients with this problem . METHODS A total of 384 patients with a history of atrial fibrillation , atrial flutter or both were r and omly assigned to receive once daily doses of placebo or azimilide ; recurrent symptomatic arrhythmias were documented using transtelephonic electrocardiogram ( ECG ) recording . Azimilide 50 mg , 100 mg or 125 mg was tested ; the primary efficacy analysis compared the time to first symptomatic recurrence in the combined azimilide 100 mg and 125 mg dose groups with that in the placebo group using the log-rank test . RESULTS In the primary efficacy analysis , the time to first symptomatic arrhythmia recurrence was significantly prolonged in the combined azimilide 100 mg and 125 mg daily dose group compared with the placebo group ( chi-square 7.96 , p = 0.005 ) ; the hazard ratio ( placebo : azimilide ) for this comparison was 1.58 ( 95 % confidence interval [ CI ] = 1.15 , 2.16 ) . In comparisons between individual doses and placebo , the hazard ratio for the 50 mg daily dose was 1.17 ( 95 % CI = 0.83 , 1.66 ; p = 0.37 ) ; for the 100 mg group , dose was 1.38 ( 95 % CI = 0.96 , 1.98 ; p = 0.08 ) , and for the 125 mg group , dose was 1.83 ( 95 % CI = 1.24 , 2.70 ; p = 0.002 ) . CONCLUSIONS Azimilide significantly lengthened the symptomatic arrhythmia-free interval in patients with a history of atrial fibrillation , atrial flutter or both",
"Rapid , reliable and safe reestablishment of sinus rhythm is the major aim of pharmacologic treatment in patients with chronic atrial fibrillation . The mainstay of therapy in this arrhythmia has been quinidine . More recently , amiodarone was shown in non-comparative studies to be superior to class IA agents under certain conditions . In 40 patients with atrial fibrillation persisting for 4 weeks up to 2 years , the efficacy and safety of either quinidine and verapamil ( days 1 to 3 , quinidine 1,500 mg/day ; days 4 to 6 , quinidine 1,500 mg + verapamil 240 mg/day ) or amiodarone therapy ( days 1 to 3 , amiodarone 1,200 mg/day intravenously ; days 4 to 14 , amiodarone 800 mg/day orally ) were r and omly examined . Responders continued on their effective medication for 3 months . Thereafter , all patients were treated with a fixed regimen of quinidine ( 480 mg/day ) plus verapamil ( 240 mg/day ) for up to 2 years . During atrial fibrillation , quinidine reduced mean ventricular cycle length by 40 ms ( -5 % ) , quinidine and verapamil increased mean cycle length by 57 ms ( 8 % ) and amiodarone by 192 ms ( 28 % , p less than 0.01 ) . In addition , quinidine and verapamil had a characteristic \" rate-smoothing \" effect on atrioventricular conduction during atrial fibrillation . The rhythm was converted to sinus rhythm after quinidine in 5 ( 25 % ) of 20 patients and after the combination of quinidine and verapamil in 11 ( 55 % ) of 20 patients . Amiodarone restored sinus rhythm in 12 ( 60 % ) of 20 patients . ( ABSTRACT TRUNCATED AT 250 WORDS",
"Abstract In summary , biplane TEE had a high sensitivity and specificity , but a low positive predictive accuracy , for detecting left atrial thrombus in 60 patients who underwent mitral valve surgery . The high falsepositive rate observed in this study appears to reflect the difficulty in differentiating severe spontaneous echo contrast from thrombus on TEE",
"BACKGROUND Currently available antiarrhythmic drugs have limited efficacy for acute termination of atrial fibrillation and flutter , especially if the arrhythmia is not of recent onset . The purpose of this multicenter study was to determine the efficacy and safety of repeated doses of intravenous ibutilide , a class III antiarrhythmic drug , in terminating atrial fibrillation or flutter . METHODS AND RESULTS Two hundred sixty-six patients with sustained atrial fibrillation ( n = 133 ) or flutter ( n = 133 ) , with an arrhythmia duration of 3 hours to 45 days , were r and omized to receive up to two 10-minute infusions , separated by 10 minutes , of ibutilide ( 1.0 and 0.5 mg or 1.0 and 1.0 mg ) or placebo . The conversion rate was 47 % after ibutilide and 2 % after placebo ( P ibutilide dosing regimens did not differ in conversion efficacy ( 44 % versus 49 % ) . Efficacy was higher in atrial flutter than fibrillation ( 63 % versus 31 % , P conversion rates were higher in patients with a shorter arrhythmia duration or a normal left atrial size . Arrhythmia termination occurred a mean of 27 minutes after start of the infusion . Of 180 ibutilide-treated patients , 15 ( 8.3 % ) developed polymorphic ventricular tachycardia during or soon after the infusion . The arrhythmia required cardioversion in 3 patients ( 1.7 % ) and was nonsustained in 12 patients ( 6.7 % ) . CONCLUSIONS Intravenous ibutilide given in repeated doses is effective in rapidly terminating atrial fibrillation and flutter and under monitored conditions is an alternative to current cardioversion options",
"This study has compared the effect on heart rate control of the addition of pindolol 15 mg bd or verapamil 40 mg tds to maintenance digoxin therapy in 12 patients with chronic atrial fibrillation . The study was performed in a r and omized cross-over fashion . Treatment effects were assessed by 24-h ambulatory electrocardiography and symptomatic improvement by symptom scores . The results show that the combination of pindolol and digoxin provides better control of atrial fibrillation . With an attenuation of daytime tachycardia , prevention of nocturnal bradycardia and reduction in the length of nocturnal pauses in rhythm . Overall heart rate variability was significantly less with digoxin and pindolol ( 523 beats min-1 h-1 ) than with digoxin and verapamil ( 745 beats min-1 h-1 ) . We conclude that , in the dosages employed , combined digoxin and pindolol therapy is superior to either digoxin and verapamil in combination or digoxin alone for the treatment of atrial fibrillation",
"54 patients with chronic atrial fibrillation were r and omly divided into two groups and treated respectively with practolol and quinidine ( 26 cases ) and with placebo and quinidine ( 28 cases ) . Sinus rhythm was restored in about the same percentage of cases in the two groups ( 42.3 and 46.4 % ) . This suggests the following conclusions : practolol is devoid of therapeutic activity in the treatment of chronic atrial fibrillation ; in agreement with similar observations made with other β-adrenergic blocking agents ( propranolol , LB 46 , and alprenolol ) , practolol seems to protect the myocardium from the onset of severe ventricular arrhythmia during the course of quinidine therapy",
"BACKGROUND Nonrheumatic atrial fibrillation is common among the elderly and is associated with an increased risk of stroke . We investigated whether anticoagulation with warfarin would reduce this risk . METHODS We conducted a r and omized , double-blind , placebo-controlled study to evaluate low-intensity anticoagulation with warfarin ( prothrombin-time ratio , 1.2 to 1.5 ) in 571 men with chronic nonrheumatic atrial fibrillation ; 525 patients had not previously had a cerebral infa rct ion , whereas 46 patients had previously had such an event . The primary end point was cerebral infa rct ion ; secondary end points were cerebral hemorrhage and death . RESULTS Among the patients with no history of stroke , cerebral infa rct ion occurred in 19 of the 265 patients in the placebo group during an average follow-up of 1.7 years ( 4.3 percent per year ) and in 4 of the 260 patients in the warfarin group during an average follow-up of 1.8 years ( 0.9 percent per year ) . The reduction in risk with warfarin therapy was 0.79 ( 95 percent confidence interval , 0.52 to 0.90 ; P = 0.001 ) . The annual event rate among the 228 patients over 70 years of age was 4.8 percent in the placebo group and 0.9 percent in the warfarin group ( risk reduction , 0.79 ; P = 0.02 ) . The only cerebral hemorrhage occurred in a 73-year-old patient in the warfarin group . Other major hemorrhages , all gastrointestinal , occurred in 10 patients : 4 in the placebo group , for a rate of 0.9 percent per year , and 6 in the warfarin group , for a rate of 1.3 percent per year . There were 37 deaths that were not preceded by a cerebral end point--22 in the placebo group and 15 in the warfarin group ( risk reduction , 0.31 ; P = 0.19 ) . Cerebral infa rct ion was more common among patients with a history of cerebral infa rct ion ( 9.3 percent per year in the placebo group and 6.1 percent per year in the warfarin group ) than among those without such a history . CONCLUSIONS Low-intensity anticoagulation with warfarin prevented cerebral infa rct ion in patients with nonrheumatic atrial fibrillation without producing an excess risk of major hemorrhage . This benefit extended to patients over 70 years of age"
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PURPOSE To up date the 1999 American Society of Clinical Oncology guideline for antiemetics in oncology . UP DATE METHODOLOGY The Up date Committee completed a review and analysis of data published from 1998 thru February 2006 . The literature review focused on published r and omized controlled trials , and systematic review s and meta-analyses of published phase II and phase III r and omized controlled trials . RECOMMENDATIONS The three-drug combination of a 5-hydroxytryptamine-3 ( 5-HT(3 ) ) serotonin receptor antagonist , dexamethasone , and aprepitant is recommended before chemotherapy of high emetic risk . For persons receiving chemotherapy of high emetic risk , there is no group of patients for whom agents of lower therapeutic index are appropriate first-choice antiemetics . These agents should be reserved for patients intolerant of or refractory to 5-HT3 serotonin receptor antagonists , neurokinin-1 receptor antagonists , and dexamethasone . The three-drug combination of a 5-HT3 receptor serotonin antagonist , dexamethasone , and aprepitant is recommended for patients receiving an anthracycline and cyclophosphamide . For patients receiving other chemotherapy of moderate emetic risk , the Up date Committee continues to recommend the two-drug combination of a 5-HT3 receptor serotonin antagonist and dexamethasone . In all patients receiving cisplatin and all other agents of high emetic risk , the two-drug combination of dexamethasone and aprepitant is recommended for the prevention of delayed emesis . The Up date Committee no longer recommends the combination of a 5-HT3 serotonin receptor antagonist and dexamethasone for the prevention of delayed emesis after chemotherapeutic agents of high emetic risk . CONCLUSION The Up date Committee recommends that clinicians administer antiemetics while considering patients ' emetic risk categories and other characteristics
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"The antiemetic effectiveness of 5-HT3 receptor antagonists in combination with dexamethasone in patients receiving short-term infusion chemotherapy has been well demonstrated . Less information is available about the efficacy of the same antiemetic combination in patients treated with regimens of chemotherapy in which the drugs are delivered in continuous infusion of several hours . The purpose of this study was to report the effectiveness of a double administration of antiemetic drugs in patients treated with strong emesis-inducing drugs for several days . In this study , 19 male and 13 female patients with osteosarcoma , ages 9 to 45 years , treated with chemotherapy , received intravenous tropisetron 5 mg plus dexamethasone 8 mg every 12 hours during the first two cycles of the preoperative treatment : cisplatin 120 mg/m2 over 48 hours followed by Adriamycin 75 mg/m2 delivered in 24 hours and continuous infusion of ifosfamide 15 g/m2 over 120 hours . The assessment of the antiemetic efficacy was performed three times every day : from 8:00 am to 4:00 pm , from 4:00 pm to 12:00 am , and from 12:00 am to 8:00 am . The patients were followed from the beginning of the treatment until 2 hours after its end , when they were discharged from hospital . Complete protection from emesis was obtained in 80 % of the 256 days of treatment : 81 % during the first cycle ( cisplatin 120 mg/m2 in 48 hours followed by Adriamycin 75 mg/m2 delivered in 24 hours ) and 79 % during the second cycle ( continuous infusion of ifosfamide 15 g/m2 in 120 hours ) . In both cycles , complete protection declined from the first to the last day of treatment ( from 100 % to 62 % during the first cycle and from 100 % to 63 % during the second cycle ) . These results indicate that when chemotherapy is administered in a protracted infusion , higher doses of antiemetic agents are necessary to achieve acceptable antiemetic activity",
"The selective 5-hydroxytryptamine3 ( 5HT3 ) antagonist ondansetron has been shown to be an effective antiemetic in patients receiving cisplatin chemotherapy . This double-blind study compared the efficacy and safety of three doses of intravenous ondansetron in the prevention of nausea and vomiting associated with high-dose ( ≥100 mg/m2 ) cisplatin chemotherapy . A total of 125 patients were r and omized ( 1∶1∶1 ) to receive 0.015 , 0.15 , or 0.30 mg/kg every 4 h for a total of 3 doses . All patients were monitored for emetic episodes , adverse events , and laboratory safety parameters for 24 h following cisplatin administration . The 0.15-mg/kg dose was superior to the 0.015-mg/kg dose with respect to the median number of emetic episodes ( P=0.033 ) and complete response ( no emetic episodes , P=0.005 ) . No statistically significant difference was found between the 0.15 and the 0.30-mg/kg groups . The most common adverse event was headache . Three 0.15-mg/kg doses of intravenous ondansetron are safe , effective , and adequate for the control of cisplatin-induced emesis",
"Granisetron ( GRN ) is widely used for patients with various cancers who suffer from chemotherapy-induced vomiting and nausea . The , pharmacokinetics of GRN has not been fully evaluated in such patients , however , and its dosage regimen is still controversial . In this study , we determined GRN levels in serum and urine from lung cancer patients and children suffering from cancer after intravenous infusion . In lung cancer patients , the interindividual variations in t(1/2beta ) , area under the concentration-time curve ( AUC ) , and Vd(beta ) were relatively smaller than expected from previous reports on healthy subjects , while t(1/2beta ) was prolonged more than 5-fold in healthy subjects . Urinary excretion of unchanged GRN in lung cancer patients was ca . 15 % of dose , consistent with previous reports , and one individual demonstrated an even higher urinary excretion ( ca . 45 % ) . The pharmacokinetic parameters of GRN in child cancer patients varied markedly among individuals , and some child patients had smaller t(1/2beta ) than adult patients . In these cases , GRN should be administered at shorter intervals . These results suggested that a pharmacokinetic study of GRN was necessary for planning a dosage regimen and managing chemotherapy-induced vomiting and nausea",
"BACKGROUND The localization of substance P in brain-stem regions associated with vomiting , and the results of studies in ferrets , led us to postulate that a neurokinin-1-receptor antagonist would be an antiemetic in patients receiving anticancer chemotherapy . METHODS In a multicenter , double-blind , placebo-controlled trial involving 159 patients who had not previously received cisplatin , we evaluated the prevention of acute emesis ( occurring within 24 hours ) and delayed emesis ( on days 2 to 5 ) after a single dose of cisplatin therapy ( 70 mg or more per square meter of body-surface area ) . Before receiving cisplatin , all the patients received granisetron ( 10 microg per kilogram of body weight intravenously ) and dexamethasone ( 20 mg orally ) . The patients were r and omly assigned to one of three treatments in addition to granisetron and dexamethasone : 400 mg of an oral trisubstituted morpholine acetal ( also known as L-754,030 ) before cisplatin and 300 mg on days 2 to 5 ( group 1 ) , 400 mg of L-754,030 before cisplatin and placebo on days 2 to 5 ( group 2 ) , or placebo before cisplatin and placebo on days 2 to 5 ( group 3 ) . Additional medication was available at any time to treat occurrences of vomiting or nausea . RESULTS In the acute-emesis phase , 93 percent of the patients in groups 1 and 2 combined and 67 percent of those in group 3 had no vomiting ( P no vomiting ( P median nausea score in the delayed-emesis phase was significantly lower in group 1 than in group 3 ( P=0.003 ) . No serious adverse events were attributed to L-754,030 . CONCLUSIONS The neurokinin-1-receptor antagonist L-754,030 prevents delayed emesis after treatment with cisplatin . Moreover , combining L-754,030 with granisetron plus dexamethasone improves the prevention of acute emesis",
"In a study of the effectiveness of high intravenous doses of metoclopramide as an antiemetic , 41 patients with advanced cancer who were being treated with cisplatin were entered into two double-blind trials . In the first trial patients were r and omly assigned to receive either metoclopramide or placebo , and in the second trial they received either metoclopramide or prochlorperazine . Patients given metoclopramide had significantly fewer episodes of emesis than patients given placebo ( medians , 1.0 vs. 10.5 ; P = 0.001 ) or prochlorperazine ( medians , 1.5 vs. 12.0 ; P = 0.005 ) . Metoclopramide was superior to placebo and to prochlorperazine in reducing the volume of emesis ( P = 0.001 and P = 0.022 , respectively ) and was more effective than placebo in shortening the duration of nausea ( P = 0.042 ) and vomiting ( P = 0.028 ) . Side effects from metoclopramide were minor , with mild sedation frequently observed ; one patient had a brief extrapyramidal reaction . We conclude that metoclopramide in high intravenous doses has greater antiemetic activity than placebo or prochlorperazine in patients receiving cisplatin chemotherapy",
"Prior studies in adults have shown that metoclopramide ( MCP ) , when given in high intravenous ( IV ) doses ( 2 mg/kg ) , is a highly effective antiemetic for chemotherapy-induced vomiting . It is well-tolerated in older adults , but younger adults have an increased disposition to acute extrapyramidal reactions ( EPRs ) . Before study ing the efficacy of MCP as an antiemetic in children , we first had to establish the safe dose range . We performed a dose-increase MCP toxicity study in children receiving highly emetic chemotherapy such as cisplatin ( 120 mg/m2 ) or cyclophosphamide ( greater than 900 mg/m2 ) , beginning with a dose of 0.2 mg/kg and increasing the dose in nine steps to 3 mg/kg . MCP was given every two hours for four doses beginning one-half hour before chemotherapy . To reduce the incidence of EPRs , we added concomitant diphenhydramine . In MCP doses less than 2 mg , toxicity was minimal . In doses greater than or equal to 2 mg , 4/27 ( 15 % ) had EPRs and 9/27 ( 33 % ) had akathisia . Children who received two consecutive days of MCP had a higher frequency of EPRs . Metoclopramide ( 2 mg/kg ) had promising antiemetic efficacy in a preliminary nonr and omized trial . Chemotherapy-experienced children vomited fewer than five times in 9/21 ( 43 % ) trials , and new patients vomited fewer than five times in 7/10 ( 70 % ) trials . MCP will become more useful as an antiemetic in children if better measures to prevent EPRs can be developed . Chemotherapy-induced emesis has the same negative implication s in children as it does in adults and optimum antiemetic regimens can only be discovered by conducting r and omized clinical trials in children",
"BACKGROUND There are few r and omised studies comparing anti-emetic drugs for the prevention of nausea and vomiting in patients treated with fractionated radiotherapy . The aim of the study was to compare the anti-emetic efficacy of 8 mg dose ondansetron twice a day with placebo . MATERIAL S AND METHODS One hundred eleven patients who were to commence a course of 10 or more daily fractionated radiotherapy including the abdomen were included in the study . The patients recorded daily emesis , nausea and bowel habit and grade d weekly symptoms of nausea , vomiting , diarrhoea and lack of appetite . The EORTC C30 question naire was completed . RESULTS 67 % of patients given ondansetron had complete control of emesis compared with 45 % of patients with placebo ( P number of emetic episodes recorded on the worst day was 1.4 for the ondansetron group and 3.1 for the placebo group ( P ondansetron had fewer days with emesis and nausea compared with placebo ( P mean sum score of patients weekly grading of symptoms showed that the ondansetron group had less inconvenience than the placebo group ( P quality of life measures showed significant differences in favour of the ondansetron group . More patients ( n = 13 ) withdrew due to lack of efficacy in the placebo group compared with patients ( n = 8) in the ondansetron group . CONCLUSIONS The present study illustrates that prophylactic anti-emetic administration of ondansetron is effective in preventing nausea and vomiting in patients undergoing fractionated radiotherapy of the abdomen",
"Palonosetron , a highly selective and potent 5‐HT3 receptor antagonist with a strong binding affinity and a long plasma elimination half‐life ( approximately 40 hours ) , has shown efficacy in Phase II trials in preventing chemotherapy‐induced nausea and vomiting ( CINV ) result ing from highly emetogenic chemotherapy . The current Phase III trial evaluated the efficacy and safety of palonosetron in preventing acute and delayed CINV after moderately emetogenic chemotherapy",
"PURPOSE To compare the efficacy of dolasetron and ondansetron in controlling nausea and vomiting in the first 24 hours ; to evaluate the efficacy when dexamethasone is added to either drug in the first 24 hours ; and to extend these comparisons over 7 days in patients receiving moderately emetogenic chemotherapy . PATIENTS AND METHODS This was a multicenter , double-blind , r and omized study with six parallel arms that used a 2 x 2 factorial design in chemotherapy-naive patients . In arm 1 , dolasetron ( 2.4 mg/kg ) was given intravenously ( I.V. ) prechemotherapy , followed 24 hours later by oral dolasetron ( 200 mg once daily ) for 6 days . Arms 2 and 3 consisted of dolasetron and dexamethasone 8 mg I.V. , followed 24 hours later by oral dexamethasone ( 8 mg once daily ) in one arm , and oral dexamethasone and dolasetron in the other , also for 6 days . In arms 4 , 5 , and 6 , ondansetron ( 32 mg I.V. or 8 mg orally twice daily ) was administered in a similar manner to arms 1 , 2 , and 3 before and 24 hours after chemotherapy . Mean nausea severity ( MNS ) was assessed on a visual analog scale ( VAS ) in a daily diary . RESULTS Of 703 patients enrolled , 696 were eligible . There were 343 dolasetron- and 353 ondansetron-treated patients ; 57 % of dolasetron-treated patients had complete protection in the first 24 hours versus 67 % of patients who received ondansetron ( P = .013 ) . MNS was also more pronounced on the dolasetron arm ( P = .051 ) . Sixty-seven percent of patients who received added dexamethasone in the first 24 hours had complete protection , compared with 55 % without dexamethasone ( P MNS was significantly reduced with the addition of dexamethasone ( P dolasetron and ondansetron had equivalent complete protection rates ( 36 % and 39 % , respectively ) . With the addition of dexamethasone , 48 % of patients compared with 28 % had complete protection ( P MNS was significantly improved with added dexamethasone ( P dolasetron was significantly less effective than ondansetron at controlling nausea and vomiting in the first 24 hours in patients receiving moderately emetogenic chemotherapy , but there was no demonstrable difference between both drugs over 7 days . The addition of dexamethasone significantly improved the efficacy of both drugs in the first 24 hours and over 7 days",
"The aim was to compare the efficacy of ondansetron and a combination of ondansetron plus dexamethasone in the prophylaxis of cisplatin-induced delayed emesis over three consecutive courses of chemotherapy . Cancer patients scheduled to receive for the first time cisplatin ( > 50 mg/m(2 ) ) in combination with other cytotoxic agents , were recruited in a multicentre , r and omised , double-blind study and treated with ondansetron 8 mg i.v . and dexamethasone 20 mg i.v . Twenty-four hours after the start of chemotherapy , patients were r and omised to treatment either with oral ondansetron 8 mg bd plus placebo on days 2 - 5 ( group A ) or with oral ondansetron 8 mg bd plus oral dexamethasone 8 mg bd on days 2 - 3 , and 4 mg bd on days 4 and 5 ( group B ) . Two hundred and thirty-six cancer patients were recruited into the study . Complete protection from delayed vomiting/nausea in group A and group B was Obtained in 50/39 % and in 63/42 % of patients , respectively in the first course ; in 55/34 % and in 64/40 % in the second and in 49/31 % and 60/37 % in the third . Logistic regression analysis reveals a statistically significant difference in incidence of emesis between the combination of ondansetron plus dexamethasone and ondansetron alone ( P incidence of nausea between the two treatment regimens . Ondansetron plus dexamethasone reduces the risk of delayed emesis following cisplatin chemotherapy as compared to ondansetron alone",
"An aprepitant ( APR ) regimen was evaluated for prevention of nausea and emesis due to moderately emetogenic chemotherapy ( MEC ) over multiple cycles",
"Ten children receiving 5 to 6 week courses of radiotherapy after brain tumor surgery were given ondansetron treatment for persistent nausea and emesis . All patients continued the ondansetron treatment until the end of their radiotherapy course . Nausea , emesis , appetite , and adverse events were scored throughout the ondansetron treatment period . Ondansetron was well tolerated by all patients and was effective at reducing symptoms in 60 % of the children",
"PURPOSE To evaluate the roles of granisetron and dexamethasone for emesis control on days 2 through 7 after the administration of cisplatin in doses of 50 mg/m2 or greater to patients who had not previously received chemotherapy . PATIENTS AND METHODS Four hundred thirty-five eligible and assessable patients were r and omized to one of two arms in a double-blind fashion : arm A ; granisetron 3 mg intravenous ( i.v . ) plus dexamethasone 10 mg i.v . prechemotherapy followed by granisetron 1 mg orally at 6 and 12 hours , then granisetron 1 mg orally and dexamethasone 8 mg orally twice daily on days 2 through 7 ( 219 patients ) ; arm B ; as in arm A but with placebo substituted for granisetron on days 2 through 7 ( 216 patients ) . All patients completed diaries in which episodes of emesis and severity of nausea were recorded . RESULTS The addition of granisetron on days 2 through 7 had no discernable impact on nausea and vomiting during this period . CONCLUSION The administration of a 5-hydroxytryptamine3 , receptor ( 5-HT3 ) antagonist , in this case granisetron , after 24 hours conferred no benefit . This negative result needs to be assessed in light of conflicting literature , but at present it does not appear that the routine use of these drugs in this setting is justified",
"PURPOSE The safety , antiemetic efficacy , and pharmacokinetics of single oral doses of dolasetron , a new highly selective 5-HT3 receptor antagonist , were evaluated in children with cancer undergoing treatment with moderately to highly emetogenic chemotherapy . PATIENTS AND METHODS A total of 32 children , ages 3 to 18 years , were enrolled in a nonr and omized , multicenter , open-label , dose-escalation study . Three oral dose levels ( 0.6 , 1.2 , or 1.8 mg/kg ) were studied . Safety , efficacy , and pharmacokinetic parameters were assessed over 24 hours at each dosage level . RESULTS The most effective dose was 1.8 mg/kg ; 60 % of the patients achieved a complete or major response ( complete response was achieved in 3 of 9 patients ( 33 % ) who received 0.6 mg/kg , 4 of 13 ( 31 % ) patients who received 1.2 mg/kg , and 5 of 10 ( 50 % ) patients who received 1.8 mg/kg of dolasetron . Overall , dolasetron was well tolerated . Adverse events were mild and similar to those reported in adults . Peak plasma concentrations ( Cmax ) of dolasetron 's active reduced metabolite , MDL 74,156 , were dose proportional and occurred , on the average , within 1 hour of oral administration . The half-life ( t1/2 ) in plasma was approximately 6 hours for all dose levels , and the mean clearance ( CLapp ) was unrelated to dose . CONCLUSIONS Oral dolasetron is safe and effective in reducing chemotherapy-induced nausea and vomiting , particularly at the 1.8-mg/kg dose level . These results support further evaluation of oral dolasetron in larger r and omized clinical trials in the pediatric cancer population",
"Total body irradiation ( TBI ) is a highly emetogenic component of the majority of conditioning regimens in use for bone marrow transplantation . Conventional antiemetic therapy fails to control nausea and vomiting induced by single fraction TBI in as many as 50 % of patients . In a double blind study of 20 patients undergoing marrow transplantation , a single 8 mg ondansetron dose was compared with placebo given immediately prior to TBI . Our routine premedication of phenobarbitone and corticosteroid was also administered to all patients . All patients had received high dose melphalan the previous evening . Only 1 of the 10 patients in the ondansetron group experienced an emetic event compared with 5 of the 10 in the comparison group ( p = 0.029 ) . No significant adverse events were observed . Ondansetron appears to have extremely useful antiemetic activity during single fraction low dose rate TBI",
"In a multicentre , international double-blind trial , patients undergoing courses of five or more daily radiotherapy treatments to the upper abdomen were r and omized to receive either oral ondansetron 8 mg t.d.s . or oral prochlorperazine 10 mg t.d.s . throughout their radiation course in order to try to prevent nausea and vomiting . A total of 192 patients were recruited , 135 of whom were included in the efficacy analysis ; of these , 70 received ondansetron and 65 prochlorperazine . Forty-three ( 61 % ) of the patients prescribed ondansetron and 23 ( 35 % ) of those given prochlorperazine had a complete response , with no emetic episodes throughout their treatment course ( P = 0.002 ) . There was , however , no significant difference between the two groups with respect to the incidence and severity of nausea . Seventeen ( 24 % ) of the patients on ondansetron and 19 ( 29 % ) of those given prochlorperazine were treatment failures , experiencing more than five emetic episodes on their worst day during the study . Both drugs were well tolerated , although constipation was seen more commonly with ondansetron",
"OBJECTIVE To compare the efficacy and side effects of ondansetron with those of high-dose metoclopramide in treating acute and delayed cisplatin-induced nausea and vomiting . DESIGN R and omized , double-blind , crossover trial . SETTING Conducted at two university hospitals , a cancer institute , and six community hospitals . PATIENTS Of 125 patients , 95 were evaluable for the acute phase and 79 for the delayed phase . Major reasons for not being evaluable were no second course ( 14 patients ) , protocol violation ( 5 patients ) , and change in cisplatin dose ( 3 patients ) for the acute phase , and rescue medication on day 1 ( 7 patients ) , protocol violation ( 3 patients ) , and inadequate data ( 4 patients ) for the delayed phase . INTERVENTIONS All patients received cisplatin , 50 to 100 mg/m2 body surface area ( median , 75 mg/m2 ) ; none had previously received chemotherapy . Thirty minutes before the cisplatin administration , ondansetron was given intravenously over 15 minutes , at a loading dose of 8 mg followed by a continuous infusion of 1 mg/h for 24 hours . Metoclopramide was given at a loading dose of 3 mg/kg body weight , followed by a continuous infusion for 8 hours ( 4 mg/kg ) . For the delayed phase ( days 2 through 6 ) , the first oral dose was given as soon as the infusion was completed ; the oral dose consisted of either metoclopramide , 20 mg three times daily , or ondansetron , 8 mg three times daily for another 5 days . MEASUREMENTS AND MAIN RESULTS In the acute phase , a major or complete response was seen in 72 % of the ondansetron-treated and 41 % of the metoclopramide-treated patients ( P less than 0.001 ) . Nausea was significantly better controlled among the ondansetron-treated patients ( P = 0.04 ) . In the delayed phase , no statistically significant difference was seen between ondansetron- and metoclopramide-treated patients . Nausea was significantly better controlled with metoclopramide ( P = 0.016 ) . CONCLUSIONS Ondansetron is significantly more effective than metoclopramide in preventing acute nausea and vomiting . In the delayed phase , the results of both drugs were disappointing , although metoclopramide 's effect on delayed nausea was superior . Patients preferred ondansetron",
"The majority of patients receiving cisplatin at a dose of 120 mg/m2 experience delayed nausea and vomiting occurring between 24 and 120 hours after chemotherapy administration . Ninety-one patients who were receiving cisplatin ( 120 mg/m2 ) as initial chemotherapy were entered into this double-blind trial . All patients received intravenous ( IV ) metoclopramide , dexamethasone , and lorazepam for the control of acute emesis during the period from 0 to 24 hours after cisplatin . Patients were then r and omized to one of three treatment regimens : placebo ; oral dexamethasone , 8 mg twice daily for two days , then 4 mg twice daily for two days ; or the combination of oral metoclopramide , 0.5 mg/kg four times daily for four days , plus oral dexamethasone administered as above . Forty-eight percent of individuals who received the two-drug combination of metoclopramide plus dexamethasone experienced delayed vomiting as opposed to 65 % who were administered dexamethasone alone and 89 % who received placebo ( P = .006 ) . Scores assessing the severity of delayed nausea and vomiting were consistently worse in individuals receiving placebo . The incidences of sleepiness , restlessness , heartburn , hiccoughs , loose bowel movements , insomnia , and acute dystonic reactions did not differ significantly among the three regimens and were mild and self-limited . The two-drug combination of oral metoclopramide plus dexamethasone is well tolerated , safe , and more effective than dexamethasone alone or placebo in controlling delayed vomiting following cisplatin",
"A prospect i ve trial was performed to better assess the risk of nausea and vomiting and the rescue value of tropisetron ( TRO ) , a 5-HT3 receptor antagonist , in 88 patients undergoing fractionated radiotherapy to the abdomen or to large supradiaphragmatic fields and failing a first anti-emetic trial with metoclopramide ( MET ) . Nausea was grade d 0 ( absent ) , 1 ( mild ) , 2 ( moderate ) and 3 ( severe ) . Nausea requiring anti-emetics ( > or = grade 2 ) was present in 64 % of the patients . MET was able to control nausea ( or = grade 2 nausea during radiation treatment ( 2 patients vomiting without nausea included ) . 34 patients required TRO , and 31 experienced immediate relief . However , nausea ( > or = grade 2 ) recurred in 7 patients from 1 to 3 weeks after starting TRO . Sex , age , field type and field size ( cm2 ) did not influence the incidence and severity of nausea and vomiting . Only 24/88 patients vomited after starting radiotherapy . MET helped to eliminate emesis in one third of these patients . TRO helped to control vomiting in 73 % of the salvaged patients . Constipation was observed in 8 patients on TRO and was a reason to stop the medication in 4 cases",
"BACKGROUND Although all first-generation 5-HT(3 ) receptor antagonists demonstrate efficacy in preventing acute chemotherapy-induced nausea and vomiting ( CINV ) , effective prevention of delayed CINV has not yet been achieved . This study compared the efficacy and tolerability of palonosetron , a novel , second-generation 5-HT(3 ) receptor antagonist , with ondansetron . PATIENTS AND METHODS In this multicenter , r and omized , double-blind , stratified , phase III study , 570 adult cancer patients were r and omized to receive a single i.v . dose of palonosetron 0.25 mg , palonosetron 0.75 mg or ondansetron 32 mg , each administered 30 min before initiation of moderately emetogenic chemotherapy . The primary end point was the proportion of patients with no emetic episodes and no rescue medication [ complete response ( CR ) ] during the 24 h after chemotherapy administration ( acute period ) . Secondary end points included efficacy in treatment of delayed CINV ( overall tolerability . RESULTS 563 patients were evaluable for efficacy . CR rates were significantly higher ( P palonosetron 0.25 mg than ondansetron during the acute ( 0 - 24 h ) ( 81.0 % versus 68.6 % , respectively ) , delayed ( 24 - 120 h ) ( 74.1 % versus 55.1 % ) and overall ( 0 - 120 h ) ( 69.3 % versus 50.3 % ) periods . CR rates achieved with palonosetron 0.75 mg were numerically higher but not statistically different from ondansetron during all three time intervals . Both treatments were well tolerated . CONCLUSIONS A single i.v . dose of palonosetron 0.25 mg was significantly superior to i.v . ondansetron 32 mg in the prevention of acute and delayed CINV",
"To compare ondansetron ( GR 38032F ) , a 5-hydroxytryptamine3-receptor antagonist , with metoclopramide in the prophylaxis of acute cisplatin-induced emesis , we conducted a double-blind crossover study in 97 patients scheduled to receive cisplatin ( 80 to 100 mg per square meter of body-surface area ) for treatment of cancer . None had received chemotherapy before this trial . Among the 76 patients who satisfactorily completed both parts of the study , complete or nearly complete control of emesis ( i.e. , no episodes of emesis occurred , or only one or two ) was achieved in 57 of 76 treatments ( 75 percent ) with ondansetron and in 32 of 76 treatments ( 42 percent ) with metoclopramide ( P less than 0.001 ) . Ondansetron was also more effective in controlling acute nausea , as assessed with a visual-analogue scale ( P = 0.019 ) or a grade d scale ( P = 0.024 ) . There was a significant preference among patients for ondansetron ( 55 vs. 26 percent ; P = 0.006 ) . Dystonic reactions were observed during three treatments with metoclopramide ; both agents were otherwise well tolerated . We conclude that ondansetron is more effective than metoclopramide in the control of cisplatin-induced nausea and vomiting , and that this suggests that serotonin is an important mediator of this side effect",
"The efficacy of granisetron hydrochloride 20 microg/kg and 40 microg/kg were compared using a cross-over method to determine the optimal dose in children with solid tumors receiving high-dose chemotherapy . Granisetron controlled the onset of vomiting in 17 of 23 patients ( 73.9 % ) who were given 40 microg/kg of granisetron , while 8 of 21 patients ( 38.1 % ) were free of vomiting in the 20 microg/kg group . The average frequency of vomiting was 7.22 times in the 20 microg/kg dose versus 4.44 times in the 40 microg/kg dose . No safety problems were associated with either dose . The 40 microg/kg dose of granisetron appears to be more optimal",
"Aprepitant is a neurokinin1 receptor antagonist that , in combination with a corticosteroid and a 5‐hydroxytryptamine3 receptor antagonist , has been shown to be very effective in the prevention of chemotherapy‐induced nausea and vomiting . At doses used for the management of chemotherapy‐induced nausea and vomiting , aprepitant is a moderate inhibitor of cytochrome P4503A4 and may be used in conjunction with corticosteroids such as dexamethasone and methylprednisolone , which are substrates of cytochrome P4503A4 . The effects of aprepitant on the these 2 corticosteroids were evaluated",
"BACKGROUND Serotonin-receptor antagonists seem to be as effective as corticosteroids in preventing emesis induced by moderately emetogenic antineoplastic agents . We compared the antiemetic effect of a combination of granisetron and dexamethasone with that of granisetron or dexamethasone administered alone . METHODS From December 1992 to January 1994 , 482 consecutive patients who were to receive moderately emetogenic chemotherapy for the first time ( 600 to 1000 mg of cyclophosphamide per square meter of body-surface area , > or = 50 mg of doxorubicin per square meter , > or = 75 mg of epirubicin per square meter , or > or = 300 mg of carboplatin per square meter , alone or in some combination ) were enrolled in a double-blind , r and omized , multi-center study evaluating the efficacy and toxicity of three antiemetic regimens . The following antiemetic regimens were used : 8 mg of dexamethasone given intravenously before chemotherapy plus 4 mg given orally immediately before chemotherapy and then every six hours for a total of four doses , 3 mg of granisetron given intravenously before chemotherapy , or a combination of granisetron and dexamethasone given in the doses used for the single-drug regimens . RESULTS We evaluated 408 patients ( 136 receiving dexamethasone , 137 receiving granisetron , and 135 receiving both drugs ) . In the first 24 hours after chemotherapy , complete protection from vomiting and complete protection from nausea were achieved in 70.6 and 55.1 percent , respectively , of the patients receiving dexamethasone , in 72.3 and 48.2 percent of those receiving granisetron , and in 92.6 and 71.9 percent of those receiving granisetron combined with dexamethasone ( P granisetron alone had less protection from delayed vomiting and nausea than those who received dexamethasone alone or the two drugs combined . All the regimens were equally well tolerated . CONCLUSION Granisetron combined with dexamethasone was the most effective regimen for the prevention of emesis induced by moderately emetogenic chemotherapy",
"We evaluated the efficacy and safety of oral ondansetron , a selective antagonist of 5-HT3 receptors , for the treatment of nausea and vomiting associated with cyclophosphamide-based chemotherapy ( > 500 mg/m2 ) . In this trial 324 chemotherapy-naive cancer patients , mostly females with breast cancer , were r and omized to receive either placebo or ondansetron 1 mg , 4 mg , or 8 mg three times per day for 3 days . There were no differences in the doses of cyclophosphamide , doxorubicin , and methotrexate between the study groups . All ondansetron dose groups were superior to the placebo control group ( p measured efficacy parameters ( complete response , number of emetic episodes , therapeutic failures , need of rescue antiemetics ) . No emetic episodes were reported by 9 ( 12 % ) , 29 ( 37 % ) , 48 ( 64 % ) , and 47 ( 66 % ) of the placebo patients and the 1-mg , 4-mg , and 8-mg dose of ondansetron patients , respectively . Nausea was reduced and food intake was improved for all the ondansetron groups . A more severe emetic response was observed in patients receiving cyclophosphamide and doxorubicin combination chemotherapy . In this subgroup of patients . 66 % , 38 % . 25 % , and 16 % of the placebo group and 1-mg , 4-mg , and 8-mg ondansetron patients , respectively , required rescue anti-emetics . No significant toxic effects were observed in this study . A higher incidence of headaches and gastrointestinal complaints ( constipation , abdominal pain ) were observed in the three ondansetron groups . In conclusion , oral ondansetron is an effective and well-tolerated antiemetic treatment in the management of cancer patients receiving ambulatory cyclophosphamide-based chemotherapy . These results support the view that serotonin and 5-HT3 receptors play an important role in cyclophosphamide-induced nausea and vomiting",
"This prospect i ve study was design ed to compare the efficacy of ondansetron with granisetron in terms of complete emesis control and time spent in an ambulatory care setting in children with acute lymphoblastic leukemia ( ALL ) undergoing moderately emetogenic cyclophosphamide-based chemotherapy . The costs for both treatments are also examined . A total of 33 children ( mean age : 7.8 + /- 4.9 year ) were studied during 66 chemotherapy cycles . Analysis was based on 33 courses of a single oral dose of granisetron and 33 courses of ondansetron incorporating 2 intravenous doses of ondansetron 0.15 mg/kg followed by 1 dose of the same dosage orally . There was no significant difference between the 2 treatments in terms of overall efficacy ( McNemar 's chi-square test ) . Twenty of 33 patients ( 60.6 % ) receiving granisetron and 15 of 33 patients ( 45.5 % ) receiving ondansetron experienced no emesis 24 h after chemotherapy ( p = .227 ) . Boys experienced greater rates of vomiting than did girls despite antiemetic treatment ; however , no apparent reason for the gender discrepancy was noted . Both antiemetic regimens have similar antiemetic efficacy for treating the moderately emetogenic effects associated with cyclophosphamide-based chemotherapy . It is possible that the granisetron regimen may be preferable because it is simpler to administer and more cost-effective",
"We compared the efficacy and safety of ondansetron ( GR 38032F ) , a selective antagonist of serotonin S3 receptors , with that of placebo in controlling the nausea and vomiting induced by cisplatin treatment in 28 patients with cancer . The patients received either three intravenous doses of ondansetron ( 0.15 mg per kilogram of body weight ) or normal saline ( placebo ) at four-hour intervals , beginning 30 minutes before the administration of cisplatin . Nausea and vomiting were markedly diminished in the group given ondansetron . The median time to the first episode of emesis was 2.8 hours in the placebo group and 11.6 hours in the ondansetron group ( P less than 0.001 ) ; the median number of episodes in 24 hours was 5.5 in the placebo group and 1.5 in the ondansetron group ( P less than 0.001 ) ; the mean ( + /- SEM ) number of regurgitations or dry heaves per episode was 3.2 + /- 0.5 in the placebo group and 1.17 + /- 0.1 in the ondansetron group ( P less than 0.001 ) . None of the 14 patients given ondansetron , but 12 of 14 given placebo , required treatment with antiemetic-rescue agents for the control of nausea and vomiting . There were no adverse effects attributable to ondansetron . The urinary excretion of 5-hydroxyindoleacetic acid , the main metabolite of serotonin , was increased in all patients two to six hours after they received cisplatin chemotherapy , and the increases paralleled the episodes of emesis . We conclude that ondansetron is an effective and safe agent for controlling the nausea and vomiting induced by cisplatin treatment . We suggest that cisplatin treatment increases the release of serotonin from enterochromaffin cells , and that ondansetron acts by blocking S3 receptors for serotonin",
"Background Aprepitant is a selective neurokinin-1 receptor antagonist that is effective for the prevention of nausea and vomiting caused by highly emetogenic chemotherapy . In vitro , aprepitant is a moderate inhibitor of the CYP3A4 enzyme , which is involved in the clearance of several chemotherapeutic agents . In this study we examined the potential for aprepitant to affect the pharmacokinetics and toxicity of intravenously administered docetaxel , a chemotherapeutic agent that is primarily metabolized by CYP3A4 . Methods A total of 11 cancer patients ( 4 male , 7 female , aged 50–68 years ) were enrolled in this multicenter , r and omized , open-label , two-period , crossover study . Patients received a single infusion of docetaxel monotherapy , 60–100 mg/m2 , on two occasions at least 3 weeks apart . During one of the cycles ( treatment A ) , patients received docetaxel alone . During the alternate cycle ( treatment B ) , they also received aprepitant 125 mg orally 1 h prior to docetaxel infusion ( day 1 ) , and a single oral dose of aprepitant 80 mg on days 2 and 3 . The pharmacokinetic profile of docetaxel was assessed over 30 h following docetaxel infusion . Blood counts were monitored on days 1 , 4 , 7 , and 14 . Results Ten patients completed the study . Concomitant administration of aprepitant did not cause any statistically or clinical ly significant changes in docetaxel pharmacokinetics . Values for docetaxel alone ( treatment A ) versus docetaxel with aprepitant ( treatment B ) were as follows : geometric mean AUC0–last was 3.26 vs 3.17 μg h/ml ( P>0.25 ; ratio B/A 0.97 ) ; geometric mean AUC0–∞ 3.51 vs 3.39 μg h/ml ( P>0.25 ; ratio B/A 0.96 ) ; geometric mean Cmax was 3.53 vs 3.37 μg/ml ( P>0.25 ; ratio B/A 0.95 ) ; and geometric mean plasma clearance was 23.3 vs 24.2 l/h/m2 ( P>0.25 ; ratio B/A 1.04 ) . The corresponding harmonic mean half-life values were 10.1 and 8.5 h. The two treatment regimens had similar tolerability profiles ; the median absolute neutrophil count nadirs were 681/mm3 during treatment with docetaxel alone and 975/mm3 during aprepitant coadministration . Conclusions Aprepitant had no clinical ly significant effect on either the pharmacokinetics or toxicity of st and ard doses of docetaxel in cancer patients . Aprepitant at clinical ly recommended doses may have a low potential to affect the pharmacokinetics of intravenous chemotherapeutic agents metabolized by CYP3A4",
"Background . A single‐institution , r and omized open trial was prospect ively performed to compare orally administered granisetron with or without intramuscularly administered methylprednisolone to metoclopramide plus methylprednisolone in the prevention of delayed nausea and vomiting induced by cisplatin‐based chemotherapy . The effects of antiemetic treatments were evaluated from days 2 to 5 of the first cycle after cisplatin administration among patients who had never before received chemotherapy",
"BACKGROUND Although ondansetron was found to be effective as an antiemetic in numerous clinical trials of highly emetogenic combination-chemotherapy regimens that included cisplatin , its role in milder emetogenic regimens has not been fully defined . To address its use with a widely used but less emetogenic regimen , we performed a double-blind , r and omized clinical trial comparing ondansetron with dexamethasone and metoclopramide in patients with breast cancer receiving chemotherapy with cyclophosphamide , methotrexate , and fluorouracil . METHODS A total of 165 women with breast cancer from 14 Canadian centers who were about to receive this chemotherapy for the first time were r and omly assigned to receive either ondansetron ( n = 85 ) or dexamethasone plus metoclopramide ( n = 80 ) , a widely used , st and ard antiemetic regimen . The patients recorded the incidence of nausea , emesis , and other side effects in diaries , and these data were compared in the two groups . RESULTS The patients who received dexamethasone and metoclopramide had significantly less nausea during the first 24 hours after chemotherapy was begun . Otherwise , there were no statistically significant differences in efficacy between the regimens . The incidence of drowsiness and increased appetite was higher in the group given dexamethasone and metoclopramide . CONCLUSIONS For women with breast cancer who are being treated with cyclophosphamide , methotrexate , and fluorouracil , the efficacy of dexamethasone and metoclopramide in controlling nausea and vomiting equaled or exceeded that of ondansetron",
"The neurokinin‐1 antagonist aprepitant ( EMEND ™ ; Merck Research Laboratories , West Point , PA ) has been shown to reduce chemotherapy‐induced nausea and vomiting when it is given with a 5‐hydroxytryptamine‐3 receptor antagonist and dexamethasone . The current study sought to define the most appropriate dose regimen of oral aprepitant",
"A double-blind double-dummy , comparative study was carried out in 30 patients receiving highly emetogenic fast dose rate , single fraction total body irradiation prior to bone marrow transplantation . Patients were r and omised into one of two groups , receiving either granisetron , a specific 5-HT3 antagonist or a combination of metoclopramide , dexamethasone phosphate and lorazepam to assess the comparative efficacy of the two regimens in the control of irradiation-induced nausea and vomiting . After 24 h eight patient ( 53 % ) treated with granisetron showed a complete response compared with two patients ( 13 % ) in the comparator group . The control of vomiting by granisetron , over both 24 h and 7-day periods ( P = 0.001 and P = 0.004 ) , was significantly better than that seen with the comparator and required significantly fewer rescue doses . The safety profiles in the two groups appeared similar , with the exception that granisetron produced less drowsiness than the comparator",
"PURPOSE This is the first study in which the NK(1)-receptor antagonist , aprepitant ( APR ) , was evaluated for the prevention of chemotherapy-induced nausea and vomiting ( CINV ) with moderately emetogenic chemotherapy . PATIENTS AND METHODS Eligible breast cancer patients were naive to emetogenic chemotherapy and treated with cyclophosphamide + /- doxorubicin or epirubicin . Patients were r and omly assigned to either an aprepitant regimen ( day 1 , APR 125 mg , ondansetron ( OND ) 8 mg , and dexamethasone 12 mg before chemotherapy and OND 8 mg 8 hours later ; days 2 through 3 , APR 80 qd ) [ DOSAGE ERROR CORRECTED ] or a control regimen ( day 1 , OND 8 mg and dexamethasone 20 mg before chemotherapy and OND 8 mg 8 hours later ; days 2 through 3 , OND 8 mg bid ) . Data on nausea , vomiting , and use of rescue medication were collected with a self-report diary . The primary efficacy end point was the proportion of patients with complete response , defined as no vomiting and no use of rescue therapy , during 120 hours after initiation of chemotherapy in cycle 1 . The secondary end point was the proportion of patients with an average item score higher than 6 of 7 on the Functional Living Index-Emesis question naire . RESULTS Of 866 patients r and omized , 857 patients ( 99 % ) were assessable . Overall complete response was greater with the aprepitant regimen than with the control regimen ( 50.8 % v 42.5 % ; P = .015 ) . More patients in the aprepitant group reported minimal or no impact of CINV on daily life ( 63.5 % v 55.6 % ; P = .019 ) . Both treatments were generally well tolerated . CONCLUSION The aprepitant regimen was more effective than the control regimen for prevention of CINV in patients receiving both an anthracycline and cyclophosphamide",
"PURPOSE The aim of this study was to determine the mechanism of action of radiation-induced emesis by determining the incidence of radiation-induced emesis following hemibody irradiation ; the effects of specific antiemetics especially ondansetron , a 5-hydroxytryptamine receptor antagonist , and to determine the relationship between radiation-induced emesis and serotonin ( 5-hydroxytryptamine ) through its active metabolite , 5-hydroxyindoleacetic acid ( 5-HIAA ) . METHODS AND MATERIAL S Forty-one patients received 53 hemibody treatments of 5 - 8 Gy following intravenous hydration . The patients were divided into three groups according to prehemibody irradiation treatment : Group A : no pretreatment antiemetics , 30 patients ; Group B : nonondansetron antiemetics ( metoclopramide , dexamethasone , prochlorperazine ) , ten patients ; and Group C : ondansetron , 13 patients . The incidence of radiation-induced emesis was determined prehemibody irradiation or baseline and at 1 h posthemibody irradiation in 38 patients and the results expressed as the percent change in 5-HIAA ( ng/ug creatinine ) . RESULTS The incidence of radiation-induced emesis was 82 % ( 14/17 ) following upper/mid hemibody irradiation and 15 % ( 2/11 ) following lower hemibody irradiation in Group A ; 50 % ( 3/6 ) and 25 % ( 1/4 ) following upper/mid and lower hemibody irradiation respectively , in Group B ; and 0 % ( 0/13 ) after upper/mid hemibody irradiation in Group C. The incidence of emesis was significantly different ( p change in 5-HIAA excretion following upper/mid hemibody irradiation were greatest in Group A and smallest in Group C ( p ondansetron , a 5-HT3 receptor antagonist , attests to the efficacy of ondansetron in radiation-induced emesis and suggests a role for serotonin in mediating radiation-induced emesis . Finally , the parallel changes in 5-HIAA and the incidence of emesis provides additional evidence for a more direct role for serotonin in radiation-induced emesis",
"BACKGROUND Nausea and vomiting are among the most unpleasant adverse side effects of cancer therapy . PROCEDURE An open-label dose-escalation study was conducted to assess the appropriate intravenous dose of dolasetron for pediatric patients undergoing chemotherapy . Patients received dolasetron in single intravenous doses of 0.6 ( n = 10 ) , 1.2 ( n = 12 ) , 1.8 ( n = 12 ) , or 2.4 ( n = 12 ) mg/kg 30 min before receiving emetogenic chemotherapy . Pharmacokinetic parameters were evaluated at each dose level and efficacy was evaluated over the first 24 hr following the administration of dolasetron . RESULTS A complete response was achieved in 10 % of patients given 0.6 mg/kg , 25 % of patients given 1 . 2 mg/kg , 67 % of patients given 1.8 mg/kg , and 33 % of patients given 2.4 mg/kg . Peak plasma concentrations ( Cmax ) were observed between 0 . 33 and 0.75 hr following dolasetron infusion . Cmax and area under plasma concentration-time ( AUC ) increased with larger doses of dolasetron , while terminal disposition half-life ( t1/2 ) and apparent clearance ( Clapp ) were not significantly changed with respect to dose . For 1.8-mg/kg dolasetron , the t1/2 was 4.98 hr and the maximum plasma concentration ( tmax ) 0.47 hr . Adverse events were mild to moderate . No serious events occurred . Conclusions . This study suggests that a single intravenous dose of 1.8 mg/kg is the optimum single intravenous dose for controlling chemotherapy-induced emesis in pediatric patients",
"Aprepitant is a novel neurokinin 1 ( NK1 ) antagonist that has been shown to improve control of chemotherapy‐induced nausea and vomiting ( CINV ) when added to a st and ard antiemetic regimen of a 5‐hydroxytriptamine‐3 antagonist plus a corticosteroid . The authors sought to evaluate further the efficacy and tolerability of aprepitant plus st and ard therapy in a large clinical trial",
"PURPOSE In early clinical trials with patients receiving highly emetogenic chemotherapy , the neurokinin antagonist aprepitant significantly enhanced the efficacy of a st and ard antiemetic regimen consisting of a type-three 5-hydroxytryptamine antagonist and a corticosteroid . This multicenter , r and omized , double-blind , placebo-controlled phase III study was performed to establish definitively the superiority of the aprepitant regimen versus st and ard therapy in the prevention of chemotherapy-induced nausea and vomiting ( CINV ) . PATIENTS AND METHODS Patients receiving cisplatin > or = 70 mg/m2 for the first time were given either st and ard therapy ( ondansetron and dexamethasone on day 1 ; dexamethasone on days 2 to 4 ) or an aprepitant regimen ( aprepitant plus ondansetron and dexamethasone on day 1 ; aprepitant and dexamethasone on days 2 to 3 ; dexamethasone on day 4 ) . Patients recorded nausea and vomiting episodes in a diary . The primary end point was complete response ( no emesis and no rescue therapy ) on days 1 to 5 postcisplatin , analyzed by a modified intent-to-treat approach . Treatment comparisons were made using logistic regression models . Tolerability was assessed by reported adverse events and physical and laboratory assessment s. RESULTS The percentage of patients with complete response on days 1 to 5 was significantly higher in the aprepitant group ( 72.7 % [ n = 260 ] v 52.3 % in the st and ard therapy group [ n = 260 ] ) , as were the percentages on day 1 , and especially on days 2 to 5 ( P st and ard dual therapy , addition of aprepitant was generally well tolerated and provided consistently superior protection against CINV in patients receiving highly emetogenic cisplatin-based chemotherapy",
"Factors related to the prevalence , prediction , and course of anticipatory nausea ( AN ) in women ( n = 77 ) receiving adjuvant chemotherapy for breast cancer were examined . Using a prospect i ve longitudinal research design , patients were interviewed both before and after each chemotherapy infusion . Fifty‐seven percent of the patients developed AN . These patients were characterized by more severe gastrointestinal side effects following the initial infusion and greater expectations for experiencing chemotherapy‐related nausea . A more rapid development of AN was related to a history of experiencing nausea across a greater variety of situations , higher IV drug doses , and less infusion‐related anxiety at the initial infusion . Although AN occurred intermittently across treatment sessions , severity was constant . Results provided strong support for the hypothesis that classical conditioning processes are instrumental in AN acquisition . The role of anxiety in the development of AN is considered as are clinical implication s for the prevention of AN and recommendations for future research",
"Cisplatin may evoke both an acute emetic response during the first 24 hours following treatment and a less well-recognized syndrome of delayed emesis . While delayed emesis is usually less severe in terms of frequency of vomiting episodes , the problem continues to result in significant morbidity . In comparison with acute emesis , the exact pathogenesis of the delayed emesis syndrome remains unclear . Although a combination of oral metoclopramide and dexamethasone is effective in many patients in preventing delayed emesis , almost 50 % continue to experience at least one emetic episode when treated with this regimen . A phase III multicenter study has evaluated oral ondansetron versus placebo in the prevention of the delayed-emesis syndrome in 50 patients during days 2 through 5 following high-dose cisplatin administration . Although the daily rates of complete emetic control , failure , and control of nausea favor ondansetron , this trial is statistically inconclusive in establishing efficacy of ondansetron as a single agent in the prevention of delayed emesis . Ondansetron was well tolerated in the dose and schedule used",
"The nausea and vomiting experienced by one in four cancer patients in anticipation of chemotherapy is probably a learned response to treatment . To determine whether behavioral approaches for altering learned responses might be useful treatments for these symptoms , we compared the effects of \" systematic desensitization \" ( a behavioral treatment in which relaxation is learned as a response to situations in which patients have had anticipatory nausea and vomiting ) with those of counseling and of no treatment . Sixty ambulatory cancer patients with anticipatory nausea and vomiting before their third and fourth chemotherapy treatments were r and omized equally to the three groups . Significantly more patients receiving desensitization reported no anticipatory nausea before their fifth and sixth chemotherapy treatments than patients given counseling ( P less than 0.05 ) or no treatment ( P less than 0.01 ) . Desensitized patients also reported significantly less severe anticipatory nausea ( P less than 0.01 ) and vomiting ( P less than 0.05 ) and a shorter duration of anticipatory nausea ( P less than 0.01 ) . We conclude that systematic desensitization appears to have an antiemetic effect in cancer patients who receive chemotherapy , and may be useful in the management of these problems",
"To prevent delayed emesis induced by cisplatin ( mean dose 90 mg/m2 ) , 120 consecutive patients were r and omized to receive , in a 7-day crossover design , oral metoclopramide ( 20 mg q.i.d . ) , dexamethasone ( 1 mg q.i.d . ) or placebo ( two tablets q.i.d . ) starting 24 hours after the end of chemotherapy . Complete protection from nausea , but not from vomiting . was significantly increased by both dexamethasone and metoclopramide with respect to placebo . Important prognostic factors favoring the appearance of delayed emesis were incomplete protection from vomiting during the first 24 hours after cisplatin , female gender , and highest cisplatin doses . Tolerability of both drugs was good . Larger and r and omized controlled trials are necessary to identify better preventive treatment of delayed emesis induced by cisplatin",
"BACKGROUND Although usually a problem of cisplatin-based chemotherapy , delayed emesis can cause severe distress in patients treated with cyclophosphamide . Dexamethasone has been shown to be effective in the control of cisplatin-induced delayed emesis , but its role against the delayed problem in patients treated with cyclophosphamide has not been demonstrated . Our study was conducted to evaluate the effect of dexamethasone in delayed emesis induced by cyclophosphamide . PATIENTS AND METHODS Ninety-eight patients were given i.v . granisetron and i.v . dexamethasone before chemotherapy , and r and omised to receive either oral dexamethasone 4 mg twice daily as maintenance or no maintenance . RESULTS Ninety-four patients were evaluable . Of those given maintenance oral dexamethasone , 57 % had complete and 30 % had major control of delayed emesis , versus 33 % and 15 % , respectively , of patients who did not receive maintenance . Side effects are mainly constipation and headache . CONCLUSION The results shows that oral dexamethasone is an effective agent against cyclophosphamide-induced delayed emesis",
"Ondansetron is a 5-hydroxytryptamine receptor antagonist which has shown activity in the prevention of emesis following cytotoxic and radiation therapy for cancer . We describe our experience using ondansetron in 25 patients undergoing fractionated total body irradiation ( TBI ) 12 Gy/3 days as conditioning for bone marrow transplantation . Antiemetic efficiency was investigated during the 3 days of TBI prior to high-dose cytotoxic chemotherapy . Twenty-two of the 25 patients ( 88 % ) achieved sufficient emesis control with less than three emetic episodes whereas the remaining 12 % experienced three to five emetic events during their worst 24-h period . Eleven patients ( 44 % ) had complete control with no vomiting at all . Of 75 ' patient days ' , 52 ( 69 % ) were without any emesis , 20 ( 27 % ) were associated with one to two and only three ( 4 % ) with three to five emetic episodes . Headache occurred in four patients ( 16 % ) . No other significant adverse effects were seen , in particular no extrapyramidal reactions due to ondansetron . Our data confirm that ondansetron plays a major role in the antiemetic management of patients undergoing TBI",
"The development of anticipatory nausea in cancer chemotherapy typically has been viewed in terms of a respondent learning model . Firm support for this etiological model has been precluded by use of retrospective research design s , however . The present study employed a prospect i ve design to identify patient and treatment-related variables characteristic of patients who subsequently develop anticipatory nausea . Seventy-one chemotherapy out patients were interviewed before and after each chemotherapy infusion during their first 6 months of treatment . Hierarchical multiple regression analysis revealed that patients who developed anticipatory nausea were characterized by more severe posttreatment nausea , more time-consuming treatment infusions , and greater state anxiety relative to patients without anticipatory nausea . In general , results supported a respondent learning conceptualization of the development of anticipatory nausea . Clinical implication s of these findings for the prevention of anticipatory nausea are suggested",
" One hundred and seventy-five patients selected at r and om were prospect ively studied . All patients were assessed at least after the first cycle of treatment by a self-report question naire which covered the occurrence of nausea and vomiting 24 before chemotherapy , as well as information regarding 22 clinical parameters . Forty-six ( 26 % ) patients developed anticipatory nausea . ' Intolerable ' posttreatment vomiting and age under 45 were statistically significant parameters ( p less than 0.05 ) in the multivariate analysis . Twenty-one ( 12 % ) of the 175 patients experienced anticipatory vomiting . Three variables , age under 45 , ' intolerable ' posttreatment vomiting and more than three cycles of treatment were found to be significant ( p less than 0.05 ) . The relative risk of developing anticipatory nausea and vomiting according to combination of significant clinical predictors in the multivariate analysis is proposed . Therefore recognition of these clinical predictors may serve as a marker for patients with high risk of presenting anticipatory nausea and vomiting , who may benefit from prophylactic behavioral approaches",
"Two large r and omized , double-blind , placebo-controlled studies with an appropriate study design have been conducted to fully evaluate the efficacy of ondansetron in the control of cisplatin-induced delayed emesis . These studies show that ondansetron and particularly ondansetron plus dexamethasone have moderate efficacy in the control of cisplatin-induced delayed emesis and nausea . The benefit of ondansetron , with or without dexamethasone , may be greatest in patients with incomplete control of acute emesis . The efficacy of ondansetron in this setting compared to its greater efficacy during the acute phase of emesis induced by cisplatin and the more prolonged phases of acute emesis induced by cyclophosphamide and carboplatin indicates that non-5-HT3-mediated emetic mechanisms maybe are relatively more important in the delayed phase of emesis following cisplatin"
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41187458-06ff-11f0-808a-c43d1ab1c353
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Anatomical changes in the gastrointestinal tract and subsequent weight loss may influence drug disposition and thus drug dosing following bariatric surgery . This review systematic ally examines the effects of bariatric surgery on drug pharmacokinetics , focusing especially on the mechanisms involved in restricting oral bioavailability . Studies with a longitudinal before-after design investigating the pharmacokinetics of at least one drug were review ed . The need for dose adjustment following bariatric surgery was examined , as well as the potential for extrapolation to other drugs subjected to coinciding pharmacokinetic mechanisms . A total of 22 original articles and 32 different drugs were assessed . The majority of available data is based on Roux-en-Y gastric bypass ( RYGBP ) ( 18 of 22 studies ) , and hence , the overall interpretation is more or less limited to RYGBP . In the case of the majority of studied drugs , an increased absorption rate was observed early after RYGBP . The effect on systemic exposure allows for a low degree of extrapolation , including between drugs subjected to the same major metabolic and transporter pathways . On the basis of current underst and ing , predicting the pharmacokinetic change for a specific drug following RYGBP is challenging . Close monitoring of each individual drug is therefore recommended in the early postsurgical phase . Future studies should focus on the long-term effects of bariatric surgery on drug disposition , and they should also aim to disentangle the effects of the surgery itself and the subsequent weight loss
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"AIMS Roux-en-Y gastric bypass ( RYGB ) alters the anatomical structure of the gastrointestinal tract , which can result in alterations in drug disposition . The aim of the present study was to evaluate the oral disposition of two compounds belonging to the Biopharmaceutical Classification System Class II - fenofibrate ( bile salt-dependent solubility ) and posaconazole ( gastric pH-dependent dissolution ) - before and after RYGB in the same individuals . METHODS A single-dose pharmacokinetic study with two model compounds - namely , 67 mg fenofibrate ( Lipanthyl ® ) and 400 mg posaconazole ( Noxafil ® ) - was performed in 12 volunteers pre- and post-RYGB . After oral administration , blood sample s were collected at different time points up to 48 h after administration . Plasma concentrations were determined by high-performance liquid chromatography in order to calculate the area under the concentration-time curve up to 48 h ( AUC0 - 48 h ) , the peak plasma concentration ( Cmax ) and the time to reach peak concentration ( Tmax ) . RESULTS After administration of fenofibrate , no relevant differences in AUC0 - 48 h , Cmax and Tmax between the pre- and postoperative setting were observed . The geometric mean of the ratio of AUC0 - 48 h post/pre-RYGB for fenofibrate was 1.10 [ 95 % confidence interval ( CI ) 0.87 , 1.40 ; P = 0.40 ] . For posaconazole , an important decrease in AUC0 - 48 h and Cmax following RYGB was shown ; the geometric mean of the AUC0 - 48 h post/pre-RYGB ratio was 0.68 ( 95 % CI 0.48 , 0.96 ; P = 0.03 ) and the geometric mean of the Cmax pre/post-RYGB ratio was 0.60 ( 95 % CI 0.39 , 0.94 ; P = 0.03 ) . The decreased exposure of posaconazole could be explained by the increased gastric pH and accelerated gastric emptying of fluids post-RYGB . No difference for Tmax was observed . CONCLUSIONS The disposition of fenofibrate was not altered after RYGB , whereas the oral disposition of posaconazole was significantly decreased following RYGB",
"AIMS Venous thromboembolism is an important cause of postoperative morbidity and mortality in bariatric surgery . Studies of direct oral anticoagulants ( DOACs ) are not available in this surgical field . The objective of this phase 1 clinical trial was to investigate pharmacokinetic and pharmacodynamic ( PK/PD ) parameters of rivaroxaban in bariatric patients . METHODS In this single-centre study , obese patients received single oral doses of rivaroxaban ( 10 mg ) 1 day prior to and 3 days after bariatric surgery . PK and PD parameters were assessed at baseline and during 24 h after drug ingestion . RESULTS Six Roux-en-Y gastric bypass patients and six sleeve gastrectomy patients completed the study . Mean rivaroxaban area under plasma concentration-time curve , peak plasma concentration , time to peak plasma concentration and terminal half-life were 971.9 μg·h l-1 ( coefficient of variation : 10.6 ) , 135.3 μg l-1 ( 26.7 ) , 1.5 h and 13.1 h ( 34.1 ) prior to and 1165.8 ( 21.9 ) , 170.0 ( 15.9 ) , 1.5 and 8.9 ( 44.6 ) postsurgery for SG patients and 933.7 μg·h l-1 ( 22.3 ) , 136.5 μg l-1 ( 10.7 ) , 1.5 h und 13.8 h ( 46.6 ) prior to and 1029.4 ( 7.4 ) , 110.8 ( 31.8 ) , 2.5 and 15 ( 60.0 ) postsurgery for Roux-en-Y gastric bypass patients , respectively . Prothrombin fragments ( F1 + 2 ) decreased during the first 12 hours and increased thereafter in the pre- and the postbariatric setting . Thrombin-antithrombin complexes dropped within 1 - 3 h in the prebariatric setting and remained low after surgery until they increased at 24 h postdose . Rivaroxaban was well tolerated and no relevant safety issues were observed . CONCLUSIONS Bariatric surgery does not appear to alter PK of rivaroxaban in a clinical ly relevant way . Effective prophylactic postbariatric anticoagulation is supported by changes in PD",
"Background A previous study of 22 patients undergoing either gastric bypass or duodenal switch showed increased systemic exposure of atorvastatin acid 3–8 weeks after surgery in the majority of patients . This study aim ed to investigate the long-term effects on systemic exposure of atorvastatin acid in the same group of patients . Methods An 8-h pharmacokinetic investigation was performed a median of 27 months ( range 21–45 months ) after surgery . Systemic exposure was measured as the area under the plasma concentration versus the time curve from 0 to 8 h postdose ( AUC0–8 ) . Linear mixed models with AUC0–8 as the dependent variable were implemented to assess the effect of time , surgical procedure , and body mass index ( BMI ) as explanatory variables . Results The study enrolled 20 patients . The systemic exposure of atorvastatin acid changed significantly over time ( p = 0.001 ) , albeit there was substantial variation between subjects . The effect of time was attenuated but remained significant after adjustment for surgical procedure and BMI ( p = 0.048 ) . The initial AUC0–8 increase seen in the majority of patients 3–8 weeks after surgery was normalized long term , with 7 of the 12 gastric bypass patients and 6 of the 8 duodenal switch patients showing decreased AUC0–8 compared with preoperative values . Conclusions The systemic exposure of atorvastatin showed a significant change over time after bariatric surgery , albeit with large inter- and intraindividual variations . The findings indicate that patients using atorvastatin or drugs with similar pharmacokinetic properties should be monitored closely for both therapeutic effects and adverse events the first years after gastric bypass and duodenal switch . Clinical Trial NCT00331565",
"Background Data on the absorption of orally administered drugs following Roux-en-Y gastric bypass ( RYGB ) surgery in obese patients are limited and inconclusive . As it is difficult to predict changes in absorption , studies on frequently used drugs in this population are necessary . Acetylsalicylic acid ( ASA ) and omeprazole are two commonly prescribed drugs in obese patients . Methods In this repeated measures study , omeprazole and salicylic acid ( SA ) serum concentrations were measured before and after RYGB in 34 morbidly obese subjects . Time to maximum concentration ( Tmax ) , lag time ( Tlag ) , maximum concentration ( Cmax ) , and area under the serum concentration versus time curve ( AUC ) were calculated for both drugs to determine possible differences in drug absorption after the procedure . Results For SA , Tmax significantly decreased after RYGB , while both Cmax and AUC0–24 significantly increased . For omeprazole , both Tmax and Tlag significantly decreased after RYGB , while Cmax significantly increased . Mean AUC0–12 significantly decreased post-surgery . The difference in AUC0–12 before and after surgery varied between subjects . Conclusions Our study shows a faster absorption of both ASA and omeprazole after RYGB . The exposure to ASA is higher post-surgery , but the st and ard dose of 80 mg does not need to be modified , considering its range in effective dose . The exposure to omeprazole is , on average , decreased after surgery . Clinicians should be aware to increase the dose of omeprazole if symptoms suggest inadequate response",
"Biliopancreatic diversion with duodenal switch is a combined restrictive and malabsorptive surgical weight loss procedure . Given that this procedure introduces a bypass of the proximal small intestine , it is a suitable model for investigating the influence of the proximal intestine on drug bioavailability . Eight‐hour pharmacokinetic profiles were obtained the day before surgery and again after surgery at ( median ) 6 weeks ( range , 4–8 weeks ) in 10 morbidly obese patients who were receiving treatment with 20–80 mg atorvastatin each morning . The bioavailability of atorvastatin acid was significantly increased , with a mean twofold higher AUC0–8 after surgery ( range 1.0–4.2 , P = 0.001 ) . Time to maximum plasma concentration ( Cmax ) increased from 1.2 h before surgery to 2.3 h after surgery ( P = 0.03 ) . The results emphasize the protective nature of the proximal small intestine against ingested exogenous compounds . Consequently , retitration to the lowest effective dose should be considered after biliopancreatic diversion with duodenal switch in the case of drugs with a high degree of intestinal first pass metabolism and a narrow therapeutic window",
"AIMS Our objective was to study in vivo the role of CYP2C and CYP3A4 in the disposition of 3-keto-desogestrel after administration of desogestrel , by using the selective inhibitors fluconazole ( CYP2C ) and itraconazole ( CYP3A4 ) . METHODS This study had a three-way crossover design and included 12 healthy females , the data from 11 of whom were analyzed . In the first ( control ) phase all subjects received a single 150 microg oral dose of desogestrel alone . In the second and third phases subjects received a 4 day pretreatment with either 200 mg fluconazole or 200 mg itraconazole once daily in a r and omized balanced order . Desogestrel was given 1 h after the last dose of the CYP inhibitor . Plasma 3-keto-desogestrel concentrations were determined for up to 72 h post dose . RESULTS Pretreatment with itraconazole for 4 days significantly increased the area under the plasma concentration-time curve ( AUC ) of 3-keto-desogestrel by 72.4 % ( 95 % confidence interval on the difference 12 % , 133 % ; P = 0.024 ) compared with the control phase , whereas fluconazole pretreatment had no significant effect ( 95 % CI on the difference -42 % , 34 % ) . Neither enzyme inhibitor affected significantly the maximum concentration ( 95 % CI on the difference 14 % , 124 % for itraconazole and -23 % , 40 % for fluconazole ) or elimination half-life ( 95 % CI on the difference -42 % , 120 % for itraconazole and -24 % , 61 % for fluconazole ) of 3-keto-desogestrel . CONCLUSIONS According to the present study , the biotransformation of desogestrel to 3-keto-desogestrel did not appear to be mediated by CYP2C9 and CYP2C19 as suggested earlier . However , the further metabolism of 3-keto-desogestrel seems to be catalyzed by CYP3A4",
"Posture has an effect on gastric emptying . In this study , we investigated whether posture influences the delay in gastric emptying induced by opioid analgesics . Ten healthy male subjects underwent 4 gastric emptying studies with the acetaminophen method . On two occasions the subjects were given a continuous infusion of remifentanil ( 0.2 μg · kg−1 · min−1 ) while lying either on the right lateral side in a 20 ° head-up position or on the left lateral side in a 20 ° head-down position . On two other occasions no infusion was given , and the subjects were studied lying in the two positions . When remifentanil was given , there were no significant differences between the two postures in maximal acetaminophen concentration ( right side , 34 μmol · L−1 ; versus left side , 16 μmol · L−1 ) , time taken to reach the maximal concentration ( 94 versus 109 min ) , or area under the serum acetaminophen concentration time curve from 0 to 60 min ( 962 versus 197 min · μmol · L−1 ) . In the control situation , there were differences between the postures in maximal acetaminophen concentration ( 138 versus 94 μmol · L−1 ; P ) and area under the serum acetaminophen concentration time curves from 0 to 60 min ( 5092 versus 3793 min · μmol · L−1 ; P difference in time taken to reach the maximal concentration ( 25 versus 47 min ) . Compared with the control situation , remifentanil delayed gastric emptying in both postures . We conclude that remifentanil delays gastric emptying and that this delay is not influenced by posture",
"Background : Patients undergoing biliopancreatic diversion ( BPD ) may develop gastric ulcers , particularly within the first postoperative year . The prophylactic use of antisecretory compounds at the usual therapeutic doses , mainly conventional H2-receptor antagonists such as ranitidine , may reduce the incidence of this complication , which occurs in ∼5 % of patients after BPD . Methods : The authors measured the plasma concentrations of ranitidine ( 300 mg orally ) in obese patients , before and 8 months after BPD , and in control subjects of normal weight . The study included 11 obese patients undergoing BPD ( age 45 ± 14 years ; preoperative and postoperative weights 124 ± 21 and 92 ± 11 kg ) and 10 normal-weight subjects ( age 37 ± 13 years , weight 67 ± 9 kg ) . Results : Postoperative ranitidine plasma concentrations showed only minor differences from preoperative levels , with slightly higher maximum concentrations occurring sooner . The mean area under the curve was on the average 30 % higher than preoperatively . All parameters , however , were similar to those in control subjects . Conclusions : BPD per se does not greatly affect the pharmacokinetic behavior of ranitidine , and therefore a conventional dosage regimen appears adequate for the prophylaxis and therapy of gastric ulcers associated with this operation",
"STUDY OBJECTIVE The extended-release ( ER ) form of venlafaxine is preferred because of improved patient adherence , but the immediate-release ( IR ) form is frequently used after Roux-en-Y gastric bypass ( RYGB ) surgery because of concerns for malabsorption . The objective of this study was to determine whether a statistically significant and predictable change in the bioavailability of venlafaxine ER capsules occurs after RYGB . DESIGN Prospect i ve nonblinded single-dose pharmacokinetic study . SETTING Clinical research unit at a large tertiary care medical practice . PATIENTS Ten adult pre-bariatric surgery patients who met the criteria for noncomplicated RYGB were enrolled and served as their own controls . INTERVENTIONS Patients were administered one venlafaxine ER 75-mg capsule at two visits-the first visit at least 1 week before undergoing RYGB and the second visit 3 - 4 months after RYGB . Blood sample s were collected at predetermined intervals over 48 hours after each dose , and the pharmacokinetics of venlafaxine were measured . MEASUREMENTS AND MAIN RESULTS Plasma levels of venlafaxine and its primary metabolite , O-desmethylvenlafaxine ( ODV ) , were compared at baseline and 3 - 4 months after RYGB . The areas under the serum concentration-time curves from 0 - 24 hours ( AUC0 - 24 ) for venlafaxine ( mean ± SD 734 ± 602 vs 630 ± 553 ng·hr/ml , p=0.22 ) and ODV ( mean ± SD 894 ± 899 vs 1083 ± 972 ng·hr/ml , p=0.07 ) were similar before and after RYGB . Using a bioequivalence approach , differences in pre-RYGB and post-RYGB values of AUC0 - 24 , peak serum concentration , and time to peak serum concentration were not statistically significant for either venlafaxine or ODV . CONCLUSION This study suggests that RYGB does not significantly alter the amount of venlafaxine or its active metabolite , ODV , absorbed from a venlafaxine ER capsule or the time over which it is absorbed",
"WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * Numerous cocktails using concurrent administration of several cytochrome P450 ( CYP ) isoform-selective probe drugs have been reported to investigate drug-drug interactions in vivo . * This approach has several advantages : characterize the inhibitory or induction potential of compounds in development toward the CYP enzymes identified in vitro in an in vivo situation , assess several enzymes in the same trial , and have complete in vivo information about potential CYP-based drug interactions . WHAT THIS STUDY ADDS * This study describes a new cocktail containing five probe drugs that has never been published . * This cocktail can be used to test the effects of a new chemical entity on multiple CYP isoforms in a single clinical study : CYP1A2 ( caffeine ) , CYP2C9 ( warfarin ) , CYP2C19 ( omeprazole ) , CYP2D6 ( metoprolol ) , and CYP3A ( midazolam ) and was design ed to overcome potential liabilities of other reported cocktails . AIMS To assess the pharmacokinetics ( PK ) of selective substrates of CYP1A2 ( caffeine ) , CYP2C9 ( S-warfarin ) , CYP2C19 ( omeprazole ) , CYP2D6 ( metoprolol ) and CYP3A ( midazolam ) when administered orally and concurrently as a cocktail relative to the drugs administered alone . METHODS This was an open-label , single-dose , r and omized , six-treatment six-period six-sequence William 's design study with a wash-out of 7 or 14 days . Thirty healthy male subjects received 100 mg caffeine , 100 mg metoprolol , 0.03 mg kg(-1 ) midazolam , 20 mg omeprazole and 10 mg warfarin individually and in combination ( cocktail ) . Poor metabolizers of CYP2C9 , 2C19 and 2D6 were excluded . Plasma sample s were obtained up to 48 h for caffeine , metoprolol and omeprazole , 12 h for midazolam , 312 h for warfarin and the cocktail . Three different vali date d liquid chromatography t and em mass spectrometry methods were used . Noncompartmental PK parameters were calculated . Log-transformed C(max ) , AUC(last ) and AUC for each analyte were analysed with a linear mixed effects model with fixed term for treatment , sequence and period , and r and om term for subject within sequence . Point estimates ( 90 % CI ) for treatment ratios ( individual/cocktail ) were computed for each analyte C(max ) , AUC(last ) and AUC . RESULTS There was no PK interaction between the probe drugs when administered in combination as a cocktail , relative to the probes administered alone , as the 90 % CI of the PK parameters was within the prespecified bioequivalence limits of 0.80 , 1.25 . CONCLUSION The lack of interaction between probes indicates that this cocktail could be used to evaluate the potential for multiple drug-drug interactions in vivo",
"STUDY OBJECTIVES To evaluate the effect of Roux-en-Y gastric bypass surgery ( RYGB ) on the pharmacokinetics of midazolam ( a CYP3A4 substrate ) and digoxin ( a P-glycoprotein substrate ) . DESIGN Prospect i ve , nonblinded , longitudinal , single-dose pharmacokinetic study in three phases : presurgery baseline and postoperative assessment s at 3 and 12 months . PATIENTS Twelve obese patients meeting current st and ards for bariatric surgery . MEASUREMENTS AND MAIN RESULTS At each study visit , patients received a single dose of oral digoxin and midazolam at 8 a.m. Blood sample s were collected at regular intervals for 24 hours after dosing . Continuous 12-lead electrocardiogram ( EKG ) , heart rate , blood pressure , and respiratory rate were monitored , and pharmacokinetic parameters from the three visits were compared . The peak plasma concentration ( Cmax ) of midazolam increased by 66 % and 71 % at 3- and 12-month post-RYGB ( p=0.017 and p=0.001 , respectively ) , whereas the median time to peak concentration ( Tmax ) was reduced by 50 % . The mean Cmax for 1'-hydroxymidazolam increased by 87 % and 80 % at 3 and 12 months ( p=0.001 and p area under the concentration-time curve ( AUC ) for midazolam nor the metabolite-to-parent AUC ratio changed significantly over time . For digoxin , the median Tmax decreased from 40 minutes at baseline to 30 and 20 minutes at 3 and 12 months , respectively . The mean AUC for digoxin , heart rate , and EKG patterns were similar across the three study phases . CONCLUSION Contemporary proximal RYGB increases the rate of drug absorption without significantly changing the overall exposure to midazolam and digoxin . The Cmax of a CYP3A4 substrate with a high extraction ratio was substantially increased after RYGB",
"OBJECTIVE Morbidly obese patients frequently present with mood and anxiety disorders , which are often treated with serotonin reuptake inhibitors ( SRIs ) . Having observed that patients treated with SRIs frequently relapse after Roux-en-Y gastric bypass surgery , the authors sought to assess whether SRI bioavailability is reduced postoperatively . METHOD Twelve gastric bypass c and i date s treated with an SRI for primary mood or anxiety disorders were studied prospect ively . Timed blood sample s for SRI plasma levels were drawn for pharmacokinetic studies before surgery and 1 , 6 , and 12 months afterward . Maximum concentration , time to maximum concentration , and area under the concentration/time curve ( AUC ) were determined . RESULTS In eight of the 12 patients , AUC values 1 month after surgery dropped to an average of 54 % ( SD=18 ) of preoperative levels ( range=36%-80 % ) ; in six of these patients , AUC values returned to baseline levels ( or greater ) by 6 months . Four patients had an exacerbation of depressive symptoms , which resolved by 12 months in three of them . Three of the four patients had a reduced AUC level at 1 month and either gained weight or failed to lose weight between 6 and 12 months . Normalization of the AUC was associated with improvement in symptom scores . CONCLUSIONS Patients taking SRIs in this study were at risk for reduced drug bioavailability 1 month after Roux-en-Y gastric bypass . The authors recommend close psychiatric monitoring after surgery",
"Context Anti-retroviral therapy ( ART ) dramatically reduced AIDS development , thus enabling patients to live as long as the general population . New challenges have emerged particularly cardiometabolic diseases and weight gain , with some HIV patients seeking bariatric surgery ( BS ) . However , BS outcomes during HIV remain poorly described , with scarce data on ART pharmacokinetic post-BS . Objective Describing sleeve gastrectomy ( SG ) results in HIV patients in terms of ART pharmacokinetic , HIV control , weight loss , and metabolic outcomes . Design , Setting , and Patients Prospect i ve study of HIV patients undergoing SG in a referral academic center , with at least 6 months follow-up . Main Outcome Measure Clinical and biological parameters , HIV medical history , and ART pharmacokinetics were gathered before and post-SG . Results Seventeen patients ( mean BMI = 44.2 ± 5.7 kg m−2 ) and major obesity-related diseases ( 47 % type-2 diabetes , 64 % obstructive sleep apnea , 70 % hypertension ) underwent SG during a mean 2 years of follow-up . They displayed an average of 20 % reduction of initial BMI and improved body composition , similarly to obese non-HIV patients . SG improved metabolic status . All patients had undetectable viral load before BS . Upon HIV follow-up , 12 patients had undetectable viral load with correct ART kinetic parameters ( 3 and 6 months ) ; 4 displayed detectable viral load along with significant decrease in raltegravir and atazanavir treatment exposure , leading to ART change with subsequent undetectable viral load ; and 1 had persistent detectable viral load despite ART change . Conclusions SG seems effective and safe in obese HIV patients . However , ART treatment should be monitored post-SG to control HIV infection . We suggest that some ART should be adapted before SG conjoints with infectious disease specialists",
"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",
"Two established caffeine-based urinary methods for measuring CYP1A2 activity were compared with each other , and also with the systemic clearance of caffeine which served as a st and ard of reference for such activity . Following a st and ardized dose , caffeine ( 137X ) and its metabolites were measured in urine and plasma of 39 healthy subjects . The measurements allowed determinations of : ( 1 ) systemic caffeine clearance ( CL(caff ) ) ; ( 2 ) the caffeine metabolite ratio ( AFMU + 1X + 1U)/17U determined in an overnight-urine specimen and referred to as CMR , and ( 3 ) the ratio ( 17X + 17U)/137X measured in urine collected between 4 and 5 h after caffeine intake and referred to as PCUR for ' paraxanthine-caffeine urinary ratio ' . The PCUR showed a bimodal distribution and a relatively wide variation , CL(caff ) and CMR were both normally distributed . The correlation between CL(caff ) and CMR was r = 0.77 ( p caffeine metabolism by oral contraceptive use was observed with both CL(caff ) and CMR but not with PCUR . Examination of possible explanations for the differences between PCUR and CMR led to the finding of a correlation between PCUR and the renal clearance of caffeine ( CLr ) with r = -0.47 ( p < 0.01 ) . Further scrutiny demonstrated that a bimodal or non-normal frequency distribution as shown by PCUR was also shown by CLr and by urine flow rate . ( ABSTRACT TRUNCATED AT 250 WORDS",
"Background and Objectives Obesity and opioid use for chronic pain in obese individuals are both important public health concerns . The pharmacokinetics of oral morphine after Roux-en-Y gastric bypass ( RYGB ) are unknown . Therefore , we aim ed to study the pharmacokinetics of oral morphine in morbidly obese patients before and after RYGB surgery , to identify the effects of RYGB and the subsequent reversal of morbid obesity on the pharmacokinetic parameters of morphine . Methods The pharmacokinetics of oral morphine ( 30 mg ) were studied in 30 obese patients before ( Visit 1 ) and then 7–15 days ( Visit 2 ) and 6 months ( Visit 3 ) after RYGB . A population pharmacokinetic model was used to describe the time course of the plasma morphine concentration , to study the effect of RYGB on morphine pharmacokinetics and to estimate inter-patient variability . Results The oral morphine time to maximum plasma concentration ( tmax ) was twofold lower and maximum plasma concentration ( Cmax ) was 1.7 times higher at Visit 2 , and tmax was 7.5 times lower and Cmax 3.3 times higher at Visit 3 than at Visit 1 . The mean oral morphine area under the plasma concentration – time curve ( AUC ) increased significantly ( 1.55-fold ) between Visits 1 and 3 . Changes in body mass index ( BMI ) after RYGB were clearly associated with decreased apparent oral morphine clearance and apparent central and peripheral morphine volumes of distribution . None of the other anthropometric parameters explained the inter-subject variability in morphine exposure better than BMI . Conclusion RYGB and the BMI reduction that followed it dramatically increased the rate of morphine absorption and slightly increased morphine exposure . The dose of immediate-release forms of morphine may be divided in obese patients after RYGB to prevent adverse events due to early and high morphine plasma peaks",
"The biological effects of a new synthetic progestagen , Org 2969 ( 13-ethyl-11-methylene-18,19-dinor-17 alpha-pregn-4-en-20-yn-17-ol ) were studied in healthy normally menstruating women . Two of them were given 0.125 mg , five 0.060 mg and two 0.030 mg of Org 2969 daily on days 1 - 20 during one menstrual cycle . Serum levels of follicle stimulating hormone , luteinizing hormone , progesterone and oestradiol were analyzed on days 8 - 23 in order to evaluate the function of the hypophyseal-ovarian axis . The serum concentrations of aspartate amino transferase , alanine amino transferase , alkaline phosphatase , gamma glutamyl transpeptidase and bilirubin were determined to evaluate possible side effects on live function on days 8 , 15 and 23 . Serum cortisol was measured on days 8 and 23 . The basal body temperature was recorded daily during the whole cycle , and endometrium biopsies were taken on days 21 or 22 of the cycle . All sample s were taken similaryl during the treatment cycle and the preceding control cycle . According to the hormone determinations , all the treatment cycles were anovulatory except in one woman receiving the lowest dose . The treatment led to decreased spinnbarkeit , arborization and sperum penetration in the cervical mucus . Liver function tests and serum cortisol remained unchanged during the treatment",
"To investigate whether Roux‐en‐Y gastric bypass ( RYGB ) affects oral desogestrel ( etonogestrel ) pharmacokinetics",
"BACKGROUND Thromboembolic disease is a potentially serious complication in bariatric surgery patients . Direct oral anticoagulants ( DOAC ) have been investigated in orthopedic surgery patients . DOAC data after bariatric surgery are still limited to the early postsurgical period . Whether postsurgical midterm adaptations due to anatomic and physiologic alterations influence drug pharmacology is currently not known . OBJECTIVE The aim of this study was to investigate the influence of weight loss and type of bariatric surgery on midterm postsurgical pharmacokinetic and pharmacodynamic parameters of rivaroxaban . SETTING University hospital . METHODS In this monocentric study , bariatric patients received a single oral dose of rivaroxaban ( 10 mg ) 6 to 8 months after sleeve gastrectomy ( SG ) or Roux-en-Y-gastric bypass ( RYGB ) . Pharmacokinetic and pharmacodynamic parameters were assessed and compared with prebariatric surgery results . RESULTS We included 6 RYGB and 6 SG patients . Percent excess weight loss was 71.4 % ( interquartile range 56.4 , 87.9 ) in the SG group and 76.6 % ( 64.5 , 85.7 ) in the RYGB group . Rivaroxaban mean areas under the curve 6 to 8 months after the bariatric procedure ( 922.4 µg × h/L , coefficient of variation 43.2 ) were comparable to those measured preoperatively ( 952.6 µg × h/L , 16.8 ) . There was no relevant difference between the 2 surgical procedure groups . Rivaroxaban led to a decrease of prothrombin fragments F1 + 2 over 12 hours after oral intake confirming in vivo efficacy . CONCLUSIONS Significant weight loss and altered anatomy after RYGB and SG procedures do not appear to affect the pharmacokinetics and pharmacodynamics of prophylactic rivaroxaban . A single dose of Rivaroxaban was well tolerated and considered safe in this trial",
"Background Bariatric surgery leads to several anatomo-physiological modifications that may affect pharmacokinetic parameters and consequently alter the therapeutic effect of drugs , such as antibiotics . The pharmacokinetics of oral amoxicillin after Roux-en-Y gastric bypass ( RYGB ) surgery is unknown . Objectives The objective of this study was to evaluate the impact of bariatric surgery on the pharmacokinetics of amoxicillin . Methods This study was performed as a r and omized , open-label , single-dose clinical trial , with two periods of treatment , in which obese subjects ( n = 8) received an amoxicillin 500 mg capsule orally before and 2 months after the RYGB surgery . The amoxicillin plasma concentration was determined by liquid chromatography coupled to mass spectrometry ( LC-MS/MS ) . Results After the surgery , the mean weight loss was 17.03 ± 5.51 kg , and mean body mass index ( BMI ) decreased from 46.21 ± 2.82 to 38.82 ± 3.32 kg/m2 . The mean amoxicillin area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration ( AUC0–tlast ) increased significantly ( 3.5-fold ) ; the maximum plasma concentration ( Cmax ) increased 2.8-fold after the bariatric surgery . No correlation was found between amoxicillin absorption , BMI , and weight loss percentage . Conclusion The alterations observed in the amoxicillin pharmacokinetics suggest that obese subjects included in this trial had a substantially increase in amoxicillin systemic exposure after RYGB surgery . However , despite this increase , its exposure was lower than the values reported for non-obese volunteers . Trial Registration Identifiers :",
"AIMS The anticoagulant rivaroxaban is an oral , direct Factor Xa inhibitor for the management of thromboembolic disorders . Metabolism and excretion involve cytochrome P450 3A4 ( CYP3A4 ) and 2J2 ( CYP2J2 ) , CYP-independent mechanisms , and P-glycoprotein ( P-gp ) and breast cancer resistance protein ( Bcrp ) ( ABCG2 ) . METHODS The pharmacokinetic effects of substrates or inhibitors of CYP3A4 , P-gp and Bcrp ( ABCG2 ) on rivaroxaban were studied in healthy volunteers . RESULTS Rivaroxaban did not interact with midazolam ( CYP3A4 probe substrate ) . Exposure to rivaroxaban when co-administered with midazolam was slightly decreased by 11 % ( 95 % confidence interval [ CI ] -28 % , 7 % ) compared with rivaroxaban alone . The following drugs moderately affected rivaroxaban exposure , but not to a clinical ly relevant extent : erythromycin ( moderate CYP3A4/P-gp inhibitor ; 34 % increase [ 95 % CI 23 % , 46 % ] ) , clarithromycin ( strong CYP3A4/moderate P-gp inhibitor ; 54 % increase [ 95 % CI 44 % , 64 % ] ) and fluconazole ( moderate CYP3A4 , possible Bcrp [ ABCG2 ] inhibitor ; 42 % increase [ 95 % CI 29 % , 56 % ] ) . A significant increase in rivaroxaban exposure was demonstrated with the strong CYP3A4 , P-gp/Bcrp ( ABCG2 ) inhibitors ( and potential CYP2J2 inhibitors ) ketoconazole ( 158 % increase [ 95 % CI 136 % , 182 % ] for a 400 mg once daily dose ) and ritonavir ( 153 % increase [ 95 % CI 134 % , 174 % ] ) . CONCLUSIONS Results suggest that rivaroxaban may be co-administered with CYP3A4 and /or P-gp substrates/moderate inhibitors , but not with strong combined CYP3A4 , P-gp and Bcrp ( ABCG2 ) inhibitors ( mainly comprising azole-antimycotics , apart from fluconazole , and HIV protease inhibitors ) , which are multi-pathway inhibitors of rivaroxaban clearance and elimination",
"AIMS The aim of the present study was to evaluate the disposition of metoprolol after oral administration of an immediate and controlled-release formulation before and after Roux-en-Y gastric bypass ( RYGB ) surgery in the same individuals and to vali date a physiologically based pharmacokinetic ( PBPK ) model for predicting oral bioavailability following RYGB . METHODS A single-dose pharmacokinetic study of metoprolol tartrate 200 mg immediate release and controlled release was performed in 14 volunteers before and 6 - 8 months after RYGB . The observed data were compared with predicted results from the PBPK modelling and simulation of metoprolol tartrate immediate and controlled-release formulation before and after RYGB . RESULTS After administration of metoprolol immediate and controlled release , no statistically significant difference in the observed area under the curve ( AUC(0 - 24 h ) ) was shown , although a tendency towards an increased oral exposure could be observed as the AUC(0 - 24 h ) was 32.4 % [ 95 % confidence interval ( CI ) 1.36 , 63.5 ] and 55.9 % ( 95 % CI 5.73 , 106 ) higher following RYGB for the immediate and controlled-release formulation , respectively . This could be explained by surgery-related weight loss and a reduced presystemic biotransformation in the proximal gastrointestinal tract . The PBPK values predicted by modelling and simulation were similar to the observed data , confirming its validity . CONCLUSIONS The disposition of metoprolol from an immediate-release and a controlled-release formulation was not significantly altered after RYGB ; there was a tendency to an increase , which was also predicted by PBPK modelling and simulation"
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Low serum concentrations of 25-hydroxyvitamin D ( 25[OH]D ) have been associated with many non-skeletal disorders . However , whether low 25(OH)D is the cause or result of ill health is not known . We did a systematic search of prospect i ve and intervention studies that assessed the effect of 25(OH)D concentrations on non-skeletal health outcomes in individuals aged 18 years or older . We identified 290 prospect i ve cohort studies ( 279 on disease occurrence or mortality , and 11 on cancer characteristics or survival ) , and 172 r and omised trials of major health outcomes and of physiological parameters related to disease risk or inflammatory status . Investigators of most prospect i ve studies reported moderate to strong inverse associations between 25(OH)D concentrations and cardiovascular diseases , serum lipid concentrations , inflammation , glucose metabolism disorders , weight gain , infectious diseases , multiple sclerosis , mood disorders , declining cognitive function , impaired physical functioning , and all-cause mortality . High 25(OH)D concentrations were not associated with a lower risk of cancer , except colorectal cancer . Results from intervention studies did not show an effect of vitamin D supplementation on disease occurrence , including colorectal cancer . In 34 intervention studies including 2805 individuals with mean 25(OH)D concentration lower than 50 nmol/L at baseline supplementation with 50 μg per day or more did not show better results . Supplementation in elderly people ( mainly women ) with 20 μg vitamin D per day seemed to slightly reduce all-cause mortality . The discrepancy between observational and intervention studies suggests that low 25(OH)D is a marker of ill health . Inflammatory processes involved in disease occurrence and clinical course would reduce 25(OH)D , which would explain why low vitamin D status is reported in a wide range of disorders . In elderly people , restoration of vitamin D deficits due to ageing and lifestyle changes induced by ill health could explain why low-dose supplementation leads to slight gains in survival
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"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",
"SETTING Vitamin D deficiency is associated with susceptibility to active tuberculosis ( TB ) in many setting s. In vitro studies and studies on human volunteers showed that two of the first-line anti-tuberculosis drugs , isoniazid and rifampicin , reduce 25-hydroxy vitamin D ( 25[OH]D ) concentrations . OBJECTIVE To study changes in vitamin D status during treatment of Tanzanian hospitalised patients with pulmonary TB ( PTB ) . DESIGN We compared serum 25[OH]D concentrations in 81 Tanzanian PTB patients before and after 2 months of treatment . RESULTS Median serum 25[OH]D concentrations increased from 91 nmol/l at baseline to 101 nmol/l after 2 months of TB treatment ( median increase 6.0 nmol/l , IQR -0.7 - 25.0 , P = 0.001 ) . Median serum parathyroid hormone concentrations increased from 1.6 to 2.0 pmol/l ( median increase 0.46 , IQR -0.2 - 1.1 , P 25[OH]D serum concentrations increased during the first 2 months of TB treatment in 81 PTB patients in northern Tanzania . Improved dietary intake and increased sunlight exposure may have contributed to the increased 25[OH]D concentrations",
"OBJECTIVE To investigate the clinical features , molecular phenotypes and clinical prognosis of breast cancer patients with type-2 diabetes mellitus , thereby providing a basis for individualized therapy of breast cancer . METHODS 105 breast cancer patients with type-2 diabetes mellitus ( DM ) presenting from January 2005 to December 2010 were enrolled in this study . 200 breast cancer non-diabetic patients in the same period were r and omly selected as the control group . The clinical data of DM group and control group were retrospectively analyzed . The SPSS12.0 software was used for statistics and survival analysis . RESULTS The mean age of the patients in DM group were of 57.2∓11.8 years , which was older compared with the control group . The percentage of postmenopausal patients was 71.4 % and the ratio of grade II+III was 98.8 % , which was higher than the control group . The neoadjuvant chemotherapy response rate of DM group was 67.5 % , which was lower than control group . The patients in DM group had later clinical stage and more lymph metastasis . The proportion of advanced breast cancer was 68.57 % and the ratio of lymph node metastasis was 66.01 % . All the difference was significant ( P in tumor size and molecular phenotype between the diabetic group with breast cancer and the control group . Disease-free survival and overall survival rates of DM group were 80.2 % and 84.2 % , which were worse than those in the control group . All the differences were significant ( P of overall survival still showed worse in DM group , but the difference was not statistically significant ( P>0.05 ) . Serum insulin at fasting and two hours postpr and ial were higher than normal value in DM group , but serum insulin levels in the control group changed in the normal range . CONCLUSION There were older patients , higher proportion of high pathological grade , more lymph node metastasis , later clinical stages in the diabetic group with breast cancer . Breast cancer patients with type-2 diabetes mellitus were at risk of a poor prognosis . Hyperinsulinemia may be the real cause of poor prognosis in breast cancer patients with type-2 diabetes",
"BACKGROUND Vitamin D has potent anticancer properties , especially against digestive-system cancers . Many human studies have used geographic residence as a marker of solar ultraviolet B and hence vitamin D exposure . Here , we considered multiple determinants of vitamin D exposure ( dietary and supplementary vitamin D , skin pigmentation , adiposity , geographic residence , and leisure-time physical activity-to estimate sunlight exposure ) in relation to cancer risk in the Health Professionals Follow-Up Study . METHODS Among 1095 men of this cohort , we quantified the relation of these six determinants to plasma 25-hydroxy-vitamin D [ 25(OH)D ] level by use of a multiple linear regression model . We used results from the model to compute a predicted 25(OH)D level for each of 47,800 men in the cohort based on these characteristics . We then prospect ively examined this variable in relation to cancer risk with multivariable Cox proportional hazards models . RESULTS From 1986 through January 31 , 2000 , we documented 4286 incident cancers ( excluding organ-confined prostate cancer and nonmelanoma skin cancer ) and 2025 deaths from cancer . From multivariable models , an increment of 25 nmol/L in predicted 25(OH)D level was associated with a 17 % reduction in total cancer incidence ( multivariable relative risk [ RR ] = 0.83 , 95 % confidence interval [ CI ] = 0.74 to 0.92 ) , a 29 % reduction in total cancer mortality ( RR = 0.71 , 95 % CI = 0.60 to 0.83 ) , and a 45 % reduction in digestive-system cancer mortality ( RR = 0.55 , 95 % CI = 0.41 to 0.74 ) . The absolute annual rate of total cancer was 758 per 100,000 men in the bottom decile of predicted 25(OH)D and 674 per 100,000 men for the top decile ; these respective rates were 326 per 100,000 and 277 per 100,000 for total cancer mortality and 128 per 100,000 and 78 per 100,000 for digestive-system cancer mortality . Results were similar when we controlled further for body mass index or physical activity level . CONCLUSIONS Low levels of vitamin D may be associated with increased cancer incidence and mortality in men , particularly for digestive-system cancers . The vitamin D supplementation necessary to achieve a 25(OH)D increment of 25 nmol/L may be at least 1500 IU/day",
"Accumulating evidence suggests that inadequate vitamin D levels may predispose people to chronic diseases . The authors aim ed to investigate whether serum 25-hydroxyvitamin D ( 25(OH)D ) level predicts mortality from cardiovascular disease ( CVD ) . The study was based on the Mini-Finl and Health Survey and included 6,219 men and women aged > or = 30 years who were free from CVD at baseline ( 1978 - 1980 ) . During follow-up through 2006 , 640 coronary disease deaths and 293 cerebrovascular disease deaths were identified . Levels of 25(OH)D were determined from serum collected at baseline . Cox 's proportional hazards model was used to assess the association between 25(OH)D and risk of CVD death . After adjustment for potential confounders , the hazard ratio for total CVD death was 0.76 ( 95 % confidence interval ( 95 % CI ) : 0.60 , 0.95 ) for the highest quintile of 25(OH)D level versus the lowest . The association was evident for cerebrovascular death ( hazard ratio = 0.48 , 95 % CI : 0.31 , 0.75 ) but not coronary death ( hazard ratio = 0.91 , 95 % CI : 0.70 , 1.18 ) . A low vitamin D level may be associated with higher risk of a fatal CVD event , particularly cerebrovascular death . These findings need to be replicated in other population s. To demonstrate a causal link between vitamin D and CVD , r and omized controlled trials are required",
"CONTEXT Inflammation is hypothesized to play a role in development of type 2 diabetes mellitus ( DM ) ; however , clinical data addressing this issue are limited . OBJECTIVE To determine whether elevated levels of the inflammatory markers interleukin 6 ( IL-6 ) and C-reactive protein ( CRP ) are associated with development of type 2 DM in healthy middle-aged women . DESIGN Prospect i ve , nested case-control study . SETTING The Women 's Health Study , an ongoing US primary prevention , r and omized clinical trial initiated in 1992 . PARTICIPANTS From a nationwide cohort of 27 628 women free of diagnosed DM , cardiovascular disease , and cancer at baseline , 188 women who developed diagnosed DM over a 4-year follow-up period were defined as cases and matched by age and fasting status with 362 disease-free controls . MAIN OUTCOME MEASURES Incidence of confirmed clinical ly diagnosed type 2 DM by baseline levels of IL-6 and CRP . RESULTS Baseline levels of IL-6 ( P and CRP ( P relative risks of future DM for women in the highest vs lowest quartile of these inflammatory markers were 7.5 for IL-6 ( 95 % confidence interval [ CI ] , 3.7 - 15.4 ) and 15.7 for CRP ( 95 % CI , 6.5 - 37.9 ) . Positive associations persisted after adjustment for body mass index , family history of diabetes , smoking , exercise , use of alcohol , and hormone replacement therapy ; multivariate relative risks for the highest vs lowest quartiles were 2.3 for IL-6 ( 95 % CI , 0.9 - 5.6 ; P for trend = .07 ) and 4.2 for CRP ( 95 % CI , 1.5 - 12.0 ; P for trend = .001 ) . Similar results were observed in analyses limited to women with a baseline hemoglobin A(1c ) of 6.0 % or less and after adjustment for fasting insulin level . CONCLUSIONS Elevated levels of CRP and IL-6 predict the development of type 2 DM . These data support a possible role for inflammation in diabetogenesis",
"In spite of the controversy over the role of r and omized clinical trials in medical research , the rationale underlying such trials remains persuasive as compared to recent suggestions for alternative non-r and omized studies such as those relying on the use of historical controls and adjustment technics . Others have suggested that recent statistical innovations for improving clinical trials , including adaptive allocation of treatment to patients and sequential stopping procedures , are underutilized . These innovations , though theoretically interesting , are not easily adapted to large-scale , complex medical trials in which there may be multiple end points and delayed response times . Ethical considerations suggest that r and omized trials are more suitable than uncontrolled experimentation in protecting the interests of patients . R and omized clinical trials remain the most reliable method for evaluating the efficacy of therapies",
"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 Being overweight or obese is associated with increased breast cancer risk and disease severity among postmenopausal women , but whether extent of mammography use and accuracy modify this association and further contribute to increases in disease severity at diagnosis among overweight and obese women is unclear . METHODS We prospect ively collected data during 1996 - 2005 on 287,115 postmenopausal women not using hormone therapy ( HT ) who underwent 614,562 mammography examinations ; 4,446 women were diagnosed with breast cancer within 12 months of a mammography examination . We calculated rates per 1,000 mammography examinations of large ( > 15 mm ) , advanced-stage ( IIb , III , or IV ) , high- grade ( 3 or 4 ) , estrogen receptor (ER)-positive and -negative , and screen-detected and non-screen-detected breast cancer across body mass index ( BMI , kg/m(2 ) ) groups defined as normal ( 18.5 - 24.9 ) , overweight ( 25.0 - 29.9 ) , obese class I ( 30.0 - 34.9 ) , and obese class II/III ( > or = 35.0 ) , adjusting for age , race/ethnicity , and mammography registry and use . All statistical tests were two-sided . RESULTS Adjusted rates per 1000 mammography examinations of overall breast cancer increased across BMI groups ( 6.6 normal , 7.4 overweight , 7.9 obese I , 8.5 obese II/III ; P(trend ) large invasive ( 2.3 normal , 2.6 overweight , 2.9 obese I , 3.2 obese II/III ; P(trend ) advanced-stage ( 0.8 normal , 0.9 overweight , 1.3 obese I , 1.5 obese II/III ; P(trend ) high nuclear grade ( 1.5 normal , 1.7 overweight , 1.7 obese I , 1.9 obese II/III ; P(trend ) = .10 ) tumors . Rates of ER-positive tumors increased across BMI groups ( P(trend ) rates of ER-negative tumors did not . Rates of screen-detected cancers were higher among overweight and obese women than normal and underweight women , but rates of non-screen-detected ( false-negative ) cancers were similar . Rates of advanced breast cancer increased across BMI groups regardless of extent of mammography use . CONCLUSIONS Patterns of mammography use and mammography accuracy are not the primary reasons for higher rates of advanced breast cancer among overweight and obese postmenopausal women not using HT ; thus , biologic differences in breast tumor development and /or progression may be important",
"BACKGROUND In cross-sectional studies , low serum levels of 25-hydroxyvitamin D are associated with higher prevalence of cardiovascular risk factors and disease . This study aim ed to determine whether endogenous 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are related to all-cause and cardiovascular mortality . METHODS Prospect i ve cohort study of 3258 consecutive male and female patients ( mean [ SD ] age , 62 [ 10 ] years ) scheduled for coronary angiography at a single tertiary center . We formed quartiles according to 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels within each month of blood drawings . The main outcome measures were all-cause and cardiovascular deaths . RESULTS During a median follow-up period of 7.7 years , 737 patients ( 22.6 % ) died , including 463 deaths from cardiovascular causes . Multivariate-adjusted hazard ratios ( HRs ) for patients in the lower two 25-hydroxyvitamin D quartiles ( median , 7.6 and 13.3 ng/mL [ to convert 25-hydroxyvitamin D levels to nanomoles per liter , multiply by 2.496 ] ) were higher for all-cause mortality ( HR , 2.08 ; 95 % confidence interval [ CI ] , 1.60 - 2.70 ; and HR , 1.53 ; 95 % CI , 1.17 - 2.01 ; respectively ) and for cardiovascular mortality ( HR , 2.22 ; 95 % CI , 1.57 - 3.13 ; and HR , 1.82 ; 95 % CI , 1.29 - 2.58 ; respectively ) compared with patients in the highest 25-hydroxyvitamin D quartile ( median , 28.4 ng/mL ) . Similar results were obtained for patients in the lowest 1,25-dihydroxyvitamin D quartile . These effects were independent of coronary artery disease , physical activity level , Charlson Comorbidity Index , variables of mineral metabolism , and New York Heart Association functional class . Low 25-hydroxyvitamin D levels were significantly correlated with variables of inflammation ( C-reactive protein and interleukin 6 levels ) , oxidative burden ( serum phospholipid and glutathione levels ) , and cell adhesion ( vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 levels ) . CONCLUSIONS Low 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are independently associated with all-cause and cardiovascular mortality . A causal relationship has yet to be proved by intervention trials using vitamin",
"CONTEXT The pathogenesis of depression is not fully understood , but studies suggest that low- grade systemic inflammation contributes to the development of depression . OBJECTIVE To test whether elevated plasma levels of C-reactive protein ( CRP ) are associated with psychological distress and depression . DESIGN We performed cross-sectional and prospect i ve analyses of CRP levels in 4 clinical ly relevant categories using data from 2 general population studies . SETTING The Copenhagen General Population and the Copenhagen City Heart studies . PARTICIPANTS We examined 73 131 men and women aged 20 to 100 years . MAIN OUTCOME MEASURES We ascertained psychological distress with 2 single-item self-reports and depression using self-reported antidepressant use , register-based prescription of antidepressants , and register-based hospitalization with depression . RESULTS In cross-sectional analyses , increasing CRP levels were associated with increasing risk for psychological distress and depression ( P = 3 × 10 - 8 to P = 4 × 10 - 105 for trend ) . For self-reported use of antidepressants , the odds ratio was 1.38 ( 95 % CI , 1.23 - 1.55 ) for CRP levels of 1.01 to 3.00 mg/L , 2.02 ( 1.77 - 2.30 ) for 3.01 to 10.00 mg/L , and 2.70 ( 2.25 - 3.25 ) for greater than 10.00 mg/L compared with 0.01 to 1.00 mg/L. For prescription of antidepressants , the corresponding odds ratios were 1.08 ( 95 % CI , 0.99 - 1.17 ) , 1.47 ( 1.33 - 1.62 ) , and 1.77 ( 1.52 - 2.05 ) , respectively ; for hospitalization with depression , 1.30 ( 1.01 - 1.67 ) , 1.84 ( 1.39 - 2.43 ) , and 2.27 ( 1.54 - 3.32 ) , respectively . In prospect i ve analyses , increasing CRP levels were also associated with increasing risk for hospitalization with depression ( P = 4 × 10 - 8 for trend ) . CONCLUSIONS Elevated levels of CRP are associated with increased risk for psychological distress and depression in the general population",
"OBJECTIVES To test whether accelerated sarcopenia in older persons with high interleukin (IL)-6 serum levels plays a role in the prospect i ve association between inflammation and disability found in many studies . DESIGN Cohort study of older women with moderate to severe disability . PARTICIPANTS Six hundred twenty older women from the Women 's Health and Aging Study in whom information on baseline IL-6 serum level was available . MEASUREMENTS Self-report of functional status , objective measures of walking performance , and knee extensor strength were assessed at baseline and over six semiannual follow-up visits . Potential confounders were baseline age , race , body mass index , smoking , depression , and medical conditions . RESULTS At baseline , women with high IL-6 were more often disabled and had lower walking speed . After adjusting for confounders , women in the highest IL-6 tertile ( IL-6>3.10 pg/mL ) were at higher risk of developing incident mobility disability ( risk ratio ( RR ) = 1.50 , 95 % confidence interval ( CI ) = 1.01 - 2.27 ) , disability in activities of daily living ( RR = 1.41 , 95 % CI = 1.01 - 1.98 ) , and severe limitation in walking ( RR = 1.61 , 95 % CI = 1.09 - 2.38 ) and experienced steeper declines in walking speed ( P in knee extensor strength was also steeper , but differences across IL-6 tertiles were not significant . After adjusting for change over time in knee extensor strength , the association between high IL-6 and accelerated decline of physical function was no longer statistically significant . CONCLUSIONS Older women with high IL-6 serum levels have a higher risk of developing physical disability and experience a steeper decline in walking ability than those with lower levels , which are partially explained by a parallel decline in muscle strength",
"Experimental and observational studies continue to demonstrate conflicting results regarding the role of several commonly used drugs as melanoma chemopreventive agents . This case-control study was design ed to assess the associations between cutaneous melanoma ( CM ) and exposure to nonsteroidal anti-inflammatory drugs ( NSAIDs ) and statins in current users . A total of 400 CM and 600 eligible age- and gender-matched community-based controls were prospect ively recruited and interviewed . We assessed participants ' demographic characteristics , CM risk factors , and current and previous use of medications . Multivariable conditional logistic regression models were used to estimate adjusted odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) for associations between NSAIDs and /or aspirin ( ASA ) , statin exposure , and CM risk . Half of the subjects were men ( mean age 60 years ) . After adjusting for confounders , use of any type of NSAIDs for more than 5 years significantly reduced the risk of melanoma development compared with the low-exposure group ( adjusted OR=0.57 ; 95 % CI=0.43 - 0.77 ) . Subgroup analyses showed that the observed risk reduction was primarily driven by continuous ASA use ( > 5 years adjusted OR=0.51 , 95 % CI=0.35 - 0.75 ) . No significant protective effect was observed with statin exposure ( OR=0.97 , 95 % CI=0.73 - 1.29 ) . Long-term use of NSAIDs , especially ASA , is associated with a significantly decreased risk of CM development . Clinical intervention studies are warranted to further investigate the potential role of ASA and other NSAIDs as chemopreventive agents for CM",
"BACKGROUND Calcium and vitamin D ( CaD ) supplementation trials including the Women 's Health Initiative ( WHI ) trial of CaD have shown nonsignificant reductions in total mortality . This report examines intervention effects on total and cause-specific mortality by age and adherence . METHODS The WHI CaD trial was a r and omized , double-blind , placebo-controlled trial that enrolled 36,282 postmenopausal women aged 51 - 82 years from 40 U.S. clinical centers . Women were assigned to 1,000 mg of elemental calcium carbonate and 400 IU of vitamin D(3 ) daily or placebo with average follow-up of 7.0 years . RESULTS The hazard ratio ( HR ) for total mortality was 0.91 ( 95 % confidence interval [ CI ] , 0.83 - 1.01 ) with 744 deaths in women r and omized to CaD versus 807 deaths in the placebo group . HRs were in the direction of reduced risk but nonsignificant for stroke and cancer mortality , but near unity for coronary heart disease and other causes of death . HRs for total mortality were 0.89 in the 29,942 women younger than 70 years ( 95 % CI , 0.79 - 1.01 ) and 0.95 in the 6,340 women aged 70 and older ( 95 % CI , 0.80 - 1.12 ; p value for age interaction = .10 ) . No statistically significant interactions were observed for any baseline characteristics . Treatment effects did not vary significantly by season . CONCLUSIONS In the WHI CaD trial , supplementation did not have a statistically significant effect on mortality rates but the findings support the possibility that these supplements may reduce mortality rates in postmenopausal women . These data can neither support nor refute recommendations for higher dose vitamin D supplementation to reduce cancer or total mortality",
"BACKGROUND Chronic inflammation has been proposed as a biological mechanism underlying the decline in physical function that occurs with aging . The purpose of this investigation was to examine the cross-sectional and prospect i ve relationships between markers of inflammation , interleukin-6 ( IL-6 ) and C-reactive protein ( CRP ) , with several measures of physical performance in older persons aged 70 to 79 years . METHODS Subjects were 880 high-functioning men and women participating in the MacArthur Study of Successful Aging ( n = 1189 ) , a subset of the Established Population s for Epidemiologic Studies of the Elderly ( n = 4030 ) . Plasma IL-6 and CRP levels were determined by enzyme-linked immunosorbent assay and log transformed to normalize the distributions . Physical function measures included h and grip strength , signature time , chair st and s ( time to complete five repetitions ) , and 6-m walk time . RESULTS Women had lower ( p IL-6 levels than men , but there was no significant difference between blacks and whites . IL-6 and CRP levels were higher ( p inflammatory markers with higher ( p IL-6 and CRP levels in less active individuals . After adjusting for age , sex , race , BMI , smoking status , use of nonsteroidal anti-inflammatory drugs , and prevalence of morbidity , those in the top two quartiles for walking speed had lower ( p = .012 ) IL-6 levels than those in the bottom quartile . In addition , there was a trend ( p = .038 ) for lower CRP levels in those with higher walking speed . CRP levels were also lower ( p = .04 ) in individuals in the top quartile for grip strength . No significant differences were noted for chair st and s or signature time performance . Repeat performance measures obtained on 405 subjects ( 67 % of those eligible at baseline ) obtained 7 years later had declined significantly ( grip strength , 18 % ; signature time , 21 % ; walking speed , 31 % ; p IL-6 and CRP were not associated with a change in performance . However , those who died or who were unable to undergo testing had higher baseline IL-6 and CRP levels ( p onset of disability in older persons and both IL-6 and CRP are associated with mortality risk , these markers of inflammation have only limited associations with physical performance , except for walking measures and grip strength at baseline , and do not predict change in performance 7 years later in a high-functioning subset of older adults "
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Objective To critically appraise and compare the measurement properties of self-administered patient-reported outcome measures ( PROMs ) focussing on the shoulder , assessing “ activity limitations . ” Study design Systematic review . The study population had to consist of patients with shoulder pain . We excluded postoperative patients or patients with generic diseases . The method ological quality of the selected studies and the results of the measurement properties were critically appraised and rated using the COSMIN checklist . Results Out of a total of 3427 unique hits , 31 articles , evaluating 7 different question naires , were included . The SPADI is the most frequently evaluated PROM and its measurement properties seem adequate apart from a lack of information regarding its measurement error and content validity . Conclusion For English , Norwegian and Turkish users , we recommend to use the SPADI . Dutch users could use either the SDQ or the SST . In German , we recommend the DASH . In Tamil , Slovene , Spanish and the Danish language s , the evaluated PROMs were not yet of acceptable validity . None of these PROMs showed strong positive evidence for all measurement properties . We propose to develop a new shoulder PROM focused on activity limitations , taking new knowledge and techniques into account
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"Background The COSMIN checklist is a tool for evaluating the method ological quality of studies on measurement properties of health-related patient-reported outcomes . The aim of this study is to determine the inter-rater agreement and reliability of each item score of the COSMIN checklist ( n = 114 ) . Methods 75 articles evaluating measurement properties were r and omly selected from the bibliographic data base compiled by the Patient-Reported Outcome Measurement Group , Oxford , UK . Raters were asked to assess the method ological quality of three articles , using the COSMIN checklist . In a one-way design , percentage agreement and intraclass kappa coefficients or quadratic-weighted kappa coefficients were calculated for each item . Results 88 raters participated . Of the 75 selected articles , 26 articles were rated by four to six participants , and 49 by two or three participants . Overall , percentage agreement was appropriate ( 68 % was above 80 % agreement ) , and the kappa coefficients for the COSMIN items were low ( 61 % was below 0.40 , 6 % was above 0.75 ) . Reasons for low inter-rater agreement were need for subjective judgement , and accustom to different st and ards , terminology and definitions . Conclusions Results indicated that raters often choose the same response option , but that it is difficult on item level to distinguish between articles . When using the COSMIN checklist in a systematic review , we recommend getting some training and experience , completing it by two independent raters , and reaching consensus on one final rating . Instructions for using the checklist are improved",
"Background The Shoulder Pain and Disability Index ( SPADI ) is a self-administered question naire that aims to measure pain and disability associated with shoulder disease . The aim of the present study was to investigate the construct validity and factor structure of the SPADI in a population -based study of patients with self-reported chronic shoulder symptoms . Methods The North West Adelaide Health Study is a representative longitudinal cohort study of people aged 18 years and over . The original sample was r and omly selected and recruited by telephone interview . Overall , 3 206 participants returned to the clinic during the second stage ( 2004 - 2006 ) and were asked to report whether they had pain , aching or stiffness on most days in either of their shoulders . Data was also collected on body mass index and shoulder range of motion ( ROM ) and demographic factors . The SPADI ( numeric rating scale ) was administered to participants with shoulder symptoms . Principal components factor analysis , with varimax rotation of factor loadings , was used to assess subscale structure of SPADI . Correlations between the SPADI , shoulder ROM and SF-36 were performed . Results Overall , 22.3 % of participants indicated that they had pain , aching or stiffness in either of their shoulders . SPADI results were available for 588 of participants with current shoulder symptoms . The internal consistency of the SPADI subscales were high ( Cronbach 's alpha > 0.92 ) . Two factors , explaining 61.4 % of the total variance were extracted by factor analysis . These were interpreted as disability and pain respectively . There was a strong negative correlation between SPADI disability subscale scores and shoulder range of motion . SPADI disability , but not pain , subscale scores were correlated with age . Conclusions The SPADI is a valid measure to assess pain and disability in people with shoulder pain in a population -based study . In this setting , the SPADI had a bidimensional structure with both pain and disability subscales ",
"Background Self-report question naires play an important role as outcome measures in shoulder research . Having an estimate of the measurement error of these question naires is of importance when assessing follow-up results after treatment and when planning intervention studies . The aim of this study was to cross-culturally adapt the Norwegian version of the OSS and WORC question naire and examine and compare agreement , reliability and construct validity of the disease-specific shoulder question naire WORC with two commonly used shoulder question naires , SPADI and OSS , in patients with rotator cuff disease . Methods 74 patients with rotator cuff disease were recruited from the outpatient clinic of the Physical Medicine and Rehabilitation Department at Ullevaal University Hospital in Oslo , Norway . A test-retest design was used , and the question naires were filled out by the patients at the clinic , with a one week interval between test administrations . Agreement ( repeatability coefficient ) , reliability ( ICC ) and construct validity were examined and compared for WORC , SPADI and OSS . Results Reliability analysis was restricted to the 55 patients ( 51 ± 10 yrs ) who reported no change between test administrations according to scoring on a global scale . The agreement , reliability and construct validity was moderate for all three question naires with ICC ranging from 0.83 to 0.85 , repeatability coefficient from 16.1 to 19.7 and Spearman rank correlations between total scores from r = 0.57 to 0.69 . There was a lower degree of floor and ceiling effects in SPADI compared to WORC and OSS . Conclusion We conclude that the agreement and reliability of the three shoulder question naires examined , WORC index , SPADI and OSS are acceptable and that differences between scores were small . The Norwegian version of the question naires is acceptable for assessing Norwegian-speaking patients with rotator cuff disease . The moderate agreement and construct validity should be taken into consideration when assessing follow-up results after treatment and in the planning of prospect i ve studies",
"The Shoulder Disability Question naire ( SDQ ) is a measure covering 16 items design ed to evaluate functional status limitation in patients with shoulder disorders . The responsiveness of the SDQ was evaluated for 180 patients with soft tissue shoulder disorders , without underlying systemic disorders . These patients participated in a r and omized placebo-controlled trial , in which ultrasound and electrotherapy appeared to be ineffective as adjuvants to st and ardized exercise therapy . At baseline and at 6-week follow-up , patients completed the SDQ and rated severity of shoulder pain and their chief complaint , while a research physiotherapist rated severity of symptoms and restriction of mobility . At the 6-week follow-up , patients also rated overall change since baseline . According to the calibrated responsiveness ratio ( CRR ) and the area under the receiver-operator characteristic curve ( AUC ) the SDQ discriminates accurately between self-rated clinical ly stable and improved subjects . The presented results suggest that the SDQ is as responsive as the compared outcome measures , and therefore is ready for use in clinical trials",
"Objective —To evaluate the responsiveness of the Shoulder Disability Question naire ( SDQ ) . Methods —The study was conducted within the framework of an observational study on shoulder disorders in primary care . After first presentation of their complaints to the general practitioner and after one and six months , participants completed the SDQ , a single question on functional status ( FSQ ) , and an ordinal 11 point scale for the severity of pain ( PSS ) . Responsiveness of the SDQ was evaluated compared with that of the FSQ and PSS , by calculating responsiveness ratios and by plotting receiver operating characteristic ( ROC ) curves . Recovery according to the patient was used as an external criterion for clinical ly relevant improvement ( complete recovery or much improved on a six point Likert scale was denoted as clinical ly relevant improvement ) . Results —A total of 349 consecutive patients with shoulder disorders were enrolled in the observational study . Response rates ranged between 96 % and 89 % . Responsiveness ratios were slightly higher for the PSS compared with the SDQ ( 2.53 versus 2.22 at one month , 2.24 versus 1.89 at six months ) . The area under the ROC curve was 0.84 for both the SDQ and the PSS , and 0.72 for the FSQ . Conclusion —The results of this study confirm the responsiveness of the SDQ , making it a useful instrument to assess functional disability in longitudinal studies",
"Background Instruments design ed to measure the subjective impact of painful shoulder conditions have become essential in shoulder research . The Shoulder Pain and Disability Index ( SPADI ) is one of the most extensively used scales of this type . The objective of this study was to investigate reproducibility and responsiveness of the SPADI in patients with adhesive capsulitis . Methods SPADI test-retest reproducibility was estimated by the \" intraclass correlation coefficient \" ( ICC ) and the \" smallest detectable difference \" ( SDD ) . Responsiveness was assessed by exploring baseline and follow-up data recorded in a recently reported clinical trial regarding hydrodilatation and corticosteroid injections in 76 patients with adhesive capsulitis . \" St and ardized response mean \" ( SRM ) and \" reliable change proportion \" ( RCP ) for SPADI were compared with corresponding figures for shoulder range-of-motion ( ROM ) . The relationship between SPADI and ROM change scores was investigated through correlation and linear regression analyses . Results Results for test-retest reproducibility indicated a smallest detectable difference of 17 points on the 0–100 scale , and an intraclass correlation coefficient of 0.89 . The SPADI was generally more responsive than ROM . Weak to moderately strong associations were identified between SPADI and ROM change scores . According to the regression model , the three variables baseline SPADI , baseline active ROM and change in active ROM together explained 60 % of the variance in SPADI improvement . Conclusion This study supports the use of SPADI as an outcome measure in similar setting",
"Objectives For the measurement of patient-reported outcomes , such as ( health-related ) quality of life , often many measurement instruments exist that intend to measure the same construct . To facilitate instrument selection , our aim was to develop a highly sensitive search filter for finding studies on measurement properties of measurement instruments in PubMed and a more precise search filter that needs less abstract s to be screened , but at a higher risk of missing relevant studies . Methods A r and om sample of 10,000 PubMed records ( 01 - 01 - 1990 to 31 - 12 - 2006 ) was used as a gold st and ard . Studies on measurement properties were identified using an exclusion filter and h and search ing . Search terms were selected from the relevant records in the gold st and ard as well as from 100 systematic review s of measurement properties and combined based on sensitivity and precision . The performance of the filters was tested in the gold st and ard as well as in two validation sets , by calculating sensitivity , precision , specificity , and number needed to read . Results We identified 116 studies on measurement properties in the gold st and ard . The sensitive search filter was able to retrieve 113 of these 116 studies ( sensitivity 97.4 % , precision 4.4 % ) . The precise search filter had a sensitivity of 93.1 % and a precision of 9.4 % . Both filters performed very well in the validation sets . Conclusion The use of these search filters will contribute to evidence -based selection of measurement instruments in all medical fields",
"Objective : To translate and adapt the original English version of the Shoulder Rating Question naire ( SRQ ) into the Dutch language ( SRQ-DLV ) and evaluate its internal consistency , reliability , validity and responsiveness to clinical changes . Design : Prospect i ve study . Setting : Outpatient departments of orthopaedics , radiology and physical therapy of an academic and a non-academic hospital . Subjects : One hundred and seven patients treated for unilateral shoulder disorder ( adhesive capsulitis 68 , calcifying tendinitis 22 , impingement syndrome or rotator cuff tear 17 ) . Methods : The original SRQ was translated and adapted following international guidelines . The SRQ-DLV was used among other measures of body function and structure , activities and societal participation in order to determine reliability , internal consistency , validity and responsiveness . Assessment s were done at baseline and three months after treatment , with the SRQ-DLV being re-administered within one week before the baseline measurement and the start of the treatment for testing reliability . Results : Cronbach 's alpha for internal consistency was 0.89 for the total question naire and 0.81 , 0.80 , 0.72 and 0.84 for the domains pain , daily activities , sports/recreational activities and work , respectively . Test-retest reliability of the SRQ-DLV and its subscales ranged from 0.63 to 0.86 . The summary score of the SRQ-DLV correlated with measures of shoulder function , daily activities and quality of life . Except for the work subscale of the SRQ-DLV , large effect sizes , reflecting its responsiveness to clinical changes after treatment , were found for both the summary and the subscales scores . Conclusions : Empirical data support that the SRQ-DLV is a reliable , valid and responsive measure to be used in clinical trials including Dutch patients with various shoulder disorders",
"The goal of this study was to compare the Oxford Shoulder Score ( OSS ) , the Shoulder Pain and Disability Index ( SPADI ) , and the Short Form 36 ( SF-36 ) for their correlation , agreement , sensitivity to change , and test-retest reliability in patients with a clinical diagnosis of subacromial impingement . All patients attending a specialist subacromial impingement clinic over a 6-month period completed the OSS , SPADI , and SF-36 at each visit . A total of 323 sets of observations were recorded in 110 patients . The first 38 of these patients were also sent the question naires to complete before their visit . There was good correlation between the OSS and SPADI scores ( correlation coefficient = 0.85 ) and good agreement between the scores on each scale ( weighted kappa = 0.79 ) . The correlation with total SF-36 was poor ( 0.37 for OSS and 0.26 for SPADI ) . The OSS and SPADI showed good effect sizes compared with the total SF-36 score and good test-retest reliability . These data support the use of the OSS or SPADI in patients with subacromial impingement",
"OBJECTIVE --To develop and vali date a question naire to quantify disability associated with shoulder symptoms . METHODS --A set of questions relevant to shoulder symptoms from a general disability interview was developed and the question naire applied to a cross-sectional population survey and a prospect i ve study of general practice attenders . Subjects included adults who reported current shoulder pain in a population survey and patients from three general practice s who attended with shoulder symptoms during a six month period . The main outcome measures were : frequency of problems with daily living related to shoulder symptoms , total score on 22-item disability question naire , and measures of shoulder movement . RESULTS --A higher proportion ( 80 % ) of patients attending their general practitioner with shoulder symptoms had five or more disabilities compared with subjects reporting shoulder pain in a community survey ( 34 % ) . The ranked frequency with which each disability was reported was similar in the two groups , although sleep disturbance was the most common problem in consulters . Self-reported disability is correlated with measures of restricted shoulder movement . CONCLUSION --This disability question naire was simple to complete and should prove useful for both general practice and population -based studies of shoulder pain",
"OBJECTIVE To compare the construct validity and responsiveness of the Shoulder Pain and Disability Index ( SPADI ) , Croft Index , and disabilities of the arm , shoulder , and h and ( DASH ) for patients with adhesive capsulitis and to compare these with pain on a visual analog scale , the Health Assessment Question naire , and the problem-elicitation technique . STUDY DESIGN AND SETTING Two r and omized double-blind placebo-controlled trials of interventions for adhesive capsulitis were performed . Both trials recruited patients from community-based physiotherapy practice s. Responsiveness at 3 weeks postbaseline was assessed using four responsiveness parameters and three external criteria for improvement . RESULTS Correlations between the shoulder-specific measures ranged from 0.55 to 0.65 at baseline and 0.49 - 0.55 for the 3-week change scores . Greater responsiveness was seen for the SPADI . The effect size for the SPADI ranged from 1.20 to 1.64 , for the Croft Index from 0.87 to 1.21 , and for the DASH from 0.55 to 0.83 . Rankings were similar across the four responsiveness parameters and the three external criteria for improvement . Correlations between the shoulder-specific and generic measures for baseline and 3-week change scores were lower than those among the shoulder-specific measures ( range : 0.17 - 0.60 ) . CONCLUSION The shoulder-specific disability measures showed acceptable construct validity and responsiveness with a small but consistent overall advantage for the SPADI",
"A shoulder pain and disability index ( SPADI ) was developed to measure the pain and disability associated with shoulder pathology . The SPADI is a self-administered index consisting of 13 items divided into two subscales : pain and disability . Thirty-seven male patients with shoulder pain were used in a study to examine the measurement characteristics of the SPADI . Test-retest reliability of the SPADI total and subscale scores ranged from 0.6377 to 0.6552 . Internal consistency ranged from 0.8604 to 0.9507 . SPADI total and subscale scores were highly negatively correlated with shoulder range of motion ( ROM ) supporting the criterion validity of the index . Principal components factor analysis with and without varimax rotation supported the construct validity of the total SPADI and its subscales . High negative correlations between changes in SPADI scores and changes in shoulder ROM indicated the SPADI detected changes in clinical status over short time intervals . The SPADI should prove useful for both clinical and research purpose"
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INTRODUCTION Despite the availability of evidence -based guidelines for the management of low back pain ( LBP ) that contain consistent messages , large evidence - practice gaps in primary care remain . OBJECTIVES To perform a systematic review and meta synthesis of qualitative studies that have explored primary care clinicians ' perceptions and beliefs about guidelines for LBP , including perceived enablers and barriers to guideline adherence . METHODS Studies investigating perceptions and beliefs about LBP guidelines were included if participants were primary care clinicians and qualitative methods had been used for both data collection and analysis . We search ed major data bases up to July 2014 . Pairs of review ers independently screened titles and abstract s , extracted data , appraised method quality using the CASP checklist , conducted thematic analysis , and synthesized the results in narrative format . RESULTS Seventeen studies , with a total of 705 participants , were included . We identified 3 key emergent themes and 8 subthemes : ( 1 ) guideline implementation and adherence beliefs and perceptions ; ( 2 ) maintaining the patient-clinician relationship with imaging referrals ; and ( 3 ) barriers to guideline implementation . Clinicians believed that guidelines were categorical , prescriptive , and constrained professional practice ; however , popular clinical practice s superseded the guidelines . Imaging referrals were used to manage consultations and to obtain definitive diagnoses . Clinicians ' perceptions reflected a lack of content knowledge and underst and ing of how guidelines are developed . DISCUSSION Addressing misconceptions and other barriers to uptake of evidence -based guidelines for managing LBP is needed to improve knowledge transfer and close the evidence - practice gap in the treatment of this common condition
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"Background Since a higher level of self-efficacy in common mental disorders is associated with earlier return-to-work ( RTW ) , it is important to know if work related self-efficacy can be increased by occupational health care . The primary aim of this study was to evaluate whether an intervention to enhance guideline adherence of occupational physicians lead to an increase in RTW self-efficacy in workers three months later . The secondary aim was to evaluate whether the intervention modified the association between RTW self-efficacy and return-to-work three months later . Methods A total of 66 occupational physicians participated in the study . They were r and omized into two groups ; the intervention group received a training , the control group did not . The training aim ed to enhance adherence to a mental health guideline that contained strategies that are supposed to enhance RTW self-efficacy . In 128 sick-listed workers guided by these occupational physicians , RTW self-efficacy , RTW , and personal , health-related and work-related variables were measured at baseline and three months later . Generalized linear mixed models analysis and linear mixed models analysis were used for the evaluations . Results In workers whose occupational physicians had received the training RTW self-efficacy increased significantly more than in workers whose occupational physicians had participated in the control group ( t = −2.626 , p ≤ .05 ) . Higher baseline RTW self-efficacy scores were significantly more often associated with full RTW than with no RTW three months later ( OR 2.20 , 95 % CI 1.18–4.07 ) , but the intervention did not affect this association . Conclusions This study showed that a training to enhance guideline adherence of occupational physicians leads to increased RTW self-efficacy in workers sick-listed with common mental disorders during the first months of sickness absence in a real-life occupational health care setting . This insight is helpful for optimizing the recovery and RTW process , and for underst and ing the role of RTW self-efficacy in this process . Trial registration IS RCT",
"OBJECTIVE To assess physiotherapists ' adherence to the Dutch guidelines for nonspecific low back pain , the motivational determinants related to guideline adherence , and the role of physiotherapists ' awareness of their performance in this respect . STUDY DESIGN & SETTING This was a cross-sectional survey among a r and om sample of 1,500 private practice physiotherapists in the Netherl and s. The actual guideline adherence was measured by means of vali date d clinical vignettes and self-reported adherence by asking the physiotherapists to report their own level of adherence . The assessment of motivational determinants was based on a theoretical framework . RESULTS The response rate was 31.5 % ( N=472 ) . The average guideline adherence rate was 50.4 % ( SD=16.8 ) . Only 38.5 % of the physiotherapists had realistic perceptions of their personal performance . Awareness levels seriously interfered with the relationship between motivational determinants and actual guideline adherence . Actual adherence was mainly related to the perceived relative advantages and awareness of adherence to the perceived social norm . CONCLUSION The moderating role of awareness in this study confirms the view that motivational determinants of a particular behavior can only be accurately assessed if people hold realistic perceptions of that behavior . Our approach illustrates the added value of a theory-based approach in guideline implementation studies",
"Introduction This cluster r and omised trial evaluated an intervention to decrease x-ray referrals and increase giving advice to stay active for people with acute low back pain ( LBP ) in general practice . Methods General practice s were r and omised to either access to a guideline for acute LBP ( control ) or facilitated interactive workshops ( intervention ) . We measured behavioural predictors ( e.g. knowledge , attitudes and intentions ) and fear avoidance beliefs . We were unable to recruit sufficient patients to measure our original primary outcomes so we introduced other outcomes measured at the general practitioner ( GP ) level : behavioural simulation ( clinical decision about vignettes ) and rates of x-ray and CT-scan ( medical administrative data ) . All those not involved in the delivery of the intervention were blinded to allocation . Results 47 practice s ( 53 GPs ) were r and omised to the control and 45 practice s ( 59 GPs ) to the intervention . The number of GPs available for analysis at 12 months varied by outcome due to missing confounder information ; a minimum of 38 GPs were available from the intervention group , and a minimum of 40 GPs from the control group . For the behavioural constructs , although effect estimates were small , the intervention group GPs had greater intention of practising consistent with the guideline for the clinical behaviour of x-ray referral . For behavioural simulation , intervention group GPs were more likely to adhere to guideline recommendations about x-ray ( OR 1.76 , 95%CI 1.01 , 3.05 ) and more likely to give advice to stay active ( OR 4.49 , 95%CI 1.90 to 10.60 ) . Imaging referral was not statistically significantly different between groups and the potential importance of effects was unclear ; rate ratio 0.87 ( 95%CI 0.68 , 1.10 ) for x-ray or CT-scan . Conclusions The intervention led to small changes in GP intention to practice in a manner that is consistent with an evidence -based guideline , but it did not result in statistically significant changes in actual behaviour . Trial Registration Australian New Zeal and Clinical Trials Registry",
"& NA ; Guidelines for the management of low back pain ( LBP ) have existed for many years , but adherence to these by health care practitioners ( HCPs ) remains suboptimal . The aim of this study was to measure the attitudes , beliefs and reported clinical behaviour of UK physiotherapists ( PTs ) and general practitioners ( GPs ) about LBP and to explore the associations between these . A cross‐sectional postal survey of GPs ( n = 2000 ) and PTs ( n = 2000 ) was conducted that included the Pain Attitudes and Beliefs Scale ( PABT.PT ) , and a vignette of a patient with non‐specific LBP ( NSLBP ) with questions asking about recommendations for work , activity and bedrest . Data from 1022 respondents ( 442 GPs and 580 PTs ) who had recently treated patients with LBP were analysed . Although the majority of HCPs reported providing advice for the vignette patient that was broadly in line with guideline recommendations , 28 % reported they would advise this patient to remain off work . Work advice was significantly related to the PABS.PT scores with higher biomedical ( F1,986 = 77.5 , p patients with NSLBP are diverse . Many HCPs held the belief that LBP necessitates some avoidance of activities and work . The attitudes and beliefs of these HCPs were associated with their self‐reported clinical behaviour regarding advice about work . Future studies need to investigate whether approaches aim ed at modifying these HCP factors can lead to improved patient outcomes",
"OBJECTIVE Identify barriers and facilitators related to the use of low-back pain guidelines as perceived by occupational therapists ( OTs ) . METHODS AND PARTICIPANTS A qualitative approach was used . Nine OTs with varied characteristics were r and omly selected . Participants were asked to use the guidelines with at least two clients . Semi-structured interviews were done to identify barriers and facilitators related to use . Transcripts of the interviews were analyzed . RESULTS Participants agreed with the guidelines , found them compatible with their current practice , and believed using them would help in preventing persistent disability . Some question ed if their work organization , based on group therapy , would limit their use of the guidelines . Because of the guidelines ' biopsychosocial perspective , they anticipated problems regarding client expectations and collaboration with other health professionals . CONCLUSIONS Participating OTs raised few barriers related to them . Barriers were mostly related to client expectations , work organization and peers . It appears the guidelines would be easily implemented by OTs , but environmental elements could limit this",
"One of the major challenges for general practitioners is to manage individuals with acute low back pain appropriately to reduce the risk of chronicity . A prospect i ve study was design ed to assess the actual management of acute low back pain in one primary care setting and to determine whether existing practice patterns conform to published guidelines . Twenty-four family physicians from public primary care centers of the Basque Health Service in Bizkaia , Basque Country ( Spain ) , participated in the study . A total of 105 patients aged 18–65 years presenting with acute low back pain over a 6-month period were included . Immediately after consultation , a research assistant performed a structured clinical interview . The patients ’ care provided by the general practitioner was compared with the Agency for Health Care Policy and Research ( AHCPR ) guidelines and guidelines issued by the Royal College of General Practitioners . The diagnostic process showed a low rate of appropriate use of history ( 27 % ) , physical examination ( 32 % ) , lumbar radiographs ( 31 % ) , and referral to specialized care ( 33 % ) . Although the therapeutic process showed a relatively high rate of appropriateness in earlier mobilization ( 77 % ) and educational advice ( 65 % ) , only 23 % of patients were taught about the benign course of back pain . The study revealed that management of acute low back pain in the primary care setting is far from being in conformance with published clinical guidelines",
"Context Do clinicians who follow depression practice guidelines have better patient outcomes ? Contribution This observational study from 45 primary care practice s found that clinicians adhered well to only one third of the guideline recommendations for depression . Most clinicians initially recognized and treated depression ; however , they often did not address suicide risk , assess alcohol use , adjust treatment appropriately , or follow through on long-term treatment plans . Better clinician adherence to recommendations was associated with a lower probability of persistent depressive symptoms among patients . Caution Data on depression-related care were based on patients ' self-report . Implication Clinicians should try harder to deliver guideline -concordant depression care . The Editors Depression practice guidelines for primary care represent expert consensus , based on systematic review of several r and omized clinical trials and other relevant literature , on how depression should be diagnosed and treated . Guidelines provide guidance for depression assessment , referral to mental health specialists , and follow-up in primary care ( 13 ) . Numerous studies document low rates of adherence to guideline recommendations on antidepressant use or psychotherapy ( 46 ) and less-than-optimal outcomes in usual care ( 7 ) . Far fewer studies have assessed adherence to the broader set of recommendations on additional aspects of care ranging from detection of depression symptoms to treatment discontinuation . National efforts to improve care ( 8) rely substantially on 1 or 2 guideline recommendations ( for example , completion of a short-term care course of antidepressant medication ) . Knowing the strengths and gaps in care for primary care patients with depression could provide a stronger basis for quality improvement . We sought to determine whether adherence to the broader set of depression guideline recommendations improves depression outcomes and , if so , to identify which guideline recommendations are most and least likely to be followed . To achieve these aims , we used expert panel methods to develop 20 guideline -based quality indicators for depression care ( 9 , 10 ) . We applied the indicators to secondary data from surveys of 1131 representative depressed patients from 45 diverse and geographically dispersed primary care practice s. We analyzed the link between performance on our measure and depression outcomes at 12 , 18 , and 24 months and assessed the level of performance on each of our indicators to identify which aspects of depression care were most and least in need of improvement . Methods We performed secondary analysis of data collected through the Quality Improvement for Depression ( QID ) collaboration ( 11 ) between 1996 and 1998 . The 4 studies in this collaboration used cluster r and omized design s to evaluate encouragement strategies for implementing Agency for Healthcare Research and Quality guidelines for depression ( 13 ) in primary care . One QID study used self-administered surveys ( 12 ) , which had some questions that were worded differently from questions in the other 3 studies . We included only the 3 QID studies that used virtually identical telephone-administered surveys . Among these 3 studies , only 1 showed statistically significant improvement in depression-specific outcomes ( 13 , 14 ) . In the QID studies , experimental-group clinician leaders were given training , material s , and protocol s to encourage them to provide collaborative care for depression-based quality improvement ( Figure ) . Additional details on the encouragement approach used by each study are published elsewhere ( 1114 ) . For our observational analyses , we combined the usual care and experimental groups . The study was approved by the institutional review board at each study site . Figure . Quasi-experimental design of studies in the Quality Improvement for Depression collaboration . Setting Patients and clinicians were recruited from 45 primary care practice s within 4 health care organizations in 13 states . Organizations included a multistate family practice network ( 11 ) , 2 staff-model managed care organizations ( Kaiser Permanente and Veterans Affairs [ 14 ] ) , and a network model managed care organization whose patients were cared for in private practice s throughout Maryl and ( 11 , 15 ) . Sample Research ers consecutively approached patients visiting participating practice s to identify those with symptoms of depression on a brief self-report depression screening instrument derived from the World Health Organization Composite International Diagnostic Interview ( CIDI ) ( 16 ) . Telephone interviewers used the full CIDI for Affective Disorders to assess consenting patients who tested positive on the CIDI screening instrument . We included 1019 patients who were positive for a major depressive disorder or dysthymia on the CIDI and 112 patients who were negative despite reporting at least 5 of 9 depression criteria ( 17 ) at recruitment ( 18 ) . In the QID studies , follow-up surveys were completed by 85 % of the enrolled patients at 12 months , 77 % at 18 months , and 78 % at 24 months . Measures We measured the process of care , case mix ( based on prognosis ) , and outcomes for depression ( Figure ) . Process-of-care measures included 139 self-report items ( 19 ) . Case-mix measures ( 20 ) included 70 items used to create 5 scales ( baseline severity of depression on the modified Center for Epidemiologic Studies Depression [ CES-D ] scale , severity of physical symptoms common among people with depression , social support , number of depression symptoms lasting 2 years , and appropriate antidepressant use during 3 months in the past 6 months ) that formed the basis for a vali date d depression prognostic index ( DPI ) ( 14 , 21 , 22 ) . Higher DPI scores indicate worse prognosis . Outcome measures included depression symptoms ( continuous ) and persistent depression ( dichotomous ) at 12 , 18 , and 24 months after baseline ( the date of study enrollment ) . We measured depression symptoms by using a modified version of the CES-D scale ( 23 , 24 ) that more closely approximates criteria from the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ; lower scores on the modified CES-D scale reflect fewer depression symptoms ( range , 0 to 100 ) . We measured the presence or absence of persistent depression by using a previously vali date d measure ( 25 ) that approximates current major depression . We defined persistent depression as scores that fell in the depressed range ( according to previously established cutoff values ) on each of 3 measures : the modified CES-D scale ( score 20 , equivalent to 16 on the original CES-D ) , the mental health composite score of the Short Form-12 ( 26 ) ( score 1 SD below the general population mean of 50 ) , and stem items from the CIDI screening instrument that identifies current probable depression ( 16 ) . Unlike the CIDI structured diagnosis instrument , the CIDI screening instrument requires the presence of depressed mood and anhedonia in the past month . Because patients must score in the depressed range on all 3 measures according to st and ard depression cutoffs ( the measures map closely to diagnostic criteria from the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ) and major symptoms must be current , the patients identified by the composite measure for persistent depression are substantially and currently impaired . Development of the Depression Quality Index We developed preliminary quality review criteria based on Agency for Healthcare Research and Quality guidelines ( 13 ) and refined them through an expert panel process . We translated quality review criteria into scored , survey-based quality indicators , without testing any indicators against outcome until the index was complete . We vali date d the index by evaluating the relationship between quality scores and depression outcomes , adjusting for case mix . We developed clinical algorithms for identifying st and ard , above-st and ard , or below-st and ard care relative to guideline statements . In st and ard care , a care process would be likely to ensure good to excellent outcomes for most patients , whereas below-st and ard care would lead to poor outcomes among some patients and above-st and ard care would have a high likelihood of leading to optimal outcomes . We then su bmi tted preliminary quality review criteria to an independent group of depression care experts ( 5 primary care practitioners and 2 mental health specialists ) from the MacArthur Foundation Initiative on Depression and Primary Care , using a modified Delphi process ( 27 ) . Seven experts participated in 3 rounds of review and revision of the criteria and 1 final round of review to assess consensus on the final measure . The consensus process result ed in 20 quality review criteria ( 19 ) . A strength of these criteria is that they account for the complexity of care decisions made over time on the basis of response to treatment . We translated the final quality review criteria into measurable quality indicators based on survey variables . Each indicator identifies a patient population ( for example , patients with persistent symptoms at 6 months ) to which a care process or processes identified by the quality review criterion applies ( for example , the patient should be seen by a mental health specialist ) . Scoring further divides the indicator into st and ard , above-st and ard , or below-st and ard care subsets on the basis of additional conditions specified in the quality review criterion ( for example , per our panel 's recommendations , care is below st and ard for suicide assessment only when the patient came for a scheduled visit with no new medical problems ) . Each indicator generates a raw score of 9 to 9 , with st and ard care as zero . Statistical Analysis We used weighting and multiple imputation to account for difficult-to-survey sub population s ( such as ethnic minority groups ) . Weighting accounted for the probability of enrollment and attrition at each step , beginning with data on patients approached for screening",
"Low back pain is the fifth most common reason for all physician visits in the United States ( 1 , 2 ) . Approximately one quarter of U.S. adults reported having low back pain lasting at least 1 whole day in the past 3 months ( 2 ) , and 7.6 % reported at least 1 episode of severe acute low back pain ( see Glossary ) within a 1-year period ( 3 ) . Low back pain is also very costly : Total incremental direct health care costs attributable to low back pain in the U.S. were estimated at $ 26.3 billion in 1998 ( 4 ) . In addition , indirect costs related to days lost from work are substantial , with approximately 2 % of the U.S. work force compensated for back injuries each year ( 5 ) . Many patients have self-limited episodes of acute low back pain and do not seek medical care ( 3 ) . Among those who do seek medical care , pain , disability , and return to work typically improve rapidly in the first month ( 6 ) . However , up to one third of patients report persistent back pain of at least moderate intensity 1 year after an acute episode , and 1 in 5 report substantial limitations in activity ( 7 ) . Approximately 5 % of the people with back pain disability account for 75 % of the costs associated with low back pain ( 8) . Many options are available for evaluation and management of low back pain . However , there has been little consensus , either within or between specialties , on appropriate clinical evaluation ( 9 ) and management ( 10 ) of low back pain . Numerous studies show unexplained , large variations in use of diagnostic tests and treatments ( 11 , 12 ) . Despite wide variations in practice , patients seem to experience broadly similar outcomes , although costs of care can differ substantially among and within specialties ( 13 , 14 ) . The purpose of this guideline is to present the available evidence for evaluation and management of acute and chronic low back pain ( see Glossary ) in primary care setting s. The target audience for this guideline is all clinicians caring for patients with low ( lumbar ) back pain of any duration , either with or without leg pain . The target patient population is adults with acute and chronic low back pain not associated with major trauma . Children or adolescents with low back pain ; pregnant women ; and patients with low back pain from sources outside the back ( nonspinal low back pain ) , fibromyalgia or other myofascial pain syndromes , and thoracic or cervical back pain are not included . These recommendations are based on a systematic evidence review summarized in 2 background papers by Chou and colleagues in this issue ( 15 , 16 ) from an evidence report by the American Pain Society ( 17 ) . The evidence report ( 17 ) discusses the evidence for the evaluation , and the 2 background papers ( 15 , 16 ) summarize the evidence for management . Methods The literature search for this guideline included studies from MEDLINE ( 1966 through November 2006 ) , the Cochrane Data base of Systematic Review s , the Cochrane Central Register of Controlled Trials , and EMBASE . The literature search included all English- language articles reporting on r and omized , controlled trials of nonpregnant adults ( age > 18 years ) with low back pain ( alone or with leg pain ) of any duration that evaluated a target medication and reported at least 1 of the following outcomes : back-specific function , generic health status , pain , work disability , or patient satisfaction . The American College of Physicians ( ACP ) and the American Pain Society ( APS ) convened a multidisciplinary panel of experts to develop the key questions and scope used to guide the evidence report , review its results , and formulate recommendations . The background papers by Chou and colleagues ( 15 , 16 ) provide details about the methods used for the systematic evidence review . This guideline grade s its recommendations by using the ACP 's clinical practice guidelines grading system , adapted from the classification developed by the Grading of Recommendations , Assessment , Development , and Evaluation ( GRADE ) work group ( Appendix Table 1 ) ( 18 ) . The evidence in this guideline was first evaluated by the ACP/APS panel by using a system adopted from the U.S. Preventive Services Task Force for grading strength of evidence , estimating magnitude of benefits , and assigning summary ratings ( Appendix Tables 2 , 3 , and 4 ) ( 19 ) . The evidence was independently review ed by the ACP 's Clinical Efficacy Assessment Subcommittee . The ratings for individual low back pain interventions discussed in this guideline are summarized in Appendix Table 5 for acute low back pain ( 4 weeks ' duration ) . This guideline considered interventions to have proven benefits only when they were supported by at least fair- quality evidence and were associated with at least moderate benefits ( or small benefits but no significant harms , costs , or burdens ) . Figures 1 and 2 present an accompanying algorithm . Appendix Table 1 . The American College of Physicians Clinical Practice Guidelines Grading System Appendix Table 2 . Methods for Grading the Strength of the Overall Evidence for an Intervention Appendix Table 3 . Definitions for Estimating Magnitude of Effects Appendix Table 4 . Recommendations and Summary Ratings Appendix Table 5 . Level of Evidence and Summary Grade s for Noninvasive Interventions in Patients with Acute Low Back Pain Appendix Table 6 . Level of Evidence and Summary Grade s for Noninvasive Interventions in Patients with Chronic or Subacute Low Back Pain Figure 1 . Initial evaluation of low back pain ( LBP Figure 2 . Management of low back pain ( LBP Recommendations : Evaluation of Low Back Pain Recommendation 1 : Clinicians should conduct a focused history and physical examination to help place patients with low back pain into 1 of 3 broad categories : nonspecific low back pain , back pain potentially associated with radiculopathy or spinal stenosis , or back pain potentially associated with another specific spinal cause . The history should include assessment of psychosocial risk factors , which predict risk for chronic disabling back pain ( strong recommendation , moderate- quality evidence ) . More than 85 % of patients who present to primary care have low back pain that can not reliably be attributed to a specific disease or spinal abnormality ( nonspecific low back pain [ see Glossary ] ) ( 20 ) . Attempts to identify specific anatomical sources of low back pain in such patients have not been vali date d in rigorous studies , and classification schemes frequently conflict with one another ( 21 ) . Moreover , no evidence suggests that labeling most patients with low back pain by using specific anatomical diagnoses improves outcomes . In a minority of patients presenting for initial evaluation in a primary care setting , low back pain is caused by a specific disorder , such as cancer ( approximately 0.7 % of cases ) , compression fracture ( 4 % ) , or spinal infection ( 0.01 % ) ( 22 ) . Estimates for prevalence of ankylosing spondylitis in primary care patients range from 0.3 % ( 22 ) to 5 % ( 23 ) . Spinal stenosis ( see Glossary ) and symptomatic herniated disc ( see Glossary ) are present in about 3 % and 4 % of patients , respectively . The cauda equina syndrome ( see Glossary ) is most commonly associated with massive midline disc herniation but is rare , with an estimated prevalence of 0.04 % among patients with low back pain ( 24 ) . A practical approach to assessment is to do a focused history and physical examination to determine the likelihood of specific underlying conditions and measure the presence and level of neurologic involvement ( 24 , 25 ) . Such an approach facilitates classification of patients into 1 of 3 broad categories : nonspecific low back pain , back pain potentially associated with radiculopathy ( see Glossary ) or spinal stenosis ( suggested by the presence of sciatica [ see Glossary ] or pseudoclaudication ) , and back pain potentially associated with another specific spinal cause . The latter category includes the small proportion of patients with serious or progressive neurologic deficits or underlying conditions requiring prompt evaluation ( such as tumor , infection , or the cauda equina syndrome ) , as well as patients with other conditions that may respond to specific treatments ( such as ankylosing spondylitis or vertebral compression fracture ) . Diagnostic triage into 1 of these 3 categories helps guide subsequent decision making . Clinicians should inquire about the location of pain , frequency of symptoms , and duration of pain , as well as any history of previous symptoms , treatment , and response to treatment . The possibility of low back pain due to problems outside the back , such as pancreatitis , nephrolithiasis , or aortic aneurysm , or systemic illnesses , such as endocarditis or viral syndromes , should be considered . All patients should be evaluated for the presence of rapidly progressive or severe neurologic deficits , including motor deficits at more than 1 level , fecal incontinence , and bladder dysfunction . The most frequent finding in the cauda equina syndrome is urinary retention ( 90 % sensitivity ) ( 24 ) . In patients without urinary retention , the probability of the cauda equina syndrome is approximately 1 in 10000 . Clinicians should also ask about risk factors for cancer and infection . In a large , prospect i ve study from a primary care setting , a history of cancer ( positive likelihood ratio , 14.7 ) , unexplained weight loss ( positive likelihood ratio , 2.7 ) , failure to improve after 1 month ( positive likelihood ratio , 3.0 ) , and age older than 50 years ( positive likelihood ratio , 2.7 ) were each associated with a higher likelihood for cancer ( 26 ) . The posttest probability of cancer in patients presenting with back pain increases from approximately 0.7 % to 9 % in patients with a history of cancer ( not including nonmelanoma skin cancer ) . In patients with any 1 of the other 3 risk factors , the likelihood of cancer only increases to approximately 1.2 % ( 26 ) . Features predicting the presence of vertebral infection have not been well studied",
"OBJECTIVE To determine the characteristics of Australian adults who seek care for low back pain ( LBP ) , including the type of care they choose and any factors associated with making those choices . DESIGN A population -based mailed survey . SUBJECTS An age , gender , and state stratified r and om sample of 2768 Australian adults selected from the Electoral Roll . METHODS A self-administered , fully structured question naire included a series of questions relating to care seeking for LBP , choice of provider , and types of treatment received . In addition , a series of questions were asked relating to demographic characteristics , socioeconomic variables , severity of LBP , cigarette smoking , anthropometric variables , perceived cause of LBP , lifetime emotional distress , job satisfaction , lifetime physical fitness , past 5-year health status , and fear of LBP causing future impairment . RESULTS The response rate was 69.1 % . The sample proved to be similar to the Australian adult population . The majority of respondents with LBP in the past 6 months did not seek care for it ( 55.5 % ) . Factors that increased care seeking were higher grade s of pain and disability severity , fear of the impact of pain on future work and life , and female sex . Factors decreasing the likelihood for seeking care were identified as the cause of pain being an accident at home and also never being married . General medical practitioners and chiropractors are the most popular providers of care . CONCLUSION This study shows that a majority of people did not seek care for their LBP . The reasons for care seeking proved to be independent of social or economic status"
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Background The increasing prevalence of obesity in the pediatric age range has become a major concern . Studies have investigated the role of physical activity ( PA ) to prevent obesity in this population . However , previous review s did not focus on the effects of PA in overweight/obese adolescents on physical fitness and risk factors for cardiovascular disease altogether . Objective The present systematic review analyzed trials investigating the effect of PA on aerobic capacity , muscle strength , body composition , hemodynamic variables , biochemical markers , and endothelial function in obese/overweight adolescents . Methods PubMed , LILACS , Web of Science , Scopus ( including Embase ) , and SPORTD iscus data bases were search ed for relevant reports without time limits . Inclusion criteria included studies published in English , with overweight and obese adolescents aged 12–17 years . The review was registered ( Number CRD42013004632 ) on PROSPERO , the International Prospect i ve Register of Systematic Review s. Results The results indicated that PA is associated with significant and beneficial changes in fat percentage , waist circumference , systolic blood pressure , insulin , low-density lipoprotein cholesterol , and total cholesterol , as well as with small non-significant changes in diastolic blood pressure , glucose , and high-density lipoprotein cholesterol . Conclusion Although limited , results from controlled trials suggest that PA intervention may improve physical fitness and risk factors for cardiovascular disease in adolescents who are overweight or obese
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"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 optimal exercise modality for reductions of abdominal obesity and risk factors for type 2 diabetes in youth is unknown . We examined the effects of aerobic exercise ( AE ) versus resistance exercise ( RE ) without caloric restriction on abdominal adiposity , ectopic fat , and insulin sensitivity and secretion in youth . Forty-five obese adolescent boys were r and omly assigned to one of three 3-month interventions : AE , RE , or a nonexercising control . Abdominal fat was assessed by magnetic resonance imaging , and intrahepatic lipid and intramyocellular lipid were assessed by proton magnetic resonance spectroscopy . Insulin sensitivity and secretion were evaluated by a 3-h hyperinsulinemic-euglycemic clamp and a 2-h hyperglycemic clamp . Both AE and RE prevented the significant weight gain that was observed in controls . Compared with controls , significant reductions in total and visceral fat and intrahepatic lipid were observed in both exercise groups . Compared with controls , a significant improvement in insulin sensitivity ( 27 % ) was observed in the RE group . Collapsed across groups , changes in visceral fat were associated with changes in intrahepatic lipid ( r = 0.72 ) and insulin sensitivity ( r = −0.47 ) . Both AE and RE alone are effective for reducing abdominal fat and intrahepatic lipid in obese adolescent boys . RE but not AE is also associated with significant improvements in insulin sensitivity",
"OBJECTIVES We sought to characterize the impact of obesity on vascular function in adolescents and to determine whether an exercise program reverses abnormalities in endothelial function . BACKGROUND Obesity , a major modifiable risk factor for cardiovascular disease , is epidemic in Western societies , with rapid rates of increase in the young . Atherosclerosis begins in childhood , and endothelial dysfunction is its earliest detectable manifestation . METHODS The influence of eight weeks of circuit training ( CT ) was examined in 19 obese subjects ( 14.3 + /- 1.5 years ) , using a r and omized , crossover protocol . Functional capacity and muscular strength were assessed by st and ard techniques . Body composition was examined using anthropometric measures and dual-energy X-ray absorptiometry . Conduit vessel endothelial function was assessed using high-resolution ultrasound and flow-mediated dilation ( FMD ) of the brachial artery . RESULTS Circuit training decreased abdominal and trunk fat and significantly improved fitness and muscular strength ( p obese group , FMD was significantly impaired relative to control subjects ( n = 20 ) at entry ( 5.3 + /- 0.9 % vs. 8.9 + /- 1.5 % , p Circuit training improved functional capacity , muscular strength , and body composition in obese adolescents . Furthermore , conduit vessel function was normalized after exercise training . If vascular dysfunction is an integral component of the pathogenesis of vascular disease , this study supports the value of an exercise program in the management of obese adolescents",
"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",
"Abstract Multiple disease-specific systematic review s on the effectiveness of physical therapy intervention for shoulder dysfunction have been inconclusive . To date , there have been two systematic review s that examined manual therapy specifically but both considered effects within diagnoses . The purpose of this systematic review was to identify the effectiveness of manual therapy to the glenohumeral joint across all painful shoulder conditions . A search of MEDLINE , CINAHL , Web of Science , and Cochrane Central Register of R and omized Controlled Trials for articles date d 1996 to June 2009 was performed . Inclusion for review were manual therapy performed to the glenohumeral joint only ; non-surgical painful shoulder disorders ; subjects 18 - 80 years ; and outcomes of range of motion , pain , function , and /or quality of life . Quality assessment was performed using the PEDro scale with subsequent data extraction . Seventeen related articles were found with seven fitting the inclusion criteria . The average PEDro score was 7.86 , meeting the cutoff score for high quality . Significant heterogeneity in outcome measures prohibited meta- analysis . Five studies demonstrated benefits utilizing manual therapy for mobility , and four demonstrated a trend towards decreasing pain values . Functional outcomes and quality -of-life measures varied greatly among all studies . Manual therapy appears to increase either active or passive mobility of the shoulder . A trend was found favoring manual therapy for decreasing pain , but the effect on function and quality of life remains inconclusive . Future research utilizing consistent outcome measurements is necessary",
"INTRODUCTION Developing effective exercise programmes for the paediatric population is a strategy for decreasing obesity and is expected to help in eventually limiting obesity-associated long-term health and societal impact . In this study , the effects of a 12-week twice weekly additional exercise training , which comprised a combination of circuit-based resistance training and aerobic exercises , in additional to typical physical education sessions , on aerobic fitness , body composition and serum C-reactive protein ( CRP ) and lipids were analysed in 13- to 14-year-old obese boys contrasted with a control group . MATERIAL S AND METHODS Both the exercise group ( EG , n = 12 ) and control group ( CG , n = 12 ) participated in the typical 2 sessions of 40-minute physical education ( PE ) per week in schools , but only EG participated in additional 2 sessions per week of 45 to 60 minutes per session of exercise training , which comprised a combination of circuit-based resistance training and aerobic exercises maintained at 65 % to 85 % maximum heart rate ( HRmax = 220 - age ) . Body composition was measured using dual energy X-ray absorptiometry ( DEXA ) . Fasting serum CRP and blood lipids were analysed pre- and postexercise programme . Aerobic fitness was measured by an objective laboratory submaximal exercise test , PWC170 ( Predicted Work Capacity at HR 170 bpm ) . RESULTS Exercise training significantly improved lean muscle mass , body mass index , fitness , resting HR , systolic blood pressure and triglycerides in EG . Serum CRP concentrations were elevated at baseline in both groups , but training did not result in a change in CRP levels . In the CG , body weight increased significantly at the end of the 12-week period . CONCLUSION This study supports the value of an additional exercise training programme , beyond the typical twice weekly physical education classes , to produce physiological benefits in the management of obesity in adolescents , including prevention of weight gain",
"Cardiovascular disease begins early in life but might be prevented or delayed by primary prevention programs design ed for children and adolescents . Regular physical activity is an important part of primary prevention programs , and school physical education programs have potential for the promotion of regular physical activity . Cardiovascular disease is the major cause of death among Hispanics and African Americans in the United States . Low levels of fitness and increased body mass index are common in African American and Hispanic adolescents . Increased physical activity and the adoption of healthy eating habits would increase fitness and reduce body mass index among these adolescents . The purpose of the study was to undertake a small-scale controlled trial to determine if Dance for Health , an intervention program design ed to provide an enjoyable aerobic program for African American and Hispanic adolescents , has a significant effect on improving aerobic capacity , helping students maintain or decrease weight , and on improving attitudes toward physical activity and physical fitness . In the first year of the program ( 1990 - 91 ) , approximately 110 boys and girls ages 10 - 13 years participated in an aerobic dance pilot program three times per week for 12 weeks . Dance for Health was revised and continued in the 1992 - 93 school year with seventh grade students and an added culturally sensitive health curriculum . Forty-three students were r and omized to Dance for Health and 38 to usual physical activity . Those in the intervention class received a health education curriculum twice a week and a dance oriented physical education class three times a week . The usual physical activity consisted mostly of playground activities . Students in the intervention had a significantly greater lowering in body mass index and resting heart rate than students in regular physical activity",
"OBJECTIVES The primary goals were to underst and the relationship among the inflammatory factors , C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , and fibrinogen , and indices of obesity in normoglycemic , insulin-resistant adolescents and to investigate the impact of a lifestyle-only intervention on these nontraditional risk factors for cardiovascular disease ( CVD ) . STUDY DESIGN R and omized controlled lifestyle-only intervention study in adolescents . Of the 21 adolescents studied , 15 obese subjects ( body mass index [ BMI ] = 37.6 + /- 3.3 kg/m 2 ) were r and omized to either a lifestyle intervention program or usual care . The lean controls were studied only at baseline . Analysis of variance ( ANOVA ) for repeated measures was used to study intervention effect and t test , one-way ANOVA , and discriminant function analysis for baseline comparisons . RESULTS The intervention group maintained weight , whereas the control group gained weight ( P = .02 ) . A redistribution of body composition and a decrease in insulin resistance were observed . Elevated circulating concentrations of CRP , fibrinogen , and IL-6 were significantly reduced ( all P previously sedentary obese adolescents redistributes the parameters of body composition in the absence of weight loss and reverses , at least in part , the inflammatory state in association with an improvement of insulin resistance",
"OBJECTIVES We sought to assess the effects of a school-based intervention program on cardiovascular disease risk factors in urban girls . METHODS We compared heart health knowledge , health behaviors , cardiovascular risk factors , and physical fitness among a group of 442 multiethnic teenaged girls ( 310 experimental participants vs 132 control participants ) . Testing was conducted before and after a 12-week program of vigorous exercises integrated with lectures and discussion s on diet , exercise , stress , and smoking . RESULTS Significant differences in body fat , systolic and diastolic blood pressure , heart health knowledge , and whether breakfast was eaten were observed between experimental participants and control participants . CONCLUSIONS An integrated program of exercise and heart health-related lectures and discussion s had a beneficial effect on health knowledge , health behaviors , and onset of risk factors for coronary artery disease among urban girls",
"PURPOSE Children with high levels of total body fat mass ( TFM ) and visceral adipose tissue ( VAT ) have elevated levels of certain risk factors for coronary artery disease and non-insulin-dependent diabetes mellitus . We tested the hypothesis that controlled physical training , without dietary intervention , would have a favorable impact on VAT and percent body fat ( % BF ) in obese children . METHODS A volunteer sample of 74 obese children , 7 - 11 yr of age , accepted r and om assignment to physical training or control groups . Before and after 4 months of intervention , measurements were obtained for VAT , TFM , % BF , daily physical activity , and cardiovascular fitness . The intervention involved 4 months of controlled physical training 5 d x wk(-1 ) , 40 min per session , at a mean heart rate ( HR ) of 157 beats x min(-1 ) . The estimated energy expenditure ( EE ) per training session was 925+/-201 kJ. RESULTS Compared with the control group , the physical training group declined significantly in % BF ( delta = -2.2 % ) ( P TFM ( delta = -3.1 % ) ( P subcutaneous abdominal adipose tissue ( delta = - 16.1 % ) ( P fat-free mass ( delta = + 6.1 % ) ( P moderate-to-very hard physical activity ( delta = + 14.1 % ) ( P VAT was significantly less in the physical training group ( delta = + 0.5 % ) as compared with that in the control group ( delta = + 8.1 % ) ( P physical training obese children : 1 ) were capable of participating in a substantial amount of high intensity physical training over a 4-month period : 2 ) accumulated significantly less VAT as compared with nonexercising controls ; and 3 ) experienced other beneficial changes in total and regional body composition",
"Objective : To examine the long-term effects of having one overweight or obese parent on child weight status and determine whether these effects vary according to parent sex . Design : Prospect i ve study : Longitudinal Study of Australian Children (LSAC).Subjects : Two-parent families ( N=3285 ) from the LSAC were included if height and weight data were available for both parents and their child at the 2004 and 2008 time points . Measurements : Child weight status category ( healthy , overweight , obese ) in 2008 when the child was aged 8–9 years . Regression modelling was used to investigate how self-reported parent weight status in 2004 influenced measured child weight status 4 years later . Results : Parent body mass index ( BMI ) was significantly correlated with child BMI , but there was no evidence of sex-specific associations between parent and child BMI correlations . The results from the regression analysis showed that having an overweight or obese father , but a healthy weight mother , significantly increased the odds of child obesity ( odds ratio : 4.18 , 95 % confidence interval ( CI ) : 1.01–17.33 and odds ratio : 14.88 , 95 % CI : 2.61–84.77 , respectively ) , but the reverse scenario ( overweight or obese mother with a healthy weight father ) was not a significant predictor of child overweight or obesity ( odds ratio : 2.52 , 95 % CI : 0.38–16.71 and odds ratio : 2.56 , 95 % CI : 0.31–21.26 , respectively ) . Conclusions : Children with overweight or obese fathers are at a higher risk of becoming obese . This suggests that interventions are urgently required to test the efficacy of treating overweight fathers as a key strategy for childhood obesity prevention and /or treatment",
"OBJECTIVE The beat-to-beat variability in electrocardiogram intervals ( RR , i.e. , heart-period variability ) provides information on cardiac autonomic activity that predicts arrhythmias and mortality rate in animals and adults . We determined the effect of physical training on heart-period variability in obese children . METHODS Thirty-five subjects were r and omly assigned to physical training and control groups . The training involved 4 months of exercise , 5 days per week , 40 minutes per day . Cardiovascular fitness was measured with submaximal heart rate during supine cycling ; percentage of body fat was measured with dual-energy absorptiometry ; and resting heart-period variability parameters were measured in a supine position . A pretraining to posttraining change score was computed for each variable . The effect of the training was determined by comparing the changes of the training and control groups . RESULTS Compared with the control group , the trained group ( 1 ) reduced submaximal heart rate and percentage of body fat ( p root mean square of successive differences , a time-domain parameter reflective of vagal tone ( p low-frequency power expressed as a percentage of total power , a frequency-domain index of combined sympathetic and vagal activity ( p ratio of low- to high-frequency power , an index of sympathetic-parasympathetic balance ( p obese children , physical training alters cardiac autonomic function favorably by reducing the ratio of sympathetic to parasympathetic activity",
"BACKGROUND Obesity and poor physical fitness constitute a health problem affecting an increasing number of children . Causes include a pervasive \" toxic \" environment that facilitates increased caloric intake and reduced physical activity . An effective strategy for prevention and treatment of childhood obesity likely includes a collaborative effort in the school setting . OBJECTIVE To determine whether a school-based fitness program can improve body composition , cardiovascular fitness level , and insulin sensitivity in overweight children . DESIGN Fifty overweight middle school children with a body mass index ( BMI ) above the 95th percentile for age were r and omized to lifestyle-focused , fitness-oriented gym classes ( treatment group ) or st and ard gym classes ( control group ) for 9 months . Children underwent evaluation of fasting insulin and glucose levels , body composition by means of dual energy absorptiometry , and maximum oxygen consumption ( V0(2)max ) treadmill testing at baseline ( before the school year ) and at end of the school year . SETTING S Rural middle school and an academic children 's hospital . MAIN OUTCOME MEASURES Baseline test results for cardiovascular fitness , body composition , and fasting insulin and glucose levels . RESULTS At baseline , there were no differences between groups before intervention ( values for age , 12 + /- 0.5 years [ all results , mean + /- SD ] ; BMI [ calculated as weight in kilograms divided by the square of height in meters ] , 31.0 + /- 3.7 ; percentage of body fat , 36.5 % + /- 4.6 % ; lean body mass , 41.4 + /- 8.6 kg ; and V0(2)max , 31.5 + /- 5.1 mL/kg per minute ) . Compared with the control group , the treatment group demonstrated a significantly greater loss of body fat ( loss , -4.1 % + /- 3.4 % vs -1.9 % + /- 2.3 % ; P = .04 ) , greater increase in cardiovascular fitness ( V0(2)max , 2.7 + /- 2.6 vs 0.4 + /- 3.3 mL/kg per minute ; P fasting insulin level ( insulin level , -5.1 + /- 5.2 vs 3.0 + /- 14.3 microIU/mL [ -35.4 + /- 36.1 vs 20.8 + /- 99.3 pmol/L ] ; P = .02 ) . CONCLUSIONS Children enrolled in fitness-oriented gym classes showed greater loss of body fat , increase in cardiovascular fitness , and improvement in fasting insulin levels than control subjects . The modification to the school physical education curriculum demonstrates that small but consistent changes in the amount of physical activity has beneficial effects on body composition , fitness , and insulin levels in children . Partnering with school districts should be a part of a public health approach to improving the health of overweight children",
"Aims : The present study was design ed to examine the possible changes in body composition , insulin-like growth factor 1 ( IGF-1 ) , insulin-like growth factor-binding protein-3 ( IGFBP-3 ) and inflammatory markers of obese children in response to a 2-month program of exercise training combined with dietary restriction . Methods : Twenty-eight obese children ( age 13.2 ± 0.7 years , body mass index 30.9 ± 1.3 ) were r and omly assigned to a diet/training group or a control group and were tested two times : once before and once at the end of the experimental period . They performed a progressive cycle ergometer test at each visit . Substrate oxidation was evaluated by indirect calorimetry . Training was individualized at the point when fat oxidation was maximal ( Lipoxmax ) . Results : Diet/training induced a significant decrease in body weight and body fat ( after vs. before , p 0.01 ) . Plasma concentrations of IGF-1 , IGFBP-3 and inflammatory markers were significantly decreased after the completion of the program . The diet/training program result ed in an increase in VO2maxACSM ( 24.6 ± 2.5 to 33.1 ± 3.1 ml/min/kg , p , exercise training improves inflammatory markers and IGF-1 and IGFBP-3 levels in obese children",
"AIM Increasing prevalence of obesity and related diseases especially in children and adolescent has gained more scientific attention . The present study was conducted to determine the effects of regular exercise on childhood obesity often associated with clinical conditions such as hypertension , dyslipidemia and diabetes already at a young age . METHODS The subjects were 40 obese children at 11 ± 1 years and with Body Mass Index ( BMI ) of at least 30 kg/m2 who volunteered to the study and r and omly classified into exercising and non-exercising control group . Physical load of the exercising group was first determined by the Karvonen protocol after which to the subjects underwent a 12-week aerobic exercise training program primary consisting of walking and jogging exercise . Blood pressure , biochemical cardiovascular risk factors and body composition were assessed before and after the exercise-training period and compared to the non-exercising control group . RESULTS In the exercising group , statistically significant changes were observed in the circumference of forearm , elbow , calf , knee , waist , chest and hip , as well as skin fold thickness of chest , subscapulae , calf , abdomen , suprailiac and leg . Similarly , total cholesterol , triglyceride , LDL , VLDL and insulin levels were found to be lower and HDL levels higher than in the non-exercising control group . CONCLUSION While treating obesity in children , a major emphasis should be directed towards increasing regular physical activity and supported with dietary interventions . By this approach the risk of other chronic diseases often associated with obesity could be minimized thereby improving the quality of life",
"OBJECTIVES The present study aim ed to assess the effect of a 6-month exercise program in obese children on flow-mediated vasodilation ( FMD ) carotid intima-media thickness ( IMT ) and cardiovascular risk factors ( RF ) . BACKGROUND Childhood obesity contributes to adult obesity and subsequent cardiovascular disease . Physical inactivity is a major RF for obesity , endothelial dysfunction , and elevated carotid IMT , culminating in early atherosclerotic disease . METHODS Sixty-seven obese subjects ( age 14.7 + /- 2.2 years ) were r and omly assigned to 6 months ' exercise or non-exercise protocol . We examined the influence of exercises ( 1 h , 3 times/week ) on FMD , IMT , and cardiovascular risk profile . RESULTS Compared with lean control subjects , obese children demonstrated at baseline significantly impaired FMD ( 4.09 + /- 1.76 % vs. 10.65 + /- 1.95 % , p increased IMT ( 0.48 + /- 0.08 mm vs. 0.37 + /- 0.05 mm , p obesity-related cardiovascular RF . Significant improvements were observed in the exercise group for IMT ( 0.44 + /- 0.08 mm , p = 0.012 , -6.3 % ) and FMD ( 7.71 + /- 2.53 % , p body mass index st and ard deviation scores , body fat mass , waist/hip ratio , ambulatory systolic blood pressure , fasting insulin , triglycerides , low-density lipoprotein/high-density lipoprotein ratio , and low-degree inflammation ( C-reactive protein , fibrinogen ) . CONCLUSIONS The present study documented increased IMT , impaired endothelial function , and various elevated cardiovascular RF in young obese subjects . Regular exercise over 6 months restores endothelial function and improves carotid IMT associated with an improved cardiovascular risk profile in obese children",
"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 .",
"The aim of the present study was to compare the effects of a multidisciplinary approach ( MTG ) and aerobic interval training ( AIT ) on cardiovascular risk factors in overweight adolescents . A total of 62 overweight and obese adolescents from Trøndelag County in Norway , referred to medical treatment at St Olav 's Hospital , Trondheim , Norway , were invited to participate . Of these , 54 adolescents ( age , 14.0 + /- 0.3 years ) were r and omized to either AIT ( 4 x 4 min intervals at 90 % of maximal heart rate , each interval separated by 3 min at 70 % , twice a week for 3 months ) or to MTG ( exercise , dietary and psychological advice , twice a month for 12 months ) . Follow-up testing occurred at 3 and 12 months . VO(2max ) ( maximal oxygen uptake ) increased more after AIT compared with MTG , both at 3 months ( 11 compared with 0 % ; P AIT enhanced endothelial function compared with MTG at both 3 months ( absolute change , 5.1 compared with 3.9 % ; P AIT was favourable compared with MTG in reducing BMI ( body mass index ) , percentage of fat , MAP ( mean arterial blood pressure ) and increasing peak oxygen pulse . In addition , AIT induced a more favourable regulation of blood glucose and insulin compared with MTG . In conclusion , the novel findings of the present proof-of-concept study was that 3 months of twice weekly high-intensity exercise sessions reduced several known cardiovascular risk factors in obese adolescents more than that observed after a multitreatment strategy , which was initiated as hospital treatment . Follow-up at 12 months confirmed that AIT improved or maintained these risk factors to a better degree than MTG",
"OBJECTIVES . Childhood overweight has increased significantly in the past 20 years , with the highest rates noted among Mexican Americans . Although this minority group is in significant need of intervention , few programs have demonstrated actual decreases in weight . In this study we evaluated an intensive healthy lifestyle program design ed to result in weight reduction for overweight Mexican American children . We hypothesized that children r and omly assigned to an intensive intervention would significantly reduce their st and ardized BMI when compared with children r and omly assigned to a self-help condition . PATIENTS AND METHODS . A total of 60 children ( 33 boys ; 55 % ) between the ages of 10 and 14 years at or above the 85th percentile for BMI were r and omly assigned to a 6-month intensive-intervention or self-help condition . RESULTS . Children in the intensive-intervention condition significantly reduced their st and ardized BMI when compared with the children in the self-help condition . The change in st and ardized BMI was significantly different at both 3 and 6 months , with intensive-intervention participants showing greater decreases in weight . CONCLUSIONS . Overall , the results were promising , suggesting that an intensive , individualized intervention may be an effective means for promoting weight loss in overweight Mexican American children",
"The prevalence of childhood overweight has increased significantly , with the highest rates noted among Mexican Americans . Many negative health outcomes are associated with overweight ; thus , there is a need for effective weight-loss interventions tailored to this group . This study evaluated 24-month outcomes of a r and omized , controlled trial involving an intensive lifestyle-based weight maintenance program targeting overweight Mexican-American children at a charter school in Houston , Texas . A total of 60 children ( 33 males , 55 % ) between the ages of 10 and 14 at or > 85th percentile for BMI were recruited . Participants were r and omized to an instructor-led intervention ( ILI ) or a self-help ( SH ) program , both aim ed at modifying eating and physical activity behaviors using behavior modification strategies . Changes in participants ' st and ardized BMI ( z BMI ) were assessed at baseline , 1 , and 2 years . Tricep skinfold , total cholesterol , triglycerides , high-density lipoprotein cholesterol , and calculated low-density lipoprotein were assessed at baseline and 1 year . ILI participants showed significantly greater decreases in z BMI at 1 and 2 years ( F = 26.8 , P improvements in body composition , as measured by tricep skinfold ( F = 9.75 , P total cholesterol ( F = 7.19 , P and triglycerides ( F = 4.35 , P improved weight and clinical outcomes in overweight Mexican-American children , and z BMI was maintained over 2 years",
"BACKGROUND This study tests the feasibility of an innovative school-based program for obesity prevention among adolescent girls . New Moves was implemented as a multicomponent , girls-only , high-school physical education class . METHODS Six schools were equally r and omized into intervention and control conditions . Data were collected at baseline , postintervention , and 8-month follow-up to assess program impact on physical activity , eating patterns , self-perceptions , and body mass index ( BMI ) among 89 girls in the intervention and 112 girls in the control conditions . Program evaluation also included interviews with school staff , parent surveys , and participant interviews and process evaluation surveys . RESULTS The feasibility of implementing New Moves was high , as indicated by strong satisfaction among participants , parents , and school staff , and by program sustainability . Participants perceived a positive program impact on their physical activity , eating patterns , and self-image . Girls in the intervention significantly progressed in their stage of behavioral change for physical activity from baseline to follow-up . However , for the majority of outcome variables , differences between intervention and control schools at postintervention and follow-up were not statistically significant . CONCLUSIONS New Moves was well received and fills a needed niche within school physical education programs . An exp and ed intervention and evaluation is needed to enhance and assess long-term program effectiveness",
"BACKGROUND Aerobic exercise improves cardiovascular health in general , but whether the impact varies with exercise intensity is not clear . OBJECTIVE The aim of the current study was to compare the effects of a high-intensity aerobic exercise training ( HIT ) vs. a low-intensity aerobic exercise training ( LIT ) on blood pressure ( BP ) , heart rate ( HR ) and heart rate variability ( HRV ) in obese adolescents . METHODS Forty-three ( 13 - 18 years ) Tanner stage ( III-IV ) matched obese adolescents were studied in a r and omized trial of either HIT ( corresponding to the ventilatory threshold I ; n = 20 ) or LIT ( corresponding to 20 % below the ventilatory threshold I ; n = 23 ) programme for a period of 6 months . All participants also received a multidisciplinary therapy that included nutritional , psychological and clinical counselling . Both HIT and LIT sessions were isocaloric , with energy expenditure set at 350 kcal . BP , HR and HRV were measured along with markers of body adiposity and insulin resistance before and after the respective interventions . RESULTS The participants in both groups had similar physical and clinical characteristics . After the 6-month intervention , systolic , diastolic and mean BP decreased ( P waist circumference , HR and HRV showed beneficial changes only in the HIT group ( P Aerobic exercise training set at a high intensity compared with the low intensity appears to have additional benefits on abdominal obesity and cardiovascular health in that it enhances the parasympathetic and autonomic modulation of the heart in obese adolescents",
"INTRODUCTION There has been a paucity of theory-based interventions to improve health outcomes in overweight adolescents . Therefore , two intervention studies were conducted to : ( a ) determine the feasibility of implementing the Creating Opportunities for Personal Empowerment ( COPE ) Healthy Lifestyles Thinking , Emotions , Exercise , and Nutrition ( TEEN ) program with overweight adolescents ; ( b ) obtain feedback that could be used to refine the program ; and ( c ) examine the preliminary efficacy of the COPE program on the adolescents ' weight and body mass index ( BMI ) . METHOD Phase I and Phase II clinical trials were conducted with 23 overweight teens . The Phase 1 trial used a pre-experimental design with one group of 11 urban adolescents . The Phase 2 trial was conducted with 12 suburban teens using a r and omized controlled pilot study . COPE teens received a 15-session cognitive-behavioral skills building program that included physical activity , while the control group received an attention control program . Weight change and BMI were the key outcomes . RESULTS COPE teens experienced a significantly greater reduction in weight and BMI than did teens in the control group , who gained weight over time . Although the COPE program was well received by all of the teens , retention of subjects across time and parent involvement in the program were challenges in the urban high school . DISCUSSION These studies provide preliminary data to indicate that the implementation of COPE is feasible and may lead to a reduction in weight and BMI in overweight teens . Implementing COPE within the context of the school day may be more successful in sustaining adolescent involvement in the program versus using an after-school format",
"OBJECTIVES To examine markers of inflammation in 9- and 15-year-olds with high waist circumference and compare these with controls , and to examine the relationships between inflammatory markers and cardiovascular disease ( CVD ) risk factors . METHODS Cross-sectional analysis of data from 2 299 Norwegian 9- and 15-year-olds participating in the \" Physical activity among Norwegian Children Study \" . In each sex and age group , the 10 participants with the highest waist circumference ( HW ) were selected ( n=40 ) for analyses , and a r and om sample of 40 participants within the same groups were included as controls . Inflammatory markers included C-reactive protein ( CRP ) , leptin , adiponectin , plasminogen activator inhibitor-1 ( PAI-1 ) , tumor necrosis factor-alpha ( TNF-alpha ) , hepatocyte growth factor ( HGF ) , resistin and interleukin-6 ( IL-6 ) . The CVD risk factors included blood pressure , glucose , insulin , triglycerides and high density lipoprotein cholesterol . RESULTS HW participants had elevated levels of CRP ( mean difference 1.50 mg/l ; 95 % confidence interval [ CI ] 0.33 to 2.66 ) , PAI-1 ( mean difference 13.3 ng/ml ; 95 % CI 4.1 to 22.5 ) and HGF ( mean difference 0.29 ng/ml ; 95 % CI 0.07 to 0.51 ) compared with controls . All CVD risk factors differed between the HW group and controls . The CVD risk factors were not associated with TNFalpha or IL-6 , but CRP , HGF and PAI-1 were related to the metabolic risk score . CONCLUSIONS Low grade systemic inflammation is already present in youth with high waist circumference . CRP , HGF and PAI-1 may be related to the adverse overall metabolic risk profile observed in these children and adolescents"
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OBJECTIVES To study the effect of combining multiple ( two or more ) micronutrients with Fe supplementation on Hb response , when compared with placebo and with Fe supplementation , in children . DATA SOURCES Electronic data bases , personal files , h and search of review s , bibliographies of books , and abstract s and proceedings of international conferences . REVIEW METHODS R and omized controlled trials evaluating change in Hb levels with interventions that included Fe and multiple-micronutrient supplementation in comparison to placebo alone or Fe alone were analysed in two systematic review s. RESULTS Twenty-five trials were included in the review comparing Fe and micronutrient supplementation with placebo . The pooled estimate ( r and om effects model ) for change in Hb with Fe and micronutrient supplementation ( weighted mean difference ) was 0.65 g/dl ( 95 % CI 0.50 , 0.80 , P baseline Hb , lower height-for-age Z score , non-intake of ' other micronutrients ' and malarial non-hyperendemic region were significant predictors of greater Hb response and heterogeneity . Thirteen trials were included in the review comparing Fe and micronutrient supplementation with Fe alone . The pooled estimate for change in Hb with Fe and micronutrient supplementation ( weighted mean difference ) was 0.14 g/dl ( 95 % CI 0.00 , 0.28 , P = 0.04 ) . None of the variables were found to be significant predictors of Hb response . CONCLUSIONS Synthesized evidence indicates that addition of multiple micronutrients to Fe supplementation may only marginally improve Hb response compared with Fe supplementation alone . However , addition of ' other micronutrients ' may have a negative effect . Routine addition of unselected multiple micronutrients to Fe therefore appears unjustified for nutritional anaemia control programmes
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"BACKGROUND Dietary supplements providing physiologic amounts of several micronutrients simultaneously have not been thoroughly tested for combating micronutrient deficiencies . OBJECTIVE We determined whether a beverage fortified with 10 micronutrients at physiologic doses influenced the iron and vitamin A status and growth of rural children ( aged 6 - 11 y ) attending primary schools . DESIGN In this r and omized , double-blind , placebo-controlled efficacy trial , children were assigned to receive the fortified beverage or an unfortified beverage at school for 6 mo . RESULTS There were nonsignificant differences at baseline between children in the fortified and nonfortified groups in iron status , serum retinol , and anthropometry . At the 6-mo follow-up , among children with anemia ( hemoglobin hemoglobin concentration in the fortified group than in the nonfortified group ( 9.2 and 0.2 g/L , respectively ) . Of those who were anemic at baseline , 69.4 % in the nonfortified group and 55.1 % in the fortified group remained anemic at follow-up ( RR : 0.79 ) , a cure rate of 21 % . The prevalence of children with low serum retinol concentrations ( incremental changes in weight ( 1.79 compared with 1.24 kg ) , height ( 3.2 compared with 2.6 cm ) , and BMI ( 0.88 compared with 0.53 ) were significantly higher in the fortified group than in the nonfortified group . CONCLUSION The fortified beverage significantly improved hematologic and anthropometric measurements and significantly lowered the overall prevalence of anemia and vitamin A deficiency",
"The effects of supplementation of the diets of 6- to 12-year-old children in a village near Shiraz in Iran with zinc plus iron or iron alone , together with the indispensable amino acids in the form of egg white protein , vitamins , minerals , and corn oil have been evaluated . Initially 48 of 59 children had zinc concentrations below the minimum found in well-nourished persons . Eight months of supplementation with zinc plus iron ( 20 mg daily of elemental zinc as carbonate and 20 mg ferrous iron as fumarate ) failed to stimulate growth or bone development or to bring about an increase in plasma zinc concentrations . However , supplementation with iron in the above amount was associated with an acceleration of growth in height and weight . The persistence of low concentrations of zinc in plasma and the failure of supplemental zinc to stimulate growth are attributed to the poor availability of both dietary and supplemental zinc result ing from sequestering action of fiber and phytate present in large amounts in the unleavened whole meal bread consumed by villagers . In addition , the results suggest that simultaneous administration of iron and zinc supplements may impair utilization of the metals",
"Growth faltering , anemia , and multiple micronutrient deficiency are common during infancy in developing countries . This South African trial was part of a multicenter study aim ed at testing the efficacy of multiple micronutrient supplementation on growth , anemia , micronutrient status , and morbidity during infancy across 4 countries . A total of 265 infants aged 6 - 12 mo were individually r and omized to 1 of 4 intervention groups : a daily multiple micronutrient supplement ( DMM ) , a daily placebo supplement ( P ) ; a multiple micronutrient supplement 1 d of the week and placebo supplement on the other days of the week ( WMM ) , and a daily iron supplement ( DI ) . For 6 mo , the blinded supplements were provided to mothers at monthly health clinic sessions , and consumption was verified during weekly household visits by community health workers , when morbidity was also checked . Weight and height of the infants were measured monthly , and blood sample s were taken at the beginning and at the end for assessing the infants micronutrient status . There were no significant differences in nutritional status of the groups at baseline with 40 % of infants with anemia ( hemoglobin stunting . There was no difference in growth or morbidity between the micronutrient supplemented groups and the P group during the 6-mo study . The DMM was the most effective intervention tested , not only for improving anemia but also for improving iron , zinc , riboflavin , and tocopherol status",
"BACKGROUND Micronutrient deficiencies remain common in preschool children in developing countries . Interventions focus on single micronutrients and often lack effectiveness . Weekly instead of daily supplementation may improve effectiveness . OBJECTIVE The efficacy of weekly and daily supplementation in reducing anemia prevalence and in improving the zinc , vitamin A , and growth status of 6 - 24-mo-old Vietnamese children was investigated . DESIGN In this double-blind , placebo-controlled trial , the daily group ( n = 55 ) received 8 mg elemental Fe ( as iron sulfate ) , 5 mg elemental Zn ( as zinc sulfate ) , 333 microg retinol , and 20 mg vitamin C 5 d/wk for 3 mo . The weekly group ( n = 54 ) received 20 mg Fe , 17 mg Zn , 1700 microg retinol , and 20 mg vitamin C once a week . A third group ( n = 54 ) received a placebo only . Venous blood sample s were collected at the start and end of the supplementation period and anthropometric measurements were taken at the start and 3 mo after the end of supplementation . RESULTS At baseline , 45.6 % of subjects had hemoglobin concentrations zinc concentrations Hemoglobin , retinol , and zinc concentrations of both the weekly and daily groups increased similarly compared with the placebo group ( P growth between the supplemented groups and the placebo group . However , the height-for-age of subjects stunted at baseline increased with z scores of 0.48 ( P hemoglobin , zinc , and retinol concentrations similarly . Neither intervention affected growth of the overall population , but growth of children stunted at baseline was improved through both types of supplementation",
"The effects on pregnancy outcome and maternal iron status of powdered milk ( PUR ) and a milk-based fortified product ( V-N ) were compared in a group of underweight gravidas . These take-home products were distributed during regular prenatal visits . Women in the V-N group had greater weight gain ( 12.29 vs 11.31 kg , p less than 0.05 ) and mean birth weights ( 3178 vs 3105 g , p less than 0.05 ) than those in the PUR group . Values for various indicators of maternal Fe status were also higher in the V-N group . Compared with self-selected noncompliers , similar in all control variables to compliers , children of women who consumed powdered milk or the milk-based fortified product had mean birth weights that were higher by 258 and 335 g , respectively . Data indicate a beneficial effect of the fortified product on both maternal nutritional status and fetal growth",
"BACKGROUND Iron deficiency is the most common micronutrient deficiency and affects > 2 billion persons worldwide , leading to anemia in > 40 % of women of reproductive age in the developing world . OBJECTIVE The objective was to determine whether weekly supplementation with iron and folate would reduce the frequency of anemia in teenage women in urban Bangladesh before they became pregnant . DESIGN Participants with a hemoglobin concentration of 80 - 120 g/L were entered into a r and omized , double-blind , placebo-controlled trial and received supplements of placebo , vitamin A , iron + folic acid , or iron + folic acid + vitamin A weekly for 12 wk . The supplements contained 2.42 mg vitamin A ( retinol ) as retinyl palmitate , 120 mg elemental Fe as ferrous sulfate , and 3.5 mg folic acid . RESULTS Hemoglobin concentrations increased significantly more after supplementation with iron + folic acid or iron + folic acid + vitamin A than after either the placebo or vitamin A alone . There was a significantly greater increase in hemoglobin after iron + folic acid + vitamin A than after iron + folic acid , but the additional effect disappeared after adjustment for baseline hemoglobin , serum vitamin A , and ferritin and the number of supplements taken . Those with the lowest baseline hemoglobin had the greatest increase in hemoglobin . Compared with the placebo , iron + folic acid + vitamin A reduced anemia by 92 % , iron deficiency by 90 % , and vitamin A deficiency by 76 % . CONCLUSION There may be significant health benefits from a program that enhances the nutritional status of iron , folate , and vitamin A in poor urban young women before they become pregnant",
"Multiple micronutrient deficiencies are highly prevalent in Indonesia , but the interventions are still focused on single micronutrients . This study aim ed to investigate the efficacy of multiple micronutrient supplements for improving micronutrient status , anemia , growth , and morbidity of Indonesian infants . In this double-blind , placebo-controlled trial , 284 infants aged 6 - 12 mo were r and omly allocated to 4 treatment groups for 23 wk ; 260 ( 92 % ) infants completed the study . Group 1 ( DMM ) received one adequate intake of multiple micronutrient supplements daily ( n = 66 ) ; group 2 ( WMM ) received 2 adequate intakes of multiple micronutrient on 1d plus 6 d of placebo ( n = 60 ) ; group 3 ( DI ) received 10 mg of iron supplement daily ( n = 69 ) ; group 4 received a placebo supplement daily ( n = 65 ) . Blood sample s were collected at baseline and at posttreatment to assess anemia and micronutrient status . Anthropometric measurements were taken monthly , and morbidity was recorded daily . At baseline , 58.1 % of infants were anemic , 34.2 % were iron deficient , 21.3 % were vitamin A deficient , and 11 % were zinc deficient . The DMM and DI supplements both corrected iron deficiency , but DMM supplements were more efficacious in improving hemoglobin levels of anemic infants than the other supplements . However , anemia still persisted in one-third of DMM infants posttreatment . The DMM supplement was more efficacious than WMM or DI supplementation in improving infant status of other micronutrients , including zinc , tocopherol , and riboflavin , whereas DI exacerbated zinc deficiency . There were no significant differences in growth and morbidity among treatment groups , and growth faltering was not prevented",
"BACKGROUND Iron and zinc deficiency are prevalent during infancy in low-income countries . OBJECTIVES The objectives were to examine whether a weekly supplement of iron , zinc , iron+zinc , or a micronutrient mix ( MM ) of 16 vitamins and minerals would alter infant development and behavior . DESIGN The participants were 221 infants from rural Bangladesh at risk of micronutrient deficiencies . Development and behavior were evaluated at 6 and 12 mo of age by using the Bayley Scales of Infant Development II and the Home Observation Measurement of Environment ( HOME ) scale . In this double-blind trial , the infants were r and omly assigned to 1 of 5 treatment conditions : iron ( 20 mg ) , zinc ( 20 mg ) , iron+zinc , MM ( 16 vitamins and minerals , including iron and zinc ) , or riboflavin weekly from 6 to 12 mo . Multivariate analyses were conducted to examine the change in development and behavior for each supplementation group , with control for maternal education , HOME score , months breastfed , anemia , growth at 6 mo , and change in growth from 6 to 12 mo . RESULTS Iron and zinc administered together and with other micronutrients had a beneficial effect on infant motor development . Iron and zinc administered individually and in combination had a beneficial effect on orientation-engagement . Two-thirds of the infants were mildly anemic , no treatment effects on hemoglobin concentration were observed , and hemoglobin was not associated with measures of development or behavior . CONCLUSION The beneficial effects of weekly iron and zinc supplementation on motor development and orientation-engagement suggest that infants benefit from these minerals when administered together",
"Different supplementation schemes to build iron stores in female Indonesian adolescents were investigated . Subjects were 273 high-school girls allocated r and omly to four treatment groups . During a 3-mo period one group received 60 mg Fe , 750 micrograms retinol , 250 micrograms folic acid , and 60 mg vitamin C per day ; a second group received 60 mg Fe , 6000 micrograms retinol , 500 mg folic acid , and 60 mg vitamin C once a week ; a third group received 120 mg Fe and the same amount of the other three micronutrients as the second group once a week ; and a fourth group received only placebos . All subjects were dewormed and supplement allocation was double blind . Blood sample s were collected at baseline , after 2 and 3 mo of supplementation , and 6 mo after the last supplement . After 2 mo of supplementation , groups supplemented weekly and daily showed similar significant improvements ( P hemoglobin and retinol concentrations , and supplementation for 3 instead of 2 mo did not significantly increase these two indicators . After 3 mo , the increase in ferritin was approximately equal to 27 micrograms/L in the daily and 14 - 15 micrograms/L in the weekly groups ( P ferritin concentration was still approximately equal to 10 - 12-micrograms/L higher ( P side effects than the other supplemented groups ( P iron status of the adolescents for approximately equal to 9 mo",
"A micronutrient-fortified rusk for weanling children was tested in a rural area near Beijing . Two hundred twenty-six children aged 6 - 13 mo were r and omly assigned by village to either a micronutrient-fortified or an unfortified rusk , daily for 3 mo . The fortified rusk contained extra zinc ; iron ; calcium ; vitamins A , D , and B-12 ; thiamin , riboflavin , niacin , and folic acid . Infants receiving the fortified rusk exhibited no decline in hemoglobin concentrations during the study whereas those receiving the unfortified rusk exhibited a significant decline . Improvements were also seen in erythrocyte porphyrin , plasma vitamin A , and riboflavin status , but these improvements were seen in both of the groups . Micronutrient fortification was probably beneficial for iron status and the fortified rusk promises to be an effective vehicle for supplementation",
"In developing countries , low food intake is often reported in children Reduced appetite may be a contributing factor . We investigated whether a combination of a multivitamin-multimineral supplement and additional iron treatment improved appetite and growth of 18- to 30-mo-old stunted and anemic Beninese children . The study was placebo-controlled using VITALIA tablets ( 11 vitamins and 10 minerals ) and ferrous fumarate tablets ( 66 mg of iron ) . One hundred fifty stunted ( height-for-age Z score assigned to one of four groups : group 1 , multivitamin-multimineral plus iron ; group 2 , multivitamin-multimineral plus placebo ; group 3 , placebo plus placebo ; and group 4 , placebo plus iron . Supplementation was daily and supervised for 6 wk . Appetite , knee-heel length , dietary intakes and morbidity were assessed before and after supplementation . Length , weight , arm circumference and hemoglobin concentration were assessed before , just after supplementation and 4 mo after the intervention . Appetite was assessed by means of an appetite test using a test food , riz-au-gras , eaten ad libitum after an overnight fast . Dietary intakes were assessed during three consecutive days in a sub sample by means of the observed weighed record method . Energy intake from the habitual breakfast was significantly correlated with that from the test food ( r = 0.49 , n = 38 , P = 0.002 ) . There were no differences among groups in changes in appetite and growth performance . The habitual diet of the children was monotonous and contained only small amounts of animal products . The morbidity status of the children was comparable in all study groups , before as well as after supplementation . We conclude that the 6-wk multivitamin-multimineral supplementation with additional iron treatment failed to improve the appetite and growth of the children",
"INTRODUCTION Anemia is the most prevalent nutritional deficiency in the world . Attempts to improve iron indexes are affected by deficiency of and interaction between other micronutrients . OBJECTIVE Our goal was to assess whether zinc added to iron treatment alone or with vitamin A improves iron indexes and affects diarrheal episodes . DESIGN This was a r and omized , placebo-controlled , double-blind trial conducted in Peru . Anemic children aged 6 - 35 mo were assigned to 3 treatment groups : ferrous sulfate ( FS ; n = 104 ) , ferrous sulfate and zinc sulfate ( FSZn ; n = 109 ) , and ferrous sulfate , zinc sulfate , and vitamin A ( FSZnA ; n = 110 ) . Vitamin A or its placebo was supplied only once ; iron and zinc were provided under supervision > /=1 h apart 6 d/wk for 18 wk . RESULTS The prevalence of anemia was 42.97 % . The increase in hemoglobin in the FS group ( 19.5 g/L ) was significantly less than that in the other 2 groups ( 24.0 and 23.8 g/L in the FSZn and FSZnA groups , respectively ) . The increase in serum ferritin in the FS group ( 24.5 mug/L ) was significantly less than that in the other 2 groups ( 33.0 and 30.8 mug/L in the FSZn and FSZnA groups , respectively ) . The median duration of diarrhea and the mean number of stools per day was significantly higher in the FS group than in other 2 groups ( P zinc to iron treatment increases hemoglobin response , improves iron indexes , and has positive effects on diarrhea . No additional effect of vitamin A was found",
"A r and omized , double-blind , placebo-controlled trial was performed to assess the efficacy of different micronutrient supplementation regimes for improving micronutrient status , preventing anemia , and growth faltering of Vietnamese infants . A population -based sample of 306 infants aged 6 - 12 mo , split in 4 treatment groups , received daily multiple micronutrient ( DMM ) , daily placebo ( P ) , weekly multiple micronutrient ( WMM ) , or daily iron ( DI ) supplements for 6 mo , 7 d/wk , under supervision . Weight and length were measured monthly , and anemia and plasma levels of ferritin , zinc , riboflavin , retinol , tocopherol , and homocysteine were determined before and after the supplementation . Z-scores for length-for-age and weight-for-age worsened significantly in all groups , but the length-for-age Z-score decreased significantly less in the DMM group ( -0.32 + /- 0.05 ) than in the P and WMM groups ( -0.49 + /- 0.05 and -0.51 + /- 0.05 , respectively , P = 0.001 ) . Hemoglobin levels increased significantly more in the DMM group [ mean ( 95%CI ) : 16.4 g/L ( 12.4 - 20.4 ) ] than in the P group [ 8.6 g/L ( 5.0 - 12.2 ) , P = 0.04 ) , with intermediate nonsignificant increases in the WMM [ 15.0 g/L ( 11.5 - 18.5 ) ] and the DI [ 12.9 g/L ( 8.4 - 17.3 ) ] groups . Ferritin changes were significantly greater in DMM ( 12.1 microg/L ) and DI ( 9.5 microg/L ) than in P ( -14.7 microg/L ) and WMM groups ( -9.7 microg/L ) . Of the other micronutrients , only tocopherol showed a significantly greater level in the DMM group compared with P. Anemia still affected a quarter and zinc deficiency affected a third of infants although there was no iron deficiency after 6 mo of supplementation with DMM , suggesting that multiple factors are causing anemia and that the dose of zinc is too small",
"BACKGROUND Iron deficiency anemia is the most prevalent nutrition problem in young children . One possible strategy to prevent iron deficiency anemia in this population group is the fortification of affordable food . OBJECTIVE This study was design ed to assess whether iron-fortified c and ies can improve iron status and are acceptable to children aged 4 - 6 y. DESIGN A double-blind , placebo-controlled intervention study was conducted in Jakarta , INDONESIA : The children were r and omly assigned to 1 of 2 treatment groups : a fortified group ( n = 57 ) and a placebo group ( n = 60 ) . Every week for 12 wk , 30 g ( 10 pieces ) c and y was given to the children . The c and y given to the fortified group contained 1 mg elemental Fe/g and very small amounts of other vitamins and minerals . RESULTS The hemoglobin concentration of the fortified group increased by 10.2 g/L ( 95 % CI : 8.3 , 12 g/L ) whereas that of the placebo group increased by 4.0 g/L ( 2.0 , 6.0 g/L ; P Anemia prevalence decreased from 50.9 % at the start of the intervention to 8.8 % after 12 wk of intervention in the fortified group ( P serum ferritin concentration was 71 % higher than at baseline in the fortified group and 28 % higher in the placebo group ( P Acceptability of the iron-fortified c and ies was good . The per capita cost of the supplement was approximately US$ 0.96 - 1.20 for the 12 wk of intervention . CONCLUSION Iron-fortified c and ies were effective for improving the iron status of young children and might be an affordable way to combat iron deficiency in children of low-to-middle income groups",
"BACKGROUND Combined supplementation with iron and zinc during infancy may be effective in preventing deficiencies of these micronutrients , but knowledge of their potential interactions when given together is insufficient . OBJECTIVE The goal was to compare the effect in infants of combined supplementation with iron and zinc and of supplementation with single micronutrients on iron and zinc status . DESIGN Indonesian infants ( n = 680 ) were r and omly assigned to daily supplementation with 10 mg Fe ( Fe group ) , 10 mg Zn ( Zn group ) , 10 mg Fe + 10 mg Zn ( Fe+Zn group ) , or placebo from 6 to 12 mo of age . Venous blood sample s were collected at the start and end of the study . Five hundred forty-nine infants completed the supplementation and had both baseline and follow-up blood sample s available for analysis . RESULTS Baseline prevalences of anemia , iron deficiency anemia ( anemia and low serum ferritin ) , and low serum zinc ( higher hemoglobin ( 119.4 compared with 115.3 g/L ; P serum ferritin ( 46.5 compared with 32.3 microg/L ; P higher serum zinc ( 11.58 compared with 9.06 micromol/L ; P on serum ferritin in the Fe and Fe+Zn groups , but at different levels . There was a significant dose effect on serum zinc in the Zn group , whereas no dose effect was found in the Fe+Zn group beyond 7 mg Zn/d . CONCLUSION Supplementation with iron and zinc was less efficacious than were single supplements in improving iron and zinc status , with evidence of an interaction between iron and zinc when the combined supplement was given",
"Anemia , micronutrient deficiencies , and growth faltering are still common in Peru . The study objective was to determine the efficacy of different micronutrient supplements in preventing growth failure , anemia , and micronutrient deficiencies in Peruvian infants . Three hundred and thirteen infants aged 6 to 12 mo participated in a double-blind , masked , controlled trial in which they were r and omly assigned to receive either a daily dose of iron ( DI ) , a daily dose of multiple micronutrients ( DMM ) , a weekly dose of multiple micronutrients , or a placebo ( P ) for 6 mo . None of the supplements tested prevented growth faltering or the morbidities common during infancy . Anemia and plasma homocysteine concentrations fell significantly in all groups during the study , but the mean change of plasma homocysteine during the trial period was significantly smaller in the DI group than in other groups , and the increase in hemoglobin concentrations was smaller in the P group than the micronutrient treatment groups . Plasma ferritin concentrations decreased least in the groups taking daily micronutrient supplements containing iron ( DI and DMM ) . There were no significant differences among groups in mean final values or changes in plasma zinc , retinol , tocopherol , or riboflavin . Although the DMM intervention was the most efficacious for preventing anemia , iron , and zinc deficiencies , 15 % , 20 % , and 50 % of this group still remained anemic , zinc deficient , and iron deficient , respectively , at the end of the study . Further research thus should investigate whether higher doses of iron and zinc , together with infection control measures , are more efficacious",
"Because infants and young children in many developing countries are deficient in both iron and zinc , and zinc can affect iron metabolism , evaluation of optimum strategies to simultaneously supplement iron and zinc is an important public health priority . This study evaluated the efficacy of weekly supplementation of iron or zinc or both on iron , zinc , and copper status in Bangladeshi infants . In a double-blind , r and omized , controlled community trial , 6-mo-old infants were assigned to receive weekly supplements of 1 mg riboflavin ( control , n = 82 ) or 1 mg riboflavin + 20 mg iron ( n = 83 ) , 20 mg zinc ( n = 83 ) , or both ( n = 85 ) for 6 mo . Hemoglobin , serum ferritin , transferrin receptor , zinc , and copper concentrations were measured at baseline and at the end of intervention . Serum Zn increased in both groups receiving zinc ; the increase was greatest among children with low baseline serum zinc concentration . Iron status indicators did not differ among the groups before or after 6 mo of supplementation . Supplementation with either zinc or iron decreased serum copper after 6 mo . Joint supplementation did not alter the individual effects of iron or zinc supplementation in these Bangladeshi children . However , the dosing regimen may not have been adequate to achieve the desired biochemical effects",
"One objective of this clinical trial was to determine whether calcium and phosphorus supplementation of infant formula affects the iron status of healthy full-term infants . One hundred three infants were r and omly assigned to receive iron-fortified , cow milk-based infant formula ( 465 mg Ca and 317 mg P/L ) or the same formula with added calcium glycerophosphate ( 1800 mg Ca and 1390 mg P/L ) for 9 mo . Reported calcium intake for supplemented infants was about four times that of control infants , ranging from a mean of 1741 mg/d at baseline to 1563 mg/d at 9 mo . There was no difference by treatment group in mean or median change from baseline of serum ferritin , total-iron-binding capacity , erythrocyte protoporphyrin , or hematocrit at 4 and 9 mo after enrollment . Incidence of iron deficiency was similar for both groups and no infant developed iron deficiency anemia during the trial . This study indicates that the well-documented inhibitory effect of calcium and phosphorus on iron absorption is not clinical ly important in infants fed iron-fortified infant formula",
"BACKGROUND Multiple micronutrient deficiencies are often the basic causative factor in stunting and anemia , 2 conditions that affect entire generations of children in deprived population s. No generally accepted recommendations for micronutrient intakes for recovery from stunting are available . OBJECTIVE The objective was to assess the effect of a highly nutrient-dense spread fortified with vitamins and minerals , with or without antiparasitic metronidazole treatment , in correcting retarded linear growth and reducing anemia in stunted children . DESIGN Saharawi refugee children ( n = 374 ) aged 3 - 6 y with initial height-for-age z scores were assigned to 1 of 5 groups : fortified spread ( FS ) , fortified spread plus metronidazole ( FS+M ) , unfortified spread ( US ) , unfortified spread plus metronidazole ( US+M ) , or control . Supervised supplementation was given daily for 6 mo . Weight , height , knee-heel length , hematologic indexes , parasitic infections , and morbidity were assessed at 0 , 3 , and 6 mo . RESULTS Linear growth of children fed FS was 30 % faster at 3 mo than in US and control groups , after which height-for-age z scores increased only slightly in the FS group and remained unchanged in the other groups . No additional benefits from metronidazole were observed . Increase in hemoglobin concentrations in the FS group at 6 mo was twofold that in the US and control groups ( 37 + /- 40 , 19 + /- 15 , and 16 + /- 17 g/L , respectively ; P anemia was reduced by nearly 90 % . CONCLUSIONS FS , and not US , induces catch-up growth in stunted children whose diets are poor in micronutrients . Our trial provides support for delivering multiple micronutrients to reverse stunting and reduce anemia in children up to age 6",
"BACKGROUND Maize-meal porridge is used for infant feeding in many African countries , including South Africa . A low-cost , finely milled , maize-meal porridge was fortified with beta-carotene , iron , and zinc ( 100 % of recommended dietary allowance ) , as well as ascorbic acid , copper , selenium , riboflavin , vitamin B-6 , vitamin B-12 , and vitamin E. OBJECTIVE We assessed whether the fortified porridge could reduce anemia and improve the micronutrient status and motor development of infants . DESIGN Infants aged 6 - 12 mo ( n = 361 ) were r and omly assigned to receive either the fortified or unfortified porridge for 6 mo . Primary outcomes were hemoglobin and serum retinol , zinc , and ferritin concentrations and motor development . Growth was assessed as a secondary outcome . Primary and secondary outcomes were assessed at baseline and 6 mo . RESULTS Two hundred ninety-two infants completed the study . The fortified-porridge group had an intervention effect of 9.4 microg/L ( 95 % CI : 3.6 , 15.1 microg/L ) for serum ferritin and 9 g/L ( 95 % CI : 6 , 12 g/L ) for hemoglobin concentrations . The proportion of infants with anemia decreased from 45 % to 17 % in the fortified-porridge group , whereas it remained > 40 % in the control group . The fortified-porridge group achieved on average 15.5 of the 25 motor development score items , whereas the control group achieved 14.4 items ( P = 0.007 ) . Serum retinol concentration showed an inconsistent effect , and no intervention effect was observed for serum zinc concentrations . CONCLUSIONS This low-cost fortified porridge can potentially have a significant effect in reducing anemia and improving iron status and motor development of infants in poor setting s. The formulation needs some adjustment in terms of zinc fortification",
"OBJECTIVE To evaluate the long-term effect on micronutrient status of a beta-carotene- , iron- and iodine-fortified biscuit given to primary school children as school feeding . DESIGN Children receiving the fortified biscuit were followed in a longitudinal study for 2.5 years ( n = 108 ) ; in addition , cross-sectional data from three subsequent surveys conducted in the same school are reported . SETTING A rural community in KwaZulu-Natal , South Africa . SUBJECTS Children aged 6 - 11 years attending the primary school where the biscuit was distributed . RESULTS There was a significant improvement in serum retinol , serum ferritin , haemoglobin , transferrin saturation and urinary iodine during the first 12 months of the biscuit intervention . However , when the school reopened after the summer holidays , all variables , except urinary iodine , returned to pre-intervention levels . Serum retinol increased again during the next 9 months , but was significantly lower in a subsequent cross-sectional survey carried out directly after the summer holidays ; this pattern was repeated in two further cross-sectional surveys . Haemoglobin gradually deteriorated at each subsequent assessment , as did serum ferritin ( apart from a slight increase at the 42-month assessment at the end of the school year ) . CONCLUSIONS This study has shown that fortification of a biscuit with beta-carotene at a level of 50 % of the Recommended Dietary Allowance ( RDA ) was enough to maintain serum retinol concentrations from day to day , but not enough to sustain levels during the long school holiday break . Other long-term solutions , such as local food production programmes combined with nutrition education , should also be examined . The choice of the iron compound used as fortificant in the biscuit needs further investigation",
"Forty boys and girls between 11 and 14.5 years with evidence of sub clinical vitamin deficiencies were allocated to two groups to receive , twice weekly , either a placebo or a multivitamin and iron supplement . Prior to supplementation and on two subsequent occasions about 5 weeks apart , the children performed an exercise regimen on a treadmill during which expired air was collected and heart rate monitored . The supplement result ed in marked improvements in riboflavin and vitamin C status and checked the decline in iron stores seen in the unsupplemented children . During the study the running performance of unsupplemented children deteriorated , and markedly so in a subgroup with initially poor nutrient status . The vitamin and iron supplement prevented this deterioration so as to produce a significant reduction in the energy cost of treadmill running in the more malnourished subgroup , relative to the changes seen in children receiving no supplement",
"BACKGROUND Vitamin A deficiency impairs iron metabolism ; vitamin A supplementation of vitamin A-deficient population s may reduce anemia . The mechanism of these effects is unclear . In vitro and in animal models , vitamin A treatment increases the production of erythropoietin ( EPO ) , a stimulant of erythropoiesis . OBJECTIVE We measured the effect of vitamin A supplementation on hemoglobin , iron status , and circulating EPO concentrations in children with poor iron and vitamin A status . DESIGN In a double-blind , r and omized trial , Moroccan schoolchildren ( n = 81 ) were given either vitamin A ( 200,000 IU ) or placebo at baseline and at 5 mo . At baseline , 5 mo , and 10 mo , hemoglobin , indicators of iron and vitamin A status , and EPO were measured . RESULTS At baseline , 54 % of children were anemic ; 77 % had low vitamin A status . In the vitamin A group at 10 mo , serum retinol improved significantly compared with the control group ( P Vitamin A treatment increased mean hemoglobin by 7 g/L ( P anemia from 54 % to 38 % ( P Vitamin A treatment increased mean corpuscular volume ( P serum transferrin receptor ( P . Vitamin A decreased serum ferritin ( P overall body iron stores remained unchanged . In the vitamin A group at 10 mo , we observed an increase in EPO ( P slope of the regression line of log10(EPO ) on hemoglobin ( P children deficient in vitamin A and iron , vitamin A supplementation mobilizes iron from existing stores to support increased erythropoiesis , an effect likely mediated by increases in circulating EPO",
"The study was conducted to look at the effectiveness of a multimicronutrient-fortified complementary food on the micronutrient status , linear growth and psychomotor development of 6- to 12-month-old infants from a black urban disadvantaged community in the Western Cape , South Africa . The study was design ed as an intervention study . In both the experimental and control groups , serum retinol concentration showed a decline over the intervention period of 6 months . The decline was less pronounced in the experimental group . This result ed in a significantly ( P serum retinol concentration at 12 months in the experimental group ( 26.8±5.8 μg/dl ) compared with the control group ( 21.4±5 μg/dl ) . Serum iron concentration also declined over the intervention period . The decline was less pronounced in the experimental group . No difference was observed in haemoglobin levels between the groups at 12 months . Serum zinc concentration did not differ significantly between the two groups at follow up . Weight gain over the 6 months period did not differ significantly between the experimental ( 2.1±0.9 kg ) and control groups ( 2.1±1.2 kg ) . There was no difference in linear growth between the experimental ( 10.0±1.5 cm ) and control group ( 10.1±2.1 cm ) at the end of the follow-up period . Weight and length at 6 months significantly predicted weight and length at 12 months . No difference was observed in psychomotor developmental scores between the two groups after 6 months of intervention . Introducing a multimicronutrient-fortified complementary food into the diet of 6- to 12-month-old infants seemed to have an arresting effect on declining serum retinol and iron concentration in the experimental group . No benefit was observed in serum zinc concentration , linear growth and psychomotor development ",
"The study assessed the effects of supplementary feeding over 180 consecutive days on iron status of infants and toddlers at six tea plantation in West Java , Indonesia . The design used was a clinical trial : two eohorts ( i.e. , 12 and 18 months old children ) and three treatment groups ( i.e. , energy + micronutrient , micronutrient alone , and placebo ) per cohort . Every day except Sunday , the infants attended day-care centers . Twenty four centers and 136 infants were selected . The infants were screened for weight and length and those meeting the criteria ( i.e. , The experimental unit was the day-care centers ( DCC ) , where each DCC was r and omly assigned to one of the three treatment . As expected , groups of energy + micronutrient and micronutrient alone of the 12 months cohort experienced a significant upward shift in hemoglobin , ferritin and TS and a downward change in FEP , while the values for the group of placebo remain about the same as at base line . In the first 6 month of treatments , the ANOVA for each iron indicator yielded significant main effects of treatment ( P hemoglobin , TS , ferritin and FEP were not significant for the 18 months cohort . In the second 6 months of treatments , the only significant of the treatment effect ( P serum ferritin on 18-month cohort . Under these circumstances , energy has a positive role in improving iron stores . It is likely that the equilibrium of hemoglobin and each iron indicators were reached in 6 months of treatment except ferritin still continued to increase up to 12 month . The effects of treatment on the improvement of iron status was stronger in 12 months than in 18 months",
"BACKGROUND Malaria and anaemia , especially that due to iron deficiency , are two leading causes of morbidity worldwide . Little is known about the relative contribution of Plasmodium falciparum infection and iron deficiency to the aetiology of anaemia in malaria-endemic areas . We undertook a r and omised comparison of different strategies for control of anaemia and malaria in infants , including an assessment of the effect of iron supplementation on malaria susceptibility . METHODS 832 infants born at one hospital in a malaria-hyperendemic area of Tanzania between January and October , 1995 , were r and omly assigned to group DI , receiving daily oral iron ( 2 mg/kg daily ) plus weekly Deltaprim ( 3.125 mg pyrimethamine plus 25 mg dapsone ) ; group IP , receiving iron plus weekly placebo ; group DP , receiving daily placebo plus weekly Deltaprim ; or group PP . supplementation was given from 8 to 24 weeks of age , and the weekly chemoprophylaxis from 8 to 48 weeks . The frequency of severe anaemia ( packed-cell volume malaria episodes was assessed through a combination of passive case detection and cross-sectional surveys . FINDINGS The groups that received iron supplementation had a lower frequency of severe anaemia than those that did not receive iron ( 0.62 vs 0.87 cases per person-year ; protective efficacy 28.8 % [ 95 % CI 6.3 - 45.8 ) . Iron supplementation had no effect on the frequency of malaria ( 0.87 vs 1.00 cases per person-year ; protective efficacy 12.8 % [ -12.8 to 32.5 ] ) . The groups that received malaria prophylaxis had lower frequencies of both severe anaemia ( 0.45 vs 1.04 episodes per person-year ; protective efficacy 57.3 % [ 43.0 - 67.9 ] ) and malaria ( 0.53 vs 1.34 episodes per person-year ; protective efficacy 60.5 % [ 48.2 - 69.9 ] ) than the groups that did not receive prophylaxis . After the end of the intervention period , children who had received malaria chemoprophylaxis had higher rates of severe anaemia and malaria than non-chemoprophylaxis groups ( relative risks 2.2 [ 1.3 - 3.7 ] and 1.8 [ 1.3 - 2.6 ] ) . INTERPRETATION Malaria chemoprophylaxis during the first year of life was effective in prevention of malaria and anaemia but apparently impaired the development of natural immunity . Iron supplementation was effective in preventing severe anaemia without increasing susceptibility to malaria . Our findings support iron supplementation of infants to prevent iron-deficiency anaemia , even in malaria-endemic areas",
"Summary Single interventions for helminthic infections and micronutrient deficiencies are effective , but it is not clear whether combined interventions will provide equal , additive or synergistic effects to improve children 's health . The study objective was to determine the impact of single and combined interventions on nutritional status and scholastic and cognitive performance of school children . A double-blind , r and omized , placebo-controlled trial in 11 rural South African primary schools r and omly allocated 579 children aged between 8 and 10 years into six study groups , half of whom received antihelminthic treatment at baseline . The de-wormed and non-de-wormed arms were further divided into three groups and given biscuits , either unfortified or fortified with vitamin A and iron or with vitamin A only , given daily for 16 weeks . The outcome measures were anthropometric , micronutrient and parasite status , and scholastic and cognitive test scores . There was a significant treatment effect of vitamin A on serum retinol ( p micronutrient status in rural primary school children ; vitamin A with de-worming had a greater impact on micronutrient status than vitamin A fortification alone and antihelminthic treatment significantly reduced the overall prevalence of parasite infection . The burden of micronutrient deficiency ( anaemia , iron and vitamin A ) and stunting in this study population was low and , coupled with the restricted duration of the intervention ( 16 weeks ) , might have limited the impact of the interventions",
"The control of childhood anaemia in malaria holoendemic areas is a major public health challenge for which an optimal strategy remains to be determined . Malaria prevention may compromise the development of partial immunity . Regular micronutrient supplementation has been suggested as an alternative but its effectiveness remains unsettled . We therefore conducted a r and omised placebo-controlled intervention trial with 207 Tanzanian children aged 5 months to 3 years on the efficacy of supervised supplementation of low-dose micronutrients including iron ( Poly Vi-Sol with iron ) three times per week , with an average attendance of > /= 90 % . The mean haemoglobin ( Hb ) level increased by 8 g/l more in children on supplement ( 95 % CI 3 - 12 ) during the 5-month study . All age groups benefited from the intervention including severely anaemic subjects . The mean erythrocyte cell volume ( MCV ) increased but Hb in children > /= 24 months improved independently of MCV and no relation was found with hookworm infection . The data therefore suggest that micronutrients other than iron also contributed to Hb improvement . In the supplement group of children who had received sulfadoxine-pyrimethamine ( SP ) treatment , the mean Hb level increased synergistically by 22 g/l ( 95 % CI 13 - 30 ) compared to 7 g/l ( 95 % CI 3 - 10 ) in those without such treatment . Supplementation did not affect malaria incidence . In conclusion , micronutrient supplementation improves childhood anaemia in malaria holoendemic areas and this effect is synergistically enhanced by temporary clearance of parasitaemia",
"INTRODUCTION Iron deficiency is widespread in the developing world and is especially common in young children who live on the Indian subcontinent . Supplementation with iron and folic acid alleviates severe anaemia and enhances neurodevelopment in deficient population s , but little is known about the risks of mortality and morbidity associated with supplementation . METHODS We did a community-based , cluster-r and omised , double-masked , placebo-controlled , 2x2 factorial trial in children aged 1 - 36 months and residing in southern Nepal . We r and omly assigned children daily oral supplementation to age 36 months with : iron ( 12.5 mg ) and folic acid ( 50 microg ; n=8337 ) , zinc alone ( 10 mg ) , iron , folic acid , and zinc ( n=9230 ) , or placebo ( n=8683 ) ; children aged 1 - 11 months received half the dose . Our primary outcome measure was all-cause mortality , and our secondary outcome measures included cause-specific mortality and incidence and severity of diarrhoea , dysentery , and acute respiratory illness . Analyses were by intention to treat . This study is registered at , number NCT00109551 . FINDINGS The iron and folic acid-containing groups of the study were stopped early in November , 2003 , on the recommendation of the data and safety monitoring board ; mortality in these groups did not differ from placebo and there was low power to detect positive or negative effects by the time enrollment was completed . We continued to enroll children to the placebo and zinc alone groups . 25,490 children participated and analyses are based on 29,097.3 person-years of follow-up . There was no difference in mortality between the groups who took iron and folic acid without or with zinc when compared with placebo ( HR 1.03 , 95 % CI 0.78 - 1.37 , and 1.00 , 0.74 - 1.34 , respectively ) . There were no significant differences in the attack rates for diarrhoea , dysentery , or respiratory infections between groups , although all the relative risks except one indicated modest , non-significant protective effects . INTERPRETATION Daily supplementation of young children in southern Nepal with iron and folic acid with or without zinc has no effect on their risk of death , but might protect against diarrhoea , dysentery , and acute respiratory illness",
"Ninety preselected children , aged between 8 and 14 years , living in two rural West African ( Gambian ) villages , were r and omly divided into three groups , matched for age and sex . One group received a placebo ( lactose ) tablet , one received riboflavin ( 5 mg ) on 5 d every week , which was sufficient to correct an endemic riboflavin deficiency , and one received a multivitamin supplement ( Protovit ; Hoffmann La Roche ) , on 5 d every week , together with FeSO4 ( 200 mg ) once weekly , and the supplements were given for 1 year . Neuromuscular tests , including arm tremor and manipulative skills , were performed on three occasions : once just before the introduction of the supplements ; again 6 weeks after commencing the supplements ; and again 1 year later . Venous blood sample s were collected at the same time as the first two sets of neuromuscular tests . These sample s were used for haematology and nutrient status indices : plasma ferritin , ascorbic acid , cyanocobalamin and pyridoxal phosphate , and erythrocyte tests for folate status , for riboflavin status ( erythrocyte glutathione reductase activation coefficient ) and thiamine status ( erythrocyte transketolase activation coefficient ) . The riboflavin in both supplements achieved a clear-cut response in biochemical status , which was dose-dependent . The pyridoxine , ascorbic acid and Fe components of the multivitamin also affected the associated biochemical indices . Although overall the arm tremor and related neuromuscular function tests did not respond significantly to the supplements , significant improvement was seen in the boys for the arm-tremor test in both the supplemented groups",
"OBJECTIVES To obtain baseline data on hemoglobin ( Hb ) levels of adolescent girls belonging to the low-socio-economic groups ; investigate the comparative efficacy of once ' weekly ' and ' daily ' administration of iron-folate tablets with respect to impact on the Hb levels ; and find out the effect of added ascorbic acid supplementation on the efficacy of iron-folate administration with respect to increment in Hb levels . DESIGN R and omized experimental . SETTING Adolescent girls of poor communities in urban areas of Delhi and rural parts of Bharatpur ( Rajasthan ) . METHODS The baseline investigations included measurements of height , weight , and Hb levels . The Hb levels of the participating subjects were measured again after 3 months and 6 months of supplementation . RESULTS 61.9 % of the subjects in the urban and 85.4 % in the rural area were anemic . The response of Hb levels to daily iron/folate supplementation was better in comparison to once-weekly supplementation . The increment in Hb levels of subjects due to addition of vitamin C to iron/folate supplementation was more than that with supplementation of iron/folate alone . CONCLUSIONS Considering compliance , feasibility and cost-factors , a public-health approach consisting of once-weekly distribution of iron/folate supplementation through schools and welfare centers is better and can be recommended as an appropriate strategy for combating anemia in adolescent girls of poor communities in developing countries like India",
"Relationships between hemoglobin level and S. hematobium , hookworm , and malarial infection before and six months after metrifonate treatment were studied in Kenyan primary school children in an area where anemia , S. hematobium and hookworm are common ( prevalences 61 % , 46 % , and 95 % , respectively ) and malaria is holoendemic . The mean hemoglobin level in children from one school , both with and without S. hematobium infection ( n = 250 ) , was significantly lower in children with higher S. hematobium egg counts , heavier hookworm infections , positive Plasmodium slides , and larger spleens . All children with light-moderate S. hematobium infection ( 1 - 500 eggs/10 ml adj ) in four schools were examined ( Exam 1 ) , allocated at r and om to either placebo ( MIP , n = 198 ) or metrifonate treatment ( MIT , n = 202 ) groups , treated , and examined again six months later ( Exam 2 ) . Hemoglobin levels rose significantly in both groups between exams , but the rise in the MIT group was 30 % higher than in the MIP group ( 1.3 vs. 1.0 g/dl , P less than 0.014 ) . The increase in hemoglobin level in the MIT group was significantly and positively correlated with decreases between exams in S. hematobium and hookworm egg counts and with higher malarial parasite counts at Exam 1 ( Pearson r 's 0.21 , 0.20 , 0.20 , respectively , P less than 0.01 ) . A stepwise multiple regression equation using hemoglobin rise between exams as the dependent variable showed that decreases in S. hematobium and hookworm egg counts were equally important determinants of hemoglobin rise and that malarial parasite count was almost as important as the changes in intensities of the helminth infections . These results show that treatment for S. hematobium with metrifonate can increase hemoglobin levels in children in an area where S. hematobium and anemia are common . They also emphasize the importance of measuring multiple parasitic infections and using multivariate statistical techniques such as multiple regression analysis in order to define the relationships between parasitic infections and morbidity",
"Sixty-nine boys and girls between 10 and 14 years , with evidence of sub clinical vitamin deficiencies and poor iron status were enrolled into the study at the beginning of the rainy season . Children were allocated to three treatment groups to receive five times weekly either a placebo , 200 mg ferrous sulphate or 5 mg riboflavin and 150 mg ascorbic acid . Before receiving the supplement , and 9 weeks later , children performed an exercise regimen on a treadmill during which expired air was collected and heart rate measured . There was a general deterioration in the running performance of the children during the study period which was not affected by either the iron or the vitamin supplement",
"Anemia-specific mortality was markedly elevated among refugee children In a r and omized , double-blind study , 215 anemic children were initially treated for malaria and helminth infection and then received 12 weeks of thrice-weekly oral iron and folic acid . Group I received placebo and chloroquine treatment for symptomatic malaria infection ( i.e. , no presumptive anti-malarial treatment given ) . Group II received placebo and monthly presumptive treatment with sulfamethoxazole-pyrimethamine ( SP ) . Group III also received monthly SP and thrice-weekly vitamins A and C ( VAC ) . Mean hemoglobin concentration increased from 6.6 to 10.2 g/dL , with no significant differences among groups . Group II had lower mean serum transferrin receptor levels ( TfR ) than group I [ P = 0.023 ] . A greater proportion of participants in group III had normal iron stores ( TfR hemoglobin levels . Monthly SP and thrice-weekly VAC contributed to improve iron stores . Monthly SP may have a role in situations where asymptomatic disease is prevalent or where access to care is limited . Because administration of VAC also hastened recovery of iron stores over administration of monthly SP alone , health care personnel could add VAC to the treatment for moderate anemia if maximum recovery of iron stores is desired",
"The effect of a combined supplement of iron , thiamine , riboflavin and vitamin C on malarial incidence in 5 to 14-year-old children was tested in a malnourished rural community in a region of The Gambia noted for high prevalence of malaria during the rainy season . 190 children , divided into 2 matched groups , received either the supplement or a matching placebo for 3 months . No significant difference in malarial incidence was observed between the 2 groups , despite a major improvement in biochemical indices of nutrient status in the supplemented group , especially for riboflavin and vitamin C. Severity of episodes was also similar between groups , but in subjects who developed parasitaemias there was a trend towards higher parasite counts in those receiving the active supplement . Nutritional interventions in malarious areas may have adverse effects on malaria , and the increase in parasitaemia was compatible with the hypothesis that a small but significant reduction in defences had occurred . However , the absence of increases in the incidence of proven malaria cases and their severity must also be taken into account , in order to make a balanced assessment of the possible increase in risk . Further investigations are needed to measure the risk in benefit rates , and to consider the effects of individual nutrients in isolation",
"OBJECTIVE To evaluate the effectiveness of a vitamin-fortified maize meal to improve the nutritional status of 1 - 3-year-old malnourished African children . DESIGN A r and omised parallel intervention study was used in which 21 experimental children and their families received maize meal fortified with vitamin A , thiamine , riboflavin and pyridoxine , while 23 control children and their families received unfortified maize meal . The maize meal was provided for 12 months to replace the maize meal habitually consumed by these households . METHODS Sixty undernourished African children with height-for-age or weight-for-age below the 5th percentile of the National Center for Health Statistics ' criteria and aged 1 - 3 years were r and omly assigned to an experimental or control group . Baseline measurements included demographic , socio-economic and dietary data , as well as height , weight , haemoglobin , haematocrit , serum retinol and retinol-binding protein ( RBP ) . Anthropometric , blood and serum variables were measured again after 12 months of intervention . Complete baseline measurements were available for 44 children and end data for only 36 . Changes in these variables from baseline to end within and between groups were assessed for significance with paired t-tests , t-tests and analysis of variances using the SPSS program , controlling for expected weight gain in this age group over 12 months . Relationships between changes in variables were examined by calculating correlation coefficients . RESULTS The children in the experimental group had a significantly ( P increase in body weight than control children ( 4.6 kg vs. 2.0 kg ) and both groups had significant ( P height . The children in the experimental group showed non-significant increases in haemoglobin and serum retinol , while the control children had a significant ( P = 0.007 ) decrease in RBP . The change in serum retinol showed a significant correlation with baseline retinol ( P = 0.014 ) , RBP ( P = 0.007 ) and weight ( P = 0.029 ) , as well as with changes in haemoglobin ( P = 0.029 ) . CONCLUSION Despite a small sample size , this study showed positive effects of a vitamin-fortified maize meal on weight gain and some variables of vitamin A status in 1 - 3-year-old African children . The study confirmed the relationship between vitamin A and iron status . The results suggest that fortification of maize meal would be an effective strategy to address micronutrient deficiencies in small children in South Africa"
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Attention-deficit hyperactivity disorder ( ADHD ) is typically diagnosed using clinical observation and subjective informant reports . Once children commence ADHD medication , robust monitoring is required to detect partial or non-responses . The extent to which neuropsychological continuous performance tests ( CPTs ) and objective measures of activity can clinical ly aid the assessment and titration process in ADHD is not fully understood . This review describes the current evidence base for the use of CPTs and objective ly measured activity to support the diagnostic procedure and medication management for children with ADHD . Four data bases ( PsycINFO , Medline , Allied and Complementary Medicine ( AMED ) , and PsycARTICLES ) were systematic ally search ed to underst and the current evidence base for ( 1 ) the use of CPTs to aid clinical assessment of ADHD ; ( 2 ) the use of CPTs to aid medication management ; and ( 3 ) the clinical utility of objective measures of activity in ADHD . Sixty relevant articles were identified . The search revealed six commercially available CPTs that had been reported on for their clinical use . There were mixed findings with regard to the use of CPTs to assess and manage medication , with contrasting evidence on their ability to support clinical decision-making . There was a strong evidence base for the use of objective measures of activity to aid ADHD/non-ADHD group differentiation , which appears sensitive to medication effects and would also benefit from further research on their clinical utility . The findings suggest that combining CPTs and an objective measure of activity may be particularly useful as a clinical tool and worthy of further pursuit
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"The effect of atomoxetine ( ATX ) on executive function has been assessed by means of question naires only . The aim of this study was therefore to evaluate the efficacy of ATX using st and ard variables of a computer-based continuous performance test ( cb-CPT ) combined with an infra-red motion-tracking device at different times of the day . One hundred twenty-eight girls and boys aged 6 to 12 years with a diagnosis of ADHD according to DSM-IV-TR criteria were r and omized in the study . The primary efficacy measures were the q-scores of the cb-CPT combined with an infra-red motion-tracking device . The test comprises 13 neuropsychological variables that can be taken to reflect hyperactivity , inattention , or impulsivity . One hundred five patients completed the study ( ATX group : n=54 ; placebo group : n=51 ) . ATX ( target dose 1.2 mg/kg/day ) over 8 weeks was significantly superior to placebo in reducing hyperactivity , inattention , and impulsivity as measured by q-scores of 10 primary variables of the cb-CPT . Both groups of patients showed a circadian pattern of neuropsychological outcomes across the day as reflected by the cb-CPT combined with an infra-red motion-tracking device . In summary , this study demonstrated a positive effect of ATX on some aspects of executive function , inhibitory control , and hyperactivity compared with placebo",
"Twenty-four-hour motor activity was assessed in a naturalistic setting in 12 hyperactive boys for four weeks ( 672 consecutive hours ) . Dextroamphetamine , 15 mg/day , or placebo was administered on alternate weeks , using a double-blind ABAB design . When the boys received dextroamphetamine , motor activity was significantly decreased for about eight hours after drug administration . This decrease was followed by a period of slight but significant increases in activity ( \" rebound \" ) . Dextroamphetamine decreased activity most strikingly during structured classroom activity ; during physical education , however , there was a significant drug-induced increase in motor activity",
"Introduction The National Institute for Health and Care Excellence ( NICE ) guidelines for attention deficit/hyperactivity disorder ( ADHD ) state that young people need to have access to the best evidence -based care to improve outcome . The current ‘ gold st and ard ’ ADHD diagnostic assessment combines clinical observation with subjective parent , teacher and self-reports . In routine practice , reports from multiple informants may be unavailable or contradictory , leading to diagnostic uncertainty and delay . The addition of objective tests of attention and activity may help reduce diagnostic uncertainty and delays in initiating treatment leading to improved outcomes . This trial investigates whether providing clinicians with an objective report of levels of attention , impulsivity and activity can lead to an earlier , and more accurate , clinical diagnosis and improved patient outcome . Methods and analysis This multisite r and omised controlled trial will recruit young people ( aged 6–17 years old ) who have been referred for an ADHD diagnostic assessment at Child and Adolescent Mental Health Services ( CAMHS ) and Community Paediatric clinics across Engl and . Routine clinical assessment will be augmented by the QbTest , incorporating a continuous performance test ( CPT ) and infrared motion tracking of activity . The participant will be r and omised into one of two study arms : QbOpen ( clinician has immediate access to a QbTest report ) : QbBlind ( report is withheld until the study end ) . Primary outcomes are time to diagnosis and diagnostic accuracy . Secondary outcomes include clinician 's diagnostic confidence and routine clinical outcome measures . Cost-effective analysis will be conducted , alongside a qualitative assessment of the feasibility and acceptability of incorporating QbTest in routine practice . Ethics and dissemination The findings from the study will inform commissioners , clinicians and managers about the feasibility , acceptability , clinical utility and cost-effectiveness of incorporating QbTest into routine diagnostic assessment of young people with ADHD . The results will be su bmi tted for publication in peer- review ed journals . The study has received ethical approval . Trial registration number NCT02209116",
"Background The aims of this study were to determine the time course of improvements in attention deficit hyperactivity disorder ( ADHD ) clinical symptoms and neurocognitive function in a realistic clinical setting , and the differences in ADHD symptom improvement using different classifications of ADHD subtypes . Methods The Child Behavior Checklist ( CBCL ) was completed by parents of ADHD children at the initial visit . The computerized Continuous Performance Test ( CPT ) , Swanson , Nolan , and Pelham , and Version IV Scale for ADHD ( SNAP-IV ) , and ADHD Rating Scale ( ADHD-RS ) were performed at baseline , one month , three months , and six months later , respectively . Patient care including drug therapy was performed at the discretion of the psychiatrist . The ADHD patients were divided into DSM-IV subtypes ( Inattentive , Hyperactive-impulsive and Combined type ) , and were additionally categorized into aggressive and non-aggressive subtypes by aggression scale in CBCL for comparisons . Results There were 50 ADHD patients with a mean age of 7.84 ± 1.64 years ; 15 of them were inattentive type , 11 were hyperactive-impulsive type , and 24 were combined type . In addition , 28 of the ADHD patients were grouped into aggressive and 22 into non-aggressive subtypes . There were significant improvements in clinical symptoms of hyperactivity and inattention , and impulsivity performance in CPT during the 6-month treatment . The clinical hyperactive symptoms were significantly different between ADHD patients sub-grouping both by DSM-IV and aggression . Non-aggressive patients had significantly greater changes in distraction and impulsivity performances in CPT from baseline to month 6 than aggressive patients . Conclusions We found that ADHD symptoms , which included impulsive performances in CPT and clinical inattention and hyperactivity dimensions , had improved significantly over 6 months under pragmatic treatments . The non-aggressive ADHD patients might have a higher potential for improving in CPT performance than aggressive ones . However , it warrant further investigation whether the different classifications of ADHD patients could be valid for predicting the improvements in ADHD patients ' clinical symptoms and neurocognitive performance",
"Twenty boys ( mean age , 9 + /- 2 years ) with attention deficit disorder with hyperactivity received three weeks each of dextroamphetamine sulfate ( 0.5 mg/kg/d ) , fenfluramine hydrochloride ( 0.6 mg/kg/d increased to 2.0 mg/kg/d ) , and placebo in a double-blind , r and om-order , crossover design . Half the boys also met criteria for conduct disorder . Dextroamphetamine produced immediate and marked improvement in disruptive , overactive behaviors . Fenfluramine had no effect on any behavioral measure at either the low or high dosage . Both drugs decreased levels of urinary norepinephrine , 3-methoxy-4-hydroxyphenylglycol ( MHPG ) , and vanillylm and elic acid . Fenfluramine , however , also produced a significant decrease in plasma MHPG levels and a larger decrease in urinary norepinephrine levels . It reduced urinary epinephrine levels as well , an effect opposite to that of dextroamphetamine . These findings suggest that different mechanisms of action are involved in the ability of the two drugs to reduce levels of MHPG and vanillylm and elic acid . Fenfluramine increased plasma prolactin levels and decreased platelet serotonin levels . Despite the structural similarity of the two drugs , some common overall effects on catecholamine metabolism , and similar effects on weight , fenfluramine had none of the motor activity or therapeutic effects of dextroamphetamine",
"OBJECTIVE This study investigated the trends in neurocognitive function and behavioral symptoms among patients with attention-deficit/hyperactivity disorder ( ADHD ) during 24 months of treatment with methylpheni date in a clinical setting . METHODS Study participants consisted of 181 ADHD patients with a mean age of 13.4±2.5 years ( ages ranged from 8 to 18 years ; 151 boys and 30 girls ) who were prescribed oral short-acting methylpheni date two or three times daily , with each dose ranging between 0.3 and 1.0 mg/kg . At baseline and 6 , 12 , 18 , and 24 months from baseline , neurocognitive function was assessed using the Test of Variables of Attention ( TOVA ) on the day the patient was off medication , and behavioral symptoms were evaluated using the Swanson , Nolan , and Pelham Version IV Scale for ADHD ( SNAP-IV ) parent form , the SNAP-IV teacher form , and the ADHD-Rating Scale ( completed by a child psychiatrist ) . RESULTS Of the 181 ADHD patients at the initial visit , 103 ( 56.9 % ) completed the study . During the 24-month methylpheni date treatment , only the commission errors in TOVA significantly improved ; however , the omission errors , response time , response time variability , response sensitivity , and ADHD score did not . The behavioral symptoms of ADHD , observed by various informants , all declined substantially , and were significantly correlated with each other during the long-term follow-up . The severity of teacher ratings was lower than that of parent and psychiatrist ratings . However , the teacher-rated inattention symptoms showed the strongest correlations with TOVA performance . CONCLUSIONS Findings suggest that neurocognitive deficits in ADHD patients , except inhibition ability , might be long lasting in realistic setting s. In addition , obtaining behavior profile assessment s from multiple informants , especially from teachers , is vital for establishing a complete underst and ing of ADHD patients",
"The motor activity of 10 hyperactive boys was measured during eight 1-hour active gym classes . Children received either dextroaomphetamine ( 0.5 mg/kg ) or placebo elixir before each class , in a double-blind design . The program for each of the classes was participation in the active sports : hockey , basketball , and /or roller skating ; the \" task \" throughout each hour was to play vigorously and continuously . The boys ' mean hourly activity following amphetamine was slightly but significantly less than that following placebo . This finding is contradictory to the hypothesis that improved attention to an active task on stimulant would result in increased motor activity , and suggests the possibility of an independent direct effect of amphetamine on the motor system",
"BACKGROUND This study examined the effects of atomoxetine ( ATX ) and OROS methylpheni date ( MPH ) on laboratory measures of inhibitory control and attention in youth with attention-deficit/hyperactivity disorder ( ADHD ) . It was hypothesized that performance would be improved by both treatments , but response profiles would differ because the medications work via different mechanisms . METHODS One hundred and two youth ( 77 male ; mean age = 10.5 ± 2.7 years ) with ADHD received ATX ( 1.4 ± 0.5 mg/kg ) and MPH ( 52.4 ± 16.6 mg ) in a r and omized , double-blind , crossover design . Medication was titrated in 4 - 6-week blocks separated by a 2-week placebo washout . Inhibitory control and attention measures were obtained at baseline , following washout , and at the end of each treatment using Conners ' Continuous Performance Test II ( CPT-II ) , which provided age-adjusted T-scores for reaction time ( RT ) , reaction time variability ( RT variability ) , and errors . Repeated- measures analyses of variance were performed , with Time ( premedication , postmedication ) and Treatment type ( ATX , MPH ) entered as within-subject factors . Data from the two treatment blocks were checked for order effects and combined if order effects were not present . CLINICAL TRIAL REGISTRATION Clinical trials.gov : NCT00183391 . RESULTS Main effects for Time on RT ( p = .03 ) , RTSD ( p = .001 ) , and omission errors ( p = .01 ) were significant . A significant Drug × Time interaction indicated that MPH improved RT , RTSD , and omission errors more than ATX ( p Changes in performance with treatment did not correlate with changes in ADHD symptoms . CONCLUSIONS MPH has greater effects than ATX on CPT measures of sustained attention in youth with ADHD . However , the dissociation of cognitive and behavioral change with treatment indicates that CPT measures can not be considered proxies for symptomatic improvement . Further research on the dissociation of cognitive and behavioral endpoints for ADHD is indicated",
"Abstract . Purpose : The purpose of this study was to investigate whether values of the respective parameters of the OPTAx test dependently differ due to the medication with methylpheni date ( MPH ) in children with hyperkinetic disorders ( HD ) suffering from hyperactivity , impulsivity , and attention deficits . Methods : The OPTAx test is an infrared motion analysis to record the movement pattern during a continuous performance test . We tested 25 children between 6 and 12 years with HD ( ICD-10 : F90.0 or F90.1 ) before and after treatment with MPH . The parameters under investigation were activity ( microevents and spatial scaling ) , impulsivity ( errors of commission ) , and attentiveness ( accuracy and variability ) . For statistical analysis a one-tailed matched pairs test ( adj . p = 0.01 ) was conducted to discriminate differences found from those occurred at r and om . A post hoc partial correlation of absolute differences in the respective parameters and the daily dose of MPH ( adj . for BMI ) was performed if p microevents , spatial scaling , errors of commission , accuracy , and variability . The partial correlation showed significant results for microevents and variability . Conclusion : The mean pre – post changes found in all parameters investigated consistently correspond with benefits desired from medication with MPH in children with HD . Absolute differences in microevents and variability seem to depend on the daily dose of MPH after adjustment for BMI",
"The Gordon Diagnostic System ( GDS ) is a portable easily operated computerized tool developed to measure impulse control , attention and vigilance . In 1988 , it was st and ardized for use among American children . The aim of this study was to evaluate the GDS for use among Swedish children . A clinical sample of 71 Swedish children , mean age 10.5 y , fulfilling the ADHD criteria according to the DSM‐IV was compared with a control sample of 88 children , mean age 10.2 y , with no known psychiatric diagnosis . The clinical sample showed lower GDS scores in all age groups , with some exceptions . The GDS scores were not associated with gender , but strongly associated with age , especially in the control sample . The accuracy of the GDS referring a specific child to either of the sample s was , as expected , not impressive . With respect to the practical usefulness , the GDS was well accepted by the children and parents in both sample s. The findings in age variation and when comparing children with ADHD and controls are in agreement with results from other studies",
"Abstract The primary objective of this study was to evaluate the efficacy of atomoxetine ( ATX ) on attention-deficit/hyperactivity disorder (ADHD)–related symptoms assessed as st and ard variables of a computer-based continuous performance test ( cb-CPT ) combined with a motion-tracking ( MT ) device . This was a 2-arm , 8-week , r and omized , double-blind , placebo-controlled study in patients with ADHD ( 6–12 years ) . Therapy with ATX started with 0.5 mg/kg per day for 1 week , followed by 7 weeks on the target dosage of 1.2 mg/kg per day . Primary outcomes were cb-CPT/MT st and ard scores after 8 weeks using mixed models for repeated measurements . In addition , investigator-rated ADHD Rating Scale ( ADHD-RS ) , Weekly Ratings of Evening and Morning Behavior ( WREMB ) , and Clinical Global Impression – Severity-ADHD ( CGI-S-ADHD ) scores were assessed . Of 128 patients r and omized , 125 were evaluated ( ATX/placebo : 63/62 ) . Baseline characteristics were comparable in both groups ( overall , 80.2 % boys ; mean [ SD ] age , 9.0 [ 1.79 ] years ; comorbid Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition diagnosis , 40.0 % oppositional defiant disorder/conduct disorder ; prior stimulant treatment , 24.8 % ; ADHD-RS total score , 36.99 [ 11.56 ] ) . At week 8 , all cb-CPT/MT q-scores were significantly reduced versus placebo ( all P effect sizes ( ESs ) of reaction time ( RT ) variation ( ES = 0.71 ) , mean RT ( ES = 0.41 ) , number of microevents ( ES = 1.00 ) , commission error rate ( ES = 0.50 ) , distance of movement ( ES = 0.90 ) , area of movement ( ES = 1.08 ) , omission error rate ( ES = 0.70 ) , time active ( ES = 0.69 ) , motion simplicity ( ES = 0.38 ) , and normalized variance of RT ( ES = 0.50 ) . Secondary end points also improved significantly in favor of ATX : ADHD-RS ( total score ES = 1.30 , P ; inattention subscore ES = 1.07 , P , WREMB ( total score ES = 1.00 , P 0.001 ; morning subscore ES = 0.59 , P = 0.002 ; evening subscore ES = 1.02 , P , CGI-S-ADHD ( ES = 1.11 , P ) . The results of this study show that ATX for 8 weeks significantly reduced ADHD-related symptoms as measured by the cb-CPT/MT",
"The aim of this study was to determine drug-dependent effects on attention and motor activity in children with attention-deficit/hyperactivity disorder ( ADHD ) in a double-blind methylpheni date ( MPH ) trial using both subjective behavior ratings and objective measures of function . In particular , we were interested in the relationship between changes of those subjective and objective measures . A total of 44 ADHD children with the combined subtype completed a r and omized , double-blind , placebo-controlled , crossover trial with 2 doses of MPH ( 0.25 ; 0.5 mg/kg body weight ) and placebo . In each condition , computerized attention tasks were performed , teacher-behavior ratings were obtained , and actigraph data were collected in both clinical and naturalistic setting s. Trend tests revealed linear effects of MPH dose on actigraph data in the test session ( p = 0.02 ) and at school ( p = 0.001 ) , as well as on sustained attention ( p hyperactive-impulsive symptoms ( 28 % ) and inattentive symptoms ( 23 % ) could be explained by objective changes of motor activity . Thus , for clinical practice , it should be taken into account that behavior ratings of ADHD symptoms seemed to be predominantly influenced by changes of motor activity",
"OBJECTIVE The purpose of this study was to investigate clinical gains from including both dextroamphetamine and methylpheni date in stimulant trials . METHOD Thirty-six medication-naïve children ages 9 - 14 years diagnosed with attention-deficit/hyperactivity disorder ( ADHD ) were enrolled for 6 weeks in a crossover trial , with 2 weeks of methylpheni date , dextroamphetamine , and placebo , in a r and omly assigned , counterbalanced sequence . Outcome measures constituted a computer-based continuous performance test combined with a motion tracking system ( Qb Test ) and an ADHD question naire rated by parents and teachers . RESULTS Group analyses found significant treatment effects of similar size for the two stimulants on both outcome measures . Single-subject analyses revealed that each stimulant produced a favourable response in 26 children ; however , an individual child frequently responded qualitatively or quantitatively differently to the two stimulants . By including both stimulants in the trial , the number of favorable responders increased from 26 ( 72 % ) to 33 ( 92 % ) . In children with favorable responses of unequal strength to the two stimulants , a shift from inferior drug to best drug was associated with a 64 % mean increase in the overall response strength score , as measured by the ADHD question naire . CONCLUSIONS The likelihood of a favorable response and optimal response strength is increased by including both stimulants in the stimulant trial . The study was first registered in clinical trials 28 September 2010 . Clinical Trials.gov Identifier : NCT01220440",
"This study investigated the relationships between computer-based testing and behavioral ratings in the assessment of stimulant-induced changes in attention and activity in a pediatric ADHD crossover trial with methylpheni date , dextroamphetamine , and a placebo . Here 36 children between 9 and 14 years old were r and omly and evenly assigned to each of six counterbalanced drug orders . A computer-based continuous performance test combined with a motion-tracking system ( cb-CPT-MTS ) and an ADHD question naire rated by teachers constituted the outcome measures . All outcome measures responded to stimulants in a comparable way at the group level , as shown by significant treatment effects of similar size for the two stimulants compared with a placebo . Computer-based and rating-based measures were unrelated in the assessment of stimulant-induced changes in attention and activity in individual children ; no significant correlations between these measures in the assessment of change from placebo to stimulant conditions across the sample were detected . Results suggest that computer-based testing and behavioral ratings can not be considered equivalent in the assessment of stimulant-induced changes in attention and activity among ADHD children",
"An acceleration-sensitive device was used to measure motor activity continuously through the day in 18 hyperactive boys in a day hospital program . The children received methylpheni date , dextroamphetamine , or placebo daily after breakfast and lunch in an 11-week double-blind crossover trial . Differential effectiveness of the two drugs in lowering motor activity was found . Methylpheni date significantly lowered activity measurements in a morning structured classroom and in less structured activities in the afternoon . Dextroamphetamine effects on activity were similar , although they did not differ significantly from placebo effects between 11:00 AM and noon in our classroom setting . Methylpheni date produced a greater decrement in motor activity than did dextroamphetamine between 11:00 AM and 1:00 PM . There were no significant differences in activity level between drug doses within each drug phase across the dose ranges used ( for methylpheni date 0.45 to 1.25 mg/kg given twice daily , and for dextroamphetamine 0.2 to 0.6 mg/kg given twice daily ) . Plasma drug concentrations did not correlate with decrements in activity for either drug"
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41187606-06ff-11f0-808a-c43d1ab1c353
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Background Recent systematic review s have demonstrated that pain associated with knee osteoarthritis ( OA ) is a complex phenomenon that involves various contributors . People with knee OA exhibit symptoms of impaired body-perception , including reduced tactile acuity , impairments in limb laterality recognition , and de grade d proprioceptive acuity . The Fremantle Back Awareness Question naire ( FreBAQ ) was developed to assess body-perception specific to the back in people with chronic low back pain . The aim of this study was to develop and assess the psychometric properties of a knee-specific version of the FreBAQ-J ( FreKAQ-J ) , determine whether people with knee pain experience perceptual impairments and investigate the relationship between disturbed self-perception and clinical status . Methods Sixty-five people with knee OA completed the FreKAQ-J. A subset of the participants completed the FreKAQ-J again two-weeks later . Rasch analysis was used to assess item order , targeting , category ordering , unidimensionality , person fit , internal consistency , and differential item functioning . Validity was investigated by examining the relationship between the FreKAQ-J and clinical valuables . Results The FreKAQ-J had acceptable internal consistency , unidimensionality , good test-retest reliability , and was functional on the category rating scale . The FreKAQ-J was significantly correlated with pain in motion , disability , pain-related catastrophizing , fear of movement , and anxiety symptomatology . Conclusions We developed FreKAQ-J by modifying the FreBAQ-J. The FreKAQ-J fits the Rasch measurement model well and is suitable for use in people with knee OA . Altered body perception may be worth evaluating when managing people with knee OA
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"Clinical research of grade d exposure in vivo with behavioral experiments in patients with chronic low back pain who reported fear of movement/(re)injury shows abrupt changes in self-reported pain-related fears and cognitions . The abrupt changes are more characteristics of insight learning rather than the usual gradual progression of trial and error learning . The educational session at the start of the exposure might have contributed to this insight . The current study examines the contribution of education and grade d exposure versus grade d activity in the reduction of pain-related fear and associated disability and physical activity . Six consecutive patients with chronic low back pain who reported substantial fear of movement/(re)injury were included in the study . After a no-treatment baseline measurement period , all the patients received a single educational session , followed again by a no-treatment period . Patients were then r and omly assigned to either a grade d exposure with behavioral experiments or an operant grade d activity program . A diary was used to assess daily changes in pain intensity , pain-related fear , pain catastrophizing , and activity goal achievement . St and ardized question naires of pain-related fear , pain vigilance , pain intensity , and pain disability were administered before and after each intervention and at the 6-month follow-up . An activity monitor was carried at baseline , during the interventions , and 1 week at 6-month follow-up . R and omization tests of the daily measures showed that improvements in pain-related fear and catastrophizing occurred after the education was introduced . The results also showed a further improvement when exposure in vivo followed the no-treatment period after the education and not during the operant grade d activity program . Performance of relevant daily activities , however , were not affected by the educational session and improved significantly only in the exposure in vivo condition . All improvements remained at half-year follow-up only in patients receiving the exposure in vivo . These patients also reported a significant decrease in pain intensity at follow-up",
"Introduction With the high incidence of knee osteoarthritis ( OA ) in Japan , there is a strong need not only for surgical therapies , but also for vali date d outcome measures . For this study , we completed cross-cultural adaptation , testing and validation of the Oxford knee score ( OKS ) for prospect i ve use in national and international clinical studies involving Japanese patients . Material s and methods The Japanese version of the OKS was developed according to the st and ard cross-cultural adaptation guidelines . For validation , the OKS was tested on 54 patients diagnosed with OA , osteonecrosis , ligament or meniscus injury . Reliability was tested using the intraclass correlation coefficient ( ICC ) . Internal consistency or homogeneity was assessed using Cronbach ’s alpha . The correlation between the Japanese OKS , WOMAC and SF-36 question naires was used to assess construct validity . Results No major difficulties were encountered with the translation and pre-testing stages . For reliability and validity , the Japanese OKS was completed without any missed responses by 53 ( 98.15 % ) and 52 ( 96.30 % ) patients at the first and second distribution , respectively . The total OKS showed good reliability with an ICC of 0.85 . Internal consistency was strong ( Cronbach ’s alpha = 0.90 ) . Strong construct validity ( ICC values of 0.51–0.84 ) was obtained against the WOMAC and SF-36 ( physical functioning , role-physical , bodily pain , and social functioning subscales ) scores . Notable “ ceiling ” effects of the OKS were reported for 11 of the 12 question naire items . Conclusion The Japanese OKS has proven to be a reliable and valid instrument for the self- assessment of knee pain and function in Japanese speaking patients with knee OA and other knee complaints",
"BACKGROUND Osteoarthritis is a degenerative disease associated with pain , reduced range of motion , and impaired function . Balneotherapy or bathing in thermal or mineral waters is used as a non-invasive treatment for various rheumatic diseases . AIM To evaluate the effectiveness of hot sulfurous and non-sulfurous waters in the treatment of knee osteoarthritis . DESIGN A r and omized , assessor-blind , controlled trial . SETTING A spa resort . POPULATION One hundred and forty patients of both genders , mean age of 64.8±8.9 years , with knee osteoarthritis and chronic knee pain . METHODS Patients were r and omized into three groups : the sulfurous water ( SW ) group ( N.=47 ) , non-sulfurous water ( NSW ) group ( N.=50 ) , or control group ( N.=43 ) who received no treatment . Patients were not blinded to treatment allocation . Treatment groups received 30 individual thermal baths ( three 20-minute baths a week for 10 weeks ) at 37 - 39 ° C . The outcome measures were pain ( visual analog scale , VAS ) , physical function ( Western Ontario and McMaster Universities Osteoarthritis Index , WOMAC ; Lequesne Algofunctional Index , LAFI ; Stanford Health Assessment Question naire , HAQ ) , and use of pain medication . Patients were assessed before treatment ( T1 ) , at treatment endpoint ( T2 ) , and two months post-intervention ( T3 ) . Intra- and intergroup comparisons were performed at a significance level of 0.05 ( P decrease in VAS pain scores ( pain during movement , at rest , and at night ) and use of pain medication , and improvement in WOMAC , LAFI and HAQ scores were observed from baseline to T2 and T3 within treatment groups ( P less pain and better functional status than those in the NSW group at T3 , showing a lasting effect of sulfurous water baths . CONCLUSIONS Both therapeutic methods were effective in the treatment of knee osteoarthritis ; however , sulfurous baths yielded longer-lasting effects than non-sulfurous water baths . CLINICAL REHABILITATION IMPACT Baths in thermal waters , especially those in sulfurous waters , are effective in reducing pain and improving physical function in patients with knee osteoarthritis",
"We have developed a 12-item question naire for patients having a total knee replacement ( TKR ) . We made a prospect i ve study of 117 patients before operation and at follow-up six months later , asking them to complete the new question naire and the form SF36 . Some also filled in the Stanford Health Assessment Question naire ( HAQ ) . An orthopaedic surgeon completed the American Knee Society ( AKS ) clinical score . The single score derived from the new question naire had high internal consistency , and its reproducibility , examined by test-retest reliability , was found to be satisfactory . Its validity was established by obtaining significant correlations in the expected direction with the AKS scores and the relevant parts of the SF36 and HAQ . Sensitivity to change was assessed by analysing the differences between the preoperative scores and those at follow-up . We also compared change in scores with the patients ' retrospective judgement of change in their condition . The effect size for the new question naire compared favourably with those for the relevant parts of the SF36 . The change scores for the new knee question naire were significantly greater ( p new question naire provides a measure of outcome for TKR that is short , practical , reliable , valid and sensitive to clinical ly important changes over time",
"Background The Hospital Anxiety and Depression Scale ( HADS ) is a common screening instrument excluding somatic symptoms of depression and anxiety , but previous studies have reported inconsistencies of its factor structure . The construct validity of the Japanese version of the HADS has yet to be reported . To examine the factor structure of the HADS in a Japanese population is needed . Methods Exploratory and confirmatory factor analyses were conducted in the combined data of 408 psychiatric out patients and 1069 undergraduate students . The data pool was r and omly split in half for a cross validation . An exploratory factor analysis was performed on one half of the data , and the fitness of the plausible model was examined in the other half of the data using a confirmatory factor analysis . Simultaneous multi-group analyses between the subgroups ( out patients vs. students , and men vs. women ) were subsequently conducted . Results A two-factor model where items 6 and 7 had dual loadings was supported . These factors were interpreted as reflecting anxiety and depression . Item 10 showed low contributions to both of the factors . Simultaneous multi-group analyses indicated a factor pattern stability across the subgroups . Conclusion The Japanese version of HADS indicated good factorial validity in our sample s. However , ambiguous wording of item 7 should be clarified in future revisions",
"Objective The aim of this study was to compare whether the effectiveness of continuous ultrasound ( US ) was superior against pulsed US and against sham US in knee osteoarthritis . Design A r and omized controlled study was carried out on 60 patients diagnosed with knee osteoarthritis according to American College of Rheumatology . The patients were r and omized into the following three treatments : ( 1 ) continuous US ( at a frequency of 1 MHz with intensity of 1 W/cm2 ) , ( 2 ) pulse US ( same frequency and intensity on 1:4 pulse ratio ) , and ( 3 ) sham US . All treatments were applied with 5-cm2 head US device five times a week for 2 weeks in addition to home exercise program including quadriceps isometric exercise , muscle strength exercises , and stretching exercises of the lower extremity muscles for at least three times per week . Assessment s were performed at baseline , at the end of the treatment , and at the end of the treatments and at the sixth month using the following measurements : Western Ontario and McMaster University Osteoarthritis Index – pain , stiffness , function , visual analog scale – pain at rest , visual analog scale – pain on movement , visual analog scale – disease severity , and 20-m walking time . Among these parameters , the Western Ontario and McMaster University Osteoarthritis Index – pain was the primary outcome . Results All groups showed a significant improvement in all parameters in both following visits ( P Western Ontario and McMaster University Osteoarthritis Index – pain was significantly higher in group I ( continuous US ) when compared to sham group ( 46.5 % vs 28.9 % , P therapeutic US provided no additional benefit in improving pain and functions in addition to exercise training",
"BACKGROUND Knee osteoarthritis ( OA ) conservative treatment aims to delay cartilage degeneration ; chondroprotective agents are a valid approach in this sense . A commercially available dietary supplement , CartiJoint Forte , containing glucosamine hydrochloride ( GH ) , chondroitin sulfate ( CS ) and Bio-Curcumin BCM-95 ® , was used in this trial . AIM The aim of this study was to assess efficacy and safety of CartiJoint Forte combined with physical therapy in treating subjects with knee OA . DESIGN A multicenter , prospect i ve , r and omized , double blind , placebo-controlled clinical trial . SETTING Out patients referred to the Rehabilitation Departments of two University Hospitals . POPULATION Fifty-three patients were r and omly assigned to an experimental group ( N=26 ) or a control group ( N.=27 ) . Experimental subjects received two tablets of CartiJoint Forte each day for 8 weeks , while those in the control group were provided with a placebo . Three subjects dropped out during the course of the study . METHODS The two groups both received 20 sessions of physical therapy during the course of the trial . Primary outcome was pain intensity , measured both at motion and at rest , using the Visual Analogue Scale ( VAS ) . A secondary outcome was an assessment of knee function by Western Ontario and McMaster Universities Arthritis Index and Lequesne Index , knee ROM , and two inflammation markers ( C-reactive protein and erythrocyte sedimentation rate ) . Each assessment was carried out at baseline ( T0 ) , at 8 weeks ( T1 ) and at 12 weeks ( T2 ) . RESULTS VAS at rest was found to be reduced between T0 and T1 , as well as between T0 and T2 ( F=13.712 ; P=0.0001 ) , with no differences between groups ( F=1.724 ; P=0.191 ) . VAS at motion revealed a significant \" group × time-check \" interaction ( F=2.491 ; P=0.032 ) , with increasing effect of time on VAS reduction ( F=17.748 ; P=0.0001 ) . This was most pronounced in the experimental group at 8 weeks ( F=3.437 ; P=0.045 ) . The Lequesne Index showed reductions at T1 and T2 compared to T0 ( F=9.535 ; P=0.0001 ) , along with group effect , since the experimental group presented a lower score at T2 ( F=7.091 ; P=0.009 ) . No significant changes were found in the knee ROM and inflammation markers . CONCLUSION CartiJoint Forte , added to physical therapy , may ameliorate pain and help to improve algofunctional score in knee OA patients . CLINICAL REHABILITATION IMPACT Treatment of knee OA with curcuminoids plus glycosaminoglycans , added to physical therapy , improves VAS at motion and Lequesne Index scores"
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41187642-06ff-11f0-808a-c43d1ab1c353
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Despite the numerous studies , there is no consensus concerning the best approach for total hip arthroplasty ( THA ) , and debates are ongoing . The purpose of this study was to perform a Bayesian network meta- analysis ( NMA ) comparing several approaches for primary THA . The focus was on peri-operative outcomes : surgical duration , total estimated blood loss , and length of the hospitalization . This Bayesian network meta- analysis was conducted according to the PRISMA extension statement for reporting systematic review s incorporating network meta-analyses of health care interventions . In October 2019 , the main data bases were accessed . All the clinical trials comparing two or more different approaches for primary THA were assessed . For the methodology quality assessment , the PEDro score was performed . The Software STATA MP was used for the statistical analyses . The NMA was performed through the routine for Bayesian hierarchical r and om-effects analysis with the inverse variance statistic method for continuous variables . Data from 4843 procedures was analysed . Between patient ’s demographic , good baseline comparability was found . The comparison total estimated blood loss detected statistically significant inconsistency ( P = 0.01 ) . The posterolateral approach reported the lowest value for the surgical duration . The test for overall inconsistency was statistically significant ( P = 0.4 ) . The posterolateral approach reported the shortest hospitalization length . The test for overall inconsistency was statistically significant ( P = 0.9 ) . The posterolateral approach reported shorter surgical duration and hospitalization length . Concerning the analysis of total estimated blood loss , no significant result was obtained . Data must be considered in the light of the limitations of the present study
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"Background For total hip arthroplasty ( THA ) , minimally invasive surgery ( MIS ) uses a smaller incision and less muscle dissection than the classic approach ( CLASS ) , and may lead to faster rehabilitation . Questions / purpose sDoes minimally invasive hip arthroplasty result in superior clinical outcomes ? Patients and Methods In this double-blind r and omized controlled trial , 120 consecutive primary noncemented THAs in 120 patients were assigned to one of two groups ( MIS or CLASS ) . The r and omization sequence was stratified for two groups of surgeons , ie , those using a posterolateral approach ( PL-CLASS or PL-MIS ) and those using an anterolateral approach ( AL-CLASS or AL-MIS ) . Length of the incisions was 18 cm for the CLASS procedures . MIS incisions were extended at the skin level to 18 cm at the end of the procedure . The primary end point was the Harris hip score ( HHS ) at 6 weeks postoperatively . Patient-centered question naires were obtained preoperatively and after 6 weeks and 1 year . Results For the patients in the MIS group ( average 7.8 cm incision length ) , statistically significant increased mean HHSs were seen compared with the CLASS group at 6 weeks and 1 year . This difference was small and mainly caused by the favorable results of the PL-MIS . In the MIS group , surgical time was longer . A learning curve was observed based on operation time and complication rate . Although not statistically significant , the perioperative complication rate was rather high in the ( anterolateral ) MIS group . Conclusions The minimal invasive approach in THA did not show a clinical ly relevant superior outcome in the first postoperative year . Level of Evidence Level I , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence",
"Introduction Minimally invasive total hip arthroplasty ( THA ) is cl aim ed to be superior to the st and ard technique , due to the potential reduction of soft tissue damage via a smaller and tissue-sparing approach . As a result of the lack of objective evidence of fewer muscle and tendon defects , controversy still remains as to whether minimally invasive total hip arthroplasty truly minimizes muscle and tendon damage . Therefore , the objective was to compare the influence of the surgical approach on abductor muscle trauma and to analyze the relevance to postoperative pain and functional recovery . Material s and methods Between June 2006 and July 2007 , 44 patients with primary hip arthritis were prospect ively included in the study protocol . Patients underwent cementless unilateral total hip arthroplasty either through a minimally invasive anterolateral approach ( ALMI ) ( n = 21 ) or a modified direct lateral approach ( mDL ) ( n = 16 ) . Patients were evaluated clinical ly and underwent MR imaging preoperatively and at 3 and 12 months postoperatively . Clinical assessment contained clinical examination , performance of abduction test and the survey of a function score using the Harris Hip Score , a pain score using a numeric rating scale ( NRS ) of 0–10 , as well as a satisfaction score using an NRS of 1–6 . Additionally , myoglobin and creatine kinase were measured preoperatively , and 6 , 24 and 96 h postoperatively . Evaluation of the MRI images included fatty atrophy ( rating scale 0–4 ) , tendon defects ( present/absent ) and bursal fluid collection of the abductor muscle . Results Muscle and tendon damage occurred in both groups , but more lateral gluteus medius tendon defects [ mDL 3/12mth . : 6 (37%)/4 ( 25 % ) ; ALMI : 3 (14%)/2 ( 9 % ) ] and muscle atrophy in the anterior part of the gluteus medius [ mean-st and ard ( 12 ) : 1.75 ± 1.8 ; mean-MIS ( 12 ) : 0.98 ± 1.1 ] were found in patients with the mDL approach . The clinical outcome was also poorer compared to the ALMI group . Significantly , more Trendelenburg ’s signs were evident and lower clinical scores were achieved in the mDL group . No differences in muscle and tendon damage were found for the gluteus minimus muscle . A higher serum myoglobin concentration was measured 6 and 24 h postoperatively in the mDL group ( 6 h : 403 ± 168 μg/l ; 24 h : 304 ± 182 μg/l ) compared to the ALMI group ( 6 h : 331 ± 143 μg/l ; 24 h : 268 ± 145 μg/l ) . Conclusion Abductor muscle and tendon damage occurred in both approaches , but the gluteus medius muscle can be spared more successfully via the minimally invasive approach and is accompanied by a better clinical outcome . Therefore , going through the intermuscular plane , without any detachment or dissection of muscle and tendons , truly minimizes perioperative soft tissue trauma . Furthermore , MRI emerges as an important imaging modality in the evaluation of muscle trauma in THA",
"Benefits of a direct anterior approach ( DAA ) versus a posterior-lateral ( PA ) approach to THA were assessed in a single-surgeon , IRB-approved , prospect i ve , r and omized clinical study . Subjects ( 43 DAA and 44 PA ) were evaluated at 6 weeks , and 3 , 6 and 12 months . The primary end point was ability to climb stairs normally and walk unlimited at each time point . Secondary end points included assessment by several outcome instruments . DAA subjects performed better during the immediate post-operative period ; they had lower VAS pain scores on the first post-operative day , more subjects climbing stairs normally and walking unlimited at 6 weeks , and higher HOOS Symptoms scores at 3 months . There were no significant differences between groups at later time points . Findings confirm previous reports of benefits of DAA versus PA in early post-operative phases",
"The purpose s of this study were to determine the impact of surgical approach on costs of total hip arthroplasty ( THA ) from a hospital perspective and to provide an up date d cost estimation of THA . A prospect i ve , microcosting analysis was performed on 118 patients undergoing a THA through an anterior , lateral , or posterior approach . We determined that overall costs ( intraoperative costs and hospital stay ) were significantly less for the anterior ( $ 7300.22 ; 95 % confidence interval [ CI ] , 7064.49 - 7535.95 ) vs lateral ( $ 7853.10 ; 95 % CI , 7577.29 - 8128.91 ; P = .031 ) and anterior vs posterior approach ( $ 8287.46 ; 95 % CI , 7906.42 - 8668.51 ; P hospital length of stay when THA was performed through an anterior approach contributed significantly to an overall reduction in costs from a hospital perspective",
"Objective The aim of the present study was to identify independent preoperative hip function characteristics sensitive for preoperative intervention that are predictive of an extended length of hospital stay ( LOS ) after primary total hip arthroplasty ( THA ) . Design This is a longitudinal cohort study . A retrospective chart analysis was conducted on prospect ively collected data of patients ( 158 ) who underwent unilateral primary elective cemented THA in a 4-yr period . The main outcome measure was LOS after primary THA . Results The median LOS was 6.0 days . The authors found an 18.5 % increased chance of requiring an LOS of more than 6 days ( odds ratio , 2.15 ; 95 % confidence interval , 1.03–4.50 ) for the patients who needed to use a walking aid preoperatively and a 23.6 % increased chance ( odds ratio , 2.74 ; 95 % confidence interval , 1.31–5.74 ) for the patients who had difficulties managing stairs . Sex , age , body mass index , comorbidity , and preoperative pain did not reach the level of significance in the multivariate analysis . Conclusions Patients who are at risk for a longer stay in the hospital after THA can be identified preoperatively on simple physical function characteristics . These findings enable the identification of appropriate patients for preoperative training to improve functional recovery and decrease the LOS after primary THA",
"Introduction We conducted a prospect i ve study to compare the exposure and implant positioning in primary total hip replacement through the anterolateral minimally invasive ( ALMI ) approach versus the posterior minimally invasive ( PMI ) approach . Material s and methods We applied these techniques to 2 consecutive groups ( 33 and 43 patients , respectively ) comparable preoperatively . All the patients received the same cementless stem and acetabular component . Results There were neither significant difference in femoral or acetabular component positioning nor in limb-length discrepancy . Acetabular exposure was easy through the ALMI approach . Femoral exposure was more difficult as fractures of the trochanter and femoral perforation in our study show . Conclusion For us , exposure and implant positioning through the ALMI approach and the PMI approach are comparable and reliable . However , we recommend caution during the initial learning curve in osteoporotic patients due to the higher rate of peroperative complications for the ALMI approach",
"Background and purpose — Criticism of the lateral approach ( LA ) for hip arthroplasty is mainly based on the risk of poor patient-reported outcomes compared to the posterior approach ( PA ) . However , there have been no controlled studies comparing patient-reported outcomes between them . In this r and omized controlled trial , we tested the hypothesis that patient-reported outcomes are better in patients who have undergone total hip arthroplasty ( THA ) with PA than in those who have undergone THA with LA , 12 months postoperatively . Patients and methods — 80 patients with hip osteoarthritis ( mean age 61 years ) were r and omized to THA using PA or the modified direct LA . We recorded outcome measures preoperatively and 3 , 6 , and 12 months postoperatively using the Hip Disability and Osteoarthritis Outcome Score – Physical Function Short Form ( HOOS-PS ) as the primary outcome . Secondary outcomes were HOOS-Pain , HOOS- Quality -Of-Life , EQ-5D , UCLA Activity Score , and limping . Results — We found no statistically significant difference in the improvements in HOOS-PS between the treatment groups at 12-month follow-up . All secondary outcomes showed similar results except for limping , where PA patients improved significantly more than LA patients . Interpretation — Contrary to our hypothesis , patients treated with PA did not improve more than patients treated with LA regarding physical function , pain , physical activity , and quality of life 12 months postoperatively . However , limping was more pronounced in the LA patients",
"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",
"Purpose The purpose of this study was to evaluate pre-operative education versus no education and mini-invasive surgery versus st and ard surgery to reach complete independence . Methods We conducted a four-arm r and omized controlled trial of 209 patients . The primary outcome criterion was the time to reach complete functional independence . Secondary outcomes included the operative time , the estimated total blood loss , the pain level , the dose of morphine , and the time to discharge . Results There was no significant effect of either education ( HR : 1.1 ; P = 0.77 ) or mini-invasive surgery ( HR : 1.0 ; 95 % ; P = 0.96 ) on the time to reach complete independence . The mini-invasive surgery group significantly reduced the total estimated blood loss ( P = 0.0035 ) and decreased the dose of morphine necessary for titration in the recovery ( P = 0.035 ) . Conclusions Neither pre-operative education nor mini-invasive surgery reduces the time to reach complete functional independence . Mini-invasive surgery significantly reduces blood loss and the need for morphine consumption",
"BACKGROUND The purpose of this study was to assess current practice s in blood management in elective orthopedic surgery in Europe . STUDY DESIGN AND METHODS For this 225-center prospect i ve survey , data were collected on 3996 patients . Actual perioperative blood loss was compared to preoperative estimates . Differences in Hb levels and other outcome variables for patients receiving allogeneic versus autologous transfusions were evaluated . The probability of allogeneic transfusion based on selected predictor variables was estimated . RESULTS A total of 2640 ( 67 % ) hip and 1305 ( 33 % ) knee arthroplasty patients were evaluated . Estimated blood loss ( median , 750 mL ) was significantly lower than computed blood loss ( median , 1944 mL ) . A total of 2762 ( 69 % ) patients received transfusions , including 1393 ( 35 % ) autologous-only and 1024 ( 25 % ) allogeneic-only . The probability of allogeneic transfusion decreased with increasing baseline Hb , but differentially so for men and women . Transfusion triggers were Hb levels of 8.93 + /- 1.83 g per dL for allogeneic transfusions , and 21 percent of these occurred when the Hb level was greater than 10 g per dL. Autologous blood transfusion was associated with a significantly lower rate ( 1 % ) of wound infections than allogeneic blood transfusion ( 4.2 % ) . CONCLUSION Accurate assessment of preoperative Hb levels , better estimation of perioperative blood loss , efficient use of autologous blood , adherence to transfusion guidelines , and pharmacologic alternatives contribute to effective and comprehensive blood and anemia management",
"Purpose . To compare outcome after total hip arthroplasty ( THA ) through the mini-incision approach versus the st and ard transgluteal approach . Methods . 80 women and 63 men aged 33 to 89 ( mean , 62 ) years with primary osteoarthritis of the hip were r and omised to undergo unilateral THA through a mini-incision approach ( Micro-hip , n=55 ) or st and ard , lateral , transgluteal approach ( Bauer , n=88 ) . Levels of haemoglobin , haematocrit , serum creatine kinase , and C-reactive protein , length of hospital stay , mobilisation , and any complication were recorded . Visual analogue scale ( VAS ) for pain was assessed . Hip function was assessed using the Harris Hip Score and the Oxford Hip Score , whereas general health was assessed using the EQ-5D general health question naire . The cup inclination and varus/ valgus of the stem position were measured using a goniometer . Results . The Micro-hip group achieved a significantly lower mean incision length ( 9.3 vs. 13.4 cm , p mean surgical time ( 60 vs. 68 minutes , p=0.021 ) , mean reduction in haemoglobin level ( 2.1 vs. 2.8 g/dl , p mean VAS for pain from hour 6 to day 6 ( all p early aseptic loosening of the cup and underwent revision surgery at month 4 . Three patients in the Bauer group and one patient in the Micro-hip group sustained intra-operative non-displaced fractures of the proximal femur , which were fixed with cerclages . Two patients in the Micro-hip group developed deep vein thrombosis during week 1 . Conclusion . THA through the Micro-hip approach achieved faster pain relief",
"BACKGROUND A number of surgical approaches are utilized in total hip arthroplasty . It has been hypothesized that the anterior approach results in less muscle damage than the posterior approach . We prospect ively analyzed biochemical markers of muscle damage and inflammation in patients treated with minimally invasive total hip arthroplasty with an anterior or posterior approach to provide objective evidence of the local soft-tissue injury at the time of arthroplasty . METHODS Twenty-nine patients treated with minimally invasive total hip arthroplasty through a direct anterior approach and twenty-eight patients treated with the same procedure through a posterior approach were prospect ively analyzed . Perioperative and radiographic data were collected to ensure cohorts with similar characteristics . Serum creatine kinase ( CK ) , C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , interleukin-1 beta ( IL-1ß ) , and tumor necrosis factor-alpha ( TNF-a ) levels were measured preoperatively , in the post-anesthesia-care unit ( except for the CRP level ) , and on postoperative days 1 and 2 . The Student t test and Fisher exact test were used to make comparisons between the two groups . Independent predictors of elevation in levels of markers of inflammation and muscle damage were determined with use of multivariate logistic regression analysis . RESULTS The levels of the markers of inflammation were slightly decreased in the direct-anterior-approach group as compared with those in the posterior-approach group . The rise in the CK level in the posterior-approach group was 5.5 times higher than that in the anterior-approach group in the post-anesthesia-care unit ( mean difference , 150.3 units/L [ 95 % CI , 70.4 to 230.2 ] ; p total hip arthroplasty approach used in this study caused significantly less muscle damage than did the posterior surgical approach , as indicated by serum CK levels . The clinical importance of the rise in the CK level needs to be delineated by additional clinical studies . The overall physiologic burden , as demonstrated by measurement of inflammation marker levels , appears to be similar between the anterior and posterior approaches . Objective measurement of muscle damage and inflammation markers provides an unbiased way of determining the immediate effects of surgical intervention in patients treated with total hip arthroplasty",
"Background The tissue sparing surgery ( TSS ) concept means not only smaller incisions but also less tissue disruption , allowing decreased blood loss and improved function . However , TSS techniques can result in more complications related to the learning curve . The aim of this study was to compare the learning curve of an experienced surgeon with different TSS approaches for total hip replacement ( THR ) from a clinical and surgical point of view , focussing especially on complications related to the use of different geometric stems . Material s and methods Sixty patients scheduled to be operated for a primary THR were enrolled in the study and were r and omly assigned to surgery by one of three different TSS approaches : lateral with mini incision ( group A ) , minimally invasive anterior ( group B ) and minimally invasive antero-lateral ( group C ) . Results from the three TSS groups were compared with a control group of 149 patients ( group D ) . Results Our results reveal significantly reduced blood loss in the TSS groups compared with the control group , with no differences between the TSS groups . We found better early functional scores in the two minimally invasive groups ( anterior and anterolateral ) , and a lower rate of complications with the antero-lateral TSS approach . Conclusion The antero-lateral TSS approach seems to be safer and less dem and ing than st and ard THR surgery , and is suitable for use with different stems",
"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",
"AIMS Our primary aim was to evaluate whether there is really less bleeding in patients for whom the minimally invasive posterior approach is used in comparison with the direct lateral approach for primary total hip arthroplasty . Our secondary aim was to evaluate the clinical functional results after six months as well as the postoperative radiographic result . METHODS In a comparative non-r and om prospect i ve study , 76 adult patients underwent elective total hip arthroplasty using one of two approaches . The minimally invasive posterior approach ( 34 cases ; mini-incision group ) was compared with the st and ard direct lateral approach ( 42 cases ; control group ) . RESULTS Lower total estimated bleeding ( means of 1083.5 ml versus 1682.3 ml ; p lower intraoperative bleeding ( means of 745.6 ml versus 1282.8 ml ; p volume of blood drained after the operation ( means of 340 ml and 399 ml ; p = 0.77 ) . There was also a difference between the two groups regarding the need for allogenic transfusion ( 8.8 % in the mini-incision group versus 28.6 % , p = 0.02 ) . We observed a better clinical result in the mini-incision group ( p = 0.002 ) despite the lack of difference between the two groups in relation to the radiographic result . DISCUSSION Our results draw attention to the possibility that other authors may have underestimated blood losses when using minimally invasive approaches . CONCLUSION The minimally invasive approach gave rise to a positive final impression with regard to lower blood loss",
"Background Newer surgical approaches to THA , such as the direct anterior approach , may influence a patient ’s time to recovery , but it is important to make sure that these approaches do not compromise reconstructive safety or accuracy . Questions / purpose sWe compared the direct anterior approach and conventional posterior approach in terms of ( 1 ) recovery of hip function after primary THA , ( 2 ) general health outcomes , ( 3 ) operative time and surgical complications , and ( 4 ) accuracy of component placement . Methods In this prospect i ve , comparative , nonr and omized study of 120 patients ( 60 direct anterior THA , 60 posterior THAs ) , we assessed functional recovery using the VAS pain score , timed up and go ( TUG ) test , motor component of the Functional Independence Measure ™ ( M-FIM ™ ) , UCLA activity score , Harris hip score , and patient-maintained subjective milestone diary and general health outcome using SF-12 scores . Operative time , complications , and component placement were also compared . Results Functional recovery was faster in patients with the direct anterior approach on the basis of TUG and M-FIM ™ up to 2 weeks ; no differences were found in terms of the other metrics we used , and no differences were observed between groups beyond 6 weeks . General health outcomes , operative time , and complications were similar between groups . No clinical ly important differences were observed in terms of implant alignment . Conclusions We observed very modest functional advantages early in recovery after direct anterior THA compared to posterior-approach THA . R and omized trials are needed to vali date these findings , and these findings may not generalize well to lower-volume practice setting s or to surgeons earlier in the learning curve of direct anterior THA.Level of Evidence Level II , therapeutic study . See Instructions for Authors for a complete description of levels of evidence",
"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",
"OBJECTIVE To explore the indications and key points of anterolateral minimally-invasive total hip arthroplasty . METHODS 110 baseline indexes matched patients admitted for unilateral total hip arthroplasty were r and omly assigned to 2 equal groups to undergo surgery through a short anterolateral incision of All operations were done by the same surgeon . The demographic data , perioperative indexes , and postoperative function indexes were recorded and statistically analyzed . RESULTS No significant differences were detected with respect to operation time , abduction angle , anteversion angle , stem alignment , and stem fixation between these 2 groups . The incision length , blood loss , perioperative transfusion , and 100 - mm visual analogue pain scale ( VAS ) score at the first 24 hours of the anterolateral approach group were ( 7.49 + /- 0.86 ) cm , ( 376.18 + /- 168.30 ) ml , ( 410.09 + /- 136.46 ) ml , and ( 30.76 + /- 21.77 ) respectively , all significantly shorter , less , or lower than those of the st and ard posterolateral approach group [ ( 15.2 + /- 1.8 ) cm , ( 605.0 + /- 225.1 ) ml , ( 629.5 + /- 232.9 ) ml , and ( 50.3 + /- 13.7 ) respectively , all P Harris hip score and Barthel index 3 months after operation of the anterolateral approach group were ( 83.80 + /- 5.64 ) and ( 93.45 + /- 6.37 ) respectively , both significantly higher than those of the st and ard posterolateral approach group [ ( 75.0 + /- 7.5 ) and ( 94.6 + /- 7.5 ) respectively , both P Harris hip score and Barthel index 3 years after operation between these 2 groups . CONCLUSIONS Fewer traumas , less blood loss and rapid recovery can be obtained through this new total hip arthroplasty approach . But experienced doctors and special instruments are prerequisite",
"Background and purpose There is still conflicting evidence about the true benefit of minimally invasive ( MI ) techniques in total hip replacement ( THR ) . The aim of this prospect i ve study was to evaluate the safeness of a MI approach during the learning curve of a single surgeon . Second , clinical and radiographic results among the MI THR group were compared with the results using a st and ard transgluteal ( Bauer ) approach . Methods 86 primary unilateral total hip arthroplasties ( THAs ) through a MI , anterior ( Micro-hip ® ) approach were performed by a single senior surgeon ( ES ) , representing a consecutive series of patients after beginning with the MI technique . Cases were compared to a matched cohort of patients who were treated with a st and ard transgluteal ( Bauer ) approach . Operation time , incision length , perioperative blood loss , haemoglobin level and blood transfusions were monitored . Complications were documented and followed up 1 year postoperatively . The Harris Hip Score ( HHS ) , range of motion , use of analgetics , the Trendelenburg sign , sensibility of the lateral femoral cutaneous nerve and the acetabular/femoral component placement as well as potential heterotopic ossifications were analysed in both the groups after 12 months postoperatively . Results 74 MI THR patients and 60 st and ard THR patients were available for the one year follow-up . Operative time was significantly longer in the MI group , reduction in the haemoglobin level during the first 24 h was significant and the length of skin incision was significantly shorter . No significant differences were found for HHS , range of motion , use of analgetics , the Trendelenburg sign , and the acetabular/femoral component placement , heterotopic ossifications and intra- and postoperative complications . Sensibility of the lateral femoral cutaneous nerve was affected in three patients in the MI group . Radiographic evaluation revealed no component migration , implant subsidence or radiolucency signs in both the groups . DicussionConsistent with recent meta- analysis we found reduced blood loss , similar clinical /radiographic outcome and similar complication rates compared to st and ard THA . Our study shows , that MI THR is a safe procedure during the learning curve of an experienced surgeon",
"Surgical approaches to the hip for total hip arthroplasty ( THA ) are termed minimally invasive when allowing for a skin incision length of 10 cm or less . The aim of this study was to explore if a minimally invasive posterior approach compared to a classic anterolateral approach negatively influenced surgical time , blood loss , implant position , or perioperative complications . Two groups of THA patients mainly differing with respect to the surgical approach were compared . Results of 76 consecutive THA via a posterior mini-incision approach were recorded prospect ively and those of 76 controls operated via a classic anterolateral approach were recorded retrospectively . THA was performed by the same surgeon in every case . Surgical time or intraoperative blood loss were not different among the groups . Total 24-h blood loss was significantly less in patients undergoing THA via minimally invasive posterior approaches . Median cup inclination was 45 degrees in both groups . Cup anteversion was 15 degrees ( classic anterolateral ) and 12 degrees ( minimally invasive posterior ) , respectively . Stem position was regarded as neutral in 80 % of THA through classic anterolateral and in 76 % through minimally invasive dorsal incisions . Complications occurred in 8 % ( classic anterolateral ) and 9 % ( minimally invasive posterior ) of THA patients . Surgical time , blood loss , risk of malpositioned implants , or complications were not increased for THA patients operated through minimally invasive posterior incisions compared to those operated via classic anterolateral approaches",
"In this prospect i ve study we compared clinical and radiological results and rehabilitation progress of 64 patients who underwent total hip arthroplasty using the st and ard lateral approach with 64 patients operated with a minimal-invasive ( MIS ) posterior approach . The outcome of our study did not show any significant differences with regard to patient 's safety such as complication rate and radiological assessment of the cup position . There was no difference in the duration of surgery , blood loss , hospital stay and postoperative leg length discrepancy . Rehabilitation milestones were achieved earlier by MIS patients and three and six months postoperatively , the Harris Hip Score of the MIS group was significantly higher",
"This prospect i ve observational study investigated the relationship between the length of hospital stay ( LOS ) and outcomes at 3 months for primary total hip arthroplasty for osteoarthritis . Mean length of postoperative stay was 9.5 + /- 2.8 days . Predictors of LOS were patient 's age , sex , and number of comorbidities ; preoperative Charnley scores and Nottingham Health Profile measures ; complications ; and hospital in which surgery took place . LOS was found to have a small negative correlation with outcome . The dominant association with improved outcome was the severity of the patients ' impairment preoperatively . These data suggest that in situations in which adequate rehabilitation and support are available after discharge , a marginal reduction in postoperative LOS -- from the average of 10.3 days observed at 1 hospital to the average of 8 days observed at another -- would not adversely affect the short-term outcome",
"BACKGROUND Controversy exists as to whether early functional outcomes differ after total hip arthroplasty performed using the direct anterior approach ( DAA ) or the posterolateral approach ( PLA ) . METHODS One hundred twenty patients were enrolled in this study and were divided into 2 groups based on surgical approach . Group A included patients who had a total hip arthroplasty with a DAA , whereas group B included those with a PLA . Patients were r and omized into the DAA or PLA groups ( n = 60 ) , and perioperative and postoperative outcomes were recorded . RESULTS When compared with the PLA , the DAA had a shorter incision length ( 9.1 vs 13.1 cm ; P shorter hospital stay ( 2.8 vs 3.3 days , P = .04 ) , and lower self-reported pain . Both serum inflammatory and muscle damage markers were lower in the DAA group . However , the PLA had shorter operative times ( 65.5 vs 83.3 min , P = .03 ) and less intraoperative blood loss ( 123.8 vs 165.9 mL , P = .04 ) . The DAA had significantly lower variance in cup inclination and anteversion . Similar rates of intraoperative complications were identified in the 2 groups . The DAA was associated with better functional recovery at 3 months based on the Harris hip score , University of California Los Angeles activity score , and gait analysis ; however , functional recovery at 6 months was similar between the 2 groups . CONCLUSION We found functional advantages in early recovery after the DAA compared with the PLA . The DAA can offer rapid functional recovery with less muscle damage , greater pain relief , and lower variance in cup inclination and anteversion . However , no functional difference was found at 6 months follow-up",
"Anterolateral minimally invasive hip surgery ( ALMIS ) is a challenging procedure that is thought to offer a more expedient and a better functional outcome . Seventy-nine patients receiving primary hip arthroplasty were r and omized . Röttinger ALMIS technique was used for 42 patients , whereas 41 received the st and ard lateral transgluteal Hardinge approach . Operative time was longer with ALMIS ( P = .000078 ) , whereas blood loss was less ( P = .008 ) . Surgical and postoperative complication rates , morphine consumption , and length and cost of hospitalization were similar . At 1 year , Harris , Postel and Merle d'Aubigné , and Short Form-36v1 scores were similar . Gait analysis revealed similar results . Computed tomographic analysis revealed no significant difference in implant position , heterotopic ossification , and loosening . Röttinger ALMIS is a valid approach for hip arthroplasty . However , it offers no advantages at 1 year",
"The purpose of this retrospective study was to compare wound complication rates between primary THAs performed via a posterior or direct anterior approach . From our prospect i ve outcomes registry , we identified 1288 primary THAs performed via a posterior approach and 505 via a direct anterior approach . The direct anterior approach result ed in a significantly greater number of wound complications that required reoperation than the posterior approach ( 7/505 ( 1.4 % ) vs. 3/1,288 ( 0.2 % ) , P=0.007 ) . As such , patients should be counseled on the potential increased risk of early wound complications with the direct anterior approach , and future research is needed to determine if alternative closure techniques can reduce the risk of wound complication",
"Purpose Total hip arthroplasty approach comparison focused on patient ’s perspective . The direct anterior approach ( DAA ) has gained immense popularity in the last decade and is widely advocated as a superior approach in terms of quicker recovery and better overall outcome . However , the question if the level of DAA promotion is justified seems to be rarely posed . Methods A single-surgeon consecutive series of patients who underwent bilateral THA , one in DAA and the other in posterior approach ( PA ) . The same implant design and same component sizes were used for the both sides . All the operations were performed by a single surgeon under the same pre- and post-operative care protocol . Results Twenty-one patients underwent bilateral THA , mean age 60.09 years . Oxford Hip Score ( OHS ) was used for functional outcome assessment . There were no statistically significant differences between two approaches in terms of functional outcome ( mean OHS for DAA series was 42.95 and that for the PA was 43.38 , p 0.07 at an alpha level of 0.05 ) . Fifteen patients gave the advantage to PA , and six patients favoured DAA . Conclusion By study design , we tried to reduce the biases and acquire approach appraisal from patient ’s perspective . We anticipated the outcome in favour of DAA , but the results favoring PA came as a surprise . Future prospect i ve r and omized studies on evaluation of DAA and other approaches not only from surgeon ’s or industry ’s point of view , performed on a larger and more uniform groups , are warranted to further explore the subjective differences between DAA and PA",
"BACKGROUND The difference in clinical results between the direct anterior approach ( DAA ) and the anterolateral approach ( ALA ) for total hip arthroplasty ( THA ) is still unclear . The purpose of this study was to compare clinical results , including nerve injuries , between DAA and ALA in one-stage bilateral THA in a prospect i ve , r and omized controlled trial . METHODS Thirty patients were recruited for primary bilateral THAs from 2014 to 2016 . The left and right hips of each patient were r and omly assigned to DAA and the others to ALA . We prospect ively compared the clinical results , incidence of lateral femoral cutaneous nerve ( LFCN ) injury , and tensor fascia lata ( TFL ) atrophy considered to be related to superior gluteal nerve injury between both approaches . RESULTS No significant difference was found in the clinical results between both sides at postoperative 1 year . Temporary symptom of LFCN injury was observed only in DAA sides ( 7/30 , 23.3 % ) . The ratio of 3-month postoperative to preoperative cross-sectional area of TFL on computed tomography was significantly lower on the side subjected to DAA ( DAA side , 78.8 ± 22.8 % ) than on the side subjected to ALA ( ALA side , 90.7 ± 17.7 % ) ( p the mean grade of fatty atrophy of TFL by Goutalier classification was significantly higher in DAA sides ( 2.00 ± 1.6 ) than in ALA sides ( 1.1 ± 1.3 ) ( p = 0.03 ) . CONCLUSIONS Excellent clinical results for both DAA and ALA were achieved . LFCN injury was found only in DAA sides . Although TFL atrophy was found in both approaches , it was found significantly more in DAA sides . Our study suggested that ALA should be used rather than DAA in terms of the risk of nerve injuries",
"The mini-posterior approach for total hip arthroplasty ( THA ) belongs to the mini-incision approaches . In comparison to st and ard approaches , less muscle trauma result ing in less pain , less blood loss and faster rehabilitation in the early postoperative period are attributed to this approach , as known for all other minimally invasive approaches . In a prospect i ve study of 100 cases of THA it could be shown that this is true when comparing the mini-posterior approach with the posterolateral approach . Lower levels of muscle enzymes as a parameter for muscle trauma , could not be seen",
"BACKGROUND The direct anterior approach ( DAA ) for total hip arthroplasty has cl aim ed to be a true tissue-sparing minimally invasive approach that has less tissue damage and a faster recovery when compared to the posterolateral approach ( PLA ) . The aim of this r and omized controlled trial is to measure the differences in serum markers and functional outcomes between the DAA and PLA for total hip arthroplasty . METHODS Forty-six patients were prospect ively included and r and omized for either the DAA ( n = 23 ) or PLA ( n = 23 ) . All surgical procedures were performed by 3 well-trained orthopedic surgeons . The degree of tissue damage was assessed by measuring creatine kinase ( CK ) and C-reactive protein levels ( CRP ) preoperatively and 2 hours , 1 day , 2 weeks , and 6 weeks postoperatively . Generalized linear mixed models analyses were used to assess differences between serum markers over time ; correction for possible confounding factors was performed . The Hip disability and Osteoarthritis Outcome Score and the Harris Hip Score were assessed preoperatively and 6 weeks postoperatively . RESULTS There were no differences in patient demographics . The DAA had a longer operative time ( P = .001 ) . CK and CRP levels increased postoperatively , but no significant differences between the groups were found on any of the time points . Functional outcomes were also similar in both approaches . CONCLUSION No difference in tissue damage measured with serum markers CK and CRP were found between the DAA and PLA for total hip arthroplasty"
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4118767e-06ff-11f0-808a-c43d1ab1c353
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The purpose of the activity reported in this article was to conduct an exhaustive search of the Journal of Music Therapy , filter the articles on the desired parameters , and organize data for analysis and interpretation . Specifically , the research er studied whether ( a ) there was a significant difference in physiological measures , ( b ) there was a significant difference in quality of life , ( c ) there was a significant difference in satisfaction levels , ( d ) there was a significant difference in pain reduction , ( e ) there was a significant difference in procedural length , ( f ) there was a significant difference in length of stay , and ( g ) whether the overall effect size and 95 % confidence level support the recommendation of music therapy in the health care setting . Twenty-four studies met criteria for inclusion in the systematic review . Results revealed an overall effect size of d = 0.61 . However , results of the 95 % confidence interval included 0 , which suggests that there may not be a statistically significant difference in the health care setting on desired measures . Further results and implication s are discussed within the article
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"The purpose of this study was to assess the effects of music therapy on pain and anxiety in pediatric burn patients during nursing procedures . Nine subjects were r and omly selected to participate in this study . Qualitative and quantitative data was collected on the patients ' pain , anxiety , heart rate , blood oxygenation , and engagement level through measurement tools and interviews . The results from the qualitative and quantitative data indicated that music therapy reduced pain , anxiety , and behavioral distress . The quantitative data were analyzed and an inverse relationship between engagement in music therapy and lower behavioral distress scores was noted . Additionally , a linear relationship between engagement and behavioral distress was noted ; significance was found but was moderated by the age of the child . However , no significant relationship was found between heart rate and behavioral distress . The results from the qualitative data from the interviews with the patients , parents , nurses and music therapist indicated that music therapy reduced pain and anxiety , and that engagement in music therapy enhanced relaxation . In addition , music therapy positively affected patients ' mood , compliance , and the relaxation level . Finally , parents/guardians and nurses involved in the study reported that music therapy helped them to feel more relaxed as well",
"Cancer patients continue to experience elevated levels of emotional distress , even after cancer treatment . Elevated emotional distress negatively impacts immune and endocrine functions and decreases life quality . This study explored the effectiveness of GIM in alleviating mood disturbance and improving quality of life in cancer patients . Eight volunteers with a cancer history were r and omly assigned to either an experimental or a wait-list control group . Experimental subjects individually participated in 10 weekly GIM sessions . All subjects completed the Profile of Mood States ( POMS ) and Quality of Life-Cancer ( QOL-CA ) question naires pretest , posttest , and at a 6-week follow-up . Individuals who participated in GIM sessions scored better on both mood scores and quality of life scores at posttest than those participating in the control group . Additionally , mood and quality of life scores continued to improve in the experimental group , even after sessions were complete . Results indicate that GIM was effective in improving mood and quality of life in these cancer patients",
"This study examined the effects of parent training in music and multimodal stimulation on the quantity and quality of parent-neonate interactions and the weight gain and length of hospitalization of premature and low birthweight ( LBW ) infants in a Neonatal Intensive Care Unit ( NICU ) . Twenty sets of parents and premature LBW infants participated in the study . Parents in the experimental group ( n = 10 ) received approximately one hour of instruction in appropriate uses of music , multimodal stimulation including massage techniques , and signs of infant overstimulation and techniques for its avoidance . Parent-neonate interactions , specifically parent actions and responses and infant stress and nonstress behaviors , were observed for subjects in both groups . Infant stress behaviors were significantly fewer and appropriateness of parent actions and responses were significantly greater for experimental infants and parents than for control subjects . Parents in the experimental group also self-reported spending significantly more time visiting in the NICU than did parents of control infants . In addition , length of hospitalization was shorter and average daily weight gain was greater for infants whose parents received training , although these differences were not significant . A one month , postdischarge follow-up showed little difference between experimental and control group parent-infant interactions in the home",
"Receiving vaccinations is a part of growing up ; however , as necessary as vaccinations are , many children find them to be frightening and painful . Music has been examined as a potential distraction during pediatric medical procedures , but research findings have been mixed , due , in part , to the fact that children were primarily instructed to merely \" listen to the music . \" The present study sought to determine if a focus of attention activity involving music would affect levels of distress and perceptions of pain in pediatric injection patients . Sixty-four 4- to 6(1/2 ) -year old children receiving routine immunizations were r and omly assigned to one of three conditions : musical story , spoken story , or st and ard care/control . Children in the two treatment conditions listened to a recorded story and pointed at corresponding pictures throughout the injection process . Observational data on distress and pain were collected , in addition to the child 's self-rating of pain . Participants in the musical story condition tended to be less distressed and report less pain than participants in the other two conditions , although these differences were not statistically significant . Subsequent analysis indicated that children who received more injections tended to benefit more from the music intervention , in terms of their perceived pain",
"The purpose of this study was to examine the effects of music , progressive muscle relaxation ( PMR ) , and music combined with progressive muscle relaxation on the reduction of anxiety , fatigue , and improvement of quality of life in family hospice caregivers . Subjects ( N = 32 ) were divided r and omly into 4 groups : control , music only , progressive muscle relaxation only , and music combined with progressive muscle relaxation and were tested twice a week for a duration of 2 weeks . A pre and posttest measuring anxiety and fatigue was administered each session . Quality of life was measured only on the first and last session . Results of three-way mixed design ANOVA indicated no significant main effect for group . However , results revealed a significant main effect for pretest and posttest on anxiety F(1 , 28 ) = 51.82 , p fatigue , F(1 , 28 ) = 32.86 , p anxiety F(3 , 84 ) = 3.53 , p fatigue F(3 , 84 ) = 5.21 , p quality of life when comparing the subject sample as a whole across the four days of treatment period , F(1 , 28 ) = 14.21 , p pre and posttest quality of life scores . There was a significant correlation between anxiety and quality of life ( r(32 ) = .75 , p anxiety and fatigue ( r(32 ) = .55 , p fatigue and quality of life ( r(32 ) = -.53 , p < .01 )",
"This study tested effectiveness of music therapy in improving health-related outcomes of cardiac rehabilitation patients . Using a r and omized , controlled trial with follow-up , the study was conducted in an outpatient cardiac rehabilitation program in Ohio . Sixty-eight of 103 recruited patients , 30 to 80 years of age , completed the protocol through posttreatment . Physiological and psychological outcomes were measured . Cardiac rehabilitation patients were r and omly assigned to cardiac rehabilitation only or to music therapy plus cardiac rehabilitation . Music therapy included musical experiences , counseling , and Music-Assisted Relaxation and Imagery . The None hypothesis of no differences in health-related outcomes between cardiac rehabilitation patients who experienced cardiac rehabilitation with and without music therapy was rejected due to changes in systolic blood pressure pre to post-treatment . Interpretation of changes at 4 months posttreatment in anxiety , general health , and social functioning are limited , due to small sample sizes at follow-up . Pre to post-music therapy session improvements were also reported . Findings suggest that some health-related outcomes may be affected positively by participation in music therapy in addition to cardiac rehabilitation . Attrition contributed to limitations in statistical power",
"Organ transplant recipients characteristically experience low levels of relaxation and high levels of anxiety , pain , and nausea . Although music therapy has demonstrated effectiveness in ameliorating these types of conditions with patients in other areas of medical hospitals , no studies have evaluated the effects of music therapy on solid organ transplant patients . The purpose of this study was to assess the impact of music therapy on anxiety , relaxation , pain , and nausea levels in recovering patients on the adult transplant unit of the hospital utilizing a pre-posttest design . Participants ( N = 58 ) received an individual 15 - 35 minute music therapy session consisting of live patient-preferred music and therapeutic social interaction . To remain consistent with the hospital 's evaluative instruments during this pilot study , participants ' self-reported levels of anxiety , relaxation , pain , and nausea , were based on separate 10-point Likert-type scales . The principal investigator observed affect and verbalizations at pre and posttest . Results indicated there were significant improvements in self-reported levels of relaxation , anxiety ( both p pain ( p nausea ( p positive verbalizations and positive affect ( p music therapy again during a future long-term hospital stay . From the results of this exploratory study , it seems that music therapy can be a viable psychosocial intervention for hospitalized postoperative solid transplant patients . Implication s for clinical practice and suggestions for future research are provided",
"The purpose of this study was to evaluate the effects of music therapy on quality of life , length of life in care , physical status , and relationship of death occurrence to the final music therapy interventions of hospice patients diagnosed with terminal cancer . Subjects were adults who were living in their homes , receiving hospice care , and were diagnosed with terminal cancer . A total of 80 subjects participated in the study and were r and omly assigned to one of two groups : experimental ( routine hospice services and clinical music therapy ) and control ( routine hospice services only ) . Groups were matched on the basis of gender and age . Quality of life was measured by the Hospice Quality of Life Index-Revised ( HQOLI-R ) , a self-report measure given every visit . Functional status of the subjects was assessed by the hospice nurse during every visit using the Palliative Performance Scale . All subjects received at least two visits and quality of life and physical status assessment s. A repeated measures ANOVA revealed a significant difference between groups on self-report quality of life scores for visits one and two . Quality of life was higher for those subjects receiving music therapy , and their quality of life increased over time as they received more music therapy sessions . Subjects in the control group , however , experienced a lower quality of life than those in the experimental group , and without music , their quality of life decreased over time . There were no significant differences in results by age or gender of subjects in either condition . Furthermore , there were no significant differences between groups on physical functioning , length of life , or time of death in relation to the last scheduled visit by the music therapist or counselor . This study provides an overview of hospice/palliative care , explains the role of music therapy in providing care , and establishes clinical guidelines grounded in research for the use of music therapy in improving the quality of life among the terminally ill",
"This study examined the physiologic and behavioral effects of music-reinforced nonnutritive sucking ( NNS ) for preterm , low birthweight ( LBW ) infants experiencing heelstick . Subjects were 60 infants , age 32 to 37 weeks post conceptional age in a neonatal intensive care unit . Infants were r and omly assigned to one of three treatment groups : pacifier-activated lullaby ( PAL ) , pacifier-only , and no-contact . Experimental infants were provided the Sondrex PAL System , which plays music contingent on infant sucking . Pacifier-only infants did not receive music reinforcement for sucking , and no-contact infants were not provided a pacifier or music at any point during the procedure . Stress level and behavior state were assessed continuously and heart , respiratory , and oxygen saturation rates were recorded at 15-second intervals for all infants . Most physiologic data results were inconclusive . However , analysis of behavior state and stress level revealed the following significant differences for the PAL and pacifier-only groups compared to the no-contact group , all of which were greatest between the PAL and no-contact groups : lower during-heelstick behavior state means , less time in undesirable behavior states , lower during- and post-heelstick stress level means , and smaller behavior state and stress level differences between intervals . In addition , the PAL group had a significantly lower pre-heelstick stress level mean than the no-contact group . Behavior state and stress level were also more stable across time for the PAL group than the other groups , and patterns of changes in oxygen saturation , behavior state , and stress level indicate that music-reinforced NNS may facilitate return to homeostasis",
"BACKGROUND Individuals undergoing cardiac catheterization are likely to experience elevated anxiety periprocedurally , with highest anxiety levels occurring immediately prior to the procedure . Elevated anxiety has the potential to negatively impact these individuals psychologically and physiologically in ways that may influence the subsequent procedure . OBJECTIVE This study evaluated the use of music therapy , with a specific emphasis on emotional-approach coping , immediately prior to cardiac catheterization to impact periprocedural outcomes . METHODS The r and omized , pretest/posttest control group design consisted of two experimental groups -- the Music Therapy with Emotional-Approach Coping group [ MT/EAC ] ( n = 13 ) , and a talk-based Emotional-Approach Coping group ( n = 14 ) , compared with a st and ard care Control group ( n = 10 ) . RESULTS MT/EAC led to improved positive affective states in adults awaiting elective cardiac catheterization , whereas a talk-based emphasis on emotional-approach coping or st and ard care did not . All groups demonstrated a significant overall decrease in negative affect . The MT/EAC group demonstrated a statistically significant , but not clinical ly significant , increase in systolic blood pressure most likely due to active engagement in music making . The MT/EAC group trended toward shortest procedure length and least amount of anxiolytic required during the procedure , while the EAC group trended toward least amount of analgesic required during the procedure , but these differences were not statistically significant . CONCLUSIONS Actively engaging in a session of music therapy with an emphasis on emotional-approach coping can improve the well-being of adults awaiting cardiac catheterization procedures",
"Music therapy has decreased anxiety levels in many medical setting s. This r and omized clinical trial examined the effectiveness of a music listening intervention , delivered by a board-certified music therapist , in patients undergoing curative radiation therapy ( RT ) . Emotional distress ( anxiety , depression , and treatment-related distress ) and symptoms ( fatigue and pain ) were measured at baseline , mid-treatment , and end of treatment in 63 patients undergoing RT . Although patients who listened to self-selected music reported lower anxiety and treatment-related distress , there was a decline in these outcomes for patients in both groups over the course of RT . Depression , fatigue , and pain were not appreciably affected by music therapy . Within the music group , there was a significant correlation between number of times music was used/week and the change in treatment-related distress , suggesting that higher doses of music produced greater declines in distress . While these findings provided some support for the use of music in reducing distress during RT , further research demonstrating clear differences between intervention and control conditions is needed . Physical symptoms were not affected by the use of music over the course of RT",
"BACKGROUND Solid organ transplant patients often experience a variety of psychosocial stressors that can lead to distress and may hinder successful recovery . Using coping-infused dialogue ( CID ) through patient- preferred live music ( PPLM ) music therapy sessions may improve mood and decrease pain while also imparting psychoeducational knowledge concerning the identification of local and global problems and coping skills . OBJECTIVE The purpose of this pilot study was to develop a coping-based medical music therapy protocol that combines coping-infused dialogue ( CID ) with patient-preferred live music ( PPLM ) and measure the effects of the result ing CID-PPLM protocol on mood ( positive and negative affect ) and pain in hospitalized transplant patients . METHODS Our study used a pre-/posttest single-session wait-list control design . Participants ( N=25 ) were r and omly assigned to experimental ( CID-PPLM ) or control ( usual care ) conditions . Participants in the CID-PPLM condition received a single 30-minute session that integrated stressor identification and knowledge of coping skills ( CID ) with patient-preferred live music ( PPLM ) . RESULTS Results indicated no between-group differences at pretest and significant correlations between pre- and posttest measures . Concerning posttest ANCOVA analyses , there were significant between-group differences in positive affect , negative affect , and pain , with experimental participants having more favorable posttest scores than control participants . Effect sizes were in the medium-to-large range for positive affect ( η2=.198 ) , negative affect ( η2=.422 ) , and pain ( η2=.303 ) . CONCLUSIONS CID through receptive PPLM may be an effective protocol for improving mood and decreasing pain in organ transplant recipients . MT interventions can be an important tool to develop rapport and enhance outcomes with patients . As greater engagement during interventions may have stronger treatment effects , we recommend future research examining patient engagement as a potential mediator of intervention effects , as well as the number of sessions required to maximize clinical outcomes",
"The purpose of this study was to assess the effects of music therapy on pain and anxiety in pediatric burn patients during a donor site dressing change . Fourteen subjects were r and omly selected to participate in this study . The experiment was conducted in the Reconstructive Unit of Shriners Burns Hospital-Boston . The experimental group 's intervention consisted of live music and was compared to a control group whose intervention was verbal interaction . Psychological , behavioral , and physiological data were assessed through the Wong Baker FACES Pain Rating Scale , the Fear Thermometer , the Nursing Assessment of Pain Index , heart rate , and respiration rate . Data were analyzed using the ANCOVA , Mann-Whitney U , and regression analysis . The results were mixed and inconclusive . The members of the experimental group reported anecdotal information about the effects of music on pain and anxiety . An exploration of the limitations of the study and suggestions for further study are discussed",
"The physiological and psychological stress that brain tumor patients undergo during the entire surgical experience can considerably affect several aspects of their hospitalization . The purpose of this study was to examine the effects of live music therapy on quality of life indicators , amount of medications administered and length of stay for persons receiving elective surgical procedures of the brain . Subjects ( N = 27 ) were patients admitted for some type of surgical procedure of the brain . Subjects were r and omly assigned to either the control group receiving no music intervention ( n = 13 ) or the experimental group receiving pre and postoperative live music therapy sessions ( n = 14 ) . Anxiety , mood , pain , perception of hospitalization or procedure , relaxation , and stress were measured using a self-report Visual Analog Scale ( VAS ) for each of the variables . The documented administration of postoperative pain medications ; the frequency , dosage , type , and how it was given was also compared between groups . Experimental subjects live and interactive music therapy sessions , including a pre-operative session and continuing with daily sessions until the patient was discharged home . Control subjects received routine hospital care without any music therapy intervention . Differences in experimental pretest and posttest scores were analyzed using a Wilcoxon Matched-Pairs Signed-Rank test . Results indicated statistically significant differences for 4 of the 6 quality of life measures : anxiety ( p = .03 ) , perception of hospitalization ( p = .03 ) , relaxation ( p = .001 ) , and stress ( p = .001 ) . No statistically significant differences were found for mood ( p > .05 ) or pain ( p > .05 ) levels . Administration amounts of nausea and pain medications were compared with a Two-Way ANOVA with One Repeated Measure result ing in no significant differences between groups and medications , F(1 , 51 ) = 0.03 ; p > .05 . Results indicate no significant differences between groups for length of stay ( t = .97 , df = 25 , p > .05 ) . This research study indicates that live music therapy using patient-preferred music can be beneficial in improving quality of life indicators such as anxiety , perception of the hospitalization or procedure , relaxation , and stress in patients undergoing surgical procedures of the brain",
"Liver and kidney transplant recipients report elevated psychological distress following transplant in comparison to other types of organ transplant recipients . Negative affective states can lead to immune dysregulation and adverse health behaviors , and therefore may contribute to disease . In contrast , positive affective states can broaden individuals ' thoughts and actions to promote the accumulation of coping re sources . Coping strategies have traditionally been conceived of as being either problem-focused or emotion-focused in nature , while contemporary theory and research supports a different division : approach-oriented strategies versus avoidance-oriented strategies . Emotional expression and processing may function as an approach-oriented coping strategy . Emotional-approach coping relates to the use of emotional expression , awareness and underst and ing to facilitate coping with significant life stressors . The current study evaluated the impact of music therapy with and without a specific emphasis on emotional-approach coping . This r and omized , controlled trial aim ed to use Active Music Engagement with Emotional-Approach Coping to improve well-being in post-operative liver and kidney transplant recipients ( N = 29 ) . Results indicated that music therapy using Emotional-Approach Coping led to significant increases in positive affect , music therapy using Active Music Engagement led to significant decreases in pain , and both conditions led to significant decreases in negative affect , an indicator of perceived stress/anxiety",
"The purpose of this research was to determine the effects of mothers ' singing on their adjustment to and bonding with their new infants as well as use of music in the home environment in the first 2 weeks after their infants ' birth . Preterm mothers were assessed for coping with their infants ' NICU stay , and premature infants ' length of hospitalization was evaluated . Fifty-four full-term infants and mothers and 20 premature infants and 16 mothers were r and omly assigned to experimental or control conditions . Mothers in both experimental groups were recorded singing songs of their choice for use at home . Recordings of each preterm mother 's voice were played 20 minutes per day , 3 to 5 times per week , at a time when she was not able to visit her infant in the NICU . All full-term and preterm mothers in experimental and control groups completed a posttest survey 2 weeks after infants were discharged . Comparisons revealed that experimental preterm and full-term mothers indicated less adjustment to their baby and lifestyle changes and less bonding compared to control mothers , though this difference was not significant . Preterm and full-term experimental mothers reported the greatest number of postpartum medical complications , which might explain their poor adjustment and bonding scores . There was a significant difference between mothers ' value of music , with preterm experimental valuing music more . Preterm and full-term experimental mothers used music with and sang to infants more compared to preterm and full-term control mothers , but not to a significant degree . Preterm mothers reported a mean score of 4.75 ( with a 5 indicating that they strongly agreed ) for the following item : knowing my infant listened to my singing helped me to cope with my infant 's stay in the NICU . Furthermore , preterm infants who listened to the CD recording of their mothers ' singing left the hospital an average of 2 days sooner than those in the control group , though this difference was not significant",
"This project investigated music therapy ( MT ) in managing anxiety associated with weaning from mechanical ventilation . The use of sedation to treat anxiety during weaning is problematic because side effects ( e.g. , respiratory depression ) are precisely the symptoms that cause the weaning process to be interrupted and consequently prolonged . Study goals were to determine the feasibility of incorporating MT into the weaning process and to evaluate the efficacy of the intervention , based on levels of anxiety , Days to Wean ( DTW ) , and patient/nurse satisfaction . Adult patients received multiple MT sessions per week while undergoing weaning trials from mechanical ventilation . Feasibility was determined by successful enrollment in the study and nurse survey . Efficacy was evaluated through anxiety , as measured by heart rate , respiratory rate , and patient/nurse survey ; DTW ; and patient/nurse satisfaction . Nurse surveys reported that MT was successfully incorporated into the milieu and 61 subjects were enrolled . Significant differences in heart rate and respiratory rate were found from the beginning to the end of MT sessions ( p mean DTW was found between study and control subjects . Patient/nurse satisfaction was high . Music therapy can be used successfully to treat anxiety associated with weaning from mechanical ventilation . Limitations and suggestions for further research are discussed"
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411876ba-06ff-11f0-808a-c43d1ab1c353
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Objective : To determine the method ological quality of studies evaluating orthopaedic shoes and orthopaedic shoe provisions . To what extent do studies evaluating orthopaedic shoes prescribed for patients with degenerative disorders of the foot , rheumatoid arthritis , diabetes mellitus and neurological foot disorders , focus on the aspects of the International Organization for St and ardization ( ISO ) definition of usability , i.e. , effectiveness , efficiency , satisfaction , and context of use ? Design : Systematic review . Methods : A systematic literature search was performed to identify r and omized controlled trials ( RCTs ) concerning orthopaedic shoes and orthopaedic shoe inserts . The method ological quality of the studies was assessed independently by two raters , based on the 19 items of the ‘ Maastricht – Amsterdam criteria list ’ . The studies were assessed against the parameters of the ISO definition of usability . Results : Eleven RCTs were included . The method ological scores ranged from 8 to 14 out of 19 possible points . Eleven studies focused on the effectiveness of the orthopaedic shoes and orthopaedic shoe inserts , two of which reported outcome measures and conclusions related to the efficiency of the studied orthopaedic shoes and orthopaedic shoe inserts . Four studies reported some form of patient satisfaction and only three studies paid attention to the context of use . Conclusions : The method ological quality of the RCTs as assessed according to the 19 different criteria varied considerably . The present review shows that current scientific literature concerning the usability of orthopaedic shoes focuses mainly on effectiveness at the expense of the other domains of usability , i.e. , efficiency , satisfaction and context of use
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"CONTEXT Hallux valgus is a common foot deformation in adults , but evidence for effectiveness of surgical and conservative treatments for this condition is limited . OBJECTIVE To compare the effectiveness of surgical and orthotic treatment with no treatment in patients with hallux valgus . DESIGN AND SETTING R and omized controlled trial conducted in 4 general community hospitals in Finl and in 1997 - 1998 , with a follow-up period of 12 months . PARTICIPANTS Two hundred nine consecutive patients ( mean age , 48 years ; 93 % women ) with a painful bunion and a hallux valgus angle 35 degrees or less . INTERVENTIONS Patients were r and omly assigned to surgery ( distal chevron osteotomy ; n = 71 ) , orthosis ( n = 69 ) , or a 1-year waiting list ( control group , n = 69 ) . MAIN OUTCOME MEASURES Pain intensity during walking on a visual analog scale ( 0 - 100 ) , patient assessment of global improvement , number of painful days , cosmetic disturbance , footwear problems , functional status , and treatment satisfaction , compared among treatment groups . RESULTS Follow-up rates at 6 and 12 months were 99 % and 98 % , respectively . At 6 months , pain intensity decreased more in the surgical group than in the control group ( adjusted mean differences , -20 [ 95 % confidence interval ( CI ) , -28 to -12 ] ) and more in orthosis than in the control groups ( adjusted mean difference , -14 [ 95 % CI , -22 to -6 . At 1 year , pain intensity decreased more in the surgical than in the control groups ( adjusted mean difference , -19 [ 95 % CI , -28 to -10 ] ) and more than in the surgical and orthosis groups ( adjusted mean difference , -14 [ 95 % CI , -22 to -5 ] ) . At 1 year , 83 % , 46 % , and 24 % in the surgery , orthosis , and control groups , respectively , thought they had improved compared with baseline ( number needed to treat ) , 1.7 between surgical and control groups ) . Number of painful days , cosmetic disturbance , and footwear problems were least and functional status and satisfaction with treatment were best in the surgical group . CONCLUSIONS Surgical osteotomy is an effective treatment for painful hallux valgus . Orthoses provide short-term symptomatic relief",
"OBJECTIVE To evaluate the efficacy of manufactured shoes specially design ed for diabetic patients ( Podiabetes by Buratto Italy ) to prevent relapses of foot ulcerations . RESEARCH DESIGN AND METHODS A prospect i ve multicenter r and omized follow-up study of patients with previous foot ulcerations was conducted . Patients were alternatively assigned to wear either their own shoes ( control group , C ; n = 36 ) or therapeutic shoes ( Podiabetes group , P ; n = 33 ) . The number of ulcer relapses was recorded during 1-year follow-up . RESULTS Both C and P groups had similar risk factors for foot ulceration ( i.e. , previous foot ulceration , mean vibratory perception threshold > 25 mV ) . After 1 year , the foot ulcer relapses were significantly lower in P than in C ( 27.7 vs. 58.3 % ; P = 0.009 ; odds ratio 0.26 [ 0.2–1.54 ] ) . In a multiple regression analysis , the use of therapeutic shoes was negatively associated with foot ulcer relapses ( coefficient of variation = −0.315 ; 95 % confidence interval = −0.54 to −0.08 ; P = 0.009 ) . CONCLUSIONS The use of specially design ed shoes is effective in preventing relapses in diabetic patients with previous ulceration",
"OBJECTIVE To assess the clinimetric value of the Dutch version of the Foot Function Index ( FFI ) in comparison with the original FFI using verbal rating scales ( FFI-5pt ) rather than visual analog scales ( VAS ) . METHODS A prospect i ve study was performed on 206 patients with nontraumatic forefoot complaints . Scoring , internal consistency , and construct validity of the FFI-5pt were compared with those of the original FFI , which rates all items on VAS . We also studied agreement between the scores at baseline and after one and 8 weeks and the scale scores with regard to sex , age , presence of osteoarthritis , limitation of mobility , bodily pain , and poor physical functioning ( using SF-36 ) . RESULTS Some items were not applicable ; removal of these items left 2 scales ( Pain and Disability ) with high internal consistency ( alpha = 0.88 to 0.94 ) and good agreement between both versions ( intraclass correlation coefficient 0.64 to 0.79 ) . Principal component analysis with varimax rotation using a forced 2 factor model fitted well ( 65 % explained variance ) . Test-retest reliability was high ( ICC 0.70 to 0.83 ) , while the stability over 8 weeks was lower , but still good ( ICC 0.63 to 0.71 ) . Responsiveness to change was low to moderate . However , a small number of patients reported an overall change ( 19 % ) . Scores of patients with limited mobility and poor physical health ( SF-36 ) were higher than those of patients with fewer physical problems , indicating good concurrent validity . CONCLUSION The FFI-5pt is a suitable generic measure . Its clinimetric properties are comparable with those of the original FFI . Its administration and data entry are less time consuming . However , responsiveness has to be more exactly assessed in an intervention study",
"CONTEXT Many people with diabetes experience lower-limb ulcers . Footwear has been implicated as a primary cause of foot ulcers , yet research is limited on the efficacy of shoe and insert combinations to prevent reulceration . OBJECTIVE To determine whether extra-depth and -width therapeutic shoes used with 2 types of inserts reduce reulceration in diabetic individuals with a history of foot ulcer . DESIGN , SETTING , AND PARTICIPANTS R and omized clinical trial of 400 diabetes patients with history of foot ulcer in 2 Washington State health care organizations who did not require custom shoes for foot deformity and were enrolled between August 1997 and December 1998 and followed up for 2 years . Data collected at regular intervals documented physical , foot , and diabetes characteristics ; footwear use ; foot lesions ; and ulcers . INTERVENTIONS Participants were r and omly assigned to receive 3 pairs of therapeutic shoes and 3 pairs of customized medium-density cork inserts with a neoprene closed-cell cover ( n = 121 ) ; to receive 3 pairs of therapeutic shoes and 3 pairs of prefabricated , tapered polyurethane inserts with a brushed nylon cover ( n = 119 ) ; or to wear their usual footwear ( controls ; n = 160 ) . MAIN OUTCOME MEASURE Foot reulceration , compared among the 3 groups . RESULTS Two-year cumulative reulceration incidence across the 3 groups was low : 15 % in the cork-insert group , 14 % in the prefabricated-insert group , and 17 % in controls . In the intent-to-treat analysis , patients assigned to therapeutic shoes did not have a significantly lower risk of reulceration compared with controls ( risk ratio [ RR ] for the cork-insert group , 0.88 ; 95 % confidence interval [ CI ] , 0.51 - 1.52 and RR the for prefabricated-insert group , 0.85 ; 95 % CI , 0.48 - 1.48 ) . All ulcer episodes in patients assigned to therapeutic shoes and 88 % wearing non study shoes occurred in patients with foot insensitivity . CONCLUSIONS This study of persons without severe foot deformity does not provide evidence to support widespread dispensing of therapeutic shoes and inserts to diabetic patients with a history of foot ulcer . Study shoes and custom cork or preformed polyurethane inserts conferred no significant ulcer reduction compared with control footwear . This study suggests that careful attention to foot care by health care professionals may be more important than therapeutic footwear but does not negate the possibility that special footwear is beneficial in persons with diabetes who do not receive such close attention to foot care by their health care providers or in individuals with severe foot deformities",
"OBJECTIVE To compare the effectiveness of total-contact casts ( TCCs ) , removable cast walkers ( RCWs ) , and half-shoes to heal neuropathic foot ulcerations in individuals with diabetes . RESEARCH DESIGN AND METHODS In this prospect i ve clinical trial , 63 patients with superficial noninfected , nonischemic diabetic plantar foot ulcers were r and omized to one of three off-loading modalities : TCC , half-shoe , or RCW . Outcomes were assessed at wound healing or at 12 weeks , whichever came first . Primary outcome measures included proportion of complete wound healing at 12 weeks and activity ( defined as steps per day ) . RESULTS The proportions of healing for patients treated with TCC , RCW , and half-shoe were 89.5 , 65.0 , and 58.3 % , respectively . A significantly higher proportion of patients were healed by 12 weeks in the TCC group when compared with the two other modalities ( 89.5 vs. 61.4 % , P = 0.026 , odds ratio 5.4 , 95 % CI 1.1 - 26.1 ) . There was also a significant difference in survival distribution ( time to healing ) between patients treated with a TCC and both an RCW ( P = 0.033 ) and half-shoe ( P = 0.012 ) . Patients were significantly less active in the TCC ( 600.1 + /- 320.0 daily steps ) compared with the half-shoe ( 1,461.8 + /- 1,452.3 daily steps , P = 0.04 ) . There was no significant difference in the average number of steps between the TCC and the RCW ( 767.6 + /- 563.3 daily steps , P = 0.67 ) or the RCW and the half-shoe ( P = 0.15 ) . CONCLUSIONS The TCC seems to heal a higher proportion of wounds in a shorter amount of time than two other widely used off-loading modalities , the RCW and the half-shoe",
"OBJECTIVES To assess the effectiveness of off-the-shelf orthopedic footwear for people with rheumatoid arthritis ( RA ) reporting chronic foot pain , in terms of self-reported pain and physical function , as well as objective ly measured gait variables using an electric footswitch walkway . METHODS A small , r and omized , controlled trial followed by a larger repeated measures analysis was used . RESULTS The control group ( n = 15 ) demonstrated no significant changes over a 2-month period in pain , physical function , or gait scores . In contrast , after supply of the footwear both the original footwear group ( n = 15 ) and the control group demonstrated significant improvements , with small to large effect sizes , in weight-bearing pain scores , physical function , gait velocity , and gait stride length without increases in use of arthritis medications or walking aids . CONCLUSION These data suggest that off-the-shelf orthopedic footwear is beneficial for people with RA even when subjects were unselected on basis of age , sex , disease duration , or disability as measured by the Stanford Health Assessment Question naire",
"A Foot Function Index ( FFI ) was developed to measure the impact of foot pathology on function in terms of pain , disability and activity restriction . The FFI is a self-administered index consisting of 23 items divided into 3 sub-scales . Both total and sub-scale scores are produced . The FFI was examined for test-retest reliability , internal consistency , and construct and criterion validity . A total of 87 patients with rheumatoid arthritis were used in the study . Test-retest reliability of the FFI total and sub-scale scores ranged from 0.87 to 0.69 . Internal consistency ranged from 0.96 to 0.73 . With the exception of two items , factor analysis supported the construct validity of the total index and the sub-scales . Strong correlation between the FFI total and sub-scale scores and clinical measures of foot pathology supported the criterion validity of the index . The FFI should prove useful for both clinical and research purpose",
"The effect of a magnetic foil placed in the PPT/Rx Firm Molded Insole on the relief of heel pain was determined using the foot function index . Nineteen patients wore the PPT/Rx Firm Molded Insoles with the magnetic foil for 4 weeks and 15 patients wore the same PPT/Rx Firm Molded Insole with no magnetic foil for the same time . Approximately 60 % of patients in both groups reported improvement . There was also no significant difference in the improvement between the magnetic foil group and the PPT/Rx Firm Molded Insole group in their scores on the post-treatment foot function index . These results suggest that the PPT/Rx Firm Molded Insole alone was effective in treating heel pain after only 4 weeks . The magnetic foil offered no advantage over the plain insole"
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411876f6-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND Hypertension is a chronic condition associated with an increased risk of mortality and morbidity . Renin is the enzyme responsible for converting angiotensinogen to angiotensin I , which is then converted to angiotensin II . Renin inhibitors are a new class of drugs that decrease blood pressure ( BP ) by preventing the formation of both angiotensin I and angiotensin II . OBJECTIVES To quantify the dose-related BP lowering efficacy of renin inhibitors compared to placebo in the treatment of primary hypertension . To determine the change in BP variability , pulse pressure , and heart rate and to evaluate adverse events ( mortality , non-fatal serious adverse events , total adverse events , withdrawal due to adverse effects and specific adverse events such as dry cough , diarrhoea and angioedema ) . SEARCH METHODS The Cochrane Hypertension Information Specialist search ed the following data bases for r and omized controlled trials ( RCTs ) up to February 2017 : the Cochrane Hypertension Specialized Register , the Cochrane Central Register of Controlled Trials ( CENTRAL ) ( 2017 , Issue 2 ) , MEDLINE ( from 1946 ) , Embase ( from 1974 ) , the World Health Organization International Clinical Trials Registry Platform , and Clinical Trials.gov . There was no restriction by language or publication status . We also search ed the European Medicines Agency ( EMA ) for clinical study reports , the Novartis Clinical Study Results Data base , bibliographic citations from retrieved references , and contacted authors of relevant papers regarding further published and unpublished work . SELECTION CRITERIA We included r and omized , double-blinded , placebo-controlled studies evaluating BP lowering efficacy of fixed-dose monotherapy with renin inhibitor compared with placebo for a minimum duration of three to 12 weeks in adult patients with primary hypertension . DATA COLLECTION AND ANALYSIS This systematic review is a comprehensive up date which includes four additional studies and extensive detail from nine clinical study reports ( CSRs ) of previously included studies obtained from EMA . The remaining three CSRs are not available . Two review authors independently assessed study eligibility and extracted data . In all cases where there was a difference between the CSR and the published report , data from the CSR was used . Dichotomous outcomes were reported as risk ratio ( RR ) with 95 % confidence intervals ( CIs ) and continuous outcomes as mean difference ( MD ) with 95 % CIs . MAIN RESULTS 12 studies ( mean duration of eight weeks ) in 7439 mostly Caucasian patients ( mean age 54 years ) with mild-to-moderate uncomplicated hypertension were eligible for inclusion in the review . Aliskiren was the only renin inhibitor evaluated . All included studies were assessed to have high likelihood of attrition , reporting and funding bias . Aliskiren has a dose-related systolic/diastolic blood pressure ( SBP/DBP ) lowering effect as compared with placebo MD with 95 % CI : aliskiren 75 mg ( MD -2.97 , 95 % CI -4.76 to -1.18)/(MD -2.05 , 95 % CI -3.13 to -0.96 ) mm Hg ( moderate- quality evidence ) , aliskiren 150 mg ( MD -5.95 , 95 % CI -6.85 to -5.06)/ ( MD -3.16 , 95 % CI -3.74 to -2.58 ) mm Hg ( moderate- quality evidence ) , aliskiren 300 mg ( MD -7.88 , 95 % CI -8.94 to -6.82)/ ( MD -4.49 , 95 % CI -5.17 to -3.82 ) mm Hg ( moderate- quality evidence ) , aliskiren 600 mg ( MD -11.35 , 95 % CI -14.43 to -8.27)/ ( MD -5.86 , 95 % CI -7.73 to -3.99 ) mm Hg ( low- quality evidence ) . There was a dose-dependent decrease in blood pressure for aliskiren 75 mg , 150 mg and 300 mg . The blood pressure lowering effect of aliskiren 600 mg was not different from 300 mg ( MD -0.61 , 95 % CI -2.78 to 1.56)/(MD -0.68 , 95 % CI -2.03 to 0.67 ) . Aliskiren had no effect on blood pressure variability . Due to very limited information available regarding change in heart rate and pulse pressure , it was not possible to meta-analyze these outcomes .Mortality and non-fatal serious adverse events were not increased . This review found that in studies of eight week duration aliskiren may not increase withdrawal due to adverse events ( low- quality evidence ) . Diarrhoea was increased in a dose-dependent manner ( RR 7.00 , 95 % CI 2.48 to 19.72 ) with aliskiren 600 mg ( low- quality evidence ) . The most frequent adverse events reported were headache , nasopharyngitis , diarrhoea , dizziness and fatigue . AUTHORS ' CONCLUSIONS Compared to placebo , aliskiren lowered BP and this effect is dose-dependent . This magnitude of BP lowering effect is similar to that for angiotensin-converting enzyme ( ACE ) inhibitors and angiotensin receptor blockers ( ARBs ) . There is no difference in mortality , nonfatal serious adverse events or withdrawal due to adverse effects with short term aliskiren monotherapy . Diarrhoea was considerably increased with aliskiren 600 mg
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"AIMS Elevated natriuretic peptides ( NPs ) are associated with an increased cardiovascular risk following acute coronary syndromes ( ACSs ) . However , the therapeutic implication s are still undefined . We hypothesized that early inhibition of renin-angiotensin-aldosterone system ( RAAS ) in patients with preserved left ventricular function but elevated NPs but following ACS would reduce haemodynamic stress as reflected by a greater reduction NP compared with placebo . METHODS AND RESULTS AVANT GARDE-TIMI 43 trial , a multinational , double-blind trial , r and omized 1101 patients stabilized after ACS without clinical evidence of heart failure or left ventricular function aliskiren , valsartan , their combination , and placebo . The primary endpoint was the change in NT-proBNP from baseline to Week 8 . NT-proBNP declined significantly in each treatment arm , including placebo , by Week 8 , though there were no differences in the reduction between treatment strategies ( 42 % in placebo , 44 % in aliskiren , 39 % in valsartan , and 36 % in combination arm ) . Although several subgroups had higher baseline levels of NP and greater reductions over the study period , there were no differences among treatment groups in any subgroup . There were no differences in clinical outcomes but there were more adverse events , including serious events and adverse events leading to early study drug discontinuation , in patients treated with active therapy . CONCLUSION In this study of a high-risk population with elevated levels of NPs but relatively preserved systolic function and no evidence of heart failure following ACS , there was no evidence for a benefit of early initiation of inhibition of RAAS with valsartan , aliskiren , or their combination compared with placebo with respect to a reduction in NP over 8 weeks of therapy . Moreover , adverse events were reported more frequently in patients assigned to active therapy",
"Aliskiren is a novel orally active renin inhibitor for the treatment of hypertension . This study evaluated the antihypertensive efficacy , safety and tolerability of aliskiren in Japanese patients with hypertension . Forty hundred and fifty-five Japanese men and women with a mean sitting diastolic blood pressure of 95–110 mmHg were r and omized to receive once-daily double-blind treatment for 8 weeks with aliskiren 75 , 150 or 300 mg or placebo . Aliskiren produced significant , dose-dependent reductions in mean sitting diastolic blood pressure ( p and mean sitting systolic blood pressure ( p in mean sitting systolic/diastolic blood pressure were 5.7/4.0 , 5.9/4.5 and 11.2/7.5 mmHg in the aliskiren 75 , 150 and 300 mg groups , respectively . After 8 weeks ' treatment , 27.8 % , 47.8 % , 48.2 % and 63.7 % of patients in the placebo and aliskiren 75 , 150 and 300 mg groups , respectively , achieved a successful treatment response ( diastolic blood pressure . Aliskiren treatment was well tolerated , with the incidence of adverse events reported in the active treatment groups ( 53–55 % ) being similar to that in the placebo group ( 50 % ) . This study , which is the first to assess the antihypertensive efficacy and safety of aliskiren in Japanese patients with hypertension , demonstrates that the once-daily oral renin inhibitor aliskiren provides significant , dose-dependent reductions in blood pressure with placebo-like tolerability",
"Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged",
"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",
"Thiazide diuretics , angiotensin-converting enzyme inhibitors , and angiotensin receptor blockers all cause reactive rises in plasma renin activity . We hypothesized that renin inhibition with aliskiren would prevent this reactive rise and also enhance blood pressure lowering . In 3 open-label studies in which blood pressure was assessed with ambulatory measurement , aliskiren was administered to patients with mild-to-moderate hypertension in combination with hydrochlorothiazide ( n=23 ) , ramipril ( n=21 ) , or irbesartan ( n=23 ) . In the diuretic combination study , the addition of 25 mg of hydrochlorothiazide to 150 mg of aliskiren daily for 3 weeks significantly lowered daytime pressure , compared with aliskiren monotherapy ( systolic/diastolic mean change from baseline [ SEM ] : daytime : −18.4 [2.1]/ −10.6 [ 1.7 ] versus −10.4 [1.8]/−5.8 [ 1.4 ] ; nighttime : −15.6 [2.7]/−8.1 [ 1.8 ] versus −8.8 [2.9]/−5.0 [ 2.2 ] ) . In the angiotensin-converting enzyme inhibitor combination study , the addition of 75 or 150 mg of aliskiren to 5 mg of ramipril alone for 3 weeks further lowered both daytime and nighttime pressures compared with ramipril monotherapy ( daytime : −10.5 [2.9]/−8.1 [ 2.1 ] and −14 [3.7]/−8.7 [ 2.3 ] versus −6.1 [2.4]/−5.9 [ 1.5 ] ; nighttime : −8.1 [2.6]/−5.3 [ 2.4 ] and −9.6 [3.4]/−5.3 [ 2.4 ] versus −2 [2.3]/−0.7 [ 2.2 ] ) . In the angiotensin receptor blocker combination study , the addition of 75 or 150 mg of aliskiren to 150 mg of irbesartan alone , for 3 weeks , result ed in significantly lower nighttime pressures compared with irbesartan monotherapy ( daytime : −14.8 [2]/−8.2 [ 1.3 ] and −13.3 [1.6]/−6.8 [ 0.9 ] versus −11.4 [1.6]/−6.5 [ 1.1 ] ; nighttime : −16.1 [2.4]/−8.6 [ 1.7 ] and −13.2 [2.7]/−7.2 [ 1.9 ] versus −9.0 [2.5]/−4.7 [ 1.9 ] ) . Aliskiren ( 150 mg ) alone significantly inhibited plasma renin activity by 65 % ( P Ramipril and irbesartan monotherapy caused 90 % and 175 % increases in plasma renin activity , respectively . By contrast , when aliskiren was coadministered with hydrochlorothiazide , ramipril , or irbesartan , plasma renin activity did not increase but remained similar to baseline levels or was decreased ( combination therapy versus untreated ; median [ interquartile range ] ; aliskiren and hydrochlorothiazide : 0.4 [ 0.2 to 1.1 ] versus 0.7 [ 0.5 to 1.3 ] ; ramipril and aliskiren : 0.5 [ 0.3 to 0.9 ] versus 0.6 [ 0.5 to 0.8 ] ; irbesartan and aliskiren : 0.4 [ 0.2 to 0.9 ] versus 0.6 [ 0.4 to 0.9 ] ) . These results suggest that renin inhibition with aliskiren in these combinations increases renin-angiotensin system suppression , improves 24-hour blood pressure control , and may ultimately provide better end-organ protection in patients with hypertension",
"IMPORTANCE Blood pressure reduction and renin-angiotensin-aldosterone system inhibition are targets for treatment of atherosclerosis . The effect of renin inhibition on coronary disease progression has not been investigated . OBJECTIVE To determine the effects of renin inhibition with aliskiren on progression of coronary atherosclerosis . DESIGN , SETTING , AND PARTICIPANTS A double-blind , r and omized , multicenter trial ( Aliskiren Quantitative Atherosclerosis Regression Intravascular Ultrasound Study ) comparing aliskiren with placebo in 613 participants with coronary artery disease , systolic blood pressure between 125 and 139 mm Hg ( prehypertension range ) , and 2 additional cardiovascular risk factors conducted at 103 academic and community hospitals in Europe , Australia , and North and South America ( enrollment from March 2009 to February 2011 ; end of follow-up : January 31 , 2013 ) . INTERVENTIONS Participants underwent coronary intravascular ultrasound ( IVUS ) imaging and were r and omized to receive 300 mg of aliskiren ( n = 305 ) or placebo ( n = 308 ) taken orally daily for 104 weeks . Disease progression was measured by repeat IVUS examination after at least 72 weeks of treatment . MAIN OUTCOMES AND MEASURES The primary efficacy parameter was the change in percent atheroma volume ( PAV ) from baseline to study completion . Secondary efficacy parameters included the change in normalized total atheroma volume ( TAV ) and the percentage of participants with atheroma regression . Safety and tolerability were also assessed . RESULTS Evaluable imaging data were available at baseline and follow-up for 458 participants ( 74.7 % ) . The primary IVUS efficacy parameter , PAV , did not differ between participants treated with aliskiren ( -0.33 % ; 95 % CI , -0.68 % to 0.02 % ) and placebo ( 0.11 % ; 95 % CI , -0.24 % to 0.45 % ) ( between-group difference , -0.43 % [ 95 % CI , -0.92 % to 0.05 % ] ; P = .08 ) . The secondary IVUS efficacy parameter , TAV , did not differ between participants treated with aliskiren ( -4.1 mm3 ; 95 % CI , -6.27 to -1.94 mm3 ) and placebo ( -2.1 mm3 ; 95 % CI , -4.21 to 0.07 mm3 ) ( between-group difference , -2.04 mm3 [ 95 % CI , -5.03 to 0.95 mm3 ] ; P = .18 ) . There were no significant differences in the proportion of participants who demonstrated regression of PAV ( 56.9 % vs 48.9 % ; P = .08 ) and TAV ( 64.4 % vs 57.5 % ; P = .13 ) in the aliskiren and placebo groups , respectively . CONCLUSIONS AND RELEVANCE Among participants with prehypertension and coronary artery disease , the use of aliskiren compared with placebo did not result in improvement or slowing of progression of coronary atherosclerosis . These findings do not support the use of aliskiren for regression or prevention of progression of coronary atherosclerosis . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00853827",
"Current guidelines from the Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure recommend first-line treatment with a thiazide diuretic but do not provide specific guidance for obese patients . The renin system is activated in obesity-associated arterial hypertension . Therefore , we tested the hypothesis that the oral direct renin inhibitor aliskiren could provide additive blood pressure lowering in obese patients with hypertension ( body mass index ≥30 kg/m2 ; mean sitting diastolic blood pressure : 95 to 109 mm Hg ) who had not responded to 4 weeks of treatment with hydrochlorothiazide ( HCTZ ) 25 mg . After a 2- to 4-week washout , 560 patients received single-blind HCTZ ( 25 mg ) for 4 weeks ; 489 nonresponders were r and omly assigned to double-blind aliskiren ( 150 mg ) , irbesartan ( 150 mg ) , amlodipine ( 5 mg ) , or placebo for 4 weeks added to HCTZ ( 25 mg ) , followed by 8 weeks on double the initial doses of aliskiren , irbesartan , or amlodipine . After 8 weeks of double-blind treatment ( 4 weeks on the higher dose ) , aliskiren/HCTZ lowered blood pressure by 15.8/11.9 mm Hg , significantly more ( P Aliskiren/HCTZ provided blood pressure reductions similar to those with irbesartan/HCTZ and amlodipine/HCTZ ( 15.4/11.3 and 13.6/10.3 mm Hg , respectively ) , with similar tolerability to placebo/HCTZ . Adverse event rates were highest with amlodipine/HCTZ because of a higher incidence of peripheral edema ( 11.1 % versus 0.8 % to 1.6 % in other groups ) . In conclusion , combination treatment with aliskiren is a highly effective and well-tolerated therapeutic option for obese patients with hypertension who fail to achieve blood pressure control with first-line thiazide diuretic treatment ",
"Background —Stopping the detrimental effects of the renin-angiotensin system at the most upstream point of the cascade offers theoretical advantages for cardiovascular protection . This study compares the antihypertensive efficacy and safety of the novel oral renin inhibitor aliskiren with placebo and an active comparator . Methods and Results —The study was a r and omized , multicenter , double-blind , placebo-controlled , active-comparator 8-week trial in patients with mild-to-moderate hypertension ( mean sitting diastolic blood pressure [ DBP ] ≥95 and After a 2-week , single-blind placebo run-in , 652 patients were r and omized to receive double-blind treatment with once-daily oral doses of aliskiren ( 150 , 300 , or 600 mg ) , irbesartan 150 mg , or placebo . Aliskiren 150 , 300 , and 600 mg effectively lowered both trough mean sitting DBP and systolic blood pressure ( SBP ) ( P reductions in trough DBP were 9.3±0.8 , 11.8±0.8 , and 11.5±0.8 mm Hg , respectively , versus 6.3±0.8 mm Hg for placebo , and the least-squares mean reductions in trough SBP were 11.4±1.3 , 15.8±1.2 , and 15.7±1.2 mm Hg , respectively , versus 5.3±1.2 mm Hg for placebo . The antihypertensive effect of aliskiren 150 mg was comparable to that of irbesartan 150 mg ( 8.9±0.7 and 12.5±1.2 mm Hg , least-squares reduction in mean sitting DBP and SBP , respectively , for irbesartan ) . Aliskiren 300 and 600 mg lowered mean sitting DBP significantly more than irbesartan 150 mg ( P ) . Aliskiren showed safety and tolerability comparable to those of placebo and irbesartan ; the incidence of adverse events and number of patients discontinuing therapy were similar in all groups . Conclusions —Once-daily oral treatment with aliskiren lowers blood pressure effectively , with a safety and tolerability profile comparable to that of irbesartan and placebo , in patients with mild-to-moderate hypertension . Aliskiren 150 mg is as effective as irbesartan 150 mg in lowering blood pressure",
"Objective To determine the st and ard of reporting of harms-related data , in r and omised controlled trials ( RCTs ) according to the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement extension for harms . Design Systematic review . Data sources The Cochrane library , Ovid MEDLINE , Scopus and ISI Web of Knowledge were search ed for relevant literature . Eligibility criteria for selecting studies We included publications of studies that used the CONSORT harms extension to assess the reporting of harms in RCTs . Results We identified 7 studies which included between 10 and 205 RCTs . The clinical areas of the 7 studies were : hypertension ( 1 ) , urology ( 1 ) , epilepsy ( 1 ) , complimentary medicine ( 2 ) and two not restricted to a clinical topic . Quality of the 7 studies was assessed by a risk of bias tool and was found to be variable . Adherence to the CONSORT harms criteria reported in the 7 studies was inadequate and variable across the items in the checklist . Adverse events are poorly defined , with 6 studies failing to exceed 50 % adherence to the items in the checklist . Conclusions Readers of RCT publications need to be able to balance the trade-offs between benefits and harms of interventions . This systematic review suggests that this is compromised due to poor reporting of harms which is evident across a range of clinical areas . Improvements in quality could be achieved by wider adoption of the CONSORT harms criteria by journals reporting RCTs",
"AIMS Direct renin inhibitors provide an alternative approach to inhibiting the renin-angiotensin-aldosterone system ( RAAS ) at the most proximal , specific , and rate-limiting step . We tested the hypothesis that direct renin inhibition would attenuate left ventricular remodelling in patients following acute myocardial infa rct ion receiving stable , individually optimized therapy , including another inhibitor of the RAAS . METHODS AND RESULTS We r and omly assigned 820 patients between ∼2 and 8 weeks following acute myocardial infa rct ion , with the left ventricular ejection fraction ( LVEF ) ≤45 % , and regional wall motion abnormalities ( ≥20 % akinetic area ) , to receive aliskiren ( n = 423 ) , titrated to 300 mg , or matched placebo ( n = 397 ) , added to the st and ard therapy . All patients were required to be on a stable dose of an ACE-inhibitor or ARB , and beta-blocker unless contraindicated or not tolerated . Echocardiograms were obtained at baseline , and following 26 - 36 weeks of treatment . The primary endpoint was change in left ventricular end-systolic volume from baseline to 36 weeks , and was evaluable in 329 patients in the placebo group and 343 patients in the aliskiren group . We observed no difference in the primary endpoint of end-systolic volume change between patients r and omized to aliskiren ( -4.4 ± 16.8 mL ) or placebo ( -3.5 ± 16.3 mL ) , or in secondary measures of end-diastolic volume , or LVEF . We also observed no differences in a composite endpoint of cardiovascular death , hospitalization for heart failure , or reduction in LVEF > 6 points . There were more investigator reported adverse events in the aliskiren group , including hypotension , increases in creatinine and hyperkalaemia . CONCLUSION Adding the direct renin inhibitor aliskiren to the st and ard therapy , including an inhibitor of the RAAS , in high-risk post-MI patients did not result in further attenuation of left ventricular remodelling , and was associated with more adverse effects . These findings do not suggest that dual RAAS blockade with aliskiren would provide additional benefit in these high-risk post-MI patients",
"Objective To measure whether the benefits of a single education and self management structured programme for people with newly diagnosed type 2 diabetes mellitus are sustained at three years . Design Three year follow-up of a multicentre cluster r and omised controlled trial in primary care , with r and omisation at practice level . Setting 207 general practice s in 13 primary care sites in the United Kingdom . Participants 731 of the 824 participants included in the original trial were eligible for follow-up . Biomedical data were collected on 604 ( 82.6 % ) and question naire data on 513 ( 70.1 % ) participants . Intervention A structured group education programme for six hours delivered in the community by two trained healthcare professional educators compared with usual care . Main outcome measures The primary outcome was glycated haemoglobin ( HbA1c ) levels . The secondary outcomes were blood pressure , weight , blood lipid levels , smoking status , physical activity , quality of life , beliefs about illness , depression , emotional impact of diabetes , and drug use at three years . Results HbA1c levels at three years had decreased in both groups . After adjusting for baseline and cluster the difference was not significant ( difference −0.02 , 95 % confidence interval −0.22 to 0.17 ) . The groups did not differ for the other biomedical and lifestyle outcomes and drug use . The significant benefits in the intervention group across four out of five health beliefs seen at 12 months were sustained at three years ( P life did not differ at three years . Conclusion A single programme for people with newly diagnosed type 2 diabetes mellitus showed no difference in biomedical or lifestyle outcomes at three years although there were sustained improvements in some illness beliefs . Trial registration Current Controlled Trials IS RCT N17844016",
"Background Paclitaxel-eluting stents decrease angiographic and clinical restenosis following percutaneous coronary intervention compared to bare metal stents . TAXUS Element is a third-generation paclitaxel-eluting stent which incorporates a novel , thinner-strut , platinum-enriched metal alloy platform . The stent is intended to have enhanced radiopacity and improved deliverability compared to other paclitaxel-eluting stents . The safety and efficacy of the TAXUS Element stent are being evaluated in the pivotal PERSEUS clinical trials . Methods / Design The PERSEUS trials include two parallel studies of the TAXUS Element stent in single , de novo coronary atherosclerotic lesions . The PERSEUS Workhorse study is a prospect i ve , r and omized ( 3:1 ) , single-blind , non-inferiority trial in subjects with lesion length ≤28 mm and vessel diameter ≥2.75 mm to ≤4.0 mm which compares TAXUS Element to the TAXUS Express2 paclitaxel-eluting stent system . The Workhorse study employs a novel Bayesian statistical approach that uses prior information to limit the number of study subjects exposed to the investigational device and thus provide a safer and more efficient analysis of the TAXUS Element stent . PERSEUS Small Vessel is a prospect i ve , single-arm , superiority trial in subjects with lesion length ≤20 mm and vessel diameter ≥2.25 mm to that compares TAXUS Element with a matched historical bare metal Express stent control . Discussion The TAXUS PERSEUS clinical trial program uses a novel statistical approach to evaluate whether design and metal alloy iterations in the TAXUS Element stent platform provide comparable safety and improved procedural performance compared to the previous generation Express stent . PERSEUS trial enrollment is complete and primary endpoint data are expected in 2010 . PERSEUS Workhorse and Small Vessel are registered at http://www . clinical trials.gov , identification numbers NCT00484315 and NCT00489541",
"Abstract —Inhibition of the first and rate-limiting step of the renin-angiotensin system has long been an elusive therapeutic goal . Aliskiren , the first known representative of a new class of completely nonpeptide , orally active , renin inhibitors , has been shown to inhibit the production of angiotensin I and II in healthy volunteers and to reduce blood pressure ( BP ) in sodium-depleted marmosets . The aim of this r and omized , double-blind , active comparator trial study was to assess the BP-lowering efficacy and safety of aliskiren . Two hundred twenty-six patients , 21 to 70 years of age , with mild to moderate hypertension , were r and omly assigned to receive 37.5 mg , 75 mg , 150 mg , or 300 mg aliskiren or 100 mg losartan daily for 4 weeks . Dose-dependent reductions in daytime ambulatory systolic pressure ( mean change , mm Hg [ SD of change ] ; −0.4 [ 11.7 ] , −5.3 [ 11.3 ] , −8.0 [ 11.0 ] , and −11.0 [ 11.0 ] , P = 0.0002 ) and in plasma renin activity ( median change % [ interquartile range ] ; −55 [ −64 , −11 ] , −60 [ −82 , −46 ] , −77 [ −86 , −72 ] , and −83 [ −92 , −71 ] , P = 0.0008 ) were observed with 37.5 , 75 , 150 , and 300 mg aliskiren . The change in daytime systolic pressure with 100 mg losartan ( −10.9 [ 13.8 ] ) was not significantly different from the changes seen with 75 , 150 , and 300 mg aliskiren . Aliskiren was well tolerated at all doses studied . This study demonstrates that aliskiren , through inhibition of renin , is an effective and safe orally active BP-lowering agent . Whether renin inhibition results in protection from heart attack , stroke , and nephropathy , similar to angiotensin-converting enzyme inhibition and angiotensin receptor blockade , needs to be research ed",
"Table of contentsI1 Introduction Mona Kanaan , Noreen Dadirai Mdege , Ada KedingO1 The HiSTORIC trial : a hybrid before- and -after and stepped wedge design RA Parker , N Mills , A Shah , F Strachan , C Keerie , CJ WeirO2 Stepped wedge trials with non-uniform correlation structure And rew Forbes , Karla HemmingO3 Challenges and solutions for the operationalisation of the ENHANCE study : a pilot stepped wedge trial within a general practice setting Sarah A Lawton , Emma Healey , Martyn Lewis , Elaine Nicholls , Clare Jinks , Valerie Tan , And rew Finney , Christian D Mallen , on behalf of the ENHANCE Study TeamO4 Early lessons from the implementation of a stepped wedge trial design investigating the effectiveness of a training intervention in busy health care setting s : the Thistle study Erik Lenguerr and , Graeme MacLennan , John Norrie , Siladitya Bhattacharya , Tim Draycott , on behalf of the Thistle groupO5 Sample size calculation for longitudinal cluster r and omised trials : a unified framework for closed cohort and repeated cross-section design sRichard Hooper , Steven Teerenstra , Esther de Hoop , S and ra EldridgeO6 Restricted r and omisation schemes for stepped-wedge studies with a cluster-level covariateAlan Girling , Monica TaljaardO7 A flexible modelling of the time trend for the analysis of stepped wedge trials : results of a simulation study Gian Luca Di Tanna , Antonio GasparriniP1 Tackling acute kidney injury – a UK stepped wedge clinical trial of hospital-level quality improvement interventions Anna Casula , Fergus Caskey , Erik Lenguerr and , Shona Methven , Stephanie MacNeill , Margaret May , Nicholas SelbyP2 Sample size considerations for quantifying secondary bacterial transmission in a stepped wedge trial of influenza vaccineLeon Danon , Hannah Christensen , Adam Finn , Margaret MayP3 Sample size calculation for time-to-event data in stepped wedge cluster r and omised trialsFumihito Takanashi , Ada Keding , Simon Crouch , Mona KanaanP4 Sample size calculations for stepped-wedge cluster r and omised trials with unequal cluster sizesCaroline A. Kristunas , Karen L. Smith , Laura J. GrayP5 The design of stepped wedge trials with unequal cluster sizesJohn N.S. MatthewsP6 Promoting Recruitment using Information Management Efficiently ( PRIME ) : a stepped wedge SWAT ( study -within-a-trial)R Al-Shahi Salman , RA Parker , A Maxwell , M Dennis , A Rudd , CJ WeirP7 Implication s of misspecified mixed effect models in stepped wedge trial analysis : how wrong can it be?Jennifer A Thompson , Katherine L Fielding , Calum Davey , Alex and er M Aiken , James R Hargreaves , Richard J HayesS1 Stepped Wedge Design s with Multiple Interventions Vivian H Lyons , Lingyu Li , James Hughes , Ali Rowhani-RahbarS2 Analysis of the cross-sectional stepped wedge cluster r and omised trialKarla Hemming , Monica Taljaard , And rew",
"OBJECTIVE We investigated whether the antiproteinuric effect of the direct renin inhibitor aliskiren is comparable to that of irbesartan and the effect of the combination . RESEARCH DESIGN AND METHODS This was a double-blind , r and omized , crossover trial . After a 1-month washout period , 26 patients with type 2 diabetes , hypertension , and albuminuria ( > 100 mg/day ) were r and omly assigned to four 2-month treatment periods in r and om order with placebo , 300 mg aliskiren once daily , 300 mg irbesartan once daily , or the combination using identical doses . Patients received furosemide in a stable dose throughout the study . The primary end point was a change in albuminuria . Secondary measures included change in 24-h blood pressure and glomerular filtration rate ( GFR ) . RESULTS Placebo geometric mean albuminuria was 258 mg/day ( range 84–2,361 ) , mean ± SD 24-h blood pressure was 140/73 ± 15/8 mmHg , and GFR was 89 ± 27 ml/min per 1.73 m2 . Aliskiren treatment reduced albuminuria by 48 % ( 95 % CI 27–62 ) compared with placebo ( P with irbesartan treatment ( P reduced albuminuria by 71 % ( 59–79 ) , more than either monotherapy ( P P = 0.028 ) . Fractional clearances of albumin were significantly reduced ( 46 , 56 , and 67 % reduction vs. placebo ) . Twenty-four-hour blood pressure was reduced 3/4 mmHg by aliskiren ( NS/P = 0.009 ) , 12/5 mmHg by irbesartan ( P the combination ( P = 0.001/P GFR was significantly reduced 4.6 ( 95 % CI 0.3–8.8 ) ml/min per 1.73 m2 by aliskiren , 8.0 ( 3.6–12.3 ) ml/min per 1.73 m2 by irbesartan , and 11.7 ( 7.4–15.9 ) ml/min per 1.73 m2 by the combination . CONCLUSIONS The combination of aliskiren and irbesartan is more antiproteinuric in type 2 diabetic patients with albuminuria than monotherapy ",
"Background The renin – angiotensin system is well recognized as a mediator of pathophysiological events in atherosclerosis . The benefits of renin inhibition in atherosclerosis , especially when used in combination with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers ( ACEIs/ARBs ) are currently not known . We hypothesized that treatment with the renin inhibitor aliskiren in patients with established cardiovascular disease will prevent the progression of atherosclerosis as determined by high-resolution magnetic resonance imaging ( MRI ) measurements of arterial wall volume in the thoracic and abdominal aortas of high-risk patients with preexisting cardiovascular disease . Methods and Results This was a single-center , r and omized , double-blind , placebo-controlled trial in patients with established cardiovascular disease . After a 2-week single-blind placebo phase , patients were r and omized to receive either placebo ( n=37 , mean±SD age 64.5±8.9 years , 3 women ) or 150 mg of aliskiren ( n=34 , mean±SD age 63.9±11.5 years , 9 women ) . Treatment dose was escalated to 300 mg at 2 weeks and maintained during the remainder of the study . Patients underwent dark-blood , 3-dimensional MRI assessment of atherosclerotic plaque in the thoracic and abdominal segments at baseline and on study completion or termination ( up to 36 weeks of drug or matching placebo ) . Aliskiren use result ed in significant progression of aortic wall volume ( normalized total wall volume 5.31±6.57 vs 0.15±4.39 mm3 , P=0.03 , and percentage wall volume 3.37±2.96 % vs 0.97±2.02 % , P=0.04 ) compared with placebo . In a subgroup analysis of subjects receiving ACEI/ARB therapy , atherosclerosis progression was observed only in the aliskiren group , not in the placebo group . Conclusions MRI quantification of atheroma plaque burden demonstrated that aliskiren use in patients with preexisting cardiovascular disease result ed in an unexpected increase in aortic atherosclerosis compared with placebo . Although preliminary , these results may have implication s for the use of renin inhibition as a therapeutic strategy in patients with cardiovascular disease , especially in those receiving ACEI/ARB therapy . Clinical Trial Registration URL : http:// Clinical Trials.gov Unique identifier : NCT01417104",
"BACKGROUND This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease , cardiovascular disease , or both . METHODS In a double-blind fashion , we r and omly assigned 8561 patients to aliskiren ( 300 mg daily ) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker . The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation ; nonfatal myocardial infa rct ion ; nonfatal stroke ; unplanned hospitalization for heart failure ; end-stage renal disease , death attributable to kidney failure , or the need for renal-replacement therapy with no dialysis or transplantation available or initiated ; or doubling of the baseline serum creatinine level . RESULTS The trial was stopped prematurely after the second interim efficacy analysis . After a median follow-up of 32.9 months , the primary end point had occurred in 783 patients ( 18.3 % ) assigned to aliskiren as compared with 732 ( 17.1 % ) assigned to placebo ( hazard ratio , 1.08 ; 95 % confidence interval [ CI ] , 0.98 to 1.20 ; P=0.12 ) . Effects on secondary renal end points were similar . Systolic and diastolic blood pressures were lower with aliskiren ( between-group differences , 1.3 and 0.6 mm Hg , respectively ) and the mean reduction in the urinary albumin-to-creatinine ratio was greater ( between-group difference , 14 percentage points ; 95 % CI , 11 to 17 ) . The proportion of patients with hyperkalemia ( serum potassium level , ≥6 mmol per liter ) was significantly higher in the aliskiren group than in the placebo group ( 11.2 % vs. 7.2 % ) , as was the proportion with reported hypotension ( 12.1 % vs. 8.3 % ) ( P addition of aliskiren to st and ard therapy with renin-angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful . ( Funded by Novartis ; ALTITUDE Clinical Trials.gov number , NCT00549757 . )",
"BACKGROUND Aliskiren is approved for the treatment of hypertension at once-daily doses of 150 or 300 mg by the US Food and Drug Administration and the European Commission . It is generally well tolerated and provides 24-hour , dose-dependent blood pressure ( BP ) reduction ; however , the effect of the 75-mg dose has been inconsistent in previous trials . OBJECTIVES This study was design ed to assess the efficacy and tolerability of once-daily administration of aliskiren 75 mg and to evaluate the dose-response relationship across all 3 doses of aliskiren ( 75 , 150 , and 300 mg ) . METHODS In this 8-week , multicenter , r and omized , double-blind , parallel-group , placebo-controlled study , patients aged > or = 18 years with stage 1 or 2 essential hypertension entered a 3- to 4-week , single-blind , placebo run-in period . Eligible patients were r and omized ( 1:1:1:1 ) to receive oral , once-daily doses of aliskiren 75 , 150 , or 300 mg or placebo . The primary efficacy variable was the change from baseline in mean sitting diastolic BP ( msDBP ) at the week-8 end point . Tolerability was assessed by monitoring and recording all adverse events ( AEs ) . RESULTS A total of 642 patients ( mean [ SD ] age , 52.0 [ 10.73 ] years ; 60.0 % male ; 80.8 % white ; mean body weight , 89.2 [ 18.4 ] kg [ range , 50 - 160 kg ] ) were included in the study . Overall , 576 patients ( 89.7 % ) completed the double-blind treatment period . The most frequent reasons for discontinuation were unsatisfactory therapeutic effect ( 27/642 r and omized patients [ 4.2 % ] ) and AEs ( 17/642 [ 2.6 % ] ) . At end point , aliskiren 150 and 300 mg significantly reduced msDBP ( both , P mean sitting systolic CONCLUSIONS This study found a positive linear dose-response relationship in BP reduction with aliskiren 75 , 150 , and 300 mg dosed once daily , but only aliskiren 150 and 300 mg provided statistically significant reductions from baseline compared with placebo . All 3 doses of aliskiren were generally well tolerated",
"The antihypertensive efficacy and safety of the direct renin inhibitor aliskiren were assessed in a pooled analysis of data from seven r and omized , multicenter studies . Data were available for 7,045 patients ( mean age 52.5 to 59.8 years , 50.2 to 72.5 % men ) with mild-to-moderate hypertension ( mean sitting diastolic blood pressure [ msDBP ] 95 to 109 mm Hg ) over treatment duration s of 6 to 8 weeks . In placebo-controlled trials , aliskiren reduced mean sitting systolic blood pressure/msDBP from baseline by 8.6 to 12.1/7.2 to 10.3 mm Hg ( 75 mg ) , 8.7 to 13.0/7.8 to 10.3 mm Hg ( 150 mg ) , 14.1 to 15.8/10.3 to 12.3 mm Hg ( 300 mg ) , and 15.7 to 15.8/11.5 to 12.5 mm Hg ( 600 mg ) , compared with 2.9 to 10.0/3.3 to 8.6 mm Hg for placebo . Aliskiren demonstrated comparable efficacy in men and women , in patients aged 65 years or > /=65 years , and lowered blood pressure ( BP ) effectively in all racial subgroups . Combination of aliskiren 150 mg or 300 mg with ramipril , amlodipine , or hydrochlorothiazide provided significant additional BP reductions compared with the respective monotherapies . The overall incidence of adverse events with aliskiren monotherapy was similar to placebo ( 39.8 % vs. 40.2 % , respectively ) . The incidence of diarrhea with aliskiren was higher than placebo due to a significantly higher rate with aliskiren 600 mg ( P ) . In conclusion , aliskiren 150 mg or 300 mg provides highly effective and consistent BP lowering with placebo-like tolerability in patients with mild-to-moderate hypertension",
"AIMS We assessed the relationship between diabetes and cardiac structure and function following myocardial infa rct ion ( MI ) and whether diabetes influences the effect of direct renin inhibition on change in left ventricular ( LV ) size . METHODS AND RESULTS The ASPIRE trial enrolled 820 patients 2 - 8 weeks after MI with ejection fraction ≤ 45 % and r and omized them to the direct renin inhibitor aliskiren ( n= 423 ) or placebo ( n = 397 ) added to st and ard medical therapy . Echocardiography was performed at baseline and after 36 weeks in 672 patients with evaluable paired studies . Compared with non-diabetic patients , diabetic patients ( n = 214 ) were at higher risk for a composite of cardiovascular ( CV ) death , heart failure hospitalization , recurrent MI , stroke , or aborted sudden death ( 14 vs. 7 % ; adjusted hazard ratio 1.63 , 95 % confidence interval 1.01 - 2.64 , P= 0.045 ) , despite similar left ventricular ejection fraction ( 37.9 ± 5.3 vs. 37.6 ± 5.2 % , P= 0.48 ) and end-systolic volume ( ESV ) ( 84 ± 25 vs. 82 ± 28 mL , P= 0.46 ) . Diabetic patients demonstrated greater concentric remodelling ( relative wall thickness 0.38 ± 0.07 vs. 0.36 ± 0.07 , P= 0.0002 ) and evidence of higher LV filling pressure ( E/E ' 11.1 ± 5.3 vs. 9.1 ± 4.3 , P= 0.0011 ) . At 36 weeks , diabetic patients experienced similar per cent reduction in ESV overall ( -4.9 ± 17.9 vs. -5.5 ± 16.9 , P= 0.67 ) but tended to experience greater reduction in ESV than non-diabetic patients when treated with aliskiren ( interaction P = 0.08 ) . CONCLUSIONS Compared with non-diabetic patients , diabetic patients are at increased risk of CV events post-MI despite no greater LV enlargement or reduction in systolic function . Diabetic patients demonstrate greater concentric remodelling and evidence of higher LV filling pressure , suggesting diastolic dysfunction as a potential mechanism for the higher risk observed among these patients",
"Objectives . To evaluate the efficacy , safety and tolerability of aliskiren in elderly patients ( ⩾65 years old ) with essential hypertension . Methods . In this double‐blind , multicenter study , 355 elderly patients with hypertension [ office mean sitting systolic blood pressure ( msSBP ) ⩾145– ambulatory systolic BP ( ASBP ) ⩾135 mmHg ] were r and omized to once‐daily treatment for 8 weeks with aliskiren 75 mg ( n = 91 ) , 150 mg ( n = 84 ) , 300 mg ( n = 94 ) or the comparator lisinopril 10 mg ( n = 86 ) . The primary efficacy variable was change in mean 24‐h ASBP . Results . At endpoint , aliskiren 75 mg , 150 mg , 300 mg and lisinopril 10 mg lowered mean 24‐h ASBP ( least‐squares mean±SEM ) by 8.4±0.8 , 7.1±0.8 , 8.7±0.8 and 10.2±0.9 mmHg , and mean 24‐h ambulatory diastolic BP by 4.5±0.5 , 3.6±0.5 , 3.9±0.5 and 6.3±0.5 mmHg , respectively , with no significant difference between aliskiren doses . The trough‐to‐peak ratio for ASBP reduction with aliskiren 75 mg , 150 mg , 300 mg and lisinopril 10 mg was 0.77 , 0.64 , 0.79 and 0.87 , respectively . All treatments lowered office msSBP and mean sitting diastolic BP ( msDBP ) compared with baseline . A significantly greater proportion of patients receiving aliskiren 300 mg achieved BP control ( msSBP/msDBP receiving aliskiren 75 mg ( 36.2 % vs 24.2 % , p = 0.033 ) . There was no evidence of dose‐related increases in the rate of adverse events with aliskiren treatment . Conclusions . Aliskiren , a novel direct renin inhibitor , provides effective 24‐h BP lowering with no evidence of dose‐related increases in the incidence of adverse events in elderly patients with hypertension . Trial registration : Clinical Trials.gov identifier : NCT00219167",
"OBJECTIVES This dose-ranging study evaluated the antihypertensive efficacy and tolerability of aliskiren in patients with mild-to-moderate hypertension . BACKGROUND Low blood pressure ( BP ) control rates among patients with hypertension indicate a need for improved treatment options . This study investigates aliskiren , the first in a new antihypertensive class called renin inhibitors . METHODS Patients with mean sitting diastolic BP 95 to 109 mm Hg were r and omized to aliskiren 150 , 300 , or 600 mg or placebo once daily for 8 weeks . Patients completing this treatment phase entered a 2-week treatment-free withdrawal period . Office BP was recorded at baseline , weeks 2 , 4 , 6 , and 8 of treatment , and 4 days and 2 weeks after cessation of treatment . A subgroup of patients underwent ambulatory BP monitoring . RESULTS In total , 672 patients were r and omized to treatment . After 8 weeks , aliskiren 150 , 300 , and 600 mg significantly reduced mean sitting BP ( systolic/diastolic ) by 13.0/10.3 , 14.7/11.1 , and 15.8/12.5 mm Hg , respectively , versus 3.8/4.9 mm Hg with placebo ( all p systolic and diastolic BP ) . The BP-lowering effect of aliskiren persisted for up to 2 weeks after treatment withdrawal . Aliskiren significantly reduced mean 24-h ambulatory BP ( p trough-to-peak ratios . Aliskiren was well tolerated ; overall adverse event rates were 40.1 % , 46.7 % , and 52.4 % with aliskiren 150 , 300 , and 600 mg , respectively , and 43.0 % with placebo . Few patients discontinued treatment due to adverse events . CONCLUSIONS Aliskiren provides significant antihypertensive efficacy in patients with hypertension , with no rebound effects on blood pressure after treatment withdrawal",
"Patients with severe hypertension ( > 180/110 mm Hg ) require large blood pressure ( BP ) reductions to reach recommended treatment goals ( tolerability and antihypertensive efficacy of the novel direct renin inhibitor aliskiren with the angiotensin converting enzyme inhibitor lisinopril in patients with severe hypertension ( mean sitting diastolic blood pressure (msDBP)⩾105 mm Hg and 183 patients were r and omized ( 2:1 ) to aliskiren 150 mg ( n=125 ) or lisinopril 20 mg ( n=58 ) with dose titration ( to aliskiren 300 mg or lisinopril 40 mg ) and subsequent addition of hydrochlorothiazide ( HCTZ ) if additional BP control was required . Aliskiren-based treatment ( ALI ) was similar to lisinopril-based treatment ( LIS ) with respect to the proportion of patients reporting an adverse event ( AE ; ALI 32.8 % ; LIS 29.3 % ) or discontinuing treatment due to AEs ( ALI 3.2 % ; LIS 3.4 % ) . The most frequently reported AEs in both groups were headache , nasopharyngitis and dizziness . At end point , ALI showed similar mean reductions from baseline to LIS in msDBP ( ALI −18.5 mm Hg vs LIS −20.1 mm Hg ; mean treatment difference 1.7 mm Hg ( 95 % confidence interval ( CI ) −1.0 , 4.4 ) ) and mean sitting systolic blood pressure ( ALI −20.0 mm Hg vs LIS −22.3 mm Hg ; mean treatment difference 2.8 mm Hg ( 95 % CI −1.7 , 7.4 ) ) . Responder rates ( msDBP of HCTZ to achieve BP control ( ALI 53.6 % ; LIS 44.8 % ) . In conclusion , ALI alone , or in combination with HCTZ , exhibits similar tolerability and antihypertensive efficacy to LIS alone , or in combination with HCTZ , in patients with severe hypertension",
"BACKGROUND Aliskiren is the first in a new class of orally effective renin inhibitors for the treatment of hypertension . METHODS In 569 patients with mild-to-moderate hypertension , blood pressure ( BP ) , plasma renin activity ( PRA ) and plasma renin concentration ( PRC ) were measured before and after 8 weeks of double-blind treatment with once-daily oral doses of aliskiren ( 150 , 300 or 600 mg ) , irbesartan 150 mg or placebo . RESULTS Aliskiren 150 , 300 and 600 mg and irbesartan 150 mg significantly reduced mean cuff sitting systolic BP ( SBP ) from baseline ( p Aliskiren 150 , 300 and 600 mg significantly reduced geometric mean PRA by 69 % , 71 % and 75 % from baseline respectively ( p Irbesartan 150 mg significantly increased PRA by 109 % ( p Aliskiren dose-dependently increased PRC from baseline by 157 % , 246 % and 497 % , at 150 , 300 and 600 mg respectively , compared with a 9 % decrease with placebo ( p PRC increased significantly more with aliskiren 300 and 600 mg compared with irbesartan 150 mg ( 105 % ; p baseline PRA and changes in SBP in any of the treatment groups , but interestingly , the slopes of the regression lines between changes in SBP and log-transformed baseline PRA were + 2.0 for placebo and -1.5 , -1.8 and -2.3 for aliskiren 150 , 300 and 600 mg respectively . The slope for irbesartan 150 mg ( -1.4 ) was similar to that for aliskiren 150 mg . CONCLUSIONS Aliskiren reduces SBP and PRA and increases PRC dose-dependently . In contrast , irbesartan reduces SBP but increases both PRC and PRA . As PRA is a measurement of angiotensin I-generating capacity , PRA can be used for measuring the ability of an antihypertensive agent to prevent the generation or action of Ang II , either directly ( renin inhibitors , beta-blockers , central alpha(2)-agonists ) or indirectly ( AT(1)-receptor blockers , ACE inhibitors )",
"BACKGROUND By blocking the renin-angiotensin-aldosterone system ( RAAS ) at its rate-limiting step , renin inhibition may provide improved RAAS suppression . We investigated the blood pressure (BP)-lowering effects of the oral direct renin inhibitor aliskiren , alone or in combination with the angiotensin receptor blocker valsartan . METHODS In this multicenter , r and omized , placebo-controlled , 8-week trial , 1123 patients with mild-to-moderate hypertension underwent a 3 to 4 week single-blind placebo run-in and were then r and omized in a modified factorial study design to receive once-daily , double-blind oral treatment with placebo , aliskiren monotherapy ( 75 , 150 , or 300 mg ) , valsartan monotherapy ( 80 , 160 , or 320 mg ) , aliskiren and valsartan in combination , or valsartan/hydrochlorothiazide ( 160/12.5 mg ) . The primary efficacy variable was the change from baseline in mean sitting diastolic BP ( DBP ) at endpoint . RESULTS Once-daily oral treatment with aliskiren 300 mg significantly ( P mean sitting DBP and systolic BP ( SBP ) compared with placebo ; aliskiren monotherapy demonstrated a safety and tolerability profile comparable to placebo . Changes in DBP and SBP were fitted to a first-order dose-response surface ( lack-of-fit test , P = .65 ) , which showed that aliskiren and valsartan alone and in combination produced dose-related reductions in DBP and SBP . Coadministration of aliskiren and valsartan produced a greater antihypertensive effect than either drug alone , comparable in magnitude to the effect of valsartan/hydrochlorothiazide , with similar tolerability to the component monotherapies and to placebo . CONCLUSIONS Aliskiren monotherapy provides antihypertensive efficacy and placebo-like tolerability in patients with hypertension . Aliskiren and valsartan in combination may provide additive BP-lowering effects with maintained tolerability",
"Objectives Aliskiren is a novel , orally active renin inhibitor . Its antihypertensive efficacy and safety , alone and in combination with hydrochlorothiazide ( HCTZ ) , were investigated in an 8-week , double-blind , placebo-controlled trial in hypertensive patients . The effects of these treatments on plasma renin activity ( PRA ) were also assessed . Methods A total of 2776 patients aged ≥ 18 years with mean sitting diastolic blood pressure ( MSDBP ) 95–109 mmHg were r and omized to receive once-daily treatment with aliskiren ( 75 , 150 or 300 mg ) , HCTZ ( 6.25 , 12.5 or 25 mg ) , the combination of aliskiren and HCTZ , or placebo , in a factorial design . The primary endpoint was the change in MSDBP from baseline to week 8 . PRA was assessed at these timepoints at selected study centers . Results Aliskiren monotherapy was superior to placebo ( P reducing MSDBP and mean sitting systolic blood pressure ( MSSBP ) . Combination treatment was superior to both component monotherapies in reducing BP ( maximum MSSBP/MSDBP reduction of 21.2/14.3 mmHg from baseline with aliskiren/HCTZ 300/25 mg ) , and result ed in more responders ( patients with MSDBP . Aliskiren monotherapy reduced PRA by up to 65 % from baseline . Although HCTZ monotherapy increased PRA by up to 72 % , PRA decreased in all of the combination therapy groups . All active treatments were well tolerated . Conclusions Aliskiren monotherapy demonstrated significant BP lowering , and its effect was considerably greater when combined with HCTZ . Renin inhibition with aliskiren neutralized the compensatory rise in PRA induced by HCTZ ",
"AIMS We studied the unclear question whether blood pressure ( BP ) lowering reduces cardiovascular disease ( CVD ) in elderly individuals with systolic BP METHODS AND RESULTS We initiated a r and omized placebo-controlled stratified 2 × 2 factorial clinical trial evaluating the effects of BP lowering in 11 000 elderly individuals with systolic blood pressure ( SBP ) between 130 and 159 mm Hg , for 5 years . Following 5-week active run-in , participants were r and omized to aliskiren ( 300 mg ) or placebo , and to an additional antihypertensive [ hydrochlorothiazide ( 25 mg ) or amlodipine ( 5 mg ) ] , or their respective placeboes . Study was terminated by sponsor after 1759 subjects ( age 72.1 ± 5.2 years , 88 % receiving at least one antihypertensive ) were r and omized and followed for 0.6 year . Study drugs were well tolerated with few serious adverse events during run-in and after r and omization , with no significant differences between treatment groups . By design , three levels of BP reductions were achieved , adjusted mean BP reductions of 3.5/1.7 mm Hg ( P by aliskiren , 6.8/3.3 mm Hg ( P by hydrochlorothiazide or amlodipine , and 10.3/5.0 mm Hg ( P by double therapy compared with placebo . Twenty-five major CVD events occurred . Non-significant trends towards fewer CVD events with greater BP reductions are evident : hazard ratios ( HR ) 0.82 [ 95 % confidence interval ( CI ) : 0.37 - 1.81 ] for 3.5 mm Hg SBP reduction ; HR 0.45 ( 95 % CI : 0.19 - 1.04 ) for 6.8 mm Hg ; and HR 0.25 ( 0.05 - 1.18 ) for 10.3 mm Hg reduction for primary composite of CV death , MI , stroke , or significant heart failure . CONCLUSIONS Sizeable reductions in BP , with potential for substantial CVD reduction , can be safely achieved using combinations of BP drugs in the elderly with normal high and Stage 1 hypertension . CLINICAL TRIAL REGISTRATION NCT01259297",
"Most patients with hypertension need more than one drug to achieve blood pressure ( BP ) control . This r and omized , double-blind , multifactorial study evaluated whether combinations of aliskiren and amlodipine provided superior BP reductions to component monotherapies in patients with hypertension ( mean sitting diastolic BP ( msDBP ) 95– Overall , 1688 patients were r and omized to once-daily monotherapy with aliskiren 150 or 300 mg or amlodipine 5 or 10 mg , combination therapy with one of four corresponding aliskiren/amlodipine doses , or placebo for 8 weeks . At week 8 end point , aliskiren/amlodipine combinations provided significant msDBP reductions from baseline of 14.0–16.5 mm Hg , compared with reductions of 8.0 and 10.2 mm Hg for aliskiren 150 and 300 mg , respectively ( P for amlodipine 5 and 10 mg , respectively ( P ) . Aliskiren/amlodipine combinations provided reductions in mean sitting systolic BP 20.6–23.9 mm Hg , compared with decreases of 10.7 and 15.4 mm Hg for aliskiren 150 and 300 mg , respectively ( P for amlodipine 5 ( P⩽0.001 ) and 10 mg ( P = NS ) , respectively . Aliskiren/amlodipine combination therapy provides greater BP lowering than either agent alone , hence offering an effective treatment option for patients with hypertension",
"Objective . To assess the antihypertensive efficacy and safety of the combination of the direct renin inhibitor aliskiren and ramipril in patients with diabetes and hypertension . Methods . In this double-blind , multicentre trial , 837 patients with diabetes mellitus and hypertension ( mean sitting diastolic blood pressure [ BP ] > 95 and were r and omised to once-daily aliskiren ( 150 mg titrated to 300 mg after four weeks ; n=282 ) , ramipril ( 5 mg titrated to 10 mg ; n=278 ) or the combination ( n=277 ) for eight weeks . Efficacy variables were cuff mean sitting diastolic BP ( msDBP ) and mean sitting systolic BP ( msSBP ) ; 24-hour ambulatory BP , plasma renin activity ( PRA ) and plasma renin concentration ( PRC ) were also assessed . Results . At week 8 , aliskiren , ramipril and aliskiren/ramipril lowered msDBP ( mean±SEM ) by 11.3±0.5 , 10.7±0.5 and 12.8±0.5 mmHg , and msSBP by 14.7±0.9 , 12.0±0.9 and 16.6±0.9 mmHg , respectively . Aliskiren/ramipril provided superior msDBP reductions to ramipril ( p=0.004 ) or aliskiren ( p=0043 ) monotherapy ; adding aliskiren to ramipril provided an additional mean BP reduction of 4.6/2.1 mmHg . Aliskiren monotherapy was non-inferior to ramipril for msDBP reduction ( p=0.0002 ) and superior for msSBP reduction (p=0.021).All treatments significantly lowered mean 24-hour ambulatory BP . Aliskiren significantly reduced PRA from baseline as monotherapy ( by 66 % , p with ramipril ( by 48 % , p large increases in PRC in all treatment groups . Aliskiren was well tolerated as monotherapy or in combination with ramipril . Conclusions . Combining aliskiren with ramipril provided a greater reduction in msDBP than either drug alone in patients with diabetes and hypertension",
"This r and omized , double-blind , placebo-controlled study assessed the efficacy , safety , and tolerability of aliskiren 75 , 150 , and 300 mg to clarify the dose-response relationship and characterize the optimum aliskiren dose when given with a light meal to elderly hypertensive patients . After washout , 754 patients aged ≥65 years with hypertension ( mean sitting systolic blood pressure [ msSBP ] ≥150 and were r and omized to aliskiren 75 , 150 , or 300 mg or placebo for 8 weeks ; medication was taken each morning with a light meal . The primary efficacy variable was change in msSBP from baseline to week 8 end point . Change from baseline in msDBP and dose-response curves for aliskiren 75 , 150 , and 300 mg were also assessed . At week 8 end point , all 3 aliskiren doses provided significantly greater least squares mean reductions in msSBP/msDBP ( 75 mg , 13/5 mm Hg ; 150 mg , 15/6 mm Hg ; 300 mg , 14/7 mm Hg ) compared with placebo ( 8/4 mm Hg ; P ) . Aliskiren was generally well tolerated at all doses . There was a significant dose-response relationship for aliskiren , with an estimated minimum effective dose of 81.9 mg . In conclusion , aliskiren 150 and 300 mg provided effective blood pressure control in elderly patients when given with a light meal",
"Substantial numbers of clinical trials are never reported in print , and among those that are , many are not reported in sufficient detail to enable judgments to be made about the validity of their results . Failure to publish an adequate account of a well- design ed clinical trial is a form of scientific misconduct that can lead those caring for patients to make inappropriate treatment decisions . Investigators , research ethics committees , funding bodies , and scientific editors all have responsibilities to reduce underreporting of clinical trials . An extended use of prospect i ve registration of trials at inception , as well as benefiting clinical research in other ways , could help people to play their respective roles in reducing underreporting of clinical trials",
"BACKGROUND The aim of this study was to assess dual renin system intervention with the maximum recommended doses of aliskiren and valsartan , compared with each drug alone in patients with hypertension . METHODS In this double-blind study , 1797 patients with hypertension ( mean sitting diastolic blood pressure 95 - 109 mm Hg and 8-h daytime ambulatory diastolic blood pressure > or = 90 mm Hg ) were r and omly assigned to receive once-daily aliskiren 150 mg ( n=437 ) , valsartan 160 mg ( 455 ) , a combination of aliskiren 150 mg and valsartan 160 mg ( 446 ) , or placebo ( 459 ) for 4 weeks , followed by forced titration to double the dose to the maximum recommended dose for another 4 weeks . The primary endpoint was change in mean sitting diastolic blood pressure from baseline to week 8 endpoint . Analyses were done by intention to treat . This trial is registered at Clinical Trials.gov with the number NCT00219180 . FINDINGS 196 ( 11 % ) patients discontinued study treatment before the end of the trial ( 63 in the placebo group , 53 in the aliskiren group , 43 in the valsartan group , and 37 in the aliskiren/valsartan group ) , mainly due to lack of therapeutic effect . At week 8 endpoint , the combination of aliskiren 300 mg and valsartan 320 mg lowered mean sitting diastolic blood pressure from baseline by 12.2 mm Hg , significantly more than either monotherapy ( aliskiren 300 mg 9.0 mm Hg decrease , p valsartan 320 mg , 9.7 mm Hg decrease , p placebo ( 4.1 mm Hg decrease , p Rates of adverse events and laboratory abnormalities were similar in all groups . INTERPRETATION The combination of aliskiren and valsartan at maximum recommended doses provides significantly greater reductions in blood pressure than does monotherapy with either agent in patients with hypertension , with a tolerability profile similar to that with aliskiren and valsartan alone",
"Background : In hypertension , changes in small arterial structure are characterized by an increased wall-to-lumen ratio ( WLR ) . These adaptive processes are modulated by the rennin – angiotensin system . It is unclear whether direct renin inhibitors exert protective effects on small arteries in hypertensive patients . Methods : In this double-blind , r and omized , placebo-controlled study ( www . clinical trials.gov : NCT01318395 ) , 114 patients with primary hypertension were r and omized to additional therapy with either placebo or aliskiren 300 mg for 8 weeks after 4 weeks of st and ardized open-label treatment with valsartan 320 mg ( run-in phase ) . Parameter of arteriolar remodelling was WLR of retinal arterioles ( 80 – 140 & mgr;m ) assessed noninvasively and in vivo by scanning laser Doppler flowmetry ( Heidelberg Engineering , Germany ) . In addition , pulse wave analysis ( SphygmoCor , AtCor Medical , Australia ) and pulse pressure ( PP ) amplification were determined . Results : In the whole study population , no clear effect of additional therapy with aliskiren on vascular parameters was documented . When analyses were restricted to patients with vascular remodelling , defined by a median of WLR more than 0.3326 ( n = 57 ) , WLR was reduced after 8 weeks by the treatment with aliskiren compared with placebo ( –0.044 ± 0.07 versus 0.0043 ± 0.07 , P = 0.015 ) . Consistently , after 8 weeks of on-top treatment with aliskiren , there was an improvement of PP amplification compared with placebo ( 0.025 ± 0.07 versus -0.034 ± 0.08 , P = 0.013 ) , indicative of less stiff arteries in the peripheral circulation . Conclusion : Thus , our data indicate that treatment with aliskiren , given on top of valsartan therapy , improves altered vascular remodelling in hypertensive patients",
"Journal publications of r and omized controlled trials ( \" literature \") have so far formed the basis for evidence of the effects of pharmaceuticals and biologicals . In the last decade , progressively accumulating evidence has shown that literature is affected by reporting bias with evident implication s for the reliability of any decision based on literature or its derivatives such as research synthesis . Another important factor is the growing body of evidence of the fragility of editorial quality control mechanisms in biomedicine and e their easy exploitation for marketing purpose s in the symbiosis between publishing and the pharmaceutical industry . Regulatory documents are probably more reliable than currently accessible other sources but there are many severe limitations to the long-term use of regulatory documents for research synthesis and decision-making . Instead of trying to reform the fields of research , industry , government , regulation and publishing , I propose basing public health decisions and reimbursement of any important interventions on independent trials and studies following the model pioneered by the Mario Negri Institute of Pharmacological Research",
"IMPORTANCE Hospitalizations for heart failure ( HHF ) represent a major health burden , with high rates of early postdischarge rehospitalization and mortality . OBJECTIVE To investigate whether aliskiren , a direct renin inhibitor , when added to st and ard therapy , would reduce the rate of cardiovascular ( CV ) death or HF rehospitalization among HHF patients . DESIGN , SETTING , AND PARTICIPANTS International , double-blind , placebo-controlled study that r and omized hemodynamically stable HHF patients a median 5 days after admission . Eligible patients were 18 years or older with left ventricular ejection fraction ( LVEF ) 40 % or less , elevated natriuretic peptides ( brain natriuretic peptide [ BNP ] ≥ 400 pg/mL or N -terminal pro-BNP [ NT-proBNP ] ≥ 1600 pg/mL ) , and signs and symptoms of fluid overload . Patients were recruited from 316 sites across North and South America , Europe , and Asia between May 2009 and December 2011 . The follow-up period ended in July 2012 . INTERVENTION All patients received 150 mg ( increased to 300 mg as tolerated ) of aliskiren or placebo daily , in addition to st and ard therapy . The study drug was continued after discharge for a median 11.3 months . MAIN OUTCOME MEASURES Cardiovascular death or HF rehospitalization at 6 months and 12 months . RESULTS In total , 1639 patients were r and omized , with 1615 patients included in the final efficacy analysis cohort ( 808 aliskiren , 807 placebo ) . Mean age was 65 years ; mean LVEF , 28 % ; 41 % of patients had diabetes mellitus , mean estimated glomerular filtration rate , 67 mL/min/1.73 m2 . At admission and r and omization , median NT-proBNP levels were 4239 pg/mL and 2718 pg/mL , respectively . At r and omization , patients were receiving diuretics ( 95.9 % ) , β-blockers ( 82.5 % ) , angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers ( 84.2 % ) , and mineralocorticoid receptor antagonists ( 57.0 % ) . In total , 24.9 % of patients receiving aliskiren ( 77 CV deaths , 153 HF rehospitalizations ) and 26.5 % of patients receiving placebo ( 85 CV deaths , 166 HF rehospitalizations ) experienced the primary end point at 6 months ( hazard ratio [ HR ] , 0.92 ; 95 % CI , 0.76 - 1.12 ; P = .41 ) . At 12 months , the event rates were 35.0 % for the aliskiren group ( 126 CV deaths , 212 HF rehospitalizations ) and 37.3 % for the placebo group ( 137 CV deaths , 224 HF rehospitalizations ; HR , 0.93 ; 95 % CI , 0.79 - 1.09 ; P = .36 ) . The rates of hyperkalemia , hypotension , and renal impairment/renal failure were higher in the aliskiren group compared with placebo . CONCLUSION AND RELEVANCE Among patients hospitalized for HF with reduced LVEF , initiation of aliskiren in addition to st and ard therapy did not reduce CV death or HF rehospitalization at 6 months or 12 months after discharge . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00894387",
"Objectives This double-blind study compared long-term efficacy , safety and tolerability of the oral direct renin inhibitor aliskiren and the angiotensin-converting enzyme inhibitor ramipril alone and combined with hydrochlorothiazide in patients with hypertension . Methods After a 2–4-week placebo run-in , 842 patients [ mean sitting diastolic blood pressure ( msDBP ) 95–109 mmHg ] were r and omized to aliskiren 150 mg ( n = 420 ) or ramipril 5 mg ( n = 422 ) . Dose titration ( to aliskiren 300 mg/ramipril 10 mg ) and subsequent hydrochlorothiazide addition ( 12.5 mg , titrated to 25 mg if required ) were permitted at weeks 6 , 12 , 18 and 21 for inadequate blood pressure control . Patients completing the 26-week active-controlled treatment period were re-r and omized to their existing regimen or placebo for a 4-week double-blind withdrawal phase . Results Six hundred and eighty-seven patients ( 81.6 % ) completed the active treatment period . At week 26 , aliskiren-based therapy produced greater mean reductions in mean sitting systolic blood pressure ( 17.9 versus 15.2 mmHg , P = 0.0036 ) and msDBP ( 13.2 versus 12.0 mmHg , P = 0.025 ) , and higher rates of systolic blood pressure control ( ramipril-based therapy . During withdrawal , blood pressure increased more rapidly after stopping ramipril than aliskiren-based therapy ; median blood pressure reached 140/90 mmHg after 1 and 4 weeks , respectively . Blood pressure reductions were maintained with continued active treatment . Aliskiren therapy was well tolerated . Overall adverse event rates were similar with aliskiren ( 61.3 % ) and ramipril ( 60.4 % ) ; cough was more frequent with ramipril ( 9.5 % ) than aliskiren ( 4.1 % ) . Conclusions Aliskiren-based therapy was well tolerated and produced sustained blood pressure reductions in patients with hypertension over 6 months , greater than those with ramipril-based therapy",
"Objectives : The objective of this study is to determine the effects of renin -- angiotensin -- aldosterone system inhibition , sympathoinhibition and diuretic therapy on endothelial function and blood pressure in obesity-related hypertension . Methods : A r and omized , four-way , double-blind , crossover study in 31 adults with previously untreated obesity-related hypertension , in which the effects of 8 weeks ’ inhibition of the renin -- angiotensin -- aldosterone system ( using aliskiren 300 mg ) , sympathoinhibition ( using moxonidine 0.4 mg ) , diuretic therapy ( using hydrochlorothiazide 25 mg ) or placebo on flow-mediated dilation and 24-h blood pressure were compared . Results : The median flow-mediated dilation during placebo was 4.0 % [ interquartile range ( IQR ) 2.9–5.5 % ] and was increased by aliskiren [ 0.81 % , 95 % confidence interval ( CI ) 0.02–1.79 ] , but not by moxonidine ( 0.20 % , 95 % CI −0.46 to 1.03 ) or hydrochlorothiazide ( 0.39 % , 95%CI −0.31%–1.26 % ) . Similarly , compared with placebo , mean 24-h blood pressure was most reduced by aliskiren ( −9.8/−6.3 mmHg ) and to a lesser degree by hydrochlorothiazide ( −5.9/−2.6 mmHg ) . Moxonidine did not significantly affect blood pressure despite reduction of muscle sympathetic nerve activity . Insulin sensitivity deteriorated during hydrochlorothiazide treatment and was unaffected by aliskiren or moxonidine . Unlike aliskiren and moxonidine , hydrochlorothiazide reduced urinary 8-iso-prostagl and in F2&agr;-VI , a marker of oxidative stress . Vascular stiffness , systemic inflammation , leptin , adiponectin and other oxidative stress markers ( plasma malondialdehyde , myeloperoxidase activity and urinary 8-hydroxydeoxyguanosine ) were unaffected by treatment . Conclusion : Renin inhibition , but not sympathoinhibition or diuretic therapy , improves endothelial function and results in larger reductions of 24-h , office , and central blood pressure in obesity-related hypertension . This adds weight to the hypothesis that inhibition of the renin -- angiotensin -- aldosterone system is an effective first step in the treatment of obesity-related hypertension",
"While the safety of renin-angiotensin system (RAS)-blocking drugs such as angiotensin-converting enzyme ( ACE ) inhibitors and angiotensin receptor blockers is well known , less is known about the new direct renin inhibitor aliskiren . The authors pooled data from 12 r and omized controlled trials of aliskiren in patients with hypertension and analyzed the incidence and types of adverse events ( AEs ) and laboratory abnormalities . Studies were characterized as short-term ( ≤2 months ) placebo-controlled or long-term ( > 2 months ) active-controlled . Relative risks for AEs of particular interest for RAS blockers were calculated . In short-term studies , AEs occurred in similar proportions of aliskiren 150 mg and 300 mg ( 33.6 % and 31.6 % , respectively ) and placebo treatment groups ( 36.8 % ) . In long-term studies , a lower proportion of patients treated with aliskiren 150 mg and 300 mg had AEs ( 33.7 % and 43.2 % , respectively ) than those treated with ACE inhibitors ( 60.1 % ) , angiotensin receptor blockers ( 53.9 % ) , and thiazide diuretics ( 48.9 % ) . Events of special interest , including angioedema , hyperkalemia , and diarrhea occurred in similar proportions of patients taking aliskiren , placebo , and comparator agents . In studies of up to 36 weeks , patients treated with aliskiren were significantly less likely to develop cough than those treated with ACE inhibitors . At the registered doses of 150 mg and 300 mg daily , aliskiren has safety and tolerability profiles similar to placebo , other RAS blockers , and diuretics . Cough rates are lower with aliskiren compared with ACE inhibitors "
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Despite advances in our underst and ing of surgical site infections following total joint arthroplasty , this serious surgical complication continues to represent a substantial economic burden for the patient , the treating institution and the healthcare system . After increasing for the past decade , infection rates have stabilized at 1.6 % ; however , the total cost is projected to increase with the total number of revision procedures performed . A systematic review of the literature was performed to identify studies that assess the efficacy of pre- , peri- and post-operative infection prevention strategies in the setting of total hip or knee arthroplasty . Preference was given to r and omized-controlled trials , data from national registries and meta-analyses within the past 5 years ; however , all relevant articles were included in this analysis . The results of the literature search returned 549 articles that addressed infection in total joint arthroplasty , of which 71 specifically addressed infection prevention . Topics that were addressed included the CDC recommendations , skin preparation techniques , hair removal techniques , surgical draping techniques , operative dress , operating room ventilation , operating room traffic and antibiotic utilization . Newer infection prevention techniques , such as preoperative antiseptic scrubbing , are affected and may help reduce the infection rate , while traditionally accepted methods of prophylaxis such as laminar-flow operating rooms and body exhaust suits may raise the infection rate
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" We r and omly allocated 50 total knee replacements to scrub teams wearing body-exhaust suits ( BES ) or Rotecno occlusive clothing . The effectiveness of the clothing was assessed using air and wound bacterial counts . Bacteria were recovered from 62 % of wounds ( 64 % BES , 60 % Rotecno ) . The mean air count was 0.5 CFU/ m3 with BES and 1.0 CFU/m3 with Rotecno ( p = 0.014 ) . The mean wound counts were 14 bacteria/wound with BES and eight bacteria/wound with Rotecno ( p = 0.171 ) . There was no correlation between the air and wound counts ( r = -0.011 , Spearman 's ) . The higher air counts suggest that Rotecno occlusive clothing is less effective than BES , but wounds were equally contaminated with both types of clothing suggesting that at very low levels of air contamination the contribution of bacteria to the wound from the air is irrelevant . Even doubling the air counts from 0.5 to 1.0 CFU/m3 had no detectable effect on the wound . This allows a re assessment to be made of other sources of contamination the effect of which would previously have been overwhelmed by contamination from air",
"An evaluation of the effect of total body exhaust clothing on air and wound contamination was made in an operating theatre with a zonal ventilation system . Sixty-four patients who underwent total hip replacement using the Charnley-Müller prosthesis were studied . The members of the surgical team wore total body exhaust suits ( TBE-suit ) , or conventional theatre clothing ( C-clothing ) at alternate operations . Nearly half of the patients in each group were given prophylactic antibiotics . Both the mean and median values of airborne bacteria in the operating theatre were significantly lower during operations with TBE-suits than with conventional theatre clothing . The lowest number , 4.0 cfu/m3 , was found at the site of the operation wound . Cultures from adhesive drapes showed growth in 46 per cent of the C-group and in 43 per cent of the TBE-group sample s. Wound washouts showed growth in 43 per cent of the C-group and in 10 per cent of the TBE-group sample s. Staphylococcus epidermidis was the most frequently isolated bacteria both from adhesive drapes and from wound washouts . The rate of superficial infections was slightly higher when C-clothing was used . Deep infections were found in one patient in the TBE-group and in two patients in the C-group . None of the infected patients had received prophylactic antibiotics",
"The effect of preoperative whole-body washing with chlorhexidine detergent on the incidence of postoperative wound infection was assessed in a placebo-controlled trial of 1989 patients . Patients bathed or showered with chlorhexidine , placebo , or conventional bar soap , on two occasions in the 24 h before operation . The overall infection rate for patients treated with chlorhexidine was 9 % , against 12.8 % in the bar soap and 11.7 % in the placebo groups ; in the ' clean ' surgery group infections were 7.2 % against 10.2 % and 10 % , respectively . The Staphylococcus aureus infection rate in the ' clean ' group was 3 % for chlorhexidine against 6 % for bar soap",
"Background : The purpose of this study was threefold : ( 1 ) to determine the scientific quality of published r and omized trials in the American Volume of The Journal of Bone and Joint Surgery from 1988 through 2000 , ( 2 ) to identify predictors of study quality , and ( 3 ) to evaluate inter-rater agreement in the scoring of study quality with use of a simple scale . Methods : H and search es of The Journal of Bone and Joint Surgery were conducted in duplicate to identify r and omized clinical trials . Of 2468 studies identified , seventy-two ( 2.9 % ) met all eligibility criteria . Two investigators each assessed the quality of the study under blinded conditions and abstract ed relevant data . Results : The mean score ( and st and ard error ) for the quality of the seventy-two r and omized trials was 68.1 % ± 1.6 % ; 60 % ( forty-three ) scored higher mean quality score than did surgical trials ( 72.8 % compared with 63.9 % , p higher quality scores . Failure to conceal r and omization , to blind outcome assessors , and to describe why patients were excluded result ed in significantly lower quality scores ( p The Detsky quality scale met accepted st and ards of interobserver reliability ( kappa , 0.87 ; 95 % confidence interval , 0.70 to 0.95 ) . Conclusions : Few studies published in The Journal of Bone and Joint Surgery were r and omized trials . More than half of the trials were limited by a lack of concealed r and omization , lack of blinding of outcome assessors , or failure to report reasons for excluding patients . Application of st and ardized guidelines for the reporting of clinical trials in orthopaedics should improve quality",
"The literature is used to analyse the significance of the use of iodine-impregnated incision drape ( Ioban ® 2 ) for the prevention of postoperative wound infections ( SSI ) . The drape has a microbiocidal effect in vitro . Consequently an antiseptic effect also occurs under the incision drape when it is applied to the skin ; at the same time , bacterial wound contamination is reduced . Overall , based on the efficacy strength of the antiseptic incision drape , a reduction of the SSI rate can , however , be confirmed only with a large sample size . A meta analysis which evaluated four prospect i ve studies and one retrospective study was able to provide significant confirmation of a reduction in the SSI rate . There are no limitations in terms of the biocompatibility of the iodine-impregnated incision drape",
"BACKGROUND Skin asepsis is a sentinel strategy for reducing risk of surgical site infections . In this study , chlorhexidine gluconate ( CHG ) skin concentrations were determined after preoperative showering/skin cleansing using 4 % CHG soap or 2 % CHG-impregnated polyester cloth . STUDY DESIGN Subjects were r and omized to one of three shower ( 4 % soap)/skin cleansing ( 2 % cloth ) groups ( n = 20 per group ) : ( group 1 A/B ) evening , ( group 2 A/B ) morning , or ( group 3 A/B ) evening and morning . After showering or skin cleansing , volunteers returned to the investigator 's laboratory where CHG skin surface concentrations were determined at five separate skin sites . CHG concentrations were compared with CHG minimal inhibitory concentration that inhibits 90 % ( MIC(90 ) ) of staphylococcal skin isolates . RESULTS CHG MIC(90 ) for 61 skin isolates was 4.8 parts per million ( ppm ) . In group 1A , 4 % CHG skin concentrations ranged from 17.2 to 31.6 ppm , and CHG concentrations were 361.5 to 589.5 ppm ( p CHG levels ranged from 51.6 to 119.6 ppm and 848.1 to 1,049.6 ppm in group 2B ( 2 % ) , respectively ( p CHG levels ranged from 101.4 to 149.4 ppm in the 4 % CHG group ( group 3A ) compared with 1,484.6 to 2,031.3 ppm in 2 % CHG cloth ( group 3B ) group ( p Effective CHG levels were not detected in the 4 % CHG group in selected sites in seven ( 35 % ) subjects in group 1A , three ( 15 % ) in group 2A , and five ( 25 % ) in group 3A . CONCLUSIONS Effective CHG levels were achieved on most skin sites after using 4 % CHG ; gaps in antiseptic coverage were noted at selective sites even after repeated application . Use of the 2 % CHG polyester cloth result ed in considerably higher skin concentrations with no gaps in antiseptic coverage . Effective decolonization of the skin before hospital admission can play an important role in reducing risk of surgical site infections",
"Despite the use of ultraclean air , there are still cases of infection in total joint arthroplasty . One possible route by which bacteria may enter the wound is indirectly by contamination of instruments during skin preparation and draping . We found that bacterial air counts were 4.4 times higher during preparation and draping for hip or knee arthroplasty using an unscrubbed , ungowned leg holder than during the operation itself . With the leg holder scrubbed and gowned during preparation and draping , the air counts were reduced but were still 2.4 fold greater than intraoperatively . On some occasions , the air counts during preparation and draping exceeded the st and ards for ultraclean air irrespective of the attire of the leg holder . We recommend that the leg is held by a scrubbed and gowned member of the team . More importantly , we consider that instrument packs should be opened only after skin preparation and draping have been completed",
"BACKGROUND Previous studies have demonstrated higher infection rates following orthopaedic procedures on the foot and ankle as compared with procedures involving other areas of the body . Previous studies also have documented the difficulty of eliminating bacteria from the forefoot prior to surgery . The purpose of the present study was to evaluate the efficacy of three different surgical skin-preparation solutions in eliminating potential bacterial pathogens from the foot . METHODS A prospect i ve study was undertaken to evaluate 125 consecutive patients undergoing surgery of the foot and ankle . Each lower extremity was prepared with one of three r and omly selected solutions : DuraPrep ( 0.7 % iodine and 74 % isopropyl alcohol ) , Techni-Care ( 3.0 % chloroxylenol ) , or ChloraPrep ( 2 % chlorhexidine gluconate and 70 % isopropyl alcohol ) . After preparation , quantitative culture specimens were obtained from three locations : the hallux nailfold ( the hallux site ) , the web spaces between the second and third and between the fourth and fifth digits ( the toe site ) , and the anterior part of the tibia ( the control site ) . RESULTS In the Techni-Care group , bacteria grew on culture of specimens obtained from 95 % of the hallux sites , 98 % of the toe sites , and 35 % of the control sites . In the DuraPrep group , bacteria grew on culture of specimens obtained from 65 % of the hallux sites , 45 % of the toe sites , and 23 % of the control sites . In the ChloraPrep group , bacteria grew on culture of specimens from 30 % of the hallux sites , 23 % of the toe sites , and 10 % of the control sites . ChloraPrep was the most effective agent for eliminating bacteria from the halluces and the toes ( p chlorhexidine and alcohol ( ChloraPrep ) was most effective for eliminating bacteria from the forefoot prior to surgery",
"BACKGROUND The actual risk of prosthetic joint infection as a result of dental procedures and the role of antibiotic prophylaxis have not been defined . METHODS To examine the association between dental procedures with or without antibiotic prophylaxis and prosthetic hip or knee infection , a prospect i ve , single-center , case-control study for the period 2001 - 2006 was performed at a 1200-bed tertiary care hospital in Rochester , Minnesota . Case patients were patients hospitalized with total hip or knee infection . Control subjects were patients who underwent a total hip or knee arthroplasty but without a prosthetic joint infection who were hospitalized during the same period on the same orthopedic floor . Data regarding demographic features and potential risk factors were collected . Logistic regression was used to assess the association of variables with the odds of infection . RESULTS A total of 339 case patients and 339 control subjects were enrolled in the study . There was no increased risk of prosthetic hip or knee infection for patients undergoing a high-risk or low-risk dental procedure who were not administered antibiotic prophylaxis ( adjusted odds ratio [ OR ] , 0.8 ; 95 % confidence interval [ CI ] , 0.4 - 1.6 ) , compared with the risk for patients not undergoing a dental procedure ( adjusted OR , 0.6 ; 95 % CI , 0.4 - 1.1 ) respectively . Antibiotic prophylaxis in high-risk or low-risk dental procedures did not decrease the risk of subsequent total hip or knee infection ( adjusted OR , 0.9 [ 95 % CI , 0.5 - 1.6 ] and 1.2 [ 95 % CI , 0.7 - 2.2 ] , respectively ) . CONCLUSIONS Dental procedures were not risk factors for subsequent total hip or knee infection . The use of antibiotic prophylaxis prior to dental procedures did not decrease the risk of subsequent total hip or knee infection",
"OBJECTIVE To determine whether patients bathed daily with chlorhexidine gluconate ( CHG ) have a lower incidence of primary bloodstream infections ( BSIs ) compared with patients bathed with soap and water . METHODS The study design was a 52-week , 2-arm , crossover ( ie , concurrent control group ) clinical trial with intention-to-treat analysis . The study setting was the 22-bed medical intensive care unit ( MICU ) , which comprises 2 geographically separate , similar 11-bed units , of the John H. Stroger Jr ( Cook County ) Hospital , a 464-bed public teaching hospital in Chicago , Illinois . The study population comprised 836 MICU patients . During the first of 2 study periods ( 28 weeks ) , 1 hospital unit was r and omly selected to serve as the intervention unit in which patients were bathed daily with 2 % CHG-impregnated washcloths ( Sage 2 % CHG cloths ; Sage Products Inc , Cary , Illinois ) ; patients in the concurrent control unit were bathed daily with soap and water . After a 2-week wash-out period at the end of the first period , cleansing methods were crossed over for 24 more weeks . Main outcome measures included incidences of primary BSIs and clinical ( culture-negative ) sepsis ( primary outcomes ) and incidences of other infections ( secondary outcomes ) . RESULTS Patients in the CHG intervention arm were significantly less likely to acquire a primary BSI ( 4.1 vs 10.4 infections per 1000 patient days ; incidence difference , 6.3 [ 95 % confidence interval , 1.2 - 11.0 ) . The incidences of other infections , including clinical sepsis , were similar between the units . Protection against primary BSI by CHG cleansing was apparent after 5 or more days in the MICU . CONCLUSION Daily cleansing of MICU patients with CHG-impregnated cloths is a simple , effective strategy to decrease the rate of primary BSIs",
"HYPOTHESIS Surgical site infections ( SSIs ) are a major contributor to patient injury , mortality , and health care costs . Despite evidence of effectiveness of antimicrobials to prevent SSIs , previous studies have demonstrated inappropriate timing , selection , and excess duration of administration of antimicrobial prophylaxis . We herein describe the use of antimicrobial prophylaxis for Medicare patients undergoing major surgery . DESIGN National retrospective cohort study with medical record review . SETTING Two thous and nine hundred sixty-five acute-care US hospitals . PATIENTS A systematic r and om sample of 34,133 Medicare in patients undergoing coronary artery bypass grafting ; other open-chest cardiac surgery ( excluding transplantation ) ; vascular surgery , including aneurysm repair , thromboendarterectomy , and vein bypass operations ; general abdominal colorectal surgery ; hip and knee total joint arthroplasty ( excluding revision surgery ) ; and abdominal and vaginal hysterectomy from January 1 through November 30 , 2001 . MAIN OUTCOME MEASURES The proportion of patients who had parenteral antimicrobial prophylaxis initiated within 1 hour before the surgical incision ; the proportion of patients who were given a prophylactic antimicrobial agent that was consistent with currently published guidelines ; and the proportion of patients whose antimicrobial prophylaxis was discontinued within 24 hours after surgery . RESULTS An antimicrobial dose was administered to 55.7 % ( 95 % confidence interval [ CI ] , 54.8%-56.6 % ) of patients within 1 hour before incision . Antimicrobial agents consistent with published guidelines were administered to 92.6 % ( 95 % CI , 92.3%-92.8 % ) of the patients . Antimicrobial prophylaxis was discontinued within 24 hours of surgery end time for only 40.7 % ( 95 % CI , 40.2%-41.2 % ) of patients . CONCLUSION Substantial opportunities exist to improve the use of prophylactic antimicrobials for patients undergoing major surgery",
"Staphylococcus aureus ( S. aureus ) is an independent risk factor for orthopaedic surgical site infection ( SSI ) . To determine whether a preoperative decolonization protocol reduces S. aureus SSIs , we conducted a prospect i ve observational study of patients undergoing elective total joint arthroplasty ( TJA ) at our institution , with two control groups . The concurrent control group comprised patients of surgeons who did not participate in the intervention study . The preintervention control group comprised patients of participating surgeons who had undergone elective TJA during the year before the study . Patients in the intervention group were screened preoperatively for S. aureus by nasal swab cultures . S. aureus carriers were decolonized with mupirocin ointment to the nares twice daily and chlorhexidine bath once daily for 5 days before surgery . All 164 of 636 participants ( 26 % ) who tested positive completed the decolonization protocol without adverse events and had no postoperative S. aureus SSIs at 1-year followup . In contrast , 1330 concurrent control patients had 12 S. aureus infections . If these infections had occurred in the 26 % of patients expected to be nasal carriers of S. aureus at a given time , the infection rate would have been 3.5 % ( 12 of 345 ) in the control group . In addition , the overall infection rate of the participating surgeons , including nonstaphylococcal infections , decreased from 2.6 % during the preintervention period to 1.5 % during the intervention period , translating to an adjusted economic gain of $ 231,741 for the hospital . The data suggest a preoperative decolonization protocol reduces S. aureus SSIs in patients undergoing TJA.Level of Evidence : Level II , therapeutic study . See the Guidelines for Authors for a complete description of levels of evidence",
"A prospect i ve study of postoperative wounds was carried out in West Dorset to determine the incidence of infection , describe the time distribution of presentation before and after discharge from hospital and identify possible contributory factors . There were 702 consecutive patients admitted to the study ( 600 in- patients and 102 day cases ) . Fifty one became infected ( 47 in- patients and 4 day cases ) , corresponding to an overall infection rate of 7.3 % . Over 50 % of infections presented during the first week after operation , and almost 90 % were diagnosed within 2 weeks of surgery Twenty-eight ( 55 % ) wounds that became infected presented after hospital discharge . Of 23 specific aetiological variables studied , four ( age , preoperative stay , shaving and the surgeon ) were shown to have a statistically significant association with the development of wound infection . A strong association between the individual surgeon and the development of a wound infection was demonstrated and this supports the need for routine surgical audit",
"A prospect i ve study of surgical wound infections ( SWI ) in hip prosthesis surgery and total hip and knee replacements at two community hospitals with common surgical staffs was begun in May 1982 . The rates of SWI during the first 7 months for four orthopedic surgeons were 9 % ( 3/32 ) for hip prosthesis surgery and 16.7 % ( 3/18 ) for total hip and knee replacement , with 12 % ( 6/50 ) overall . To reduce infections , each orthopedic surgeon agreed to intraoperative surveillance ( IOS ) of two procedures ( hip prosthesis or total hip or knee replacement ) by the infection control nurse at each hospital . Significant IOS findings were too many persons in the operating room ( five to nine persons ) , operating room doors opened frequently ( 25 to 50 times ) , inconsistent use of prophylactic antibiotics , and excessive conversation . In January 1984 , IOS data and recommendations were shared with each orthopedic surgeon , the operating room staff , and the anesthesia personnel . Subsequently , a statistically significant drop in SWI was realized for total hip and knee replacement ( 1/36 versus 5/36 , p = 0.05 ) and overall ( 3/73 versus 14/116 , p = 0.05 ) . The drop in SWI for hip prosthesis surgery was not statistically significant ( 2/37 versus 9/80 , p greater than 0.10 ) . IOS and individualized communication were effective in reducing SWI",
"BACKGROUND Postoperative surgical site infections ( SSIs ) are a common complication of joint surgery . Prevention depends on adequate preoperative skin antisepsis . In previous studies , use of a 2 % chlorhexidine gluconate ( CHG ) no-rinse cloth reduced SSI rates in general surgery patients . METHODS Patients admitted for a total joint procedure used a skin antisepsis protocol incorporating 2 % CHG no-rinse cloths to do a site-specific wash on the night before surgery and in the holding area just before surgery . RESULTS In the 3 quarters before implementation of the protocol , the SSI rate was 3.19 % . In the 3 quarters after the 2 % CHG cloth was introduced , the SSI rate decreased to 1.59 % , representing a 50.16 % reduction in SSIs . CONCLUSIONS The rate of SSI was cut in half after the introduction of 2 % CHG no-rinse cloths in the place of a povidone-iodine ( Betadine ) skin antiseptic in orthopaedic patients undergoing total joint procedures . Further testing using r and omization comparative protocol s are required to conclude that the decreased SSI was in fact a direct result of the 2 % CHG protocol",
"To determine the value of ultraclean air in operating rooms , 8,052 operations for total hip- or knee-joint replacement were followed up for 1 - 4 years . For operations done in ultraclean air , bacterial contamination of the wound , deep joint sepsis , and major wound sepsis were substantially less than for operations done in conventionally ventilated rooms . Sepsis was also less frequent when prophylactic antibiotics had been given . The two pre caution s acted independently so that the incidence of sepsis after operation in ultraclean air and with antibiotics was much less than that when either was used alone . Wound sepsis was associated with an enhanced risk of joint sepsis . Staphylococcus aureus was the commonest joint pathogen , but infections with other organisms , often considered to be of low pathogenicity , were almost as numerous . Most S. aureus infections were traced to sources in the operating room",
"Postoperative wound infections in clean surgery were studied to compare the effect of preoperative whole body disinfection with chlorhexidine soap with that of local washing and no washing at all , respectively . The study includes 1530 operations for biliary tract disease , inguinal hernia and breast cancer . The overall infection rate was 3.4 % . Among patient who had a preoperative shower with Chlorhexidine the wound infection rate was significantly reduced",
"BACKGROUND Deep infection following shoulder surgery is a rare but devastating problem . The use of an effective skin-preparation solution may be an important step in preventing infection . The purpose s of the present study were to examine the native bacteria around the shoulder and to determine the efficacy of three different surgical skin-preparation solutions on the eradication of bacteria from the shoulder . METHODS A prospect i ve study was undertaken to evaluate 150 consecutive patients undergoing shoulder surgery at one institution . Each shoulder was prepared with one of three r and omly selected solutions : ChloraPrep ( 2 % chlorhexidine gluconate and 70 % isopropyl alcohol ) , DuraPrep ( 0.7 % iodophor and 74 % isopropyl alcohol ) , or povidone-iodine scrub and paint ( 0.75 % iodine scrub and 1.0 % iodine paint ) . Aerobic and anaerobic cultures were obtained prior to skin preparation for the first twenty patients , to determine the native bacteria around the shoulder , and following skin preparation for all patients . RESULTS Coagulase-negative Staphylococcus and Propionibacterium acnes were the most commonly isolated organisms prior to skin preparation . The overall rate of positive cultures was 31 % in the povidone-iodine group , 19 % in the DuraPrep group , and 7 % in the ChloraPrep group . The positive culture rate for the ChloraPrep group was lower than that for the povidone-iodine group ( p ChloraPrep and DuraPrep were more effective than povidone-iodine in eliminating coagulase-negative Staphylococcus from the shoulder region ( p eliminate Propionibacterium acnes from the shoulder region . No infections occurred in any of the patients treated in this study at a minimum of ten months of follow-up . CONCLUSIONS ChloraPrep is more effective than DuraPrep and povidone-iodine at eliminating overall bacteria from the shoulder region . Both ChloraPrep and DuraPrep are more effective than povidone-iodine at eliminating coagulase-negative Staphylococcus from the shoulder"
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Objective To evaluate the extent to which circulating biomarker and supplements of vitamin D are associated with mortality from cardiovascular , cancer , or other conditions , under various circumstances . Design Systematic review and meta- analysis of observational studies and r and omised controlled trials . Data sources Medline , Embase , Cochrane Library , and reference lists of relevant studies to August 2013 ; correspondance with investigators . Study selection Observational cohort studies and r and omised controlled trials in adults , which reported associations between vitamin D ( measured as circulating 25-hydroxyvitamin D concentration or vitamin D supplement given singly ) and cause specific mortality outcomes . Data extraction Data were extracted by two independent investigators , and a consensus was reached with involvement of a third . Study specific relative risks from 73 cohort studies ( 849 412 participants ) and 22 r and omised controlled trials ( vitamin D given alone versus placebo or no treatment ; 30 716 participants ) were meta-analysed using r and om effects models and were grouped by study and population characteristics . Results In the primary prevention observational studies , comparing bottom versus top thirds of baseline circulating 25-hydroxyvitamin D distribution , pooled relative risks were 1.35 ( 95 % confidence interval 1.13 to 1.61 ) for death from cardiovascular disease , 1.14 ( 1.01 to 1.29 ) for death from cancer , 1.30 ( 1.07 to 1.59 ) for non-vascular , non-cancer death , and 1.35 ( 1.22 to 1.49 ) for all cause mortality . Subgroup analyses in the observational studies indicated that risk of mortality was significantly higher in studies with lower baseline use of vitamin D supplements . In r and omised controlled trials , relative risks for all cause mortality were 0.89 ( 0.80 to 0.99 ) for vitamin D3 supplementation and 1.04 ( 0.97 to 1.11 ) for vitamin D2 supplementation . The effects observed for vitamin D3 supplementation remained unchanged when grouped by various characteristics . However , for vitamin D2 supplementation , increased risks of mortality were observed in studies with lower intervention doses and shorter average intervention periods . Conclusions Evidence from observational studies indicates inverse associations of circulating 25-hydroxyvitamin D with risks of death due to cardiovascular disease , cancer , and other causes . Supplementation with vitamin D3 significantly reduces overall mortality among older adults ; however , before any widespread supplementation , further investigations will be required to establish the optimal dose and duration and whether vitamin D3 and D2 have different effects on mortality risk
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"BACKGROUND Low serum 25-hydroxyvitamin D ( 25-[OH]D ) levels have been associated with lower FEV(1 ) , impaired immunologic control , and increased airway inflammation . Because many patients with chronic obstructive pulmonary disease ( COPD ) have vitamin D deficiency , effects of vitamin D supplementation may extend beyond preventing osteoporosis . OBJECTIVE To explore whether supplementation with high doses of vitamin D could reduce the incidence of COPD exacerbations . DESIGN R and omized , single-center , double-blind , placebo-controlled trial . ( Clinical Trials.gov registration number : NCT00666367 ) SETTING University Hospitals Leuven , Leuven , Belgium . PATIENTS 182 patients with moderate to very severe COPD and a history of recent exacerbations . INTERVENTION 100,000 IU of vitamin D supplementation or placebo every 4 weeks for 1 year . MEASUREMENTS The primary outcome was time to first exacerbation . Secondary outcomes were exacerbation rate , time to first hospitalization , time to second exacerbation , FEV(1 ) , quality of life , and death . RESULTS Mean serum 25-(OH)D levels increased significantly in the vitamin D group compared with the placebo group ( mean between-group difference , 30 ng/mL [ 95 % CI , 27 to 33 ng/mL ] ; P median time to first exacerbation did not significantly differ between the groups ( hazard ratio , 1.1 [ CI , 0.82 to 1.56 ] ; P = 0.41 ) , nor did exacerbation rates , FEV(1 ) , hospitalization , quality of life , and death . However , a post hoc analysis in 30 participants with severe vitamin D deficiency ( serum 25-[OH]D levels exacerbations in the vitamin D group ( rate ratio , 0.57 [ CI , 0.33 to 0.98 ] ; P = 0.042 ) . LIMITATION This was a single-center study with a small sample size . CONCLUSION High-dose vitamin D supplementation in a sample of patients with COPD did not reduce the incidence of exacerbations . In participants with severe vitamin D deficiency at baseline , supplementation may reduce exacerbations . PRIMARY FUNDING SOURCE Applied Biomedical Research Program , Agency for Innovation by Science and Technology ( IWT-TBM )",
"Background Recently , serum 25-hydroxyvitamin D ( 25OHD ) levels were shown to be associated with the survival of patients with colorectal cancer . However , 25OHD levels were measured a median of 6 years before diagnosis or were predicted levels . In this study , we directly measured serum 25OHD levels at surgery and examined the association with survival among patients with colorectal cancer . Methods We started a prospect i ve cohort study to find prognostic factors in patients with colorectal cancer from 2003 to 2008 and stored serum sample s and clinical data . As part of a post-hoc analysis , serum 25OHD levels were measured by radioimmunoassay . Association between overall survival and serum 25OHD levels were computed using the Cox proportional hazard model adjusted for month of serum sampling as well as age at diagnosis , gender , cancer stage , residual tumor after surgery , time period of surgery , location of tumor , adjuvant chemotherapy and number of lymph nodes with metastasis at surgery . Unadjusted and adjusted hazard ratios ( HR ) and 95 % confidence intervals ( 95 % CI ) were determined . Results Serum 25OHD levels were measured in 257 patients . Only 3 % had sufficient levels ( 30 ng/ml and greater ) . Based on month of blood sampling , an annual oscillation of 25OHD levels was seen , with levels being lower in spring and higher in late summer . Higher 25OHD levels were associated with better overall survival under multi-variate analysis ( HR , 0.91 : 95 % CI , 0.84 to 0.99 , P = 0.027 ) . Conclusions These results suggest that higher 25OHD levels at surgery may be associated with a better survival rate of patients with colorectal cancer",
"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",
"Introduction Vitamin D has been postulated to be involved in cancer prognosis . Thus far , only two studies reported on its association with recurrence and survival after breast cancer diagnosis yielding inconsistent results . Therefore , the aim of our study was to assess the effect of post-diagnostic serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations on overall survival and distant disease-free survival . Methods We conducted a prospect i ve cohort study in Germany including 1,295 incident postmenopausal breast cancer patients aged 50 - 74 years . Patients were diagnosed between 2002 and 2005 and median follow-up was 5.8 years . Cox proportional hazards models were stratified by age at diagnosis and season of blood collection and adjusted for other prognostic factors . Fractional polynomials were used to assess the true dose-response relation for 25(OH)D. Results Lower concentrations of 25(OH)D were linearly associated with higher risk of death ( hazard ratio ( HR ) = 1.08 per 10 nmol/L decrement ; 95 % confidence interval ( CI ) , 1.00 to 1.17 ) and significantly higher risk of distant recurrence ( HR = 1.14 per 10 nmol/L decrement ; 95%CI , 1.05 to 1.24 ) . Compared with the highest tertile ( ≥ 55 nmol/L ) , patients within the lowest tertile ( HR for overall survival of 1.55 ( 95%CI , 1.00 to 2.39 ) and a HR for distant disease-free survival of 2.09 ( 95%CI , 1.29 to 3.41 ) . In addition , the association with overall survival was found to be statistically significant only for 25(OH)D levels of blood sample s collected before start of chemotherapy but not for those of sample s taken after start of chemotherapy ( P for interaction = 0.06 ) . Conclusions In conclusion , lower serum 25(OH)D concentrations may be associated with poorer overall survival and distant disease-free survival in postmenopausal breast cancer patients",
"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",
"PURPOSE To compare the safety and activity of DN-101 , a new high-dose oral formulation of calcitriol design ed for cancer therapy , and docetaxel with placebo and docetaxel . PATIENTS AND METHODS Patients with progressive metastatic and rogen-independent prostate cancer and adequate organ function received weekly docetaxel 36 mg/m2 intravenously for 3 weeks of a 4-week cycle combined with either 45 microg DN-101 or placebo taken orally 1 day before docetaxel . The primary end point was prostate-specific antigen ( PSA ) response within 6 months of enrollment , defined as a 50 % reduction confirmed at least 4 weeks later . RESULTS Two hundred fifty patients were r and omly assigned . Baseline characteristics were similar in both arms . Within 6 months , PSA responses were seen in 58 % in DN-101 patients and 49 % in placebo patients ( P = .16 ) . Overall , PSA response rates were 63 % ( DN-101 ) and 52 % ( placebo ) , P = .07 . Patients in the DN-101 group had a hazard ratio for death of 0.67 ( P = .04 ) in a multivariate analysis that included baseline hemoglobin and performance status . Median survival has not been reached for the DN-101 arm and is estimated to be 24.5 months using the hazard ratio , compared with 16.4 months for placebo . Grade 3/4 adverse events occurred in 58 % of DN-101 patients and in 70 % of placebo-treated patients ( P = .07 ) . Most common grade 3/4 toxicities for DN-101 versus placebo were neutropenia ( 10 % v 8 % ) , fatigue ( 8 % v 16 % ) , infection ( 8 % v 13 % ) , and hyperglycemia ( 6 % v 12 % ) . CONCLUSION This study suggests that DN-101 treatment was associated with improved survival , but this will require confirmation because survival was not a primary end point . The addition of weekly DN-101 did not increase the toxicity of weekly docetaxel",
"Background Several studies have shown an association between vitamin D deficiency and cardiovascular risk . Vitamin D status is assessed by determination of 25-hydroxyvitamin D [ 25(OH)D ] in serum . Methods We assessed the prognostic utility of 25(OH)D in 982 chest-pain patients with suspected acute coronary syndrome ( ACS ) from Salta , Northern Argentina . 2-year follow-up data including all-cause mortality , cardiac death and sudden cardiac death were analyzed in quartiles of 25(OH)D , applying univariate and multivariate analysis . Results There were statistically significant changes in seasonal 25(OH)D levels . At follow-up , 119 patients had died . The mean 25(OH)D levels were significantly lower among patients dying than in long-term survivors , both in the total population and in patients with a troponin T ( TnT ) release ( n = 388 ) . When comparing 25(OH)D in the highest quartile to the lowest quartile in a multivariable Cox regression model for all-cause mortality , the hazard ratio ( HR ) for cardiac death and sudden cardiac death in the total population was 0.37 ( 95 % CI , 0.19–0.73 ) , p = 0.004 , 0.23 ( 95 % CI , 0.08–0.67 ) , p = 0.007 , and 0.32 ( 95 % CI , 0.11–0.94 ) , p = 0.038 , respectively . In patients with TnT release , the respective HR was 0.24 ( 95 % CI , 0.10–0.54 ) , p = 0.001 , 0.18 ( 95 % CI , 0.05–0.60 ) , p = 0.006 and 0.25 ( 95 % CI , 0.07–0.89 ) , p = 0.033 . 25(OH)D had no prognostic value in patients with no TnT release . Conclusion Vitamin D was shown to be a useful biomarker for prediction of mortality when obtained at admission in chest pain patients with suspected ACS . Trial registration Clinical Trials.gov",
"BACKGROUND Patients with kidney disease are at high risk of developing 25-hydroxyvitamin D [ 25(OH)D ] deficiency . OBJECTIVE We studied the association between serum 25(OH)D status and clinical outcomes of chronic peritoneal dialysis patients . DESIGN We measured serum 25(OH)D concentrations in 230 prevalent peritoneal dialysis patients and then followed these patients prospect ively for 3 y or until death . RESULTS Serum 25(OH)D was deficient or insufficient ( ie , of fatal or nonfatal cardiovascular events ( 95 % CI : 0.35 , 0.91 ; P = 0.018 ) . However , the association was gradually lost when additional adjustment was made in a stepwise fashion for residual glomerular filtration rate ( P = 0.078 ) and echocardiographic measures ( P = 0.39 ) . Kaplan-Meier estimates showed a significantly greater fatal or nonfatal cardiovascular event-free survival probability among patients with serum 25(OH)D > 45.7 nmol/L ( median ) than among patients with concentrations 45.7 nmol/L had a significantly higher cardiovascular event-free survival probability than did patients with 25(OH)D risk of cardiovascular events in chronic peritoneal dialysis patients . Furthermore , serum 25(OH)D status appeared to show a differential influence on the cardiovascular outcomes of peritoneal dialysis patients depending on the degree of left ventricular hypertrophy and systolic dysfunction ",
"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",
"CONTEXT Observational studies relating circulating 25-hydroxyvitamin D ( 25OHD ) and dietary vitamin D intake to cardiovascular disease ( CVD ) have reported conflicting results . OBJECTIVE Our objective was to investigate the association of 25OHD , dietary vitamin D , PTH , and adjusted calcium with CVD and mortality in a Scottish cohort . DESIGN AND SETTING The MIDSPAN Family Study is a prospect i ve study of 1040 men and 1298 women from the West of Scotl and recruited in 1996 and followed up for a median 14.4 yr . PARTICIPANTS Locally resident adult offspring of a general population cohort were recruited from 1972 - 1976 . MAIN OUTCOME MEASURES CVD events ( n = 416 ) and all-cause mortality ( n = 100 ) were evaluated . RESULTS 25OHD was measured using liquid chromatography-t and em mass spectrometry in available plasma ( n = 2081 ) . Median plasma 25OHD was 18.6 ng/ml , and median vitamin D intake was 3.2 μg/d ( 128 IU/d ) . Vitamin D deficiency ( 25OHD dietary vitamin D intake , PTH , or adjusted calcium were associated with CVD events or with mortality . Vitamin D deficiency was not associated with CVD ( fully adjusted hazard ratio = 1.00 ; 95 % confidence interval = 0.77 - 1.31 ) . Results were similar after excluding patients who reported an activity-limiting longst and ing illness at baseline ( 18.8 % ) and those taking any vitamin supplements ( 21.7 % ) . However , there was some evidence vitamin D deficiency was associated with all-cause mortality ( fully adjusted hazard ratio = 2.02 ; 95 % confidence interval = 1.17 - 3.51 ) . CONCLUSION Vitamin D deficiency was not associated with risk of CVD in this cohort with very low 25OHD . Future trials of vitamin D supplementation in middle-aged cohorts should be powered to detect differences in mortality outcomes as well as CVD",
"OBJECTIVE To evaluate vitamin D as a predictor of all-cause mortality , progression from normoalbuminuria to micro- or macroalbuminuria , and the development of background or proliferative retinopathy in patients with type 1 diabetes . RESEARCH DESIGN AND METHODS A prospect i ve observational follow-up study in which an inception cohort of type 1 diabetic patients was followed from onset of diabetes diagnosed between 1979 and 1984 . Plasma vitamin D [ 25(OH)D3 ] levels were determined by high performance liquid chromatography/t and em mass spectrometry in 227 patients before the patients developed microalbuminuria . Values equal to or below the 10 % percentile ( 15.5 nmol/L ) were considered severe vitamin D deficiency . RESULTS Median ( range ) vitamin D was 44.6 ( 1.7–161.7 ) nmol/L. Vitamin D level was not associated with age , sex , urinary albumin excretion rate ( UAER ) , or blood pressure . During follow-up , 44 ( 18 % ) patients died . In a Cox proportional hazards model , the hazard ratio for mortality in subjects with severe vitamin D deficiency was 2.7 ( 1.1–6.7 ) , P = 0.03 , after adjustment for UAER , HbA1c , and conventional cardiovascular risk factors ( age , sex , blood pressure , cholesterol , smoking ) . Of the 220 patients , 81 ( 37 % ) developed microalbuminuria and 27 ( 12 % ) of these progressed to macroalbuminuria . Furthermore , 192 ( 87 % ) patients developed background retinopathy , whereas 34 ( 15 % ) progressed to proliferative retinopathy . Severe vitamin D deficiency at baseline did not predict the development of these microvascular complications . CONCLUSIONS In patients with type 1 diabetes , severe vitamin D deficiency independently predicts all-cause mortality but not development of microvascular complications in the eye and kidney . Whether vitamin D substitution in type 1 diabetic patients can improve the prognosis remains to be investigated",
"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",
"Background / Objectives : Vitamin D deficiency is associated with cardiovascular disease , osteoporosis , poor muscle strength , falls , fractures and mortality . Although older adults are at a higher risk of vitamin D deficiency , the relationship of serum 25-hydroxyvitamin D ( 25(OH)D ) with all-cause and cardiovascular disease mortality has not been well characterized in the elderly . We hypothesized that low serum 25(OH)D levels predicted mortality in older adults . Subjects/ Methods : Serum 25(OH)D as well as all-cause and cardiovascular disease mortality were examined in 1006 adults , aged ⩾65 years , who participated in the InCHIANTI ( Invecchiare in Chianti , Aging in the Chianti Area ) study , a population -based , prospect i ve cohort study of aging in Tuscany , Italy . Serum 25(OH)D levels were measured at the time of enrollment in 1998–1999 , and participants were followed up for mortality . Results : During 6.5 years of follow-up , 228 ( 22.7 % ) participants died , of whom 107 died due to cardiovascular diseases . Compared with participants in the highest quartile of serum 25(OH)D ( > 26.5 ng/ml ) ( to convert to nmol/l , multiply by 2.496 ) , those in the lowest quartile ( increased risk of all-cause mortality ( Hazard Ratio ( H.R. ) 2.11 , 95 % Confidence Interval ( 95 % C.I. ) : 1.22–3.64 , P=0.007 ) and cardiovascular disease mortality ( H.R. 2.64 , 95 % C.I. : 1.14–4.79 , P=0.02 ) , in multivariate Cox proportional hazards models that adjusted for age , sex , education , season , physical activity and other potential confounders . Conclusions : Older community-dwelling adults with low serum 25(OH)D levels are at higher risk of all-cause and cardiovascular disease mortality ",
"CONTEXT Epidemiological and experimental evidence suggests that high levels of vitamin D , a potent immunomodulator , may decrease the risk of multiple sclerosis . There are no prospect i ve studies addressing this hypothesis . OBJECTIVE To examine whether levels of 25-hydroxyvitamin D are associated with risk of multiple sclerosis . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve , nested case-control study among more than 7 million US military personnel who have serum sample s stored in the Department of Defense Serum Repository . Multiple sclerosis cases were identified through Army and Navy physical disability data bases for 1992 through 2004 , and diagnoses were confirmed by medical record review . Each case ( n = 257 ) was matched to 2 controls by age , sex , race/ethnicity , and date s of blood collection . Vitamin D status was estimated by averaging 25-hydroxyvitamin D levels of 2 or more serum sample s collected before the date of initial multiple sclerosis symptoms . MAIN OUTCOME MEASURES Odds ratios of multiple sclerosis associated with continuous or categorical levels ( quantiles or a priori-defined categories ) of serum 25-hydroxyvitamin D within each racial/ethnic group . RESULTS Among whites ( 148 cases , 296 controls ) , the risk of multiple sclerosis significantly decreased with increasing levels of 25-hydroxyvitamin D ( odds ratio [ OR ] for a 50-nmol/L increase in 25-hydroxyvitamin D , 0.59 ; 95 % confidence interval , 0.36 - 0.97 ) . In categorical analyses using the lowest quintile ( 25-hydroxyvitamin D levels higher than 99.1 nmol/L , was significantly different from 1.00 ( OR , 0.38 ; 95 % confidence interval , 0.19 - 0.75 ; P = .006 ) . The inverse relation with multiple sclerosis risk was particularly strong for 25-hydroxyvitamin D levels measured before age 20 years . Among blacks and Hispanics ( 109 cases , 218 controls ) , who had lower 25-hydroxyvitamin D levels than whites , no significant associations between vitamin D and multiple sclerosis risk were found . CONCLUSION The results of our study suggest that high circulating levels of vitamin D are associated with a lower risk of multiple sclerosis",
"Purpose To investigate the association between serum 25-hydroxyvitamin D [ 25(OH)D ] concentration , a marker of vitamin D status , and risk of all-cause and cardiovascular mortality in a general older population with relatively low average serum 25(OH)D concentrations . Methods The study population included 552 men and 584 women aged 53–73 years who were free of CVD and cancer at baseline in 1998–2001 from the prospect i ve , population -based Kuopio Ischaemic Heart Disease Risk Factor ( KIHD ) Study . Deaths were ascertained by a computer linkage to the national cause of death register . All deaths that occurred from the study entry to December 31 , 2008 , were included . Cox proportional hazards regression models were used to analyze the association between serum 25(OH)D and risk of death . Results The mean serum 25(OH)D concentration was 43.7 nmol/L ( SD 17.8 ) , with a strong seasonal variation . During the average follow-up of 9.1 years , 87 participants died , 35 from cardiovascular disease ( CVD ) . After multivariable-adjustments , the hazard ratios ( HR ) for all cause death in the tertiles of serum 25(OH)D were 1 , 1.68 ( 95 % CI : 0.92 , 3.07 ) and 2.06 ( 95 % CI : 1.12 , 3.80 ) , p for trend = 0.02 . Conclusions Our study supports the accumulating evidence from epidemiological studies that vitamin D deficiency is associated with increased risk of death . Large-scale primary prevention trials with vitamin D supplementation are warranted",
"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",
"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",
"Prospect i ve epidemiologic data on the association between vitamin D and mortality are limited , particularly in Asian population s. Among subjects in Linxian , China , the authors aim ed to test whether baseline serum 25-hydroxyvitamin D ( 25(OH)D ) concentrations in a prospect i ve cohort were associated with all-cause mortality and cause-specific mortality rates over 24 years of follow-up ( 1986 - 2010 ) . Serum 25(OH)D concentrations were measured in 1,101 subjects using an immunoassay . Hazard ratios and 95 % confidence intervals were calculated using Cox regression models that were adjusted for age , sex , tobacco smoking , alcohol drinking , and hypertension . The 25th , 50th , and 75th percentile concentrations of 25(OH)D were 19.6 , 31.9 , and 48.4 nmol/L , respectively . During follow-up , 793 subjects died , including 279 who died of cerebrovascular accident , 217 who died of cancer , and 200 cardiovascular disease deaths . All-cause mortality was not associated with 25(OH)D concentrations using continuous models ( for every 15 nmol/L , hazard ratio = 1.01 , 95 % confidence interval : 0.97 , 1.05 ) or quartile models ( fourth vs. first quartiles , hazard ratio = 1.06 , 95 % confidence interval : 0.87 , 1.30 ; P for trend = 0.731 ) . The authors also found no association with the cause-specific mortality outcomes . Results were similar for men and women . This study showed that prediagnostic serum 25(OH)D concentrations were not associated with all-cause or cause-specific mortality rates in this Chinese population who had low levels of vitamin",
"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",
"BACKGROUND AND OBJECTIVES Cardiovascular disease is the main cause of mortality in chronic kidney disease ( CKD ) patients . Vitamin D might have beneficial effects on vascular health . The aim of this study was to determine the prevalence of vitamin D deficiency ( 25-hydroxyvitamin D [ 25D ] of patients at different CKD stages and the relationships between vitamin D serum levels , vascular calcification and stiffness , and the mortality risk . DESIGN , SETTING , PARTICIPANTS & MEASUREMENTS One hundred forty CKD patients ( 85 men , mean age 67 + /- 12 yr ; CKD stages 2 [ 8 % ] , 3 [ 26 % ] , 4 [ 26 % ] , 5 [ 7 % ] , and 5D [ ( 33 % ] ) were allocated for a prospect i ve study . Serum levels of 25D and 1,25-dihydroxyvitamin D , aortic calcification score , and pulse wave velocity ( PWV ) were evaluated . RESULTS There was a high prevalence of vitamin D deficiency ( 42 % ) and insufficiency ( 34 % ) . Patients with 25D survival rate than patients with 25D > 16.7 ng/ml ( mean follow-up , 605 + /- 217 d ; range , 10 to 889 ; P = 0.05 ) . Multivariate adjustments ( included age , gender , diabetes , arterial pressure , CKD stage , phosphate , albumin , hemoglobin , aortic calcification score and PWV ) confirmed 25D level as an independent predictor of all-cause mortality . CONCLUSIONS Vitamin D deficiency and insufficiency were highly prevalent in this CKD cohort . Low 25D levels affected mortality independently of vascular calcification and stiffness , suggesting that 25D may influence survival in CKD patients via additional pathways that need to be further explored",
"The beneficial biologic effects attributed to vitamin D suggest a potential to influence overall mortality . Evidence addressing this hypothesis is limited , especially for African Americans who have a high prevalence of vitamin D insufficiency . The authors conducted a nested case-control study within the prospect i ve Southern Community Cohort Study to relate baseline serum levels of 25-hydroxyvitamin D ( 25(OH)D ) with subsequent mortality . Cases were 1,852 participants who enrolled from 2002 to 2009 and died > 12 months postenrollment . Controls ( n = 1,852 ) were matched on race , sex , age , enrollment site , and blood collection date . The odds ratios for quartile 1 ( 21.64 ng/mL ) levels of 25(OH)D were 1.60 ( 95 % confidence interval ( CI ) : 1.20 , 2.14 ) for African Americans and 2.11 ( 95 % CI : 1.39 , 3.21 ) for non-African Americans . The effects were strongest for circulatory disease death , where quartile 1 versus quartile 4 odds ratios were 2.53 ( 95 % CI : 1.44 , 4.46 ) and 3.25 ( 95 % CI : 1.33 , 7.93 ) for African Americans and non-African Americans , respectively . The estimated odds of total mortality were minimized in the 25(OH)D range of 35 - 40 ng/mL. These findings provide support for the hypothesis that vitamin D status may have an important influence on mortality for both African Americans and non-African Americans",
"Low pretreatment vitamin D status has been associated with worsened disease outcomes in patients with cancer at various sites . Its prognostic significance in head and neck cancer ( HNC ) patients has not been studied . Patients with HNC who participated in a r and omized trial were evaluated for : ( i ) total intake of vitamin D from diet and supplements using a vali date d food frequency question naire ( all trial participants , n = 540 ) and ( ii ) pretreatment serum 25‐hydroxyvitamin D through a radioimmunoassay ( n = 522 ) . The association of dietary/serum measures of vitamin D status with HNC recurrence , second primary cancer ( SPC ) incidence , and overall mortality was evaluated using multivariate Cox proportional hazard models . There was no significant association between dietary or serum vitamin D measures and the three HNC outcomes . The hazard ratios ( HRs ) comparing the highest with the lowest quartile of dietary/supplemental vitamin D intake were 1.10 ( 95 % confidence interval ( CI ) : 0.66–1.84 ) for recurrence , 1.05 ( 95 % CI : 0.63–1.74 ) for SPC , and 1.27 ( 95 % CI : 0.87–1.84 ) for overall mortality . HRs comparing the uppermost to the lowest quartile of serum 25‐hydroxyvitamin D levels were 1.12 ( 95 % CI : 0.65–1.93 ) for recurrence , 0.72 ( 95 % CI : 0.40–1.30 ) for SPC , and 0.85 ( 95 % CI : 0.57–1.28 ) for overall mortality . There was no effect modification by cancer stage , season of initial treatment , or trial arm . Among patients with HNC , vitamin D status before treatment does not influence disease outcomes . Our results contrast with those from most published studies , which suggest prognostic significance of vitamin D status in cancer patients at least in subgroups",
"In prospect i ve studies , disease rates during follow-up are typically analyzed with respect to the values of factors measured during an initial baseline survey . However , because of \" regression dilution , \" this generally tends to underestimate the real associations of disease rates with the \" usual \" levels of such risk factors during some particular exposure period . The \" regression dilution ratio \" describes the ratio of the steepness of the uncorrected association to that of the real association . To assess the relevance of the usual value of a risk factor during particular exposure periods ( e.g. , first , second , and third decades ) to disease risks , regression dilution ratios can be derived by relating baseline measurements of the risk factor to replicate measurements from a reasonably representative sample of study participants after an interval equivalent to about the midpoint of each exposure period ( e.g. , at 5 , 15 , and 25 years , respectively ) . This report illustrates the impact of this time interval on the magnitude of the regression dilution ratios for blood pressure and blood cholesterol . The analyses were based on biennial re measurements over 30 years for participants in the Framingham Study ( Framingham , Massachusetts ) and a 26-year resurvey for a sample of men in the Whitehall Study ( London , Engl and ) . They show that uncorrected associations of disease risk with baseline measurements underestimate the strength of the real associations with usual levels of these risk factors during the first decade of exposure by about one-third , the second decade by about one-half , and the third decade by about two-thirds . Hence , to correct appropriately for regression dilution , replicate measurements of such risk factors may be required at varying intervals after baseline for at least a sample of participants",
"BACKGROUND Evidence is accumulating that vitamin D supplementation of patients with low 25-hydroxyvitamin D concentrations is associated with lower cardiovascular morbidity and total mortality during long-term follow-up . Little is known , however , about the effect of low concentrations of the vitamin D hormone calcitriol on total mortality . We therefore evaluated the predictive value of circulating calcitriol for midterm mortality in patients of a specialized heart center . METHODS This prospect i ve cohort study included 510 patients , 67.7 % with heart failure ( two-thirds in end stage ) , 64.3 % hypertension , 33.7 % coronary heart disease , 20.2 % diabetes , and 17.3 % renal failure . We followed the patients for up to 1 year after blood collection . For data analysis , the study cohort was stratified into quintiles of circulating calcitriol concentrations . RESULTS Patients in the lowest calcitriol quintile were more likely to have coronary heart disease , heart failure , hypertension , diabetes , and renal failure compared to other patients . They also had low 25-hydroxyvitamin D concentrations and high concentrations of creatinine , C-reactive protein , and tumor necrosis factor alpha . Eighty-two patients ( 16.0 % ) died during follow-up . Probability of 1-year survival was 66.7 % in the lowest calcitriol quintile , 82.2 % in the second quintile , 86.7 % in the intermediate quintile , 88.8 % in the fourth quintile , and 96.1 % in the highest quintile ( P survivors and nonsurvivors was best when a cutoff value of 25 ng/L was applied ( area under the ROC curve 0.72 ; 95 % CI 0.66 - 0.78 ) . CONCLUSIONS Decreased calcitriol levels are linked to excess midterm mortality in patients of a specialized heart center",
"Background Declining serum concentrations of 25-hydroxyvitamin D seen in the fall and winter as distance increases from the equator may be a factor in the seasonal increased prevalence of influenza and other viral infections . This study was done to determine if serum 25-hydroxyvitamin D concentrations correlated with the incidence of acute viral respiratory tract infections . Methodology / Findings In this prospect i ve cohort study serial monthly concentrations of 25-hydroxyvitamin D were measured over the fall and winter 2009–2010 in 198 healthy adults , blinded to the nature of the substance being measured . The participants were evaluated for the development of any acute respiratory tract infections by investigators blinded to the 25-hydroxyvitamin D concentrations . The incidence of infection in participants with different concentrations of vitamin D was determined . One hundred ninety-five ( 98.5 % ) of the enrolled participants completed the study . Light skin pigmentation , lean body mass , and supplementation with vitamin D were found to correlate with higher concentrations of 25-hydroxyvitamin D. Concentrations of 38 ng/ml or more were associated with a significant ( p developing acute respiratory tract infections and with a marked reduction in the percentages of days ill . Conclusions / Significance Maintenance of a 25-hydroxyvitamin D serum concentration of 38 ng/ml or higher should significantly reduce the incidence of acute viral respiratory tract infections and the burden of illness caused thereby , at least during the fall and winter in temperate zones . The findings of the present study provide direction for and call for future interventional studies examining the efficacy of vitamin D supplementation in reducing the incidence and severity of specific viral infections , including influenza , in the general population and in sub population s with lower 25-hydroxyvitamin D concentrations , such as pregnant women , dark skinned individuals , and the obese",
"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",
"CONTEXT Lower serum 25-hydroxyvitamin D concentrations are associated with greater risks of many chronic diseases across large , prospect i ve community-based studies . Substrate 25-hydroxyvitamin D must be converted to 1,25-dihydroxyvitamin D for full biological activity , and complex metabolic pathways suggest that interindividual variability in vitamin D metabolism may alter the clinical consequences of measured serum 25-hydroxyvitamin D. OBJECTIVE To investigate whether common variation within genes encoding the vitamin D-binding protein , megalin , cubilin , CYP27B1 , CYP24A1 , and the vitamin D receptor ( VDR ) modify associations of low 25-hydroxyvitamin D with major clinical outcomes . DESIGN , SETTING , AND PARTICIPANTS Examination of 141 single-nucleotide polymorphisms in a discovery cohort of 1514 white participants ( who were recruited from 4 US regions ) from the community-based Cardiovascular Health Study . Participants had serum 25-hydroxyvitamin D measurements in 1992 - 1993 and were followed up for a median of 11 years ( through 2006 ) . Replication meta-analyses were conducted across the independent , community-based US Health , Aging , and Body Composition ( n = 922 ; follow-up : 1998 - 1999 through 2005 ) , Italian Invecchiare in Chianti ( n = 835 ; follow-up : 1998 - 2000 through 2006 ) , and Swedish Uppsala Longitudinal Study of Adult Men ( n = 970 ; follow-up : 1991 - 1995 through 2008 ) cohort studies . MAIN OUTCOME MEASURE Composite outcome of incident hip facture , myocardial infa rct ion , cancer , and mortality over long-term follow-up . RESULTS Interactions between 5 single-nucleotide polymorphisms and low 25-hydroxyvitamin D concentration were identified in the discovery phase and 1 involving a variant in the VDR gene replicated in independent meta- analysis . Among Cardiovascular Health Study participants , low 25-hydroxyvitamin D concentration was associated with hazard ratios for risk of the composite outcome of 1.40 ( 95 % CI , 1.12 - 1.74 ) for those who had 1 minor allele at rs7968585 and 1.82 ( 95 % CI , 1.31 - 2.54 ) for those with 2 minor alleles at rs7968585 . In contrast , there was no evidence of an association ( estimated hazard ratio , 0.93 [ 95 % CI , 0.70 - 1.24 ] ) among participants who had 0 minor alleles at this single-nucleotide polymorphism . CONCLUSION Known associations of low 25-hydroxyvitamin D with major health outcomes may vary according to common genetic differences in the vitamin D receptor",
"Accumulating evidence suggests that inadequate vitamin D levels may predispose people to chronic diseases . The authors aim ed to investigate whether serum 25-hydroxyvitamin D ( 25(OH)D ) level predicts mortality from cardiovascular disease ( CVD ) . The study was based on the Mini-Finl and Health Survey and included 6,219 men and women aged > or = 30 years who were free from CVD at baseline ( 1978 - 1980 ) . During follow-up through 2006 , 640 coronary disease deaths and 293 cerebrovascular disease deaths were identified . Levels of 25(OH)D were determined from serum collected at baseline . Cox 's proportional hazards model was used to assess the association between 25(OH)D and risk of CVD death . After adjustment for potential confounders , the hazard ratio for total CVD death was 0.76 ( 95 % confidence interval ( 95 % CI ) : 0.60 , 0.95 ) for the highest quintile of 25(OH)D level versus the lowest . The association was evident for cerebrovascular death ( hazard ratio = 0.48 , 95 % CI : 0.31 , 0.75 ) but not coronary death ( hazard ratio = 0.91 , 95 % CI : 0.70 , 1.18 ) . A low vitamin D level may be associated with higher risk of a fatal CVD event , particularly cerebrovascular death . These findings need to be replicated in other population s. To demonstrate a causal link between vitamin D and CVD , r and omized controlled trials are required",
"Vitamin D insufficiency is common globally and low levels are linked to higher cancer incidence . Although vitamin D insufficiency is related to inferior prognosis in some cancers , no data exist for chronic lymphocytic leukemia/small lymphocytic lymphoma ( CLL/SLL ) . We evaluated the relationship of 25(OH)D serum levels with time-to-treatment ( TTT ) and overall survival ( OS ) in newly diagnosed CLL patients participating in a prospect i ve cohort study ( discovery cohort ) and a separate cohort of previously untreated patients participating in an observational study ( confirmation cohort ) . Of 390 CLL patients in the discovery cohort , 119 ( 30.5 % ) were 25(OH)D insufficient . After a median follow-up of 3 years , TTT ( hazard ratio[HR ] = 1.66 ; P = .005 ) and OS ( HR = 2.39 ; P = .01 ) were shorter for 25(OH)D-insufficient patients . In the validation cohort , 61 of 153 patients ( 39.9 % ) were 25(OH)D insufficient . After a median follow-up of 9.9 years , TTT ( HR = 1.59 ; P = .05 ) and OS ( HR 1.63 ; P = .06 ) were again shorter for 25(OH)D-insufficient patients . On pooled multivariable analysis of patients in both cohorts adjusting for age , sex , Rai stage , CD38 status , ZAP-70 status , immunoglobulin heavy chain variable ( IGHV ) gene mutation status , CD49d status , and cytogenetic abnormalities assessed by interphase fluorescent in situ hybridization testing , 25(OH)D insufficiency remained an independent predictor of TTT ( HR = 1.47 ; P = .008 ) , although the association with OS was not significant ( HR = 1.47 ; P = .07 ) . Vitamin D insufficiency is associated with inferior TTT and OS in CLL patients . Whether normalizing vitamin D levels in deficient CLL patients would improve outcome merits clinical testing",
"BACKGROUND The majority of dialysis patients suffer from vitamin D deficiency , which might contribute to an adverse health outcome . We aim ed to eluci date whether European dialysis patients with low 25-hydroxyvitamin D ( 25(OH)D ) levels are at increased risk of mortality and specific fatal events . METHODS This was a prospect i ve cohort study of incident dialysis patients in the Netherl and s ( the NECOSAD ) . We selected all patients with measured 25(OH)D at 12 months after the start of dialysis , the baseline for our study . By Cox regression analyses , we assessed the impact of 25(OH)D levels on short-term ( 6 months of follow-up ) as well as longer-term mortality ( 3 years of follow-up ) . Associations of 25(OH)D levels with cardiovascular and non-cardiovascular mortality were also determined . RESULTS The data from 762 patients ( 39 % females , age 59 ± 15 years , 25(OH)D = 18 ± 11 ng/mL ) were available . Fifty-one and 213 patients died during a follow-up of 6 months and 3 years , respectively . After adjustments for possible confounders , the hazard ratio ( HR ) ( with 95 % CI ) for mortality was 2.0 ( 1.0 - 3.8 ) for short-term and 1.5 ( 1.0 - 2.1 ) for longer-term mortality when comparing patients with 25(OH)D levels ≤ 10 ng/mL with those presenting with 25(OH)D levels > 10 ng/mL. Adjusted HRs for cardiovascular mortality were 2.7 ( 1.1 - 6.5 ) and 1.7 ( 1.1 - 2.7 ) for short- and longer-term mortality , respectively . For non-cardiovascular mortality , we observed no relevant association overall . The impact of 25(OH)D levels on clinical events was modified by parathyroid hormone ( PTH ) status , with low 25(OH)D levels meaningfully affecting outcomes only in patients with PTH levels above the median of 123 pmol/L. CONCLUSIONS Vitamin D deficiency in dialysis patients is associated with an adverse health outcome , in particular with short-term cardiovascular mortality . Intervention studies are urgently needed to evaluate whether vitamin D supplementation improves health outcomes of dialysis patients",
"PURPOSE Previous studies have suggested that higher plasma 25-hydroxyvitamin D(3 ) [ 25(OH)D ] levels are associated with decreased colorectal cancer risk and improved survival , but the prevalence of vitamin D deficiency in advanced colorectal cancer and its influence on outcomes are unknown . PATIENTS AND METHODS We prospect ively measured plasma 25(OH)D levels in 515 patients with stage IV colorectal cancer participating in a r and omized trial of chemotherapy . Vitamin D deficiency was defined as 25(OH)D lower than 20 ng/mL , insufficiency as 20 to 29 ng/mL , and sufficiency as ≥ 30 ng/mL. We examined the association between baseline 25(OH)D level and selected patient characteristics . Cox proportional hazards models were used to calculate hazard ratios ( HR ) for death , disease progression , and tumor response , adjusted for prognostic factors . RESULTS Among 515 eligible patients , 50 % of the study population was vitamin D deficient , and 82 % were vitamin D insufficient . Plasma 25(OH)D levels were lower in black patients compared to white patients and patients of other race ( median , 10.7 v 21.1 v 19.3 ng/mL , respectively ; P .001 ) , and females compared to males ( median , 18.3 v 21.7 ng/mL , respectively ; P = .0005 ) . Baseline plasma 25(OH)D levels were not associated with patient outcome , although given the distribution of plasma levels in this cohort , statistical power for survival analyses were limited . CONCLUSION Vitamin D deficiency is highly prevalent among patients with stage IV colorectal cancer receiving first-line chemotherapy , particularly in black and female patients",
"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",
"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",
"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",
"PURPOSE Vitamin D insufficiency is common in the United States , with low levels linked in some studies to higher cancer incidence , including non-Hodgkin 's lymphoma ( NHL ) . Recent data also suggest that vitamin D insufficiency is related to inferior prognosis in some cancers , although there are no data for NHL . PATIENTS AND METHODS We tested the hypothesis that circulating 25-hydroxyvitamin D [ 25(OH)D ] levels are predictive of event-free survival ( EFS ) and overall survival ( OS ) in a prospect i ve cohort of 983 newly diagnosed patients with NHL . 25(OH)D and 1,25-dihydroxyvitamin D [ 1,25(OH)(2)D ] levels were measured by liquid chromatography-t and em mass spectrometry . RESULTS Mean age at diagnosis was 62 years ( range , 19 to 94 years ) ; 44 % of patients had insufficient 25(OH)D levels ( Median follow-up was 34.8 months ; 404 events and 193 deaths ( 168 from lymphoma ) occurred . After adjusting for known prognostic factors and treatment , 25(OH)D insufficient patients with diffuse large B-cell lymphoma ( DLBCL ) had inferior EFS ( hazard ratio [ HR ] , 1.41 ; 95 % CI , 0.98 to 2.04 ) and OS ( HR , 1.99 ; 95 % CI , 1.27 to 3.13 ) ; 25(OH)D insufficient patients with T-cell lymphoma also had inferior EFS ( HR , 1.94 ; 95 % CI , 1.04 to 3.61 ) and OS ( HR , 2.38 ; 95 % CI , 1.04 to 5.41 ) . There were no associations with EFS for the other NHL subtypes . Among patients with DLBCL and T-cell lymphoma , higher 1,25(OH)(2)D levels were associated with better EFS and OS , suggesting that any putative tumor 1-α-hydroxylase activity did not explain the 25(OH)D associations . CONCLUSION 25(OH)D insufficiency was associated with inferior EFS and OS in DLBCL and T-cell lymphoma . Whether normalizing vitamin D levels in these patients improves outcomes will require testing in future trials",
"BACKGROUND recent systematic review s have cast doubt on the association between vitamin D and cardiovascular disease . No prior studies have investigated the association between 25-hydroxyvitamin D ( 25[OH]D ) , 1,25-dihydroxyvitamin D ( 1,25[OH](2)D ) , or intact parathyroid hormone and cardiovascular mortality in a temperate climate . METHODS a total of 1073 community-dwelling older adults were evaluated in 1997 - 1999 ; serum levels of 25(OH)D ( mean 42 ng/mL ) , 1,25(OH)(2)D ( median 29 pg/mL ) , and intact parathyroid hormone ( median 46 pg/mL ) were measured ; mean estimated glomerular filtration rate was 74 mL/min/1.73 m(2 ) . Participants were followed up to 10.4 ( mean 6.4 ) years with 111 cardiovascular deaths . RESULTS in unadjusted Cox proportional hazards models , higher levels of 1,25(OH)(2)D were protective against cardiovascular mortality , whereas higher levels of intact parathyroid hormone predicted increased risk of cardiovascular death . After adjusting for age alone or multiple covariates , there was no significant association between 25(OH)D , 1,25(OH)(2)D , or intact parathyroid hormone and cardiovascular mortality ; results did not differ by an estimated glomerular filtration rate ≥ 60 mL/min/1.73 m(2 ) or Caucasian , middle-income , community-dwelling older adults living in sunny southern California , serum levels of 25(OH)D , 1,25(OH)(2)D , and intact parathyroid hormone were not independently associated with cardiovascular mortality",
"CONTEXT Previous 25-hydroxyvitamin D [ 25(OH)D ] and mortality studies have included mostly individuals of European descent . Whether the relationship is similar in Blacks and to what extent differences in 25(OH)D explain racial disparities in mortality is unclear . OBJECTIVE The objective of the study was to examine the relationship between 25(OH)D , PTH , and mortality in Black and white community-dwelling older adults over 8.5 yr of follow-up . DESIGN AND SETTING Health ABC is a prospect i ve cohort study conducted in Memphis , TN , and Pittsburgh , PA . PARTICIPANTS Well-functioning Blacks and whites aged 71 - 80 yr with measured 25(OH)D and PTH ( n = 2638 ; 49 % male , 39 % Black ) were included in the study . MAIN OUTCOME MEASURE Multivariate-adjusted proportional hazards models estimated the hazard ratios ( HR ) for all-cause , cardiovascular , cancer , and noncancer , noncardiovascular mortality ( n = 691 deaths ) . RESULTS Mean 25(OH)D concentrations were higher in whites than in Blacks [ mean ( sd ) : 29.0 ( 9.9 ) and 20.8 ( 8.7 ) ng/ml , respectively ; P . Serum 25(OH)D by race interactions were not significant , however . Lower 25(OH)D concentrations were associated with higher mortality in Blacks and whites combined [ HR ( 95 % confidence interval [ CI ] 2.27 ( 1.59 - 3.24 ) , 1.48 ( 1.20 - 1.84 ) , and 1.25 ( 1.02 - 1.52 ) for higher mortality than whites [ HR ( 95 % CI ) 1.22 ( 1.01 , 1.48 ) ] ; after including 25(OH)D in the model , the association was attenuated [ 1.09 ( 0.90 - 1.33 ) ] . The mortality population attributable risks ( 95 % CI ) for 25(OH)D concentrations less than 20 ng/ml and less than 30 ng/ml in Blacks were 16.4 % ( 3.1 - 26.6 % ) and 37.7 % ( 11.6 - 55.1 % ) and in whites were 8.9 % ( 3.9 - 12.7 % ) and 11.1 % ( -2.7 to 22.0 % ) , respectively . PTH was also associated with mortality [ HR ( 95 % CI ) 1.80 ( 1.33 - 2.43 ) for ≥70 vs. increased mortality in Black and white community-dwelling older adults . Because 25(OH)D concentrations were much lower in Blacks , the potential impact of remediating low 25(OH)D concentrations was greater in Blacks than whites",
"PURPOSE A cohort study was carried out to test the hypothesis that higher vitamin D levels reduce the risk of relapse from melanoma . METHODS A pilot retrospective study of 271 patients with melanoma suggested that vitamin D may protect against recurrence of melanoma . We tested these findings in a survival analysis in a cohort of 872 patients recruited to the Leeds Melanoma Cohort ( median follow-up , 4.7 years ) . RESULTS In the retrospective study , self-reports of taking vitamin D supplements were nonsignificantly correlated with a reduced risk of melanoma relapse ( odds ratio = 0.6 ; 95 % CI , 0.4 to 1.1 ; P = .09 ) . Nonrelapsers had higher mean 25-hydroxyvitamin D(3 ) levels than relapsers ( 49 v 46 nmol/L ; P = .3 ; not statistically significant ) . In the cohort ( prospect i ve ) study , higher 25-hydroxyvitamin D(3 ) levels were associated with lower Breslow thickness at diagnosis ( P = .002 ) and were independently protective of relapse and death : the hazard ratio for relapse-free survival ( RFS ) was 0.79 ( 95 % CI , 0.64 to 0.96 ; P = .01 ) for a 20 nmol/L increase in serum level . There was evidence of interaction between the vitamin D receptor ( VDR ) BsmI genotype and serum 25-hydroxyvitamin D(3 ) levels on RFS . CONCLUSION Results from the retrospective study were consistent with a role for vitamin D in melanoma outcome . The cohort study tests this hypothesis , providing evidence that higher 25-hydroxyvitamin D(3 ) levels , at diagnosis , are associated with both thinner tumors and better survival from melanoma , independent of Breslow thickness . Patients with melanoma , and those at high risk of melanoma , should seek to ensure vitamin D sufficiency . Additional studies are needed to establish optimal serum levels for patients with melanoma",
"Background : Individuals with higher blood 25-hydroxyvitamin D [ 25(OH)D ] levels have a lower risk of developing colorectal cancer ( CRC ) , but the influence of 25(OH)D on mortality after CRC diagnosis is unknown . Methods : The association between prediagnostic 25(OH)D levels and CRC-specific ( N = 444 ) and overall mortality ( N = 541 ) was prospect ively examined among 1,202 participants diagnosed with CRC between 1992 and 2003 in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) cohort . Multivariable Cox proportional hazards models were used to calculate HRs and corresponding 95 % CIs according to 25(OH)D quintiles and genetic variation within the VDR and CASR genes . Potential dietary , lifestyle , and metabolic effect modifiers were also investigated . Results : There were 541 deaths , 444 ( 82 % ) due to CRC . Mean follow-up was 73 months . In multivariable analysis , higher 25(OH)D levels were associated with a statistically significant reduction in CRC-specific ( Ptrend = 0.04 ) and overall mortality ( Ptrend = 0.01 ) . Participants with 25(OH)D levels in the highest quintile had an adjusted HR of 0.69 ( 95 % CI : 0.50–0.93 ) for CRC-specific mortality and 0.67 ( 95 % CI : 0.50–0.88 ) for overall mortality , compared with the lowest quintile . Except for a possible interaction by prediagnostic dietary calcium intake ( Pinteraction = 0.01 ) , no other potential modifying factors related to CRC survival were noted . The VDR ( FokI and BsmI ) and CASR ( rs1801725 ) genotypes were not associated with survival . Conclusions : High prediagnostic 25(OH)D levels are associated with improved survival of patients with CRC . Impact : Our findings may stimulate further research directed at investigating the effects of blood vitamin D levels before , at , and after CRC diagnosis on outcomes in CRC patients . Cancer Epidemiol Biomarkers Prev ; 21(4 ) ; 582–93 . © 2012 AACR",
"CONTEXT Vitamin D deficiency and frailty are common with aging , but the association between these conditions is uncertain . OBJECTIVE To determine the association between 25-hydroxyvitamin D ( 25(OH)D ) levels and prevalent and incident frailty status among older women . DESIGN Cross-sectional and longitudinal analyses of a prospect i ve cohort study . SETTING Four U.S. centers . PARTICIPANTS 6307 women aged≥69 years . MAIN OUTCOME MEASURES Frailty status classified as robust , intermediate stage , or frail at baseline ; and robust , intermediate stage , frail , or dead ( all-cause mortality ) at follow-up an average of 4.5 years later . RESULTS At baseline , there was a U-shaped association between 25(OH)D level and odds of frailty with the lowest risk among women with levels 20.0 - 29.9 ng/ml ( referent group ) . Compared with this group , the odds of frailty were higher among those with levels Among 4551 nonfrail women at baseline , the odds of frailty/death ( vs. robust/intermediate ) at follow-up appeared higher among those with levels 15.0 - 19.9 ng/ml ( MOR 1.21 , 95 % CI 0.99 - 1.49 ) , but the CI overlapped 1.0 . The odds of death ( vs. robust/intermediate/frail at follow-up ) was higher among those with levels of 25(OH)D among older women were moderately associated with a higher odds of frailty at baseline . Among nonfrail women at baseline , lower levels ( increased risk of incident frailty or death at follow-up",
"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",
" Multiple sclerosis ( MS ) patients were r and omized , in a double blind design , and placed into either a vitamin D supplemented group or a placebo control group . As expected , serum 25-hydroxyvitamin D levels increased significantly following 6 month vitamin D supplementation ( 17+/-6 ng/ml at baseline to 28+/-8 ng/ml at 6 months ) . Vitamin D supplementation also significantly increased serum transforming growth factor (TGF)-beta 1 levels from 230+/-21 pg/ml at baseline to 295+/-40 pg/ml 6 months later . Placebo treatment had no effect on serum TGF-beta 1 levels . Tumor necrosis factor (TNF)-alpha , interferon (IFN)-gamma , and interleukin (IL)-13 were not different following vitamin D supplementation . IL-2 mRNA levels decreased following vitamin D supplementation but the differences did not reach significance . Vitamin D supplementation of MS patients for 6 months was associated with increased vitamin D status and serum TGF-beta 1",
"BACKGROUND In cross-sectional studies , low serum levels of 25-hydroxyvitamin D are associated with higher prevalence of cardiovascular risk factors and disease . This study aim ed to determine whether endogenous 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are related to all-cause and cardiovascular mortality . METHODS Prospect i ve cohort study of 3258 consecutive male and female patients ( mean [ SD ] age , 62 [ 10 ] years ) scheduled for coronary angiography at a single tertiary center . We formed quartiles according to 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels within each month of blood drawings . The main outcome measures were all-cause and cardiovascular deaths . RESULTS During a median follow-up period of 7.7 years , 737 patients ( 22.6 % ) died , including 463 deaths from cardiovascular causes . Multivariate-adjusted hazard ratios ( HRs ) for patients in the lower two 25-hydroxyvitamin D quartiles ( median , 7.6 and 13.3 ng/mL [ to convert 25-hydroxyvitamin D levels to nanomoles per liter , multiply by 2.496 ] ) were higher for all-cause mortality ( HR , 2.08 ; 95 % confidence interval [ CI ] , 1.60 - 2.70 ; and HR , 1.53 ; 95 % CI , 1.17 - 2.01 ; respectively ) and for cardiovascular mortality ( HR , 2.22 ; 95 % CI , 1.57 - 3.13 ; and HR , 1.82 ; 95 % CI , 1.29 - 2.58 ; respectively ) compared with patients in the highest 25-hydroxyvitamin D quartile ( median , 28.4 ng/mL ) . Similar results were obtained for patients in the lowest 1,25-dihydroxyvitamin D quartile . These effects were independent of coronary artery disease , physical activity level , Charlson Comorbidity Index , variables of mineral metabolism , and New York Heart Association functional class . Low 25-hydroxyvitamin D levels were significantly correlated with variables of inflammation ( C-reactive protein and interleukin 6 levels ) , oxidative burden ( serum phospholipid and glutathione levels ) , and cell adhesion ( vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 levels ) . CONCLUSIONS Low 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are independently associated with all-cause and cardiovascular mortality . A causal relationship has yet to be proved by intervention trials using vitamin",
"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",
"OBJECTIVE Few studies have examined the relationship between vitamin D levels and incident cardiovascular events in large well-characterized patient cohorts . Therefore , our objective was to determine if low vitamin D levels predicted vascular complications of diabetes . METHODS Prospect i ve analysis of 936 veterans with type 2 diabetes ( 59.7 ± 8.4 years , 96.9 % male ) who participated in the Veteran Affairs Diabetes Trial ( VADT ) was conducted . 25(OH)-vitamin D was measured a median of two years after entry and participants were subsequently followed 3.7 years . Hazard ratios ( HRs ) were calculated for cardiovascular endpoints in relation to 25(OH)-vitamin D quartile . For microvascular endpoints , logistic regression was used to calculate odds ratios . RESULTS After adjusting for age , minority status , treatment arm and history of prior event , individuals in the lowest vitamin D quartile ( i.e. , 1 - 15.9 ng/ml ) were at similar risk of MI [ HR = 1.13 ( 95 % CI : 0.53 , 2.42 ) ] , CHD [ HR = 0.87 ( 95 % CI : 0.49 , 1.55 ) ] , congestive heart failure [ HR = 1.44 ( 95 % CI : 0.67 , 3.06 ) ] , and death from any cause [ HR = 1.04 ( 95 % CI : 0.53 , 2.04 ) ] as individuals in the highest vitamin D quartile ( i.e. , 29.9 - 77.2 ng/ml ) . Similarly , there were no differences in the odds associated with retinopathy or renal disease onset or progression in the lowest versus highest vitamin D quartile . CONCLUSIONS These data indicate that vitamin D status had no significant impact on the incidence of vascular events in a cohort of high-risk veterans with diabetes in which traditional risk factors were managed according to current treatment guidelines",
"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",
"Abstract Objectives To assess the efficacy and cost effectiveness of a home safety programme and a home exercise programme to reduce falls and injuries in older people with low vision . Design R and omised controlled trial . Setting Dunedin and Auckl and , New Zeal and . Participants 391 women and men aged ≥(1 ) 75 with visual acuity of 6/24 or worse who were living in the community ; 92 % ( 361 of 391 ) completed one year of follow-up . Interventions Participants received a home safety assessment and modification programme delivered by an occupational therapist ( n = 100 ) , an exercise programme prescribed at home by a physiotherapist plus vitamin D supplementation ( n = 97 ) , both interventions ( n = 98 ) , or social visits ( n = 96 ) . Main outcome measures Numbers of falls and injuries result ing from falls , costs of implementing the home safety programme . Results Fewer falls occurred in the group r and omised to the home safety programme but not in the exercise programme ( incidence rate ratios 0.59 ( 95 % confidence interval 0.42 to 0.83 ) and 1.15 ( 0.82 to 1.61 ) , respectively ) . However , within the exercise programme , stricter adherence was associated with fewer falls ( P = 0.001 ) . A conservative analysis showed neither intervention was effective in reducing injuries from falls . Delivering the home safety programme cost $ NZ650 ( £ 234 , 344 euros , $ US432 ) ( at 2004 prices ) per fall prevented . Conclusion The home safety programme reduced falls and was more cost effective than an exercise programme in this group of elderly people with poor vision . The Otago exercise programme with vitamin D supplementation was not effective in reducing falls or injuries in this group , possibly due to low levels of adherence . Trial registration number IS RCT N15342873",
"CONTEXT Low 25-hydroxyvitamin D [ 25(OH)D ] and high PTH may contribute to increased mortality risk in older adults . OBJECTIVE The aim of the study was to test the association between 25(OH)D , PTH , and mortality in older men . DESIGN AND SETTING The prospect i ve Osteoporotic Fractures in Men ( MrOS ) study was conducted at six U.S. clinical centers . PARTICIPANTS We studied community-dwelling men at least 65 yr old ( n = 1490 ) . MAIN OUTCOME MEASURE Multivariate-adjusted proportional hazards models estimated the hazard ratio ( HR ) for mortality ; cause of death was classified as cancer , cardiovascular , and other by central review of death certificates . RESULTS During 7.3 yr of follow-up , 330 ( 22.2 % ) participants died : 97 from cancer , 110 from cardiovascular disease , and 106 from other causes . The adjusted HR per sd decrease in 25(OH)D for all-cause mortality was 1.01 ( 95 % CI , 0.89 , 1.14 ) ; no association between 25(OH)D and cardiovascular or other-cause mortality was seen . Unexpectedly , lower 25(OH)D levels were modestly associated with a decreased risk of cancer mortality ( adjusted HR per sd decrease , 0.80 ; 95 % CI , 0.64 , 0.99 ) . Analyzing 25(OH)D as a categorical variable did not alter these results . Higher PTH levels ( log-transformed ) were associated with an increased risk of all-cause mortality ( adjusted HR per sd increase , 1.15 ; 95 % CI , 1.03 , 1.29 ) and cardiovascular mortality ( adjusted HR per sd increase in PTH , 1.21 ; 95 % CI , 1.00 , 1.45 ) . CONCLUSIONS In contrast to previous studies , lower 25(OH)D levels were not associated with an increased risk of all-cause or cause-specific mortality in older men . Higher PTH levels were associated with a modest increase in mortality risk",
"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",
"Background : In chronic kidney disease and dialysis patients , vitamin D deficiency is associated with mortality . In some observational studies , calcitriol analogue therapy was associated with a better survival rate in hemodialysis ( HD ) patients . The aim of this study was to determine the relationship between serum 25-hydroxyvitamin D ( 25-OHD ) levels and alfacalcidol therapy with HD patients ’ outcomes . Methods : We measured baseline 25-OHD levels using a cross-sectional analysis in 648 HD prevalent patients from the regional ARNOS French cohort . A 42-month survival analysis was applied according to serum 25-OHD level and calcitriol analogue therapy . Results : The prevalence of 25-OHD insufficiency native vitamin D supplementation . A baseline 25-OHD level above the median value ( 18 ng/ml ) was associated with lower all-cause mortality [ hazard ratio ( HR ) , 0.73 ( 0.5–0.96 ) ; p = 0.02 ] after adjustment for age , gender , dialysis vintage , calcemia , phosphatemia , cardiovascular disease , and diabetes . Only in monovariate analysis was low-dose oral alfacalcidol therapy associated with a better survival rate in patients with and without 25-OHD deficiency [ HR , 0.7 ( 0.5–0.92 ) ; p = 0.05 ] . Conclusions : Our study shows that , among prevalent HD patients , low 25-OHD levels affect mortality . Alfacalcidol therapy , especially in small doses , may provide compensation , but this needs to be further confirmed using prospect i ve controlled studies comparing native and active vitamin D compounds",
"Abstract Introduction . Increased mortality in patients with low serum concentrations of S-25(OH)D has been described , though no causal relationship has been shown . The aim of this cohort study was to investigate the possible association between S-25(OH)D status and all-cause mortality in 5,147 patients attending a university hospital in Denmark from 2003–2008 . Methods . Serum was analyzed for ionized calcium ( S-Ca2 + ) , parathyroid hormone ( S-PTH ) and S-25(OH)D. Kaplan-Meier curves were used to analyze the association between S-25(OH)D quartiles , S-PTH-quartiles and all-cause mortality . Cox regression analyzed associations of age , gender , concentrations of ionized calcium , S-PTH and S-25(OH)D with all-cause mortality . Results . Log rank tests for both S-25(OH)D and S-PTH quartiles showed a significant difference across the quartiles . The Cox regression analysis showed a hazard ratio ( HR ) for death of 1.02 ( 95 % CI : 1.01 ; 1.03 ) for S-PTH per pmol/L increase , 1.07 ( 95 % CI : 1.05 ; 1.10 ) for S-25(OH)D per 10 nmol/L decrease and 0.54 ( 95 % CI : 0.24 ; 1.20 ) for S-Ca2 + per mmol/L increase . Discussion . This study supports growing evidence , that low serum concentrations of 25(OH)D are associated with an increased all-cause mortality ; however the nature of the study prevents the finding of a causal relationship . In the Cox regression analysis S-25(OH)D concentrations in the blood were inversely associated with all-cause mortality . Prospect i ve controlled studies are needed to confirm a causal relationship between low S-25(OH)D concentrations and mortality",
"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",
"Vitamin D deficiency is associated with osteoporosis , poor muscle strength , falls , and fractures . The relationship between serum vitamin D concentrations and mortality in older community-dwelling women has not been well characterized . We hypothesized that women with lower 25-hydroxyvitamin D ( 25[OH]D ) concentrations were at higher risk of mortality . We examined the association between serum 25[OH]D concentrations and all-cause mortality in a prospect i ve , population -based study of 714 community-dwelling women , aged 70 to 79 years , the Women 's Health and Aging Studies I and II in Baltimore , Md. The studies were originally design ed to evaluate the causes and course of physical disability in older women living in the community . Vital status was determined through follow-up interviews and matching with the National Death Index . During a median of 72 months of follow-up , 100 ( 14 % ) of 714 women died . Women in the lowest quartile of 25(OH)D ( risk of death ( hazards ratio , 2.45 ; 95 % confidence interval , 1.12 - 5.36 ; P = .02 ) compared to women in the highest quartile ( > 27.0 ng/mL or 67.4 nmol/L ) of 25(OH)D in a multivariate Cox proportional hazards model adjusting for demographics , season , and conventional risk factors . Older community-dwelling women with low 25(OH)D levels are at an increased risk of death",
"OBJECTIVE Vitamin D deficiency has been linked to cardiovascular disease and mortality in hemodialysis ( HD ) patients . The purpose of the present cross-sectional study was to analyze the Vitamin D status of dialysis patients from a single center , study determinants of Vitamin D deficiency , and assess its implication s on outcome . METHODS A prospect i ve observational study of 115 prevalent dialysis patients was carried out , in which clinical and dialysis-related characteristics including routine biochemistry were studied in relation to levels of 25-hydroxyvitamin-D ( 25[OH]D , chemiluminescence ) . Survival was assessed after a median follow-up period of 413 days . RESULTS 25(OH)D deficiency and insufficiency was present in 51 % and 42 % of the patients , respectively . Only 7 % of the patients showed normal 25(OH)D levels . Peritoneal dialysis patients presented the lowest 25(OH)D levels . Also , a significant difference was found between on-line hemodiafiltration ( OL-HDF ) and conventional HD ( 11 [ 6 to 16 ] versus 19 [ 13 to 27 ] ng/mL ; P conventional HD had 8.35 greater odds ( 95 % CI [ 2.04 to 34.20 ] ) of 25(OH)D deficiency than OL-HDF even after adjustment for sex , parathyroid hormone , pH , and Charlson comorbidity index . During the follow-up period , 18 patients died . Both crude and adjusted ( hazard ratio , 6.96 ; 95 % CI [ 1.44 to 33.64 ] ) Cox analysis identified 25(OH)D deficiency as a mortality risk factor . CONCLUSION This observational study underlines the high prevalence of hypovitaminosis D in dialysis patients and its strong implication s on outcome . Furthermore , our results suggest that OL-HDF was associated with a better preservation of the vitamin D status as compared with conventional HD",
"BACKGROUND This post hoc nested case-control analysis of the TNT study was design ed to investigate whether baseline vitamin D level is a significant predictor of cardiovascular risk among statin-treated patients and whether changes in vitamin D after treatment with atorvastatin are associated with improved cardiovascular outcomes . METHODS A total of 10,001 patients with stable coronary heart disease were r and omized to atorvastatin 80 or 10 mg for a median of 4.9 years . This analysis included 1,509 patients ( 497 with a subsequent cardiovascular event and 1,012 without an event ) with vitamin D levels determined at baseline and 1 year . Event rates were analyzed by Cox proportional hazard model by baseline vitamin D levels , with vitamin D as a continuous variable , and with change in vitamin D level as the predictor . RESULTS Vitamin D deficiency ( or insufficiency ( 15- baseline vitamin D levels or change in vitamin D levels and cardiovascular events or mortality . Modeling of events with vitamin D as a continuous variable similarly showed no relationship of vitamin D to events . These findings held true after adjustment for seasonal variations in vitamin D and other confounders . CONCLUSION In statin-treated patients with stable coronary heart disease , vitamin D levels did not predict cardiovascular risk . Changes in plasma concentrations of vitamin D after 1 year of treatment made no contribution to the efficacy of atorvastatin therapy",
"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",
"BACKGROUND Prospect i ve epidemiologic data on the association between vitamin D and all-cause and cause-specific mortality are limited . OBJECTIVE This study aim ed to determine whether 25-hydroxyvitamin D [ 25(OH)D ] concentrations were prospect ively and independently associated with cardiovascular disease ( CVD ) , cancer , and all-cause mortality in postmenopausal women . DESIGN A sub study in 2429 postmenopausal women within the Women 's Health Initiative ( WHI ) with measured baseline 25(OH)D concentrations were followed for 10 y for death from CVD , cancer , and all-cause mortality . Proportional hazards models were performed to evaluate quartiles of month-adjusted 25(OH)D concentrations , with adjustment for potential confounders . Sequential model building and analysis for multiplicative interaction were performed to evaluate the effects of central adiposity on the association of low 25(OH)D with all-cause mortality . RESULTS Of the 2429 women , 224 deaths occurred , with 79 deaths from CVD and 62 deaths from cancer . Multivariate-adjusted HRs that compared quartiles 1 ( lowest ) to 4 ( highest ) of 25(OH)D for all-cause mortality ( HR : 1.25 ; 95 % CI : 0.80 , 1.95 ) , CVD mortality ( HR : 1.27 ; 95 % CI : 0.81 , 1.99 ) , and cancer mortality ( HR : 1.39 ; 95 % CI : 0.88 , 2.19 ) were not significant . There was a potential interaction ( P = 0.08 ) between abdominal obesity and low 25(OH)D concentrations that showed an increased risk of the lowest quartile of 25(OH)D concentrations ( HR : 1.85 ; 95 % CI : 1.00 , 3.44 ) with increased mortality in women with a normal waist circumference but no increased risk in women with abdominal obesity ( HR : 0.96 ; 95 % CI : 0.52 , 1.76 ) . CONCLUSION Body fat distribution may play an important role in the modulation of the effect of low vitamin D concentrations on health . This trial was registered at clinical trials.gov as NCT 00000611",
"We prospect ively investigated relationships between blood markers of Fe , vitamin B12 , folate , vitamin C and vitamin D status and subsequent all-cause mortality in 208 men and 191 women aged 75 years or over living in the community in Aberdeen , Scotl and . The participants had been recruited for a cross-sectional study in 1999 - 2000 when they completed health and lifestyle question naires and had blood sample s taken for analysis of serum ferritin , serum vitamin B12 , erythrocyte folate , plasma vitamin C and serum 25-hydroxycholecalciferol . Mortality was ascertained on national data bases up to December 2005 , with a median time of follow up of 69.2 ( range 1.0 - 79.9 ) months . Participants were divided into sex-specific quintiles of baseline levels for each nutrient , and hazard ratios were estimated with Cox proportional hazard models adjusted for age and sex with the significance of linear trends in the associations assessed by logistic regression . There was no significant association between blood markers of Fe , vitamin B12 or folate status at baseline and mortality , but vitamin D status at baseline was inversely related to mortality ( P for trend C there was no evidence of a linear trend but participants in the lowest quintile of plasma levels had a significantly higher risk of death than those in the highest quintile . R and omized controlled trials of lifestyle changes which improve vitamin status are needed to assess whether these associations could be causal",
"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",
"This article summarizes the new 2011 report on dietary requirements for calcium and vitamin D from the Institute of Medicine ( IOM ) . An IOM Committee charged with determining the population needs for these nutrients in North America conducted a comprehensive review of the evidence for both skeletal and extraskeletal outcomes . The Committee concluded that available scientific evidence supports a key role of calcium and vitamin D in skeletal health , consistent with a cause- and -effect relationship and providing a sound basis for determination of intake requirements . For extraskeletal outcomes , including cancer , cardiovascular disease , diabetes , and autoimmune disorders , the evidence was inconsistent , inconclusive as to causality , and insufficient to inform nutritional requirements . R and omized clinical trial evidence for extraskeletal outcomes was limited and generally uninformative . Based on bone health , Recommended Dietary Allowances ( RDAs ; covering requirements of ≥97.5 % of the population ) for calcium range from 700 to 1300 mg/d for life-stage groups at least 1 yr of age . For vitamin D , RDAs of 600 IU/d for ages 1–70 yr and 800 IU/d for ages 71 yr and older , corresponding to a serum 25-hydroxyvitamin D level of at least 20 ng/ml ( 50 nmol/liter ) , meet the requirements of at least 97.5 % of the population . RDAs for vitamin D were derived based on conditions of minimal sun exposure due to wide variability in vitamin D synthesis from ultraviolet light and the risks of skin cancer . Higher values were not consistently associated with greater benefit , and for some outcomes U-shaped associations were observed , with risks at both low and high levels . The Committee concluded that the prevalence of vitamin D inadequacy in North America has been overestimated . Urgent research and clinical priorities were identified , including re assessment of laboratory ranges for 25-hydroxyvitamin D , to avoid problems of both undertreatment and overtreatment",
"It was reported that low bone mineral density ( BMD ) , osteoporotic fractures and low serum 25-hydroxyvitamin D ( 25-OHVD ) levels increase the risk of mortality in elderly Caucasian people . However , there is no data available on the relationship between bone mineral density or 25-OHVD levels and mortality in elderly Asian women . To determine whether or not low bone mineral density ( BMD ) or low 25-OHVD levels contribute to increased mortality risk , we conducted a prospect i ve observational study in 1232 ambulatory postmenopausal female volunteers . Information was obtained from the subjects on baseline BMD , the serum levels of biochemical indices including 25-OHVD , prevalent fractures , co-morbidities and lifestyle variables . The participants were observed for a total of 6.9+/-3.6 years ( mean+/-SD ) and a total of 107 participants ( 8.7 % ) were dead during the observation . Mortality was assessed and confirmed on the certificates or hospital records or information from their family . In addition to traditional risks for mortality , such as age ( Hazard ratio , 1.73 , 95 % CI , 1.51 - 1.98 , P 25-OHVD level all-cause mortality by using multivariate Cox 's regression analysis . It is suggested that prevalent osteoporosis , prevalent malignancy or lower levels of 25-OHVD represent powerful risk factors for mortality",
"Vitamin D recently has been proposed to play an important role in a broad range of organ functions , including cardiovascular ( CV ) health ; however , the CV evidence -base is limited . We prospect ively analyzed a large electronic medical records data base to determine the prevalence of vitamin D deficiency and the relation of vitamin D levels to prevalent and incident CV risk factors and diseases , including mortality . The data base contained 41,504 patient records with at least one measured vitamin D level . The prevalence of vitamin D deficiency ( ≤30 ng/ml ) was 63.6 % , with only minor differences by gender or age . Vitamin D deficiency was associated with highly significant ( p prevalence of diabetes , hypertension , hyperlipidemia , and peripheral vascular disease . Also , those without risk factors but with severe deficiency had an increased likelihood of developing diabetes , hypertension , and hyperlipidemia . The vitamin D levels were also highly associated with coronary artery disease , myocardial infa rct ion , heart failure , and stroke ( all p with incident death , heart failure , coronary artery disease/myocardial infa rct ion ( all p stroke ( p = 0.003 ) , and their composite ( p vitamin D deficiency in the general healthcare population and an association between vitamin D levels and prevalent and incident CV risk factors and outcomes . These observations lend strong support to the hypothesis that vitamin D might play a primary role in CV risk factors and disease . Given the ease of vitamin D measurement and replacement , prospect i ve studies of vitamin D supplementation to prevent and treat CV disease are urgently needed",
"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",
"OBJECTIVE Ecologic and observational studies have suggested an association between serum 25-hydroxyvitamin D ( 25(OH)D ) levels and cardiovascular disease ( CVD ) risk factors , CVD mortality , and cancer mortality . Based on this , low serum 25(OH)D levels should be associated with higher all-cause mortality in a general population . This hypothesis was tested in the present study . DESIGN The Tromsø study is a longitudinal population -based multi purpose study initiated in 1974 with focus on lifestyle-related diseases . Our data are based on the fourth Tromsø study carried out in 1994 - 1995 . METHODS Information about death and cause of death was registered by obtaining information from the National Directory of Residents and the Death Cause Registry . Serum 25(OH)D was measured in 7161 participants in the fourth Tromsø study . Results are presented for smokers ( n=2410 ) and non-smokers ( n=4751 ) separately as our immunoassay seems to overestimate 25(OH)D levels for smokers . RESULTS During a mean 11.7 years of follow-up , 1359 ( 19.0 % ) participants died . In multivariate regression models , there was a significantly increased risk of all-cause mortality ( hazard ratio ( HR ) 1.32 , confidence interval ( CI ) 1.07 - 1.62 ) among non-smoking participants in the lowest 25(OH)D quartile when compared with participants in the highest quartile . Equivalent results for smokers were not significant ( HR 1.06 , CI 0.83 - 1.35 ) . CONCLUSIONS Low serum 25(OH)D levels were associated with increased all-cause mortality for non-smokers , but the results did not reach statistical significance for smokers . However , low 25(OH)D levels are known to be associated with impaired general health , and r and omized controlled studies are needed to address the question of causality",
"BACKGROUND Vitamin D insufficiency was shown to be associated with adverse musculoskeletal and nonskeletal outcomes in numerous observational studies . However , some studies did not control for confounding factors such as age or seasonal variation of 25-hydroxyvitamin D [ 25(OH)D ] . OBJECTIVE We sought to determine the effect of vitamin D status on health outcomes . DESIGN Healthy community-dwelling women ( n = 1471 ) with a mean age of 74 y were followed in a 5-y trial of calcium supplementation . 25(OH)D was measured at baseline in all women . Skeletal and nonskeletal outcomes were evaluated according to seasonally adjusted vitamin D status at baseline . RESULTS Fifty percent of women had a seasonally adjusted 25(OH)D concentration or = 50 nmol/L. Women with a seasonally adjusted 25(OH)D concentration incidence of stroke and cardiovascular events that did not persist after adjustment for between-group differences in age or comorbidities . Women with a seasonally adjusted 25(OH)D concentration adverse consequences for any musculoskeletal outcome , including fracture , falls , bone density , or grip strength or any nonskeletal outcomes , including death , myocardial infa rct ion , cancer , heart failure , diabetes , or adverse changes in blood pressure , weight , body composition , cholesterol , or glucose . CONCLUSIONS Vitamin D insufficiency is more common in older , frailer women . Community-dwelling older women with a seasonally adjusted 25(OH)D concentration placebo-controlled trials are needed to determine whether vitamin D supplementation in individuals with vitamin D insufficiency influences health outcomes . This trial was registered at www.anzctr.org.au as ACTRN 012605000242628"
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CONTEXT The European Association of Urology Guideline Panel for Renal Cell Carcinoma ( RCC ) has prepared evidence -based guidelines and recommendations for RCC management . OBJECTIVES To provide an up date of the 2010 RCC guideline based on a st and ardised methodology that is robust , transparent , reproducible , and reliable . EVIDENCE ACQUISITION For the 2014 up date , the panel prioritised the following topics : percutaneous biopsy of renal masses , treatment of localised RCC ( including surgical and nonsurgical management ) , lymph node dissection , management of venous thrombus , systemic therapy , and local treatment of metastases , for which evidence synthesis was undertaken based on systematic review s adhering to Preferred Reporting Items for Systematic Review s and Meta-analyses ( PRISMA ) guidelines . Relevant data bases ( Medline , Cochrane Library , trial registries , conference proceedings ) were search ed ( January 2000 to November 2013 ) including r and omised controlled trials ( RCTs ) and retrospective or controlled studies with a comparator arm . Risk of bias ( RoB ) assessment and qualitative and quantitative synthesis of the evidence were performed . The remaining sections of the document were up date d following a structured literature assessment . EVIDENCE SYNTHESIS All chapters of the RCC guideline were up date d. For the various systematic review s , the search identified a total of 10,862 articles . A total of 151 studies reporting on 78,792 patients were eligible for inclusion ; where applicable , data from RCTs were included and meta-analyses were performed . For RCTs , there was low RoB across studies ; however , clinical and method ological heterogeneity prevented data pooling for most studies . The majority of studies included were retrospective with matched or unmatched cohorts based on single or multi-institutional data or national registries . The exception was for systemic treatment of metastatic RCC , in which several RCTs have been performed , result ing in recommendations based on higher levels of evidence . CONCLUSIONS The 2014 guideline has been up date d by a multidisciplinary panel using the highest method ological st and ards , and provides the best and most reliable contemporary evidence base for RCC management . PATIENT SUMMARY The European Association of Urology Guideline Panel for Renal Cell Carcinoma has thoroughly evaluated available research data on kidney cancer to establish international st and ards for the care of kidney cancer patients
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[
"BACKGROUND Besides clinical tumour size , other anatomical aspects of the renal tumour are routinely considered when evaluating the feasibility of elective nephron-sparing surgery ( NSS ) . OBJECTIVE To propose an original , st and ardised classification of renal tumours suitable for NSS based on their anatomical features and size and to evaluate the ability of this classification to predict the risk of overall complications result ing from the surgery . DESIGN , SETTING , AND PARTICIPANTS We enrolled prospect ively 164 consecutive patients who underwent NSS for renal tumours at a tertiary academic referral centre from January 2007 to December 2008 . INTERVENTION Open partial nephrectomy without vessel clamping . MEASUREMENTS All tumours were classified by integrating size with the following anatomical features : anterior or posterior face , longitudinal , and rim tumour location ; tumour relationships with renal sinus or urinary collecting system ; and percentage of tumour deepening into the kidney . We generated an algorithm evaluating each anatomical parameter and tumour size ( the preoperative aspects and dimensions used for an anatomical [ PADUA ] score ) to predict the risk of complications . RESULTS AND LIMITATIONS Overall rates of complication were significantly correlated to all the evaluated anatomical aspects , excluding clinical size and anterior or posterior location of the tumour . By multivariate analysis , PADUA scores were independent predictors of the occurrence of any grade complications ( hazard ratio [ HR ] for score 8 - 9 vs 6 - 7 : 14.535 ; HR for score ≥10 vs 6 - 7 : 30.641 ) . Potential limitations were the limited number of patients with T1b tumours included in the study and the lack of laparoscopically treated patients . Further external validation of the PADUA score is needed . CONCLUSIONS The PADUA score is a simple anatomical system that can be used to predict the risk of surgical and medical perioperative complications in patients undergoing open NSS . The use of an appropriate score can help clinicians stratify patients suitable for NSS into subgroups with different complication risks and can help research ers evaluate the real comparability among patients undergoing NSS with different surgical approaches",
"BACKGROUND The evidence for meat intake and renal cell carcinoma ( RCC ) risk is inconsistent . Mutagens related to meat cooking and processing , and variation by RCC subtype may be important to consider . OBJECTIVE In a large US cohort , we prospect ively investigated intake of meat and meat-related compounds in relation to risk of RCC , as well as clear cell and papillary RCC histologic subtypes . DESIGN Study participants ( 492,186 ) completed a detailed dietary assessment linked to a data base of heme iron , heterocyclic amines ( HCA ) , polycyclic aromatic hydrocarbons ( PAHs ) , nitrate , and nitrite concentrations in cooked and processed meats . Over 9 ( mean ) y of follow-up , we identified 1814 cases of RCC ( 498 clear cell and 115 papillary adenocarcinomas ) . HRs and 95 % CIs were estimated within quintiles by using multivariable Cox proportional hazards regression . RESULTS Red meat intake [ 62.7 g ( quintile 5 ) compared with 9.8 g ( quintile 1 ) per 1000 kcal ( median ) ] was associated with a tendency toward an increased risk of RCC [ HR : 1.19 ; 95 % CI : 1.01 , 1.40 ; P-trend = 0.06 ] and a 2-fold increased risk of papillary RCC [ P-trend = 0.002 ] . Intakes of benzo(a)pyrene ( BaP ) , a marker of PAHs , and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine ( PhIP ) , an HCA , were associated with a significant 20 - 30 % elevated risk of RCC and a 2-fold increased risk of papillary RCC . No associations were observed for the clear cell subtype . CONCLUSIONS Red meat intake may increase the risk of RCC through mechanisms related to the cooking compounds BaP and PhIP . Our findings for RCC appeared to be driven by strong associations with the rarer papillary histologic variant . This study is registered at clinical trials.gov as NCT00340015",
"BACKGROUND Most early stage kidney cancers are renal cell carcinomas ( RCCs ) , and most are diagnosed incidentally by imaging as small renal masses ( SRMs ) . Indirect evidence suggests that most small RCCs grow slowly and rarely metastasize . OBJECTIVE To determine the progression and growth rates for newly diagnosed SRMs stratified by needle core biopsy pathology . DESIGN , SETTING , AND PARTICIPANTS A multicenter prospect i ve phase 2 clinical trial of active surveillance of 209 SRMs in 178 elderly and /or infirm patients was conducted from 2004 until 2009 with treatment delayed until progression . INTERVENTION Patients underwent serial imaging and needle core biopsies . MEASUREMENTS We measured rates of change in tumor diameter ( growth measured by imaging ) and progression to ≥ 4 cm , doubling of tumor volume , or metastasis with histology on biopsy . RESULTS AND LIMITATIONS Local progression occurred in 25 patients ( 12 % ) , plus 2 progressed with metastases ( 1.1 % ) . Of the 178 subjects with 209 SRMs , 127 with 151 SRMs had>12 mo of follow-up with two or more images , with a mean follow-up of 28 mo . Their tumor diameters increased by an average of 0.13 cm/yr . Needle core biopsy in 101 SRMs demonstrated that the presence of RCC did not significantly change growth rate . Limitations included no central review of imaging and pathology and a short follow-up . CONCLUSIONS This is the first SRM active surveillance study to correlate growth with histology prospect ively . In the first 2 yr , the rate of local progression to higher stage is low , and metastases are rare . SRMs appear to grow very slowly , even if biopsy proven to be RCC . Many patients with SRMs can therefore be initially managed conservatively with serial imaging , avoiding the morbidity of surgical or ablative treatment",
"BACKGROUND Currently two pretreatment prognostic models with limited accuracy ( 65 - 67 % ) can be used to predict survival in patients with localized renal cell carcinoma ( RCC ) . OBJECTIVE We set out to develop a more accurate pretreatment model for predicting RCC-specific mortality after nephrectomy for all stages of RCC . DESIGN , SETTING , AND PARTICIPANTS The data originated from a series of prospect ively recorded contemporary cases of patients treated with radical or partial nephrectomy between 1984 and 2006 . Model development was performed using data from 2474 patients from five centers and external validation was performed using data from 1972 patients from seven centers . MEASUREMENTS The probability of RCC-specific mortality was modeled using Cox regression . The significance of the predictors was confirmed using competing risks analyses , which account for mortality from other causes . RESULTS AND LIMITATIONS Median follow-up in patients who did not die of RCC-specific causes was 4.2 yr and 3.5 yr in the development and validation cohorts , respectively . The freedom from cancer-specific mortality rates in the nomogram development cohort were 75.4 % at 5 yr after nephrectomy and 68.3 % at 10 yr after nephrectomy . All variables except gender achieved independent predictor status . In the external validation cohort the nomogram predictions were 88.1 % accurate at 1 yr , 86.8 % accurate at 2 yr , 86.8 % accurate at 5 yr , and 84.2 % accurate at 10 yr . CONCLUSIONS Our model substantially exceeds the accuracy of the existing pretreatment models . Consequently , the proposed nomogram-based predictions may be used as benchmark data for pretreatment decision making in patients with various stages of RCC",
"PURPOSE We report on a prospect i ve r and omized comparison of transperitoneal versus retroperitoneal laparoscopic radical nephrectomy for renal tumor . MATERIAL S AND METHODS Between June 1999 and June 2001 , 102 consecutive eligible patients with a computerized tomography identified renal tumor were prospect ively r and omized to undergo either a transperitoneal ( group 1 , 50 patients ) or retroperitoneal ( group 2 , 52 patients ) laparoscopic radical nephrectomy with intact specimen extraction . Exclusion criteria for the study included body mass index greater than 35 or a history of prior major abdominal surgery in the quadrant of interest . Both groups were matched regarding age ( 63 versus 65 years , p = 0.69 ) , BMI ( 29 versus 28 , p = 0.89 ) , American Society of Anesthesiologists class ( 2.7 versus 2.8 , p = 0.37 ) , laterality ( right side 46 % versus 48 % , p = 0.85 ) and mean tumor size ( 5.3 versus 5.0 cm , p = 0.73 ) . RESULTS All 102 procedures were technically successful without the need for open conversion . Compared to the transperitoneal approach , the retroperitoneal approach was associated with a shorter time to renal artery control ( 91 versus 34 minutes , p time to renal vein control ( 98 versus 45 minutes , p shorter total operative time ( 207 versus 150 minutes , p = 0.001 ) . However , the transperitoneal and retroperitoneal approaches were similar in terms of estimated blood loss ( 180 versus 242 cc , p = 0.13 ) , hospital stay ( 43 versus 45 hours , p = 0.55 ) , intraoperative complications ( 10 % versus 7.7 % , p = 0.30 ) , postoperative complications ( 20 % versus 13.5 % , p = 0.14 ) and postoperative analgesia requirements ( 27 versus 26 mg MSO4 equivalent p = 0.13 ) . Pathology revealed renal cell carcinoma in 84 % and 75 % of cases , respectively , with no positive surgical margin in any case . CONCLUSIONS Laparoscopic radical nephrectomy can be performed efficiently and effectively with the transperitoneal or the retroperitoneal approach . While renal hilar control and total operative time may be quicker with retroperitoneoscopy , the approaches are similar in terms of other patient outcomes evaluated",
"BACKGROUND Interferon alfa is widely used for metastatic renal-cell carcinoma but has limited efficacy and tolerability . Temsirolimus , a specific inhibitor of the mammalian target of rapamycin kinase , may benefit patients with this disease . METHODS In this multicenter , phase 3 trial , we r and omly assigned 626 patients with previously untreated , poor-prognosis metastatic renal-cell carcinoma to receive 25 mg of intravenous temsirolimus weekly , 3 million U of interferon alfa ( with an increase to 18 million U ) subcutaneously three times weekly , or combination therapy with 15 mg of temsirolimus weekly plus 6 million U of interferon alfa three times weekly . The primary end point was overall survival in comparisons of the temsirolimus group and the combination-therapy group with the interferon group . RESULTS Patients who received temsirolimus alone had longer overall survival ( hazard ratio for death , 0.73 ; 95 % confidence interval [ CI ] , 0.58 to 0.92 ; P=0.008 ) and progression-free survival ( P interferon alone . Overall survival in the combination-therapy group did not differ significantly from that in the interferon group ( hazard ratio , 0.96 ; 95 % CI , 0.76 to 1.20 ; P=0.70 ) . Median overall survival times in the interferon group , the temsirolimus group , and the combination-therapy group were 7.3 , 10.9 , and 8.4 months , respectively . Rash , peripheral edema , hyperglycemia , and hyperlipidemia were more common in the temsirolimus group , whereas asthenia was more common in the interferon group . There were fewer patients with serious adverse events in the temsirolimus group than in the interferon group ( P=0.02 ) . CONCLUSIONS As compared with interferon alfa , temsirolimus improved overall survival among patients with metastatic renal-cell carcinoma and a poor prognosis . The addition of temsirolimus to interferon did not improve survival . ( Clinical Trials.gov number , NCT00065468 [ Clinical Trials.gov ] . )",
"PURPOSE Laparoscopic partial nephrectomy is an increasingly performed , minimally invasive alternative to open partial nephrectomy . We compared early postoperative outcomes in 1,800 patients undergoing open partial nephrectomy by experienced surgeons with the initial experience with laparoscopic partial nephrectomy in patients with a single renal tumor 7 cm or less . MATERIAL S AND METHODS Data on 1,800 consecutive open or laparoscopic partial nephrectomies were collected prospect ively or retrospectively in tumor registries at 3 large referral centers . Demographic , intraoperative , postoperative and followup data were compared between the 2 groups . RESULTS Compared to the laparoscopic partial nephrectomy group of 771 patients the 1,028 undergoing open partial nephrectomy were a higher risk group with a greater percent presenting symptomatically with decreased performance status , impaired renal function and tumor in a solitary functioning kidney ( p partial nephrectomy group were more than 4 cm and central ly located and more proved to be malignant ( p laparoscopic partial nephrectomy was associated with shorter operative time ( p decreased operative blood loss ( p shorter hospital stay ( p intraoperative complications was comparable in the 2 groups . However , laparoscopic partial nephrectomy was associated with longer ischemia time ( p postoperative complications , particularly urological ( p number of subsequent procedures ( p Renal functional outcomes were similar 3 months after laparoscopic and open partial nephrectomy with 97.9 % and 99.6 % of renal units retaining function , respectively . Three-year cancer specific survival for patients with a single cT1N0M0 renal cell carcinoma was 99.3 % and 99.2 % after laparoscopic and open partial nephrectomy , respectively . CONCLUSIONS Early experience with laparoscopic partial nephrectomy is promising . Laparoscopic partial nephrectomy offered the advantages of less operative time , decreased operative blood loss and a shorter hospital stay . When applied to patients with a single renal tumor 7 cm or less , laparoscopic partial nephrectomy was associated with additional postoperative morbidity compared to open partial nephrectomy . However , equivalent functional and early oncological outcomes were achieved",
"OBJECTIVE Modern imaging modalities increase the detection of small ( ) renal tumors , of which about 20 % are benign . As a result , minimal invasive treatments , such as radiofrequency ablation and cryotherapy , and surveillance strategies are gaining popularity . Information that would be helpful when choosing the most appropriate management strategy for this patient group could be obtained from pretherapeutic image-guided biopsy . METHODS Under computed tomography (CT)-fluoroscopic guidance 78 patients with solid renal tumors prospect ively underwent 18-gauge core biopsy . In addition , using the same sheath , fine-needle aspiration was taken in 44 patients and analyzed cytologically . The renal masses were subsequently removed surgically and evaluated histologically . RESULTS Mean patient age was 63+/-13.5 yr ; mean tumor size was 4+/-1.8 cm . The sensitivity of core biopsy and fine-needle aspiration for the detection of renal cell carcinoma ( RCC ) was 93.5 % and 90.6 % , respectively ; Fuhrman grade was correctly predicted in 76 % and 28 % and the correct histologic subtype was identified 91 % and 86 % , respectively . Cytology from fine-needle aspiration revealed a sensitivity in detecting malignant and benign lesions of 100 % and 75 % , respectively . Two of the renal tumors diagnosed as oncocytomas on core biopsy were hybrid tumors with scattered areas of oncocytomas and chromophobe RCC . Complications of CT-guided biopsy included one marginal pneumothorax , which resolved under conservative management , and four small perirenal hematomas detected at follow-up ultrasonography not requiring further therapy . CONCLUSION CT-guided percutaneous preoperative renal tumor biopsy had a high diagnostic accuracy , particularly in predicting malignancy",
"PURPOSE To integrate stage , grade , and Eastern Cooperative Oncology Group ( ECOG ) performance status ( PS ) into a clinical ly useful tool capable of stratifying the survival of renal cell carcinoma ( RCC ) patients . PATIENTS AND METHODS The medical records of 661 patients undergoing nephrectomy at University of California Los Angeles between 1989 and 1999 were evaluated . Median age was 61 years , male-to-female ratio was 2.2:1 , and median follow-up was 37 months . Survival time was the primary end point assessed . Sixty-four possible combinations of stage , grade , and ECOG PS were analyzed and collapsed into distinct groups . The internal validity of the categorized was challenged by a univariate analysis and a multivariate analysis testing for the accountability of each UCLA Integrated Staging System ( UISS ) category against independent variables shown to have impact on survival . RESULTS Combining and stratifying 1997 tumor-node-metastasis stage , Fuhrman 's grade and ECOG PS result ed in five survival stratification groups design ated UISS , and numbered I to V. The projected 2- and 5-year survival for the UISS groups are as follows for the groups : I , 96 % and 94 % ; II , 89 % and 67 % ; III , 66 % and 39 % ; IV , 42 % and 23 % ; and V , 9 % and 0 % , respectively . UISS accounted for the significant variables in the variate analysis . CONCLUSION A novel system for staging and predicting survival for RCC integrating clinical variables is offered . UISS is simple to use and is superior to stage alone in differentiating patients ' survival . Our data suggests that UISS is an important prognostic tool for counseling patients with various stages of kidney cancer . Further prospect i ve large-scale validation with external data is awaited",
"Previous studies suggest that obesity is related to increased risk of renal cell carcinoma ( RCC ) ; however , only a few studies report on measures of central vs. peripheral adiposity . We examined the association between anthropometric measures , including waist and hip circumference and RCC risk among 348,550 men and women free of cancer at baseline from 8 countries of the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) . During 6.0 years of follow-up we identified 287 incident cases of RCC . Relative risks were calculated using Cox regression , stratified by age and study center and adjusted for smoking status , education , alcohol consumption , physical activity , menopausal status , and hormone replacement therapy use . Among women , an increased risk of RCC was conferred by body weight ( relative risk [ RR ] in highest vs. lowest quintile = 2.13 ; 95 % confidence interval [ CI ] = 1.16 - 3.90 ; p-trend = 0.003 ) , body mass index ( BMI ) ( RR = 2.25 ; 95 % CI = 1.14 - 4.44 ; p-trend = 0.009 ) , and waist ( RR = 1.67 ; 95 % CI = 0.94 - 2.98 ; p-trend = 0.003 ) and hip circumference ( RR = 2.30 ; 95 % CI = 1.22 - 4.34 ; p-trend = 0.01 ) ; however , waist and hip circumference were no longer significant after controlling for body weight . Among men , hip circumference ( RR = 0.44 ; 95 % CI = 0.20 - 0.98 ; p-trend = 0.03 ) was related significantly to decreased RCC risk only after accounting for body weight . Height was not related significantly to RCC risk . Our findings suggest that obesity is related to increased risk of RCC irrespective of fat distribution among women , whereas low hip circumference is related to increased RCC risk among men . Our data give further credence to public health efforts aim ing to reduce the prevalence of obesity to prevent RCC , in addition to other chronic diseases",
"BACKGROUND Percutaneous needle core biopsy has become established in the management of small renal masses ≤ 4 cm ( SRMs ) . Recent series have reported success rates of ≥ 80 % . Nondiagnostic results continue to be problematic . OBJECTIVE To determine the results of SRM biopsy and the outcomes of nondiagnostic biopsy and repeat biopsy . DESIGN , SETTING , AND PARTICIPANTS Patients undergoing renal tumor biopsy ( RTB ) for suspected renal cell carcinoma ( RCC ) were included in a prospect ively maintained data base . MEASUREMENTS The data base was analyzed retrospectively to determine the pathology and outcomes of SRM biopsy . Outcomes of patients with nondiagnostic biopsy were determined . Patients undergoing repeat biopsy were identified and their outcomes analyzed . RESULTS AND LIMITATIONS Three hundred forty-five biopsies were performed ( mean diameter : 2.5 cm ) . Biopsy was diagnostic in 278 cases ( 80.6 % ) and nondiagnostic in 67 cases ( 19.4 % ) . Among diagnostic biopsies , 221 ( 79.4 % ) were malignant , 94.1 % of which were RCC . Histologic subtyping and grading of RCC was possible in 88.0 % and 63.5 % of cases , respectively . Repeat biopsy was performed in 12 of the 67 nondiagnostic cases , and a diagnosis was possible in 10 ( 83.3 % ) . Eight lesions were malignant and two were oncocytic neoplasms . Pathology was available for 15 masses after initial nondiagnostic biopsy ; 11 ( 73 % ) were malignant . Larger tumor size and a solid nature on imaging predicted a successful biopsy on multivariate analysis . Grade 1 complications were experienced in 10.1 % of cases , with no major bleeding and no seeding of the biopsy tract . There was one grade 3a complication ( 0.3 % ) . This is a retrospective study and some data are unavailable on factors that may affect biopsy success rates . Repeat biopsy was not st and ard practice prior to this analysis . CONCLUSIONS RTB can be performed safely and accurately in the investigation of renal masses ≤ 4 cm . A nondiagnostic biopsy should not be considered a surrogate for the absence of malignancy . Repeat biopsy can be performed with similar accuracy , providing a diagnosis for most patients",
"CONTEXT AND OBJECTIVES The European Association of Urology Guideline Group for renal cell carcinoma ( RCC ) has prepared these guidelines to help clinicians assess the current evidence -based management of RCC and to incorporate the present recommendations into daily clinical practice . EVIDENCE ACQUISITION The recommendations provided in the current up date d guidelines are based on a thorough review of available RCC guidelines and review articles combined with a systematic literature search using Medline and the Cochrane Central Register of Controlled Trials . EVIDENCE SYNTHESIS A number of recent prospect i ve r and omised studies concerning RCC are now available with a high level of evidence , whereas earlier publications were based on retrospective analyses , including some larger multicentre validation studies , meta-analyses , and well- design ed controlled studies . CONCLUSIONS These guidelines contain information for the treatment of an individual patient according to a current st and ardised general approach . Up date d recommendations concerning diagnosis , treatment , and follow-up can improve the clinical h and ling of patients with RCC"
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411877e6-06ff-11f0-808a-c43d1ab1c353
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In this systematic review and meta- analysis of r and omized controlled trials ( RCTs ) , the effects of vitamin D supplementation on biomarkers of inflammation and oxidative stress in diabetic patients are summarized . The following data bases were search ed up to December 2017 : MEDLINE , EMBASE , Web of Science , and Cochrane Central Register of Controlled Trials . The quality of the relevant extracted data was assessed according to the Cochrane risk of bias tool . Data were pooled using the inverse variance method and expressed as mean difference with 95 % Confidence Intervals ( 95 % CI ) . Heterogeneity between studies was assessed by the Cochran Q statistic and I-squared tests ( I2 ) . Overall , 33 studies were included in the meta-analyses . Vitamin D supplementation were found to significantly reduce serum high-sensitivity C-reactive protein ( hs-CRP ) ( WMD 0.27 ; 95 % CI , - 0.35 , - 0.20 ; p malondialdehyde ( MDA ) levels ( WMD - 0.43 , 95 % CI - 0.62 , - 0.25 , p diabetic patients . In addition , vitamin D supplementation were found to increase markers of nitric oxide ( NO ) release ( WMD 4.33 , 95 % CI 0.96 , 7.70 ) , total serum antioxidant capacity ( TAC ) ( WMD 57.34 , 95 % CI 33.48 , 81.20 , p total glutathione ( GSH ) levels ( WMD 82.59 , 95 % CI 44.37 , 120.81 , p that in diabetic patients , taking vitamin D had significant effects on hs-CRP and MDA levels , and significantly increased NO , TAC and GSH levels
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"Objectives : To study the effect of Vitamin D3 supplementation on metabolic control in an obese type 2 diabetes Emirati population . Methods : This r and omized double-blind clinical trial was conducted with 87 vitamin D-deficient obese , type 2 diabetic participants . The vitamin D-group ( n=45 ) and the placebo group ( n=42 ) were matched for gender , age , HbA1c and 25-hydroxy vitamin D ( 25(OH ) D ) at the baseline . The study was divided into two phases of 3 months each ; in phase 1 , the vitamin D-group received 6000 IU vitamin D3/day followed by 3000 IU vitamin D3/day in phase 2 , whereas the placebo group ( n=42 ) received matching placebo . Results : After supplementation , serum 25(OH ) D peaked in the vitamin D-group in phase 1 ( 77.2±30.1 nmol/l , P=0.003 ) followed by a decrease in the phase 2 ( 61.4±18.8 nmol/l , P=0.006 ) , although this was higher compared with baseline . In the placebo group , no difference was observed in the serum 25(OH ) D levels throughout the intervention . Relative to baseline serum , parathyroid hormone decreased 24 % ( P=0.003 ) in the vitamin D-group in phase 2 , but remained unchanged in the placebo group . No significant changes were observed in blood pressure , fasting blood glucose , HbA1c , C-peptide , creatinine , phosphorous , alkaline phosphatase , lipids , C-reactive protein or thyroid stimulating hormone concentrations compared with baseline in either group . Conclusions : Six months of vitamin D3 supplementation to vitamin D-deficient obese type 2 diabetes patients in the UAE normalized the vitamin D status and reduced the incidence of eucalcemic parathyroid hormone elevation but showed no effect on the metabolic control",
"Trialists and epidemiologists often employ different terminology to refer to biases in r and omized trials and observational studies , even though many biases have a similar structure in both types of study . We use causal diagrams to represent the structure of biases , as described by Cochrane for r and omized trials , and provide a translation to the usual epidemiologic terms of confounding , selection bias , and measurement bias . This structural approach clarifies that an explicit description of the inferential goal -the intention-to-treat effect or the per- protocol effect-is necessary to assess risk of bias in the estimates . Being aware of each other 's terminologies will enhance communication between trialists and epidemiologists when considering key concepts and methods for causal inference",
"AIMS Patients with type 2 diabetes ( T2DM ) and chronic kidney disease ( CKD ) have impaired endothelial function . Vitamin D and its analogs may play a role in regulation of endothelial function and inflammation . We studied effects of paricalcitol compared to placebo on endothelial function and markers of inflammation and oxidative stress in patients with T2DM and CKD . METHODS A double blind , r and omized , placebo-controlled trial was conducted in 60 patients with T2DM and stage 3 or 4 CKD . Paricalcitol 1 mcg or placebo was administered orally once daily for three months . Brachial artery flow mediated dilatation ( FMD ) , nitroglycerine mediated dilation ( NMD ) , and plasma concentrations of inflammatory cytokines , tumor necrosis factor -α and interleukin-6 , highly-sensitive C-reactive protein ; endothelial surface proteins , intercellular adhesion molecule -1 and monocyte chemo attractant protein-1 , and plasma glucose , insulin , free fatty acids , and urinary isoprostane were measured at baseline and end of three months . RESULTS 27 patients in the paricalcitol group and 28 patients in the control group completed the study , though analysis of FMD at both time points was possible in 23 patients in each group . There was no significant difference in the change in FMD , NMD or the biomarkers examined after paricalcitol or placebo treatment . CONCLUSIONS Treatment with paricalcitol at this dose and duration did not affect brachial artery FMD or biomarkers of inflammation and oxidative stress . The lack of significance may be due to the fact that the study patients had advanced CKD and that effects of paricalcitol are not additive to the effects of glycemic , lipid and anti-hypertensive therapies",
"BACKGROUND Chronic low- grade systemic inflammation presented in Type 2 diabetes mellitus plays a major role in disease progression as well as development of micro- and macro-vascular complications of diabetes . Therefore , reducing inflammation can be beneficial in prevention of diabetes complications . OBJECTIVES To investigate the association between insulin resistance and inflammatory markers , and assessing the effects of oral Calcitriol on inflammatory cytokines in type 2 diabetic patients . METHODS In this double-blind r and omized placebo-controlled trial , 70 participants with type-2 diabetes were r and omly divided to two groups . One group received two capsules of Calcitriol ( 0.25 μg 1,25-dihydroxy cholecalciferol per each capsule ) per day . The second group received placebo tablets . At the beginning of the study , we assessed insulin resistance and its relation to inflammatory profile . Serum high sensitive C-reactive protein ( hs CRP ) , interleukin-6 and interleukin-18 were also measured at the beginning and the end of the 12-week supplementation trial . RESULTS Mean calcium , phosphorus and vitamin D concentrations in the study participants were 8.98 ± 0.79 mg/dL , 3.86 ± 0.50 mg/dL and 40.91 ± 30.9 ng/mL , respectively . IL-18 and hsCRP had significant positive associations with insulin resistance markers and negative associations with insulin sensitivity markers . At the end of the 12-week supplementation trial , no significant difference was seen in serum levels of hsCRP , IL-6 and IL-18 between the two groups , while these values were adjusted for baseline values . CONCLUSION Inflammation was associated with insulin resistance in diabetic patients . No anti-inflammatory effect of Calcitriol in terms of decreasing hsCRP , IL-6 and IL-18 detected",
"BACKGROUND & AIMS Low levels of serum 25-hydroxy vitamin D ( 25(OH)D ) are common in type 2 diabetic patients and cause several complications particularly , in postmenopausal women due to their senile and physiological conditions . This study aim ed to assess the effects of vitamin D-fortified low fat yogurt on glycemic status , anthropometric indexes , inflammation , and bone turnover in diabetic postmenopausal women . METHODS In a r and omized , placebo-controlled , double-blind parallel-group clinical trial , 59 postmenopausal women with type 2 diabetes received fortified yogurt ( FY ; 2000 IU vitamin D in 100 g/day ) or plain yogurt ( PY ) for 12 weeks . Glycemic markers , anthropometric indexes , inflammatory , and bone turnover markers were assessed at baseline and after 12 weeks . RESULTS After intervention , in FY group ( vs PY group ) , were observed : significant increase in serum 25(OH)D and decrease of PTH ( stable values in PY ) ; significant improvement in serum fasting insulin , HOMA-IR , HOMA-B , QUICKI , and no changes in serum fasting glucose and HbA1c ( significant worsening of all indexes in PY ) ; significant improvement in WC , WHR , FM , and no change in weight and BMI ( stable values in PY ) ; significant increase of omentin ( stable in PY ) and decrease of sNTX ( significant increase in PY ) . Final values of glycemic markers ( except HbA1c ) , omentin , and bone turnover markers significantly improved in FY group compared to PY group . Regarding final values of serum 25(OH)D in FY group , subjects were classified in insufficient and sufficient categories . Glycemic status improved more significantly in the insufficient rather than sufficient category ; whereas the other parameters had more amelioration in the sufficient category . CONCLUSIONS Daily consumption of 2000 IU vitamin D-fortified yogurt for 12 weeks improved glycemic markers ( except HbA1c ) , anthropometric indexes , inflammation , and bone turnover markers in postmenopausal women with type 2 diabetes . TRIAL REGISTRATION www.i rct .ir ( I RCT 2013110515294N1 )",
"Background Non-alcoholic fatty liver disease ( NAFLD ) is the most common hepatic disorder worldwide , reaching prevalence up to 90 % in obese patients with type 2 diabetes ( T2D ) , and representing an independent risk factor for cardiovascular mortality . Furthermore , the coexistence of T2D and NAFLD leads to higher incidence of diabetes ’ complications and additive detrimental liver outcomes . The existence of a close association between NAFLD and hypovitaminosis D , along with the anti-inflammatory and insulin-sensitizing properties of vitamin D , have been largely described , but vitamin D effects on hepatic fat content have never been tested in a r and omized controlled trial . We assessed the efficacy and safety of 24-week oral high-dose vitamin D supplementation in T2D patients with NAFLD . Methods This r and omized , double-blind , placebo-controlled trial was carried out at the Diabetes Centre of Sapienza University , Rome , Italy , to assess oral treatment with cholecalciferol ( 2000 IU/day ) or placebo in T2D patients with NAFLD . The primary endpoint was reduction of hepatic fat fraction ( HFF ) measured by magnetic resonance ; as hepatic outcomes , we also investigated changes in serum transaminases , CK18-M30 , N-terminal Procollagen III Propeptide ( P3NP ) levels , and Fatty Liver Index ( FLI ) . Secondary endpoints were improvement in metabolic ( fasting glycaemia , HbA1c , lipids , HOMA-IR , HOMA-β , ADIPO-IR , body fat distribution ) and cardiovascular ( ankle-brachial index , intima-media thickness , flow-mediated dilatation ) parameters from baseline to end of treatment . Results Sixty-five patients were r and omized , 26 ( cholecalciferol ) and 29 ( placebo ) subjects completed the study . 25(OH ) vitamin D significantly increased in the active treated group ( 48.15 ± 23.7 to 89.80 ± 23.6 nmol/L , P no group differences were found in HFF , transaminases , CK18-M30 , P3NP levels or FLI after 24 weeks . Vitamin D neither changed the metabolic profile nor the cardiovascular parameters . Conclusions Oral high-dose vitamin D supplementation over 24 weeks did not improve hepatic steatosis or metabolic/cardiovascular parameters in T2D patients with NAFLD . Studies with a longer intervention period are warranted for exploring the effect of long time exposure to vitamin D.Trial registration This trial was approved on July 2011 by the Ethics Committee of Policlinico Umberto I , Sapienza University of Rome , Italy , and registered at www . clinical trialsregister.eu number 2011 - 003010 - 17",
"Background This study was carried out to determine the effects of vitamin D and omega-3 fatty acids co- supplementation on biomarkers of inflammation , oxidative stress and pregnancy outcomes in gestational diabetes ( GDM ) patients . Methods This r and omized , double-blind , placebo-controlled trial was conducted among 120 GDM women . Participants were r and omly divided into four groups to receive : 1 ) 1000 mg omega-3 fatty acids containing 180 mg eicosapentaenoic acid ( EPA ) and 120 mg docosahexaenoic acid ( DHA ) twice a day + vitamin D placebo ( n = 30 ) ; 2 ) 50,000 IU vitamin D every 2 weeks + omega-3 fatty acids placebo ( n = 30 ) ; 3 ) 50,000 IU vitamin D every 2 weeks + 1000 mg omega-3 fatty acids twice a day ( n = 30 ) and 4 ) vitamin D placebo + omega-3 fatty acids placebo ( n = 30 ) for 6 weeks . Results Subjects who received vitamin D plus omega-3 fatty acids supplements compared with vitamin D , omega-3 fatty acids and placebo had significantly decreased high-sensitivity C-reactive protein ( −2.0 ± 3.3 vs. -0.8 ± 4.4 , −1.3 ± 2.4 and + 0.9 ± 2.7 mg/L , respectively , P = 0.008 ) , malondialdehyde ( −0.5 ± 0.5 vs. −0.2 ± 0.5 , −0.3 ± 0.9 and + 0.5 ± 1.4 μmol/L , respectively , P ( + 92.1 ± 70.1 vs. + 55.1 ± 123.6 , + 88.4 ± 95.2 and + 1.0 ± 90.8 mmol/L , respectively , P = 0.001 ) and glutathione ( + 95.7 ± 86.7 vs. + 23.0 ± 62.3 , + 30.0 ± 66.5 and −7.8 ± 126.5 μmol/L , respectively , P = 0.001 ) . In addition , vitamin D and omega-3 fatty acids co-supplementation , compared with vitamin D , omega-3 fatty acids and placebo , result ed in lower incidences of newborns ’ hyperbilirubinemiain ( P = 0.037 ) and newborns ’ hospitalization ( P = 0.037 ) . Conclusion Overall , vitamin D and omega-3 fatty acids co-supplementation for 6 weeks among GDM women had beneficial effects on some biomarkers of inflammation , oxidative stress and pregnancy outcomes",
"Background / Aims Recent epidemiological studies revealed a striking inverse relationship between vitamin D levels , glucose intolerance/insulin resistance ( IR ) , and cardiovascular disease . However , few interventional studies have evaluated the effect of vitamin D supplementation on cardiovascular risk , such as IR and arterial stiffness , in diabetes . We investigated the role of vitamin D supplementation on cardiovascular risk in type 2 diabetes patients , including metabolic parameters , IR , and arterial stiffness . Methods We enrolled patients who were taking antidiabetic medications or managed their diabetes using lifestyle changes . We excluded patients who were taking vitamin D or calcium supplements . We r and omized participants into the vitamin D group ( cholecalciferol 2,000 IU/day + calcium 200 mg/day , n = 40 ) or the placebo group ( calcium 200 mg/day , n = 41 ) . We compared their IR ( homeostasis model of assessment [HOMA]-IR ) and arterial stiffness ( brachial-ankle pulse wave velocity and radial augmentation index ) before and after 24 weeks of intervention . Results The baseline characteristics of the two groups were similar . A total of 62 participants ( placebo , 30 ; vitamin D , 32 ) completed the study protocol . At the end of the study period , the 25-hydroxyvitamin D [ 25(OH)D ] levels were significantly higher in the vitamin D group than in the placebo group ( 35.4 ± 8.5 ng/mL vs. 18.4 ± 7.3 ng/mL , p in HOMA-IR or changes in arterial stiffness ( placebo , 21 , vitamin D , 24 ) between the groups . Conclusions Our data suggest that high-dose vitamin D supplementation might be effective in terms of elevating 25(OH)D levels . However , we identified no beneficial effects on cardiovascular risk in type 2 diabetes , including IR and arterial stiffness",
"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",
"BACKGROUND Vitamin D ( VitD ) deficiency is prevalent in adolescents with type 1 diabetes ( T1D ) and is associated with diabetes-related vascular complications in adulthood . The objective of this clinical trial was to assess VitD treatment on endothelial function ( EF ) and markers of renal inflammation , in this patient group . METHODS Adolescents with T1D with suboptimal levels of VitD ( were treated for 12 to 24 weeks with a VitD analog ( VitD3 ) at doses of 1000 or 2000 IU daily . The primary end-point assessed the change in reactive hyperemia index ( lnRHI ) , a measure of EF . Secondary end-points included changes in blood pressure , lipid profile , HbA1c and albumin creatinine ratio ( ACR ) . Urinary cytokine/chemokine inflammatory profile was also assessed in a subset of subjects posttreatment . RESULTS Two hundred and seventy-one subjects were screened for VitD status and 31 VitD deficient subjects with a mean age of 15.7 ± 1.4 years were enrolled and completed the study . Mean 25-OH-VitD levels significantly increased ( 33.0 ± 12.8 vs 67.0 ± 23.2 nmol/L , P improvement in EF following VitD supplementation ( lnRHI 0.58 ± 0.20 vs 0.68 ± 0.21 , P = .03 ) . VitD supplementation did not significantly impact systolic blood pressure/diastolic blood pressure ( SBP/DBP ) , lipids , HbA1c and ACR and no adverse effects were seen . Several urinary inflammatory cytokines/chemokines : MCP-3 ( P ) ( P = .01 ) , interleukin-10 ( IL-10 ) ( P = .01 ) , also significantly decreased post-VitD-treatment . CONCLUSIONS Treatment with VitD was associated with an improvement in EF and reduced expression of urinary inflammatory markers in adolescents with T1D . This data is suggestive of an additional benefit of VitD supplementation on early markers of microvascular complications",
"Abstract Aims To assess whether a single parental dose of 25-hydroxy vitamin D [ 25(OH)Vit D ] could improve glucose control and inflammation in type 2 diabetic patients ( T2D ) with ischemic heart disease ( IHD ) . Methods A r and omized , placebo-controlled , double-blind trial was performed on 95 patients ( 47—placebo and 48—vitamin D groups ) . Participants were r and omized using a r and omization table to a single dose of either vitamin D ( 300,000 IU , IM ) or a matching placebo . Fasting blood sugar ( FBS ) , glycosylated hemoglobin ( HbA1c ) , 25(OH)Vit D and high-sensitivity C-reactive protein ( hs-CRP ) were measured at baseline and at 8 weeks . Results No significant differences in baseline values were noted between groups , except in HbA1c , which was lower in the placebo group . In the supplemented group , the level of serum 25(OH)Vit D increased ( 29.6 ± 20.8 vs. 44.5 ± 19.2 ng/mL ) and those of FBS and HbA1c decreased significantly [ 186.5 ± 64.1 vs. 165.1 ± 58.5 mg/dL and 8.2 ± 2.0 % ( 66.3 ± 21.8 mmol/mol ) vs. 7.7 ± 1.8 % ( 61.7 ± 20.0 mmol/mol ) , respectively ] ( all p of outcome variables ( HbA1c , FBS , 25(OH)Vit D and hs-CRP ) from baseline between the vitamin D versus placebo group , using ANCOVA , adjusted for the baseline of each variable itself , season at study entry , age and body mass index . During trial , only HbA1c level decreased significantly [ 0.48 % ( st and ard error : 0.17 ) , p = 0.04 ] . No any adverse effect was seen . Conclusions A single parenteral dose of vitamin D in T2D patients with IHD improved glycemic control , but not inflammatory status . Clinical trial registryAustralian New Zeal and Clinical Trial Registry . Clinical trial numberACTRN12614000529640",
"A growing body of evidence suggests that immune activation and inflammatory mediators may play a key role in the development and progression of left ventricle ( LV ) hypertrophy . The present study was design ed to test the hypothesis that the cardioprotective effect of cholecalciferol ( Vit-D3 ) is mediated via the regulation of messenger RNA ( mRNA ) expression of pro-inflammatory cytokines . Rats were r and omly divided into four groups : control group received normal saline ( 0.9 % NaCl ) i.p . for 14 days ; Vit-D3 group received Vit-D3 at a dose of 12 μg/kg/day by gavage for 14 days ; ISO group received saline for 7 days , and at day 7 , ISO ( 5 mg/kg/day ) was injected i.p . for 7 consecutive days to induce cardiac hypertrophy ; and Vit-D3 + ISO group was treated with Vit-D3 for 14 days , and at day 7 , ISO was administered for 7 consecutive days . Heart/body weight ratio , troponin-T , creatine kinase-MB , and tumor necrosis factor-α ( TNF-α ) levels of LV tissue were estimated . Levels of mRNA expression of NF-кB (NF-кB)/p65 and inhibitory kappa B (IкB)-α were determined by real-time PCR . Vit-D3 administration before and during induction of cardiac hypertrophy significantly reduced ( P . The histopathological examination further confirmed these results . In addition , Vit-D3 significantly decreased ( P and increased ( P in LV tissues compared to ISO group . Based on these findings , it was concluded that the administration of cholecalciferol markedly attenuated the development of ISO-induced cardiac hypertrophy likely through downregulation of TNF-α /NF-кb/p65 signaling pathways . However , it should be pointed out that other signaling pathways may contribute to the cardioprotective effect of Vit-D3 which requires further investigation",
"CONTEXT Systemic inflammation is thought to have a central role in diabetic long-term complications . OBJECTIVE The aim of this study was to investigate the effects of vitamin D either with or without extra calcium on certain inflammatory biomarkers in the subjects with type 2 diabetes ( T2D ) . DESIGN , SETTING , AND PARTICIPANTS This was a double-blind , r and omized , controlled trial conducted over 12 wk in 90 T2D subjects aged 30 - 60 yr from both sexes . INTERVENTION Subjects were r and omly allocated to one of three groups to receive two 250-ml bottles a day of plain Persian yogurt drink or doogh ( PD , containing 150 mg calcium and no detectable vitamin D(3)/250 ml ) , vitamin D-fortified doogh ( DD , containing 500 IU vitamin D(3 ) and 150 mg calcium/250 ml ) , or calcium + vitamin D(3)-fortified doogh ( CDD , containing 500 IU vitamin D(3 ) and 250 mg calcium/250 ml ) . OUTCOME MEASURES The changes in inflammatory markers were evaluated . RESULTS Compared to the baseline values , highly sensitive C-reactive protein , IL-1β , IL-6 , fibrinogen , and retinol binding protein-4 concentrations significantly decreased in both the DD and CDD groups . Although the decrement in highly sensitive C-reactive protein and fibrinogen was more in CDD compared to DD ( -4.0 ± 8.5 vs. -1.3 ± 2.8 mg/liter , and -0.40 ± 0.74 and -0.20 ± 0.52 mg/liter , respectively ) , the differences were not significant . There was a significant increase in serum adiponectin in both the DD and CDD groups ( 51.3 ± 65.3 vs. 57.1 ± 33.8 μg/liter ; P adiponectin changes in CDD were significantly higher than in PD ( P = 0.021 ) . CONCLUSIONS Daily intake of vitamin D-fortified doogh improved inflammatory markers in T2D subjects , and extra calcium conferred additional benefit only for the antiinflammatory adipokine , i.e. adiponectin",
"BACKGROUND Cardiovascular mortality is high among diabetic patients due to abnormalities in the plasma lipid and lipoprotein metabolism , and increased oxidative stress . This study aim ed to investigate the effects of active vitamin D on serum lipids and oxidative stress markers in type 2 diabetic patients . METHODS A double-blind r and omized placebo-controlled trial was carried out in 70 participants with type 2 diabetes , aged 30 - 75 years of age . The participants were r and omly assigned to two groups . One group received two capsules of calcitriol ( 0.25 µg 1,25-dihydroxycholecalciferol per capsule ) per day . The second group received placebo tablets . All participants received their oral hypoglycemic drugs as prescribed by the endocrinologist . At the beginning , after 6 weeks , and at the end of the 12-week supplementation trial , serum total cholesterol , low-density lipoprotein ( LDL ) , high-density lipoprotein ( HDL ) , triglyceride ( TG ) , and serum malondialdehyde ( MDA ) levels were measured . RESULTS There was a significant reduction in total cholesterol , LDL-cholesterol , TG , and MDA levels in both treatment and placebo groups ( P 0.05 ) . Serum HDL-cholesterol level decreased significantly in the placebo group ( P CONCLUSION Active vitamin D reduced lipid profile and oxidative stress markers in diabetic patients compared to the control group , but these alterations were not statistically",
"It has previously been reported that the influence of vitamin D on the metabolism of calcium and phosphorus is associated with diabetes , cardiovascular disease , Alzheimer 's disease , cancer and other systemic diseases , and is considered an important indicator of general health . The present study was conducted to determine the effect of various doses of vitamin D supplementation on glucose metabolism , lipid concentrations , inflammation and the levels of oxidative stress of pregnant women with gestational diabetes mellitus ( GDM ) . The present r and omized , double-blind placebo-controlled clinical trial was conducted on 133 pregnant women with GDM during weeks 24 - 28 of pregnancy . The patients were r and omly divided into four groups . The control group ( n=20 ) received a placebo ( sucrose ; one granule/day ) , the low dosage group ( n=38 ) received the daily recommended intake of 200 IU vitamin D ( calciferol ) daily , the medium dosage group ( n=38 ) received 50,000 IU monthly ( 2,000 IU daily for 25 days ) and the high dosage group ( n=37 ) received 50,000 IU every 2 weeks ( 4,000 IU daily for 12.5 days ) . The general characteristics and dietary intakes of the patients with GDM were similar between each group . Using ELISA kits , it was determined that insulin , homeostatic model assessment -insulin resistance and total cholesterol were significantly reduced by high dosage vitamin D supplementation ( P Total antioxidant capacity and total glutathione levels were significantly elevated as a result of high dosage vitamin D supplementation ( P vitamin D supplementation ( 50,000 IU every 2 weeks ) significantly improved insulin resistance in pregnant women with GDM",
"Introduction Chronic kidney disease ( CKD ) patients ’ are at risk of low vitamin D and chronic inflammation . We studied the effect of 12 weeks calcitriol and calcium carbonate supplementation on inflammatory mediators serum ; interleukin-6 ( IL-6 ) , interleukin-10 ( IL-10 ) and highly sensitive C-reactive protein ( hs-CRP ) . Material and methods A prospect i ve r and omized study in CKD stages 2 - 4 with serum 25-hydroxyvitamin D ( 25-OHD ) levels r and omized into the Vitamin D + Calcium ( Vitamin D + C ) or Calcium group . Serums were analyzed at baseline , week 6 and 12 . Results Fifty patients , median age of 53 ( 13.5 ) years were recruited . Their median IL-10 was 13.35 ( 25.22 ) pg/ml . At week 12 , serum IL-6 was reduced in both groups ( p = 0.001 ) , serum IL-10 was maintained in the Vitamin D + C group ( p = 0.06 ) and was reduced in the Calcium group ( p = 0.001 ) . CKD-diabetic patients had reduced serum IL-6 in both study groups ( p = 0.001 ) and a reduction was seen in the Vitamin D + C group of the non-diabetics counterparts ( p = 0.005 ) . Serum IL-10 was reduced in the Calcium group ( p serum 25-OHD rose in both groups , regardless of their diabetic status ( p calcitriol supplementation maintained IL-10 , had no effects on hs- CRP and had no additional benefit compared to calcium carbonate in reducing serum IL-6 except in non-diabetics",
"Introduction A deficiency of 25-hydroxyvitamin D ( 25(OH)D ) ( the st and ard biomarker for vitamin D status ) can have multiple impacts on the cardiovascular system . The aim of the study was to assess of the influence of 25(OH)D on severity of coronary atherosclerosis and lipid profile . Material and methods The study involved prospect ively 637 patients subject to coronary catheterization . The stage of coronary atherosclerosis was assessed using the Coronary Artery Surgery Study score ( CASSS ) . Plasma concentration of 25(OH)D was measured using an electrochemiluminescent immunoassay . The levels of total cholesterol ( TC ) , high-density cholesterol ( HDL-C ) and triglycerides ( TG ) were measured using the enzymatic method , and the concentration of low-density cholesterol ( LDL-C ) was calculated with the Friedewald equation . Results The average level of 25(OH)D was 15.85 ng/ml . A higher level of 25(OH)D was observed in men ( 16.28 ng/ml vs. 15.1 ng/ml ; p = 0.027 ) . The study did not reveal any significant correlation between the level of 25(OH)D and severity of coronary atherosclerosis . It was observed however that the increase of 25(OH)D level results in an increased number of patients without significant lesions in the coronary arteries . In the whole group of women and men in the age group of 70–80 years an inverse relationship was observed between the level of 25(OH ) and the severity of coronary atherosclerosis . The whole study group showed a statistically significant inverse correlation of the 25(OH)D level with TC ( p = 0.0057 ) , LDL-C ( p = 0.00037 ) and TG ( p = 0.00017 ) . Conclusions Women and men over 70 years showed an inverse correlation of the 25(OH)D level and the stage of coronary atherosclerosis . Deficiency of 25(OH)D affects the levels of TC , LDL-C and TG",
"Recent evidence suggests that low vitamin D concentrations are associated with increased levels of inflammatory markers . However , there are limited studies investigating associations between vitamin D levels and inflammatory markers in the general population and much of this evidence in older adults is inconclusive . Therefore , this study investigates the cross-sectional association of serum 25-hydroxyvitamin D ( 25(OH)D ) levels with inflammatory markers in 5870 older English adults from wave 6 ( 2012–2013 ) of the English Longitudinal Study of Ageing ( ELSA ) . ELSA is a large prospect i ve observational study of community-dwelling people aged 50 years and over in Engl and . Serum 25(OH)D levels , C-reactive protein ( CRP ) levels , plasma fibrinogen levels , white blood cell count ( WBC ) , age , season of blood collection , waist circumference , total non-pension household wealth , measures of health and health behaviours that included depression , number of cardiovascular , non-cardiovascular conditions and difficulties in activities of daily living , smoking , and physical activity were measured . There was a significant negative association between low 25(OH)D levels ( ≤30 nmol/l ) and CRP ( OR 1·23 , 95 % CI 1·00 , 1·51 ) and WBC ( OR 1·35 , 95 % CI 1·13 , 1·60 ) that remained after adjustment for a wide range of covariates of clinical significance . However , for fibrinogen , the association did not remain significant when waist circumference was entered in the final model . Our findings showed that 25(OH)D levels were associated with two out the three inflammatory markers investigated . The independent and inverse association between serum 25(OH)D levels and inflammation suggests a potential anti-inflammatory role for vitamin D in older English individuals from the general population",
"BACKGROUND Both poor vitamin D status and oxidative stress ( OS ) have been independently associated with late diabetic complications , including cardiovascular disease ( CVD ) . The present study aim ed to examine the effect of daily intake of vitamin D alone or in combination with calcium as a fortified Persian yogurt drink ( doogh ) on OS over 12 weeks . METHODS Ninety patients with type 2 diabetes aged 30 - 50 years from both sexes were r and omly allocated to one of the three groups to receive two 250-mL bottles of doogh a day , which was either plain ( PD ; containing 150 mg per 250 mL of calcium and no detectable vitamin D ) , vitamin D-fortified ( DD ; containing 150 mg of calcium + 500 IU vitamin D per 250 mL ) or calcium-vitamin D-fortified ( CDD ; 250 mg od calcium + 500 IU vitamin D per 250 mL ) . RESULTS Although mean ( SD ) serum concentrations of protein carbonyl significantly decreased in both DD and CDD groups [ -2.07 ( 4.39 ) nm , P = 0.015 and -4.4 ( 7.64 ) nm , P = 0.003 , respectively ] , the change in PD group was not significant [ -0.54 ( 6.96 ) nm , P = 0.674 ] . A similar pattern was observed for cardiac myeloperoxidase [ PD : -19.4 ( 75.9 ) μg L(-1 ) , P = 0.173 ; DD : -21.8 ( 54.2 ) μg L(-1 ) , P = 0.035 , CDD : -48.5 ( 76.9 ) μg L(-1 ) , P = 0.002 ] . Superoxide dismutase increased significantly only in DD and CDD [ 56.9 ( 74.0 ) U L(-1 ) , P respectively ] . Changes of serum advanced glycation end-products showed a significant between-group difference among PD , DD and CDD [ 239.4 ( 388.4 ) U L(-1 ) , -58.1 ( 147.6 ) U L(-1 ) and -143.7 ( 475.9 ) U L(-1 ) × 10(3 ) , respectively , P = 0.003 ] , which remained significant after controlling for changes of fasting serum glucose ( P = 0.013 ) and glycated haemoglobin ( P = 0.015 ) . CONCLUSIONS The findings of the present study demonstrated an OS attenuating effect of vitamin D. However , extra calcium did not convey additional benefit",
"Aims /hypothesisThis study was design ed to assess the effects of calcium and vitamin D supplementation on the metabolic status of pregnant women with gestational diabetes mellitus ( GDM ) . Methods This r and omised placebo-controlled trial was performed at maternity clinics affiliated to Kashan University of Medical Sciences , Kashan , Iran . Participants were 56 women with GDM at 24–28 weeks ’ gestation ( 18 to 40 years of age ) . Subjects were r and omly assigned to receive calcium plus vitamin D supplements or placebo . All study participants were blinded to group assignment . Individuals in the calcium – vitamin D group ( n = 28 ) received 1,000 mg calcium per day and a 50,000 U vitamin D3 pearl twice during the study ( at study baseline and on day 21 of the intervention ) , and those in the placebo group ( n = 28 ) received two placebos at the mentioned times . Fasting blood sample s were taken at study baseline and after 6 weeks of intervention . Results The study was completed by 51 participants ( calcium – vitamin D n = 25 , placebo n = 26 ) . However , as the analysis was based on an intention-to-treat approach , all 56 women with GDM ( 28 in each group ) were included in the final analysis . After the administration of calcium plus vitamin D supplements , we observed a significant reduction in fasting plasma glucose ( −0.89 ± 0.69 vs + 0.26 ± 0.92 mmol/l , p ( −13.55 ± 35.25 vs + 9.17 ± 38.50 pmol/l , p = 0.02 ) and HOMA-IR ( −0.91 ± 1.18 vs + 0.63 ± 2.01 , p = 0.001 ) and a significant increase in QUICKI ( + 0.02 ± 0.03 vs −0.002 ± 0.02 , p = 0.003 ) compared with placebo . In addition , a significant reduction in serum LDL-cholesterol ( −0.23 ± 0.79 vs + 0.26 ± 0.74 mmol/l , p = 0.02 ) and total cholesterol : HDL-cholesterol ratio ( −0.49 ± 1.09 vs + 0.18 ± 0.37 , p = 0.003 ) and a significant elevation in HDL-cholesterol levels ( + 0.15 ± 0.25 vs −0.02 ± 0.24 mmol/l , p = 0.01 ) was seen after intervention in the calcium – vitamin D group compared with placebo . In addition , calcium plus vitamin D supplementation result ed in a significant increase in GSH ( + 51.14 ± 131.64 vs −47.27 ± 203.63 μmol/l , p = 0.03 ) and prevented a rise in MDA levels ( + 0.06 ± 0.66 vs + 0.93 ± 2.00 μmol/l , p = 0.03 ) compared with placebo . Conclusions /interpretationCalcium plus vitamin D supplementation in women with GDM had beneficial effects on their metabolic profile . Trial registration www.i rct .ir I RCT 201311205623N11 Funding The study was supported by a grant ( no. 92110 ) from Kashan University of Medical Sciences",
"CONTEXT To the best of our knowledge , no study has examined the effects of vitamin D-calcium cosupplementation on inflammatory biomarkers and adipocytokines in vitamin D-insufficient type 2 diabetics . OBJECTIVE This study was performed to assess the effects of vitamin D and calcium supplementation on inflammatory biomarkers and adipocytokines in vitamin D-insufficient people with type 2 diabetes . METHODS Totally , 118 diabetic patients were enrolled in this r and omized , placebo-controlled clinical trial . After matching for age , sex , body mass index , type and dose of hypoglycemic agents , and duration of diabetes , subjects were r and omly assigned into 4 groups receiving the following : 1 ) 50000 IU/wk vitamin D + calcium placebo ; 2 ) 1000 mg/d calcium + vitamin D placebo ; 3 ) 50 000 IU/wk vitamin D + 1000 mg/d calcium ; or 4 ) vitamin D placebo + calcium placebo for 8 weeks . Blood sampling was done for the quantification of inflammatory biomarkers and adipocytokines at the study baseline and after 8 weeks of intervention . RESULTS Calcium ( changes from baseline : -75 ± 19 ng/ml , P = .01 ) and vitamin D alone ( -56 ± 19 ng/mL , P = .01 ) and joint calcium-vitamin D supplementation ( -92 ± 19 ng/mL , P = .01 ) result ed in a significant reduction in serum leptin levels compared with placebo ( -9 ± 18 ng/mL ) . This was also the case for serum IL-6 , such that calcium ( -2 ± 1 pg/mL , P and vitamin D alone ( -4 ± 1 pg/mL , P the calcium ( -3.1 ± 1.3 , P , vitamin D ( -3.1 ± 1.3 , P joint calcium-vitamin D groups ( -3.4 ± 1.3 , P reductions in serum TNF-α concentrations compared with placebo ( 0.1 ± 1.2 ) . Individuals who received joint calcium-vitamin D supplements tended to have a decrease in serum high-sensitivity C-reactive protein levels compared with placebo after controlling for baseline levels ( -1.14 ± 0.25 vs 0.02 ± 0.24 ng/mL , P = .09 ) . CONCLUSION Joint calcium-vitamin D supplementation might improve systemic inflammation through decreasing IL-6 and TNF-α concentrations in vitamin D-insufficient people with type 2 diabetes",
"BACKGROUND Suboptimal vitamin D status is associated with endothelial dysfunction and an increased risk of cardiovascular diseases but it is unclear whether vitamin D supplementation is beneficial . The aim was to investigate the effect of vitamin D supplementation on endothelial function in patients with type 2 diabetes mellitus ( DM ) . METHODS In a double-blind , placebo-controlled trial , we r and omized 100 type 2 DM patients to vitamin D supplement ( 5000 IU/day , n = 50 ) or placebo ( controls , n = 50 ) for 12 weeks . Assessment of vascular function with brachial artery flow-mediated dilatation ( FMD ) , circulating levels of endothelial progenitor cells ( EPCs ) and brachial-ankle pulse wave velocity , and metabolic parameter , high-sensitivity C-reactive protein ( hsCRP ) and oxidative stress markers were performed before and after the supplementation . RESULTS After 12 weeks , vitamin D treated patients had significant increases in serum 25-hydroxyvitamin D [ 25(OH)D ] concentration ( treatment effect 34.7 ng/mL , 95 % CI 26.4 - 42.9 , P serum ionized calcium ( treatment effect 0.037 mmol/L , 95 % CI 0.007 - 0.067 , P = 0.018 ) ; decreased serum parathyroid hormone concentration ( treatment effect -0.55 pmol/L , 95 % CI -1.08 to -0.02 , P = 0.042 ) compared to patients who received placebo . Nevertheless , vitamin D supplementation did not improve vascular function as determined by FMD , circulating EPC count or baPWV ( all P > 0.05 ) . Furthermore , hsCRP , oxidative stress markers , low- and high-density lipoprotein and glycated hemoglobin were also similar between two groups ( all P > 0.05 ) . CONCLUSION In patients with type 2 DM , 12 weeks oral supplementation of vitamin D did not significantly affect vascular function or serum biomarkers of inflammation and oxidative stress . CLINICAL TRIAL NUMBER HKCTR-867 , www.hk clinical trials.com",
"BACKGROUND & AIMS Vitamin D supplementation has the potential to alleviate the cardiovascular damage in diabetic patients . The present study was design ed to evaluate long term impact of high doses of vitamin D on arterial properties , glucose homeostasis , adiponectin and leptin in patients with type 2 diabetes mellitus . METHODS AND RESULTS In r and omized , placebo-controlled study 47 diabetic patients were assigned into two groups : Group 1 received oral daily supplementation with vitamin D at a dose of 1000 U/day for 12 months . Group 2 received matching placebo capsules . Blood sampling for metabolic parameters , including fasting glucose , lipid profile , HbA1C , insulin , hs-CRP , 25 OH Vit D , adiponectin and leptin was performed at baseline and at the end of the study . Insulin resistance was assessed by homeostasis model assessment ( HOMA-IR ) . Central aortic augmentation index ( AI ) was evaluated using SphygmoCor . RESULTS The two groups were similar at baseline in terms of hemodynamic parameters . After 12 months , AI decreased significantly during the treatment period in patients received vitamin D ( p Glucose homeostasis parameters , leptin as well as leptin adiponectin ratio did not change in both groups . 25 OH Vit D level significantly increased ( p = 0.022 ) and circulating adiponectin marginally increased ( p = 0.065 ) during 12 month treatment period in active treatment and did not change in placebo group . CONCLUSIONS High doses of vitamin D supplementation in diabetic patients was associated with significant decrease in AI during one year treatment . This beneficial vascular effect was not associated with improvement in glucose homeostasis parameters",
"In-vitro studies suggest that vitamin D reduces inflammation by inhibiting nuclear factor kappa-B ( NFκB ) activity . Yet , no trials have examined the effects of vitamin D supplementation on NFκB activity in-vivo in humans . We conducted a double-blind r and omized trial ( RCT ) examining effects of vitamin D supplementation on inflammatory markers and NFκB activity in peripheral blood mononuclear cells ( P BMC s ) . Sixty-five overweight/obese , vitamin D-deficient ( 25-hydroxyvitamin D [ 25(OH)D ] ≤ 50 nmol/L ) adults were r and omized to a single 100,000 IU bolus followed by 4,000 IU daily cholecalciferol or matching placebo for 16 weeks . We measured BMI , % body fat , serum 25(OH)D , high-sensitivity C-reactive protein ( hsCRP ) , tumour necrosis factor ( TNF ) , monocyte chemoattractant protein-1 ( MCP-1 ) , interferon-gamma ( IFN-γ ) , several interleukins , and NFκB activity in P BMC s. Fifty-four participants completed the study . Serum 25(OH)D concentrations increased with vitamin D supplementation compared to placebo ( p groups did not differ in any inflammatory markers or NFκB activity ( all p > 0.05 ) . Results remained non-significant after adjustment for age , sex , and % body fat , and after further adjustment for sun exposure , physical activity , and dietary vitamin D intake . Although in-vitro studies report anti-inflammatory effects of vitamin D , our RCT data show no effect of vitamin D supplementation on inflammatory markers or NFκB activity in-vivo in humans"
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Exercise tests are often used to evaluate the functional status of patients with COPD . However , to the best of our knowledge , a comprehensive systematic comparison of these tests has not been performed . We systematic ally review ed studies reporting the repeatability and /or reproducibility of these tests , and studies comparing their sensitivity to therapeutic intervention . A systematic review identified primary manuscripts in English reporting relevant data on the following exercise tests : 6-minute walk test ( 6MWT ) and 12-minute walk test , incremental and endurance shuttle walk tests ( ISWT and ESWT , respectively ) , incremental and endurance cycle ergometer tests , and incremental and endurance treadmill tests . We identified 71 relevant studies . Good repeatability ( for the 6MWT and ESWT ) and reproducibility ( for the 6MWT , 12-minute walk test , ISWT , ESWT , and incremental cycle ergometer test ) were reported by most studies assessing these tests , providing patients were familiarized with them beforeh and . The 6MWT , ISWT , and particularly the ESWT were reported to be sensitive to therapeutic intervention . Protocol variations ( eg , track layout or supplemental oxygen use ) affected performance significantly in several studies . This review shows that while the validity of several tests has been established , for others further study is required . Future work will assess the link between these tests , physiological mechanisms , and patient-reported measures
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"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",
"OBJECTIVE To evaluate the applicability of the incremental ( shuttle ) walk test in patients with chronic obstructive pulmonary disease and compare the performance of those patients on the shuttle walk test to that of the same patients on the encouraged 6-minute walk test . METHODS A cross-sectional study was conducted , in which 24 patients with chronic obstructive pulmonary disease were selected . In r and om order , patients were , after an initial practice period , su bmi tted to a shuttle walk test and an encouraged 6-minute walk test . RESULTS The patients obtained a higher heart rate ( expressed as a percentage of that predicted based on gender and age ) on the encouraged 6-minute walk test ( 84.1 + /- 11.4 % ) than on the shuttle walk test ( 76.4 + /- 9.7 % ) ( p = 0.003 ) . The post-test sensation of dyspnea ( Borg scale ) was also higher on the encouraged 6-minute walk test . On average , the patients walked 307.0 + /- 89.3 meters on the shuttle walk test and 515.5 + /- 102.3 meters on the encouraged 6-minute walk test ( p distance walked ( r = 0.80 , p shuttle walk test is simple and easy to implement in patients with chronic obstructive pulmonary disease . The encouraged 6-minute walk test produced higher post-test heart rate and greater post-test sensation of dyspnea than did the shuttle walk test",
"BACKGROUND Previous studies have shown positive effects from noninvasive ventilation ( NIV ) or supplemental oxygen on exercise capacity in patients with COPD . However , the best adjunct for promoting physiologic adaptations to physical training in patients with severe COPD remains to be investigated . METHODS Twenty-eight patients ( mean + /- SD age 68 + /- 7 y ) with stable COPD ( FEV(1 ) 34 + /- 9 % of predicted ) undergoing an exercise training program were r and omized to either NIV ( n = 14 ) or supplemental oxygen ( n = 14 ) during group training to maintain peripheral oxygen saturation ( S(pO2 ) ) > /= 90 % . Physical training consisted of treadmill walking ( at 70 % of maximal speed ) 3 times a week , for 6 weeks . Patients were assessed at baseline and after 6 weeks . Assessment s included physiological adaptations during incremental exercise testing ( ratio of lactate concentration to walk speed , oxygen uptake [ V ( O2 ) ] , and dyspnea ) , exercise tolerance during 6-min walk test , leg fatigue , maximum inspiratory pressure , and health-related quality of life . RESULTS Two patients in each group dropped out due to COPD exacerbations and lack of exercise program adherence , and 24 completed the training program . Both groups improved 6-min walk distance , symptoms , and health-related quality of life . However , there were significant differences between the NIV and supplemental-oxygen groups in lactate/speed ratio ( 33 % vs -4 % ) , maximum inspiratory pressure ( 80 % vs 23 % ) , 6-min walk distance ( 122 m vs 47 m ) , and leg fatigue ( 25 % vs 11 % ) . In addition , changes in S(pO2)/speed , V ( O2 ) , and dyspnea were greater with NIV than with supplemental-oxygen . CONCLUSIONS NIV alone is better than supplemental oxygen alone in promoting beneficial physiologic adaptations to physical exercise in patients with severe COPD",
"The effects of adding L-carnitine to a whole-body and respiratory training program were determined in moderate-to-severe chronic obstructive pulmonary disease ( COPD ) patients . Sixteen COPD patients ( 66 + /- 7 years ) were r and omly assigned to L-carnitine ( CG ) or placebo group ( PG ) that received either L-carnitine or saline solution ( 2 g/day , orally ) for 6 weeks ( forced expiratory volume on first second was 38 + /- 16 and 36 + /- 12 % , respectively ) . Both groups participated in three weekly 30-min treadmill and threshold inspiratory muscle training sessions , with 3 sets of 10 loaded inspirations ( 40 % ) at maximal inspiratory pressure . Nutritional status , exercise tolerance on a treadmill and six-minute walking test , blood lactate , heart rate , blood pressure , and respiratory muscle strength were determined as baseline and on day 42 . Maximal capacity in the incremental exercise test was significantly improved in both groups ( P Blood lactate , blood pressure , oxygen saturation , and heart rate at identical exercise levels were lower in CG after training ( P Inspiratory muscle strength and walking test tolerance were significantly improved in both groups , but the gains of CG were significantly higher than those of PG ( 40 + /- 14 vs 14 + /- 5 cmH2O , and 87 + /- 30 vs 34 + /- 29 m , respectively ; P Blood lactate concentration was significantly lower in CG than in PG ( 1.6 + /- 0.7 vs 2.3 + /- 0.7 mM , P exercise tolerance and inspiratory muscle strength in COPD patients , as well as reduce lactate production",
"STUDY OBJECTIVE To determine whether exercise training with coaching is more effective than exercise training alone in reducing dyspnea and the anxiety and distress associated with it and improving exercise performance , self-efficacy for walking , and dyspnea with activities of daily living . DESIGN R and omized clinical trial of 51 dyspnea-limited patients with COPD assigned to monitored ( n = 27 ) or coached ( n = 24 ) exercise groups . SETTING Outpatient area of university teaching hospital . INTERVENTION Both groups completed 12 supervised treadmill training sessions ( phase 1 ) over 4 weeks followed by 8 weeks of home walking ( phase 2 ) . The CE group also received coaching during training . MEASUREMENTS Perceived work of breathing , dyspnea intensity , distress associated with dyspnea , and anxiety associated with dyspnea were rated on a visual analog scale during incremental treadmill testing and after 6-min walks before and after phase 1 . Dyspnea with activities of daily living , self-efficacy for walking , state anxiety , and 6-min walks were measured before and after both phases . RESULTS Dyspnea and the associated distress and anxiety improved significantly for both groups relative to work performed and in relation to ventilation ( p laboratory dyspnea was accompanied by improvements in dyspnea with activities of daily living ( p self-efficacy for home walking ( p Coaching with exercise training was no more effective than exercise training alone in improving exercise performance , dyspnea , and the anxiety and distress associated with it , dyspnea with activities , and self-efficacy for walking",
"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",
"Exercise tolerance is an important outcome measure in patients with COPD , mostly because there is evidence that exercise testing is superior to other functional measurements obtained at rest in demonstrating the positive effect of a specific intervention . We assessed the effect of a 5-day treatment with formoterol 12 microg twice daily on lung function , exercise capacity and dyspnea in 22 stable COPD patients , and compared 6-MWT with 12-MWT in evaluating formoterol efficacy . All subjects entered a crossover design . They underwent 6-MWT or 12-MWT in a r and omised order and soon after started the 5-day treatment . After a 3-day washout , patients who had first performed 6-MWT , underwent 12-MWT , and the contrary . Formoterol induced a progressively significant increase in pre-drug FEV1 and IC and also significant changes in these parameters 2 h after its inhalation at each test day . Moreover , it increased the walked distance by 53.6 m at the end of 6-MWT and 59.9 m at the end of 12-MWT . Formoterol also induced a significant change in Borg score for dyspnea caused by the 6-MWT when compared with the pre-treatment values , whereas it significantly changed dyspnea induced by 12-MWT only after the first dose . Our study not only strengthens the importance of walking tests as a useful tool for evaluating the impact of a bronchodilator on some COPD patient-centred outcomes , but also indicates that 6-MWT seems to be a more appropriate instrument than 12-MWT for assessing the exercise response to a bronchodilator in COPD",
"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",
"Background : The incremental shuttle walking test ( SWT ) has recently been proposed as a more valid and reproducible alternative to the conventional 6-min walking test ( 6MWT ) in the evaluation of exercise tolerance in patients with chronic obstructive pulmonary disease ( COPD ) . Objective : To compare the cardiorespiratory performance obtained during two sessions of SWT with that obtained during two sessions of 6MWT . Methods : We examined 18 patients ( forced expiratory volume in 1 s : 48 ± 14 % ) recovering from an acute exacerbation of COPD that had required hospitalization . In the same afternoon , each patient performed two SWT and two 6MWT , with an interval of at least 30 min between each test ; the sequence of the tests was r and omized . Results : Mean walking distance was greater in the second SWT test than in the first SWT . The changes from baseline in systolic blood pressure , heart rate , respiratory rate , oxygen saturation and dyspnea Borg index at the end of the test were similar between the two 6MWT and the two SWT . There was a highly significant correlation between walking distances measured during SWT and during 6MWT ( ρ : 0.85 , p Neither SWT nor 6MWT correlated with functional data of COPD . Conclusions : SWT , though being considered to be closer to a submaximal exercise test than 6MWT , does not induce a greater cardiorespiratory performance than 6MWT in patients recovering from acute exacerbation of COPD",
"OBJECTIVE To evaluate the functional impact of an individualized outpatient pulmonary rehabilitation program in end-stage chronic obstructive pulmonary disease ( COPD ) . METHODS Patients with end-stage COPD were admitted into a 6-week comprehensive outpatient pulmonary rehabilitation program that was \" packaged \" for each patient . We compared spirometric parameters , exercise tolerance , level of breathlessness , and intensity of work before and after rehabilitation . RESULTS Of 45 eligible patients , only 14 consented to participate in the study . All 14 patients had forced expiratory volume in 1 second level of breathlessness was between 7 ( moderate to severely breathless ) and 10 ( maximally breathless ) on the Visual Analogue Scale in all patients . After the program , there was significant improvement in the FEV 1 P = 0.04 ) , forced vital capacity P = 0.0045 ) , 6-minute walk test P = 0.00047 ) , and shuttle-walk test ( 9 of 14 patients ) . All patients had some improvement in level of dyspnea . CONCLUSIONS Individualized outpatient pulmonary rehabilitation in end-stage COPD can produce a measurable improvement in spirometry and exercise tolerance with a favorable impact on the level of physical activity",
"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 ",
"INTRODUCTION Common modalities of clinical exercise testing for outcome measurement after pulmonary rehabilitation ( PR ) include walk tests , progressive cycle ergometry , and cycle endurance testing . We hypothesized that patients ' responses to PR , as measured by those 3 tests , are differentially correlated , and we design ed a study to investigate the tests ' capacity to detect changes after PR . METHODS We prospect ively tested 37 male patients with stable chronic obstructive pulmonary disease who completed a comprehensive 6-week PR program that included supervised exercise training that emphasized steady-state lower-limb aerobic exercise . Before and after the PR program the patients underwent 6-minute walk test , progressive cycle ergometry , and cycle endurance testing ( at 80 % of the peak work rate achieved during progressive cycle ergometry ) . The exercise performance indices of interest were the peak oxygen uptake ( VO2max ) and maximum work-rate ( Wmax ) during progressive cycle ergometry , the cycling endurance time , and the 6-minute walk distance ( 6MWD ) . RESULTS After PR there were statistically significant improvements in 6MWD ( 16 % , p VO2max ( 53 % , p=0.004 ) , Wmax ( 30 % , p=0.001 ) , and cycling endurance time ( 144 % , p changes in VO2max and Wmax were significantly correlated ( r=0.362 , p=0.027 ) , as were the changes in endurance time and Wmax ( r=0.406 , p=0.013 ) . There was no significant correlation between changes in any other exercise index . CONCLUSIONS Among the frequently used exercise tests in PR , the most responsive index is the endurance time . The correlation between the post-PR changes in the various exercise indices is poor",
"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",
"OBJECTIVES We hypothesized that lung-volume reduction surgery for pulmonary emphysema would improve body mass index , airflow obstruction , dyspnea , and exercise capacity ( BODE ) index , a multidimensional predictor of survival in chronic obstructive pulmonary disease . We also aim ed to identify preoperative predictors of improvement in the BODE index . METHODS In a prospect i ve cohort study of patients undergoing lung-volume reduction surgery at our center , with the methodology of the National Emphysema Treatment Trial , we compared clinical characteristics before and 1 year after surgery with the Wilcoxon signed rank test . Changes in the BODE index were correlated with preoperative variables with the Spearman correlation coefficient . RESULTS Twenty-three patients with predominantly upper-lobe pulmonary emphysema underwent lung-volume reduction surgery ( 14 by video-assisted thoracoscopic surgery , 9 by median sternotomy ) . There were no postoperative or follow-up deaths . The BODE index improved from a median of 5 ( interquartile range 4 - 5 ) before surgery to 3 ( interquartile range 2 - 4 ) 1 year after surgery ( P lung function and dyspnea components of the BODE index . Lower preoperative 6-minute walk distance and lower postwalk Borg fatigue scores were each associated with greater improvement in the BODE index after 1 year . CONCLUSION Lung-volume reduction surgery for pulmonary emphysema improved the BODE index in patients with predominantly upper-lobe disease . Lower preoperative 6-minute walk distance correlated with greater improvement in the BODE index",
"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",
"OBJECTIVES Autonomic modulation is adversely impacted in patients with chronic obstructive pulmonary disease ( COPD ) . The purpose of the present investigation is to assess the effects of a 6-week aerobic exercise training program on autonomic modulation of heart rate in patients with COPD . METHODS Forty patients of both sexes with moderate-to-severe COPD were r and omly allocated to aerobic exercise training ( PT , n=20 ) or to usual care ( Control , n=20 ) . The training program consisted of lower and upper limb stretching and 30 min of treadmill exercise , 3 times per week for a 6-week period . Physiological data during symptom-limited exercise testing and the six-minute walk test ( 6MWT ) were assessed . In addition , R-R intervals were obtained at rest and during the 6MWT . Heart rate variability was analyzed by time ( rMSSD and SDNN index ) and frequency domains ( high frequency -- HF , low frequency -- LF and HF/LF ratio ) . RESULTS Peak oxygen consumption significantly improved in the training group only ( p blood lactate , minute ventilation , dyspnea at peak exercise , sympathetic activity , and parasympathetic activity at rest and during submaximal exercise . Lastly , a positive and significant correlation was found between change in 6MWT distance and rMSSD index ( r=0.65 and p=0.001 ) . CONCLUSIONS Neural control of heart rate , in addition to other clinical ly valuable measures , is positively altered in moderate-severe COPD patients following 6 weeks of aerobic exercise training . The improvement in submaximal performance after exercise training was associated with parasympathetic activity",
"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 purpose of this study was to demonstrate that clinical ratings of dyspnea and physiologic function are separate dimensions underlying the pathophysiology of chronic obstructive pulmonary disease ( COPD ) . We used principal-components factor analysis to confirm these dimensions using data collected prospect ively in 86 symptomatic patients with COPD . Three different instruments were used to rate dyspnea : a modified Medical Research Council ( MRC ) scale , the oxygen cost diagram ( OCD ) , and the baseline dyspnea index ( BDI ) . Measures of physiologic function included st and ard spirometric measures ( forced vital capacity [ FVC ] and forced expiratory volume in one second [ FEV1 ] ) and maximal inspiratory ( PImax ) and expiratory ( PEmax ) mouth pressures . Age of the 65 male and 21 female subjects was 62.9 + /- 1.2 yr ( mean + /- SEM ) . All three clinical scales were significantly correlated with physiologic function ( range of r values , 0.32 to 0.45 ; p less than 0.05 ) , except for the relationship between the MRC scale and PEmax ( r = -0.14 ; p = NS ) . The factor analysis yielded three factors that accounted for 71.9 % of the total variance of the data : clinical ratings of dyspnea ( MRC scale , OCD , and BDI ) loaded on the first factor ; maximal respiratory pressures and gender loaded on the second factor ; and lung function and age loaded on the third factor . Additional post hoc factor analysis provided similar results when the sample was divided into two subgroups by r and omization , by severity of dyspnea ratings , or by severity of airflow obstruction . We conclude that dyspnea ratings , maximal respiratory pressures , and lung function are separate factors or quantities that independently characterize the condition of patients with COPD . ( ABSTRACT TRUNCATED AT 250 WORDS",
"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",
"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",
"The reproducibility of the 12 minute walking distance ( 12 MD ) was assessed in ten men with chronic airways obstruction , and the 12 MD was used , together with spirometry , transfer factor and three subjective assessment s of breathlessness to evaluate the effects on respiratory function of prednisone 30 mg daily given orally in double-blind placebo-controlled fashion for two weeks . Like others , we found the 12 MD reproducible on a single day with a mean variation of 3.1 % . Tests performed two weeks apart showed greater variability ranging from 0.2 % to 30.9 % , ( mean 9.1 % ) . During placebo and prednisone therapy the 12 MD and assessment s of breathlessness correlated significantly with each other and with TLCO , but not with spirometry . Following steroid therapy there was a significant increase in mean TLCO but no significant change in 12 MD , spirometry or subjective assessment s. Changes in 12 MD and TLCO correlated significantly with each other and with changes in subjective assessment s. Changes in FEV1 correlated with changes in breathlessness , and also with variability in FEV1 while receiving placebo . Individuals with the greatest changes in 12 MD and FEV1 were those with the greatest variability on placebo . The variability of the 12 MD and FEV1 should be measured in individuals before using these tests to assess response to steroid therapy",
"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",
"BACKGROUND The current recommendations of 8 to 12 min for the optimal targeted duration of symptom-limited maximal cardiopulmonary exercise testing ( CPET ) to attain maximal oxygen consumption are based on results from healthy individuals and may not be applicable to patients with severe COPD . We aim ed to determine the optimal duration for a CPET to attain the peak oxygen consumption ( VO2peak ) in a group of patients with severe COPD using different carefully conducted workload protocol s. METHODS We studied 11 subjects with severe COPD ( mean FEV1 , 32 % predicted ; 95 % confidence interval [ CI ] , 27 to 38 % predicted ) . They completed four incremental , symptom-limited exercise tests on a cycle ergometer using four protocol s ( 4 , 8 , and 16 W/min continuous ramp protocol s , and 8 W/min step protocol ) using a r and omized double-blind design . RESULTS The mean duration of these 44 tests was 6.3 min ( 95 % CI , 5.0 to 9.0 min ) . The duration of the exercise tests differed significantly for the protocol s used , as follows : 16-W ramp protocol , 4.0 min ( 95 % CI , 3.0 to 5.1 min ) ; 8-W ramp protocol , 6.6 min ( 95 % CI , 5.0 to 9.0 min ) ; 8-W step protocol , 6.0 min ( 95 % CI , 4.0 to 8.0 min ) ; and 4-W ramp protocol , 8.7 min ( 95 % CI , 4.4 to 13.0 min ; p maximal workload significantly increased as the ramp slope increased from 4 to 8 to 16 W/min ( maximal workload , 35.6 vs 50.7 vs 64.3 W , respectively ; p Maximal minute ventilation , heart rate , Borg ratings , and VO2 peak , were not different among the four protocol s. No differences were found between the ramp and step protocol s. CONCLUSIONS In patients with severe COPD ( Global Initiative for Chronic Obstructive Lung Disease stages III-IV ) , a targeted duration of 5 to 9 min for a CPET appears to be more appropriate than the 8 to 12 min proposed in the current guidelines . Maximal workload , in contrast to VO2peak , is highly dependent on the ramp incrementation rate",
"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",
"Oxygen ( O2 ) has been reported to improve exercise tolerance in some patients with chronic obstructive pulmonary disease ( COPD ) despite only mild resting hypoxemia ( PaO2 greater than 60 mm Hg ) . To confirm these prior studies and evaluate potential mechanisms of benefit , we measured dyspnea scores by numeric rating scale during cycle ergometry endurance testing and correlated the severity of dyspnea with right ventricular systolic pressure ( RVSP ) measured by Doppler echocardiography during a separate supine incremental exercise test . Both sets of exercise were performed according to a r and omized double-blind crossover protocol in which patients breathed compressed air or 40 % O2 . We studied 12 patients with severe COPD ( FEV1 0.89 + /- 0.09 L [ mean + /- SEM ] , FEV1/FVC 37 + /- 2 % , DLCO 9.8 + /- 1.5 ml/min/mm Hg[47 % of predicted ] , PaO2 71 + /- 2.6 mm Hg ) . With endurance testing on compressed air , PaO2 did not change significantly in the group as whole ( postexercise PaO2 63 + /- 5.1 mm Hg , p = NS ) , but did fall to less than 55 mm Hg in four patients from this group . Duration of exercise increased on 40 % O2 from 10.3 + /- 1.6 to 14.2 + /- 1.5 min ( p = 0.005 ) , and the rise in dyspnea scores was delayed . Oxygen delayed the rise in RVSP with incremental exercise in all patients and lowered the mean RVSP at maximum exercise from 71 + /- 8 to 64 + /- 7 mm Hg ( p less than 0.03 ) . Improvement in duration of exercise correlated with decrease in dyspnea ( r2 = 0.66 , p = 0.001 ) but not with decreases in heart rate , minute ventilation , or RVSP . ( ABSTRACT TRUNCATED AT 250 WORDS",
"The aim of this study was to compare the effects of interval training ( 3-min intervals ) with continuous training on peak exercise capacity ( W peak ) , physiological response , functional capacity , dyspnoea , mental health and health-related quality of life ( HRQoL ) in patients with moderate or severe COPD . Sixty patients exercised twice weekly for 16 weeks after r and omisation to interval- or continuous training . Target intensity was 80 % of baseline W peak in the interval group ( I-group ) and 65 % in the continuous group ( C-group ) . Patients were tested by spirometry , ergometer cycle test , cardiopulmonary test and a 12 min walk test . Dyspnoea was measured by the dyspnoea scale from Chronic Obstructive Disease Question naire ( CRDQ ) , mental health by Hospital Anxiety and Depression scale ( HAD ) and HRQoL by the Medical Outcomes Survey Short Form 36 ( SF-36 ) . After training , W peak , peak oxygen uptake ( VO(2 ) peak ) and exhaled carbon dioxide ( VCO(2 ) peak ) increased significantly in both groups , no significant differences between the groups . Minute ventilation ( V(E ) peak ) increased only in the C-group . At identical work rates ( isotime ) VO(2 ) , VCO(2 ) and V(E ) were significantly more decreased in the I-group than in the C-group ( p Functional capacity , dyspnoea , mental health , and HRQoL improved significantly in both groups , no difference between the groups . Interval training and continuous training were equally potent in improving peak exercise capacity , functional exercise capacity , dyspnoea , mental health and HRQoL in patients with moderate or severe COPD . At isotime , the physiological response to training differed between the groups , in favour of the interval training",
"OBJECTIVES To compare conventional exercise-based assessment of pulmonary rehabilitation ( PR ) with improvement in training exercises employed during a PR program , and to describe the cardiopulmonary response of different training exercises during PR of patients with chronic obstructive pulmonary disease ( COPD ) . DESIGN Observational study . SETTING Inpatient PR . PARTICIPANTS Patients with moderate to very severe COPD ( N=18 ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Cardiopulmonary responses to interval cycling , arm exercise , and a test of functional activities of daily living ( ADLs ) were evaluated during the PR training program using a mobile telemetric breath-by-breath system . The effects of PR were evaluated by comparing pre-PR and post-PR training activities , incremental and constant work-rate cycling , and a 6-minute walk test . RESULTS Interval cycling and the ADLs test were moderate-intensity to heavy-intensity exercises ( 70%-80 % of maximal oxygen consumption ) , while the arm exercise was a low-intensity activity ( 40 % of maximal oxygen consumption ) . After 12 weeks of PR , cycle load , arm weights , and walking distances during training activities had increased alongside increased muscle mass . At iso-intensities , no cardiopulmonary changes in the training exercises were observed . Exercise duration of constant work-rate cycling and 6-minute walk distance increased by 160 % and 14 % , respectively , after PR , with concurrent right-shifts of anaerobic threshold and a decrease in heart rate . CONCLUSIONS Supervised increases in weight , load , and walking distance during training activities were useful clinical outcomes for patients , demonstrating the beneficial effects of progressive training on physical performance . However , for physiologic evaluation of PR , conventional tests , such as maximal incremental cycling , endurance cycling , and a 6-minute walk test , had greater validity . Physiologic evaluation of the training exercises showed that the training program complied with the training recommendations for PR",
"BACKGROUND Walking is a familiar daily activity that is generally limited by breathlessness , whereas cycling is an uncommon physical effort typically limited by leg discomfort . The hypothesis was that patients with COPD would exhibit greater improvements in exercise endurance and relief of breathlessness with bronchodilator therapy during treadmill walking compared with cycling . METHODS In this r and omized , 2 x 2 , double-blind , placebo-controlled , crossover trial , 20 patients with COPD ( age , 64 + /- 7 years ; FEV(1 ) , 56 + /- 14 % predicted ) performed constant-load endurance exercise on the treadmill and cycle ergometer at 85 % of capacity after inhaling normal saline ( NS ) or arformoterol ( ARF ) ( 15 microg ) . RESULTS Increases in endurance times and consistency of responses were greater with treadmill walking ( Delta : 157 + /- 286 s ; P = .024 ; 80 % improved ) than with cycle exercise ( Delta : 110 + /- 219 s ; P = .038 ; 65 % improved ) with ARF compared with NS . However , these changes were not significantly different . The slope of breathlessness-time ( mean Delta = -29 % ; P = .007 ) and the magnitude of oxygen desaturation were significantly lower with ARF compared with NS during treadmill , but not cycle , exercise . Inspiratory capacity values were similar between modes of exercise when comparing the same study medication . CONCLUSIONS Improved endurance times support both constant-load treadmill and cycle exercise to assess the efficacy of bronchodilator therapy in patients with COPD . Unique differences in physiologic and perceptual responses with bronchodilation demonstrate advantages of treadmill walking as an exercise stimulus . TRIAL REGISTRATION clinical trials.gov ; Identifier : NCT00754546",
"This study reports on the development and test-retest reproducibility of a modified shuttle walking and step testing protocol s to assess exertional dyspnea in patients with COPD . Patients with COPD r and omly performed four externally paced 3-min bouts of shuttle walking at 1.5 , 2.5 , 4.0 and 6.0 km·h− 1 or stepping at constant rate of 18 , 22 , 26 and 32 steps·min− 1 . Walking and stepping procedures were repeated once , on a separate occasion . Ventilation , heart rate , gas exchange parameters and dyspnea Borg scores were obtained at the end of each exercise bout . Most patients completed walking or stepping at the slow and middle speed cadences but only 33 % completed walking at 6.0 km·h− 1 and 40 % completed stepping at 32 steps·min− 1 . Walking and stepping at progressively faster pace caused a progressive increase in ventilation and dyspnea . Test-retest Pearson correlation coefficients for ventilation , heart rate , gas exchange parameters and dyspnea scores over the four exercise bouts , all exceeded 0.80 . Intra-class correlation coefficients were at least as strong as Pearson coefficients . Bl and & Altman representation showed that for repeated Borg scores , 92 and 96 % of points lied within 2 SD of the mean difference between test-retest values for walking and stepping . The majority of moderate and severe COPD patients completed the 3-min shuttle waking testing at 1.5 to 4.0 km·h− 1 and the 3-min of step testing at rates between 18 and 26 steps·min− 1 . Both field tests were highly reproducible in patients with COPD",
"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"
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41187868-06ff-11f0-808a-c43d1ab1c353
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Fatigue is a disabling , multifaceted symptom that is highly prevalent and stubbornly persistent . Although fatigue is a frequent complaint among patients with fibromyalgia , it has not received the same attention as pain . Reasons for this include lack of st and ardized nomenclature to communicate about fatigue , lack of evidence -based guidelines for fatigue assessment , and a deficiency in effective treatment strategies . Fatigue does not occur in isolation ; rather , it is present concurrently in varying severity with other fibromyalgia symptoms such as chronic widespread pain , unrefreshing sleep , anxiety , depression , cognitive difficulties , and so on . Survey-based and preliminary mechanistic studies indicate that multiple symptoms feed into fatigue and it may be associated with a variety of physiological mechanisms . Therefore , fatigue assessment in clinical and research setting s must consider this multi-dimensionality . While no clinical trial to date has specifically targeted fatigue , r and omized controlled trials , systematic review s , and meta-analyses indicate that treatment modalities studied in the context of other fibromyalgia symptoms could also improve fatigue . The Outcome Measures in Rheumatology ( OMERACT ) Fibromyalgia Working Group and the Patient Reported Outcomes Measurement Information System ( PROMIS ) have been instrumental in propelling the study of fatigue in fibromyalgia to the forefront . The ongoing efforts by PROMIS to develop a brief fibromyalgia-specific fatigue measure for use in clinical and research setting s will help define fatigue , allow for better assessment , and advance our underst and ing of fatigue
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"The purpose of this study was to compare the effects of aerobic training with a muscle-strengthening program in patients with fibromyalgia . Thirty women with fibromyalgia were r and omized to either an aerobic exercise ( AE ) program or a strengthening exercise ( SE ) program for 8 weeks . Outcome measures included the intensity of fibromyalgia-related symptoms , tender point count , fitness ( 6-min walk distance ) , hospital anxiety and depression ( HAD ) scale , and short-form health survey ( SF-36 ) . There were significant improvements in both groups regarding pain , sleep , fatigue , tender point count , and fitness after treatment . HAD-depression scores improved significantly in both groups while no significant change occurred in HAD-anxiety scores . Bodily pain subscale of SF-36 and physical component summary improved significantly in the AE group , whereas seven subscales of SF-36 , physical component summary , and mental component summary improved significantly in the SE group . When the groups were compared after treatment , there were no significant differences in pain , sleep , fatigue , tender point count , fitness , HAD scores , and SF-36 scores . AE and SE are similarly effective at improving symptoms , tender point count , fitness , depression , and quality of life in fibromyalgia",
"Objective : Assess the efficacy of duloxetine 60/120 mg ( N = 162 ) once daily compared with placebo ( N = 168 ) in the treatment of patients with fibromyalgia , during six months of treatment . Methods : This was a phase-III , r and omized , double-blind , placebo-controlled , parallel-group study assessing the efficacy and safety of duloxetine . Results : There were no significant differences between treatment groups on the co- primary efficacy outcome measures , change in the Brief Pain Inventory ( BPI ) average pain severity from baseline to endpoint ( P = 0.053 ) and the Patient ’s Global Impressions of Improvement ( PGI-I ) at endpoint ( P = 0.073 ) . Duloxetine-treated patients improved significantly more than placebo-treated patients on the Fibromyalgia Impact Question naire pain score , BPI least pain score and average interference score , Clinical Global Impressions of Severity scale , area under the curve of pain relief , Multidimensional Fatigue Inventory mental fatigue dimension , Beck Depression Inventory-II total score , and 36-item Short Form Health Survey mental component summary and mental health score . Nausea was the most common treatment-emergent adverse event in the duloxetine group . Overall discontinuation rates were similar between groups . Conclusions : Although duloxetine 60/120 mg/day failed to demonstrate significant improvement over placebo on the co- primary outcome measures , in this supportive study , duloxetine demonstrated significant improvement compared with placebo on numerous secondary measures",
"OBJECTIVE A subset of fibromyalgia ( FM ) patients have a dysfunctional hypothalamic-pituitary-insulin-like growth factor 1 ( IGF-1 ) axis , as evidence d by low serum levels of IGF-1 and a reduced growth hormone ( GH ) response to physiologic stimuli . There is evidence that pyridostigmine ( PYD ) improves the acute response of GH to exercise in FM patients . The purpose of this study was to evaluate the clinical effectiveness of 6 months of PYD and group exercise on FM symptoms . METHODS FM patients were r and omized to 1 of the following 4 groups : PYD plus exercise , PYD plus diet recall but no exercise , placebo plus exercise , and placebo plus diet recall but no exercise . The primary outcome measures were the visual analog scale ( VAS ) score for pain , tender point count , and total myalgic score . Secondary outcome measures were the total score on the Fibromyalgia Impact Question naire ( FIQ ) and FIQ VAS scores for individual symptoms ( fatigue , poor sleep , stiffness , and anxiety ) , as well as quality of life ( QOL ) and physical fitness ( lower body strength/endurance , upper and lower body flexibility , balance , and time on the treadmill ) . RESULTS A total of 165 FM patients completed baseline measurements ; 154 ( 93.3 % ) completed the study . The combination of PYD and exercise did not improve pain scores . PYD groups showed a significant improvement in sleep and anxiety in those who completed the study and in QOL in those who complied with the therapeutic regimen as compared with the placebo groups . Compared with the nonexercise groups , the 2 exercise groups demonstrated improvement in fatigue and fitness . PYD was generally well tolerated . CONCLUSION Neither the combination of PYD plus supervised exercise nor either treatment alone yielded improvement in most FM symptoms . However , PYD did improve anxiety and sleep , and exercise improved fatigue and fitness . We speculate that PYD may have improved vagal tone , thus benefiting sleep and anxiety ; this notion warrants further study",
"OBJECTIVE To evaluate the effects of using a gamma-hydroxybutyrate ( GHB ) administered in divided doses at night in 11 patients previously diagnosed with fibromyalgia ( FM ) . METHODS Subjects completed daily diaries assessing their pain and fatigue levels and slept in the sleep laboratory before and one month after initiating GHB treatment . Polysomnographic recordings were evaluated for sleep stages , sleep efficiency and the presence of the alpha anomaly in non-REM sleep . RESULTS There was a significant improvement in both fatigue and pain , with an increase in slow wave sleep and a decrease in the severity of the alpha anomaly . CONCLUSION Further controlled studies are needed to characterize the clinical improvement and the polysomnographic changes we observed",
"This article describes an ongoing , long-term clinical exercise program for women with fibromyalgia syndrome ( FMS ) , some of whom also have chronic fatigue and immune dysfunction syndrome ( CFIDS ) . The recorded outcomes from the most recent year of the program also are reported . Participants engaged in sessions lasting 50 - 70 minutes , 5 days per week ; each session involved aerobic activity , resistance training , and other dynamic exercise . One group was in the program for 3 years and another group was in the program for 2 years . Program outcomes for the year ( comparing beginning and end-of-year results ) are presented for both groups on physical fitness , psychosocial , and FMS/CFIDS symptoms . The outcomes support that all of the women appear to have benefited from the program in numerous ways , suggesting that the program works . Also , those outcomes are in agreement with past research reported in this journal . Implication s for clinical nurse specialists working with FMS/CFIDS patients are discussed",
"OBJECTIVE Fibromyalgia ( FMS ) is a chronic syndrome characterized by widespread pain , troubled sleep , disturbed mood , and fatigue . Several analgesic strategies have been evaluated but the results are moderate and inconsistent . Antidepressant agents are now considered the treatment of choice in most patients . It has been recently suggested that FMS may be associated with metabolic alterations including a deficit of carnitine . In this multicenter r and omized clinical trial we evaluated the efficacy of acetyl L-carnitine ( LAC ) in patients with overt FMS . METHODS One hundred and two patients meeting the American College of Rheumatology criteria for FMS were r and omized into the study . The treatment consisted of 2 capsules/day of 500 mg LAC or placebo plus one intramuscular ( i.m . ) injection of either 500 mg LAC or placebo for 2 weeks . During the following 8 weeks the patients took 3 capsules daily containing either 500 mg LAC or placebo . The patients were seen during treatment after 2 ( visit 3 ) , 6 ( visit 4 ) and 10 weeks ( visit 5 ) . The patients were also visited 4 weeks after treatment discontinuation ( follow-up visit ) . Outcome measures included the number of positive tender points , the sum of pain threshold ( kg/cm2 or \" total myalgic score \" ) , the Short Form 36 ( SF36 ) , a 100 mm visual analog scale ( VAS ) for self-perceived stiffness , fatigue , tiredness on awakening , sleep , work status , depression , and muscular-skeletal pain , and the Hamilton depression scale . RESULTS The \" total myalgic score \" and the number of positive tender points declined significantly and equally in both groups until the 6th week of treatment . At the 10th week both parameters remained unchanged in the placebo group but they continued to improve in the LAC group with a statistically significant between-group difference . Most VAS scores significantly improved in both groups . A statistically significant between-group difference was observed for depression and musculo-skeletal pain . Significantly larger improvements in SF36 question naire were observed in LAC than in placebo group for most parameters . Treatment was well-tolerated . CONCLUSION Although this experience deserves further studies , these results indicate that LAC may be of benefit in patients with FMS , providing improvement in pain as well as the general and mental health of these patients",
"OBJECTIVE Fibromyalgia ( FM ) syndrome is a chronic pain condition characterized by diffuse muscle pain , increased negative mood , and sleep disturbance . Until recently , sleep disturbance in persons with FM has been modeled as the result of the disease process or its associated pain . The current study examined sleep disturbance ( i.e. , sleep duration and sleep quality ) as a predictor of daily affect , stress reactivity , and stress recovery . DESIGN AND MEASURES A hybrid of daily diary and ecological momentary assessment methodology was used to evaluate the psychosocial functioning of 89 women with FM . Participants recorded numeric ratings of pain , fatigue , and positive and negative affect 3 times throughout the day for 30 consecutive days . At the end of each day , participants completed daily diary records of positive and negative life events . In addition , participants reported on their sleep duration and sleep quality each morning . RESULTS After accounting for the effects of positive events , negative events , and pain on daily affect scores , it was found that sleep duration and quality were prospect ively related to affect and fatigue . Furthermore , the effects of inadequate sleep on negative affect were cumulative . In addition , an inadequate amount of sleep prevented affective recovery from days with a high number of negative events . CONCLUSIONS These results lend support to the hypothesis that sleep is a component of allostatic load and has an upstream role in daily functioning",
"Objective : To determine the incidence and duration of response of clinical ly meaningful improvements with pregabalin across several key symptoms of fibromyalgia ( FM ) . Methods : This was a post hoc analysis of data from a multicenter , double-blind , placebo-controlled , r and omized , withdrawal study , originally design ed to evaluate the efficacy of pregabalin monotherapy for durability of effect on FM pain based on pain and Patient Global Impression of Change ( PGIC ) criteria . Responder criteria for Fibromyalgia Impact Question naire total score ( ≥16-point change ) , Medical Outcomes Study Sleep Scale Sleep Disturbance subscale ( ≥15.8-point change ) , and the 36-item Short-Form Health Survey Vitality scale ( ≥10-point change ) were used to evaluate the incidence and duration of improvements in function , sleep , and fatigue for pregabalin versus placebo among pain and PGIC responders . A composite responder index consisting of pain , PGIC , function , and sleep endpoints was used to explore multidimensional response . Results : Approximately 80 % of patients meeting pain and PGIC improvement criteria at r and omization had clinical ly meaningful improvement in fatigue , sleep , or function . Higher proportions of patients in the pregabalin group maintained a clinical ly meaningful response , and pregabalin-treated patients had a significantly longer time to loss of therapeutic response compared with the placebo group . Composite responder Kaplan-Meier analysis , performed with patients demonstrating clinical ly meaningful improvements in pain , PGIC , function , and sleep at r and omization showed a significantly longer median time to loss of therapeutic response for pregabalin-treated patients . Discussion : The results from this post hoc analysis indicate that pregabalin provides long-term effects across multiple domains of FM ( Clinical Trials.gov registry ID : NCT00151489 )",
"In two investigations , we studied vulnerability to the negative effects of stress among women in chronic pain from 2 types of musculoskeletal illnesses , fibromyalgia syndrome ( FMS ) and osteoarthritis ( OA ) . In Study 1 , there were 101 female participants 50 to 78 years old : 50 had FMS , 29 had OA knee pain and were scheduled for knee surgery , and 22 had OA but were not planning surgery . Cross-sectional analyses showed that the three groups were comparable on demographic variables , personality attributes , negative affect , active coping , and perceived social support . As expected , FMS and OA surgery women reported similar levels of bodily pain , and both groups scored higher than OA nonsurgery women . However , women with FMS reported poorer emotional and physical health , lower positive affect , a poorer quality social milieu , and more frequent use of avoidant coping with pain than did both groups of women with OA . Moreover , the perception and use of social support were closely tied to perceived social stress only among the FMS group . In Study 2 , we experimentally manipulated negative mood and stress in 41 women 37 to 74 years old : 20 women had FMS , and 21 women had OA . Participants from each group were r and omly assigned to either a negative mood induction or a neutral mood ( control ) condition , and then all participants discussed a stressful interpersonal event for 30 min . Stress-related increases in pain were exacerbated by negative mood induction among women with FMS but not women with OA , and pain during stress was associated with decreases in positive affect in women with FMS but not women with OA . These findings suggest that among women with chronic pain , those with FMS may be particularly vulnerable to the negative effects of social stress . They have fewer positive affective re sources , use less effective pain-coping strategies , and have more constrained social networks than their counterparts with OA , particularly those who experience similar levels of pain . They also seem to experience more prolonged stress-related increases in pain under certain circumstances , all of which may contribute to a lowering of positive affect and increased stress reactivity over time",
"BACKGROUND Fibromyalgia is a chronic pain syndrome associated with sleep disorders , fatigue and psychological symptoms . Combinations therapies , such as electrotherapy and therapeutic exercises have been used in the clinical practice . AIM To assess the efficacy of high-frequency transcutaneous electrical nerve stimulation ( TENS ) as an adjuvant therapy to aerobic and stretching exercises , for the treatment of fibromyalgia . DESIGN Controlled clinical trial . SETTING Unit of rehabilitation of a public hospital . POPULATION Twenty-eight women aged 52.4±7.5 years , with fibromyalgia . METHODS A visual analogue scale measured pain intensity ; tender points pain threshold , by dolorimetry ; and quality of life , by the Fibromyalgia Impact Question naire . All subjects participated in an eight-week program consisting of aerobic exercises , followed by static stretching of muscle chains . In TENS group , high-frequency ( 150 Hz ) was applied on bilateral tender points of trapezium and supraspinatus . RESULTS TENS group had a greater pain reduction ( mean change score=-2.0±2.9 cm ) compared to Without TENS group ( -0.7±3.7 cm ) . There was a difference between mean change scores of each group for pain threshold ( right trapezium : 0.2±1 kg/cm² in TENS group and -0.2±1.2 kg/cm² in Without TENS group ) . In the evaluation of clinical ly important changes , patients receiving TENS had relevant improvement of pain , work performance , fatigue , stiffness , anxiety and depression compared to those not receiving TENS . CONCLUSION It has suggested that high-frequency TENS as an adjuvant therapy is effective in relieving pain , anxiety , fatigue , stiffness , and in improving ability to work of patients with fibromyalgia . CLINICAL REHABILITATION IMPACT High-frequency TENS may be used as a short-term complementary treatment of fibromyalgia",
"The purpose of the study was to evaluate the efficacy of an extract of Panax ginseng in patients with fibromyalgia . A r and omized , double-blind , controlled clinical trial was carried out over 12 weeks to compare the effects of P. ginseng ( 100 mg/d ) with amitriptyline ( 25 mg/d ) and placebo in 38 patients with fibromyalgia : 13 in Group I ( amitriptyline ) , 13 in Group II ( placebo ) , and 12 in Group III ( P. ginseng ) . Ratings on the Visual Analogue Scale ( VAS ) revealed a reduction in pain in the P. ginseng group ( p improvement in fatigue ( p improvement in sleep ( p anxiety , improvements occurred in the P. ginseng group compared to baseline ( p amitriptyline treatment result ed in significantly greater improvements ( p P. ginseng reduced the number of tender points and improved patients ' quality of life ( using the Fibromyalgia Impact Question naire - FIQ ) ; however , there were no differences between groups . The beneficial effects experienced by patients for all parameters suggest a need for further studies to be performed on the tolerability and efficacy of this phytotherapic as a complementary therapy for fibromyalgia",
"Objectives A recent meta- analysis concluded that multicomponent treatments are effective for some fibromyalgia ( FM ) symptoms . The objective of this study was to examine whether a psychoeducational intervention implemented in primary care is more effective than usual care for improving the functional status of patients with FM . Methods This study was based on a r and omized controlled trial . The 484 patients with FM included in a data base of the Viladecans Hospital ( Barcelona , Spain ) were eligible for screening . Finally , 108 patients were r and omly assigned to the intervention and 108 patients were assigned to usual care . The intervention comprised nine 2-hour sessions ( 5 sessions of education and 4 sessions of autogenic relaxation ) . The patients were assessed before and after the intervention with a battery of instruments ( measuring sociodemographic data , medical comorbidities , functional status , trait anxiety , and social desirability ) . Results The posttreatment drop-out rate was 9.7 % ( intervention : 6.5 % ; control : 13 % ) . The intention-to-treat analyses showed significant differences between the groups at posttreatment : the intervention group improved in physical impairment , days not feeling well , pain , general fatigue , morning fatigue , stiffness , anxiety , and depression ( medium effect size in most cases ) . The patients who responded to the intervention reported less trait anxiety at baseline than nonresponders . The absolute risk reduction with the intervention was 36.1 % ( 95 % confidence interval : 23.3 - 48.8 ) and the number needed to treat was 3 ( 95 % confidence interval : 2.0 - 4.3 ) . Discussion A 2-month psychoeducational intervention improves the functional status of FM patients to a greater extent than usual care , at least in the short-term . The social desirability bias did not explain the reported outcomes . Trait anxiety was associated with response to treatment . Trial Registration NCT00550966",
"OBJECTIVE To assess the efficacy and safety of duloxetine , a serotonin and norepinephrine reuptake inhibitor , in subjects with primary fibromyalgia , with or without current major depressive disorder . METHODS This study was a r and omized , double-blind , placebo-controlled trial conducted in 18 outpatient research centers in the US . A total of 207 subjects meeting the American College of Rheumatology criteria for primary fibromyalgia were enrolled ( 89 % female , 87 % white , mean age 49 years , 38 % with current major depressive disorder ) . After single-blind placebo treatment for 1 week , subjects were r and omly assigned to receive duloxetine 60 mg twice a day ( n = 104 ) or placebo ( n = 103 ) for 12 weeks . Co- primary outcome measures were the Fibromyalgia Impact Question naire ( FIQ ) total score ( score range 0 - 80 , with 0 indicating no impact ) and FIQ pain score ( score range 0 - 10 ) . Secondary outcome measures included mean tender point pain threshold , number of tender points , FIQ fatigue , tiredness on awakening , and stiffness scores , Clinical Global Impression of Severity ( CGI-Severity ) scale , Patient Global Impression of Improvement ( PGI-Improvement ) scale , Brief Pain Inventory ( short form ) , Medical Outcomes Study Short Form 36 , Quality of Life in Depression Scale , and Sheehan Disability Scale . RESULTS Compared with placebo-treated subjects , duloxetine-treated subjects improved significantly more ( P = 0.027 ) on the FIQ total score , with a treatment difference of -5.53 ( 95 % confidence interval -10.43 , -0.63 ) , but not significantly more on the FIQ pain score ( P = 0.130 ) . Compared with placebo-treated subjects , duloxetine-treated subjects had significantly greater reductions in Brief Pain Inventory average pain severity score ( P = 0.008 ) , Brief Pain Inventory average interference from pain score ( P = 0.004 ) , number of tender points ( P = 0.002 ) , and FIQ stiffness score ( P = 0.048 ) , and had significantly greater improvement in mean tender point pain threshold ( P = 0.002 ) , CGI-Severity ( P = 0.048 ) , PGI-Improvement ( P = 0.033 ) , and several quality -of-life measures . Duloxetine treatment improved fibromyalgia symptoms and pain severity regardless of baseline status of major depressive disorder . Compared with placebo-treated female subjects ( n = 92 ) , duloxetine-treated female subjects ( n = 92 ) demonstrated significantly greater improvement on most efficacy measures , while duloxetine-treated male subjects ( n = 12 ) failed to improve significantly on any efficacy measure . The treatment effect on significant pain reduction in female subjects was independent of the effect on mood or anxiety . Duloxetine was safely administered and well tolerated . CONCLUSION In this r and omized , controlled , 12-week trial ( with a 1-week placebo lead-in phase ) , duloxetine was an effective and safe treatment for many of the symptoms associated with fibromyalgia in subjects with or without major depressive disorder , particularly for women , who had significant improvement across most outcome measures",
"OBJECTIVE To evaluate the efficacy , tolerability , and safety of multiple fixed dosages of esreboxetine for the treatment of fibromyalgia . METHODS Patients meeting the American College of Rheumatology criteria for fibromyalgia were r and omized to receive esreboxetine at dosages of 4 mg/day ( n=277 ) , 8 mg/day ( n=284 ) , or 10 mg/day ( n=283 ) or matching placebo ( n=278 ) for 14 weeks . The primary efficacy outcomes were the weekly mean pain score and the Fibromyalgia Impact Question naire ( FIQ ) total score at week 14 . Secondary efficacy measures included scores for the Patient 's Global Impression of Change ( PGIC ) scale , the Global Fatigue Index ( GFI ) , and the 36-item Short-Form health survey ( SF-36 ; physical function scale only ) at week 14 . The safety profile of esreboxetine was evaluated based on adverse events and other safety measures . RESULTS Patients receiving all dosages of esreboxetine demonstrated statistically significant improvements in the pain score ( P≤0.025 ) , the FIQ score ( P≤0.023 ) , and the PGIC score ( P≤0.007 ) compared with patients in the placebo group . Additionally , patients receiving esreboxetine at dosages of 4 mg/day and 8 mg/day showed statistically significant improvements in the GFI score compared with those receiving placebo ( P=0.001 ) . No significant differences in SF-36 physical function scores were observed between patients receiving esreboxetine ( any dosage ) and those receiving placebo . Adverse events were mostly mild to moderate in severity ; insomnia , constipation , dry mouth , nausea , dizziness , hot flush , headache , hyperhidrosis , and palpitations were reported most frequently . CONCLUSION Esreboxetine was generally well tolerated and was associated with significant improvements in pain , FIQ , PGIC , and fatigue scores compared with placebo . The lack of a dose-response relationship in both the efficacy and safety analyses suggests that esreboxetine at a dosage of 4 mg/day would offer clinical benefit with the least risk of drug exposure",
"Abstract : The aim of the study was to determine the possible effect of melatonin treatment on disturbed sleep , fatigue and pain symptoms observed in fibromyalgia ( FM ) patients . Twenty-one consecutive patients with FM were included in an open 4-week- duration pilot study . Before and after treatment with melatonin 3 mg at bedtime , patients were evaluated using tender point count by palpation of 18 classic anatomical regions , pain score in four pre design ated areas , pain severity on a 10 cm visual analogue scale ( VAS ) , sleep disturbances , fatigue , depression , anxiety , and patient and physician global assessment s , also by a VAS . Urine 6-sulphatoxymelatonin levels ( aMT-6S ) were measured in the patients and 20 age- and sex-matched controls . Nineteen patients completed the study . One patient withdrew because of migraine and another was lost to follow-up . At day 30 , median values for the tender point count and severity of pain at selected points , patient and physician global assessment s and VAS for sleep significantly improved with melatonin treatment . Other variables improved but did not reach statistical significance . Adverse events were mild and transient . Lower levels of aMT-6S were found in FM patients compared with normal median controls ( ±SD , 9.16 ± 7.9 μg/24 h vs 16.8 ± 12.8 μg/24 h ) ( p= 0.06 ) . Although this is an open study , our preliminary results suggest that melatonin can be an alternative and safe treatment for patients with FM . Double-blind placebo controlled studies are needed",
"OBJECTIVE To determine the prevalence and characteristics of fibromyalgia in the general population . METHODS A r and om sample of 3,006 persons in Wichita , KS , were characterized according to the presence of no pain , non-widespread pain , and widespread pain . A sub sample of 391 persons , including 193 with widespread pain , were examined and interviewed in detail . RESULTS The prevalence of fibromyalgia was 2.0 % ( 95 % confidence interval [ 95 % CI ] 1.4 , 2.7 ) for both sexes , 3.4 % ( 95 % CI 2.3 , 4.6 ) for women , and 0.5 % ( 95 % CI 0.0 , 1.0 ) for men . The prevalence of the syndrome increased with age , with highest values attained between 60 and 79 years ( > 7.0 % in women ) . Demographic , psychological , dolorimetry , and symptom factors were associated with fibromyalgia . CONCLUSION Fibromyalgia is common in the population , and occurs often in older persons . Characteristic features of fibromyalgia -- pain threshold and symptoms -- are similar in community and clinic population s , but overall severity , pain , and functional disability are more severe in the clinic population",
"OBJECTIVE Fibromyalgia syndrome ( FMS ) is characterized by widespread musculoskeletal pain and lowered pain threshold . Other prominent symptoms include disordered sleep and fatigue . FMS affects an estimated 2 % of the population , predominantly women . This trial was design ed to evaluate the efficacy and safety of pregabalin , a novel alpha(2)-delta lig and , for treatment of symptoms associated with FMS . METHODS This multicenter , double-blind , 8-week , r and omized clinical trial compared the effects of placebo with those of 150 , 300 , and 450 mg/day pregabalin on pain , sleep , fatigue , and health-related quality of life in 529 patients with FMS . The primary outcome variable was the comparison of end point mean pain scores , derived from daily diary ratings of pain intensity , between each of the pregabalin treatment groups and the placebo group . RESULTS Pregabalin at 450 mg/day significantly reduced the average severity of pain in the primary analysis compared with placebo ( -0.93 on a 0 - 10 scale ) ( P /=50 % improvement in pain at the end point ( 29 % , versus 13 % in the placebo group ; P = 0.003 ) . Pregabalin at 300 and 450 mg/day was associated with significant improvements in sleep quality , fatigue , and global measures of change . Pregabalin at 450 mg/day improved several domains of health-related quality of life . Dizziness and somnolence were the most frequent adverse events . Rates of discontinuation due to adverse events were similar across all 4 treatment groups . CONCLUSION Pregabalin at 450 mg/day was efficacious for the treatment of FMS , reducing symptoms of pain , disturbed sleep , and fatigue compared with placebo . Pregabalin was well tolerated and improved global measures and health-related quality of life",
"OBJECTIVES To study the effects of a 3-month multidisciplinary intervention based on exercise and psychological therapy on symptomatology and quality of life in women with fibromyalgia . METHODS Seventy-five women with fibromyalgia volunteered to participate and were allocated to a 3-month ( 3-times/week ) multidisciplinary ( pool , l and -based and psychological session based on the Acceptance and Commitment Therapy ) intervention ( n=41 ) , or to a usual care group ( n=34 ) . Sixty-five women with fibromyalgia completed the study protocol ( n=33 multidisciplinary intervention , aged 51.4±7.4 years and n=32 usual care group , aged 50.0±7.3 years ) . The outcomes variables were Fibromyalgia Impact Question naire ( FIQ ) , Short Form Health Survey 36 ( SF-36 ) , Hospital Anxiety and Depression Scale , V and erbilt Pain Management Inventory and Rosenberg Self-Esteem Scale . RESULTS We observed a significant interaction effect ( group*time ) for the FIQ total score , the subscales fatigue , stiffness , anxiety and depression , and the subscales of SF-36 physical role , bodily pain , vitality and social functioning . Post-hoc analysis revealed significant improvements in total score of FIQ ( p ) , fatigue ( p=0.001 ) , stiffness ( p ) , anxiety ( p=0.011 ) , depression ( p=0.008 ) , physical role ( p=0.002 ) , bodily pain ( p ) , vitality ( p and social functioning ( p subscale depression ( p=0.006 ) and social functioning ( p=0.019 ) . CONCLUSIONS A 3-month low-moderate intensity multidisciplinary intervention improved fibromyalgia symptomatology and quality of life in women with fibromyalgia",
"Background Fibromyalgia engulfs patients in a downward , reinforcing cycle of unrestorative sleep , chronic pain , fatigue , inactivity , and depression . In this study we tested whether a mostly raw vegetarian diet would significantly improve fibromyalgia symptoms . Methods Thirty people participated in a dietary intervention using a mostly raw , pure vegetarian diet . The diet consisted of raw fruits , salads , carrot juice , tubers , grain products , nuts , seeds , and a dehydrated barley grass juice product . Outcomes measured were dietary intake , the fibromyalgia impact question naire ( FIQ ) , SF-36 health survey , a quality of life survey ( QOLS ) , and physical performance measurements . Results Twenty-six subjects returned dietary surveys at 2 months ; 20 subjects returned surveys at the beginning , end , and at either 2 or 4 months of intervention ; 3 subjects were lost to follow-up . The mean FIQ score ( n = 20 ) was reduced 46 % from 51 to 28 . Seven of the 8 SF-36 subscales , bodily pain being the exception , showed significant improvement ( n = 20 , all P for trend QOLS , scaled from 0 to 7 , rose from 3.9 initially to 4.9 at 7 months ( n = 20 , P for trend 0.000001 ) . Significant improvements ( n = 18 , P shoulder pain at rest and after motion , abduction range of motion of shoulder , flexibility , chair test , and 6-minute walk . 19 of 30 subjects were classified as responders , with significant improvement on all measured outcomes , compared to no improvement among non-responders . At 7 months responders ' SF-36 scores for all scales except bodily pain were no longer statistically different from norms for women ages 45–54 . Conclusion This dietary intervention shows that many fibromyalgia subjects can be helped by a mostly raw vegetarian diet",
"OBJECTIVE To evaluate the efficacy and safety of pregabalin for symptomatic relief of pain associated with fibromyalgia ( FM ) and for management of FM . METHODS This multicenter , double-blind , placebo-controlled trial r and omly assigned 748 patients with FM to receive placebo or pregabalin 300 , 450 , or 600 mg/day ( dosed twice daily ) for 13 weeks . The primary outcome variable for study objective 1 , symptomatic relief of pain associated with FM , was comparison of endpoint mean pain scores between each pregabalin group and placebo . The outcome variable for study objective 2 , management of FM , included endpoint mean pain scores , Patient Global Impression of Change ( PGIC ) , and Fibromyalgia Impact Question naire (FIQ)-Total Score . Secondary outcomes included assessment s of sleep , fatigue , and mood disturbance . RESULTS Patients in all pregabalin groups showed statistically significant improvement in endpoint mean pain score and in PGIC response compared with placebo . Improvements in FIQ-Total Score for the pregabalin groups were numerically but not significantly greater than those for the placebo group . Compared with placebo , all pregabalin treatment groups showed statistically significant improvement in assessment s of sleep and in patients ' impressions of their global improvement . Dizziness and somnolence were the most frequently reported adverse events . CONCLUSION Pregabalin at 300 , 450 , and 600 mg/day was efficacious and safe for treatment of pain associated with FM . Pregabalin monotherapy provides clinical ly meaningful benefit to patients with FM",
"Objective . This double-blind , 1-year extension study investigated the longterm efficacy and safety of milnacipran 100 , 150 , and 200 mg/day in the treatment of fibromyalgia ( FM ) in completers of a 3-month European double-blind lead-in study of milnacipran 200 mg/day versus placebo . Methods . A total of 468 patients with FM successfully completing the lead-in study were either blindly maintained on milnacipran 200 mg/day ( MLN200:MLN200 , n = 198 ) or ( if previously receiving placebo ) rer and omized to milnacipran 100 mg/day ( PBO : MLN100 , n = 91 ) , 150 mg/day ( PBO : MLN150 , n = 92 ) , or 200 mg/day ( PBO : MLN200 , n = 87 ) for an additional 12 months ( including a 4-week dose escalation ) . The main efficacy endpoint was a 2-measure composite responder rate ( relative to lead-in study baseline ) incorporating the weekly-recall pain score recorded on a visual analog scale and the Patient Global Impression of Change score . A panel of other assessment s including the Fibromyalgia Impact Question naire explored the multidimensional aspects of FM . Descriptive analyses using the last observation carried forward approach were performed . Results . At the 1-year endpoint , the proportion of composite responders ( relative to the lead-in study baseline ) ranged from 27.5 % ( PBO : MLN100 ) to 35.9 % ( MLN200:MLN200 ) , and had increased from the extension study baseline by 15.2 % ( PBO : MLN150 ) to 20.7 % ( PBO : MLN200 and MLN200:MLN200 ) . At endpoint , an improvement from both baselines was shown in all groups on pain , fatigue , sleep , and quality of life measures . Up to 1 year , all doses of milnacipran were safe and well tolerated . The most common drug-related adverse events were hyperhidrosis and nausea . Conclusion . Over 1 year , milnacipran 100 , 150 , and 200 mg/day exhibited sustained and safe therapeutic effects on predominant symptoms of FM . Registered as trial no. NCT00757731",
"Low energy lasers are widely used to treat a variety of musculoskeletal conditions including fibromyalgia , despite the lack of scientific evidence to support its efficacy . A r and omised , single-blind , placebo-controlled study was conducted to evaluate the efficacy of low-energy laser therapy in 40 female patients with fibromyalgia . Patients with fibromyalgia were r and omly allocated to active ( Ga-As ) laser or placebo laser treatment daily for two weeks except weekends . Both the laser and placebo laser groups were evaluated for the improvement in pain , number of tender points , skinfold tenderness , stiffness , sleep disturbance , fatigue , and muscular spasm . In both groups , significant improvements were achieved in all parameters ( p sleep disturbance , fatigue and skinfold tenderness in the placebo laser group ( p>0.05 ) . It was found that there was no significant difference between the two groups with respect to all parameters before therapy whereas a significant difference was observed in parameters as pain , muscle spasm , morning stiffness and tender point numbers in favour of laser group after therapy ( p side effects . Our study suggests that laser therapy is effective on pain , muscle spasm , morning stiffness , and total tender point number in fibromyalgia and suggests that this therapy method is a safe and effective way of treatment in the cases with fibromyalgia",
"INTRODUCTION There is a need for the development and evaluation of occupational therapy interventions enabling participation and contributing to self-management for individuals with multiple chronic conditions . This pilot study aim ed to assess the feasibility and potential impact of an occupation-based self-management programme for community living individuals with multiple chronic conditions . METHODS Sixteen participants completed a six-week programme . Assessment s were conducted at baseline , immediately post-intervention and at eight-week follow-up . Sixteen participants provided immediate follow-up data and 15 participants provided eight-week follow-up data . Outcome measures included participation in occupations ; perceptions of occupational performance and satisfaction ; self-efficacy ; depression , anxiety and quality of life . Focus groups explored participants ' perceptions of the programme . RESULTS The findings are promising and indicate that the programme delivery was feasible . Significant differences were found immediately post-intervention in frequency of activity participation ( P = 0.008 ) , including domestic ( P = 0.040 ) and work/leisure activities ( P = 0.015 ) , self-perceptions of occupational performance ( P = 0.017 ) and satisfaction with same ( P = 0.023 ) . At eight-week follow-up , significant differences continued to be found in frequency of activity participation ( P = 0.018 ) , including work/leisure activities ( P = 0.038 ) , perceptions of occupational performance ( P = 0.010 ) and satisfaction ( P = 0.008 ) and self-efficacy ( P = 0.050 ) . No differences were found in anxiety , depression or quality of life at follow-up periods . Focus group data supported the programme 's impact on activity participation and self-efficacy . CONCLUSION Despite the small sample in this pilot study there were significant improvements in occupational performance and the findings provide support for the programme . However , there is a need to test the intervention rigorously with a definitive r and omised trial in a primary care setting",
"Objective : To evaluate the efficacy of a treatment programme for patients with fibromyalgia ( FM ) based on self management , using pool exercises and education . Methods : R and omised controlled trial with a 6 month follow up to evaluate an outpatient multidisciplinary programme ; 164 patients with FM were allocated to an immediate 6 week programme ( n = 84 ) or to a waiting list control group ( n = 80 ) . The main outcomes were changes in quality of life , functional consequences , patient satisfaction and pain , using a combination of patient question naires and clinical examinations . The question naires included the Fibromyalgia Impact Question naire ( FIQ ) , Psychological General Well-Being ( PGWB ) index , regional pain score diagrams , and patient satisfaction measures . Results : 61 participants in the treatment group and 68 controls completed the programme and 6 month follow up examinations . Six months after programme completion , significant improvements in quality of life and functional consequences of FM were seen in the treatment group as compared with the controls and as measured by scores on both the FIQ ( total score p = 0.025 ; fatigue p = 0.003 ; depression p = 0.031 ) and PGWB ( total score p = 0.032 ; anxiety p = 0.011 ; vitality p = 0.013 , ) . All four major areas of patient satisfaction showed greater improvement in the treatment than the control groups ; between-group differences were statistically significant for “ control of symptoms ” , “ psychosocial factors ” , and “ physical therapy ” No change in pain was seen . Conclusion : A 6 week self management based programme of pool exercises and education can improve the quality of life of patients with FM and their satisfaction with treatment . These improvements are sustained for at least 6 months after programme completion",
"OBJECTIVE The aim of this multicenter study was to evaluate the efficacy , safety , and tolerability of noninvasive cortical electrostimulation in the management of fibromyalgia ( FM ) . DESIGN A prospect i ve , r and omized , double-blind , placebo-controlled design was used . Setting . Subjects received therapy at two different outpatient clinical locations . PATIENTS There were 77 subjects meeting the American College of Rheumatology 1990 classification criteria for FM . Intervention . Thirty-nine ( 39 ) active treatment ( AT ) FM patients and 38 placebo controls received 22 applications of either noninvasive cortical electrostimulation or a sham therapy over an 11-week period . OUTCOME MEASURES The primary outcome measures were the number of tender points ( TePs ) and pressure pain threshold ( PPT ) . Secondary outcome measures were responses to the Fibromyalgia Impact Question naire ( FIQ ) , Symptom Checklist-90 ( SCL-90 ) , Beck Depression Inventory-II , and a novel sleep question naire , all evaluated at baseline and at the end of treatment . RESULTS Intervention provided significant improvements in TeP measures : compared with placebo , the AT patients improved in the number of positive TePs ( -7.4 vs -0.2 , P PPT ( 19.6 vs -3.2 , P total FIQ score ( -15.5 vs -5.6 , P=0.03 ) , FIQ pain ( -2.0 vs -0.6 , P=0.03 ) , FIQ fatigue ( -2.0 vs -0.4 , P=0.02 ) , and FIQ refreshing sleep ( -2.1 vs -0.7 , P=0.02 ) ; and while FIQ function improved ( -1.0 vs -0.2 ) , the between-group change had a 14 % likelihood of occurring due to chance ( P=0.14 ) . There were no significant side effects observed . CONCLUSIONS Noninvasive cortical electrostimulation in FM patients provided modest improvements in pain , TeP measures , fatigue , and sleep ; and the treatment was well tolerated . This form of therapy could potentially provide worthwhile adjunctive symptom relief for FM patients",
"OBJECTIVE To investigate the effects of supervised aerobic exercise ( AE ) and a combined program of supervised aerobic , muscle strengthening , and flexibility exercises ( combined exercise [ CE ] ) on important health outcomes in women with fibromyalgia syndrome ( FMS ) . DESIGN R and omized controlled trial . SETTING Community-based supervised intervention . PARTICIPANTS Women ( N=64 ) with a diagnosis of FMS according to the American College of Rheumatology criteria . INTERVENTION Participants were r and omly allocated to 1 of 3 groups : supervised AE , supervised CE , or usual-care control . Exercise sessions were performed twice weekly ( 45 - 60min/session ) for 24 weeks . MAIN OUTCOME MEASURES The primary outcome measure was the Fibromyalgia Impact Question naire ( FIQ ) . Exploratory outcome measures were the 36-Item Short-Form Health Survey , Beck Depression Inventory ( BDI ) , aerobic capacity ( 6-minute walk test ) , h and -grip strength , and range of motion in the shoulders and hips . RESULTS Compliance with both interventions was excellent , with women in the exercise groups attending more than 85 % of sessions . A 14 % to 15 % improvement from baseline in total FIQ score was observed in the exercise groups ( P≤.02 ) and was accompanied by decreases in BDI scores of 8.5 ( P the SF-36 Physical Functioning ( P=.003 ) and Bodily Pain ( P=.003 ) domains and was more effective than AE for evoking improvements in the Vitality ( P=.002 ) and Mental Health ( P=.04 ) domains . Greater improvements also were observed in shoulder/hip range of motion and h and grip strength in the CE group . CONCLUSION Given the equivalent time commitment required for AE and CE , our results suggest that women with FMS can gain additional health benefits by engaging in a similar volume of CE",
"OBJECTIVE The aim of this study was to investigate the effectiveness of a 6-week traditional exercise program with supplementary whole-body vibration ( WBV ) in improving health status , physical functioning , and main symptoms of fibromyalgia ( FM ) in women with FM . METHODS Thirty-six ( 36 ) women with FM ( mean + /- st and ard error of the mean age 55.97 + /- 1.55 ) were r and omized into 3 treatment groups : exercise and vibration ( EVG ) , exercise ( EG ) , and control ( CG ) . Exercise therapy , consisting of aerobic activities , stretching , and relaxation techniques , was performed twice a week ( 90 min/day ) . Following each exercise session , the EVG underwent a protocol with WBV , whereas the EG performed the same protocol without vibratory stimulus . The Fibromyalgia Impact Question naire ( FIQ ) was administered at baseline and 6 weeks following the initiation of the treatments . Estimates of pain , fatigue , stiffness , and depression were also reported using the visual analogue scale . RESULTS A significant 3 x 2 ( group x time)-repeated measures analysis of variance interaction was found for pain ( p = 0.018 ) and fatigue ( p = 0.002 ) but not for FIQ ( p = 0.069 ) , stiffness ( p = 0.142 ) , or depression ( p = 0.654 ) . Pain and fatigue scores were significantly reduced from baseline in the EVG , but not in the EG or CG . In addition , the EVG showed significantly lower pain and fatigue scores at week 6 compared to the CG , whereas no significant differences were found between the EG and CG ( p > 0.05 ) . CONCLUSION Results suggest that a 6-week traditional exercise program with supplementary WBV safely reduces pain and fatigue , whereas exercise alone fails to induce improvements",
"Introduction Fatigue is one of the most disabling symptoms associated with fibromyalgia that greatly impacts quality of life . Fatigue was assessed as a secondary objective in a 2-phase , 24-week study in out patients with American College of Rheumatology-defined fibromyalgia . Methods Patients were r and omized to duloxetine 60 - 120 mg/d ( N = 263 ) or placebo ( N = 267 ) for the 12-week acute phase . At Week 12 , all placebo-treated patients were switched to double-blind treatment with duloxetine for the extension phase . Fatigue was assessed at baseline and every 4 weeks with the Multidimensional Fatigue Inventory ( MFI ) scales : General Fatigue , Physical Fatigue , Mental Fatigue , Reduced Activity , and Reduced Motivation . Other assessment s that may be associated with fatigue included Brief Pain Inventory ( BPI ) average pain , numerical scales to rate anxiety , depressed mood , bothered by sleep difficulties , and musculoskeletal stiffness . Treatment-emergent fatigue-related events were also assessed . Changes from baseline to Week 12 , and from Week 12 to Week 24 , were analyzed by mixed-effects model repeated measures analysis . Results At Week 12 , duloxetine versus placebo significantly ( all p MFI scale , BPI pain , anxiety , depressed mood , and stiffness . Improvement in ratings of being bothered by sleep difficulties was significant only at Weeks 4 and 8 . At Week 24 , mean changes in all measures indicated improvement was maintained for patients who received duloxetine for all 24 weeks ( n = 176 ) . Placebo-treated patients switched to duloxetine ( n = 187 ) had significant within-group improvement in Physical Fatigue ( Weeks 16 , 20 , and 24 ) ; General Fatigue ( Weeks 20 and 24 ) ; Mental Fatigue ( Week 20 ) ; and Reduced Activity ( Weeks 20 and 24 ) . These patients also experienced significant within-group improvement in BPI pain , anxiety , depressed mood , bothered by sleep difficulties , and stiffness . Overall , the most common ( > 5 % incidence ) fatigue-related treatment-emergent adverse events were fatigue , somnolence , and insomnia . Conclusions Treatment with duloxetine significantly improved multiple dimensions of fatigue in patients with fibromyalgia , and improvement was maintained for up to 24 weeks . Trial registration Clinical Trials.gov registry NCT00673452",
"Non-invasive unilateral repetitive transcranial magnetic stimulation ( rTMS ) of the motor cortex induces analgesic effects in focal chronic pain syndromes , probably by modifying central pain modulatory systems . Neuroimaging studies have shown bilateral activation of a large number of structures , including some of those involved in pain processing , suggesting that such stimulation may induce generalized analgesic effects . The goal of this study was to assess the effects of unilateral rTMS of the motor cortex on chronic widespread pain in patients with fibromyalgia . Thirty patients with fibromyalgia syndrome ( age : 52.6 + /- 7.9 ) were r and omly assigned , in a double-blind fashion , to two groups , one receiving active rTMS ( n = 15 ) and the other sham stimulation ( n = 15 ) , applied to the left primary motor cortex in 10 daily sessions . The primary outcome measure was self-reported average pain intensity over the last 24 h , measured at baseline , daily during the stimulation period and then 15 , 30 and 60 days after the first stimulation . Other outcome measures included : sensory and affective pain scores for the McGill pain Question naire , quality of life ( assessed with the pain interference items of the Brief Pain Inventory and the Fibromyalgia Impact Question naire ) , mood and anxiety ( assessed with the Hamilton Depression Rating Scale , the Beck Depression Inventory and the Hospital Anxiety and Depression Scale ) . We also assessed the effects of rTMS on the pressure pain threshold at tender points ipsi- and contralateral to stimulation . Follow-up data were obtained for all the patients on days 15 and 30 and for 26 patients ( 13 in each treatment group ) on day 60 . Active rTMS significantly reduced pain and improved several aspects of quality of life ( including fatigue , morning tiredness , general activity , walking and sleep ) for up to 2 weeks after treatment had ended . The analgesic effects were observed from the fifth stimulation onwards and were not related to changes in mood or anxiety . The effects of rTMS were more long-lasting for affective than for sensory pain , suggesting differential effects on brain structures involved in pain perception . Only few minor and transient side effects were reported during the stimulation period . Our data indicate that unilateral rTMS of the motor cortex induces a long-lasting decrease in chronic widespread pain and may therefore constitute an effective alternative analgesic treatment for fibromyalgia",
"OBJECTIVE To assess the efficacy and safety of pramipexole , a dopamine 3 receptor agonist , in patients with fibromyalgia . METHODS In this 14-week , single-center , double-blind , placebo-controlled , parallel-group , escalating-dose trial , 60 patients with fibromyalgia were r and omized 2:1 ( pramipexole : placebo ) to receive 4.5 mg of pramipexole or placebo orally every evening . The primary outcome was improvement in the pain score ( 10-cm visual analog scale [ VAS ] ) at 14 weeks . Secondary outcome measures were the Fibromyalgia Impact Question naire ( FIQ ) , the Multidimensional Health Assessment Question naire ( MDHAQ ) , the pain improvement scale , the tender point score , the 17- question Hamilton Depression Inventory ( HAM-d ) , and the Beck Anxiety Index ( BAI ) . Patients with comorbidities and disability were not excluded . Stable dosages of concomitant medications , including analgesics , were allowed . RESULTS Compared with the placebo group , patients receiving pramipexole experienced gradual and more significant improvement in measures of pain , fatigue , function , and global status . At 14 weeks , the VAS pain score decreased 36 % in the pramipexole arm and 9 % in the placebo arm ( treatment difference -1.77 cm ) . Forty-two percent of patients receiving pramipexole and 14 % of those receiving placebo achieved > or = 50 % decrease in pain . Secondary outcomes favoring pramipexole over placebo included the total FIQ score ( treatment difference -9.57 ) and the percentages of improvement in function ( 22 % versus 0 % ) , fatigue ( 29 % versus 7 % ) , and global ( 38 % versus 3 % ) scores on the MDHAQ . Compared with baseline , some outcomes showed a better trend for pramipexole treatment than for placebo , but failed to reach statistical significance , including improvement in the tender point score ( 51 % versus 36 % ) and decreases in the MDHAQ psychiatric score ( 37 % versus 28 % ) , the BAI score ( 39 % versus 27 % ) , and the HAM-d score ( 29 % versus 9 % ) . No end points showed a better trend for the placebo arm . The most common adverse events associated with pramipexole were transient anxiety and weight loss . No patient withdrew from the study because of inefficacy or an adverse event related to pramipexole . CONCLUSION In a subset of patients with fibromyalgia , approximately 50 % of whom required narcotic analgesia and /or were disabled , treatment with pramipexole improved scores on assessment s of pain , fatigue , function , and global status , and was safe and well-tolerated",
"OBJECTIVE To evaluate the effectiveness of a modified Myers ' formula of intravenous nutrient therapy ( IVNT ) on the symptoms of fibromyalgia ( FM ) in therapy-resistant FM patients . METHODS In this pilot clinical trial , 7 participants with therapy resistant FM were given IVNT once per week for 8 weeks . Patient 's pain levels , fatigue , and activities of daily living were evaluated weekly . RESULTS All participants reported decreased pain levels , decreased fatigue , and increased activities of daily living . Participants noted increased energy levels within 24 - 48 hours of the initial infusion . At the end of the study , all participants reported increased energy and activities of daily living as well as a 60 % reduction in pain ( P=.005 ) and an 80 % decrease in fatigue ( P=-.005 ) . No participants , however , reported complete or lasting resolution of pain or fatigue . No side effects were reported . DISCUSSION Anecdotal reports have indicated benefit for IVNT for patients with chronic pain , including FM . However , except for 2 reports , the medical literature is devoid of any studies of IVNT for the treatment of FM . In this pilot study , 7 participants received IVNT once a week for 8 weeks . All participants had long-st and ing FM ( at least 8 years ) and had tried conventional therapies , such as antidepressants , nonsteroidal anti-inflammatory drugs , and exercise , without significant or lasting relief . All had improvement in symptoms and increases in their activities of daily living , although no participant reported complete resolution of symptoms . IVNT appears to be safe to reduce FM symptoms",
"& NA ; A mounting body of literature recommends that treatment for fibromyalgia ( FM ) encompass medications , exercise and improvement of coping skills . However , there is a significant gap in determining an effective counterpart to pharmacotherapy that incorporates both exercise and coping . The aim of this r and omized controlled trial was to evaluate the effects of a comprehensive yoga intervention on FM symptoms and coping . A sample of 53 female FM patients were r and omized to the 8‐week Yoga of Awareness program ( gentle poses , meditation , breathing exercises , yoga‐based coping instructions , group discussion s ) or to wait‐listed st and ard care . Data were analyzed by intention to treat . At post‐treatment , women assigned to the yoga program showed significantly greater improvements on st and ardized measures of FM symptoms and functioning , including pain , fatigue , and mood , and in pain catastrophizing , acceptance , and other coping strategies . This pilot study provides promising support for the potential benefits of a yoga program for women with FM",
"Fatigue , which may occasionally be the chief manifestation , is present in more than 90 % of patients with fibromyalgia . It is a significant cause of morbidity and is quite disabling in its ability to disrupt quality of life . The cause of fatigue is complex , but disturbances in sleep architecture may have a role to play . Modafinil , a nonamphetamine wake-promoting agent and a popular treatment of narcolepsy , displays its antifatigue properties through a potentially central prohistaminergic interplay and may conceptually be postulated to lower fatigue in fibromylagia patients as well . Modafinil , unlike amphetamines , is well tolerated with less peripheral hemodynamic alterations combined with low abuse and tolerance sequelae . It also improves vigilance in sleep-deprived patients . Modafinil has been suggested as a possible treatment of fatigue in multiple sclerosis , parkinsonism , depression , primary biliary cirrhosis among other disorders with some demonstrable benefit . Since fatigue constitutes a significant proportion of the morbidity associated with fibromyalgia , we have conducted a retrospective chart review of 98 patients who have fibromyalgia , were being treated by a rheumatologist and 2 nurse practitioners in a private practice setting , and had been given a prescription for modafinil . Patients were involved in this usual practice setting , and the clinicians documented patient encounters in a st and ard medical record format . The charts were review ed by 5 outside psychiatric clinicians from SUNY Upstate Medical University ’s Depression and Anxiety Disorders Research Program . The study team attempted to exclude charts where there may have been other medical comorbidities that may have induced fatigue and also excluded charts where the initiation of modafinil coincided with the initiation of any other off-label fibromyalgia treatment ( i.e. , duloxetine , amytriptyline , tramadol , etc ) . An analog rating scale was created for this chart review as notes had to be read by study clinicians and retrospective assessment s were made regarding any change in fatigue . This simple scale used a method of visual quantitation of subjective symptomatology change with regard to fatigue . This ranged from a level of 1 , indicative of low fatigue , to 10 , as a representative of the diametrically opposite extreme of marked symptom fatigue . The 5 clinician raters were calibrated to 0.8 accuracy to decrease inter-rater reliability bias . Progress notes were also scanned for reported side effects and for reasons why modafinil may have been discontinued . The average age of the patients was 47 years , and the average dose of modafinil was 162 mg/d , with an average duration of treatment spanning 2 years . The average number of concomitant medications was eight . The mean pre and postfatigue analog scale scores were analyzed and significant statistical difference was demonstrated whereby modafinil augmentation lowered patient fatigue levels from 7.2 0.13 ( severe fatigue ) to 4.4 0.18 ( low-moderate fatigue ( P 0.001 ) . The net mean improvement in fatigue as a target symptom was approximately 28 % . There is often little focus on the fatigue that is commonly reported by these patients . Our simple , retrospective study may be the first that focuses on the use of modafinil for alleviating this symptom . In our retrospective chart review , we found a majority of patients to be involved in both polypharmacy regimens and nonpharmacologic treatment ( i.e. , biofeedback ) as well . The timing of modafinil addition and fatigue amelioration suggests that this agent may be able to effectively treat the fatigue associated with fibromyalgia . It is also a well-tolerated drug with a minimum of side effects reported . These observations should encourage the development of prospect i ve controlled studies",
"OBJECTIVES Group exercises may be useful in fibromyalgia syndrome ( FMS ) . The ' Body movement and perception ' ( BMP ) method is based on low impact exercises , awareness of body perception and relaxation , aim ed at treating small groups of patients following the Resseguier method ( RM ) and integrating RM with exercises derived from soft gymnastics . We assessed the effects of BMP method on FMS . METHODS 40 women with FMS ( age and disease duration : 51.7±7.2 and 4.9±3.8 years ) participated in an open pilot study . BMP sessions were performer twice a week ( 50 minutes each ) for 8 weeks . Patients were assessed at enrolment ( T0 ) and at the end of the study ( T1 ) by a self-administered question naire ( temporal characteristics of pain , pain interference in working and recreational activities and in night-time rest , awareness of pain , fatigue , irritability , well-being , quality of movement , ability to focus on perception and to perceive whole body , postural selfcontrol , ability to relax ) and a clinical evaluation ( tender points , assumption of analgesics/NSAIDs , distribution of pain , pain in sitting and st and ing position , pain during postural passages and gait , postural body alignment , muscular contractures ) . RESULTS At T1 , FMS patients significantly improved with respect to T0 in pain , fatigue , irritability , well-being , quality of movement , postural self-control , ability to relax mind and body , movement perception , tender point scores , assumption of analgesic/NSAIDs , body alignment and muscle contractures ( p FMS patients , rehabilitation with BMP improves pain and well being , reduces the number of tender points and muscle contractures , thus it is useful in FMS management",
"OBJECTIVE Patients with fibromyalgia ( FM ) consistently have adrenal hyporesponsiveness and low dehydroepi and rosterone ( DHEA ) levels . DHEA is promoted for and used by patients with FM . We tested the efficacy and safety of DHEA supplementation in ameliorating the symptoms of FM . METHODS In a double-blind crossover study , postmenopausal women with FM were r and omized to DHEA supplementation ( 50 mg/day ) or placebo for 3 months , with a one-month washout period in between . Patients were assessed monthly for well-being and pain and by medical evaluations at the beginning and the end of each treatment period . The primary outcome was well being ; secondary outcomes were pain , fatigue , cognition , sexuality , functional impairment , depression , and anxiety . RESULTS A total of 52 patients were r and omized , 47 patients completed the DHEA treatment period , and 45 the placebo treatment period . After 3 months of treatment with 50 mg of DHEA , median DHEA sulfate blood levels had tripled , but there was no improvement in well-being , pain , fatigue , cognitive dysfunction , functional impairment , depression , or anxiety , nor in objective measurements made by physicians . And rogenic side effects ( greasy skin , acne , and increased growth of body hair ) were more common during the DHEA treatment period ( p = 0.02 ) . CONCLUSION DHEA does not improve quality of life , pain , fatigue , cognitive function , mood , or functional impairment in FM",
"OBJECTIVES Although qigong is an important part of Traditional Chinese medicine ( TCM ) based on a philosophy similar to acupuncture , few studies of qigong exist in the Western medicine literature . To evaluate qigong therapy as a modality in treating chronic pain conditions such as fibromyalgia syndrome ( FMS ) , we report a pilot trial of 10 women with severe FMS who experienced significant improvement after external qigong therapy ( EQT ) . DESIGN Ten patients with FMS completed five to seven sessions of EQT over 3 weeks with pre- and posttreatment assessment and a 3-month follow-up . Each treatment lasted approximately 40 minutes . OUTCOME MEASURES Tender point count ( TPC ) and Fibromyalgia Impact Question naire ( FIQ ) were the primary measures . McGill Pain Question naire ( MPQ ) , Beck Depression Inventory ( BDI ) , anxiety , and self-efficacy were the secondary outcomes . RESULTS Subjects demonstrated improvement in functioning , pain , and other symptoms . The mean TPC was reduced from 136.6 to 59.5 after EQT treatment ; mean MPQ decreased from 27.0 to 7.2 ; mean FIQ from 70.1 to 37.3 ; and mean BDI from 24.3 to 8.3 ( all p other FMS symptoms , and two reported they were completely symptom-free . Results from the 3-month follow-up indicated some slight rebound from the post-treatment measures , but still much better than those observed at baseline . CONCLUSIONS Treatment with EQT result ing in complete recovery for some FMS patients suggests that TCM may be very effective for treating pain and the multiplicity of symptoms associated with FMS . Larger controlled trials of this promising intervention are urgently needed",
"BACKGROUND This study compared Raloxifen ( Evista ) with placebo in treatment of fibromyalgia . METHODS One hundred menopausal women with fibromyalgia enrolled in a double-blind r and omized study from Feb 2005 until Oct 2006 . We compared efficacy of Raloxifen , and placebo over 16 weeks of treatment . Fifty patients received Raloxifen 49 of which ( 98 % ) completed the study and 47 ( 94 % ) of 50 patients who received placebo completed the study . Raloxifen in 60 mg or identical placebo dose was given every other day over 16 weeks and patients were followed up . Improved recovery for a treatment group was assessed by a significantly higher mean score from baseline to the end of the treatment trial , compared with patients treated with placebo , on measures of Stanford Health Assessment Question naire ( HAQ ) ; Iranian version of Hospital Anxiety and Depression question naire ( IHAD ) ; sleep disturbance ; number of tender points ; reduction of pain and fatigue based on Visual Analogue Score ( VAS ) . RESULTS Raloxifen produced a significantly higher response rate than placebo in treating fibromyalgia by improving pain and fatigue , reducing of the tender point count , sleep disturbance and recovery of usual activities as measured by the Stanford Health Assessment Question naire ( HAQ ) . The significant effect of Raloxifen on HAD score among patients with fibromyalgia was not seen . CONCLUSION Raloxifen was superior to placebo in the treatment of menopausal patients with fibromyalgia",
"OBJECTIVE To determine the intermediate and long-term outcomes of fibromyalgia in patients seen in rheumatology centers in which there is special interest in the syndrome . METHODS We conducted a longitudinal outcome study by mailed comprehensive Health Assessment Question naire administered every 6 months to 538 patients , from 6 rheumatology centers , whose median duration of disease at first assessment was 7.8 years . The final assessment took place after 7 years . In addition , there was study followup on 85 patients who had attended the Wichita center for > 10 years . RESULTS Although functional disability worsened slightly and health satisfaction improved slightly , measures of pain , global severity , fatigue , sleep disturbance , anxiety , depression , and health status were markedly abnormal at study initiation and were essentially unchanged over the study period . Correlations between first and last assessment values were as high as r = 0.82 . For some variables , abnormalities were 3 times greater at one center compared with another . CONCLUSION Patients with established fibromyalgia , seen in rheumatology centers in which there a special interest in the disease and followed up for as long as 7 years , have markedly abnormal scores for pain , functional disability , fatigue , sleep disturbance , and psychological status , and these values do not change substantially over time . Half the patients are dissatisfied with their health , and 59 % rate their health as fair or poor . There are marked differences in disease severity among the various centers , but < 14 % of the variance in outcomes can be explained by demographic or center factors . Values at the first assessment are predictive of final values",
"OBJECTIVE To evaluate the effects of 6 months of pool exercise combined with a 6 session education program for patients with fibromyalgia syndrome ( FM ) . METHODS The study population comprised 58 patients , r and omized to a treatment or a control group . Patients were instructed to match the pool exercises to their threshold of pain and fatigue . The education focused on strategies for coping with symptoms and encouragement of physical activity . The primary outcome measurements were the total score of the Fibromyalgia Impact Question naire ( FIQ ) and the 6 min walk test , recorded at study start and after 6 mo . Several other tests and instruments assessing functional limitations , severity of symptoms , disabilities , and quality of life were also applied . RESULTS Significant differences between the treatment group and the control group were found for the FIQ total score ( p = 0.017 ) and the 6 min walk test ( p physical function , grip strength , pain severity , social functioning , psychological distress , and quality of life . CONCLUSION The results suggest that a 6 month program of exercises in a temperate pool combined with education will improve the consequences of FM",
"Multidisciplinary treatment has proven to be the best therapeutic option to fibromyalgia ( FM ) and physiotherapy has an important role in this approach . Considering the controversial results of electrotherapy in this condition , the aim of this study was to assess the effects of combined therapy with pulsed ultrasound and interferential current ( CTPI ) on pain and sleep in FM . Seventeen patients fulfilling FM criteria were divided into two groups , CTPI and SHAM , and su bmi tted to pain and sleep evaluations . Pain was evaluated by body map ( BM ) of the painful areas ; quantification of pain intensity by visual analog scale ( VAS ) ; tender point ( TP ) count and tenderness threshold ( TT ) . Sleep was assessed by inventory and polysomnography ( PSG ) . After 12 sessions of CTPI or SHAM procedure , patients were evaluated by the same initial protocol . After treatment , CTPI group showed , before and after sleep , subjective improvement of pain in terms of number ( BM ) and intensity ( VAS ) of painful areas ( P in TP count and increase in TT ( P Subjective sleep improvements observed after CTPI treatment included decrease in morning fatigue and in non‐refreshing sleep complaint ( P decrease in sleep latency ( P percentage of stage 1 ( P increase in the percentage of slow wave sleep ( P and in sleep cycle count ( P ) . Decrease in arousal index ( P ) , number of sleep stage changes ( P and wake time after sleep onset ( P regarding pain or sleep parameters were verified after SHAM procedure . This study shows that CTPI can be an effective therapeutic approach for pain and sleep manifestations in FM",
"Abstract . The purpose of this study was to examine the effectiveness of low power laser ( LPL ) and low-dose amitriptyline therapy and to investigate effects of these therapy modalities on clinical symptoms and quality of life ( QOL ) in patients with fibromyalgia ( FM ) . Seventy-five patients with FM were r and omly allocated to active gallium-arsenide ( Ga-As ) laser ( 25 patients ) , placebo laser ( 25 patients ) , and amitriptyline therapy ( 25 patients ) . All groups were evaluated for the improvement in pain , number of tender points , skin fold tenderness , morning stiffness , sleep disturbance , muscular spasm , and fatigue . Depression was evaluated by a psychiatrist according to the Hamilton Depression Rate Scale and DSM IV criteria . Quality of life of the FM patients was assessed according to the Fibromyalgia Impact Question naire ( FIQ ) . In the laser group , patients were treated for 3 min at each tender point daily for 2 weeks , except weekends , at each point with approximately 2 J/cm2 using a Ga-As laser . The same unit was used for the placebo treatment , for which no laser beam was emitted . Patients in the amitriptyline group took 10 mg daily at bedtime throughout the 8 weeks . Significant improvements were indicated in all clinical parameters in the laser group ( P=0.001 ) and significant improvements were indicated in all clinical parameters except fatigue in the amitriptyline group ( P=0.000 ) , whereas significant improvements were indicated in pain ( P=0.000 ) , tender point number ( P=0.001 ) , muscle spasm ( P=0.000 ) , morning stiffness ( P=0.002 ) , and FIQ score ( P=0.042 ) in the placebo group . A significant difference was observed in clinical parameters such as pain intensity ( P=0.000 ) and fatigue ( P=0.000 ) in favor of the laser group over the other groups , and a significant difference was observed in morning stiffness ( P=0.001 ) , FIQ ( P=0.003 ) , and depression score ( P=0.000 ) after therapy . A significant difference was observed in morning stiffness ( P=0.001 ) , FIQ ( P=0.003 ) , and depression ( P=0.000 ) in the amitriptyline group compared to the placebo group after therapy . Additionally , a significant difference was observed in depression score ( P=0.000 ) in the amitriptyline group in comparison to the laser group after therapy . Our study suggests that both amitriptyline and laser therapies are effective on clinical symptoms and QOL in fibromyalgia and that Ga-As laser therapy is a safe and effective treatment in cases with FM . Additionally , the present study suggests that the Ga-As laser therapy can be used as a monotherapy or as a supplementary treatment to other therapeutic procedures in FM",
"Brain tryptophan is low in fibromyalgia . Intake of protein rich in large neutral amino acids is reported to lower brain tryptophan . This study was undertaken to assess whether any reduction of such proteins by exclusion of animal protein from the diet reduced pain and morbidity in fibromyalgia patients . It was an open , r and omized controlled trial . 37 subjects with fibromyalgia were enrolled in the vegetarian diet and 41 in the amitriptyline groups . The outcome was assessed with the help of frequencies of fatigue , insomnia & non-restorative sleep , pain score on a 10-point VAS and tender point count . Fatigue , insomnia and non-restorative sleep were present in 41 , 26 and 32 subjects before and in 3 , 0 and 0 subjects respectively at six weeks of treatment in the amitriptyline group . The pain score and tender point count were 6.2 + /- 1.9 & 16.1 + /- 2.3 before and 2.3 + /- 1.3 & 6.4 + /- 3.0 after treatment . All these differences were significant ( P fatigue , insomnia and non-restorative sleep were present in 36 , 24 and 27 subjects before and in 34 , 29 and 29 subjects at six weeks of treatment . The pain score and tender point count were 5.7 + /- 1.8 and 15.7 + /- 2.4 before and 5.0 + /- 1.8 & 14.7 + /- 3.6 after treatment . All these differences were insignificant except that in the pain score . The decrease in the pain score , though significant , was much smaller than that in the amitriptyline group . So , it may be concluded that vegetarian diet is a poor option in the treatment of fibromyalgia",
"We design ed a r and omized , rater blind study to assess the efficacy of EEG Biofeedback ( Neurofeedback-NFB ) in patients with fibromyalgia syndrome ( FMS ) . Eighteen patients received twenty sessions of NFB-sensory motor rhythm ( SMR ) treatment ( NFB group ) during 4 weeks , and eighteen patients were given 10 mg per day escitalopram treatment ( control group ) for 8 weeks . Visual Analog Scales for pain and fatigue , Hamilton and Beck Depression and Anxiety Inventory Scales , Fibromyalgia Impact Question naire and Short Form 36 were used as outcome measures which were applied at baseline and 2nd , 4th , 8th , 16th , 24th weeks . Mean amplitudes of EEG rhythms ( delta , theta , alpha , SMR , beta1 and beta2 ) and theta/SMR ratio were also measured in NFB group . All post-treatment measurements showed significant improvements in both of the groups ( for all parameters p NFB group displayed greater benefits than controls ( for all parameters p Therapeutic efficacy of NFB was found to begin at 2nd week and reached to a maximum effect at 4th week . On the other h and , the improvements in SSRI treatment were also detected to begin at 2nd week but reached to a maximum effect at 8th week . No statistically significant changes were noted regarding mean amplitudes of EEG rhythms ( p > 0.05 for all ) . However , theta/SMR ratio showed a significant decrease at 4th week compared to baseline in the NFB group ( p efficacy of NFB as a treatment for pain , psychological symptoms and impaired quality of life associated with fibromyalgia",
"Objective . This r and omized , double-blind , placebo-controlled , multicenter study investigated the efficacy and safety of milnacipran in the treatment of fibromyalgia ( FM ) in a European population . Methods . Out patients diagnosed with FM according to 1990 American College of Rheumatology criteria ( N = 884 ) were r and omized to placebo ( n = 449 ) or milnacipran 200 mg/day ( n = 435 ) for 17 weeks ( 4-week dose escalation , 12-week stable dose , 9-day down-titration ) , followed by a 2-week posttreatment period . The primary efficacy criterion was a 2-measure composite responder analysis requiring patients to achieve simultaneous improvements in pain ( ≥ 30 % improvement from baseline in visual analog scale , 24-hour morning recall ) and a rating of “ very much ” or “ much ” improved on the Patient Global Impression of Change scale . If responder analysis was positive , Fibromyalgia Impact Question naire ( FIQ ) was included as an additional key primary efficacy measure . Results . At the end of the stable dose period ( Week 16 ) , milnacipran 200 mg/day showed significant improvements from baseline relative to placebo in the 2-measure composite responder criteria ( p = 0.0003 ) and FIQ total score ( p = 0.015 ) . Significant improvements were also observed in multiple secondary efficacy endpoints , including Short-Form 36 Health Survey ( SF-36 ) Physical Component Summary ( p = 0.025 ) , SF-36 Mental Component Summary ( p = 0.007 ) , Multidimensional Fatigue Inventory ( p = 0.006 ) , and Multiple Ability Self-Report Question naire ( p = 0.041 ) . Milnacipran was safe and well tolerated ; nausea , hyperhidrosis , and headache were the most common adverse events . Conclusion . Milnacipran is an effective and safe treatment for pain and other predominant symptoms of FM . Registered as trial no. NCT00436033",
"Abstract . The aim of this study was to evaluate the effectiveness of balneotherapy on patients with fibromyalgia ( FM ) at the Dead Sea . Forty-eight patients with FM were r and omly assigned to a treatment group receiving sulfur baths and a control group . All participants stayed for 10 days at a Dead Sea spa . Physical functioning , FM-related symptoms , and tenderness measurements ( point count and dolorimetry ) were assessed at four time points : prior to arrival at the Dead Sea , after 10 days of treatment , and 1 and 3 months after leaving the spa . Physical functioning and tenderness moderately improved in both groups . With the exception of tenderness threshold , the improvement was especially notable in the treatment group and it persisted even after 3 months . Relief in the severity of FM-related symptoms ( pain , fatigue , stiffness , and anxiety ) and reduced frequency of symptoms ( headache , sleep problems , and subjective joint swelling ) were reported in both groups but lasted longer in the treatment group . In conclusion , treatment of FM at the Dead Sea is effective and safe and may become an additional therapeutic modality in FM . Future studies should address the outcome and possible mechanisms of this treatment in FM patients",
"Fibromyalgia ( FM ) is a complex disorder that affects up to 5 % of the general population worldwide . Its pathophysiological mechanisms are difficult to identify and current drug therapies demonstrate limited effectiveness . Both mitochondrial dysfunction and coenzyme Q10 ( CoQ10 ) deficiency have been implicated in FM pathophysiology . We have investigated the effect of CoQ10 supplementation . We carried out a r and omized , double-blind , placebo-controlled trial to evaluate clinical and gene expression effects of forty days of CoQ10 supplementation ( 300 mg/day ) on 20 FM patients . This study was registered with controlled-trials.com ( IS RCT N 21164124 ) . An important clinical improvement was evident after CoQ10 versus placebo treatment showing a reduction of FIQ ( p reduction in pain ( p , fatigue , and morning tiredness ( p the pain visual scale ( p reduction in tender points ( p recovery of inflammation , antioxidant enzymes , mitochondrial biogenesis , and AMPK gene expression levels , associated with phosphorylation of the AMPK activity . These results lead to the hypothesis that CoQ10 have a potential therapeutic effect in FM , and indicate new potential molecular targets for the therapy of this disease . AMPK could be implicated in the pathophysiology of FM",
"The effect of electroconvulsive therapy ( ECT ) on depression and other symptoms of fibromyalgia was studied in a prospect i ve 3‐month trial in 13 patients with fibromyalgia and concomitant depression . All the patients met the DSM‐IV diagnostic criteria for Major Depressive Disorder and fulfilled the American College of Rheumatology diagnostic criteria for fibromyalgia . The Montgomery and Åsberg Depression Rating Scale ( MADRS ) and the clinical global impression scale ( CGI ) were used to assess the severity of depression and the clinical change of the patients . The fibromyalgia impact question naire ( FIQ ) was used to evaluate the severity of the fibromyalgia symptoms . The intensity of pain was evaluated using a 6‐point scale ( 0=no pain , 5=very severe pain ) , and tender point palpation . All assessment s were performed at baseline and at follow‐up visits , which took place one week , one month and three months after ECT . There was a significant improvement in depression after ECT according to MADRS . Using CGI , six patients were much or very much improved , while four patients were minimally improved and three patients had no change . There was significant improvement in four out of ten FIQ item scores , “ feel good ” , “ fatigue ” , “ anxiety ” and “ depression ” . No significant change was found in the FIQ item scores “ physical function ” , “ pain ” , “ stiffness ” and “ morning tiredness ” or number of tender points and self‐reported pain . We conclude that ECT is a safe and effective treatment for depression in fibromyalgia patients , but has no effect on the pain or other physical symptoms of these patients",
"BACKGROUND Pre clinical and clinical studies have suggested that milnacipran , a dual norepinephrine-serotonin reuptake inhibitor , may be efficacious in the treatment of fibromyalgia ( FM ) . OBJECTIVE This study was conducted to evaluate the efficacy and tolerability of milnacipran in treating the multiple domains of FM . METHODS This was a multicenter , double-blind , placebo-controlled trial . Adult patients ( age 18 - 70 years ) who met 1990 American College of Rheumatology criteria for FM were r and omized to receive milnacipran 100 mg/d , milnacipran 200 mg/d , or placebo for 15 weeks . Because this was a pivotal registration trial , the primary end points were chosen to investigate efficacy for 2 potential indications : the treatment of FM and the treatment of FM pain . Thus , the 2 primary efficacy end points were rates of FM composite responders and FM pain composite responders . FM composite responders were defined as patients concurrently experiencing clinical ly meaningful improvements in the following 3 domain criteria : pain ( > or = 30 % improvement , as recorded in an electronic diary ) ; patients ' global status ( a rating of very much improved or much improved on the Patient Global Impression of Change [ PGIC ] scale ) ; and physical function ( a > or = 6-point improvement on the 36-item Short-Form Health Survey [ SF-36 ] Physical Component Summary score ) . FM pain composite responders were defined as those who met the pain and PGIC criteria . Adverse events reported by patients or observed by investigators were recorded throughout the trial . RESULTS Of 2270 patients screened , 1196 were r and omized to receive milnacipran 100 mg/d ( n = 399 ) , milnacipran 200 mg/d ( n = 396 ) , or placebo ( n = 401 ) . The majority of patients were female ( 96.2 % ) and white ( 93.5 % ) . The population had a mean age of 50.2 years , a mean baseline weight of 180.8 pounds , and a mean baseline body mass index of 30.6 kg/m(2 ) . Compared with placebo , significantly greater proportions of milnacipran-treated patients were FM composite responders ( 100 mg/d : P = 0.01 ; 200 mg/d : P = 0.02 ) and FM pain composite responders ( 100 mg/d : P = 0.03 ; 200 mg/d : P = 0.004 ) . Milnacipran was associated with significant improvements in pain after 1 week of treatment ( 100 mg/d : P = 0.004 ; 200 mg/d : P = 0.04 ) , as well as significant improvements in multiple secondary efficacy end points , including global status ( PGIC : P physical function ( SF-36 physical functioning domain-100 mg/d : P fatigue ( Multidimensional Fatigue Inventory- 100 mg/d : P = 0.04 ) . The most commonly reported adverse events with milnacipran were nausea ( 100 mg/d , 34.3 % ; 200 mg/d , 37.6 % ) , headache ( 18.0 % and 17.7 % , respectively ) , and constipation ( 14.3 % and 17.9 % ) . Adverse events result ed in premature study discontinuation in 19.5 % and 23.7 % of those who received milnacipran 100 and 200 mg/d , respectively , compared with 9.5 % of placebo recipients . CONCLUSION In these adult patients with FM , both doses of milnacipran ( 100 and 200 mg/d ) were associated with significant improvements in pain and other symptoms . Clinical Trials Identification Number : NCT00098124",
"& NA ; We assessed for the first time the long‐term maintenance of repetitive transcranial magnetic stimulation (rTMS)‐induced analgesia in patients with chronic widespread pain due to fibromyalgia . Forty consecutive patients were r and omly assigned , in a double‐blind fashion , to 2 groups : one receiving active rTMS ( n = 20 ) and the other , sham stimulation ( n = 20 ) , applied to the left primary motor cortex . The stimulation protocol consisted of 14 sessions : an “ induction phase ” of 5 daily sessions followed by a “ maintenance phase ” of 3 sessions a week apart , 3 sessions a fortnight apart , and 3 sessions a month apart . The primary outcome was average pain intensity over the last 24 hours , measured before each stimulation from day 1 to week 21 and at week 25 ( 1 month after the last stimulation ) . Other outcomes measured included quality of life , mood and anxiety , and several parameters of motor cortical excitability . Thirty patients completed the study ( 14 in the sham stimulation group and 16 in the active stimulation group ) . Active rTMS significantly reduced pain intensity from day 5 to week 25 . These analgesic effects were associated with a long‐term improvement in items related to quality of life ( including fatigue , morning tiredness , general activity , walking , and sleep ) and were directly correlated with changes in intracortical inhibition . In conclusion , these results suggest that TMS may be a valuable and safe new therapeutic option in patients with fibromyalgia . The analgesic effects induced by repetitive transcranial magnetic stimulation of the motor cortex can be maintained over 6 months in patients with fibromyalgia , using monthly stimulation",
"OBJECTIVE To examine the effectiveness of concurrent strength and endurance training on muscle strength , aerobic and functional performance , and symptoms in postmenopausal women with fibromyalgia ( FM ) . DESIGN R and omized controlled trial . SETTING Local gym and university research laboratory . PARTICIPANTS Twenty-six women with FM . INTERVENTION Progressive and supervised 21-week concurrent strength and endurance training . MAIN OUTCOME MEASURES Muscle strength of leg extensors , upper extremities , and trunk ; peak oxygen uptake ( Vo(2)peak ) , maximal workload ( Wmax ) , and work time ; 10-m walking and 10-step stair-climbing time and self-reported functional capacity ( Health Assessment Question naire ) ; and symptoms of FM . RESULTS After concurrent strength and endurance training , the groups differed significantly in Wmax ( P=.001 ) , work time ( P=.001 ) , concentric leg extension force ( P=.043 ) , walking ( P=.001 ) and stair-climbing ( P time , and fatigue ( P=.038 ) . The training led to an increase of 10 % ( P=.004 ) in Wmax and 13 % ( P=.004 ) in work time on the bicycle but no change in Vo(2)peak . CONCLUSIONS Concurrent strength and endurance training in low to moderate volume improves the muscle strength of leg extensors , Wmax , work time , and functional performance as well as perceived symptoms , fatigue in particular . Concurrent strength and endurance training is beneficial to postmenopausal women with FM without adversities , but more extensive studies are needed to confirm the results",
"Objective . To determine the effects of sodium oxybate ( SXB ) on sleep physiology and sleep/wake-related symptoms in patients with fibromyalgia syndrome ( FM ) . Methods . Of 304 patients with FM ( American College of Rheumatology tender point criteria ) in the screened study population , 209 underwent polysomnography , 195 were r and omized , and 151 completed this 8-week , double-blind , placebo-controlled study of SXB 4.5 g and 6 g/night . We evaluated changes in objective sleep measures and subjective symptoms , including daytime sleepiness [ Epworth Sleepiness Scale ( ESS ) ] , fatigue visual analog scale ( FVAS ) , sleep [ Jenkins Scale for Sleep ( JSS ) ] , and daytime functioning [ Functional Outcome of Sleep Question naire ( FOSQ ) , SF-36 Vitality domain , and Fibromyalgia Impact Question naire ( FIQ ) general and morning tiredness ] . Results . Pretreatment screening revealed an elevated incidence of maximum alpha EEG-intrusion > 24 min/hour of sleep ( 66 % ) , periodic limb movements of sleep ( 20.1 % ≥ 5/hour ) , and moderate to severe obstructive sleep apnea disorder ( 15.3 % apnea-hypopnea index ≥ 15/hour ) . Compared with placebo , both doses of SXB achieved statistically significant improvements in ESS , morning FVAS , JSS , FOSQ , SF-36 Vitality , and FIQ general and morning tiredness ; both doses also demonstrated decreased rapid eye movement ( REM ) sleep ( all p ≤ 0.040 ) . SXB 6 g/night improved afternoon , evening and overall FVAS , reduced wakefulness after sleep onset , and increased Stage 2 , slow-wave , and total non-REM sleep ( all p ≤ 0.032 ) versus placebo . Moderate correlations ( ≥ 0.40 ) were noted between changes in subjective sleep and pain measures . Adverse events occurring significantly more frequently with SXB than placebo were nausea , pain in extremity , nervous system disorders , dizziness , restlessness , and renal/urinary disorders ( including urinary incontinence ) . Conclusion . This large cohort of patients with FM demonstrated that SXB treatment improved EEG sleep physiology and sleep-related FM symptoms",
"OBJECTIVE Fibromyalgia ( FM ) is a common musculoskeletal condition characterized by widespread pain , tenderness , and a variety of other somatic symptoms . Current treatments are modestly effective . Arguably , the best studied and most effective compounds are tricyclic antidepressants ( TCA ) . Milnacipran , a nontricyclic compound that inhibits the reuptake of both serotonin and norepinephrine , may provide many of the beneficial effects of TCA with a superior side effect profile . METHODS One hundred twenty-five patients with FM were r and omly assigned in a 3:3:2 ratio to receive milnacipran twice daily , milnacipran once daily , or placebo for 3 months in a double-blind dose-escalation trial ; 92 % of twice-daily and 81 % of once-daily participants achieved dose escalation to the target milnacipran dose of 200 mg . RESULTS The primary endpoint was reduction of pain . Both the once- and twice-daily groups showed statistically significant improvements in pain , as well as improvements in global well being , fatigue , and other domains . Response rates for patients receiving milnacipran were equal in patients with and without comorbid depression , but placebo response rates were considerably higher in depressed patients , leading to significantly greater overall efficacy in the nondepressed group . CONCLUSION In this Phase II study , milnacipran led to statistically significant improvements in pain and other symptoms of FM . The effect sizes were equal to those previously found with TCA , and the drug was generally well tolerated",
"PURPOSE To assess the efficacy of fluoxetine in the treatment of patients with fibromyalgia . SUBJECTS AND METHODS Sixty out patients ( all women , aged 21 - 71 years ) with fibromyalgia were r and omly assigned to receive fluoxetine ( 10 - 80 mg/d ) or placebo for 12 weeks in a double-blind , parallel-group , flexible-dose study . The primary outcome measures were the Fibromyalgia Impact Question naire total score ( score range , 0 [ no impact ] to 80 ) and pain score ( score range , 0 - 10 ) . Secondary measures included the McGill Pain Question naire , change in the number of tender points , and total myalgic score . RESULTS In the intent-to-treat analysis , women who received fluoxetine ( mean [ + /- SD ] dose , 45 + /- 25 mg/d ) had significant ( P = 0.005 ) improvement in the Fibromyalgia Impact Question naire total score compared with those who received placebo , with a difference of -12 ( 95 % confidence interval [ CI ] : -19 to -4 ) . They also had significant ( P = 0.002 ) improvement in the Fibromyalgia Impact Question naire pain score ( difference , -2.2 [ 95 % CI : -3.6 to -0.9 ] ) , as well as in the Fibromyalgia Impact Question naire fatigue ( P = 0.05 ) and depression ( P = 0.01 ) scores and the McGill Pain Question naire ( P = 0.01 ) , when compared with subjects who received placebo . Although counts for the number of tender points and total myalgic scores improved more in the fluoxetine group than in the placebo group , these differences were not statistically significant . CONCLUSIONS In a 12-week , flexible-dose , placebo-controlled trial , fluoxetine was found to be effective on most outcome measures and generally well tolerated in women with fibromyalgia",
"OBJECTIVE To determine the efficacy of an Internet-based Arthritis Self-Management Program ( ASMP ) as a re source for arthritis patients unable or unwilling to attend small-group ASMPs , which have proven effective in changing health-related behaviors and improving health status measures . METHODS R and omized intervention participants were compared with usual care controls at 6 months and 1 year using repeated- measures analyses of variance . Patients with rheumatoid arthritis , osteoarthritis , or fibromyalgia and Internet and e-mail access ( n = 855 ) were r and omized to an intervention ( n = 433 ) or usual care control ( n = 422 ) group . Measures included 6 health status variables ( pain , fatigue , activity limitation , health distress , disability , and self-reported global health ) , 4 health behaviors ( aerobic exercise , stretching and strengthening exercise , practice of stress management , and communication with physicians ) , 5 utilization variables ( physician visits , emergency room visits , chiropractic visits , physical therapist visits , and nights in hospital ) , and self-efficacy . RESULTS At 1 year , the intervention group significantly improved in 4 of 6 health status measures and self-efficacy . No significant differences in health behaviors or health care utilization were found . CONCLUSION The Internet-based ASMP proved effective in improving health status measures at 1 year and is a viable alternative to the small-group ASMP",
"Purpose . Fibromyalgia is a syndrome of unknown origin with a high prevalence . Multimodal approaches seem to be the treatment of choice in fibromyalgia . A multidisciplinary program was developed and implemented for patients with fibromyalgia in the primary care setting . The program included education ( seven sessions ) and physical therapy ( 25 sessions ) . Method . Patients were referred to the program by their general practitioner or by a medical specialist . A prospect i ve non-controlled treatment study was performed , patients were evaluated before , after and three months after the program ( single group time series design ) . The following measurements were performed : The Fibromyalgia Impact Question naire , R AND 36 , the Pain Coping and Cognition List , the Tampa scale for kinesiophobia , two physical tests and a qualitative evaluation . Data of 65 patients with fibromyalgia were analysed , of whom 97 % were female . The mean age was 44 and the mean duration of pain was nine years . Results . Data of 65 patients with fibromyalgia were analysed , patients significantly improved on the domains feeling good , pain , fatigue , stiffness , quality of life , catastrophizing and on the physical tests . Conclusion . The multidisciplinary program fibromyalgia implemented in primary care seems feasible and the results are promising",
"Objective The aim of this study was to compare pool-based exercise and balneotherapy in fibromyalgia syndrome ( FMS ) patients . Methods Fifty female patients diagnosed with FMS according to the American College of Rheumatism ( ACR ) criteria were r and omly assigned to two groups : group 1 ( n=25 ) with pool-based exercise , and in group 2 ( n=25 ) balneotherapy was applied in the same pool without any exercise for 35 min three times a week for 12 weeks . In both groups , pre- ( week 0 ) and post-treatment ( weeks 12 and 24 ) evaluation was performed by one of the authors , who was blind to the patient group . Evaluation parameters included pain , morning stiffness , sleep , tender points , global evaluation by the patient and the physician , fibromyalgia impact question naire , chair test , and Beck depression inventory . Statistical analysis was done on data collected from three evaluation stages . Results Twenty-four exercise and 22 balneotherapy patients completed the study . Pretreatment ( week 0 ) measurements did not show any difference between the groups . In group 1 , statistically significant improvement was observed in all parameters ( P chair test at both weeks 12 and 24 . In group 2 , week 12 measurements showed significant improvement in all parameters ( P chair test and Beck depression inventory . Week 24 evaluation results in group 2 showed significant improvements in pain and fatigue according to visual analogue scale ( VAS ) , 5-point scale , number of tender points , algometric and myalgic scores , and patient and physician global evaluation ( P morning stiffness , sleep , fibromyalgia impact question naire ( FIQ ) , chair test , and Beck depression inventory parameters in this group . Comparison of the two groups based on the post-treatment ( weeks 12 and 24 ) percent changes and difference scores relative to pretreatment ( week 0 ) values failed to show a significant difference between the groups for any parameter except Beck depression inventory ( P pool-based exercise had a longer-lasting effect on some of the FMS symptoms , but statistical analysis failed to show a significant superiority of pool-based exercise over balneotherapy without exercise . While we believe that exercise is a gold st and ard in FMS treatment , we also suggest in light of our results that balneotherapy is among the valid treatment options in FMS , and further research regarding the type and duration of the exercise programs is necessary",
"Fibromyalgia syndrome is a systemic disorder of widespread pain which is thought to result from abnormal pain processing within the central nervous system . There are no currently approved treatments for this indication . Antidepressants appear , however , to be effective , especially those with an action on noradrenergic neurotransmission . The objective of the present study was to test the efficacy of the dual action noradrenaline and serotonin reuptake inhibitor antidepressant , milnacipran , in the treatment of fibromyalgia . The 125 patients , who were enrolled in a double-blind , placebo-controlled , flexible dose escalation trial , were r and omized to receive placebo or milnacipran for 4 weeks of dose escalation ( up to 200 mg/day ) , followed by 8 weeks at a constant dose . The study evaluated the efficacy and safety of milnacipran for the treatment of pain and associated symptoms such as fatigue , depressed mood and sleep . 75 % of milnacipran-treated patients reported overall improvement , compared with 38 % in the placebo group ( p milnacipran-treated patients reported at least 50 % reduction in pain intensity , compared with 14 % of placebo-treated patients ( p milnacipran patients escalated to the highest dose ( 200 mg/day ) with no tolerability issues . Most adverse events were mild to moderate in intensity , and transient in duration . These results suggest that milnacipran may have the potential to relieve not only pain but several of the other symptoms associated with fibromyalgia",
"OBJECTIVE To assess the efficacy and safety of milnacipran at a dosage of 100 mg/day ( 50 mg twice daily ) for monotherapy treatment of fibromyalgia . METHODS A double-blind , placebo-controlled trial was performed to assess 1,025 patients with fibromyalgia who were r and omized to receive milnacipran 100 mg/day ( n = 516 ) or placebo ( n = 509 ) . Patients underwent 4 - 6 weeks of flexible dose escalation followed by 12 weeks of stable-dose treatment . Two composite responder definitions were used as primary end points to classify the response to treatment . The 2-measure composite response required achievement of ≥30 % improvement from baseline in the pain score and a rating of \" very much improved \" or \" much improved \" on the Patient 's Global Impression of Change ( PGIC ) scale . The 3-measure composite response required satisfaction of these same 2 improvement criteria for pain and global status as well as improvement in physical function on the Short Form 36 ( SF-36 ) physical component summary ( PCS ) score . RESULTS After 12 weeks of stable-dose treatment , a significantly greater proportion of milnacipran-treated patients compared with placebo-treated patients showed clinical ly meaningful improvements , as evidence d by the proportion of patients meeting the 2-measure composite responder criteria ( P . Milnacipran-treated patients also demonstrated significantly greater improvements from baseline on multiple secondary outcomes , including 24-hour and weekly recall pain score , PGIC score , SF-36 PCS and mental component summary scores , average pain severity score on the Brief Pain Inventory , Fibromyalgia Impact Question naire total score ( all P 0.001 versus placebo ) , and Multidimensional Fatigue Inventory total score ( P = 0.036 versus placebo ) . Milnacipran was well tolerated by most patients , with nausea being the most commonly reported adverse event ( placebo-adjusted rate of 15.8 % ) . CONCLUSION Milnacipran administered at a dosage of 100 mg/day improved pain , global status , fatigue , and physical and mental function in patients with fibromyalgia",
"& NA ; The major objective of this research was to evaluate the predictors of fatigue in patients with fibromyalgia ( FM ) , using cross‐sectional and daily assessment method ologies . In the cross‐sectional phase of the research involving a sample of 105 FM patients , greater depression and lower sleep quality were concurrently associated with higher fatigue . While pain was correlated with fatigue , it did not independently contribute to fatigue in the regression equation . For a subset of patients from the cross‐sectional sample ( n=63 ) who participated in a week of prospect i ve daily assessment of their pain , sleep quality , and fatigue , multiple regression analysis of aggregated ( averaged ) daily scores revealed that previous day 's pain and sleep quality predicted next day 's fatigue . Depression from the cross‐sectional phase was not related to aggregated daily fatigue scores . A path analytic framework was tested with disaggregated ( removing between subjects variability ) data in which pain was predicted to contribute to lower sleep quality which , in turn , was predicted to lead to greater fatigue . The results revealed that poor sleep quality fully accounted for the positive relationship between pain and fatigue , thus substantiating the mediational role of sleep quality . The findings are indicative of a dysfunctional , cyclical pattern of heightened pain and non‐restful sleep underlying the experience of fatigue in FM",
"Objective . Increasing research interest and emerging new therapies for treatment of fibromyalgia ( FM ) have led to a need to develop a consensus on a core set of outcome measures that should be assessed and reported in all clinical trials , to facilitate interpretation of the data and underst and ing of the disease . This aligns with the key objective of the Outcome Measures in Rheumatology ( OMERACT ) initiative to improve outcome measurement through a data driven , interactive consensus process . Methods . Through patient focus groups and Delphi processes , working groups at previous OMERACT meetings identified potential domains to be included in the core data set . A systematic review has shown that instruments measuring these domains are available and are at least moderately sensitive to change . Most instruments have been vali date d in multiple language s. This pooled analysis study aims to develop the core data set by analyzing data from 10 r and omized controlled trials ( RCT ) in FM . Results . Results from this study provide support for the inclusion of the following in the core data set : pain , tenderness , fatigue , sleep , patient global assessment , and multidimensional function/health related quality of life . Construct validity was demonstrated with outcome instruments showing convergent and divergent validity . Content and criterion validity were confirmed by multivariate analysis showing R square values between 0.4 and 0.6 . Low R square value is associated with studies in which one or more domains were not assessed . Conclusion . The core data set was supported by high consensus among attendees at OMERACT 9 . Establishing an international st and ard for RCT in FM should facilitate future metaanalyses and indirect comparisons",
"OBJECTIVE To investigate the effects of 21 weeks ' progressive strength training on neuromuscular function and subjectively perceived symptoms in premenopausal women with fibromyalgia ( FM ) . METHODS Twenty one women with FM were r and omly assigned to experimental ( FMT ) or control ( FMC ) groups . Twelve healthy women served as training controls ( HT ) . The FMT and HT groups carried out progressive strength training twice a week for 21 weeks . The major outcome measures were muscle strength and electromyographic ( EMG ) recordings . Secondary outcome measures were pain , sleep , fatigue , physical function capacity ( Stanford Health Assessment Question naire ) , and mood ( short version of Beck 's depression index ) . RESULTS Female FMT subjects increased their maximal and explosive strength and EMG activity to the same extent as the HT group . Moreover , the progressive strength training showed immediate benefits on subjectively perceived fatigue , depression , and neck pain of training patients with FM . CONCLUSIONS The strength training data indicate comparable trainability of the neuromuscular system of women with FM and healthy women . Progressive strength training can safely be used in the treatment of FM to decrease the impact of the syndrome on the neuromuscular system , perceived symptoms , and functional capacity . These results confirm the opinion that FM syndrome has a central rather than a peripheral or muscular basis",
"OBJECTIVE Fibromyalgia ( FM ) is associated with the sleep phenomenon of alpha intrusion , and with low growth hormone secretion . Sodium oxybate has been shown to increase both slow-wave sleep and growth hormone levels . This double blind , r and omized , placebo controlled crossover trial was conducted to evaluate the effects of sodium oxybate on the subjective symptoms of pain , fatigue , and sleep quality and the objective polysomnographic ( PSG ) sleep variables of alpha intrusion , slow-wave ( stage 3/4 ) sleep , and sleep efficiency in patients with FM . METHODS Patients received either 6.0 g/day sodium oxybate or placebo for 1 month , with an intervening 2 week washout period . Efficacy measures included PSG evaluations , tender point index ( TPI ) , and subjective measurements from daily diary entries . Safety measures included clinical laboratory values , vital signs , and adverse events . RESULTS Twenty-four female patients were included in the study ; 18 completed the trial . TPI was decreased from baseline by 8.5 , compared with an increase of 0.4 for placebo ( p = 0.0079 ) . Six of the 7 pain/fatigue scores ( overall pain , pain at rest , pain during movement , end of day fatigue , overall fatigue , and morning fatigue ) were relieved by 29 % to 33 % with sodium oxybate , compared with 6 % to 10 % relief with placebo ( p Alpha intrusion , sleep latency , and rapid-eye-movement sleep were significantly decreased , while slow-wave ( stage 3/4 ) sleep was significantly increased , compared with placebo ( p placebo : morning alertness ( improved by 18 % with sodium oxybate , compared with 2 % for placebo ; p = 0.0033 ) and quality of sleep ( improved by 33 % and 10 % , respectively ; p = 0.0003 ) . CONCLUSION Sodium oxybate effectively reduced the symptoms of pain and fatigue in patients with FM , and dramatically reduced the sleep abnormalities ( alpha intrusion and decreased slow-wave sleep ) associated with the nonrestorative sleep characteristic of this disorder",
"S-adenosylmethionine is a relatively new anti-inflammatory drug with analgesic and anti-depressant effects . Efficacy of 800 mg orally administered s-adenosylmethionine daily versus placebo for six weeks was investigated in 44 patients with primary fibromyalgia in double-blind setting s. Tender point score , isokinetic muscle strength , disease activity , subjective symptoms ( visual analog scale ) , mood parameters and side effects were evaluated . Improvements were seen for clinical disease activity ( P = 0.04 ) , pain experienced during the last week ( P = 0.002 ) , fatigue ( P = 0.02 ) , morning stiffness ( P = 0.03 ) and mood evaluated by Face Scale ( P = 0.006 ) in the actively treated group compared to placebo . The tender point score , isokinetic muscle strength , mood evaluated by Beck Depression Inventory and side effects did not differ in the two treatment groups . S-adenosylmethionine has some beneficial effects on primary fibromyalgia and could be an important option in the treatment hereof",
"BACKGROUND Some positive therapeutic effects in fibromyalgia syndrome ( FS ) were reported with both tricyclic and new antidepressant drugs as well as serotonergic agents ( 5HT2 and 5HT3 receptor blockers ) . METHODS In the present study , a novel antidepressant drug mirtazapine , 15 - 30 mg/day , has been used in 29 patients with FS in an open trial . RESULTS Twenty-six patients completed the six-week study . Ten ( 38 % ) were considered responders on account of the reduction of > or = 40 % on pain , fatigue and sleep disturbances and remission of depressive symptoms at the end of study . Eighteen patients had at least moderate depression before mirtazapine treatment and 8 patients presented mild depressive symptoms . Reduction on main symptoms of FS after 6 weeks of mirtazapine treatment significantly correlated with the reduction in depression . However , the percentage of responders and patients with > or = 40 % reduction on main symptoms of fibromyalgia was similar in high and low depression groups . CONCLUSIONS The results obtained suggest that mirtazapine may be promising method of FS treatment . Further double-blind placebo-controlled studies are required to confirm these results",
"The objective of this study was to test the efficacy of intravenously administered S-adenosyl-L-methionine ( SAMe ) in patients with fibromyalgia ( FM ) . Thirty-four out- patients with fibromyalgia symptoms received SAMe 600 mg i.v . or placebo daily for 10 days in a cross-over trial . There was no significant difference in improvement in the primary outcome : tender point change between the two treatment groups . There was a tendency towards statistical significance in favour of SAMe on subjective perception of pain at rest ( p = 0.08 ) , pain on movement ( p = 0.11 ) , and overall well-being ( p = 0.17 ) and slight improvement only on fatigue , quality of sleep , morning stiffness , and on the Fibromyalgia Impact Question naire for pain . No effect could be observed on isokinetic muscle strength , Zerrsen self- assessment question naire , and the face scale . No effect of SAMe in patients with FM was found in this short term study",
"OBJECTIVES To document 1 ) the content validity and 2 ) measure improvements in fatigue , using the Fatigue Visual Analogue Scale ( VAS ) assessment tool in patients with fibromyalgia . METHODS The relevance and comprehensiveness of the Fatigue VAS were tested through a qualitative analysis of 20 subjects ' verbatim transcripts from semi-structured qualitative interviews . Data from two r and omised , controller trials in fibromyalgia ( n=1121 ) were used to conduct correlation analyses with the Fatigue and Tiredness items from the Fibromyalgia Impact Question naire ( FIQ ) and the Short Form-36 Vitality scale . Known-groups and cross classification analyses were conducted to demonstrate the ability to measure improvement in fatigue using the Fatigue VAS . RESULTS All subjects spontaneously reported that fatigue was an important symptom to capture in fibromyalgia . The Fatigue VAS was well understood by most subjects ( n=18/20 ) . High correlations ( Pearson r>0.75 ) and good agreement ( k>0.66 ) were found between the Fatigue VAS and the FIQ tiredness items no. 16 and 17 and SF-36 ™ Vitality scale . In both clinical trials there was a substantial separation of approximately 20 points on the mean change in the Fatigue VAS score between responders ( > 30 % improvement in pain VAS ) and non-responders . CONCLUSIONS Previous studies have confirmed that fatigue is a major component of the fibromyalgia experience . This current study reports that fibromyalgia patients spontaneously rated fatigue as a highly significant feature of their illness , and supports the use of the Fatigue VAS as a valid question naire in fibromyalgia clinical trials",
"Objective : The aim of the present study is to evaluate the effectiveness of spa therapy in the management of fibromyalgia . Methods : Thirty women with fibromyalgia were r and omly assigned to either a spa therapy group or a control group . The spa therapy group ( n = 16 ) had spa treatment for 2 weeks in addition to their medical treatment . The control group ( n = 14 ) continued to have their medical treatment and /or daily exercises . An investigator who was blinded for the intervention assessed all the patients for 9 months . Improvements in Fibromyalgia Impact Question naire ( FIQ ) , pain and number of tender points were primary outcomes . Secondary outcome measures were improvement in sleep disturbance , fatigue , gastrointestinal symptoms , anxiety , Beck Depression Inventory and patient ’s global evaluation . Results : the spa group was found to be superior to the control group at the end of intervention in terms of FIQ , pain , tender point count , fatigue and patients ’ global assessment . This superiority remained for 6 months in FIQ , 1 month in pain and tender point count . Conclusion : It was concluded that the addition of spa therapy to medical therapy has both short- and long-term beneficial effects in female patients with fibromyalgia",
"Objective . To evaluate the safety and efficacy of milnacipran , a dual norepinephrine and serotonin reuptake inhibitor , in the treatment of fibromyalgia ( FM ) . Methods . A 27-week , r and omized , double-blind , multicenter study compared milnacipran 100 and 200 mg/day with placebo in the treatment of 888 patients with FM . Two composite responder definitions were used to classify each patient ’s individual response to therapy . “ FM responders ” concurrently satisfied response criteria for improvements in pain ( visual analog scale 24-h morning recall ) , patient global impression of change ( PGIC ) , and physical functioning ( SF-36 Physical Component Summary ) ; while “ FM pain responders ” concurrently satisfied response criteria for improvements in pain and PGIC . Results . At the primary endpoint , after 3-month stable dose treatment , a significantly higher percentage of milnacipran-treated patients met criteria as FM responders versus placebo ( milnacipran 200 mg/day , p = 0.017 ; milnacipran 100 mg/day , p = 0.028 ) . A significantly higher percentage of patients treated with milnacipran 200 mg/day also met criteria as FM pain responders versus placebo ( p = 0.032 ) . Significant pain reductions were observed after Week 1 with both milnacipran doses . At 15 weeks , milnacipran 200 mg/day led to significant improvements over placebo in pain ( realtime , daily and weekly recall ; all measures , p PGIC ( p fatigue ( p = 0.016 ) , cognition ( p = 0.025 ) , and multiple SF-36 domains . Milnacipran was safe and well tolerated by the majority of patients during 27 weeks of treatment ; nausea and headache were the most common adverse events . Conclusion . Milnacipran is safe and effective for the treatment of multiple symptoms of FM",
"A prospect i ve , r and omized , placebo-controlled , multicenter , double-blind trial in fibromyalgia patients demonstrated that peroral daily treatment with 5 mg tropisetron for 10 days produced a significant reduction in pain and other symptoms . The aim of the present study was to determine whether intravenous administration of 2 mg tropisetron daily for a limited period of time would produce quicker and more favorable results . In the first cohort 18 fibromyalgia patients received a single intravenous injection of 2 mg tropisetron . In the second cohort 24 fibromyalgia patients were treated with 2 mg intravenous tropisetron daily for 5 days . Pain intensity was measured with the visual analog scale and the pain score . Pain at tender and control points ( dolorimeter ) as well as 17 ancillary symptoms before and after treatment were evaluated . Pain intensity was followed-up by means of a patient diary until recurrence . Dolorimetry revealed that a single intravenous injection of 2 mg tropisetron significantly reduced pain and enhanced pain threshold . These effects , however , lasted for only a few days . Of 18 patients in the first cohort , only three showed no response to therapy . Of the 24 patients in the second cohort , 23 showed pain reduction when 2 mg tropisetron was administered daily for 5 days . Pain relief lasted for 2 weeks to 2 months in 20 of these patients . Two patients stopped filling in the pain diary . Twelve ancillary symptoms such as sleep disturbances , fatigue , morning stiffness were also significantly improved by the latter treatment . In the global assessment 16 out of 24 patients showed significant improvement and seven showed slight improvement . Only one patient experienced no improvement . Tolerability was good . In conclusion , intravenous injection of 2 mg of the 5-hydroxytryptamine3 receptor antagonist tropisetron once daily for 5 days produced a longer-lasting therapeutic effect on fibromyalgia symptoms than did peroral daily treatment with 5 mg of this drug . The results achieved are currently being evaluated in a r and omized , placebo-controlled , double-blind trial",
"BACKGROUND Esreboxetine is an investigational , highly selective norepinephrine reuptake inhibitor that has been reported to have antinociceptive effects in pre clinical pain models . OBJECTIVE This study assessed the efficacy and safety profile of esreboxetine in the management of fibromyalgia . METHODS This was a multicenter , r and omized , double-blind , placebo-controlled trial in patients aged ≥18 years who met American College of Rheumatology criteria for fibromyalgia . Eligible patients were required to have a score ≥40 mm on the 100-mm visual analog scale of the Short-Form McGill Pain Question naire at screening and r and omization , and a mean score ≥4 on an 11-point pain rating scale ( from 0 = no pain to 10 = worst possible pain ) based on the weekly mean pain score in the week before r and omization . After a 1-week baseline period and a 2-week , single-blind , placebo run-in period , patients were r and omized to receive esreboxetine or placebo for 8 weeks , followed by a 1-week follow-up period . Esreboxetine dosing was started at 2 mg/d and was escalated by 2 mg/d every 2 weeks until attainment of a dose of 8 mg/d or the maximum tolerated dose . The primary efficacy outcome was the change from baseline to week 8 in weekly mean pain scores , as derived from patients ' daily pain ratings on the 11-point scale . Additional primary efficacy outcomes included changes in the Fibromyalgia Impact Question naire ( FIQ ) total score and the Patient Global Impression of Change ( PGIC ) . The safety profile was evaluated based on observed and spontaneously reported adverse events , laboratory tests , and other safety measures . RESULTS One hundred thirty-four patients were r and omized to each study group , but 1 patient in the placebo group did not receive treatment . Thus , the study population consisted of 267 patients ( 89.5 % female ; 88.4 % white ; mean age , ∼50 years [ range , 20 - 84 years ] ) . Twenty-seven patients in each group discontinued the study . Adverse events were the most common reason for discontinuation in the esreboxetine group ( 11 patients ) , compared with 3 discontinuing due to adverse events in the placebo group . Patient default ( withdrawal of consent and loss to follow-up ) was the most common reason for discontinuation in the placebo group ( 13 patients ) , compared with 10 in the esreboxetine group . The esreboxetine group had significantly greater improvement in the weekly mean pain score compared with the placebo group ( mean [ SE ] change from baseline : -1.55 [ 0.16 ] vs -0.99 [ 0.16 ] , respectively ; P = 0.006 ) . A significantly greater percentage of patients in the esreboxetine group reported a ≥30 % reduction in pain scores compared with the placebo group ( 37.6 % [ 50/133 ] vs 22.6 % [ 30/133 ] ; P = 0.004 ) . Esreboxetine was associated with significant improvement compared with placebo in the FIQ total score ( mean change from baseline : -15.63 [ 1.56 ] vs -8.07 [ 1.54 ] ; P esreboxetine group than in the placebo group reported their condition much or very much improved ( odds ratio = 2.42 ; 90 % CI , 1.549 - 3.786 ; P ) . Esreboxetine also was associated with significant improvements in secondary outcomes compared with placebo . These included fatigue , as reflected in scores on the Multidimensional Assessment of Fatigue ( mean [ SE ] change from baseline : -6.39 [ 0.75 ] vs -2.82 [ 0.75 ] , respectively ; P on measures of patient function and health-related quality of life , including the 36-item Short Form Health Survey ( SF-36 ) Physical Component Summary ( mean change from baseline : 4.36 [ 0.59 ] vs 1.86 [ 0.59 ] ; P = 0.002 ) , the SF-36 Mental Component Summary ( mean change from baseline : 4.25 [ 0.83 ] vs 1.81 [ 0.83 ] ; P = 0.019 ) , and the Sheehan Disability Scale total score ( mean change from baseline : -6.50 [ 0.64 ] vs -2.79 [ 0.61 ] ; P the esreboxetine group than in the placebo group reported at least one adverse event ( 71.6 % vs 57.1 % ) , most commonly constipation ( 17.2 % vs 5.3 % ) , insomnia ( 15.7 % vs 3.0 % ) , dry mouth ( 15.7 % vs 2.3 % ) , and headache ( 10.4 % vs 2.3 % ) . CONCLUSIONS In this 8-week trial in patients with fibromyalgia , esreboxetine was associated with significant reductions in pain scores compared with placebo . It was also associated with improvements in outcomes relevant to fibromyalgia , including the PGIC , function , and fatigue . Clinical Trials.gov identifier : NCT00357825",
"OBJECTIVE Sleep problems are a common symptom of fibromyalgia ( FM ) . The objective of this study was to evaluate the Medical Outcomes Study ( MOS ) Sleep Scale as a measure of FM-related sleep problems . METHODS Analyses were based on data from the 1056 and 1077 studies , two r and omized , double-blind , placebo-controlled trials of pregabalin for adults with FM . MOS Sleep Scale scores of study patients were compared with United States normative scores using a one- sample Z test . Subscale structure of the MOS was evaluated by confirmatory factor analyses , internal consistency was evaluated using Cronbach 's alpha reliability coefficients . Estimated clinical ly important differences ( CID ) in MOS Sleep Disturbance subscale scores were evaluated using mixed-effects models of change in subscale scores as a function of the Patient Global Impression of Change ( PGIC ) . RESULTS 1056 and 1077 included 748 and 745 patients , respectively . Most patients were female ( 1056 : 94.4 % , 1077 : 94.5 % ) and white ( 1056 : 90.2 % , 1077 : 91.0 % ) . Mean ages were 48.8 years ( 1056 ) and 50.1 years ( 1077 ) . Baseline MOS Sleep Scale scores were statistically ( P Cronbach 's alpha coefficients were acceptable , at least 0.70 , for all multi-item scales at baseline and end-of- study assessment s in both studies , with the exception of the Sleep Adequacy subscale at baseline . The estimated CID for the MOS Sleep Disturbance subscale was 7.9 . CONCLUSIONS The MOS Sleep Scale is an appropriate measure of FM-related sleep problems . These analyses provide the foundation for further use and evaluation of the MOS Sleep Scale in FM patients",
"OBJECTIVE Multidisciplinary treatments ( MTs ) are usually recommended for reducing fibromyalgia ( FM ) symptoms and include physical exercise , drug management , education , and cognitive behavior therapy ( CBT ) . However , there is no evidence that CBT adds efficacy to the other therapeutic components . This r and omized controlled trial analyzed the response of FM patients to two MTs , with and without CBT , according to the presence of concurrent symptoms . METHODS Eighty-three women with FM were r and omly assigned to MT or combined MT and CBT . The MT included medical intervention , physical training , education , and discussion of the syndrome . The CBT focused on coping with stress , modifying lifestyles , and changing pain behaviors . Demographic and clinical data , information regarding tender points , and question naire responses about functional capability [ Fibromyalgia Impact Question naire ( FIQ ) ] , health status [ 36-item Short Form Health Survey ( SF-36 ) ] , and mental health [ Symptom Checklist-90-Revised ( SCL-90-R ) ] were obtained at the beginning , at the end of the 15-week treatment , and at 6-month follow-up . Subgroups are identified in relation to treatment response . RESULTS Sixty-six women ( 80 % ) completed treatment . Although the variance of the total sample had changed at posttreatment ( F=2.67 , P=.031 ) , there was no significant effect for the TimexTreatment interaction ( F=1.65 , P=.16 ) . Univariate tests detected a significant fall in the FIQ score . The subgroup of patients with fatigue showed a better response with MT+CBT than with MT . At 6-month follow-up , the statistical differences had been maintained . Intention-to-treat analysis ratified these results . CONCLUSIONS MT improves functional capability and reduces symptom impact . CBT increases mildly the effect of MT in patients with fatigue",
"The aim of this exploratory study was to systematic ally assess the potential effectiveness and tolerability of quetiapine , an atypical antipsychotic , for the treatment of patients with fibromyalgia . This was a unicentre , open-label study conducted in thirty-five out patients , 18 years or older , who met the ACR criteria for fibromyalgia and who had not satisfactorily responded to their previous fibromyalgia treatment . Quetiapine , flexibly dosed ( 25 - 100 mg/day ) , was added to their original treatment regimen for 12 weeks . The primary outcome measure was the mean change from baseline to endpoint in the Fibromyalgia Impact Question naire ( FIQ ) total score . Secondary efficacy measures included mean changes from baseline to endpoint in the scores of the Clinical Global Impression ( CGI ) of Severity scale , Pittsburgh Sleep Quality Index ( PSQI ) , Beck Depression Inventory ( BDI ) , State-Trait Anxiety Inventory ( STAI ) , 12-Item Short Form Health Survey ( SF-12 ) , and individual items of the FIQ . Thirty ( 85.7 % ) patients ( mean age 47+/-7.9 , 93.3 % females ) had a postbaseline evaluation and constituted the intent-to-treat efficacy sample . Mean FIQ total score decreased significantly by 10.2 points from a baseline of 63.2 to 53.0 at study endpoint ( p FIQ stiffness and FIQ fatigue subscores but not in FIQ pain subscore . Large effect sizes were observed for the FIQ total ( 1.04 ) , CGI-severity ( 1.00 ) and PSQI ( 1.07 ) , while moderate effect sizes ( i.e. > or = 0.50 ) were encountered in the FIQ fatigue , FIQ stiffness and SF-12 mental component summary . Quetiapine was safely administered and well tolerated . Despite the lack of effect on pain , the significant and relevant improvement in overall efficacy measures and quality of life suggests that quetiapine may be a valuable drug for treatment of patients with fibromyalgia that should be further tested in double-blind , placebo-controlled trials",
"Objective : Written expression of traumatic experiences , an intervention found to have health benefits in rheumatoid arthritis , asthma , and breast cancer , was tested in a r and omized , controlled trial with female fibromyalgia patients . It was hypothesized that relative to controls , patients engaging in the writing intervention would experience improved status on psychological well-being and physical health variables . Methods : Patients ( N = 92 ) were r and omized into a trauma writing group , a control writing group , or usual care control group . The two writing groups wrote in the laboratory for 20 minutes on 3 days at 1-week intervals . Psychological well-being , pain , and fatigue were the primary outcome variables . Assessment s were made at pretreatment , posttreatment , 4-month follow-up , and 10-month follow-up . Results : The trauma writing group experienced significant reductions in pain ( effect size [ ES ] = 0.49 ) and fatigue ( ES = 0.62 ) and better psychological well-being ( ES = 0.47 ) at the 4-month follow-up relative to the control groups . Benefits were not maintained at the 10-month follow-up . Conclusion : Fibromyalgia patients experienced short-term benefits in psychological and health variables through emotional expression of personal traumatic experiences . ED = written emotional disclosure ; RA = rheumatoid arthritis ; QOL = Quality of Life Scale ; STAI-S = state version , State-Trait Anxiety Inventory ; BDI = Beck Depression Inventory ; MOS = Medical Outcome Study ; CLINHAQ = Clinical Health Assessment Question naire ; FIQ = Fibromyalgia Impact Question naire ; VAS = visual analogue scale ; NW = neutral writing group ; UC = usual-care control group ; ANOVA = analysis of variance ; ES = effect size",
"& NA ; This 14‐week , phase 3 , double‐blind , r and omized , controlled trial evaluated sodium oxybate ( SXB ) 4.5 and 6 g per night versus placebo in patients with fibromyalgia ( FM ) . SXB is the sodium salt of γ‐hydroxybutyrate ( GHB ) . GHB is an endogenous compound , synthesized from γ‐aminobutyric acid ( GABA ) and found broadly in the central nervous system and body . Among 548 r and omized patients , a ⩾30 % reduction in pain was experienced by 54.2 % and 58.5 % of patients treated with SXB 4.5 and 6 g , respectively , versus 35.2 % for placebo with a 100‐mm Visual Analog Scale ( VAS ) ( P to placebo , both SXB doses significantly reduced fatigue ( with a 100‐mm VAS ; P and sleep disturbance ( with the Jenkins Sleep Scale ; P significant improvements in function as measured by the FM Impact Question naire ( P = 0.003 and P = 0.001 for 4.5 and 6 g per night , respectively ) . On the Short‐Form 36 Health Survey , SXB‐related improvement was significant on the Physical , but not the Mental , Component Scale . The proportion of patients who reported a global improvement of “ much ” or “ very much ” better on the Patient Global Impression of Change was significantly greater in both SXB groups versus placebo ( P ) . Headache , nausea , dizziness , vomiting , diarrhea , anxiety , and sinusitis were the most commonly reported adverse events , with an incidence at least twice that of placebo . These results exp and the evidence from previous clinical trials suggesting that SXB is effective and safe in FM . This study exp and s evidence from previous trials that sodium oxybate provides safe , effective treatment for multiple symptoms experienced by patients with fibromyalgia",
"Following development of the core domain set for fibromyalgia ( FM ) in Outcome Measures in Rheumatology Clinical Trials ( OMERACT ) meetings 7 to 9 , the FM working group has progressed toward the development of an FM responder index and a disease activity score based on these domains , utilizing outcome indices of these domains from archived r and omized clinical trials in FM . Possible clinical domains that could be included in a responder index and disease activity score include pain , fatigue , sleep disturbance , cognitive dysfunction , mood disturbance , tenderness , stiffness , and functional impairment . Outcome measures for these domains demonstrate good to adequate psychometric properties , although measures of cognitive dysfunction need to be further developed . The approach used in the development of responder indices and disease activity scores for rheumatoid arthritis and ankylosing spondylitis represents heuristic models for our work , but FM is challenging in that there is no clear algorithm of treatment that defines disease activity based on treatment decisions , nor are there objective markers that define thresholds of severity or response to treatment . The process of developing c and i date dichotomous responder definitions and continuous quantitative disease activity measures is described , along with participant discussion s from OMERACT 10 . Final results of this work will be published in a separate report pending completion of analyses"
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411878a4-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND The needs of children with autism spectrum disorder ( ASD ) are complex and this is reflected in the number and diversity of outcomes assessed and measurement tools used to collect evidence about children 's progress . Relevant outcomes include improvement in core ASD impairments , such as communication , social awareness , sensory sensitivities and repetitiveness ; skills such as social functioning and play ; participation outcomes such as social inclusion ; and parent and family impact . OBJECTIVES To examine the measurement properties of tools used to measure progress and outcomes in children with ASD up to the age of 6 years . To identify outcome areas regarded as important by people with ASD and parents . METHODS The MeASURe ( Measurement in Autism Spectrum disorder Under Review ) research collaboration included ASD experts and review method ologists . We undertook systematic review of tools used in ASD early intervention and observational studies from 1992 to 2013 ; systematic review , using the COSMIN checklist ( Consensus-based St and ards for the selection of health Measurement Instruments ) of papers addressing the measurement properties of identified tools in children with ASD ; and synthesis of evidence and gaps . The review design and process was informed throughout by consultation with stakeholders including parents , young people with ASD , clinicians and research ers . RESULTS The conceptual framework developed for the review was drawn from the International Classification of Functioning , Disability and Health , including the domains ' Impairments ' , ' Activity Level Indicators ' , ' Participation ' , and ' Family Measures ' . In review 1 , 10,154 papers were sifted - 3091 by full text - and data extracted from 184 ; in total , 131 tools were identified , excluding observational coding , study -specific measures and those not in English . In review 2 , 2665 papers were sifted and data concerning measurement properties of 57 ( 43 % ) tools were extracted from 128 papers . Evidence for the measurement properties of the review ed tools was combined with information about their accessibility and presentation . Twelve tools were identified as having the strongest supporting evidence , the majority measuring autism characteristics and problem behaviour . The patchy evidence and limited scope of outcomes measured mean these tools do not constitute a ' recommended battery ' for use . In particular , there is little evidence that the identified tools would be good at detecting change in intervention studies . The obvious gaps in available outcome measurement include well-being and participation outcomes for children , and family quality -of-life outcomes , domains particularly valued by our informants ( young people with ASD and parents ) . CONCLUSIONS This is the first systematic review of the quality and appropriateness of tools design ed to monitor progress and outcomes of young children with ASD . Although it was not possible to recommend fully robust tools at this stage , the review consoli date s what is known about the field and will act as a benchmark for future developments . With input from parents and other stakeholders , recommendations are made about priority targets for research . FUTURE WORK Priorities include development of a tool to measure child quality of life in ASD , and validation of a potential primary outcome tool for trials of early social communication intervention . STUDY REGISTRATION This study is registered as PROSPERO CRD42012002223 . FUNDING The National Institute for Health Research Health Technology Assessment programme
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"A r and omized control trial comparing two social-communication interventions in young children with autism examined far-transfer of the use of picture exchange to communicate . Thirty-six children were r and omly assigned to one of two treatment conditions , one of which was the Picture Exchange Communication System ( PECS ) . All children had access to picture symbols during assessment s. Post-treatment measurement of the number of picture exchanges in a far-transfer , assessment context favored the PECS intervention . These findings were interpreted as support for the hypothesis that the PECS curriculum can successfully teach a generalized means of showing coordinated attention to object and person without requiring eye contact to children with ASD",
"BACKGROUND Delays and deficits in joint attention and symbolic play constitute two important developmental problems in young children with autism . These areas of deficit have been well studied in autism but have rarely been the focus of treatment efforts ( see Kasari , Freeman , & Paparella , 2001 ) . In this study , we examine the efficacy of targeted interventions of joint attention and symbolic play . METHODS Participants were 58 children with autism aged 3 and 4 years ( 46 boys ) . Children were r and omized to a joint attention intervention , a symbolic play intervention , or control group . Interventions were conducted 30 minutes daily for 5 - 6 weeks . Both structured assessment s of joint attention and play skills and mother-child interactions were collected pre and post intervention by independent assessors . RESULTS Results indicate that both intervention groups improved significantly over the control group on certain behaviors . Children in the joint attention intervention initiated significantly more showing and responsiveness to joint attention on the structured joint attention assessment and more child-initiated joint attention in the mother-child interaction . The children in the play group showed more diverse types of symbolic play in interaction with their mothers and higher play levels on both the play assessment and in interaction with their mothers . CONCLUSIONS This r and omized controlled trial provides promising data on the specificity and generalizability of joint attention and play interventions for young children with autism . Future studies need to examine the long-term effects of these early interventions on children 's development",
"The teaching of imitation skills is often the first step in interventions for young learners with intellectual disabilities . The main goal of this study was to determine the smallest detectable difference ( SDD ) at 95 % confidence of the Preschool Imitation and Praxis Scale ( PIPS ) in preschoolers with intellectual disabilities . Two raters independently scored videotapes of the imitation performance of 44 preschoolers ( 27 with Down syndrome , 10 with Non-Specific Mental Retardation and 7 with Low-functioning Autism ) between 13 and 58 months of age ( mean age 39.6 months , SD 11.9 months ) . Results revealed that the PIPS demonstrated acceptable interrater reliability on item level ( weighted kappa values ranged from 0.52 to 0.96 ) and scale level ( ICC = 0.986 ; 95 % CI : 0.975 - 0.993 ) . The SDD of the PIPS was 7.2 % , indicating that the change score rated by different raters for an individual child with an intellectual disability is valid and that the PIPS can be used by early interventionists and research ers as an outcome measure to determine children 's maturation or improvement ",
"We piloted a 2-week “ Autism-1 - 2 - 3 ” early intervention for children with autism and their parents immediately after diagnosis that targeted at ( 1 ) eye contact , ( 2 ) gesture and ( 3 ) vocalization/words . Seventeen children were r and omized into the Intervention ( n = 9 ) and Control ( n = 8) groups . Outcome measures included the Autism Diagnostic Observation Schedule , Ritvo-Freeman Real Life Rating Scale , Symbolic Play Test , and Parenting Stress Index . Children with autism improved in language /communication , reciprocal social interaction , and symbolic play . Parents perceived significant improvement in their children ’s language , social interaction , and their own stress level . This intervention can serve as short-term training on communication and social interaction for children with autism , and reduce the stress of their parents during the long waiting time for public health services",
"Children with autism exhibit significant deficits in imitation skills . Reciprocal Imitation Training ( RIT ) , a naturalistic imitation intervention , was developed to teach young children with autism to imitate during play . This study used a r and omized controlled trial to evaluate the efficacy of RIT on elicited and spontaneous imitation skills in 21 young children with autism . Results found that children in the treatment group made significantly more gains in elicited and spontaneous imitation , replicating previous single-subject design studies . Number of spontaneous play acts at pre-treatment was related to improvements in imitation during the intervention , suggesting that children with a greater play repertoire make greater gains during RIT",
"PURPOSE This r and omized group experiment compared the efficacy of 2 communication interventions ( Responsive Education and Prelinguistic Milieu Teaching [ RPMT ] and the Picture Exchange Communication System [ PECS ] ) on spoken communication in 36 preschoolers with autism spectrum disorders ( ASD ) . METHOD Each treatment was delivered to children for a maximum total of 24 hr over a 6-month period . Spoken communication was assessed in a rigorous test of generalization at pretreatment , posttreatment , and 6-month follow-up periods . RESULTS PECS was more successful than RPMT in increasing the number of nonimitative spoken communication acts and the number of different nonimitative words used at the posttreatment period . Considering growth over all 3 measurement periods , an exploratory analysis showed that growth rate of the number of different nonimitative words was faster in the PECS group than in the RPMT group for children who began treatment with relatively high object exploration . In contrast , analogous slopes were steeper in the RPMT group than in the PECS group for children who began treatment with relatively low object exploration",
"This study aim ed to determine if a joint attention intervention would result in greater joint engagement between caregivers and toddlers with autism . The intervention consisted of 24 caregiver-mediated sessions with follow-up 1 year later . Compared to caregivers and toddlers r and omized to the waitlist control group the immediate treatment ( IT ) group made significant improvements in targeted areas of joint engagement . The IT group demonstrated significant improvements with medium to large effect sizes in their responsiveness to joint attention and their diversity of functional play acts after the intervention with maintenance of these skills 1 year post-intervention . These are among the first r and omized controlled data to suggest that short-term parent-mediated interventions can have important effects on core impairments in toddlers with autism . Clinical Trials # : NCT00065910",
"OBJECTIVE A consumer-oriented efficacy assessment in clinical trials should measure changes in chief complaint and consumer request ( symptoms of most concern to patient/caregiver ) , which may be diluted in change scores of multisymptom scales . METHOD In the Research Units on Pediatric Psychopharmacology ( RUPP ) Autism Network 8-week double-blind trial of risperidone versus placebo , the chief concerns of parents were collected at 0 , 4 , and 8 weeks ( endpoint ) , in addition to st and ardized primary measures . Blinded clinical judges rated change from baseline to 4 and 8 weeks on a 9-point scale ( 1 = normalized , 5 = unchanged , 9 = disastrous ) ; 94 participants had usable data . RESULTS The most common symptoms identified by parents were tantrums , aggression , and hyperactivity . Interrater reliability was excellent . Mean ratings at endpoint were 2.8 + /- 1.2 on risperidone and 4.5 + /- 1.3 on placebo ( p Clinical Global Impression-Improvement and Aberrant Behavior Checklist Irritability subscale ( primary dimensional measure ) . Effect size d was 1.4 , compared to 1.2 on the Aberrant Behavior Checklist Irritability subscale . Effect sizes varied twofold by symptom category , largest for self-injury ( 2.11 ) and tantrums ( 1.95 ) . CONCLUSIONS Risperidone was superior to placebo in reducing symptoms of most concern to parents of autistic children with irritable behavior . Rating individualized participant-chosen target symptoms seems a reliable , sensitive , efficient , and consumer-friendly way to assess treatment effect and might have clinical application",
"In the interest of more systematic ally documenting the early signs of autism , and of testing specific hypotheses regarding their underlying neurodevelopmental substrates , we have initiated a longitudinal study of high-risk infants , all of whom have an older sibling diagnosed with an autistic spectrum disorder . Our sample currently includes 150 infant siblings , including 65 who have been followed to age 24 months , who are the focus of this paper . We have also followed a comparison group of low-risk infants . Our measures include a novel observational scale ( the first , to our knowledge , that is design ed to assess autism-specific behavior in infants ) , a computerized visual orienting task , and st and ardized measures of temperament , cognitive and language development . Our preliminary results indicate that by 12 months of age , siblings who are later diagnosed with autism may be distinguished from other siblings and low-risk controls on the basis of : ( 1 ) several specific behavioral markers , including atypicalities in eye contact , visual tracking , disengagement of visual attention , orienting to name , imitation , social smiling , reactivity , social interest and affect , and sensory-oriented behaviors ; ( 2 ) prolonged latency to disengage visual attention ; ( 3 ) a characteristic pattern of early temperament , with marked passivity and decreased activity level at 6 months , followed by extreme distress reactions , a tendency to fixate on particular objects in the environment , and decreased expression of positive affect by 12 months ; and ( 4 ) delayed expressive and receptive language . We discuss these findings in the context of various neural networks thought to underlie neurodevelopmental abnormalities in autism , including poor visual orienting . Over time , as we are able to prospect ively study larger numbers and to examine interrelationships among both early-developing behaviors and biological indices of interest , we hope this work will advance current underst and ing of the neurodevelopmental origins of 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",
"This study evaluated the effectiveness of low intensity behavioral treatment ( on average 6.5h per week ) supplementing preschool services in 3 - 6-year-old children with autism spectrum disorder and severe to mild intellectual disability . Treatment was implemented in preschools ( i.e. , daycare centers ) and a discrete trial teaching approach was used . Twelve children in the treatment group were compared to 22 children receiving regular intervention . At pre-treatment , both groups did not differ on chronological age , developmental age , diagnosis and level of adaptive skills . Eight months into treatment , children receiving behavioral treatment displayed significantly higher developmental ages and made more gains in adaptive skills than children from the control group . No significant differences between groups were found on autistic symptom severity and emotional and behavioral problems",
"Children with autism exhibit deficits in their quantity and quality of joint attention . Early autism intervention studies rarely document improvement in joint attention quality . The purpose of this study was to determine whether there was a change in joint attention quality for preschoolers with autism who were r and omized to a joint attention intervention , symbolic play intervention , or a control group . Quality was defined as shared positive affect during joint attention as well as shared positive affect and utterances during joint attention . Interactions of group and time were found for both types of joint attention quality . During the follow up visits , the joint attention and symbolic play intervention groups produced more of these two types of joint attention quality than the control group",
"BACKGROUND This prospect i ve study compared outcome for pre-school children with autism spectrum disorders ( ASD ) receiving autism-specific nursery provision or home-based Early Intensive Behavioural Interventions ( EIBI ) in a community setting . METHODS Forty-four 23- to 53-month-old children with ASD participated ( 28 in EIBI home-based programmes ; 16 in autism-specific nurseries ) . Cognitive , language , play , adaptive behaviour skills and severity of autism were assessed at intake and 2 years later . RESULTS Both groups showed improvements in age equivalent scores but st and ard scores changed little over time . At follow-up , there were no significant group differences in cognitive ability , language , play or severity of autism . The only difference approaching significance ( p = .06 ) , in favour of the EIBI group , was for Vinel and Daily Living Skills st and ard scores . However , there were large individual differences in progress , with intake IQ and language level best predicting overall progress . CONCLUSIONS Home-based EIBI , as implemented in the community , and autism-specific nursery provision produced comparable outcomes after two years of intervention",
"OBJECTIVE This study was carried out to examine the efficacy of a 12-week , low-intensity ( 1-hour/wk of therapist contact ) , parent-delivered intervention for toddlers at risk for autism spectrum disorders ( ASD ) aged 14 to 24 months and their families . METHOD A r and omized controlled trial involving 98 children and families was carried out in three different sites investigating the efficacy of a parent delivery of the Early Start Denver model ( P-ESDM ) , which fosters parental use of a child-centered responsive interaction style that embeds many teaching opportunities into play , compared to community treatment as usual . Assessment s were completed at baseline and 12 weeks later , immediately after the end of parent coaching sessions . RESULTS There was no effect of group assignment on parent-child interaction characteristics or on any child outcomes . Both groups of parents improved interaction skills , and both groups of children demonstrated progress . Parents receiving P-ESDM demonstrated significantly stronger working alliances with their therapists than did the community group . Children in the community group received significantly more intervention hours than those in the P-ESDM group . For the group as a whole , both younger child age at the start of intervention and a greater number of intervention hours were positively related to the degree of improvement in children 's behavior for most variables . CONCLUSIONS Parent-implemented intervention studies for early ASD thus far have not demonstrated the large effects seen in intensive-treatment studies . Evidence that both younger age and more intervention hours positively affect developmental rates has implication s for clinical practice , service delivery , and public policy",
"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",
"Objectives For the measurement of patient-reported outcomes , such as ( health-related ) quality of life , often many measurement instruments exist that intend to measure the same construct . To facilitate instrument selection , our aim was to develop a highly sensitive search filter for finding studies on measurement properties of measurement instruments in PubMed and a more precise search filter that needs less abstract s to be screened , but at a higher risk of missing relevant studies . Methods A r and om sample of 10,000 PubMed records ( 01 - 01 - 1990 to 31 - 12 - 2006 ) was used as a gold st and ard . Studies on measurement properties were identified using an exclusion filter and h and search ing . Search terms were selected from the relevant records in the gold st and ard as well as from 100 systematic review s of measurement properties and combined based on sensitivity and precision . The performance of the filters was tested in the gold st and ard as well as in two validation sets , by calculating sensitivity , precision , specificity , and number needed to read . Results We identified 116 studies on measurement properties in the gold st and ard . The sensitive search filter was able to retrieve 113 of these 116 studies ( sensitivity 97.4 % , precision 4.4 % ) . The precise search filter had a sensitivity of 93.1 % and a precision of 9.4 % . Both filters performed very well in the validation sets . Conclusion The use of these search filters will contribute to evidence -based selection of measurement instruments in all medical fields",
"ABSTRACT . It is well recognized that delayed \" first words \" is among the most common presenting symptoms of autistic spectrum disorders ( ASD ) . However , data on earlier language and communication development in children with ASD are limited to retrospective reports from parents and from home videos . In this study , we prospect ively collected parent report data on early communication and language development in 97 infant siblings of children with ASD and 49 low-risk controls . Parents completed the MacArthur Communicative Development Inventory-Infant Form at 12 and 18 months . Analysis compared 3 groups defined on the basis of diagnostic assessment at 24 months : ( 1 ) siblings with ASD ( n = 15 ) , ( 2 ) siblings not meeting diagnostic criteria for ASD ( n = 82 ) , and ( 3 ) low-risk controls , none of whom had ASD ( n = 49 ) . Children with ASD showed delays in early language and communication compared with non-ASD siblings and controls . At 12 months , the ASD group was reported to underst and significantly fewer phrases and to produce fewer gestures . At 18 months , they showed delays in their underst and ing of phrases , comprehension and production of single words , and use of gestures . Siblings not diagnosed with ASD also used fewer play-related gestures at 18 months than low-risk controls , even when children with identified language delays were excluded . Overall , this prospect i ve study confirms that delays in communication and language development are apparent early in life in children with ASD , and emphasizes that developmental surveillance should include monitoring for delays in gesture , which may be among the earliest signs of ASD",
"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",
"Autism is commonly associated with sensory and self-regulatory disturbances . This article presents a r and omized controlled study evaluating the effect of a 5-month intervention directed toward improving sensory impairment , digestion , and sleep in 46 children with autism The intervention , Qigong Sensory Training ( QST ) , is a qigong massage intervention based in Chinese medicine . It is two-pronged : Trainers work with children directly 20 times over 5 months , and parents give the massage daily to their children . Improvement was evaluated in two setting s -- preschool and home -- by teachers ( blind to group ) and parents . Teacher evaluations showed that treated children had significant classroom improvement of social and language skills and reduction in autistic behavior compared with wait-list control participants . These findings were confirmed by parent data , indicating that the gains had generalized across context s. A model and supporting data for underst and ing and treating sensory and self-regulation problems in autism is presented",
"This r and omized group experiment compared the efficacy of 2 communication interventions ( Responsive Education and Prelinguistic Milieu Teaching [ RPMT ] and the Picture Exchange Communication System [ PECS ] ) in 36 preschoolers with autism spectrum disorders . Each treatment was delivered 3 times per week , in 20-min sessions , for 6 months . The results revealed that the RPMT facilitated the frequency of generalized turn taking and generalized initiating joint attention more than did the PECS . The latter effect occurred only for children who began treatment with at least some initiating joint attention . In contrast , the PECS facilitated generalized requests more than the RPMT in children with very little initiating joint attention prior to treatment . These effect sizes were large",
" An intervention group ( n=23 ) of preschool children with autism was identified on the basis of parent preference for early intensive behavioral intervention and a comparison group ( n=21 ) identified as receiving treatment as usual . Prospect i ve assessment was undertaken before treatment , after 1 year of treatment , and again after 2 years . Groups did not differ on assessment s at baseline but after 2 years , robust differences favoring intensive behavioral intervention were observed on measures of intelligence , language , daily living skills , positive social behavior , and a statistical measure of best outcome for individual children . Measures of parental well-being , obtained at the same three time points , produced no evidence that behavioral intervention created increased problems for either mothers or fathers of children receiving it",
"Goal attainment scaling ( GAS ) holds promise as an idiographic approach for measuring outcomes of psychosocial interventions in community setting s. GAS has been criticized for untested assumptions of scaling level ( i.e. , interval or ordinal ) , inter-individual equivalence and comparability , and reliability of coding across different behavioral observation methods . We tested assumptions of e quality between GAS descriptions for outcome measurement in a r and omized trial ( i.e. , measurability , equidistance , level of difficulty , comparability of behavior sample s collected from teachers vs. research ers and live vs. videotape ) . Results suggest GAS descriptions can be evaluated for equivalency , that teacher collected behavior sample s are representative , and that varied sources of behavior sample s can be reliably coded . GAS is a promising measurement approach . Recommendations are provided to ensure method ological quality",
"CONTEXT Autism represents an unusual pattern of development beginning in the infant and toddler years . OBJECTIVES To examine the stability of autism spectrum diagnoses made at ages 2 through 9 years and identify features that predicted later diagnosis . DESIGN Prospect i ve study of diagnostic classifications from st and ardized instruments including a parent interview ( Autism Diagnostic Interview-Revised [ ADI-R ] ) , an observational scale ( Pre-Linguistic Autism Diagnostic Observation Schedule/Autism Diagnostic Observation Schedule [ ADOS ] ) , and independent clinical diagnoses made at ages 2 and 9 years compared with a clinical research team 's criterion st and ard diagnoses . SETTING Three inception cohorts : consecutive referrals for autism assessment to ( 1 ) state-funded community autism centers , ( 2 ) a private university autism clinic , and ( 3 ) case controls with developmental delay from community clinics . PARTICIPANTS At 2 years of age , 192 autism referrals and 22 developmentally delayed case controls ; 172 children seen at 9 years of age . MAIN OUTCOME MEASURES Consensus best-estimate diagnoses at 9 years of age . RESULTS Percentage agreement between best-estimate diagnoses at 2 and 9 years of age was 67 , with a weighted kappa of 0.72 . Diagnostic change was primarily accounted for by movement from pervasive developmental disorder not otherwise specified to autism . Each measure at age 2 years was strongly prognostic for autism at age 9 years , with odds ratios of 6.6 for parent interview , 6.8 for observation , and 12.8 for clinical judgment . Once verbal IQ ( P = .001 ) was taken into account at age 2 years , the ADI-R repetitive domain ( P = .02 ) and the ADOS social ( P = .05 ) and repetitive domains ( P = .005 ) significantly predicted autism at age 9 years . CONCLUSIONS Diagnostic stability at age 9 years was very high for autism at age 2 years and less strong for pervasive developmental disorder not otherwise specified . Judgment of experienced clinicians , trained on st and ard instruments , consistently added to information available from parent interview and st and ardized observation",
"The Nova Scotia early intensive behavior intervention model -NS EIBI ( Bryson et al. , 2007 ) for children with autistic spectrum disorders was design ed to be feasible and sustainable in community setting s. It combines parent training and naturalistic one-to-one behavior intervention employing Pivotal Response Treatment - PRT ( R. Koegel & Koegel , 2006 ) . We followed 45 children ( 33 males , mean baseline age = 50 months ) for 12months . Mean gains of 14.9 and 19.5 months were observed on expressive and receptive language measures , respectively , for children with an IQ of 50 or more at baseline versus 6.1 and 8.4 months for children with IQs less than 50 . Behavior problems decreased significantly over the 1-year treatment for both groups , but autism symptoms decreased only for those with an IQ of 50 or more",
"This r and omized controlled trial compared results obtained after 12 months of nonintensive parent training plus care-as-usual and care-as-usual alone . The training focused on stimulating joint attention and language skills and was based on the intervention described by Drew et al. ( Eur Child Adolesc Psychiatr 11:266–272 , 2002 ) . Seventy-five toddlers with autism spectrum disorder ( 65 autism , 10 PDD-NOS , mean age = 34.4 months , SD = 6.2 ) were enrolled . Analyses were conducted on a final sample of 67 children ( lost to follow-up = 8) . No significant intervention effects were found for any of the primary ( language ) , secondary ( global clinical improvement ) , or mediating ( child engagement , early precursors of social communication , or parental skills ) outcome variables , suggesting that the ‘ Focus parent training ’ was not of additional value to the more general care-as-usual",
"& NA ; This study reports on the results of a r and omized controlled trial that evaluated a caregiverbased intervention program for children with autism in community day‐care centers . Thirty‐five preschool children with a DSM III‐R diagnosis of autism or pervasive developmental disorder were r and omized to an experimental or control group . Children in the experimental group were enrolled in day care and their parents and child care workers received a 12‐week intervention consisting of lectures and on‐site consultations to day‐care centers . In addition , supportive work was undertaken with families . Control subjects received day care alone . In the experimental group , there were greater gains in language abilities , significant increases in caregivers ' knowledge about autism , greater perception of control on the part of mothers , and greater parent satisfaction . We conclude that this research design demonstrated that the intervention was significantly superior to day care alone",
"Young children with pervasive developmental disorder were r and omly assigned to intensive treatment or parent training . The intensive treatment group ( 7 with autism , 8 with pervasive developmental disorder not otherwise specified -- NOS ) averaged 24.52 hours per week of individual treatment for one year , gradually reducing hours over the next 1 to 2 years . The parent training group ( 7 with autism , 6 with pervasive developmental disorder NOS ) received 3 to 9 months of parent training . The groups appeared similar at intake on all measures ; however , at follow-up the intensive treatment group outperformed the parent training group on measures of intelligence , visual-spatial skills , language , and academics , though not adaptive functioning or behavior problems . Children with pervasive developmental disorder NOS may have gained more than those with autism",
"This study attempted to find clinical variables evaluated at age 2 that would predict mental retardation ( MR , IQ/cognition-adaptation developmental quotient [ C-A DQ] 57 children with pervasive developmental disorder ( PDD ) . About two-thirds of subjects had MR at both initial and outcome evaluations . The C-A DQ at initial evaluation was significantly lower in mentally retarded PDD ( MRPDD ) than in high-functioning ( IQ > or= 70 ) PDD ( HFPDD ) . MRPDD changed less than HFPDD in IQ/C-A DQ between ages 2 and 5 . The C-A DQ at age 2 was a potent predictor for MR at age 5 and the total score and three item scores of Childhood Autism Rating Scale-Tokyo Version evaluated at age 2 were also useful in predicting MR at age 5",
"OBJECTIVE To examine the predictive validity of symptom severity , cognitive and language measures taken at ages 2 and 3 years to outcome at age 7 in a sample of children diagnosed with autism at age 2 . METHOD Twenty-six children diagnosed with autism at age 2 were re-assessed at ages 3 and 7 years . At each age symptom severity , cognitive and language assessment s were completed . RESULTS The pattern of autistic symptom severity varied over time by domain . Across time , children moved across diagnostic boundaries both in terms of clinical diagnosis and in terms of instrument diagnosis on the Autism Diagnostic Interview-Revised ( ADI-R ) . On all measures group variability in scores increased with age . Although non-verbal IQ ( NVIQ ) for the group as a whole was stable across the 3 assessment s , this masked considerable individual instability . St and ard assessment s at age 2 did not predict outcome at age 7 even within the same domain of functioning . In contrast , st and ard assessment s at age 3 did predict outcome . However , a measure of rate of non-verbal communicative acts taken from an interactive play-based assessment at age 2 was significantly associated with language , communication and social outcomes at age 7 . CONCLUSIONS The trajectory of autism symptoms over time differed in different domains , suggesting that they may be , at least in part , separable . Variability in language , NVIQ and symptom severity increased over time . Caution is required when interpreting the findings from assessment s of children with autism at age 2 years . At this age measures of rate of non-verbal communication might be more informative than scores on st and ard psychometric tests . Predictive validity of assessment s at age 3 years was greater",
"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",
"A recent r and omized controlled trial ( RCT ) of a dual parent and trainer-delivered qigong massage intervention for young children with autism result ed in improvement of measures of autism as well as improvement of abnormal sensory responses and self-regulation . The RCT evaluated the effects of the parent-delivered component of the intervention . Forty-seven children were r and omly assigned to treatment and wait-list control groups . Treatment group children received the parent-delivered program for 4 mo . Trained therapists provided parent training and support . Improvement was evaluated in two setting s -- preschool and home -- by teachers ( blind to group ) and parents . Results showed that the parent-delivered program was effective in improving measures of autism ( medium effect size ) and sensory and self-regulatory responses ( large effect size ) . Teacher data on measures of autism were confirmed by parent data . Results indicate that the parent-delivered component of the program provided effective early intervention for autism that was suitable for delivery at home",
"This project evaluated the effectiveness of a TEACCH-based home program intervention for young children with autism . Parents were taught how to work with their preschool autistic child in the home setting , focusing on cognitive , academic , and prevocational skills essential to later school success . To evaluate the efficacy of the program , two matched groups of children were compared , a treatment group and a no-treatment control group , each consisting of 11 subjects . The treatment group was provided with approximately 4 months of home programming and was tested before and after the intervention with the Psychoeducational Profile-Revised ( PEP-R ) . The control group did not receive the treatment but was tested at the same 4-month interval . The groups were matched on age , pretest PEP-R scores , severity of autism , and time to follow-up . Results demonstrated that children in the treatment group improved significantly more than those in the control group on the PEP-R subtests of imitation , fine motor , gross motor , and nonverbal conceptual skills , as well as in overall PEP-R scores . Progress in the treatment group was three to four times greater than that in the control group on all outcome tests . This suggests that the home program intervention was effective in enhancing development in young children with autism",
"The objective of this preliminary study was to evaluate a novel intensive therapy program in young children with pervasive developmental disorder ( PDD ) . Twenty-three children treated at the Mifne Institute in Israel between 1997 and 1999 were assessed . Videos taken before coming to Mifne and after intensive treatment at the institute and before and after another 6 months of continued treatment at children 's homes were coded and blind rated by trained personnel using the Childhood Autism Rating Scale ( CARS ) and the Social Behavior Rating Scale ( SBRS ) . Total scores on both scales improved significantly after 3 weeks and after 6 months . There were some significant improvements at item level although the magnitude of the changes was modest . Despite the small number of participants , the modest increase in test scores , and the retrospective study design , these preliminary results are promising . There is a case for performing a full prospect i ve , comparative investigation of this treatment approach",
"This study evaluated the impact of intensive behavioral treatment on the development of young autistic children . The treatment reported in this study was home based and was implemented by parents of autistic children with the assistance of community-based clinicians . Although treatment was unable to be observed directly , parents reported that therapy was based on methods developed by Lovaas et al. ( 1981 ) . Treatment differed from that described in previous reports of intensive behavior therapy for this population in that it was implemented outside an academic setting and for a shorter period . In addition , children received fewer hours per week of therapy than in previous reports . Children in the experimental treatment group were pairwise matched to children in a control group ( who received conventional school-based and brief one-on-one interventions ) on the basis of pretreatment chronological and mental age , diagnosis ( autism vs. PDD ) , and length of treatment . The groups did not differ on pretreatment IQ . Children receiving the experimental treatment had significantly higher posttreatment IQ scores . Smaller , but still statistically significant effects on symptom severity were also found , though experimental subjects still met diagnostic criteria for autism or PDD",
"BACKGROUND The Picture Exchange Communication System ( PECS ) is a common treatment choice for non-verbal children with autism . However , little empirical evidence is available on the usefulness of PECS in treating social-communication impairments in autism . AIMS To test the effects of PECS on social-communicative skills in children with autism , concurrently taking into account st and ardized psychometric data , st and ardized functional assessment of adaptive behaviour , and information on social-communicative variables coded in an unstructured setting . METHODS & PROCEDURES Eighteen preschool children ( mean age = 38.78 months ) were assigned to two intervention approaches , i.e. PECS and Conventional Language Therapy ( CLT ) . Both PECS ( Phases I-IV ) and CLT were delivered three times per week , in 30-min sessions , for 6 months . Outcome measures were the following : Autism Diagnostic Observation Schedule ( ADOS ) domain scores for Communication and Reciprocal Social Interaction ; Language and Personal-Social subscales of the Griffiths ' Mental Developmental Scales ( GMDS ) ; Communication and Social Abilities domains of the Vinel and Adaptive Behavior Scales ( VABS ) ; and several social-communicative variables coded in an unstructured setting . OUTCOMES & RESULTS Results demonstrated that the two groups did not differ at Time 1 ( pre-treatment assessment ) , whereas at Time 2 ( post-test ) the PECS group showed a significant improvement with respect to the CLT group on the VABS social domain score and on almost all the social-communicative abilities coded in the unstructured setting ( i.e. joint attention , request , initiation , cooperative play , but not eye contact ) . CONCLUSIONS & IMPLICATION S These findings showed that PECS intervention ( Phases I-IV ) can improve social-communicative skills in children with autism . This improvement is especially evident in st and ardized measures of adaptive behaviour and measures derived from the observation of children in an unstructured setting",
"This article evaluates the effectiveness of a developmentally based early intervention programme . Two groups of children were compared , a treatment group and a no-treatment control group . St and ardized assessment s were administered before and after the intervention period by an independent clinician . Pre-treatment comparisons revealed that the control group had a significantly higher pre-treatment IQ ; but the two groups were comparable for age , mental age , socioeconomic status and number of hours of non-experimental therapy . Results demonstrated that children in the treatment group improved significantly more than those in the control group on measures of joint attention , social interaction , imitation , daily living skills , motor skills and an adaptive behaviour composite . A measure of requesting behaviour fell short of statistical significance . The total stress index reduced for treatment group parents and increased for the control group parents ( but not significantly ) . The results of the study are considered to support the efficacy of this treatment approach",
"CONTEXT To our knowledge , no prospect i ve studies of the developmental course of early and later diagnosis of autism spectrum disorders from 14 months of age exist . OBJECTIVE To examine patterns of development from 14 to 24 months in children with early and later diagnosis of autism spectrum disorders . DESIGN Prospect i ve , longitudinal design in which 125 infants at high and low risk for autism were tested from age 14 to 36 months . Comprehensive st and ardized assessment s included measures of social , communication , and play behavior . SETTING Testing occurred at a major medical and research institution as part of a large , ongoing longitudinal study . PARTICIPANTS Low-risk controls ( n = 18 ) and siblings of children with autism , grouped on the basis of outcome diagnostic classification at 30 or 36 months : autism spectrum disorders ( early diagnosis , n = 16 ; later diagnosis , n = 14 ) , broader autism phenotype ( n = 19 ) , and non-broader autism phenotype ( n = 58 ) . MAIN OUTCOME MEASURES Social , communication , and symbolic abilities were assessed . RESULTS Social , communication , and play behavior in the early-diagnosis group differed from that in all other groups by 14 months of age . By 24 months , the later-diagnosis group differed from the non-autism spectrum disorder groups in social and communication behavior , but not from the early-diagnosis group . Examination of growth trajectories suggests that autism may involve developmental arrest , slowing , or even regression . CONCLUSION This study provides insight into different patterns of development of children with early vs later diagnosis of autism spectrum disorders",
"This prospect i ve , longitudinal , study charted the developmental profiles of young children with Autism Spectrum Disorders ( ASD ) identified through routine developmental surveillance . 109 children with Autistic Disorder ( AD ) , ‘ broader ’ ASD , and developmental and /or language delays ( DD/LD ) were assessed using the Mullen Scales of Early Learning ( MSEL ) at 12-months ( n = 10 assessment s ) , 18-months ( n = 45 assessment s ) , and 24-months ( n = 99 assessment s ) . The children with AD performed most poorly , overall , than the ASD and DD/LD groups on the MSEL . Furthermore , the children with AD/ASD displayed an uneven cognitive profile , with poorer performance on verbal ( particularly receptive language ) relative to nonverbal skills . There was also evidence of developmental slowing in verbal skills from 18- to 24-months for children on the spectrum , especially those with AD . Given that the poor receptive , relative to expressive , language profile emerges very early in life for children with AD/ASD , this cognitive profile may serve as an additional red flag to social attention and communication deficits . Receptive language should therefore be stringently monitored in any developmental surveillance program for autism spectrum disorders in the second year of life",
"BACKGROUND Psychosocial treatments are the mainstay of management of autism in the UK but there is a notable lack of a systematic evidence base for their effectiveness . R and omised controlled trial ( RCT ) studies in this area have been rare but are essential because of the developmental heterogeneity of the disorder . We aim ed to test a new theoretically based social communication intervention targeting parental communication in a r and omised design against routine care alone . METHODS The intervention was given in addition to existing care and involved regular monthly therapist contact for 6 months with a further 6 months of 2-monthly consolidation sessions . It aim ed to educate parents and train them in adapted communication tailored to their child 's individual competencies . Twenty-eight children with autism were r and omised between this treatment and routine care alone , stratified for age and baseline severity . Outcome was measured at 12 months from commencement of intervention , using st and ardised instruments . RESULTS All cases studied met full Autism Diagnostic Interview ( ADI ) criteria for classical autism . Treatment and controls had similar routine care during the study period and there were no study dropouts after treatment had started . The active treatment group showed significant improvement compared with controls on the primary outcome measure -- Autism Diagnostic Observation Schedule ( ADOS ) total score , particularly in reciprocal social interaction-- and on secondary measures of expressive language , communicative initiation and parent-child interaction . Suggestive but non-significant results were found in Vinel and Adaptive Behaviour Scales ( Communication Sub-domain ) and ADOS stereotyped and restricted behaviour domain . CONCLUSIONS A R and omised Treatment Trial design of this kind in classical autism is feasible and acceptable to patients . This pilot study suggests significant additional treatment benefits following a targeted ( but relatively non-intensive ) dyadic social communication treatment , when compared with routine care . The study needs replication on larger and independent sample s. It should encourage further RCT design s in this area",
"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",
"The development of imitation during the second year of life plays an important role in domains of sociocognitive development such as language and social learning . Deficits in imitation ability in persons with autism spectrum disorder ( ASD ) from toddlerhood into adulthood have also been repeatedly documented , raising the possibility that early disruptions in imitation contribute to the onset of ASD and the deficits in language and social interaction that define the disorder . This study prospect ively examined the development of imitation between 12 and 24 months of age in 154 infants at familial risk for ASD and 78 typically developing infants who were all later assessed at 36 months for ASD or other developmental delays . The study established a developmental measure of imitation ability and examined group differences over time , using an analytic Rasch measurement model . Results revealed a unidimensional latent construct of imitation and verified a reliable sequence of imitation skills that was invariant over time for all outcome groups . Results also showed that all groups displayed similar significant linear increases in imitation ability between 12 and 24 months and that these increases were related to individual growth in both expressive language and ratings of social engagement but not in fine motor development . The group of children who developed ASD by age 3 years exhibited delayed imitation development compared with the low-risk typical outcome group across all time-points , but were indistinguishable from other high-risk infants who showed other cognitive delays not related to ASD",
" Guidance on effective interventions for disruptive behavior in young children with autism spectrum disorders ( ASDs ) is limited . We present feasibility and initial efficacy data on a structured parent training program for 16 children ( ages 3–6 ) with ASD and disruptive behavior . The 6-month intervention included 11 Core and up to 2 Optional sessions . The program was acceptable to parents as evidence d by an attendance rate of 84 % for Core sessions . Fourteen of 16 families completed the treatment . An independent clinician rated 14 of 16 subjects as much improved or very much improved at Week 24 . Using last observation carried forward , the parent-rated Aberrant Behavior Checklist-Irritability subscale decreased 54 % from 16.00 ( SD = 9.21 ) to 7.38 ( SD = 6.15 )",
"Sensory impairment is a common and significant feature of children on the autism spectrum . In 2005 , a qigong massage intervention based on Chinese medicine and delivered by a doctor of Chinese medicine was shown to improve sensory impairment and adaptive behavior in a small controlled study of young children with autism . In 2006 , the Qigong Sensory Training ( QST ) program was developed to train early intervention professionals to provide the QST intervention . This article describes the preliminary evaluation of the QST program as piloted with 15 professionals and 26 children and outcomes testing using st and ardized tests of sensory impairment and adaptive behavior . Results of outcomes comparing delivery by QST-trained therapists with delivery by a doctor of Chinese medicine showed that both groups improved and that there was no difference in outcome between the two groups . The intervention and training program are described , and implication s for future research are discussed",
"In this pilot study , we tested the effects of a novel intervention ( JASPER , Joint Attention Symbolic Play Engagement and Regulation ) on 3 to 5 year old , minimally verbal children with autism who were attending a non-public preschool . Participants were r and omized to a control group ( treatment as usual , 30 h of ABA-based therapy per week ) or a treatment group ( substitution of 30 min of JASPER treatment , twice weekly during their regular program ) . A baseline of 12 weeks in which no changes were noted in core deficits was followed by 12 weeks of intervention for children r and omized to the JASPER treatment . Participants in the treatment group demonstrated greater play diversity on a st and ardized assessment . Effects also generalized to the classroom , where participants in the treatment group initiated more gestures and spent less time unengaged . These results provide further support that even brief , targeted interventions on joint attention and play can improve core deficits in minimally verbal children with ASD",
"Acupuncture increases brain levels of arginine-vasopressin ( AVP ) and oxytocin ( OXT ) , which are known to be involved in the modulation of mammalian social behavior . Transcutaneous electrical acupoint stimulation ( TEAS ) is often used clinical ly to produce a similar stimulation to that of acupuncture on the acupoints . In the present study , TEAS was applied to children with autism to assess its therapeutic efficacy . Seventy-six autistic children receiving rehabilitation training were divided into 2 groups : a treatment group receiving TEAS 30min per day , 5 days per week for 12 weeks ( n=37 ) and a control group without TEAS treatment ( n=39 ) . A series of rating scales was used in outcome assessment . Plasma levels of AVP and OXT were determined by enzyme immunoassay ( EIA ) before and after treatment . The TEAS group showed a significant improvement over the control in their emotional response , fear or anxiety , level/consistency of intellective relations and general impressions on the Childhood Autism Rating Scale ( CARS ) as well as improvements in the sensory and related factors in the Autism Behavior Checklist ( ABC ) . In addition , the varieties of accepted food increased after TEAS treatment . It appears that TEAS was effective in autistic children who showed passive and aloof behavior , but not in those who were active but odd . The plasma level of AVP was significantly higher in the TEAS group than in the control group after the intervention . In addition , the change in the plasma AVP level paralleled the improvement of some of the behavior factors in CARS , including adaptation to environmental change , listening response , perceptive response and fear or anxiety . It is concluded that TEAS is effective for the treatment of autistic children with a passive and aloof social interaction style . Changes in plasma levels of AVP and possibly OXT may be involved in mediating the therapeutic effect of TEAS",
"OBJECTIVE To examine prospect ively the emergence of behavioral signs of autism in the first years of life in infants at low and high risk for autism . METHOD A prospect i ve longitudinal design was used to compare 25 infants later diagnosed with an autism spectrum disorder ( ASD ) with 25 gender-matched low-risk children later determined to have typical development . Participants were evaluated at 6 , 12 , 18 , 24 , and 36 months of age . Frequencies of gaze to faces , social smiles , and directed vocalizations were coded from video and rated by examiners . RESULTS The frequency of gaze to faces , shared smiles , and vocalizations to others were highly comparable between groups at 6 months of age , but significantly declining trajectories over time were apparent in the group later diagnosed with ASD . Group differences were significant by 12 months of age on most variables . Although repeated evaluation documented loss of skills in most infants with ASD , most parents did not report a regression in their child 's development . CONCLUSIONS These results suggest that behavioral signs of autism are not present at birth , as once suggested by Kanner , but emerge over time through a process of diminishment of key social communication behaviors . More children may present with a regressive course than previously thought , but parent report methods do not capture this phenomenon well . Implication s for onset classification systems and clinical screening are also discussed",
"CONTEXT The presence of autistic-like traits in relatives of individuals with autism spectrum disorder ( ASD ) is well recognized , but , to our knowledge , the emergence of these traits early in development has not been studied . OBJECTIVE To prospect ively investigate the emergence of autistic-like traits in unaffected ( no ASD diagnosis ) infant siblings of prob and s diagnosed as having ASD . DESIGN Two groups of children unaffected with ASD were assessed prospect ively-siblings of prob and s diagnosed as having ASD ( high risk [ HR ] ) and control subjects with no family history of ASD ( low risk [ LR ] ) . Scores on a measure of autistic-like traits at 12 months of age were used in a cluster analysis of the entire sample . SETTING A prospect i ve study of infant siblings of prob and s with ASD from 3 diagnostic centers in Canada . PARTICIPANTS The study included 170 HR and 90 LR children , none of whom was diagnosed as having ASD at age 3 years . MAIN OUTCOME MEASURES The Autism Observation Scale for Infants was used to measure autistic-like traits and derive clusters at 12 months of age . Clusters were compared on ASD symptoms , cognitive abilities , and social-emotional difficulties at age 3 years . RESULTS Two clusters were identified . Cluster 1 ( n = 37 ; 14.2 % of total sample ) had significantly higher levels of autistic-like traits compared with cluster 2 . Within cluster 1 , 33 children came from the siblings ( 19.4 % of HR group ) and only 4 came from the control subjects ( 4.5 % of LR group ) . At age 3 years , children from cluster 1 had more social-communication impairment ( effect size > 0.70 ; P lower cognitive abilities ( effect size = -0.59 ; P internalizing problems ( effect size = 0.55 ; P = .01 ) . Compared with control subjects , HR siblings had a relative risk of 4.3 ( 95 % CI,1.6 - 11.9 ) for membership in cluster 1 . CONCLUSIONS Study findings suggest the emergence of autistic-like traits resembling a broader autism phenotype by 12 months of age in approximately 19 % of HR siblings who did not meet ASD diagnostic criteria at age 3 years ",
"Longitudinal research has demonstrated that responsive parental behaviors reliably predict subsequent language gains in children with autism spectrum disorder . To investigate the underlying causal mechanisms , we conducted a r and omized clinical trial of an experimental intervention ( Focused Playtime Intervention , FPI ) that aims to enhance responsive parental communication ( N = 70 ) . Results showed a significant treatment effect of FPI on responsive parental behaviors . Findings also revealed a conditional effect of FPI on children ’s expressive language outcomes at 12-month follow up , suggesting that children with baseline language skills below 12 months ( n = 24 ) are most likely to benefit from FPI . Parents of children with more advanced language skills may require intervention strategies that go beyond FPI ’s focus on responsive communication",
"The Vinel and Adaptive Behavior Scales were used to investigate patterns of adaptive behavior in children with autism who were under 36 months of age . Subjects were 30 children with autism and 30 children with developmental delay matched on CA and MA . Relative to controls , the autistic group demonstrated weaker socialization and communication skills and greater discrepancies between adaptive behavior and MA . Different patterns of relations between adaptive behavior domains and cognitive and language skills were obtained for the two groups . Preliminary support for the utility of adaptive behavior profiles in identifying subgroups of children with autism is provided . Results are discussed in terms of their implication s for early diagnosis of autism",
"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",
"INTRODUCTION There is debate about the type and intensity of early childhood intervention that is most helpful for children with developmental problems . The aim of the study was to determine whether a home-based programme provided over 12 months result ed in sustained improvement in development and behaviour 12 months after the intervention ceased . The characteristics of the children and families who benefited most from the intervention were also studied . METHOD R and omized controlled trial . Participants A total of 59 children , aged 3 - 5 years , attending two early childhood intervention centres in Melbourne , Australia . Intervention Half of the subjects received an additional home-based programme consisting of 40 weekly visits . MAIN OUTCOME MEASURES Bayley Scales of Infant Development and Wechsler Preschool and Primary Scale of Intelligence Revised , Preschool Behaviour Checklist , Bayley Behaviour Rating Scale and Behaviour Screening Question naire . All tests administered pre-intervention , following the intervention and 12 months later . Secondary outcome measures Family stress , support and empowerment . RESULTS Fifty-four children completed the assessment s 12 months after conclusion of the intervention . Compared with the control group , improvement in aspects of cognitive development in the children who received the extra intervention was sustained 1 year later ( P= 0.007 ) while significant behavioural differences post intervention were not . Analyses of the data by the Reliable Change Index indicated improvement of clinical significance occurred in non-verbal areas . In contrast to the control group who deteriorated , language skills in the intervention group remained stable . Improvements were significantly associated with higher stress in the families . CONCLUSION Improvements following the provision of a home-based programme to preschool children with developmental disabilities were sustained 1 year later . Children from highly stressed families appeared to benefit most , reinforcing the importance of involving families in early childhood intervention programmes",
"This study examined the measurement tools and target symptoms/skills used to assess treatment response during Autism Spectrum Disorder ( ASD ) intervention trials from 2001 through 2010 . Data from 195 prospect i ve trials were analyzed . There were 289 unique measurement tools , of which 61.6 % were used only once , and 20.8 % were investigator- design ed . Only three tools were used in more than 2 % of the studies , and none were used in more than 7 % of studies . Studies investigated an average of 11.4 tool-symptom combinations per trial , with as many as 45 in one study . These results represent a lack of consistency in outcome measurements in ASD intervention trials . These findings highlight the need to set guidelines for appropriate outcome measurement in the ASD field",
"Although early intensive behavior interventions have been efficient in producing positive behavior outcome in young children with Autism Spectrum Disorder , there is a considerable variety in the children 's progress . Research has suggested that parental and treatment factors are likely to affect children 's response to treatment . The purpose of the current study was to examine the interrelating factors that impact children 's progress , highlighting the influence of parent inclusion in treatment provision captured by parental stress , how faithfully the parents followed the treatment protocol s and the intensity of treatment provided at home . Twenty-four children received cross- setting staff- and parent-mediated EIBI , including continuous parent training and supervision . A comparison group of 20 children received eclectic intervention . St and ardized tests were carried out by independent examiners at intake and after six months . The intervention group outperformed the eclectic group in measures of autism severity , developmental and language skills . Parent training and constant parent-mediated treatment provision led to reduced challenging behaviors from the children , increased treatment fidelity and child direct behavior change as measured by performance in correct responding on behavior targets . Variables of treatment progress and potential predictors of child outcome were analyzed in detail and mapped with regard to their relationships drawn from multiple regression analysis . Particularly , the study highlights an association between parental stress and staff treatment fidelity that interferes with decision making in treatment planning and consequently with positive behavior outcome . Such results provide important scientific and clinical information on parental and treatment factors likely to affect a child 's response to treatment",
"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",
"UNLABELLED The relations between cognition and autism severity , head size and intervention outcome , were examined . Change in cognitive level with intervention was measured in children with autism and compared to children with developmental disabilities ( DD ) . Eighty-one children ( mean age 25.9 months ) with autism ( n=44 ) and DD ( n=37 ) were assessed at pre- and post 1 year of intervention . Cognitive abilities and autism severity were measured by st and ardized tests . Three pre-intervention cognitive level groups : normal ( IQ>90 ) , borderline ( 70 impaired ( 50 autism symptoms than the borderline and the normal cognitive groups . However , following intervention the groups did not differ in the change in core autism symptoms . IQ scores increased significantly more in the autism group than in the DD group . IQ improvements correlated significantly with reduction in autism symptoms and mostly in stereotyped behaviors . CONCLUSIONS Cognitive ability in autism is associated with autism severity . Two distinct subtypes based on cognitive level are identified . However , baseline cognitive level can not predict the progress rate in autism symptoms with intervention . Improvement of social-communicative behaviors and the intensive intervention are related to significant cognitive increments in autism",
"PURPOSE The Preschool Language Scale , Fourth Edition ( PLS-4 ; Zimmerman , Steiner , & Pond , 2002 ) was used to examine syntactic and semantic language skills in preschool children with autism spectrum disorders ( ASD ) to determine its suitability for use with this population . We expected that PLS-4 performance would be better in more intellectually able children and that receptive skills would be relatively more impaired than expressive abilities , consistent with previous findings in the area of vocabulary . METHOD Our sample consisted of 294 newly diagnosed preschool children with ASD . Children were assessed via a battery of developmental measures , including the PLS-4 . RESULTS As expected , PLS-4 scores were higher in more intellectually able children with ASD , and overall , expressive communication was higher than auditory comprehension . However , this overall advantage was not stable across nonverbal developmental levels . Expressive skills were significantly better than receptive skills at the youngest developmental levels , whereas the converse applied in children with more advanced development . CONCLUSIONS The PLS-4 can be used to obtain a general index of early syntax and semantic skill in young children with ASD . Longitudinal data will be necessary to determine how the developmental relationship between receptive and expressive language skills unfolds in children with ASD",
"We developed and evaluated a new parent report instrument — Parent Observation of Early Markers Scale (POEMS)—to monitor the behavioral development of infants at risk for autism spectrum disorder ( ASD ) because they have older affected siblings . Parents of 108 at-risk infants ( 74 males , 34 females ) completed the POEMS from child age 1–24 months . The POEMS had acceptable psychometric properties and promising predictive validity . Most concerning items were social and communication deficits , and intolerance to waiting . Results provide preliminary evidence that prospect i ve parent report measures can help to detect early ASD symptoms in infants at biological risk . We invite research ers to join us in multi-center studies of the POEMS",
"Earlier intervention improves outcomes for children with autism spectrum disorders ( ASDs ) , but existing identification tools are at the limits of st and ardization with 18-month-olds . We assessed potential behavioural markers of ASD at 18 months in a high-risk cohort of infant siblings of children with ASD . Prospect i ve data were collected using the Autism Diagnostic Observation Schedule ( ADOS ) and Autism Observation Scale for Infants ( AOSI ) on 155 infant siblings and 73 low-risk controls at 18 months . Infants were classified into three groups ( ASD sibs , non-ASD sibs , controls ) based on blind best-estimate diagnosis at age 3 . Fisher 's exact tests , followed by discriminant function analyses , revealed that the majority of informative ADOS items came from the social and behavioural domains , and AOSI items measuring behavioural reactivity and motor control contributed additional information . Findings highlight the importance of considering not only social-communication deficits , but also basic dimensions of temperament including state regulation and motor control when assessing toddlers with suspected ASD",
"The aim of this study was to pilot test a classroom-based intervention focused on facilitating play and joint attention for young children with autism in self-contained special education classrooms . Thirty-three children with autism between the ages of 3 and 6 years participated in the study with their classroom teachers ( n = 14 ) . The 14 preschool special education teachers were r and omly assigned to one of three groups : ( 1 ) symbolic play then joint attention intervention , ( 2 ) joint attention then symbolic intervention , and ( 3 ) wait-list control period then further r and omized to either group 1 or group 2 . In the intervention , teachers participated in eight weekly individualized 1-h sessions with a research er that emphasized embedding strategies targeting symbolic play and joint attention into their everyday classroom routines and activities . The main child outcome variables of interest were collected through direct classroom observations . Findings indicate that teachers can implement an intervention to significantly improve joint engagement of young children with autism in their classrooms . Furthermore , multilevel analyses showed significant increases in joint attention and symbolic play skills . Thus , these pilot data emphasize the need for further research and implementation of classroom-based interventions targeting play and joint attention skills for young children with autism"
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411878e0-06ff-11f0-808a-c43d1ab1c353
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Background Physical activity ( PA ) is essential for children throughout their growth and maturation . It improves physiological and psychological health and limits the risk of developing metabolic disorders . However , some chronic physiological and metabolic diseases may lead to decreased PA . The diversity of outcomes in the literature offers no consensus for physical activity and sedentary levels in children with juvenile idiopathic arthritis ( JIA ) or inflammatory bowel disease ( IBD ) . Methods A literature review and a meta- analysis were carried out with original studies from a Medline data base search . Only high- quality studies ( STROBE checklist ) written in English comparing PA level or sedentary behavior ( SB ) between children with the disorders and their healthy peers were considered . The aim was to examine PA and SB in children with JIA or IBD compared to their healthy peers . Results The literature review and meta- analysis identified decreased PA and increased time spent in SB in these population s , which may exacerbate both their lower physical fitness and the symptoms of their health disorders . Conclusion Results nevertheless show discrepancies due to the different material s and methods used and the variables measured . Further studies are needed to establish a gold st and ard method for assessing PA level in these population
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"Objectives Pain is a very common symptom of juvenile idiopathic arthritis ( JIA ) . Disease activity alone can not explain symptoms of pain in all children , suggesting other factors may be relevant . The objectives of this study were to describe the different patterns of pain experienced over time in children with JIA and to identify predictors of which children are likely to experience ongoing pain . Methods This study used longitudinal- data from patients ( aged 1–16 years ) with new-onset JIA . Baseline and up to 5-year follow-up pain data from the Childhood Arthritis Prospect i ve Study ( CAPS ) were used . A two-step approach was adopted . First , pain trajectories were modelled using a discrete mixture model . Second , multinomial logistic regression was used to determine the association between variables and trajectories . Results Data from 851 individuals were included ( 4 years , median follow-up ) . A three-group trajectory model was identified : consistently low pain ( n=453 ) , improved pain ( n=254 ) and consistently high pain ( n=144 ) . Children with improved pain or consistently high pain differed on average at baseline from consistently low pain . Older age at onset , poor function/disability and longer disease duration at baseline were associated with consistently high pain compared with consistently low pain . Early increases in pain and poor function/disability were also associated with consistently high pain compared with consistently low pain . Conclusions This study has identified routinely collected clinical factors , which may indicate those individuals with JIA at risk of poor pain outcomes earlier in disease . Identifying those at highest risk of poor pain outcomes at disease onset may enable targeted pain management strategies to be implemented early in disease thus reducing the risk of poor pain outcomes",
"Introduction Prevalence of insulin resistance and the metabolic syndrome has been reported to be high in rheumatoid arthritis ( RA ) patients . Tumor necrosis factor ( TNF ) , a pro-inflammatory cytokine with a major pathogenetic role in RA , may promote insulin resistance by inducing Ser312 phosphorylation ( p-Ser312 ) of insulin receptor substrate (IRS)-1 and downregulating phosphorylated (p-)AKT . We examined whether anti-TNF therapy improves insulin resistance in RA patients and assessed changes in the insulin signaling cascade . Methods Prospect i ve study of RA patients receiving anti-TNF agents ( infliximab , n = 49 , adalimumab , n = 11 , or etanercept , n = 1 ) due to high disease activity score in 28 joints ( DAS28 > 5.1 ) . A complete biochemical profile was obtained at weeks 0 and 12 of treatment . Insulin resistance , insulin sensitivity and pancreatic beta cell function were measured by the Homeostasis Model Assessment ( HOMA-IR ) , the Quantitative Insulin Sensitivity Check Index ( QUICKI ) and the HOMA-B respectively . Protein extracts from peripheral blood mononuclear cells were assayed by western blot for p-Ser312 IRS-1 and p-AKT . RA patients treated with abatacept ( CTLA4.Ig ) were used as a control group for insulin signaling studies . Results At study entry , RA patients with high insulin resistance ( HOMA-IR above median ) had significantly higher mean DAS28 ( P = 0.011 ) , serum triglycerides ( P = 0.015 ) , and systolic blood pressure levels ( P = 0.024 ) than patients with low insulin resistance . After 12 weeks of anti-TNF therapy , patients with high insulin resistance demonstrated significant reduction in HOMA-IR ( P HOMA-B ( P = 0.001 ) , serum triglycerides ( P = 0.039 ) , and increase in QUICKI ( P serum HDL-C ( P = 0.022 ) . Western blot analysis in seven active RA patients with high insulin resistance showed reduction in p-Ser312 IRS-1 ( P = 0.043 ) and increase in p-AKT ( P = 0.001 ) over the study period . In contrast , the effect of CTLA4.Ig on p-Ser312 IRS-1 and p-AKT levels was variable . Conclusions Anti-TNF therapy improved insulin sensitivity and reversed defects in the insulin signaling cascade in RA patients with active disease and high insulin resistance . The impact of these biochemical changes in modifying cardiovascular disease burden in active RA patients remains to be seen",
"Background : Reports from individual referral centres suggest that a significant proportion of children with inflammatory bowel disease ( IBD ) present after prolonged delays and with impaired growth . Aims : To prospect ively document the presenting features , delay in presentation , disease localisation , and growth in newly diagnosed cases of IBD . Methods : For 13 months , between June 1998 and June 1999 , 3247 paediatricians , adult gastroenterologists , and surgeons across the UK and Irel and were prospect ively surveyed each month and asked to report every newly diagnosed case of childhood IBD . Results : A total of 739 new IBD cases aged less than 16 years were identified . Only one quarter of Crohn ’s disease ( CD ) cases presented with the “ classic triad ” of diarrhoea , weight loss , and abdominal pain ; nearly half did not report diarrhoea . The median delay from onset of symptoms to diagnosis was 5 months ( mean 11 months ) , with one fifth having symptoms of more than one year . Delays were most common in CD and in younger children . Short stature was noted only in those with CD and not with ulcerative colitis . One fifth of CD cases had disease activity in the jejunum and this group had significantly reduced stature . Ileo-colonic involvement was documented in most CD cases , with only a small minority having isolated ileal or isolated colonic disease . Pan-colitis was reported in most UC cases , with very few having only an isolated proctitis . Conclusions : Many children are diagnosed after prolonged delays and have growth failure . Improved knowledge of the presenting features of IBD , and earlier investigation of suspected cases , may help reduce the delays noted",
"Objective . Few studies based in well-defined North American population s have examined the occurrence of juvenile idiopathic arthritis ( JIA ) , and none has been based in an ethnically diverse population . We used computerized healthcare information from the Kaiser Permanente Northern California membership to vali date JIA diagnoses and estimate the incidence and prevalence of the disease in this well-characterized population . Methods . We identified children aged ≤ 15 years with ≥ 1 relevant International Classification of Diseases , 9th edition , diagnosis code of 696.0 , 714 , or 720 in computerized clinical encounter data during 1996–2009 . In a r and om sample , we then review ed the medical records to confirm the diagnosis and diagnosis date and to identify the best-performing case-finding algorithms . Finally , we used the case-finding algorithms to estimate the incidence rate and point prevalence of JIA . Results . A diagnosis of JIA was confirmed in 69 % of individuals with at least 1 relevant code . Forty-five percent were newly diagnosed during the study period . The age- and sex-st and ardized incidence rate of JIA per 100,000 person-years was 11.9 ( 95 % CI 10.9–12.9 ) . It was 16.4 ( 95 % CI 14.6–18.1 ) in girls and 7.7 ( 95 % CI 6.5–8.9 ) in boys . The peak incidence rate occurred in children aged 11–15 years . The prevalence of JIA per 100,000 persons was 44.7 ( 95 % CI 39.1–50.2 ) on December 31 , 2009 . Conclusion . The incidence rate of JIA observed in the Kaiser Permanente population , 1996–2009 , was similar to that reported in Rochester , Minnesota , USA , but 2 to 3 times higher than Canadian estimates",
"BACKGROUND AND AIMS Physical activity is important for muscle and bone strength in the growing child and may be impaired in paediatric patients with inflammatory bowel disease ( IBD ) even during quiescent disease . The SenseWearPro(2 ) armb and allows to measure physical activity under everyday life conditions . METHODS Thirty-nine IBD patients ( 27 Crohn 's disease , 12 ulcerative colitis , 24 boys ) in remission ( n=26 ) or with only mild disease activity ( n=13 ) were compared to 39 healthy age and sex-matched controls . Body weight , height , body mass index ( BMI ) , lean body mass as phase angle α ( determined by bioelectrical impedance analysis ) , and dynamometric grip force were expressed as age- and sex-related Z-scores . SenseWearPro(2 ) armb and s were applied for three consecutive days to record number of steps , duration of physical activity and sleeping time . Quality of life was assessed with the German KINDL and IMPACT III question naires , energy intake with prospect i ve food protocol s. Differences between patients and pair-matched controls were analysed by paired t-test . RESULTS Patients showed lower Z-scores for phase angle α ( difference -0.72 ; 95 % CI [ -1.10 ; -0.34 ] ) and lower grip strength ( -1.02 [ -1.58 ; -0.47 ] ) than controls . They tended towards lesser number of steps per day ( -1339 [ -2760 ; 83 ] ) and shorter duration of physical activity ( -0.44 h [ -0.94 ; 0.06 ] ) , particularly in females and patients with mild disease . Quality of life and energy intake did not differ between patients and controls . CONCLUSION In spite of quiescent disease lean body mass and physical activity were reduced . Interventions to encourage physical activity may be beneficial in this lifelong disease",
"Objective . Pain and reduced physical activity levels are common in children with juvenile idiopathic arthritis ( JIA ) . Currently , there is no consensus about the role of physical activity in managing pain in JIA . The purpose of our study was to assess the relationship between physical activity level and pain in children ages 11 to 18 years with JIA . Methods . A r and om sample of 50 patients with JIA were approached by mailed question naires . Physical activity was determined using the Physical Activity Question naire ( PAQ ) . Pain measures included the Numerical Rating Scale ( pain severity ) , SUPER-KIDZ body diagram ( number of painful areas ) , and the Child Activities Limitations Inventory-21 ( pain interference ) . Generalized linear models were used to assess the relationship between physical activity and pain , as well as the roles of sex and age . Results . The response rate was 84 % . Thirty-four respondents completed the question naire package . The median age was 15 years . The mean PAQ score was 2.16/5 . Physical activity declines with increasing age in youth with JIA ( r = 0.53 , p = 0.0014 ) . Lower physical activity is associated with greater pain interference ( r = 0.39 , p = 0.0217 ) and more severe pain ( r = 0.35 , p = 0.0422 ) . Conclusion . Children with JIA report significantly less activity than healthy children based on PAQ scores , with physical activity declining throughout adolescence . Physical activity is inversely related to pain interference and severity in children with JIA . Our findings suggest that physical activity interventions may play an important role in the management of pain in JIA"
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4118791c-06ff-11f0-808a-c43d1ab1c353
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Occupational therapy practitioners are key health care providers for people with musculoskeletal disorders of the distal upper extremity . It is imperative that practitioners underst and the most effective and efficient means for remediating impairments and supporting clients in progressing to independence in purpose ful occupations . This systematic review provides an up date to a previous review by summarizing articles published between 2006 and July 2014 related to the focused question , What is the evidence for the effect of occupational therapy interventions on functional outcomes for adults with musculoskeletal disorders of the forearm , wrist , and h and ? A total of 59 articles were review ed . Evidence for interventions was synthesized by condition within bone , joint , and general h and disorders ; peripheral nerve disorders ; and tendon disorders . The strongest evidence supports postsurgical early active motion protocol s and splinting for various conditions . Very few studies have examined occupation-based interventions . Implication s for occupational therapy practice and research are provided
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"STUDY DESIGN R and omized clinical trial . OBJECTIVE The aim of this study was to evaluate the effect of ischemic compression therapy in the treatment of chronic carpal tunnel syndrome . METHOD Fifty-five patients suffering from carpal tunnel syndrome were r and omized to two groups . Thirty-seven patients received 15 experimental treatments which consisted of ischemic compressions at trigger points located in the axilla of the shoulder , the length of the biceps muscle , at the bicipital aponeurosis and at the pronator teres muscle in the hollow of the elbow . Eighteen patients received the control treatment involving ischemic compression on trigger points located in the deltoid muscle , supraspinatus muscle and infraspinatus muscle . Of the 18 patients forming the control group , 13 agreed to receive the experimental treatments after the 15 control treatments . Outcome measures included a vali date d 18- question question naire to assess the severity of symptoms and functional status in carpal tunnel syndrome , and a quantification of the patients ' perceived improvement , using a scale from 0 % to 100 % . Outcome measures evaluations were completed at baseline , after 15 treatments , 30 days following the last treatment , and 6 months later . RESULTS For the disability question naire , a significant reduction of symptoms was noted only in the experimental group . In the experimental group the outcome at baseline was 33.5 ( SD , 10.3 ) ; after 15 treatments it was 18.6 ( SD , 7.0 ) . The control group outcome at baseline was 36.3 ( SD , 15.2 ) ; after 15 treatments it was 26.4 ( SD , 9.9 ) and after the crossover ( 15 control treatments plus 15 experimental treatments ) 20.2 ( SD , 12.2 ) . A significant between group difference ( P improvement after 15 treatments : 67 ( SD , 26 ) percent and 50 ( SD , 25 ) percent respectively for the experimental and control groups . CONCLUSION This practice -based clinical trial suggests that myofascial therapy using ischemic compression the length of the biceps , at the bicipital aponeurosis , at the pronator teres and at the subscapularis muscles could be a useful approach to reduce symptoms associated with the carpal tunnel syndrome . Patients ' perceived improvement in functional capacities persisted over a 6-month period",
"OBJECTIVE Capener splinting is a common treatment for extension deficit of the proximal interphalangeal ( PIP ) joint . This study compared the effect of daily splint total end range time ( TERT ) of 6 - 12 hr versus 12 - 16 hr . METHOD Twenty-two participants with extension deficits of the PIP joint were r and omly allocated to a daily TERT of 6 - 12 hr or 12 - 16 hr . Progress after 8 wk of splinting was evaluated . RESULTS No significant difference was found in change in extension range of motion ( ROM ) between groups ( active ROM , F[4 , 17 ] = 2.19 , p = .13 ; passive ROM , F[4 , 17 ] = 0.95 , p = .46 ; torque ROM , F[4 , 17 ] = 1.49 , p = .26 ) . Considerable crossover between groups result ed in a similar average daily TERT ( 9.5 hr for the 6 - 12 hr group vs. 11.5 hr for the 12 - 16 hr group ) . CONCLUSION Further research with a larger sample is needed to determine whether longer daily TERT is beneficial . Our results suggest , however , that most patients find it difficult to wear splints > 12 hr/day",
"STUDY DESIGN R and omized clinical trial . INTRODUCTION Although orthotic immobilization has become the preferable treatment choice for closed mallet injuries , it is unclear whether orthosis self-removal has an impact on the final outcome . PURPOSE To evaluate the treatment efficacy of cast immobilization of closed mallet fingers using Quickcast ( ® ) ( QC ) compared to a removable , lever-type thermoplastic orthosis ( LTTP ) . METHODS 57 subjects were r and omized in 2 groups . DIPj extensor lag and the Gaberman success scale were used as primary outcomes . RESULTS LTTP subjects result ed in greater extensor lag than QC subjects ( x = 5 ° ; p = 0.05 ) at 12 weeks from baseline , and high edema and older age negatively affected DIPj extensor lag . No other differences were found between groups . CONCLUSION Cast immobilization seems to be slightly more effective than the traditional approach probably for its greater capacity to reduce edema . LEVEL OF EVIDENCE 1B",
"OBJECTIVE This pilot study compared the effectiveness of 3 postoperative rehabilitation protocol s for patients with Zones V and VI extensor tendon lacerations . METHOD Twenty-seven patients were recruited from 3 sites and r and omly assigned to 1 of 3 established treatment protocol s : immobilization , early passive motion ( EPM ) , and early active motion ( EAM ) . Outcome measures were collected at 3 , 6 , and 12 wk after treatment and included total active motion ( TAM ) . RESULTS At the end of Week 12 , data on 24 injured digits of 18 patients were available for analysis . When data at Weeks 3 , 6 , and 12 were compared , patients in all groups showed steady improvement in TAM , but digits under the EAM treatment improved to a greater extent over time ( F[2 , 46 ] = 75.6 , p Patients with Zones V and VI extensor tendon injuries treated with the EAM protocol recovered range of motion more rapidly",
"OBJECTIVE To determine the effect of 2 different postoperative therapy approaches after operative stabilization of the wrist fractures : treatment by a physical therapist with 12 sessions and an unassisted home exercise program . DESIGN R and omized controlled cohort study . SETTING Hospital-based care , primary center of orthopedic surgery . PARTICIPANTS Volunteers ( N=48 ) with fractures of the distal radius after internal fixation with locking plates . There were 46 patients available for follow-up after exclusion of 2 participants due to physiotherapy sessions in excess of the study protocol . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Evaluation of grip strength using a Jamar dynamometer , range of motion ( ROM ) , and Patient Related Wrist Evaluation ( PRWE ) . RESULTS After a 6-week period of postoperative treatment , the patients ( n=23 ) performing an independent home exercise program using a training diary showed a significantly greater improvement of the functionality of the wrist . Grip strength reached 54 % ( P=.003 ) , and ROM in extension and flexion 79 % ( P Ulnar and radial abduction was also higher in this group . In contrast , patients who were treated by a physical therapist achieved grip strength equal to 32 % , and ROM in extension and flexion of 52 % of the uninjured side . Patients who were performing the home training after operation recorded an improved wrist function with a nearly 50 % lower value ( P PRWE score . CONCLUSIONS In the postoperative rehabilitation of wrist fractures , instructions in a home exercise program are an effective alternative to prescribed physical therapy treatment",
"PURPOSE To clarify the efficacy and detrimental effects of orthoses used to maintain finger extension following surgical release of Dupuytren contracture . METHODS We conducted a single-center , r and omized , controlled trial to investigate the effect of night extension orthoses on finger range of motion and h and function for 3 months following surgical release of Dupuytren contracture . We also wanted to determine how well finger extension was maintained in the total sample . We r and omized 56 patients to receive a night extension orthosis plus h and therapy ( n = 26 ) or h and therapy alone ( n = 30 ) . The primary outcome was total active extension of the operated fingers ( ° ) . Secondary outcomes were total active flexion of the operated fingers ( ° ) , active distal palmar crease ( cm ) , grip strength ( kg ) , and self-reported h and function using the Disabilities of the Arm , Shoulder , and H and question naire ( 0 - 100 scale ) . RESULTS There were no statistically significant differences between the no-orthosis and orthosis groups for total active extension or for any of the secondary outcomes . Between the first postoperative measure and 3 months after surgery , 62 % of little fingers had maintained or improved total active extension . CONCLUSIONS The use of a night extension orthosis in combination with st and ard h and therapy has no greater effect on maintaining finger extension than h and therapy alone in the 3 months following surgical release of Dupuytren contracture . Our results indicate that the practice of providing every patient with a night extension orthosis following surgical release of Dupuytren contracture may not be justified except for cases in which extension loss occurs after surgery . Our results also challenge clinicians to research ways of maintaining finger extension in a greater number of patients",
"Background Dupuytren 's disease is a progressive fibroproliferative disorder which can result in fixed flexion contractures of digits and impaired h and function . St and ard treatment involves surgical release or excision followed by post-operative h and therapy and splinting , however the evidence supporting night splinting is of low quality and equivocal . Methods A multi-centre , pragmatic , open , r and omised controlled trial was conducted to evaluate the effect of night splinting on self-reported function , finger extension and satisfaction in patients undergoing fasciectomy or dermofasciectomy . 154 patients from 5 regional hospitals were r and omised after surgery to receive h and therapy only ( n = 77 ) or h and therapy with night-splinting ( n = 77 ) . Primary outcome was self-reported function using the Disabilities of the Arm , Shoulder and H and ( DASH ) question naire . Secondary outcomes were finger range of motion and patient satisfaction . Primary analysis was by intention to treat . Results 148 ( 96 % ) patients completed follow-up at 12 months . No statistically significant differences were observed on the DASH question naire ( 0 - 100 scale : adjusted mean diff . 0.66 , 95%CI - 2.79 to 4.11 , p = 0.703 ) , total extension deficit of operated digits ( degrees : adjusted mean diff 5.11 , 95%CI -2.33 to 12.55 , p = 0.172 ) or patient satisfaction ( 0 - 10 numerical rating scale : adjusted mean diff -0.35 , 95%CI -1.04 to 0.34 , p = 0.315 ) at 1 year post surgery . Similarly , in a secondary per protocol analysis no statistically significant differences were observed between the groups in any of the outcomes . Conclusions No differences were observed in self-reported upper limb disability or active range of motion between a group of patients who were all routinely splinted after surgery and a group of patients receiving h and therapy and only splinted if and when contractures occurred . Given the added expense of therapists ' time , thermoplastic material s and the potential inconvenience to patients having to wear a device , the routine addition of night-time splinting for all patients after fasciectomy or dermofasciectomy is not recommended except where extension deficits reoccur . Trial registration The trial was registered as an International St and ard R and omised Controlled Trial IS RCT",
"OBJECTIVE To evaluate the effectiveness of three different physiotherapeutic approaches in the management of the rheumatoid h and . METHODS In a r and omized controlled trial , participants with rheumatoid arthritis ( RA ) recruited from a rheumatology department in Mid-Staffordshire , UK ( February 1999 to January 2001 ) were r and omized to three groups . All received joint protection ( JP ) information delivered by a therapist at baseline . Group 1 participants received a set of additional h and -strengthening and mobilizing home exercises , group 2 a different set of additional h and -stretching exercises and group 3 the JP information alone . The primary outcome was the Arthritis Impact Measurement Scales II ( AIMS II ) ( upper limb ; h and and finger function subscales ) . Outcomes were assessed at baseline and 1 , 3 and 6 months . Analysis was by intention to treat . RESULTS Sixty-seven participants ( mean age 59.6 yr ) were recruited : group 1 n = 21 , group 2 n = 24 and group 3 n = 22 . A 78 % follow-up was achieved at 6 months . There was a mean fall ( SD ) in AIMS II upper limb function 0 - 6 month change scores in group 1 of 1.00 ( 1.07 ) . In groups 2 and 3 there was a mean increase in AIMS II scores of 0.18 ( 1.54 ) and 0.30 ( 1.22 ) , respectively . The differences in AIMS change scores between group 1 and groups 2 and 3 were statistically significant ( P = 0.007 ) and remained so after adjustment for multiple testing ( P = 0.012 ) . CONCLUSION Statistically significant improvements in arm function have been demonstrated following a programme of home-strengthening h and exercises in RA patients compared with simple stretches or advice alone",
"OBJECTIVE To compare Stack , dorsal , and custom splinting techniques in people with acute type 1a or b mallet finger . DESIGN Multi-center r and omized controlled trial . SETTING Outpatient h and therapy clinics ( 2 public hospitals and 1 private clinic ) . PARTICIPANTS Patients ( N=64 ) with acute type 1a or b mallet finger . INTERVENTIONS Prefabricated Stack splint ( control ) , dorsal padded aluminum splint , or custom-made thermoplastic thimble splint . All were worn for 8 weeks continuously , with a 4 week graduated withdrawal and exercise program . MAIN OUTCOME MEASURES The primary outcome was extensor lag at 12 and 20 weeks . Secondary outcomes were incidence of treatment failure , complications , range of motion of the distal interphalangeal joint , pain ( visual analog scale ) patient compliance , and patient satisfaction . RESULTS There was no difference in the primary outcome between groups at 12 or 20 weeks ; however , the Stack and dorsal splints had significant rates of treatment failure ( 23.8 % in both groups , compared to none in the thermoplastic group ; P=.04 ) . There was a medium negative correlation between patient compliance and degree of extensor lag . No significant differences between groups were observed for patient satisfaction or pain . CONCLUSIONS As splints for mallet finger must be worn continuously for 6 to 8 weeks , and compliance correlates with favorable outcomes , treating practitioners must ensure the splint provided is robust enough for daily living requirements and does not cause complications , which are intolerable to the patient . In this study , no extensor lag difference was found between the 3 splint types , but custom-made thermoplastic splints were significantly less likely to result in treatment failure",
"To define the role of phonophoresis and iontophoresis of corticosteroids in conjunction with wrist splint use in the treatment of carpal tunnel syndrome ( CTS ) compared to wrist splint use alone , 52 CTS subjects were analyzed based on clinical and electrophysiological criteria . A prospect i ve , r and omized controlled trial was carried out to assess symptom severity , motor skills , and h and function according to the Boston Symptom Severity Scale ( BSSS ) , grip strength , and nine-hole peg test ( NHPT ) , respectively , on the initial visit and in the 3rd month after treatment . The patients underwent conservative interventions r and omly as follows : ( 1 ) 3 weeks of phonophoresis with betamethasone in conjunction with wrist splint use ( group I , n : 18 ) or ( 2 ) 3 weeks of iontophoresis with betamethasone in conjunction with wrist splint use ( group II , n : 16 ) or ( 3 ) wrist splint use alone ( control , group III , n : 18 ) . The mean age of the patients was 43.7 ± 8.4 ( range 24–57 ) years . Groups I , II , and III showed a significant and further improvement in BSSS at the 3rd month evaluations compared with baseline ( P in grip strength or NHPT ( P > 0.05 ) . There was a statistically significant difference between the phonophoresis and control groups after treatment only regarding BSSS , in favor of phonophoresis ( P = 0.012 ) . We recommend the use of wrist splints especially with phonophoresis for relief of symptoms in patients with CTS . Our results demonstrated no superiority among the treatment groups . Further , transdermal steroid treatments are not key determinants of efficacy with respect to motor skills and h and dexterity ",
"Abstract Purpose : To investigate the effects of mirror therapy ( MT ) in restoring h and function in patients with active range of motion ( AROM ) impairments following orthopaedic injuries . Method : In a r and omized controlled trial ( RCT ) , 30 patients with active ROM impairment ( 8 men and 22 women ; mean age : 38 years ) were measured . Intervention group received MT , 30 min a day , five days a week for three weeks , as well , half an hour conventional rehabilitation after each MT session . Patients in the control group received the same treatment programme , but instead of mirror , they observed directly the affected h and . In addition , both groups performed a 15 min home programme , including MT for intervention group and AROM with direct observation of the affected h and for control group , twice daily . Outcome measures , including total active motion ( TAM ) and Disabilities of Arm , Shoulder and H and ( DASH ) question naire , were administered pre- and post-treatment and three weeks later . This study was registered as an RCT , no. NCT01503762 in http:// clinical trials.gov/. Results : Final analysis was performed on 23 patients . The mean ( SD ) changes at post-test from baseline TAM was 154 ( 32 ) in the MT ( N = 12 ) and 61 ( 24 ) in the control group ( N = 11 ) ; mean difference ( 95 % CI ) 93 ( 68–118 ) , p = 0.001 . The mean ( SD ) change at post-test from baseline DASH was −34 ( 7 ) in the MT ( N = 12 ) and −15 ( 11 ) in the control group ( N = 11 ) ; mean difference ( 95 % CI ) 19 ( −27 to −11 ) , p = 0.001 . Conclusions : Despite significant improvement at post-test in both groups and maintenance of improvement during the follow-up period , MT combined with conventional rehabilitation produced more improvement in h and function than control group . Implication s for Rehabilitation H and orthopaedic injuries can result in disabilities in activities of daily living . Mirror therapy ( MT ) provides perception of two healthy limbs through reflection of the healthy limb as the injured limb . In a r and omized controlled trial , our study shows positive effects of MT combined with a classical rehabilitation programme to improve h and function in patients with orthopaedic injuries",
"OBJECTIVE To evaluate the effects of cross-education ( contralateral effect of unilateral strength training ) during recovery from unilateral distal radius fractures on muscle strength , range of motion ( ROM ) , and function . DESIGN R and omized controlled trial ( 26-wk follow-up ) . SETTING Hospital , orthopedic fracture clinic . PARTICIPANTS Women older than 50 years with a unilateral distal radius fracture . Fifty-one participants were r and omized and 39 participants were included in the final data analysis . INTERVENTIONS Participants were r and omized to st and ard rehabilitation ( Control ) or st and ard rehabilitation plus strength training ( Train ) . St and ard rehabilitation included forearm casting for 40.4±6.2 days and h and exercises for the fractured extremity . Nonfractured h and strength training for the training group began immediately postfracture and was conducted at home 3 times/week for 26 weeks . MAIN OUTCOME MEASURES The primary outcome measure was peak force ( h and grip dynamometer ) . Secondary outcomes were ROM ( flexion/extension ; supination/pronation ) via goniometer and the Patient Rated Wrist Evaluation question naire score for the fractured arm . RESULTS For the fractured h and , the training group ( 17.3±7.4 kg ) was significantly stronger than the control group ( 11.8±5.8 kg ) at 12 weeks postfracture ( P no significant strength differences between the training and control groups at 9 ( 12.5±8.2 kg ; 11.3±6.9 kg ) or 26 weeks ( 23.0±7.6 kg ; 19.6±5.5 kg ) postfracture , respectively . Fractured h and ROM showed that the training group had significantly improved wrist flexion/extension ( 100.5 ° ±19.2 ° ) than the control group ( 80.2 ° ±18.7 ° ) at 12 weeks postfracture ( P for flexion/extension ROM at 9 ( 78.0 ° ±20.7 ° ; 81.7 ° ±25.7 ° ) or 26 weeks ( 104.4 ° ±15.5 ° ; 106.0 ° ±26.5 ° ) or supination/pronation ROM at 9 ( 153.9 ° ±23.9 ° ; 151.8 ° ±33.0 ° ) , 12 ( 170.9 ° ±9.3 ° ; 156.7 ° ±20.8 ° ) or 26 weeks ( 169.4 ° ±11.9 ° ; 162.8 ° ±18.1 ° ) , respectively . There were no significant differences in Patient Rated Wrist Evaluation question naire scores between the training and control groups at 9 ( 54.2±39.0 ; 65.2±28.9 ) , 12 ( 36.4±37.2 ; 46.2±35.3 ) , or 26 weeks ( 23.6±25.6 ; 19.4±16.5 ) , respectively . CONCLUSIONS Strength training for the nonfractured limb after a distal radius fracture was associated with improved strength and ROM in the fractured limb at 12 weeks postfracture . These results have important implication s for rehabilitation strategies after unilateral injuries ",
"OBJECTIVE To compare the effectiveness and acceptability of silver ring splints ( SRS ) and commercial prefabricated thermoplastic splints ( PTS ) in treating swan neck deformities in patients with rheumatoid arthritis ( RA ) . METHODS Consecutive patients with RA and a mobile swan neck deformity were included in a r and omized , crossover trial . In 2 different sequences , patients used both splints for 4 weeks , with a washout period of 2 weeks . Afterward , patients used the preferred splint for another 12 weeks . The primary outcome measure was dexterity measured with the Sequential Occupational Dexterity Assessment ( SODA ) . Secondary outcome measures included other measures of h and function , satisfaction with the splints , and splint preference . RESULTS Fifty patients were included , and 47 ( 94 % ) of those completed the study . Eighteen patients ( 36 % ) had 1 swan neck deformity , whereas the other patients had 2 or more . The improvement of the total SODA score with the SRS ( 11.2 ; 95 % confidence interval [ 95 % CI ] 8.1 , 14.3 ) and PTS ( 10.8 ; 95 % CI 7.5 , 14.1 ) was similar ( difference -0.5 ; 95 % CI -2.2 , 1.2 ) . In addition , there were no significant differences in change scores regarding the other clinical outcome measures , or satisfaction . Twenty-four patients preferred the SRS , 21 preferred the PTS , and 2 patients chose neither . A comparison in the 12-week followup period yielded similar clinical outcomes , with the exception of a significantly higher score in 3 items of satisfaction in the SRS group . CONCLUSION For patients with RA and a mobile swan neck deformity , SRS and PTS are equally effective and acceptable",
"PURPOSE The aim of the study was to compare the long term effects of low - level laser therapy ( LLLT ) and pulsed magnetic field ( PMF ) in the rehabilitation of patients with carpal tunnel syndrome ( CTS ) . METHODS The study included 38 patients with idiopathic CTS , confirmed by electroneurographic ( ENG ) examination . All patients were r and omly assigned to 2 groups : group L ( 18 patients ) treated with LLLT and group M ( 20 patients ) with PMF therapy . Clinical assessment , including day and night pain , the presence of paresthesia , functional tests ( Phalen , Tinel , armb and tests ) and pain severity according to the Visual Analogue Scale ( VAS ) was conducted before treatment , after the first series of 10 sessions , after a two-week break , after the second series of 10 sessions and six months after the last series . RESULTS After LLLT a significant reduction of day and night pain was observed at each stage of treatment and 6 months after the last series ( p day and night pain was demonstrated only after the second series ( p incidence of Phalen 's symptoms were noticed in both groups , however , only in group L the improvement was significant ( p reduction of pain intensity was observed at every stage of treatment ( p LLL as well as PMF therapy clinical improvement was observed , the most significant differences were registered after the second series and persisted for up to 6 months in both groups",
"BACKGROUND Rheumatoid arthritis ( RA ) most frequently affects smaller joints in the h and s and feet . Among the most common deformations result ing from the progression of the disease are ulnar deviation , Boutonniere deformity , swan neck deformity , contractures and limited range of movement in the h and and wrist joints , muscular atrophy of long and short muscles . The topic of this article is the influence of using Kinesiology Taping method on the functioning of the h and of the patient suffering from rheumatoid arthritis . MATERIAL AND METHODS The research involved 20 patients suffering from rheumatoid arthritis ( 16 women , 4 men ) , treated in the Hospital in Kup . Average age of patients was 62.2 . Research subjects , apart from pharmacological treatment in the hospital ward , received st and ard physiotherapy . In case of 10 patients additional K-Active Tape applications were used to correct ulnar positioning of the h and and improve h and functioning . Prior to physiotherapy , all patients were given a h and functioning test and a dynamometer measurement was made . The tests were repeated after the 2-week rehabilitation process has been completed . The results were subjected to statistical analysis with the use of the Wilcoxon test and the U Mann-Whitney test . The assessment of the correlation between analysed parameters was made with the use of linear correlation test . RESULT In the group where Kinesiology Tape applications were used , h and muscle strength increased significantly ( p st and ard physiotherapy . H and muscle strength increase correlated with the tempo of carrying out the h and functioning test ( r>0.8 ) . CONCLUSION Results suggest Kinesiology Taping method useful for physiotherapy of rheumatoid h and",
"STUDY DESIGN Prospect i ve cohort . INTRODUCTION Many variables are believed to influence the success of dynamic splinting , yet their relationship with contracture resolution is unclear . PURPOSE OF THE STUDY To identify the predictors of outcome with dynamic splinting of the stiff h and after trauma . METHODS Forty-six participants ( 56 joints ) completed eight weeks of dynamic splinting , and the relationship between 13 clinical variables and outcome was explored . RESULTS Improvement in passive range of motion , active range of motion ( AROM ) , and torque range of motion averaged 21.8 ° , 20.0 ° , and 13.0 ° , respectively ( average daily total end range time , 7.96 hours ) . Significant predictors included joint stiffness ( modified Weeks Test ) , time since injury , diagnosis , and deficit ( flexion/extension ) . For every degree change in ROM on the modified Weeks Test , AROM improved 1.09 ° ( st and ard error , 0.2 ) . Test-retest reliability of the modified Weeks Test was high ( intraclass correlation coefficient [ 2 , 1]=0.78 ) . CONCLUSIONS Better progress with dynamic splinting may be expected in joints with less pretreatment stiffness , shorter time since injury ( < 12 weeks ) , and in flexion rather than extension deficits . Further research is needed to determine the accuracy with which the modified Weeks Test may predict contracture resolution . LEVEL OF EVIDENCE 2b",
"Objective : To investigate the effects of adding core stabilisation exercises to traditional rehabilitation in patients with arm injuries . Design : R and omized controlled trial . Setting : Outpatient clinic . Subjects : Twenty-seven patients with elbow and wrist injuries were r and omized to a stabilisation or control group . Interventions : The stabilisation group received core stabilisation training and traditional arm rehabilitation and the control group received traditional arm rehabilitation alone for three days/week for six weeks . Main measures : Pre- and post-treatment assessment s comprising an analysis of compensatory movement patterns and trunk muscle strength as well as functional measurements of the arm , including pain , range of motion , disabilities of arm , shoulder and h and question naire and endurance and fatigue severity were performed . Results : Inter-group comparison revealed significantly greater improvements in the degree of mean change ( SD ) in total compensation ( in degrees ) of the head ( –14.47 ( 21.65 ) ) and trunk ( –5.56 ( 5.71 ) ) as well as total compensation ( –50.02 ( 48.62 ) ) for the stabilisation group than for the control group ( p Increase in trunk muscle strength ( 2.43 ( 3.46 ) ) was statistically significant in the stabilisation group compared with the control group . No significant differences were found for functional measures , including pain , range of motion , disabilities of arm , shoulder and h and or endurance and fatigue severity between the groups , although trends towards greater improvement were observed in the stabilisation group . Conclusions : Adding core stabilisation exercises to traditional arm rehabilitation for patients with traumatic arm injury reduces compensatory movement patterns . Trends towards better functional outcomes in the stabilisation group are worth testing in a large-scale trial",
"The objective of this study is to investigate the efficacy of low-level laser therapy ( LLLT ) in patients with carpal tunnel syndrome ( CTS ) . Sixty patients with CTS were included in this placebo-controlled and double-blind study and r and omly assigned to three treatment groups : active laser with a dosage of 1.2 J/per painful point , active laser with a dosage of 0.6 J/per painful point , and placebo groups . A total of 5 points across the median nerve trace were irradiated with Gal-Al-As diode laser . All groups were treated 5 times per week for 3 weeks . Clinical assessment s included pain intensity , grip strength , symptom severity score ( SSS ) , functional status score ( FSS ) , nerve conduction studies , and cross-sectional area ( CSA ) of the median nerve as measured by ultrasonography . Compared to baseline , post-treatment VAS scores ( group 1 , P grip strength ( P SSS scores ( group 1 , P FSS scores ( P sensorial nerve velocity measurements on the palmar region showed a significant improvement in both active laser groups ( P LLLT was no more effective than placebo in CTS",
"Objective : To investigate whether progressive early digit mobilization result ed in better outcomes for h and stiffness and related functional results , as well as the effects on the bone healing process . Design : Prospect i ve , pilot r and omized controlled trial . Setting : A university hospital in southern Taiwan . Participants : Twenty-two patients with distal radius fracture r and omized into two groups : early digit mobilization or control . Interventions : The intervention group received 45 minutes per treatment session and three sessions per week until the external fixator was removed 6 weeks after fracture . The control group received usual home programmes . After removing fixators , both groups received regular rehabilitation programmes until 12 weeks after surgery . Main measures : H and strength , dexterity and functional outcomes were obtained using a dynamometer , Purdue pegboard and self-report assessment , respectively , and X-rays of the distal radius were taken to reveal bone healing 1 , 3 , 6 and 12 weeks after surgery . A motion tracking system measured various kinematic parameters . Results : The recovery rates between the groups showed statistically significant differences in both thumb workspace ( 81.55 % vs. 69.54 % , P = 0.04 ) and finger workspace ( 89.22 % vs. 59.97 % , P = 0.03 ) 12 weeks after injury . However , no statistical differences were found in finger dexterity , strength and self-reported outcomes . The radiographic assessment showed no significant differences between the groups for radial inclination , radial height and volar tilt throughout the examinations . Conclusions : The findings suggest that early rehabilitative intervention for digits is applicable for distal radius fracture treatment , and does not produce additional bone deformities",
"In carpal tunnel syndrome ( CTS ) , manual therapy interventions ( MTI ) reduce tissue adhesion and increase wrist mobility . We evaluated the efficacy of a MTI in relieving CTS signs and symptoms . Twenty-two CTS patients ( pts ) ( 41 h and s ) were treated with a MTI , consisting in 6 treatments ( 2/week for 3 weeks ) of soft tissues of wrist and h and s and of carpal bones . Pts were assessed for h and sensitivity , paresthesia , h and strength , h and and forearm pain , night awakening ; Phalen test , thenar eminence hypotrophy and Boston Carpal Tunnel Question naire ( BCTQ ) Symptom Severity Scale ( SSS ) and Functional Status Scale ( FSS ) . Median nerve was studied by sensory nerve conduction velocity ( SNCV ) and distal motor latency ( DML ) . CTS was scored as minimal , mild , medium , severe and extreme . We considered as control group the same pts assessed before treatment : at baseline ( T0a ) and after 12 weeks ( T0b ) . Pts were evaluated at the end of treatment ( T1 ) and after 24-week ( T2 ) follow-up . At T0b , versus T0a , forearm pain and Phalen test positivity were increased and h and strength reduced ( p BCTQ – SSS and BCTQ – FSS scores improved at T1 versus T0b ( p number of pts with paresthesia , night awakening , hypoesthesia , Phalen test , h and strength reduction and h and sensitivity was reduced with the lacking of symptoms maintained at T2 ( p in SNCV , DML and CTS scoring were shown . MTI improved CTS signs and symptoms , with benefits maintained at follow-up . Thus , it may be valid as a conservative therapy",
"STUDY DESIGN R and omized controlled clinical trial . INTRODUCTION Manual edema mobilization ( MEM ) is a method of edema reduction based on the lymphatic system 's ability to drain and resolve subacute edema . PURPOSE OF THE STUDY To investigate the effect of a modified MEM approach and compare it with a traditional edema technique in patients with subacute h and /arm edema after a distal radius fracture . METHOD The patients were r and omized into one of two treatment groups : a group that received traditional edema treatment and a group that received a modified MEM treatment . All patients were examined for edema , active range of motion ( AROM ) , pain , and activities of daily living ( ADL ) . The number of edema sessions and the number of all sessions were counted . RESULT No statistically significant changes were observed in edema reduction , AROM , pain , and ADL at six and nine weeks between the treatment groups . A statistically significant improvement was observed in ADL after three weeks after inclusion ( p=0.03 ) in the modified MEM group compared with the control group . Furthermore , fewer edema treatment sessions were needed ( p=0.03 ) in the modified MEM group . At six weeks , we observed a difference between the two groups ' needs for further edema treatment ( p=0.04 ) . CONCLUSION Neither the traditional nor the modified MEM treatment program was superior in terms of edema reduction , although the modified MEM result ed in fewer sessions to decrease subacute h and /arm edema compared with using traditional edema reduction techniques in patients after distal radius fracture . LEVEL OF EVIDENCE 1",
"STUDY DESIGN Systematic review . INTRODUCTION Controversy exists as to which rehabilitation protocol provides the best outcomes for patients after surgical repair of the extensor tendons of the h and . PURPOSE OF THE STUDY To determine which rehabilitation protocol yields the best outcomes with respect to range of motion and grip strength in extensor zones V-VIII of the h and . METHODS A comprehensive literature review and assessment was undertaken by two independent review ers . Method ological quality of r and omized controlled trials and cohort studies was assessed using the Scottish Intercollegiate Guidelines Network scale . RESULTS Seventeen articles were included in the final analysis ( κ=0.9 ) . From this total , seven evaluated static splinting , 12 evaluated dynamic splinting , and four evaluated early active splinting . Static splinting yielded \" excellent/good \" results ranging from 63 % ( minimum ) to 100 % ( maximum ) on the total active motion ( TAM ) classification scheme and TAM ranging from 185 ° ( minimum ) to 258 ° ( maximum ) across zones V-VIII . Dynamic splinting studies demonstrated a percentage of \" excellent/good \" results ranging from 81 % ( minimum ) and 100 % ( maximum ) and TAM ranging from 214 ° ( minimum ) and 261 ° ( maximum ) . Early active splinting studies showed \" excellent/good \" results ranging from 81 % ( minimum ) and 100 % ( maximum ) . Only one study evaluated TAM in zones V-VIII , which ranged from 160 ° ( minimum ) and 165 ° ( maximum ) when using two different early active modalities . CONCLUSIONS The available level 3 evidence suggests better outcomes when using dynamic splinting over static splinting . Additional studies comparing dynamic and early active motion protocol s are required before a conclusive recommendation can be made . LEVEL OF EVIDENCE 2",
"OBJECTIVE The purpose of this placebo-controlled study was to investigate the therapeutic effects of the 830-nm diode laser on carpal tunnel syndrome ( CTS ) . BACKGROUND DATA Many articles in the literature have demonstrated that low-level laser therapy ( LLLT ) may help to alleviate various types of nerve pain , especially for CTS treatment . We placed an 830-nm laser directly above the transverse carpal ligament , which is between the pisiform and navicular bones of the tested patients , to determine the therapeutic effect of LLLT . MATERIAL S AND METHODS Thirty-six patients with mild to moderate degree of CTS were r and omly divided into two groups . The laser group received laser treatment ( 10 Hz , 50 % duty cycle , 60 mW , 9.7 J/cm(2 ) , at 830 nm ) , and the placebo group received sham laser treatment . Both groups received treatment for 2 wk consisting of a 10-min laser irradiation session each day , 5 d a week . The therapeutic effects were assessed on symptoms and functional changes , and with nerve conduction studies ( NCS ) , grip strength assessment , and with a visual analogue scale ( VAS ) , soon after treatment and at 2-wk follow-up . RESULTS Before treatment , there were no significant differences between the two groups for all assessment s ( p > 0.05 ) . The VAS scores were significantly lower in the laser group than the placebo group after treatment and at follow-up ( p grip strengths or for symptoms and functional assessment s ( p > 0.05 ) . However , there were statistically significant differences in these variables at 2-wk follow-up ( p ability and finger and h and strength for mild and moderate CTS patients with no side effects",
"QUESTION Do dynamic splints reduce contracture following distal radial fracture ? DESIGN Assessor-blinded , r and omised controlled trial . PARTICIPANTS Forty out patients with contracture following distal radial fracture . INTERVENTION The control group received routine care consisting of exercises and advice for 8 weeks . In addition to routine care , during the day the experimental group received a dynamic splint , which stretched the wrist into extension but allowed intermittent movement . OUTCOME MEASURES The primary outcomes were passive wrist extension and the Patient Rated H and Wrist Evaluation ( PRHWE ) . The secondary outcomes were active wrist extension , flexion , radial deviation , and ulnar deviation , and the performance and satisfaction items of the Canadian Occupational Performance Measure ( COPM ) . All outcomes were measured at commencement , at the end of 8 weeks of treatment , and at 12 weeks ( ie , 1 month follow-up ) . RESULTS The mean between-group difference for passive wrist extension and PRHWE at 8 weeks were 4 deg ( 95 % CI -4 to 12 ) and -2 points ( 95 % CI -8 to 4 ) , respectively . The corresponding values at 12 week follow-up were 6 deg ( 95 % CI 1 to 12 ) and 2 points ( 95 % CI -5 to 9 ) . There were no sufficiently important between-group differences for any of the secondary outcome measures at 8 or 12 weeks . CONCLUSION It is unclear whether dynamic splints following distal radial fracture have therapeutic effects on passive wrist extension or PRHWE , but they clearly do not have any therapeutic effects on active wrist extension , flexion , radial or ulnar deviation , or on the performance or satisfaction items of the COPM . The ongoing use of dynamic splints following distal radial fracture is difficult to justify . TRIAL REGISTRATION ACTRN12608000309381",
"OBJECTIVE To compare the effectiveness of an intensive lumbrical splint/stretch combination with 3 less intensive lumbrical splint/stretch combinations on carpal tunnel symptoms and function . DESIGN R and omized Clinical Trial . SETTING Outpatient h and therapy clinics . PARTICIPANTS Volunteers ( N=124 ) with mild to moderate carpal tunnel syndrome . INTERVENTIONS A 4-week home regimen of nocturnal splints ( lumbrical splints or cock-up splints ) combined with stretches ( lumbrical intensive or general ) performed 6 times daily . MAIN OUTCOME MEASURES The effect of the intervention on carpal tunnel symptoms and function was examined with the Carpal Tunnel Symptom Severity and Function Question naire ( CTQ ) and Disabilities of the Arm , Shoulder , and H and ( DASH ) . We also evaluated whether subjects obtained surgery at 24 weeks . RESULTS There were significant main effects over time for all outcome measures at 4 , 12 , and 24 weeks . There was a significant interaction effect for the CTQ-Function and DASH at 12 weeks . Post hoc analyses indicated significant differences between the lumbrical splint/general stretch and general splint/lumbrical stretch groups and the other 2 groups . At 24 weeks , a significantly greater percentage of subjects in the general splint/lumbrical stretch group achieved a clinical ly important improvement on the CTQ-Function . By 24 weeks , only 25.5 % of subjects had elected to undergo surgery . CONCLUSIONS A combination of a cock-up splint with lumbrical intensive stretches was the most effective combination for improvements in functional gains at 24 weeks postbaseline . Our findings support further evaluation of this combination as a method of conservative carpal tunnel syndrome treatment",
"Objective : To evaluate the effectiveness of a functional thumb orthosis on the dominant h and of patients with rheumatoid arthritis and boutonniere thumb . Methods : Forty patients with rheumatoid arthritis and boutonniere deformity of the thumb were r and omly distributed into two groups . The intervention group used the orthosis daily and the control group used the orthosis only during the evaluation . Participants were evaluated at baseline as well as after 45 and 90 days . Assessment s were preformed using the O'Connor Dexterity Test , Jamar dynamometer , pinch gauge , goniometry and the Health Assessment Question naire . A visual analogue scale was used to assess thumb pain in the metacarpophalangeal joint . Results : Patients in the intervention group experienced a statistically significant reduction in pain . The thumb orthosis did not disrupt grip and pinch strength , function , Health Assessment Question naire score or dexterity in either group . Conclusion : The use of thumb orthosis for type I and type II boutonniere deformities was effective in relieving pain",
"We compared the effectiveness of physiotherapy and corticosteroid injection treatment in the management of mild trigger fingers . Mild trigger fingers are those with mild crepitus , uneven finger movements and actively correctable triggering . This is a single-centred , prospect i ve , block r and omized study with 74 patients ; 39 patients for steroid injection and 35 patients for physiotherapy . The study duration was from Jun 2009 until August 2010 . Evaluation was done at 6 weeks , 3 months and 6 months post-treatment . At 3 months , the success rate ( absence of pain and triggering ) for those receiving steroid injection was 97.4 % and physiotherapy 68.6 % . The group receiving steroid injection also had lower pain score , higher rate of satisfaction , stronger grip strength and early recovery to near normal function ( findings were all significant , p corticosteroid injections had a significant recurrence rate of pain but not triggering . The physiotherapy group had no recurrence of pain or triggering due to the type of triggering responsive to physiotherapy or possibly due to awareness of physiotherapy exercises . Perhaps they were able to institute self-treatment on early onset of symptoms of trigger fingers . We conclude that corticosteroid injection has a better outcome compared to physiotherapy in the treatment of mild trigger fingers but physiotherapy may have a role in prevention of recurrence",
"BACKGROUND The effect of formal occupational therapy on recovery after open reduction and volar plate fixation of a fracture of the distal part of the radius is uncertain . We hypothesized that there would be no difference in wrist function and arm-specific disability six months after open reduction and volar plate fixation of a distal radial fracture between patients who receive formal occupational therapy and those with instructions for independent exercises . METHODS Ninety-four patients with an unstable distal radial fracture treated with open reduction and volar locking plate fixation were enrolled in a prospect i ve r and omized controlled trial comparing exercises done under the supervision of an occupational therapist with surgeon-directed independent exercises . The primary study question addressed combined wrist flexion and extension six months after surgery Secondary study questions addressed wrist motion , grip strength , Gartl and and Werley scores , Mayo wrist scores , and DASH ( Disabilities of the Arm , Shoulder and H and ) scores at three months and six months after surgery . RESULTS There was a significant difference in the mean arc of wrist flexion and extension six months after surgery ( 118 ° versus 129 ° ) , favoring patients prescribed independent exercises . Three months after surgery , there was a significant difference in mean pinch strength ( 80 % versus 90 % ) , mean grip strength ( 66 % versus 81 % ) , and mean Gartl and and Werley scores , favoring patients prescribed independent exercises . At six months , there was a significant difference in mean wrist extension ( 55 ° versus 62 ° ) , ulnar deviation ( 82 % versus 93 % ) , mean supination ( 84 ° versus 90 ° ) , mean grip strength ( 81 % versus 92 % ) , and mean Mayo score , favoring patients prescribed independent exercises . There were no differences in arm-specific disability ( DASH score ) at any time point . CONCLUSIONS Prescription of formal occupational therapy does not improve the average motion or disability score after volar locking plate fixation of a fracture of the distal part of the radius"
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41187962-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND AND AIM Clinical evidence which investigated the effects of l-carnitine , a vitamin-like substance , on weight loss had led to inconsistent results . This study therefore aim ed to examine the effect of l-carnitine supplementation on body weight and composition by including the maximum number of r and omized controlled trials ( RCTs ) and to conduct a dose-response analysis , for the first time . METHODS AND RESULTS Online data bases were search ed up to January 2019 . In total , 37 RCTs ( with 2292 participants ) were eligible . Meta- analysis showed that l-carnitine supplementation significantly decreased body weight [ Weighted mean difference ( WMD ) = -1.21 kg , 95 % confidence interval ( CI ) : -1.73 , -0.68 ; P body mass index ( BMI ) ( WMD = -0.24 kg/m2 , 95 % CI : -0.37 , -0.10 ; P = 0.001 ) , and fat mass ( WMD = -2.08 kg , 95 % CI : -3.44 , -0.72 ; P = 0.003 ) . No significant effect was seen for waist circumference ( WC ) and body fat percent . The meta- analysis of high- quality RCTs only confirmed the effect on body weight . A non-linear dose-response association was seen between l-carnitine supplementation and body weight reduction ( P l-carnitine per day provides the maximum effect in adults . This association was not seen for BMI , WC and body fat percent . CONCLUSIONS l-carnitine supplementation provides a modest reducing effect on body weight , BMI and fat mass , especially among adults with overweight/obesity
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"This study examined the impact of L-acetylcarnitine treatment on metabolic parameters and body composition in patients with lipodystrophy syndrome secondary to antiretroviral treatment in human immunodeficiency virus ( HIV ) infection . A total of 9 HIV-1 infected patients with lipodystrophy syndrome ( 4F/5 M , age 41+/-5 years , HIV duration 8+/-2 years , BMI 23.7+/-3.4 kg/m(2 ) , on protease inhibitors and nucleoside analogue Reverse Transcriptase inhibitors ) were evaluated before and after 8 months of therapy with L-acetylcarnitine ( 2 g/die ) and 9 matched healthy subjects served as control subjects . In all patients fasting plasma glucose , insulin concentrations ( for evaluation of surrogate indexes of insulin sensitivity ) , lipid profile , lipid oxidation ( by indirect calorimetry ) , body composition ( by DEXA ) , and intramyocellular triglyceride ( IMCL ) content of the calf muscles ( by (1)H NMR spectroscopy ) were assessed . After this therapy , in HIV-1 patients , the IMCL content of the soleus had significantly decreased ( p=0.03 ) . Plasma FFAs ( 0.79+/-0.31 to 0.64+/-0.25 ; p Respiratory Quotient ( 0.83+/-0.18 to 0.72+/-0.16 ; p Insulin sensitivity was significantly lower prior ( HOMA-IS 0.56+/-0.30 ) and nonstatistically different than controls after therapy ( 0.72+/-0.49 vs. 0.78+/-0.42 ) whilst the percentage of fat in the legs increased ( p=0.05 ) . Eight months of L-acetylcarnitine treatment increased lipid oxidation , decreased intramyocellular triglyceride content , and induced a more physiological distribution of fat deposits",
"L-Carnitine ( L-C ) transports fatty acids into mitochondria for oxidation and is marketed as a weight loss supplement . In a double-blind investigation to test the weight loss efficacy of L-C , 36 moderately overweight premenopausal women were pair matched on Body Mass Index ( BMI ) and r and omly assigned to two groups ( N = 18 ) . For 8 weeks the L-C group ingested 2 g twice daily of L-C , while the placebo ( P ) group ingested the same amount of lactose . All subjects walked for 30 min ( 60 - 70 % maximum heart rate ) 4 days/week . Body composition , resting energy expenditure ( REE ) and substrate utilization were estimated before and after treatment . For the subjects who completed the study ( 15 P , 13 L-C ) , no significant changes in mean total body mass ( TBM ) , fat mass FM , and resting lipid utilization occurred over time , nor were there any significant differences between groups for any variable . Conversely REE increased significantly for all subjects , but no between group differences existed . Five of the L-C group experienced nausea or diarrhea and consequently did not complete the study . Eight weeks of L-C ingestion and walking did not significantly alter the TBM or FM of overweight women , thereby casting doubt on the efficacy of L-C supplementation for weight loss",
"Abstract Introduction : Limited data are available assessing the effects of oral carnitine supplementation on mental health parameters and biomarkers of oxidative stress of women with polycystic ovary syndrome (PCOS).This study was design ed to determine the effects of oral carnitine supplementation on mental health parameters and biomarkers of oxidative stress in women with PCOS . Methods : In the current r and omized , double-blind , placebo-controlled trial , 60 patients diagnosed with PCOS were r and omized to take either 250 mg carnitine supplements ( n = 30 ) or placebo ( n = 30 ) for 12 weeks . Results : After 12 weeks ’ intervention , compared with the placebo , carnitine supplementation result ed in a significant improvement in Beck Depression Inventory total score ( −2.7 ± 2.3 versus −0.2 ± 0.7 , p 0.001 ) , General Health Question naire scores ( −6.9 ± 4.9 versus −0.9 ± 1.5 , p 0.001 ) and Depression Anxiety and Stress Scale scores ( −8.7 ± 5.9 versus −1.2 ± 2.9 , p = 0.001 ) . In addition , changes in plasma total antioxidant capacity ( TAC ) ( + 84.1 ± 151.8 versus + 4.6 ± 64.5 mmol/L , p = 0.01 ) , malondialdehyde ( MDA ) ( −0.4 ± 1.0 versus + 0.5 ± 1.5 μmol/L , p = 0.01 ) and MDA/TAC ratio ( −0.0005 ± 0.0010 versus + 0.0006 ± 0.0019 , p = 0.003 ) in the supplemented group were significantly different from the changes in these indicators in the placebo group . Conclusions : Overall , our study demonstrated that carnitine supplementation for 12 weeks among patients with PCOS had favorable effects on parameters of mental health and biomarkers of oxidative stress ",
"Background Chemotherapy-induced peripheral neuropathy ( CIPN ) is a common and disabling side effect of taxanes . Acetyl-L-carnitine ( ALC ) was unexpectedly found to increase CIPN in a r and omized trial . We investigated the long-term patterns of CIPN among patients in this trial . Methods S0715 was a r and omized , double-blind , multicenter trial comparing ALC ( 1000 mg three times a day ) with placebo for 24 weeks in women undergoing adjuvant taxane-based chemotherapy for breast cancer . CIPN was measured by the 11-item neurotoxicity ( NTX ) component of the FACT-Taxane scale at weeks 12 , 24 , 36 , 52 , and 104 . We examined NTX scores over two years using linear mixed models for longitudinal data . Individual time points were examined using linear regression . Regression analyses included stratification factors and the baseline score as covariates . All statistical tests were two-sided . Results Four-hundred nine subjects were eligible for evaluation . Patients receiving ALC had a statistically significantly ( P = .01 ) greater reduction in NTX scores ( worse CIPN ) of -1.39 points ( 95 % confidence interval [ CI ] = -2.48 to -0.30 ) than the placebo group . These differences were particularly evident at weeks 24 ( -1.68 , 95 % CI = -3.02 to -0.33 ) , 36 ( -1.37 , 95 % CI = -2.69 to -0.04 ) , and 52 ( -1.83 , 95 % CI = -3.35 to -0.32 ) . At 104 weeks , 39.5 % on the ALC arm and 34.4 % on the placebo arm reported a five-point ( 10 % ) decrease from baseline . For both treatment groups , 104-week NTX scores were statistically significantly different compared with baseline ( P NTX scores were reduced from baseline and remained persistently low . Twenty-four weeks of ALC therapy result ed in statistically significantly worse CIPN over two years . Underst and ing the mechanism of this persistent effect may inform prevention and treatment strategies . Until then , the potential efficacy and harms of commonly used supplements should be rigorously studied",
"Lipoprotein ( a ) [ Lp(a ) ] is an independent risk factor for cardiovascular disease . There are currently limited therapeutic options to lower Lp(a ) levels . l-Carnitine has been reported to reduce Lp(a ) levels . The aim of this study was to compare the effect of l-carnitine/simvastatin co-administration with that of simvastatin monotherapy on Lp(a ) levels in subjects with mixed hyperlipidemia and elevated Lp(a ) concentration . Subjects with levels of low-density lipoprotein cholesterol ( LDL-C ) > 160 mg/dL , triacylglycerol ( TAG ) > 150 mg/dL and Lp(a ) > 20 mg/dL were included in this study . Subjects were r and omly allocated to receive l-carnitine 2 g/day plus simvastatin 20 mg/day ( N = 29 ) or placebo plus simvastatin 20 mg/day ( N = 29 ) for a total of 12 weeks . Lp(a ) was significantly reduced in the l-carnitine/simvastatin group [ −19.4 % , from 52 ( 20–171 ) to 42 ( 15–102 ) mg/dL ; p = 0.01 ] , but not in the placebo/simvastatin group [ −6.7 % , from 56 ( 26–108 ) to 52 ( 27–93 ) mg/dL , p = NS versus baseline and p = 0.016 for the comparison between groups ] . Similar significant reductions in total cholesterol , LDL-C , apolipoprotein ( apo ) B and TAG were observed in both groups . Co-administration of l-carnitine with simvastatin was associated with a significant , albeit modest , reduction in Lp(a ) compared with simvastatin monotherapy in subjects with mixed hyperlipidemia and elevated baseline Lp(a ) levels",
"BACKGROUND Centenarians are characterized by weakness , decreasing mental health , impaired mobility , and poor endurance . L-Carnitine is an important contributor to cellular energy metabolism . OBJECTIVE This study evaluated the efficacy of L-carnitine on physical and mental fatigue and on cognitive functions of centenarians . DESIGN This was a placebo-controlled , r and omized , double-blind , 2-phase study . Sixty-six centenarians with onset of fatigue after even slight physical activity were recruited to the study . The 2 groups received either 2 g levocarnitine once daily ( n = 32 ) or placebo ( n = 34 ) . Efficacy measures included changes in total fat mass , total muscle mass , serum triacylglycerol , total cholesterol , HDL cholesterol , LDL cholesterol , Mini-Mental State Examination ( MMSE ) , Activities of Daily Living , and a 6-min walking corridor test . RESULTS At the end of the study period , the levocarnitine-treated centenarians , compared with the placebo group , showed significant improvements in the following markers : total fat mass ( -1.80 compared with 0.6 kg ; P total muscle mass ( 3.80 compared with 0.8 kg ; P plasma concentrations of total carnitine ( 12.60 compared with -1.70 mumol ; P plasma long-chain acylcarnitine ( 1.50 compared with -0.1 micromol ; P plasma short-chain acylcarnitine ( 6.0 compared with -1.50 micromol ; P physical fatigue ( -4.10 compared with -1.10 ; P mental fatigue ( -2.70 compared with 0.30 ; P fatigue severity ( -23.60 compared with 1.90 ; P MMSE ( 4.1 compared with 0.6 ; P levocarnitine produces a reduction of total fat mass , increases total muscular mass , and facilitates an increased capacity for physical and cognitive activity by reducing fatigue and improving cognitive functions",
"Background : The effects of L-carnitine on the hemodynamic state of chronic hemodialysis patients have been debated . In order to clarify the effect of administered L-carnitine on cardiac function and hypotensive episodes during the hemodialysis procedure , a r and omized double-blind placebo-controlled study was performed for 3 months . Methods and Results : Twenty stable out patients undergoing hemodialysis treatment were divided into two groups : controls ( placebo ) and treated patients ( L-carnitine 900 mg p.o . daily ) . After 3 months , cardiac function was reevaluated by echocardiography , and hypotensive episodes during hemodialysis were assessed . Free and acyl carnitine levels increased significantly from 22.3 ± 7.1 to 140.3 ± 57.5 μmol/l and from 15.8 ± 2.8 to 94.8 ± 50.4 μmol/l , respectively , in the treated group . The ejection fraction significantly increased from 61.8 ± 16.0 to 64.4 ± 13.8 % ( p no difference in other echocardiographic parameters between the two groups . Hypotensive episodes significantly decreased from 4.0 ± 1.7 to 1.3 ± 0.9 times per month ( p patients ' body weight did not change significantly . Conclusions : Beneficial effects of L-carnitine on the hemodynamic state of chronic hemodialysis patients were observed . L-Carnitine supplementation might be considered especially for chronic hemodialysis patients with unstable hemodynamic conditions",
"BACKGROUND Patients with type 2 diabetes are under high oxidative stress , and levels of hyperglycemia correlate strongly with levels of LDL oxidation . Carnitine favorably modulates oxidative stress . OBJECTIVE This objective of this study was to evaluate the efficacy of L-carnitine on the reduction of oxidized LDL cholesterol in patients with type 2 diabetes . DESIGN Eighty-one patients with diabetes were r and omly assigned to 1 of 2 treatment groups for 3 mo . The 2 groups received either 2 g L-carnitine once daily ( n = 41 ) or placebo ( n = 40 ) . The following variables were assessed at baseline , after washout , and at 1 , 2 , and 3 mo of treatment : body mass index , fasting plasma glucose , glycosylated hemoglobin , total cholesterol , LDL cholesterol , HDL cholesterol , triglycerides , apolipoprotein A1 , apolipoprotein B-100 , oxidized LDL cholesterol , thiobarbituric acid-reactive substances , and conjugated dienes . RESULTS At the end of the study period , the L-carnitine-treated patients showed significant improvements compared with the placebo group in the following markers : oxidized LDL levels decreased by 15.1 compared with 3.0 U/L ( P LDL cholesterol decreased by 0.45 compared with 0.16 mmol/L ( P triglycerides decreased by 1.02 compared with 0.09 mmol/L ( P apolipoprotein A1 concentrations decreased by 0.12 compared with 0.03 mg/dL ( P apolipoprotein B-100 concentrations decreased by 0.13 compared with 0.04 mg/dL ( P thiobarbituric acid-reactive substance concentrations decreased by 1.92 compared with 0.05 ( P conjugated diene concentrations decreased by 0.72 compared with 0.11 in the placebo group ( P L-carnitine reduces oxidized LDL cholesterol levels in patients with type 2 diabetes",
"The effects of adding L-carnitine to a whole-body and respiratory training program were determined in moderate-to-severe chronic obstructive pulmonary disease ( COPD ) patients . Sixteen COPD patients ( 66 + /- 7 years ) were r and omly assigned to L-carnitine ( CG ) or placebo group ( PG ) that received either L-carnitine or saline solution ( 2 g/day , orally ) for 6 weeks ( forced expiratory volume on first second was 38 + /- 16 and 36 + /- 12 % , respectively ) . Both groups participated in three weekly 30-min treadmill and threshold inspiratory muscle training sessions , with 3 sets of 10 loaded inspirations ( 40 % ) at maximal inspiratory pressure . Nutritional status , exercise tolerance on a treadmill and six-minute walking test , blood lactate , heart rate , blood pressure , and respiratory muscle strength were determined as baseline and on day 42 . Maximal capacity in the incremental exercise test was significantly improved in both groups ( P Blood lactate , blood pressure , oxygen saturation , and heart rate at identical exercise levels were lower in CG after training ( P Inspiratory muscle strength and walking test tolerance were significantly improved in both groups , but the gains of CG were significantly higher than those of PG ( 40 + /- 14 vs 14 + /- 5 cmH2O , and 87 + /- 30 vs 34 + /- 29 m , respectively ; P Blood lactate concentration was significantly lower in CG than in PG ( 1.6 + /- 0.7 vs 2.3 + /- 0.7 mM , P exercise tolerance and inspiratory muscle strength in COPD patients , as well as reduce lactate production",
"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",
"OBJECTIVES Carnitine deficiency impairs fatty acid beta-oxidation and may partly explain weight gain in valproate-treated patients . The aim of this study was to determine whether l-carnitine supplementation improves weight loss outcomes in bipolar patients taking sodium valproate . METHODS Sixty bipolar patients with clinical ly significant weight gain thought to be related to sodium valproate , who had been taking sodium valproate for > or=6 months , were r and omized to l-carnitine ( 15 mg/kg/day ) or placebo for 26 weeks , in conjunction with a moderately energy-restricted , low-fat diet . The primary outcome measure was weight change . RESULTS l-carnitine had no effect on mean weight loss compared with placebo ( -1.9 kg versus - 0.9 kg ) ( F = 0.778 , df = 1,58 , p = 0.381 ) . The number of people in each group able to lose any weight was identical ( = 0 , p = 1.0 ) ; more patients in the carnitine group ( nine versus five ) achieved a clinical ly significant weight loss ( > or=5 % ) but this was not statistically significant ( p = 1.0 , Fisher 's exact test ) . CONCLUSIONS At the dose prescribed in this study carnitine supplementation did not improve weight loss outcomes in valproate-treated bipolar patients consuming an energy-restricted , low-fat diet",
"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",
"Background Resting and postpr and ial oxidative stress is elevated in those with metabolic disorders such as diabetes . Antioxidant supplementation may attenuate the rise in oxidative stress following feeding . Therefore we sought to determine the effects of acetyl L-carnitine arginate ( ALCA ) on resting and postpr and ial biomarkers of glucose and lipid metabolism , as well as oxidative stress . Methods Twenty-nine pre-diabetic men and women were r and omly assigned to either 3 g·day-1 of ALCA ( n = 14 ; 31 ± 3 yrs ) or placebo ( n = 15 ; 35 ± 3 yrs ) in a double-blind design , to consume for eight weeks . Fasting blood sample s were taken from subjects both pre and post intervention . After each fasting sample was obtained , subjects consumed a high fat , high carbohydrate meal and additional blood sample s were taken at 1 , 2 , 4 , and 6 hours post meal . Sample s were analyzed for a variety of metabolic variables ( e.g. , glucose , HbA1c , lipid panel , C-reactive protein , nitrate/nitrite , and several markers of oxidative stress ) . Area under the curve ( AUC ) was calculated for each variable measured post meal , both pre and post intervention . Results ALCA , but not placebo , result ed in an increase in nitrate/nitrite ( 25.4 ± 1.9 to 30.1 ± 2.8 μmol·L-1 ) from pre to post intervention , with post intervention values greater compared to placebo ( p = 0.01 ) . No other changes of statistical significance were noted ( p > 0.05 ) , although ALCA result ed in slight improvements in glucose ( 109 ± 5 to 103 ± 5 mg·dL-1 ) , HbA1c ( 6.6 ± 1.1 to 6.2 ± 1.2 % ) , and HOMA-IR ( 3.3 ± 1.3 to 2.9 ± 1.2 ) . AUC postpr and ial data were not statistically different between ALCA and placebo for any variable ( p > 0.05 ) . However , nitrate/nitrite demonstrated a moderate effect size ( r = 0.35 ) for increase from pre ( 139.50 ± 18.35 μmol·L-1·6 hr-1 ) to post ( 172.40 ± 21.75 μmol·L-1·6 hr-1 ) intervention with ALCA , and the magnitude of decrease following feeding was not as pronounced as with placebo . ConclusionS upplementation with ALCA results in an increase in resting nitrate/nitrite in pre-diabetics , without any statistically significant change in other metabolic or oxidative stress variables measured at rest or post meal",
"INTRODUCTION Dyslipidemia and high serum lipoprotein(a ) are among the risk factors for cardiovascular diseases in hemodialysis patients . Statins as a first line of therapy in hyperlipidemia does not always reduce the serum lipoprotein(a ) level . Several studies have reported the lipid-lowering effects of carnitine and coenzyme Q10 in hemodialysis patients . This study was design ed to investigate the effects of carnitine and coenzyme Q10 on serum lipid profile and lipoprotein(a ) level in maintenance hemodialysis patients . MATERIAL S AND METHODS This was a r and omized placebo-controlled trial . We studied on hemodialysis patients who were on treatment with atorvastatin or lovastatin to assess the efficacy of supplement therapy . They were divided into 4 groups to receive carnitine , coenzyme Q10 , both carnitine and coenzyme Q10 , and placebo . After a 3-month experiment , blood sample s were collected to measure serum levels of lipoprotein(a ) , triglyceride , total cholesterol , high-density lipoprotein cholesterol and low-density lipoprotein cholesterol . RESULTS Fifty-two hemodialysis patients , 27 men and 25 women , completed the course of the study . Three months after supplement therapy , serum levels of lipoprotein(a ) reduced significantly in the carnitine , coenzyme Q10 , and combination groups compared to the baseline values and the 3-month value of lipoprotein(a ) in the placebo group ( P = .01 ) . Serum levels of triglyceride and other lipoproteins did not significantly alter . CONCLUSIONS Our study showed that supplementation with carnitine and coenzyme Q10 could reduce serum levels of lipoprotein(a ) in maintenance hemodialysis patients treated with statins",
"OBJECTIVE To determine whether acetyl-L-carnitine ( ALC ) , a metabolite necessary for energy metabolism and essential fatty acid anabolism , might help attention-deficit/hyperactivity disorder ( ADHD ) . Trials in Down 's syndrome , migraine , and Alzheimer 's disease showed benefit for attention . A preliminary trial in ADHD using L-carnitine reported significant benefit . METHOD A multi-site 16-week pilot study r and omized 112 children ( 83 boys , 29 girls ) age 5 - 12 with systematic ally diagnosed ADHD to placebo or ALC in weight-based doses from 500 to 1500 mg b.i.d . The 2001 revisions of the Conners ' parent and teacher scales ( including DSM-IV ADHD symptoms ) were administered at baseline , 8 , 12 , and 16 weeks . Analyses were ANOVA of change from baseline to 16 weeks with treatment , center , and treatment-by-center interaction as independent variables . RESULTS The primary intent-to-treat analysis , of 9 DSM-IV teacher-rated inattentive symptoms , was not significant . However , secondary analyses were interesting . There was significant ( p = 0.02 ) moderation by subtype : superiority of ALC over placebo in the inattentive type , with an opposite tendency in combined type . There was also a geographic effect ( p = 0.047 ) . Side effects were negligible ; electrocardiograms , lab work , and physical exam unremarkable . CONCLUSION ALC appears safe , but with no effect on the overall ADHD population ( especially combined type ) . It deserves further exploration for possible benefit specifically in the inattentive type",
"Background Cachexia , a > 10 % loss of body-weight , is one factor determining the poor prognosis of pancreatic cancer . Deficiency of L-Carnitine has been proposed to cause cancer cachexia . Findings We screened 152 and enrolled 72 patients suffering from advanced pancreatic cancer in a prospect i ve , multi-centre , placebo-controlled , r and omized and double-blinded trial to receive oral L-Carnitine ( 4 g ) or placebo for 12 weeks . At entry patients reported a mean weight loss of 12 ± 2,5 ( SEM ) kg . During treatment body-mass-index increased by 3,4 ± 1,4 % under L-Carnitine and decreased ( −1,5 ± 1,4 % ) in controls ( p Moreover , nutritional status ( body cell mass , body fat ) and quality -of-life parameters improved under L-Carnitine . There was a trend towards an increased overall survival in the L-Carnitine group ( median 519 ± 50 d versus 399 ± 43 d , not significant ) and towards a reduced hospital-stay ( 36 ± 4d versus 41 ± 9d , n.s . ) . Conclusion While these data are preliminary and need confirmation they indicate that patients with pancreatic cancer may have a clinical ly relevant benefit from the inexpensive and well tolerated oral supplementation of L-Carnitine ",
"Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness , cataplexy , and rapid eye movement ( REM ) sleep abnormalities . A genome-wide association study ( GWAS ) identified a novel narcolepsy-related single nucleotide polymorphism ( SNP ) , which is located adjacent to the carnitine palmitoyltransferase 1B ( CPT1B ) gene encoding an enzyme involved in β-oxidation of long-chain fatty acids . The mRNA expression levels of CPT1B were associated with this SNP . In addition , we recently reported that acylcarnitine levels were abnormally low in narcolepsy patients . To assess the efficacy of oral l-carnitine for the treatment of narcolepsy , we performed a clinical trial administering l-carnitine ( 510 mg/day ) to patients with the disease . The study design was a r and omized , double-blind , cross-over and placebo-controlled trial . Thirty narcolepsy patients were enrolled in our study . Two patients were withdrawn and 28 patients were included in the statistical analysis ( 15 males and 13 females , all with HLA-DQB1 * 06:02 ) . l-carnitine treatment significantly improved the total time for dozing off during the daytime , calculated from the sleep logs , compared with that of placebo-treated periods . l-carnitine efficiently increased serum acylcarnitine levels , and reduced serum triglycerides concentration . Differences in the Japanese version of the Epworth Sleepiness Scale ( ESS ) and the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) vitality and mental health subscales did not reach statistical significance between l-carnitine and placebo . This study suggests that oral l-carnitine can be effective in reducing excessive daytime sleepiness in narcolepsy patients . Trial Registration University hospital Medical Information Network ( UMIN )",
"Therapeutic modulation of low-density lipoprotein ( LDL ) size could be of benefit in reducing the risk of cardiovascular events in diabetic patients . This study evaluated the efficacy of L-carnitine on the size of LDL particles in type 2 diabetes mellitus patients treated with simvastatin . Eighty diabetic patients were r and omly assigned to 1 of 2 treatment groups for 3 months . The 2 groups received either simvastatin monotherapy 20 mg ( n = 40 ) or L-carnitine 2 g/d and simvastatin 20 mg ( n = 40 ) . The following variables were assessed at baseline ; after washout ; and at 1 , 2 , and 3 months of treatment : body mass index , fasting plasma glucose , glycosylated hemoglobin , total cholesterol , LDL cholesterol , LDL subclasses , LDL size , high-density lipoprotein cholesterol , triglycerides , apolipoprotein A-1 , and apolipoprotein B-100 . After 12 weeks , comparing the 2 groups , we observed a decrease in fasting plasma glucose ( 1.45 vs 0.61 mmol/L , P glycosylated hemoglobin ( 0.2 % vs 0.4 % , P total cholesterol ( 2.07 vs 1.45 mmol/L , P LDL ( 1.65 vs 1.29 mmol/L , P triglycerides ( 1.36 vs 0.41 mmol/L , P apo B-100 ( 49 vs 9 g/L , P small-sized LDL proportion ( 10.8 % vs 4.9 % , P LDL particle size increased ( 6 vs 3 A , P HDL increased ( 0.2 vs 0.11 mmol/L , P small-sized LDL proportion and an increase in LDL particle size",
"BACKGROUND A previous study has demonstrated that L-carnitine reduces plasma lipoprotein(a ) ( Lp[a ] ) levels in patients with hypercholesterolemia . OBJECTIVE To test a tolerable Lp(a)-reducing agent in diabetic patients , we assessed the effect of a dietary supplementation of L-carnitine on plasma lipid levels , particularly Lp(a ) , of patients with type 2 diabetes mellitus ( DM ) and hypercholesterolemia . METHODS In this 6-month , r and omized , double-masked , placebo-controlled clinical trial , patients were enrolled , assessed , and followed up at the Diabetic and Metabolic Diseases Center of the Department of Internal Medicine and Therapeutics at the University of Pavia , Pavia , Italy . All study patients had newly diagnosed type 2 DM that was managed through dietary restriction alone throughout the study , as well as hypercholesterolemia . Patients were r and omized to 1 of 2 groups . One group received L-carnitine , one 1-g tablet BID . The other group received a corresponding placebo . We assessed body mass index , fasting plasma glucose , postpr and ial plasma glucose , glycosylated hemoglobin , fasting plasma insulin , total cholesterol , low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , triglycerides , apolipoprotein ( apo ) A-I , apo B , and Lp(a ) at baseline and at 1 , 3 , and 6 months of treatment . RESULTS This study included 94 patients . The treatment group included 24 men and 22 women ( mean [ SD ] age , 52 [ 6 ] years ) . The placebo group included 23 men and 25 women ( mean [ SD ] age , 50 [ 7 ] years ) . The baseline characteristics of the groups did not differ significantly . The mean ( SD ) body weight , height , and body mass index were 78.2 ( 5.8 ) kg , 1.70 ( 0.04 ) m , and 27.3 ( 2.5 ) kg/m(2 ) , respectively , in the L-carnitine group and 77.6 ( 6.4 ) kg , 1.71 ( 0.05 ) m , and 26.8 ( 2.2 ) kg/m(2 ) , respectively , in the placebo group . In the treatment group , Lp(a ) was significantly reduced at 3 and 6 months compared with baseline ( P Lp(a ) value in patients taking L-carnitine compared with those taking placebo . Between-group differences in other variables did not reach a level of significance at months 3 and 6 . No drug-related adverse events were reported or observed . CONCLUSION In this preliminary study , after 3 and 6 months , L-carnitine significantly lowered the plasma Lp(a ) level compared with placebo in selected hypercholesterolemic patients with newly diagnosed type 2 DM",
"Background / Objectives : Pemphigus vulgaris ( PV ) , as an autoimmune disease including mucosa and the skin , is associated with several complications and comorbidities . The present study planned to determine the effect of L-carnitine ( LC ) supplementation on biomarkers of oxidative stress ( OS ) , antioxidant capacity and lipid profile in PV patients .Subjects/ Methods Fifty two control and patients with PV , participated in the current r and omized , double-blind , placebo-controlled clinical trial . The patients were allocated r and omly to receive 2 g per day LC tartrate subdivided into two equal doses of 1 g before breakfast and dinner ( n=26 ) or placebo ( n=26 ) for 8 weeks . Anthropometric , lipid profile and OS values were determined at baseline and end of intervention period . Results : LC intake significantly reduced serum levels of triglycerides , total- , LDL- cholesterol and oxidative stress index ( OSI ; P levels of total antioxidant capacity ( TAC ) ( P=0.05 ) and serum carnitine ( P serum total oxidant capacity ( P=0.15 ) and HDL- cholesterol ( P=0.06 ) in comparison to the placebo . Conclusions : LC consumption may have favorable results on TAC , OSI and lipid profiles in patients with PV . The results were in line with the idea that LC supplementation can be associated with positive effects on metabolic status and OS of patients with PV",
"The aim of the study was to evaluate the effects of 12-month treatment with sibutramine plus L-carnitine compared with sibutramine alone on body weight , glycemic control , insulin resistance , and inflammatory state in type 2 diabetes mellitus patients . Two hundred fifty-four patients with uncontrolled type 2 diabetes mellitus ( glycated hemoglobin [ HbA(1c ) ] > 8.0 % ) in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and r and omized to take sibutramine 10 mg plus L-carnitine 2 g or sibutramine 10 mg in monotherapy . We evaluated at baseline and after 3 , 6 , 9 , and 12 months these parameters : body weight , body mass index , HbA(1c ) , fasting plasma glucose , postpr and ial plasma glucose , fasting plasma insulin , homeostasis model assessment of insulin resistance index , total cholesterol , low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , triglycerides , leptin , tumor necrosis factor-α , adiponectin , vaspin , and high-sensitivity C-reactive protein . Sibutramine plus L-carnitine gave a faster improvement of fasting plasma glucose , postpr and ial plasma glucose , lipid profile , leptin , tumor necrosis factor-α , and high-sensitivity C-reactive protein compared with sibutramine alone . Furthermore , there was a better improvement of body weight , HbA(1c ) , fasting plasma insulin , homeostasis model assessment of insulin resistance index , vaspin , and adiponectin with sibutramine plus L-carnitine compared with sibutramine alone . Sibutramine plus L-carnitine gave a better and faster improvement of all the analyzed parameters compared with sibutramine alone without giving any severe adverse effect",
" 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 ",
"BACKGROUND Fat metabolism is known to be altered in hypertriglyceridemia . Fat oxidation requires carnitine , which can be obtained either from the diet ( animal or dairy products ) or through synthesis in the body using both lysine and vitamin B(6 ) . OBJECTIVE The goal of this study was to investigate the effect of lysine , vitamin B(6 ) , and carnitine supplementation on both glycemia and the lipid profiles , specifically triglyceride ( TG ) levels , in men with hypertriglyceridemia . METHODS This 12-week , r and omized , placebo-controlled clinical trial was conducted at a Lebanese medical center . A total of 85 hypertriglyceridemic ( TG > 150 mg/dL ) male patients were r and omized to 1 of 5 groups and given supplements of lysine ( 1 g/d ) , vitamin B(6 ) ( 50 mg/d ) , lysine ( 1 g/d ) + vitamin B(6 ) ( 50 mg/d ) , carnitine ( 1 g/d ) , or placebo for 12 weeks . The lipid profile ( TG , total cholesterol , LDL-C , and HDL-C ) and fasting plasma glucose levels were assessed at baseline and at 6 and 12 weeks . RESULTS Adults ( ∼50 years ) Lebanese males from a low socioeconomic status in Beirut were given the appropriate supplements . Vitamin B(6 ) supplementation was associated with a significant reduction in total cholesterol and HDL-C of ∼10 % . In addition , plasma TG was reduced by 36.6 mg/dL at 6 weeks , whereas levels in the placebo group increased by 18 mg/dL ; this difference failed to reach statistical significance . No major changes in the lipid profile were observed in the lysine and carnitine groups or when lysine was added to vitamin B(6 ) . CONCLUSION Vitamin B(6 ) supplementation in these male patients with hypertriglyceridemia reduced plasma total cholesterol and HDL-C concentrations ",
"Aim : The aim of the present study was to compare the effects of simvastatin and L-carnitine coadministration versus simvastatin monotherapy on lipid profile , lipoprotein(a ) ( Lp(a ) ) and apoprotein(a ) ( Apo(a ) ) levels in type II diabetic patients . Patients / methods : In this double-blind , r and omized clinical trial , 75 patients were assigned to one of two treatment groups for 4 months . Group A received simvastatin monotherapy ; group B received L-carnitine and simvastatin . The following variables were assessed at baseline , after washout and at 1 , 2 , 3 and 4 months of treatment : body mass index , fasting plasma glucose , glycated hemoglobin , total cholesterol , low-density lipoprotein ( LDL ) cholesterol , high-density lipoprotein ( HDL ) cholesterol , triglycerides , Apolipoprotein A1 , Apo B , lipoprotein(a ) and apoprotein(a ) . Results : At the end of treatment in the carnitine and simvastatin combined group compared with the simvastatin alone group , we observed a significant decrease in glycemia ( p tryglicerides ( p Apo B ( p Lp(a ) ( p apo(a ) ( p HDL significantly increased ( p carnitine and simvastatin result ed in a significant reduction in Lp(a ) and apo(a ) and may represent a new therapeutic option in reducing plasma Lp(a ) levels , LDL cholesterol and Apo B100",
"To evaluate the effects of 1-year treatment with orlistat plus L-carnitine compared to orlistat alone on body weight , glycemic and lipid control , and inflammatory parameters in obese type 2 diabetic patients . Two hundred and fifty-eight patients with uncontrolled type 2 diabetes mellitus ( T2DM ) [ glycated hemoglobin ( HbA(1c ) ) > 8.0 % ] in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and r and omized to take orlistat 120 mg three times a day plus L-carnitine 2 g one time a day or orlistat 120 mg three times a day . We evaluated the following parameters at baseline and after 3 , 6 , 9 , and 12 months : body weight , body mass index ( BMI ) , glycated hemoglobin ( HbA(1c ) ) , fasting plasma glucose ( FPG ) , postpr and ial plasma glucose ( PPG ) , fasting plasma insulin ( FPI ) , homeostasis model assessment insulin resistance index ( HOMA-IR ) , total cholesterol ( TC ) , low-density lipoprotein cholesterol ( LDL-C ) , high-density lipoprotein cholesterol ( HDL-C ) , triglycerides ( Tg ) , adiponectin ( ADN ) , leptin , tumor necrosis factor-α ( TNF-α ) , vaspin , and high-sensitivity C-reactive protein ( Hs-CRP ) . We observed a better decrease in body weight , glycemic profile , HOMA-IR , LDL-C , and ADN and a faster improvement in FPI , TC , Tg , leptin , TNF-α , Hs-CRP with orlistat plus L-carnitine compared to orlistat alone . We also recorded an improvement in vaspin with orlistat plus l-carnitine not reached with orlistat alone . Orlistat plus L-carnitine gave a better improvement in body weight , glycemic and lipid profile compared to orlistat alone ; furthermore , a faster and better improvement in inflammatory parameters was observed with orlistat plus L-carnitine compared to orlistat alone",
"OBJECTIVE We studied the effects of l-carnitine supplement on serum amyloid A ( SAA ) , a systemic inflammation marker , and vascular inflammation markers in hemodialysis patients . DESIGN This was a r and omized , double-blind , placebo-controlled trial . SETTING The study was performed in Soodeh Hemodialysis Center in Islamshahr , Iran . PATIENTS We included 36 hemodialysis patients ( 15 men and 21 women ) . INTERVENTION The patients on hemodialysis were r and omly assigned to either a carnitine or a placebo group . Patients in the carnitine group received 1,000 mg/day oral l-carnitine for 12 weeks , whereas patients in the placebo group received a corresponding placebo during the study . MAIN OUTCOME MEASURES Serum free carnitine , SAA , soluble intercellular adhesion molecule type 1 , soluble intercellular adhesion molecule type 2 , soluble vascular cell adhesion molecule type 1 , sE-selectin , sP-selectin , and oxidized low-density lipoprotein were measured at baseline and at the end of week 12 of the study . RESULTS Mean serum free carnitine concentration increased significantly to 150 % of baseline in the carnitine group at the end of week 12 ( P serum SAA showed a significant 32 % decrease ( P serum concentrations of free carnitine and SAA in the placebo group during the study . There were no significant differences between the two groups in mean changes in serum soluble intercellular adhesion molecule type 1 , soluble intercellular adhesion molecule type 2 , soluble vascular cell adhesion molecule type 1 , sE-selectin , sP-selectin , and oxidized low-density lipoprotein concentrations . CONCLUSION The study indicates that l-carnitine supplement reduces serum SAA , which is a risk factor for cardiovascular diseases in hemodialysis patients , but has no effect on vascular inflammation markers",
"BACKGROUND Patients on long-term hemodialysis become deficient in carnitine and are frequently treated with carnitine supplementation to offset their renal anemia , lipid abnormality and cardiac dysfunction . The therapeutic value of carnitine supplementation on left ventricular hypertrophy ( LVH ) in patients with normal cardiac systolic function remains uncertain . METHODS AND RESULTS The cardiac morphology and function of 10 patients given 10 mg/kg of L-carnitine orally , immediately after hemodialysis sessions 3 times per week for a 12-month period were compared with 10 untreated control patients . Using echocardiography , left ventricular fractional shortening ( LVFS ) and left ventricular mass index ( LVMI ) were measured before and after the study period . As a result , amounts of serum-free carnitine increased from 28.4+/-4.7 to 58.5+/-12.1 micromol/L. The LVMI decreased significantly from 151.8+/-21.2 to 134.0+/-16.0 g/m(2 ) in treated patients ( p LVMI in untreated control patients did not change significantly ( ie , from 153.3+/-28.2 to 167.1+/-43.1 g/m(2 ) ) . However , LVFS values remained unchanged in both groups . Although L-carnitine promoted a 31 % reduction in erythropoietin requirements , hematocrit and blood pressure did not change during the study period . CONCLUSIONS Supplementation with L-carnitine induced regression of LVH in patients on hemodialysis , even for those with normal systolic function",
"Aim Levocarnitine is an important contributor to cellular energy metabolism . This study aims to evaluate the effects of levocarnitine supplementation on body composition , lipid profile and fatigue in elderly subjects with rapid muscle fatigue . Method This was a placebo-controlled , r and omised , double-blind , two-phase study . Eighty-four elderly subjects with onset of fatigue following slight physical activity were recruited to the study . Prior to r and omisation all patients entered a 2-week normalisation phase where they were given an ‘ ad libitum ’ diet , according to the National Cholesterol Education Program ( Step 2 ) . Subjects were asked to record their daily food intake every 2 days . Before the 30-day treatment phase , subjects were r and omly assigned to two groups ( matched for male/female ratio , age and body mass index ) . One group received levocarnitine 2 g twice daily ( n = 42 ) and the other placebo ( n = 42 ) . Efficacy measures included changes in total fat mass , total muscle mass , serum triglyceride , total cholesterol , high-density lipoprotein-cholesterol ( HDL-C ) , low-density lipoprotein-cholesterol ( LDL-C ) , apolipoprotein (apo)A1 , and apoB levels . The Wessely and Powell scale was used to evaluate physical and mental fatigue . Subjects were assessed at the beginning and end of the study period . Results At the end of the study , compared with placebo , the levocarnitine-treated patients showed significant improvements in the following parameters : total fat mass ( −3.1 vs −0.5 kg ) , total muscle mass ( + 2.1 vs + 0.2 kg ) , total cholesterol ( −1.2 vs + 0.1 mmol/L ) , LDL-C ( −1.1 vs −0.2 mmol/L ) , HDL-C ( + 0.2 vs + 0.01 mmol/ L ) , triglycerides ( −0.3 vs 0.0 mmol/L ) , apoA1 ( −0.2 vs 0.0 g/L ) , and apoB ( −0.3 vs −0.1 g/L ) . Wessely and Powell scores decreased significantly by 40 % ( physical fatigue ) and 45 % ( mental fatigue ) in subjects taking levocarnitine , compared with 11 % and 8 % , respectively , in the placebo group ( p No adverse events were reported in any treatment group . Conclusion Administration of levocarnitine to healthy elderly subjects result ed in a reduction of total fat mass , an increase of total muscle mass , and appeared to exert a favourable effect on fatigue and serum lipids",
"Scattered reports indicate that L-carnitine may suppress proinflammatory cytokines in sick individuals without renal disease and may improve protein synthesis or nitrogen balance either in patients without renal disease or in maintenance hemodialysis ( MHD ) or chronic peritoneal dialysis patients . We conducted an experimental study in MHD patients to evaluate the effects of L-carnitine treatment on inflammatory and protein-energy nutritional status . MHD patients were assigned to receive intravenous injections of L-carnitine 20 mg/kg ( n = 48 ) or placebo ( n = 65 ) thrice weekly at the end of each hemodialysis treatment for 6 months . The carnitine-treated group showed a statistically significant decrease in serum C-reactive protein and increase in serum albumin and transferrin , blood hemoglobin , and body mass index . Conversely , in the placebo-treated group , a significant decrease was reported for serum albumin , serum transferrin , and body mass index , whereas the other considered measures did not change significantly . These preliminary findings suggest that in MHD patients , L-carnitine therapy may suppress inflammation , particularly among those patients with C-reactive protein > or =3 mg/dL , and may improve protein-energy nutritional status",
"INTRODUCTION Carnitine supplementation may improve the general health and quality of life of hemodialysis patients by improving adipokines levels . The aim of the study was to investigate the effects of L-carnitine supplementation on leptin levels , adiponectin levels , and body weight of hemodialysis patients . MATERIAL S AND METHODS Fifty hemodialysis patients were r and omly divided into the carnitine group , who received oral L-carnitine , 1 g/L for 3 months , and the control group . Anthropometric measurements and serum levels of adipokines were measured at baseline and at the end of the intervention . RESULTS Forty-two participants completed the study . Serum leptin concentrations decreased after 12 weeks of the intervention in both groups , but these changes were not significant . The mean change of leptin concentration were , -1.7 ± 19.0 µg/mL and -7.1 ± 20.0 µg/mL in the carnitine group and the control group , respectively ( P = .39 ) . The mean adiponectin levels at baseline and after the intervention were 8.6 ± 11.19 µg/mL and 9.8 ± 4.1 µg/mL in the carnitine group ( P = .67 ) and 5.0 ± 2.5 µg/mL and 11.2 ± 5.4 µg/mL in the control group , respectively ( P increased significantly in the control group only . The decrease in body mass index was not significant . CONCLUSIONS This study showed that a daily supplementation of 1000 mg oral syrup of L-carnitine for 12 weeks did not affect leptin and adiponectin levels or the body weight or body mass index of hemodialysis patients",
"OBJECTIVE To evaluate the effects of one year of treatment with sibutramine plus L-carnitine compared to sibutramine on body weight , glycemic control , and insulin resistance state in type 2 diabetic patients . METHODS Two hundred and fifty-four patients with uncontrolled type 2 diabetes mellitus ( T2DM ) [ glycated hemoglobin ( HbA(1c ) ) > 8.0 % ] in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and r and omised to take sibutramine 10 mg plus L-carnitine 2 g or sibutramine 10 mg in monotherapy . We evaluated at baseline , and after 3 , 6 , 9 , and 12 months these parameters : body weight , body mass index ( BMI ) , glycated hemoglobin ( HbA(1c ) ) , fasting plasma glucose ( FPG ) , post-pr and ial plasma glucose ( PPG ) , fasting plasma insulin ( FPI ) , homeostasis model assessment insulin resistance index ( HOMA-IR ) , total cholesterol ( TC ) , low density lipoprotein-cholesterol ( LDL-C ) , high density lipoprotein-cholesterol ( HDL-C ) , triglycerides ( Tg ) , retinol binding protein-4 ( RBP-4 ) , resistin , visfatin , high sensitivity-C reactive protein ( Hs-CRP ) . RESULTS There was a decrease in body weight , BMI , HbA(1c ) , FPI , HOMA-IR , and RBP-4 in both groups , even when the values obtained with sibutramine plus L-carnitine were lower than the values obtained in sibutramine group . There was a faster decrease of FPG , PPG , TC , LDL-C , resistin and Hs-CRP with sibutramine plus L-carnitine even when no differences between the two groups were obtained . Furthermore , only sibutramine plus L-carnitine improved Tg , and visfatin . CONCLUSION Sibutramine plus L-carnitine gave a faster improvement of lipid profile , insulin resistance parameters , glycemic control , and body weight compared to sibutramine",
" BACKGROUND AND OBJECTIVE A phase III r and omised study was carried out to establish the most effective and safest treatment to improve the primary endpoints of cancer cachexia : lean body mass ( LBM ) , resting energy expenditure ( REE ) , fatigue ; and relevant secondary endpoints : appetite , quality of life , grip strength , Glasgow Prognostic Score ( GPS ) and proinflammatory cytokines . PATIENTS Three hundred and thirty-two assessable patients with cancer-related anorexia/cachexia syndrome ( CACS ) were r and omly assigned to one of five arms of treatment : 1 - -medroxyprogesterone 500 mg/d or megestrol acetate 320 mg/d ; 2 - -oral supplementation with eicosapentaenoic acid ( EPA ) ; 3 - -L-carnitine 4 g/d ; 4 - -thalidomide 200 mg/d ; 5 - -a combination of the above . Treatment duration : 4 months . RESULTS Analysis of variance showed a significant difference between the treatment arms . A post hoc analysis showed the superiority of arm 5 over the others for all primary endpoints . An analysis of changes from baseline showed that LBM ( by dual-energy X-ray absorptiometry and by L3 computed tomography ) significantly increased in arm 5 . REE decreased significantly and fatigue improved significantly in arm 5 . Appetite increased significantly in arm 5 . IL-6 decreased significantly in arm 5 and 4 . GPS significantly decreased in arms 5 , 4 and 3 . Total daily physical activity showed that total energy and active energy expenditure increased significantly in arm 5 . Eastern Cooperative Oncology group-Performance Status ( ECOG-PS ) significantly decreased in arms 5 , 4 and 3 . Toxicity was substantially negligible , comparable between treatment arms . CONCLUSIONS The most effective treatment for all three primary efficacy endpoints as well as secondary endpoints appetite , IL-6 , GPS and ECOG PS was the combination regimen that included all selected agents",
"PURPOSE A phase III , r and omized study was carried out to establish the most effective and safest treatment to improve the primary endpoints of cancer cachexia-lean body mass ( LBM ) , resting energy expenditure ( REE ) , and fatigue- and relevant secondary endpoints : appetite , quality of life , grip strength , Glasgow Prognostic Score ( GPS ) and proinflammatory cytokines . PATIENTS AND METHODS Three hundred thirty-two assessable patients with cancer-related anorexia/cachexia syndrome were r and omly assigned to one of five treatment arms : arm 1 , medroxyprogesterone ( 500 mg/day ) or megestrol acetate ( 320 mg/day ) ; arm 2 , oral supplementation with eicosapentaenoic acid ; arm 3 , L-carnitine ( 4 g/day ) ; arm 4 , thalidomide ( 200 mg/day ) ; and arm 5 , a combination of the above . Treatment duration was 4 months . RESULTS Analysis of variance showed a significant difference between treatment arms . A post hoc analysis showed the superiority of arm 5 over the others for all primary endpoints . An analysis of changes from baseline showed that LBM ( by dual-energy X-ray absorptiometry and by L3 computed tomography ) significantly increased in arm 5 . REE decreased significantly and fatigue improved significantly in arm 5 . Appetite increased significantly in arm 5 ; interleukin (IL)-6 decreased significantly in arm 5 and arm 4 ; GPS and Eastern Cooperative Oncology Group performance status ( ECOG PS ) score decreased significantly in arm 5 , arm 4 , and arm 3 . Toxicity was quite negligible , and was comparable between arms . CONCLUSION The most effective treatment in terms of all three primary efficacy endpoints and the secondary endpoints appetite , IL-6 , GPS , and ECOG PS score was the combination regimen that included all selected agents",
"The purpose of this study was to evaluate the effect of glycine propionyl-L-carnitine ( GPLC ) supplementation and endurance training for 8 wk on aerobic- and anaerobic-exercise performance in healthy men and women ( age 18 - 44 yr ) . Participants were r and omly assigned to 1 of 3 groups : placebo ( n=9 ) , 1 g/d GPLC ( n=11 ) , or 3 g/d GPLC ( n=12 ) , in a double-blind fashion . Muscle carnitine ( vastus lateralis ) , VO(2peak ) , exercise time to fatigue , anaerobic threshold , anaerobic power , and total work were measured at baseline and after an 8-wk aerobic-training program . There were no statistical differences ( p > .05 ) between or within the 3 groups for any performance-related variable or muscle carnitine concentrations after 8 wk of supplementation and training . These results suggest that up to 3 g/d GPLC for 8 wk in conjunction with aerobic-exercise training is ineffective for increasing muscle carnitine content and has no significant effects on aerobic- or anaerobic-exercise performance",
"Our study wants to evaluate the effects of one year treatment with orlistat plus L-carnitine compared to orlistat alone on body weight , glycemic and lipid control , and insulin resistance state in type 2 diabetic patients . Two hundred and fifty-eight patients with uncontrolled type 2 diabetes mellitus ( T2DM ) [ glycated hemoglobin ( HbA(1c ) ) > 8.0 % ] in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and r and omised to take orlistat 120 mg three times a day plus L-carnitine 2 g one time a day or orlistat 120 mg three times a day . We evaluated at baseline , and after 3 , 6 , 9 , and 12 months these parameters : body weight , body mass index ( BMI ) , HbA(1c ) , fasting plasma glucose ( FPG ) , post-pr and ial plasma glucose ( PPG ) , fasting plasma insulin ( FPI ) , homeostasis model assessment insulin resistance index ( HOMA-IR ) , total cholesterol ( TC ) , low density lipoprotein-cholesterol ( LDL-C ) , high density lipoprotein-cholesterol ( HDL-C ) , triglycerides ( Tg ) , retinol binding protein-4 ( RBP-4 ) , resistin , visfatin , high sensitivity-C reactive protein ( Hs-CRP ) . We observed a faster , and better decrease of body weight , HbA(1c ) , FPG , PPG , LDL-C , HOMA-IR with orlistat plus L-carnitine compared to orlistat . A faster improvement of TC , Tg , FPI , resistin , RBP-4 , visfatin , and Hs-CRP was reached with orlistat plus L-carnitine compared to orlistat . We can safely conclude that the association of orlistat plus L-carnitine was better than orlistat in improving body weight , glycemic and lipid profile , insulin resistance , and inflammatory parameters and no significant adverse events were recorded",
"Considering the pathologic importance of oxidative stress and altered lipid metabolism in osteoarthritis ( OA ) , this study aim ed to investigate the effect of l-carnitine supplementation on oxidative stress , lipid profile , and clinical status in women with knee OA . We hypothesized that l-carnitine would improve clinical status by modulating serum oxidative stress and lipid profile . In this r and omized double-blind , placebo-controlled trial , 72 overweight or obese women with mild to moderate knee OA were r and omly allocated into 2 groups to receive 750 mg/d l-carnitine or placebo for 8 weeks . Dietary intake was evaluated using 24-hour recall for 3 days . Serum malondialdehyde ( MDA ) , total antioxidant capacity ( TAC ) and lipid profile , visual analog scale for pain intensity , and patient global assessment of severity of disease were assessed before and after supplementation . Only 69 patients ( 33 in the l-carnitine group and 36 in the placebo group ) completed the study . l-Carnitine supplementation result ed in significant reductions in serum MDA ( 2.46 ± 1.13 vs 2.16 ± 0.94 nmol/mL ) , total cholesterol ( 216.09 ± 34.54 vs 206.12 ± 39.74 mg/dL ) , and low-density lipoprotein cholesterol ( 129.45 ± 28.69 vs 122.05 ± 32.76 mg/dL ) levels compared with baseline ( P group . Serum triglyceride , high-density lipoprotein cholesterol , and TAC levels did not change significantly in both groups ( P > .05 ) . No significant differences were observed in dietary intake , serum lipid profile , MDA , and TAC levels between groups after adjusting for baseline values and covariates ( P > .05 ) . There were significant intragroup and intergroup differences in pain intensity and patient global assessment of disease status after supplementation ( P Collectively , l-carnitine improved clinical status without changing oxidative stress and lipid profile significantly in women with knee OA",
"AIM Evaluation of the effect of acetyl-L-carnitine ( ALCAR ) vs. amisulpride measured by total Hamilton Depression Rating Scale score ( HAM-D(21 ) ) in patients with pure dysthymia ( DSM IV ) . Two hundred and four patients were r and omised and treated with ALCAR 500 mg b.i.d . or amisulpride 50 mg u.i.d . in a double-blind study , for 12 weeks . RESULTS A solid improvement of HAM-D(21 ) was observed in both treatment groups throughout the study . The results did not disclose statistically significant differences between treatments , although the confidence interval for the non-inferiority of the primary end-point exceeded the pre-established limit of 2 by 0.46 points . According to a non-inferiority margin of 3 ( considered acceptable by recent published data ) the primary end-point could have been fully satisfied . CDRS , MADRS and CGI , employed to further measure the clinical outcome , reported similar results in both treatment groups . The greater tolerability of ALCAR is of clinical relevance considering the chronicity of dysthymia , which often requires prolonged treatment",
"Background : Hypercoagulability is an important risk factor for thrombosis and its complications in hemodialysis patients . This study was design ed to investigate the effects of l-carnitine supplement on plasma coagulation and anticoagulation factors in hemodialysis patients . Methods : Thirty-six hemodialysis patients were r and omly assigned to either a carnitine or a placebo group . Patients in the carnitine group received 1000 mg/day oral l-carnitine for 12 weeks , whereas patients in the placebo group received a corresponding placebo . At baseline and the end of week 12 , 5 mL blood was collected after a 12- to 14-hour fast and plasma fibrinogen concentration , activity of plasma protein C , coagulation factors V , VII , IX , and serum concentrations of tissue plasminogen activator ( tPA ) , plasminogen activator inhibitor type-1 ( PAI-1 ) , free carnitine , and C-reactive protein ( CRP ) were measured . Results : In the carnitine group , mean serum free carnitine concentration increased significantly to 150 % of baseline ( p plasma fibrinogen and serum CRP had 98 mg/dL ( p activity of plasma protein C , coagulation factors V , VII , IX , and serum PAI-1 to tPA ratio . Conclusion : l-Carnitine supplement reduces serum CRP , a marker of systemic inflammation , and plasma fibrinogen , an inflammation-related coagulation factor , in hemodialysis patients . Therefore , l-carnitine may play an effective role in preventing cardiovascular diseases in these patients",
"OBJECTIVE To investigate the effects of propionyl l-carnitine ( PLC ) on clinical and functional parameters , and markers of the overall oxidation state in patients with peripheral arterial disease ( PAD ) associated with non-insulin-dependent diabetes mellitus ( NIDDM ) . DESIGN AND SETTING R and omised , double-blind , clinical trial , conducted in the Unit of Medical Angiology of the University of Catania . PATIENTS AND INTERVENTIONS Seventy-four patients with NIDDM-associated PAD were treated with PLC ( 2 g/day ) or placebo for 12 months . MAIN OUTCOME MEASURES Ankle/brachial index ( ABI ) and the distance of pain-free walking were evaluated at baseline , 6 and 12 months . Malondialdehyde , 4-hydroxynonenal , oxidation time of low-density lipoproteins , and nitrite/nitrate ratio were measured as indices of the overall oxidation profiles at baseline and 12 months . RESULTS In the PLC group , ABI progressively increased ( 0.78 , 0.83 , and 0.88 at 0 , 6 and 12 months , respectively ) . The distance of pain-free walking also improved ( 366.4 , 441.9 and 519.8 m , respectively ) . In the placebo group , these parameters were relatively unchanged . Significant improvements in all parameters of the oxidative profile were seen in the PLC-treated group , with only minor variations observed in the placebo group . CONCLUSIONS These results suggest that adjunct therapy with PLC may be warranted in type 2 diabetes-associated PAD",
"Inflammation , oxidative stress , and high concentration of serum lipoprotein ( a ) [ Lp ( a ) ] are common complications in hemodialysis patients . The present study was design ed to investigate the effects of L-carnitine supplement on serum inflammatory cytokines , C-reactive protein ( CRP ) , Lp ( a ) , and oxidative stress in hemodialysis patients with Lp ( a ) hyperlipoproteinemia [ hyper Lp ( a ) ] . This was an unblinded , r and omized clinical trial . Thirty-six hyper Lp ( a ) hemodialysis patients ( 23 men and 13 women ) were r and omly assigned to either a carnitine or control group . Patients in the carnitine group received 1000 mg/d oral L-carnitine for 12 weeks , whereas patients in the control group did not receive any L-carnitine supplement . At baseline and the end of week 12 , 5 mL of blood were collected after a 12- to 14-hours fast and serum free carnitine , CRP , interleukin-1β , interleukin-6 ( IL-6 ) , tumor necrosis factor-α , Lp ( a ) , and oxidized low-density lipoprotein were measured . Serum free carnitine concentration increased significantly by 86 % in the carnitine group at the end of week 12 compared with baseline ( P while serum CRP and IL-6 showed a significant decrease of 29 % ( P in serum free carnitine , CRP , and IL-6 in the control group . There were no significant differences between the two groups in mean changes of serum interleukin-1β , tumor necrosis factor-α , Lp ( a ) , and oxidized low-density lipoprotein concentrations . L-carnitine supplement reduces inflammation in hemodialysis patients , but has no effect on hyper Lp ( a ) and oxidative stress "
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4118799e-06ff-11f0-808a-c43d1ab1c353
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Purpose Patient-specific instruments ( PSIs ) are already in relatively common use , and their post-operative radiographic results are equal to those for total knee arthroplasty ( TKA ) with conventional instrumentation . PSI use requires a preoperative MRI scan , CT scan , or a combination of MRI and a long-leg st and ing radiograph . However , there is no consensus as to which of these modalities , MRI or CT , is the preferred imaging modality when performing TKA with PSIs . Methods This systematic literature review and meta- analysis studied the differences in alignment outliers between CT- and MRI-based PSI for TKA . A search of the Cochrane Data base of Systematic Review s , MEDLINE / PubMed and Embase was conducted , without restriction on date of publication . Only level I evidence studies written in English that included TKA with the use of MRI- and CT-based PSI were selected . A meta- analysis was then performed of the rate of outliers in the biomechanical axis and individual femoral and tibial component alignment . Where considerable heterogeneity among studies was present or the data did not provide sufficient information for performing the meta- analysis , a qualitative synthesis was undertaken . Results Twelve r and omized controlled trials , study ing 841 knees , were eligible for data extraction and meta- analysis . MRI-based PSI result ed in a significantly lower proportion of coronal plane outliers with regard to the lateral femoral component ( OR 0.52 , 95 % CI 0.30–0.89 , P = 0.02 ) , without significant heterogeneity ( n.s . ) . There were no significant differences regarding the biomechanical axis or frontal femoral and individual tibial component alignment . Conclusion This systematic review and meta- analysis demonstrate that alignment with MRI-based PSI is at least as good as , if not better than , that with CT-based PSI . To prevent for malalignment , MRI should be the imaging modality of choice when performing TKA surgery with PSI.Level of evidence
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"BACKGROUND Long-leg radiographs ( LLR ) are often used in orthopaedics to assess limb alignment in patients undergoing total knee arthroplasty ( TKA ) . However , there are still concerns about the adequacy of measurements performed on LLR . We assessed the reliability and validity of measurements on LLR using three-dimensional computed tomography ( 3D CT)-scan as a gold st and ard . METHODS Six different surgeons measured the mechanical axis and position of the femoral and tibial components individually on 24 LLR . Intraclass correlation coefficients ( ICC ) were calculated to obtain reliability and Bl and -Altman plots were constructed to assess agreement between measurements on LLR and measurements on 3D CT-scan . RESULTS ICC agreement for the six observer measurements on LLR was 0.70 for the femoral component and 0.80 for the tibial component . The mean difference between measurements performed on LLR and 3D CT-scan was 0.3 ° for the femoral component and -1.1 ° for the tibial component . Variation of the difference between LLR and 3D CT-scan for the femoral component was 1.1 ° and 0.9 ° for the tibial component . 95 % of the differences between measurements performed on LLR and 3D CT-scan were between -1.9 and 2.4 ° ( femoral component ) and between -2.9 and 0.7 ( tibial component ) . CONCLUSION Measurements on LLR show moderate to good reliability and , when compared to 3D CT-scan , show good validity . CLINICAL TRIAL REGISTRATION NUMBER institutional review board Atrium-Orbis-Zuyd , number : 11-T-15 . LEVEL OF EVIDENCE Prospect i ve cohort study , Level II",
"Purpose To compare the femoral and tibial components rotational alignment in total knee arthroplasty ( TKA ) performed either with conventional or with patient-specific instrumentation . Methods Forty-five patients underwent primary TKA and were prospect ively r and omized into two groups : 22 patients into the conventional instrumentation group ( group A ) and 23 patients into the Signature ™ patient-specific instrumentation group ( group B ) . All patients underwent computed tomography of the operated knee in the first week after surgery to measure the components rotation . Results The femoral component rotation was 0.0 ° ( −0.25 , 1.0 ) in group A , and 0.0 ° ( 0.0 , 1.0 ) in group B. The tibial component rotation was −16.0 ° ( −18.5 , 11.8 ) in group A , and −16.0 ° ( −19.0 , −14.0 ) in group B. There were no significant differences between the two groups in tibial and femoral components rotation . The difference between the tibial component rotation and the neutral tibial rotation was similar in both groups [ 2.0 ° ( −0.5 , 6.3 ) in group A and 2.0 ° ( −1.0 , 4.0 ) in group B ] , but the dispersion around the median was different between the two groups . The amplitude of the difference between tibial rotation and neutral position was 27 ° ( −13 , 14 ) in group A and 9 ° ( −3 , 6 ) in group B. Conclusions There is a smaller chance of internal malrotation of the tibial component with the Signature ™ patient-specific instrumentation system , with less dispersion and amplitude of the tibial component rotation around the neutral position . Level of evidence II",
"Abstract Purpose It was our hypothesis that patient-specific instrumentation ( PSI ) can improve the accuracy of the rotational alignment in TKA based on the concept of the system and on the potential to clearly identify pre-operatively during planning the classical anatomical l and marks that serve as references to set-up the rotation both for the femur and tibia . Material s and methods In this prospect i ve comparative r and omized study , 40 patients ( 20 in each group ) operated in our institution between September 2012 and January 2013 by the 2 senior authors were included . R and omization of patients into one of the two groups was done by the Hospital Informatics Department with the use of a systematic sampling method . All patients received the same cemented high-flex mobile bearing TKA . In the PSI group , implant position was compared to the planed position using previously vali date d dedicated software . The position of the implants ( frontal and sagittal ) was compared in the 2 groups on st and ard X-rays , and the rotational position was analysed on post-operative CT-scan . Results 90 % of the patients add tibial rotation where the variations were much higher . Mean HKA was 179 ° ( 171–185 ) in the PSI group with 4 outliers ( 2 varus : 171 ° and 172 ° :184 ° and 185 ° ) and 178.3 ° with 2 outliers ( 171 ° and 176 ° ) in the control group . No difference was observed between the two groups concerning the frontal and sagittal position of the implants on the ML and AP X-rays . No significant difference of femoral rotation was observed between the two groups with a mean of 0.4 ° in the PSI group and 0.2 ° in the control group ( p : n.s ) . Mean tibial rotation was 8 ° of internal rotation in the PSI group and 15 ° of internal rotation in the st and ard group ( p : n.s ) . Conclusion Based on our results , we were unable to confirm our hypothesis as PSI can not improve rotation in TKA . More work needs to be done to more clearly define the place of PSI in TKA , to keep on improving the accuracy of the system and to better define the individual targets in TKA in terms of frontal , sagittal and rotational positioning of the implant for each patient . Level of evidence Prospect i ve comparative r and omized study , Level II",
"Background Recently , patient-specific guides ( PSGs ) have been introduced , cl aim ing a significant improvement in accuracy and reproducibility of component positioning in TKA . Despite intensive marketing by the manufacturers , this cl aim has not yet been confirmed in a controlled prospect i ve trial . Questions / purpose sWe ( 1 ) compared three-planar component alignment and overall coronal mechanical alignment between PSG and conventional instrumentation and ( 2 ) logged the need for applying changes in the suggested position of the PSG . Methods In this r and omized controlled trial , we enrolled 128 patients . In the PSG cohort , surgical navigation was used as an intraoperative control . When the suggested cut deviated more than 3 ° from target , the use of PSG was ab and oned and marked as an outlier . When cranial-caudal position or size was adapted , the PSG was marked as modified . All patients underwent long-leg st and ing radiography and CT scan . Deviation of more than 3 ° from the target in any plane was defined as an outlier . Results The PSG and conventional cohorts showed similar numbers of outliers in overall coronal alignment ( 25 % versus 28 % ; p = 0.69 ) , femoral coronal alignment ( 7 % versus 14 % ) ( p = 0.24 ) , and femoral axial alignment ( 23 % versus 17 % ; p = 0.50 ) . There were more outliers in tibial coronal ( 15 % versus 3 % ; p = 0.03 ) and sagittal 21 % versus 3 % ; p = 0.002 ) alignment in the PSG group than in the conventional group . PSGs were ab and oned in 14 patients ( 22 % ) and modified in 18 ( 28 % ) . Conclusions PSGs do not improve accuracy in TKA and , in our experience , were somewhat impractical in that the procedure needed to be either modified or ab and oned with some frequency . Level of Evidence Level I , therapeutic study . See instructions for authors for a complete description of levels of evidence",
"BACKGROUND Patient-specific femoral and tibial cutting blocks produced with use of data from preoperative computed tomography ( CT ) or magnetic resonance imaging ( MRI ) scans have been employed recently to optimize component alignment in total knee arthroplasty . We report the results of a r and omized controlled trial in which CT scans were used to compare postoperative component alignment between patients treated with custom instruments and those managed with traditional instruments . METHODS The in-hospital data and early clinical outcomes , including Knee Society scores , were determined in a r and omized clinical trial of forty-seven patients who had undergone a total of forty-eight primary total knee arthroplasties with patient-specific instruments ( twenty-two knees ) or st and ard instruments ( twenty-six knees ) . Orientation of the implants was compared by using three-dimensional CT data . RESULTS No significant differences were found between the study and control groups with respect to any clinical outcome after a minimum of six months of follow-up . The patient-specific tibial cutting block was ab and oned in favor of a st and ard external alignment jig in seven of the twenty-two study knees because of possible malalignment . A detailed analysis of intent-to-treat and per- protocol groups of study and control knees did not show any significant improvement in component alignment , including femoral component rotation in the axial plane , in the patients treated with the custom instruments . The percentage of outliers -- defined as less than -3 ° or more than 3 ° from the correct orientation of the tibial slope -- was significantly higher in the group treated with use of patient-specific blocks than it was in the control group , in both the intent-to-treat ( 32 % versus 8 % , p = 0.032 ) and the per- protocol ( 47 % versus 6 % , p = 0.0008 ) analysis . CONCLUSIONS There were no significant improvements in clinical outcomes or knee component alignment in patients treated with patient-specific cutting blocks as compared with those treated with st and ard instruments . The group treated with patient-specific cutting blocks had a significantly higher prevalence of malalignment in terms of tibial component slope than the knees treated with st and ard instruments ",
"Abstract Published clinical trials who studied the accuracy of patient-specific guides ( PSG ) for total knee arthroplasty exclude patients with articular deformity of the knee joint . We prospect ively analysed a series of 30 patients with post-traumatic osteoarthritis of the knee joint with use of PSG . At 1 year post-operative , the achieved biomechanical ( HKA ) axis and varus/valgus of the femur and tibia components were measured on anterior – posterior ( AP ) long-st and ing weight-bearing radiographs . Flexion/extension of the femoral and AP slope of the tibia component was measured on st and ard lateral radiographs . Percentages > 3 ° deviation of the pre-operative planned HKA axis and individual implant components were considered as outliers . Approved and used implant size , median blood loss ( ml ) and operation time ( min ) were obtained from the operation records . Pre- and 1-year post-operative patient-reported outcome measures ( PROMs ) were performed . Eighty-three per cent of the patients had a HKA axis restored . Varus/valgus outliers were 0.0 and 6.7 % for the femoral and tibial components , respectively . Percentages of outliers of flexion/extension were 36.7 % for the femoral component and 10.0 % for the AP slope of the tibial component . Median blood loss was 300 ml ( 50–700 ) , while operation time was 67 min ( 44–144 ) . In 20 % of all cases , the approved implant size was changed into one size smaller . One-year post-operative PROMs improved significantly . We conclude that the accuracy of CT-based PSG is not impaired in patients with post-traumatic osteoarthritis and this modality can restore biomechanical limb alignment",
"Summary Background Optimal positioning of implants and restoration of neutral mechanical axis are two primary surgical goals in total knee arthroplasty ( TKA ) . Despite modern instruments and improved surgical techniques , malalignment remains an important cause of early failure after TKA . The aim of this prospect i ve r and omized study was to compare the value of a new patient-matched instrument system ( PMI ) ( SignatureTM ; Biomet , Inc , Warsaw , Indiana ) to that of st and ard TKA surgical instrumentation ( STD ) in terms of coronal mechanical alignment , time of operation and blood loss . Patients and methods A total of 38 patients waiting for primary TKA were enrolled and r and omized into two groups ( 19 PMI and 19 STD ) . Magnetic resonance imaging was performed in all patients in the PMI group , and specific instruments for the femur and tibia were design ed preoperatively . All patients were operated on using the st and ard medial parapatellar approach with no use of tourniquet . Mechanical axis , time for the operation , and blood loss were evaluated . Results Patients in both groups had comparable age , body mass index , preoperative mechanical axis , Knee Society Score , and level of hemoglobin . Postoperative results showed that the PMI group fell significantly closer to neutral mechanical axis ( STD : 2.7 ± 1.7 , PMI : 1.7 ± 0.9 ; P = 0.013 ) with no outliers and a reduced time for the operation . There was no difference in the evaluation blood loss . Conclusions The use of PMI can contribute in achieving better mechanical axis with reduction in outliers and decreased operation time . Due to small differences between PMI and st and ard instruments , additional research are needed to confirm these preliminary results , and to discover potential benefits and functional improvements in the long-term outcome",
"Purpose This prospect i ve , double-blind , r and omised controlled trial was design ed to address the following research questions : firstly , is there a significant difference in outliers in alignment in the frontal and sagittal plane between PSG TKA and conventional TKA . Secondly , is there a significant difference in operation time , blood loss and length of hospital stay between the two techniques . We hypothesise that there will be fewer outliers with PSG TKA and that operation time , blood loss and length of hospital stay can be significantly reduced with PSG . Methods A total of 180 patients were r and omised for PSG TKA ( group 1 ) or conventional TKA ( group 2 ) in two centres . Patients were stratified per hospital . Alignment of the mechanical axis of the leg and flexion/extension and varus/valgus of the individual prosthesis components were measured on digital , st and ing , long-leg and st and ard lateral radiographs by two independent outcome assessors in both centres . Percentages of outliers ( > 3 ° ) were determined . We compared blood loss , operation time and length of hospital stay . Results There was no statistically significant difference in mean mechanical axis or outliers in mechanical axis between groups . No statistically significant difference was found for the alignment of the individual components in the frontal plane nor for the percentages of outliers . There was a statistically significant difference in outliers for the femoral component in the sagittal plane , with a higher percentage of outliers in the group 1 ( p = 0.017 ) . No such significant result was found for the tibial component in that plane . All interclass correlation coefficients were good . Blood loss was 100 mL less in group 1 ( p ) . Operation time was 5 min shorter in group 1 ( p 0.001 ) . Length of hospital stay was identical with a mean of 3.6 days ( p = 0.657 ) . Conclusions The results in terms of obtaining a neutral mechanical axis and a correct position of the prosthesis components did not differ between groups . A small reduction in operation time and blood loss was found with the PSG system . Future research should especially focus on cost-effectiveness analysis and functional outcome of PSG TKA.Level of evidence",
"The primary purpose of this prospect i ve , r and omized study was to determine if patient-specific instrumentation ( PSI ) for total knee arthroplasty ( TKA ) shortened surgical time . Secondarily the number of instrument trays and alignment were also compared to cases performed with traditional instrumentation ( TI ) . Fifty-two cases ( 26 per group ) were r and omized and videotaped to measure the length of surgery , as well as each individual surgical step . Component alignment and mechanical axis was measured radiographically for each patient . Total surgical time was over 4 minutes shorter for patients in the TI group ( 57.4 minutes vs. 61.8 minutes ; P instrument trays were used in the TI group ( 7.3 vs. 2.5 ; P difference in mechanical alignment between groups on postoperative long alignment radiographs ( P=0.77 ) . In conclusion , PSI did not shorten surgical time or improve alignment compared with TI in this prospect i ve , r and omized trial , but did reduce the required number of trays",
"Magnetic resonance imaging ( MRI ) or computed tomography-based patient-specific instrumentation ( PSI ) may allow for reliable alignment and fewer outliers when compared with conventionally instrumented total knee arthroplasty ( TKA ) . However , some authors have suggested that frequent intraoperative surgeon-directed changes may still be required . This study evaluated the accuracy of PSI to predict component sizing and alignment during TKA . A total of 84 patients ( 89 knees ) who underwent a TKA using a PSI system were evaluated . An MRI-based preoperative plan of every knee was provided and approved by the surgeons . This demonstrated the proposed prosthetic component alignment , as well as the femoral , tibial , and bearing insert component size and position . Intraoperative changes to these components were prospect ively recorded and compared with the computerized preoperative plan . Major changes were defined as any changes in femoral or tibial resection , size , and position of the components . Minor changes were defined as any change in the size of the polyethylene bearing insert . The preoperative plan was able to correctly predict the size of the implanted tibial and femoral component in 93 and 95.5 % of the cases , respectively . Thirteen major intraoperative changes were made . In one knee , the proposed femoral resection was not acceptable ( because of the presence of significant amount of osteophytes ) and was ab and oned in favor of a manual extramedullary guide . In another patient , the proposed femoral and tibial components were upsized . In two other patients , the femoral components were downsized , in four patients , the tibial components were downsized , and in another patient , it was upsized . There were also 16 minor changes , which included 2-mm upsizing of the polyethylene liner in 13 knees and 4-mm upsizing in 3 knees . Surgical experience is necessary to recognize improper component size , incorrect surgical resection , or nonideal alignment when performing TKA using PSI . The authors believe that the design and manufacture of PSI combined with a comprehensive templating result ed in excellent intraoperative concordance of the preoperative plan at the default setting s with minimal changes",
"Abstract Purpose The current study investigated the accuracy in achieving proper lower limb alignment and individual component positions after total knee arthroplasty ( TKA ) with 3 different instrumentation techniques . It was hypothesized that patient-specific instruments ( PSI ) would achieve more accurate lower limb alignment and component positions compared to conventional instruments ( CON ) . Methods Ninety knees in 81 patients were r and omized in 1:1:1 ratio into CON , computer navigation ( NAV ) and PSI groups to receive TKA . The surgical routines were st and ardized . The lower limb mechanical axis and individual component positions were assessed on st and ard radiographs . Tourniquet time , operation time and patients ’ functional scores were documented . Results Conventional instruments and PSI were more likely to result in an excessively flexed femoral component ( p = 0.001 ) compared to NAV . Number of outliers in postoperative lower limb alignment , and other components positions in the coronal and sagittal plane showed no statistically significant difference . The mean tourniquet time and operation time was significantly shorter in CON and PSI groups than NAV group ( p early complications occurred in the PSI group ( p = 0.015 ) . At 3-month follow-up , there was no difference in terms of the knee range of motion and patients ’ function among the 3 groups . Conclusion No significant radiological and clinical benefit could be demonstrated in using PSI over CON or NAV in TKA . Routine use of PSI is not recommended because of the extra cost and waiting time . Level of evidence",
"Purpose The aim of this study was to compare radiological results of total knee arthroplasties ( TKAs ) performed with patient-specific computed tomography (CT)-based instrumentation and conventional technique . The main study hypothesis was that CT-based patient-specific instrumentation ( PSI ) increases the accuracy of TKA . Methods A prospect i ve , r and omized controlled trial was carried out between January and December 2011 . A group of 112 patients who met the inclusion and exclusion criteria were enrolled in this study and r and omly assigned to an experimental or control group . The experimental group comprised 52 patients operated on with the aid of the Signature ™ CT-based implant positioning system . The control group consisted of 60 patients operated on using conventional instrumentation . The radiographic evaluation of implant positioning and overall coronal alignment was performed 12 months after the surgery by using st and ing anteroposterior radiographs of the entire lower limb and st and ard lateral radiographs . Results Of the 112 patients initially enrolled for the study , 95 were included in the subsequent analyses . There were no statistically significant differences between groups in respect to coronal and sagittal component positioning and overall coronal alignment , except for frontal tibial component positioning . For this parameter , better results were obtained in the control group , with borderline statistical significance . Conclusions Our study did not reveal superiority of the CT-based PSI system over conventional instrumentation . Further high- quality investigations of patient-specific systems are absolutely indispensable to assess their utility for TKA . In our opinion , the surgeon applying PSI technology is required to have advanced knowledge and considerable experience with the conventional method",
"Abstract Purpose The purpose of the study was to evaluate the accuracy of the planning of the patient-specific pin guides in total knee arthroplasty ( TKA ) . This planning was performed primarily by a technician of the company and offered to the surgeon . All parameters of the implantation can either be modified or accepted by the surgeon . The hypothesis was that the plan needs preoperative intervention by the surgeon . Methods A prospect i ve study in 50 patients was carried out . All patients received the same posterior-stabilised implant with patient-specific instrumentation . All surgical parameters ( coronal , sagittal , rotational alignment , femoral and tibial resection levels and implant sizes ) were checked by the orthopaedic surgeon and changed if necessary . Results Preoperatively , the femoral size was changed in 8 patients ( 16 % ) , the femoral flexion in 23 patients ( 46 % ) , the femoral shift in 34 patients ( 68 % ) , the tibial size in 24 patients ( 48 % ) and the tibial rotation in all patients . The epicondylar axis was accepted in 47 patients ( 94 % ) in the technician plan . Mean planning time was 8 ± 4 min . Intraoperatively , the femoral anterior – posterior size was in 50 patients ( 100 % ) the same as in the surgeon and in 42 patients ( 84 % ) the same as in the technician plan ( p = 0.003 ) . The tibial component implanted was in 42 patients ( 84 % ) the same as in the surgeon and in 19 patients ( 38 % ) the same as in the technician plan ( p A femoral distal recut was necessary in 31 patients ( 62 % ) and a change of the tibial proximal cut in 17 patients ( 34 % ) during surgery . Intraoperatively , no changes of the femoral and tibial alignment , the femoral anterior – posterior size , the femoral flexion , the femoral shift , the femoral and tibial rotation were necessary . Postoperatively , the coronal mechanical overall axis was within ±3 ° in 47 patients ( 94 % ) with a maximum deviation of 5.6 ° . Conclusions Significant changes of the technician plan were necessary to get an accurate preoperative plan . Intraoperative changes were significant less compared to the surgeon than to the technician plan . No major changes ( alignment , femoral anterior – posterior size and rotation ) of the surgeon plan were necessary . Surgeons using patient-specific pin guides in TKA may verify the default plan provided by the technician . A blind reply on the technician plan may be not recommended . Level of evidence Therapeutic study , Level III",
"AIMS This prospect i ve r and omised controlled trial was design ed to evaluate the outcome of both the MRI- and CT-based patient-specific matched guides ( PSG ) from the same manufacturer . PATIENTS AND METHODS A total of 137 knees in 137 patients ( 50 men , 87 women ) were included , 67 in the MRI- and 70 in the CT-based PSG group . Their mean age was 68.4 years ( 47.0 to 88.9 ) . Outcome was expressed as the biomechanical limb alignment ( centre hip-knee-ankle : HKA-axis ) achieved post-operatively , the position of the individual components within 3 ° of the pre-operatively planned alignment , correct planned implant size and operative data ( e.g. operating time and blood loss ) . RESULTS The patient demographics ( e.g. age , body mass index ) , correct planned implant size and operative data were not significantly different between the two groups . The proportion of outliers in the coronal and sagittal plane ranged from 0 % to 21 % in both groups . Only the number of outliers for the posterior slope of the tibial component showed a significant difference ( p = 0.004 ) with more outliers in the CT group ( n = 9 , 13 % ) than in the MRI group ( 0 % ) . CONCLUSION The post-operative HKA-axis was comparable in the MRI- and CT-based PSGs , but there were significantly more outliers for the posterior slope in the CT-based PSGs . TAKE HOME MESSAGE Alignment with MRI-based PSG is at least as good as , if not better , than that of the CT-based PSG , and is the preferred imaging modality when performing TKA with use of PSG . Cite this article : Bone Joint J 2016;98-B:786 - 92",
"The number of total knee arthroplasty ( TKA ) procedures continuously increases , with good to excellent results . In the last few years , new surgical techniques have been developed to improve prosthesis positioning . In this context , patient-specific instrumentation is included . The goal of this study was to compare the perioperative parameters and the spatial positioning of prosthetic components in TKA procedures performed with patient-specific instrumentation vs traditional TKA . In this prospect i ve comparative r and omized study , 15 patients underwent TKA with 3-dimensional magnetic resonance imaging ( MRI ) preoperative planning ( patient-specific instrumentation group ) and 15 patients underwent traditional TKA ( non-patient-specific instrumentation group ) . All patients underwent postoperative computed tomography ( CT ) examination . In the patient-specific instrumentation group , preoperative data planning regarding femoral and tibial bone resection was correlated with intraoperative measurements . Surgical time , length of hospitalization , and intraoperative and postoperative bleeding were compared between the 2 groups . Positioning of implants on postoperative CT was assessed for both groups . Data planned with 3-dimensional MRI regarding the depth of bone cuts showed good to excellent correlation with intraoperative measurements . The patient-specific instrumentation group showed better perioperative outcomes and good correlation between the spatial positioning of prosthetic components planned preoperatively and that seen on postoperative CT . Less variability was found in the patient-specific instrumentation group than in the non-patient-specific instrumentation group in spatial orientation of prosthetic components . Preoperative planning with 3-dimensional MRI in TKA has a better perioperative outcome compared with the traditional method . Use of patient-specific instrumentation can also improve the spatial positioning of both prosthetic components",
"Background Patient-specific instrumentation in TKA has the proposed benefits of improving coronal and sagittal alignment and rotation of the components . In contrast , the literature is inconsistent if the use of patient-specific instrumentation improves alignment in comparison to conventional instrumentation . Depending on the manufacturer , patient-specific instrumentation is based on either MRI or CT scans . However , it is unknown whether one patient-specific instrumentation approach is more accurate than the other and if there is a potential benefit in terms of reduction of duration of surgery . Questions / purpose sWe compared the accuracy of MRI- and CT-based patient-specific instrumentation with conventional instrumentation and with each other in TKAs . The three approaches also were compared with respect to vali date d outcomes scores and duration of surgery . Methods A r and omized clinical trial was conducted in which 90 patients were enrolled and divided into three groups : CT-based , MRI-based patient-specific instrumentation , and conventional instrumentation . The groups were not different regarding age , male/female sex distribution , and BMI . In all groups , coronal and sagittal alignments were measured on postoperative st and ing long-leg and lateral radiographs . Component rotation was measured on CT scans . Clinical outcomes ( Knee Society and WOMAC scores ) were evaluated preoperatively and at a mean of 3 months postoperatively and the duration of surgery was analyzed for each patient . MRI- and CT-based patient-specific instrumentation groups were first compared with conventional instrumentation , the patient-specific instrumentation groups were compared with each other , and all three approaches were compared for clinical outcome measures and duration of surgery . Results Compared with conventional instrumentation MRI- and CT-based patient-specific instrumentation showed higher accuracy regarding the coronal limb axis ( MRI versus conventional , 1.0 ° [ range , 0 ° –4 ° ] versus 4.5 ° [ range , 0 ° –8 ° ] , p p = 0.02 ) , femoral rotation ( MRI versus conventional , 1.0 ° [ range , 0 ° –2 ° ] versus 4.0 ° [ range , 1 ° –7 ° ] , p ) , and tibial slope ( MRI versus conventional , 1.0 ° [ range , 0 ° –2 ° ] versus 3.5 ° [ range , 1 ° –7 ° ] , p MRI-based patient-specific instrumentation showed a smaller deviation in the postoperative coronal mechanical limb axis compared with CT-based patient-specific instrumentation ( MRI versus CT , 1.0 ° [ range , 0 ° –4 ° ] versus 3.0 ° [ range , 0 ° –5 ° ] , p = 0.03 ) , while there was no difference in femoral rotation or tibial slope . Although there was a significant reduction of the duration of surgery in both patient-specific instrumentation groups in comparison to conventional instrumentation ( MRI versus conventional , 58 minutes [ range , 53–67 minutes ] versus 76 minutes [ range , 57–83 minutes ] , p the postoperative Knee Society pain and function and WOMAC scores among the groups . Conclusions Although this study supports that patient-specific instrumentation increased accuracy compared with conventional instrumentation and that MRI-based patient-specific instrumentation is more accurate compared with CT-based patient-specific instrumentation regarding coronal mechanical limb axis , differences are only subtle and of question able clinical relevance . Because there are no differences in the long-term clinical outcome or survivorship yet available , the widespread use of this technique can not be recommended . Level of Evidence Level I , therapeutic study . See the Instructions to Authors for a complete description of levels of evidence",
"Patient specific cutting guides generated by preoperative Magnetic Resonance Imaging ( MRI ) of the patient 's extremity have been proposed as a method of improving the consistency of Total Knee Arthroplasty ( TKA ) alignment and adding efficiency to the operative procedure . The cost of this option was evaluated by quantifying the savings from decreased operative time and instrument processing costs compared to the additional cost of the MRI and the guide . Coronal plane alignment was measured in an unselected consecutive series of 200 TKAs , 100 with st and ard instrumentation and 100 with custom cutting guides . While the cutting guides had significantly lower total operative time and instrument processing time , the estimated $ 322 savings was overwhelmed by the $ 1,500 additional cost of the MRI and the cutting guide . All measures of coronal plane alignment were equivalent between the two groups . The data does not currently support the proposition that patient specific guides add value to TKA",
"BACKGROUND The purpose of this study was to assess whether custom cutting blocks improve accuracy of component alignment compared to conventional TKA instrumentation . METHODS Eighty primary TKA patients were enrolled in an open-label r and omized prospect i ve clinical trial and were divided into two groups , 40 custom cutting blocks and 40 conventional TKA instrumentations . The primary outcome was prosthetic alignment with respect to mechanical axis and epicondylar axis . Secondary outcomes included operative time , 24-hour postoperative blood loss and hemoglobin at discharged . RESULTS There were no statistical significant differences in the postoperative mechanical axis between the custom cutting blocks group and conventional TKA group , ( 95 % vs. 87.5 % within 3 ° of neutral mechanical alignment , p=0.192 ) . The average rotational alignment was statistically significantly different in the custom cutting blocks group ( 1.0 ° ±0.6 ° vs. 1.6 ° ±1.8 ° external rotation from epicondylar axis , p in operation time between custom cutting blocks group and conventional group , skin to skin [ 57.5±2.3 min vs. 62.1±1.5 , p proportion of patients with postoperative blood loss within 24 h. CONCLUSIONS Custom cutting blocks technique was a surgical procedure which provided better accuracy in rotational alignment but no statistical differences in mechanical axis , less operative time and reduced blood loss than the conventional TKA instrumentation in the majority of patients",
"Patient-specific cutting guides ( PSCGs ) are design ed to improve the accuracy of alignment of total knee replacement ( TKR ) . We compared the accuracy of limb alignment and component positioning after TKR performed using PSCGs or conventional instrumentation . A total of 80 patients were r and omised to undergo TKR with either of the different forms of instrumentation , and radiological outcomes and peri-operative factors such as operating time were assessed . No significant difference was observed between the groups in terms of tibiofemoral angle or femoral component alignment . Although the tibial component in the PSCGs group was measurably closer to neutral alignment than in the conventional group , the size of the difference was very small ( 89.8 ° ( sd 1.2 ) vs 90.5 ° ( sd 1.6 ) ; p = 0.030 ) . This new technology slightly shortened the bone-cutting time by a mean of 3.6 minutes ( p and the operating time by a mean 5.1 minutes ( p = 0.019 ) , without tangible differences in post-operative blood loss ( p = 0.528 ) or need for blood transfusion ( p = 0.789 ) . This study demonstrated that both PSCGs and conventional instrumentation restore limb alignment and place the components with the similar accuracy . The minimal advantages of PSCGs in terms of consistency of alignment or operative time are unlikely to be clinical ly relevant",
"Background Patient-specific CT-based instrumentation may reduce implant malpositioning and improve alignment in TKA . However , it is not known whether this innovation is an advance that benefits patients . Questions / purpose sWe evaluated ( 1 ) the precision of patient-specific TKA by comparing the incidence of outliers in postoperative alignment between TKAs using patient-specific instruments and TKAs using conventional instruments , and ( 2 ) the reliability of patient-specific instruments by intraoperatively investigating whether the surgery could be completed with patient-specific instruments alone . Methods In this r and omized controlled trial , we compared patient-specific TKA instruments from one manufacturer ( n = 50 ) with conventional TKA instruments ( n = 50 ) . Postoperative hip-knee-ankle angles , femoral component rotation , and coronal and sagittal alignments of each component were measured . The validity of the patient-specific instrument was examined using cross-checking procedures with conventional instruments during the surgeries . When the procedure could not be completed accurately with patient-specific instruments , the procedure was converted to TKA using conventional instruments , and the frequency of this occurrence was tallied . Results Outliers in the hip-knee-ankle angle were comparable between groups ( 12 % in the patient-specific instrument group and 10 % in the conventional instrument group ) . Other parameters such as sagittal alignment and femoral component rotation did not differ in terms of outliers . Patient-specific guides were ab and oned in eight knees ( 16 % ) during the surgery because of malrotation of the femoral components and decreased slope of the tibia . Conclusions Accuracy was comparable between TKAs done with patient-specific instruments and those done with conventional instruments . However , the patient-specific instrument procedures had to be aborted frequently , incurring expenses that did not benefit patients .Level of Evidence Level II , therapeutic study . See Instructions for Authors for a complete description of levels of evidence"
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BACKGROUND Probiotic therapies with different strains demonstrated some beneficial effects , although some studies did not show any significant effects . This study assessed systematic ally the current knowledge on the effect of probiotic bacteria on duration of acute rotavirus diarrhea in children compared with control . METHODS The PubMed , Cochrane Controlled Trial Register ( CCTR ) and Ovid ( Wolters Kluwer Health ) were search ed between 1980 to June 15 , 2013 . R and omized controlled trials including the administration of probiotics for treatment of rotavirus diarrhea in infants and children were review ed . RESULTS A total number of 1244 articles were found through the aforementioned search . 203 articles were selected after the first screening of title and abstract . The intervention group included subjects who received probiotic strains and dosage in any conditions . Placebo or any similar vehicle without probiotic was used in the controlled trials . Finally , 14 articles were selected . The outcomes from each study were considered in the duration of diarrhea . Statistical analyses were performed with Stata software . The pooled estimate of efficacy of probiotics in prevention or treatment of disease yielded in all studies a mean difference of 0.41 ( CI 95 % : -0.56 to -0.25 ; p efficacy of lactobacillus rhamnosus GG and other probiotics significantly reduced the duration of diarrhea . Among trials , the overall reduction of LGG was 0.47 ( CI 95 % : -0.80 to -0.14 ; P= 0.020 ) . CONCLUSION In conclusion , probiotics exert positive effect in reducing the duration of acute rotavirus diarrhea compared with control
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"Objective To compare the efficacy of five probiotic preparations recommended to parents in the treatment of acute diarrhoea in children . Design R and omised controlled clinical trial in collaboration with family paediatricians over 12 months . Setting Primary care . Participants Children aged 3 - 36 months visiting a family paediatrician for acute diarrhoea . Intervention Children 's parents were r and omly assigned to receive written instructions to purchase a specific probiotic product : oral rehydration solution ( control group ) ; Lactobacillus rhamnosus strain GG ; Saccharomyces boulardii ; Bacillus clausii ; mix of L delbrueckii var bulgaricus , Streptococcus thermophilus , L acidophilus , and Bifidobacterium bifidum ; or Enterococcus faecium SF68 . Main outcome measures Primary outcomes were duration of diarrhoea and daily number and consistency of stools . Secondary outcomes were duration of vomiting and fever and rate of admission to hospital . Safety and tolerance were also recorded . Results 571 children were allocated to intervention . Median duration of diarrhoea was significantly shorter ( P L rhamnosus strain GG ( 78.5 hours ) and the mix of four bacterial strains ( 70.0 hours ) than in children who received oral rehydration solution alone ( 115.0 hours ) . One day after the first probiotic administration , the daily number of stools was significantly lower ( P L rhamnosus strain GG and in those who received the probiotic mix than in the other groups . The remaining preparations did not affect primary outcomes . Secondary outcomes were similar in all groups . Conclusions Not all commercially available probiotic preparations are effective in children with acute diarrhoea . Paediatricians should choose bacterial preparations based on effectiveness data . Trial registration number Current Controlled Trials IS RCT N56067537",
"In a controlled trial in Petrozavodsk , Karelia , the effects of oral rehydration and Lactobacillus strain GG ( LGG ) on recovery from acute diarrhoea ( 27 % rotavirus , 21 % bacterial aetiology ) were studied in 123 children aged between 1 and 36 months of age . On admission to hospital , the patients were first r and omized to receive either isotonic oral rehydration solution ( ORS ) with osmolality 311mosmol/l and sodium 90mmol/l ( WHO‐ORS ) , or a hypotonic ORS with osmolality 224mosmol/l and sodium 60mmol/l ( Light‐ORS ) , and thereafter r and omized to receive either 5 × 109 colony forming units of LGG or a matching placebo . The two ORS performed equally for acute rehydration , and oral rehydration with either ORS was associated with a shorter duration of diarrhoea than intravenous rehydration ( p= 0.036 ) . Patients receiving LGG had a significantly shorter duration of watery diarrhoea [ mean ( SD ) 2.7 ( 2.2 ) days ] than those receiving the placebo [ 3.7 ( 2.8 ) days , p= 0.03 ] . LGG significantly shortened the duration of rotavirus diarrhoea but not diarrhoea with confirmed bacterial aetiology",
"Background Evidence suggests that probiotics reduce rotavirus diarrhoea duration . Although there are several probiotic strains potentially useful , daily practice is often limited by the type and number of products locally available . In general , information about combined products is scarce . In this study we compare the effect of two probiotic products in the treatment of diarrhoea in children less than 2 years of age . Methods A R and omized double-blind controlled clinical trial in children hospitalized for acute rotavirus diarrhoea , in the Paediatric Centre Albina Patino , Cochabamba , Bolivia . Participants were children aged 1 - 23 months , who were r and omly assigned to receive one of three treatments : Oral rehydration therapy plus placebo ; Oral rehydration solution plus Saccharomyces boulardii ; or Oral rehydration solution plus a compound containing Lactobacillus acidophilus , Lactobacillus rhamnosus , Bifidobacterium longum and Saccharomyces boulardii . Sample size was 20 per group and the outcomes were duration of diarrhoea , of fever , of vomiting and of hospitalization . Results 64 cases finished the protocol . On admission , patients ' characteristics were similar . Median duration of diarrhoea ( p = 0.04 ) in children who received the single species product ( 58 hours ) was shorter than in controls ( 84.5 hrs ) . Comparing children that received the single probiotic product and controls showed shorter duration of fever ( 18 vs 67 hrs ) ( p = 0.0042 ) and the mixed probiotic of vomiting ( 0 vs 42.5 hrs ) ( p = 0.041 ) . There was no effect on duration of hospitalization ( p = 0.31 ) . When experimental groups were merged , statistical significance of changes increased ( total duration of diarrhoea , fever and vomiting P = 0.025 , P = 0.025 and P = 0.014 , respectively ) . Conclusions Both products decreased the duration of diarrhoea compared to oral rehydration solution alone . This decrease was significant only for the single species product which also decreased the duration of fever . With the multiple species product there was no vomiting subsequent to the initiation of treatment . The quantity of probiotic bacteria needed for optimum treatment of gastroenteritis remains to be determined , particularly when multiple species are included in the product . Trial Registration Clinical Trials ( NCT ) :",
"BACKGROUND Oral administration of live Lactobacillus casei strain GG is associated with the reduction of duration of diarrhea in children admitted to the hospital because of diarrhea . The purpose s of this work were to investigate the clinical efficacy of oral administration of Lactobacillus in children with mild diarrhea who were observed as out patients , and to see whether Lactobacillus GG can reduce the duration of rotavirus excretion . METHODS Duration of diarrhea was recorded in 100 children seen by family pediatricians and r and omly assigned to receive oral rehydration or oral rehydration followed by the administration of lyophilized Lactobacillus casei , strain GG . Rotavirus was looked for in the stools of all children and in those in whom results were positive , stools were examined again 6 days after the onset of diarrhea . RESULTS In 61 children results were positive for rotavirus and in 39 results were negative . Duration of diarrhea was reduced from 6 to 3 days in children receiving Lactobacillus GG , with a similar pattern in rotavirus-positive and -negative children . Six days after the onset of diarrhea , stools in only 4 out of 31 children that received Lactobacillus GG were positive for rotavirus compared with positive findings in 25 out of 30 control subjects . CONCLUSIONS Oral administration of Lactobacillus GG is effective in rotavirus-positive and rotavirus-negative ambulatory children with diarrhea . Furthermore , it reduces the duration of rotavirus excretion",
"Background . Previous studies have shown that selected strains of lactobacilli that are administered orally result in a modest reduction of diarrhea duration . However , duration alone is not considered optimal for therapeutic evaluation of any agent in diarrhea . Objective . To examine the effect of a new probiotic , Lactobacillus paracasei strain ST11 ( ST11 ) , in acute childhood diarrhea by using evaluation criteria recommended by the World Health Organization . Methods . In a r and omized , double-blind , placebo-controlled clinical trial , 230 male infants and young children , 4 to 24 months of age , presenting with diarrhea of , and fed 1010 colony-forming units of lyophilized ST11 or placebo daily for 5 days . Stool output and frequency , oral rehydration solution intake , and excretion of rotavirus were monitored daily . Results . No effect of ST11 treatment on severe rotavirus diarrhea was observed . However , the probiotic treatment did significantly reduce cumulative stool output ( 225 ± 218 vs 381 ± 240 mL/kg ) , stool frequency ( 27.9 ± 17 vs 42.5 ± 26 ) , and oral rehydration solution intake ( 180 ± 207 vs 331 ± 236 mL/kg ) in children with less-severe nonrotavirus diarrhea compared with those receiving placebo treatment . A significantly higher proportion of nonrotavirus children receiving ST11 had their diarrhea resolve within 6 days of therapy ( ST11 versus placebo : 76 % vs 49 % ) . Conclusions . ST11 has a clinical ly significant benefit in the management of children with nonrotavirus-induced diarrhea , but it is ineffective in those with rotavirus diarrhea",
"The effect of viable or heat inactivated human Lactobacillus casei strain GG on rotavirus immune responses in patients with rotavirus diarrhoea was assessed . Rotavirus serum IgA enzyme immunoassay antibody responses were higher in infants treated with viable L casei strain GG than in those treated with inactivated L casei strain GG . There was a significant difference at convalescence with rotavirus specific IgA secreting cells found in 10/12 infants receiving viable but only 2/13 infants receiving inactivated L casei strain GG . The results indicate that viable L casei strain GG stimulate rotavirus specific IgA antibody responses , theoretically significant in the prevention of reinfections",
"BACKGROUND Probiotic dairy products are increasingly gaining popularity . Although the role of probiotic bacteria in the prevention and treatment of pediatric and antibiotic associated diarrhea is fairly well established , their role in the prevention of adult infectious diarrhea has not been well investigated . METHODS Five hundred forty-one , young male military recruits were enrolled and r and omly assigned to receive a yogurt containing Lactobacillus casei ( n = 275 ) or a nonprobiotic yogurt ( n = 266 ) . The incidence and duration of diarrhea were documented and stool sample s examined for bacteria and parasites . RESULTS Five hundred and two participants were eligible for final analysis , 254 receiving probiotic yogurt and 248 in the control group . Seventy-one participants ( 14.14 % ) experienced diarrhea during the study period . The incidence of diarrhea in the probiotic group and the control group was 12.2 % and 16.1 % , respectively ( P = .207 ) . The mean duration of diarrhea was 3 + /- 1.95 days in the probiotic group and 2.6 + /- 1.08 days in the control group ( P = .276 ) . CONCLUSION Our study demonstrated a nonsignificant trend for reduction of the incidence of diarrhea among healthy young adults consuming yogurt containing Lactobacillus casei . Further study is needed to evaluate the role of probiotics in adults",
"OBJECTIVE : The incidence of nosocomial infections , predominantly gastrointestinal and respiratory , in children in developed countries is high , ranging from 5 % to 44 % . There is no effective strategy for preventing these infections . The objective of our study was to investigate the role of Lactobacillus GG ( LGG ) in preventing nosocomial gastrointestinal and respiratory tract infections at a pediatric hospital . METHODS : We conducted a r and omized , double-blind , placebo-controlled trial of 742 hospitalized children . They were r and omly allocated to receive for their hospitalization LGG at a dose of 109 colony-forming units in 100 mL of a fermented milk product ( LGG group , n = 376 ) or placebo that was the same postpasteurized fermented milk product without LGG ( placebo group , n = 366 ) . RESULTS : In the LGG group , compared with the placebo group , we found a significantly reduced risk for gastrointestinal infections ( relative risk [ RR ] : 0.40 [ 95 % confidence interval ( CI ) : 0.25–0.70 ] ; number needed to treat : 15 [ 95 % CI : 9–34 ) ] , respiratory tract infections ( RR : 0.38 [ 95 % CI : 0.18–0.85 ] ; number needed to treat : 30 [ 95 % CI : 16–159 ] ) , vomiting episodes ( RR : 0.5 [ 95 % CI : 0.3–0.9 ] ) , diarrheal episodes ( RR : 0.24 [ 95 % CI : 0.10–0.50 ] ) , episodes of gastrointestinal infections that lasted > 2 days ( RR : 0.40 [ 95 % CI : 0.25–0.70 ] ) , and episodes of respiratory tract infections that lasted > 3 days ( RR : 0.4 [ 95 % CI : 0.2–0.9 ] ) . Groups did not differ in hospitalization duration ( P = .1 ) . CONCLUSIONS : LGG administration can be recommended as a valid measure for decreasing the risk for nosocomial gastrointestinal and respiratory tract infections in pediatric facilities",
"OBJECTIVE Nosocomial diarrhea is a major problem in pediatric hospitals worldwide . We evaluated the efficacy of orally administered Lactobacillus GG ( LGG ) in the prevention of this disease in young children . STUDY DESIGN Eighty-one children aged 1 to 36 months who were hospitalized for reasons other than diarrhea were enrolled in a double-blind trial and r and omly assigned at admission to receive LGG ( n = 45 ) at a dose of 6 x 10(9 ) colony-forming units or a comparable placebo ( n = 36 ) twice daily orally for the duration of their hospital stay . RESULTS LGG reduced the risk of nosocomial diarrhea ( > or =3 loose or watery stools/24 h ) in comparison with placebo ( 6.7 % vs 33.3 % ; relative risk : 0.2 ; [ 95 % CI : 0.06 - 0.6 ] ; number needed to treat : 4 [ 95 % CI : 2 - 10 ] ) . The prevalence of rotavirus infection was similar in LGG and placebo groups ( 20 % vs 27.8 % , respectively ; relative risk : 0.72 ; 95 % CI : 0.33 - 1.56 ) . However , the use of LGG compared with placebo significantly reduced the risk of rotavirus gastroenteritis ( 1/45 [ 2.2 % ] vs 6/36 [ 16.7 % ] , respectively ; relative risk : 0.13 ; 95 % CI : 0.02 - 0.79 ; number needed to treat : 7 ; 95 % CI : 3 - 40 ) . CONCLUSIONS Prophylactic use of LGG significantly reduced the risk of nosocomial diarrhea in infants , particularly nosocomial rotavirus gastroenteritis",
"BACKGROUND Addition of a medication to the World Health Organization protocol for treatment of acute diarrhea in children is controversial . In this trial , the clinical efficacy of a medication ( Lactéol Fort sachets ; Laboratoire du Lactéol du Docteur Boucard , Houdan France ) containing lyophilized heat-killed Lactobacillus acidophilus LB was assessed as an adjunct to oral rehydration therapy . METHODS Children aged 3 to 24 months with acute diarrhea and mild or moderate dehydration were enrolled in the study . Children received oral rehydration therapy for the first 4 hours . After this first rehydration phase , undiluted milk formula or breast milk was fed alternately with oral rehydration solution . Children were fed rice gruel as tolerated . They received either one sachet containing 10 billion of lyophilized heat-killed L. acidophilus LB or placebo at admission and at 12-hour intervals for five doses . RESULTS Seventy-three children ( 37 L. acidophilus LB , 36 placebo ) were enrolled , of whom 40 ( 17 L. acidophilus LB , 23 placebo ) received an antibiotic before inclusion . Rotavirus was identified in approximately 50 % of the children in each group . After 24 hours of treatment , the number of rotavirus-positive children with watery stools was significantly lower ( p = 0.012 ) in the L. acidophilus LB group . Mean duration of diarrhea was decreased ( p = 0.034 ) with L. acidophilus LB ( 43.4 hours ) versus placebo ( 57.0 hours ) . This decreased duration was particularly marked in children with no antibiotic therapy before inclusion ( 31.1 hours ) : 42.9 hours for the L. acidophilus LB group versus 74.0 hours for the placebo group ( p = 0.016 ) . CONCLUSIONS Addition of L. acidophilus LB to oral rehydration therapy was effective in the treatment of children with acute diarrhea by decreasing the duration of diarrhea",
"BACKGROUND Certain lactic acid bacteria may accelerate recovery from acute diarrhea . Lactobacillus reuteri is a commonly occurring Lactobacillus species with therapeutic potential in diarrhea . DESIGN Prospect i ve , r and omized , placebo-controlled trial in two hospitals . METHODS Children between 6 and 36 months of age admitted for rotavirus-associated diarrhea were r and omized into three groups to receive either 10(10 ) or 10(7 ) colony-forming units ( cfu ) of L. reuteri or a matching placebo once a day for up to 5 days . RESULTS The main effect of L. reuteri was on the duration of watery diarrhea . The mean ( + /-SD ) duration of watery diarrhea after initiation of treatment was 2.5 ( 1.5 ) days in the placebo group ( n = 25 ) vs. 1.9 ( 0.9 ) days in the small dosage ( n = 20 ) and 1.5 ( 1.1 ) days in the large dosage ( n = 21 ) L. reuteri recipients ( P = 0.01 ) . By the second day of treatment watery diarrhea persisted in 80 % of the placebo , 70 % of the small dosage and 48 % of the large dosage L. reuteri recipients ( P = 0.04 , large dosage vs. placebo ) . Stool cultures for lactobacilli confirmed that administration of L. reuteri result ed in good colonization of the GI tract . The mean ( + /-SD ) of total Lactobacillus count 2 days after treatment initiation was 2.8 ( 1.6 ) log 10 cfu/g in the placebo group , 4.5 ( 2.0 ) log 10 cfu/g in the small dosage L. reuteri group and 6.1 ( 1.2 ) log 10 cfu/g in the large dosage L. reuteri group ( P = 0.0004 ) . CONCLUSIONS L. reuteri effectively colonized the gastrointestinal tract after administration and significantly shortened the duration of watery diarrhea associated with rotavirus . There was a correlation between the dosage of L. reuteri and the clinical effect",
"BACKGROUND The probiotic Lactobacillus GG is effective in promoting a more rapid recovery of acute , watery diarrhea in children with rotavirus enteritis . Very limited information is available , however , on the potential role of such agents in non-rotaviral diarrheal episodes . Furthermore , no evidence is available concerning the efficacy of Lactobacillus GG administered in the oral rehydration solution during oral rehydration therapy . A multicenter trial was conducted to evaluate the efficacy of Lactobacillus GG administered in the oral rehydration solution to patients with acute-onset diarrhea of all causes . METHODS Children 1 month to 3 years of age with acute-onset diarrhea were enrolled in a double-blind , placebo-controlled investigation . Patients were r and omly allocated to group A , receiving oral rehydration solution plus placebo , or group B , receiving the same preparation but with a live preparation of Lactobacillus GG ( at least 10(10 ) CFU/250 ml ) . After rehydration in the first 4 to 6 hours , patients were offered their usual feedings plus free access to the same solution until diarrhea stopped . RESULTS One hundred forty children were enrolled in group A , and 147 in group B. There were no differences at admission between the groups in age , sex , previous types of feeding , previous duration of diarrhea , use of antibiotics , weight , height , weight-height percentile , prevalence of fever , overall status , degree of dehydration , and percentage of in- versus out patients . Duration of diarrhea after enrollment was 71.9 + /- 35.8 hours in group A versus 58.3 + /- 27.6 hours in group B ( mean + /- SD ; P = 0.03 ) . In rotavirus-positive children , diarrhea lasted 76.6 + /- 41.6 hours in group A versus 56.2 + /- 16.9 hours in groups B ( P Diarrhea lasted longer than 7 days in 10.7 % of group A versus 2.7 % of group B patients ( P Hospital stays were significantly shorter in group B than in group A. CONCLUSIONS Administering oral rehydration solution containing Lactobacillus GG to children with acute diarrhea is safe and results in shorter duration of diarrhea , less chance of a protracted course , and faster discharge from the hospital",
"Background . Certain strains of lactobacilli have been shown to promote recovery from rotavirus enteritis in hospitalized children . Few studies have examined the effect of probiotics in nonhospitalized children with mild diarrhea . Methods . We studied in a r and omized placebo-controlled trial the effect of lyophilized Lactobacillus rhamnosus 19070 - 2 and Lactobacillus reuteri DSM 12246 , 1010 colony-forming units of each strain twice daily for 5 days , on acute diarrhea in children in a cohort of children recruited from local day-care centers . The duration of diarrhea and assessment of stool consistency were recorded by the parents . Results . In patients treated with the selected Lactobacillus strains , the mean duration of diarrhea after intervention was reduced ( 76 h in patients treated with probiotics vs. 116 h in the placebo group;P = 0.05 ) . In patients with diarrhea for before start of treatment ( early intervention ) , a more pronounced effect of probiotics was found . The time to recovery after early treatment was 79 h vs. 139 h in the placebo group ( P = 0.02 ) ; 1 of 17 patients treated early vs. 6 of 13 in the control group still had loose stools 120 h after start of treatment ( P = 0.03 ) . Conclusions . In children from day-care centers with mild gastroenteritis , the combination of L. rhamnosus 19070 - 2 and L. reuteri DSM 12246 was effective in reducing the duration of diarrhea",
"Background Recent studies have shown that probiotics , most commonly Lactobacillus GG , may be useful in treating acute gastroenteritis . However , beneficial effects appear to be limited to a modest decrease in the duration of diarrhea . No studies have evaluated this therapy in moderate to severe dehydrating diarrhea in a metabolic facility . Methods Male children less than 2 years of age were admitted to a metabolic unit of the Department of Pediatrics at the Federal University of Bahia , Brazil , with moderate dehydration and were r and omized in a double-blind , placebo-controlled fashion . Oral rehydration solution ( ORS ) was administered per protocol and either placebo or Lactobacillus GG was given in combination with the ORS . Output of urine , stool , and vomitus was recorded along with stool weight , nude body weight , and st and ard laboratory assessment s for hydration . Results There was no significant reduction in diarrhea duration and stool output in the Lactobacillus GG group . However , Kaplan-Meier survival analysis demonstrated that , even in moderate to severe diarrhea , resolution of the illness occurred so rapidly , that statistically significant benefits of probiotic therapy could not be demonstrated . Conclusion Our data implies that colonization must occur before benefits of probiotics can be realized . Probiotics are , therefore , likely to be of limited benefit in treating diarrheal illnesses of short duration such as viral enteritis . The beneficial effects of probiotics may be limited to prophylactic usage in high-risk population ",
"BACKGROUND Recent studies suggest that oral bacteriotherapy with probiotics might be useful in the management of atopic dermatitis ( AD ) . OBJECTIVE The purpose of this investigation was to evaluate the clinical and anti-inflammatory effect of probiotic supplementation in children with AD . METHODS In a double-blind , placebo-controlled , crossover study , 2 probiotic Lactobacillus strains ( lyophilized Lactobacillus rhamnosus 19070 - 2 and Lactobacillus reuteri DSM 122460 ) were given in combination for 6 weeks to 1- to 13-year-old children with AD . The patients ' evaluations were registered after each intervention ( ie , better , unchanged , or worse ) . The clinical severity of the eczema was evaluated by using the scoring atopic dermatitis ( SCORAD ) score . As inflammatory markers , eosinophil cationic protein in serum and cytokine production by P BMC s were measured . RESULTS After active treatment , 56 % of the patients experienced improvement of the eczema , whereas only 15 % believed their symptoms had improved after placebo ( P = .001 ) . The total SCORAD index , however , did not change significantly . The extent of the eczema decreased during active treatment from a mean of 18.2 % to 13.7 % ( P = .02 ) . The treatment response was more pronounced in allergic patients ( at least one positive skin prick test response and elevated IgE levels ) , and in this group the SCORAD score decreased ( P = .02 compared with nonallergic patients ) . During active treatment , serum eosinophil cationic protein levels decreased ( P = .03 ) . No significant changes in the production of the cytokines IL-2 , IL-4 , IL-10 , or IFN-gamma were found . CONCLUSIONS A combination of L rhamnosus 19070 - 2 and L reuteri DSM 122460 was beneficial in the management of AD . The effect was more pronounced in patients with a positive skin prick test response and increased IgE levels",
"To determine the effect of a human Lactobacillus strain ( Lactobacillus casei sp strain GG , Gefilac ) on recovery from acute diarrhea ( 82 % rotavirus ) , 71 well-nourished children between 4 and 45 months of age were studied . After oral rehydration , the patients r and omly received either Lactobacillus GG-fermented milk product , 125 g ( 10(10 - 11 ) colony-forming units ) twice daily ( group 1 ) ; Lactobacillus GG freeze-dried powder , one dose ( 10(10 - 11 ) colony-forming units ) twice daily ( group 2 ) ; or a placebo , a pasteurized yogurt ( group 3 ) 125 g twice daily ; each diet was given for 5 days , in addition to normal full diet otherwise free of fermented dairy products . The mean ( SD ) duration of diarrhea after commencing the therapy was significantly shorter in group 1 ( 1.4 [ 0.8 ] days ) and in group 2 ( 1.4 [ 0.8 ] days ) than in group 3 ( 2.4 [ 1.1 ] days ) ; F = 8.70 , P less than 0.001 . After rehydration , each dietary group maintained a positive weight trend . The urinary lactulose-mannitol recovery ratios ( means [ 95 % confidence intervals ] ) on admission were 0.09 ( 0.03 , 0.24 ) in group 1 , 0.12 ( 0.07 , 0.22 ) in group 2 , and 0.08 ( 0.04 , 0.18 ) in group 3 ; no significant alterations in intestinal permeability were observed at retesting after 2 days of realimentation . The result indicates that early nutritional repletion after rehydration causes no mucosal disruption and is beneficial for recovery from diarrhea . It is further suggested that Lactobacillus GG in the form of fermented milk or freeze-dried powder is effective in shortening the course of acute diarrhea",
"OBJECTIVE To assess the clinical efficacy of Lactobacillus sporogenes ( Bacillus coagulans ) , as probiotic preparation , against dehydrating diarrhoea in children . METHODS Double-blind , r and omised , placebo-controlled , hospital-based clinical trial with children aged 6 - 24 months who had diarrhoea with some dehydration . Children received tablets of L. sporogenes ( B. coagulans ) or placebo ( control group ) and oral rehydration salt solution for correction of initial dehydration as well as maintenance therapy . Duration , frequency , volume of diarrhoea and intake of ORS of two groups were compared as outcome variables . RESULTS One hundred and forty-eight children participated , of whom 78 ( Study group ) received L. sporogenes ( B. coagulans ) and 70 received placebo ( Control group ) . Differences in recovery rate ( P=0.2 ) , duration ( P=0.5 ) , frequency ( P=0.05 ) , volume ( P=0.1 ) of diarrhoea , intake of ORS ( P=0.2 ) and other fluids ( P=0.1 ) were not significant between both groups . Neither did a subgroup analysis of children who had rotavirus as sole enteropathogens show any significant differences in duration ( P=0.5 ) , frequency ( P=0.6 ) , volume ( P=0.8 ) of diarrhoea , intake of ORS ( P=0.8 ) and other fluids ( P=0.8 ) among both groups . CONCLUSION L. sporogenes ( B. coagulans ) , as an adjunct to ORS , had no therapeutic impact on management of acute dehydrating diarrhoea of diverse etiology including rotavirus associated diarrhoea in children",
"We conducted a double-blind r and omized placebo-controlled study to evaluate efficacy and tolerability of VSL♯3 ( CD Pharma India ) in the treatment of acute rotavirus diarrhea in children . The patients were r and omly assigned to receive 4 days of oral treatment with VSL♯3 probiotic mixture or placebo in addition to usual care for diarrhea . Results : Out of 230 rotavirus-positive acute diarrhea children , 224 children completed the study , ( 113 in the drug group and 111 in the placebo group ) . At recruitment on Day 1 , there were no significant differences between the 2 groups in terms of frequency of vomiting , mean loose stool frequency , stool consistency , and mean frequency of oral rehydration salts ( ORS ) and intravenous fluids administered . On Day 2 , a lower mean stool frequency and improved stool consistency was noted in the drug group , which achieved statistical significance . This was also reflected in the lower volume of ORS administration in the drug group . Even on Day 3 , mean loose stool frequency and frequency of ORS use and frequency of intravenous fluid use was significantly lower in the drug group . The differences in the frequency of loose stools persisted till 8 hours of Day 4 . After this , as the placebo group also showed spontaneous improvement the difference between the 2 groups in terms of the overall stools frequency became comparable . However , the overall ORS requirement continued to be significantly lower in the drug group even on Day 4 . The overall recovery rates were significantly better in the drug group compared with placebo . No side effects were noted with the use of the probiotic mixture . Use of probiotic mixture VSL♯3 in acute rotavirus diarrhea result ed in earlier recovery and reduced frequency of ORS administration reflecting decreased stool volume losses during diarrhea",
"A prospect i ve , placebo-controlled , triple blind clinical trial was carried out in Pakistan to determine the effect of Lactobacillus GG on the course of acute diarrhea in hospitalized children . Forty children ( mean age , 13 months ) were enrolled and after rehydration received either oral Lactobacillus GG ( n = 21 ) or placebo ( n = 19 ) twice daily for 2 days , in addition to the usual diet . The clinical course of diarrhea was followed during the treatment period . Features on admission into the study groups were similar and were characterized by severe diarrhea , malnutrition and inappropriate management before presentation . Response was evident on Day 2 when the frequency of both vomiting and diarrhea was less in the Lactobacillus group . In those who had presented with acute nonbloody diarrhea ( n = 32 ) , the percentage of children with persistent watery diarrhea at 48 hours was significantly less in the Lactobacillus group : 31 % vs. 75 % ( P No significant difference was observed by 48 hours in those presenting with bloody diarrhea . The relevance of this finding to the management of diarrhea in the tropics is discussed",
"Objective : The effectiveness of probiotic therapy for acute rotavirus infectious diarrhoea in an indigenous setting with bacterial/parasitic diarrhoea is unclear . In the present study , we assessed the efficacy of probiotics in Australian Aboriginal children in the Northern Territory admitted to hospital with diarrhoeal disease . Patients and Methods : A r and omised double-blind placebo-controlled study was conducted in Aboriginal children ( ages 4 months–2 years ) , admitted to hospital with acute diarrhoeal disease ( > 3 loose stools per day ) . Children received either oral Lactobacillus GG ( 5 × 109 colony-forming units 3 times per day for 3 days ; n = 33 ) or placebo ( n = 31 ) . Small intestinal functional capacity was assessed by the noninvasive 13C-sucrose breath test on days 1 and 4 . Results : Both groups showed mean improvement in the sucrose breath test after 4 days ; however , there was no difference ( mean , 95 % confidence interval ) between probiotic ( 2.9 [ cumulative percentage of dose recovered at 90 minutes ] ; 1.7–4.2 ) and placebo ( 3.7 ; 2.3–5.2 ) groups . Probiotics did not change the duration of diarrhoea , total diarrhoea stools , or diarrhoea score compared with placebo . There was a significant ( P in diarrhoea frequency on day 2 between probiotics ( 3.3 [ loose stools ] ; 2.5–4.3 ) and placebo ( 4.7 ; 3.8–5.7 ) groups . Conclusions : Lactobacillus GG did not appear to enhance short-term recovery following acute diarrhoeal illness in this setting",
"BACKGROUND In previous studies , nitazoxanide has demonstrated a cytoprotective effect against rotavirus , reducing the duration of diarrhea in comparison to placebo . We design ed a r and omized , single-blind , controlled trial in order to assess the effectiveness of nitazoxanide and probiotics in comparison with a control group . METHODS Seventy-five children aged from 28 days to 24 months , with rotavirus diarrhea , were r and omly assigned to receive either oral nitazoxanide ( 15 mg/kg/day ) twice a day for three days , a combination of oral probiotics , 1 g twice a day for five days , or only oral or systemic rehydration solutions . The duration of diarrhea and of hospitalization were the primary outcome measures , and daily stool frequency , vomiting , and fever were some of the secondary outcome measures analyzed . RESULTS The median duration of hospitalization was significantly shorter ( p = 0.017 ) in patients who received nitazoxanide ( 81 h ) and probiotics ( 72 h ) compared to patients who received oral rehydration solution alone ( 108 h ) . Similarly , the median duration of diarrhea was significantly reduced ( p = 0.009 ) in children who received nitazoxanide ( 54 h ) and probiotics ( 48 h ) compared to the control group ( 79 h ) . CONCLUSIONS Treatment with nitazoxanide and probiotics is effective in the management of children with acute rotavirus diarrhea . Small differences in favor of nitazoxanide were found in comparison with probiotics . Nitazoxanide is an important treatment option for rotavirus diarrhea",
"BACKGROUND & AIMS The aim of our study was to investigate the role of Lactobacillus GG ( LGG ) in the prevention of gastrointestinal and respiratory tract infections in children who attend day care centers . METHODS We conducted a r and omized , double-blind , placebo-controlled trial in 281 children who attend day care centers . They were r and omly allocated to receive LGG at a dose of 10(9 ) colony-forming units in 100ml of a fermented milk product ( LGG group , n=139 ) or placebo that was the same post-pasteurized fermented milk product without LGG ( placebo group , n=142 ) during the 3-month intervention period . RESULTS Compared to the placebo group , children in the LGG group had a significantly reduced risk of upper respiratory tract infections ( RR 0.66 , 95 % CI 0.52 to 0.82 , NNT 5 , 95 % CI 4 to 10 ) , a reduced risk of respiratory tract infections lasting longer than 3 days ( RR 0.57 , 95 % CI 0.41 to 0.78 , NNT 5 , 95 % CI 4 to 11 ) , and a significantly lower number of days with respiratory symptoms ( p no risk reduction in regard to lower respiratory tract infections ( RR 0.82 , 95 % CI 0.24 to 2.76 ) . Compared with the placebo group , children in the LGG group had no significant reduction in the risk of gastrointestinal infections ( RR 0.63 , 95 % CI 0.38 to 1.06 ) , vomiting episodes ( RR 0.60 , 95 % CI 0.29 to 1.24 ) , and diarrheal episodes ( RR 0.63 , 95 % CI 0.35 to 1.11 ) as well as no reduction in the number of days with gastrointestinal symptoms ( p=0.063 ) . CONCLUSION LGG administration can be recommended as a valid measure for decreasing the risk of upper respiratory tract infections in children attending day care centers",
"Objective To evaluate the efficacy and safety of Bifilacℳ on reducing the episodes ( frequency ) and duration of diarrhea induced by rotaviral infection and to evaluate the efficacy of Bifilacℳ to ameliorate the associated symptoms like dehydration and duration of rotaviral shedding in faeces . Methods 80 children aged between 3 months and 3 years were enrolled and divided into 2 groups , one group received st and ard therapy + placebo , the other group received st and ard therapy + probiotic ( Bifilac ) r and omly . Children assessed for frequency and duration of diarrhea . Degree of dehydration , duration and volume of oral rehydration salt [ ORS ] therapy , duration and volume of Intra venous fluids and duration of rotaviral shedding . Results When compared to the placebo , Bifilac showed clinical as well as statistically significant reduction in Number of episodes ( frequency ) of diarrhea in a day , mean duration of diarrhea ( in days ) degree of dehydration , duration and volume of oral rehydration salt [ ORS ] therapy , duration and volume of intravenous fluid [ IVF ] therapy , duration of rotaviral shedding ( P<0.01 ) . Conclusion The synbiotic , bifilac , appears to be a safe and very effective adjuvant in the management of acute rotaviral diarrhea"
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Lung cancer is the leading cause of cancer-related death worldwide . For early stages of the disease , lung resection surgery remains the best treatment with curative intent , but significant morbidity is associated , especially among patients with poor pulmonary function and cardiorespiratory fitness . In those cases , the implementation of a preoperative exercise-based intervention could optimize patient 's functional status before surgery and improve postoperative outcomes and enhance recovery . The aim of this systematic review is to provide the current body of knowledge regarding the effectiveness of a preoperative exercise-based intervention on postoperative and functional outcomes in patients with lung cancer su bmi tted to lung resection surgery . A systematic review of the literature using CINAHL , EMBASE , MEDLINE , Pubmed , PEDro and SCOPUS was undertaken in September 2015 yielding a total of 1656 references . Two independent review ers performed the assessment of the potentially eligible records against the inclusion criteria and finally , 21 articles were included in the review . Articles were included if they examined the effects of an exercise-based intervention on at least one of the selected outcomes : pulmonary function , ( functional ) exercise capacity , health-related quality of life ( HRQoL ) and postoperative outcomes ( length of stay and postoperative complications ) . Fourteen studies were further selected for a meta- analysis to quantify the mean effect of the intervention and generate 95 % confidence intervals ( CIs ) using the Cochrane Review Manager 5.0.25 . For two of the outcomes included ( exercise capacity and HRQoL ) , studies showed large heterogeneity and thus , a meta- analysis was considered inappropriate . Pulmonary function ( forced vital capacity and forced expiratory volume in 1 s ) was significantly enhanced after the intervention [ st and ardized mean difference ( SMD ) = 0.38 ; 95 % CI 0.14 , 0.63 and SMD = 0.27 , 95 % CI 0.11 , 0.42 , respectively ] . In comparison with the patients in the control groups , patients in the experimental groups spent less days in the hospital ( mean difference = -4.83 , 95 % CI -5.9 , -3.76 ) and had a significantly reduced risk for developing postoperative complications ( risk ratios = 0.45 ; 95 % CI 0.28 , 0.74 ) . In conclusion , preoperative exercise-based training improves pulmonary function before surgery and reduces in-hospital length of stay and postoperative complications after lung resection surgery for lung cancer
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"Introduction The aim of this study was to assess the effects of preoperative pulmonary rehabilitation ( PPR ) on preoperative clinical status changes in patients with chronic obstructive pulmonary disease ( COPD ) and non-small cell lung cancer ( NSCLC ) , and net effects of PPR and cancer resection on residual pulmonary function and functional capacity . Material and methods This prospect i ve single group study included 83 COPD patients ( 62 ±8 years , 85 % males , FEV1 = 1844 ±618 ml , Tiffeneau index = 54 ±9 % ) with NSCLC , on 2–4-week PPR , before resection . Pulmonary function , and functional and symptom status were evaluated by spirometry , 6-minute walking distance ( 6MWD ) and Borg scale , on admission , after PPR and after surgery . Results Following PPR significant improvement was registered in the majority of spirometry parameters ( FEV1 by 374 ml , p ) and dyspnoeal symptoms ( by 1.0 Borg unit , p preoperative increments of FEV1 and 6MWD ( r s = 0.503 , p = 0.001 ) . Negative correlations were found between basal FEV1 and its percentage increment ( r s = –0.479 , p = 0.001 ) and between basal 6MWD and its percentage change ( r s = –0.603 , p most spirometry parameters and 6MWD were recorded , while Tiffeneau index , FEF25 and dyspnoea severity remained stable ( p = NS ) . Conclusions Preoperative pulmonary rehabilitation significantly enhances clinical status of COPD patients before NSCLC resection . Preoperative increase of exercise tolerance was the result of pulmonary function improvement during PPR . The beneficial effects of PPR were most emphasized in patients with initially the worst pulmonary function and the weakest functional capacity",
"BACKGROUND The impact of short-term preoperative pulmonary rehabilitation on exercise capacity of patients with chronic obstructive pulmonary disease undergoing lobectomy for non-small cell lung cancer is evaluated . METHODS A prospect i ve observational study was design ed . Inclusion criteria consisted of an indication to lung resection because of a clinical stage I or II non-small cell lung cancer and a chronic obstructive disease on preoperative pulmonary function test . In such conditions , maximal oxygen consumption by a cardio-pulmonary exercise test was evaluated ; when this result ed as being pulmonary rehabilitation programme lasting 4 weeks was considered . Twelve patients fulfilled inclusion criteria , completed the preoperative rehabilitation programme and underwent a new functional evaluation prior to surgery . The postoperative record of these patients was collected . RESULTS On completion of pulmonary rehabilitation , the resting pulmonary function test and diffuse lung capacity of patients was unchanged , whereas the exercise performance was found to have significantly improved ; the mean increase in maximal oxygen consumption proved to be at 2.8 ml/kg/min ( p Eleven patients underwent lobectomy ; no postoperative mortality was noted and mean hospital stay was 17 days . Postoperative pulmonary complication was recorded in 8 patients . CONCLUSIONS Short-term preoperative pulmonary rehabilitation could improve the exercise capacity of patients with chronic obstructive pulmonary disease who are c and i date s for lung resection for non-small cell lung cancer",
"STUDY OBJECTIVES The study evaluated the impact of the additional imposed work of breathing ( WBimp ) generated by two different spirometers on postoperative incentive spirometry performance in patients at high risk and moderate risk for postoperative pulmonary complications ( PPCs ) . Additionally , we investigated whether maximal inspiratory pressure ( PImax ) is an easy estimate of the WBimp imposed by incentive spirometers . DESIGN Prospect i ve , r and omized , single-blind clinical trial . SETTING ICU of a university hospital . INTERVENTIONS AND MEASUREMENTS Thirty male patients were assigned to a group at high risk for PPCs ( group A ; inspiratory capacity [ IC ] , On the first or second postoperative day WBimp , IC , and PImax were recorded without spirometers ( baseline ) and during incentive spirometry with the Mediflo spirometer ( Medimex ; Hamburg , Germany ) ( high WBimp ) and the Coach spirometer ( Kendall ; Neustadt , Germany ) ( low WBimp ) using a pneumotachograph . In group A , the baseline and the ICs for both spirometers only differed slightly . In group B , the IC was significantly reduced for the Mediflo ( p PImax was significantly increased for both the Mediflo and the Coach ( p PImax was positively correlated with WBimp ( r = 0.8 ) . CONCLUSIONS Incentive spirometers differ considerably in their additional Wbimp with a potential impact on the efficacy of postoperative incentive spirometry performance . PImax might be an easy clinical estimate for the WBimp during incentive spirometry . Incentive spirometers with low WBimp permit increased maximal sustained inspiration and , thus , enhanced incentive spirometry performance , and , therefore , it might be more suitable for use in postoperative respiratory care",
"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 purpose of this study was to investigate the impact of pulmonary rehabilitation on surgical morbidity and lung function in lung cancer patients with chronic obstructive pulmonary disease ( COPD ) . METHODS Prospect ively , 22 lung cancer patients with COPD who underwent lobectomy between 2000 and 2003 were enrolled for this study as a rehabilitation group ( Rehab . Group ) . The criteria of COPD were preoperative forced expiratory volume in 1 second (FEV1)/forced vital capacity ( FVC ) Preoperatively patients performed aggressive pulmonary exercise for two weeks and received chest physiotherapy postoperatively . As a historical control , 60 patients with lung cancer who fulfilled the same criteria but did not receive rehabilitation between 1995 and 1999 ( control group ) were entered in this study . RESULTS Patient background s were all equivalent between the two groups . However , FEV1 and FEV1/FVC were significantly lower in the Rehab . Group ( p Prolonged oxygen supplement and tracheostomy tended to be more frequent in the control group . The ratio of actual postoperative to predicted postoperative FEV1 was significantly better in the Rehab . Group ( p = 0.047 ) . Furthermore , postoperative hospital stay was significantly longer in the control group ( p = 0.0003 ) . CONCLUSION Despite lower FEV1 and FEV1/FVC in the Rehab . Group , postoperative pulmonary complications and long hospital stay could be effectively prevented and FEV1 was well preserved by rehabilitation and physiotherapy",
"Background Systemic inflammation plays an important role in the initiation , promotion , and progression of lung carcinogenesis . In patients with non-small cell lung cancer ( NSCLC ) , fibrinogen levels correlate with neoplasia . Here we compared the effects of pulmonary rehabilitation ( PR ) with chest physical therapy ( CPT ) on fibrinogen and albumin levels in patients with LC and previous inflammatory lung disease awaiting lung resection . Methods We conducted a r and omized clinical trial with 24 patients who were r and omly assigned to Pulmonary Rehabilitation ( PR ) and Chest Physical Therapy ( CPT ) groups . Each group underwent training 5 days weekly for 4 weeks . All patients were assessed before and after four weeks of training through clinical assessment , measurement of fibrinogen and albumin levels , spirometry , 6-minute Walk Test ( 6MWT ) , quality of life survey , and anxiety and depression scale . PR involved strength and endurance training , and CPT involved lung expansion techniques . Both groups attended educational classes . Results A mixed between-within subjects analysis of variance ( ANOVA ) revealed a significant interaction between time ( before and after intervention ) and group ( PR vs. CPT ) on fibrinogen levels ( F(1 , 22 ) = 0.57 , p effect of time ( F(1 , 22 ) = 0.68 , p = 0.004 ) . Changes in albumin levels were not statistically significant relative to the interaction effect between time and group ( F(1 , 22 ) = 0.96 , p = 0.37 ) nor the main effects of time ( F(1 , 22 ) = 1.00 , p = 1.00 ) and group ( F(1 , 22 ) = 0.59 , p = 0.45 ) . A mixed between-within subjects ANOVA revealed significant interaction effects between time and group for the peak work rate of the unsupported upper limb exercise ( F(1 , 22 ) = 0.77 , p = 0.02 ) , endurance time ( F(1 , 22 ) = 0.60 , p = 0.001 ) , levels of anxiety ( F(1 , 22 ) = 0.60 , p = 0.002 ) and depression ( F(1 , 22 ) = 0.74 , p = 0.02 ) , and the SF-36 physical component summary ( F(1 , 22 ) = 0.83 , p = 0.07 ) . Conclusion PR reduced serum fibrinogen levels , improved functional parameters , and quality of life of patients with LC and inflammatory lung disease awaiting lung resection . Trial registration Current Controlled Trials RBR-3nm5bv",
"OBJECTIVES The aim of the study was to develop a multistr and ed pragmatic rehabilitation programme for operable lung cancer patients , that looks into feasibility , process indicators , outcome measures , local adaptability , compliance and potential cost benefit . METHODS An outpatient-based complex intervention , rehabilitation for operated lung cancer ( ROC ) programme , was developed to optimize physical status , prepare for the inpatient journey and support through recovery after surgery . It includes exercise classes , smoking cessation , dietary advice and patient education and was tested in an enriched cohort study within a regional thoracic unit over 18 months . RESULTS A multistr and ed pragmatic rehabilitation programme pre- and post-surgery is feasible . Fifty-eight patients received the intervention and 305 received st and ard care . Both groups were matched for age , lung function comorbidity and type of surgery . Patients in the intervention group attended exercise classes twice a week until surgery , which was not delayed . Patients attended four sessions presurgery ( range 1 - 15 ) , result ing in an improvement of 20 m ( range -73 - 195 , P = 0.001 ) in a 6-min walk test and 0.66 l in forced expiratory volume in 1 s ( range -1.85 from 1.11 , P = 0.009 ) from baseline to presurgery . Fifty-four percentage of smokers in the intervention group stopped smoking . Sixteen percentage of patients were identified as being at risk of malnourishment and received nutritional intervention . There was a trend in patients in the intervention group towards experiencing fewer postoperative pulmonary complications than those in the non-intervention group ( 9 vs 16 % , respectively , P = 0.21 ) and fewer readmissions to hospital because of complications ( 5 vs 14 % respectively , P = 0.12 ) . CONCLUSION Chronic obstructive pulmonary disease-type pulmonary rehabilitation before and after lung cancer surgery is viable , and preliminary results suggest improvement in physical measures . A multicentre , r and omized controlled trial is warranted to confirm clinical efficacy . IS RCT N REGISTRATION NUMBER IS RCT N00061628",
"Background There is emerging evidence regarding the efficacy of exercise training to improve exercise capacity for individuals with non-small cell lung cancer ( NSCLC ) . Cardiopulmonary exercise testing ( CPET ) is the gold st and ard measure of exercise capacity ; however this laboratory test has limitations for use in research and clinical practice . Alternative field walking tests are the six-minute walk test ( 6MWT ) , incremental-shuttle walk test ( ISWT ) and endurance-shuttle walk test ( ESWT ) ; however there is limited information about their clinimetric properties in NSCLC . Aims : In NSCLC to determine the 1 ) criterion validity of the 6MWT , ISWT and ESWT against CPET ; 2 ) construct validity of the 6MWT , ISWT and ESWT against measures of function , strength , respiratory function and health-related quality of life ( HRQoL ) ; and 3 ) clinical applicability of the tests . Methods Twenty participants ( 40 % male , mean ± SD age 66.1 ± 6.5 years ) with stage I-IIIb NSCLC completed the 6MWT , ISWT , ESWT and CPET within six months of treatment . Testing order was r and omised . Additional measures included Eastern Cooperative Oncology Group Performance-Status ( ECOG-PS , function ) , respiratory function , h and -grip dynamometry and HRQoL. Correlations and regression analyses were used to assess relationships . Results The ISWT demonstrated criterion validity with a moderate relationship between ISWT distance and CPET peak oxygen consumption ( r = 0.61 , p = 0.007 ) . Relationships between CPET and six minute walk distance ( 6MWD ) ( r = 0.24 , p = 0.329 ) or ESWT time ( r = 0.02 , p = 0.942 ) were poor . Moderate construct validity existed for the 6MWD and respiratory function ( forced vital capacity % predicted r = 0.53 , p = 0.019 ; forced expiratory volume in the first second % predicted r = 0.55 , p = 0.015 ) . There were no relationships between the walking tests and measures of function , strength or HRQoL. The ESWT had a ceiling effect with 18 % reaching maximum time . No floor effects were seen in the tests . The mean ± SD time required to perform the individual 6MWT , ISWT and ESWT was 12.8 ± 2.5 , 14.7 ± 3.7 and 16.3 ± 5.0 min respectively ; in comparison to CPET which was 51.2 ± 12.7 min . Only one assessor was required to perform all field walking tests and no adverse events occurred . Conclusions The ISWT is a promising measure of functional exercise capacity in lung cancer . Findings need to be confirmed in a larger sample prior to translation into practice",
"Background Lack of appropriate reporting of method ological details has previously been shown to distort risk of bias assessment s in r and omized controlled trials . The same might be true for observational studies . The goal of this study was to compare the Newcastle-Ottawa Scale ( NOS ) assessment for risk of bias between review ers and authors of cohort studies included in a published systematic review on risk factors for severe outcomes in patients infected with influenza . Methods Cohort studies included in the systematic review and published between 2008–2011 were included . The corresponding or first authors completed a survey covering all NOS items . Results were compared with the NOS assessment applied by review ers of the systematic review . Inter-rater reliability was calculated using kappa ( K ) statistics . Results Authors of 65/182 ( 36 % ) studies completed the survey . The overall NOS score was significantly higher ( p . Inter-rater reliability by item ranged from slight ( K = 0.15 , 95 % confidence interval [ CI ] = −0.19 , 0.48 ) to poor ( K = −0.06 , 95 % CI = −0.22 , 0.10 ) . Reliability for the overall score was poor ( K = −0.004 , 95 % CI = −0.11 , 0.11 ) . Conclusions Differences in assessment and low agreement between review ers and authors suggest the need to contact authors for information not published in studies when applying the NOS in systematic review",
"Background To decrease the risk of postoperative complication , improving general and pulmonary conditioning preoperatively should be considered essential for patients scheduled to undergo lung surgery . Objective The aim of this study is to develop a short-term beneficial program of preoperative pulmonary rehabilitation for lung cancer patients . Methods From June 2009 , comprehensive preoperative pulmonary rehabilitation ( CHPR ) including intensive nutritional support was performed prospect ively using a multidisciplinary team-based approach . Postoperative complication rate and the transitions of pulmonary function in CHPR were compared with historical data of conventional preoperative pulmonary rehabilitation ( CVPR ) conducted since June 2006 . The study population was limited to patients who underwent st and ard lobectomy . Results Postoperative complication rate in the CVPR ( n = 29 ) and CHPR ( n = 21 ) were 48.3 % and 28.6 % ( p = 0.2428 ) , respectively . Those in patients with Charlson Comorbidity Index scores ≥2 were 68.8 % ( n = 16 ) and 27.3 % ( n = 11 ) , respectively ( p = 0.0341 ) and those in patients with preoperative risk score in Estimation of Physiologic Ability and Surgical Stress scores > 0.3 were 57.9 % ( n = 19 ) and 21.4 % ( n = 14 ) , respectively ( p = 0.0362 ) . Vital capacities of pre- and post intervention before surgery in the CHPR group were 2.63±0.65 L and 2.75±0.63 L ( p = 0.0043 ) , respectively ; however , their transition in the CVPR group was not statistically significant ( p = 0.6815 ) . Forced expiratory volumes in one second of pre- and post intervention before surgery in the CHPR group were 1.73±0.46 L and 1.87±0.46 L ( p = 0.0012 ) , respectively ; however , their transition in the CVPR group was not statistically significant ( p = 0.6424 ) . Conclusions CHPR appeared to be a beneficial and effective short-term preoperative rehabilitation protocol , especially in patients with poor preoperative conditions",
"OBJECTIVE This study investigates whether targeted postoperative respiratory physiotherapy decreased the incidence of postoperative pulmonary complications and length of stay for patients undergoing elective pulmonary resection via open thoracotomy . METHODS Seventy-six patients participated in a prospect i ve , single-blind , parallel-group , r and omised trial with concealed allocation , assessor blinding and intention-to-treat analysis . Treatment group participants received daily respiratory physiotherapy interventions until discharge . Control group participants received st and ard medical/nursing care involving a clinical pathway . The presence of postoperative pulmonary complications was assessed on a daily basis during hospitalisation using a st and ardised diagnostic tool . Length of stay was recorded . RESULTS Postoperative pulmonary complications developed in two participants ( 4.8 % ) in the treatment group and in one participant ( 2.9 % ) in the control group ; the difference ( treatment minus control ) was 1.8 % ( 95 % confidence interval ( CI ) -10.6 % to 13.1 % ) ( p=1.00 ) . No significant difference was found between groups for length of stay ( treatment group , median 6.0 days ; control group 6.0 days ) ( p=0.87 ) . A preoperative forced expiratory volume in 1s of 1.5l or less ( p=0.005 ) and a history of chronic obstructive pulmonary disease ( p=0.008 ) were associated with a greater number of criteria for a postoperative pulmonary complication being met . CONCLUSIONS In this patient population , given the low incidence of postoperative pulmonary complications , targeted respiratory physiotherapy may not be required in addition to st and ard care involving a clinical pathway following pulmonary resection via open thoracotomy . These results should be extrapolated with caution to those patients undergoing pulmonary resection with poor preoperative lung function",
"OBJECTIVE To assess the outcomes of a 6-month comprehensive multidisciplinary outpatient pulmonary rehabilitation programme in patients with chronic obstructive pulmonary disease according to age . DESIGN Prospect i ve cohort study . PATIENTS A total of 140 patients with chronic obstructive pulmonary disease ( Global Initiative for Chronic Obstructive Lung Disease ( GOLD ) 3 - 4 ) admitted to our centre for pulmonary rehabilitation . METHODS Patients were divided into 3 groups : group A ( . All the patients received an education and individualized training programme . Pulmonary rehabilitation efficacy was evaluated at 6 months of treatment and 12 months post-treatment . RESULTS A total of 116 patients completed the pulmonary rehabilitation programme : 59 in group A ( 85.5 % ) , 40 in group B ( 80 % ) and 17 in group C ( 80.9 % ) . All the parameters studied ( number of sessions , 6-min walking distance , isometric quadriceps strength , health-related quality of life , maximal load , peak oxygen uptake , maximal inspiratory and expiratory pressures ) were significantly improved in each of the groups at 3 and 6 months compared with baseline . Moreover , percentage changes from baseline at 6 months for all of the parameters studied were not significantly different between age-groups . CONCLUSION Pulmonary rehabilitation is efficient in elderly patients with severe and very severe chronic obstructive pulmonary disease , and their compliance with pulmonary rehabilitation was similar to that seen in younger groups . Therefore , elderly patients with chronic obstructive pulmonary disease should not be denied pulmonary rehabilitation ",
"Introduction : A stepwise approach to the functional assessment of lung resection c and i date s is widely accepted , and this approach incorporates the measurement of exercise peak Vo2 when spirometry and radionuclear studies suggest medical inoperability . A new functional operability ( FO ) algorithm incorporates peak exercise Vo2 earlier in the preoperative assessment to determine which patients require preoperative radionuclear studies . This algorithm has not been studied in a multicenter study . Methods : The CALGB ( Cancer and Leukemia Group B ) performed a prospect i ve multi-institutional study to investigate the use of primary exercise Vo2 measurement for the prediction of surgical risk . Patients with known or suspected resectable non-small cell lung cancer ( NSCLC ) were eligible . Exercise testing including measurement of peak oxygen uptake ( Vo2 ) , spirometry , and single breath diffusion capacity ( DLCO ) was performed on each patient . Nuclear perfusion scans were obtained on selected high-risk patients . After surgery , morbidity and mortality data were collected and correlated with preoperative data . Mortality and morbidity were retrospectively compared by algorithm-based risk groups . Results : Three hundred forty-six patients with suspected lung cancer from nine institutions underwent thoracotomy with or without resection ; 57 study patients did not undergo thoracotomy . Patients who underwent surgery had a median survival time of 30.9 months , whereas patients who did not undergo surgery had a median survival time of 15.6 months . Among the 346 patients who underwent thoracotomy , 15 patients died postoperatively ( 4 % ) , and 138 patients ( 39 % ) exhibited at least one cardiorespiratory complication postoperatively . We found that patients who had a peak exercise Vo2 of complications ( p = 0.0001 ) and were also more likely to have a poor outcome ( respiratory failure or death ) if the peak Vo2 was 58 patients who did not meet FO algorithm criteria for operability , but who still tolerated lung resection with a 2 % mortality rate . Conclusions : Our data provide multicenter validation for the use of exercise Vo2 for preoperative assessment of lung cancer patients , and we encourage an aggressive approach when evaluating these patients for surgery",
"BACKGROUND Secondary to clinical outcome , health-related quality of life ( QOL ) after resection of non-small cell lung cancer ( NSCLC ) is of particular interest . However , few studies have explored QOL following lung resection . METHODS Between January 1998 and December 2004 , a total of 159 patients with NSCLC underwent surgical resection and were enrolled in this prospect i ve study . QOL and clinical data were assessed prior to resection and for up to 24 months after surgery by applying the European Organization for Research and Treatment of Cancer core question naire and the lung-specific question naire , the European Organization for Research and Treatment of Cancer lung-specific module . QOL was calculated , and QOL following bilobectomy/lobectomy was compared with QOL after pneumonectomy . RESULTS Overall , the 5-year survival rate was 42 % . Mean survival of the pneumonectomy group was slightly lower than that of the bilobectomy/lobectomy group , although the difference was not statistically significant ( p = 0.058 ) . The rate of complications was not significantly different between the two groups . After a postoperative drop , most QOL indicators remained near baseline for up to 24 months , with the exception of physical function ( p pain ( p = 0.034 ) , and dyspnoea ( p QOL was significantly better ( difference > 10 points ) after bilobectomy/lobectomy than after pneumonectomy . However , differences were statistically significant only with regards to physical function ( at 3 months ) , social function ( at 3 and 6 months ) , role function ( at 3 , 6 , and 12 months ) , global health ( at 3 and 6 months ) , and pain ( at 6 months ) . CONCLUSIONS Patients who underwent lung resection for NSCLC failed to make a complete recovery after 24 months . Patients who underwent pneumonectomy had significantly worse QOL values and a decreased tendency to recover , compared with patients who underwent bilobectomy/lobectomy . Therefore , major lung resection has a much more serious impact on the QOL of affected patients than does major visceral surgery",
"OBJECTIVE To evaluate the effect of 4 weeks of pulmonary rehabilitation ( PR ) versus chest physical therapy ( CPT ) on the preoperative functional capacity and postoperative respiratory morbidity of patients undergoing lung cancer resection . DESIGN R and omized single-blinded study . SETTING A teaching hospital . PARTICIPANTS Patients undergoing lung cancer resection ( N=24 ) . INTERVENTIONS Patients were r and omly assigned to receive PR ( strength and endurance training ) versus CPT ( breathing exercises for lung expansion ) . Both groups received educational classes . MAIN OUTCOME MEASURES Functional parameters assessed before and after 4 weeks of PR or CPT ( phase 1 ) , and pulmonary complications assessed after lung cancer resection ( phase 2 ) . RESULTS Twelve patients were r and omly assigned to the PR arm and 12 to the CPT arm . Three patients in the CPT arm were not su bmi tted to lung resection because of inoperable cancer . During phase 1 evaluation , most functional parameters in the PR group improved from baseline to 1 month : forced vital capacity ( FVC ) ( 1.47L [ 1.27 - 2.33L ] vs 1.71L [ 1.65 - 2.80L ] , respectively ; P=.02 ) ; percentage of predicted FVC ( FVC% ; 62.5 % [ 49%-71 % ] vs 76 % [ 65%-79.7 % ] , respectively ; P 6-minute walk test ( 425.5±85.3 m vs 475±86.5 m , respectively ; P maximal inspiratory pressure ( 90±45.9cmH(2)O vs 117.5±36.5cmH(2)O , respectively ; P and maximal expiratory pressure ( 79.7±17.1cmH(2)O vs 92.9±21.4cmH(2)O , respectively ; P lower incidence of postoperative respiratory morbidity ( P=.01 ) , a shorter length of postoperative stay ( 12.2±3.6d vs 7.8±4.8d , respectively ; P=.04 ) , and required a chest tube for fewer days ( 7.4±2.6d vs 4.5±2.9d , respectively ; P=.03 ) compared with the CPT arm . CONCLUSIONS These findings suggest that 4 weeks of PR before lung cancer resection improves preoperative functional capacity and decreases the postoperative respiratory morbidity ",
"BACKGROUND We planned to investigate the effect of preoperative short period intensive physical therapy on lung functions , gas-exchange , and capacity of diffusion , and ventilation-perfusion distribution of patients with non-small cell lung cancer . METHODS Sixty patients with lung cancer , who were deemed operable , were r and omly allocated into two groups . Intensive physical therapy was performed in patients in the study group before operation . Both groups received routine physical therapy after operation . RESULTS There was no difference in pulmonary function tests between the two groups . Intensive physical therapy statistically significantly increased peripheral blood oxygen saturation . At least one complication was noted in 5 patients ( 16.7 % ) in the control group , and 2 ( 6.7 % ) , in the study group . However , there was no statistically significant difference ( p = 0,4 ) . The hospital stay has been found to be statistically significantly shortened by intensive physical therapy ( p Ventilation-perfusion distribution was found to be significantly effected by intensive physical therapy . The change was prominent in the the contralateral lung ( p Intensive physical therapy appeared to increase oxygen saturation , reduce hospital stay , and change the ventilation/perfusion distribution . It had a significant , positive effect on the exercise capacity of patients",
"The aim of this study was to explore the effects of presurgical exercise training on quality of life ( QOL ) in patients with malignant lung lesions . Using a single-group prospect i ve design , patients were enrolled in supervised aerobic exercise training for the duration of surgical wait time ( mean 59.7 days ) . Participants completed assessment s of cardiorespiratory fitness ( peak oxygen consumption ) and QOL using the Functional Assessment of Cancer Therapy-Lung scales , including the trial outcome index ( TOI ) and the lung cancer subscale ( LCS ) at baseline , immediately presurgery , and postsurgery ( mean , 57 days ) . 9 participants provided complete data . Repeated- measures analysis indicated a significant effect for time on TOI ( P = .006 ) and LCS ( P = .009 ) . Paired analysis revealed that QOL was unchanged after exercise training ( ie , baseline to presurgery ) , but there were significant and clinical ly meaningful declines from presurgery to postsurgery in the LCS ( −3.6 , P = .021 ) and TOI ( −8.3 , P = .018 ) . Change in peak oxygen consumption from presurgery to postsurgery was significantly associated with change in the LCS ( r = 0.70 , P = .036 ) and TOI ( r = 0.70 , P = .035 ) . Exercise training did not improve QOL from baseline to presurgery . Significant declines in QOL after surgery seem to be related to declines in cardiorespiratory fitness . A r and omized controlled trial is needed to further investigate these relationships",
"PURPOSE To create a maximum tolerated 45-minute aerobic training program for patients with chronic obstructive pulmonary disease ( COPD ) and to compare its outcomes with those of commonly prescribed moderate exercise . DESIGN Prospect i ve , r and omized trial . SETTING A work physiology laboratory . PATIENTS AND METHODS The maximum exercise intensities that 7 COPD patients could sustain for 45 minutes were determined on a bilevel exercise ergometer . The patients then exercised 45 minutes daily , 5 days a week for 6 weeks , working 2.03+/-0.4 kJ/kg per session . They were matched with 6 COPD patients who pushed an O2 cart for 45 minutes daily , 5 days a week for 6 weeks , working 1.44+/-.35 kJ/kg per session . RESULTS A 45 minute maximal regimen was established by alternating 1-minute peak exercise at peak VO2-levels with 4 minutes at the ventilatory anaerobic threshold or at 40 % of peak VO2 . Maximal bilevel training significantly decreased dyspnea at rest ( p blood lactate level during submaximal exercise ( p peak VO2 and total physical work ( p maximum inspiratory and expiratory pressures ( p grip and forearm strength and endurance ( p maximum voluntary ventilation while decreasing the ventilatory equivalent during exercise ( p 12-minute walk ( p COPD patients that can significantly improve both skeletal and respiratory muscle strength and endurance as well as dyspnea and physiologic parameters",
"Complete surgical resection is the most effective curative treatment for lung cancer . However , many patients with lung cancer also have severe COPD which increases their risk of postoperative complications and their likelihood of being considered \" inoperable . \" Preoperative pulmonary rehabilitation ( PR ) has been proposed as an intervention to decrease surgical morbidity but there is no established protocol and no r and omized study has been published to date . We tested two preoperative PR interventions in patients undergoing lung cancer resection and with moderate-severe COPD in a r and omized single blinded design . Outcomes were length of hospital stay and postoperative complications . The first study tested 4 weeks of guideline -based PR vs. usual care : that study proved to be very difficult to recruit as patients and providers were reluctant to delay surgery . Nine patients were r and omized and no differences were found between arms . The second study tested ten preoperative PR sessions using a customized protocol with nonst and ard components ( exercise prescription based on self efficacy , inspiratory muscle training , and the practice of slow breathing ) ( n=10 ) vs. usual care ( n=9 ) . The PR arm had shorter length of hospital stay by 3 days ( p=0.058 ) , fewer prolonged chest tubes ( 11 % vs. 63 % , p=0.03 ) and fewer days needing a chest tube ( 8.8 vs. 4.3 days p=0.04 ) compared to the controlled arm . A ten-session preoperative PR intervention may improve post operative lung reexpansion evidence d by shorter chest tube times and decrease the length of hospital stay , a crude estimator of post operative morbidity and costs . Our results suggest the potential for short term preoperative pulmonary rehabilitation interventions in patients with moderate-severe COPD undergoing curative lung resection . 4 weeks of conventional preoperative PR seems non feasible",
"OBJECTIVES Peak VO2 , as measure of physical performance is central to a correct preoperative evaluation in patients with both non-small-cell lung cancer ( NSCLC ) and chronic obstructive pulmonary disease ( COPD ) because it is closely related both to operability criteria and the rate of postoperative complications . Strategies to improve peak VO2 , as a preoperative pulmonary rehabilitation programme ( PRP ) , should be considered favourably in these patients . In order to clarify the role of pulmonary rehabilitation , we have evaluated the effects of 3-week preoperative high-intensity training on physical performance and respiratory function in a group of patients with both NSCLC and COPD who underwent lobectomy . METHODS We studied 40 patients with both NSCLC and COPD , age Patients were r and omly divided into two groups ( R and S ) : Group R underwent an intensive preoperative PRP , while Group S underwent only lobectomy . We evaluated peak VO2 in all patients at Time 0 ( T0 ) , after PRP/before surgery in Group R/S ( T1 ) and 60 days after surgery , respectively , in both groups ( T2 ) . RESULTS There was no difference between groups in peak VO2 at T0 , while a significant difference was observed both at T1 and T2 . In Group R , peak VO2 improves significantly from T0 to T1 : 14.9 ± 2.3 - 17.8 ± 2.1 ml/kg/min ± st and ard deviation ( SD ) , P S peak VO2 did not change from T0 to T1 and significantly deteriorates from T1 to T2 : 14.5 ± 1.2 - 11.4 ± 1.2 ml/kg/min ± SD , P CONCLUSIONS PRP was a valid preoperative strategy to improve physical performance in patients with both NSCLC and COPD and this advantage was also maintained after surgery",
"The aim of this study was to investigate the effects of systematic rehabilitation programs on the quality of life ( QOL ) in patients undergoing lung resection of malignant lung lesions . In this prospect i ve population -based cohort study , QOL in patients prior to , as well as 3 and 6 months after surgery , was investigated . Using a single-group design , 48 patients ( 7 females and 41 males ) with suspected operable lung cancer were included in this study . The demographic characteristics and the clinical history of the patients were recorded . QOL [ assessed using the European Organization for Research and Treatment of Cancer Quality of Life Question naire Core 3.0 ( EORTC QLQ-C30 ) ] was evaluated at baseline ( immediately before ) , and 3 and 6 months after surgical resection . The systematic rehabilitation program , including breathing control , breathing exercises , relaxation training , upper and lower extremity exercises , mobilization and additional incorporating physiotherapy programs , was design ed to meet each patient 's individual needs . The χ2 and Fisher 's tests showed no statistically significant difference in the two groups in terms of age , gender , behavior , clinical stage , adjuvant therapy and Karnofsky scores . QOL analysis of baseline was homogeneous between the experimental and control groups . Three months after the rehabilitation process , the experimental group demonstrated an increase in the general QOL functional scales and a decrease of symptom scales compared to the control group . These changes were statistically significant in the functional scales of global health ( P physical function ( P role function ( P emotional function ( P symptom scales of fatigue ( P and appetite loss ( P=0.001 ) . Six months after the intervention , the outcome was the same as 3 months after the intervention in functional scale domains . However , in the symptom scales , the symptoms in the experimental group were improved compared to the control group . The domains had been significant in the scales of fatigue ( P , dyspnea ( P , pain ( P , insomnia ( P , appetite loss ( P and constipation ( P significant recovery . In conclusion , systematic rehabilitation programs may be beneficial for lung cancer patients by reducing respiratory symptoms , pain , and improving health-related QOL . Consequently , the findings of this study suggest that systematic rehabilitation programs , prepared by taking into consideration the individual requirements of lung cancer patients , should be incorporated into lung cancer treatment",
"OBJECTIVES We examined the Nationwide Inpatient Sample ( NIS ) data base to compare short-term postoperative outcomes following open and thoracoscopic lobectomy . Thoracoscopic ( video-assisted thoracic surgery ) lobectomy has been demonstrated to be associated with fewer postoperative complications compared with open thoracotomy lobectomy in several large case series . However , as no r and omized trial has been performed , there are many who question this . METHODS We examined the NIS data base for all patients undergoing lobectomy as their principal procedure either via thoracoscopic or open thoracotomy from 2007 to 08 . We compared the postoperative outcomes of these two groups of patients after propensity matching these groups based on several preoperative variables . RESULTS Over a 2-year-period , 68 350 patients underwent a lobectomy by either thoracoscopy [ n = 10 554 ( 15 % ) ] or thoracotomy [ n = 57 796(85 % ) ] . Thirty-two percent of thoracoscopic lobectomies ( n = 3421 ) were performed in either rural or non-teaching urban centres . Although in propensity-matched cohorts there was no difference in operative mortality , thoracoscopic lobectomy was associated with a lower incidence of postoperative complications [ n = 4146 ( 40.8 % ) vs n = 13 913 ( 45.1 % ) , P shorter length of stay ( 5.0 vs 7.0 days ; P incidences of supraventricular arrhythmias , myocardial infa rct ion , pulmonary embolism and empyema were lower . CONCLUSIONS This large national data base study demonstrates that thoracoscopic lobectomy is associated with fewer in-hospital postoperative complications compared with open lobectomy . Thoracoscopic lobectomy appears to be applicable to the wider general thoracic surgical community",
"It is pleasing to see increased research activity that focuses on therapeutic management of dyspnoea and , in particular , greater recognition of the important role that breathing techniques can provide in the amelioration of symptoms associated with Chronic Obstructive Pulmonary Disease ( COPD ) . For many years , the concept of breathing exercises has been poorly understood and , therefore , treatments underutilised . Pursed lip breathing ( PLB ) sits within that poorly defined toolbox termed ‘ breathing exercises ’ . Traditionally , breathing exercises are insufficiently described , the terminology used is at best , arbitrary , and frequently the same name is given to different interventions . Generally , there is little attempt to st and ardise the therapy delivered or the breathing technique performed . The American Thoracic Society guidelines describe the technique of PLB as involving ‘ a nasal inspiration followed by expiratory blowing against partially closed lips , avoiding forceful exhalation ’ . Bhatt et al. in the article published in this edition of Chronic Respiratory Disease ‘ Volitional pursed lips breathing in stable COPD patients improves exercise ’ make the further distinction that ‘ exhalation should continue slowly over 4 to 6 seconds without cheek puffing or forced exhalation ’ . This description of PLB enables better st and ardisation of a technique that has been the focus of debate for many years . The primary contention surrounding PLB is not so much whether it is effective ; over a decade ago , there was sufficient evidence to say that PLB reduces respiratory rate , minute ventilation , and carbon dioxide level ; increases tidal volume , arterial oxygen pressure , and oxygen saturation ; and we ourselves showed positive effects on respiratory rate and time to recovery post exercise . As such , many people with COPD spontaneously adopt this technique ; the contention around PLB concerns its use in people with COPD who do not naturally perform the technique and whether reductions in respiratory rate and oxygen saturation translate into improved exercise tolerance and perception of dyspnoea . Bhatt ’s article addresses this question nicely . Giving patients adequate training in the technique and excluding any subjects who used it automatically ( none did ) they performed , in a r and omised order , two 6-minute walk tests ( 6MWT ) , including an earlier practice test , with and without the use of PLB . These were patients with severe lung impairment ( mean FEV1 38 % predicted ) . Interestingly , the population was , on average , relatively young ( mean age 53 years ) with a fairly short duration of symptoms for such impairment suggesting that these may be patients who have not had sufficient time , or experience , to develop additional coping strategies such as PLB . One memorable patient from our clinic , when asked why he used PLB , told us it was because he was taught it by another patient in the rehabilitation class and finding it helpful he had continued to use it . Clinical ly we see patients adopting PLB during periods of acute illness , and the use of PLB at rest is an indicator of increased work of breathing . In Bhatt ’s article , use of PLB in this group of patients with severe COPD , unaccustomed to the technique , result ed in a small but statistically significant improvement in a 6-minutewalk distance ( 6MWD ) ; the improvement however just failed to reach the lower confidence interval of the minimally clinical ly important difference in 6MWD . Whether these effects are accompanied by improvements in the perception of dyspnoea are as yet unknown . Furthermore , since oxygen saturation was not recorded , we can not make a comment on the role of PLB in patients who show exercise desaturation . In this study , as in others , there was no",
"Systemic inflammation plays an important role in the initiation , promotion , and progression of lung carcinogenesis . The effects of interventions to lower inflammation have not been explored . Accordingly , we conducted a pilot study to explore the effects of exercise training on changes in biomarkers of systemic inflammation among patients with malignant lung lesions . Using a single-group design , 12 patients with suspected operable lung cancer were provided with structured exercise training until surgical resection . Participants underwent cardiopulmonary exercise testing , 6 min walk testing , pulmonary function testing , and blood collection at baseline and immediately prior to surgical resection . Systemic inflammatory markers included intracellular adhesion molecule (ICAM)-1 , macrophage inflammatory protein-1alpha , interleukin (IL)-6 , IL-8 , monocyte chemotactic protein-1 , C-reactive protein , and tumor necrosis factor-alpha . The overall exercise adherence rate was 78 % , with patients completing a mean of 30 + /- 25 sessions . Mean peak oxygen consumption increased 2.9 mL.kg-1.min-1 from baseline to presurgery ( p = 0.016 ) . Results indicate that exercise training result ed in a significant reduction in ICAM-1 ( p = 0.041 ) . Changes in other inflammatory markers did not reach statistical significance . Change in cardiorespiratory fitness was not associated with change in systemic inflammatory markers . This exploratory study provides an initial step for future studies to eluci date the potential role of exercise , as well as identify the underlying mechanisms of action , as a means of modulating the relationship between inflammation and cancer pathogenesis"
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41187a52-06ff-11f0-808a-c43d1ab1c353
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Background / objectives Conjugated linoleic acid ( CLA ) is a polyunsaturated fatty acid with attractive biological activities . Numerous studies have been conducted on the inflammation-lowering effects of CLA in in vitro and animal models . However , the effects of CLA treatment on the inflammatory markers in humans are controversial . Therefore , the objective of this study was to perform a systematic review and meta- analysis on controlled clinical trials ( RCT ) assessing the effects of CLA supplementation on the circulating inflammatory markers , including C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , and tumor necrosis factor-α (TNF-α).Subjects/ methods The literature search of RCTs was performed using Pubmed / Medline , Scopus , ScienceDirect , Web of science , Cochrane , and Google Scholar data bases from inception to March 2017 . Weighted mean differences were estimated and the pooled effect size was calculated by a r and om effects model . Results Of the 427 identified studies , eleven RCTs , including 420 subjects were included in the statistical analysis . Findings suggested that CLA supplementation increased blood levels of CRP by 0.89 mg/l ( 95 % CI : 0.11 , 1.68 ; P = 0.025 ) and TNF-α levels by 0.39 pg/ml ( 95 % CI : 0.23 , 0.55 ; P were marginally decreased by 0.32 pg/ml ( 95 % CI : −0.71 , 0.07 ; P = 0.11 ) following CLA supplementation . There was a significant heterogeneity for the impact of CLA on CRP and IL-6 , but not TNF-α . Conclusions This meta- analysis showed that CLA supplementation may increase inflammatory markers ( CRP and TNF-α ) . There are concerns about using CLA supplementation as an anti-obesity agent among the obese population for at least a short duration
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"BACKGROUND AND AIM Some studies recently reported a favourable effect for cis-9 , trans-11 conjugated linoleic acid ( CLA ) on plasma lipoprotein profile of healthy subjects . Aim of this crossover intervention study was to evaluate the influence of a short-term dietary intake of a cheese derived from sheep 's milk naturally rich in CLA on several atherosclerotic biomarkers , in comparison with a commercially available cheese . METHODS AND RESULTS Ten subjects ( 6 F ; 4 M ) with a median age of 51.5 followed for 10 weeks a diet containing 200 g/week of cheese naturally rich in CLA ( intervention period ) and for the same period a diet containing a commercially available cheese of the same quantity ( placebo period ) . Consumption of the dairy product naturally rich in cis-9 , trans-11 CLA determined a significant ( p inflammatory parameters such as interleukin-6 ( pre : 8.08+/-1.57 vs. post : 4.58+/-0.94 pg/mL ) , interleukin-8 ( pre : 45.02+/-5.82 vs. post : 28.59+/-2.64 pg/mL ) , and tumour necrosis factor-alpha ( pre : 53.58+/-25.67 vs. post : 32.09+/-17.42 pg/mL ) whereas no significant differences in the placebo period were observed . With regard to haemorheological parameters , the test period significantly ameliorated erythrocytes ' filtration rate ( pre : 7.61+/-0.71 % vs. post : 9.12+/-0.97 % ; p=0.03 ) with respect to the placebo period . Moreover , a reduction in the extent of platelet aggregation , induced by arachidonic acid [ pre : 87.8+/-1.76 % vs. post : 77.7+/-3.56 % ; p=0.04 ] was observed during the test period in comparison with the placebo period . CONCLUSIONS Dietary short-term intake of the tested dairy product naturally rich in cis-9 , trans-11 CLA appeared to cause favourable biochemical changes of atherosclerotic markers",
"Studies on animal and human subjects have shown that greatly increasing the amount of linseed ( also known as flaxseed ) oil ( rich in the n-3 polyunsaturated fatty acid ( PUFA ) alpha-linolenic acid ( ALNA ) ) or fish oil ( FO ; rich in the long-chain n-3 PUFA eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) ) in the diet can decrease a number of markers of immune function . The immunological effects of more modest doses of n-3 PUFA in human subjects are unclear , dose-response relationships between n-3 PUFA supply and immune function have not been established and whether ALNA has the same effects as its long-chain derivatives is not known . Therefore , the objective of the present study was to determine the effect of enriching the diet with different doses of FO or with a modest dose of ALNA on a range of functional responses of human monocytes and lymphocytes . In a r and omised , placebo-controlled , double-blind , parallel study , forty healthy males aged 18 - 39 years were r and omised to receive placebo or 3.5 g ALNA/d or 0.44 , 0.94 or 1.9 g (EPA+DHA)/d in capsules for 12 weeks . The EPA : DHA ratio in the FO used was 1.0:2.5 . ALNA supplementation increased the proportion of EPA but not DHA in plasma phospholipids . FO supplementation decreased the proportions of linoleic acid and arachidonic acid and increased the proportions of EPA and DHA in plasma phospholipids . The interventions did not alter circulating mononuclear cell subsets or the production of tumour necrosis factor-alpha , interleukin ( IL ) 1beta , IL-2 , IL-4 , IL-10 or interferon-gamma by stimulated mononuclear cells . There was little effect of the interventions on lymphocyte proliferation . The two higher doses of FO result ed in a significant decrease in IL-6 production by stimulated mononuclear cells . It is concluded that , with the exception of IL-6 production , a modest increase in intake of either ALNA or EPA+DHA does not influence the functional activity of mononuclear cells . The threshold of EPA+DHA intake that results in decreased IL-6 production is between 0.44 and 0.94 g/d",
"BACKGROUND & AIMS Metabolic effects of dietary fat quality in people with type 2 diabetes are not well-understood . The study objective was to evaluate effects of conjugated linoleic acid ( CLA ) and safflower ( SAF ) oils on glycemia , blood lipids , and inflammation . The hypothesis we tested is that dietary oils improve glycemia , lipids , and inflammatory markers in a time-dependent way that follows accumulation of linoleic acid and CLA isomers in serum of subjects supplemented with dietary oils . METHODS Fifty-five post-menopausal , obese women with type 2 diabetes enrolled , and 35 completed this r and omized , double-masked crossover study . Treatments were 8 g daily of CLA and SAF for 16 weeks each . We used a multiple testing procedure with pre-determined steps analysis to determine the earliest time that a significant effect was detected . RESULTS CLA did not alter measured metabolic parameters . SAF decreased HbA1c ( -0.64 ± 0.18 % , p = 0.0007 ) and C-reactive protein ( -13.6 ± 8.2 mg/L , p = 0.0472 ) , increased QUICKI ( 0.0077 ± 0.0035 , p = 0.0146 ) with a minimum time to effect observed 16 weeks after treatment . SAF increased HDL cholesterol ( 0.12 ± 0.05 mmol/L , p = 0.0228 ) with the minimum time to detect an effect of SAF at 12 weeks . The minimum time to detect an increase of c9t11-CLA , t10c12-CLA , and linoleic acid in serum of women supplemented CLA or SAF , respectively , was four weeks . CONCLUSIONS We conclude that 8 g of SAF daily improved glycemia , inflammation , and blood lipids , indicating that small changes in dietary fat quality may augment diabetes treatments to improve risk factors for diabetes-related complications",
"BACKGROUND & AIMS The study examined the value of n-3 LC-PUFA-enriched yogurt as means of improving cardiovascular health . DESIGN Fifty three mildly hypertriacylglycerolemic subjects ( TAG ≥ 1.7 mmol/L ) participated in a r and omized , placebo-controlled , double-blind , parallel design ed study . The subjects consumed 1 ) control yoghurt ; 2 ) yoghurt enriched with 0.8 g n-3 LC-PUFA/d ; or 3 ) yoghurt enriched with 3 g n-3 LC-PUFA/d for a period of 10 wks . Blood sample s were taken at the beginning and the end of the study period . RESULTS Following daily intake of 3 g n-3 LC-PUFA for 10 weeks , n-3 LC-PUFA levels increased significantly in plasma and red blood cells ( RBC ) with concomitant increase in the EPA-derived mediators ( PGE₃ , 12- , 15- , 18-HEPE ) in plasma whilst cardiovascular risk factors such as HDL , TAG , AA/EPA ratio , and n-3 index were improved ( P decrease of TAG and increase in HDL were associated with the CD36 genotype . CONCLUSION The observed increase of n-3 LC-PUFA in RBC and plasma lipids due to intake of n-3 LC-PUFA enriched yoghurt result ed in a reduction of cardiovascular risk factors and inflammatory mediators showing that daily consumption of n-3 PUFA enriched yoghurt can be an effective way of supplementing the daily diet and improving cardiovascular health ",
"BACKGROUND Conjugated linoleic acid ( CLA ) is marketed as a safe , simple , and effective dietary supplement to promote the loss of body fat and weight . However , most previous studies have been of short duration and inconclusive , and some recent studies have question ed the safety of long-term supplementation with CLA . OBJECTIVE Our aim was to assess the effect of 1-y supplementation with CLA ( 3.4 g/d ) on body weight and body fat regain in moderately obese people . DESIGN One hundred twenty-two obese healthy subjects with a body mass index ( in kg/m2 ) > 28 underwent an 8-wk dietary run-in with energy restriction ( 3300 - 4200 kJ/d ) . One hundred one subjects who lost > 8 % of their initial body weight were subsequently r and omly assigned to a 1-y double-blind CLA ( 3.4 g/d ; n = 51 ) or placebo ( olive oil ; n = 50 ) supplementation regime in combination with a modest hypocaloric diet of -1250 kJ/d . The effects of treatment on body composition and safety were assessed with the use of dual-energy X-ray absorptiometry and with blood sample s and the incidence of adverse events , respectively . RESULTS After 1 y , no significant difference in body weight or body fat regain was observed between the treatments . The CLA group ( n = 40 ) regained a mean ( + /-SD ) 4.0 + /- 5.6 kg body weight and 2.1 + /- 5.0 kg fat mass compared with a regain of 4.0 + /- 5.0 kg body weight and 2.7 + /- 4.9 kg fat mass in the placebo group ( n = 43 ) . No significant differences in reported adverse effects or indexes of insulin resistance were observed , but a significant increase in the number of leukocytes was observed with CLA supplementation . CONCLUSION A 3.4-g daily CLA supplementation for 1 y does not prevent weight or fat mass regain in a healthy obese population",
"BACKGROUND Atherosclerosis is a chronic inflammatory disease . We previously reported that a diet high in alpha-linolenic acid ( ALA ) reduces lipid and inflammatory cardiovascular disease risk factors in hypercholesterolemic subjects . OBJECTIVE The objective was to evaluate the effects of a diet high in ALA on serum proinflammatory cytokine concentrations and cytokine production by cultured peripheral blood mononuclear cells ( P BMC s ) from subjects fed the experimental diets . DESIGN A r and omized , controlled , 3-diet , 3-period crossover study design was used . Hypercholesterolemic subjects ( n = 23 ) were assigned to 3 experimental diets : a diet high in ALA ( ALA diet ; 6.5 % of energy ) , a diet high in linoleic acid ( LA diet ; 12.6 % of energy ) , and an average American diet ( AAD ) for 6 wk . Serum interleukin (IL)-6 , IL-1beta , and tumor necrosis factor-alpha ( TNF-alpha ) concentrations and the production of IL-6 , IL-1beta , and TNF-alpha by P BMC s were measured . RESULTS IL-6 , IL-1beta , and TNF-alpha production by P BMC s and serum TNF-alpha concentrations were lower ( P ALA diet than with the LA diet or AAD . P BMC production of TNF-alpha was inversely correlated with ALA ( r = -0.402 , P = 0.07 ) and with eicosapentaenoic acid ( r = -0.476 , P = 0.03 ) concentrations in P BMC lipids with the ALA diet . Changes in serum ALA were inversely correlated with changes in TNF-alpha produced by P BMC s ( r = -0.423 , P antiinflammatory effects by inhibiting IL-6 , IL-1beta , and TNF-alpha production in cultured P BMC s. Changes in P BMC ALA and eicosapentaenoic acid ( derived from dietary ALA ) are associated with beneficial changes in TNF-alpha release . Thus , the cardioprotective effects of ALA are mediated in part by a reduction in the production of inflammatory cytokines",
"A mixture of trans-10 , cis-12 ( t10,c12 ) and cis-9 , trans-11 ( c9,t11 ) conjugated linoleic acid ( CLA mixture ) reduced atherosclerosis in animals , thus the effect of these isomers on endothelial dysfunctions leading to inflammation and atherosclerosis is of interest . We gave 75 healthy postmenopausal women a daily supplement of 5.5 g of oil rich in either CLA mixture , an oil rich in the naturally occurring c9,t11 CLA ( CLA milk ) , respectively , or olive oil for 16 wk in a double-blind , r and omized , parallel intervention study . We sample d blood and urine before and after the intervention . The ratios of total cholesterol : HDL cholesterol and concentrations of C-reactive protein , fibrinogen , and plasminogen activator inhibitor-1 were significantly higher in women supplemented with the CLA mixture than in those supplemented with CLA milk . Plasma triacylglycerol was significantly higher and HDL cholesterol was lower in women supplemented with the CLA mixture than with olive oil . Both CLA supplements increased lipid peroxidation , a marker of in vivo oxidative stress measured as urinary free 8-iso-prostagl and in F(2alpha ) . However , the CLA mixture increased lipid peroxidation more than the CLA milk did . The plasma cytokines interleukin-6 and tumor necrosis factor-alpha were not affected by the treatments , nor were any of the other variables measured . In conclusion , oil containing trans-10,cis-12 CLA has several adverse effects on classical and novel markers of coronary vascular disease , whereas the c9,t11 CLA isomer is more neutral , except for a small but significant increase in lipid peroxidation compared with olive oil",
"Conjugated linoleic acid ( CLA ) alters body composition in animal models , but few studies have examined the effects of CLA supplementation on body composition and clinical safety measures in obese humans . In the present study , we performed a r and omized , double-blind , placebo-controlled trial to examine the changes in body composition and clinical laboratory values following CLA ( 50:50 ratio of cis-9 , trans-11 and trans-10 , cis-12 isomers ) supplementation for 12 wk in otherwise healthy obese humans . Forty-eight participants ( 13 males and 35 females ) were r and omized to receive placebo ( 8 g safflower oil/d ) , 3.2 g/d CLA , or 6.4 g/d CLA for 12 wk . Changes in body fat mass and lean body mass were determined by dual-energy X-ray absorptiometry . Resting energy expenditure was assessed by indirect calorimetry . Clinical laboratory values and adverse-event reporting were used to monitor safety . Lean body mass increased by 0.64 kg in the 6.4 g/d CLA group ( P serum HDL-cholesterol and sodium , hemoglobin , and hematocrit , and significant increases in serum alkaline phosphatase , C-reactive protein , and IL-6 , and white blood cells occurred in the 6.4 g/d CLA group , although all values remained within normal limits . The intervention was well tolerated and no severe adverse events were reported , although mild gastrointestinal adverse events were reported in all treatment groups . In conclusion , whereas CLA may increase lean body mass in obese humans , it may also increase markers of inflammation in the short term",
"BACKGROUND We recently showed that trans-10,cis-12 ( t10,c12 ) conjugated linoleic acid ( CLA ) causes insulin resistance in obese men . However , metabolic effects of the c9,t11 CLA isomer are still unknown in obese men . Because c9,t11 CLA is the predominant CLA isomer in foods and is included in dietary weight-loss products , it is important to conduct r and omized controlled studies that use c9,t11 CLA preparations . OBJECTIVE We investigated the effects of c9,t11 CLA supplementation on insulin sensitivity , body composition , and lipid peroxidation in a group at high risk for cardiovascular disease . DESIGN In a r and omized , double-blind , placebo-controlled study , 25 abdominally obese men received 3 g c9,t11 CLA/d or placebo ( olive oil ) . Before and after 3 mo of supplementation , we assessed insulin sensitivity ( hyperinsulinemic euglycemic clamp ) , lipid metabolism , body composition , and urinary 8-iso-prostagl and in F(2alpha ) ( a major F(2)-isoprostane ) and 15-keto-dihydro-prostagl and in F(2alpha ) , markers of in vivo oxidative stress and inflammation , respectively . RESULTS All subjects completed the study . Compared with placebo , c9,t11 CLA decreased insulin sensitivity by 15 % ( P 8-iso-prostagl and in F(2alpha ) and 15-keto-dihydro-prostagl and in F(2alpha ) excretion by 50 % ( P insulin sensitivity was independent of changes in serum lipids , glycemia , body mass index , and body fat but was abolished after adjustment for changes in 8-iso-prostagl and in F(2alpha ) concentrations . There were no differences between groups in body composition . CONCLUSIONS A CLA preparation containing the purified c9,t11 CLA isomer increased insulin resistance and lipid peroxidation compared with placebo in obese men . Because c9,t11 CLA occurs in commercial supplements as well as in the diet , the present results should be confirmed in larger studies that also include women",
"High linoleic acid ( LA ) intakes have been suggested to reduce alpha-linolenic acid [ ALA , 18:3(n-3 ) ] metabolism to eicosapentaenoic acid [ EPA , 20:5(n-3 ) ] and docosahexaenoic acid [ DHA , 22:6(n-3 ) ] , and favor high arachidonic acid [ ARA , 20:4(n-6 ) ] . We used a r and omized cross-over study with men ( n = 22 ) to compare the effect of replacing vegetable oils high in LA with oils low in LA in foods , while maintaining constant ALA , for 4 wk each , on plasma ( n-3 ) fatty acids . Nonvegetable sources of fat , except fish and seafoods , were unrestricted . We determined plasma phospholipid fatty acids at wk 0 , 2 , 4 , 6 , and 8 , and triglycerides , cholesterol , serum CRP , and IL-6 , and platelet aggregation at wk 0 , 4 , and 8 . LA and ALA intakes were 3.8 + /- 0.12 % and 1.0 + /- 0.05 % , and 10.5 + /- 0.53 % and 1.1 + /- 0.06 % energy with LA : ALA ratios of 4:0 and 10:1 during the low and high LA diets , respectively . The plasma phospholipid LA was higher and EPA was lower during the high than during the low LA diet period ( P DHA declined over the 8-wk period ( r = -0.425 , P plasma phospholipid ARA : EPA ratios were ( mean + /- SEM ) 20.7 + /- 1.52 and 12.9 + /- 1.01 after 4 wk consuming the high or low LA diets , respectively ( P EPA ( r = -0.729 , P ARA : EPA ( r = 0.432 , P LA intake did not influence ALA , ARA , DPA , DHA , or total , LDL or HDL cholesterol , CRP or IL-6 , or platelet aggregation . In conclusion , high LA intakes decrease plasma phospholipid EPA and increase the ARA : EPA ratio , but do not favor higher ARA",
"Consumption of industrial trans fatty acids ( iTFA ) increases LDL cholesterol , decreases HDL cholesterol , and is strongly associated with a higher risk of cardiovascular disease ( CVD ) . However , changes in circulating cholesterol can not explain the entire effect . Therefore , we studied whether iTFA and conjugated linoleic acid ( CLA ) affect markers of inflammation and oxidative stress . Sixty-one healthy adults consumed each of 3 diets for 3 wk , in r and om order . Diets were identical except for 7 % of energy provided by oleic acid ( control diet ) , iTFA , or CLA . At the end of the 3 wk , we measured plasma inflammatory markers IL-6 , C-reactive protein , tumor necrosis factor receptors I and II ( TNF-RI and -RII ) , monocyte chemotactic protein-1 and E-selectin , and urinary 8-iso-PGF(2α ) , a marker of lipid peroxidation . Consumption of iTFA caused 4 % lower TNF-RI concentrations and 6 % higher E-selectin concentrations compared with oleic acid ( control ) and had no significant effect on other inflammatory markers . CLA did not significantly affect inflammatory markers . The urine concentration of 8-iso-PGF(2α ) [ geometric mean ( 95 % CI ) ] was greater after the iTFA [ 0.54 ( 0.48 , 0.60 ) nmol/mmol creatinine ] and the CLA [ 1.2 ( 1.1 , 1.3 ) nmol/mmol creatinine ] diet periods than after the control period [ 0.45 ( 0.41 , 0.50 ) nmol/mmol creatinine ; P iTFA and CLA did not substantially affect plasma concentrations of inflammatory markers , but they increased the urine 8-iso-PGF(2α ) concentration . However , it is unlikely this plays a major role in the mechanism by which iTFA increase the risk of CVD . However , more research is needed to fully underst and the implication s of these findings",
"BACKGROUND Cardiovascular disease is the major cause of morbidity , mortality , and disability in Iranian people . Inflammation and oxidative processes are key components of cardiovascular disease . The aim of this study was to evaluate the effect of conjugated linoleic acids ( CLA ) and omega-3 fatty acid ( ω-3 fatty acids ) supplementation on inflammation markers and oxidative stress in atherosclerotic patients . METHODS This study was a two-month clinical , r and omized trial . 90 volunteers who referred to Emam Reza Heart Clinic of Shiraz University of Medical Sciences ( Shiraz , Iran ) from February to March 2011 and had the inclusion criteria of this study were selected . Participants were classified into 3 groups receiving 3 g/d CLA , 1920 mg/d ω-3 , or placebo for 2 months . C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , malondialdehyde ( MDA ) , and glutathione peroxidase ( GPx ) were measured before and after supplementation . RESULTS The hs-CRP level decreased significantly in both the omega-3 and CLA group ( P . IL-6 reduced significantly in the ω-3 group , but the reduction of IL-6 levels in the CLA group was not significant . GPx increased in the CLA and omega-3 groups ( P . MDA level decreased significantly in both omega-3 and CLA groups ( P in CRP levels in the ω-3 group relative to the control group . However , other indices did not cause any significant change in the ω-3 and CLA groups in comparison to the control group . CONCLUSION Diet supplementation with CLA and ω-3 can have a beneficial effect on some indices of inflammatory and oxidative stress",
"BACKGROUND Because studies suggest that the dietary supplement conjugated linoleic acid ( CLA ) has immunomodulatory activities that might benefit common colds , we performed two studies of CLA effects in experimental human rhinovirus ( HRV ) infection . METHODS The first study explored whether CLA supplementation ( Safflorin ; Loders Croklaan , BV , Wormerveer , the Netherl and s ) altered the virological or clinical course of experimental HRV infection , and the second explored whether CLA affected the frequency and severity of HRV cold-associated sore throat and cough . The trials were r and omized , double-blinded and placebo-controlled . In total , 50 healthy volunteers aged 18 - 45 years and susceptible to HRV type-39 ( serum neutralizing antibody titre Participants ingested CLA 2 g/day or placebo for 4 weeks before and 4 days following intranasal HRV inoculation . The primary endpoint for study 1 was the frequency of colds and for study 2 was the symptom severity scores for sore throat and cough . RESULTS In study 1 , 10/24 ( 42 % ) placebo compared with 7/21 ( 33 % ) CLA participants developed colds ( P = 0.53 ) . CLA was associated with significant reductions in mean scores for cough ( 0 CLA versus 0.9 placebo ) and sore throat ( 0.8 CLA versus 2.9 placebo ) . In study 2 , clinical colds developed in 19/33 ( 58 % ) placebo and 27/43 ( 63 % ) CLA participants . Symptom scores for cough ( 0.9 CLA versus 1.0 placebo ) and sore throat ( 2.6 CLA versus 3.2 placebo ) were not significantly different . Similarly no differences in nasal viral titres or serological responses were found . CONCLUSIONS CLA dietary supplementation had no consistent effects on the virological or clinical course of experimental HRV colds . A larger study would be required to detect more subtle effects of CLA on HRV cold-associated symptoms",
"Both ( n-3 ) long-chain PUFA ( LCPUFA ) and linoleic acid [ LA , 18:2(n-6 ) ] improve cardiovascular disease ( CVD ) risk factors , but a high-LA intake may weaken the effect of ( n-3 ) LCPUFA . In a controlled , double-blind , 2 x 2-factorial 8-wk intervention , we investigated whether fish oil combined with a high- or low-LA intake affects overall CVD risk profile . Healthy men ( n = 64 ) were r and omized to 5 mL/d fish oil capsules ( FO ) [ mean intake 3.1 g/d ( n-3 ) LCPUFA ] or olive oil capsules ( control ) and to oils and spreads with either a high ( S/B ) or a low ( R/K ) LA content , result ing in a 7.3 g/d higher LA intake in the S/B groups than in the R/K groups . Diet , ( n-3 ) LCPUFA in peripheral blood mononuclear cells , blood pressure ( BP ) , heart rate ( HR ) , and plasma CVD risk markers were measured before and after the intervention . FO lowered fasting plasma triacylglycerol ( TAG ) ( P ial TAG measured after the intervention ( P monocyte chemoattractant protein-1 , neither the FO nor fat intervention affected fasting plasma cholesterol , glucose , insulin , fibrinogen , C-reactive protein , interleukin-6 , vascular cell adhesion molecule-1 , P-selectin , oxidized LDL , cluster of differentiation antigen 40 lig and ( CD40L ) , adiponectin , or fasting or postpr and ial BP or HR after adjustment for body weight changes . In conclusion , neither fish oil supplementation nor the LA intake had immediate pronounced effects on the overall CVD risk profile in healthy men , but fish oil lowered plasma TAG in healthy subjects with initially low concentrations",
"Background —Conjugated linoleic acids ( CLAs ) , a group of fatty acids shown to have beneficial effects in animals , are also used as weight loss supplements . Recently , we reported that the t 10 c 12 CLA-isomer caused insulin resistance in abdominally obese men via unknown mechanisms . The aim of the present study was to examine whether CLA has isomer-specific effects on oxidative stress or inflammatory biomarkers and to investigate the relationship between these factors and induced insulin resistance . Methods and Results —In a double-blind placebo-controlled trial , 60 men with metabolic syndrome were r and omized to one of 3 groups receiving t 10 c 12 CLA , a CLA mixture , or placebo for 12 weeks . Insulin sensitivity ( euglycemic clamp ) , serum lipids , in vivo lipid peroxidation ( determined as urinary 8-iso-PGF2&agr ; [ F2-isoprostanes ] ) , 15-ketodihydro PGF2&agr ; , plasma vitamin E , plasma C-reactive protein , tumor necrosis factor-&agr ; , and interleukin-6 were assessed before and after treatment . Supplementation with t 10 c 12 CLA markedly increased 8-iso-PGF2&agr ; ( 578 % ) and C-reactive protein ( 110 % ) compared with placebo ( P 8-iso-PGF2&agr ; , but not in C-reactive protein , were significantly and independently related to aggravated insulin resistance . Oxidative stress was related to increased vitamin E levels , suggesting a compensatory mechanism . Conclusions —t 10 c 12 CLA supplementation increases oxidative stress and inflammatory biomarkers in obese men . The oxidative stress seems closely related to induced insulin resistance , suggesting a link between the fatty acid-induced lipid peroxidation seen in the present study and insulin resistance . These unfavorable effects of t 10 c 12 CLA might be of clinical importance with regard to cardiovascular disease , in consideration of the widespread use of dietary supplements containing this fatty acid",
"Objectives —To determine the effect of dietary supplementation with conjugated linoleic acid ( CLA ) on body mass index ( BMI ) , body fat distribution , endothelial function , and markers of cardiovascular risk . Methods and Results —Forty healthy volunteers with BMI > 27 kg/m2 were r and omized to receive a CLA isomeric mixture or olive oil in a 12-week double-blind study . Subcutaneous body fat and abdominal/hepatic fat content were assessed using skin-fold thicknesses and computed tomography scanning , respectively . Endothelial function was assessed by brachial artery flow-mediated dilatation ( FMD ) . Plasma isoprostanes were measured as an index of oxidative stress . CLA supplementation did not result in a significant change in BMI index or total body fat . There was a significant decrease in limb ( −7.8 mm , P but not torso skin-fold thicknesses or abdominal or liver fat content . Brachial artery FMD declined ( −1.3 % , P=0.013 ) , and plasma F2-isoprostanes increased ( + 91pg/mL , P=0.042 ) . Conclusions —A CLA isomeric mixture had at most modest effects on adiposity and worsened endothelial function . On the basis of these results , the use of the isomeric mixture of CLA as an aid to weight loss can not be recommended",
"Background : Little information about the effects of conjugated linoleic acids ( CLAs ) on inflammation and immune function in humans is available . This study investigated the effects of CLAs , with and without Vitamin E on immunity and inflammatory parameters in adults with active rheumatoid arthritis ( RA ) . Methods : In a double-blind clinical trial , 78 patients were r and omly divided into four groups , each group receiving one of the following daily supplement for 3 months ; group C : 2.5 g CLAs , group E : 400 mg Vitamin E , group CE : CLAs plus Vitamin E , group P : Placebo . Cytokines , matrix metalloproteinase 3 ( MMP-3 ) and citrullinated antibody ( CCP-A ) were measured by ELISA method and Vitamin E by high-performance liquid chromatography . Results : Consider statistical methods there were no significant differences between groups in cytokines interleukin-2 ( IL-2 ) , IL-4 , tumor necrosis factor-α ( TNF-α ) , IL-1β , IL-2/IL-4 , CCP-A white blood cells and neutrophils , lymphocyte , monocytes , and eosinophils numbers . TNF-α decreased in all groups , but its reduction was significant in group CE . IL-1β increased in groups P ( P = 0.004 ) and E ( P = 0.041 ) but the difference between group P and CE was significant . IL-4 decreased in groups C , CE and E ( P = 0.03 , P = 0.03 , P = 0.07 respectively ) . IL2 did not change significantly within groups . CCP-A increased in groups P ( P = 0.035 ) and E ( P = 0.05 ) , while it decreased in groups CE ( P = 0.034 ) . CCP-A and MMP-3 decrease were significant between groups P and CE . MMP-3 reduction was significant in group CE . Conclusions : Co-supplementation CLAs and Vitamin E may be effective in the level of inflammatory markers in RA patients",
"Human , animal , and in vitro research indicates a beneficial effect of appropriate amounts of omega-3 ( n-3 ) polyunsaturated fatty acids ( PUFA ) on bone health . This is the first controlled feeding study in humans to evaluate the effect of dietary plant-derived n-3 PUFA on bone turnover , assessed by serum concentrations of N-telopeptides ( NTx ) and bone-specific alkaline phosphatase ( BSAP ) . Subjects ( n = 23 ) consumed each diet for 6 weeks in a r and omized , 3-period crossover design : 1 ) Average American Diet ( AAD ; [ 34 % total fat , 13 % saturated fatty acids ( SFA ) , 13 % monounsaturated fatty acids ( MUFA ) , 9 % PUFA ( 7.7 % LA , 0.8 % ALA ) ] ) , 2 ) Linoleic Acid Diet ( LA ; [ 37 % total fat , 9 % SFA , 12 % MUFA , 16 % PUFA ( 12.6 % LA , 3.6 % ALA ) ] ) , and 3 ) α-Linolenic Acid Diet ( ALA ; [ 38 % total fat , 8 % SFA , 12 % MUFA , 17 % PUFA ( 10.5 % LA , 6.5 % ALA ) ] ) . Walnuts and flaxseed oil were the predominant sources of ALA . NTx levels were significantly lower following the ALA diet ( 13.20 ± 1.21 nM BCE ) , relative to the AAD ( 15.59 ± 1.21 nM BCE ) ( p level following the LA diet was 13.80 ± 1.21 nM BCE . There was no change in levels of BSAP across the three diets . Concentrations of NTx were positively correlated with the pro-inflammatory cytokine TNFα for all three diets . The results indicate that plant sources of dietary n-3 PUFA may have a protective effect on bone metabolism via a decrease in bone resorption in the presence of consistent levels of bone formation",
"Background Dietary alpha-linolenic acid ( ALA ) has been associated with reduced risk of development of atherosclerosis . Adiponectin is a hormone specifically secreted by adipocytes and considered to have anti-atherogenic properties . Aim of the study We examined the effect of increased dietary intake of ALA on plasma concentration of adiponectin . Methods Thirty-five non-diabetic , dyslipidemic men , 38–71 years old , were r and omly allocated to take either 15 ml of flaxseed oil rich in ALA ( 8.1 g/day ; n = 18 ) , or 15 ml of safflower oil per day , containing the equivalent n-6 fatty acid ( 11.2 g/day linoleic acid , LA ; n = 17 ) ( control group ) . The intervention period lasted for 12 weeks . Results Plasma levels of adiponectin did not change after the increase in dietary intake of ALA in the flaxseed oil supplementation group , compared to the control group . No changes in body mass index , serum lipid concentrations , LDL density , or plasma TNF-α were found in the flaxseed oil versus the control group . Conclusions Dietary ALA has no effect on plasma adiponectin concentration in dyslipidemic men",
"Objective : To investigate the effects of increased alpha-linolenic acid (ALA)-intake on intima – media thickness ( IMT ) , oxidized low-density lipoprotein ( LDL ) antibodies , soluble intercellular adhesion molecule-1 ( sICAM-1 ) , C-reactive protein ( CRP ) , and interleukins 6 and 10 . Design : R and omized double-blind placebo-controlled trial . Subjects : Moderately hypercholesterolaemic men and women ( 55±10 y ) with two other cardiovascular risk factors (n=103).Intervention : Participants were assigned to a margarine enriched with ALA ( fatty acid composition 46 % LA , 15 % ALA ) or linoleic acid ( LA ) ( 58 % LA , 0.3 % ALA ) for 2 y. Results : Dietary ALA intake was 2.3 en% among ALA users , and 0.4 en% among LA users . The 2-y progression rate of the mean carotid IMT ( ALA and LA : + 0.05 mm ) and femoral IMT ( ALA:+0.05 mm ; LA:+0.04 mm ) was similar , when adjusted for confounding variables . After 1 and 2 y , ALA users had a lower CRP level than LA users ( net differences −0.53 and −0.56 mg/l , respectively , P in oxidized LDL antibodies , and levels of sICAM-1 , interleukins 6 and 10 . Conclusions : A six-fold increased ALA intake lowers CRP , when compared to a control diet high in LA . The present study found no effects on markers for atherosclerosis . Sponsorship : The Dutch ‘ Praeventiefonds ’",
"A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms , evaluate new therapeutic approaches , and make go or no-go decisions to carry new drug c and i date s forward into clinical trials . Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent . Here , we show that , although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans , the responses in corresponding mouse models correlate poorly with the human conditions and also , one another . Among genes changed significantly in humans , the murine orthologs are close to r and om in matching their human counterparts ( e.g. , R2 between 0.0 and 0.1 ) . In addition to improvements in the current animal model systems , our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases",
"OBJECTIVE To examine the effects of two different conjugated linoleic acid ( CLA ) isomers at two different intakes on body composition in overweight humans . RESEARCH METHODS AND PROCEDURES Eighty-one middle-aged , overweight , healthy men and women participated in this bicentric , placebo-controlled , double-blind , r and omized study . For 6 weeks ( run-in period ) , all subjects consumed daily a drinkable dairy product containing 3 g of high oleic acid sunflower oil . Volunteers were then r and omized over five groups receiving daily either 3 g of high oleic acid sunflower oil , 1.5 g of cis-9,trans-11 ( c9t11 ) CLA , 3 g of c9t11 CLA , 1.5 g of trans-10,cis-12 ( t10c12 ) CLA , or 3 g of t10c12 CLA administrated as triacylglycerol in a drinkable dairy product for 18 weeks . Percentage body fat mass and fat and lean body mass were assessed at the end of the run-in and experimental periods by DXA . Dietary intake was also recorded . RESULTS Body fat mass changes averaged 0.1 + /- 0.9 kg ( mean + /- SD ) in the placebo group and -0.3 + /- 1.4 , -0.8 + /- 2.1 , 0.0 + /- 2.3 , and -0.9 + /- 1.7 kg in the 1.5-g c9t11 , 3-g c9t11 , 1.5-g t10c12 , and 3-g t10c12 groups , respectively . Changes among the groups were not significantly different ( p = 0.444 ) . Also , lean body mass and dietary intake were not significantly different among the treatments . DISCUSSION A daily consumption of a drinkable dairy product containing up to 3 g of CLA isomers for 18 weeks had no statistically significant effect on body composition in overweight , middle-aged men and women",
"Conjugated linoleic acid ( CLA ) refers to geometric and positional isomers of linoleic acid . Animal studies have shown that CLA modulates the immune system and suggest that it may have a therapeutic role in inflammatory disorders . This double-blind placebo-controlled intervention trial investigated the effects of CLA supplementation on indices of immunity relating to cardiovascular disease ( CVD ) in a cohort of healthy middle-aged male volunteers . Subjects were r and omly assigned to supplement their diet with 2.2 g 50:50 isomeric blend of cis 9 , trans 11 ( c9 , t11)-CLA and trans 10 , cis 12 ( t10 , c12)-CLA or placebo daily for 8 weeks . Interleukin ( IL ) 2 , IL-10 and tumour necrosis factor ( TNF ) alpha were measured in the supernatant of cultured unstimulated and concanavalin A ( Con A)-stimulated peripheral blood mononuclear cells ( P BMC ) by ELISA . Serum IL-6 and plasma CRP were measured by ELISA and plasma fibrinogen by automated clotting assay . Gene expression was investigated by real-time RT-PCR . CLA supplementation significantly reduced Con A-stimulated P BMC IL-2 secretion ( 37.1 % ; P=.02 ) . CLA supplementation had no significant effect on transcription of IL-2 . CLA supplementation had no direct significant effects on P BMC TNFalpha or IL-10 secretion . Other inflammatory markers associated with CVD , including IL-6 , CRP and fibrinogen , were not affected by CLA supplementation . This study showed that CLA supplementation reduced P BMC IL-2 secretion from Con A-stimulated P BMC but lacked effect on other markers of the human inflammatory response",
"Objective : To assess the effects of dietary supplementation using two isomeric blends of conjugated linoleic acid ( CLA ) on immune function in healthy human volunteers . Design : Double-blind , r and omised , placebo-controlled intervention trial . Subjects and intervention : A total of 55 healthy volunteers ( n=20 males , n=35 females ) were r and omised into one of three study groups who received 3 g/day of a fatty acid blend containing a 50:50 cis-9 , trans-11 : trans-10 , cis-12 CLA isomer blend ( 2 g CLA ) , and 80:20 cis-9 , trans-11 : trans-10 , cis-12 ( 80:20 ) CLA isomer blend ( 1.76 g CLA ) or linoleic acid ( control , 2 g linoleic acid ) for 8 weeks . Results : Supplementation with the 80:20 CLA isomer blend significantly ( P≤0.05 ) enhanced PHA-induced lymphocyte proliferation . CLA decreased basal interleukin (IL)-2 secretion ( P≤0.01 ) and increased PHA-induced IL-2 and tumor necrosis factor α ( TNFα ) production ( P≤0.01 ) . However , these effects were not solely attributable to CLA as similar results were observed with linoleic acid . CLA supplementation had no significant effect on peripheral blood mononuclear cells IL-4 production , or on serum-soluble intercellular adhesion molecule-1 ( sICAM-1 ) or plasma prostagl and in E2 ( PGE2 ) or leukotreine B4 ( LTB4 ) concentrations . Conclusions : This study shows that CLA supplementation had a minimal effect on the markers of human immune function . Furthermore , supplementation with CLA had no immunological benefit compared with linoleic acid . Sponsorship : CLA supplements were provided by Loders Croklaan",
"The usefulness of conjugated linoleic acid ( CLA ) as a nutraceutical remains ambiguous . Our objective was , therefore , to investigate the effect of CLA on body composition , blood lipids , and safety biomarkers in overweight , hyperlipidemic men . A double-blinded , 3-phase crossover trial was conducted in overweight ( BMI ≥ 25 kg/m(2 ) ) , borderline hypercholesterolemic [ LDL-cholesterol ( C ) ≥ 2.5 mmol/L ] men aged 18 - 60 y. During three 8-wk phases , each separated by a 4-wk washout period , 27 participants consumed under supervision in r and om order 3.5 g/d of safflower oil ( control ) , a 50:50 mixture of trans 10 , cis 12 and cis 9 , trans 11 ( c9 , t11 ) CLA : Clarinol G-80 , and c9 , t11 isomer : c9 , t11 CLA . At baseline and endpoint of each phase , body weight , body fat mass , and lean body mass were measured by DXA . Blood lipid profiles and safety biomarkers , including insulin sensitivity , blood concentrations of adiponectin , and inflammatory ( high sensitive-C-reactive protein , TNFα , and IL-6 ) and oxidative ( oxidized-LDL ) molecules , were measured . The effect of CLA consumption on fatty acid oxidation was also assessed . Compared with the control treatment , the CLA treatments did not affect changes in body weight , body composition , or blood lipids . In addition , CLA did not affect the β-oxidation rate of fatty acids or induce significant alterations in the safety markers tested . In conclusion , although no detrimental effects were caused by supplementation , these results do not confirm a role for CLA in either body weight or blood lipid regulation in humans ",
"OBJECTIVE To explore the efficacy of conjugated linoleic acid supplementation on some inflammatory factors in young healthy males during exhaustive exercise . METHODS The r and omised double-blind controlled study was conducted at Ardabil University of Medical Sciences , Iran , from December 2012 to March2013 , and comprised healthy male athletes 18 - 24 years of age . The subjects were r and omly distributed into control and intervention groups . About 5.6 g/day conjugated linoleic acid supplement and oral paraffin ( placebo ) were given to intervention and control groups respectively daily for two weeks . Fasting blood sample s were taken at baseline and at the end of the two weeks of intervention . The subjects underwent exhaustive exercise and then fasting blood sample s were taken . Serum levels of tumour necrosis factor alpha , interleukin-6 , high-sensitivity C-reactive protein , matrix metalloproteinases-2 and 9 were measured . RESULTS There were 23 subjects in the study , with 13(56.5 % ) in the supplemented group and 10(43.4 % ) in the control group . Serum levels of matrix metalloproteinases-2 and tumour necrosis factor alpha were significantly decreased in the supplemented group ( p serum levels of matrix metalloproteinases-2 , high-sensitivity C-reactive protein and tumour necrosis factor alpha significantly decreased in the supplemented group compared to the control group(p administration of conjugated linoleic acid reduced the inflammatory factors following exhaustive exercise in young healthy males",
"The healthy Nordic diet has been previously shown to have health beneficial effects among subjects at risk of CVD . However , the extent of food changes needed to achieve these effects is less explored . The aim of the present study was to investigate the effects of exchanging a few commercially available , regularly consumed key food items ( e.g. spread on bread , fat for cooking , cheese , bread and cereals ) with improved fat quality on total cholesterol , LDL-cholesterol and inflammatory markers in a double-blind r and omised , controlled trial . In total , 115 moderately hypercholesterolaemic , non-statin-treated adults ( 25 - 70 years ) were r and omly assigned to an experimental diet group ( Ex-diet group ) or control diet group ( C-diet group ) for 8 weeks with commercially available food items with different fatty acid composition ( replacing SFA with mostly n-6 PUFA ) . In the Ex-diet group , serum total cholesterol ( P and LDL-cholesterol ( P -11 % in total cholesterol and LDL-cholesterol , respectively . No difference in change in plasma levels of inflammatory markers ( high-sensitive C-reactive protein , IL-6 , soluble TNF receptor 1 and interferon-γ ) was observed between the groups . In conclusion , exchanging a few regularly consumed food items with improved fat quality reduces total cholesterol , with no negative effect on levels of inflammatory markers . This shows that an exchange of a few commercially available food items was easy and manageable and led to clinical ly relevant cholesterol reduction , potentially affecting future CVD risk",
"Isomers of conjugated linoleic acids ( CLA ) reduce fat mass ( FM ) and increase insulin sensitivity in some , but not all , murine studies . In humans , this effect is still debatable . In this study , we compared the effect of 2 CLA supplements on total and regional FM assessed by dual energy X-ray absorptiometry , changes in serum insulin and glucose concentrations , and adipose tissue ( AT ) gene expression in humans . In a double-blind , parallel , 16-wk intervention , we r and omized 81 healthy postmenopausal women to 1 ) 5.5 g/d of 40/40 % of cis9,trans11-CLA ( c9,t11-CLA ) and trans10,cis12-CLA ( t10,c12-CLA ) ( CLA-mix ) ; 2 ) cis9 , trans11-CLA ( c9,t11-CLA ) ; or 3 ) control ( olive oil ) . We assessed all variables before and after the intervention . The CLA-mix group had less total FM ( 4 % ) and lower-body FM ( 7 % ) than the control ( P = 0.02 and serum insulin concentrations were greater in the CLA-mix group ( 34 % ) than the control group ( P = 0.02 ) in the highest waist circumference tertile only . AT mRNA expression of glucose transporter 4 , leptin , and lipoprotein lipase was lower , whereas expression of tumor necrosis factor-alpha was higher in the CLA-mix group than in the control group ( P total and lower-body FM in postmenopausal women and greater serum insulin concentrations in the highest waist circumference tertile . Future research is needed to confirm the insulin desensitizing effect of the CLA mixture and the effect on the mRNA expression of adipocyte-specific genes in humans",
"BACKGROUND AND AIMS Little is known about the effect of various dietary fatty acids on pro- and anti-inflammatory processes . We investigated the effect of 5 oils containing various amounts of alpha-linolenic acid ( ALA ) , linoleic acid ( LA ) , oleic acid ( OA ) and docosahexaenoic acid ( DHA ) on plasma inflammatory biomarkers and expression levels of key inflammatory genes and transcription factors in whole blood cells . METHODS AND RESULTS In a r and omized , crossover controlled nutrition intervention , 114 adult men and women with abdominal obesity and at least one other criterion for the metabolic syndrome consumed 5 experimental isoenergetic diets for 4 weeks each , separated by 4-week washout periods . Each diet provided 60 g/3000 kcal of different oils : 1 ) control corn/safflower oil blend ( CornSaff ; LA-rich ) , 2 ) flax/safflower oil blend ( FlaxSaff ; ALA-rich ) , 3 ) conventional canola oil ( Canola ; OA-rich ) , 4 ) high oleic canola oil ( CanolaOleic ; highest OA content ) , 5 ) DHA-enriched high oleic canola oil ( CanolaDHA ; OA- and DHA-rich ) . Gene expression in whole blood cells was assessed in a subset of 62 subjects . CanolaDHA increased plasma adiponectin concentrations compared with the control CornSaff oil treatment ( + 4.5 % , P = 0.04 ) and FlaxSaff ( + 6.9 % , P = 0.0008 ) . CanolaDHA also reduced relative expression levels of interleukin (IL)1B compared with CornSaff and Canola ( -11 % and -13 % , respectively , both P = 0.03 ) . High-sensitivity C-reactive protein concentrations were lower after Canola than after FlaxSaff ( -17.8 % , P = 0.047 ) . CONCLUSION DHA-enriched canola oil exerts anti-inflammatory effects compared with polyunsaturated fatty acids from plant sources",
"Background Conjugated linoleic acids ( CLA ) are naturally occurring fatty acids that have multiple biological properties including the regulation of metabolic , proliferative and immune processes",
"Background : Dietary conjugated linoleic acid ( CLA ) represents a group of positional and geometric isomers of conjugated dienoic derivatives of linoleic acid . The effects of dietary CLA on blood lipids and body composition in humans remain controversial . Objective : To examine whether consumption of milk enriched naturally or synthetically with cis 9 , trans 11 ( c-9 , t-11 ) and trans 10 , cis 12 ( t-10 , c-12 ) CLA isomers alters blood lipid indices , including concentrations of total cholesterol , low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , and triacyglycerol ; indices of liver function including plasma alanine transaminase and total bilirubin ; C-reactive protein ; tumor necrosis factor-alpha ; and body weight and composition in moderately overweight , borderline hyperlipidemic humans . Design : A r and omized , 3-phase , crossover , single-blind clinical trial was carried out in moderately overweight , borderline hyperlipidemic individuals who consumed ( 1 ) milk naturally enriched in CLA ( 4.2 % ) containing c-9 , t-11 only providing 1.3 g/d of CLA ; ( 2 ) milk enriched with a 4.2 % synthetic mixture of t-10 , c-12 and c-9 , t-11 CLA isomers providing 1.3 g/d of CLA ; or ( 3 ) untreated milk as a control providing 0.2 g/d CLA . Dietary phases were each 8 weeks in duration and were separated by 4-week washout periods . Plasma lipid levels were measured in blood sample s collected at the beginning and end of each dietary phase . Magnetic resonance imaging was carried out at the beginning and end of each dietary phase to assess any changes in regional body fat composition . Results : Compared with the control intervention , consumption of the two CLA-enriched milks failed to alter plasma total cholesterol , low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , or triacyglycerol concentrations ; body weight ; or fat composition . CLA consumption did not significantly affect plasma alanine transaminase , total bilirubin , C-reactive protein , or tumor necrosis factor-alpha concentrations . Conclusion : Results from this study fail to support the role of milk enriched naturally with CLA containing c-9 , t-11 or synthetically with c-9 , t-11 and t-10 , c-12 CLA isomers in modulation of lipid profiles or body composition in moderately overweight , borderline hyperlipidemic individuals",
"Conjugated linoleic acid ( CLA ) is shown to have chemoprotective properties in various experimental cancer models . CLA is easily oxidised and it has been suggested that an increased lipid oxidation may contribute to the antitumorigenic effects . This report investigates the urinary levels of 8‐iso‐PGF2α , a major isoprostane and 15‐keto‐dihydro‐PGF2α , a major metabolite of PGF2α , as indicators of non‐enzymatic and enzymatic lipid peroxidation after dietary supplementation of CLA in healthy human subjects for 3 months . A significant increase of both 8‐iso‐PGF2α and 15‐keto‐dihydro‐PGF2α in urine was observed after 3 months of daily CLA intake ( 4.2 g/day ) as compared to the control group ( P Conjugated linoleic acid had no effect on the serum α‐tocopherol levels . However , γ‐tocopherol levels in the serum increased significantly ( P=0.015 ) in the CLA‐treated group . Thus , CLA may induce both non‐enzymatic and enzymatic lipid peroxidation in vivo . Further studies of the mechanism behind , and the possible consequences of , the increased lipid peroxidation after CLA supplementation are urgently needed",
"Recent studies have shown that estrogen ( E ) likely plays a dominant role in inhibiting bone resorption in normal elderly men . Because both E and T inhibit osteoclast development and activity , stimulate osteoclast apoptosis , and inhibit osteoblast production of IL-6 , it is unclear why T is less potent than E in inhibiting bone resorption in vivo . Osteoprotegerin ( OPG ) binds to and inactivates RANKL , the final mediator of osteoclastogenesis . In vitro , OPG production is stimulated by E , and preliminary data suggest that T has the opposite effect . Thus , we analyzed serum for OPG levels from a study in which 59 elderly men ( mean age , 68 yr ) were made acutely hypogonadal using a GnRH agonist and were also placed on an aromatase inhibitor to block conversion of and rogens to estrogens . They were studied first under conditions of physiologic E and T replacement , and then r and omized to no replacement , replacement with E alone , T alone , or both E and T. E alone result ed in an 18.6 + /- 7.9 % ( mean + /- SEM ) increase in serum OPG levels ( P OPG levels ( by 10.0 + /- 8.5 % ; P serum OPG levels . Serum TNF-alpha , IL-6 , and IL-6 soluble receptor levels increased significantly in the men who had both E and T withdrawn , and the increases in TNF-alpha and IL-6sR were absent in the men treated with either E or T. However , due to the variability in these cytokine measurements , the ANOVA models were not significant for E or T effects . Taken together , these data suggest that in vivo , T decreases OPG levels , whereas E tends to have the opposite effect . These differential effects of E vs. T on OPG production may explain , at least in part , why T has weaker effects than E on inhibiting bone resorption in vivo in humans",
"INTRODUCTION AND AIMS Chronic inflammation plays a major role in lung deterioration in cystic fibrosis ( CF ) patients and anti-inflammatory strategies have beneficial effects . To study the changes seen after a one-year course of low-dose dietary supplements with a mixture of fatty acids in adult patients with CF in chronic inflammation , pulmonary status ( lung function , respiratory exacerbations and antibiotic consumption ) , quality of life and anthropometric parameters . PATIENTS AND METHOD Seventeen adult subjects with CF received 324 mg of eicosapentaenoic , 216 mg of docosahexaenoic , 480 mg of linoleic and 258 mg of gammalinolenic acid daily . We assessed inflammation markers , spirometry parameters , number and severity of respiratory exacerbations , antibiotic consumption , quality of life ( St George 's QoL ) , anthropometric parameters and serum phospholipid fatty acid composition . RESULTS At the end of the treatment period TNF alpha levels fell significantly and its soluble receptors ( 60 and 80 ) rose significantly . Levels of IgG and IgM anti-oxidized LDL antibodies fell significantly . Spirometry improved significantly . Annual respiratory exacerbations and days of antibiotic treatment fell significantly . The improvement in QoL was not significant . Serum levels of docosahexaenoic , total omega-3 and linoleic acid rose significantly and more favourable profiles were seen in monoenoic acids , arachidonic acid and the arachidonic/docosahexaenoic ratio . The fat-free mass and h and grip dynamometry improved significantly . CONCLUSIONS Low-dose supplements of n-3 and gammalinolenic fatty acids over a long period ( one year ) appears to improve pulmonary status ( lung function , respiratory exacerbations and antibiotic consumption ) , inflammatory and anthropometric parameters in adults with CF"
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41187a8e-06ff-11f0-808a-c43d1ab1c353
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OBJECTIVES The aim of this study was to systematic ally review the medical literature to evaluate the impact of AV nodal ablation in patients with heart failure and coexistent atrial fibrillation ( AF ) receiving cardiac resynchronization therapy ( CRT ) . BACKGROUND CRT has a substantial evidence base in patients in sinus rhythm with significant systolic dysfunction , symptomatic heart failure , and prolonged QRS duration . The role of CRT is less well established in AF patients with coexistent heart failure . AV nodal ablation has recently been suggested to improve outcomes in this group . METHODS Electronic data bases and reference lists through September 15 , 2010 , were search ed . Two review ers independently evaluated citation titles , abstract s , and articles . Studies reporting the outcomes after AV nodal ablation in patients with AF undergoing CRT for symptomatic heart failure and left ventricular dyssynchrony were selected . Data were extracted from 6 studies , including 768 CRT-AF patients , composed of 339 patients who underwent AV nodal ablation and 429 treated with medical therapy aim ed at rate control alone . RESULTS AV nodal ablation in CRT-AF patients was associated with significant reductions in all-cause mortality ( risk ratio : 0.42 [ 95 % confidence interval : 0.26 to 0.68 ] ) , cardiovascular mortality ( risk ratio : 0.44 [ 95 % confidence interval : 0.24 to 0.81 ] ) , and improvement in mean New York Heart Association functional class ( risk ratio : -0.52 [ 95 % confidence interval : -0.87 to -0.17 ] ) . CONCLUSIONS AV nodal ablation was associated with a substantial reduction in all-cause mortality and cardiovascular mortality and with improvements in New York Heart Association functional class compared with medical therapy in CRT-AF patients . R and omized controlled trials are warranted to confirm the efficacy and safety of AV nodal ablation in this patient population
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[
"AIMS The European cardiac resynchronization therapy ( CRT ) survey is a joint initiative taken by the Heart Failure Association and the European Heart Rhythm Association of the European Society of Cardiology . The primary aim of this survey is to describe current European practice associated with CRT implantations . METHODS AND RESULTS A total of 140 centres from 13 European countries contributed data from consecutive patients successfully implanted with a CRT device with or without an ICD between November 2008 and June 2009 . The total number of patients enrolled was 2438 . The median age of the patients was 70 years ( IQR 62 - 76 ) and 31 % were > or = 75 years . It was found that 78 % were in NYHA functional class III or IV and 22 % in I or II . The mean ejection fraction was 27 % + /- 8 and the mean QRS duration 157 ms + /- 32 . The QRS duration was Atrial fibrillation was reported in 23 % . It was found that 26 % of patients had a previously implanted permanent pacemaker or ICD ; 76 % of procedures were performed by an electrophysiologist ; 82 % had an elective admission for implantation and the median duration of hospitalization was 3 days ( IQR 2 - 7 ) ; and 73 % received a CRT-D device which was more often implanted in men , younger patients , and with ischaemic aetiology . The mean QRS duration was reduced to 133 ms + /- 27 ( P Peri-procedural complication rates were comparable to the rates reported in r and omized trials . CONCLUSION This CRT survey provides important information describing current European practice with regard to patient demographics , selection criteria , procedural routines , and status at discharge . These data should be useful for benchmarking individual patient management and national practice against wider experience",
"OBJECTIVES The main objective of this study was to assess if the benefits of biventricular ( BiV ) pacing observed during the crossover phase were sustained over 12 months . BACKGROUND MUltisite STimulation In Cardiomyopathies ( MUSTIC ) is a r and omized controlled study intended to evaluate the effects of BiV pacing in patients with New York Heart Association ( NYHA ) class III heart failure and intraventricular conduction delay . METHODS Of 131 patients included , 42/67 in sinus rhythm ( SR ) and 33/64 in atrial fibrillation ( AF ) were followed up longitudinally at 9 and 12 months by 6-min walked distance , peak oxygen uptake ( peak VO(2 ) ) , quality of life by the Minnesota score , NYHA class , echocardiography , and left ventricular ejection fraction by radionuclide technique . RESULTS At 12 months , all SR and 88 % of AF patients were programmed to BiV pacing . Compared with baseline , the 6-min walked distance increased by 20 % ( SR ) ( p = 0.0001 ) and 17 % ( AF ) ( p = 0.004 ) ; the peak VO(2 ) by 11 % ( SR ) and 9 % ( AF ) ; quality of life improved by 36 % ( SR ) ( p = 0.0001 ) and 32 % ( AF ) ( p = 0.002 ) ; NYHA class improved by 25 % ( SR ) ( p = 0.0001 ) and 27 % ( AF ) ( p = 0.0001 ) . The ejection fraction improved by 5 % ( SR ) and 4 % ( AF ) . Mitral regurgitation decreased by 45 % ( SR ) and 50 % ( AF ) . CONCLUSIONS The clinical benefits of BiV pacing appeared to be significantly maintained over a 12-month follow-up period",
"Objective : To compare the effects of cardiac resynchronisation therapy ( CRT ) in patients with heart failure ( HF ) in either atrial fibrillation ( AF ) or sinus rhythm ( SR ) . Design : Prospect i ve observational study . Patients : 295 consecutive patients with HF ( permanent AF in 66 , paroxysmal AF in 20 , SR in 209 ; New York Heart Association ( NYHA ) class III or IV ; left ventricular ejection fraction ( LVEF ) ⩽35 % , QRS ⩾120 ms ) . Interventions : All patients underwent CRT without atrioventricular junction ablation . Main outcome measures : The primary end point was the composite of cardiovascular death or unplanned hospitalisation for major cardiovascular events . Secondary end points included the composite of cardiovascular death or hospitalisation for worsening HF . Cardiovascular mortality , total mortality and changes in NYHA class , 6-minute walking distance , quality of life ( Minnesota Living with Heart Failure question naire ) and echocardiographic variables were also considered . Results : Over a follow-up period of up to 6.8 years , no differences emerged between patients in AF or SR in any of the mortality or morbidity end points . The AF and SR groups derived similar improvements in mean NYHA class ( −1.3 vs –1.2 ) , 6-minute walking distance ( 92.3 vs 78.4 m ) and quality of life scores ( −25.2 vs –18.7 ) ( all p seen in left ventricular end-systolic ( −25.9 vs –34.5 ml , both p ) and end-diastolic ( −20.2 ml , p = 0.001 vs 26.2 ml , p ) volumes and improvements in LVEF ( 4.69 % vs 7.86 % , both p Conclusions : Cardiac resynchronisation therapy leads to similar prognostic and symptomatic benefits in patients in AF and SR , even without atrioventricular junction ablation . Echocardiographic improvements are also comparable",
"OBJECTIVES The goal of this study was to investigate the effects of cardiac resynchronization therapy ( CRT ) in heart failure patients with permanent atrial fibrillation ( AF ) and the role of atrioventricular junction ( AVJ ) ablation . BACKGROUND Cardiac resynchronization therapy has been proven effective in heart failure patients with sinus rhythm ( SR ) . However , little is known about the effects of CRT in heart failure patients with permanent AF . METHODS Efficacy of CRT on ventricular function , exercise performance , and reversal of maladaptive remodeling process was prospect ively compared in 48 patients with permanent AF in whom ventricular rate was controlled by drugs , thus result ing in apparently adequate delivery of biventricular pacing ( > 85 % of pacing time ) , and in 114 permanent AF patients , who had undergone AVJ ablation ( 100 % of resynchronization therapy delivery ) . The clinical and echocardiographic long-term outcomes of both groups were compared with those of 511 SR patients treated with CRT . RESULTS Both SR and AF groups showed significant and sustained improvements of all assessed parameters ( model p ejection fraction ( p reverse remodeling effect ( p improved exercise tolerance ( p Heart failure patients with ventricular conduction disturbance and permanent AF treated with CRT showed large and sustained long-term ( up to 4 year ) improvements of left ventricular function and functional capacity , similar to patients in SR , only if AVJ ablation was performed",
"INTRODUCTION The precise role of irregular ventricular response in atrial fibrillation ( AF ) has not been fully eluci date d. This study examined the independent effects of rhythm regularity in patients with chronic AF . METHODS AND RESULTS This study included 50 patients who had chronic lone AF and a normal ventricular rate . Among these patients , 21 who underwent AV junction ablation and implantation of a VVIR pacemaker constituted the ablation group ; the other 29 patients were the medical group . Acute hemodynamic findings were measured in 21 ablation patients before ablation ( during AF , baseline ) and 15 minutes after ablation ( during right ventricular pacing ) . Compared with baseline data , ablation and pacing therapy increased cardiac output ( 4.7 + /- 0.8 vs 5.2 + /- 0.9 L/min ; P = 0.05 ) , decreased pulmonary capillary wedge pressure ( 16 + /- 5 vs 13 + /- 4 mmHg ; P = 0.001 ) , and decreased left ventricular end-diastolic pressure ( 14 + /- 4 vs 11 + /- 3 mmHg ; P ablation group patients showed lower scores in general quality of life ( -20 % ; P overall symptoms ( -24 % ; P overall activity scale ( -23 % ; P = 0.004 ) , and significant increase of left ventricular ejection fraction ( 44 % + /- 6 % vs 49 % + /- 5 % ; P = 0.02 ) by echocardiographic examination . CONCLUSION AV junction ablation and pacing in patients with chronic AF and normal ventricular response may confer acute and long-term benefits beyond rate control by eliminating rhythm irregularity",
"BACKGROUND One third of chronic heart failure patients have major intraventricular conduction and uncoordinated ventricular contraction . Non-controlled studies suggest that biventricular pacing may improve haemodynamics and well-being by reducing ventricular asynchrony . The aim of this trial was to assess the clinical efficacy and safety of this new therapy in patients with chronic atrial fibrillation . METHODS Fifty nine NYHA class III patients with left ventricular systolic dysfunction , chronic atrial fibrillation , slow ventricular rate necessitating permanent ventricular pacing , and a wide QRS complex ( paced width > or=200 ms ) , were implanted with transvenous biventricular-VVIR pacemakers . This single-blind , r and omized , controlled , crossover study compared the patients ' parameters , as monitored during two 3-month treatment periods of conventional right-univentricular vs biventricular pacing . The primary end-point was the 6-min walked distance , secondary end-points were peak oxygen uptake , quality -of-life , hospitalizations , patients ' preferred study period and mortality . RESULTS Because of a higher than expected drop-out rate ( 42 % ) , only 37 patients completed both crossover phases . In the intention-to-treat analysis , we did not observe a significant difference . However , in the patients with effective therapy the mean walked distance increased by 9.3 % with biventricular pacing ( 374+/-108 vs 342+/-103 m in univentricular;P = 0.05 ) . Peak oxygen uptake increased by 13 % ( P=0.04 ) . Hospitalizations decreased by 70 % and 85 % of the patients preferred the biventricular pacing period ( P exercise tolerance in NYHA class III heart failure patients with chronic atrial fibrillation and wide paced-QRS complexes . Further r and omized controlled studies are required to definitively vali date this therapy in such patients",
"The prevalence of atrial fibrillation ( AF ) in patients with heart failure is high , but data about the effects of cardiac resynchronization therapy ( CRT ) in patients with chronic AF are scarce . In this prospect i ve observational study of 263 consecutive patients , CRT was performed in 96 patients ( 37 % ) with chronic AF and 167 patients ( 63 % ) with sinus rhythm ( SR ) . Echocardiographic and clinical parameters were evaluated at baseline and 3 and 12 months . Reverse left ventricular ( LV ) remodeling is defined as LV end-systolic volume decrease > or = 10 % . Hospitalization rates for heart failure in the year before and after implantation were compared . Baseline characteristics between patients with and without AF were similar , but the AF group had smaller LV end-systolic and end-diastolic volumes and larger left atrial dimensions . New York Heart Association class , 6-minute walking distance , quality -of-life score , LV ejection fraction , and mitral regurgitation improved significantly at 3 and 12 months in both groups , and the changes were similar . Reverse LV remodeling after 3 and 12 months was 74 % and 82 % ( AF group ) versus 77 % and 83 % , respectively ( SR group , p = 0.79 ) . After 1 year , cardioversion had occurred in 25 % of patients with AF . In the year after implantation , significant decreases in hospitalizations for heart failure in both groups ( 84 % and 90 % ) were documented . Long-term mortality was almost equal in both groups . In conclusion , this large-scale study shows that the benefit of CRT in patients with chronic AF and heart failure is similar to that in patients with SR . Patients with chronic AF and heart failure should be considered c and i date s for CRT"
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41187ad4-06ff-11f0-808a-c43d1ab1c353
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The aim of this systematic review was to evaluate the evidence from r and omised controlled trials ( RCTs ) evaluating the effectiveness of interactive digital interventions ( IDIs ) for physical activity ( PA ) and health related quality of life ( HRQoL ) in people with Inflammatory Arthritis [ rheumatoid arthritis ( RA ) , juvenile idiopathic arthritis ( JIA ) axial Spondyloarthritis ( AS ) and psoriatic arthritis ( PsA ) ] . Seven electronic data bases identified published and unpublished studies . Two review ers conducted independent data extraction and quality assessment using the Cochrane risk of bias tool ( RoB ) . The primary outcome was change in objective PA after the intervention ; secondary outcomes included self-reported PA and HRQoL after the intervention and objective or self-reported PA at least 1 year later . Five manuscripts , reporting four RCTs ( three high and one low RoB ) representing 492 ( 459 RA , 33 JIA ) participants were included . No trials study ing PsA or AS met the inclusion criteria . Interventions ranged from 6 to 52 weeks and included 3–18 Behaviour Change Techniques . Due to heterogeneity of outcomes , a narrative synthesis was conducted . No trials reported any significant between group differences in objective PA at end of intervention . Only one low RoB trial found a significant between group difference in self-reported vigorous [ MD Δ 0.9 days ( 95 % CI 0.3 , 1.5 ) ; p = 0.004 ] , but not moderate , PA in people with RA but not JIA . There were no between group differences in any other secondary outcomes . There is very limited evidence for the effectiveness of IDIs on PA and HRQoL in RA and JIA and no evidence for their effectiveness in PsA or AS
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"BACKGROUND : Interactive Health Communication Applications ( IHCAs ) are computer-based , usually web-based health information packages for patients that combine information with at least one of social support , decision support , or behaviour change support . These are innovations in health care and their effects on health are uncertain . OBJECTIVES : To assess the effects of IHCAs for people with chronic disease . SEARCH STRATEGY : We design ed a four-part search strategy . First , we search ed electronic bibliographic data bases for published work ; second , we search ed the grey literature and third , we search ed for ongoing and recently completed clinical trials in the appropriate data bases . Finally , research ers of included studies were contacted , and reference lists from relevant primary and review articles were followed up . As IHCAs require relatively new technology , the search commenced at 1990 where possible . SELECTION CRITERIA : R and omised controlled trials ( RCTs ) of Interactive Health Communication Applications for adults and children with chronic disease . DATA COLLECTION AND ANALYSIS : One review er screened abstract s. Two review ers screened all c and i date studies to determine eligibility , apply quality criteria , and extract data from included studies . Authors of included RCTs were contacted for missing data . Results of RCTs were pooled using a r and om effects model and st and ardised mean differences ( SMDs ) were calculated to provide net effect sizes . MAIN RESULTS : We screened 24,757 unique citations and retrieved 958 papers for further assessment , yielding 28 RCTs involving 4042 participants . One of these had an inadequate method of concealment of allocation , and sensitivity analyses were performed to determine the effects of including or excluding these data in the meta-analyses . Results in the abstract are from the meta-analyses excluding data from this study .IHCAs were found to have a positive effect on knowledge ( SMD 0.49 ; 95 % confidence interval ( CI ) 0.14 to 0.84 ) and on social support ( SMD 0.47 ; 95 % CI 0.28 to 0.66 ) . IHCAs were found to have no effect on self-efficacy ( SMD 0.15 ; 95 % CI -0.13 to 0.43 ) or behavioural outcomes ( SMD -0.09 ; 95 % CI -0.49 to 0.32 ) . IHCAs had a negative effect on clinical outcomes ( SMD -0.32 ; 95 % CI -0.63 to -0.02 ) . REVIEW ERS ' CONCLUSIONS : The number and range of IHCAs is increasing rapidly ; however there is a shortage of high quality evaluative data . Consumers who wish to increase their knowledge or social support amongst people with a similar problem may find an IHCA helpful . However , consumers whose primary aim is to achieve optimal clinical outcomes should not use an IHCA at present . Further research is needed to determine the reason for this negative effect on clinical outcomes , whether an optimal IHCA can achieve behaviour change and improved health outcomes , and if so , what are the essential features of such an IHCA , and the extent to which they differ according to patient group or condition",
"OBJECTIVES To investigate the maintenance of physical activity 12 months after two 1-year Internet-based physical activity interventions in patients with RA . METHODS This follow-up study was a r and omized comparison of an Internet-based individualized training ( IT ) and a general training ( GT ) programme in sedentary RA patients . Outcome measures included physical activity ( meeting public health recommendations for moderate physical activity , i.e. 30 min for at least 5 days/week ; or vigorous physical activity , i.e. 20 min for at least 3 days/week ) , functional ability and quality of life ( QoL ) . RESULTS Of the 152 RA patients who completed the initial study , 110 ( 72 % ) were available at follow-up . At 24 months , the proportions of patients meeting public health recommendations for moderate intensity physical activity were significantly higher compared with baseline in both the IT and GT groups ( 19 and 24 % , respectively , P meeting the recommendation for vigorous activity was only significantly higher compared with baseline in the IT group ( P proportions of patients meeting moderate or vigorous physical activity recommendations at 24 months . Apart from a significantly higher RAQoL score in the IT group at 24 months compared with baseline , there were no significant differences within or between the programmes regarding functional ability or QoL. CONCLUSION In RA patients , the effectiveness of both an individualized and a general 1-year Internet-based physical activity programme is sustained with respect to moderate intensity physical activity up to 12 months after the interventions",
"Evidence -based medicine integrates clinical expertise , patients ' values and preferences , and the best available evidence from the medical literature . Evidence -based orthopedics is a model to assist surgeons to improve the process of asking questions , obtaining relevant information efficiently , and making informed decisions with patients . With an increasing appreciation for higher levels of evidence , orthopedic surgeons should move away from lower forms of evidence . The adoption of r and omized trials and high- quality prospect i ve studies to guide patient care requires 2 prerequisites : ( 1 ) greater appreciation for the conduct of r and omized trials in orthopedics and ( 2 ) improved education and training in evidence -based method ologies in surgery",
"OBJECTIVE To compare the accuracy of existing classification criteria for the diagnosis of psoriatic arthritis ( PsA ) and to construct new criteria from observed data . METHODS Data were collected prospect ively from consecutive clinic attendees with PsA and other inflammatory arthropathies . Subjects were classified by each of 7 criteria . Sensitivity and specificity were compared using conditional logistic regression analysis . Latent class analysis was used to calculate criteria accuracy in order to confirm the validity of clinical diagnosis as the gold st and ard definition of \" case\"-ness . Classification and Regression Trees methodology and logistic regression were used to identify items for new criteria , which were then constructed using a receiver operating characteristic curve . RESULTS Data were collected on 588 cases and 536 controls with rheumatoid arthritis ( n = 384 ) , ankylosing spondylitis ( n = 72 ) , undifferentiated arthritis ( n = 38 ) , connective tissue disorders ( n = 14 ) , and other diseases ( n = 28 ) . The specificity of each set of criteria was high . The sensitivity of the Vasey and Espinoza method ( 0.97 ) was similar to that of the method of McGonagle et al ( 0.98 ) and greater than that of the methods of Bennett ( 0.44 ) , Moll and Wright ( 0.91 ) , the European Spondylarthropathy Study Group ( 0.74 ) , and Gladman et al ( 0.91 ) . The CASPAR ( ClASsification criteria for Psoriatic ARthritis ) criteria consisted of established inflammatory articular disease with at least 3 points from the following features : current psoriasis ( assigned a score of 2 ; all other features were assigned a score of 1 ) , a history of psoriasis ( unless current psoriasis was present ) , a family history of psoriasis ( unless current psoriasis was present or there was a history of psoriasis ) , dactylitis , juxtaarticular new bone formation , rheumatoid factor negativity , and nail dystrophy . These criteria were more specific ( 0.987 versus 0.960 ) but less sensitive ( 0.914 versus 0.972 ) than those of Vasey and Espinoza . CONCLUSION The CASPAR criteria are simple and highly specific but less sensitive than the Vasey and Espinoza criteria",
"OBJECTIVE To determine the efficacy of an Internet-based Arthritis Self-Management Program ( ASMP ) as a re source for arthritis patients unable or unwilling to attend small-group ASMPs , which have proven effective in changing health-related behaviors and improving health status measures . METHODS R and omized intervention participants were compared with usual care controls at 6 months and 1 year using repeated- measures analyses of variance . Patients with rheumatoid arthritis , osteoarthritis , or fibromyalgia and Internet and e-mail access ( n = 855 ) were r and omized to an intervention ( n = 433 ) or usual care control ( n = 422 ) group . Measures included 6 health status variables ( pain , fatigue , activity limitation , health distress , disability , and self-reported global health ) , 4 health behaviors ( aerobic exercise , stretching and strengthening exercise , practice of stress management , and communication with physicians ) , 5 utilization variables ( physician visits , emergency room visits , chiropractic visits , physical therapist visits , and nights in hospital ) , and self-efficacy . RESULTS At 1 year , the intervention group significantly improved in 4 of 6 health status measures and self-efficacy . No significant differences in health behaviors or health care utilization were found . CONCLUSION The Internet-based ASMP proved effective in improving health status measures at 1 year and is a viable alternative to the small-group ASMP",
"OBJECTIVE To determine the effects of participation in a low-impact aerobic exercise program on fatigue , pain , and depression ; to examine whether intervention groups compared with a control group differed on functional ( grip strength and walk time ) and disease activity ( total joint count , erythrocyte sedimentation rate , and C-reactive protein ) measures and aerobic fitness at the end of the intervention ; and to test which factors predicted exercise participation . METHODS A convenience sample of 220 adults with rheumatoid arthritis ( RA ) , ages 40 - 70 , was r and omized to 1 of 3 groups : class exercise , home exercise using a videotape , and control group . Measures were obtained at baseline ( T1 ) , after 6 weeks of exercise ( T2 ) , and after 12 weeks of exercise ( T3 ) . RESULTS Using structural equation modeling , overall symptoms ( latent variable for pain , fatigue , and depression ) decreased significantly at T3 ( P exercise group compared with the control group . There were significant interaction effects of time and group for the functional measures of walk time and grip strength : the treatment groups improved more than the control group ( P measures of disease activity . Fatigue and perceptions of benefits and barriers to exercise affected participants ' amount of exercise , supporting previous research . CONCLUSION This study supported the positive effects of exercise on walk time and grip strength , and demonstrated that fatigue and perceived benefits /barriers to exercise influenced exercise participation . Furthermore , overall symptoms of fatigue , pain , and depression were positively influenced in this selective group of patients with RA ages 40 - 70 years",
"The objective of this RCT was to assess the efficacy of an online pain self-management program with adults who had a self-reported doctor diagnosis of arthritis pain ( N = 228 ) . Participants were recruited via flyers and online postings then r and omized to the experimental condition or the wait-list control condition . Individuals in the experimental condition reported significantly ( 1 ) increased arthritis self-efficacy and ( 2 ) reduced pain catastrophizing from baseline to follow up compared to those in the control condition . High user engagement ( > 204.5 min on the website ) was also significantly associated with improved self-management outcomes . These findings suggest that use of an online self-management program may positively impact self-efficacy and catastrophizing among adults with arthritis pain at 6 month follow up . Nonsignificant findings for hypothesized variables such as pain intensity and health behaviors are also discussed . Future longitudinal research is needed to assess if cognitive changes associated with participation in an online self-management program leads to reduced pain",
"BACKGROUND PAH trials traditionally use 6MW as the primary endpoint . Concerns regarding a \" ceiling effect \" masking efficacy have led to exclusion of patients with milder disease from most trials ( BL 6MW>450 m ) . STRIDE I evaluated the selective endothelin A receptor antagonist , sitaxsentan ( SITAX ) , in a 12-week r and omized , double-blind , trial ( 178 patients ) employing placebo ( PBO ) , 100 mg or 300 mg SITAX orally once daily in PAH and included patients with NYHA class II , congenital heart disease and a BL 6MW>450 m , groups often excluded from previous trials . METHODS We analyzed 6MW effects For All Pts ( intention-to treat ) and those meeting Traditional enrollment criteria , defined as patients with NYHA class III or IV and 6MW The 100 mg and 300 mg SITAX arms are pooled based on similar treatment effects on 6MW . CONCLUSION Existence of a \" ceiling effect \" is supported by these data . The magnitude of the treatment effect and statistical power when using 6MW as the endpoint . Comparisons between PAH trials that do not adjust for the effects of differing enrollment criteria require caution",
"Background Rheumatoid arthritis ( RA ) is chronic systematic disease that affects people during the most productive period of their lives . Web-based health interventions have been effective in many studies ; however , there is little evidence and few studies showing the effectiveness of online social support and especially gamification on patients ’ behavioral and health outcomes . Objective The aim of this study was to look into the effects of a Web-based intervention that included online social support features and gamification on physical activity , health care utilization , medication overuse , empowerment , and RA knowledge of RA patients . The effect of gamification on website use was also investigated . Methods We conducted a 5-arm parallel r and omized controlled trial for RA patients in Ticino ( Italian-speaking part of Switzerl and ) . A total of 157 patients were recruited through brochures left with physicians and were r and omly allocated to 1 of 4 experimental conditions with different types of access to online social support and gamification features and a control group that had no access to the website . Data were collected at 3 time points through question naires at baseline , posttest 2 months later , and at follow-up after another 2 months . Primary outcomes were physical activity , health care utilization , and medication overuse ; secondary outcomes included empowerment and RA knowledge . All outcomes were self-reported . Intention-to-treat analysis was followed and multilevel linear mixed models were used to study the change of outcomes over time . Results The best-fit multilevel models ( growth curve models ) that described the change in the primary outcomes over the course of the intervention included time and empowerment as time-variant predictors . The growth curve analyses of experimental conditions were compared to the control group . Physical activity increased over time for patients having access to social support sections plus gaming ( unst and ardized beta coefficient [B]=3.39 , P=.02 ) . Health care utilization showed a significant decrease for patients accessing social support features ( B=–0.41 , P=.01 ) and patients accessing both social support features and gaming ( B=–0.33 , P=.03 ) . Patients who had access to either social support sections or the gaming experience of the website gained more empowerment ( B=2.59 , P=.03 ; B=2.29 , P=.05 ; respectively ) . Patients who were offered a gamified experience used the website more often than the ones without gaming ( t 91=–2.41 , P=.02 ; U=812 , P=.02 ) . Conclusions The Web-based intervention had a positive impact ( more desirable outcomes ) on intervention groups compared to the control group . Social support sections on the website decreased health care utilization and medication overuse and increased empowerment . Gamification alone or with social support increased physical activity and empowerment and decreased health care utilization . This study provides evidence demonstrating the potential positive effect of gamification and online social support on health and behavioral outcomes . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 57366516 ; http://www.controlled-trials . com/IS RCT N57366516 ( Archived by webcite at http://www.webcitation.org/6PBvvAvvV )",
"OBJECTIVE To compare the effectiveness of 2 Internet-based physical activity interventions for patients with rheumatoid arthritis ( RA ) . METHODS A total of 160 physically inactive patients with RA who had a computer with Internet access were r and omly assigned to an Internet-based physical activity program with individual guidance , a bicycle ergometer , and group contacts ( individualized training [ IT ] group ; n = 82 ) or to an Internet-based program providing only general information on exercises and physical activity ( general training [ GT ] group ; n = 78 ) . Outcome measures included quantity of physical activity ( question naire and activity monitor ) , functional ability , quality of life , and disease activity ( baseline , 3 , 6 , 9 , and 12 months ) . RESULTS The proportion of physically active patients was significantly greater in the IT than in the GT group at 6 ( 38 % versus 22 % ) and 9 months ( 35 % versus 11 % ; both P in physical activity as measured with an activity monitor , functional ability , quality of life , or disease activity . CONCLUSION An Internet-based physical activity intervention with individually tailored supervision , exercise equipment , and group contacts is more effective with respect to the proportion of patients who report meeting physical activity recommendations than an Internet-based program without these additional elements in patients with RA . No differences were found regarding the total amount of physical activity measured with an activity monitor",
"This study investigated factors related to an initial exercise experience to explain exercise maintenance in 120 adults with rheumatoid arthritis or osteoarthritis . Integral secondary analysis was used to incorporate data from a prospect i ve , controlled trial of exercise ( Minor et al. : Arthritis Rheum 32:1396 , 1989 ) with data collected at 18 months follow-up . The dependent variable was self-directed exercise ( min/wk ) reported at 3 , 9 , and 18 or more months after exercise class participation . Predictor variables included physical , psychosocial , disease , and programmatic factors . The all possible regressions search procedure result ed in three explanatory models ( p = .0001 ) . At 3 months the model ( R2 = .45 ) included initial aerobic capacity , depression , and anxiety ; and changes in depression and social activity . The 9-month model ( R 2 = .35 ) consisted of initial anxiety and physical activity , change in depression , support of friends for exercise , and exercise behavior at prior assessment . At 18 or more months ( R2 = .42 ) , model variables were initial aerobic capacity , change in pain , and exercise behavior at the two prior assessment s. Neither disease nor program factors appeared as significant . This limited study indicates that factors associated with exercise behavior in this sample are similar to those in the general population ; explanatory factors change over time , and changes ascribed to a trial behavior may influence subsequent decision making"
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41187b24-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND Gallstones are present in about 10 % to 15 % of the adult western population . Between 1 % and 4 % become symptomatic in a year . Cholecystectomy for symptomatic gallstones is mainly performed after the acute cholecystitis episode settles because of the fear of higher morbidity and conversion from laparoscopic cholecystectomy to open cholecystectomy during acute cholecystitis . OBJECTIVES The aim was to compare the early laparoscopic cholecystectomy ( less than seven days of onset of symptoms ) versus delayed laparoscopic cholecystectomy ( more than six weeks after index admission ) with regards to benefits and harms . SEARCH STRATEGY We search ed The Cochrane Hepato-Biliary Group Controlled Trials Register , the Cochrane Central Register of Controlled Trials ( CENTRAL ) in The Cochrane Library , MEDLINE , EMBASE , and Science Citation IndexExp and ed until November 2005 . SELECTION CRITERIA We considered for inclusion all r and omised clinical trials comparing early versus delayed laparoscopic cholecystectomy for acute cholecystitis . DATA COLLECTION AND ANALYSIS We collected the data on the characteristics of the trial , method ological quality of the trials , mortality , morbidity , conversion rate , operating time , and hospital stay from each trial . We analysed the data with both the fixed-effect and the r and om-effects models using RevMan Analysis . For each outcome we calculated the odds ratio ( OR ) with 95 % confidence intervals ( CI ) based on intention-to-treat analysis . MAIN RESULTS We included five trials with 451 patients r and omised : 223 to the early group and 228 to the delayed group . Surgery was performed on 222 patients in the early group and on 216 patients in the delayed group . There was no mortality in any of the trials . Four of the five trials were of high method ological quality . There was no statistically significant difference between the two groups for any of the outcomes including bile duct injury ( OR 0.63 , 95 % CI 0.15 to 2.70 ) and conversion to open cholecystectomy ( OR 0.84 , 95 % CI 0.53 to 1.34 ) . Various other analyses including ' available case analysis ' , risk difference , statistical methods to overcome the ' zero-event trials ' showed no statistically significant difference between the two groups in any of the outcomes measured . A total of 40 patients ( 17.5 % ) from the delayed group had to undergo emergency laparoscopic cholecystectomy due to non-resolving or recurrent cholecystitis ; 18 ( 45 % ) of these had to undergo conversion to open procedure . The total hospital stay was about three days shorter in the early group compared with the delayed group . AUTHORS ' CONCLUSIONS Early laparoscopic cholecystectomy during acute cholecystitis seems safe and shortens the total hospital stay . The majority of the outcomes occurred rarely ; hence , the confidence intervals are wide . Therefore , further r and omised trials on the issue are needed
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"Abstract . The prospect ively collected data from 530 cholecystectomies performed in a university clinic from October 1989 to March 1991 were analyzed after 1 to 3 years of follow-up . The aim of this study was to compare the results of laparoscopic cholecystectomy ( LC ) for acute cholecystitis with that for routine symptomatic gallbladders . The preoperative , intraoperative , and postoperative parameters of 424 routine ( noninflamed ) LCs and 54 LCs for acutely inflamed gallbladders were compared under the “ intention to treat ” principle . Operating time was longer in the inflamed group ( median 97 minutes versus 75 minutes;p adhesions ( 20 % versus 8 % ) , more blood loss ( 48 % versus 19 % ) , a higher incidence of bile spillage ( 28 % versus 12 % ) , and lost stones ( 19 % versus 8 % ) were encountered in patients with acute cholecystitis . Common bile duct ( CBD ) injuries were also more frequent in that group ( 5.5 % versus 0.2%;p = 0.005 ) . The rate of conversion to open surgery was higher than with routine LCs ( 13 % versus 4 % ) . There were two deaths in the routine LC group and none in the acutely inflamed group . There was no difference in postoperative pain intensity or postoperative fatigue according to visual analog scale measurements . Patients with acute cholecystitis stayed only 1 day longer ( median 4 days versus 3 days ) in hospital . The quality of life scores indicate return to almost normal values by the 14th postoperative day . Long-term follow-up ( 1–3 years ) did not reveal any delayed clinical adverse effects . In summary , LC for inflamed gallbladders has a higher conversion rate than LC for routine symptomatic gallbladders . If successfully performed , it has definite benefit for the patient in terms of better postoperative recovery . The trade-off is that the risk of CBD injury is significantly higher",
"Background We assessed the role of mangafodipir-enhanced magnetic resonance ( MR ) cholangiography in the detection and location of bile duct leaks after laparoscopic cholecystectomy . Methods In a prospect i ve study , 34 patients with clinical suspicion of bile duct leak after laparoscopic cholecystectomy underwent MR imaging . Our protocol included conventional heavily T2-weighted MR cholangiography and three-dimensional T1-weighted MR cholangiography after an intravenous bolus injection of mangafodipir trisodium . All studies were performed on a 1.5-T or 1-T scanner . Contrast-enhanced MR cholangiograms were evaluated for the presence and location of bile duct leaks . Correlation was obtained in all cases with surgery ( n = 15 ) , endoscopic retro grade cholangiography ( n = 5 ) , percutaneous drainage ( n = 5 ) , and clinical follow-up ( n = 9 ) . Results In 20 of 34 patients , bile duct leakage was proved by surgery , endoscopic retro grade cholangiography , or drainage . Contrast enhancement displayed the leakage in 19 of 20 patients and ruled out leaks in the other 14 patients ( 95 % sensitivity , 100 % specificity ) . The leak site was depicted in 14 patients and contrast-enhanced MR cholangiography successfully located the origin of the leak in 11 patients . Conclusions Contrast-enhanced MR cholangiography with intravenous mangafodipir trisodium can accurately diagnose the presence and location of bile duct leaks in patients who have undergone laparoscopic cholecystectomy",
"Although laparoscopic cholecystectomy has rapidly developed in the treatment of gall bladder disease in the absence of controlled clinical trial data its outcome parameters compared with open cholecystectomy remain unclear . A prospect i ve audit of the introduction of laparoscopic cholecystectomy in the west of Scotl and over a two year period was carried out to attempt to assess this new procedure . A total of 45 surgeons in 19 hospitals performing laparoscopic cholecystectomy su bmi tted prospect i ve data from September 1990 - 1992 . A total of 2285 cholecystectomies were audited ( a completed data collection rate of 99 % ) . Laparoscopic cholecystectomy was attempted in 1683 ( 74 % ) patients and completed in 1448 patients ( median conversion rate to the open procedure 17 % ) . The median operation time in the completed laparoscopic cholecystectomy patients was 100 minutes ( range 30 - 330 ) and overall hospital stay three days ( 1 - 33 ) . There were nine deaths ( 0.5 % ) after laparoscopic cholecystectomy although only two were directly attributable to the laparoscopic procedure . In the laparoscopic cholecystectomy group there were 99 complications ( 5.9 % ) , 53 ( 3 % ) of these were major requiring further invasive intervention . Forty patients ( 2.4 % ) required early or delayed laparotomy for major complications such as bleeding or bile duct injuries . There were 11 ( 0.7 % ) bile duct injuries in the laparoscopic cholecystectomy series , five were noted during the initial procedure and six were recognised later result ing from jaundice or bile leaks . Ductal injuries occurred after a median of 20 laparoscopic cholecystectomies . In conclusion laparoscopic cholecystectomy has rapidly replaced open cholecystectomy in the treatment of gall bladder disease . Although the overall death and complication rate associated with laparoscopic cholecystectomy is similar to open cholecystectomy , the bile duct injury rate is higher",
" Five hundred and forty-seven middle-aged women , selected at r and om from the population of Malmö , Sweden , were invited to a screening survey for gallstone disease ; 424 participated ( 77.5 % ) . Forty-one had previously been operated on for gallbladder disease . The prevalence of gallstone disease , on the basis of a positive finding at ultrasonography and cholecystography , was 11 % . The predictive value of a positive finding at ultrasonography was 86 % . Six out of 10 women with gallstone were classified as asymptomatic . Body weight , blood pressure , liver enzymes , fasting blood glucose , and blood lipids , including apolipoprotein-A , did not differ significantly in women with and without gallstone disease . At least 9 out of 10 gallstones appeared to be cholesterol stones . Approximately half were of a size that would make them accessible for dissolution therapy",
"Background : The role of laparoscopic cholecystectomy for acute cholecystitis is not yet clearly established . The aim of this prospect i ve r and omized study was to evaluate the safety and feasibility of laparoscopic cholecystectomy for acute cholecystitis and to compare the results with delayed cholecystectomy . Methods : Between January 2001 and November 2002 , 40 patients with a diagnosis of acute cholecystitis were assigned r and omly to early laparoscopic cholecystectomy within 24 h of admission ( early group , n = 20 ) or to initial conservative treatment followed by delayed laparoscopic cholecystectomy , 6 to 12 weeks later ( delayed group , n = 20 ) . Results : There was no significant difference in the conversion rates ( early , 25 % vs delayed , 25 % ) , operating times ( early , 104 min vs delayed , 93 min ) , postoperative analgesia requirements ( early , 5.3 days vs delayed , 4.8 days ) , or postoperative complications ( early , 15 % vs delayed , 20 % ) . However , the early group had significantly more blood loss ( 228 vs 114 ml ) and shorter hospital stay ( 4.1 vs 10.1 days ) . Conclusions : Early laparoscopic cholecystectomy for acute cholecystitis is safe and feasible , offering the additional benefit of a shorter hospital stay . It should be offered to patients with acute cholecystitis , provided the surgery is performed within 72 to 96 h of the onset of symptoms",
"BACKGROUND Studies of ERCP-related morbidity seldom include a sufficient patient follow-up . The aim of this study was to characterize and to evaluate the frequency of complications , cardiopulmonary untoward events in particular . METHODS All patients undergoing ERCP during a 2-year period were included in this prospect i ve study . Complications were assessed at the time of ERCP and by postal/telephone contact at 30-days after the procedure . RESULTS A total of 1177 ERCPs were included in the analysis , of which 56.2 % were therapeutic . The 30-day complication rate was 15.9 % ; the procedure-related mortality rate was 1.0 % . Post-ERCP pancreatitis occurred in 3.8 % of patients ( 3 deaths ) . Hemorrhage or perforation occurred with 0.9 % and 1.1 % , respectively , of the procedures ( 3 deaths ) . One perforation that result ed in the death of the patient occurred after placement of an endoprosthesis . Cholangitis occurred in relation to 5 % of the ERCP procedures ( 3 deaths ) . Cardiorespiratory complications occurred in 2.3 % ( 2 deaths ) . Dilated bile duct ( p = 0.0001 ) , placement of stent ( p = 0.001 ) , and use of more than 40 mg of hyoscine-N-butyl bromide ( p Risk of pancreatitis was increased with age under 40 years ( p = 0.0078 ) , placement of stent ( p = 0.031 ) , and a dilated bile duct ( p = 0.036 ) . CONCLUSIONS This prospect i ve study confirms that the complication rate of ERCP including therapeutic procedures is high . Cardiopulmonary complications were not as common as expected , despite being the special focus of the study",
"Abstract . This prospect i ve study determines the indications for and the optimal timing of laparoscopic cholecystectomy ( LC ) following the onset of acute cholecystitis . It also evaluates preoperative and operative factors associated with conversion from laparoscopic cholecystectomy to open cholecystectomy in the presence of acute cholecystitis . Having been established as the procedure of choice for elective cholelithiasis , LC is now also used for management of acute cholecystitis . Under these circumstances the procedure may be difficult and challenging . Certain favorable and unfavorable conditions may be present that influence the conversion and complication rates . Information about these conditions may be helpful for elucidating the optimal circumstances for LC or when the procedure is best avoided . We performed LC on an emergency basis as soon as the diagnosis was made on all patients presenting with acute cholecystitis from January 1994 to December 1995 . All preoperative , operative , and postoperative data were collected on st and ardized forms . Of the 137 patients registered , 130 were eligible for the audit . Seven patients found by laparoscopic intraoperative cholangiography to have choledocholithiasis were converted for common bile duct exploration and were excluded from the study . Altogether 93 patients ( 72 % ) underwent successful LC and 37 ( 28 % ) needed conversion to open cholecystectomy . The conversion rate of acute gangrenous cholecystitis ( 49 % ) was significantly higher than that for uncomplicated acute cholecystitis ( 4.5 % ) ( p hydrops ( 28.5 % ) and empyema of the gallbladder ( 28.5 % ) ( p= 0.004 ) . The difference in conversion between the group with acute necrotizing ( gangrenous ) cholecystitis and the two groups with hydrops and empyema of the gallbladder was not statistically significant ( p= 0.07 ) . The complication rates of acute cholecystitis , hydrops , empyema of the gallbladder , and gangrenous cholecystitis were 9.0 % , 9.5 % , 14.0 % , and 20.0 % , respectively ( p= NS ) . Patients with an operative delay of 96 hours or less from the onset of acute cholecystitis had a conversion rate of 23 % , whereas a delay of more than 96 hours was associated with a conversion rate of 47 % ( p= 0.022 ) . The complication rate was 8.5 % in the laparoscopic group and 27 % in the converted group ( p= 0.013 ) . Patients over 65 years of age , with a history of biliary disease , a nonpalpable gallbladder , WBC count over 13,000/cc , and acute gangrenous cholecystitis were independently associated with a high LC conversion rate ; male patients , finding large bile stones , serum bilirubin over 0.8 mg/dl , and WBC count over 13,000/cc were independently associated with a high complication rate following laparoscopic surgery with or without conversion . Generally , LC can be performed safely for acute cholecystitis , with acceptably low conversion and complication rates . Different forms of cholecystitis carry various conversion and complication rates in selected cases . LC for acute cholecystitis should be performed within 96 hours of the onset of disease . Predictors of conversion and complications may be helpful when planning the laparoscopic approach to acute cholecystitis",
"OBJECTIVE A prospect i ve r and omized study was undertaken to compare early with delayed laparoscopic cholecystectomy for acute cholecystitis . SUMMARY BACKGROUND DATA Laparoscopic cholecystectomy for acute cholecystitis is associated with high complication and conversion rates . It is not known whether there is a role for initial conservative treatment followed by interval elective operation . METHOD During a 26-month period , 99 patients with a clinical diagnosis of acute cholecystitis were r and omly assigned to early laparoscopic cholecystectomy within 72 hours of admission ( early group , n = 49 ) or delayed interval surgery after initial medical treatment ( delayed group , n = 50 ) . Thirteen patients ( four in the early group and nine in the delayed group ) were excluded because of refusal of operation ( n = 6 ) , misdiagnosis ( n = 5 ) , contraindication for surgery ( n = 1 ) , or loss to follow-up ( n = 1 ) . RESULTS Eight of 41 patients in the delayed group underwent urgent operation at a median of 63 hours ( range , 32 to 140 hours ) after admission because of spreading peritonitis ( n = 3 ) and persistent fever ( n = 5 ) . Although the delayed group required less frequent modifications in operative technique and a shorter operative time , there was a tendency toward a higher conversion rate ( 23 % vs. 11 % ; p = 0.174 ) and complication rate ( 29 % vs. 13 % ; p = 0.07 ) . For 38 patients with symptoms exceeding 72 hours before admission , the conversion rate remained high after delayed surgery ( 30 % vs. 17 % ; p = 0.454 ) . In addition , delayed laparoscopic cholecystectomy prolonged the total hospital stay ( 11 days vs. 6 days ; p recuperation period ( 19 days vs. 12 days ; p morbidity and conversion rate of laparoscopic cholecystectomy for acute cholecystitis . Early operation within 72 hours of admission has both medical and socioeconomic benefits and is the preferred approach for patients managed by surgeons with adequate experience in laparoscopic cholecystectomy",
" A r and om sample of 4,807 men and women , aged 30 , 40 , 50 , and 60 years , who lived in the western part of Copenhagen County , was drawn from the National Central Person Registry . A total of 226 subjects who were not of Danish origin were omitted . The response rate was 78.8 % ( 3,608/4,581 ) . Each person had his or her gallbladder examined by ultrasonography . The examinations took place between November 1982 and February 1984 . The overall prevalence of gallstone disease ( cases with stones and cholecystectomized cases ) in males aged 30 , 40 , 50 , and 60 years was 1.8 % , 1.5 % , 6.7 % , and 12.9 % , respectively . The corresponding prevalence in females was 4.8 % , 6.1 % , 14.4 % , and 22.4 % , respectively . Differences according to sex were significant in all age groups . Differences between the 40- and 50-year and 50- and 60-year age groups were significant in both sexes . Among subjects with gallstone disease , the disease was unknown to the prob and in the majority of males and in the 30-year-old females , but only in half of the women aged 40 , 50 , and 60 years . The prevalence of clinical ly diagnosed gallstones was not significantly different between respondents and nonrespondents",
"The aim of this prospect i ve , r and omized study was to determine whether laparoscopic cholecystectomy should be performed as an early or a delayed operation in patients with acute cholecystitis . After diagnostic workup , patients were r and omized to one of two groups : ( 1 ) early laparoscopic cholecystectomy ( i.e. , within 7 days after onset of symptoms ) or ( 2 ) initial conservative treatment followed by delayed laparoscopic cholecystectomy 6 to 8 weeks later . Seventy-four patients were placed in the early-operation group , and 71 patients were assigned to the delayed-operation strategy . There was no significant difference in conversion rates ( early 31 % vs. delayed 29 % ) , operating times ( early 98 [ range 30 to 355 ] minutes vs. delayed 100 [ 45 to 280 ] minutes ) , or complications . Failure with the conservative treatment strategy was noted in 26 % of these patients . The total hospital stay was significantly shorter in the early group ( 5 [ range 3 to 63 ] days ) vs. the delayed group ( 8 [ range 4 to 50 ] days ; P conversion rate , early laparoscopic cholecystectomy offered significant advantages in the management of acute cholecystitis compared to a conservative strategy . The greatest advantage was a reduced total hospital stay",
"The rapid introduction of laparoscopic cholecystectomy has been associated with an apparently increased incidence of bile duct injury which has provoked worldwide concern . The true incidence and mechanism of iatrogenic ductal injury during the development of this procedure remain unclear . To assess this , the introduction of laparoscopic cholecystectomy in the West of Scotl and has been audited prospect ively over a 5‐year period . All cases of biliary ductal injury have been independently review ed . Some 48 surgeons undertaking laparoscopic cholecystectomy in 19 hospitals su bmi tted prospect i ve data between September 1990 and September 1995 . A total of 5913 laparoscopic cholecystectomies were attempted with 98·3 per cent completion of data collection . During this period 37 laparoscopic bile duct injuries occurred . The annual incidence peaked at 0·8 per cent and has fallen to 0·4 per cent in the final year of audit . Injuries occurred after a median personal experience of 51 ( range 3–247 ) laparoscopic chole cystectomies in 22 surgeons . Major bile duct injuries occurred in 20 of 37 patients , giving an incidence of 0·3 per cent . Five mechanisms for laparoscopic ductal injury were identified , including tenting , confluence and diathermy injuries as well as the classical and variant classical types . Ductal injuries were discovered at operation in 18 patients with consequent repair giving a good clinical outcome in 17 . Contributory factors ( severe inflammation , aberrant anatomy and poor visualization ) were present in only 13 of 37 cases . This audit suggests that , at least in the introductory period , laparoscopic cholecystectomy is associated with an overall bile duct injury rate higher than that reported previously after open cholecystectomy , although the incidence of major ductal injury is similar . The late downward trend in bile duct injury , however , suggests there may be a prolonged learning curve for this procedure . Improved underst and ing of the mechanism of injury may lead to yet further reductions in this complication",
"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 .",
"BACKGROUND The management of bile leaks has evolved in the laparoscopic era . This study characterizes risk factors for their developmental and their clinical course and management . METHODS Data on a cohort of patients who developed bile leaks after cholecystectomy in the laparoscopic era were gathered prospect ively and retrospectively from an ongoing surgical data base and following a review of hospital charts . RESULTS Sixty-four patients ( mean age 56 + /- 17.1 years , 72 % women ) were included over a 5-year study period . The incidence of leaks was 1.1 % among patients entered in a laparoscopic cholecystectomy data base . Intraoperative complications were encountered in 36 % . Rates of intraoperative complication and conversion to open surgery were greater among patients who developed leaks ( 5.2 % vs 0.6 % and 33 % vs 6.3 % , respectively , p abdominal pain ( 89 % ) , fever ( 74 % ) , and tenderness ( 81 % ) . Ultrasound diagnosed a suspected leak in 73 % , which ERCP showed as originating from the cystic duct stump in 77 % . Biliary obstruction was noted in 20 ( 31 % ) patients ( 14 with stones ) . Treatments included percutaneous ( 13 % ) , endoscopic ( 28 % ) , primary or secondary operative procedures ( 14 % ) , or a combination thereof ( 45 % ) . CONCLUSION A complication at laparoscopic cholecystectomy increases the likelihood of a subsequent bile leak . Most patients present early with a patent cystic duct stump in the absence of biliary obstruction . Endoscopic therapy is successful in the majority of cases , but otherwise percutaneous or operative procedures may be needed",
"BACKGROUND The management of stones in the common bile duct in the laparoscopic era is controversial . The three major options are preoperative endoscopic retro grade cholangiography ( ERCP ) , laparoscopic exploration of the common bile duct ( LECBD ) , or postoperative ERCP . METHODS Between August , 1995 , and August , 1997 , 471 laparoscopic cholecystectomies were done in our department . In 427 ( 91 % ) , satisfactory peroperative cholangiography was obtained . In 80 ( 17 % ) of these cases there were stones in the common bile duct , 40 patients were r and omised to LECBD and 40 to postoperative ERCP . If LECBD failed , patients had either open exploration of the common bile duct or postoperative ERCP . If one postoperative ERCP failed , the procedure was repeated until the common bile duct was cleared of stones or an endoprosthesis was placed to prevent stone impaction . The primary endpoints were duct-clearance rates , morbidity , operating time , and hospital stay . Analyses were by intention to treat . FINDINGS Age and sex distribution of patients was similar in the r and omised groups . Duct clearance after the first intervention was 75 % in both groups . By the end of treatment , duct clearance was 100 % in the laparoscopic group compared with 93 % in the ERCP group . Duration of treatment was a median of 90 min ( range 25 - 310 ) in the laparoscopic group ( including ERCPs for failed LECBD ) compared with 105 min ( range 60 - 255 ) in the postoperative ERCP group ( p = 0.1 , 95 % CI for difference -5 to 40 ) . Hospital stay was a median of 1 day ( range 1 - 26 ) in the laparoscopic group compared with 3.5 days ( range 1 - 11 ) in the ERCP group ( p = 0.0001 , 95 % CI 1 - 2 ) . INTERPRETATION LECBD is as effective as ERCP in clearing the common bile duct of stones . There is a non-significant trend to shorter time in the operating theatre and a significantly shorter hospital stay in patients treated by LECBD",
"Background : The aim of this prospect i ve , r and omized study was to determine if health related quality of life is affected by the choice of surgical strategy in the management of acute cholecystitis . Material and Methods : After diagnostic workup , patients were r and omized to one of two groups : ( 1 ) early laparoscopic cholecystectomy ( i.e. within 7 days after onset of symptoms ) or ( 2 ) initial conservative treatment followed by delayed laparoscopic cholecystectomy . Seventy-four patients entered the early operation group and 71 patients were assigned to the delayed operation strategy . Assessment s of quality of life were made at 1 , 3 and 6 months after surgery , and in the delayed operation group also one month after the initial conservative treatment . Results : The gastrointestinal symptom scores were significantly better in three dimensions ( diarrhea , indigestion , abdominal pain ) one month after surgery for the acute operation group ( p symptoms in the period of time waiting for their elective operation . Psychological general well-being showed no major differences between the groups . Conclusion : Cholecystectomy in the acute phase of acute cholecystitis offers a significant reduction of gastrointestinal symptoms during the first postoperative month and to that associated improved quality of life in this group of patients",
"BACKGROUND The aim of the present study was to compare the risk of observation versus that of cholecystectomy in acute cholecystitis in patients r and omly allocated to delayed operation or conservative treatment . METHODS One-hundred- and -eighty patients were considered for participation in the study ; 71 were excluded according to predefined criteria and 45 did not join for other reasons . The remaining 64 patients were r and omized to cholecystectomy ( n = 31 ) or observation ( n = 33 ) . R and omized patients were contacted regularly and followed up for a median of 67 months . All gallstone-related hospital contacts were registered in both r and omized and excluded patients . RESULTS Gallstone-related complications or emergency admissions for pain occurred in six patients in the operation group ( 19 % ; 95 % CI 5%-33 % ) and in 12 patients ( 36 % ; 9 % CI 20%-53 % ) in the observation group . Twenty-seven of 31 patients r and omized to cholecystectomy had a cholecystectomy at a median of 3.6 months after r and omization , and , of these , 3 ( 11 % ; 95 % CI 0%-23 % ) suffered a major and 7 ( 26 % ; 95 % CI 9%-42 % ) a minor complication . Ten patients r and omized to observation later had their gallbladders removed , 1 ( 10 % ; 95 % CI 0%-29 % ) patient had a major and 1 ( 10 % ; 95 % CI 0%-29 % ) a minor complication . We found no mortality after cholecystectomy . CONCLUSIONS We found a certain risk of subsequent gallstone-related events following conservative treatment of acute cholecystitis , but the data also show that cholecystectomy should not necessarily be compulsory after acute cholecystitis",
"Objective : Prospect ively evaluate whether for patients having laparoscopic cholecystectomy with failed trans-cystic duct clearance of bile duct ( BD ) stones they should have laparoscopic choledochotomy or postoperative endoscopic retro grade cholangiography ( ERCP ) . Summary Background Data : Clinical management of BD stones found at laparoscopic cholecystectomy in the last decade has focused on pre-cholecystectomy detection with ERCP clearance in those with suspected stones . This clinical algorithm successfully clears the stones in most patients , but no stones are found in 20 % to 60 % of patients and rare unpredictably severe ERCP morbidity can result in this group . Our initial experience of 300 consecutive patients with fluoroscopic cholangiography and intraoperative clearance demonstrated that , for the pattern of stone disease we see , 66 % of patients ’ BD stones can be cleared via the cystic duct with dramatic reduction in morbidity compared to the 33 % requiring choledochotomy or ERCP . Given the limitations of the preoperative approach to BD stone clearance , this trial was design ed to explore the limitations , for patients failing laparoscopic trans-cystic clearance , of laparoscopic choledochotomy or postoperative ERCP . Methods : Across 7 metropolitan hospitals after failed trans-cystic duct clearance , patients were intraoperatively r and omized to have either laparoscopic choledochotomy or postoperative ERCP . Exclusion criteria were : ERCP prior to referral for cholecystectomy , severe cholangitis or pancreatitis requiring immediate ERCP drainage , common BD diameter of less than 7 mm diameter , or if bilio-enteric drainage was required in addition to stone clearance . Drain decompression of the cleared BD was used in the presence of cholangitis , an edematous ampulla due to instrumentation or stone impaction and technical difficulties from local inflammation and fibrosis . The ERCP occurred prior to discharge from hospital . Mechanical and extracorporeal shockwave lithotripsy was available . Sphincter balloon dilation as an alternative to sphincterotomy to allow stone extraction was not used . Major endpoints for the trial were operative time , morbidity , retained stone rate , reoperation rate , and hospital stay . Results : From June 1998 to February 2003 , 372 patients with BD stones had successful trans-cystic duct clearance of stones in 286 , leaving 86 patients r and omized into the trial . Total operative time was 10.9 minutes longer in the choledochotomy group ( 158.8 minutes ) , with slightly shorter hospital stay 6.4 days versus 7.7 days . Bile leak occurred in 14.6 % of those having choledochotomy with similar rates of pancreatitis ( 7.3 % versus 8.8 % ) , retained stones ( 2.4 % versus 4.4 % ) , reoperation ( 7.3 % versus 6.6 % ) , and overall morbidity ( 17 % versus 13 % ) . Conclusions : These data suggest that the majority of secondary BD stones can be diagnosed at the time of cholecystectomy and cleared trans-cystically , with those failing having either choledochotomy or postoperative ERCP . However , because of the small trial size , a significant chance exists that small differences in outcome may exist . We would avoid choledochotomy in ducts less than 7 mm measured at the time of operative cholangiogram and severely inflamed friable tissues leading to a difficult dissection . We would advocate choledochotomy as a good choice for patients after Billroth 11 gastrectomy , failed ERCP access , or where long delays would occur for patient transfer to other locations for the ERCP",
"BACKGROUND Recent management guidelines and r and omised clinical trials have provided evidence -based guidance to the management of acute biliary pancreatitis and acute cholecystitis . METHODS A question naire was sent to the 1086 members of the Association of Surgeons of Great Britain and Irel and . There were 583 responders ( 54 % ) . RESULTS A policy of cholecystectomy during the index admission or within 4 weeks in fit patients recovering from mild acute biliary pancreatitis was adopted by 58 % of surgeons , and was significantly associated with an upper gastrointestinal and hepato-pancreato-biliary subspecialty interest and a volume of more than 50 cholecystectomies per annum ( OR , 0.43 ; 95 % CI , 0.26 - 0.72 ; P = 0.001 : and OR , 0.46 ; 95 % CI , 0.29 - 0.74 ; P = 0.001 , respectively ) . A policy of urgent cholecystectomy for acute cholecystitis was adopted by 20 % of surgeons , and was significantly associated with an upper gastrointestinal/hepato-pancreato-biliary subspecialty interest and the ' routine ' adoption of laparoscopic approach to cholecystectomy ( OR , 0.34 ; 95 % CI , 0.19 - 0.60 ; P of cholelithiasis in patients with acute biliary pancreatitis in the UK remains suboptimal . Moreover , only a minority of surgeons offer patients presenting with acute cholecystitis the benefits of early laparoscopic cholecystectomy . The management of acute biliary disease may be improved if these cases were concentrated in the h and s of surgeons with upper gastrointestinal/hepato-pancreato-biliary interest and those who perform laparoscopic cholecystectomy regularly",
"Treatment of acute cholecystitis is still under debate . The aim of this study was to evaluate the efficacy of early laparoscopic cholecystectomy ( ELC ) in comparison with conservative treatment followed by delayed laparoscopic cholecystectomy ( DLC ) in the management of acute cholecystitis . This prospect i ve comparative study involved two groups of patients presenting with acute cholecystitis within 72 hours of the onset of symptoms . ELC was performed in 82 consecutive patients , whereas DLC was performed in 87 patients who previously underwent medical treatment . Surgical variables , hospital stay , and postoperative morbidity were evaluated in both groups . Time of surgery and conversion rate were lower in the ELC group . Postoperative morbidity was similar in both groups . Overall hospital stay was shorter in the ELC group . ELC within 72 hours of the onset of acute cholecystitis is a safe procedure with better results than DLC in terms of surgical timing , conversion rate , and hospital stay",
"The aim of this prospect i ve r and omized study was to define the optimum management between early and delayed laparoscopic cholecystectomy for patients with acute cholecystitis",
"Background / Aim : Delay of laparoscopic cholecystectomy after the diagnosis of biliary colic may increase the probability of recurrent emergency admission while awaiting elective cholecystectomy . The aim of this study was to compare the possible advantages and safety of urgent laparoscopic cholecystectomy ( ULC ) with elective laparoscopic cholecystectomy ( ELC ) in patients with biliary colic . Patients and Methods : Between 2001 and 2003 , 75 patients with biliary colic were included in this study . The patients were classified into following two groups : patients who had ULC in 24 h were in group I ( n = 28 ) and patients who had ELC ( mean interval 4.22 ± 1.42 months ) were in group II ( n = 35 ) . Conversion to open cholecystectomy , operative time , postoperative hospital stay , costs , and complications were evaluated . Results : In group II , 9 patients made a total of 13 return visits to the emergency department with recurrent attacks of biliary colic or complications of gallstone disease . Mean operative time increased from 35.1 ± 6.74 min for urgent laparascopic cholecystectomy to 49.9 ± 6.12 min for ELC ( p > 0.05 ) and hospital stay time increased from 1.06 ± 0.4 to 2.31 ± 2.36 days ( p 0.05 ) . Conversion to open cholecystectomy increased from 0 % in group I to 17.2 % in group II ( p be the most medically efficacious and cost-effective treatment",
"Objective : A single institution retrospective analysis of 200 patients with major bile duct injuries was completed . Three patients died without surgery due to uncontrolled sepsis . One hundred seventy-five patients underwent surgical repair , with a 1.7 % postoperative mortality and a complication rate of 42.9 % . Summary Background Data : The widespread application of laparoscopic cholecystectomy ( LC ) has led to a rise in the incidence of major bile duct injuries ( BDI ) . Despite the frequency of these injuries and their complex management , the published literature contains few substantial reports regarding the perioperative management of BDI . Methods : From January 1990 to April 2003 , a prospect i ve data base of all patients with a BDI following LC was maintained . Patients ’ charts were retrospectively review ed to analyze perioperative surgical management . Results : Over 13 years , 200 patients were treated for a major BDI following LC . Patient demographics were notable for 150 women ( 75 % ) with a mean age of 45.5 years ( median 44 years ) . One hundred eighty-eight sustained their BDI at an outside hospital . The mean interval from the time of BDI to referral was 29.1 weeks ( median 3 weeks ) . One hundred nine patients ( 58 % ) were referred within 1 month of their injury for acute complications including bile leak , biloma , or jaundice . Twenty-five patients did not undergo a surgical repair at our institution . Three patients ( 1.5 % ) died after delayed referral before an attempt at repair due to uncontrolled sepsis . Twenty-two patients , having intact biliary-enteric continuity , underwent successful balloon dilatation of an anastomotic stricture . A total of 175 patients underwent definitive biliary reconstruction , including 172 hepaticojejunostomies ( 98 % ) and 3 end-to-end repairs . There were 3 deaths in the postoperative period ( 1.7 % ) . Seventy-five patients ( 42.9 % ) sustained at least 1 postoperative complication . The most common complications were wound infection ( 8 % ) , cholangitis ( 5.7 % ) , and intraabdominal abscess/biloma ( 2.9 % ) . Minor biliary stent complications occurred in 5.7 % of patients . Early postoperative cholangiography revealed an anastomotic leak in 4.6 % of patients and extravasation at the liver dome-stent exit site in 10.3 % of patients . Postoperative interventions included percutaneous abscess drainage in 9 patients ( 5.1 % ) and new percutaneous transhepatic cholangiography and stent placement in 4 patients ( 2.3 % ) . No patient required reoperation in the postoperative period . The mean postoperative length of stay was 9.5 days ( median 9 days ) . The timing of operation ( early , intermediate , delayed ) , presenting symptoms , and history of prior repair did not affect the incidence of the most common perioperative complications or length of postoperative hospital stay . Conclusions : This series represents the largest single institution experience reporting the perioperative management of BDI following LC . Although perioperative complications are frequent , nearly all can be managed nonoperatively . Early referral to a tertiary care center with experienced hepatobiliary surgeons and skilled interventional radiologists would appear to be necessary to assure optimal results"
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Successful treatment of first-episode psychosis is one of the major factors that impacts long-term prognosis . Currently , there are no satisfactory biological markers ( biomarkers ) to predict which patients with a first-episode psychosis will respond to which treatment . In addition , a non-negligible rate of patients does not respond to any treatment or may develop side effects that affect adherence to the treatments as well as negatively impact physical health . Thus , there clearly is a pressing need for defining biomarkers that may be helpful to predict response to treatment and sensitivity to side effects in first-episode psychosis . The present systematic review provides ( 1 ) trials that assessed biological markers associated with antipsychotic response or side effects in first-episode psychosis and ( 2 ) potential biomarkers associated with biological disturbances that may guide the choice of conventional treatments or the prescription of innovative treatments . Trials including first-episode psychoses are few in number . Most of the available data focused on pharmacogenetics markers with so far only preliminary results . To date , these studies yielded-beside markers for metabolism of antipsychotics-no or only a few biomarkers for response or side effects , none of which have been implemented in daily clinical practice . Other biomarkers exploring immunoinflammatory , oxidative , and hormonal disturbances emerged as biomarkers of first-episode psychoses in the last decades , and some of them have been associated with treatment response . In addition to pharmacogenetics , further efforts should focus on the association of emergent biomarkers with conventional treatments or with innovative therapies efficacy , where some preliminary data suggest promising results
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"Rationale To enhance the effectiveness of antipsychotics in first-episode psychosis is crucial in order to achieve the most favourable prognosis . Difference in effectiveness between antipsychotics is still under debate . Objective The purpose of this study is to determine the long-term ( 3-year ) effectiveness and efficacy of haloperidol , risperidone and olanzapine in first-episode schizophrenia-spectrum disorders . Method This is a prospect i ve , r and omized , open-label study . Data for the present investigation were obtained from a large epidemiologic and 3-year longitudinal intervention programme of first-episode psychosis . One hundred seventy-four patients were r and omly assigned to haloperidol ( N = 56 ) , olanzapine ( N = 55 ) , or risperidone ( N = 63 ) and followed up for 3 years . The primary effectiveness measure was all-cause of treatment discontinuation . In addition , an analysis based on per- protocol population s was conducted in the analysis for clinical efficacy . Results The treatment discontinuation rate for any cause differed significantly between treatment groups ( χ2 = 10.752 ; p = 0.005 ) , with a higher rate in haloperidol than in risperidone and olanzapine . The difference in the discontinuation rate between risperidone and olanzapine showed a tendency towards significance ( χ2 = 3.022 ; p = 0.082 ) . There was a significant difference in the mean time to all-cause discontinuation between groups ( log-rank χ2 = 12.657;df = 2 ; p = 0.002 ) . There were no significant advantages to any of the three treatments in reducing the psychopathology severity . Conclusions After 3 years of treatment , a lower effectiveness was observed in haloperidol compared to second-generation antipsychotics ( SGAs ) . The use of SGAs for the treatment of early phases of nonaffective psychosis may enhance the effectiveness of antipsychotics",
"This study examined the possible association between the polymorphism in the dopamine receptor DRD4 gene and response to risperidone among 24 Israeli Jewish adolescent in patients with first-episode schizophrenia . Response was categorically determined by a change of > 40 % on the Brief Psychiatric Rating Scale ( BPRS ) . No significant association was found between the DRD4 genotype and clinical response , although carriers of response rate ( 10/20 vs. 0/4 , P=0.11 ) . Studies in larger groups of adolescent schizophrenia patients are warranted to clarify the possible association between DRD4 exon III repeat alleles and the response to risperidone",
"In the present study , including 66 schizophrenic patients and 73 healthy controls , the effect of atypical antipsychotic treatment over a period of 14 weeks on psychotic symptoms and plasma levels of glutamate and monoaminergic metabolites was investigated . Treatment induced a modest reduction of psychotic symptoms in 42 % of the patients ( response criterion : Brief Psychiatric Rating Scale [ BPRS ] decrease > /=40 % ) . Poor response was associated with severity of psychopathology , age and duration of disease . Glutamate at baseline was significantly higher in patients as compared to controls ( p glutamate , not related to response , was observed . Glutamate levels correlated significantly with negative symptom scores at baseline and weeks 3 , 6 and 14 ( p serotonin ( 5-HT ) in plasma and 5-HT in platelets were significantly lower in the poor responders as compared to controls ( p 5-HT parameters . No differences in plasma levels of HVA , 5-HIAA and their ratio were observed between controls and response groups . The results of this study suggest an effect of atypical antipsychotics on glutamatergic neurotransmission and an association between lower pretreatment peripheral 5-HT parameters and response",
"Recent trials support the hypothesis of the role of inflammation in the pathogenesis of schizophrenia . The overall therapeutic benefit of anti-inflammatory medication , in particular cyclo-oxygenase-2 ( COX-2 ) inhibitors in schizophrenia , is still controversial . There are suggestions that therapy with COX-2 inhibitors may influence the early stages of the disease . Taking these findings into account , we conducted a double-blind , placebo-controlled , r and omized trial of celecoxib augmentation to amisulpride treatment in patients with a first manifestation of schizophrenia . Forty-nine patients diagnosed with schizophrenia were r and omly assigned . They were treated either with amisulpride ( 200 - 1000 mg ) plus celecoxib ( 400 mg ) or amisulpride ( 200 - 1000 mg ) plus placebo . Inclusion criterion was the diagnosis of schizophrenia during the past two years according to DSM-IV . The trial lasted six weeks . At weekly intervals an assessment of the psychopathology was performed using the Positive and Negative Symptom Scale ( PANSS ) and the Global Clinical Impression Scale ( CGI ) . A significantly better outcome was observed in the patient group treated with amisulpride plus celecoxib compared to the group with amisulpride plus placebo ( PANSS negative : p=0.03 ; PANSS global ; p=0.05 and PANSS total : p=0.02 ) . In addition , ratings by the CGI scale during therapy with amisulpride and celecoxib showed a significantly better result ( p significantly superior therapeutic effect could be observed in the celecoxib group compared to placebo in the treatment of early stage schizophrenia . This is the first time an improvement in patients ' negative symptoms has been demonstrated with celecoxib . In future , further trials are needed to investigate the effect of COX-2 inhibitors on prodromal and negative symptoms of schizophrenia",
"Tobacco consumption has been recognized as a factor mediating the interindividual variations in olanzapine 's pharmacokinetics and pharmacodynamics . The primary objective of this study was to describe the dose effect of smoking on the dose-plasma concentration relationship and the pharmacokinetics of oral olanzapine in male schizophrenic patients using high-performance liquid chromatography coupled with electrochemical detector . Twenty-seven male schizophrenic in patients were recruited and were stratified into the following groups according to smoking behaviors : non-smokers ( n=9 ) , light-smokers ( 1 - 4 cigarettes per day ; n=9 ) , and heavy-smokers ( > or=5 cigarettes per day ; n=9 ) . Plasma olanzapine concentrations were determined up to 120 h following a single oral dose of 10 mg olanzapine . The pharmacokinetic parameters were calculated by the non-compartment method using WinNonlin software . Results show that there was a significant correlation among non-smokers ( n=9 ; 0.79 ; p=0.01 ) or combined with light-smokers ( n=18 ; 0.62 ; p peak plasma olanzapine concentrations ( Cmax ) and their individual dose-corrected by body weight , but this correlation did not appear in heavy-smokers . There were no significant differences between non-smokers and light-smokers except for significant decreased AUC0 - ->120 by 45.1 % in light-smokers . The mean C(max ) and the mean area under the plasma concentration-time curve from time zero to 120 h ( AUC0 - ->120 ) of the heavy-smoking patients was 9.3+/-4.3 ng/ml ( 65.2 % reduction compared to the non-smokers ) and 302.4+/-167.8 h ng/ml ( 67.6 % reduction compared to the non-smokers ) , respectively . In summary , a daily consumption of 5 cigarettes is probably sufficient for induction of olanzapine metabolism . Smoking cessation is recommended for olanzapine therapy to have better prediction for therapeutic dosages particularly in heavy-smokers . Compared to non-smokers , heavy-smokers therefore require a 50 - 100 % increase in olanzapine doses . Therapeutic drug monitoring will need to be considered when schizophrenic patients change their smoking behaviors",
"BACKGROUND It is difficult to improve negative symptoms and cognitive impairments in schizophrenia . A previous pilot study has shown that minocycline , a semi-synthetic second-generation tetracycline , is effective in treating for negative and /or cognitive symptoms in schizophrenia . OBJECTIVES The present study was design ed to examine the efficacy and safety of minocycline for the treatment of negative symptoms and cognitive impairments in patients with schizophrenia . METHODS Ninety-two patients with early stage schizophrenia treated with risperidone entered this 16-week , double blind , r and omized , placebo-controlled clinical trial . Subjects were r and omly assigned to receive minocycline ( 200 mg per day ) or the placebo . The primary outcome was evaluated using the Scale for the Assessment of Negative Symptoms ( SANS ) . Secondary outcomes included the response rate of SANS , the Positive and Negative Syndrome Scale ( PANSS ) , the Clinical Global Impression Scale ( CGI ) , and cognitive tests . RESULTS Subjects receiving minocycline had greater improvements on SANS total scores and PANSS negative subscale scores ( P Rates of treatment response ( 43.6 % ) in the minocycline group were significantly higher than those in the placebo group ( 10.0 % ) after 16weeks of treatment . There was no significant difference between the seven cognitive domains ( P>0.05 ) , except for the attention domain ( P=0.044 ) . CONCLUSIONS The addition of minocycline to atypical antipsychotic drugs in early schizophrenia had significant efficacy on negative symptoms but had a slight effect on the attention domains of patients with schizophrenia . It may be considered as a new adjunct treatment for negative symptoms of schizophrenia . Clinical trials.gov identifier : NCT01493622",
"Polyunsaturated fatty acids ( PUFAs ) are the major constituents of cell membrane phospholipids . As such , they have multiple important biological roles , including in receptor binding , neurotransmission , signal transduction , and eicosanoid synthesis . A growing body of studies suggests significant reductions in PUFA levels in people with schizophrenia ( Berger et al , 2006 ) . Concordant with these findings , fatty acids , particularly the omega-3 PUFA , may have a beneficial role in the treatment of first-episode schizophrenia , and in the prevention of schizophrenia , while results in chronic schizophrenia have been mixed ( Peet , 2008 ) . We have recently tested whether supplementation with omega-3 PUFA could reduce the rate of transition to first-episode psychosis in an ultra-high risk ( UHR ) cohort . In our study , we r and omized 81 individuals aged 13–25 years to 12 weeks of either 1.2 g/day of omega-3 PUFA or placebo , followed by a 40-week monitoring period . In all , 2 of 41 ( 4.9 % ) of those receiving the active agent transitioned to psychosis , compared with 11 of 40 ( 27.5 % ) in the placebo group , a statistically significant difference ( Amminger et al , 2010 ) . While PUFAs have been investigated in schizophrenia , their role in the onset of psychotic symptoms is unclear . Therefore , we examined the relationship between omega-3 PUFA ( ie , alpha-linolenic acid ( ALA ) , eicosapentaenoic acid ( EPA ) , docosapentaenoic acid ( DPA ) , and docosahexaenoic acid ( DHA ) ) levels in erythrocyte membrane phosphatidylethanolamine and measures of psychopathology in our UHR cohort at baseline . Erythrocyte membrane phospholipid composition closely reflects that of neuronal membranes , and provides an easily accessible indicator of brain phospholipids . While ALA , EPA , and DHA did not correlate significantly with any symptom measure , low levels of DPA and the summary score of all assessed omega-3 fatty acids ( ie , ALA , EPA , DPA , and DHA ) correlated with more severe negative symptoms . These correlations remained significant after adjustment for potential confounders ( ie , age , sex , and nicotine use ) . Reduced DPA has been previously reported in neuroleptic-naive first-episode schizophrenia patients ( Reddy et al , 2004 ) . Given our intervention study provided support for the ‘ dose – response ' criterion ( McNamara , 2011 ) , as an increase in erythrocyte omega-3 PUFA levels reduced the rate of transition to psychosis and correlated with functional improvement , we tested if the subjects with the lowest erythrocyte omega-3 levels at baseline were at higher risk for transitioning to psychosis . To eliminate treatment effects , we only investigated those participants who had received placebo . Cox regression analyses with adjustment for age , sex , and nicotine use indicated that no single omega-3 PUFA or their summary score predicted conversion to psychosis . Following studies reporting lower levels of arachidonic acid ( AA ) and nervonic acid ( NA ) , as well as DHA , in people with schizophrenia ( Assies et al , 2001 ) , we also examined if these fatty acids predicted transition to psychosis . While AA was not found to be predictive , low NA levels at baseline significantly predicted transition to psychosis ( Amminger et al , su bmi tted ) . As NA is a major constituent of the myelin sheath , low levels of NA could reflect suboptimal myelination in those UHR individuals who develop a psychotic disorder . The finding is consistent with the well-established finding of white matter abnormalities in schizophrenia ( Ellison-Wright and Bullmore , 2009 ) . Notably , the observation that supplementation with omega-3 PUFAs may prevent transition to psychosis suggests that omega-3 fatty acids may offset the risk conferred by decreased levels of NA . A r and omized controlled multicenter phase III clinical trial of omega-3 PUFA is now underway to replicate the findings ( Australian New Zeal and Clinical Trials Registry - ACTRN12608000475347 )",
"One branch of the tryptophan catabolic cascade is the kynurenine pathway , which produces neurotoxic [ 3-hydroxykynurenine ( 3-OHKY ) , quinolinic acid ] and neuroinhibitory ( kynurenic acid ) compounds . Kynurenic acid acts as a competitive antagonist at the glycine site of N-methyl-d-asparate receptors at high concentrations and as a non-competitive antagonist on the α7-nicotinic acetylcholine receptor at low concentrations . Kynurenine compounds also influence cognitive functions known to be disrupted in schizophrenia . Alterations in tryptophan metabolism are therefore of potential significance for the pathophysiology of this disorder . In this paper , tryptophan metabolites were measured from plasma using high-pressure liquid chromatography coupled with electrochemical coulometric array detection , and relationships were tested between these metabolic signatures and clinical symptoms for 25 first-episode neuroleptic-naive schizophrenia patients . Blood sample s were collected and clinical and neurological symptoms were rated at baseline and again at 4 wk following initiation of treatment . Level of 3-OHKY and total clinical symptom scores were correlated when patients were unmedicated and neuroleptic-naive , and this relationship differed significantly from the correlation observed for patients 4 wk after beginning treatment . Baseline psychosis symptoms were predicted only by neurological symptoms . Moreover , baseline 3-OHKY predicted clinical change at 4 wk , with the lowest concentrations of 3-OHKY being associated with the greatest improvement in symptoms . Taken together , our findings suggest a neurotoxic product of tryptophan metabolism , 3-OHKY , predicts severity of clinical symptoms during the early phase of illness and before exposure to antipsychotic drugs . Baseline level of 3-OHKY may also predict the degree of clinical improvement following brief treatment with antipsychotics",
"BACKGROUND Current antipsychotics have only a limited effect on 2 core aspects of schizophrenia : negative symptoms and cognitive deficits . Minocycline is a second-generation tetracycline that has a beneficial effect in various neurologic disorders . Recent findings in animal models and human case reports suggest its potential for the treatment of schizophrenia . These findings may be linked to the effect of minocycline on the glutamatergic system , through inhibition of nitric oxide synthase and blocking of nitric oxide-induced neurotoxicity . Other proposed mechanisms of action include effects of minocycline on the dopaminergic system and its inhibition of microglial activation . OBJECTIVE To examine the efficacy of minocycline as an add-on treatment for alleviating negative and cognitive symptoms in early-phase schizophrenia . METHOD A longitudinal double-blind , r and omized , placebo-controlled design was used , and patients were followed for 6 months from August 2003 to March 2007 . Seventy early-phase schizophrenia patients ( according to DSM-IV ) were recruited and 54 were r and omly allocated in a 2:1 ratio to minocycline 200 mg/d . All patients had been initiated on treatment with an atypical antipsychotic ( risperidone , olanzapine , quetiapine , or clozapine ; 200 - 600 mg/d chlorpromazine-equivalent doses ) . Clinical , cognitive , and functional assessment s were conducted , with the Scale for the Assessment of Negative Symptoms ( SANS ) as the primary outcome measure . RESULTS Minocycline was well tolerated , with few adverse events . It showed a beneficial effect on negative symptoms and general outcome ( evident in SANS , Clinical Global Impressions scale ) . A similar pattern was found for cognitive functioning , mainly in executive functions ( working memory , cognitive shifting , and cognitive planning ) . CONCLUSIONS Minocycline treatment was associated with improvement in negative symptoms and executive functioning , both related to frontal-lobe activity . Overall , the findings support the beneficial effect of minocycline add-on therapy in early-phase schizophrenia . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00733057",
"A side-effect of treatment with antipsychotic drugs for schizophrenia is increased body fat , which leads to further morbidity and poor adherence to treatment . The 5-hydroxytryptamine 2C receptor ( 5-HT2C ) has been associated with this effect ; we aim ed to establish whether a genetic polymorphism of the promoter region of this receptor affects weight gain after drug treatment in first-episode patients with schizophrenia . We noted significantly less weight gain in patients with the -759 T variant allele ( p=0.0003 ) than in those without this allele , who were more likely to have substantial ( > 7 % ) weight gain ( p=0.002 ) . We have identified a genetic factor that is associated with antipsychotic drug-induced weight gain",
"OBJECTIVE To investigate if ethyl-eicosapentaenoic acid ( E-EPA ) augmentation improves antipsychotic efficacy and tolerability in first-episode psychosis ( FEP ) . METHOD We performed a 12-week , r and omized , double-blind , placebo-controlled trial of 2-g E-EPA augmentation in 80 FEP patients . Sixty-nine patients were eligible for analysis ; a post hoc analysis was computed for a subgroup of nonaffective FEP patients ( N = 53 ) . The first participant was included in November 2000 and the last participant completed the trial in August 2003 . Primary outcome measures were symptom change scores and time to first response , while tolerability measures and cumulative antipsychotic dose were secondary outcome measures . RESULTS Analysis of covariance controlling for baseline symptoms found no significant mean difference between E-EPA and placebo at week 12 for symptom change scores . Cox regression analysis revealed a significant treatment by diagnosis interaction ( p = .024 ) for time to first response favoring E-EPA in nonaffective psychosis . Post hoc analysis for cumulative response rates further confirmed a higher response rate at week 6 ( 42.9 % [ 15/35 ] vs. 17.6 % [ 6/34 ] for all participants , p = .036 ; 54.2 % [ 13/24 ] vs. 17.2 % [ 5/29 ] for the nonaffective psychosis subset , p = .008 ) ; however , the difference at week 12 was no longer significant . Analysis of secondary outcome measures revealed that E-EPA-augmented participants needed 20 % less antipsychotic medication between weeks 4 through 6 ( p = .03 ) , had less extrapyramidal side effects in the initial 9 weeks ( p constipation ( p = .011 ) and fewer sexual side effects ( p = .016 ) than those treated with antipsychotic medication alone . CONCLUSION The findings suggest that E-EPA may accelerate treatment response and improve the tolerability of antipsychotic medications . However , it was not possible to demonstrate a sustained symptomatic benefit of E-EPA in early psychosis , possibly due to a ceiling effect , since a high proportion of first-episode patients already achieve symptomatic remission with antipsychotic medication alone . Further controlled trials in nonaffective early psychosis seem warranted . TRIAL REGISTRATION Australian Clinical Trials Registry identifier 12605000267651 ( http://actr.org.au )",
"BACKGROUND Impaired antioxidant defense and increased lipid peroxidation has been reported in chronic schizophrenic patients . Recently , we have reported an impaired antioxidant defense in never medicated first-episode schizophrenic and schizophreniform patients . We report now a concomitant increase in plasma lipid peroxides . METHODS The plasma lipid peroxides [ thiobarbituric acid reactive substances ( TBARS ) ] were analyzed by chemical and high performance liquid chromatography procedures in 26 patients admitted for a first episode of schizophrenic ( N = 17 ) or schizophreniform psychosis ( N = 9 ) and 16 normal control subjects . The patients had a duration of 4.5 days ( SD 2.8 ) of psychosis at the time of the study . RESULTS Plasma TBARS levels were significantly higher in the patients than in normal controls ( P TBARS levels were above the normal range in 16 of the 26 patients . Higher TBARS levels were associated with a greater severity of negative symptoms and lower red blood cell activity of the glutathione peroxidase . CONCLUSIONS The findings indicate ongoing oxidative injury at the very onset of psychosis . If valid , this would indicate the need for adjunctive antioxidant treatment from the beginning of the course of nonaffective psychoses . This might prevent a deteriorating course and development of the deficit syndrome",
"The genetic factors determining the progression of prodromal syndromes to first episode schizophrenia have remained enigmatic to date . In a unique prospect i ve multicentre trial , we assessed whether variants at the d-amino acid oxidase activator (DAOA)/G72 locus influence progression to psychosis . Young subjects with a prodromal syndrome were observed prospect ively for up to 2 years to assess the incidence of progression to schizophrenia or first episode psychosis . Of the 82 prob and s with a prodromal syndrome , 21 prob and s experienced progression to psychosis within the observation period . Assessment of nine common variants in the DAOA/G72 locus yielded two variants with the predictive value for symptom progression : all four prob and s with the rs1341402 CC genotype developed psychosis compared with 17 out of 78 prob and s with the TT or CT genotypes ( χ2 = 12.348 ; df = 2 ; p = 0.002 ) . The relative risk for progression to psychosis was significantly increased in the CC genotype : RR = 4.588 ( 95 % CI = 2.175–4.588 ) . Similarly , for rs778294 , 50 % of prob and s with the AA genotype , but only 22 % of prob and s with a GG or GA genotype progressed to psychosis ( χ2 = 7.027 ; df = 2 ; p = 0.030 ) . Moreover , haplotype analysis revealed a susceptibility haplotype for progression to psychosis . This is one of the first studies to identify a specific genetic factor for the progression of prodromal syndromes to schizophrenia , and further underscores the importance of the DAOA/G72 gene for schizophrenia",
"Immune system factors including complement pathway activation are increasingly linked to the etiology and pathophysiology of schizophrenia . Complement protein , C1q , binds to and helps to clear immune complexes composed of immunoglobulins coupled to antigens . The antigenic stimuli for C1q activation in schizophrenia are not known . Food sensitivities characterized by elevated IgG antibodies to bovine milk caseins and wheat glutens have been reported in individuals with schizophrenia . Here , we examined the extent to which these food products might comprise the antigen component of complement C1q immune complexes in individuals with recent onset schizophrenia ( n=38 ) , non-recent onset schizophrenia ( n=61 ) and non-psychiatric controls ( n=63 ) . C1q seropositivity was significantly associated with both schizophrenia groups ( recent onset , odds ratio (OR)=8.02 , p≤0.008 ; non-recent onset , OR=3.15 , p≤0.03 ) compared to controls ( logistic regression models corrected for age , sex , race and smoking status ) . Casein- and /or gluten-IgG binding to C1q was significantly elevated in the non-recent onset group compared to controls ( OR=4.36 , p≤0.01 ) . Significant amounts of C1q-casein/gluten-related immune complexes and C1q correlations with a marker for gastrointestinal inflammation in non-recent onset schizophrenia suggests a heightened rate of food antigens in the systemic circulation , perhaps via a disease-associated altered intestinal permeability . In individuals who are in the early stages of disease onset , C1q activation may reflect the formation of immune complexes with non-casein- or non-gluten-related antigens , the presence of C1q autoantibodies , and /or a dissociated state of immune complex components . In conclusion , complement activation may be a useful biomarker to diagnose schizophrenia early during the course of the disease . Future prospect i ve studies should evaluate the impacts of casein- and gluten-free diets on C1q activation in schizophrenia",
"OBJECTIVE All antipsychotics act on the dopamine D(2 ) receptor . The present study extends prior pharmacogenetic investigations of the D(2 ) receptor gene ( DRD2 ) by examining , in first-episode schizophrenia patients , promoter region variation as a predictor of response time to two first-line atypical antipsychotics . METHOD Patients experiencing their first episode of schizophrenia ( N=61 ) were genotyped for two DRD2 promoter region polymorphisms ( A-241 G and -141C Ins/Del ) and were r and omly assigned to receive 16 weeks of treatment with either risperidone or olanzapine . Time until sustained response ( two consecutive ratings without significant positive symptoms ) for rare allele carriers versus wild types was examined by using Kaplan-Meier curves . RESULTS Relative to wild type homozygotes , G carriers ( A-241 G ) exhibited a significantly faster time until response , whereas -141C Del carriers took a significantly longer time to respond . Diplotype analysis revealed similar results . CONCLUSIONS These findings suggest that variation in the D(2 ) receptor gene can , in part , explain variation in the timing of clinical response to antipsychotics in patients with first-episode schizophrenia",
"The objective was to evaluate the efficacy and safety of add-on artemether in first-episode , untreated people with schizophrenia , who were Toxoplasma gondii seropositive , and explore the change in T. gondii antibodies during treatment . In this eight-week , double-blind , r and omized , placebo-controlled trial , 100 T. gondii seropositive participants with schizophrenia were r and omized to either the artemether or placebo group . Participants in the artemether group received 80 mg artemether once per day during the second week ( days 8 - 14 ) and the fourth week ( days 22 - 28 ) . Participants in the placebo group received identical looking placebo capsules . Psychopathology , adverse side effects and cognitive function were measured using st and ardized instruments . The group × time interaction effects for the scores of the Positive and Negative Syndrome Scale ( PANSS ) subscales and performances on all cognitive components were not significant , only the main effect of group was significant . Compared to the placebo group , artemether group participants showed significantly greater reduction in the PANSS negative symptom scale ( F(1,46 ) = 4.7 , p = 0.03 ) and the Clinical Global Impressions Scale ( F(1,96 ) = 6.2 , p = 0.01 ) scores , but there were no significant differences in the PANSS positive symptom and general psychopathology scales ( p > 0.05 ) . There were also no significant differences between the two groups in performance on any of the Brief Assessment of Cognition in Schizophrenia ( BACS ) cognitive domains . The artemether-risperidone combination is safe and well tolerated , but artemether as an adjunct to risperidone does not appear to alleviate cognitive deficits of schizophrenia . Trial Registration Chinese Clinical Trial Register ( ChiCTR ) TRC-13003145",
"OBJECTIVE Few long-term studies have compared the efficacy and safety of typical and atypical antipsychotic medications directly in patients with a first episode of psychosis who met the criteria for schizophrenia or a related psychotic disorder . This study compared the acute and long-term effectiveness of haloperidol with that of olanzapine in patients with first-episode psychosis in a large , controlled clinical trial . METHOD Patients with first-episode psychosis ( N=263 ) were r and omly assigned under double-blind conditions to receive haloperidol or olanzapine and were followed for up to 104 weeks . Domains measured included psychopathology , psychosocial variables , neurocognitive functioning , and brain morphology and metabolism . This report presents data from clinical measures of treatment response and safety data from the 12-week acute treatment phase . RESULTS Haloperidol and olanzapine were associated with substantial and comparable baseline-to-endpoint reductions in symptom severity , which did not differ significantly in last-observation-carried-forward analyses . However , in a mixed-model analysis , olanzapine-treated subjects had significantly greater decreases in symptom severity as measured by the Positive and Negative Syndrome Scale total score and negative and general scales and by the Montgomery-Asberg Depression Rating Scale but not as measured by the Positive and Negative Syndrome Scale positive scale and by the Clinical Global Impression severity rating . Olanzapine-treated patients experienced a lower rate of treatment-emergent parkinsonism and akathisia but had significantly more weight gain , compared with the haloperidol-treated patients . Overall , significantly more olanzapine-treated subjects than haloperidol-treated subjects completed the 12-week acute phase of the study ( 67 % versus 54 % ) . CONCLUSIONS As expected on the basis of previous studies , both olanzapine and haloperidol were effective in the acute reduction of psychopathological symptoms in this group of patients with first-episode psychosis . However , olanzapine had several relative advantages in therapeutic response . Although the nature of adverse events differed between the two agents , retention in the study was greater with olanzapine . Retention in treatment is important in this patient population , given their risk of relapse . Longer-term results are needed to determine whether treatment with atypical antipsychotics results in superior outcomes for a first episode of schizophrenia",
"We have previously reported that risperidone might improve negative symptoms in schizophrenia by influencing noradrenergic neurons . In the present study , we focused on the clinical efficacy and mechanisms of risperidone towards positive symptoms in the acute phase of schizophrenia . Thirty-four patients meeting DSM-IV criteria for schizophrenia and treated with risperidone alone were evaluated regarding their clinical improvement using the Positive and Negative Syndrome Scale ( PANSS ) before and 2 weeks after risperidone administration , and blood sample s were also drawn at the same times . Plasma concentrations of homovanillic acid ( HVA ) and 3-methoxy-4-hydroxyphenylglycol were analysed by high-performance liquid chromatography with electrochemical detection . Plasma HVA levels in the responders to the risperidone treatment ( more than 50 % improvement in scores of positive symptoms in PANSS ) were higher than those of non-responders before risperidone administration . Furthermore , there was a negative trend between changes in plasma HVA levels and improvement of total scores for positive symptoms in PANSS . These results suggest that higher levels of plasma HVA before risperidone administration might be a predictor of a good response to risperidone treatment , and the influence of risperidone on dopaminergic activity might be associated with its efficacy in treating symptoms of schizophrenia in the acute phase",
"Many antipsychotic medications carry a substantial liability for weight gain , and one mechanism common to all antipsychotics is binding to the dopamine D2 receptor . We therefore examined the relationship between -141C Ins/Del ( rs1799732 ) , a functional promoter region polymorphism in DRD2 , and antipsychotic-induced weight gain in 58 first episode schizophrenia patients enrolled in a r and omized trial of risperidone versus olanzapine . Carriers of the deletion allele ( n=29 ) were compared with Ins/Ins homozygotes ( noncarriers , n=29 ) in a mixed model encompassing 10 weight measurements over 16 weeks . Deletion allele carriers showed significantly more weight gain after 6 weeks of treatment regardless of assigned medication . Although deletion carriers were prescribed higher doses of olanzapine ( but not risperidone ) , dose did not seem to account for the genotype effects on weight gain . Given earlier evidence that deletion carriers show reduced symptom response to medication , additional study of appropriate treatment options for these patients seems warranted",
"Dynamic testing of the hypothalamic-pituitary-adrenal axis in schizophrenia has yielded conflicting results , which may be related to patient selection and previous exposure to psychotropic medication . The objective of this study was to determine the pattern of corticotropin ( ACTH ) and cortisol release in response to metoclopramide ( a dopamine antagonist ) , which appears to be unique in its ability to release vasopressin ( AVP ) , in drug naive patients with schizophrenia experiencing their first episode of psychosis . In this study , we examined AVP , ACTH and cortisol release in response to metoclopramide in 10 drug-naive , first-episode male patients with a DSM IV diagnosis of paranoid schizophrenia and compared them to healthy control subjects matched for age , sex and smoking status . Patients , as compared to controls had higher levels of baseline plasma cortisol ( 375.5+/-47.4/l vs. 273.8+/-42.2 nmol/l , respectively ; t=2.48 , df=9 , p plasma ACTH ( 14.9+/-0.85 vs. 11.3+/-0.57 pg/ml , respectively ; t=4.29 , df=9 , p AVP levels were lower in patients though this did not reach statistical significance ( 0.89+/-0.09 vs. 1.3+/-0.08 pmol/l , respectively ; t=1.97 , df=9 , p metoclopramide over time between the two groups yielded a significant group by time interaction for cortisol ( F=11.3 , df=6 , 108 , p Tukey 's test revealed significant differences between the two groups at + 30 , + 45 , + 60 , + 90 and + 120 min for cortisol ( p and cortisol responses in patients ( r=0.65 , df=8 , p Male patients with paranoid schizophrenia release greater amounts of ACTH and cortisol in responses to metoclopramide-induced AVP secretion than control subjects ",
"D-fenfluramine has been identified as a highly selective serotonin ( 5-HT ) releaser and re-uptake inhibitor . The objective of our study was to investigate prolactin response to D-fenfluramine challenge in non-medicated , first episode schizophrenics . We hypothesized that 5-HT reactivity can predict a response to the neuroleptic treatment . Twenty-three in patients , 11 males and 12 females , at the Prague Psychiatric Center participated in the study . Inclusion criteria were : ICD-10 diagnosis of schizophrenia , first episode or duration of illness shorter than 36 months . D-fenfluramine challenge test was performed before 4 weeks of the haloperidol treatment . During the test , prolactin plasma levels were measured . The Brief Psychiatric Rating Scale ( BPRS ) was administered before and after the treatment . A statistically significant negative correlation was found between prolactin response to the D-fenfluramine challenge and improvement of psychopathology measured by the change in total BPRS score ( p = 0.0004 ) , in positive ( p = 0.0403 ) , negative ( p = 0.0267 ) , and anxiety-depression symptoms of BPRS ( p = 0.0014 ) . Our data support the original hypothesis that there is a relationship between 5-HT system activity and treatment response . The higher responsiveness of the 5-HT system in first episode , non-medicated schizophrenics , was associated with a poorer treatment response to haloperidol , an antidopaminergic neuroleptic",
"BACKGROUND Evidence for basal hypothalamic-pituitary-adrenal ( HPA ) axis dysfunction in schizophrenia is less consistent than that seen in major depression . Potential reasons include sampling procedures and the use of patients on antipsychotic medications which may suppress the HPA axis . Therefore , the objective of this study was to determine whether first episode , drug naïve patients with schizophrenia have evidence of basal HPA axis dysfunction by measuring plasma levels of AVP , ACTH and cortisol from 13:00 to 16:00 h , a time frame which is believed to reflect 24 h concentrations of HPA axis activity . METHOD In this cross-sectional study , plasma levels of AVP , ACTH and cortisol were measured in 12 ( 7 males and 5 females ) ( mean age + /-SD=33.6+/-12.6 years ) patients with DSM-IV schizophrenia and compared with those found in age- and sex-matched healthy controls . RESULTS Patients and controls did not differ in terms of their 13:00 h cortisol and AVP . However , patients with schizophrenia had higher levels of ACTH as compared to control subjects at 13:00 h ( 41.3+/-14.6 vs. 12.4+/-1.1 pg/ml respectively ; t=1.99 , df=11 , p mean ( + /-SE ) AUC of ACTH ( 26.3+/-6.2 vs. 13.9 nmol/l , respectively ; t=2.86 , df=11 , p cortisol ( 279.4+/-26.0 vs. 213.1+/-18.4 nmol/l , respectively ; t=3.72 , df=11 , p mean ( + /-SE ) AUC of AVP ( 0.87+/-0.24 vs. 1.42+/-0.34 pmol/l , respectively ; t=2.29 , df=11 , p basal overactivity of the pituitary-adrenal axis",
"OBJECTIVE The objective of this prospect i ve , naturalistic study , conducted in first-episode psychosis patients from a Central -European population , was to assess the utility of Cytochrome P-450 2D6 ( CYP2D6 ) genotype testing under normal clinical setting . METHODS A total of 35 patients diagnosed for the first time with schizophrenia or acute schizophrenia-like psychotic disorder and treated with risperidone were enrolled in the study . These patients underwent sequentiation of the CYP2D6 gene and evaluations of symptoms and severity of adverse effects using the PANSS and UKU scales , respectively . Doses of antipsychotics and other co-medication were monitored as well . In statistical analysis , Fisher 's exact test was used to compare ratios and the Wilcoxon rank-sum test was used in the comparison of continual variables . RESULTS PM patients showed a significantly lower reduction in psychotic symptoms and a greater severity of psychotic symptoms following risperidone treatment and higher doses of antipsychotics not metabolized by CYP2D6 , which were used as co-medication . CONCLUSIONS Based on these results , patients with the PM genotype experiencing first-episode schizophrenia do n't appear to be optimal recipients of risperidone treatment . However , as the main limitation of this study was the relatively small sample -size , replication with a larger scale study is needed to confirm these findings",
"Classical antipsychotics like haloperidol are suggested to increase oxidative stress and oxidative cell injury in the brain . Pro-oxidant effect of haloperidol may influence the course and treatment outcomes of schizophrenia . Dietary supplementation of either antioxidants or omega-3 fatty acids was found to improve symptoms of schizophrenia . Thus we decided to assess the impact of combining omega-3 fatty acids , vitamins E and C supplementation on treatment outcome and side effects in schizophrenia patients treated with haloperidol . Ongoing haloperidol treatment of 17 schizophrenia patients was supplemented with 1000 mg capsule of omega-3 fatty acids ( 180 mg EPA+120 mg DHA ) bid , vitamin E 400 IU bid and vitamin C 1000 mg/day . Patients were assessed with Brief Psychiatric Rating Scale ( BPRS ) , Scale for the Assessment of Negative Symptoms ( SANS ) , Simpson Angus Scale ( SAS ) and Barnes Akathisia Rating Scale ( BARS ) over a 4 month period . Gluthatione peroxidase , superoxide dismutase , malondialdehyde , vitamin E and C levels were also evaluated at baseline and at the end of study . BPRS , SANS , SAS and BARS scores obtained at follow-up visits were significantly lower compared to baseline . Superoxide dismutase level was significantly lower at the end of study . No significant differences were detected in other laboratory parameters . Our results support the beneficial effect of the supplementation on positive and negative symptoms of schizophrenia as well as the severity of side effects induced by haloperidol . The effect of supplementation on akathisia is especially noteworthy and it has not been investigated in previous studies",
"BACKGROUND Dehydroepi and rosterone ( DHEA ) and its sulphate form ( DHEA ) are neuroactive steroids with antiglucocorticoid properties . An imbalance in the ratio of cortisol to DHEA(S ) has been implicated in the pathophysiology of stress-related psychiatric disorders . This study prospect ively investigated circulating cortisol , DHEAS and their ratio in first-episode psychosis ( FEP ) patients compared to healthy controls , and their relationship to perceived stress , psychotic , negative and mood symptoms . METHODS Blood cortisol and DHEAS levels were obtained in 39 neuroleptic-naïve or minimally-treated FEP patients and 25 controls . Twenty-three patients and 15 controls received repeat assessment s after 12 weeks . Perceived stress was assessed using the Perceived Stress Scale and symptoms were assessed in patients using st and ard rating scales . RESULTS At baseline , no differences were observed in cortisol , DHEAS or the cortisol/DHEAS ratio between patients and controls . There were also no group differences in the change in these biological variables during the study period . Within FEP patients , decreases in cortisol and the cortisol/DHEAS ratio over time were directly related to the improvement in depression ( r = 0.45 ; p = 0.031 , r = 0.52 ; p = 0.01 ) , negative ( r = 0.51 ; p = 0.006 , r = 0.55 ; p = 0.008 ) and psychotic symptoms ( cortisol only , r = 0.53 ; p = 0.01 ) . Perceived stress significantly correlated with DHEAS ( r = 0.51 ; p = 0.019 ) and the cortisol/DHEAS ratio ( r = -0.49 ; p = 0.024 ) in controls , but not patients , possibly reflecting an impaired hormonal response to stress in FEP patients . CONCLUSIONS These findings further support the involvement of the stress system in the pathophysiology of psychotic disorders , with implication s for treatment strategies that modulate these neurosteroids",
"We used magnetic resonance imaging to examine the effect of ethyl-eicosapentaenoic acid ( E-EPA ) on hippocampal T(2 ) relaxation time in first episode psychosis patients at baseline and after 12 weeks of follow-up . There was an increase in T(2 ) in the placebo group but not in the E-EPA group , suggesting a neuroprotective effect of E-EPA treatment . In addition , the smaller the increase in T(2 ) , the greater the improvement in negative symptoms"
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41187bb0-06ff-11f0-808a-c43d1ab1c353
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Background : Women are at substantially greater risk for anterior cruciate ligament ( ACL ) injuries than are men . Purpose : To conduct a systematic review and meta- analysis of the literature to clarify the effect of the menstrual cycle and contraceptives on the laxity of and noncontact injuries to the ACL . Study Design : Systematic review ; Level of evidence , 4 . Methods : Search es were conducted using MEDLINE ( 1946–August 2016 ) , the Cochrane Library Data base , clinical trial registries , and related reference lists . Search terms included athletic injuries , knee injuries , ligaments , joint instability , menstrual cycle , ovulation , hormones , and contraceptives . Investigators independently dually abstract ed and review ed study details and quality using predefined criteria and evaluated overall strength of evidence using the GRADE ( Grading of Recommendations Assessment , Development and Evaluation ) criteria . Results : Twenty-one studies totaling 68,758 participants were included : 5 on the menstrual cycle and ACL injury , 7 on hormonal contraceptives and ACL injury , as well as 13 on menstrual cycle and ligament laxity . Four of 5 studies of women not using hormonal contraception indicated that the luteal phase was the least associated with ACL injuries . The 2 largest and highest quality studies on hormonal contraceptives suggested that hormonal contraceptives may be protective against ACL injury . Six of 12 studies on ACL laxity provided quantitative data for meta- analysis , finding significantly increased laxity during the ovulatory phase compared with the follicular phase . Conclusion : The literature suggests an association between hormonal fluctuations and ACL injury . Recent studies have suggested that oral contraceptives may offer up to a 20 % reduction in risk of injury . The literature on ACL injuries and the menstrual cycle has more than doubled over the past decade , permitting quantitative analysis for the first time . However , the overall strength of this evidence is low . Promising potential directions for future research include long-term observational studies with ongoing hormonal assays and large interventional trials of follicular suppression , including newer hormonal methods
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"BACKGROUND Females experience a disproportionate number of anterior cruciate ligament injuries compared to males . Increased estradiol concentration has been suggested to alter ligament properties and strength . Determining whether the knee responds differently to an external load at various hormonal levels may be helpful in further explaining the gender disparity . METHODS Estradiol , progesterone and testosterone were quantified at menses , near ovulation and at the mid-luteal phase . With one knee serving as the control limb and the other as the experimental limb , displacement at 134N and stiffness between 90 and 134N were recorded with a knee ligament arthrometer on both knees before and after a loading protocol . The protocol consisted of three , 3-min , posterior to anterior normalized loads directed to the posterior calf with a ligament testing device . FINDINGS The loading protocol produced a measurable increase in displacement but not stiffness . Neither displacement nor stiffness measures however were affected by day of the menstrual cycle . No consistent relationships between hormonal concentrations and displacement or stiffness were evident . INTERPRETATION Following a controlled , static external load , displacement and stiffness were not affected differently by day of the menstrual cycle",
"Background Ovulatory menstrual cycles are essential for women ’s fertility and needed to prevent bone loss . There is a medical/cultural expectation that clinical ly normal menstrual cycles are inevitably ovulatory . Currently within the general population it is unknown the proportion of regular , normal-length menstrual cycles that are ovulatory . Thus , the objective of this study was to determine the population point prevalence of ovulation in premenopausal , normally menstruating women . The None hypothesis was that such cycles are ovulatory . Methods This is a single-cycle , cross-sectional , population -based study —a sub- study of the HUNT3 health study in the semi-rural county ( Nord Trøndelag ) in mid-Norway . Participants included > 3,700 spontaneously ( no hormonal contraception ) menstruating women , primarily Caucasian , ages 20–49.9 from that county . Participation rate was 51.9 % . All reported the date previous flow started . A single , r and om serum progesterone level was considered ovulatory if ≥9.54 nmol/L on cycle days 14 to -3 days before usual cycle length ( CL ) . Results Ovulation was assessed in 3,168 women mean age 41.7 ( interquartile range , [ IQR ] 36.8 to 45.5 ) , cycle length 28 days ( d ) ( IQR 28 to 28 ) and body mass index ( BMI ) 26.3 kg/m2 ( 95 % CI 26.1 to 26.4 ) . Parity was 95.6 % , 30 % smoked , 61.3 % exercised regularly and 18 % were obese . 1,545 women with a serum progesterone level on cycle days 14 to -3 were presumed to be in the luteal phase . Of these , 63.3 % of women had an ovulatory cycle ( n = 978 ) and 37 % ( n = 567 ) were anovulatory . Women with/ without ovulation did not differ in age , BMI , cycle day , menarche age , cigarette use , physical activity , % obesity or self-reported health . There were minimal differences in parity ( 96.7 % vs. 94.5 % , P = 0.04 ) and major differences in progesterone level ( 24.5 vs. 3.8 nmol/L , P = 0.001 ) . Conclusion Anovulation in a r and om population occurs in over a third of clinical ly normal menstrual cycles",
"For 714 consecutive patients who underwent autogenous patellar tendon graft anterior cruciate ligament reconstructions we intraoperatively measured intercondylar notch width . We prospect ively recorded height , weight , sex , and which patients subsequently tore their contralateral anterior cruciate ligament or the 10-mm autograft . The patients were divided into two groups based on notch width ( group 1 , 15 mm ; group 2 , 16 mm ) . The mean notch width was 13.9 2.2 mm for women and 15.9 2.5 mm for men . There was no statistically significant difference in notch width between height groups for women or men . Analysis showed that , with height and weight as covariates , women had statistically significantly narrower notches than men . Twenty-three of 388 patients in group 1 and 4 of 326 patients in group 2 tore their contralateral anterior cruciate ligaments . Within groups , no statistically significant differences in contralateral tear rates existed between men and women . Once the men and women had reconstructions with equally sized 10-mm autografts , there was no difference in graft tear rate between groups or between men and women . Our results show that patients with narrower notches have a higher incidence of tearing their contralateral anterior cruciate ligament . After reconstruction with a 10-mm autograft , the incidence of graft rupture is the same for men and women",
"Introduction Anterior cruciate ligament ( ACL ) injuries are more common among female athletes compared to male athletes . Several studies have been reported to explain the gender difference in ACL injury rates and several risk factors underlying gender disparity are believed to exist . Hormonal effects are considered to be one of the etiological factors for female non-contact ACL injuries . The objectives of this study were to determine if ACL injuries occurred r and omly or correlated with a specific phase of the female menstrual cycle in teenaged female athletes and then to determine if pre-menstrual and menstrual dysfunctions influenced these ACL injuries . Material s and methods Eighteen of 37 consecutive female athletes , with ACL injuries , met the study criteria : teenage , with regular menstrual cycle , and non-contact injury . The menstrual history , athletic activity , and injury history were collected . Results Seventy-two percent of the subjects had premenstrual symptoms and 83 % had menstrual symptoms . The subjective activity level at the follicular phase was significantly lowest between the phases . A significant statistical association was found between the phase of the menstrual cycle and ACL injuries ( P = 0.0002 ) . There were more injuries in the ovulatory phase than expected , and fewer injuries occurred in the other phases . Conclusion The results showed a significant increase in non-contact ACL injuries in teenage female athletes during the ovulatory phase of the menstrual cycle and the subjective activity level and the premenstrual and menstrual symptoms might not affect the likelihood of the injuries . These findings suggest that sex hormones might play a role in the incidence of female non-contact ACL injuries",
"BACKGROUND No definitive explanation for the difference in rate of male and female noncontact ACL injury has been found . The hormonal environment , known to be different in men and women has been hypothesized as a possible source for this difference in injury rate . PURPOSE To confirm earlier work looking at periodicity of noncontact ACL injury . To increase sample size by adding ankle sprains . To determine the rate of noncontact ACL injury and ankle sprains in collegiate basketball and soccer . To determine if the use of oral contraceptives affects the rate of noncontact ACL injury and ankle sprains . METHODS Data was collected from a sample of NCAA schools over the 2000 - 2001 basketball and the 2001 - 2002 basketball and soccer seasons . RESULTS Recall and prospect i ve data collection of length of menstrual cycle did not produce equivalent results . Periodicity was present only in the recall group of \" off pill \" users . The rate of noncontact ACL injury and noncontact ankle sprains was twice as high in basketball as in soccer . There was no difference in rate of injuries between those athletes using hormonal therapy and those athletes not using hormonal therapy . CONCLUSIONS Noncontact ACL injuries and ankle sprains occurred at significantly higher rates in basketball than in soccer but this rate difference was not linked to hormonal therapy usage . The overall rate of noncontact ACL injury and ankle sprain to women 's collegiate basketball and soccer players is very low",
"Background Noncontact anterior cruciate ligament injuries occur two to eight times more often in women than in men . Changes in ligament laxity and strength have been associated with female hormones such as relaxin . Hypothesis Relaxin receptors are present within the female anterior cruciate ligament . Study Design Controlled laboratory study . Methods Remnants of anterior cruciate ligament were harvested from five women and five men undergoing routine ligament reconstruction . Relaxin was biotinylated and analyzed for biologic activity with use of the mouse interpubic ligament bioassay . Immunohistochemical localization of relaxin receptors was performed with appropriate negative controls and competitive binding assays to determine receptor specificity and saturability . Results Anterior cruciate ligament sections from women but not from men showed uniform specific binding that was limited to synovial lining cells , stromal fibroblasts , and cells lining blood vessels . Specific binding was confirmed in the presence of a 2000-fold excess of human insulin , the structural homolog of relaxin , and competitive inhibition was demonstrated in the presence of a 2000-fold excess of unlabeled relaxin . Conclusions Relaxin exhibits specific saturable binding in the female anterior cruciate ligament , where specific relaxin receptors were present . Clinical Relevance The high incidence of anterior cruciate ligament rupture in female athletes may be partially explained by the effects of relaxin"
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41187bec-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND Cancer Care Ontario 's Program in Evidence -Based Care ( pebc ) recently created an evidence -based consensus guideline on the systemic treatment of early breast cancer . The evidence for the guideline was compiled using a systematic review to answer the question " What is the optimal systemic therapy for patients with early-stage , operable breast cancer , when patient and disease factors are considered ? " The question was addressed in three parts : cytotoxic chemotherapy , endocrine treatment , and her2 ( human epidermal growth factor receptor 2)-targeted therapy . METHODS For the systematic review , the literature in the medline and embase data bases was search ed for the period January 2008 to May 2014 . The St and ards and Guidelines Evidence directory of cancer guidelines and the Web sites of major oncology guideline organizations were also search ed . The basic search terms were " breast cancer " and " systemic therapy " ( chemotherapy , endocrine therapy , targeted agents , ovarian suppression ) , and results were limited to r and omized controlled trials ( rcts ) , guidelines , systematic review s , and meta-analyses . RESULTS Several hundred documents that met the inclusion criteria were retrieved . Meta-analyses from the Early Breast Cancer Trialists ' Collaborative Group encompassed many of the rcts found . Several additional studies that met the inclusion criteria were retained , as were other guidelines and systematic review s. SUMMARY The results of the systematic review constitute a comprehensive compilation of high-level evidence , which was the basis for the 2014 pebc guideline on systemic therapy for early breast cancer . The review of the evidence for systemic endocrine therapy ( adjuvant tamoxifen , aromatase inhibitors , and ovarian ablation and suppression ) is presented here ; the evidence for chemotherapy and her2-targeted treatment- and the final clinical practice recommendations -are presented separately in this supplement
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"BACKGROUND Previously reported information from B-14 , a National Surgical Adjuvant Breast and Bowel Project ( NSABP ) r and omized , placebo-controlled clinical trial , demonstrated that patients with estrogen receptor (ER)-positive breast cancer and negative axillary lymph nodes experienced a prolonged benefit from 5 years of tamoxifen therapy . When these women were rer and omized to receive either placebo or more prolonged tamoxifen therapy , they obtained no additional advantage from tamoxifen through 4 years of follow-up . Because the optimal duration of tamoxifen administration continues to be controversial and because there have been 3 more years of follow-up and a substantial increase in the number of events since our last report , an up date of the B-14 study is appropriate . METHODS Patients ( n = 1172 ) who had completed 5 years of tamoxifen therapy and who were disease free were rer and omized to receive placebo ( n = 579 ) or tamoxifen ( n = 593 ) . Survival , disease-free survival ( DFS ) , and relapse-free survival ( RFS ) were estimated by the Kaplan-Meier method ; the differences between the treatment groups were assessed by the log-rank test . Relative risks of failure ( with 95 % confidence intervals ) were determined by the Cox proportional hazards model . P values were two-sided . RESULTS Through 7 years after reassignment of tamoxifen-treated patients to either placebo or continued tamoxifen therapy , a slight advantage was observed in patients who discontinued tamoxifen relative to those who continued to receive it : DFS = 82 % versus 78 % ( P = .03 ) , RFS = 94 % versus 92 % ( P = .13 ) , and survival = 94 % versus 91 % ( P = .07 ) , respectively . The lack of benefit from additional tamoxifen therapy was independent of age or other characteristics . CONCLUSION Through 7 years of follow-up after rer and omization , there continues to be no additional benefit from tamoxifen administered beyond 5 years in women with ER-positive breast cancer and negative axillary lymph nodes",
"BACKGROUND The Austrian Breast and Colorectal Cancer Study Group trial-12 ( ABCSG-12 ) bone sub study assesses zoledronic acid for preventing bone loss associated with adjuvant endocrine therapy and reports on long-term findings of bone-mineral density ( BMD ) during 3 years of treatment and 2 years after completing adjuvant treatment with or without zoledronic acid . The aim of this sub study is to gain insight into bone health in this setting . METHODS ABCSG-12 is a r and omised , open-label , phase III , 4-arm trial comparing tamoxifen ( 20 mg/day orally ) and goserelin ( 3.6 mg subcutaneously every 28 days ) versus anastrozole ( 1 mg/day orally ) and goserelin ( 3.6 mg subcutaneously every 28 days ) , both with or without zoledronic acid ( 4 mg intravenously every 6 months ) for 3 years in premenopausal women with endocrine-responsive breast cancer . This prospect i ve bone sub protocol measured BMD at 0 , 6 , 12 , 36 , and 60 months . The primary endpoint of the bone sub study ( secondary endpoint in the main trial ) was change in BMD at 12 months , assessed by dual-energy X-ray absorptiometry in assessable patients . Analyses were intention to treat . Statistical significance was assessed by t tests . The ABCSG-12 trial is registered on the Clinical Trials.gov website , number NCT00295646 . FINDINGS 404 patients were prospect ively included in the bone sub study and r and omly assigned to endocrine therapy alone ( goserelin and anastrozole or goserelin and tamoxifen ; n=199 ) or endocrine therapy concurrent with zoledronic acid ( goserelin , anastrozole , and zoledronic acid or goserelin , tamoxifen , and zoledronic acid ; n=205 ) . After 3 years of treatment , endocrine therapy alone caused significant loss of BMD at the lumbar spine ( -11.3 % , mean difference -0.119 g/cm(2 ) [ 95 % CI -0.146 to -0.091 ] , p trochanter ( -7.3 % , mean difference -0.053 g/cm(2 ) [ -0.076 to -0.030 ] , p receive zoledronic acid , anastrozole caused greater BMD loss than tamoxifen at 36 months at the lumbar spine ( -13.6 % , mean difference -0.141 g/cm(2 ) [ -0.179 to -0.102 ] vs -9.0 % , mean difference -0.095 g/cm(2 ) [ -0.134 to -0.057 ] , p acid still had decreased BMD at both sites compared with baseline ( lumbar spine -6.3 % , mean difference -0.067 g/cm(2 ) [ -0.106 to -0.027 ] , p=0.001 ; trochanter -4.1 % , mean difference -0.03 g/cm(2 ) [ -0.062 to 0.001 ] , p=0.058 ) . Patients who received zoledronic acid had stable BMD at 36 months ( lumbar spine + 0.4 % , mean difference 0.004 g/cm(2 ) [ -0.024 to 0.032 ] ; trochanter + 0.8 % , mean difference 0.006 g/cm(2 ) [ -0.018 to 0.028 ] ) and increased BMD at 60 months at both sites ( lumbar spine + 4.0 % , mean difference 0.039 g/cm(2 ) [ 0.005 - 0.075 ] , p=0.02 ; trochanter + 3.9 % , mean difference 0.028 g/cm(2 ) [ 0.003 - 0.058 ] , p=0.07 ) compared with baseline . INTERPRETATION Goserelin plus tamoxifen or anastrozole for 3 years without concomitant zoledronic acid caused significant bone loss . Although there was partial recovery 2 years after completing treatment , patients receiving endocrine therapy alone did not recover their baseline BMD levels . Concomitant zoledronic acid prevented bone loss during therapy and improved BMD at 5 years",
"Tamoxifen and aromatase inhibitors are associated with side effects which can significantly impact quality of life ( QoL ) . We assessed QoL in the Tamoxifen Exemestane Adjuvant Multinational ( TEAM ) Trial and compared these data with reported adverse events in the main data base . 2,754 Dutch postmenopausal early breast cancer patients were r and omized between 5 years of exemestane , or tamoxifen ( 2.5–3 years ) followed by exemestane ( 2.5–2 years ) . 742 patients were invited to participate in the QoL side study and complete question naires at 1 ( T1 ) and 2 ( T2 ) years after start of endocrine treatment . Question naires comprised the EORTC QLQ-C30 and BR23 question naires , supplemented with FACT-ES questions . 543 patients completed question naires at T1 and 454 patients ( 84 % ) at T2 . Overall QoL and most functioning scales improved over time . The only clinical ly relevant and statistically significant difference between treatment types concerned insomnia ; exemestane-treated patients reported more insomnia than tamoxifen-treated patients . Discrepancy was observed between QoL issue scores reported by the patients and adverse events reported by physicians . Certain QoL issues are treatment- and /or time-specific and deserve attention by health care providers . There is a need for careful inquiry into QoL issues by those prescribing endocrine treatment to optimize QoL and treatment adherence",
"Purpose : To assess the predictive value of Ki67 expression in postmenopausal hormone receptor – positive early-breast cancer patients , who were either treated with adjuvant tamoxifen ( TAM ) alone or with TAM followed by anastrozole ( ANA ) . Experimental Design : Expression of Ki67 was determined central ly by immunohistochemistry on whole tissue sections of postmenopausal endocrine-responsive breast cancers from patients who had been enrolled in the prospect ively r and omized Austrian Breast and Colorectal Cancer Study Group Trial 8 , and had received TAM for 5 years , or TAM for 2 years followed by ANA for 3 years . Ki67 expression was evaluated both as a continuous variable and dichotomized to low ( ≤10 % ) and high ( > 10 % ) . Recurrence-free survival ( RFS ) and overall survival ( OS ) were analyzed using Cox models adjusted for clinical and pathologic parameters . Results : Patients with a high Ki67 expression ( 394/1,587 ; 23 % ) had a significantly shorter RFS ( adjusted HR for recurrence = 1.90 , 95 % CI : 1.37–2.64 , P = 0.0001 ) and OS ( adjusted HR for death = 1.78 , 95 % CI : 1.18–2.70 , P = 0.006 ) . In women with breast tumors expressing medium or high ER levels ( n = 1,438 ) , the interaction between Ki67 and adjuvant endocrine treatment was significant for RFS ( P = 0.03 ) . TAM followed by ANA was superior to TAM alone in patients with low Ki67 ( adjusted HR = 0.53 , 95 % CI : 0.34–0.83 , P = 0.005 ) but not in high Ki67 disease ( adjusted HR = 1.18 , 95 % CI : 0.66–1.89 , P = 0.68 ) . Conclusions : Adjuvant sequencing of TAM and ANA is superior to TAM alone , particularly in postmenopausal women with medium or high ER expressing , low proliferating breast cancer . Clin Cancer Res ; 17(24 ) ; 7828–34 . © 2011 AACR",
"BACKGROUND MA.17 evaluated letrozole or placebo after 5 years of tamoxifen and showed significant improvement in disease-free survival ( DFS ) for letrozole [ hazard ratio ( HR ) 0.57 , P = 0.00008 ] . The trial was unblinded and placebo patients were offered letrozole . PATIENTS AND METHODS An intent-to-treat analysis of all outcomes , before and after unblinding , on the basis of the original r and omization was carried out . RESULTS In all , 5187 patients were r and omly allocated to the study at baseline and , at unblinding , 1579 ( 66 % ) of 2383 placebo patients accepted letrozole . At median follow-up of 64 months ( range 16 - 95 ) , 399 recurrences or contralateral breast cancers ( CLBCs ) ( 164 letrozole and 235 placebo ) occurred . Four-year DFS was 94.3 % ( letrozole ) and 91.4 % ( placebo ) [ HR 0.68 , 95 % confidence interval ( CI ) 0.55 - 0.83 , P = 0.0001 ] and showed superiority for letrozole in both node-positive and -negative patients . Corresponding 4-year distant DFS was 96.3 % and 94.9 % ( HR 0.80 , 95 % CI 0.62 - 1.03 , P = 0.082 ) . Four-year overall survival was 95.1 % for both groups . The annual rate of CLBC was 0.28 % for letrozole and 0.46 % for placebo patients ( HR 0.61 , 95 % CI 0.39 - 0.97 , P = 0.033 ) . CONCLUSIONS Patients originally r and omly assigned to receive letrozole within 3 months of stopping tamoxifen did better than placebo patients in DFS and CLBC , despite 66 % of placebo patients taking letrozole after unblinding",
"Introduction Extended adjuvant endocrine therapy for breast cancer with aromatase inhibitors may potentially alter the lipid profile of postmenopausal patients and thus increase the risk of developing cardiovascular disease . In this study , a sub protocol of the ATENA ( Adjuvant post-Tamoxifen Exemestane versus Nothing Applied ) trial , we compared the effect of the steroidal aromatase inactivator exemestane on the lipid profile of postmenopausal patients with operable breast cancer , in the adjuvant setting , with that of observation alone after completion of 5 to 7 years of primary treatment with tamoxifen . Methods In this open-label , r and omized , parallel-group study , 411 postmenopausal patients with operable breast cancer , who had been treated with tamoxifen for 5 to 7 years , were r and omized to either 5 additional years of exemestane ( 25 mg/day ; n = 211 ) or observation only ( n = 200 ) . Assessment s of total cholesterol ( TC ) , high-density lipoprotein ( HDL ) , low-density lipoprotein ( LDL ) , and total serum triglycerides ( TRG ) were performed at baseline and then during each follow-up visit , performed at either 6 or 12 months , according to the center 's clinical practice , until completing 24 months in the study . Results TC and LDL levels increased significantly across time for both arms ; TC increase was more pronounced for the observation arm , and that was sustained up to 24 months . HDL levels decreased significantly across time for the exemestane arm , whereas no significant change was detected across time for the observation arm . Triglyceride levels decreased significantly across time on both arms , with no difference detected in changes from baseline between the exemestane and the observation arms . Conclusions Exemestane lacks the beneficial effect of tamoxifen on lipids ; however , sequential adjuvant treatment with exemestane in postmenopausal breast cancer patients after cessation of 5 to 7 years of tamoxifen does not appear to alter the lipid profile significantly compared with that of an observational arm . Trial Registration Clinical Trials.gov ID : NCT00810706",
"PURPOSE In postmenopausal women with estrogen receptor-positive early breast cancer , surgery is usually followed by a 5-year course of tamoxifen . This report presents results of a prospect i ve , open-label , r and omized study , design ed to evaluate the benefits of switching to anastrozole after 2 years of tamoxifen treatment , compared with continuing on tamoxifen for 5 years . PATIENTS AND METHODS After receiving tamoxifen treatment for 2 years , eligible patients ( n = 979 ) were r and omly assigned to switch to anastrozole ( 1 mg/d ) or continue tamoxifen ( 20 or 30 mg/d ) for an additional 3 years . Patients were monitored every 6 months during years 1 to 3 and annually thereafter . The primary efficacy variable was disease-free survival , including local or distant recurrence , new contralateral breast cancer , or death . Secondary variables were overall survival and assessment of safety . RESULTS Switching to anastrozole result ed in a significant reduction in the risk of disease recurrence ( hazard ratio [ HR ] , 0.66 ; 95 % CI , 0.44 to 1.00 ; P = .049 ) , and improved overall survival ( HR , 0.53 ; 95 % CI , 0.28 to 0.99 ; P = .045 ) compared with continuing on tamoxifen . Fewer patients who switched to anastrozole reported serious adverse events ( 22.7 % v 30.8 % ) compared with those who continued on tamoxifen , mainly due to more patients in the tamoxifen group with endometrial events . The overall safety profile for anastrozole was consistent with previous reports and no new safety issues were identified . CONCLUSION Postmenopausal women who have taken tamoxifen for 2 years as adjuvant therapy are less likely to experience a recurrence of breast cancer and have improved overall survival if they switch to anastrozole compared with continuing to receive tamoxifen",
"BACKGROUND Clinical trial data have shown that among breast cancer patients who were disease free after 5 years of adjuvant treatment with tamoxifen , further extended treatment with the nonsteroidal aromatase inhibitor letrozole reduces breast cancer recurrence . We examined the efficacy and tolerability of extended adjuvant therapy with another aromatase inhibitor , anastrozole , for 3 years among women who had completed 5 years of adjuvant therapy . METHODS Austrian Breast and Colorectal Cancer Study Group ( ABCSG ) Trial 6a is an extension of ABCSG Trial 6 , in which hormone receptor-positive postmenopausal patients received 5 years of adjuvant tamoxifen , with or without the aromatase inhibitor aminoglutethimide , for the first 2 years of therapy . For ABCSG Trial 6a , patients who were disease free at the end of Trial 6 were r and omly assigned to receive either 3 years of anastrozole or no further treatment . Efficacy data were analyzed with the use of a Cox proportional hazards regression model with two-sided P values and Kaplan-Meier curves , and tolerability data were estimated using logistic regression analysis with odds ratios and 95 % confidence intervals ( CIs ) . RESULTS ABCSG Trial 6a included 856 patients . At a median follow-up of 62.3 months , women who received anastrozole ( n = 387 ) had a statistically significantly reduced risk of recurrence ( locoregional recurrence , contralateral breast cancer , or distant metastasis ) compared with women who received no further treatment ( n = 469 ; hazard ratio = 0.62 ; 95 % CI = 0.40 to 0.96 , P = .031 ) . Anastrozole was well tolerated , and no unexpected adverse events were reported . CONCLUSIONS These data confirm the benefit of extending adjuvant tamoxifen therapy beyond 5 years with anastrozole compared with no further treatment . Further research is required to define the optimum length of extended adjuvant therapy and to investigate the possibility of tailoring this period to suit different disease types",
"Novel genetic profiling tests of breast cancer tissue have been shown to be prognostic for overall survival and predictive of local and distant rates of recurrence in breast cancer patients . One of these tests , Oncotype DXtrade mark , is a diagnostic test comprised of a 21-gene assay applied to paraffin-embedded breast cancer tissue , which allows physicians to predict subgroups of hormone-receptor-positive , node-negative patients who may benefit from hormonal therapy alone or require adjuvant chemotherapy to attain the best survival outcome . The results of the assay are converted to a recurrence score ( 0 - 100 ) that has been found to be predictive of 10- and 15-year local and distant recurrence in node-negative , estrogen-receptor-positive breast cancer patients . Previous studies have shown that patients with high recurrence scores benefit from adjuvant chemotherapy , whereas patients with low recurrence scores do not . To evaluate the ability to guide treatment decisions in the group with a mid-range recurrence score , the North American Cooperative Groups developed the Trial Assessing IndiviuaLized Options for Treatment for breast cancer , a r and omized trial of chemotherapy followed by hormonal therapy versus hormonal therapy alone on invasive disease-free survival-ductal carcinoma in situ ( IDFS-DCIS ) survival in women with node-negative , estrogen-receptor-positive breast cancer with a recurrence score of 11 - 25 . The study was initiated in May 2006 and approximately 4500 patients will be r and omized . This article describes the rationale , methodology , statistical ana-lysis and implication s of the results on clinical practice",
" Health-related quality of life ( HRQOL ) , symptoms of depression , and adverse events ( AEs ) were compared between Japanese postmenopausal patients with hormone-sensitive breast cancer ( BC ) who received adjuvant tamoxifen , exemestane , or anastrozole in an open-labeled , r and omized , multicenter trial design ated as the National Surgical Adjuvant Study of Breast Cancer ( N-SAS BC ) 04 sub study of the Tamoxifen Exemestane Adjuvant Multinational ( TEAM ) trial . During the first year of treatment , HRQOL and symptoms of depression were analyzed using the Functional Assessment of Cancer Therapy-Breast ( FACT-B ) and its Endocrine Symptom Subscale ( ES ) , and the Center for Epidemiologic Studies Depression Scale ( CES-D ) , respectively . In addition , predefined AEs were analyzed . A total of 166 eligible patients were r and omly assigned to receive adjuvant tamoxifen , exemestane , or anastrozole . FACT-B scores increased after treatment began and remained significantly higher in the tamoxifen group than in the exemestane group or anastrozole group during the first year ( P = 0.045 ) . FACT-B scores were similar in the exemestane group and anastrozole group . ES scores and CES-D scores were similar in all treatment groups . Arthralgia and fatigue were less frequent , but vaginal discharge was more frequent in the tamoxifen group than in the exemestane group or anastrozole group . HRQOL was better in Japanese postmenopausal women treated with tamoxifen than those treated with exemestane or anastrozole . HRQOL and AEs were similar with exemestane and anastrozole . Given the results of the TEAM trial , upfront use of tamoxifen followed by an aromatase inhibitor ( AI ) may be an important option for adjuvant endocrine therapy in Japanese postmenopausal women",
"Background Systematic review s have found that luteinizing hormone – releasing hormone ( LHRH ) agonists are effective in treating premenopausal women with early breast cancer . Methods We conducted long-term follow-up ( median 12 years ) of 2706 women in the Zoladex In Premenopausal Patients ( ZIPP ) , which evaluated the LHRH agonist goserelin ( 3.6 mg injection every 4 weeks ) and tamoxifen ( 20 or 40 mg daily ) , given for 2 years . Women were r and omly assigned to receive each therapy alone , both , or neither , after primary therapy ( surgery with or without radiotherapy/chemotherapy ) . Hazard ratios and absolute risk differences were used to assess the effect of goserelin treatment on event-free survival ( breast cancer recurrence , new tumor or death ) , overall survival , risk of recurrence of breast cancer , and risk of dying from breast cancer , in the presence or absence of tamoxifen . Results Fifteen years after the initiation of treatment , for every 100 women not given tamoxifen , there were 13.9 ( 95 % confidence interval [ CI ] = 17.5 to 19.4 ) fewer events among those who were treated with goserelin compared with those who were not treated with goserelin . However , among women who did take tamoxifen , there were 2.8 fewer events ( 95 % CI = 7.7 fewer to 2.0 more ) per 100 women treated with goserelin compared with those not treated with goserelin . The risk of dying from breast cancer was also reduced at 15 years : For every 100 women given goserelin , the number of breast cancer deaths was lower by 2.6 ( 95 % CI = 6.6 fewer to 2.1 more ) and 8.5 ( 95 % CI = 2.2 to 13.7 ) in those who did and did not take tamoxifen , respectively , although in the former group the difference was not statistically significant . Conclusions Two years of goserelin treatment was as effective as 2 years of tamoxifen treatment 15 years after starting therapy . In women who did not take tamoxifen , there was a large benefit of goserelin treatment on survival and recurrence , and in women who did take tamoxifen , there was a marginal potential benefit on these outcomes when goserelin was added",
"Postmenopausal women with localised , early breast cancer ( n = 285 ) were enrolled in a prospect i ve sub protocol of the ‘ arimidex , tamoxifen , alone or in combination ’ ( ATAC ) trial to assess gynaecological abnormalities arising during treatment with anastrozole ( 1 mg/day ) or tamoxifen ( 20 mg/day ) . After 6 years ' follow-up , there appeared to be non-significantly fewer endometrial abnormalities with anastrozole than with tamoxifen ( 12.4 % vs 20.2 % , odds ratio 0.52 ; 95 % confidence intervals 0.20 , 1.32 ; p = 0.17 ) . The time to first endometrial abnormality was non-significantly longer for patients receiving anastrozole compared with tamoxifen ( hazard ratio 0.57 ; 95 % confidence intervals 0.26 , 1.22 ; p = 0.15 ) , with most abnormalities occurring within the first year of treatment . Fewer patients treated with anastrozole appeared to require medical intervention for endometrial abnormalities , compared with patients on tamoxifen . This study showed that there was no significant difference in endometrial pathology between anastrozole and tamoxifen treatment groups",
"Clinical trials conducted in Western countries have shown that aromatase inhibitors are associated with better disease-free survival ( DFS ) than tamoxifen in postmenopausal early breast cancer . Because pharmacogenetic differences in drug-metabolizing genes may cause ethnic differences , assessment of the efficacy and tolerability of aromatase inhibitors in non-white women is warranted . This open-label , r and omized clinical trial included 706 postmenopausal Japanese women with hormone-receptor-positive breast cancer , who had received tamoxifen for 1 to 4 years as adjuvant therapy . This study was closed early after entry of ~28 % of the initially planned patients . They were r and omly assigned to either switch to anastrozole or to continue tamoxifen for total treatment duration of 5 years . Primary endpoints were DFS and adverse events . At a median follow-up of 42 months , the unadjusted hazard ratio was 0.69 ( 95 % confidence interval , 0.42–1.14 ; P = 0.14 ) for DFS and 0.54 ( 95 % CI , 0.29–1.02 ; P = 0.06 ) for relapse-free survival ( RFS ) , both in favor of anastrozole . The incidence of thromboembolic events in the tamoxifen group and bone fractures in the anastrozole group was not excessively high . Switching from tamoxifen to anastrozole was likely to decrease disease recurrence in postmenopausal Japanese breast cancer patients . Ethnic differences in major adverse events may be attributable to a low baseline risk of these events in Japanese",
"Background : There exists evidence that body mass index ( BMI ) impacts on the efficacy of aromatase inhibitors in patients with breast cancer . The relationship between BMI and the efficacy of tamoxifen is conflicting . We investigated the impact of BMI on the efficacy of single tamoxifen and tamoxifen plus an aromatase inhibitor in the well-defined prospect i ve study population of the ABCSG-06 trial . Methods : ABCSG-06 investigated the efficacy of tamoxifen vs tamoxifen plus aminoglutethimide in postmenopausal women with hormone receptor-positive breast cancer . Taking BMI at baseline , patients were classified as normal weight ( BMI = 18.5–24.9 kg m−2 ) , overweight ( BMI = 25–29.9 kg m−2 ) , and obese ( 30 kg m−2 ) according to WHO criteria . Results : Overweight+obese patients had an increased risk for distant recurrences ( hazard ratio ( HR ) : 1.51 ; Cox P=0·018 ) and a worse overall survival ( OS ; HR : 1·49 ; Cox P=0·052 ) compared with normal weight patients . Analysing patients treated with single tamoxifen only , no difference between overweight+obese patients and normal weight patients regarding distant recurrence-free survival ( HR : 1.35 ; Cox P=0·24 ) and OS ( HR : 0.99 ; Cox P=0·97 ) could be observed . In contrast , in the group of patients treated with the combination of tamoxifen plus aminoglutethimide , overweight+obese patients had an increased risk for distant recurrences ( 1.67 ; Cox P=0·03 ) and a worse OS ( 1.47 ; Cox P=0·11 ) compared with normal weight patients . Conclusion : BMI impacts on the efficacy of aromatase inhibitor-based treatment but not single tamoxifen",
"BACKGROUND Aromatase inhibitors are more effective than is tamoxifen in prevention of breast-cancer recurrence , but at the expense of increased musculoskeletal side-effects , such as carpal tunnel syndrome . The aim of this study was to assess risk factors and the prognostic value of musculoskeletal symptoms during treatment with the steroidal aromatase inhibitor exemestane or with tamoxifen after 2 - 3 years of tamoxifen . METHODS In the Intergroup Exemestane Study , postmenopausal women treated for early invasive breast cancer who remained disease free and on treatment after 2 - 3 years of tamoxifen were r and omised to switch to exemestane or to continue tamoxifen for the remainder of the 5-year period of endocrine treatment . The primary endpoint for this retrospective analysis was occurrence of carpal tunnel syndrome and any musculoskeletal events , analysed in the safety population , which consisted of all patients who had received any trial treatment . As well as case-report forms , question naires were distributed retrospectively to gain more details of cases of carpal tunnel syndrome . The relation between musculoskeletal symptoms reported by 6 months from r and omisation and survival from 9 months onwards was assessed by Cox proportional hazards models . The trial is registered , number IS RCT N11883920 . It has completed accrual and follow-up is continuing for enrolled participants . FINDINGS After a median follow-up of 91·0 months ( IQR 83·0 - 99·2 ) , carpal tunnel syndrome had been reported for 66 ( 2·8 % ) of 2319 patients in the exemestane group compared with 13 ( 0·6 % ) of 2338 in the tamoxifen group ( odds ratio [ OR ] 5·23 , 99 % CI 2·39 - 11·49 ; p . More events occurred during treatment in the exemestane group than in the tamoxifen group ( 66 [ 2·8 % ] vs seven [ 0·3 % ] , adjusted OR 9·90 , 99 % CI 3·52 - 27·82 ; p had musculoskeletal symptoms than in the tamoxifen group ( 901 of 2338 , 38·5 % ; OR 1·48 , 99 % CI 1·32 - 1·67 , p ) . More events occurred during treatment in the exemestane group than in the tamoxifen group ( 984 [ 42·4 % ] vs 776 [ 33·2 % ] , adjusted OR 1·59 , 99 % CI 1·32 - 1·91 ; p 73 on-treatment cases of carpal tunnel syndrome , 58 ( 79·5 % ) completed question naires were available . 27 patients ( 46·6 % ) had bilateral carpal tunnel syndrome and 31 ( 53·4 % ) had unilateral disease ; 40 ( 69·0 % ) underwent surgical release . The disorder greatly affected daily-life activities in 21 ( 36·2 % ) cases . Occurrence of musculoskeletal symptoms , including carpal tunnel syndrome , was associated with improved disease-free survival in unadjusted analysis ( p=0·023 ) , but not with overall survival ( p=0·36 ) . However , after adjustment for possible confounding factors , musculoskeletal symptoms were not associated with disease-free survival ( hazard ratio [ HR ] 0·96 , 95 % CI 0·82 - 1·14 , p=0·67 ) or overall survival ( HR 1·02 , 95 % CI 0·84 - 1·25 , p=0·82 ) . INTERPRETATION Occurrence of carpal tunnel syndrome is higher in patients with breast cancer given exemestane than in those treated with tamoxifen , and surgical release might be necessary in most cases . Development of musculoskeletal symptoms in the first 6 months of treatment is not an independent biomarker of improved disease outcome . Further investigation is warranted into the relation between treatment-emergent musculoskeletal symptoms and clinical outcome in patients with breast cancer receiving hormonal therapy . FUNDING Pfizer",
"Background A population of breast cancer patients exists who , for various reasons , never received adjuvant post-operative tamoxifen ( TAM ) . This study was aim ed to evaluate the role of late TAM in these patients . Methods From 1997 to 2003 , patients aged 35 to 75 years , operated more than 2 years previously for monolateral breast cancer without adjuvant TAM , with no signs of metastases and no contraindication to TAM were r and omized to TAM 20 mg/day orally for 2 years or follow-up alone . Events were categorized as locoregional relapse , distant metastases , metachronous breast cancer , tumours other than breast cancer and death from any causes , whichever occurred first . The sample size ( 197 patients per arm , plus 10 % allowance ) was based on the assumption of a 30 % decrease in the number of events occurring at a rate of 5 % annually in the 10 years following r and omization . Four hundred and thirty-three patients were r and omized in the study ( TAM 217 , follow-up 216 ) . Patients characteristics ( TAM/follow-up ) included : median age 55/55 years , median time from surgery 25/25 months ( range , 25 - 288/25 - 294 ) , in situ carcinoma 18/24 , oestrogen receptor ( ER ) positive in 75/68 , negative in 70/57 , unknown in 72/91 patients . Previous adjuvant treatment included chemotherapy in 131/120 and an LHRH analogue in 11/13 patients . Results Thirty-six patients prematurely discontinued TAM after a median of 1 month , mostly because of subjective intolerance . Eighty-three events ( TAM 39 , follow-up 44 ) occurred : locoregional relapse in 10/8 , distant metastases in 14/16 , metachronous breast cancer in 4/10 , other tumours in 11/10 patients . Less ER-positive secondary breast cancers occurred in the TAM treated patients than in follow-up patients ( 1 vs 10 , p = 0.005 ) . Event-free survival was similar in both groups of patients . Conclusions This 5-year analysis revealed significantly less metachronous ER-positive breast cancers in the TAM treated patients . No other statistically significant differences have emerged thus far",
"PURPOSE The Tamoxifen and Exemestane Adjuvant Multinational ( TEAM ) trial included a prospect ively planned pathology sub study testing the predictive value of progesterone receptor ( PgR ) expression for outcome of estrogen receptor-positive ( ER-positive ) early breast cancer treated with exemestane versus tamoxifen . PATIENTS AND METHODS Pathology blocks from 4,781 TEAM patients r and omly assigned to exemestane versus tamoxifen followed by exemestane for 5 years of total therapy were collected central ly , and tissue microarrays were constructed from sample s from 4,598 patients . Quantitative analysis of hormone receptors ( ER and PgR ) was performed by using image analysis and immunohistochemistry , and the results were linked to outcome data from the main TEAM trial and analyzed relative to disease-free survival and treatment . RESULTS Of 4,325 eligible ER-positive patients , 23 % were PgR-poor ( Allred . No treatment-by-marker effect for PgR was observed for exemestane versus tamoxifen ( PgR-rich hazard ratio [ HR ] , 0.83 ; 95 % CI , 0.65 to 1.05 ; PgR-poor HR , 0.85 ; 95 % CI , 0.61 to 1.19 ; P = .88 for interaction ) . Both PgR and ER expression were associated with patient prognosis in univariate ( PgR HR , 0.53 ; 95 % CI , 0.43 to 0.65 ; P Preferential exemestane versus tamoxifen treatment benefit was not predicted by PgR expression ; conversely , patients with ER-rich tumors may derive additional benefit from exemestane . Quantitative analysis of ER and PgR expression provides highly significant information on risk of early relapse ( within 1 to 3 years ) during treatment",
"BACKGROUND Treatment of breast cancer with aromatase inhibitors is associated with damage to bones . NCIC CTG MA.27 was an open-label , phase 3 , r and omised controlled trial in which women with breast cancer were assigned to one of two adjuvant oral aromatase inhibitors-exemestane or anastrozole . We postulated that exemestane-a mildly and rogenic steroid-might have a less detrimental effect on bone than non-steroidal anastrozole . In this companion study to MA.27 , we compared changes in bone mineral density ( BMD ) in the lumbar spine and total hip between patients treated with exemestane and patients treated with anastrozole . METHODS In MA.27 , postmenopausal women with early stage hormone ( oestrogen ) receptor-positive invasive breast cancer were r and omly assigned to exemestane 25 mg versus anastrozole 1 mg , daily . MA.27B recruited two groups of women from MA.27 : those with BMD T-scores of -2·0 or more ( up to 2 SDs below sex-matched , young adult mean ) and those with at least one T-score ( hip or spine ) less than -2·0 . Both groups received vitamin D and calcium ; those with baseline T-scores of less than -2·0 also received bisphosphonates . The primary endpoints were percent change of BMD at 2 years in lumbar spine and total hip for both groups . We analysed patients according to which aromatase inhibitor and T-score groups they were allocated to but BMD assessment s ceased if patients deviated from protocol . This study is registered with Clinical Trials.gov , NCT00354302 . FINDINGS Between April 24 , 2006 , and May 30 , 2008 , 300 patients with baseline T-scores of -2·0 or more were accrued ( 147 allocated exemestane , 153 anastrozole ) ; and 197 patients with baseline T-scores of less than -2·0 ( 101 exemestane , 96 anastrozole ) . For patients with T-scores greater than -2·0 at baseline , mean change of bone mineral density in the spine at 2 years did not differ significantly between patients taking exemestane and patients taking anastrozole ( -0·92 % , 95 % CI -2·35 to 0·50 vs -2·39 % , 95 % CI -3·77 to -1·01 ; p=0·08 ) . Respective mean loss in the hip was -1·93 % ( 95 % CI -2·93 to -0·93 ) versus -2·71 % ( 95 % CI -4·32 to -1·11 ; p=0·10 ) . Likewise for those who started with T-scores of less than -2·0 , mean change of spine bone mineral density at 2 years did not differ significantly between the exemestane and anastrozole treatment groups ( 2·11 % , 95 % CI -0·84 to 5·06 vs 3·72 % , 95 % CI 1·54 to 5·89 ; p=0·26 ) , nor did hip bone mineral density ( 2·09 % , 95 % CI -1·45 to 5·63 vs 0·0 % , 95 % CI -3·67 to 3·66 ; p=0·28 ) . Patients with baseline T-score of -2·0 or more taking exemestane had two fragility fractures and two other fractures , those taking anastrozole had three fragility fractures and five other fractures . For patients who had baseline T-scores of less than -2·0 taking exemestane , one had a fragility fracture and four had other fractures , whereas those taking anastrozole had five fragility fractures and one other fracture . INTERPRETATION Our results demonstrate that adjuvant treatment with aromatase inhibitors can be considered for breast cancer patients who have T-scores less than -2·0 . FUNDING Canadian Cancer Society Research Institute , Pfizer , Canadian Institutes of Health Research",
"Summary Background For women with oestrogen receptor (ER)-positive early breast cancer , treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis . We aim ed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years . Methods In the worldwide Adjuvant Tamoxifen : Longer Against Shorter ( ATLAS ) trial , 12 894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were r and omly allocated to continue tamoxifen to 10 years or stop at 5 years ( open control ) . Allocation ( 1:1 ) was by central computer , using minimisation . After entry ( between 1996 and 2005 ) , yearly follow-up forms recorded any recurrence , second cancer , hospital admission , or death . We report effects on breast cancer outcomes among the 6846 women with ER-positive disease , and side-effects among all women ( with positive , negative , or unknown ER status ) . Long-term follow-up still continues . This study is registered , number IS RCT N19652633 . Findings Among women with ER-positive disease , allocation to continue tamoxifen reduced the risk of breast cancer recurrence ( 617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls , p=0·002 ) , reduced breast cancer mortality ( 331 deaths vs 397 deaths , p=0·01 ) , and reduced overall mortality ( 639 deaths vs 722 deaths , p=0·01 ) . The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 ( recurrence rate ratio [ RR ] 0·90 [ 95 % CI 0·79–1·02 ] during years 5–9 and 0·75 [ 0·62–0·90 ] in later years ; breast cancer mortality RR 0·97 [ 0·79–1·18 ] during years 5–9 and 0·71 [ 0·58–0·88 ] in later years ) . The cumulative risk of recurrence during years 5–14 was 21·4 % for women allocated to continue versus 25·1 % for controls ; breast cancer mortality during years 5–14 was 12·2 % for women allocated to continue versus 15·0 % for controls ( absolute mortality reduction 2·8 % ) . Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease , and an intermediate effect among 4800 women with unknown ER status . Among all 12 894 women , mortality without recurrence from causes other than breast cancer was little affected ( 691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls ; RR 0·99 [ 0·89–1·10 ] ; p=0·84 ) . For the incidence ( hospitalisation or death ) rates of specific diseases , RRs were as follows : pulmonary embolus 1·87 ( 95 % CI 1·13–3·07 , p=0·01 [ including 0·2 % mortality in both treatment groups ] ) , stroke 1·06 ( 0·83–1·36 ) , ischaemic heart disease 0·76 ( 0·60–0·95 , p=0·02 ) , and endometrial cancer 1·74 ( 1·30–2·34 , p=0·0002 ) . The cumulative risk of endometrial cancer during years 5–14 was 3·1 % ( mortality 0·4 % ) for women allocated to continue versus 1·6 % ( mortality 0·2 % ) for controls ( absolute mortality increase 0·2 % ) . Interpretation For women with ER-positive disease , continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality , particularly after year 10 . These results , taken together with results from previous trials of 5 years of tamoxifen treatment versus none , suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis . Funding Cancer Research UK , UK Medical Research Council , AstraZeneca UK , US Army , EU-Biomed",
"Introduction International Breast Cancer Study Group ( IBCSG ) Trial 11 - 93 is the largest trial evaluating the role of the addition of chemotherapy to ovarian function suppression/ablation ( OFS ) and tamoxifen in premenopausal patients with endocrine-responsive early breast cancer . Methods IBCSG Trial 11 - 93 is a r and omized trial comparing four cycles of adjuvant chemotherapy ( AC : doxorubicin or epirubicin , plus cyclophosphamide ) added to OFS and 5 years of tamoxifen versus OFS and tamoxifen without chemotherapy in premenopausal patients with node-positive , endocrine-responsive early breast cancer . There were 174 patients r and omized from May 1993 to November 1998 . The trial was closed before the target accrual was reached due to low accrual rate . Results Patients r and omized tended to have lower risk node-positive disease and the median age was 45 . After 10 years median follow up , there remains no difference between the two r and omized treatment groups for disease-free ( hazard ratio = 1.02 ( 0.57–1.83 ) ; P = 0.94 ) or overall survival ( hazard ratio = 0.97 ( 0.44–2.16 ) ; P = 0.94 ) . Conclusion This trial , although small , offers no evidence that AC chemotherapy provides additional disease control for premenopausal patients with lower-risk node-positive endocrine-responsive breast cancer who receive adequate adjuvant endocrine therapy . A large trial is needed to determine whether chemotherapy adds benefit to endocrine therapy for this population",
"This study compared the efficacy and safety of a 3-monthly 10.8-mg depot goserelin ( ZoladexTM ) injection with the current 3.6 mg monthly dose in pre-menopausal Japanese women with estrogen receptor-positive ( ER+ ) early breast cancer . This was a multicenter , open-label , r and omized study . Primary endpoint was a non-inferiority analysis ( 10.8/3.6 mg ) of the area under the concentration – time curve ( AUC ) of estradiol ( E2 ) over the first 24 weeks . Secondary endpoints included E2 and follicle-stimulating hormone ( FSH ) concentrations , menstruation , and safety and tolerability . In total , 170 patients were r and omized to receive goserelin 10.8 mg every 3 months ( n = 86 ) or 3.6 mg every month ( n = 84 ) . Mean AUCs for E2 were similar between treatment groups ( 18.32 and 18.95 pg/ml·week for goserelin 10.8 and 3.6 mg , respectively ) . AUC ratio was 0.974 ( 95 % confidence interval , 0.80 , 1.19 ) , indicating non-inferiority for goserelin 10.8 mg . Serum E2 and FSH remained suppressed throughout the study and no patient experienced menses after week 16 . No clinical ly important differences in safety and tolerability were observed between the two groups . In terms of E2 suppression , 3-monthly goserelin 10.8 mg was non-inferior to monthly goserelin 3.6 mg in pre-menopausal women with ER+ breast cancer",
"Background : The antiestrogen tamoxifen may have partial estrogen-like effects on the postmenopausal uterus . Aromatase inhibitors ( AIs ) are increasingly used after initial tamoxifen in the adjuvant treatment of postmenopausal early breast cancer due to their mechanism of action : a potential benefit being a reduction of uterine abnormalities caused by tamoxifen . Patients and methods : Sonographic uterine effects of the steroidal AI exemestane were studied in 219 women participating in the Intergroup Exemestane Study : a large trial in postmenopausal women with estrogen receptor-positive ( or unknown ) early breast cancer , disease free after 2–3 years of tamoxifen , r and omly assigned to continue tamoxifen or switch to exemestane to complete 5 years adjuvant treatment . The primary end point was the proportion of patients with abnormal ( ≥5 mm ) endometrial thickness ( ET ) on transvaginal ultrasound 24 months after r and omisation . Results : The analysis included 183 patients . Two years after r and omisation , the proportion of patients with abnormal ET was significantly lower in the exemestane compared with tamoxifen arm ( 36 % versus 62 % , respectively ; P = 0.004 ) . This difference emerged within 6 months of switching treatment ( 43.5 % versus 65.2 % , respectively ; P = 0.01 ) and disappeared within 12 months of treatment completion ( 30.8 % versus 34.7 % , respectively ; P = 0.67 ) . Conclusion : Switching from tamoxifen to exemestane significantly reverses endometrial thickening associated with continued tamoxifen",
"BACKGROUND On average , aromatase inhibitors are better than tamoxifen when used as initial or sequential therapy for postmenopausal women with endocrine-responsive early breast cancer . Because there may be contraindications to their use based on side-effects or cost , we investigated subgroups in which aromatase inhibitors may be more or less important . PATIENTS AND METHODS Breast International Group 1 - 98 trial r and omized 6182 women among four groups comparing letrozole and tamoxifen with sequences of each agent ; 5177 ( 84 % ) had central ly confirmed estrogen receptor ( ER ) positivity . We assessed whether central ly determined ER , progesterone receptor ( PgR ) , human epidermal growth factor receptor 2 , and Ki-67 labeling index , alone or in combination with other prognostic features , predicted the magnitude of letrozole effectiveness compared with either sequence or tamoxifen monotherapy . RESULTS Individually , none of the markers significantly predicted differential treatment effects . Sub population treatment effect pattern plot analysis of a composite measure of prognostic risk revealed three patterns . Estimated 5-year disease-free survival for letrozole monotherapy , letrozole→tamoxifen , tamoxifen→letrozole , and tamoxifen monotherapy were 96 % , 94 % , 93 % , and 94 % , respectively , for patients at lowest risk ; 90 % , 91 % , 93 % , and 86 % , respectively , for patients at intermediate risk ; and 80 % , 76 % , 74 % , and 69 % , respectively , for patients at highest risk . CONCLUSION A composite measure of risk informs treatment selection better than individual biomarkers and supports the choice of 5 years of letrozole for patients at highest risk for recurrence",
"BACKGROUND Adjuvant therapy with an aromatase inhibitor improves outcomes , as compared with tamoxifen , in postmenopausal women with hormone-receptor-positive breast cancer . METHODS In two phase 3 trials , we r and omly assigned premenopausal women with hormone-receptor-positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years . Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin , oophorectomy , or ovarian irradiation . The primary analysis combined data from 4690 patients in the two trials . RESULTS After a median follow-up of 68 months , disease-free survival at 5 years was 91.1 % in the exemestane-ovarian suppression group and 87.3 % in the tamoxifen-ovarian suppression group ( hazard ratio for disease recurrence , second invasive cancer , or death , 0.72 ; 95 % confidence interval [ CI ] , 0.60 to 0.85 ; P rate of freedom from breast cancer at 5 years was 92.8 % in the exemestane-ovarian suppression group , as compared with 88.8 % in the tamoxifen-ovarian suppression group ( hazard ratio for recurrence , 0.66 ; 95 % CI , 0.55 to 0.80 ; P deaths ( 4.1 % of the patients ) , overall survival did not differ significantly between the two groups ( hazard ratio for death in the exemestane-ovarian suppression group , 1.14 ; 95 % CI , 0.86 to 1.51 ; P=0.37 ) . Selected adverse events of grade 3 or 4 were reported for 30.6 % of the patients in the exemestane-ovarian suppression group and 29.4 % of those in the tamoxifen-ovarian suppression group , with profiles similar to those for postmenopausal women . CONCLUSIONS In premenopausal women with hormone-receptor-positive early breast cancer , adjuvant treatment with exemestane plus ovarian suppression , as compared with tamoxifen plus ovarian suppression , significantly reduced recurrence . ( Funded by Pfizer and others ; TEXT and SOFT Clinical Trials.gov numbers , NCT00066703 and NCT00066690 , respectively . )",
"BACKGROUND MA17 showed improved outcomes in postmenopausal women given extended letrozole ( LET ) after completing 5 years of adjuvant tamoxifen . PATIENTS AND METHODS Exploratory subgroup analyses of disease-free survival ( DFS ) , distant DFS ( DDFS ) , overall survival ( OS ) , toxic effects and quality of life ( QOL ) in MA17 were performed based on menopausal status at breast cancer diagnosis . RESULTS At diagnosis , 877 women were premenopausal and 4289 were postmenopausal . Extended LET was significantly better than placebo ( PLAC ) in DFS for premenopausal [ hazard ratio ( HR ) = 0.26 , 95 % confidence interval ( CI ) 0.13 - 0.55 ; P = 0.0003 ] and postmenopausal women ( HR = 0.67 ; 95 % CI 0.51 - 0.89 ; P = 0.006 ) , with greater DFS benefit in those premenopausal ( interaction P = 0.03 ) . In adjusted post-unblinding analysis , those who switched from PLAC to LET improved DDFS in premenopausal ( HR = 0.15 ; 95 % CI 0.03 - 0.79 ; P = 0.02 ) and postmenopausal women ( HR = 0.45 ; 95 % CI 0.22 - 0.94 ; P = 0.03 ) . CONCLUSIONS Extended LET after 5 years of tamoxifen was effective in pre- and postmenopausal women at diagnosis , and significantly better in those premenopausal . Women premenopausal at diagnosis should be considered for extended adjuvant therapy with LET if menopausal after completing tamoxifen ",
"Although several r and omized clinical trials in the 1980s indicated a benefit from the use of tamoxifen in the treatment of early-stage breast cancer , questions have remained regarding the optimal duration of drug administration . In 1982 , the National Surgical Adjuvant Breast and Bowel Project ( NSABP ) initiated a r and omized trial to compare 5 years of tamoxifen to placebo among breast cancer patients with estrogen receptor-positive tumors and no evidence of axillary node involvement . By 1987 , evidence of a substantial benefit for tamoxifen led the NSABP to extend this trial to determine whether longer duration tamoxifen therapy would be additionally beneficial . This study r and omized patients who had completed 5 years of tamoxifen free of breast cancer recurrence or other events to either tamoxifen or placebo for an additional 5 years . By 1994 , 1172 women had entered the study and accrual was closed . In late 1995 , the trial was terminated on the basis of interim findings indicating that a benefit for continuing tamoxifen would not be realized . The closure has prompted controversy among cancer research ers , because there are currently at least three tamoxifen duration trials in progress , whereas results from two other studies evaluating 5-year duration therapy versus longer therapy were recently published . Here , we provide details of the statistical rationale contributing to our decision to recommend early closure of the study . We then consider other possible approaches to assessing the appropriateness of early termination in the face of evidence against a benefit , including Bayesian methods , which can be used to incorporate a range of prior beliefs regarding the efficacy of a treatment with accruing information from the trial . We also briefly discuss results of the other published studies",
"PURPOSE Anastrozole ( ANA ) alone delivers significant disease-free survival benefits over tamoxifen ( TAM ) monotherapy in postmenopausal women with early estrogen receptor-positive breast cancer . The ABCSG-8 ( Austrian Breast and Colorectal Cancer Study Group 8) study is a large phase III clinical trial addressing the sequence strategy containing ANA in comparison with 5 years of TAM in a low- to intermediate-risk group of postmenopausal patients . PATIENTS AND METHODS Endocrine receptor-positive patients with G1 or G2 tumors were eligible . After surgery , patients were r and omly assigned to 5 years of TAM or 2 years of TAM followed by 3 years of ANA . Adjuvant chemotherapy and G3 and T4 tumors were exclusion criteria . Intention-to-treat and censored analyses of on-treatment recurrence-free survival ( RFS ) were performed , and exploratory survival end points and toxicity were investigated . RESULTS Information from 3,714 patients , including 17,563 woman-years , with a median of 60 months of follow-up was available for this analysis . Median age was 63.8 years , 75 % were node negative , and 75 % had T1 tumors . Sequencing of ANA after identical 2-year treatment with TAM in both arms did not result in a statistically significant improvement of RFS ( hazard ratio [ HR ] , 0.80 ; 95 % CI , 0.63 to 1.01 ; P = .06 ) . Exploratory analyses of distant relapse-free survival indicated a 22 % improvement ( HR , 0.78 ; 95 % CI , 0.60 to 1.00 ) . On-treatment adverse events and serious adverse events were consistent with known toxicity profiles of ANA and TAM treatment . CONCLUSION Despite a low overall rate of recurrence in a population with breast cancer at limited risk of relapse , the a priori sequence strategy of 2 years of TAM followed by 3 years of ANA led to small outcome and toxicity benefits ",
"PURPOSE National Cancer Institute of Canada Clinical Trials Group trial MA.17 r and omly assigned 5,187 postmenopausal , hormone-receptor-positive patients with early breast cancer who completed 5 years of tamoxifen to receive either letrozole or placebo . At 30 months median follow-up , letrozole significantly improved disease-free survival ( DFS ) in all patients and overall survival ( OS ) in node-positive patients . Breast cancer incidence increases with age and more than 1,300 women age 70 years or older were enrolled onto MA.17 , making it ideal to explore the benefits , toxicities , and quality of life ( QOL ) impact of letrozole on older women . PATIENTS AND METHODS In this study , 5,169 r and omly assigned patients were divided into three age groups : younger than 60 years ( n = 2,152 ) , 60 to 69 years ( n = 1,694 ) , and > or= 70 years ( n = 1,323 ) . Log-rank test was used to compare differences in DFS , distant-disease-free survival , and OS between age and treatment groups , and Cox models were used to estimate hazard ratios and associated 95 % CIs . QOL was measured using the Medical Outcomes Short Form-36 and the Menopause-Specific Quality -of-Life question naire . RESULTS At 4 years , DFS demonstrated statistically significant differences favoring letrozole only in patients age younger than 60 years ( hazard ratio = 0.46 ; P = .0004 ) ; there was no interaction between age and treatment , indicating a similar effect of letrozole among all age groups . There was no difference in toxicity or QOL at 24 months among letrozole- and placebo-treated patients age > or= 70 years . CONCLUSION Healthy patients age 70 years and older completing 5 years of tamoxifen should be considered for extended adjuvant therapy with letrozole",
"BACKGROUND Little data exist on whether efficacy benefits or side-effects persist after 5 years of adjuvant treatment with an aromatase inhibitor . We aim ed to study long-term outcomes in the Arimidex , Tamoxifen , Alone or in Combination ( ATAC ) trial that compares anastrozole with tamoxifen after a median follow-up of 100 months . METHODS We analysed postmenopausal women with localised invasive breast cancer . The primary endpoint disease-free survival ( DFS ) , and the secondary endpoints time to recurrence ( TTR ) , incidence of new contralateral breast cancer ( CLBC ) , time to distant recurrence ( TTDR ) , overall survival ( OS ) , and death after recurrence were assessed in the total population ( intention to treat ; ITT : anastrozole , n=3125 ; tamoxifen , n=3116 ; total 6241 ) and the hormone-receptor-positive sub population , the clinical ly important subgroup for which endocrine treatment is now known to be effective ( 84 % of ITT : anastrozole , n=2618 ; tamoxifen , n=2598 ; total 5216 ) . After treatment completion , fractures and serious adverse events continued to be collected blindly ( safety population : anastrozole , n=3092 ; tamoxifen , n=3094 ; total 6186 ) . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N18233230 . FINDINGS At a median follow-up of 100 months ( range 0 - 126 ) , DFS , TTR , TTDR , and CLBC were improved significantly in the ITT and hormone-receptor-positive population s. For hormone-receptor-positive patients : DFS hazard ratio ( HR ) 0.85 ( 95 % CI 0.76 - 0.94 ) , p=0.003 ; TTR HR 0.76 ( 0.67 - 0.87 ) , p=0.0001 ; TTDR HR 0.84 ( 0.72 - 0.97 ) , p=0.022 ; and CLBC HR 0.60 ( 0.42 - 0.85 ) , p=0.004 . Absolute differences in time to recurrence increased over time ( TTR 2.8 % [ anastrozole 9.7%vs tamoxifen 12.5 % ] at 5 years and 4.8 % [ anastrozole 17.0%vs tamoxifen 21.8 % ] at 9 years ) and recurrence rates remained significantly lower on anastrozole compared with tamoxifen after treatment completion ( HR 0.75 [ 0.61 - 0.94 ] , p=0.01 ) . The fewer deaths after recurrence ( anastrozole 245 vs tamoxifen 269 ) was not significant ( HR 0.90 [ 0.75 - 1.07 ] , p=0.2 ) , and no effect was noted for OS ( anastrozole 472 vs tamoxifen 477 ) HR 0.97 [ 0.86 - 1.11 ] , p=0.7 ) . Fracture rates were higher in patients receiving anastrozole than in those receiving tamoxifen during active treatment ( number [ annual rate ] : 375 [ 2.93 % ] vs 234 [ 1.90 % ] ; incidence rate ratio [ IRR ] 1.55 [ 1.31 - 1.83 ] , p risk of cardiovascular morbidity or mortality between anastrozole and tamoxifen treatment groups . INTERPRETATION These data show long-term safety findings and establish clearly the long-term efficacy of anastrozole compared with tamoxifen as initial adjuvant treatment for postmenopausal women with hormone-sensitive , early breast cancer , and provide statistically significant evidence of a larger carryover effect after 5 years of adjuvant treatment with anastrozole compared with tamoxifen ",
"TPS104 Background : Multi-gene tumor assays have provided clinical ly useful prognostic information for patients with HR receptor and node-positive breast cancer . The 21-gene RS was shown to be prognostic for patients treated with tamoxifen alone , and exploratory studies suggested that it may be predictive of benefit from chemotherapy . In retrospective analyses from S8814 , patients with low RS appeared to get no benefit from adjuvant CAF chemotherapy , while those with higher RS did . These retrospective data require validation , especially since more modern chemotherapy might be more effective than the regimen used in S8814 . In January 2011 SWOG activated a trial to test the efficacy of using modern chemotherapy regimens in node positive patients with low RS , whose prognosis is still moderately poor but may not benefit from adjuvant chemotherapy based on tumor biology predicted by the RS value . The trial is similar to the Tailor RX study , but focuses on a node-positive population with low and intermediate RS . METHODS Phase III r and omized clinical trial of best endocrine therapy vs. best endocrine therapy and chemotherapy . Patients with 1 to 3 positive lymph nodes , HR-positive and HER2-negative invasive breast cancer with RS ≤ 25 are eligible for r and omization . Approximately , 9,400 patients will be screened to r and omize 4000 , stratified by RS ( 0 - 13 vs. 14 - 25 ) , menopausal status , and axillary surgery ( sentinel node vs.full dissection ) . Patients will be informed of their RS . Trial is powered on finding a significant interaction of treatment assignment and the continuous RS value and subsequently deriving a cutpoint for using the assay to guide treatment decisions . Patients who consent to screening are required to consent to banking of the tumor tissue and blood for further studies . Patient Reported Outcomes will be collected pre , post screening and post-r and omization . The study also has a cost-effectiveness analysis . Status : Open nationwide through participating NCI-funded cooperative groups . NCT01272037",
"Long-term endocrine therapy for breast cancer may have clinical implication s as drugs that potentially alter the lipid profile may increase the risk of developing cardiovascular disease . In this study , a companion sub protocol to the ATENA ( Adjuvant post-Tamoxifen Exemestane versus Nothing Applied ) trial , we compared the effect of the steroidal aromatase inactivator exemestane on the lipid profile of post-menopausal women with operable breast cancer in the adjuvant setting to that of observation alone following deprivation of 5–7 years primary treatment with tamoxifen . In this open-label , r and omized , parallel group study , 340 post-menopausal patients with operable breast cancer who had been treated with tamoxifen for 5–7 years were r and omized to either 5 additional years of exemestane ( 25 mg/day ; n=172 ) or observation alone ( n=168 ) . Assessment s of total cholesterol , high-density lipoprotein ( HDL ) , low-density lipoprotein ( LDL ) and total serum triglycerides ( TRG ) were performed at baseline , and at 6 and 12 months . Total TRG levels were significantly reduced compared with baseline for the exemestane and the observational arm . Both total cholesterol and LDL levels were significantly increased above that of baseline values by 6 months , maintained through to 12 months , with no significant difference between the two treatment arms . There was no significant alteration observed for HDL over time or between the two arms . We conclude that sequential adjuvant treatment with exemestane in post-menopausal operable breast cancer patients following cessation of 5–7 years of tamoxifen does not appear to significantly alter the lipidemic profile for at least 12 months compared with an observational arm",
"Trials of adjuvant endocrine therapy for breast cancer have shown that aromatase inhibitors have little impact on global health-related quality of life ( HRQoL ) , but have significant effects on patient-reported endocrine symptoms ( ESs ) . There are few studies of HRQoL and psychological distress during preoperative endocrine therapy performed to determine endocrine responsiveness . The NEOS trial is a multicenter , phase 3 r and omized controlled trial in postmenopausal women with hormone receptor-positive breast cancer . The primary aim of the trial was to evaluate the need for adjuvant chemotherapy in patients with clinical T1c-T2N0M0 , hormone receptor-positive tumors who responded to neoadjuvant letrozole ( LET ) administered for 24–28 weeks before surgery . The primary endpoint was disease-free survival and the secondary endpoints included adverse events , HRQoL , and cost-effectiveness . In a HRQoL sub- study , subjects were assessed at baseline and 4 and 16 weeks after starting neoadjuvant LET , using the functional assessment of cancer therapy-breast and its ES subscale , and the hospital anxiety and depression scale . HRQoL and psychosocial distress were analyzed in the uncontrolled phase during 24–28 weeks of neoadjuvant LET therapy in the NEOS trial . From May 16 , 2008 , to December 14 , 2011 , 503 patients were recruited into the HRQoL sub- study . The full analysis set included 497 patients with a mean age of 63-years old . The question naire response rates at enrollment and 4 and 16 weeks were 94.4 , 90.7 , and 89.1 % , respectively . There were no significant changes in the FACT-G or B-trial outcome index over time , but the social and family well-being score and the ES subscale deteriorated significantly , and the number of patients with clinical ly significant hot flush increased significantly . Anxiety , depression , and emotional well-being improved significantly after neoadjuvant LET . Neoadjuvant endocrine therapy with LET had no impact on global HRQoL , but did influence endocrine-related symptoms such as hot flush . This study is registered as UMIN000001090",
"BACKGROUND Aromatase inhibitors improved disease-free survival compared with tamoxifen when given as an initial adjuvant treatment or after 2 - 3 years of tamoxifen to postmenopausal women with hormone-receptor-positive breast cancer . We therefore compared the long-term effects of exemestane monotherapy with sequential treatment ( tamoxifen followed by exemestane ) . METHODS The Tamoxifen Exemestane Adjuvant Multinational ( TEAM ) phase 3 trial was conducted in hospitals in nine countries . Postmenopausal women ( median age 64 years , range 35 - 96 ) with hormone-receptor-positive breast cancer were r and omly assigned in a 1:1 ratio to open-label exemestane ( 25 mg once a day , orally ) alone or following tamoxifen ( 20 mg once a day , orally ) for 5 years . R and omisation was by use of a computer-generated r and om permuted block method . The primary endpoint was disease-free survival ( DFS ) at 5 years . Main analyses were by intention to treat . The trial is registered with Clinical Trials.gov , NCT00279448 , NCT00032136 , and NCT00036270 ; NTR 267 ; Ethics Commission Trial27/2001 ; and UMIN , C000000057 . FINDINGS 9779 patients were assigned to sequential treatment ( n=4875 ) or exemestane alone ( n=4904 ) , and 4868 and 4898 were analysed by intention to treat , respectively . 4154 ( 85 % ) patients in the sequential group and 4186 ( 86 % ) in the exemestane alone group were disease free at 5 years ( hazard ratio 0·97 , 95 % CI 0·88 - 1·08 ; p=0·60 ) . In the safety analysis , sequential treatment was associated with a higher incidence of gynaecological symptoms ( 942 [ 20 % ] of 4814 vs 523 [ 11 % ] of 4852 ) , venous thrombosis ( 99 [ 2 % ] vs 47 [ 1 % ] ) , and endometrial abnormalities ( 191 [ 4 % ] vs 19 [ . Musculoskeletal adverse events ( 2448 [ 50 % ] vs 2133 [ 44 % ] ) , hypertension ( 303 [ 6 % ] vs 219 [ 5 % ] ) , and hyperlipidaemia ( 230 [ 5 % ] vs 136 [ 3 % ] ) were reported more frequently with exemestane alone . INTERPRETATION Treatment regimens of exemestane alone or after tamoxifen might be judged to be appropriate options for postmenopausal women with hormone-receptor-positive early breast cancer . FUNDING Pfizer",
"BACKGROUND Multiple studies suggest better efficacy of chemotherapy in invasive ductal breast carcinomas ( IDC ) than invasive lobular breast carcinomas ( ILC ) . However , data on efficacy of adjuvant endocrine therapy regimens and histological subtypes are sparse . This study assessed endocrine therapy efficacy in IDC and ILC . The influence of semi-quantitative oestrogen receptor ( ER ) expression by Allred score was also investigated . METHODS Dutch and Belgian patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational ( TEAM ) trial were r and omized to exemestane ( 25 mg daily ) alone or following tamoxifen ( 20 mg daily ) for 5 years . Inclusion was restricted to IDC and ILC patients . Histological subtype was assessed locally ; ER expression was central ly review ed according to Allred score ( ER-poor ( relapse-free survival ( RFS ) , which was the time from r and omization to disease relapse . FINDINGS Overall , 2140 ( 82 % ) IDC and 463 ( 18 % ) ILC patients were included . RFS was similar for both endocrine treatment regimens in IDC ( hazard ratio ( HR ) for exemestane was 0.83 ( 95%confidence interval ( CI ) 0.67 - 1.03 ) ) , and ILC ( HR 0.69 ( 95%CI 0.45 - 1.06 ) ) . Irrespective of histological subtype , patients with ER-rich Allred scores allocated to exemestane alone had an improved RFS ( multivariable HR 0.71 ( 95%CI 0.56 - 0.89 ) ) . In contrast , patients with ER-poor Allred scores allocated to exemestane had a worse RFS ( multivariable HR 2.33 ( 95%CI 1.32 - 4.11 ) ) . Significant effect modification by ER-Allred score was confirmed ( multivariable p=0.003 ) . INTERPRETATION Efficacy of endocrine therapy regimens was similar for IDC and ILC . However , ER-rich patients showed superior efficacy to upfront exemestane , while ER-poor patients had better outcomes with sequential therapy , irrespective of histological subtype , emphasising the relevance of quantification of ER expression",
"BACKGROUND In this Tamoxifen Exemestane Adjuvant Multinational Japan sub- study , we evaluated the time course of changes in serum lipids in postmenopausal women with hormone-sensitive early breast cancer treated with exemestane , anastrozole , or tamoxifen for postoperative adjuvant therapy . PATIENTS AND METHODS A total of 154 breast cancer patients were assigned to receive exemestane , anastrozole , or tamoxifen in this r and omized open-label study . Serum lipid parameters including triglyceride ( TG ) , total cholesterol ( TC ) , high-density lipoprotein cholesterol ( HDL-C ) , and low-density lipoprotein cholesterol ( LDL-C ) were measured during 1 year of treatment . RESULTS TC and LDL-C rapidly decreased in patients treated with tamoxifen at 3 months . Compared with anastrozole and exemestane patients , TC and LDL-C were significantly lower at all assessment time points in tamoxifen patients ( P TG increased in tamoxifen patients ; it was significantly higher compared with exemestane patients at all assessment time points ( P HDL-C slightly decreased in exemestane patients ; it was significantly lower compared with anastrozole patients at 3 months and 1 year ( P = 0.0179 and 0.0013 , respectively ) . CONCLUSION Changes of lipid profiles in Japanese postmenopausal women treated with tamoxifen were relatively favorable , while exemestane and anastrozole had no clinical ly significant effect on the serum lipids",
"OBJECTIVES In 2003 the International Breast Cancer Study Group ( IBCSG ) initiated the TEXT and SOFT r and omized phase III trials to answer two questions concerning adjuvant treatment for premenopausal women with endocrine-responsive early breast cancer : 1-What is the role of aromatase inhibitors ( AI ) for women treated with ovarian function suppression ( OFS ) ? 2-What is the role of OFS for women who remain premenopausal and are treated with tamoxifen ? METHODS TEXT r and omized patients to receive exemestane or tamoxifen with OFS . SOFT r and omized patients to receive exemestane with OFS , tamoxifen with OFS , or tamoxifen alone . Treatment was for 5 years from r and omization . RESULTS TEXT and SOFT successfully met their enrollment goals in 2011 . The 5738 enrolled women had lower-risk disease and lower observed disease-free survival ( DFS ) event rates than anticipated . Consequently , 7 and 13 additional years of follow-up for TEXT and SOFT , respectively , were required to reach the targeted DFS events ( median follow-up about 10.5 and 15 years ) . To provide timely answers , protocol amendments in 2011 specified analyses based on chronological time and median follow-up . To assess the AI question , exemestane + OFS versus tamoxifen + OFS , a combined analysis of TEXT and SOFT became the primary analysis ( n = 4717 ) . The OFS question became the primary analysis from SOFT , assessing the unique comparison of tamoxifen + OFS versus tamoxifen alone ( n = 2045 ) . The first reports are anticipated in mid- and late-2014 . CONCLUSIONS We present the original design s of TEXT and SOFT and adaptations to ensure timely answers to two questions concerning optimal adjuvant endocrine treatment for premenopausal women with endocrine-responsive breast cancer . Trial Registration TEXT : Clinical trials.govNCT00066703 SOFT : Clinical trials.govNCT00066690",
"PURPOSE Chemotherapy , tamoxifen , and ovarian ablation/suppression ( OA/OS ) are effective adjuvant approaches for premenopausal , steroid hormone receptor-positive breast cancer . The value of combined therapy has not been clearly established . PATIENTS AND METHODS Premenopausal women with axillary lymph node-positive , steroid hormone receptor-positive breast cancer ( 1,503 eligible patients ) were r and omly assigned to six cycles of cyclophosphamide , doxorubicin , and fluorouracil ( CAF ) , CAF followed by 5 years of monthly goserelin ( CAF-Z ) , or CAF followed by 5 years of monthly goserelin and daily tamoxifen ( CAF-ZT ) . The primary end points were time to recurrence ( TTR ) , disease-free survival ( DFS ) , and overall survival ( OS ) for CAF-Z versus CAF , and CAF-ZT versus CAF-Z. RESULTS With a median follow-up of 9.6 years , the addition of tamoxifen to CAF-Z improved TTR and DFS but not OS . There was no overall advantage for addition of goserelin to CAF . CONCLUSION Addition of tamoxifen to CAF-Z improves outcome for premenopausal node-positive , receptor-positive breast cancer . The role of OA/OS alone or with other endocrine agents should be studied more intensely",
"BACKGROUND Tamoxifen , for many years the ' gold st and ard ' in the adjuvant setting for the management of endocrine sensitive early breast cancer , is associated with an increased risk of endometrial cancer and other life-threatening events . Moreover , many women relapse during or after tamoxifen therapy due to the development of resistance . This provided the rationale for a switching trial with anastrozole , the up date d results of which are reported here . PATIENTS AND METHODS This trial investigated the efficacy of switching to anastrozole for women already receiving tamoxifen . After 2 - 3 years of tamoxifen treatment , postmenopausal , node-positive , ER-positive patients were r and omized to receive either anastrozole 1 mg/day or to continue tamoxifen , 20 mg/day , giving a total duration of 5-years treatment . The primary end point was disease-free survival and secondary endpoints were event-free survival , overall survival and safety . RESULTS A total of 448 patients were enrolled . At a median follow-up time of 64 months ( range 12 - 93 ) , 63 events had been reported in the tamoxifen group compared with 39 in the anastrozole group [ HR 0.57 ( 95 % CI 0.38 - 0.85 ) P = 0.005 ] . Relapse-free and overall survival were also longer in the anastrozole group [ HR 0.56 ( 95 % CI 0.35 - 0.89 ) P = 0.01 and 0.56 ( 95 % CI 0.28 - 1.15 ) P = 0.1 ] . However , the latter difference was not statistically significant . Overall more patients in the anastrozole group experienced at least one adverse event ( 209 versus 151 : P = 0.000 ) . However , numbers of patients experiencing serious adverse events were comparable ( 37 versus 40 , respectively : P = 0.7 ) . CONCLUSIONS Switching to anastrozole after the first 2 - 3 years of treatment was confirmed to improve event-free and relapse-free survival of postmenopausal , node-positive , ER-positive early breast cancer patients already receiving adjuvant tamoxifen",
"PURPOSE Somatostatin analogs act directly on breast cancer cells and indirectly on insulin and insulin-like growth factor 1 ( IGF-1 ) levels . This trial was undertaken to assess whether octreotide would lower insulin and IGF-1 levels and reduce risk of breast cancer recurrence . PATIENTS AND METHODS The NCIC CTG MA.14 ( NCIC Clinical Trials Group MA.14 ) trial r and omly assigned postmenopausal women to 5 years of tamoxifen 20 mg daily ( TAM ) or TAM plus 2 years of octreotide 90 mg depot intramuscular injections monthly ( TAM-OCT ) as adjuvant therapy . The primary end point was event-free survival ( EFS ) . Secondary end points were relapse-free survival ( RFS ) , overall survival ( OS ) , toxicity , and effects of treatment on IGF physiology . RESULTS Among 667 women with a median follow-up of 7.9 years , 220 events occurred-108 with TAM-OCT and 112 with TAM . Adjusted hazard ratios ( HRs ; TAM-OCT to TAM ) were 0.93 for EFS ( 95 % CI , 0.71 to 1.22 ; P = .62 ) , 0.84 for RFS ( 95 % CI , 0.59 to 1.18 ; P = .31 ) , and 0.97 for OS ( 95 % CI , 0.69 to 1.37 ; P = .86 ) . Among patients with normal baseline gallbladder imaging , cholecystectomy was required in 23.0 % of those receiving TAM-OCT but in only 1.4 % of those receiving TAM ( P IGF-1 , IGF binding protein 3 , and C-peptide levels . Older age ( P = .02 ) , tumor size ( P = .001 ) , nodal status ( P = .01 ) , high C-peptide levels ( P higher body mass index ( BMI ) in models excluding C-peptide ( P and C-peptide levels were statistically significant . Octreotide did not add significant clinical benefit . High C-peptide levels ( surrogate for insulin secretion rate ) and high BMI were associated with poor outcome",
"From January 1 , 1990 to December 31 , 1994 , DBCG conducted a r and omised trial in 1 615 postmenopausal women with operable , high-risk , receptor-positive or -unknown breast cancer . The patients were after surgery r and omised to Tamoxifen for 1 year ( TAM1 ) , Tamoxifen for 2 years ( TAM 2 ) or Tamoxifen for 6 months followed by megestrol acetate for 6 months ( TAM/MA ) . When the preplanned sample size of 1 500 patients was reached it was decided to continue r and omisation to TAM1 or TAM2 and the study was finally closed December 31 , 1996 . With a median follow-up of more than 10 years , there was no difference in disease-free survival ( DFS ) or overall survival ( OS ) among the three treatment arms . Similar results were obtained in the original and extended comparisons of Tamoxifen for 1 versus 2 years . A multivariate analysis in the per- protocol treated patients did not show significant differences in hazard ratios for DFS or OS among the three arms . Side-effects were rare but more common in the TAM2 and TAM/MA arms",
"5 Background : In estrogen-receptor-positive ( ER+ ) early breast cancer , 5 years of tamoxifen reduces breast cancer death rates by about a third throughout years 0 - 14 . It has been uncertain how 10 years of tamoxifen compares with this . METHODS During 1991 - 2005 , 6,953 women with ER+ ( n=2755 ) , or ER untested ( 4198 , estimated 80 % ER+ if status known ) invasive breast cancer from 176 UK centres were , after 5 years of tamoxifen , r and omized to stop tamoxifen or continue to year 10 . Annual follow-up recorded compliance , recurrence , mortality , and hospital admissions . RESULTS Allocation to continue tamoxifen reduced breast cancer recurrence ( 580/3468 vs 672/3485 , p=0.003 ) . This reduction was time dependent : rate ratio 0.99 during years 5 - 6 [ 95%CI 0.86 - 1.15 ] , 0.84 [ 0.73 - 0.95 ] during years 7 - 9 , and 0.75 [ 0.66 - 0.86 ] later . Longer treatment also reduced breast cancer mortality ( 392 vs 443 deaths after recurrence , p=0.05 ) , rate ratio 1.03 [ 0.84 - 1.27 ] during years 5 - 9 and 0.77 [ 0.64 - 0.92 ] later ; and overall mortality ( 849 vs 910 deaths , p=0.1 ) , rate ratio 1.05 [ 0.90 - 1.22 ] during years 5 - 9 and 0.86 [ 0.75 - 0.97 ] later . Non-breast-cancer mortality was little affected ( 457 vs 467 deaths , rate ratio 0.94 [ 0.82 - 1.07 ] ) . There were 102 vs 45 endometrial cancers RR=2.20 ( 1.31 - 2.34 , p deaths ( absolute hazard 0.5 % , p=0.02 ) . Combining the similar results of aTTom and its international counterpart ATLAS ( Lancet 2013 ) enhances statistical significance of recurrence ( p breast cancer mortality ( p=0.002 ) and overall survival ( p=0.005 ) benefits . CONCLUSIONS aTTom confirms that , in ER+ disease , continuing tamoxifen to year 10 rather than just to year 5 produces further reductions in recurrence , from year 7 onward , and breast cancer mortality after year 10 . Taken together with the reduction in breast cancer deaths seen in trials of 5 years of tamoxifen vs none , these results indicate that 10 years of adjuvant tamoxifen , compared to no tamoxifen , reduces breast cancer mortality by about one third in the first 10 years following diagnosis and by a half subsequently . CLINICAL TRIAL INFORMATION IS RCT N17222211",
"BACKGROUND The Arimidex , Tamoxifen , Alone or in Combination ( ATAC ) trial was design ed to compare the efficacy and safety of anastrozole ( 1 mg ) with tamoxifen ( 20 mg ) , both given orally every day for 5 years , as adjuvant treatment for postmenopausal women with early-stage breast cancer . In this analysis , we assess the long-term outcomes after a median follow-up of 120 months . METHODS We used a proportional hazards model to assess the primary endpoint of disease-free survival , and the secondary endpoints of time to recurrence , time to distant recurrence , incidence of new contralateral breast cancer , overall survival , and death with or without recurrence in all r and omised patients ( anastrozole n=3125 , tamoxifen n=3116 ) and hormone-receptor-positive patients ( anastrozole n=2618 , tamoxifen n=2598 ) . After treatment completion , we continued to collect data on fractures and serious adverse events in a masked fashion ( safety population : anastrozole n=3092 , tamoxifen n=3094 ) . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N18233230 . FINDINGS Patients were followed up for a median of 120 months ( range 0 - 145 ) ; there were 24,522 woman-years of follow-up in the anastrozole group and 23,950 woman-years in the tamoxifen group . In the full study population , there were significant improvements in the anastrozole group compared with the tamoxifen group for disease-free survival ( hazard ratio [ HR ] 0·91 , 95 % CI 0·83 - 0·99 ; p=0·04 ) , time to recurrence ( 0·84 , 0·75 - 0·93 ; p=0·001 ) , and time to distant recurrence ( 0·87 , 0·77 - 0·99 ; p=0·03 ) . For hormone-receptor-positive patients , the results were also significantly in favour of the anastrozole group for disease-free survival ( HR 0·86 , 95 % CI 0·78 - 0·95 ; p=0·003 ) , time to recurrence ( 0·79 , 0·70 - 0·89 ; p=0·0002 ) , and time to distant recurrence ( 0·85 , 0·73 - 0·98 ; p=0·02 ) . In hormone-receptor-positive patients , absolute differences in time to recurrence between anastrozole and tamoxifen increased over time ( 2·7 % at 5 years and 4·3 % at 10 years ) and recurrence rates remained significantly lower on anastrozole than tamoxifen after treatment completion ( HR 0·81 , 95 % CI 0·67 - 0·98 ; p=0·03 ) , although the carryover benefit was smaller after 8 years . There was weak evidence of fewer deaths after recurrence with anastrozole compared with tamoxifen treatment in the hormone-receptor-positive subgroup ( HR 0·87 , 95 % CI 0·74 - 1·02 ; p=0·09 ) , but there was little difference in overall mortality ( 0·95 , 95 % CI 0·84 - 1·06 ; p=0·4 ) . Fractures were more frequent during active treatment in patients receiving anastrozole than those receiving tamoxifen ( 451 vs 351 ; OR 1·33 , 95 % CI 1·15 - 1·55 ; p p=0·9 ) . Treatment-related serious adverse events were less common in the anastrozole group than the tamoxifen group ( 223 anastrozole vs 369 tamoxifen ; OR 0·57 , 95 % CI 0·48 - 0·69 ; p p=0·3 ) . No differences in non-breast cancer causes of death were apparent and the incidence of other cancers was similar between groups ( 425 vs 431 ) and continue to be higher with anastrozole for colorectal ( 66 vs 44 ) and lung cancer ( 51 vs 34 ) , and lower for endometrial cancer ( six vs 24 ) , melanoma ( eight vs 19 ) , and ovarian cancer ( 17 vs 28 ) . No new safety concerns were reported . INTERPRETATION These data confirm the long-term superior efficacy and safety of anastrozole over tamoxifen as initial adjuvant therapy for postmenopausal women with hormone-sensitive early breast cancer",
"520 Background : Adjuvant zoledronic acid ( ZOL ) significantly improved disease-free survival ( DFS ) in premenopausal patients ( pts ) with endocrine-responsive early breast cancer in ABCSG-12 ( Gnant et al. NEJM 2009 ) . The ZOL anticancer effect was confirmed in other prospect i ve trials , such as ZO-FAST and the postmenopausal ( > 5 yrs ) cohort of AZURE . Long-term follow-up of ABCSG-12 ( > 6 yr ) now allows pre-planned subgroup analyses that more precisely identify the ZOL benefit , and interactions with pt and tumor characteristics . METHODS Premenopausal pts with early breast cancer ( N = 1,803 ) were r and omized to ovarian function suppression with goserelin ( 3.6 mg q28d ) and tamoxifen ( TAM ; 20 mg/d ) or anastrozole ( ANA ; 1 mg/d ) ± ZOL ( 4 mg q6mo ) for 3 yr . Endpoints included DFS and overall survival ( OS ) , both analyzed using log-rank test and Cox models . Preplanned subgroup analyses included sub population treatment effect pattern plot ( STEPP ) . RESULTS At 68 mo median follow-up , ZOL significantly reduced the risk of DFS events by 32 % vs no ZOL ( HR = 0.68 ; P = .009 ) ; in addition , there was a strong trend toward reduced risk of death ( HR = 0.66 ; P = .08 ) with ZOL vs no ZOL . Multivariate analyses showed no interaction between ZOL benefit and ANA/TAM or any classic tumor parameter ( eg , T , N , grade , ER ) . However , a strong interaction between ZOL and pt age was demonstrated . Pts > 40 yr of age ( n = 1,390 ) derived significant DFS benefits from ZOL ( HR = 0.58 ; 0.40 - 0.83 ; P = .003 ) , whereas there was no apparent benefit in pts of age . ZOL reduced the risk of death by 42 % in pts > 40 yr of age ( P = .05 ) , with presumed complete ovarian blockade . In several age subgroups > 40 yr , HRs for both DFS and OS . CONCLUSIONS ABCSG-12 long-term follow-up at 68 mo suggests that anticancer benefits of adjuvant ZOL mainly occur in pts with a low-estrogen environment . As in the postmenopausal ( > 5 yrs ) cohort of AZURE , ZOL leads to highly significant DFS and OS benefits . This suggests that both estrogen deprivation and reduction of bone-turnover-derived growth factors in the bone marrow microenvironment are needed for sufficient suppression of dormant micrometastases",
"PURPOSE To determine whether the addition of aminoglutethimide to tamoxifen is able to improve the outcome in postmenopausal patients with hormone receptor-positive , early-stage breast cancer . PATIENTS AND METHODS A total of 2,021 postmenopausal women were r and omly assigned to receive either tamoxifen for 5 years alone or tamoxifen in combination with aminoglutethimide ( 500 mg/d ) for the first 2 years of treatment . Tamoxifen was administered at 40 mg/d for the first 2 years and at 20 mg/d for 3 years . RESULTS All r and omized and eligible patients were included in the analysis according to the intention-to-treat principle . After a median follow-up of 5.3 years , the 5-year disease-free survival in the aminoglutethimide plus tamoxifen group was 83.6 % versus 83.7 % in the monotherapy group ( P = .89 ) . The corresponding data for overall survival at 5 years were 91.4 % and 91.2 % , respectively ( P = .74 ) . More patients failed to complete combination treatment ( 13.7 % ) because of side effects as compared to tamoxifen alone ( 5.2 % ; P = .0001 ) . CONCLUSION Aminoglutethimide given for 2 years in addition to tamoxifen for 5 years does not improve the prognosis of postmenopausal patients with receptor-positive , lymph node-negative or lymph node-positive breast cancer",
"To investigate whether the health-related quality of life ( HRQOL ) of patients switching from tamoxifen to anastrozole in a r and omized trial is identical to that of those who continued tamoxifen after 1–4 years of adjuvant tamoxifen in Japanese postmenopausal breast cancer patients . Eligible patients for the r and omized trial , the National Surgical Adjuvant Study of Breast Cancer 03 , were recurrence-free postmenopausal women who had received definitive surgery for primary breast cancer with positive hormone receptor(s ) , and had been taking tamoxifen for 1–4 years postoperatively . They were r and omly assigned to continue tamoxifen or to switch to anastrozole for a total duration of five years . Subjects were asked to reply to a self-administered QOL question naire survey to assess HRQOL ( FACT-B [ breast cancer scale ] , FACT-ES [ endocrine symptom scale ] ) and psychological distress ( CES-D : Center for Epidemiologic Studies Depression scale ) at r and omization ( baseline ) , 3 months , 1 , and 2 years after r and omization , respectively . At baseline 694 patients ( 346 in the tamoxifen group and 348 in the anastrozole group ) responded to the survey . The total scores of FACT-G , FACT-ES , and those of the FACT-G physical well-being subscale were statistically significantly better in the tamoxifen group than in the anastrozole group ( P = 0.042 , 0.038 , and 0.005 , respectively ) . However , there was no statistically significant difference between the treatment groups in the CES-D scores . Continuation of tamoxifen treatment after adjuvant tamoxifen for 1–4 years may provide Japanese breast cancer patients with better HRQOL than by switching to anastrozole",
"Ovarian ablation improves survival in premenopausal early breast cancer , but the potential added value by luteinizing hormone-releasing hormone ( LHRH ) agonists to tamoxifen is still not clear . The purpose of our study is to examine the efficacy of the LHRH agonist goserelin for adjuvant therapy of premenopausal breast cancer , the role of interaction between goserelin and tamoxifen and the impact of estrogen receptor ( ER ) content . A total of 927 patients were included in the Stockholm part of the Zoladex in Premenopausal Patients ( ZIPP ) trial . They were r and omly allocated in a 2 × 2 factorial study design to goserelin , tamoxifen , the combination of goserelin and tamoxifen or no endocrine therapy for 2 years , with or without chemotherapy . This is formally not a preplanned subset analysis presenting the end point first event . In this Stockholm sub- study , at a median follow-up of 12.3 years , goserelin reduced the risk of first event by 32 % ( P = 0.005 ) in the absence of tamoxifen , and tamoxifen reduced the risk by 27 % ( P = 0.018 ) in the absence of goserelin . The combined goserelin and tamoxifen treatment reduced the risk by 24 % ( P = 0.021 ) compared with no endocrine treatment . In highly ER-positive tumours , there were 29 % fewer events among goserelin treated ( P = 0.044 ) and a trend towards greater risk reduction depending on the level of ER content . The greatest risk reduction from goserelin treatment was observed among those not receiving tamoxifen ( HR : 0.52 , P = 0.007 ) . In conclusion , goserelin as well as tamoxifen reduces the risk of recurrence in endocrine responsive premenopausal breast cancer . Women with strongly ER-positive tumours may benefit more from goserelin treatment . The combination of goserelin and tamoxifen is not superior to either modality alone . With the limitations of a subset trial , these data have to be interpreted cautiously",
"BACKGROUND Analysis of the Austrian Breast and Colorectal Cancer Study Group trial-12 ( ABCSG-12 ) at 48 months ' follow-up showed that addition of zoledronic acid to adjuvant endocrine therapy significantly improved disease-free survival . We have now assessed long-term clinical efficacy including disease-free survival and disease outcomes in patients receiving anastrozole or tamoxifen with or without zoledronic acid . METHODS ABSCG-12 is a r and omised , controlled , open-label , two-by-two factorial , multicentre trial in 1803 premenopausal women with endocrine-receptor-positive early-stage ( stage I-II ) breast cancer receiving goserelin ( 3.6 mg every 28 days ) , comparing the efficacy and safety of anastrozole ( 1 mg per day ) or tamoxifen ( 20 mg per day ) with or without zoledronic acid ( 4 mg every 6 months ) for 3 years . R and omisation ( 1:1:1:1 ratio ) was computerised and based on the Pocock and Simon minimisation method to balance the four treatment arms across eight prognostic variables ( age , neoadjuvant chemotherapy , pathological tumour stage ; lymph-node involvement , type of surgery or locoregional therapy , complete axillary dissection , intraoperative radiation therapy , and geographical region ) . Treatment allocation was not masked . The primary endpoint was disease-free survival ( defined as disease recurrence or death ) and analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00295646 ; follow-up is ongoing . FINDINGS At a median follow-up of 62 months ( range 0 - 114.4 months ) , more than 2 years after treatment completion , 186 disease-free survival events had been reported ( 53 events in 450 patients on tamoxifen alone , 57 in 453 patients on anastrozole alone , 36 in 450 patients on tamoxifen plus zoledronic acid , and 40 in 450 patients on anastrozole plus zoledronic acid ) . Zoledronic acid reduced risk of disease-free survival events overall ( HR 0.68 , 95 % CI 0.51 - 0.91 ; p=0.009 ) , although the difference was not significant in the tamoxifen ( HR 0.67 , 95 % CI 0.44 - 1.03 ; p=0.067 ) and anastrozole arms ( HR 0.68 , 95 % CI 0.45 - 1.02 ; p=0.061 ) assessed separately . Zoledronic acid did not significantly affect risk of death ( 30 deaths with zoledronic acid vs 43 deaths without ; HR 0.67 , 95 % CI 0.41 - 1.07 ; p=0.09 ) . There was no difference in disease-free survival between patients on tamoxifen alone versus anastrozole alone ( HR 1.08 , 95 % CI 0.81 - 1.44 ; p=0.591 ) , but overall survival was worse with anastrozole than with tamoxifen ( 46 vs 27 deaths ; HR 1.75 , 95 % CI 1.08 - 2.83 ; p=0.02 ) . Treatments were generally well tolerated , with no reports of renal failure or osteonecrosis of the jaw . Bone pain was reported in 601 patients ( 33 % ; 349 patients on zoledronic acid vs 252 not on the drug ) , fatigue in 361 ( 20 % ; 192 vs 169 ) , headache in 280 ( 16 % ; 147 vs 133 ) , and arthralgia in 266 ( 15 % ; 145 vs 121 ) . INTERPRETATION Addition of zoledronic acid improved disease-free survival in the patients taking anastrozole or tamoxifen . There was no difference in disease-free survival between patients receiving anastrozole and tamoxifen overall , but those on anastrozole alone had inferior overall survival . These data show persistent benefits with zoledronic acid and support its addition to adjuvant endocrine therapy in premenopausal patients with early-stage breast cancer . FUNDING AstraZeneca ; Novartis",
"PURPOSE To up date the ASCO clinical practice guideline on adjuvant endocrine therapy on the basis of emerging data on the optimal duration of treatment , particularly adjuvant tamoxifen . METHODS ASCO convened the Up date Committee and conducted a systematic review of r and omized clinical trials from January 2009 to June 2013 and analyzed three historical trials . Guideline recommendations were based on the Up date Committee 's review of the evidence . Outcomes of interest included survival , disease recurrence , and adverse events . RESULTS This guideline up date reflects emerging data on duration of tamoxifen treatment . There have been five studies of tamoxifen treatment beyond 5 years of therapy . The two largest studies with longest reported follow-up show a breast cancer survival advantage with 10-year duration s of tamoxifen use . In addition to modest gains in survival , extended therapy with tamoxifen for 10 years compared with 5 years was associated with lower risks of breast cancer recurrence and contralateral breast cancer . RECOMMENDATIONS Previous ASCO guidelines recommended treatment of women who have hormone receptor-positive breast cancer and are premenopausal with 5 years of tamoxifen , and those who are postmenopausal a minimum of 5 years of adjuvant therapy with an aromatase inhibitor or tamoxifen followed by an aromatase inhibitor ( in sequence ) . If women are pre- or perimenopausal and have received 5 years of adjuvant tamoxifen , they should be offered 10 years total duration of tamoxifen . If women are postmenopausal and have received 5 years of adjuvant tamoxifen , they should be offered the choice of continuing tamoxifen or switching to an aromatase inhibitor for 10 years total adjuvant endocrine therapy",
"BACKGROUND Most recurrences in women with breast cancer receiving 5 years of adjuvant tamoxifen occur after 5 years . The MA.17 trial , which was design ed to determine whether extended adjuvant therapy with the aromatase inhibitor letrozole after tamoxifen reduces the risk of such late recurrences , was stopped early after an interim analysis showed that letrozole improved disease-free survival . This report presents up date d findings from the trial . METHODS Postmenopausal women completing 5 years of tamoxifen treatment were r and omly assigned to a planned 5 years of letrozole ( n = 2593 ) or placebo ( n = 2594 ) . The primary endpoint was disease-free survival ( DFS ) ; secondary endpoints included distant disease-free survival , overall survival , incidence of contralateral tumors , and toxic effects . Survival was examined using Kaplan-Meier analysis and log-rank tests . Planned subgroup analyses included those by axillary lymph node status . All statistical tests were two-sided . RESULTS After a median follow-up of 30 months ( range = 1.5 - 61.4 months ) , women in the letrozole arm had statistically significantly better DFS and distant DFS than women in the placebo arm ( DFS : hazard ratio [ HR ] for recurrence or contralateral breast cancer = 0.58 , 95 % confidence interval [ CI ] = 0.45 to 0.76 ; P Overall survival was the same in both arms ( HR for death from any cause = 0.82 , 95 % CI = 0.57 to 1.19 ; P = .3 ) . However , among lymph node-positive patients , overall survival was statistically significantly improved with letrozole ( HR = 0.61 , 95 % CI = 0.38 to 0.98 ; P = .04 ) . The incidence of contralateral breast cancer was lower in women receiving letrozole , but the difference was not statistically significant . Women receiving letrozole experienced more hormonally related side effects than those receiving placebo , but the incidences of bone fractures and cardiovascular events were the same . CONCLUSION Letrozole after tamoxifen is well-tolerated and improves both disease-free and distant disease-free survival but not overall survival , except in node-positive patients",
"PURPOSE Controversy exists regarding estrogen ( ER ) and progesterone ( PgR ) receptor expression on efficacy of adjuvant endocrine therapy . In the ATAC ( Arimidex , Tamoxifen , Alone or in Combination ) trial , the benefit of anastrozole over tamoxifen was substantially greater in ER+/PgR-than ER+/PgR+ tumors . In BIG 1 - 98 ( Breast International Group ) , the benefits of letrozole over tamoxifen were the same in ER+ tumors irrespective of PgR. MA.17 r and omized postmenopausal women after 5 years of tamoxifen , to letrozole or placebo . We present outcomes according to tumor receptor status . PATIENTS AND METHODS Disease-free survival ( DFS ) and other outcomes were assessed in subgroups by ER and PgR status using Cox 's proportional hazards model , adjusting for nodal status and prior adjuvant chemotherapy . RESULTS The DFS hazard ratio ( HR ) for letrozole versus placebo in ER+/PgR+ tumors ( N = 3,809 ) was 0.49 ( 95 % CI , 0.36 to 0.67 ) versus 1.21 ( 95 % CI , 0.63 to 2.34 ) in ER+/PgR-tumors ( n = 636 ) . ER+/PgR+ letrozole patients experienced significant benefit in distant DFS ( DDFS ; HR = 0.53 ; 95 % CI , 0.35 to 0.80 ) and overall survival ( OS ; HR = 0.58 ; 95 % CI , 0.37 to 0.90 ) . A statistically significant difference in treatment effect between ER+/PgR+ and ER+/PgR-subgroups for DFS was observed ( P = .02 ) , but not for DDFS ( P = .06 ) or OS ( P = .09 ) . CONCLUSION These results suggest greater benefit for letrozole in DFS , DDFS , and OS in patients with ER+/PgR+ tumors , implying greater activity of letrozole in tumors with a functional ER . However , because this is a subset analysis and receptors were not measured central ly , we caution against using these results for clinical decision making",
"Adjuvant ! © Online ( Adjuvant ! ) is a user-friendly , web-based tool that provides estimates of adjuvant therapy outcomes for individual patients . While reliable evidence underpins estimates for most patient cohorts , there is a paucity of data on the effect of adding chemotherapy to complete estrogen blockade for premenopausal women with estrogen-receptor positive breast cancer . International Breast Cancer Study Group ( IBCSG ) Trial 11 - 93 enrolled 174 premenopausal women with estrogen-receptor positive , node-positive breast cancer . Among these patients , 55 % had one positive axillary lymph node and 97 % had three or fewer positive nodes . Patients were r and omized to receive ovarian function suppression plus 5 years of tamoxifen with or without anthracycline-based chemotherapy . Estimated hazard rates and corresponding 10-year relapse-free survival percentages obtained from Trial 11 - 93 data were compared with those predicted using Adjuvant!. The 10-year relapse-free survival percentages predicted from Adjuvant ! were 64.4 % ( 95 % CI , 61.9–67.2 % ) for endocrine therapy alone and 74.9 % ( 95 % CI , 73.1–76.8 % ) for chemoendocrine therapy . By contrast , these estimates in Trial 11 - 93 were 76.4 % ( 95 % CI , 65.8–84.0 % ) for endocrine therapy alone and 74.9 % ( 95 % CI , 64.5–82.7 % ) for chemoendocrine therapy . The Adjuvant ! estimate for the endocrine-alone control group is lower than that observed in Trial 11 - 93 ( P = 0.03 ) , while the estimates for the two chemoendocrine therapy groups are similar . Adjuvant ! appears to underestimate the effectiveness of adjuvant endocrine therapy alone for premenopausal women with endocrine responsive breast cancer , thus overestimating the added benefit , if any , from chemotherapy for this patient population",
"BACKGROUND To measure bone mineral density ( BMD ) reduction produced by letrozole as compared with tamoxifen and the benefit of the addition of zoledronic acid . PATIENTS AND METHODS A phase 3 trial comparing tamoxifen , letrozole or letrozole+zoledronic acid in patients with hormone receptor-positive early breast cancer was conducted ; triptorelin was given to premenopausal patients . Two comparisons were planned : letrozole versus tamoxifen and letrozole+zoledronic acid versus letrozole . Primary end point was the difference in 1-year change of T-score at lumbar spine ( LTS ) measured by dual energy X-ray absorptiometry scan . RESULTS Out of 483 patients enrolled , 459 were available for primary analyses . Median age was 50 ( range 28 - 80 ) . The estimated mean difference ( 95 % confidence interval [ CI ] ) in 1-year change of LTS was equal to -0.30 ( 95 % CI -0.44 to -0.17 ) in the letrozole versus tamoxifen comparison ( P letrozole+zoledronic acid versus letrozole comparison ( P Bone damage by letrozole decreased with increasing baseline body mass index in premenopausal , but not postmenopausal , patients ( interaction test P=0.004 and 0.47 , respectively ) . CONCLUSIONS In the HOBOE ( HOrmonal BOne Effects ) trial , the positive effect of zoledronic acid on BMD largely counteracts damage produced by letrozole as compared with tamoxifen . Letrozole effect is lower among overweight/obese premenopausal patients ",
"PURPOSE To explore potential differences in efficacy , treatment completion , and adverse events ( AEs ) in elderly women receiving adjuvant tamoxifen or letrozole for five years in the Breast International Group ( BIG ) 1 - 98 trial . METHODS This report includes the 4,922 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1 - 98 trial . The median follow-up was 40.4 months . Sub population Treatment Effect Pattern Plot ( STEPP ) analysis was used to examine the patterns of differences in disease-free survival and incidences of AEs according to age . In addition , three categoric age groups were defined : \" younger postmenopausal \" patients were younger than 65 years ( n = 3,127 ) , \" older \" patients were 65 to 74 years old ( n = 1,500 ) , and \" elderly \" patients were 75 years of age or older ( n = 295 ) . RESULTS Efficacy results for sub population s defined by age were similar to the overall trial results : Letrozole significantly improved disease-free survival ( DFS ) , the primary end point , compared with tamoxifen . Elderly patients were less likely to complete trial treatment , but at rates that were similar in the two treatment groups . The incidence of bone fractures , observed more often in the letrozole group , did not differ by age . In elderly patients , letrozole had a significantly higher incidence of any grade 3 to 5 protocol -specified non-fracture AE compared with tamoxifen ( P = .002 ) , but differences were not significant for thromboembolic or cardiac AEs . CONCLUSION Adjuvant treatment with letrozole had superior efficacy ( DFS ) compared with tamoxifen in all age groups . On the basis of a small number of patients older than 75 years ( 6 % ) , age per se should not unduly affect the choice of adjuvant endocrine therapy",
"PURPOSE To compare the endocrine effects of 6 months of adjuvant treatment with letrozole + triptorelin or tamoxifen + triptorelin in premenopausal patients with early breast cancer within an ongoing phase 3 trial ( Hormonal Adjuvant Treatment Bone Effects study ) . PATIENTS AND METHODS Prospect ively collected hormonal data were available for 81 premenopausal women , of whom 30 were assigned to receive tamoxifen + triptorelin and 51 were assigned letrozole + triptorelin + /- zoledronate . Serum 17-beta-estradiol ( E2 ) , follicle-stimulating hormone ( FSH ) , luteinizing hormone ( LH ) , Delta4- and rostenedione , testosterone , dehydroepi and rosterone-sulfate , progesterone , adrenocorticotropic hormone ( ACTH ) , and cortisol were measured at baseline and after 6 months of treatment . For each hormone , 6-month values were compared between treatment groups by the Wilcoxon-Mann-Whitney exact test . RESULTS Median age was 44 years for both groups of patients . Letrozole + triptorelin ( + /- zoledronate ) induced a stronger suppression of median E2 serum levels ( P = .0008 ) , LH levels ( P = .0005 ) , and cortisol serum levels ( P tamoxifen + triptorelin . Median FSH serum levels were suppressed in both groups , but such suppression was lower among patients receiving letrozole , who showed significantly higher median FSH serum levels ( P testosterone , progesterone , ACTH , and rostenedione , and dehydroepi and rosterone between the two groups of patients . CONCLUSION Letrozole in combination with triptorelin induces a more intense estrogen suppression than tamoxifen + triptorelin in premenopausal patients with early breast cancer",
"PURPOSE In patients with hormone-dependent postmenopausal breast cancer , st and ard adjuvant therapy involves 5 years of the nonsteroidal aromatase inhibitors anastrozole and letrozole . The steroidal inhibitor exemestane is partially non-cross-resistant with nonsteroidal aromatase inhibitors and is a mild and rogen and could prove superior to anastrozole regarding efficacy and toxicity , specifically with less bone loss . PATIENTS AND METHODS We design ed an open-label , r and omized , phase III trial of 5 years of exemestane versus anastrozole with a two-sided test of superiority to detect a 2.4 % improvement with exemestane in 5-year event-free survival ( EFS ) . Secondary objectives included assessment of overall survival , distant disease-free survival , incidence of contralateral new primary breast cancer , and safety . RESULTS In the study , 7,576 women ( median age , 64.1 years ) were enrolled . At median follow-up of 4.1 years , 4-year EFS was 91 % for exemestane and 91.2 % for anastrozole ( stratified hazard ratio , 1.02 ; 95 % CI , 0.87 to 1.18 ; P = .85 ) . Overall , distant disease-free survival and disease-specific survival were also similar . In all , 31.6 % of patients discontinued treatment as a result of adverse effects , concomitant disease , or study refusal . Osteoporosis/osteopenia , hypertriglyceridemia , vaginal bleeding , and hypercholesterolemia were less frequent on exemestane , whereas mild liver function abnormalities and rare episodes of atrial fibrillation were less frequent on anastrozole . Vasomotor and musculoskeletal symptoms were similar between arms . CONCLUSION This first comparison of steroidal and nonsteroidal classes of aromatase inhibitors showed neither to be superior in terms of breast cancer outcomes as 5-year initial adjuvant therapy for postmenopausal breast cancer by two-way test . Less toxicity on bone is compatible with one hypothesis behind MA.27 but requires confirmation . Exemestane should be considered another option as up-front adjuvant therapy for postmenopausal hormone receptor-positive breast cancer",
"PURPOSE Tamoxifen , which is actually the gold st and ard adjuvant treatment in estrogen receptor-positive early breast cancer , is associated with an increased risk of endometrial cancer and other life-threatening events . Moreover , many women relapse during or after tamoxifen therapy because of the development of resistance . Therefore new approaches are required . PATIENTS AND METHODS We conducted a prospect i ve r and omized trial to test the efficacy of switching postmenopausal patients who were already receiving tamoxifen to the aromatase inhibitor anastrozole . After 2 to 3 years of tamoxifen treatment , patients were r and omly assigned either to receive anastrozole 1 mg/d or to continue receiving tamoxifen 20 mg/d , for a total duration of treatment of 5 years . Disease-free survival was the primary end point . Event-free survival , overall survival , and safety were secondary end points . RESULTS Four hundred forty-eight patients were enrolled . All women had node-positive , estrogen receptor-positive tumors . At a median follow-up time of 36 months , 45 events had been reported in the tamoxifen group compared with 17 events in the anastrozole group ( P = .0002 ) . Disease-free and local recurrence-free survival were also significantly longer in the anastrozole group ( hazard ratio [ HR ] = 0.35 ; 95 % CI , 0.18 to 0.68 ; P = .001 and HR = 0.15 ; 95 % CI , 0.03 to 0.65 ; P = .003 , respectively ) . Overall , more adverse events were recorded in the anastrozole group compared with the tamoxifen group ( 203 v 150 , respectively ; P = .04 ) . However , more events were life threatening or required hospitalization in the tamoxifen group than in the anastrozole group ( 33 of 150 events v 28 of 203 events , P = .04 ) . CONCLUSION Switching to anastrozole after the first 2 to 3 years of treatment is well tolerated and significantly improves event-free and recurrence-free survival in postmenopausal patients with early breast cancer",
"AIM Immediate adjuvant tamoxifen reduces disease recurrence and improves survival in patients with early breast cancer . However , is it too late to administer tamoxifen to patients who have already undergone treatment , but were unable to benefit from this adjuvant therapy ? The French National Cancer Centers ( FNCLCC ) have investigated the efficacy of delayed tamoxifen administration in a r and omized controlled trial . PATIENTS AND METHODS From September 1986 to October 1989 , women with primary breast cancer , who had undergone surgery , radiotherapy , and /or received adjuvant chemotherapy but not hormone therapy more than two years earlier , were r and omized to receive either 30 mg/day tamoxifen or no treatment . The 10-year disease-free and overall survival rates of the two groups of patients and of various subgroups were determined according to the Kaplan-Meyer method and compared by the log-rank test . RESULTS This intention-to-treat analysis comprised 250 Introduction women in the tamoxifen group and 244 in the control group . Patient characteristics ( age , T stage , number of positive nodes , receptor status , and interval since tumor treatment ) were comparable in both groups . Delayed adjuvant tamoxifen significantly improved overall survival only in node-positive patients and in patients with estrogen receptor-positive ( ER+ ) or progesterone receptor-positive ( PR+ ) tumors . Disease-free survival , however , was significantly improved in the global population and in several patient subgroups ( node-positive , ER+ , PR+ ) . Patients in whom the interval between primary treatment and delayed adjuvant tamoxifen was greater than five years also had significantly improved disease-free survival . CONCLUSIONS Overall and disease-free survival results indicate that delayed adjuvant tamoxifen administration ( 30 mg/day ) is justified in women with early breast cancer , even if this treatment is initiated two or more years after primary treatment",
"PURPOSE Among postmenopausal women with endocrine-responsive breast cancer , the aromatase inhibitor letrozole , when compared with tamoxifen , has been shown to significantly improve disease-free survival ( DFS ) and time to distant recurrence ( TDR ) . We investigated whether letrozole monotherapy prolonged overall survival ( OS ) compared with tamoxifen monotherapy . PATIENTS AND METHODS Of 8,010 postmenopausal women with hormone receptor-positive , early breast cancer enrolled on the Breast International Group ( BIG ) 1 - 98 study , 4,922 were r and omly assigned to 5 years of continuous adjuvant therapy with either letrozole or tamoxifen . Of 2,459 patients enrolled in the tamoxifen treatment arm , 619 ( 25.2 % ) selectively crossed over to either adjuvant or extended letrozole after initial trial results were presented in January 2005 . To gain better estimates of relative treatment effects in the presence of selective crossover , we used inverse probability of censoring weighted ( IPCW ) modeling . RESULTS Weighted Cox models , by using IPCW , estimated a statistically significant , 18 % reduction in the hazard of an OS event with letrozole treatment ( hazard ratio [ HR ] , 0.82 ; 95 % CI , 0.70 to 0.95 ) . Estimates of 5-year OS on the basis of IPCW were 91.8 % and 90.4 % for letrozole and tamoxifen , respectively . The HRs of DFS and TDR events by using IPCW modeling were 0.83 ( 95 % CI , 0.74 to 0.94 ) and 0.80 ( 95 % CI , 0.67 to 0.94 ) , respectively ( P DFS , OS , and TDR ) . Median follow-up was 74 months . CONCLUSION Adjuvant treatment with letrozole , compared with tamoxifen , significantly reduces the risk of death , the risk of recurrent disease , and the risk of recurrence at distant sites in postmenopausal women with hormone receptor-positive breast cancer",
"BACKGROUND AND METHODS The Scottish Adjuvant Tamoxifen Trial ( main trial ) was initiated in April 1978 to assess the effect of tamoxifen given to patients with breast cancer immediately after mastectomy ( or mastectomy plus radiation therapy ) ( adjuvant arm ) or only after the patients had had a relapse ( control arm ) ; 1323 patients were r and omly assigned ( 667 to the adjuvant arm and 656 to the control arm ) . Results have been reported for the follow-up period from 2.5 through 8 years . In this article , we report up date d results after a median follow-up of 15 years . If agreeable and eligible , patients who were disease free at 5 years in the adjuvant arm of the main trial were entered into a duration trial and r and omly assigned either to stop taking tamoxifen ( 169 patients ) or to continue taking it indefinitely until relapse or death ( 173 patients ) . For this up date , we analyzed information on death , recurrence , survival , and other malignancies for all but 21 of the 560 living patients from the original and duration trials to determine the probabilities of total survival , systemic relapse of disease , and death from breast cancer . All statistical tests are two-sided . RESULTS The beneficial effect of adjuvant tamoxifen given for 5 years on the probability of total survival ( P = .006 ) , systemic relapse ( P = .007 ) , and death from breast cancer ( P = .002 ) has been maintained through 15 years . No additional benefit was observed in those r and omly assigned to continue taking tamoxifen beyond 5 years . CONCLUSION Information from this study suggests that , if adjuvant tamoxifen is given to women with operable breast cancer , it need not be for more than 5 years",
"Background : Use of aromatase inhibitors in women with postmenopausal breast cancer accompanies risks of bone loss . We evaluated changes in bone mineral density ( BMD ) and bone turnover markers in patients treated with exemestane , anastrozole or tamoxifen for hormone-sensitive postmenopausal early breast cancer . Patients and Methods : Sixty-eight patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational Japan bone sub study were r and omly assigned to receive tamoxifen , exemestane or anastrozole . During a 2-year study period , lumbar spine BMD was measured using dual-energy X-ray absorptiometry , and urinary type I collagen cross-linked N-telopeptide ( NTX ) and serum bone-specific alkaline phosphatase ( BAP ) were also measured . Results : BMD at 2 years of treatment was higher in tamoxifen patients compared with exemestane and anastrozole patients ; however , the intergroup difference was not significant ( p = 0.2521 and p = 0.0753 , respectively ) . BMD was higher in exemestane patients compared with anastrozole patients ; however , the intergroup difference was not significant ( p = 0.7059 and p = 0.8134 , respectively ) . NTX and BAP were significantly lower in tamoxifen patients compared with exemestane and anastrozole patients at 1 and 2 years of treatment ( p bone protection compared with exemestane or anastrozole . The effect of exemestane and anastrozole on bone loss may be comparable in Japanese postmenopausal women",
"BACKGROUND The incidence of local recurrence ( LR ) after conservative surgery for early breast cancer without adjuvant therapy is unacceptably high even with favourable tumours . The aim of this study was to examine the effect of adjuvant therapies in tumours with excellent prognostic features . METHODS Patients with primary invasive breast cancer wide local excision ( WLE ) with clear margins were r and omised into a 2 × 2 clinical trial of factorial design with or without radiotherapy and with or without tamoxifen . Trial entry was allowed to either comparison or both . FINDINGS The actuarial breast cancer specific survival in 1135 r and omised patients at 10 years was 96 % . Analysis by intention to treat showed that LR after WLE was reduced in patients r and omised to radiotherapy ( RT ) ( HR 0.37 , CI 0.22 - 0.61 p to tamoxifen ( HR 0.33 , CI 0.15 - 0.70 p that LR after WLE alone was 1.9 % per annum ( PA ) versus 0.7 % with RT alone and 0.8 % with tamoxifen alone . No patient r and omised to both adjuvant treatments developed LR . Analysis by treatment received showed LR at 2.2%PA for surgery alone versus 0.8 % for either adjuvant radiotherapy or tamoxifen and 0.2 % for both treatments . CONCLUSIONS Even in these patients with tumours of excellent prognosis , LR after conservative surgery without adjuvant therapy was still very high . This was reduced to a similar extent by either radiotherapy or tamoxifen but to a greater extent by the receipt of both treatments",
"PURPOSE The interim analysis of the National Cancer Institute of Canada Clinical Trials Group MA.17 trial showed that letrozole was significantly better than placebo in disease-free survival ( DFS ) for postmenopausal women with hormone receptor-positive breast cancer following about 5 years of tamoxifen therapy . When patients were unblinded , those on placebo were offered letrozole . Longer-term efficacy of letrozole , especially survival , was of particular interest because the median follow-up of the first interim analysis was only 2.5 years . Efficacy was difficult to assess because more than 60 % of placebo patients crossed over to letrozole after being unblinded . PATIENTS AND METHODS Two statistical approaches were used to adjust for the potential effects of treatment crossover : one was based on the inverse probability of censoring weighted ( IPCW ) Cox model and the other on a Cox model with time-dependent covariates . RESULTS With a median follow-up of 64 months , the hazard ratios ( HRs ) of letrozole and placebo from the IPCW analyses were HR of 0.52 ( 95 % CI , 0.45 to 0.61 ; P DFS , HR of 0.51 ( 95 % CI , 0.42 to 0.61 ; P distant disease-free survival ( DDFS ) , and HR of 0.61 ( 95 % CI , 0.52 to 0.71 ; P overall survival ( OS ) . The results from the analyses based on the Cox model with time-dependent covariates were similar for letrozole and placebo : HR of 0.58 ( 95 % CI , 0.47 to 0.72 ; P DFS , HR of 0.68 ( 95 % CI , 0.52 to 0.88 ; P = .004 ) for DDFS , and HR of 0.76 ( 95 % CI , 0.60 to 0.96 ; P = .02 ) for OS . CONCLUSION Exploratory analyses based on longer follow-up and adjusting for treatment crossover suggest that extended adjuvant letrozole was superior to placebo in DFS , DDFS , and OS",
"BACKGROUND Postmenopausal women with hormone receptor-positive early breast cancer have persistent , long-term risk of breast-cancer recurrence and death . Therefore , trials assessing endocrine therapies for this patient population need extended follow-up . We present an up date of efficacy outcomes in the Breast International Group ( BIG ) 1 - 98 study at 8·1 years median follow-up . METHODS BIG 1 - 98 is a r and omised , phase 3 , double-blind trial of postmenopausal women with hormone receptor-positive early breast cancer that compares 5 years of tamoxifen or letrozole monotherapy , or sequential treatment with 2 years of one of these drugs followed by 3 years of the other . R and omisation was done with permuted blocks , and stratified according to the two-arm or four-arm r and omisation option , participating institution , and chemotherapy use . Patients , investigators , data managers , and medical review ers were masked . The primary efficacy endpoint was disease-free survival ( events were invasive breast cancer relapse , second primaries [ contralateral breast and non-breast ] , or death without previous cancer event ) . Secondary endpoints were overall survival , distant recurrence-free interval ( DRFI ) , and breast cancer-free interval ( BCFI ) . The monotherapy comparison included patients r and omly assigned to tamoxifen or letrozole for 5 years . In 2005 , after a significant disease-free survival benefit was reported for letrozole as compared with tamoxifen , a protocol amendment facilitated the crossover to letrozole of patients who were still receiving tamoxifen alone ; Cox models and Kaplan-Meier estimates with inverse probability of censoring weighting ( IPCW ) are used to account for selective crossover to letrozole of patients ( n=619 ) in the tamoxifen arm . Comparison of sequential treatments to letrozole monotherapy included patients enrolled and r and omly assigned to letrozole for 5 years , letrozole for 2 years followed by tamoxifen for 3 years , or tamoxifen for 2 years followed by letrozole for 3 years . Treatment has ended for all patients and detailed safety results for adverse events that occurred during the 5 years of treatment have been reported elsewhere . Follow-up is continuing for those enrolled in the four-arm option . BIG 1 - 98 is registered at clinical trials.govNCT00004205 . FINDINGS 8010 patients were included in the trial , with a median follow-up of 8·1 years ( range 0 - 12·4 ) . 2459 were r and omly assigned to monotherapy with tamoxifen for 5 years and 2463 to monotherapy with letrozole for 5 years . In the four-arm option of the trial , 1546 were r and omly assigned to letrozole for 5 years , 1548 to tamoxifen for 5 years , 1540 to letrozole for 2 years followed by tamoxifen for 3 years , and 1548 to tamoxifen for 2 years followed by letrozole for 3 years . At a median follow-up of 8·7 years from r and omisation ( range 0 - 12·4 ) , letrozole monotherapy was significantly better than tamoxifen , whether by IPCW or intention-to-treat analysis ( IPCW disease-free survival HR 0·82 [ 95 % CI 0·74 - 0·92 ] , overall survival HR 0·79 [ 0·69 - 0·90 ] , DRFI HR 0·79 [ 0·68 - 0·92 ] , BCFI HR 0·80 [ 0·70 - 0·92 ] ; intention-to-treat disease-free survival HR 0·86 [ 0·78 - 0·96 ] , overall survival HR 0·87 [ 0·77 - 0·999 ] , DRFI HR 0·86 [ 0·74 - 0·998 ] , BCFI HR 0·86 [ 0·76 - 0·98 ] ) . At a median follow-up of 8·0 years from r and omisation ( range 0 - 11·2 ) for the comparison of the sequential groups with letrozole monotherapy , there were no statistically significant differences in any of the four endpoints for either sequence . 8-year intention-to-treat estimates ( each with SE ≤1·1 % ) for letrozole monotherapy , letrozole followed by tamoxifen , and tamoxifen followed by letrozole were 78·6 % , 77·8 % , 77·3 % for disease-free survival ; 87·5 % , 87·7 % , 85·9 % for overall survival ; 89·9 % , 88·7 % , 88·1 % for DRFI ; and 86·1 % , 85·3 % , 84·3 % for BCFI . INTERPRETATION For postmenopausal women with endocrine-responsive early breast cancer , a reduction in breast cancer recurrence and mortality is obtained by letrozole monotherapy when compared with tamoxifen montherapy . Sequential treatments involving tamoxifen and letrozole do not improve outcome compared with letrozole monotherapy , but might be useful strategies when considering an individual patient 's risk of recurrence and treatment tolerability . FUNDING Novartis , United States National Cancer Institute , International Breast Cancer Study Group",
"PURPOSE The National Cancer Institute of Canada Clinical Trials Group MA.17 trial examined the efficacy of letrozole ( LET ) started within 3 months of 5 years of adjuvant tamoxifen in postmenopausal hormone receptor-positive early-stage breast cancer . When the trial was unblinded , patients who received placebo ( PLAC ) were offered LET . PATIENTS AND METHODS This cohort analysis describes the outcomes of women assigned PLAC at the initial r and om assignment after unblinding . Efficacy outcomes of women who chose LET ( PLAC-LET group ) were compared with those who did not ( PLAC-PLAC group ) by the hazard ratios and by P values calculated from Cox models that adjusted for imbalances between the groups . Toxicity analyses included only events that occurred after unblinding . RESULTS There were 1,579 women in the PLAC-LET group ( median time from tamoxifen , 2.8 years ) and 804 in the PLAC-PLAC group . Patients in the PLAC-LET group were younger ; had a better performance status ; and were more likely to have had node-positive disease , axillary dissection , and adjuvant chemotherapy than those in the PLAC-PLAC group . At a median follow-up of 5.3 years , disease-free survival ( DFS ; adjusted hazard ratio [ HR ] , 0.37 ; 95 % CI , 0.23 to 0.61 ; P distant DFS ( HR , 0.39 ; 95 % CI , 0.20 to 0.74 ; P = .004 ) were superior in the PLAC-LET group . More self-reported new diagnoses of osteoporosis and significantly more clinical fractures occurred in the women who took LET ( 5.2 % v 3.1 % , P = .02 ) . CONCLUSION Interpretation of this cohort analysis suggests that LET improves DFS and distant DFS even when there has been a substantial period of time since the discontinuation of prior adjuvant tamoxifen",
"PURPOSE Patients with early-stage , hormone receptor-positive breast cancer have considerable residual risk for recurrence after completing 5 years of adjuvant tamoxifen . In May 2001 , the National Surgical Adjuvant Breast and Bowel Project ( NSABP ) initiated accrual to a r and omized , placebo-controlled , double-blind clinical trial to evaluate the steroidal aromatase inhibitor exemestane as extended adjuvant therapy in this setting . PATIENTS AND METHODS Postmenopausal patients with clinical T(1 - 3)N(1)M(0 ) breast cancer who were disease free after 5 years of tamoxifen were r and omly assigned to 5 years of exemestane ( 25 mg/d orally ) or 5 years of placebo . Our primary aim was to test whether exemestane prolongs disease-free survival ( DFS ) . In October 2003 , results of National Cancer Institute of Canada ( NCIC ) MA.17 showing benefit from adjuvant letrozole in this setting necessitated termination of accrual to B-33 , unblinding , and offering of exemestane to patients in the placebo group . RESULTS At the time of unblinding , 1,598 patients had been r and omly assigned ; 72 % in the exemestane group continued on exemestane and 44 % in the placebo group elected to receive exemestane . With 30 months of median follow-up , original exemestane assignment result ed in a borderline statistically significant improvement in 4-year DFS ( 91 % v 89 % ; relative risk [ RR ] = 0.68 ; P = .07 ) and in a statistically significant improvement in 4-year relapse-free survival ( RFS ; 96 % v 94 % ; RR = 0.44 ; P = .004 ) . Toxicity , assessed up to time of unblinding , was acceptable for the adjuvant setting . CONCLUSION Despite premature closure and crossover to exemestane by a substantial proportion of patients , original exemestane assignment result ed in non-statistically significant improvement in DFS and in statistically significant improvement in RFS",
"PURPOSE We compared the endocrine effects of 6 and 12 months of adjuvant letrozole versus tamoxifen in postmenopausal patients with hormone-responsive early breast cancer within an ongoing phase III trial . PATIENTS AND METHODS Patients were r and omly assigned to receive tamoxifen , letrozole , or letrozole plus zoledronic acid . Serum values of estradiol , follicle-stimulating hormone ( FSH ) , luteinizing hormone ( LH ) , testosterone , dehydroepi and rosterone-sulphate ( DHEA-S ) , progesterone , and cortisol were measured at baseline and after 6 and 12 months of treatment . For each hormone , changes from baseline at 6 and 12 months were compared between treatment groups , and differences over time for each group were analyzed . Results Hormonal data were available for 139 postmenopausal patients with a median age of 62 years , with 43 patients assigned to tamoxifen and 96 patients assigned to letrozole alone or combined with zoledronic acid . Baseline values were similar between the two groups for all hormones . Many significant changes were observed between drugs and for each drug over time . Namely , three hormones seemed significantly affected by one drug only : estradiol that decreased and progesterone that increased with letrozole and cortisol that increased with tamoxifen . Both drugs affected FSH ( decreasing with tamoxifen and slightly increasing with letrozole ) , LH ( decreasing more with tamoxifen than with letrozole ) , testosterone ( slightly increasing with letrozole but not enough to differ from tamoxifen ) , and DHEA-S ( increasing with both drugs but not differently between them ) . Zoledronic acid did not have significant impact on hormonal levels . CONCLUSION Adjuvant letrozole and tamoxifen result in significantly distinct endocrine effects . Such differences can explain the higher efficacy of letrozole as compared with tamoxifen",
"PURPOSE The effects of ovarian function suppression ( OFS ) on survival and patient-reported outcomes were evaluated in a phase III trial in which premenopausal women were r and omly assigned to tamoxifen with or without OFS . PATIENTS AND METHODS Premenopausal women with axillary node-negative , hormone receptor-positive breast cancer tumors measuring ≤ 3 cm were r and omly assigned to tamoxifen alone versus tamoxifen plus OFS ; adjuvant chemotherapy was not permitted . Primary end points were disease-free survival ( DFS ) and overall survival ( OS ) . Secondary end points included toxicity and patient-reported outcomes . Patient-reported outcome data included health-related quality of life , menopausal symptoms , and sexual function . These were evaluated at baseline , 6 months , 12 months , and then annually for up to 5 years after registration . RESULTS In all , 345 premenopausal women were enrolled : 171 on tamoxifen alone and 174 on tamoxifen plus OFS . With a median follow-up of 9.9 years , there was no significant difference between arms for DFS ( 5-year rate : 87.9 % v 89.7 % ; log-rank P = .62 ) or OS ( 5-year rate : 95.2 % v 97.6 % ; log-rank P = .67 ) . Grade 3 or higher toxicity was more common in the tamoxifen plus OFS arm ( 22.4 % v 12.3 % ; P = .004 ) . Patients treated with tamoxifen plus OFS had more menopausal symptoms , lower sexual activity , and inferior health-related quality of life at 3-year follow-up ( P OFS results in more menopausal symptoms and sexual dysfunction , which contributes to inferior self-reported health-related quality of life . Because of early closure , this study is underpowered for drawing conclusions about the impact on survival when adding OFS to tamoxifen"
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41187c28-06ff-11f0-808a-c43d1ab1c353
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OBJECTIVE To summarize the literature that has examined the association between a motor vehicle collision ( MVC ) related neck injury and future neck pain ( NP ) in comparison with the population that has not been exposed to neck injury from an MVC . LITERATURE SURVEY Neck injury result ing from an MVC is associated with a high rate of chronicity . Prognosis studies indicate 50 % of injured people continue to experience NP a year after the collision . This is difficult to interpret due to the high prevalence of NP in the general population . METHODOLOGY We performed a systematic review of the literature using five electronic data bases , search ing for risk studies on exposure to an MVC and future NP published from 1998 to 2018 . The outcome of interest was future NP . Eligible risk studies were critically appraised using the modified Quality in Prognosis Studies ( QUIPS ) instrument . The results were summarized using best- evidence synthesis principles , a r and om effects meta- analysis , metaregression , and testing for publication bias was performed with the pooled data . SYNTHESIS Eight articles were identified of which seven were of lower risk of bias . Six studies reported a positive association between a neck injury in an MVC and future NP compared to those without a neck injury in an MVC . Pooled analysis of the six studies indicated an unadjusted relative risk of future NP in the MVC exposed population with neck injury of 2.3 ( 95 % CI [ 1.8 , 3.1 ] ) , which equates to a 57 % attributable risk under the exposed . In two studies where exposed participants were either not injured or injury status was unknown , there was no increased risk of future NP . CONCLUSIONS There was a consistent positive association among studies that have examined the association between MVC-related neck injury and future NP . These findings are of potential interest to clinicians , insurers , patients , governmental agencies , and the courts . LEVEL OF EVIDENCE
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"Study Design . A prospect i ve 10-year follow-up study of patients with whiplash-associated disorders ( WAD ) and asymptomatic volunteers . Objective . To clarify long-term impact of whiplash injury on patient 's symptoms and on magnetic resonance imaging ( MRI ) findings of the cervical spine . Summary of Background Data . Long-term prognosis of WAD has not been fully eluci date d. Methods . Between 1993 and 1996 , we conducted cross-sectional comparative study of 508 acute WAD patients and 497 asymptomatic volunteers , all of whom underwent MRI of the cervical spine . For this follow-up study , 133 WAD patients and 223 control subjects were recruited again . All participants underwent follow-up MRI and physical examination , and answered to question naires regarding neck symptoms . Evaluation of MRI included decrease in signal intensity of discs , posterior disc protrusion , disc space narrowing , and foraminal stenosis using 2 to 4 numerical grade s. Increase in the numerical grade s by one or more was considered to be progression of degenerative changes . Results . Progression of decrease in signal intensity was observed in 109 WAD patients ( 82.0 % ) , and 132 control subjects ( 59.2 % ) , ( age , sex adjusted odds ratio [ OR ] : 3.06 ) , posterior disc protrusion in 101 ( 75.9 % ) and in 155 ( 69.5 % ) ( OR = 1.46 ) , disc space narrowing in 33 ( 24.8 % ) and in 59 ( 26.5 % ) ( OR = 0.98 ) , and foraminal stenosis in 6 ( 4.5 % ) , and in 20 ( 9.0 % ) ( OR = 0.52 ) , respectively . Neck pain was observed in 34 WAD patients ( 25.6 % ) and 22 control subjects ( 9.9 % ) ( P neck pain and progression in each MR finding in either group . Conclusion . The results of this study suggest that , although some WAD patients are more likely to suffer from long-lasting neck pain , MRI findings can not explain the symptoms",
"Study Design . Population ‐based , cross‐sectional mailed survey . Objective . To determine the lifetime , period , and point prevalence of neck pain and its related disability among Saskatchewan adults and investigate the presence and strength of nonresponse bias . Summary of Background Data . In Europe , the life‐time and point prevalence of neck pain is almost as high as the prevalence of low back pain . Similarly , chronic neck pain is highly prevalent and a common source of disability in the working‐age population . However , no studies specifically have documented the prevalence of neck pain and its related disability in North America . Methods . The Saskatchewan Health and Back Pain Survey was mailed to 2184 r and omly selected Saskatchewan adults aged 20‐69 years . Fifty‐five percent of the study population participated . The presence of nonresponse bias was investigated through logistic regression and wave analysis . The Chronic Pain Question naire was used to classify the severity of chronic neck pain . Results . The age‐st and ardized lifetime prevalence of neck pain is 66.7 % ( 95 % confidence interval , 63.8‐69.5 ) , and the point prevalence is 22.2 % ( 95 % confidence interval , 19.7‐24.7 ) . The age‐st and ardized 6‐month prevalence of low‐intensity and low‐disability neck pain is 39.7 % ( 95 % confidence interval , 36.7‐42.7 ) , whereas it is 10.1 % ( 95 % confidence interval , 8.2‐11.9 ) for high‐intensity and low‐disability neck pain and 4.6 % ( 95 % confidence interval , 3.3‐5.8 ) for significantly disabling neck pain . The prevalence of low‐intensity and low‐disability neck pain decreases with age . More women experience high‐disability neck pain than men . Wave analysis suggests that the point prevalence and 6‐month prevalence of high‐intensity and low‐disability neck pain are overestimated in this survey . Conclusion . This cross‐sectional study shows that neck pain is highly prevalent in Saskatchewan and that it significantly disables 4.6 % ( 95 % confidence interval , 3.3‐5.8 ) of the adult population",
"The authors undertook a case-control study of chronic neck pain and whiplash injuries in nine states in the United States to determine whether whiplash injuries contributed significantly to the population of individuals with chronic neck and other spine pain . Four hundred nineteen patients and 246 controls were r and omly enrolled . Patients were defined as individuals with chronic neck pain , and controls as those with chronic back pain . The two groups were surveyed for cause of chronic pain as well as demographic information . The two groups were compared using an exposure-odds ratio . Forty-five per cent of the patients attributed their pain to a motor vehicle accident . An OR of 4.0 and 2.1 was calculated for men and women , respectively . Based on the results of the present study , it reasonable to infer that a significant proportion of individuals with chronic neck pain in the general population were originally injured in a motor vehicle accident",
"& 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",
"Objective : To prospect ively examine the course of pain and other neurologic complaints in patients with acute whiplash injury and in controls with acute ankle injury . Methods : Patients with acute whiplash ( n = 141 ) and ankle-injured controls ( n = 40 ) were consecutively sample d , and underwent interview and examination after 1 week and 1 , 3 , 6 , and 12 months . Outcome measures were pain intensity , pain frequency , and associated symptoms . Results : Initial overall pain intensity above lower extremities ( pain in neck , head , shoulder-arm , and low back ) was similar in patients with whiplash ( median Visual Analogue Scale [VAS]0–100 of 20 [ 25th and 75th percentile , 4 , 39 ] ) and ankle-injured controls ( median VAS0–100 of 15 [ 5 , 34 ] ) . Whiplash-injured patients reported median overall VAS0–100 pain intensity above lower extremities of 23 ( 12 , 40 ) after 11 days and 14 ( 12 , 40 ) after 1 year . Controls reported pain intensity of 0 ( 0 , 4 ) after 12 days and 0 ( 0 , 9 ) after 1 year . Reported overall pain frequency above lower extremities was 96 % after 11 days and 74 % after 1 year in whiplash-injured patients and 33 % after 12 days and 47 % after 1 year in controls . Associated neurologic symptoms were two to three times more common after whiplash injury . Correlation was found between pain intensity and associated symptoms in whiplash-injured patients but not controls . Conclusion : Pain occurs with high frequency but low intensity after whiplash and ankle injury . Associated neurologic symptoms were not correlated to pain in ankle-injured controls , but were correlated to pain in patients with whiplash injury . Persistent symptoms in whiplash-injured patients may be caused by both specific neck injury – related factors and nonspecific post-traumatic reactions . Disability was only encountered in the whiplash group",
"The objective of this population -based cohort study was to investigate the association between a lifetime history of neck injury from a motor vehicle collision and the development of troublesome neck pain . The current evidence suggests that individuals with a history of neck injury in a traffic collision are more likely to experience future neck pain . However , these results may suffer from residual confounding . Therefore , there is a need to test this association in a large population -based cohort with adequate control of known confounders . We formed a cohort of 919 r and omly sample d Saskatchewan adults with no or mild neck pain in September 1995 . At baseline , participants were asked if they ever injured their neck in a motor vehicle collision . Six and twelve months later , we asked about the presence of troublesome neck pain ( grade II – IV ) on the chronic pain grade question naire . Multivariable Cox regression was used to estimate the association between a lifetime history of neck injury in a motor vehicle collision and the onset of troublesome neck pain while controlling for known confounders . The follow-up rate was 73.5 % ( 676/919 ) at 6 months and 63.1 % ( 580/919 ) at 1 year . We found a positive association between a history of neck injury in a motor vehicle collision and the onset of troublesome neck pain after controlling for bodily pain and body mass index ( adjusted HRR = 2.14 ; 95 % CI 1.12–4.10 ) . Our analysis suggests that a history of neck injury in a motor vehicle collision is a risk factor for developing future troublesome neck pain . The consequences of a neck injury in a motor vehicle collision can have long lasting effects and predispose individuals to experience recurrent episodes of neck pain",
"OBJECTIVES In Lithuania , there is little awareness of the notion that chronic symptoms may result from rear end collisions via the so-called whiplash injury . After most such collisions no contact with the health service is established . An opportunity therefore exists to study post-traumatic pain without the confounding factors present in western societies . METHODS In a prospect i ve , controlled inception cohort study , 210 victims of a rear end collision were consecutively identified from the daily records of the Kaunas traffic police . Neck pain and headache were evaluated by mailed question naires shortly after the accident , after 2 months , and after 1 year . As controls , 210 sex and age matched subjects were r and omly taken from the population register of the same geographical area and evaluated for the same symptoms immediately after their identification and after 1 year . RESULTS Initial pain was reported by 47 % of accident victims ; 10 % had neck pain alone , 18 % had neck pain together with headache , and 19 % had headache alone . The median duration of the initial neck pain was 3 days and maximal duration 17 days . The median duration of headache was 4.5 hours and the maximum duration was 20 days . After 1 year , there were no significant differences between the accident victims and the control group concerning frequency and intensity of these symptoms . CONCLUSIONS In a country were there is no preconceived notion of chronic pain arising from rear end collisions , and thus no fear of long term disability , and usually no involvement of the therapeutic community , insurance companies , or litigation , symptoms after an acute whiplash injury are self limiting , brief , and do not seem to evolve to the so-called late whiplash syndrome"
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41187c64-06ff-11f0-808a-c43d1ab1c353
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QUESTION What are physiotherapists ' perceptions about identifying and managing the cognitive , psychological and social factors that may act as barriers to recovery for people with low back pain ( LBP ) ? DESIGN Systematic review and qualitative meta synthesis of qualitative studies in which physiotherapists were question ed , using focus groups or semi-structured interviews , about identifying and managing cognitive , psychological and social factors in people with LBP . PARTICIPANTS Qualified physiotherapists with experience in treating patients with LBP . OUTCOME MEASURES Studies were synthesis ed in narrative format and thematic analysis was used to provide a collective insight into the physiotherapists ' perceptions . RESULTS Three main themes emerged : physiotherapists only partially recognised cognitive , psychological and social factors in LBP , with most discussion around factors such as family , work and unhelpful patient expectations ; some physiotherapists stigmatised patients with LBP as dem and ing , attention-seeking and poorly motivated when they presented with behaviours suggestive of these factors ; and physiotherapists question ed the relevance of screening for these factors because they were perceived to extend beyond their scope of practice , with many feeling under-skilled in addressing them . CONCLUSION Physiotherapists partially recognised cognitive , psychological and social factors in people with LBP . Physiotherapists expressed a preference for dealing with the more mechanical aspects of LBP , and some stigmatised the behaviours suggestive of cognitive , psychological and social contributions to LBP . Physiotherapists perceived that neither their initial training , nor currently available professional development training , instilled them with the requisite skills and confidence to successfully address and treat the multidimensional pain presentations seen in LBP . REGISTRATION CRD 42014009964 . [ Synnott A , O'Keeffe M , Bunzli S , Dankaerts W , O'Sullivan P , O'Sullivan K ( 2015 ) Physiotherapists may stigmatise or feel unprepared to treat people with low back pain and psychosocial factors that influence recovery : a systematic review .Journal of Physiotherapy61 : 68 - 76 ]
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"Background Psychosocial prognostic factors are important in the development of chronic pain , but treatment providers often lack knowledge and skills to assess and address these risk factors . Objective The aim of this study was to examine the effects on outcomes ( pain and disability ) in patients of a course about psychosocial prognostic factors for physical therapists . Design This study was a r and omized , controlled trial . Setting The setting was primary care practice . Participants Forty-two primary care physical therapists attended an 8-day university course ( over 8 weeks ) aim ed at identifying and addressing psychosocial risk factors . Intervention The physical therapists were r and omly assigned to either the course or a waiting list . They treated consecutive patients with acute and subacute musculoskeletal pain both before and after the course . Measurements We measured physical therapists ' attitudes and beliefs about psychosocial factors , knowledge , and skills before and after the course . We measured patients ' pain , disability , catastrophizing , and mood at the start of treatment and at a 6-month follow-up . Methods The physical therapists were r and omly assigned to either the course or a waiting list . They treated consecutive patients with acute and subacute musculoskeletal pain both before and after the course . Results Pain and disability outcomes in all patients of physical therapists who had participated in the course or in patients at risk of developing long-term disability who had higher levels of catastrophizing or depression were not significantly different from those outcomes in patients of physical therapists who had not participated in the course . Pain and disability outcomes in patients with a low risk of developing long-term disability— and pain outcomes in patients with a high risk of developing long-term disability — were not dependent upon whether the attitudes and beliefs of their physical therapists changed during the course . However , disability outcomes in patients with a high risk of developing long-term disability may have been influenced by whether the attitudes and beliefs of their physical therapists changed . Limitations A limitation of this study was that actual practice behavior was not measured . Conclusions An 8-day university course for physical therapists did not improve outcomes in a group of patients as a whole or in patients with a risk of developing long-term disability . However , patients who had a risk of developing long-term disability and had higher levels of catastrophizing or depression may have shown greater reductions in disability if the attitudes and beliefs of their physical therapists changed during the course",
"Background and Objective : Psychological factors are assumed to predict persistent or recurrent musculoskeletal pain . The influence of psychological factors in patients with low-back pain ( LBP ) or shoulder pain was explored to study whether there is similarity regarding the factors that predict persisting pain and disability . Methods : Patients presenting in primary care with a new episode of shoulder pain or non-specific (sub)acute low back pain ( LBP ) were enrolled in a prospect i ve study . In both patient groups , pain catastrophising , distress , somatisation and fear-avoidance beliefs were measured at baseline . Primary outcome measures at 3 months were ( 1 ) persistent symptoms , and ( 2 ) Multivariate logistic regression analysis was used to study the associations between psychological factors and outcome . Results : A total of 587 patients with shoulder pain and 171 patients with LBP were enrolled in the study . In patients with shoulder pain , most associations of psychological factors with outcome were weak and not significant . Only in patients with longer symptom duration at baseline ( ⩾3 months ) were higher scores on catastrophising significantly associated with persistent symptoms ( p = 0.04 ) . In patients with LBP , psychological factors were more strongly associated with poor outcome , although most associations were not significant . Conclusion : Psychological factors , with the exception of fear-avoidance beliefs , are more strongly associated with persistent pain and disability in patients with LBP than in those with shoulder pain . This seems to indicate that in a primary care population the influence of psychological factors on outcome may vary across patients with different types of pain ",
"& NA ; Guidelines for the management of low back pain ( LBP ) have existed for many years , but adherence to these by health care practitioners ( HCPs ) remains suboptimal . The aim of this study was to measure the attitudes , beliefs and reported clinical behaviour of UK physiotherapists ( PTs ) and general practitioners ( GPs ) about LBP and to explore the associations between these . A cross‐sectional postal survey of GPs ( n = 2000 ) and PTs ( n = 2000 ) was conducted that included the Pain Attitudes and Beliefs Scale ( PABT.PT ) , and a vignette of a patient with non‐specific LBP ( NSLBP ) with questions asking about recommendations for work , activity and bedrest . Data from 1022 respondents ( 442 GPs and 580 PTs ) who had recently treated patients with LBP were analysed . Although the majority of HCPs reported providing advice for the vignette patient that was broadly in line with guideline recommendations , 28 % reported they would advise this patient to remain off work . Work advice was significantly related to the PABS.PT scores with higher biomedical ( F1,986 = 77.5 , p patients with NSLBP are diverse . Many HCPs held the belief that LBP necessitates some avoidance of activities and work . The attitudes and beliefs of these HCPs were associated with their self‐reported clinical behaviour regarding advice about work . Future studies need to investigate whether approaches aim ed at modifying these HCP factors can lead to improved patient outcomes",
"Background The impact of the relationship ( therapeutic alliance ) between patients and physical therapists on treatment outcome in the rehabilitation of patients with chronic low back pain ( LBP ) has not been previously investigated . Objective The purpose of this study was to investigate whether the therapeutic alliance between physical therapists and patients with chronic LBP predicts clinical outcomes . Design This was a retrospective observational study nested within a r and omized controlled trial . Methods One hundred eighty-two patients with chronic LBP who volunteered for a r and omized controlled trial that compared the efficacy of exercises and spinal manipulative therapy rated their alliance with physical therapists by completing the Working Alliance Inventory at the second treatment session . The primary outcomes of function , global perceived effect of treatment , pain , and disability were assessed before and after 8 weeks of treatment . Linear regression models were used to investigate whether the alliance was a predictor of outcome or moderated the effect of treatment . Results The therapeutic alliance was consistently a predictor of outcome for all the measures of treatment outcome . The therapeutic alliance moderated the effect of treatment on global perceived effect for 2 of 3 treatment contrasts ( general exercise versus motor control exercise , spinal manipulative therapy versus motor control exercise ) . There was no treatment effect modification when outcome was measured with function , pain , and disability measures . Limitations Therapeutic alliance was measured at the second treatment session , which might have biased the interaction during initial stages of treatment . Data analysis was restricted to primary outcomes at 8 weeks . Conclusions Positive therapeutic alliance ratings between physical therapists and patients are associated with improvements of outcomes in LBP . Future research should investigate the factors explaining this relationship and the impact of training interventions aim ed at optimizing the alliance",
"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",
"Background Musculoskeletal complaints have a significant impact on work in terms of reduced productivity , sickness absence and long term incapacity for work . This study sought to explore GPs ’ and physiotherapists ’ perceptions of sickness certification in patients with musculoskeletal problems . Methods Eleven ( 11 ) GPs were sample d from an existing general practice survey , and six ( 6 ) physiotherapists were selected r and omly using ‘ snowball ’ sampling techniques , through established contacts in local physiotherapy departments . Semi-structured qualitative interviews were conducted with respondents lasting up to 30 minutes . The interviews were audio recorded and transcribed verbatim , following which they were coded using N-Vivo qualitative software and analysed thematically using the constant comparative methodology , where themes were identified and contrasted between and within both groups of respondents . Results Three themes were identified from the analysis : 1 ) Approaches to evaluating patients ’ work problems 2 ) Perceived ability to manage ‘ work and pain ’ , and 3 ) Policies and penalties in the work-place . First , physiotherapists routinely asked patients about their job and work difficulties using a structured ( protocol -driven ) approach , whilst GPs rarely used such structured measures and were less likely to enquire about patients ’ work situation . Second , return to work assessment s revealed a tension between GPs ’ gatekeeper and patient advocacy roles , often resolved in favour of patients ’ concerns and needs . Some physiotherapists perceived that GPs ’ decisions could be influenced by patients ’ dem and for a sick certificate and their close relationship with patients made them vulnerable to manipulation . Third , the workplace was considered to be a specific source of strain for patients acting as a barrier to work resumption , and over which GPs and physiotherapists could exercise only limited control . Conclusion We conclude that healthcare professionals need to take account of patients ’ work difficulties , their own perceived ability to offer effective guidance , and consider the ‘ receptivity ’ of employment context s to patients ’ work problems , in order to ensure a smooth transition back to work",
"OBJECTIVE To identify core elements of what patients with chronic low back pain perceive as good clinical communication and interaction with a specialist ( \" The Good Back-Consultation \" ) . DESIGN Qualitative study including observation of consultations and a subsequent patient interview . Quantitative data were also recorded . SUBJECTS Thirty-five patients with chronic low back pain referred to a specialist . METHODS Thirty-five consultations were observed with respect to history-taking , clinical examination and interaction between patient and doctor . Patients were subsequently interviewed about how they perceived the consultation . Fourteen specialists with various specialty branches and 35 patients ( 18 males ) participated . For 3 of the specialists a positive effect ( return to work ) on patients with chronic low back pain had been documented in previous r and omized controlled trials . Qualitative data analysis was performed using a template method . RESULTS Most patients thought that the history-taking and clinical examination had been thorough and satisfactory . Patients emphasized the importance of being given an explanation during the examination of what was being done and found , of receiving underst and able information on the causes of the pain , of receiving reassurance , discussing psychosocial issues and discussing what can be done . The most important characteristic of \" The Good Back-Consultation \" was that the specialist took the patient seriously . CONCLUSION The findings may represent an important potential for enhancing clinical communication with patients",
"Study Design . We conducted an observational study using mailed question naires to 3 r and om sample s of general practitioners from Victoria and New South Wales , Australia in 1997 , 2000 , and 2004 . Objective . To determine whether general practitioners ’ beliefs about low back pain ( LBP ) differ according to whether they have a special interest in back pain , musculoskeletal , or occupational medicine ; and whether these beliefs are modified by having had continuing medical education ( CME ) about back pain in the previous 2 years . Summary of Background Data . Physician surveys continue to demonstrate that general practitioners only partially manage LBP in an evidence -based way . Identified barriers to changing physician behavior , in regard to management of back pain , have included patient factors such as their past back pain experiences and preferences for care as well as physician beliefs about the association of pain and activity ; although the influence of physician special interests has not been studied . Methods . Back pain beliefs of different subsets ( special interests vs. no special interests and CME vs. no CME ) were compared using relative risks ( RRs ) adjusted for state and survey . The analysis was then repeated including all special interests and recent back pain CME in the model . Results . Responses were received from 3831 general practitioners ( overall response rate [ RR ] : 38.2 % ) . Physicians with a special interest in LBP were more likely to believe that complete bed rest and avoidance of work is appropriate for acute low back pain ( RR : 1.89 [ 95 % CI : 1.53–2.33 ] and 1.55 [ 95 % CI : 1.31–1.83 ] , respectively ) and lumbar spine radiographs are useful ( RR : 1.36 [ 95 % CI : 1.21–1.51 ] ) . The disparity between those with and without a special interest in LBP was still evident after adjusting for the presence of other special interests and recent CME . After adjusting for the presence of other special interests and recent CME , therewere no important differences in back pain beliefs between those with and without a special interest in musculoskeletal medicine , while those with a special interest in occupational medicine and those who had received recent CME had better beliefs . Conclusion . A special interest in back pain is associated with back pain management beliefs contrary to the best available evidence . This has serious implication s for management of back pain in the community",
"Study Design . A cross-sectional , descriptive vignette survey of practicing , musculoskeletal physical therapists . Objectives . The aim of this study was to determine if musculoskeletal physical therapists , in the United Kingdom , recognize when patients with low back pain ( LBP ) are at risk of chronicity due to psychosocial factors . A secondary aim was to explore the advice they give to patients about work and activities . Summary of Background Data . Psychosocial factors have been shown to be important in the progression from acute LBP to chronic disability . Early identification of individuals at risk of developing chronic disability is important to enable targeted intervention . Methods . Three vignettes were written based on acute LBP patients attending for physical therapy and incorporated into a self-completed postal question naire sent to a simple r and om sample of musculoskeletal physical therapists in the United Kingdom ( n = 900 ) . After one reminder , 20 % of nonresponders were sent a further question naire ( n = 80 ) . Data were analyzed using the Statistical Package for the Social Sciences ( SPSS version 11 ) . Results . The response rate was 57.7 % ( n = 518 ) with 453 meeting all inclusion criteria . The sample consisted of physical therapists working in the musculoskeletal field across all practice setting s. Most correctly rated the chronicity risk of the low- and high-risk patient vignettes . Advice to restrict work and activity was common . Conclusions . Most physical therapists recognize when patients are at high risk of developing chronicity , yet many recommend the patient limit their activity levels and not work . Advice to “ not work ” is associated with more severe perceived spinal pathology , suggesting persistence of the biomedical model for LBP",
"AIM The aim of this study is to examine the effects of an 8-day university-based training course , aim ed at identifying and addressing psychosocial prognostic factors during physiotherapy treatment , in shifting therapists towards a more biopsychosocial orientation as measured by changes in beliefs/attitudes , knowledge , skills and behaviour . METHOD We combined a r and omized controlled trail with a pre-post design . Forty-two physiotherapists applied for a university-accredited training course design ed to enhance knowledge and management of psychosocial factors in their practice with patients suffering from musculoskeletal pain . The course participants were r and omized either to receiving the course or to a waiting list for training . Attitudes and beliefs towards , and knowledge of psychosocial factors , patient vignettes and a video of an imaginary patient were tested before and after training . The patients of the course participants were asked to fill out a question naire with background questions at treatment start . The patients also received a question naire about the physical therapists ' behaviour and patient satisfaction 6 weeks after treatment start . RESULTS The results show that physical therapists ' attitudes and believes became more biopsychosocially and less biomedically orientated , they were less convinced that pain justifies disability and limitation of activities , and their knowledge and skills on psychosocial risk factors increased after a university-accredited training course . Yet despite these changes their patients perceived their practice behaviour before and after the course as similar and were equally satisfied with their treatment and treatment result . CONCLUSION A course , which enhanced biopsychosocial attitudes and beliefs , as well as increased such knowledge and skills did not change the way patients perceived their physical therapists . A future question is whether it improves patient outcome",
"RATIONALE The concept of evidence -based medicine is important in providing efficient health care . The process uses research findings as the basis for clinical decision making . Evidence -based practice helps optimize current health care and enables the practitioners to be suitably accountable for the interventions they provide . Little work has been undertaken to examine how allied health professionals change their clinical practice in light of the latest evidence . The use of opinion leaders to disseminate new evidence around the management of low back pain into practice has been proposed . AIMS The aim of this study was to investigate if physiotherapists ' clinical management of patients with low back pain would change following an evidence -based education package , which utilized local opinion leaders and delivered the best evidence . METHOD Thirty musculoskeletal physiotherapists from a Community Trust in North Staffordshire were cluster r and omized by location of work , to two groups . The intervention group received an evidence -based programme on the management of low back pain , including advice regarding increasing activity levels and return to normal activity and challenging patients ' fears and beliefs about their pain . The control group received a st and ard in-service training package on the management of common knee pathologies . The physiotherapists ' clinical management of patients with low back pain was measured prior to training and 6 months post training . Outcome measures were based on physiotherapists completing ' discharge summary ' question naires , which included information relating to the use and importance of therapies for treating their low back pain patients . RESULTS There were few significant differences in treatment options between the intervention and control groups post training . Whilst there was some indication that physiotherapists were already utilizing aspects of psychosocial management for patients with low back pain , there was little change in what physiotherapists perceived to be important to patient recovery and actual clinical practice following the intervention . CONCLUSIONS Psychosocial factors have been identified as an important factor in the recovery of patients with low back pain . This project incorporated the latest evidence on the management of low back pain and utilized the theory of opinion leaders to disseminate this evidence into clinical practice . Whilst there were some limitations in the overall size of the study , the results help to give an insight into the challenges faced by the health care system and research ers alike to ensure quality evidence is actually utilized by practitioners for the benefits of patient care"
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41187ca0-06ff-11f0-808a-c43d1ab1c353
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OBJECTIVE To systematic ally determine the impact of growth hormone therapy on adult height of children with idiopathic short stature . DESIGN Systematic review . DATA SOURCES Cochrane Central Register of Controlled Trials , Medline , and the bibliographic references from retrieved articles of r and omised and non-r and omised controlled trials from 1985 to April 2010 . DATA EXTRACTION Height in adulthood ( st and ard deviation score ) and overall gain in height ( SD score ) from baseline measurement in childhood . STUDY SELECTION R and omised and non-r and omised controlled trials with height measurements for adults . Inclusion criteria were initial short stature ( defined as height > 2 SD score below the mean ) , peak growth hormone responses > 10 μg/L , prepubertal stage , no previous growth hormone therapy , and no comorbid conditions that would impair growth . Adult height was considered achieved when growth rate was Three r and omised controlled trials ( 115 children ) met the inclusion criteria . The adult height of the growth hormone treated children exceeded that of the controls by 0.65 SD score ( about 4 cm ) . The mean height gain in treated children was 1.2 SD score compared with 0.34 SD score in untreated children . A slight difference of about 1.2 cm in adult height was observed between the two growth hormone dose regimens . In the seven non-r and omised controlled trials the adult height of the growth hormone treated group exceeded that of the controls by 0.45 SD score ( about 3 cm ) . CONCLUSIONS Growth hormone therapy in children with idiopathic short stature seems to be effective in partially reducing the deficit in height as adults , although the magnitude of effectiveness is on average less than that achieved in other conditions for which growth hormone is licensed . The individual response to therapy is highly variable , and additional studies are needed to identify the responders
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[
"GH is often used to treat children with idiopathic short stature despite the lack of definitive , long-term studies of efficacy . We performed a r and omized , double-blind , placebo-controlled trial to determine the effect of GH on adult height in peripubertal children . Subjects ( n = 68 ; 53 males and 15 females ) , 9 - 16 yr old , with marked , idiopathic short stature [ height or predicted height received either GH ( 0.074 mg/kg ) or placebo sc three times per week until they were near adult height . At study termination , adult height measurements were available for 33 patients after mean treatment duration of 4.4 yr . Adult height was greater in the GH-treated group ( -1.81 + /- 0.11 SDS , least squares mean + /- sem ) than in the placebo-treated group ( -2.32 + /- 0.17 SDS ) by 0.51 SDS ( 3.7 cm ; P GH effect was demonstrated in terms of adult height SDS minus baseline height SDS and adult height SDS minus baseline predicted height SDS . Modified intent-to-treat analysis in 62 patients treated for at least 6 months indicated a similar GH effect on last observed height SDS ( 0.52 SDS ; 3.8 cm ; P GH treatment increases adult height in peripubertal children with marked idiopathic short stature",
"BACKGROUND Short-term studies have demonstrated acceleration of growth rate following administration of biosynthetic human growth hormone ( r-hGH ) to short normal children . We describe the effect of such treatment on final height . METHODS This was an open study of consecutive referrals to a growth disorder clinic from which 16 short children ( height st and ard deviation score [ SDS ] -2.17 [ range -1.8 to -3.3 ] ; height velocity SDS -0.44 [ 0.33 ] ; peak serum GH response to stimulation 27.9 mU/L [ 9.2 ] were treated with r-hGH , and 7 short children who declined treatment ( height SDS -2.34 [ 0.61 ] ; height velocity SDS -0.36 [ 0.28 ] ; peak serum GH response 28.2 mU/L [ 6.8 ] ) acted as an observation group . Subcutaneous r-hGH dose ranged between 12.2 and 21.0 U/m2 per week ( 0.02 - 0.04 mg/kg per day ) for the first 2 years of treatment and 20 U/m2 per week thereafter , 3 untreated children were lost to long-term follow-up . FINDINGS r-hGH significantly increased the difference in final height compared with pretreatment predicted height ( + 0.42 SDS [ 0.79 ] , p = 0.03 ) but this change was not significantly greater than that of the observation group ( + 0.16 SDS [ 0.20 ] ) . Treatment had no effect on the timing of puberty . Boys progressed slightly faster through puberty , associated with an acceleration in bone-age maturation . No untoward effects on glucose metabolism were observed . Long-term therapy did not alter body-fat distribution or blood pressure . INTERPRETATION Long-term therapy in this group of children appears safe but the small increment in final height , approximately 2.8 cm in boys and 2.5 cm in girls , does not justify the widespread use of r-hGH for short normal children",
"OBJECTIVES To investigate in an open-label r and omized study , the effect of two doses of growth hormone ( GH ) on final height and height velocity during the first 2 years of treatment of children with idiopathic short stature ( mean baseline height st and ard deviation score [ SDS ] -3.2 ) . STUDY DESIGN Patients were treated with GH at 0.24 mg/kg/week , 0.24 mg/kg/week for the first year and at 0.37 mg/kg/week thereafter ( 0.24 - ->0.37 ) , or 0.37 mg/kg/week . Final height was evaluated in 50 patients at study completion ( mean treatment duration , 6.5 years ) . RESULTS Patients who received 0.37 mg/kg/week ( n = 72 ) experienced a significantly greater increase in height velocity than those who received 0.24 mg/kg/week ( n = 70 ) ( treatment difference = 0.8 cm/year ; P = .003 ) or 0.24 - ->0.37 mg/kg/week ( n = 67 ) ( treatment difference = 0.9 cm/year ; P = .001 ) . For the 50 patients for whom final height measurements were available , mean height SDS increased by 1.55 , 1.52 , and 1.85 SDS , respectively , for the three dose groups . For the primary comparison between the 0.37 mg/kg/week and 0.24 mg/kg/week dose groups , the mean treatment difference ( adjusted for differences in baseline predicted height SDS ) was 0.57 SDS ( 3.6 cm ; P = .025 ) . Mean overall height gains ( final height minus baseline predicted height ) were 7.2 cm and 5.4 cm for the 0.37 mg/kg/week and 0.24 mg/kg/week dose groups , respectively , without dose effects on safety parameters . Final height measurements were within the normal adult height range for 94 % of patients r and omized to 0.37 mg/kg/week who continued to final height . CONCLUSION GH treatment dose-dependently increases height velocity and final height in children with idiopathic short stature",
"CONTEXT The effect of GH therapy in short non-GH-deficient children , especially those with idiopathic short stature ( ISS ) , has not been clearly established owing to the lack of controlled trials continuing until final height ( FH ) . OBJECTIVE The aim of the study was to investigate the effect on growth to FH of two GH doses given to short children , mainly with ISS , compared with untreated controls . DESIGN AND SETTING A r and omized , controlled , long-term multicenter trial was conducted in Sweden . INTERVENTION Two doses of GH ( Genotropin ) were administered , 33 or 67 microg/kg.d ; control subjects were untreated . SUBJECTS A total of 177 subjects with short stature were enrolled . Of these , 151 were included in the intent to treat ( AllITT ) population , and 108 in the per protocol ( AllPP ) population . Analysis of ISS subjects included 126 children in the ITT ( ISSITT ) population and 68 subjects in the PP ( ISSPP ) population . MAIN OUTCOME MEASURES We measured FH sd score ( SDS ) , difference in SDS to midparenteral height ( diff MPHSDS ) , and gain in heightSDS . RESULTS After 5.9+/-1.1 yr on GH therapy , the FHSDS in the AllPP population treated with GH vs. controls was -1.5+/-0.81 ( 33 microg/kg.d , -1.7+/-0.70 ; and 67 microg/kg.d , -1.4+/-0.86 ; P MPHSDS was -0.2+/-1.0 vs. -1.0+/-0.74 ( P gain in heightSDS was 1.3+/-0.78 vs. 0.2+/-0.69 ( P GH therapy was safe and had no impact on time to onset of puberty . A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four population s. CONCLUSION GH treatment significantly increased FH in ISS children in a dose-dependent manner , with a mean gain of 1.3 SDS ( 8 cm ) and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls",
"We measured adult heights ( Ht ) of 94 healthy GH-sufficient children ( peak GH > 10 ng/mL , polyclonal RIA ) whose Ht at presentation were more than 2 SD below the mean for chronological age , with normal weight-to-Ht ratios , normal body proportions , and pathologic growth velocity for chronological age . Group 1 ( n 36 , 6 females ) received st and ardized doses ( 0.3 mg/kg x week ) of GH ( mean duration = 41 months ) , while group 2 ( n = 58 , 17 females ) received no treatment . Our conclusion was that the mean final Ht SD score in the GH-treated group ( -1.5 ) was significantly greater than in the untreated group ( -2.1 ) ; P short stature was evident in both groups : the midparental Ht SD score was -1.1 in the treated and -1.0 in the untreated group . Midparental Ht was met or exceeded by 42 % of the GH-treated group but only 15 % of the untreated group . Final Ht was not significantly different from predicted Ht , except from GH-treated girls , who exceeded their predicted Ht . Although the mean Ht gains ( 6.8 cm in girls and 3 cm in boys ) were modest and variable , GH treatment provided significantly better Ht outcomes for the majority of children with idiopathic growth failure",
"We report the effect of growth hormone ( GH ) treatment for 4 to 10 years in 15 prepubertal non-GH-deficient short children ( 10 boys , 5 girls , aged 7.4 to 13.2 years ) . In 7 patients , GH was administered at a dosage of 0.5 U/kg per week ( group 1 : 4 boys , 3 girls ) and in 8 patients ( group 2 : 6 boys , 2 girls ) at a dosage of 1.0 U/kg per week . After the first year , mean linear growth velocity had significantly increased in both groups . The increase in growth velocity was sustained during the first 4 years and then declined to pretreatment values in the majority of subjects . Treatment with GH did not induce an earlier onset of puberty , but there was a tendency toward faster skeletal maturation . The mean final height st and ard deviation score ( SDS ) was similar in the two groups and was significantly higher than the height SDS for chronologic age before treatment , but it did not differ from mean pretreatment predicted adult height SDS nor from mean target height SDS in both groups . Final height was significantly correlated with target height in both groups . These preliminary observations indicate that GH treatment does not generally increase final height over target height in short non-GH-deficient children",
"Idiopathic short stature ( ISS ) includes a heterogeneous group of patients with common characteristics to those of familial short stature and constitutional delay . Some authors state that these children can often respond to GH treatment , thus increasing their adult height . The aims of this study were to determine the effect of GH treatment ( 0.5 - 0.7 IU/kg/week ) and the influence of some initial variables on adult height in patients with ISS . It was a non-r and omized , observational study of 30 boys with ISS and a historical control group of 42 patients . The patients were followed until achieving their adult height . The mean height gain of the treated group attributable to GH was 4.5 cm . A stepwise regression model considering predicted adult height and target height as independent variables and final height as dependent variable gave an R2 coefficient of 0.38 . We conclude that GH significantly increases final height in boys with ISS",
"Recombinant human GH therapy to children with idiopathic short stature ( ISS ) increases growth velocity , but its effect on final height ( FH ) is still uncertain . The aim of this study was to investigate the effect of recombinant human GH on FH of patients with ISS who were treated according to two protocol s in comparison to untreated historical controls . In study 1 ( n = 24 ) , all patients were treated with 14 IU ( 4.6 mg)/m(2 ) body surface x wk in the first year ; thereafter the dosage was doubled if the growth response was insufficient . In study 2 ( n = 34 ) , patients were r and omized into three arms : 18 IU ( 6 mg)/m(2 ) x wk ; 27 IU ( 9 mg)/m(2 ) x wk ; and 18 IU/m(2 ) x wk in the first year , followed by 27 IU/m(2 ) x wk thereafter . Observed or estimated FH was available for 53 patients . Thirty-four untreated controls from the same centers were available for comparison . Mean FH SD score in GH-treated children was -2.1 , vs. -2.4 in controls ( -2.4 ) ( NS ) , but height SD score gain ( 1.3 vs. 0.7 ) and the difference between FH and predicted adult height ( 4.0 vs. 0.8 cm ) were significantly greater . The growth response on an initial dosage of 27 IU/m(2 ) x wk ( 6.9 cm ) was significantly better than on other regimens ( 2.8 cm ) . We conclude that a GH dosage of 27 IU ( 9 mg)/m(2 ) x wk to prepubertal children with ISS leads to a mean FH gain of approximately 7 cm , whereas regimens starting on lower dosages are less efficacious",
"BACKGROUND There are few data on the long-term outcome of growth-hormone treatment in short normal children . We assessed the impact of growth-hormone treatment on pubertal development and near-final height in girls . METHODS In a r and omised controlled trial , we studied ten girls , with a mean age of 8.07 years and height 2 SDs or more below the mean for their age , and eight short untreated controls matched for age , and 20 short untreated girls who did not give consent for r and omisation . The girls received either 30 IU/m2 somatropin per week as daily subcutaneous injections or no treatment . We assessed pubertal staging and height gain every 6 months . FINDINGS Eight treated girls completed a mean of 6.2 years ' therapy . By a mean age of 16.4 years , their mean height SD score had changed significantly from -2.42 to -1.14 ( p=0.008 ) and they were , on average , 7.5 cm taller than the girls in the control group ( height SD scores did not change significantly from -2.55 ) and 6.0 cm taller than the non-consent group . The timing of each pubertal stage , and the age and amplitude of peak height velocity were similar for all groups . INTERPRETATION Growth-hormone therapy effectively increased height SD score among short normal girls started on treatment in early to mid childhood , with no untoward effect on pubertal progression"
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41187cdc-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND Arthritis of the knee is a common problem causing pain and disability . If severe , knee arthritis can be surgically managed with a total knee arthroplasty . Rehabilitation following knee arthroplasty often includes continuous passive motion ( CPM ) . CPM is applied by a machine that passively and repeatedly moves the knee through a specified range of motion ( ROM ) . It is believed that CPM increases recovery of knee ROM and has other therapeutic benefits . However , it is not clear whether CPM is effective . OBJECTIVES To assess the benefits and harms of CPM and st and ard postoperative care versus similar postoperative care , with or without additional knee exercises , in people with knee arthroplasty . This review is an up date of a 2003 and 2010 version of the same review . SEARCH METHODS We search ed the following data bases : the Cochrane Central Register of Controlled Trials ( CENTRAL ) ( The Cochrane Library 2012 , Issue 12 ) , MEDLINE ( January 1966 to 24 January 2013 ) , EMBASE ( January 1980 to 24 January 2013 ) , CINAHL ( January 1982 to 24 January 2013 ) , AMED ( January 1985 to 24 January 2013 ) and PEDro ( to 24 January 2013 ) . SELECTION CRITERIA R and omised controlled trials in which the experimental group received CPM , and both the experimental and control groups received similar postoperative care and therapy following total knee arthroplasty in people with arthritis . DATA COLLECTION AND ANALYSIS Two review authors independently selected trials for inclusion , extracted data and assessed risk of bias . The primary outcomes of interest were active knee flexion ROM , pain , quality of life , function , participants ' global assessment of treatment effectiveness , incidence of manipulation under anaesthesia and adverse events . The secondary outcomes were passive knee flexion ROM , active knee extension ROM , passive knee extension ROM , length of hospital stay , swelling and quadriceps strength . We estimated effects for continuous data as mean differences or st and ardised mean differences ( SMD ) , and effects for dichotomous data as risk ratios ; all with 95 % confidence intervals ( CI ) . If appropriate , we performed meta-analyses using r and om-effects models . MAIN RESULTS We identified 684 papers from the electronic search es after removal of duplicates and retrieved the full reports of 62 potentially eligible trials . Twenty-four r and omised controlled trials of 1445 participants met the inclusion criteria ; four of these trials were new to this up date .There was moderate- quality evidence to indicate that CPM does not have clinical ly important short-term effects on active knee flexion ROM : mean knee flexion was 78 degrees in the control group , CPM increased active knee flexion ROM by 2 degrees ( 95 % CI 0 to 5 ) or absolute improvement of 2 % ( 95 % CI 0 % to 4 % ) . The medium- and long-term effects are similar although the quality of evidence is lower . There was low- quality evidence to indicate that CPM does not have clinical ly important short-term effects on pain : mean pain was 3 points in the control group , CPM reduced pain by 0.4 points on a 10-point scale ( 95 % CI -0.8 to 0.1 ) or absolute reduction of -4 % ( 95 % CI -8 % to 1%).There was moderate- quality evidence to indicate that CPM does not have clinical ly important medium-term effects on function : mean function in the control group was 56 points , CPM decreased function by 1.6 points ( 95 % CI -6.1 to 2.0 ) on a 100-point scale or absolute reduction of -2 % ( 95 % CI -5 % to 2 % ) . The SMD was -0.1 st and ard deviations ( SD ) ( 95 % CI -0.3 to 0.1).There was moderate- quality evidence to indicate that CPM does not have clinical ly important medium-term effects on quality of life : mean quality of life was 40 points in the control group , CPM improved quality of life by 1 point on a 100-point scale ( 95 % CI -3 to 4 ) or absolute improvement of 1 % ( 95 % CI -3 % to 4%).There was very low- quality evidence to indicate that CPM reduces the risk of manipulation under anaesthesia ; risk of manipulation in the control group was 7.2 % , risk of manipulation in the experimental group was 1.6 % , CPM decreased the risk of manipulation by 25 fewer manipulations per 1000 ( 95 % CI 9 to 64 ) or absolute risk reduction of -4 % ( 95 % CI -8 % to 0 % ) . The risk ratio was 0.3 ( 95 % CI 0.1 to 0.9).There was low- quality evidence to indicate that CPM reduces the risk of adverse events ; risk of adverse events in the control group was 16.3 % , risk of adverse events in the experimental group was 17.9 % , CPM decreased the risk of adverse event by 150 fewer adverse events per 1000 ( 95 % CI 103 to 216 ) or absolute risk reduction of -1 % ( 95 % CI -5 % to 3 % ) . The risk ratio was 0.9 ( 95 % CI 0.6 to 1.3 ) . The estimates for risk of manipulation and adverse events are very imprecise and the estimate for the risk of adverse events does not distinguish between a clinical ly important increase and decrease in risk . There was insufficient evidence to determine the effect of CPM on participants ' global assessment of treatment effectiveness . AUTHORS ' CONCLUSIONS CPM does not have clinical ly important effects on active knee flexion ROM , pain , function or quality of life to justify its routine use . It may reduce the risk of manipulation under anaesthesia and risk of developing adverse events although the quality of evidence supporting these findings are very low and low , respectively . The effects of CPM on other outcomes are unclear
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"& NA ; This prospect i ve study was performed to investigate whether postoperative alternate flexion and extension splinting ( daily change in position of immobilization by splinting ) was useful in restoring full range of motion ( ROM ) after total knee arthroplasty as compared with continuous passive motion . The alternate flexion and extension splinting group and the continuous passive motion group were each composed of 34 knees . Final ROM was measured at an average of 3.5 years postoperatively . Squatting was possible in 31 knees ( 45.6 % ) of the alternate flexion and extension splinting group . The postoperative ROM of the osteoarthritic knees ( 131.8 ° ± 12.3 ° ) was significantly greater than that of the rheumatoid knees ( 121.9 ° ± 22.4 ° ) ( p The postoperative ROM of the alternate flexion and extension splinting group ( 135.1 ° ± 11.9 ° ) also was significantly greater than that of the continuous passive motion group ( 120.0 ° ± 19.7 ° ) ( p between the posterior slope of tibial cutting and the postoperative ROM . It is suggested that alternate flexion and extension splinting is effective in restoring full ROM after total knee arthroplasty",
"Purpose . Continuous passive motion is frequently used post-operatively to increase knee range of motion after total knee arthroplasty in spite of little conclusive evidence . The aim of this study was to examine whether continuous passive motion ( CPM ) as an adjunct to active exercises had any short time effects ( after one week and three months ) on pain , range of motion , timed walking and stair climbing . Method . A r and omized controlled trial was conducted . A total of 63 patients undergoing primary TKA were r and omly assigned into an experimental group receiving CPM and active exercises and a control group receiving active exercises only . Outcomes were assessed by goniometer , visual analogue scale ( VAS ) , timed ‘ Up and Go ’ test ( TUG ) , timed 40 m walking distance and timed stair climbing . Results . There were no statistical differences between the treatment groups for any outcome measures either at one week or after three months . For the whole group , a significant and 50 % reduction in pain score was found after three months ( p knee flexion range of motion ( p number of patients able to climb stairs were found after three months ( p CPM was not found to have an additional short-time effect compared with active physiotherapy . After three months considerable pain relief was obtained for the whole group , the patients preoperative ROM was not restored and the number of patients able to climb stairs had decreased",
" Sixty primary total knee arthroplasties in 43 Chinese patients were included into a prospect i ve study . Twenty-six patients who had unilateral knee arthroplasty were r and omized to receive continuous passive motion ( CPM ) or immobilization in the first week . The 2 groups of patients were comparable in demographic data and preoperative knee range of motion ( ROM ) . In 17 patients who had 1-stage sequential bilateral arthroplasties , one side had CPM and the other side was immobilized . The active knee ROM was assessed regularly until 1 year after the operation . For all patients , the early active knee ROM in the CPM group was significantly better than the immobilization group . There was no difference after 7 days , however . For patients who had 1-stage bilateral total knee arthroplasties , the active knee ROM was significantly better on the CPM side until day 28 . After 4 weeks , there was no difference between the CPM group and the immobilization group . Immobilization after total knee arthroplasty does not preclude good ROM",
"68 consecutive patients who had primary knee arthroplasties because of arthrosis were r and omized to postoperative continuous passive motion ( CPM ) or active physical therapy ( APT ) . Rehabilitation in both groups was initiated on the first postoperative day . The CPM group sustained less postoperative knee swelling with more rapid initial improvement in knee flexion than did the APT group , but there were no differences between the groups in knee flexion at discharge . Postoperative pain rating and hospitalization times were similar in the two groups",
"A prospect i ve r and omized single blind investigation after total knee arthroplasty was performed to evaluate two rehabilitation protocol s ( one with CPM and the other without CPM ) . A series of 87 consecutive total knee arthroplasties in 76 patients ( 72 women and 4 men ) was analyzed . The average age of the patients was 64.7 years . Kinesitherapy with CPM was performed in 30 ( 34.5 % ) cases , where as in 57 ( 65.5 % ) cases kinesitherapy without CPM was performed . Early functional results according to the HSS scale were assessed on the 14th day after surgery . In the group treated with CPM there were 26.7 % excellent results , 70.0 % good results and 3.3 satisfactory results . The group treated without CPM there were 26.3 % excellent results , 70.2 % good results and 3.5 % satisfactory results . No statistically significant differences were noted between the results yielded by these two rehabilitation protocol",
"A prospect i ve , controlled , r and omized trial of continuous passive motion and immobilization after knee arthroplasty revealed that continuous passive motion significantly improved early and late flexion of the knee , reduced the duration of stay in the hospital , and did not increase the incidence of superficial infection or problems with wound-healing . Flexion of the knee beyond 40 degrees progressively diminished viability of the edges of the wound , particularly the lateral edge . On the basis of these results , a protocol for continuous passive motion was design ed to minimize the detrimental effects on viability of the wound",
"A r and omised , controlled study of the use of postoperative continuous passive motion ( CPM ) and immobilisation regimen after total condylar knee arthroplasty was performed . CPM result ed in a significant increase in both the early and late range of knee flexion . This increase occurred in both rheumatoid and osteoarthritic patients . The improvement of 10 degrees at 12 months allowed additional important function to be attained . CPM result ed in significantly earlier discharge from hospital . It did not increase the clinical incidence of wound healing problems , nor did it significantly increase the postoperative fixed flexion deformity or the extension lag . CPM can be recommended as a safe and effective modality to achieve more rapid and more successful postoperative rehabilitation after knee arthroplasty",
"This study was conducted to compare postoperative total knee arthroplasty rehabilitation protocol s. The hypothesis of this study was that patients undergoing total knee arthroplasty could achieve range of motion and hospital discharge in the same period using a postoperative rehabilitation protocol that did not use a continuous passive motion machine . This r and omized prospect i ve study compared 46 total knee arthroplasties in which a continuous passive motion machine was used with 37 total knees that were rehabilitated with early passive flexion of the knee ( named drop and dangle protocol ) . Postoperative physical therapy regimens were otherwise the same for both groups . Surgical technique was the same for both groups except for closure which was performed in the drop and dangle group with the knee at 90 ° to 95 ° flexion . Only patients with osteoarthritis were included in the study , and in both groups of patients received the same prosthetic components . Patients in the drop and dangle group were discharged from the hospital 1 day earlier ( p = 0.01 ) and had a statistically better extension range of 2.8 ° at 6 months ( p = 0.03 ) . Knees in the drop and dangle group had less drainage ( p = 0.06 ) . Range of motion and hospital discharge can be achieved in a similar time interval with the drop and dangle technique as with using a continuous passive motion device , and that such a device is not required for postoperative knee rehabilitation",
"Background Adequate and intensive rehabilitation is an important requirement for successful total knee arthroplasty . Although research suggests that Continuous Passive Motion ( CPM ) should be implemented in the first rehabilitation phase after surgery , there is substantial debate about the duration of each session and the total period of CPM application . A Cochrane review on this topic concluded that short-term use of CPM leads to greater short-term range of motion . It also suggested , however , that future research should concentrate on the treatment period during which CPM should be administered . Methods In a r and omised controlled trial we investigated the effectiveness of prolonged CPM use in the home situation as an adjunct to st and ardised PT . Efficacy was assessed in terms of faster improvements in range of motion ( RoM ) and functional recovery , measured at the end of the active treatment period , 17 days after surgery . Sixty patients with knee osteoarthritis undergoing TKA and experiencing early postoperative flexion impairment were r and omised over two treatment groups . The experimental group received CPM + PT for 17 consecutive days after surgery , whereas the usual care group received the same treatment during the in-hospital phase ( i.e. about four days ) , followed by PT alone ( usual care ) in the first two weeks after hospital discharge . From 18 days to three months after surgery , both groups received st and ardised PT . The primary focus of rehabilitation was functional recovery ( e.g. ambulation ) and regaining RoM in the knee . Results Prolonged use of CPM slightly improved short-term RoM in patients with limited RoM at the time of discharge after total knee arthroplasty when added to a semi-st and ard PT programme . Assessment at 6 weeks and three months after surgery found no long-term effects of this intervention Neither did we detect functional benefits of the improved RoM at any of the outcome assessment s. Conclusion Although results indicate that prolonged CPM use might have a small short-term effect on RoM , routine use of prolonged CPM in patients with limited RoM at hospital discharge should be reconsidered , since neither long-term effects nor transfer to better functional performance was detected . Trial Registration IS RCT",
"Effect of continuous passive motion ( CPM ) protocol s on outcomes after total knee arthroplasty . In this prospect i ve r and omized controlled study , 147 patients were assigned to 1 of 3 treatment groups : CPM from 0 degrees to 40 degrees and increased by 10 degrees per day , CPM from 90 degrees to 50 degrees ( early flexion ) and gradually progressed into full extension over a 3-day period , and a no-CPM group . The CPM was administered twice a day for 3 hours over a 5-day period . All patients participated in the same postoperative physiotherapy program . Patients were assessed preoperatively , day 5 , 3 months , and 1 year postoperatively . The early flexion group had significantly more range of flexion than both the st and ard and control groups at day 5 . There was no significant difference between the groups for any other variable tested at any time frame . Key words : total knee arthroplasty , CPM , rehabilitation , outcomes",
"Continuous passive motion ( CPM ) , though of doubtful value , is yet routinely practice d post-total knee arthroplasty ( TKA ) . We prospect ively distributed 84 patients with TKA to 1 of the 3 st and ard rehabilitation regimes : no-CPM , 1-day-CPM , and 3-day-CPM . We recorded a unique \" Timed up and go \" test besides pain , Western Ontario and McMaster Universities ( WOMAC ) , short form-12 ( SF-12 ) , range of motion , knee and calf swelling , and wound healing parameters . Our st and ardized and elaborate measurements preoperatively and on postoperative days 3 , 5 , 14 , 42 , and 90 showed no statistically significant difference among the 3 groups in each parameter . We concluded that CPM gives no benefit in immediate functional recovery post-TKA , and in fact , the postoperative knee swelling persisted longer . We have since then discontinued its use in our patients without any untoward effect",
"OBJECTIVES We prospect ively evaluated the effects of continuous passive motion ( CPM ) started after two different time intervals following total knee arthroplasty ( TKA ) on short- and long-term results , in comparison with st and ard physical therapy . METHODS Eighty-six patients were r and omized to three groups following TKA for primary osteoarthritis . The control group ( n=28 ) received only conventional physical therapy . Group I and II , each consisting of 29 patients , were treated with conventional physical therapy combined with CPM that was started on the first and third postoperative days , respectively , and continued until discharge with three one-hour sessions daily . Preoperative and postoperative measurements of the knee range of motion were recorded . Clinical and functional results were assessed using the Knee Society rating system . The patients were followed-up for at least two years ( range 26 to 52 months ) . RESULTS The duration of CPM was 22 hours in group I , and 19 hours in group II ( p>0.05 ) . Knee flexion values measured in the CPM groups on day 3 and at discharge showed significant differences with those of the control group , but no significant differences were found between the groups after the first postoperative month in this respect ( p>0.05 ) . The mean duration to reach 100 degrees of passive knee flexion ( p=0.03 ) and the mean length of hospital stay ( p=0.04 ) in the CPM groups were shorter by three and two days compared to the control group , respectively . Clinical and functional knee scores showed significant improvements in all the groups postoperatively ( p0.05 ) . CONCLUSION Even though CPM protocol s applied following TKA may shorten the length of hospital stay , CPM applications do not offer additional short- and long-term benefits over st and ard physical therapy with respect to knee flexion and clinical and functional results",
"The authors report the results of a prospect i ve study examining the benefits of daily continuous passive motion combined with physical therapy , compared with physical therapy alone , in 103 consecutive osteoarthritic patients undergoing primary total knee arthroplasty . The first 51 patients received continuous passive motion initiated in the recovery room and the next 52 patients did not receive continuous passive motion . Both groups underwent an identical physical therapy protocol starting on the first postoperative day . At discharge , there was a significant increase in active flexion in the continuous passive motion group . There were no significant differences regarding pain , wound healing , knee swelling , wound drainage , pulmonary embolism , or length of hospital stay between the 2 groups . At 2 years , there were no clinical differences in the motion or knee scores . Knee manipulation was done for manipulations in the noncontinuous passive motion group and none in the continuous passive motion group . The entire costs associated with the 5 manipulations was $ 48,274 or $ 937 per patient not receiving continuous passive motion . The average daily inpatient rental of the machine was $ 60 per day . Continuous passive motion is efficacious in increasing short-term flexion and decreasing the need for knee manipulation without increasing costs",
"OBJECTIVE To evaluate the efficacy of continuous passive motion ( CPM ) in the postoperative management of patients undergoing total knee arthroplasty . DESIGN A r and omized controlled single-blind trial of CPM plus st and ardized rehabilitation vs st and ard rehabilitation alone . SETTING A referral hospital for arthritis and musculoskeletal care . PATIENTS Consecutive patients with end-stage osteoarthritis or rheumatoid arthritis undergoing primary total knee arthroplasty who had at least 90 degrees of passive knee flexion . One hundred fifty-four patients were eligible and 102 patients agreed to participate and were r and omized . Ninety-three patients completed the study protocol . INTERVENTION Continuous passive motion machines programmed for rate and specified arc of motion within 24 hours of surgery with range increased daily as tolerated with st and ardized rehabilitation program compared with st and ardized rehabilitation program alone . MAIN OUTCOME MEASURES Primary outcomes were pain , active and passive knee range of motion , swelling ( or circumference ) , quadriceps strength at postoperative day 7 , as well as complications , length of stay , and active and passive range of motion and function at 6 weeks . RESULTS Use of CPM increased active flexion and decreased swelling and the need for manipulations but did not significantly affect pain , active and passive extension , quadriceps strength , or length of hospital stay . At 6 weeks there were no differences between the two groups in either range of motion or function . In this series , use of CPM result ed in a net savings of $ 6764 over conventional rehabilitation in achieving these results . CONCLUSION For the average patient undergoing total knee arthroplasty , CPM is more effective in improving range of motion , decreasing swelling , and reducing the need for manipulation than is conventional therapy and lowers cost",
"There is insufficient information on continuous passive motion ( CPM ) parameters in total knee arthroplasty patients for optimal patient outcomes . We compared CPM duration and increments on active and passive range of motion ( ROM ) in patients who underwent a unilateral total knee arthroplasty due to degenerative joint disease . Forty-five total knee arthroplasty patients were r and omly assigned to either a control group , a short CPM duration ( 3 - 5 hours per day ) group with CPM ROM increased 5 degrees twice daily , a short CPM duration group with CPM ROM increased daily to patient tolerance , a long CPM duration ( 10 - 12 hours per day ) group with CPM ROM increased 5 degrees twice daily , or a long CPM duration group with CPM ROM increased daily to patient tolerance . Active and passive flexion and extension were measured goniometrically on each postoperative day that the patient was treated by physical therapy . No statistically significant differences between groups were found for baseline and final postoperative ROM . The CPM groups did not maintain the parameters assigned and were combined , revealing an enhanced rate of change of flexion . Most patients opted for a CPM duration of between 4 and 8 hours per day and the patient-preferred CPM incremental increase in ROM was 6 - 7 degrees/day",
"BACKGROUND AND PURPOSE The primary purpose of this r and omized controlled trial was to determine which method of mobilization - ( 1 ) st and ardized exercises ( SE ) and continuous passive motion ( CPM ) , ( 2 ) SE and slider board ( SB ) therapy , using an inexpensive , nontechnical device that requires minimal knee active range of motion ( ROM ) , or ( 3 ) SE alone-achieved the maximum degree of knee ROM in the fIrst 6 months following primary total knee arthroplasty ( TKA ) . The secondary purpose was to compare health-related quality of life among these 3 groups . SUBJECTS The subjects were 120 patients ( n=40/group ) who received a TEA at a teaching hospital between June 1997 and July 1998 and who agreed to participate in the study . METHODS Subjects were examined preoperatively , at discharge , and at 3 and 6 months after surgery . The examination consisted of measurement of knee ROM and completion of the Western Ontario and McMaster Universities ( WOMAC ) Osteoarthritis Index and the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) . RESULTS The 3 treatment groups were similar with respect to age , sex , and diagnosis at the start of the study . There were no differences in knee ROM or in WOMAC Osteoarthritis Index or SF-36 scores at any of the measurement intervals . The rate of postoperative complications also was not different among the groups . DISCUSSION AND CONCLUSION When postoperative rehabilitation regimens that focus on early mobilization of the patient are used , adjunct ROM therapies ( CPM and SB ) that are added to daily SE sessions are not required . Six months after TEA , patients attain a satisfactory level of knee ROM and function",
"Regular passive ROM exercise ( PROME ) by a physical therapist is often incorporated in rehabilitation protocol s after total knee arthroplasty ( TKA ) . This r and omized , controlled trial examined whether or not the incorporation of PROME to a postoperative rehabilitation protocol would offer a better clinical outcome after TKA . Fifty consecutive patients who underwent bilateral TKAs staged 2 weeks apart received PROME for one knee and not for the other . The pain level ( 7D and 14D ) , patient ’s preference ( before discharge , 6 M ) , maximum flexion ( 7D , 14D , 3 M , 6 M ) and American Knee Society and WOMAC scores ( 6 M ) were determined in the knees with and without PROME and compared . There were no significant differences in the maximum flexion , pain level , patient ’s preference , AKS scores and WOMAC scores . This study demonstrates that the incorporation of PROME does not offer additional clinical benefits to the patients after TKA . Our findings may suggest that encouraging patients to perform active ROM exercise would be a better option and that a physiotherapy session by a physical therapist can focus on more functional rehabilitation , such as preparing to return to daily activities",
"Objective Continuous passive motion ( CPM ) has been shown to increase significantly the amount of knee flexion for patients with total knee arthroplasty in the acute care hospital . Whether there is any additional benefit to using CPM for these patients who are transferred to a rehabilitation hospital is not known . There have been no prospect i ve , r and omized , controlled studies in this area . Design Fifty-one such patients on an inpatient rehabilitation service were r and omly assigned to two groups . Group 1 ( n = 23 ) received CPM for 5 consecutive hours per day plus physical therapy , whereas group 2 ( n = 28 ) received only physical therapy . Knee flexion was measured by a blinded physical therapist on admission , on the third and seventh days of hospitalization , and at the time of discharge . Results The results indicated no significant difference in passive range of motion between group 1 and group 2 . Patients in group 1 achieved an average increase in passive range of motion of 16 degrees , whereas those in group 2 achieved an average of 19 degrees ( P = 0.33 ) . Conclusion Although power analysis indicated the need for differences in results for 32 patients per group to achieve significance , the difference between the two groups suggested neither statistical nor clinical significance . We concluded that the use of CPM in the rehabilitation hospital is likely of no added benefit to patients admitted after single total-knee replacement",
"A vigorous rehabilitation program following discharge from the hospital is necessary for patients having a total knee arthroplasty to maintain and improve range of motion and function . To compare the effectiveness of the continuous passive motion ( CPM ) machine as a home therapy program versus professional physical therapy , a prospect i ve , comparative , r and omized clinical study of 103 consecutive primary total knee arthroplasties in 80 patients ( 23 bilateral ) was performed . The CPM group consisted of 37 patients ( 49 knees ) , and the physical therapy group consisted of 43 patients ( 54 knees ) . At 2 weeks , knee flexion was similar in the two groups , but a flexion contracture was noted in the CPM group ( 4.2 degrees ) . This difference is felt by the authors to be clinical ly insignificant . At 6 months , there were no differences in knee scores , knee flexion , presence of flexion contracture , or extensor lag between the two groups . The cost for the CPM machine group was $ 10,582 ( $ 286 per patient ) , and the cost for professional therapy was $ 23,994 ( $ 558 per patient ) . We conclude that the CPM machine after the hospital discharge of patients having total knee replacement is an adequate rehabilitation alternative with lower cost and with no difference in results compared with professional therapy",
" Twenty-two primary total knee arthroplasties were prospect ively r and omized into one of two treatment protocol s. Ten of these patients were managed in the hospital after surgery by means of a postoperative splint . The remaining 12 patients were placed immediately postoperatively in the recovery room into the continuous passive motion ( CPM ) device . The study compares the range of motion , analgesic use , hospital stay , and the volume of hemovac output in the two groups . These cases demonstrated two statistically significant findings with the use of CPM : ( 1 ) decreased use of narcotic analgesics and ( 2 ) decreased length of hospital stay",
"The use of continuous passive motion after total knee arthroplasty remains controversial . A new approach , starting continuous passive motion at 70 degrees to 100 degrees flexion in the recovery room ( Group I ) was evaluated . A r and omized , prospect i ve study of 210 consecutive total knee arthroplasties was performed at two institutions . The control population ( Group II ) started continuous passive motion at 0 degree to 30 degrees , and progressed toward 100 degrees flexion . Flexion at postoperative Day 3 ( Group I = 82.5 degrees , Group II = 72.8 degrees ) , and at discharge ( Group I = 89.1 degrees , Group II = 84.3 degrees ) were significantly different . There was no significant difference between the groups at 4 weeks ( Group I = 5.0 degrees-104.1 degrees , Group II = 5.6 degrees-102.0 degrees ) , 6 weeks ( Group I = 2.3 degrees-104.8 degrees , Group II = 2.7 degrees-103.6 degrees ) , 12 weeks ( Group I = 1.7 degrees-107.7 degrees , Group II = 4.7 degrees-108.2 degrees ) , or at 1 year ( Group I = 0.5 degree-113.2 degrees , Group II = 1.8 degrees-110.5 degrees ) . In Group I , wound necrosis developed in one patient that required a gastrocnemius flap . This major complication was caused by a tight dressing , and not necessarily to the accelerated flexion continuous passive motion . This investigation shows that continuous passive motion using accelerated flexion allows increased flexion during the hospital stay without increased risk of complications , pain , or blood loss . This has significant implication s for achieving safe , early discharge . However , no difference was found at followup of 4 weeks or greater , and this did not add significantly to the final outcome",
"Three rehabilitation modalities relating to in-hospital postoperative care following unilateral total knee arthroplasty ( UTKA ) were studied regarding their effect on pain management and UTKA outcome : ( 1 ) continuous passive motion ( CPM ) ; ( 2 ) CPM with transcutaneous electrical nerve stimulation ( TENS ) ; and ( 3 ) CPM with continuous cooling pad ( CCP ) . Phase I : CPM . Twenty-two UTKA patients were r and omized into two postoperative care groups : ( 1 ) 12 with CPM ; and ( 2 ) 10 with no CPM . Total hospitalization pain medication consumption was significantly less for the CPM group ( P less than .05 ) . Phase II : CPM With TENS . Forty-eight UTKA patients were r and omized into three postoperative care groups : ( 1 ) 18 with an ipsilateral thigh TENS unit delivering sensory threshold stimulation ; ( 2 ) 18 with a subthreshold TENS unit ; and ( 3 ) 12 with no TENS unit . All groups used CPM . No significant difference was found regarding pain medication consumption . Phase III : CPM With CCP . Thirty consecutive UTKA patients were divided into two postoperative care groups : ( 1 ) 15 with a CCP unit ; and ( 2 ) 15 with no CCP unit . Both groups used CPM . No significant difference was found regarding total or intramuscular hospitalization pain medication consumption . However , oral hospitalization pain medication consumption was significantly less for the CCP group ( P less than .01 ) . This postoperative UTKA study demonstrates significantly decreased total in-hospital pain medication consumption when comparing CPM vs no CPM , significantly decreased oral in-hospital pain medication consumption when comparing CPM with CCP vs CPM without CCP , but no difference when comparing CPM with TENS vs CPM without TENS . ( ABSTRACT TRUNCATED AT 250 WORDS",
"In a prospect i ve study , 32 knees in 32 patients were r and omized to either a cylinder plaster cast ( 17 knees ) or hinged cast-brace ( 15 knees ) after high tibial osteotomy for medial gonarthrosis . At 6 weeks , 3 months , and still 1 year after surgery , the range of motion was better in the cast-brace group . There was no difference in the other clinical results at 3 months and at 1 year after surgery , nor in changes of osseous correction or in the final knee alignment . All the patients in the cast-brace group were satisfied with early motion",
"To determine the justification of a continuous passive motion machine in the treatment of postoperative total knee arthroplasties , a comparative study of 50 consecutive patients with simultaneous bilateral total knee arthroplasties was undertaken . The patients served as their own controls because one r and omly selected knee was placed in the machine while the remaining knee was treated with physical therapy only . There was no significant difference in the range of motion during the eight days of hospitalization or the follow-up visits at two weeks , two months , six months , and one year . There was a significant decrease in the swelling about the knee . The continuous passive motion treated knees appeared to be generally weaker as revealed by more extensor lags and flexor tightness at discharge from the hospital . Also , increased costs incurred from the need for additional equipment and increased staff time made the machine neither cost-effective nor beneficial ",
"OBJECTIVE To evaluate whether extended use of continuous passive motion ( CPM ) may allay the pain of walking , diminish disease effect , and increase the usual walking speed in patients with osteoarthritis ( OA ) of the hip . METHODS This pilot study comprised 21 patients with Kellgren-Lawrence grade 2 - 4 OA of the hip who used CPM for periods of 1.2 to 7.6 h daily throughout a 12 week trial . RESULTS Significant improvements were found in the patients ' assessment of pain on visual analog scale , Sickness Impact Profile , self-selected walking speed , and the number of subjects who decreased their medication usage . None of these improvements was related to the radiographic grade of the patients ' OA or the daily duration of CPM . CONCLUSION Although regular exercise is now routinely recommended to patients with OA , there has been relatively little study of specific exercise programs . As such investigations are undertaken , we believe CPM should be included among the options that are studied",
"We report a prospect i ve r and omly controlled trial to examine the effectiveness of continuous passive motion ( CPM ) in improving postoperative function and range of movement after total knee arthroplasty ( TKA ) . We allocated 53 patients ( 57 knees ) to one of three postoperative regimes : no CPM ( n = 19 ) ; CPM at 0 to 40 degrees ( 0 to 40 CPM ; n = 18 ) ; and CPM at 0 to 70 degrees ( 0 to 70 CPM ; n = 20 ) . Those in the CPM groups had CPM for 48 hours and all patients had an identical regime of physiotherapy . There was an even distribution of various cemented and cementless TKAs in each group . Patients were assessed preoperatively and at one week and at one year postoperatively . At one week , there was a statistically significant increase in the range of flexion and total range of movement in the 0 to 70 CPM group compared with the no-CPM group . At one year we found no significant differences in mean flexion , overall range of movement , fixed flexion deformity or functional results in the three groups . Those who had CPM had a significant increase in analgesic requirement ( p = 0.04 ) . There was an increased mean blood drainage postoperatively in those who had 0 to 70 CPM ( 1558 ml ) compared with those with no CPM ( 956 ml ) ( t = 2.96 , p = 0.005 ) and with 0 to 40 CPM ( 1017 ml ) ( t = 2.62 , p = 0.01 ) . Our findings show that CPM had no significant advantage in terms of improving function or range of movement , and that its use increased blood loss and analgesic requirements",
"We have carried out a prospect i ve r and omised , single blind clinical trial to investigate the effect of continuous passive motion on range of knee flexion , lack of extension , pain levels and analgesic use after total knee replacement surgery . 85 subjects were r and omly allocated to control or study group . All subjects followed the existing rehabilitation protocol , which permits immediate active range of motion exercises and mobilisation with the study group using continuous passive motion for 1 h , twice a day . Outcome measures employed were range of motion , pain assessed on a visual analogue scale and analgesic use according to the WHO ladder . Blinded evaluation was carried out preoperatively , at time of discharge from hospital , 6 weeks , 6 and 12 months postoperation . No significant difference was observed between groups at all time intervals for each outcome variable using Wilcoxon Rank sum tests . The results substantiate previous findings that short duration continuous passive motion following total knee arthroplasty does not influence outcome of range of motion or reported pain",
"BACKGROUND Continuous passive motion ( CPM ) has shown positive effects on tissue healing , edema , hemarthrosis , and joint function ( L. Brosseau et al. , 2004 ) . CPM has also been shown to increase short-term early flexion and decrease length of stay ( LOS ) ( L. Brosseau et al. , 2004 ; C. M. Chiarello , C. M. S. Gundersen , & T. O'Halloran , 2004 ) . The benefits of CPM for the population of patients undergoing computer-assisted total knee arthroplasty ( TKA ) have not been examined . PURPOSE The primary objective of this study was to determine whether the use of CPM following computer-assisted TKA result ed in differences in range of motion , edema/drainage , functional ability , and pain . METHODS This was an experimental , prospect i ve , r and omized study of patients undergoing unilateral , computer-assisted TKA . The experimental group received CPM thrice daily and physical therapy ( PT ) twice daily during their hospitalization . The control group received PT twice daily and no CPM during the hospital stay . Both groups received PT after discharge . Measurement included Knee Society scores , Western Ontario McMaster Osteoarthritis Index values , range of motion , knee circumference , and HemoVac drainage . Data were collected at various intervals from preoperatively through 3 months . RESULTS Although the control group was found to be higher functioning preoperatively , there was no statistically significant difference in flexion , edema or drainage , function , or pain between groups through the 3-month study period",
"The purpose of this study was to prospect ively compare the postoperative use of passive motion ( PM ) and st and ard h and therapy after surgical treatment of Dupuytren 's disease for extent and rate of recovery of joint motion . Our data indicate that metacarpophalangeal joint contractures improved completely to a mean of 0 degrees , regardless of the postoperative protocol . Contractures at the proximal interphalangeal joint showed incomplete recovery in both study groups , with a mean residual contracture of 28 degrees for PM patients and 38 degrees for control patients . Contractures of the metacarpophalangeal-proximal interphalangeal joints in the same finger showed complete metacarpophalangeal joint recovery to a mean of 0 degrees but incomplete proximal interphalangeal joint recovery with a mean residual contracture of 30 degrees in PM patients and 22 degrees in control patients . We conclude that the use of a PM machine in the rehabilitation of Dupuytren 's disease does not offer an advantage in the postoperative management of this condition",
"We r and omly allocated 54 patients to active physical therapy only or this combined with 2 hours of passive knee motion twice daily from 2 - 12 days after total knee arthroplasty . The range of knee motion was measured on the 14th postoperative day . We found no difference between the groups . We concluded that 4 hours ' passive motion daily in addition to early , active physical therapy does not improve the range of knee motion or promote mobilization after arthroplasty",
"Sixty-two patients undergoing primary total knee arthroplasty were studied prospect ively . There were 42 patients in whom continuous passive motion ( CPM ) was used after surgery and 20 controls . The two groups were comparable with respect to age , diagnosis , sex , weight , and preoperative deformity and motion . The mean length of time required for CPM patients to achieve 90 degrees of flexion ( 9.1 days ) was shorter than that for the control group ( 13.8 days ) . At the time of discharge from the hospital , however , there was no significant difference between the groups in amount of either flexion or extension . All patients had venograms performed after arthroplasty ; the incidence of positive studies indicating thrombophlebitis was 45 % in CPM patients and 75 % in controls . These data demonstrate that CPM after knee arthroplasty enables patients to recover motion more quickly and affords some protection against deep vein thrombosis",
"The authors report the results of a prospect i ve r and omized clinical trial using continuous passive motion after total knee arthroplasty . One hundred twenty patients were assigned r and omly to one treatment group : No continuous passive motion ( Group I ) , continuous passive motion from 0 ° to 50 ° and increased as tolerated ( Group II ) , and continuous passive motion from 70 ° to 110 ° ( Group III ) . The continuous passive motion was initiated in the recovery room and was maintained for a maximum of 24 hours at which point all patients began identical postoperative physiotherapy regimens . Patients were assessed preoperatively , during their hospital stay , at 6 weeks , 12 weeks , 26 weeks , and 52 weeks after their surgery . There were no statistical differences between any of the treatment groups regarding cumulative analgesic requirements , range of motion at any measured interval , length of stay ( Group I , 5.1 days ; Group II , 5.2 days ; Group III , 5 days ) or Knee Society scores . The current study does not support the use of short-term continuous passive motion after total knee replacement . A st and ard and a high flexion continuous passive motion protocol failed to show any advantage over physiotherapy alone in the parameters evaluated",
"BACKGROUND AND PURPOSE This r and omized clinical trial was conducted to compare the effectiveness of 3 in-hospital rehabilitation programs with and without continuous passive motion ( CPM ) for range of motion ( ROM ) in knee flexion and knee extension , functional ability , and length of stay after primary total knee arthroplasty ( TKA ) . SUBJECTS Eighty-one subjects who underwent TKA for a diagnosis of osteoarthritis were recruited . METHODS All subjects were r and omly assigned to 1 of 3 groups immediately after TKA : a control group , which received conventional physical therapy intervention only ; experimental group 1 , which received conventional physical therapy and 35 minutes of CPM applications daily ; and experimental group 2 , which received conventional physical therapy and 2 hours of CPM applications daily . All subjects were evaluated once before TKA and at discharge . The primary outcome measure was active ROM in knee flexion at discharge . Active ROM in knee extension , Timed \" Up & Go \" Test results , Western Ontario and McMaster Universities Osteoarthritis Index question naire scores , and length of stay were the secondary outcome measures . RESULTS The characteristics of and outcome measurements for the subjects in the 3 groups were similar at baseline . No significant difference among the 3 groups was demonstrated in primary or secondary outcomes at discharge . DISCUSSION AND CONCLUSION The results of this study do not support the addition of CPM applications to conventional physical therapy in rehabilitation programs after primary TKA , as applied in this clinical trial , because they did not further reduce knee impairments or disability or reduce the length of the hospital stay"
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BACKGROUND Azapirones are a group of drugs that work at the 5-HT1A receptor and are used to treat patients suffering from generalized anxiety disorder ( GAD ) . However , several studies have shown conflicting results . Whether azapirones are useful as first line treatment in general anxiety disorders still needs to be answered . OBJECTIVES To assess the efficacy and the acceptability of azapirones for the treatment of GAD . SEARCH STRATEGY Initially the Cochrane Collaboration Depression , Anxiety and Neurosis Controlled Trials Register ( CCDANCTR ) and The Cochrane Central Register of Controlled Trials ( CENTRAL ) were search ed , incorporating results of group search es of MEDLINE ( 1966 to June 2005 ) , EMBASE ( 1980 to June 2005 ) , CINAHL ( 1982 to June 2005 ) , PsycLIT ( 1974 to June 2005 ) , PSYNDEX ( 1977 to June 2005 ) , and LILACS ( 1982 to June 2005 ) . Subsequently the revised Cochrane Collaboration Depression , Anxiety and Neurosis Controlled Trials Registers ( CCDANCTR- Studies and CCDANCTR-References ) were search ed on 21 - 10 - 2005 . Reference lists of relevant papers and major text books of anxiety disorder were examined . Authors , other experts in the field and pharmaceutical companies were contacted for knowledge of suitable trials , published or unpublished . Specialist journals concerning azapirones were h and search ed . SELECTION CRITERIA R and omized controlled trials of azapirones , including buspirone versus placebo and /or other medication and /or psychological treatment , were included . Participants were males and females of all ages with a diagnosis of generalized anxiety disorder . DATA COLLECTION AND ANALYSIS Data were extracted from the original reports independently by CC , MA and MT . The main outcomes studied were related to the objectives stated above . Data were analysed for generalized anxiety disorder versus placebo , versus other medication and versus psychological treatment separately . Data were analysed using Review Manager Version 4.2.7 . MAIN RESULTS Thirty six trials were included in the review , reporting on 5908 participants r and omly allocated to azapirones and /or placebo , benzodiazepines , antidepressants , psychotherapy or kava kava . Azapirones , including buspirone , were superior to placebo in treating GAD . The calculated number needed to treat for azapirones using the Clinical Global Impression scale was 4.4 ( 95 % confidence interval ( CI ) 2.16 to 15.4 ) . Azapirones may be less effective than benzodiazepines and we were unable to conclude if azapirones were superior to antidepressants , kava kava or psychotherapy . Azapirones appeared to be well tolerated . Fewer participants stopped taking benzodiazepines compared to azapirones . The length of studies ranged from four to nine weeks , with one study lasting 14 weeks . AUTHORS ' CONCLUSIONS Azapirones appeared to be useful in the treatment of GAD , particularly for those participants who had not been on a benzodiazepine . Azapirones may not be superior to benzodiazepines and do not appear as acceptable as benzodiazepines . Side effects appeared mild and non serious in the azapirone treated group . Longer term studies are needed to show that azapirones are effective in treating GAD , which is a chronic long-term illness
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"Buspirone , a new nonbenzodiazepine anxiolytic agent , was compared with clorazepate in a double-blind , multicenter trial conducted with 336 out patients who had moderate to severe anxiety . The two treatments were equally effective for relief of symptoms , including anxiety with associated depression . Although both agents were generally well tolerated , the profile of side effects was dissimilar . Drowsiness and depression occurred significantly ( p less than 0.055 ) more frequently with clorazepate , whereas nausea and headache occurred significantly ( p less than 0.055 ) more frequently with buspirone . Clorazepate-treated patients were significantly ( p less than 0.055 ) more likely to have had an adverse experience that was considered drug related or that interfered with the therapeutic effect . In this study , buspirone was shown to be an effective antianxiety agent , causing significantly less sedation than clorazepate",
" Two groups of 12 out patients each ( six men and six women ) with generalized anxiety disorder , participated in this study . Each patient was treated single-blind with placebo during the first 7 days ( baseline ) , followed by a double-blind drug treatment period of 4 consecutive weeks ( active ) and ending again with 7 days single-blind placebo treatment ( washout ) . One group received buspirone 5 mg three times a day in the first week and continued with 10 mg in the morning , 5 mg in the afternoon , and 5 mg in the evening during the second , third , and fourth weeks . The other group received diazepam 5 mg three times a day in all 4 weeks . On the evening of the seventh day of each treatment week the Hamilton Rating Scale for Anxiety and the Symptom Check List ( 90 items ) were applied to assess the therapeutic effects , followed by an on-the-road driving test that started 1.5 hours after the last drug or placebo intake . The test consisted of operating an instrumented vehicle over a 100 kilometer highway circuit while attempting to maintain a constant speed and a steady lateral position within the right traffic lane . Two patients in the diazepam group were unable to complete their test after the first and second treatment week , respectively , because of serious sedative reactions . Both buspirone and diazepam were equally effective in reducing overall anxiety symptoms . The specific profiles showed that buspirone also reduced concomitant depressive symptoms and symptoms of interpersonal sensitivity and anger-hostility . In contrast , diazepam was found to be slightly more effective in reducing somatic symptoms and to positively affect sleep disturbances . Moreover , abrupt discontinuation of diazepam result ed in a relapse of psychic anxiety symptoms comparable with the placebo-baseline level and a partial relapse of somatic anxiety symptoms . Chronic treatment with buspirone had no significant effects on lateral position and speed control . In contrast , diazepam significantly impaired control of lateral position in the first 3 weeks of treatment . There was no significant impairment in the fourth treatment week and the placebo-washout week . Speed control was significantly impaired only in the first week . The relevance of the trend toward decreasing performance impairment during chronic treatment remains to be established",
"Nondirective ( ND ) , applied relaxation ( AR ) , and cognitive behavioral ( CBT ) therapies for generalized anxiety disorder ( GAD ) were compared . The latter 2 conditions were generally equivalent in outcome but superior to ND at post assessment . The 3 conditions did not differ on several process measures , and ND created the greatest depth of emotional processing . Follow-up results indicated losses in gains in ND , maintained gains in the other 2 conditions , especially CBT , and highest endstate functioning for CBT . AR and CBT thus contain active ingredients in the treatment of GAD ; support exists for further development of imagery exposure methods or cognitive therapy because of their likely role in promoting maintenance of change with this disorder . Expectancy for improvement was also associated with outcome , suggesting the need for further research on this construct for underst and ing the nature of GAD and its amelioration",
"The anxiolytic activity , the tolerance , and the withdrawal symptoms of buspirone and oxazepam were compared in two groups of 14 and 12 out patients , respectively , suffering from generalized anxiety in a double-blind study with r and om allocation of patients . The 6-week active period was preceded and followed by 1 and 2 weeks on placebo , respectively . Clinical assessment s were performed before and after the predrug placebo period and every 2 weeks thereafter and included Hamilton anxiety and depression scales and AMDP anxiety subscale . The initial daily dose was 15 mg buspirone or 45 mg oxazepam in 3 intakes and the mean final daily doses were 22.2 and 55.8 mg , respectively . Results showed a slower anxiolytic activity of buspirone compared to oxazepam with less improvement after 2 weeks of treatment . The rebound anxiety following abrupt discontinuation of the drug and the level of side effects did not significantly differ between the two compounds",
" Fifty-one out- patients presenting with generalised anxiety disorder were included in a double-blind trial , and treated with either buspirone ( a new non-benzodiazepine antianxiety drug ) or diazepam over 6 or 12 weeks , after which they were abruptly withdrawn and continued on placebo to 14 weeks . Ratings of anxiety and other symptoms were administered fortnightly and additional withdrawal symptoms noted . Forty patients completed the study ; 8 of the 11 drop-outs were taking buspirone . Both drugs reduced anxiety , diazepam more rapidly , but with greater withdrawal symptoms , particularly after 6 weeks . Regular treatment with diazepam for 6 weeks leads to a significant risk of pharmacological dependence that is not present with buspirone",
"Enciprazine is a propanolamine derivative with a pre clinical profile similar to buspirone but with less affinity for the postsynaptic dopamine receptor ( Linden et al. 1988 ) . We report on the outcome , using intent-to-treat data , of a 5-week , double-blind trial comparing three dose strengths of enciprazine ( 5 mg t.i.d . , 10 mg t.i.d . , and 20 mg t.i.d . ) to placebo . A dose escalation was permitted after 2 weeks of active drug treatment , which 61 percent of patients overall took advantage of . A \" last observation carried forward \" ( LOCF ) analysis found a mean improvement in Hamilton Anxiety Scale ( HAM-A ) scores by Week 5 of -11.0 for the combined enciprazine treatment groups , and -4.4 for the placebo group ( p less than .05 ) . Fifty-two percent of enciprazine patients were judged to be \" much \" or \" very much \" improved , whereas none of the placebo patients were judged to have comparable improvement . Enciprazine was well-tolerated , with low levels of sedative and asthenic side effects reported . The compound appears to have promise as an anxiolytic agent",
"Pooled data for 427 patients with generalized anxiety disorders were analyzed retrospectively from six double-blind trials evaluating buspirone , a nonbenzodiazepine anxiolytic , in the treatment of generalized anxiety disorder . After a 4- to 7-day washout period , patients were allocated at r and om to receive treatment over a 4-week period . Buspirone dose ranged from 10 to 60 mg . Patients were assessed on entry and at weekly intervals using the 14 symptom groups ( items ) of the Hamilton Anxiety Rating Scale ( HAM-A ) . Buspirone improved all symptom groups significantly ; onset of anxiolytic activity was observed at week 1 in 3 groups of psychic symptoms of anxiety . Within 2 weeks , 8 of the 14 symptom groups were improved significantly by buspirone versus placebo , and symptoms of anxiety improved further up to the 4-week end point . Psychic symptoms of anxiety improved earlier in general than the somatic symptoms of anxiety . At the end of treatment , analyses of the HAM-A scores indicated that all of the 14 symptom groups ( individual items ) , the total HAM-A score , and the 2 composite Psychic and Somatic Anxiety Factors were significantly improved with buspirone as compared to placebo . The beneficial effects of buspirone were not compromised by any significant side effects",
"The safety and antianxiety and antidepressive effects of buspirone ( average 16.5 mg/day ) were compared in a double-blind trial with those of diazepam ( 15 mg/day ) . The two drugs were nearly equivalent in relieving symptoms of both anxiety and depression in 100 patients . Scores on the impaired cognition factor of the SCL-56 and confusion factor of the POMS showed significantly greater improvement with buspirone than with diazepam . Side effects , such as sedation and drowsiness , were significantly more frequent and severe with diazepam . Buspirone may be particularly indicated for anxious patients with associated depression",
"The efficacy and safety of buspirone ( Buspar ) , diazepam ( Valium ) , and placebo were compared in a 3-week double-blind study of 131 patients with scores of at least 15 on the Hamilton Rating Scale for Anxiety . Active drugs were administered orally in 5-mg tablets to a maximum dose of 10 mg t.i.d . Buspirone was given to 43 patients , diazepam to 46 and placebo to 42 . There was significant improvement in all three treatment groups at 1 and 2 weeks , with further significant improvement with both active drugs , but not with placebo , at 3 weeks . The incidence of side effects reported voluntarily by patients was similar with the two active drugs , but drowsiness was significantly more frequent with diazepam",
" Thirty-six patients with generalised anxiety disorder , panic disorder or agoraphobia with panic attacks , diagnosed by DSM-III criteria , were treated with a new non-benzodiazepine anti-anxiety drug , buspirone , and with diazepam and placebo , in a cross-over design . Each patient took buspirone , diazepam and placebo for one week each in flexible dosage and balanced order . Ratings of symptomatology using the Comprehensive Psychopathological Rating Scale were made after each week 's treatment and a sub-scale used for measuring anxiety change alone was used separately . There was no overall difference in efficacy between the drugs , but when the scores for individual symptoms were analysed , diazepam was significantly superior to the other treatments for the symptom of muscle tension only . The results suggest that the common practice of giving short-term therapy with tranquilising drugs for anxiety in primary care is pharmacologically suspect",
"The anxiolytic properties of buspirone were assessed in a 4-week double-blind study in 240 anxious patients , 81 of whom received buspirone , 81 diazepam , and 78 placebo . Patients were required to have scores greater than or equal to 9 on the Covi and greater than or equal to 18 on the Hamilton Rating Scale for Anxiety , and to endorse at least 5 items on a 17-item Anxiety Entry Checklist . Among 212 evaluable patients , those who improved most were married , well-educated females who had both a positive family adjustment and a low level of depression . Diazepam produced relatively equal improvement in females and males . Diazepam seems more effective in reducing somatic symptoms , while buspirone appears more effective in reducing symptoms associated with cognitive and interpersonal problems . Main differences between the drugs were seen in side effect profiles",
"The efficacy and safety of alprazolam and buspirone for treating generalized anxiety disorder ( GAD ) were compared in a 6-week , double-blind , r and omized , placebo-controlled study of 94 out patients . Mean daily doses at the end of the study were 1.9 mg alprazolam and 18.7 mg buspirone . As judged by the Hamilton Anxiety Rating Scale , Hamilton Depression Rating Scale , Physician 's Global Improvement Scale , and other efficacy scales , alprazolam and buspirone were similar in efficacy , but more effective than placebo , for treating anxiety and depression symptoms in these patients . Clinical ly important differences were noted between drugs in the onset of effect , with alprazolam producing rapid and sustained improvement within the first week of treatment and buspirone producing more gradual , continuous improvement throughout the study . Significantly more buspirone-treated than alprazolam-treated patients failed to complete the study , primarily because of side effects or inefficacy . No clinical ly important differences were noted between alprazolam and buspirone in side effects , vital signs , or laboratory test results . Alprazolam-treated patients most frequently reported central nervous system-related side effects ( drowsiness and sedation ) , while buspirone-treated patients most frequently reported gastrointestinal system-related side effects ( appetite disturbances and abdominal complaints )",
"BACKGROUND The objective of this r and omized , double-blind study was to compare the efficacy and safety of venlafaxine extended release ( XR ) and buspirone in out patients with generalized anxiety disorder ( GAD ) but without concomitant major depressive disorder . METHOD Male and female out patients at least 18 years old who met the DSM-IV criteria for GAD and had scores of 18 or higher on the Hamilton Rating Scale for Anxiety ( HAM-A ) were r and omly assigned to treatment with either venlafaxine XR ( 75 or 150 mg/day ) , buspirone ( 30 mg/day in 3 divided doses ) , or placebo for 8 weeks . The primary efficacy variables were changes in anxiety as determined by final on-therapy HAM-A total and psychic anxiety scores and Clinical Global Impressions scale ( CGI ) scores . Other key efficacy variables were HAM-A anxious mood and tension scores and the anxiety subscale scores of the patient-rated Hospital Anxiety and Depression scale ( HAD ) . RESULTS The efficacy analysis included 365 patients and the safety analysis , 405 . At week 8 , adjusted mean HAM-A psychic anxiety , anxious mood , and tension scores were significantly lower for venlafaxine XR-treated patients than for placebo-treated patients . On the HAD anxiety subscale , venlafaxine XR , 75 or 150 mg/day , was significantly more efficacious than placebo at all time points except weeks 1 ( both dosages ) and 2 ( 150-mg/day dosage only ) and significantly more efficacious than buspirone at all time points except week 1 . On the CGI-Improvement scale , scores for venlafaxine XR ( both dosages ) and buspirone were numerically superior to those for placebo at all time points , and statistical significance was observed at weeks 3 , 4 , 6 , and 8 for venlafaxine XR and at weeks 6 and 8 for buspirone . The adverse events were not essentially different between treatment groups . CONCLUSION Venlafaxine XR is an effective , safe , and well-tolerated once-daily anxiolytic agent in patients with GAD without comorbid major depressive disorder . This agent was significantly superior to buspirone on the HAD anxiety subscale . Buspirone demonstrated statistical significance versus placebo on a measure of anxiolytic response",
"Two hundred thirty patients with generalized anxiety and Hamilton Rating Scale for Anxiety ( HAM-A ) scores greater than or equal to 18 were subdivided at r and om , according to a double-blind design , into one group treated with 5 - 10 mg of oral buspirone t.i.d . or one group treated with 10 - 20 mg of oral oxazepam t.i.d . for 6 weeks . No anxiolytic treatment was allowed 3 months prior to trial entry . Analysis of demographic variables revealed no significant imbalance between the two treatment groups . Twenty patients were excluded from efficacy analysis because of treatment withdrawal before the first efficacy evaluation on Day 7 . Another 4 patients were excluded because they were taking concomitant psychotropic medication . The remaining 206 patients displayed a decrease in HAM-A scores ( mean + /- SD ) from 23.9 + /- 4.1 to 10.6 + /- 7.7 in the buspirone group and from 23.9 + /- 4.2 to 11.5 + /- 8.0 in the oxazepam group . The two treatment groups were also found to be virtually identical in an \" intent to treat \" analysis of all 230 patients as well as in other ratings ( Hamilton Rating Scale for Depression , Raskin Depression Scale , Covi Anxiety Scale , Physicians Question naire , global ratings , and Hopkins Symptom Checklist [HSCL]-56 ) . However , oxazepam was never superior to buspirone in any of the efficacy analyses . Of the 230 patients , 127 spontaneously reported adverse events , including drowsiness , dizziness , headache , nausea , and nervousness . Adverse events were relatively similar in the two groups . In conclusion , buspirone and oxazepam appear to be equally effective in the treatment of generalized anxiety encountered by general practitioners . This outcome , in addition to a previously documented absence of any dependency liability , makes buspirone a clinical ly important anxiolytic drug",
"The effects of the anxiolytic drugs diazepam ( 5 mg ) or buspirone ( 5 or 10 mg ) were studied in comparison with placebo on memory function in 39 subjects diagnosed with generalized anxiety disorder . Neither drug altered the immediate recall of a list of 16 nouns or impaired digit span , a second test of immediate memory . Diazepam selectively impaired the recall of nouns after a 20 min delay when compared with placebo . In contrast , neither dose of buspirone altered the delayed recall of the word list . The implication s of such different effects of anxiolytic drugs on memory function for the clinical treatment of anxiety are discussed",
"Buspirone has previously been demonstrated to be efficacious in the treatment of anxiety . This four-week double-blind parallel study compared buspirone to diazepam and placebo in the treatment of 119 out patients diagnosed as having generalized anxiety disorder . After a seven-day placebo washout period , eligible patients were r and omized to one of three treatment groups . Buspirone ( 5 mg ) and diazepam ( 5 mg ) were administered BID and individually titrated to an optimal therapeutic dose by the end of week two . Buspirone and diazepam were equally effective in reducing Hamilton Anxiety ( HAM-A ) total and psychic factor scores from baseline values . Buspirone alone was significantly better than plecebo in reducing the HAM-A somatic factor score . Sixty-seven percent of both active treatment groups who were classified as “ ill ” on the baseline global psychopathology rating scale achieved a “ not ill ” status by study end . There were no significant differences between treatment groups at endpoint on the 56-item Symptom Checklist self-rating scale . Buspirone was demonstrated to be as effective as diazepam in relieving anxiety in this outpatient sample",
"OBJECTIVE : To compare the relative efficacy and safety of lesopitron 40–80 mg/d versus lorazepam 2–4 mg/d and placebo in a subgroup of patients with anxiety history taken from a larger study of patients with a primary diagnosis of generalized anxiety disorder ( GAD ) . DESIGN : Six-week , r and omized , double-blind , parallel , placebo and lorazepam-controlled , Phase II , single-center , outpatient study . SETTING : Outpatient clinic . PATIENTS : One hundred sixty-one patients with GAD were r and omized in the main study ; 68 with a documented history of GAD or anxiety disorder not otherwise specified were included in the subgroup . METHODS : After a one-week placebo lead-in , patients were r and omized to receive placebo , lesopitron , or lorazepam twice daily for six weeks , followed by a one-week taper period . Efficacy was assessed using the Hamilton Rating Scale for Anxiety ( HAM-A ) and the Clinical Global Impressions scale . Safety was assessed through physical examinations , monitoring of vital signs , 12-lead electrocardiograms , laboratory analyses , and adverse event monitoring . RESULTS : An overall mean improvement in the HAM-A total score between baseline and end point for all three treatment groups was seen , with mean changes of 3.4 ( 95 % CI 2.0 to 4.8 ) , 6.1 ( 95 % CI 4.1 to 8.1 ) , and 6.1 ( 95 % CI 4.6 to 7.6 ) for the placebo , lesopitron , and lorazepam groups , respectively ( omnibus p = 0.044 , uncorrected ) . Positive treatment effects were also observed in the subgroup population on several other measures and suggest that additional therapeutic trials may be warranted . Future trials could be stratified on the basis of referral status ( symptomatic volunteer vs. clinical patient with preexisting illness ) or previous exposure to anxiolytics , and use a fixed-dose rather than flexible-fixed-dose design . CONCLUSIONS : The subgroup analysis represents a comparison of treatment outcome in GAD patients presenting with a history of previous episodes of GAD or anxiety disorder not otherwise specified compared with those who were experiencing their first episode of GAD and reported no anxiety history . Although the overall study analysis was equivocal , for the approximately 40 % of patients with recurrent anxiety disorder , beneficial effects for both lesopitron and lorazepam are suggested",
"Forty-four patients with DSM-III-R generalized anxiety disorder participated in this double-blind , r and omized study . Patients were on a benzodiazepine before the study and were stabilized on 3 to 5 mg/day lorazepam for 5 weeks ( weeks 0 to 5 ) . Thereafter , they were r and omized to 15 mg/day buspirone or placebo for the following 6 weeks ( weeks 6 to 11 ) . During the first 2 weeks of double-blind , r and omized treatment ( weeks 6 to 7 ) , lorazepam was tapered off . During weeks 12 to 13 , patients received single-blind placebo . Assessment included the Hamilton Rating Scale for Anxiety , the State-Trait Anxiety Inventory , the Zung and Eddy Self-Rating Scale of Anxiety Symptoms , the Hamilton Rating Scale for Depression , and the Rome Depression Inventory , completed at weeks 0 , 5 , 6 , 7 , 8 , 9 , 11 , and 13 . Side effects were assessed through the Dosage Treatment Emergent Symptoms at the same times . The benzodiazepine-withdrawal syndrome was evaluated through a 27-symptom checklist ( Clinical -Rated Benzodiazepine Withdrawal Symptom Schedule ) at weeks 0 , 5 , 6 , 7 , 11 , and 13 . The results showed that buspirone was more effective than placebo and comparable to lorazepam . Buspirone-treated patients showed no rebound anxiety or benzodiazepine-withdrawal syndrome compared with placebo . Buspirone caused fewer side effects than lorazepam and was not different from placebo in this respect . Finally , buspirone maintained its anxiolytic effect for at least 2 weeks after the discontinuation of treatment",
"Ipsapirone is a partial 5-HT1A , agonist which appears promising for the pharmacologic treatment of anxiety . In this four-week , double-blind , 19-center study , 249 out patients with generalized anxiety disorder were r and omized to one of four treatments : ipsapirone , 5 or 10 mg t.i.d . , diazepam 5 mg t.i.d . , or placebo . Both active treatments were significantly superior to placebo in reducing anxiety symptoms , although response to ipsapirone was not significant until week 2 while diazepam had a more rapid onset . Five mg t.i.d . was the optimal ipsapirone dose . At 10 mg t.i.d . adverse experiences prompted more patients to discontinue treatment . Adverse experiences that were reported significantly more often for ipsapirone than placebo included asthenia , nausea , dizziness , paresthesias and sweating . Sedation was the most common diazepam-related side effect . The results of this study when combined with others suggest that 5 mg t.i.d . of ipsapirone is an effective and well-tolerated anxiolytic without many of the risks of benzodiazepine therapy . Dosage escalation by patients is unlikely because of an increased risk of side effects",
"Benzodiazepines have been prescribed for the treatment of Generalized Anxiety Disorder ( GAD ) for nearly three decades due to their proven anxiolytic efficacy , despite a considerable side effect and abuse liability profile . A new class of compounds , the azapirones , have been developed as an alternative to benzodiazepine treatment . Ipsapirone is a novel anxiolytic azapirone which has high specificity for the 5-HT1A receptor and which has the potential for offering certain advantages over buspirone . The present 5-week study investigated three doses of ipsapirone ( 2.5 mg , 5.0 mg and 7.5 mg tid ) versus placebo in 267 GAD out patients . Efficacy was evaluated using the Hamilton Anxiety Rating Scale ( HAM-A ) , Zung Anxiety Scale ( Zung-A ) , and Clinical Global Impression ( CGI ) . The study design consisted of a 1-week placebo run-in , a 4-week double-blind treatment period , and a 1-week placebo washout . The 5.0 mg group demonstrated consistently superior improvement in all efficacy variables during the treatment period , with significant differences ( p adverse events , primarily dizziness , nausea , sedation , and asthenia , was found to be dose proportional , with significant increase in the 7.5 mg group , which may account for the diminished effectiveness seen with this dose . Our results suggest that ipsapirone may represent a viable treatment for GAD",
"Two double-blind studies are described in which buspirone was compared with placebo and diazepam ( Study A ) or clorazepate ( Study B ) in out patients with moderate to severe anxiety . Results , assessed on the Hamilton Rating Scales for Depression and Anxiety , the SCL-56 , the Profile of Mood States , and the Covi and Raskin scales , indicated that buspirone consistently relieved both anxiety and associated depression . In Study B , trends in favor of buspirone were seen on several SCL-56 items and the Hamilton somatic factor ; significant differences in this direction were found for several POMS items . Sedation was seen less often with buspirone than either diazepam or clorazepate",
"Earlier findings suggest that housing conditions in laboratory animals and life events in humans influence the efficacy of anxiolytic drugs . Here we report on the impact of social isolation on buspirone efficacy in male mice and rats as assessed by the elevated plus-maze . In addition , the impact of social support on buspirone efficacy was assessed in male patients . When administered 30 min before testing and irrespective of housing conditions , buspirone significantly suppressed locomotor activity both in mice ( 6 mg/kg ) and rats ( 10 mg/kg ) and , as such , other behavioral changes observed at this time point must be seen as behaviorally nonselective . However , these locomotor disruptive effects of buspirone were not evident in either species at longer injection-test intervals ( 2 and 4 h ) . When given 2 h prior to testing , a low ( 3 mg/kg ) but not high ( 10 mg/kg ) dose of buspirone increased the frequency of open arm exploration in rats ( but not mice ) irrespective of housing conditions . At the longest injection-test interval used ( 4 h ) , buspirone increased the duration of open arm exploration in individually housed , but not group-housed , rats . Similar , though somewhat less robust , effects were observed in male mice at this time . In a double-blind placebo-controlled study with male patients , chronic buspirone treatment ( 3 x 10 mg daily for 6 weeks ) produced a highly significant reduction in scores on the Hamilton Rating Scale for Anxiety ( HAM-A ) . Multiple regression analysis of social support received by patients indicated that the support of nonrelatives ( but not of family or other relatives ) was a strong positive predictor of buspirone efficacy . Taken together , our data support the hypothesis that social conditions affect the anxiolytic efficacy of buspirone . Results are discussed in relation to differences in the social organization of the three species investigated",
"BACKGROUND This study was design ed to evaluate the anxiolytic efficacy of buspirone in patients with a diagnosis of generalized anxiety disorder ( GAD ) with coexisting mild depressive symptoms . METHOD Patients who participated in this multicenter study scored > /= 18 on the Hamilton Rating Scale for Anxiety ( HAM-A ) and between 12 and 17 on the Hamilton Rating Scale for Depression ( HAM-D ) . Following a 7- to 10-day placebo lead-in phase , patients who continued to qualify were r and omly assigned to receive either buspirone titrated from 15 to 45 mg/day ( N = 80 ) or placebo ( N = 82 ) for the next 6 weeks . 121 patients completed 6 weeks of treatment . The primary efficacy measure was the HAM-A , taken weekly during the study . RESULTS Buspirone-treated patients averaged a 12.4-point reduction from their baseline total HAM-A score of 24.9 , while their counterparts on placebo averaged a 9.5-point reduction from their mean baseline total HAM-A score of 25.6 . This 2.9-point difference in HAM-A reductions between treatment groups was significantly different ( p Buspirone patients decreased their HAM-D scores by an average 5.7 points from their mean baseline total HAM-D score of 15.8 , while placebo patients decreased their HAM-D scores by an average 3.5 points from their mean baseline score of 16.3 ( p adverse events was similar for both treatment groups , but buspirone-treated patients reported significantly more nausea , dizziness , somnolence , and sweating than placebo patients . CONCLUSION Buspirone is superior to placebo in improving anxiety and depressive symptoms in GAD patients who have coexisting depressive symptoms",
"Lesopitron , a 5-hydroxytryptamine 1A agonist , is a new potential anxiolytic of the azapirone class . It has greater potency in animal models of anxiety than buspirone , gepirone , or ipsapirone , and it lacks the antidopaminergic effects associated with buspirone . Lesopitron has been tolerated at single doses up to 50 mg and repeated dosages of 45 mg/day in healthy volunteers . Forty-two patients with generalized anxiety disorder ( GAD ) were enrolled in this double-blind bridging study to determine the safety and tolerability of fixed doses of lesopitron ( 20 , 25 , 30 , 40 , 45 , 50 , and 60 mg two times a day ) over a 6 1/2-day inpatient administration period . Each of the seven panels included six patients ( four drug/two placebo ) . One patient in the 25-mg , two-times-a-day panel voluntarily withdrew because of increased anxiety symptoms . One patient experienced severe orthostatic hypotension at 60 mg two times a day , and moderate to severe adverse events ( dizziness , lightheadedness , nausea , headache ) occurred in two other patients at this dosage . The most commonly reported adverse events in all the panels were headache , dizziness , and nausea . Lesopitron is rapidly absorbed in patients , having a time to maximum concentration ( Tmax ) ranging from 0.5 to 1 hour , and its elimination half-life ranged from 1.1 to 5.6 hours . Peak plasma concentrations showed high interindividual variability for lesopitron , but increased linearly with dose for the main metabolite , 5-hydroxylesopitron . We defined the maximum tolerated dose in GAD patients as 50 mg two times a day , twice as high as the highest dose tested in healthy volunteers",
"Risk of withdrawal was investigated in a prospect i ve , double-blind comparison of clorazepate dipotassium , a benzodiazepine with a long half-life , and the nonbenzodiazepine buspirone hydrochloride in the long-term treatment of anxious out patients . Patients were treated with therapeutic doses of clorazepate dipotassium ( 15 to 60 mg/d ) or buspirone hydrochloride ( 10 to 40 mg/d ) for six continuous months before their tranquilizer therapy was blindly and abruptly stopped . There was a significant increase in symptom severity consistent with a withdrawal reaction for the clorazepate group but not the buspirone group . For the clorazepate group , there was a suggestion that previous discontinuous exposure to benzodiazepines might sensitize patients to subsequent withdrawal effects . For the buspirone group , a higher dropout rate raised questions about patient satisfaction with therapy in this rather chronically anxious population",
"BACKGROUND Very few studies have examined the combination of drug and psychological treatment in generalised anxiety disorder ( GAD ) . Theoretically , buspirone should be a useful drug to combine with a learning-based therapy . METHODS Sixty patients with GAD were r and omly assigned to treatment with buspirone or placebo , combined with anxiety management training or non-directive therapy for a period of 8 weeks . RESULTS Forty-four patients with a mean Hamilton Anxiety Scale score of 28 completed treatment . There were no significant differences between treatment groups . All groups showed significant improvement after 8 weeks compared to baseline . There were no baseline differences between those who completed the trial and those who did not but patients given buspirone were more likely to drop out . CONCLUSIONS A short course of psychological therapy , whether or not accompanied by active medication , was an effective treatment for patients diagnosed as having quite severe symptoms of GAD . CLINICAL IMPLICATION S AND LIMITATIONS : Dropouts led to a sample size which may have been too small to detect group differences . Cognitive therapy may have been more effective",
"We report the findings of a r and omized , double-blind , placebo-controlled , parallel , generalized anxiety disorder ( GAD ) outpatient study . The purpose of the study was to compare the efficacy , safety , and tolerability of ipsapirone , an azapirone and 5-HT1A agonist , given at a total daily dose of 10 mg to 30 mg , with a total daily dose of 2 mg to 6 mg of lorazepam or placebo in 90 out patients with GAD of moderate or greater severity . At baseline , all patients had a Hamilton Anxiety Scale ( HAM-A ) score of > or = 18 and Covi anxiety score of > or = 8 . After a 1-week single-blind washout , patients entered a 4-week double-blind period with an optional extension for another 4 weeks , followed by a 2-week single-blind placebo washout . Ipsapirone and lorazepam ratings on the HAM-A and Clinical Global Impressions ( CGI ) were significantly ( p placebo at the end of the acute and maintenance periods of the trial , with a 50 percent HAM-A reduction on active drugs vs. 20 percent on placebo . The anxiety of patients receiving lorazepam , but not ipsapirone , rebounded during the final placebo washout",
"This r and omized , double-blind clinical trial involving 198 generalized anxiety disorder ( GAD ) patients was conducted to more clearly define gepirone 's role for the treatment of anxiety in daily dosages of 10 to 45 mg compared with diazepam and placebo . A secondary goal was to test for possible discontinuation symptoms after abrupt discontinuation of therapy . After a 1-week washout period , patients were treated for 8 weeks and then abruptly shifted under single-blind conditions for 2 weeks on placebo . The highest attrition rate occurred with patients on gepirone ( 58 % ) and the lowest on diazepam ( 34 % ) . Medication intake for week 4 was 19.5 + /- 12.5 mg/day diazepam and 19.0 + /- 11.5 mg/day gepirone and was similar at week 8 . The major adverse events were light-headedness , nausea , and insomnia for gepirone and drowsiness and fatigue for diazepam . Clinical improvement data showed gepirone 's anxiolytic response to be delayed , being significant from placebo beginning at week 6 , whereas diazepam caused significantly more relief than placebo from week 1 onward . Taper results showed that only diazepam , but not gepirone , caused a temporary worsening of anxiety symptoms or rebound",
"Abstract In this double-blind , placebo-controlled 10-week trial , the anxiolytic properties of the nonbenzodiazepine buspirone were compared with the benzo diazepine lorazepam and placebo in 125 out patients with generalized anxiety disorder according to DSM-III . After a 3- to 7-day wash-out period , patients were allocated at r and om to receive orally 3 × 5 mg buspirone ( n = 58 ) , 3 × 1 mg lorazepam ( n = 57 ) , or placebo ( n = 10 ) over a 4-week period . The study also comprised a 2-week taper period and a 4-week placebo-control period to assess the stability of clinical improvement . The patient´s clinical state was estimated on entry and at weekly intervals by general practitioners using the Hamilton Rating Scale for Anxiety ( HAM-A ) and Clinical Global Impression ( CGI ) assessment and by a self-rating scale ( State Trait Anxiety Inventory X2 = STAI-X2 ) . Lorazepam treatment result ed in descriptively , but not significantly , greater improvement on the Hamilton Rating Scale for Anxiety during the whole treatment ( week 0–4 ) and taper period ( week 5 , 6 ) than did buspirone . After treatment with active drugs had been discontinued , the 4-week placebo control period showed buspirone-treated patients to display a stability of clinical improvement , while the symptoms of lorazepam-treated patients worsened at week 7–10 . Both buspirone and lorazepam were more efficacious in reducing anxiety symptoms than placebo during the treatment and taper period ; however , in contrast to the active drugs ( buspirone , lorazepam ) , patients of the placebo group showed further clinical improvement during the control period , especially in the HAM-A score , so differences between placebo and active drugs became smaller at the end of the study",
"OBJECTIVE The authors sought to observe the long-term clinical course of anxiety disorders over 12 years and to examine the influence of comorbid psychiatric disorders on recovery from or recurrence of panic disorder , generalized anxiety disorder , and social phobia . METHOD Data were drawn from the Harvard/Brown Anxiety Disorders Research Program , a prospect i ve , naturalistic , longitudinal , multicenter study of adults with a current or past history of anxiety disorders . Probabilities of recovery and recurrence were calculated by using st and ard survival analysis methods . Proportional hazards regression analyses with time-varying covariates were conducted to determine risk ratios for possible comorbid psychiatric predictors of recovery and recurrence . RESULTS Survival analyses revealed an overall chronic course for the majority of the anxiety disorders . Social phobia had the smallest probability of recovery after 12 years of follow-up . Moreover , patients who had prospect ively observed recovery from their intake anxiety disorder had a high probability of recurrence over the follow-up period . The overall clinical course was worsened by several comorbid psychiatric conditions , including major depression and alcohol and other substance use disorders , and by comorbidity of generalized anxiety disorder and panic disorder with agoraphobia . CONCLUSIONS These data depict the anxiety disorders as insidious , with a chronic clinical course , low rates of recovery , and relatively high probabilities of recurrence . The presence of particular comorbid psychiatric disorders significantly lowered the likelihood of recovery from anxiety disorders and increased the likelihood of their recurrence . The findings add to the underst and ing of the nosology and treatment of these disorders",
"OBJECTIVE Patients with generalized anxiety disorder ( N=107 ) who had been long-term benzodiazepine users ( average duration of use=8.5 years ) were enrolled in a benzodiazepine discontinuation program that assessed the effectiveness of concomitant imipramine ( 180 mg/day ) and buspirone ( 38 mg/day ) compared to placebo in facilitating benzodiazepine discontinuation . METHOD After a benzodiazepine stabilization period taking either diazepam , lorazepam , or alprazolam , patients were treated for 4 weeks with imipramine , buspirone , or placebo under double-blind conditions while benzodiazepine intake was kept stable ( treatment phase ) . Patients then entered a 4 - 6 week benzodiazepine taper and a 5-week posttaper phase with imipramine , buspirone , and placebo treatment being continued until 3 weeks into the posttaper phase , at which time all patients were switched to placebo for 2 weeks . Benzodiazepine plasma levels were assayed weekly . Benzodiazepine-free status was assessed 3 and 12 months posttaper . RESULTS Study subjects were long-term benzodiazepine users with an average of three unsuccessful prior taper attempts . The success rate of the taper in this study was significantly higher for patients who received imipramine ( 82.6 % ) , and nonsignificantly higher for patients who received buspirone ( 67.9 % ) , than for patients who received placebo ( 37.5 % ) . The imipramine effect remained highly significant even after the analysis adjusted for three other independent predictors of taper success : benzodiazepine dose , level of anxious symptoms at baseline , and duration of benzodiazepine therapy . CONCLUSIONS Management of benzodiazepine discontinuation can be facilitated significantly by co-prescribing imipramine before and during the benzodiazepine taper . Daily benzodiazepine dose , severity of baseline symptoms of anxiety and depression , and duration of benzodiazepine use were additional significant predictors of successful taper outcome",
"This multicentre study was conducted to evaluate the efficacy and consequences of progressive or abrupt withdrawal of clobazam in the treatment of Generalized Anxiety Disorder in a double blind study in comparison to lorazepam and buspirone . 128 out patients suffering from Generalized Anxiety Disorder according to DMS III criteria were included in the study and treated for three weeks . They were r and omly divided into 4 groups : group 1 : 32 patients receiving clobazam , abruptly withdrawn and replaced by a placebo ; group 2 : 29 patients receiving clobazam with progressive withdrawal over 3 weeks , clobazam being replaced by a placebo ; group 3 : 33 patients receiving lorazepam with progressive withdrawal over 3 weeks , lorazepam being replaced by a placebo ; group 4 : 34 patients receiving buspirone , abruptly withdrawn and replaced by a placebo . The dosages were increased progressively during the first week of treatment . At the end of this time , the patients received either 30 mg clobazam or 30 mg buspirone or 3 mg lorazepam daily . After the first week , the Hamilton Anxiety Rating Scale ( HARS ) showed a significant improvement in clobazam and lorazepam groups but not in buspirone group . All the drugs were equally effective after three weeks of treatment . The anti-anxiety activity persisted after withdrawal of the studied drug in the 4 groups , without any signs of rebound anxiety or withdrawal syndrome . No clinical ly relevant differences were found between the 4 groups regarding safety . The side-effects reported were mainly drowsiness in clobazam and lorazepam groups , nausea and headache in buspirone group . In conclusion , clobazam like lorazepam improved anxiety more quickly than buspirone ; after 3 weeks of therapy , efficacy was comparable with the 3 drugs and persisted after treatment discontinuation",
"In double-blind trials with hundreds of patients , buspirone has proven to be as effective an anxiolytic as the benzodiazepines . It causes less sedation and motor impairment than diazepam , and may be particularly useful in geriatric patients . We conducted a 4 week double-blind , r and omized trial of buspirone versus diazepam and placebo in thirty adult out patients with generalized anxiety disorder . Maximum doses were 40 mg of diazepam or buspirone or eight placebo tablets a day . There were no significant differences in outcome between the three groups on any physician or subject measures . Some implication s of this finding are discussed",
"In a 8-week double-blind placebo controlled study , 48 out patients with generalized anxiety disorder were r and omized to diazepam , buspirone , a non-benzodiazepine anxiolytic , or placebo . During the treatment phase of 4 weeks duration diazepam was found to be significantly better than placebo and buspirone . Following abrupt withdrawal by placebo substitution the diazepam group showed a gradual relapse maximal after two weeks while the buspirone and the placebo groups did not differ . There were more cases of rebound anxiety with diazepam as compared to buspirone or placebo . In addition , there were three early terminations related to rebound anxiety in the diazepam group while there were none in the placebo and buspirone groups . There were significantly more new symptoms in the diazepam group than in the placebo or buspirone group",
"Abstract The efficacy of hydroxyzine and buspirone , controlled by placebo , was investigated in a double-blind , parallel group , multicentre study conducted in France and the UK . A total of 244 patients with generalised anxiety disorder in primary care was allocated r and omly to treatments with hydroxyzine ( 12.5 mg morning and mid-day , 25 mg evening ) , buspirone ( 5 mg morning and mid-day , 10 mg evening ) or placebo ( three capsules/day ) for 4 weeks , preceded by a 1-week single-blind placebo run-in and followed by 1-week single-blind placebo administration . Rating scales were applied on days -7,0,7,14,12,28 and 35 . Seventy percent of the patients were female ; the average age was 41 ± 11 years , and the mean Hamilton Anxiety Score at day 0 was 26.5 ± 4.2 . Only 31 of the 244 patients dropped out , but equally in the three groups . Intention-to-treat LOCF analyses on the primary variable showed a significant difference only between hydroxyzine and placebo with respect to improvement on the Hamilton Anxiety Scale ( 10.75 versus 7.23 points , respectively ) . Secondary variables such as CGI and self-ratings ( HAD scale ) showed both hydroxyzine and buspirone to be more efficacious than placebo . Thus , hydroxyzine is a useful treatment for GAD",
" One hundred and sixty patients ( mean age 39.8 years ; 67 % female ) diagnosed with generalized anxiety disorder ( GAD ) who had completed a prospect i ve , 8 week , double-blind comparison of lorazepam ( mean daily dose 4.2 mg ) and ipsapirone ( mean daily dose 19.5 mg ) were rapidly tapered by a substitution of half-strength medication for 3 days , then substitution of matched placebo for an additional 11 days . Patients treated with ipsapirone showed no rebound anxiety on discontinuation , nor any other significant increase in withdrawal symptomatology compared to patients who had been prospect ively treated with placebo . In contrast , patients treated with lorazepam showed significant emergent anxiety and /or withdrawal-related symptomatology by almost all clinical measures employed . Overall , 25 % of patients treated with lorazepam showed rebound anxiety , and 40 % of them utilized reserve medication because they found drug discontinuation to be intolerable . The clinical implication s for discontinuation of benzodiazepines after short-term therapy are discussed",
"BACKGROUND The development of effective and well-tolerated anxiolytic agents is an area of critical clinical importance . Abecarnil , a beta carboline , is a partial benzodiazepine-receptor agonist that has demonstrated promise as an anxiolytic agent . In this study , we examine the efficacy , safety , and discontinuation-related effects of abecarnil , buspirone , and placebo in the acute and long-term treatment of patients who have generalized anxiety disorder . METHOD This is a double-blind , placebo-controlled study of two dosages of abecarnil and buspirone . In total , 464 patients were r and omized . After a placebo run-in week , patients entered a 6-week double-blind treatment period , followed by an optional 18-week maintenance period for treatment responders . After abrupt discontinuation of the acute or maintenance treatment , patients entered a 3-week placebo-substitution follow-up period . Treatment response was assessed with the Hamilton Rating Scale for Anxiety and the Clinical Global Impressions ( CGI ) Scale . RESULTS Compared with placebo , abecarnil showed significant anxiolytic activity early in the treatment period , particularly in the high-dosage group , though these differences did not maintain statistical significance at the end of the trial . Buspirone was associated with a slower onset of action and better symptom relief than placebo after 6 weeks of therapy . Withdrawal symptoms emerged in patients who abruptly discontinued abecarnil ( particularly at the higher dosage ) only in those receiving a longer duration of treatment . CONCLUSION The results of this study need to be understood in the context of a high placebo-response rate , which hampers the ability to demonstrate significant drug-placebo differences . This study suggests that abecarnil may be an effective anxiolytic agent ; further attention is warranted to assess its spectrum of clinical effectiveness",
"OBJECTIVE An 8-week r and omized , reference-controlled , double-blind , multi-centre clinical trial investigated Kava-Kava LI 150 in Generalized Anxiety Disorder ( GAD ; ICD-10 : F41.1 ) . METHOD 129 out- patients received either 400 mg Kava LI 150 , 10 mg Buspirone or 100 mg Opipramol daily for 8 weeks . At week 9 , subjects were seen to check for symptoms of withdrawal or relapse . Primary outcome measures comprised the HAMA scale and the proportion of responders at week 8 . Secondary measures were the Boerner Anxiety Scale ( BOEAS ) , SAS , CGI , a self-rating scale for well-being ( Bf-S ) , a sleep question naire ( SF-B ) , a quality -of-life question naire ( AL ) and global judgements by investigator and patients . RESULTS In 127 patients ( ITT ) no significant differences could be observed regarding all efficacy and safety measures . About 75 % of patients were classified as responders ( 50 % reduction of HAMA score ) in each treatment group , about 60 % achieved full remission . CONCLUSION Kava-Kava LI150 is well tolerated and as effective as Buspirone and Opipramol in the acute treatment of out- patients suffering from GAD",
"Buspirone is an antianxiety compound that has been extensively evaluated in clinical trials : it has proved superior to placebo and comparable to diazepam in the treatment of patients with generalized anxiety disorder . In this study , 33 out patients with generalized anxiety disorder were entered into a crossover study of 3 weeks each of placebo , buspirone 10 to 30 mg daily , and diazepam 10 to 30 mg daily . Psychiatrist and patient ratings were made , together with psychological tests and EEG and skin conductance measures before and after each treatment . Of the nine dropouts , six were on buspirone at the time of dropout . For the remaining 24 patients , the mean daily doses attained of buspirone and diazepam were both 20 mg . On most clinical ratings diazepam was superior to buspirone and placebo , which did not differ . Diazepam produced minor psychomotor changes and the expected major effects on the EEG . Buspirone was without effect . Side effects on buspirone were mainly nausea and giddiness and on diazepam , drowsiness . The lack of efficacy of buspirone is discussed in terms of the previous benzodiazepine exposure--23/24 patients had had previous exposure and only 10 were able to tolerate a pretrial placebo washout period . The implication s are considerable for the introduction of any new antianxiety agent not cross-tolerant with the benzodiazepines into a chronically anxious group of patients with previous long-term benzodiazepine therapy",
"1 . The purpose of this study was to compare the effects and abrupt discontinuation of buspirone 15 or 20 mg tid and lorazepam 3 or 4 mg tid following 8 weeks of treatment . A total of 43 out patients with generalized anxiety disorder were included in the study and 39 entered the withdrawal phase . 2 . Clinical assessment s were performed at baseline , 2 , 4 , 6 and 8 weeks ( active phase ) and after 9 and 10 weeks ( withdrawal phase ) . These included the Hamilton anxiety scale , the visual analogue scale , the CHESS 84 ( a check list for the evaluation of somatic symptoms ) and the Lader tranquilizer withdrawal scale ( translated in french ) . 3 . Results show similar efficacy for lorazepam and buspirone during the active phase with a higher significant difference for buspirone on the CHESS 84 in relation with neurovegetatives symptoms : lorazepam D0 : 16.30 + /- 3.14 D56 : 5.10 + /- 0.93 ( p buspirone D0 : 18.82 + /- 3.4 D56 : 4.73 + /- 1.18 ( p withdrawal phenomena was observed for both drugs using HAM-A lorazepam D63 : 12.59 + /- 2.26 D70 : 12.0 + /- 1.75 ( p = ns ) buspirone D63 : 10.05 + /- 1.28 D70 : 10.32 + /- 1.82 ( p = ns ) and the same significant difference using Lader scale : lorazepam D63 : 4.44 + /- 0.89 D70 : 6.96 + /- 1.28 ( p buspirone D63 : 2.95 + /- 0.66 D70 : 4.15 + /- 0.92 ( p buspirone was as effective as lorazepam at D56 in monitored out patients with generalized anxiety disorder . ( ABSTRACT TRUNCATED AT 250 WORDS",
"This r and omized , double-masked , comparative study evaluated the efficacy and safety of buspirone 30 mg/d , administered twice a day ( BID ) or three times a day ( TID ) , in patients with generalized anxiety disorder ( GAD ) , commonly called persistent anxiety . Patients who participated had GAD according to criteria of the Diagnostic and Statistical Manual of Mental Disorders . Third Edition , Revised , modified to include patients for whom the symptom duration was at least 4 weeks and scored > or = 18 on the Hamilton Rating Scale for Anxiety ( HAM-A ) . After a 7-day placebo lead-in phase , patients who continued to qualify were r and omized to receive buspirone , titrated from 15 mg/d ( 5 mg TID ) to 30 mg/d , as either a BID or TID regimen , for 8 weeks . Of the 137 patients who began the study , 120 patients were included in the data evaluation . Both buspirone BID and TID treatment groups demonstrated significant reductions in mean HAM-A total scores and improvement on Clinical Global Impression measures , with no significant differences detected between the two treatment groups for either measure at any time point . The overall incidence of adverse events was similar for both treatment groups , except for a significantly greater incidence of amblyopia in patients receiving buspirone 15 mg BID . In summary , there was no appreciable difference in efficacy or safety between buspirone 15 mg BID or 10 mg TID in patients with persistent anxiety"
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41187d5e-06ff-11f0-808a-c43d1ab1c353
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OBJECTIVE To eluci date the benefits of using probiotics in the prevention of necrotizing enterocolitis ( NEC ) and its complications in preterm newborns . METHOD This was a systematic review of r and omized controlled trials , which included studies retrieved from three data bases ( MEDLINE , Embase , and LILACS ) , using a combination of the terms ( necrotizing enterocolitis ) AND ( probiotics ) . RESULTS 11 r and omized trials were included , totaling 2,887 patients , 1,431 in the probiotic group and 1,456 in the control group . There was a reduction in the incidence of NEC ( NNT=25 ) , overall death ( NNT=34 ) , and neonatal sepsis ( NNT=34 ) in the probiotic group compared to the control group . Patients that received probiotic supplementation had lower food re introduction time ( p hospitalization time ( p probiotics . There was no difference in mortality caused by NEC . CONCLUSION In premature newborns , the use of probiotics is effective as a prophylaxis for NEC and its complications
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"UNLABELLED The aim of the study is to compare the role of killed ( KP ) Lactobacillus acidophilus with living ( LP ) in reducing incidence of sepsis ( NS ) and necrotizing enterocolitis ( NEC ) in neonates . R and omized double blind placebo study , included 150 neonates admitted to NICU at day 1 , sixty received oral ( LP ) and 60 received ( KP ) and 30 received placebo . One gram of stools was collected on admission , at day 7 , at end of the study , as well as on suspected NEC or NS and was sent for culture . RESULTS LP and KP were preventive factors for NEC with absolute risk reduction ( AAR ) 16 , 15 % , respectively and 18 % for NS compared to placebo . Incidence of NEC and NS did not differ significantly between neonates supplemented with LP and those with KP . Preterm neonates supplemented with KP showed significantly lower incidence of NEC compared to placebo , while incidence of NS showed no significant difference between both groups . There is significant reduction in NS and NEC among neonates with positive Lactobacillus colonization of gut compared to those none colonized at day 7 ( 27.9 vs. 85.9 % , 0 vs. 7.8 % ) and at day 14 ( 48.7 vs. 91.7 % for NS and 0 vs. 20.8 % for NEC ) . Overall comparison between the three groups showed statistical significant reduction in the incidence of NEC . Present conclusions are that early gut colonization with beneficial bacteria lowers the incidence of NEC and NS . KP retained similar benefits to live bacteria",
"ABSTRACT The gastrointestinal microbiota of preterm infants in a neonatal intensive care unit differs from that of term infants . In particular , the colonization of preterm infants by bifidobacteria is delayed . A double-blind , placebo-controlled , r and omized clinical study was performed on 69 preterm infants to investigate the role of Bifidobacterium lactis Bb12 supplementation in modifying the gut microbiota . Both culture-dependent and culture-independent approaches were used to study the gut microbiota . Bifidobacterial numbers , determined by fluorescence in situ hybridization , were significantly higher in the probiotic than in the placebo group ( log10 values per g of fecal wet weight : probiotic , 8.18 + 0.54 [ st and ard error of the mean ] ; placebo , 4.82 + 0.51 ; P bifidobacterial numbers was also obtained with the culture-dependent method . The infants supplemented with Bb12 also had lower viable counts of Enterobacteriaceae ( log10 values of CFU per g of fecal wet weight : probiotic , 7.80 + 0.34 ; placebo , 9.03 + 0.35 ; P = 0.015 ) and Clostridium spp . ( probiotic , 4.89 + 0.30 ; placebo , 5.99 + 0.32 ; P = 0.014 ) than the infants in the placebo group . Supplementation of B. lactis Bb12 did not reduce the colonization by antibiotic-resistant organisms in the study population . However , the probiotic supplementation increased the cell counts of bifidobacteria and reduced the cell counts of enterobacteria and clostridia",
"BACKGROUND It is known that the bifidobacteria flora play important roles in mucosal host defense and can prevent infectious diseases . Because bacterial population s develop during the first day of life , the authors examined whether the early administration of bifidobacteria has a positive effect on the health of low birth weight infants . METHODS The effects of oral administration of Bifidobacterium breve ( B. breve ) supplements were studied in a controlled trial with low birth weight infants ( average birth weight 1489 g ) . The infants were divided into three groups : Group A and B received a dose of 1.6 x 10(8 ) cells of B. breve supplement twice a day , commencing either from several hours after birth ( group A ) or 24 h after birth ( group B ) . Group C , the control group , received no supplement . RESULTS There were no significant differences in birth weight , treatment with antibiotics , and the starting time of breast-feeding among the three groups . A Bifidobacterium-predominant flora was formed at an average of 2 weeks after birth in group A and at an average of 4 weeks after birth in group B , while no Bifidobacterium was isolated in eight out of 10 infants in group C during the observation period of 7 weeks . In comparison between group A and B , Bifidobacterium was detected significantly earlier in group A , and the number of Enterobacteriaceae present in the infants at 2 weeks after birth was significantly lower in group A. CONCLUSION The results of the present study suggest that very early administration of B. breve to low birth weight infants is useful in promoting the colonization of the Bifidobacterium and the formation of a normal intestinal flora",
"Necrotizing enterocolitis ( NEC ) continues to be a major cause of morbidity and mortality in premature infants . Although the pathogenesis of NEC remains unclear , abnormal bacterial colonization has been postulated as playing a central role . Various factors impact bacterial colonization following delivery . Compared to term infants , the bacterial colonization pattern in prematurely born infants is markedly different , with a greater predilection for colonization with pathogenic bacteria . Probiotic and prebiotic administration offers the opportunity to manipulate the intestinal bacterial environment , favoring the growth of commensal bacteria . Experimental data from animal studies and data from human trials suggest that probiotics decrease the incidence of NEC . These preliminary studies support the need for a large , r and omized , controlled trial to further investigate the role of probiotics in the prevention of NEC",
"Background : Nosocomial infections endanger preterm infants . Objective : The aim of the present controlled r and omized trial was to investigate whether Bifidobacterium lactis reduces the incidence of nosocomial infections in infants with very low birth weight ( VLBW ; Patients and Methods : In a r and omized controlled trial , 183 VLBW infants were stratified according to gestational age ( 23–26 and 27–29 weeks ) and early antibiotic therapy ( days 1–3 , yes or no ) and r and omly assigned to have their milk feedings supplemented with B. lactis ( 6 × 2.0 × 109 CFU/kg/day , 12 billion CFU/kg/day ) or placebo for the first 6 weeks of life . Primary outcome was the ‘ incidence density ’ of nosocomial infections defined as periods of elevated C-reactive protein ( > 10 mg/l ) from day 7 after initiation of milk feedings until the 42nd day of life ( number of nosocomial infections/total number of patient days ) . The main secondary outcome was necrotizing enterocolitis ( NEC ; ≧stage 2 ) . Results : There were 93 infants in the B. lactis group and 90 in the placebo group . There was no significant difference between the two groups with regard to the incidence density of nosocomial infections ( 0.021 vs. 0.016 ; p = 0.9 , χ2 test ) . There were 2 cases of NEC in the B. lactis group and 4 in the placebo group . None of the blood cultures grew B. lactis . Conclusion : In the present setting , B. lactis at a dosage of 6 × 2.0 × 109 CFU/kg/day ( 12 billion CFU/kg/day ) did not reduce the incidence density of nosocomial infections in VLBW infants . No adverse effect of B. lactis was observed",
"BACKGROUND Saccharomyces boulardii ( SB ) is a yeast that acts both as a probiotic and as a polyamine producer . Probiotics prevent the overgrowth of pathogens in the gut while polyamines enhance intestinal maturation . The aim of this r and omized study was to investigate the ability of SB to modify the gut microbial ecology and its function . METHODS A total of 87 healthy babies with gestational age 28 - 32 weeks were studied . They were r and omly assigned to receive a preterm formula to which SB or maltodextrins was added for 30 days . Evaluations were made on the following : SB tolerance and weight gain , faecal flora analysis , intestinal D-xylose absorption and faecal lipid excretion . RESULTS SB was well tolerated by the infants . There was no difference in weight gain between the two groups . Median log of colony forming units per gram of faeces for Escherichia coli and enterococci was significantly lower in the SB group [ E. coli : 2.67 ( 0.045 ) vs. 2.75 ( 0.058 ) , P number of bifidobacteria and staphylococci in the stools was significantly higher in the SB group [ bifidobacteria : 2.65 ( 0.083 ) vs. 2.27 ( 0.075 ) , P D-Xylose and lipid absorption was not improved by SB [ median blood D-xylose : 1.5 ( 0.4 ) mmol/l vs. 1.35 ( 0.3 ) mmol/l , P>0.1 ; median stool steatocrit : 64 % ( 3.05 % ) vs. 65 % ( 2.72 % ) P>0.5 ] . CONCLUSIONS An SB-supplemented formula is well tolerated by preterm infants , it has a beneficial effect on stool flora bringing it closer to that of breast fed babies but it does not improve D-xylose or lipid gut absorption",
"The objectives of this study were to determine whether or not the probiotic Lactobacillus GG can colonise the immature bowel of premature infants and if so , does colonisation result in a reduction of the size of the bowel reservoir of nosocomial pathogens such as enterobacteriaceae , enterococci , yeasts or staphylococci , and does colonisation with Lactobacillus GG have any effect on the clinical progress and outcome . Twenty preterm infants with a gestational age of 33 weeks or less who were resident on a neonatal unit were studied from the initiation of milk feeds until discharge . The infants were r and omised to receive either milk feeds or milk feeds supplemented with Lactobacillus GG 10(8 ) colony forming units twice a day for two weeks . The clinical features of the two groups of infants were similar . Orally administered Lactobacillus GG was well tolerated and did colonise the bowel of premature infants . However , colonisation with Lactobacillus GG did not reduce the faecal reservoir of potential pathogens and there was no evidence that colonisation had any positive clinical benefit for this particular group of infants",
"BACKGROUND Preterm infants have increased intestinal permeability which can render them susceptible to infections from enterobacteriae . OBJECTIVES The primary objective was to investigate whether probiotic administration to preterm infants decreases intestinal permeability . Secondary outcomes studied were : somatic growth , tolerance , rates of sepsis and necrotizing enterocolitis . METHODS In a prospect i ve r and omized case-control study 41 stable preterm infants of 27 to 36 weeks gestation and 34 matched comparison infants consecutively admitted to the neonatal unit were studied . The study group received a preterm formula supplemented with Bifidobacter lactis ( 2 x 10(7 ) cfu/g of dry milk ) while the control group received the same formula but without supplementation . Intestinal permeability was measured within two days of birth and then seven and thirty days later using the sugar absorption test . Additionally anthropometric parameters were recorded throughout the study as well as acceptance and tolerance of the formula . RESULTS All infants tolerated the study formula well . Median counts of stool bifidobacteria and lactulose/mannitol ratios at baseline were comparable . After 7 days of supplementation median bifidobacteria counts were significantly higher in the study group than in the control group ( p=0.0356 ) and they remained higher to the end of the study ( p at day 30=0.075 ) . The L/M ratio in the study group was significantly lower at day 30 of the study as compared to the control group ( p=0.003 ) . Head growth was significantly higher in the study group ( p=0.001 ) . CONCLUSIONS The administration of a bifidobacter supplemented infant formula decreases intestinal permeability of preterm infants and leads to increased head growth",
"Studies were carried out on premature infants in the neonatal intensive care unit to determine the effect of feeding of lactobacilli on colonization of the gastrointestinal tract by antibiotic-resistant gram-negative enteric organisms . Thirty premature infants were matched by birth weight and gestational age , r and omized and fed double blind either lactobacilli-containing formula or non-lactobacilli-containing formula within 72 hours of delivery . The two study groups were screened weekly by culture for stool lactobacilli , for gram-negative bacteria and for antibiotic resistance of these bacteria . Lactobacilli were cultured from the stools of 13 of 15 patients receiving lactobacilli and from 3 of 15 patients not receiving lactobacilli ( P Gram-negative enteric organisms were isolated during 40 of the 86 weeks ( 47 % ) of hospitalization for patients receiving lactobacilli and during 28 of 57 weeks ( 49 % ) for patients not receiving lactobacilli . There was no significant difference between the study groups in the number of resistant organisms or in the proportion of resistant organisms per gram-negative enteric isolates ( 4 of 40 vs. 0 of 28 ) . These results suggest that facultative gram-negative enteric bacterial colonization , with either total or aminoglycoside-resistant strains , is not decreased by oral feedings of Lactobacillus acidophilus in premature infants",
"Background : It has been suggested that probiotics can reduce the overgrowth of pathogens in the bowels of preterm infants and contribute to the reduction of the incidence of nosocomial infections in neonatal intensive care units ( NICUs ) . The purpose of this study was to evaluate the effectiveness of Lactobacillus GG supplementation in reducing the incidence of urinary tract infections ( UTIs ) , bacterial sepsis and necrotizing enterocolitis ( NEC ) in preterm infants . Methods : A double-blind study was conducted in 12 Italian NICUs . Newborn infants with a gestational age were r and omized to receive st and ard milk feed supplemented with Lactobacillus GG ( Dicoflor ® , Dicofarm , Rome , Italy ) in a dose of 6 × 109 colony-forming units ( cfu ) once a day until discharge , starting with the first feed or placebo . Results : Five hundred eighty-five patients were studied . The probiotics group ( n = 295 ) and the placebo group ( n = 290 ) exhibited similar clinical characteristics . The duration of Lactobacillus GG and placebo supplementation was 47.3 ± 26.0 and 48.2 ± 24.3 days , respectively . Although UTIs ( 3.4 vs. 5.8 % ) and NEC ( 1.4 vs. 2.7 % ) were found less frequently in the probiotic group compared to the control group , these differences were not significant . Bacterial sepsis was more frequent in the probiotics group ( 4.4 % , n = 11 ) than in the placebo group ( 3.8 % , n = 9 ) , but the difference was not significant . Conclusion : Seven days of Lactobacillus GG supplementation starting with the first feed is not effective in reducing the incidence of UTIs , NEC and sepsis in preterm infants . Further studies are required to confirm our results in lower birthweight population",
"BACKGROUND Colonization by C and ida species is the most important predictor of the development of invasive fungal disease in preterm neonates , and the enteric reservoir is a major site of colonization . We evaluated the effectiveness of an orally supplemented probiotic ( Lactobacillus casei subspecies rhamnosus ; Dicoflor [ Dicofarm spa ] ; 6 x 10(9 ) cfu/day ) in the prevention of gastrointestinal colonization by C and ida species in preterm , very low birth weight ( i.e. , METHODS Over a 12-month period , a prospect i ve , r and omized , blind , clinical trial that involved 80 preterm neonates with a very low birth weight was conducted in a large tertiary neonatal intensive care unit . During the first 3 days of life , the neonates were r and omly assigned to receive either an oral probiotic added to human ( maternal or pooled donors ' ) milk ( group A ) or human milk alone ( group B ) for 6 weeks or until discharge from the NICU , if the neonate was discharged before 6 weeks . On a weekly basis , specimens obtained from various sites ( i.e. , oropharyngeal , stool , gastric aspirate , and rectal specimens ) were collected from all patients for surveillance culture , to assess the occurrence and intensity of fungal colonization in the gastrointestinal tract . RESULTS The incidence of fungal enteric colonization ( with colonization defined as at least 1 positive culture result for specimens obtained from at least 1 site ) was significantly lower in group A than in group B ( 23.1 % vs. 48.8 % ; relative risk , 0.315 [ 95 % confidence interval , 0.120 - 0.826 ] ; P = .01 ) . The numbers of fungal isolates obtained from each neonate ( P = .005 ) and from each colonized patient ( P = .005 ) were also lower in group A than in group B. L. casei subspecies rhamnosus was more effective in the subgroup of neonates with a birth weight of 1001 - 1500 g. There were no changes in the relative proportions of the different C and ida strains . No adverse effects potentially associated with the probiotic were recorded . CONCLUSIONS Orally administered L. casei subspecies rhamnosus significantly reduces the incidence and the intensity of enteric colonization by C and ida species among very low birth weight neonates",
"Background / Objective : The identification of probiotic species involved in gut homeostasis and their potential therapeutic benefits have led to an interest in their use for preventing necrotizing enterocolitis ( NEC ) . Although bifidobacterium and lactobacilli sp. have been used to reduce the incidence of NEC in clinical trials . Lactobacillus sporogenes has not been used in the prevention of NEC in very low-birth weight infants yet . The objective of this study was to evaluate the efficacy of orally administered L sporogenes in reducing the incidence and severity of NEC in very low-birth weight ( VLBW ) infants . Subjects/ Methods : A prospect i ve , blinded , r and omized controlled trial was conducted in preterm infants with a gestational age of The infants in the study group were given L. sporogenes with a dose of 350 000 000 c.f.u . added to breast milk or formula , once a day , starting with the first feed until discharged . The infants in the control group were fed without L. sporogenes supplementation . The primary outcome measurement was death or NEC ( Bell 's stage ⩾2 ) . Results : A total of 221 infants were studied : 110 in the study group and 111 in the control group . There was no significant difference in the incidence of death or NEC between the groups . Feeding intolerance was significantly lower in the probiotics group than in the control group ( 44.5 % ( n : 49 ) vs 63.1 % ( n : 70 ) , respectively ; P=0.006 ) . Conclusions : L. sporogenes supplementation at the dose of 350 000 000 c.f.u/day is not effective in reducing the incidence of death or NEC in VLBW infants , however , it could improve the feeding tolerance ",
"BACKGROUND Although recent reports suggest that supplementation with probiotics may enhance intestinal function in premature infants , the mechanisms are unclear , and questions remain regarding the safety and efficacy of probiotics in extremely low-birth-weight infants . OBJECTIVE The objective was to evaluate the efficacy of probiotics on the digestive tolerance to enteral feeding in preterm infants born with a very low or extremely low birth weight . DESIGN In a bicentric , double-blind , r and omized controlled clinical trial that was stratified for center and birth weight , 45 infants received enteral probiotics ( Bifidobacterium longum BB536 and Lactobacillus rhamnosus GG ; BB536-LGG ) and 49 received placebo . The primary endpoint was the percentage of infants receiving > 50 % of their nutritional needs via enteral feeding on the 14th day of life . A triangular test was used to perform sequential analysis . RESULTS The trial was discontinued after the fourth sequential analysis concluded a lack of effect . The primary endpoint was not significantly different between the probiotic ( 57.8 % ) and placebo ( 57.1 % ) groups ( P = 0.95 ) . However , in infants who weighed > 1000 g , probiotic supplementation was associated with a shortening in the time to reach full enteral feeding ( P = 0.04 ) . Other than colonization by the probiotic strains , no alteration in the composition of intestinal microbiota or changes in the fecal excretion of calprotectin was observed . No colonization by probiotic strains was detected in infants who weighed gastrointestinal tolerance to enteral feeding in very-low-birth-weight infants but may improve gastrointestinal tolerance in infants weighing > 1000 g. This trial was registered at clinical trials.gov as NCT 00290576",
"AIM To investigate the colonisation withBifidobacterium breve of the bowels of very low birthweight ( VLBW ) infants . METHODS The adverse effects of B breve were examined in 66 VLBW infants ( preliminary study ) . A prospect i ve r and omised clinical study of 91 VLBW infants was also completed and these infants were followed up for three years . Precise viable bacterial counts of serial stool specimens were examined for the first eight weeks after birth in 10 infants . The colonisation rates of administered bacteria were examined using immunohistochemical staining of stool specimens with a B breve specific monoclonal antibody . RESULTS In the preliminary study there were no side effects attributable to the bacteria . Immunohistochemical staining of stool specimens showed that the colonisation rates of the administered bacteria were 73 % at 2 weeks of age , but only 12 % in the control group . Early administration of B brevesignificantly decreased aspirated air volume from the stomach and improved weight gain . CONCLUSIONS B breve can colonise the immature bowel very effectively and is associated with fewer abnormal abdominal signs and better weight gain in VLBW infants , probably as a result of stabilisation of their intestinal flora and accelerated feeding schedules",
"Objective : To compare the effect of 2 prebiotic/probiotic products on weight gain , stool microbiota , and stool short-chain fatty acid ( SCFA ) content of premature infants . Patients and Methods : This r and omized , blinded , placebo-controlled trial included 90 premature infants treated with either a dietary supplement containing 2 lactobacillus species plus fructooligosaccharides ( CUL , Culturelle , ConAgra , Omaha , NE ) , a supplement containing several species of lactobacilli and bifidobacteria plus fructooligosaccharides ( PBP , ProBioPlus DDS , UAS Laboratories , Eden Prairie , MN ) , or placebo ( a dilute preparation of Pregestamil formula ) twice daily for 28 days or until discharge if earlier . The primary outcome was weight gain . Secondary outcomes were stool bacterial analysis by culture and 16S rDNA quantitative polymerase chain reaction and stool SCFA content measured by high performance liquid chromatography . Results : Both prebiotic/probiotic combinations contained more bacterial species than noted on the label . No significant effect on infant growth of either prebiotic/probiotic supplement was observed . By cultures , 64 % of infants receiving PBP became colonized with bifidobacteria , compared with 18 % of infants receiving CUL and 27 % of infants receiving placebo ( chi-square , P = 0.064 ) . No differences were noted between groups in colonization rates for lactobacilli , Gram-negative enteric bacteria , or staphylococci . By 16S rDNA polymerase chain reaction analysis , the bifidobacteria content in the stools of the infants receiving PBP was higher than in the infants receiving CUL or placebo ( Kruskal-Wallis , P = 0.011 ) . No significant differences in stool SCFA content were detected between groups . No adverse reactions were noted . Conclusions : Infants receiving PBP were more likely to become colonized with bifidobacteria . No significant differences in weight gain or stool SCFA content were detected"
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QUESTION What is the optimal chemotherapy regimen in advanced gastric cancer ? PERSPECTIVES Gastric cancer is the second leading cause of cancer mortality worldwide . Despite low incidence rates for gastric cancer in Ontario , the overall prognosis is bleak , with 5-year survival rates of approximately 23 % in Canada . Even with the considerable body of research available on chemotherapy for advanced gastric cancer , uncertainty remains . There is no recognized st and ard treatment , and there appears to be geographic variation in practice . OUTCOMES Outcomes of interest were overall survival , objective response rate ( complete plus partial responses ) , time to disease progression , adverse effects , and quality of life . METHODOLOGY After a systematic review , a practice guideline containing clinical recommendations relevant to patients in Ontario was drafted . The practice guideline was review ed and approved by the Gastrointestinal Disease Site Group ( gi dsg ) and the Report Approval Panel of the Program in Evidence -Based Care . External review by Ontario practitioners was obtained through a survey , the results of which were incorporated into the practice guideline . PRACTICE GUIDELINE The gi dsg makes the following recommendations : To improve survival , a platinum agent should be included in any combination chemotherapy regimen . Within a combination chemotherapy regimen , oral capecitabine is preferred over intravenous 5-fluorouracil (5fu)-that is , epirubicin-cisplatin-capecitabine is preferred over the prior st and ard regimen , epirubicin-cisplatin-5fu (ecf).Epirubicin-oxaliplatin-capecitabine ( eox ) is a reasonable alternative to ecf . The choice between ecf and eox should be based on patient preference . Trastuzumab in combination with cisplatin and a fluoropyrimidine ( 5fu or oral capecitabine ) is recommended for advanced gastric cancer positive for the human epidermal growth factor receptor 2 ( her2/neu )
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"UNLABELLED Various chemotherapies have been used to treat inoperable gastric cancer . Most combination therapies include cisplatin ( CDDP ) and fluoropyrimidine ( 5-FUs ) , which are thought of as key drugs . In the present study , we r and omly compared mitomycin ( MMC ) and CDDP plus doxifluridine ( 5'-DFUR ) , which is an oral 5-FU and an intermediate metabolite of capecitabine ( Xeloda ) , with CDDP plus 5'-DFUR in advanced unresectable gastric cancer . Regimen A was CDDP ( 70 mg/m2 , by 2-hour intravenous drip infusion on day 1 ) , MMC ( 7 mg/m2 , injected intravenously on day 2 ) , and oral 5'-DFUR ( 1200 mg/m2 , on days 4 to 7 , 11 to 14 , 18 to 21 and 25 to 28 ; 3 days rest and 4 days administration ) . Regimen B was identical to regimen A without MMC . RESULTS The response rate was 25.0 % ( 8/32 patients ) in Regimen A , 17.2 % ( 5/29 ) in Regimen B ( p=0.541 ) . The median survival time was 241 days in Regimen A and 179 days in Regimen B ( p=0.498 ) . In Regimen A , although no significant difference was observed , end points such as response rate and suvival improved . Thus , we concluded that a r and omized controlled phase III study with more subjects should be conducted",
"BACKGROUND Irinotecan , in combination with 5-fluorouracil ( 5-FU ) or cisplatin , has demonstrated efficacy against advanced gastric cancer ( AGC ) . PATIENTS AND METHODS Chemotherapy-naive AGC patients were r and omly assigned to receive irinotecan 150 mg/m(2 ) on day 1 , leucovorin 20 mg/m(2 ) and a 22-h infusion of 5-FU 1000 mg/m(2 ) on days 1 and 2 ( ILF ) or ILF plus cisplatin 30 mg/m(2 ) on day 2 ( PILF ) . Treatment was repeated every 2 weeks . RESULTS Of 91 registered patients , 45 patients were treated with ILF and 45 with PILF . For both arms , 687 chemotherapy cycles were delivered ( median = 7 for ILF and 8 for PILF ) . Both ILF and PILF were generally well tolerated and there was no relevant difference in the occurrence of overall grade 3/4 toxic effects between the two arms . Four patients died during treatment : one in the ILF and three in the PILF arm . The objective response rate was 42 % for both arms . There was no significant difference in therapeutic efficacy between ILF and PILF with respect to progression-free survival ( 4.8 versus 6.2 months ; P = 0.523 ) and overall survival ( 10.7 versus 10.5 months ; P = 0.850 ) . CONCLUSION Both ILF and PILF are active as first-line chemotherapy for AGC . The addition of cisplatin , however , has no clear advantage over ILF",
" 30 patients with advanced metastatic gastric adenocarcinoma , having a measurable indicator lesion , were r and omized ( 1:2 ) to receive ( intravenously ) either weekly 5-fluorouracil alone ( 15 mg/kg ) or combination treatment with cyclophosphamide ( 20 mg/kg ) given on day 1 and 5-FU ( 15 mg/kg ) given weekly on weeks 2 - 5 , beginning on day 8 . The combination cycle was repeated at 6-week intervals . Although the toxic effects of therapy were similar in both arms , the addition of cyclophosphamide to the single-agent 5-FU regimen did not increase either the frequency of objective response ( 5-FU 18 % , combination 16 % ) or improve the median survival of patients with advanced measurable gastric carcinoma ( 5-FU 4.4 months , combination 5.2 months ) . Patients with pretreatment weight loss greater than 10 % had significantly ( p less than 0.05 ) shorter median survival ( 2.8 versus 5.6 months ) compared to patients without weight loss",
"BACKGROUND To compare capecitabine/cisplatin with 5-fluorouracil/cisplatin as first-line treatment for advanced gastric cancer ( AGC ) . PATIENTS AND METHODS In this r and omised , open-label , phase III study , patients received cisplatin ( 80 mg/m(2 ) i.v . day 1 ) plus oral capecitabine ( 1000 mg/m(2 ) b.i.d . , days 1 - 14 ) ( XP ) or 5-FU ( 800 mg/m(2)/day by continuous infusion , days 1 - 5 ) ( FP ) every 3 weeks . The primary end point was to confirm noninferiority of XP versus FP for progression-free survival ( PFS ) . RESULTS A total of 316 patients were r and omised to XP ( n = 160 ) or FP ( n = 156 ) . In the per- protocol population , median PFS for XP ( n = 139 ) versus FP ( n = 137 ) was 5.6 versus 5.0 months . The primary end point was met with an unadjusted hazard ratio ( HR ) of 0.81 [ 95 % confidence interval ( CI ) 0.63 - 1.04 , P Median overall survival was 10.5 versus 9.3 months for XP versus FP ( unadjusted HR = 0.85 , 95 % CI 0.64 - 1.13 , P = 0.008 versus noninferiority margin of 1.25 ) . The most common treatment-related grade 3/4 adverse events in XP versus FP patients were as follows : neutropenia ( 16 % versus 19 % ) , vomiting ( 7 % versus 8 % ) , and stomatitis ( 2 % versus 6 % ) . CONCLUSIONS XP showed significant noninferiority for PFS versus FP in the first-line treatment of AGC . XP can be considered an effective alternative to FP",
"BACKGROUND We aim ed to establish the superiority ( or noninferiority if superiority was not achieved ) in terms of time to progression ( TTP ) of irinotecan/5-fluorouracil ( IF ) over cisplatin/5-fluorouracil ( CF ) in chemonaive patients with adenocarcinoma of the stomach/esophagogastric junction . PATIENTS AND METHODS Patients received either IF : i.v . irinotecan 80 mg/m(2 ) 30 min , folinic acid 500 mg/m(2 ) 2 h , 5-fluorouracil ( 5-FU ) 2000 mg/m(2 ) 22 h , for 6/7 weeks or CF : cisplatin 100 mg/m(2 ) 1 - 3 h , with 5-FU 1000 mg/m(2)/day 24 h , days 1 - 5 , every 4 weeks . RESULTS In all , 333 patients were r and omized and treated ( IF 170 , CF 163 ) . Patient characteristics were balanced except more IF patients had Karnofsky performance status 100 % . TTP for IF was 5.0 months [ 95 % confidence interval ( CI ) 3.8 - 5.8 ] and 4.2 months ( 95 % CI 3.7 - 5.5 ) for CF ( P = 0.088 ) . Overall survival ( OS ) was 9.0 versus 8.7 months , response rate 31.8 % versus 25.8 % , time to treatment failure ( TTF ) 4.0 versus 3.4 months for IF and CF , respectively . The difference in TTF was statistically significant ( P = 0.018 ) . IF was better in terms of toxic deaths ( 0.6 % versus 3 % ) , discontinuation for toxicity ( 10.0 % versus 21.5 % ) , severe neutropenia , thrombocytopenia and stomatitis , but not diarrhea . CONCLUSION IF did not yield a significant TTP or OS superiority over CF , and the results of noninferiority of IF were borderline . However , IF may provide a viable , platinum-free front-line treatment alternative for metastatic gastric cancer",
"From January , 1985 , through January , 1987 , 165 patients with advanced gastric cancer were r and omized to receive epirubicin ( E ) alone ( 90 mg/m2 day 1 ) , 5-Fluorouracil ( 5-FU ) alone ( 500 mg/m2 days 1–5 ) , or the combination of E ( 90 mg/m2 day 1 ) and 5-FU ( 400 mg/m2 days 1–5 ) . Courses were repeated every four weeks . Patients were stratified by extent ( locally advanced vs. metastatic ) , evaluability ( measurable vs. non-measurable ) and by history of prior radiotherapy ( yes vs. no ) . R and omization to single arm epirubicin was stopped after 26 patients were enrolled . Objective responses occurred in only 1/16 ( 6 % ) of the patients treated with E alone , 1/40 ( 5 % ) with 5-FU alone and 4/33 ( 12 % ) with both 5-FU and E. There were no significant differences in all eligible patients with respect to time to progression or overall survival in the three treatment arms . Toxicity was primarily hematologic and more pronounced in the combination arm . Neither 5-FU alone , epirubicin alone , or the combination have a major impact in the treatment of gastric carcinoma",
"BACKGROUND Trastuzumab , a monoclonal antibody against human epidermal growth factor receptor 2 ( HER2 ; also known as ERBB2 ) , was investigated in combination with chemotherapy for first-line treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer . METHODS ToGA ( Trastuzumab for Gastric Cancer ) was an open-label , international , phase 3 , r and omised controlled trial undertaken in 122 centres in 24 countries . Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumours showed overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation . Participants were r and omly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin given every 3 weeks for six cycles or chemotherapy in combination with intravenous trastuzumab . Allocation was by block r and omisation stratified by Eastern Cooperative Oncology Group performance status , chemotherapy regimen , extent of disease , primary cancer site , and measurability of disease , implemented with a central interactive voice recognition system . The primary endpoint was overall survival in all r and omised patients who received study medication at least once . This trial is registered with Clinical Trials.gov , number NCT01041404 . FINDINGS 594 patients were r and omly assigned to study treatment ( trastuzumab plus chemotherapy , n=298 ; chemotherapy alone , n=296 ) , of whom 584 were included in the primary analysis ( n=294 ; n=290 ) . Median follow-up was 18.6 months ( IQR 11 - 25 ) in the trastuzumab plus chemotherapy group and 17.1 months ( 9 - 25 ) in the chemotherapy alone group . Median overall survival was 13.8 months ( 95 % CI 12 - 16 ) in those assigned to trastuzumab plus chemotherapy compared with 11.1 months ( 10 - 13 ) in those assigned to chemotherapy alone ( hazard ratio 0.74 ; 95 % CI 0.60 - 0.91 ; p=0.0046 ) . The most common adverse events in both groups were nausea ( trastuzumab plus chemotherapy , 197 [ 67 % ] vs chemotherapy alone , 184 [ 63 % ] ) , vomiting ( 147 [ 50 % ] vs 134 [ 46 % ] ) , and neutropenia ( 157 [ 53 % ] vs 165 [ 57 % ] ) . Rates of overall grade 3 or 4 adverse events ( 201 [ 68 % ] vs 198 [ 68 % ] ) and cardiac adverse events ( 17 [ 6 % ] vs 18 [ 6 % ] ) did not differ between groups . INTERPRETATION Trastuzumab in combination with chemotherapy can be considered as a new st and ard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer . FUNDING F Hoffmann-La Roche",
"Leucovorin ( LV ) enhances the activity of 5-fluorouracil ( 5FU ) . Based on these data , we performed a r and omized trial with 5FU , epirubicin ( EPI ) , mitomycin C(MMC ) with/ without LV in advanced gastric cancer ( AGC ) . The purpose of our study was to investigate if the addition of LV improved the response rate of the combination 5FU EPI , MMC ( FEM ) over FEM . From January 1988 until April 1994 , 88 patients with recurrent or metastatic AGC were r and omly received 5FU , EPI , MMC with ( group A ) or without ( group B ) LV . Between the two arms of the study no difference was noticed in sex , performance status , primary site of tumor , and lymph node metastases . Therapy included group A ( 5FU 600 mg/m2/day , i.v . bolus , on days 1 , 8 , 29 , 36 , and EPI 45 mg/m2/day , i.v . bolus , on days 1 and 29 , MMC 10 mg/m2/day , i.v . bolus , on day 1 ) and group B ( the same as group A plus LV 200 mg/m2/day by 2 h intravenous infusion with 5FU intravenous push at midinfusion ) . No significant difference in response rate was noticed between the two treatment arms ; there were two ( 5 % ) patients with complete response in group A , and five ( 12 % ) in A and 11 ( 26 % ) partial responders in group B ( p patients achieving stable disease was observed in group B ; 19 ( 44 % ) in comparison to group A 10 ( 24 % ) ( p progressive disease in group A 25 ( 59 % ) than in group B 12 ( 28 % ) ( p mean duration of response : group A , 15.8 ( 6 - 31 ) weeks ; and group B , 17.6 ( 6 - 28 ) weeks . The mean time to progression was for group A [ 11.4 ( 6 - 35 ) weeks ] and for group B [ 17.6 ( 8 - 33 ) weeks ] . Mean survival was for group A [ 27.4 ( 12 - 59 ) weeks ] and for group B [ 30.6 ( 17 - 53 ) weeks ] , for 50 % of patients . Causes of death were , for group A , 40 patients from disease progression and two sudden deaths ; for group B , causes of death were for 41 patients disease progression and two sudden deaths . There were two patients in group A and one in group B that were not evaluable because they ab and oned therapy after the first cycle . Toxicity was increased in group B ; anemia , nausea and vomiting , and alopecia ( p Neutropenia , thrombocytopenia , mucositis , and fatigue of any grade were significantly more common and severe in group B. Significant dose reductions due to toxicity were required more commonly in group B. We conclude that the response rate was increased in the schedule with the addition of LV , at the cost of increased toxicity and with no difference in survival . A r and omized trial comparing FEM-LV with new generation regimens would determine whether the addition of LV qualifies FAM equally active with these",
"PURPOSE A combination of docetaxel and fluorouracil ( DF ) was evaluated in an outpatient setting and compared with epirubicin , cisplatin , and fluorouracil ( ECF ) , which served as an internal control arm to avoid selection bias . PATIENTS AND METHODS Patients with metastatic or locally advanced gastric adenocarcinoma without prior chemotherapy were r and omly assigned to receive either ECF ( epirubicin 50 mg/m(2 ) day 1 , cisplatin 60 mg/m(2 ) day 1 , and fluorouracil 200 mg/m(2 ) days 1 through 21 , every 3 weeks ) or DF ( docetaxel 75 mg/m(2 ) day 1 , and fluorouracil 200 mg/m(2 ) days 1 through 21 , every 3 weeks ) . RESULTS Ninety patients were r and omly assigned . Toxicity was rarely severe . Major toxic effects included diarrhea , stomatitis , and leukopenia in the DF arm and nausea , vomiting , and leukopenia in the ECF arm . Forty-three of 45 patients in each arm were assessable . In the DF arm , two patients ( 4.4 % , intent to treat ) experienced a confirmed complete tumor remission as best response , and 15 patients ( 33.3 % ) experienced a confirmed partial remission ( overall response rate [ ORR ] , 37.8 % ; 95 % CI , 25.9 % to 51.9 % ) . Two patients ( 4.4 % ) in the ECF arm showed confirmed complete remission , and 14 ( 31.1 % ) showed confirmed partial remission ( ORR , 35.6 % ; 95 % CI , 24.8 % to 48.7 % ) . For the DF and ECF arms , the median survival was 9.5 and 9.7 months , and the median time to tumor progression 5.5 and 5.3 months , respectively . CONCLUSION DF can be safely given in an ambulant setting . Compared with ECF , the dual combination of DF shows promising efficacy and may be an alternative treatment option that avoids cisplatin",
"Three hundred five patients with advanced pancreatic and gastric carcinoma were r and omly assigned to treatment with fluorouracil , fluorouracil plus doxorubicin ( Adriamycin ) ( FA ) , or fluorouracil plus doxorubicin plus mitomycin ( mitomycin C ) ( FAM ) . All regimens were equivalent with regard to patient survival . There is no reasonable likelihood that either the FA or FAM regimen could produce a meaningful survival advantage over fluorouracil alone . Interval to disease progression , objective response rates , and palliative effects ( improved performance , body weight , or symptoms ) were essentially equivalent among the three regimens . With regard to toxicity , the FAM regimen produced more anorexia , nausea , vomiting , leukopenia , thrombocytopenia , and cumulative bone marrow suppression . Fluorouracil alone produced more stomatitis and diarrhea . Because of a failure to produce improved survival or palliation , unrewarded toxicity , and excessive cost , neither the FA nor FAM regimen can be recommended for the treatment of advanced pancreatic or gastric cancer",
"Abstract Background : To investigate the activity and toxicity of high dose ( HD ) infusional 5-FU in comparison to EAP regimen as first-line chemotherapy in patients with advanced gastric cancer . Patients and methods : Histologically confirmed measurable advanced gastric cancer , age Treatment : EAP arm : doxorubicin ( 40 mg/m2 ) , etoposide ( 360 mg/m2 ) , and cisplatin ( 80 mg/m2 ) every 28 d ; HD 5-FU arm : 5-FU 2.6 g/m2 24 h infusion , biweekly . Results : Sixty patients were r and omized . Patient characteristics ( arms EAP/HD 5-FU ) : Median age 57/55 yr , median PS 1/1 , LAD ( patients ) 3/8 , M1 ( patients ) 27/22 . Median number of cycles ( range ) : EAP arm 4 ( 2–8 ) , HD 5-FU arm 2 ( 1–8 ) . Worst toxicity per cycle ( grade 3 and 4 in% ) : Neutropenia 20/3 , thrombocytopenia 9/0 , anemia 9/13 , diarrhea 3/10 , nausea 17/7 , vomiting 10/0 for EAP and HD 5-FU arms , respectively . All patients were eligible for response in both arms . Confirmed response rate ( 95%CI ) : EAP arm 34 % [16–50%]/HD 5-FU arm 10 % ( 0–21 % ) , no change : 46/40 % , progression of disease : 20/50 , respectively . Overall survival ( range ) : EAP arm A 7 mo [ 3–27 ] , HD 5-FU arm 6 mo ( 4–25 ) . Conclusions : Infusional HD 5-FU showed a low incidence of severe toxicity . But given the low efficacy of 5-FU in the dosage we applied in the study , it can not be recommended as a single treatment for further studies . Assessment of higher dose intensity and /or dose density of 5-FU , with introduction of other active drugs in combination , could be an option for further studies",
"PURPOSE To compare the efficacy and tolerability of etoposide , leucovorin , and bolus fluorouracil ( ELF ) or infusional fluorouracil plus cisplatin ( FUP ) with that of the reference protocol of fluorouracil , doxorubicin , and methotrexate ( FAMTX ) in advanced gastric cancer . PATIENTS AND METHODS A total of 399 patients with advanced adenocarcinoma of the stomach were r and omized and analyzed for toxicity , tumor response , and progression-free and overall survival . Only review ed and confirmed responses were considered . The analysis of remission was based on assessable patients with documented measurable lesions . The intent-to-treat principle , log-rank test , and Cox regression model were used for the statistical analysis of time-to-event end points . RESULTS The overall response rate for 245 eligible patients with measurable disease was 9 % with ELF , 20 % with FUP , and 12 % with FAMTX , with no significant differences . One hundred twelve patients were eligible for efficacy in assessable , nonmeasurable disease . No change was observed in 66 % of patients treated with ELF , 56 % with FUP , and 55 % with FAMTX . Two patients achieved a complete tumor regression ( one each for ELF and FAMTX ) . With a median follow-up time of 4.5 years , the median survival times were 7.2 months with ELF , 7.2 months with FUP , and 6.7 months with FAMTX , respectively , with no significant differences . Nonhematologic and hematologic toxicities of ELF , FUP , and FAMTX were acceptable , with neutropenia being the major toxicity for all three regimens . Seven treatment-related deaths occurred ( two with FUP and five with FAMTX ) . CONCLUSION All three investigated regimens demonstrate modest clinical efficacy and should not be regarded as st and ard treatment for advanced gastric cancer . New strategies should be considered to achieve a better clinical efficacy in the treatment of advanced gastric cancer ",
"Two hundred forty‐one patients with unresectable gastric adenocarcinoma were entered between December 1978 and March 1981 , into a prospect ively r and omized comparison of three chemotherapy regimens to identify therapeutic activity and determine patient tolerability : ( 1 ) 5‐fluorouracil plus Adriamycin ( FA ) ; ( 2 ) FA plus methyl‐CCNU ( FAMe ) ; and ( 3 ) FA plus mitomycin C ( FAMi ) . Patients were stratified by stage and performance status prior to r and omization . Treatment groups were well balanced with respect to known prognostic discriminants . The primary endpoint to evaluate treatment effect was patient survival . Pair‐wise comparisions using a proportional hazards model adjusted for stage and performance status documented a significant survival advantage for FAMe compared with FA ( P was primarily hematologic and was seen more frequently in patients receiving FAMe . Further investigations of the FAMe regimen in the surgical adjuvant setting and combined with radiotherapy for patients with locally unresectable gastric cancer are under development . Cancer 53:13‐17 , 1984",
"A r and omized controlled trial involving 13 institutions in Japan was conducted in order to compare the efficacy of tegafur plus mitomycin C ( MMC ) ( Regimen A ) and UFT ( a combination of uracil and tegafur at a molar ratio of 4 to 1 ) plus MMC ( Regimen B ) for patients with advanced gastric cancer , who had not received any prior cancer chemotherapy . Regimen A ( tegafur+MMC ) consisted of 5 mg of MMC/m2/week given intravenously , and 500 mg of tegafur/m2/day given orally . Regimen B consisted of the same schedule of MMC and 375 mg of UFT/m2/day given orally . One hundred and eighty‐six patients with primary gastric cancer were entered ; 183 were eligible and 3 were ineligible for the study . A total of 169 were evaluable for efficacy of the treatment , including 90 patients with Regimen A and 79 with Regimen B. A response rate of 7.8 % ( 7/90 cases ) for Regimen A and one of 25.3 % ( 20/79 cases ) for Regimen B were obtained , indicating a significantly higher response rate for Regimen B according to the Criteria for Evaluating Efficacy of Chemotherapy /Radiation Therapy in the Treatment of Gastric Cancer ( P= 0.004 ) , Regarding side effects , no marked differences in either severity or incidence were observed between the two groups . The group assigned to Regimen B showed a significant survival advantage after adjustment for major prognostic factors using a proportional hazards model ( P=0.0398 ) . Moreover , a close correlation of antitumor effect and survival duration was found when the above criteria were used",
"Background A prospect i ve r and omized clinical study was performed in patients with locally advanced or metastatic gastric cancer . The purpose of the study was to determine the activity of high doses of 5-fluorouracil and epirubicin ( FE ) vs the same combination + cisplatin ( FEP ) , and particularly the value of cisplatin in the combination . Patients and Methods A total of 122 patients was included in the study ; 110 of them were assessable . In the FE arm , the treatment involved 1000 mg/m2 in a 6-hr infusion of 5-fluorouracil on days 1 , 2 , 3 , 4 and 5 and 120 mg/m2 of epirubicin iv on day 1 . In the FEP arm , the same combination of cytostatics + cisplatin ( 30 mg/m2 ) was administered on days 2 and 4 . The cycles were repeated after 4 weeks . Altogether , 468 cycles of chemotherapy were given ( FE , 240 ; FEP , 228 ) . Results In the FE arm , 56 patients were assessable , with 2 complete and 14 partial remissions ( 28.6 % ) ; in the FEP arm , 4 complete and 19 partial remissions ( 42.6 % ) were observed in 54 assessable patients . Median survival in the FE group was 7.1 months and in the FEP group 9.6 months . The survival difference was statistically significant ( Cox 's test , P effects included grade 2 and 3 alopecia ( FE , 93 % ; FEP , 94 % ) and grade 2 and 3 vomiting ( FE , 20 % ; FEP , 35 % ) . Grade 3 and 4 leukopenia was observed in 9 % of patients in the FE group and in 13 % of patients in the FEP group , with 6 cases of febrile neutropenia ( FE , 4 % ; FEP , 7 % ) . Stenocardia was registered in 1 patient in the FE group and in 2 patients in the FEP group . No treatment-related death was registered . Conclusions The addition of cisplatin to high doses of 5-fluorouracil and epirubicin result ed in a statistically significant better survival of treated patients",
"PURPOSE We report the results of a prospect ively r and omized study that compared the combination of epirubicin , cisplatin , and protracted venous infusion fluorouracil ( 5-FU ) ( ECF regimen ) with the st and ard combination of 5-FU , doxorubicin , and methotrexate ( FAMTX ) in previously untreated patients with advanced esophagogastric cancer . PATIENTS AND METHODS Two hundred seventy-four patients with adenocarcinoma or undifferentiated carcinoma were r and omized and analyzed for survival , tumor response , toxicity , and quality of life ( QL ) . RESULTS The overall response rate was 45 % ( 95 % confidence interval [ CI ] , 36 % to 54 % ) with ECF and 21 % ( 95 % CI , 13 % to 29 % ) with FAMTX ( P = .0002 ) . Toxicity was tolerable and there were only three toxic deaths . The FAMTX regimen caused more hematologic toxicity and serious infections , but ECF caused more emesis and alopecia . The median survival duration was 8.9 months with ECF and 5.7 months with FAMTX ( P = .0009 ) ; at 1 year , 36 % ( 95 % CI , 27 % to 45 % ) of ECF and 21 % ( 95 % CI , 14 % to 29 % ) of FAMTX patients were alive . The median failure-free survival duration was 7.4 months with ECF and 3.4 months with FAMTX ( P = .00006 ) . The global QL scores were better for ECF at 24 weeks , but the remaining QL data showed no differences between either arm of the study . Hospital-based cost analysis on a subset of patients was similar for each arm and translated into an increment cost of $ 975 per life-year gained . CONCLUSION The ECF regimen results in a survival and response advantage , tolerable toxicity , better QL and cost-effectiveness compared with FAMTX chemotherapy . This regimen should now be considered the st and ard treatment for advanced esophagogastric cancer",
"This report summarizes the results of a r and omized multi‐institutional clinical trial in advanced gastric carcinoma comparing four combination chemotherapy regimens : 5‐FU , Adriamycin + mitomycin C ( FAMi ) ; 5‐FU , Adriamycin + methyl‐CCNU ( FAMe ) ; 5‐FU , ICRF‐159 + methyl‐CCNU ( FIMe ) ; and 5‐FU + methyl‐CCNU ( FMe ) . One‐hundred‐eighty‐one evaluable patients received chemotherapy . These objective tumor response rates were observed among the 59 patients with measurable indicator lesions : FAMi , 3/12 ( 25 % ) ; FAMe , 3/10 ( 30 % ) ; FIMe , 4/19 ( 21 % ) ; FMe , 1/18 ( 6 % ) . The survival distributions for the four treatment groups were significantly different ( P median survivals observed ( in weeks from the onset of chemotherapy ) : FAMi , 29.6 ; FAMe , 34.4 ; FMe , 22.9 ; FIMe , 17.4 . Two nontreatment variables were found to be significantly associated with survival when analyzed using the Cox covariate model : pretreatment performance status ( P measurable metastatic disease ( P improved survival : FAMi therapy ( P 0.01 ) , and FAMe therapy ( P = 0.07 ) . Toxicity was , in general , moderate and consisted primarily of gastrointestinal side effects and myelosuppression . We conclude that the FAMi and FAMe regimens are superior to the FIMe and FMe regimens in the management of advanced gastric cancer",
"PURPOSE Patients with advanced gastric or gastroesophageal adenocarcinoma need more efficacious and safer treatments than established today . S-1 , a contemporary oral fluoropyrimidine , can provide that advantage . PATIENTS AND METHODS This study was conducted in 24 countries and 146 centers . One thous and fifty-three patients were stratified ( center , number of metastatic sites , prior adjuvant therapy , and measurable cancer ) and r and omly assigned . Patients received either S-1 at 50 mg/m(2 ) divided in two daily doses for 21 days and cisplatin at 75 mg/m(2 ) intravenously on day 1 , repeated every 28 days ( 527 patients ) or infusional fluorouracil at 1,000 mg/m(2)/24 hours for 120 hours and cisplatin at 100 mg/m(2 ) intravenously on day 1 , repeated every 28 days ( 526 patients ) . The primary end point was superiority in overall survival ( OS ) from cisplatin/S-1 compared with cisplatin/infusional fluorouracil in patients with advanced , untreated gastric , or gastroesophageal adenocarcinoma . The secondary end points were response rate , progression-free survival , time to treatment failure , and safety . RESULTS The median OS was 8.6 months in the cisplatin/S-1 arm and 7.9 months in the cisplatin/infusional fluorouracil arm ( HR , 0.92 ; 95 % CI , 0.80 to 1.05 ; P = .20 ) . Significant safety advantages were observed in the cisplatin/S-1 arm compared with the cisplatin/infusional fluorouracil arm for the rates of grade 3/4 neutropenia ( 32.3 % v 63.6 % ) , complicated neutropenia ( 5.0 % v 14.4 % ) , stomatitis ( 1.3 % v 13.6 % ) , hypokalemia ( 3.6 % v 10.8 % ) , and treatment-related deaths ( 2.5 % v 4.9 % ; P Cisplatin/S-1 did not prolong OS of patients with advanced gastric or gastroesophageal adenocarcinoma compared with cisplatin/infusional fluorouracil , but it did result in a significantly improved safety profile",
"In a prospect i ve phase III multicenter trial , 213 patients with advanced measurable or nonmeasurable gastric cancer were r and omized to receive methotrexate ( MTX ) , fluorouracil ( 5-FU ) , and Adriamycin ( doxorubicin ; Farmitalia Carlo Erba , Milan , Italy ) ( FAMTX ) or 5-FU , Adriamycin , and mitomycin ( FAM ) . The results show a significantly superior response rate ( 41 % v 9 % [ P less than .0001 ] ) , and survival ( median , 42 weeks v 29 weeks [ P = .004 ] ) for FAMTX . There was a cumulative thrombocytopenia in FAM and not in FAMTX . The FAMTX protocol should be the reference treatment in future clinical trials that seek to improve the therapeutic outcome in advanced gastric cancer",
"PURPOSE The purpose of this study was to define the contribution of docetaxel to combination chemotherapy in the outcome of patients with advanced gastric or gastroesophageal adenocarcinoma . We compared the overall response rate ( ORR ) and safety of docetaxel plus cisplatin ( DC ) with DC plus fluorouracil ( DCF ) to select either DC or DCF as the experimental treatment in the ensuing phase III part of trial V-325 . PATIENTS AND METHODS In this phase II r and omized study , untreated patients with confirmed advanced gastric or gastroesophageal adenocarcinoma received either DCF ( docetaxel 75 mg/m2 , cisplatin 75 mg/m2 on day 1 , and fluorouracil 750 mg/m2/d as continuous infusion on days 1 to 5 ) or DC ( docetaxel 85 mg/m2 and cisplatin 75 mg/m2 on day 1 ) every 3 weeks . An independent data monitoring committee ( IDMC ) was to select one of the two regimens based primarily on ORR and safety profile . RESULTS Of 158 r and omly assigned patients , 155 ( DCF , n = 79 ; DC , n = 76 ) received treatment . The confirmed ORR was 43 % for DCF ( n = 79 ) and 26 % for DC ( n = 76 ) . Median time to progression was 5.9 months for DCF and 5.0 months for DC . Median overall survival time was 9.6 months for DCF and 10.5 months for DC . The most frequent grade 3 and 4 events per patient included neutropenia ( DCF = 86 % ; DC = 87 % ) and GI ( DCF = 56 % ; DC = 30 % ) . CONCLUSION Both regimens were active , but DCF produced a higher confirmed ORR than DC . Toxicity profiles of DCF were considered manageable . The IDMC chose DCF for the phase III part of V-325 , which compares DCF with cisplatin plus fluorouracil",
"BACKGROUND Phase I/II clinical trials of S-1 plus cisplatin for advanced gastric cancer have yielded good responses and the treatment was well tolerated . In this S-1 Plus cisplatin versus S-1 In RCT In the Treatment for Stomach cancer ( SPIRITS ) trial , we aim ed to verify that overall survival was better in patients with advanced gastric cancer treated with S-1 plus cisplatin than with S-1 alone . METHODS In this phase III trial , chemotherapy-naive patients with advanced gastric cancer were enrolled between March 26 , 2002 , and Nov 30 , 2004 , at 38 centres in Japan , and r and omly assigned to S-1 plus cisplatin or S-1 alone . In patients assigned to S-1 plus cisplatin , S-1 ( 40 - 60 mg depending on patient 's body surface area ) was given orally , twice daily for 3 consecutive weeks , and 60 mg/m(2 ) cisplatin was given intravenously on day 8 , followed by a 2-week rest period , within a 5-week cycle . Those assigned to S-1 alone received the same dose of S-1 twice daily for 4 consecutive weeks , followed by a 2-week rest period , within a 6-week cycle . The primary endpoint was overall survival . Secondary endpoints were progression-free survival , proportions of responders , and safety . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00150670 . FINDINGS 305 patients were enrolled ; seven patients were ineligible or withdrew consent , therefore , 148 patients were assigned to S-1 plus cisplatin and 150 patients were assigned to S-1 alone . Median overall survival was significantly longer in patients assigned to S-1 plus cisplatin ( 13.0 months [ IQR 7.6 - 21.9 ] ) than in those assigned to S-1 alone ( 11.0 months [ 5.6 - 19.8 ] ; hazard ratio for death , 0.77 ; 95 % CI 0.61 - 0.98 ; p=0.04 ) . Progression-free survival was significantly longer in patients assigned to S-1 plus cisplatin than in those assigned to S-1 alone ( median progression-free survival 6.0 months [ 3.3 - 12.9 ] vs 4.0 months [ 2.1 - 6.8 ] ; p S-1 plus cisplatin who had target tumours , one patient had a complete response and 46 patients had partial responses , ie , a total of 54 % ( range 43 - 65 ) . Of 106 patients assigned S-1 alone who had target tumours , one patient had a complete response and 32 had partial responses , ie , a total of 31 % ( 23 - 41 ) . We recorded more grade 3 or 4 adverse events including leucopenia , neutropenia , anaemia , nausea , and anorexia , in the group assigned to S-1 plus cisplatin than in the group assigned to S-1 alone . There were no treatment-related deaths in either group . INTERPRETATION S-1 plus cisplatin holds promise of becoming a st and ard first-line treatment for patients with advanced gastric cancer",
"BACKGROUND We evaluated capecitabine ( an oral fluoropyrimidine ) and oxaliplatin ( a platinum compound ) as alternatives to infused fluorouracil and cisplatin , respectively , for untreated advanced esophagogastric cancer . METHODS In a two-by-two design , we r and omly assigned 1002 patients to receive triplet therapy with epirubicin and cisplatin plus either fluorouracil ( ECF ) or capecitabine ( ECX ) or triplet therapy with epirubicin and oxaliplatin plus either fluorouracil ( EOF ) or capecitabine ( EOX ) . The primary end point was noninferiority in overall survival for the triplet therapies containing capecitabine as compared with fluorouracil and for those containing oxaliplatin as compared with cisplatin . RESULTS For the capecitabine-fluorouracil comparison , the hazard ratio for death in the capecitabine group was 0.86 ( 95 % confidence interval [ CI ] , 0.80 to 0.99 ) ; for the oxaliplatin-cisplatin comparison , the hazard ratio for the oxaliplatin group was 0.92 ( 95 % CI , 0.80 to 1.10 ) . The upper limit of the confidence intervals for both hazard ratios excluded the predefined noninferiority margin of 1.23 . Median survival times in the ECF , ECX , EOF , and EOX groups were 9.9 months , 9.9 months , 9.3 months , and 11.2 months , respectively ; survival rates at 1 year were 37.7 % , 40.8 % , 40.4 % , and 46.8 % , respectively . In the secondary analysis , overall survival was longer with EOX than with ECF , with a hazard ratio for death of 0.80 in the EOX group ( 95 % CI , 0.66 to 0.97 ; P=0.02 ) . Progression-free survival and response rates did not differ significantly among the regimens . Toxic effects of capecitabine and fluorouracil were similar . As compared with cisplatin , oxaliplatin was associated with lower incidences of grade 3 or 4 neutropenia , alopecia , renal toxicity , and thromboembolism but with slightly higher incidences of grade 3 or 4 diarrhea and neuropathy . CONCLUSIONS Capecitabine and oxaliplatin are as effective as fluorouracil and cisplatin , respectively , in patients with previously untreated esophagogastric cancer . ( Current Controlled Trials number , IS RCT N51678883 [ controlled-trials.com ] . )",
" Although many drug combination therapies have been proposed , there is no st and ard therapy for patients with advanced gastric carcinoma . The superiority of combination therapy over monochemotherapy has not been demonstrated convincingly . To explore the role of monochemotherapy , the authors evaluated 5‐fluorouracil ( 5‐FU ) , modulated by 6S‐leucovorin ( 6S‐LV ) and a cisplatin‐containing regimen , which was comprised of epirubicin , etoposide , and cisplatin with the addition of the reversal agent lonidamine ( EEP‐L )",
"By r and om assignment a total of 176 eligible patients with advanced nonmeasurable pancreatic carcinoma were treated with 5-fluorouracil ( 5-FU ) either alone or in combination with a nitrosourea ( streptozotocin ) , in combination with a \" lactone \" ( spironolactone ) , or in combination with both . By r and om assignment a total of 179 patients with advanced nonmeasurable gastric carcinoma were treated with 5-FU either alone or in combination with a nitrosourea ( methyl CCNU ) , in combination with a lactone ( testolactone ) , or in combination with both . The median survival period for all pancreatic carcinoma patients was 17 weeks , and for all gastric carcinoma patients 30 weeks . The addition of the nitrosoureas or the lactones or a combination of both produced no improvement in length of patient survival for either primary carcinoma when compared to treatment with 5-FU alone",
"PURPOSE The purpose of this study was to evaluate the therapeutic effectiveness of fluorouracil ( 5-FU ) , doxorubicin , and methyl lomustine ( CCNU ) ( FAMe ) , 5-FU , doxorubicin , and cisplatin ( FAP ) , and FAMe alternating with triazinate ( TZT ) when compared with a st and ard therapy of 5-FU alone in patients with advanced gastric cancer . PATIENTS AND METHODS Two hundred fifty-two eligible patients selected for study had proven locally unresectable and /or metastatic gastric adenocarcinoma . The majority had nonmeasureable disease . They were r and omly assigned to receive one of the three drug combination regimens or to 5-FU alone administered by rapid injection in 5-day course . Survival was the primary study end point . RESULTS None of the three drug combinations showed a significant advantage over 5-FU alone in improved performance score , weight gain , or patient survival . Each of the three combinations was more toxic than 5-FU alone . CONCLUSION FAMe , FAP , or FAMe alternating with TZT can not be recommended for the therapy of advanced gastric carcinoma . Therapy of this disease should remain an experimental endeavor . It would seem reasonable to prove the value of any new treatment approach by a r and omized comparison to simple therapy with 5-FU alone",
"PURPOSE The combination of cisplatin , epirubicin , and leucovorin preceding fluorouracil ( PELF ) includes three novel agents compared with the st and ard combination of fluorouracil , doxorubicin , and mitomycin ( FAM ) in the treatment of advanced gastric carcinoma . We report the results of a prospect i ve r and omized comparison of the two combinations in previously untreated patients . PATIENTS AND METHODS One hundred thirty assessable patients were entered onto the trial ; 52 received FAM and 85 PELF . A 1:2 unbalanced r and omization in favor of the experimental treatment was chosen . Approximately 90 % of patients had measurable tumor masses . RESULTS The overall response rates ( complete responses [ CRs ] and partial responses [ PRs ] ) were 15 % and 43 % for the FAM and the PELF regimens , respectively , with a statistically significant advantage for the experimental treatment ( P = .001 ) . Time to progression ( median , 2.6 and 4.7 months ) , duration of response ( median , 10.7 and 10.2 months ) , and survival duration s ( median , 5.6 and 8.1 months ) were not significantly different between the FAM and PELF regimens , respectively . The PELF combination was more toxic compared with FAM , but generally tolerable . CONCLUSION This study showed that the PELF combination is about three times more effective than the FAM combination in inducing objective responses . Due to tolerability , it is not recommended for routine clinical use . However , it should be considered , among other second-generation chemotherapy combinations , in future r and omized studies aim ed to improve the therapeutic outcome in gastric carcinoma",
"PURPOSE This r and omized phase II trial evaluated two docetaxel-based regimens to see which would be most promising according to overall response rate ( ORR ) for comparison in a phase III trial with epirubicin-cisplatin-fluorouracil ( ECF ) as first-line advanced gastric cancer therapy . PATIENTS AND METHODS Chemotherapy-naïve patients with measurable unresectable and /or metastatic gastric carcinoma , a performance status of ECF ( epirubicin 50 mg/m(2 ) on day 1 , cisplatin 60 mg/m(2 ) on day 1 , and fluorouracil [ FU ] 200 mg/m(2)/d on days 1 to 21 ) , TC ( docetaxel initially 85 mg/m(2 ) on day 1 [ later reduced to 75 mg/m(2 ) as a result of toxicity ] and cisplatin 75 mg/m(2 ) on day 1 ) , or TCF ( TC plus FU 300 mg/m(2)/d on days 1 to 14 ) . Study objectives included response ( primary ) , survival , toxicity , and quality of life ( QOL ) . RESULTS ORR was 25.0 % ( 95 % CI , 13 % to 41 % ) for ECF , 18.5 % ( 95 % CI , 9 % to 34 % ) for TC , and 36.6 % ( 95 % CI , 23 % to 53 % ) for TCF ( n = 119 ) . Median overall survival times were 8.3 , 11.0 , and 10.4 months for ECF , TC , and TCF , respectively . Toxicity was acceptable , with one toxic death ( TC arm ) . Grade 3 or 4 neutropenia occurred in more treatment cycles with docetaxel ( TC , 49 % ; TCF , 57 % ; ECF , 34 % ) . Global health status/QOL substantially improved with ECF and remained similar to baseline with both docetaxel regimens . CONCLUSION Time to response and ORR favor TCF over TC for further evaluation , particularly in the neoadjuvant setting . A trend towards increased myelosuppression and infectious complications with TCF versus TC or ECF was observed",
"One hundred and forty‐six previously untreated patients with advanced gastric cancer were assigned at r and om to therapy with the following regimens : 1 ) Methyl CCNU alone ; 2 ) Methyl CCNU with cyclophosphamide induction ; 3 ) 5‐fluorouracil ( 5‐FU ) + methyl CCNU ; and 4 ) 5‐FU + methyl CCNU with cyclophosphamide induction . Cyclophosphamide induction produced an objective response rate of only 8 % . In addition , it added to hematologic toxicity and detracted from the therapeutic activity of subsequent treatment . Methyl CCNU was relatively ineffective therapy with an overall objective response rate of 8 % . The response rate to 5‐FU + methyl CCNU without cyclophosphamide induction was 40 % and this was significantly superior to all other regimens . The survival time of all patients treated with 5‐FU + methyl CCNU was significantly superior to that of all patients treated with methyl CCNU alone",
"PURPOSE The chemotherapy regimens of high-dose methotrexate , high-dose fluorouracil ( FU ) , Adriamycin ( doxorubicin ; Adria Laboratories , Columbus , OH ) , and leucovorin ( FAMTX ) and etoposide , Adriamycin , and cisplatin ( EAP ) have both been reported in nonr and om assignment trials to have high overall response rates and substantial complete response rates in patients with gastric cancer , as well as major toxicities of myelosuppression . Here we report a prospect i ve , stratified , r and om-assignment comparison of the two combinations in previously untreated patients with advanced gastric cancer . PATIENTS AND METHODS Sixty patients were entered onto the trial , 30 receiving EAP and 30 FAMTX . All patients had measurable or assessable tumor masses . Patient entry was stopped at the point when significant toxicity differences were seen at interim analysis . RESULTS Response rates were similar between the two arms ( FAMTX , 33 % [ 95 % confidence interval ( CI ) , 16 % to 50 % ] ; EAP , 20 % [ 95 % Cl , 6 % to 34 % ] ) . Three FAMTX and no EAP patients had complete remissions . The median survival for the two arms were similar ( EAP , 6.1 months ; FAMTX , 7.3 months ) . At 1 year , 7 % of EAP and 17 % of FAMTX patients were alive . EAP caused significantly more myelosuppression ( leukopenia , P = .002 ; anemia , P = .03 ; thrombocytopenia , P = .0001 ) than did FAMTX . EAP also result ed in significantly longer hospitalizations per study month ( 8 v 5 days ) . Four EAP patients died of lethal toxicity , whereas no FAMTX patients died of treatment-related causes ( P = .04 ) . CONCLUSIONS FAMTX is at least as active as EAP and is significantly less toxic . Although both regimens remain investigational , the toxicities of FAMTX are more manageable . Further studies involving FAMTX in both the adjuvant and advanced disease setting are underway",
"A r and omized trial was conducted by the Southwest Oncology Group ( SWOG ) in advanced carcinoma of the stomach and pancreas . Patients were assigned to receive monthly 5‐fluorouracil 96‐hour continuous infusions with either bolus mitomycin‐C or oral methyl‐CCNU . Mitomycin‐C and methyl‐CCNU were administered every eight weeks . The 5 FU‐mitomycin combination produced a 14 % and 22 % response rate in disseminated stomach and pancreatic carcinoma , respectively . The combination of infusion 5 FU and methyl‐CCNU achieved responses in 9 % and 5 % of stomach and pancreatic tumors , respectively . There was ho significant difference in survival between limbs for either tumor . Median survival in gastric carcinoma on the 5 FU‐mitomycin regimen was 25 weeks vs. 18 weeks on the 5 FU‐methyl‐CCNU arm . In pancreatic carcinoma median survival on the mitomycin limb was 19 weeks as compared to 17 weeks on the methyl‐CCNU program . Leukopenia was greater for the first course on the mitomycin limb . Regression analysis demonstrated that performance status was the most important pretreatment characteristic for predicting survival in both tumors . Neither 5 FU infusion combination appears to significantly alter the dismal prognosis of advanced upper gastrointestinal neoplasms",
"BACKGROUND 5-Fluorouracil ( 5-FU ) , doxorubicin and methotrexate ( FAMTX ) and cisplatin , epirubicin , leucovorin and 5-FU ( PELF ) have both been reported to be superior to the combination 5-FU , doxorubicin and mitomycin C ( FAM ) in advanced gastric carcinoma . On the basis of the presence and dose intensity of the included agents , we hypothesised that PELF would be superior to FAMTX . PATIENTS AND METHODS Two hundred patients with untreated advanced gastric carcinoma were r and omised to receive PELF or FAMTX for a maximum of six cycles or until disease progression . RESULTS The complete response ( CR ) rates to PELF and FAMTX were , respectively , 13 % [ 95 % confidence intervals ( CI ) 6 % to 20 % ] and 2 % ( 95 % CI 0 % to 5 % ; P = 0.003 ) , and the objective response rates [ CR plus partial response ( PR ) rates ] 39 % ( 95 % CI 29 % to 49 % ) and 22 % ( 95 % CI 13 % to 30 % ; P = 0.009 ) , thus significantly favouring the PELF combination . The survival rates after 12 months ( 30.8 % versus 22.4 % ) and 24 months ( 15.7 % versus 9.5 % ) were also higher among patients receiving PELF , but these differences were not statistically significant . The toxicities were qualitatively different but quantitatively similar . Both regimens seem to be feasible provided that careful patient monitoring is assured . CONCLUSIONS PELF is significantly more active than FAMTX and deserves further research in the adjuvant setting",
" Fifty-seven patients with advanced gastric carcinoma were r and omized to receive 15 mg/kg/week of 5-fluorouracil by either the iv or oral route . Toxic effects of treatment included nausea and vomiting ( 40 % with the oral route versus 35 % with the iv route ) and myelosuppression , with a wbc count of less than 4000/mm3 ( 28 % with the oral route versus 32 % with the iv route ) . The frequency of partial response was 12 % ( three of 25 patients ) for the oral route and 16 % ( five of 32 patients ) for the iv route . Only two of 36 patients with liver metastases responded . No advantage was seen for the oral versus the iv route of 5-fluorouracil in the treatment of advanced gastric carcinoma",
"BACKGROUND It is not yet established whether doses of epirubicin equitoxic to adriamycin are more effective in the treatment of locally advanced or metastatic gastric cancer . PATIENTS AND METHODS Seventy patients with advanced gastric cancer were r and omised to receive fluorouracil ( 500 mg/m2 days 1 - 5 every three weeks ) or epirubicin ( 100 mg/m2 every three weeks ) , with doses escalating to a maximum dose of 700 mg/m2 of fluorouracil or 140 mg/m2 of epirubicin . RESULTS No patients attained complete response . Partial response was seen in 3 patients in the epirubicin arm ( 8 % ) compared with 2 patients in the fluorouracil arm ( 6 % ) . No statistically significant difference between the two treatments was seen in either response or survival . Severe side effects , particularly alopecia , and nausea and vomiting were more common in the epirubicin arm ( 45 % and 37 % , respectively ) compared with the fluorouracil arm ( 12 % and 8 % , respectively ) . CONCLUSIONS Our trial demonstrates that fluorouracil and epirubicin as single agents have comparable but insufficient activity in advanced gastric cancer",
"BACKGROUND To identify the most effective of two combinations , irinotecan/5-fluorouracil (5-FU)/folinic acid ( FA ) and irinotecan/cisplatin , in the treatment of advanced gastric cancer , for investigation in a phase III trial . PATIENTS AND METHODS Patients were r and omized to receive irinotecan [ 80 mg/m2 intravenously ( i.v . ) ] , FA ( 500 mg/m2 i.v . ) and a 22-h infusion of 5-FU ( 2000 mg/m2 i.v . ) , weekly for 6 weeks with a 1-week rest , or irinotecan ( 200 mg/m2 i.v . ) and cisplatin ( 60 mg/m2 i.v . ) , on day 1 for 3 weeks . RESULTS A total of 115 patients were eligible for analysis in the per- protocol population . The overall response rate in the irinotecan/5-FU/FA arm ( n=59 ) was 42.4 % , with a complete response rate of 5.1 % . Corresponding figures for the irinotecan/cisplatin arm ( n=56 ) were 32.1 % and 1.8 % , respectively . The median time to progression was 6.5 months ( irinotecan/5-FU/FA ) and 4.2 months ( irinotecan/cisplatin ) ( P major toxicity was grade 3/4 neutropenia , which was more pronounced with irinotecan/cisplatin than with irinotecan/5-FU/FA ( 65.7 % versus 27 % ) . Diarrhea was the main grade 3/4 non-hematological toxicity with both irinotecan/5-FU/FA ( 27.0 % ) and irinotecan/cisplatin ( 18.1 % ) . CONCLUSIONS Both combinations were active , with acceptable safety profiles . Irinotecan/5-FU/FA was selected as the most effective combination for investigation in a phase III trial in advanced gastric cancer",
"PURPOSE In the r and omized , multinational phase II/III trial ( V325 ) of untreated advanced gastric cancer patients , the phase II part selected docetaxel , cisplatin , and fluorouracil ( DCF ) over docetaxel and cisplatin for comparison against cisplatin and fluorouracil ( CF ; reference regimen ) in the phase III part . PATIENTS AND METHODS Advanced gastric cancer patients were r and omly assigned to docetaxel 75 mg/m2 and cisplatin 75 mg/m2 ( day 1 ) plus fluorouracil 750 mg/m2/d ( days 1 to 5 ) every 3 weeks or cisplatin 100 mg/m2 ( day 1 ) plus fluorouracil 1,000 mg/m2/d ( days 1 to 5 ) every 4 weeks . The primary end point was time-to-progression ( TTP ) . RESULTS In 445 r and omly assigned and treated patients ( DCF = 221 ; CF = 224 ) , TTP was longer with DCF versus CF ( 32 % risk reduction ; log-rank P Overall survival was longer with DCF versus CF ( 23 % risk reduction ; log-rank P = .02 ) . Two-year survival rate was 18 % with DCF and 9 % with CF . Overall response rate was higher with DCF ( chi2 P = .01 ) . Grade 3 to 4 treatment-related adverse events occurred in 69 % ( DCF ) v 59 % ( CF ) of patients . Frequent grade 3 to 4 toxicities for DCF v CF were : neutropenia ( 82 % v 57 % ) , stomatitis ( 21 % v 27 % ) , diarrhea ( 19 % v 8 % ) , lethargy ( 19 % v 14 % ) . Complicated neutropenia was more frequent with DCF than CF ( 29 % v 12 % ) . CONCLUSION Adding docetaxel to CF significantly improved TTP , survival , and response rate in gastric cancer patients , but result ed in some increase in toxicity . Incorporation of docetaxel , as in DCF or with other active drug(s ) , is a new therapy option for patients with untreated advanced gastric cancer",
"Thirty-eight patients of advanced adenocarcinoma of the stomach were r and omly administered intensive courses of either 5-FU or mitomycin C by intravenous route , The 5-FU administration result ed in a slightly better response than mitomycin C , although the toxic effects of the two drugs were more or less the same . The selection of drug regime in the present study has been based on cost , availability , potential toxicity , and minimal alteration of the patients ' life style",
"4536 Background : To compare the efficacy and tolerance of two oxaliplatin-based regimens as first-line treatment of advanced gastric cancer . METHODS Chemotherapy-naïve patients with measurable recurrent or metastatic gastric adenocarcinoma , PS ( ECOG ) 0 - 2 and adequate organ functions were r and omly assigned to receive either irinotecan 200mg/m2 and oxaliplatin 80mg/m2 ( IO ) , every 21 days or oxaliplatin 85mg/m2 on day 1 , 5-FU 400 mg/m2 ( over 1 hour infusion ) + 600mg/m2 ( over 22 hours infusion ) on days 1 and 2 , leucovorin ( LV ) 200mg/m2 on days 1 and 2 ( FOLFOX4 ) every 2 weeks . Study endpoints : Overall Response Rate ( ORR ) , Toxicity Time to Progression ( TTP ) and Survival ( S ) . RESULTS 138 patients were enrolled and all were evaluable for response . Median number of cycles administered was 5.5 ( range 1 - 10 ) for IO and 7 ( range 1 - 18 ) for FOLFOX4 . In an intent-to treat analysis the ORR ( RR+CR ) was 29.4 % for IO arm and 34.3 % for FOLFOX4 arm ( p= 0.587 ) . The median response duration was 5.63 months ( mo ) for IO arm and 6,6mo for FOLFOX4 arm . Median TTP was 4.2mo and 6,1mo for IO and FOLFOX4 arm respectively ( p= 0.012 ) . Median OS was 9.4mo for IO and 11.97mo for FOLFOX4 ( p= 0.456 ) . Toxicity was acceptable , with one toxic death in each arm . Grade 3 - 4 vomiting ( 7.3 % ) , diarrhea ( 11.8 % ) , neutropenia ( 22 % ) and febrile neutropenia ( 5.9 % ) occurred more frequently in IO arm , while anaemia ( 4.3 % ) and grade II neurotoxicity ( 11.4 % ) was more frequent in FOLFOX4 arm . CONCLUSIONS Both regimens are well tolerated and active in advanced gastric cancer . Based on the TTP and toxicity profile , the FOLFOX4 regimen merits to be further evaluated in prospect i ve phase III trials . No significant financial relationships to disclose",
" One hundred nineteen patients with advanced gastric cancer were included in a study comparing EEP vs. FEM chemotherapy . The response rate was higher ( 30 % ) in patients on EEP than in those treated with FEM ( p = 0.05 ) . Severe leukopenia , anemia , alopecia and infection were significantly more frequent on EEP . In addition , because of its intrinsic toxicity , EEP chemotherapy has a negative impact on the performance status of patients treated with this regimen , more than half of whom presented at least one episode of severe symptomatic toxicity while on EEP chemotherapy . The median time to progression and median survival for EEP-FEM were 2.08 - 3.4 and 4.2 - 7.9 months , respectively . Our data do not support the use of EEP chemotherapy in patients with AGC",
"In a prospect i ve phase III multicenter trial , 189 patients with advanced measurable and nonmeasurable gastric cancer were r and omized to receive 5-fluorouracil ( 5-FU ) combined with Adriamycin ( FA ) or FA plus methyl-CCNU ( MeFA ) . The response rate in patients with measurable disease was 10 % ( three of 29 ) , and 18 % ( five of 28 ) , respectively . No difference in the duration of survival was detected ( P = .14 ; log rank test ) . Median survivals were 21 and 32 weeks , respectively . Toxicity was moderate , but there have been two toxic deaths among the patients who received FA . Because of the low response rate and the short survival , neither regimen can be recommended for the treatment of advanced gastric cancer",
"This r and omized controlled clinical trial was design ed to compare the safety and effectiveness of different sequences of treatment with cisplatin ( CDDP ) and 5-fluorouracil ( 5-FU ) in patients with unresectable advanced and post-operative recurrent gastric cancer . Patients with unresectable advanced or post-operative recurrent gastric cancer were r and omly assigned by a registration center to group A or B. Group A received CDDP ( 80 mg/m(2 ) ) as a continuous 2-h intravenous infusion on day 1 and 5-FU ( 700 mg/m(2 ) ) as a continuous intravenous infusion on days 2 - 5 . Group B was given 5-FU ( 700 mg/m(2 ) ) as a continuous intravenous infusion on days 1 - 4 , followed by CDDP ( 80 mg/m(2 ) ) as a continuous 2-h intravenous infusion on day 5 . Each course of chemotherapy was repeated every 28 days . A total of 74 patients were enrolled . One patient died accidentally , and 5 could not be evaluated . Response was assessable in 68 patients . The response rate was 31.3 % ( 10/32 ) in group A as compared with 13.9 % ( 5/36 ) in group B. Although the response rate was higher in Group A , the difference was not significant ( p=0.085 ) . The response rate in patients with diffuse type tumors was significantly lower in group B. There was no difference between the groups in response among patients with intestinal type tumors . The median overall survival was 239 and 174 days and time to progression was 175 and 140 days in group A and group B , respectively . Although there were trends toward longer survival and time to progression in group A , the differences between the groups were not statistically significant . There was also no difference in the type or incidence of adverse reactions . The results of this controlled study indicate that the overall response rate was slightly but not significantly higher in patients who received CDDP before 5-FU . Among patients with diffuse type tumors , the response rate was significantly lower when 5-FU was administered before CDDP . Our results suggest that CDDP should be given before 5-FU in patients with gastric cancer when treated with a combination of CDDP and 5-FU",
"PURPOSE To compare fluorouracil ( FU ) alone with FU plus cisplatin ( FP ) and with uracil and tegafur plus mitomycin ( UFTM ) for patients with advanced gastric cancer in a prospect i ve , r and omized , controlled trial . PATIENTS AND METHODS A total of 280 patients with advanced gastric cancer were r and omly allocated and analyzed for survival , response , and toxicity . The survival curves were compared between groups by log-rank test on an intent-to-treat basis . RESULTS At the interim analysis , the UFTM arm showed a significantly inferior survival with higher incidences of hematologic toxic effects than did control arm FU alone , and the registration to UFTM was terminated . Both investigational regimens , FP and UFTM , had a significantly higher incidence of hematologic toxic effects than FU alone , although the effects were manageable . The overall response rates of the FU-alone , FP , and UFTM arms were 11 % , 34 % , and 9 % , respectively . The median progression-free survival was 1.9 months with FU alone , 3.9 months with FP , and 2.4 months with UFTM , respectively . Although FP demonstrated a higher response rate ( P progression-free survival than did FU alone ( P overall survival were observed between the arms . The median survival times and 1-year survival rates were 7.1 months and 28 % with FU , 7.3 months and 29 % with FP , and 6.0 months and 16 % with UFTM , respectively . CONCLUSION Neither investigational regimen , FP nor UFTM , showed a survival advantage as compared with FU alone . FU alone will remain a reference arm in our future trial for advanced gastric cancer",
"Taxanes have clearly demonstrated activities against gastric cancer . We compared the combination of paclitaxel plus 5-fluorouracil ( 5-FU ) ( PF ) with docetaxel plus 5-FU ( DF ) as first-line chemotherapy in patients with measurable metastatic gastric cancer . Seventy-seven patients were r and omly assigned to receive paclitaxel 175 mg/m2 or docetaxel 75 mg/m2 on day 1 , in combination with 5-FU 500 mg/m2 continuous infusion on days 1–5 . Treatment was repeated every 3 weeks . Of 314 chemotherapy cycles delivered ( median 5 in both groups ) , dose reduction was required more frequently in the DF group , being 9 and 19 % , respectively ( P grade 3 or 4 toxicities than DF ( 68 versus 85 % ; P=0.09 ) . Global quality of life was similar in both groups , but substantive differences in many symptom scores including pain , dyspnea , constipation and diarrhea favored PF . There were no significant differences in therapeutic efficacy between PF and DF with respect to response rate ( 42 versus 33 % , respectively ; P=0.53 ) , and failure-free ( 3.6 versus 4.2 months ; P=0.92 ) and overall survival ( 9.9 versus 9.3 months ; P=0.42 ) . Both PF and DF appear to have efficacy against metastatic gastric cancer , with different , but acceptable , safety profiles",
"A multi-institutional cooperative study of patients with locally advanced , recurrent , or metastatic gastric adenocarcinoma who had not previously received chemotherapy was conducted , prospect ively r and omizing patients to receive either doxorubicin or the three-drug combination , 5-fluorouracil ( 5-FU ) , doxorubicin ( Adriamycin ; Adria Laboratories , Columbus , Ohio ) , and BCNU ( FAB ) . The 187 evaluable patients were initially stratified according to the presence of measurable or evaluable disease and performance status . There was a significantly higher response rate observed for FAB ( 40 % ) compared with doxorubicin ( 13 % ) among the 145 measurable-disease patients . Duration of response and survival were significantly longer for FAB in the measurable-disease group , but for the total patient population an early advantage for FAB in time to disease progression and survival was lost with continued follow-up . Median survival was 33 weeks for patients receiving FAB and 19 weeks for those receiving doxorubicin . Significant pretreatment factors adversely affecting survival included poor performance status , weight loss of greater than 10 % , and more than two sites of metastases . Toxicity was not severe in either treatment arm , and only thrombocytopenia occurred significantly more often with FAB . It is contended that in the treatment of advanced gastric cancer , chemotherapy only exerts a relatively short-term and modest beneficial effect , most apparent in patients with intermediate tumor bulk . 5-FU remains the most active single agent , and combination chemotherapy has not yet proven its overall worth . Further studies are indicated comparing the most active combinations with 5-FU using optimal doses and schedules , and consideration must be given to the incorporation of no-treatment controls",
"PURPOSE This multicentric , r and omized , two-stage phase II trial evaluated three simplified weekly infusional regimens of fluorouracil ( FU ) or FU plus folinic acid ( FA ) and cisplatin ( Cis ) with the aim to select a regimen for future phase III trials . PATIENTS AND METHODS A total of 145 patients with advanced gastric cancer where r and omly assigned to weekly FU 3,000 mg/m2/24 hours ( HD-FU ) , FU 2,600 mg/m2/24 hours plus dl-FA 500 mg/m2 or l-FA 250 mg/m2 ( HD-FU/FA ) , or FU 2000 mg/m2/24 hours plus FA plus biweekly Cis 50 mg/m2 , each administered for 6 weeks with a 1-week rest . The primary end point was the response rate . RESULTS Confirmed responses were observed in 6.1 % ( two of 33 ) of the eligible patients treated with HD-FU , in 25 % ( 12 of 48 , including one complete remission [ CR ] ) with HD-FU/FA , and in 45.7 % ( 21 of 46 , including four CRs ) with HD-FU/FA/Cis . The HD-FU arm was closed after stage 1 because the required minimum number of responses was not met . The median progression-free survival of all patients in the HD-FU , HD-FU/FA , and HD-FU/FA/Cis arm was 1.9 , 4.0 , and 6.1 months , respectively . The median overall survival was 7.1 , 8.9 , and 9.7 months , and the survival rate at 1 year was 24.3 % , 30.3 % , and 45.3 % , respectively . Grade 4 toxicities were rare . The most relevant grade 3/4 toxicities were neutropenia in 1.9 % , 5.4 % , and 19.6 % , and diarrhea in 2.7 % , 1.9 % , and 3.9 % of the cycles in the HD-FU , HD-FU/FA , and HD-/FU/Cis arms , respectively . CONCLUSION Weekly infusional FU/FA plus biweekly Cis is effective and safe in patients with gastric cancer",
"A total of 71 patients with advanced gastric carcinoma were r and omized to receive either folinic acid + fluorouracil ( arm A ) or the same combination with the addition of 4-epidoxorubicin ( arm B ) . Of the 62 evaluable patients ( 31 in both arms ) , six patients achieved a CR ( 10 % ) and 16 a PR ( 25.5 % ) with an overall response rate of 35.5 % ( 29 % in arm A and 42 % in arm B ; p = .28 ) . Median duration of response was 6 and 7 months for arm A and B , respectively ( p = .6 ) . Responder patients showed a significantly better median survival duration than nonresponders ( p = .01 ) ; in arm B the median survival duration was 16 months for responder patients in contrast to 7 months for nonresponders ( p = .004 ) . Toxicity was mild without significant differences between the two groups . There was one death due to hematological toxicity ( arm A ) . The EPI-FA-FU combination appears effective and well tolerated with the additional advantage of being able to be administered in the outpatient clinic",
"A consortium of Northern California and Japanese investigators studied 142 patients with advanced gastric adenocarcinoma . Patients were r and omized to one of two combination chemotherapy programs in each nation ( one common therapy shared and one therapy unique to each nation ) . Median duration of survial ranged between 5 and 45 weeks , depending on performance status , extent of disease , and chemotherapy program . More importantly , there was considerable comparability with respect to toxicity and outcome between patients in the US and Japan . Overall median survival was 26 weeks for Japanese and 27 weeks for US patients . This study helps provide the basis for future comparative multinational trials",
"LBA4007 Background : The median survival for patients ( pts ) with AGC in most phase III studies is less than 1 year . The addition of bevacizumab ( bev ) to chemotherapy ( chemo ) is supported by a strong pre clinical rationale and by phase II evaluation . AVAGAST is the first r and omized study to compare the efficacy and safety of bev + chemo vs placebo + chemo . METHODS Pts with inoperable , locally advanced or metastatic stomach/gastroesophageal junction adenocarcinoma with no prior therapy were r and omized 1:1 to capecitabine ( cape , or 5-FU ) + cisplatin ( cis ) and either bev ( 7.5 mg/kg iv ) or placebo q3w . Stratification variables : geographical region , fluoropyrimidine treatment , disease status . Cis was given for 6 cycles ; bev/placebo + cape/5-FU were given until disease progression or unmanageable toxicity . PRIMARY OBJECTIVE compare overall survival ( OS ) ; secondary objectives : compare progression-free survival ( PFS ) , overall response rate ( ORR ) , and safety ( as overseen by an independent DSMB ) . RESULTS From Sep 2007 to Dec 2008 , 774 pts were enrolled . Treatment arms were balanced . Approx 95 % of pts were metastatic . Two-thirds of pts were male , 49 % of pts were from Asia/Pacific , 32 % from Europe and 19 % from the Americas . Median OS was 10.1 months with chemo + placebo and 12.1 months with chemo + bev in the intent-to-treat population ( HR 0.87 ; p=0.1002 ) . Median OS according to geographical region was 6.8 vs. 11.5 months ( HR 0.63 ) in the Americas , 8.6 vs. 11.1 months ( HR 0.85 ) in Europe and 12.1 vs. 13.9 months in Asia-Pacific ( HR 0.97 ) . Secondary endpoints and AEs of special interest for Bev are summarized below ( Table ) . CONCLUSIONS While the primary endpoint was not met ( median OS HR 0.87 ; p=0.1002 ) , there was a significant improvement in PFS and ORR and an acceptable safety profile for bev + chemo in patients with AGC . [ Table : see text ] [ Table : see text ]",
"PURPOSE We report the results of a prospect ively r and omized study that compared the combination of epirubicin , cisplatin , and protracted venous-infusion fluorouracil ( PVI 5-FU ) ( ECF ) with the combination of mitomycin , cisplatin , and PVI 5-FU ( MCF ) in previously untreated patients with advanced esophagogastric cancer . PATIENTS AND METHODS Five hundred eighty patients with adenocarcinoma , squamous carcinoma , or undifferentiated carcinoma were r and omized to receive either ECF ( epirubicin 50 mg/m(2 ) every 3 weeks , cisplatin 60 mg/m(2 ) every 3 weeks and PVI 5-FU 200 mg/m(2)/d ) or MCF ( mitomycin 7 mg/m(2 ) every 6 weeks , cisplatin 60 mg/m(2 ) every 3 weeks , and PVI 5-FU 300 mg/m(2)/d ) and analyzed for survival , response , toxicity , and quality of life ( QOL ) . RESULTS The overall response rate was 42.4 % ( 95 % confidence interval [ CI ] , 37 % to 48 % ) with ECF and 44.1 % ( 95 % CI , 38 % to 50 % ) with MCF ( P = .692 ) . Toxicity was tolerable , and there were only two toxic deaths . ECF result ed in more grade 3/4 neutropenia and grade 2 alopecia , but MCF caused more thrombocytopenia and plantar-palmar erythema . Median survival was 9.4 months with ECF and 8.7 months with MCF ( P = .315 ) ; at 1 year , 40.2 % ( 95 % CI , 34 % to 46 % ) of ECF and 32.7 % ( 95 % CI , 27 % to 38 % ) of MCF patients were alive . Median failure-free survival was 7 months with both regimens . Global QOL scores were better with ECF at 3 and 6 months . CONCLUSION This study confirms response , survival , and QOL benefits of ECF observed in a previous r and omized study . The equivalent efficacy of MCF was demonstrated , but QOL was superior with ECF . ECF remains one of the reference treatments for advanced esophagogastric cancer"
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41187dd6-06ff-11f0-808a-c43d1ab1c353
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Background Obesity has been proposed as a risk factor for prostate cancer ( PCa ) . In obesity , serum levels of the appetite-regulating hormones — leptin , adiponectin , and ghrelin — become deregulated . Objective To explore whether serum levels of appetite-regulating hormones associate with the incidence of PCa , the incidence of advanced disease , or PCa-specific mortality . Methods PRISMA guidelines were followed . A systematic search for relevant articles published until March 2019 was performed using the data bases PubMed , EMBASE , and Web of Science . Observational studies with data on serum levels of leptin , adiponectin , or ghrelin and PCa outcome were included . Meta- analysis was used to combine risk estimates . Meta-relative risks ( mRRs ) were calculated using r and om effects models . When available , raw data was pooled . Publication bias was assessed by funnel plot and Begg ’s test . Results Thirty-five studies were eligible for inclusion . The qualitative analysis indicated that leptin was not consistently associated with any PCa outcome , although several cohorts reported decreased adiponectin levels in men who later developed advanced PCa . Based on the meta- analysis , there was no significant effect of leptin on PCa incidence ( mRR = 0.93 ( 95 % CI 0.75–1.16 ) , p = 0.52 ) or advanced PCa ( mRR = 0.90 ( 95 % CI 0.74–1.10 ) , p = 0.30 ) . There were insufficient studies to estimate the mRR of PCa incidence for men with the highest levels of adiponectin . The combined risk of advanced PCa for men with the highest levels of adiponectin was reduced but did not reach significance ( mRR = 0.81 ( 95 % CI 0.61–1.08 ) , p = 0.15 ) . Conclusions The current evidence does not suggest an association between leptin and PCa outcome . However , there may be an inverse association between adiponectin and the incidence of advanced PCa that should be investigated by further studies . Serum ghrelin has not been largely investigated
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"INTRODUCTION High expression of leptin receptors have been observed in the prostate cancer in various clinical studies ; however the association of serum leptin with carcinoma prostate remains unresolved . We studied association , between serum leptin and carcinoma prostate in Asian ( Indian ) population and its association with obesity . MATERIAL AND METHODS 30 prospect i ve cases of cancer prostate and 30 age matched controls were included in this study . Body mass index ( BMI ) was estimated and categorized in 4 groups by WHO criteria . Waist hip ratio ( WHR ) was calculated and divided into three groups . Serum leptin was estimated by s and wich ELISA technique ( DRG leptin ELISA kit , Marburg , Germany ) . RESULTS Both the groups were comparable for age , WHR and BMI . Serum leptin was significantly higher in patients with cancer prostate as compared to controls ( median 14.18 ng/ml vs. 1.63 ng/ml ; p level of leptin was found to have positive correlation with BMI and WHR in controls ( r=0.485 , p=0.007 ; r=0.314 , p=0.091 , respectively ) however , no correlation was observed in patients with cancer prostate ( r=0.071 , p=0.711 ; r=0.067 , p=0.725 , respectively ) . There was no correlation between leptin and PSA . The serum leptin level was not related to the Gleason 's score and stage of the carcinoma . CONCLUSIONS This study shows that Prostate cancer is associated with raised serum leptin which is independent of obesity and serum PSA . It hints the role of leptin in pathogenesis of this tumor . It may not be a surrogate marker of aggressiveness . For validation , further studies including a large patient population is required",
"Recent studies indicate that adipose tissue and adipocytokines might affect the development of prostate cancer ( PCa ) . Leptin would have a stimulating effect on prostate cancer cells by inducing promotion and progression , whereas adiponectin would have a protective effect . The aim of this study was to determine the relation between body composition , leptin , and adiponectin levels with the prevalence and aggressiveness of PCa in men of Mendoza , Argentina . Seventy volunteers between 50 and 80 years ( 35 healthy men as control group and 35 with PCa ) were selected . The PCa group was subclassified according to the Gleason Score ( GS ) . Digital rectal examination , transrectal ultrasound , and prostatic biopsy were performed ; PSA , testosterone , leptin , and adiponectin levels were determined ; and a nutritional interview including anthropometric measurements and a food frequency question naire was carried out . Statistical analysis was performed by Student t test , ANOVA I , and Bonferroni ( p Body mass index and percentage of body fat mass were not statistically different between PCa and control groups . However , body fat mass was higher in subjects with more aggressive tumors ( p = 0.032 ) . No differences were observed regarding leptin levels between the groups . Nevertheless , leptin levels were higher in subjects with high GS ( p Adiponectin levels showed no statistical differences regarding the presence and aggressiveness of the tumor ( p = 0.131 ) . Finally , consumption and nutrient intake did not differ in the studied groups . In conclusion , body composition and leptin are related to the PCa aggressiveness but not with its prevalence",
"Abstract Purpose Hyperinsulinemia is hypothesized to influence prostate cancer risk . Thus , we evaluated the association of circulating C-peptide , which is a marker of insulin secretion , and leptin , which is secreted in response to insulin and influences insulin sensitivity , with prostate cancer risk . Methods We identified prostate cancer cases ( n = 1,314 ) diagnosed a mean of 5.4 years after blood draw and matched controls ( n = 1,314 ) in the Health Professionals Follow-up Study . Plasma C-peptide and leptin concentrations were measured by ELISA . Odds ratios ( ORs ) and 95 % confidence intervals ( CI ) were estimated taking into account the matching factors age and history of a PSA test before blood draw and further adjusting for body mass index , diabetes , and other factors . Results Neither C-peptide ( quartile [Q]4 vs. Q1 : OR 1.05 , 95 % CI 0.82–1.34 , p-trend = 0.95 ) nor leptin ( Q4 vs. Q1 : OR 0.85 , 95 % CI 0.65–1.12 , p-trend = 0.14 ) was associated with prostate cancer risk . Further , neither was associated with risk of advanced or lethal disease ( n = 156 cases ; C-peptide : Q4 vs. Q1 , OR 1.18 , 95 % CI 0.69–2.03 , p-trend = 0.78 ; leptin : Q4 vs. Q1 , OR 0.74 , 95 % CI 0.41–1.36 , p-trend = 0.34 ) . Conclusions In this large prospect i ve study , circulating C-peptide and leptin concentrations were not clearly associated with risk of prostate cancer overall or aggressive disease . Well into the PSA era , our findings do not appear to be supportive of the hypothesis that hyperinsulinemia influences risk of total or aggressive prostate cancer ",
"OBJECTIVES To search for any relation between plasma adiponectin levels and the cellular differentiation or progression of prostate cancer ( PCa ) . PCa is becoming an increasingly important public health problem , particularly for those countries with a trend toward an aging population . Because insulin resistance in the setting of obesity is associated with the development of PCa , we hypothesized that decreased adiponectin levels might underlie the association between PCa and obesity/insulin resistance . METHODS In this study , we investigated plasma adiponectin levels in 30 patients with PCa , 41 subjects with benign prostatic obstruction , and 36 healthy individuals . The body mass index and age of the groups were similar . Patients with PCa were stratified into two groups according to the spread of the disease as organ-confined and advanced disease and into three groups according to grade ( low , intermediate , and high grade determined by a Gleason sum of less than 5 , between 5 and 7 , and more than 7 , respectively ) . RESULTS Plasma adiponectin levels were significantly lower in the PCa group than in the benign prostatic obstruction group or controls ( P plasma adiponectin levels were significantly lower in the advanced disease group than in the organ-confined PCa group ( P = 0.012 ) . Significant negative associations were found between plasma adiponectin levels and prostate-specific antigen levels or biopsy Gleason scores in the PCa group . The plasma adiponectin levels of those with high- grade PCa were also significantly lower than those for both the low- grade and intermediate- grade groups ( P plasma adiponectin levels are not only lower in patients with PCa but are also negatively associated with the histologic grade and disease stage . Future prospect i ve studies are recommended to establish any causal relation between PCa and plasma adiponectin levels",
"Background : Adiponectin has been reported to have a prohibitory effect on prostate cancer . The goal of this study was to evaluate the diagnostic value of adiponectin multimers for prostate cancer . Methods : Total adiponectin , high- and low-molecular-weight ( HMW , LMW ) , ratios of these measures , and body mass index ( BMI ) were compared in a prospect i ve prostate cancer – screened cohort . Multivariable logistic regression was used to assess the association between adiponectin measures , their interaction with BMI , and risk of prostate cancer and Gleason score upgrading from biopsy to prostatectomy . Results : A total of 228 prostate cancer cases and 239 controls were analyzed : 72 ( 31.6 % ) of the cancer cases were high grade ( Gleason grade ≥7 ) . Only percent HMW had a statistically significant relationship with prostate cancer ( P = 0.04 ) . Among normal and overweight men , the risk of prostate cancer increased as percent HMW increased [ OR = 1.24 for a doubling of percent HMW , 95 % confidence interval ( CI ) , 0.41–3.75 and OR = 1.81 ; 95 % CI , 1.02–3.20 , respectively ] , whereas among obese men , the risk of prostate cancer decreased ( OR = 0.62 ; 95 % CI , 0.32–1.18 ) . Among 97 patients who underwent radical prostatectomy , there was no association between Gleason score upgrading and any of the adiponectin multimers . Conclusion : This study was unable to confirm the utility of total adiponectin as a biomarker for prostate cancer risk . For the adiponectin multimers , only HMW showed increases with prostate cancer but not in all weight classes . Impact : Although adiponectin may play a role in the pathogenesis of prostate cancer , our results do not support adiponectin multimers as biomarkers of detection . Cancer Epidemiol Biomarkers Prev ; 23(2 ) ; 309–15 . © 2013 AACR",
"Ghrelin system comprises a complex family of peptides , receptors ( GHSRs ) , and modifying enzymes [ e.g. ghrelin-O-acyl-transferase ( GOAT ) ] that control multiple pathophysiological processes . Aberrant alternative splicing is an emerging cancer hallmark that generates altered proteins with tumorigenic capacity . Indeed , In1-ghrelin and truncated-GHSR1b splicing variants can promote development/progression of certain endocrine-related cancers . Here , we determined the expression levels of key ghrelin system components in neuroendocrine tumor ( NETs ) and explored their potential functional role . Twenty-six patients with NETs were prospect ively/retrospectively studied [ 72 sample s from primary and metastatic tissues ( 30 normal/42 tumors ) ] and clinical data were obtained . The role of In1-ghrelin in aggressiveness was studied in vitro using NET cell lines ( BON-1/QGP-1 ) . In1-ghrelin , GOAT and GHSR1a/1b expression levels were elevated in tumoral compared to normal/adjacent tissues . Moreover , In1-ghrelin , GOAT , and GHSR1b expression levels were positively correlated within tumoral , but not within normal/adjacent sample s , and were higher in patients with progressive vs. with stable/cured disease . Finally , In1-ghrelin increased aggressiveness ( e.g. proliferation/migration ) of NET cells . Altogether , our data strongly suggests a potential implication of ghrelin system in the pathogenesis and /or clinical outcome of NETs , and warrant further studies on their possible value for the future development of molecular biomarkers with diagnostic/prognostic/therapeutic value",
"BACKGROUND In a previous study of Chinese men , we found that men with a higher waist-to-hip ratio ( WHR ) have a higher prostate cancer risk . Because leptin and insulin are related to body fat distribution , we examined whether leptin and insulin were associated with prostate cancer risk . METHODS Blood sample s were collected from 128 case patients with incident prostate cancer and from 306 healthy control subjects r and omly selected from residents of Shanghai , CHINA : Epidemiologic information and anthropometric measurements were collected in personal interviews . Serum leptin , insulin , and sex hormone levels were measured by radioimmunoassay , and insulin-like growth factor-I ( IGF-I ) was measured by enzyme-linked immunosorbent assay . Multiple logistic regression analyses were used to estimate odds ratios for prostate cancer in relation to serum insulin and leptin levels . All statistical tests were two-sided . RESULTS After adjustment for body mass index , WHR , IGF-I , and sex hormone levels , higher serum insulin levels were associated with a statistically significantly elevated risk of prostate cancer ( P prostate cancer compared with men in the lowest tertile . Regardless of the tertile level of WHR , higher serum insulin levels were associated with an increased risk of prostate cancer : Men in the highest tertiles of WHR ( > 0.900 ) and insulin ( > 8.83 microU/mL ) had 8.55 times ( 95 % CI = 2.80 to 26.10 ) the prostate cancer risk of men in the lowest tertiles of both , and those in the lowest tertile of WHR ( leptin levels and prostate cancer risk was not statistically significant . CONCLUSION Our results suggest that serum insulin levels may influence the risk of prostate cancer in Chinese men . Further research , especially prospect i ve studies , is needed to confirm these findings in high-risk population s and to clarify the underlying mechanisms involved",
"Factors related to insulin resistance have been implicated in prostate cancer development , however , few analytical studies support such an association . We performed a case control study on 392 prostate cancer cases and 392 matched controls nested in a prospect i ve cohort in Northern Sweden . Plasma concentrations of C-peptide , leptin , glycated haemoglobin ( HbA1c ) and fasting and post-load glucose were analysed and homeostatic model assessment of insulin resistance ( HOMA-IR ) was calculated . Conditional logistic regression analyses were used to calculate odds ratios ( OR ) of prostate cancer . High levels of C-peptide , HOMA-IR , leptin and HbA1c were associated with significant decreases in risk of prostate cancer , with ORs for top vs. bottom quartile for C-peptide of 0.59 ( 95 % Confidence Interval [ CI ] , 0.40 - 0.89 ; p(trend ) = 0.008 ) , HOMA-IR 0.60 ( 95 % CI , 0.38 - 0.94 ; p(trend ) = 0.03 ) , leptin 0.55 ( 95 % CI , 0.36 - 0.84 ; p(trend ) = 0.006 ) and HbA1c 0.56 ( 95 % CI , 0.35 - 0.91 ; p(trend ) = 0.02 ) . All studied factors were strongly inversely related to risk among men less than 59 years of age at blood sampling , but not among older men , with a significant heterogeneity between the groups for leptin ( p(heterogeneity ) = 0.006 ) and fasting glucose ( p(heterogeneity ) = 0.03 ) . C-peptide and HOMA-IR were strongly inversely related to non-aggressive cancer but were non-significantly positively related to risk of aggressive disease ( p(heterogeneity ) = 0.007 and 0.01 , respectively ) . Our data suggest that and rogens , which are inversely associated with insulin resistance , are important in the early prostate cancer development , whereas insulin resistance related factors may be important for tumour progression",
"Experimental and prevalent case-control studies suggest an association between biomarkers of inflammation , endothelial function , and adiposity and cancer risk , but results from prospect i ve studies have been limited . The authors ' objective was to prospect ively examine the relations between these biomarkers and cancer risk . A nested case-control study was design ed within the Supplémentation en Vitamines et Minéraux Antioxydants ( SU.VI.MAX ) Study , a nationwide French cohort study , to include all first primary incident cancers diagnosed between 1994 and 2007 ( n = 512 ) . Cases were matched with r and omly selected controls ( n = 1,024 ) on sex , age ( in 2-year strata ) , body mass index ( weight (kg)/height (m)(2 ) ; SU.VI.MAX intervention group . Conditional logistic regression was used to study the associations between prediagnostic levels of high-sensitivity C-reactive protein ( hs-CRP ) , adiponectin , leptin , soluble intercellular adhesion molecule 1 ( sICAM-1 ) , soluble vascular cell adhesion molecule 1 , soluble E-selectin , and monocyte chemoattractant protein 1 and cancer risk . All statistical tests were 2-sided . Plasma sICAM-1 level was positively associated with breast cancer risk ( for quartile 4 vs. quartile 1 , multivariate odds ratio ( OR ) = 1.86 , 95 % confidence interval ( CI ) : 1.06 , 3.26 ; P(trend ) = 0.048 ) . Plasma hs-CRP level was positively associated with prostate cancer risk ( for quartile 4 vs. quartile 1 , multivariate OR = 3.04 , 95 % CI : 1.28 , 7.23 ; P(trend ) = 0.03 ) . These results suggest that prediagnostic hs-CRP and sICAM-1 levels are associated with increased prostate and breast cancer risk , respectively",
"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",
"Purpose The aim of this study was to investigate the clinical significance of 7 circulating adipokines according to body mass index ( BMI ) in Korean men with localized prostate cancer ( PCa ) undergoing radical prostatectomy ( RP ) . Material s and Methods Sixty-two of 65 prospect ively enrolled patients with clinical ly localized PCa who underwent RP between 2015 and 2016 were evaluated . Patients were classified into 2 groups according to their BMI : non-obese ( interleukin-2 , insulin-like growth factor 1 ( IGF-1 ) , chemerin , C-X-C motif chemokine 10 , adiponectin , leptin , and resistin . Multivariate logistic regression analysis was used to identify the independent predictors of advanced tumor stage . Results We found that obese patients with PCa who underwent RP had a higher incidence of tumors with a high Gleason score ( ≥8 ) , pathological T3 ( pT3 ) stage , and positive extraprostatic extension than patients with a normal BMI . Additionally , patients with obesity showed significantly lower serum adiponectin and higher serum leptin levels , but did not show differences in other adipokines . Multivariate analysis demonstrated that IGF-1 ( odds ratio [OR]=1.03 ) was identified as a predictor of advanced tumor stage ( ≥pT3 ) in the overall population . However , only leptin remained an independent predictive factor for advanced tumor stage ( ≥pT3 ) ( OR=1.15 ) in patients with obesity . Conclusions In conclusion , our results indicate that a higher leptin level in obese men can be considered a risk factor for aggressive PCa . This prospect i ve study provides greater insight into the role of circulating adipokines in Korean patients with PCa undergoing RP , particularly in patients with obesity",
"BACKGROUND Obesity is associated with prostate cancer ( PCA ) grade , but the mechanism behind this relationship is not understood . Adiponectin is an adipokine that has been linked with the development of hormonally sensitive carcinomas , including prostate cancer . We evaluated the relationship between serum adiponectin and Gleason score ( GS ) in a prospect i ve series of patients seen in a single institution . METHODS Localized PCA patients evaluated at Dana-Farber Cancer Institute between 2001 and 2005 who enrolled in a prospect i ve serum banking protocol were eligible for this study . Patients with prior hormonal therapy and /or metastatic disease were excluded . High- grade disease was defined as biopsy or radical prostatectomy ( RP ) GS of 7 or higher . Logistic regression models were used to assess the relationship between high- grade disease and adiponectin levels while adjusting for other potential prognostic variables . RESULTS There were 539 patients included in this study , of whom 199 had undergone RP . Median age was 60 years . Median PSA was 5.1 ng/dl . Biopsy GS of 7 or higher was seen in 46.9 % of patients . For biopsy GS , higher PSA , older age , and higher BMI were significantly associated with increased odds of GS 7 or higher , but adiponectin was not . In men undergoing RP , there was a significant inverse relationship between pathologic GS and adiponectin dichotomized at the median , due to a significantly higher rate of upgrading in patients with lower adiponectin ( P = 0.014 ) . CONCLUSIONS Although there was no association between biopsy GS and adiponectin , in patients who had undergone RP , lower adiponectin was independently associated with high- grade prostate cancer",
"BACKGROUND Adipocytokines may mediate the association between adiposity and lethal prostate cancer outcomes . METHODS In the Physicians ' Health Study , we prospect ively examined the association of prediagnostic plasma concentrations of adiponectin and leptin with risk of developing incident prostate cancer ( 654 cases diagnosed 1982 - 2000 and 644 age-matched controls ) and , among cases , risk of dying from prostate cancer by 2007 . RESULTS Adiponectin concentrations were not associated with risk of overall prostate cancer . However , men with higher adiponectin concentrations had lower risk of developing high- grade or lethal cancer ( metastatic or fatal disease ) . The relative risk ( 95 % CI ) comparing the highest quintile to the lowest ( Q5 vs Q1 ) was 0.25 ( 95 % CI 0.07 - 0.87 ; P(trend ) = 0.02 ) for lethal cancer . Among all the cases , higher adiponectin concentrations predicted lower prostate cancer-specific mortality [ hazard ratio (HR)(Q5 vs Q1)= 0.39 ; 95 % CI 0.17 - 0.85 ; P(trend ) = 0.02 ] , independent of body mass index ( BMI ) , plasma C-peptide ( a marker of insulin secretion ) , leptin , clinical stage , and tumor grade . This inverse association was apparent mainly among men with a BMI > or=25 kg/m(2 ) ( HR(Q5 vs Q1)= 0.10 ; 95 % CI 0.01 - 0.78 ; P(trend ) = 0.02 ) , but not among men of normal weight ( P(trend ) = 0.51 ) . Although the correlation of leptin concentrations with BMI ( r = 0.58 , P adiponectin ( r = -0.17 , P prostate cancer risk or mortality . CONCLUSIONS Higher prediagnostic adiponectin ( but not leptin ) concentrations predispose men to a lower risk of developing high- grade prostate cancer and a lower risk of subsequently dying from the cancer , suggesting a mechanistic link between obesity and poor prostate cancer outcome"
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41187e12-06ff-11f0-808a-c43d1ab1c353
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PURPOSE A systematic review of behavioural intervention for the treatment of adults with muscle tension voice disorders ( MTVD ) . METHOD A search of 12 electronic data bases and reference lists for studies published between the years 1990 - 2014 was conducted using the PRISMA guidelines . Inclusion and exclusion criteria included type of publication , participant characteristics , intervention , outcome measures and report of outcomes . Method ological quality rating scales and confidence in diagnostic scale supported the literature evaluation . RESULT Seven papers met the inclusion criteria . Significant improvement on at least one outcome measure was reported for all studies . Effect sizes were small-to-large . Method ological qualities of research were varied . No study explicitly reported treatment fidelity and cumulative intervention intensity could only be calculated for two out of seven studies . Outcome measures were used inconsistently and less than half of the measures had reported reliability values . Confidence in the accuracy of subject diagnosis on average was rated as low . Specific " active ingredients " for therapeutic change were not identified . CONCLUSION Voice therapy for the treatment of MTVD is associated with positive treatment outcomes ; however , there is an obvious need for systematic and high quality research design s to exp and the evidence base for the behavioural treatment of MTVD
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"INTRODUCTION AND OBJECTIVES Laryngeal electromyography , together with clinical evaluation , is a valuable tool in voice disorder management . It assesses the integrity of laryngeal nerves and muscles , contributing to the diagnosis of many diseases , especially laryngeal movement disorders . Our purpose was to describe the experience of the first Spanish series with laryngeal electromyography in evaluating voice disorders . METHODS A prospect i ve study was design ed to evaluate laryngeal movement disorders with laryngeal electromyography . Both the cricothyroid and thyroarytenoid muscles were tested routinely and , in some cases , the posterior cricoarytenoid muscle . The laryngeal electromyography technique and result interpretation were performed by a laryngologist and a neurophysiologist . RESULTS We included 110 patients , with the most common symptom being dysphonia . Laryngeal electromyography was performed in 85 % of cases . Primary diagnosis before electromyography was laryngeal immobility . Positive predictive value for diagnosis in cases of paralysis was 88 % . CONCLUSIONS Laryngeal electromyography is a useful adjunct , together with clinical evaluation , for diagnosis and management of motion abnormalities in the larynx in patients who present with dysphonia",
"OBJECTIVES Epidemiologic studies of the prevalence and risk factors of voice disorders in the general adult population are rare . The purpose of this investigation was to 1 ) determine the prevalence of voice disorders , 2 ) identify variables associated with increased risk of voice disorders , and 3 ) establish the functional impact of voice disorders on the general population . STUDY DESIGN Cross-sectional telephone survey . METHODS A r and om sample ( n = 1,326 ) of adults in Iowa and Utah was interviewed using a question naire that addressed three areas related to voice disorders : prevalence , potential risk factors , and occupational consequences/effects . RESULTS The lifetime prevalence of a voice disorder was 29.9 % , with 6.6 % of participants reporting a current voice disorder . Stepwise logistic regression identified specific factors that uniquely contributed to increased odds of reporting a chronic voice disorder including sex ( women ) , age ( 40 - 59 years ) , voice use patterns and dem and s , esophageal reflux , chemical exposures , and frequent cold/sinus infections . However , tobacco or alcohol use did not independently increase the odds of reporting of a chronic voice disorder . Voice disorders adversely impacted job performance and attendance , with 4.3 % of participants indicating that their voice had limited or rendered them unable to do certain tasks in their current job . Furthermore , 7.2 % of employed respondents reported that they were absent from work 1 or more days in the past year because of their voice , and 2 % reported more than 4 days of voice-related absence . CONCLUSIONS The results of this large epidemiologic study provide valuable information regarding the prevalence of voice disorders , factors that contribute to voice disorder vulnerability , and the functional impact of voice problems on the general population",
"Objectives To determine the utility of spectral analysis in the differentiation of adductor-type spasmodic dysphonia ( AdSD ) from muscle tension dysphonia ( MTD ) . Study Design Prospect i ve blinded study . Methods Forty-seven sample s of AdSD-connected speech spectrograms from 27 subjects and 17 sample s of MTD-connected speech spectrograms from 15 subjects were selected from clinical charts and de-identified . These spectrograms were review ed independently and blindly by two speech language pathologists experienced in spectrography . The speech language pathologists design ated the spectrogram as consistent with AdSD and MTD , and these design ations were compared with actual clinical diagnoses . Results The ability to differentiate AdSD from MTD with spectral analysis was 94 % for rater # 1 and 98 % for rater # 2 . No MTD subjects were incorrectly diagnosed as having SD ( 100 % specificity ) . Conclusions This study suggests that experienced speech language pathologists can distinguish AdSD from MTD with a high degree of sensitivity and specificity based on spectral analysis . Spectral analysis is especially useful in cases where perceptual analysis and clinical evaluation alone are insufficient",
"Recent literature suggests a revival of interest in single-case methodology ( e.g. , the r and omised n-of-1 trial is now considered Level 1 evidence for treatment decision purpose s by the Oxford Centre for Evidence -Based Medicine ) . Consequently , the availability of tools to critically appraise single-case reports is of great importance . We report on a major revision of our method quality instrument , the Single-Case Experimental Design Scale . Three changes result ed in a radically revised instrument , now entitled the Risk of Bias in N-of-1 Trials ( RoBiNT ) Scale : ( i ) item content was revised and increased to 15 items , ( ii ) two subscales were developed for internal validity ( IV ; 7 items ) and external validity and interpretation ( EVI ; 8 items ) , and ( iii ) the scoring system was changed from a 2-point to 3-point scale to accommo date currently accepted st and ards . Psychometric evaluation indicated that the RoBiNT Scale showed evidence of construct ( discriminative ) validity . Inter-rater reliability was excellent , for pairs of both experienced and trained novice raters . Intraclass correlation coefficients of summary scores for individual ( experienced ) raters : ICCTotalScore = .90 , ICCIVSubscale = .88 , ICCEVISubscale = .87 ; individual ( novice ) raters : ICCTotalScore = .88 , ICCIVSubscale = .87 , ICCEVISubscale = .93 ; consensus ratings between experienced and novice raters ( ICCTotalScore = .95 , ICCIVSubscale = .93 , ICCEVISubscale = .93 . The RoBiNT Scale thus shows sound psychometric properties and provides a comprehensive yet efficient examination of important features of single-case methodology",
"Background Childhood Apraxia of Speech is an impairment of speech motor planning that manifests as difficulty producing the sounds ( articulation ) and melody ( prosody ) of speech . These difficulties may persist through life and are detrimental to academic , social , and vocational development . A number of published single subject and case series studies of speech treatments are available . There are currently no r and omised control trials or other well design ed group trials available to guide clinical practice . Methods / Design A parallel group , fixed size r and omised control trial will be conducted in Sydney , Australia to determine the efficacy of two treatments for Childhood Apraxia of Speech : 1 ) Rapid Syllable Transition Treatment and the 2 ) Nuffield Dyspraxia Programme – Third edition . Eligible children will be English speaking , aged 4–12 years with a diagnosis of suspected CAS , normal or adjusted hearing and vision , and no comprehension difficulties or other developmental diagnoses . At least 20 children will be r and omised to receive one of the two treatments in parallel . Treatments will be delivered by trained and supervised speech pathology clinicians using operationalised manuals . Treatment will be administered in 1-hour sessions , 4 times per week for 3 weeks . The primary outcomes are speech sound and prosodic accuracy on a customised 292 item probe and the Diagnostic Evaluation of Articulation and Phonology inconsistency subtest administered prior to treatment and 1 week , 1 month and 4 months post-treatment . All post assessment s will be completed by blinded assessors . Our hypotheses are : 1 ) treatment effects at 1 week post will be similar for both treatments , 2 ) maintenance of treatment effects at 1 and 4 months post will be greater for Rapid Syllable Transition Treatment than Nuffield Dyspraxia Programme treatment , and 3 ) generalisation of treatment effects to untrained related speech behaviours will be greater for Rapid Syllable Transition Treatment than Nuffield Dyspraxia Programme treatment . This protocol was approved by the Human Research Ethics Committee , University of Sydney ( # 12924 ) . Discussion This will be the first r and omised control trial to test treatment for CAS . It will be valuable for clinical decision-making and providing evidence -based services for children with CAS.Trial Registration Australian New Zeal and Clinical Trials Registry :",
"The objectives of this study were to determine appropriate acoustic and outcome measures for the evaluation of a method of laryngeal manual therapy ( LMT ) used in the treatment of patients with muscle tension dysphonia ( MTD ) . The effects of this technique were also investigated . The study was based on the hypotheses that the vertical position of the larynx in the vocal tract would lower , that the quality of the voice would normalize , and that a reduction in any vocal tract discomfort ( VTD ) would occur after LMT . This was a small , prospect i ve , repeated measures pilot study in which each member of the research team was \" blinded \" to all other stages of the study and during which all data were anonymized until the final stage of data analysis . Ten subjects presenting with MTD completed outcome measures and provided audiorecordings immediately before , immediately after , and 1 week after LMT . The Kay CSL 4150 was used for signal acquisition and for some acoustic measurements . Spectrographic evaluation was accomplished with Praat . A new perceptual , self-rating scale , the VTD scale , and a new proforma for use by the clinician for palpatory evaluation , were developed for the study . Relative average perturbation during connected speech was significantly reduced after LMT , indicating a reduction in abnormal vocal function . The severity and frequency of VTD was shown to have reduced after LMT . This pilot study showed positive evidence for LMT as a method of therapy in the treatment of hyperfunctional voice disorders . Its effects were shown to be measurable with both acoustical analysis and the VTD scale",
"The aim of this article is to present a set of evidence levels , accompanied by 14 quality or rigor questions , to foster a critical review of published single‐subject research articles . In developing these guidelines , we review ed levels of evidence and quality /rigor criteria that are in wide use for group research design s , e.g. r and omized controlled trials , such as those developed by the Treatment Outcomes Committee of the American Academy for Cerebral Palsy and Developmental Medicine . We also review ed method ological articles on how to conduct and critically evaluate single‐subject research design s ( SSRDs ) . We then subjected the quality questions to interrater agreement testing and refined them until acceptable agreement was reached . We recommend that these guidelines be implemented by clinical research ers who plan to conduct single‐subject research or who incorporate SSRD studies into systematic review s , and by clinicians who aim to practise evidence ‐based medicine and who wish to critically review pediatric single‐subject research",
"BACKGROUND speechBITE ( http://www.speechbite.com ) is an online data base established in order to help speech and language therapists gain faster access to relevant research that can used in clinical decision-making . In addition to containing more than 3000 journal references , the data base also provides method ological ratings on the PEDro-P ( an adapted version of the PEDro ) scale to assist clinicians in identifying the scientific quality of r and omized ( RCTs ) and non-r and omized control trials ( N RCTs ) . While reliability of the PEDro scale has been established by similar allied health data bases , the reliability of the PEDro-P scale has yet to be reported . AIMS To examine the reliability of PEDro-P scale ratings undertaken by raters on the speechBITE data base and benchmark these results to the published reliability for the original PEDro scale . Both the total score ( out of ten ) as well as each of the 11 scale items were included in this analysis . METHODS & PROCEDURES speechBITE 's volunteer rater network of 17 members rated the first 100 RCTs and N RCTs on the website . The criterion and overall scores for these ratings were compared with previously published reliability studies using the PEDro scale . Intra-class correlations and per cent agreement measures were used to establish and benchmark reliability . OUTCOMES & RESULTS The speechBITE PEDro-P ratings ranged from fair to excellent for both the total score and for each of the 11 scale items . Furthermore , reliability was equal to that of other data bases . CONCLUSIONS & IMPLICATION S speechBITE users can be confident of the reliability of ratings published on the website . Further analysis of differences between this study and previous PEDro scale reliability studies are discussed",
"In a previous study , female patients in all age categories with a nonorganic dysphonia were found to report significantly more autonomic symptoms and complaints than healthy controls . This could not be confirmed for the male subgroup . The present study is to corroborate and nuance this observation by investigating larger groups , and to determine if , after voice therapy , the number of autonomic symptoms and complaints-particularly those ones that have no obvious relation to voice function-decreases . It is a prospect i ve study with a matched control group ; 184 patients with nonorganic dysphonia and 126 normal controls answered a question naire of 46 questions with 3 subsets and a consistency control . One hundred and one patients received functional voice therapy and completed the question naire before and after treatment . A matched control group of 42 normal subjects also filled in the question naire two times , with an interval of about 6 months . Neurovegetative symptoms and complaints-voice related and not related-are reported in highly significant excess by patients ( especially but not exclusively females ) with habitual nonorganic voice disorder . After therapy , there is a highly significant reduction in the number of autonomic symptoms and complaints ( related or not related to voice ) , to such an extent that patients report on average no more general neurovegetative symptoms and complaints than healthy controls ( even less ) . The number of neurovegetative symptoms and complaints connected with voice function is also strongly reduced in patients after therapy , but remains in significant excess when compared with controls",
"Rating scales that assess method ological quality of clinical trials provide a means to critically appraise the literature . Scales are currently available to rate r and omised and non-r and omised controlled trials , but there are none that assess single-subject design s. The Single-Case Experimental Design ( SCED ) Scale was developed for this purpose and evaluated for reliability . Six clinical research ers who were trained and experienced in rating method ological quality of clinical trials developed the scale and participated in reliability studies . The SCED Scale is an 11-item rating scale for single-subject design s , of which 10 items are used to assess method ological quality and use of statistical analysis . The scale was developed and refined over a 3-year period . Content validity was addressed by identifying items to reduce the main sources of bias in single-case methodology as stipulated by authorities in the field , which were empirically tested against 85 published reports . Inter-rater reliability was assessed using a r and om sample of 20/312 single-subject reports archived in the Psychological Data base of Brain Impairment Treatment Efficacy ( PsycBITETM ) . Inter-rater reliability for the total score was excellent , both for individual raters ( overall ICC = 0.84 ; 95 % confidence interval 0.73–0.92 ) and for consensus ratings between pairs of raters ( overall ICC = 0.88 ; 95 % confidence interval 0.78–0.95 ) . Item reliability was fair to excellent for consensus ratings between pairs of raters ( range k = 0.48 to 1.00 ) . The results were replicated with two independent novice raters who were trained in the use of the scale ( ICC = 0.88 , 95 % confidence interval 0.73–0.95 ) . The SCED Scale thus provides a brief and valid evaluation of method ological quality of single-subject design s , with the total score demonstrating excellent inter-rater reliability using both individual and consensus ratings . Items from the scale can also be used as a checklist in the design , reporting and critical appraisal of single-subject design s , thereby assisting to improve st and ards of single-case methodology",
"Since April 1997 , in Melbourne , Australia , speech pathologists have collaborated to establish a prospect i ve data base of functional outcomes of speech , swallowing and voice for patients undergoing head and neck cancer treatments . Staff at eight acute care hospitals , all of which offer speech pathology for head and neck cancer services in Victoria , are contributing data , collated central ly , in an agreed pro forma . Early results are given ( after 12 months ' data collection ) . The implication s for clinical ly-based research , and the future potential for benchmarking outcomes --by expansion of the rehabilitation data base beyond the current participating sites -- is discussed . This paper outlines the rationale of establishing the data base is multicentered , and explores some of the complexities involved , including the challenges inherent in long-term accurate data collection in the head and neck cancer patient population . This work represents the development of an appropriate , usable tool for data collection on functional outcomes",
"Voice therapy changes how people use and care for their voices . Speech- language pathologists ( SLPs ) have a multitude of choices from which to modify patient 's vocal behaviors . Six SLPs performed 1461 voice therapy sessions and quantified the percentage of time spent in eight component parts of indirect and four component parts of direct voice therapy across five common voice disorders . Voice therapy data collection forms were prospect ively completed immediately following each therapy visit . The SLPs were free to choose the component parts of voice therapy best suited for their respective patients . Results showed that direct voice therapy represented more than 75 % of the treatment time across all voice therapy sessions . In the components of direct voice therapy , there was no statistical difference between percentages of time spent in resonant voice and flow phonation across all voice disorders . However , a significant difference was found for the time spent addressing transfer to conversational speech for muscle tension dysphonia , lesions , and scar than for vocal immobility and atrophy . Interestingly , while SLPs used a more common approach to direct voice therapy across voice disorders , they tended to vary the use of indirect components of therapy across voice disorders with certain components being addressed in greater length for specific voice disorders . Collectively , these results indicate that although SLPs may individualize their approach to indirect voice therapy , when it comes to direct voice therapy , SLPs have a common approach to voice therapy regardless of voice disorder",
"Transnasal flexible laryngoscopy ( TFL ) is an examination of laryngeal anatomy and physiology using continuous light . TFL is being used increasingly by voice pathologists in treatment but with little scientific evidence to support it . The purpose of this study was to evaluate the effectiveness and efficiency of TFL as a therapeutic tool . The study used a prospect i ve r and omized controlled trial . Fifty dysphonic subjects were recruited and r and omly assigned to either a traditional treatment group or a TFL-assisted treatment group . The effectiveness of voice therapy in both treatment groups was measured with a package of voice outcome measures . Subjects in both treatment groups demonstrated statistically significant improvements after voice therapy ( perceptual auditory rating of voice quality measurement p instrumental electroglottographic measurement p patient question naire measurement p time taken to complete treatment in both groups was recorded . The average ( median ) time taken to complete voice therapy in the TFL-assisted treatment group was 2 hours less than in the traditional treatment group ( p Voice therapy with TFL as a therapy tool was effective and more efficient than traditional voice therapy",
"OBJECTIVE This study evaluated the treatment effects of vocal function exercises on muscle tension dysphonia ( MTD ) in tonal language speakers . DESIGN Single-blinded , r and omized , controlled , clinical trial . METHODS Forty female primary school teachers from Northern Vietnam , diagnosed with MTD , were r and omly allocated into a treatment group ( n = 22 ) , which used a full vocal exercise protocol ( FE ) ( modified for use with Vietnamese speakers ) , and a control group ( n = 18 ) which was treated with a partial vocal exercise protocol ( PE ) . The treatment duration was 4 weeks for both groups . MAIN OUTCOME MEASURES Acoustic and perceptual data were used as primary outcome measures . Acoustic parameters included frequency and amplitude perturbation , harmonics-to-noise ratio ( HNR ) , mean fundamental frequency of the broken and rising tones , and parameters representing pitch movement in the rising tone . Perceptual analyses were performed on pre- and posttreatment sample s of the sustained /a/ sound using anchor vocal sample s. Self-report data , collected via a posttreatment question naire , comprised the secondary outcome measure . RESULTS Significant changes in perturbation , HNR , and perceptual data were observed in the FE group but not in the PE group . The FE group showed increased size and speed of pitch change . Participants from both groups showed positive changes in some tonal parameters after treatment . However , the magnitude of change and the number of participants with positive changes were larger in the FE group . CONCLUSION The data showed that vocal function exercises may be a cost-effective treatment for MTD",
"OBJECTIVE To assess the relationship between tongue trill performance duration and auditory perception and acoustic changes in dysphonic women . STUDY DESIGN Prospect i ve clinical study , with intrasubject comparison . METHODS Twenty-seven women who had vocal nodules were in the experimental group ( EG ) ( tongue trills ) , and 10 were also in the control group ( CG ) ( placebo exercises ) . The voices were recorded before and after experimental and placebo exercises at the first ( m1 ) , third ( m3 ) , fifth ( m5 ) , and seventh ( m7 ) minutes of performance . These recordings were r and omized , and the auditory perception analysis was carried out by three judges trained in voice analysis . Individual recordings were analyzed using the Consensus Auditory-Perceptual Evaluation of Voice ( CAPE-V ) protocol , the r and omized pairs of recordings were compared , and the better voice was chosen . VoxMetria software ( CTS , Parana , Brazil , www.ctsinformatica.com.br ) was used to assess the acoustic . RESULTS In the EG , the CAPE-V results showed a predominance of vocal improvement , statistically proven , at m5 of tongue trill exercise , with the best overall rating , the least roughness and breathiness , and increase in pitch level . At m7 , strain was significantly higher . In the paired comparison analysis , voices at m5 were considered the best of all moments . There was an increase of the F(0 ) and glottal-to-noise excitation after m3 and a decrease in noise as in m1 . In the CG , vocal changes were discrete compared with those in the EG . CONCLUSION Tongue trill performance duration interfered with the vocal response of dysphonic women , with positive response predominance at m5 . At m7 , there was an increase of vocal tension and a drop in vocal quality",
"OBJECTIVES /HYPOTHESES To assess the utility of a targeted voice hygiene ( VH ) program compared to VH plus voice training intervention ( VH+VT ) for the prevention and treatment of voice problems in student teachers . STUDY DESIGN Prospect i ve , r and omized . METHODS Thirty-one student teachers with low ( good ) and high ( poor ) voice h and icap index ( VHI ) scores in Pittsburgh and Hong Kong were r and omly assigned to ( 1 ) a targeted , individually tailored VH program , ( 2 ) the VH program plus resonant VT ( VH+VT ) , or ( c ) a control group . Participants assigned to intervention groups were monitored for their adherence to their programs for their first 4 weeks of student teaching . VHI data were collected again 4 weeks postintervention ( both sites ) and 8 weeks postintervention , following a no-contact washout period ( Pittsburgh ) . RESULTS Descriptive data analysis indicated that across both sites , for initially healthy participants , the VH program was sufficient to prevent worsening of VHI scores that occurred in all control participants over the first 4 - 8 weeks of student teaching . The addition of VT did not consistently enhance protective benefits over VH alone . In contrast , for participants with initially poor VHI scores , the VH program failed to produce VHI benefits over the control condition . The addition of VT was required to optimize results for that cohort . CONCLUSIONS Preliminary data suggest that a minimalist , individually tailored VH program may be sufficient to prevent voice problems from teaching in healthy student teachers . However , for student teachers with existing voice problems , VT may be required to optimize results of intervention",
"Forty-five patients diagnosed as having non-organic dysphonia were assigned in rotation to one of three groups . Patients in one group received no treatment and acted as a control group . Patients in the other two groups received a programme of either ' indirect ' therapy or ' direct with indirect ' therapy , respectively . A self-report question naire of vocal performance , observed ratings of voice quality , and computer-derived acoustic measurements ( signal-to-noise ratio , pitch perturbation and amplitude perturbation ) were carried out on all patients before and after treatment to evaluate the changes in voice quality over time . There was a significant difference between the three groups on the self-report question naire , voice quality ratings and pitch perturbation measurements ( P = 15 control patients showed no significant change on any of the measures . Seven patients who received indirect treatment showed significant improvement in voice quality following treatment . Fourteen out of 15 patients who received direct treatment showed significant improvement in voice quality",
"BACKGROUND Lately , the number of systematic review s published has increased substantially . Many systematic review s exclude trials published in language s other than English . However , there is little empirical evidence to support this action . We looked for differences in the completeness of reporting between trials published in other language s and those published in English , to see whether the exclusion of trials published in other language s is justified . METHODS We compared completeness of reporting , design characteristics , and analytical approaches of 133 r and omised controlled trials ( RCTs ) published in English between 1989 and 1994 and 96 published in French , German , Italian , or Spanish during the same time . RCTs were identified by h and search ing of journals ( seven in English and six in the other language s ) . FINDINGS We found no significant differences between trials published in English and other- language trials for any single item in the completeness of reporting scale ( r and omisation , double-blinding , withdrawals ) , or for the overall score ( percentage of maximum possible score 51.0 % for trials in English , 46.2 % for trials in other language s ; 95 % CI for difference -1.1 to 10.5 ) . Other- language trials were more likely than English- language trials to have adult participants , to use two or more interventions , and to compare two or more active treatments without an untreated control group . Trials in other language s were less likely to report a clearly prespecified primary outcome or any rationale for sample size estimation . INTERPRETATION These results provide evidence for inclusion of all trial reports , irrespective of the language in which they are published , in systematic review s. Their inclusion is likely to increase precision and may reduce systematic errors . We hope that our findings will prove useful to those developing guidelines and policies for the conduct of reporting of systematic review",
"In previous studies , female patients in all age categories with a nonorganic dysphonia were found to report significantly more autonomic symptoms and complaints than healthy controls . After voice therapy , there was a highly significant reduction in the amount of autonomic symptoms and complaints ( related or not related to voice ) . The present prospect i ve study with a matched control group is design ed to test the hypothesis that a specific kind of therapy is more efficient than the usual approaches in reducing these neurovegetative symptoms and complaints . Two matched groups of 34 patients diagnosed with nonorganic dysphonia and referred for voice therapy answered a question naire of 46 questions with 3 subsets and a consistency control . They received either \" coordination therapy \" (CTh)--a holistic approach addressing functional , personal and emotional aspects -- or a conventional voice therapy ( approximately 15 sessions ) . All patients again filled in a similar question naire after approximately 6 months . After therapy , there is in general a highly significant reduction in the amount of autonomic symptoms and complaints ( related or not related to voice ) , to such an extent that patients report on average no more general neurovegetative symptoms and complaints than those of healthy controls . Symptoms and complaints of other nature ( validity control ) are not influenced . When compared with patients receiving conventional therapy , those who received CTh demonstrate a significantly higher reduction for the subset \" neurovegetative symptoms/complaints related to voice and speech .",
"There is an increasing need for studies of efficacy of behavior readjustment therapy procedures in human communicative disorders . Legal , social , scientific and professional considerations point up the need for more careful documentation of the effects of treatment techniques used by phoniatricians and speech- language pathologists . This study is conducted in order to evaluate the efficacy of the accent method of voice therapy ( AM ) . The AM is one of the holistic approaches for behavior readjustment voice therapy . It tackles collectively and simultaneously the various parameters of voice such as pitch , loudness and timbre . The results of intervention utilizing the AM in this clinical trial are assessed in a relatively controlled setup . Patients with voice problems result ing from various etiologic vocal pathologies are distributed r and omly into two groups . Group 1 ( G1 ) is given the full aspect of the AM , that is , voice hygiene advice plus the accent exercises to correct the faulty vocal technique ( habit ) . Group 2 ( G2 ) receives only voice hygiene advice . The AM is administered in individual sessions 20 min each , twice a week , while the voice hygiene advice counseling is given once a week . The assessment of the vocal pathology is done following a diagnostic protocol utilizing subjective as well as quasi- objective measures of evaluation . The initial assessment presents the baseline ( pretest ) data for both groups . The follow-up evaluations are done at mid intervention ( mid-test ) , that is , 10 sessions for G1 and 5 sessions for G2 , and at the termination of intervention/therapy ( post-test ) . The difference in improvement between G1 and G2 at the end of the observation was generally significant in favor of G1 . There were significant improvements in G1 in certain items specific for the various etiologic categories . The improvement from pretest to mid-test to post-test values followed a linear tendency . The significance of the results is discussed and the conclusions are outlined and criticized"
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PURPOSE To identify and appraise the literature on clinical measures of spasticity that has been investigated in people after stroke . METHODS The literature search involved four data bases ( PubMed , CINAHL , Embase and The Cochrane Library ) up to February 2014 . The selected studies included those that aim ed to measure spasticity using a clinical assessment tool among adult patients post-stroke . Two independent raters review ed the included articles using a critical appraisal scale and a structured data extraction form . RESULTS A total of 40 studies examining 15 spasticity assessment tools in patients post-stroke were review ed . None of the review ed measurement tools demonstrated satisfactory results for all psychometric properties evaluated , and the majority lacked evidence concerning validity and absolute reliability . CONCLUSION This systematic review found limited evidence to support the use of most of clinical measures of spasticity for people post-stroke . Future research examining the application and psychometric properties of these measures is warranted . Implication s for Rehabilitation There is a need for objective clinical tools for measuring spasticity that are clinical ly feasible and easily interpreted by clinicians . This review identified various clinical measures of spasticity that have been investigated in people after stroke . Insufficient evidence of psychometric properties precludes recommending one tool over the others . Future research should focus on investigating the psychometric properties of clinical measures of spasticity
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"Background and Purpose — There is currently no consensus on ( 1 ) the percentage of patients who develop spasticity after ischemic stroke , ( 2 ) the relation between spasticity and initial clinical findings after acute stroke , and ( 3 ) the impact of spasticity on activities of daily living and health-related quality of life . Methods — In a prospect i ve cohort study , 301 consecutive patients with clinical signs of central paresis due to a first-ever ischemic stroke were examined in the acute stage and 6 months later . At both times , the degree and pattern of paresis and muscle tone , the Barthel Index , and the EQ-5D score , a st and ardized instrument of health-related quality of life , were evaluated . Spasticity was assessed on the Modified Ashworth Scale and defined as Modified Ashworth Scale > 1 in any of the examined joints . Results — Two hundred eleven patients ( 70.1 % ) were reassessed after 6 months . Of these , 42.6 % ( n=90 ) had developed spasticity . A more severe degree of spasticity ( Modified Ashworth Scale ≥3 ) was observed in 15.6 % of all patients . The prevalence of spasticity did not differ between upper and lower limbs , but in the upper limb muscles , higher degrees of spasticity ( Modified Ashworth Scale ≥3 ) were more frequently ( 18.9 % ) observed than in the lower limbs ( 5.5 % ) . Regression analysis used to test the differences between upper and lower limbs showed that patients with more severe paresis in the proximal and distal limb muscles had a higher risk for developing spasticity ( P≤0.001 ) . Spasticity of the upper and lower limb was more frequent in patients with hemihypesthesia than in patients without sensory deficits ( P≤0.001 ) . Patients with spasticity showed a lower Barthel Index and EQ-5D score compared with the group without spasticity . Conclusions — Spasticity was present in 42.6 % of patients with initial central paresis . However , severe spasticity was relatively rare . Predictors for the development of spasticity were a severe degree of paresis and hemihypesthesia at stroke onset",
"OBJECTIVES This study investigated the reliability of joint resting position ( EJP ) , resistance to passive movement ( ERM ) , and the angle of appearance of the resistance ( EAR ) as measures of muscle hypertonus of elbow flexors in patients after stroke . Previously , similar measures had been found reliable when applied to measuring shoulder and wrist hypertonus in patients after stroke . METHOD Forty-five subjects with stroke were r and omly selected from occupational therapy admissions at two rehabilitation centers . Tone of elbow flexors was measured twice at the same sitting by two examiners . EJP and EAR were measured with a goniometer , and ERM was measured with a resistance rating scale . Correlations were calculated between first and second measurements by center and by high tone and poor upper extremity function subgroups ( with correction for multiple correlations ) to determine reliability . RESULTS Each of the three measures was highly reliable as demonstrated by a high correlation in at least one of the subgroups ( Center 1 : EJP , r = .964 for high tone subgroup ; ERM , r = .789 , EAR , r = .902 , both in poor upper extremity function subgroup ; and Center 2 : EJP , r = .892 , ERM , r = .938 , both in poor upper extremity function subgroup ; EAR , r = .666 for all subjects ; all p values < .05 ) . Correlations were especially high when data for subjects with high upper extremity function were eliminated . CONCLUSION Reliability of these three methods of measuring upper extremity muscle tone enhances their usefulness as well as therapists ' confidence in their judicial application",
"The objective of this study is to develop a portable device for quantifying the velocity-dependent properties of spastic elbow muscles . Based on a motor-driven system , validation tests of the portable system such as accuracy and response of sensors were first examined . Furthermore , simulated modules ( inertia , damper and spring ) as well as elbow joints ( 15 control and 15 hemiplegic subjects ) were manually stretched under four different frequencies ( 1/3 , 1/2 , 1 and 3/2 Hz ) through 60 degrees range of motion . Joint resistance and displacement during sinusoidal stretch were collected for further analysis . Two quantitative parameters ( i.e. , viscous components under each frequency and averaged viscosity across four frequencies ) were derived to estimate the velocity-dependent properties of elbow joint . Tests of simulated modules confirm the manual stretch protocol and data analysis are valid in estimating the velocity-dependent component during a sinusoidal stretch . Compared to normal control , viscous component in each stretch frequency and averaged viscosity were significantly higher in subjects with spasticity ( P viscous component and averaged viscosity were found highly correlated with the modified Ashworth scale . These findings suggest that measurements of viscous component and averaged viscosity during manual sinusoidal stretching using the portable device could be clinical ly useful in evaluating spasticity",
"The Modified Ashworth Scale ( MAS ) is currently a widely used clinical scale to evaluate muscle spasticity . However , it lacks reliability and the validity , of the MAS as a clinical measure of muscle spasticity has been challenged . The aim of the present study was to examine the validity of the MAS in patients with wrist flexor spasticity after stroke by using the Hslope/Mslope ( Hslp/Mslp ) ratio as the new index of alpha motoneuron excitability . Twenty-seven adult patients ( 14 women and 13 men ) with first ever stroke result ing in hemiplegia with a mean ( SD , range ) age of 57.9 ( 11.6 , 37 - 75 ) were included in the study . The main outcome measures were the MAS for the clinical assessment of spasticity , and the Hslp/Mslp for the neurophysiological evaluation . There was not a significant correlation between the MAS scores and Hslp/Mslp ratio ( r = 0.38 , p > 0.05 ) . The mean of the Hslp/Mslp did not show a hierarchical increase with the MAS scores . The findings indicate that the MAS is not a valid and ordinal level measure of muscle spasticity",
"Patients with neurological conditions may be affected by spasticity . The Modified Modified Ashworth Scale ( MMAS ) is a clinical tool used to measure spasticity . The purpose of the present study was to investigate the inter-rater reliability of the MMAS during the assessment of elbow flexor spasticity in adult patients with post-stroke hemiplegia . Twenty-one adult patients with stroke ( 5 women , 16 men ) with a median age of 60 years ( interquartile range , 47 - 68 ) were tested . Elbow flexors on the affected side were examined . Inter-rater reliability for two inexperienced raters was very good . The weighted Kappa value was 0.81 ( St and ard Error = 0.097 , 95 % CI : 0.62 - 1.00 , p = 0.0002 ) . The weighted percentage agreement was 97.4 % . The agreement between raters occurred mostly on score 1 ( 38.1 % ) followed by score 0 ( 23.8 % ) . The MMAS yielded reliable measurements between raters when used on patients post-stroke with elbow flexor spasticity",
"Background : The modified Ashworth scale ( MAS ) is the most widely used method for assessing muscle spasticity in clinical practice and research . However , the validity of this scale has been challenged . Objectives : To compare the MAS with objective neurophysiological tests of spasticity . Methods : The MAS was recorded in patients with post-stroke lower limb muscle spasticity and correlated with the excitability of the α motor neurones . The latter was evaluated by measuring the latency of the Hoffmann reflex ( H reflex ) and the ratio of the amplitude of the maximum H reflex ( Hmax ) to that of the compound action motor potential of the soleus muscle ( Mmax ) . Results : Data on 24 r and omly recruited patients were analysed . Patients were divided into two groups according to their MAS score : 14 had a MAS score of 1 ( group A ) and 10 scored 2 ( group B ) . The two groups were comparable with respect to age and sex , but in group A there was a longer period since the stroke . The H reflex latency was reduced and the Hmax : Mmax ratio was increased in both groups . The Hmax : Mmax ratio values were higher for group B but the differences were not statistically significant . Conclusions : There is a relation between the MAS scores and α motor neurone excitability , although it is not linear . This suggests that the MAS measures muscle hypertonia rather than spasticity",
"BACKGROUND It is widely stated that stroke is the most common cause of severe disability . We aim ed to examine whether this cl aim is supported by any evidence . METHODS We conducted secondary analysis of the Office of National Statistics 1996 Survey of Disability , United Kingdom . This was a multistage stratified r and om sample of 8683 noninstitutionalized individuals aged between 16 and 101 years , mean 62 years , response rate 83 % ( n = 8816 ) . The outcome used was the Office of Population Censuses and Surveys severity scale for disability . Odds ratios and population -attributable fractions were calculated to examine the associations between diagnoses and disability . RESULTS Logistic regression modelling suggests that , after adjustment for comorbidity and age , those with stroke had the highest odds of reporting severe overall disability ( odds ratio 4.88 , 95 % confidence interval [ CI ] 3.37 - 6.10 ) . Stroke was also associated with more individual domains of disability than any of the other conditions considered . Adjusted population -attributable fractions were also calculated and indicated that musculoskeletal disorders had the highest population -attributable fraction ( 30.3 % , 95 % CI 26.2 - 34.1 ) followed by mental disorders ( 8.2 % , 95 % CI 6.9 - 9.5 ) and stroke ( 4.5 % , 95 % CI 3.6 - 5.3 ) . CONCLUSION Stroke is not the most common cause of disability among the noninstitutionalized United Kingdom population . However , stroke is associated with the highest odds of reporting severe disability . Importantly , stroke is associated with more individual domains of disability compared with other conditions and might be considered to be the most common cause of complex disability",
"Ashworth Scales are the most widely used tests to assess the severity of muscle spasticity . These scales offer qualitative and subjective information ; consequently , there are issues concerning validity and reliability . This article presents the results of a study comparing interrater reliability of the original and of the modified Ashworth Scales for measuring muscle spasticity in elbow flexors . Fifteen patients with hemiplegia ( nine men and six women ) with a median age of 52 years ( interquartile range , 28–64 ) participated in this study . Two physiotherapists rated the muscle tone of elbow flexors according to ratings criteria of the Ashworth and the modified Ashworth Scales . Kappa values for the original Ashworth and the modified Ashworth Scales were 0.17 ( SE = 0.21 ; p = 0.41 ) and 0.21 ( SE = 0.12 ; p = 0.08 ) , respectively . The scales showed similar levels of reliability ( χ2 = 0.0285 , df = 1 , p = 0.7 ) . The Ashworth Scales are not reliable for the assessment of muscle spasticity . In the absence of interrater reliability , the validity of the measurements may also be question ed",
"BACKGROUND the central tenet of the neurofacilitatory approach to stroke therapy is that muscle tone needs to be normal before normal movement can occur . A reliable clinical measure of the full spectrum of muscle tone is needed to test : ( i ) the purported relationship between muscle tone , other motor impairments and disability , and ( ii ) the effectiveness of stroke therapy to restore movement . AIM the purpose of the study was to test the inter-rater reliability of clinical categorization of muscle tone ( spastic/normal/flaccid ) and also a visual analogue scale with anchor points of ' lowest tone possible ' ( score 0 ) and ' highest tone possible ' ( score 100 ) . METHODS four independent raters assessed tone of elbow flexors and knee extensors of 14 stroke rehabilitation in patients using the categorical scale . Six independent raters assessed tone of elbow flexors and knee extensors of 25 chronic stroke patients and two healthy volunteers using the visual analogue scale . All assessment orders were r and omized . RESULTS both scales were unreliable , with K coefficients for the categorical scale ranging from -0.046 to 0.56 for the categorical scale , and intra-class correlation coefficients for the visual analogue scale of 0.595 for elbow flexors and 0.451 for knee extensors . Assessment order effects for the visual analogue scale were non-significant for elbow flexors ( P= 0.545 ) and knee extensors ( P= 0.911 ) . CONCLUSIONS these results , and those of earlier studies , suggest that clinical measures of muscle tone are consistently unreliable . Systematic investigation of the therapy rationale for planning and evaluating treatment is required before relevant clinical measures can be developed"
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Accumulating evidence suggests that , independent of physical activity levels , sedentary behaviours are associated with increased risk of cardio-metabolic disease , all-cause mortality , and a variety of physiological and psychological problems . Therefore , the purpose of this systematic review is to determine the relationship between sedentary behaviour and health indicators in school-aged children and youth aged 5 - 17 years . Online data bases ( MEDLINE , EMBASE and PsycINFO ) , personal libraries and government documents were search ed for relevant studies examining time spent engaging in sedentary behaviours and six specific health indicators ( body composition , fitness , metabolic syndrome and cardiovascular disease , self-esteem , pro-social behaviour and academic achievement ) . 232 studies including 983,840 participants met inclusion criteria and were included in the review . Television ( TV ) watching was the most common measure of sedentary behaviour and body composition was the most common outcome measure . Qualitative analysis of all studies revealed a dose-response relation between increased sedentary behaviour and unfavourable health outcomes . Watching TV for more than 2 hours per day was associated with unfavourable body composition , decreased fitness , lowered scores for self-esteem and pro-social behaviour and decreased academic achievement . Meta- analysis was completed for r and omized controlled studies that aim ed to reduce sedentary time and reported change in body mass index ( BMI ) as their primary outcome . In this regard , a meta- analysis revealed an overall significant effect of -0.81 ( 95 % CI of -1.44 to -0.17 , p = 0.01 ) indicating an overall decrease in mean BMI associated with the interventions . There is a large body of evidence from all study design s which suggests that decreasing any type of sedentary time is associated with lower health risk in youth aged 5 - 17 years . In particular , the evidence suggests that daily TV viewing in excess of 2 hours is associated with reduced physical and psychosocial health , and that lowering sedentary time leads to reductions in BMI
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"OBJECTIVE To test the feasibility , acceptability , and potential efficacy of after-school dance classes and a family-based intervention to reduce television viewing , thereby reducing weight gain , among African-American girls . DESIGN Twelve-week , 2-arm parallel group , r and omized controlled trial . SETTING Low-income neighborhoods . PARTICIPANTS Sixty-one 8 - 10-year-old African-American girls and their parents/guardians . INTERVENTIONS The treatment intervention consisted of after-school dance classes at 3 community centers , and a 5-lesson intervention , delivered in participants ' homes , and design ed to reduce television , videotape , and video game use . The active control intervention consisted of disseminating newsletters and delivering health education lectures . MAIN OUTCOME MEASURES Implementation and process measures , body mass index , waist circumference , physical activity measured by accelerometry , self-reported media use , and meals eaten with TV . RESULTS Recruitment and retention goals were exceeded . High rates of participation were achieved for assessment s and intervention activities , except where transportation was lacking . All interventions received high satisfaction ratings . At follow up , girls in the treatment group , as compared to the control group , exhibited trends toward lower body mass index ( adjusted difference = -.32 kg/m2 , 95 % confidence interval [ CI ] -.77 , .12 ; Cohen 's d = .38 st and ard deviation units ) and waist circumference ( adjusted difference = -.63 cm , 95 % CI -1.92 , .67 ; d = .25 ) ; increased after-school physical activity ( adjusted difference = 55.1 counts/minute , 95 % CI -115.6 , 225.8 ; d = .21 ) ; and reduced television , videotape , and video game use ( adjusted difference = -4.96 hours/week , 95 % CI -11.41 , 1.49 ; d = .40 ) . The treatment group reported significantly reduced household television viewing ( d = .73 , P = .007 ) and fewer dinners eaten while watching TV ( adjusted difference = -1.60 meals/week , 95 % CI -2.99 , -.21 ; d = .59 ; P = .03 ) . Treatment group girls also reported less concern about weight ( d = .60 ; P = .03 ) , and a trend toward improved school grade s ( d = .51 ; P = .07 ) . CONCLUSIONS This study confirmed the feasibility , acceptability , and potential efficacy of using dance classes and a family-based intervention to reduce television viewing , thereby reducing weight gain , in African-American girls",
"OBJECTIVE . The objective of this study was to determine whether a generalizable best- practice individualized behavioral intervention reduced BMI z score relative to st and ard dietetic care among overweight children . METHODS . The design consisted of an assessor-blinded , r and omized , controlled trial involving 134 overweight children ( 59 boys , 75 girls ; BMI ≥ 98th centile relative to United Kingdom 1990 reference data for children aged 5–11 years ) who were r and omly assigned to a best- practice behavioral program ( intervention ) or st and ard care ( control ) . The intervention used family-centered counseling and behavioral strategies to modify diet , physical activity , and sedentary behavior . BMI z score , weight , objective ly measured physical activity and sedentary behavior , fat distribution , quality of life , and height z score were recorded at baseline and at 6 and 12 months . RESULTS . The intervention had no significant effect relative to st and ard care on BMI z score from baseline to 6 months and 12 months . BMI z score decreased significantly in both groups from baseline to 6 and 12 months . For those who complied with treatment , there was a significantly smaller weight increase in those in the intervention group compared with control subjects from baseline to 6 months . There were significant between-group differences in favor of the intervention for changes in total physical activity , percentage of time spent in sedentary behavior , and light-intensity physical activity . CONCLUSIONS . A generalizable , best- practice individualized behavioral intervention had modest benefits on objective ly measured physical activity and sedentary behavior but no significant effect on BMI z score compared with st and ard care among overweight children . The modest magnitude of the benefits observed perhaps argues for a longer-term and more intense intervention , although such treatments may not be realistic for many health care systems",
"BACKGROUND Epidemiological studies have shown television watching to be a risk factor for the development of obesity in children . The effect of reducing television watching and other sedentary behaviors as a component of a comprehensive obesity treatment program has not been thoroughly tested . OBJECTIVE To compare the influence of targeting decreases in sedentary behavior vs. increases in physical activity in the comprehensive treatment of obesity in 8- to 12-year-old children . DESIGN R and omized , controlled outcome study . SETTING Childhood obesity research clinic . DESIGN Ninety families with obese 8- to 12-year-old children were r and omly assigned to groups that were provided a comprehensive family-based behavioral weight control program that included dietary , and behavior change information but differed in whether sedentary or physically active behaviors were targeted and the degree of behavior change required . RESULTS Results during 2 years showed that targeting either decreased sedentary behaviors or increased physical activity was associated with significant decreases in percent overweight and body fat and improved aerobic fitness . Self-reported activity minutes increased and targeted sedentary time decreased during treatment . Children substituted nontargeted sedentary behaviors for some of their targeted sedentary behaviors . CONCLUSION These results support reducing sedentary behaviors as an adjunct in the treatment of pediatric obesity",
"BACKGROUND The proportion of overweight adolescents has increased , but the behavioral risk factors for overweight youth are not well understood . OBJECTIVE To examine how diet , physical activity , and sedentary behaviors relate to overweight status in adolescents . DESIGN AND SETTING Baseline data from the Patient-Centered Assessment and Counseling for Exercise Plus Nutrition Project , a r and omized controlled trial of adolescents to determine the effects of a clinic-based intervention on physical activity and dietary behaviors . PARTICIPANTS A total of 878 adolescents aged 11 to 15 years , 42 % of whom were from minority background s. MAIN OUTCOME MEASURE Centers for Disease Control and Prevention body mass index-for-age percentiles divided into 2 categories : normal weight ( or=85th percentile ) . RESULTS Overall , 45.7 % of the sample was classified as AR + O with a body mass index for age at the 85th percentile or higher . More girls from minority background s ( 54.8 % ) were AR + O compared with non-Hispanic white girls ( 42 % ) ( chi(2)(1 ) = 7.6 ; P = .006 ) . Bivariate analyses indicated that girls and boys in the AR + O group did fewer minutes per day of vigorous physical activity , consumed fewer total kilojoules per day , and had fewer total grams of fiber per day than those in the normal-weight group . Boys in the AR + O group also did fewer minutes per day of moderate physical activity and watched more minutes per day of television on nonschool days than normal-weight boys . Final multivariate models indicated that independent of socioeconomic status ( as assessed by household education level ) , girls had a greater risk of being AR + O if they were Hispanic or from another minority background ( odds ratio [ OR ] = 1.65 ; 95 % confidence interval [ CI ] , 1.09 - 2.49 ) and a reduced risk of being AR + O as minutes per day of vigorous physical activity increased ( OR = 0.93 ; 95 % CI , 0.89 - 0.97 ) . A low level of vigorous physical activity was the only significant risk factor for boys being AR + O ( OR = 0.92 ; 95 % CI , 0.89 - 0.95 ) . Analyses based on meeting behavioral guidelines supported these findings and showed that failing to meet the 60 min/d moderate to vigorous physical activity guideline was associated with overweight status for both girls and boys . In addition , boys who failed to meet sedentary behavior and dietary fiber guidelines were more likely to be overweight . CONCLUSIONS Of the 7 dietary and physical activity variables examined in this cross-sectional study , insufficient vigorous physical activity was the only risk factor for higher body mass index for adolescent boys and girls . Prospect i ve studies are needed to clarify the relative importance of dietary and physical activity behaviors on overweight in adolescence",
"Background : Youth may choose to be sedentary rather than physically active . Purpose : The purpose of this study was to use behavioral economics methods to investigate how experimental changes in the amount of sedentary behaviors influenced physical activity . Methods : Fifty-eight 8-to 16-year-old youth were studied in a within-subject crossover design with three 3-week phases : baseline , increasing , and decreasing targeted sedentary behaviors by 25 % to 50 % . Results : At baseline , boys were more active than girls ( 518.9 vs. 401.2 accelerometer counts/min , p = .02 ) , and obese youth more sedentary than nonobese youth ( 240.5 vs. 174.4 min/day , p = .003 ) . During the increase sedentary behavior phase , targeted sedentary behaviors increased by 52.1 % , with girls increasing sedentary behaviors more than boys ( 114.7 vs. 79.8 min/day , p = .04 ) . Physical activity decreased ( −48.3 counts/min , p when sedentary behaviors increased , with obese youth decreasing total and moderate to vigorous physical activity ( MVPA ) more than nonobese youth ( −110.4 vs. 8.9 counts/min , p sedentary behavior phase , targeted sedentary behaviors decreased by 55.6 % from baseline as nonobese youth increased physical activity , whereas obese youth decreased physical activity ( 55.8 vs. −48.0 counts/min , p = .042 ; 1.1 vs. −2.1 % MVPA , p = .021 ) . Youth who substituted physical activity when sedentary behaviors were increased had greater st and ardized body mass index ( z-body mass index = 1.4 vs. 0.4 , p = .018 ) , whereas youth who substituted physical activity when sedentary behaviors were decreased were less active at baseline ( 396.1 vs. 513.7 counts/min , p = .035 ) . Conclusions : Behavioral economics provides a methodology to underst and changes in physical activity when sedentary behaviors are modified and to identify factors associated with substitution of physically active for sedentary behaviors",
"BACKGROUND Television is a source from which children gain information about life and experience different types of behavior . The Child Behavior Checklist ( CBCL ) has not been used thoroughly to evaluate the behavioral effects of television viewing on children . OBJECTIVE To examine the competency and problem behavior correlates of television viewing in school-aged children using the CBCL . DESIGN Cross-sectional survey . SETTING Two r and omly selected grade schools , one from a high-income district and the other from a low-income district . PARTICIPANTS Students in grade s 2 and 3 and their parents . MAIN OUTCOME MEASURES A question naire on children 's time spent watching television and engaging in other daily activities and the CBCL were sent to the parents of 888 second- and third- grade students . RESULTS Results of the question naire reported that the overall mean + /- SD daily television viewing time was 2.5 + /- 1.3 hours . Overall television viewing time had a negative correlation with social and school achievement ( r = -0.17 , P Withdrawn ( r = 0.11 , P = .004 ) , social problem ( r = 0.14 , P = .001 ) , thought problem ( r = 0.11 , P = .03 ) , attention problem ( r = 0.20 , P delinquent behavior ( r = 0.12 , P aggressive behavior ( r = 0.22 , P externalization ( r = 0.19 , P total problem ( r = 0.15 , P television . Stepwise logistic regression analysis revealed that the only significant variables associated with a risk of watching television for more than 2 hours were age , gender , social subscale , and attention problem subscale scores of the CBCL . CONCLUSION As evaluated by the CBCL , television viewing time is positively associated with social problems , delinquent behavior , aggressive behavior , externalization , and total problem scores . Older age , male gender , and decreasing social subscale and increasing attention problem subscale scores on the CBCL increases the risk of watching television for more than 2 hours",
"Background Schools are the most frequent target for intervention programs aim ed at preventing child obesity ; however , the overall effectiveness of these programs has been limited . It has therefore been recommended that interventions target multiple ecological levels ( community , family , school and individual ) to have greater success in changing risk behaviors for obesity . This study examined the immediate and short-term , sustained effects of the Switch program , which targeted three behaviors ( decreasing children 's screen time , increasing fruit and vegetable consumption , and increasing physical activity ) at three ecological levels ( the family , school , and community ) . Methods Participants were 1,323 children and their parents from 10 schools in two states . Schools were matched and r and omly assigned to treatment and control . Measures of the key behaviors and body mass index were collected at baseline , immediately post-intervention , and 6 months post-intervention . Results The effect sizes of the differences between treatment and control groups ranged between small ( Cohen 's d = 0.15 for body mass index at 6 months post-intervention ) to large ( 1.38 ; parent report of screen time at 6 months post-intervention ) , controlling for baseline levels . There was a significant difference in parent-reported screen time at post-intervention in the experimental group , and this effect was maintained at 6 months post-intervention ( a difference of about 2 hours/week ) . The experimental group also showed a significant increase in parent-reported fruit and vegetable consumption while child-reported fruit and vegetable consumption was marginally significant . At the 6-month follow-up , parent-reported screen time was significantly lower , and parent and child-reported fruit and vegetable consumption was significantly increased . There were no significant effects on pedometer measures of physical activity or body mass index in the experimental group . The intervention effects were moderated by child sex ( for fruit and vegetable consumption , physical activity , and weight status ) , family involvement ( for fruit and vegetable consumption ) , and child body mass index ( for screen time ) . The perception of change among the experimental group was generally positive with 23 % to 62 % indicating positive changes in behaviors . Conclusion The results indicate that the Switch program yielded small-to-modest treatment effects for promoting children 's fruit and vegetable consumption and minimizing screen time . The Switch program offers promise for use in youth obesity prevention",
"OBJECTIVE To evaluate the impact of a school-based health behavior intervention known as Planet Health on obesity among boys and girls in grade s 6 to 8 . DESIGN R and omized , controlled field trial with 5 intervention and 5 control schools . Outcomes were assessed using preintervention ( fall 1995 ) and follow-up measures ( spring 1997 ) , including prevalence , incidence , and remission of obesity . PARTICIPANTS A group of 1295 ethnically diverse grade 6 and 7 students from public schools in 4 Massachusetts communities . INTERVENTION Students participated in a school-based interdisciplinary intervention over 2 school years . Planet Health sessions were included within existing curricula using classroom teachers in 4 major subjects and physical education . Sessions focused on decreasing television viewing , decreasing consumption of high-fat foods , increasing fruit and vegetable intake , and increasing moderate and vigorous physical activity . MAIN OUTCOME MEASURES Obesity was defined as a composite indicator based on both a body mass index and a triceps skinfold value greater than or equal to age- and sex-specific 85th percentiles . Because schools were r and omized , rather than students , the generalized estimating equation method was used to adjust for individual-level covariates under cluster r and omization . RESULTS The prevalence of obesity among girls in intervention schools was reduced compared with controls , controlling for baseline obesity ( odds ratio , 0.47 ; 95 % confidence interval , 0.24 - 0.93 ; P = .03 ) , with no differences found among boys . There was greater remission of obesity among intervention girls vs. control girls ( odds ratio , 2.16 ; 95 % confidence interval , 1.07 - 4.35 ; P = .04 ) . The intervention reduced television hours among both girls and boys , and increased fruit and vegetable consumption and result ed in a smaller increment in total energy intake among girls . Reductions in television viewing predicted obesity change and mediated the intervention effect . Among girls , each hour of reduction in television viewing predicted reduced obesity prevalence ( odds ratio , 0.85 ; 95 % confidence interval , 0.75 - 0.97 ; P = .02 ) . CONCLUSION Planet Health decreased obesity among female students , indicating a promising school-based approach to reducing obesity among youth",
"OBJECTIVE : To evaluate the 6-month impact of a physical activity ( PA ) multilevel intervention on activity patterns and psychological predictors of PA among adolescents . The intervention was directed at changing knowledge and attitudes and at providing social support and environmental conditions that encourage PA of adolescents inside and outside school . SUBJECTS AND DESIGN : R and omised , controlled ongoing field trial ( ICAPS ) in middle-school 's first-level adolescents from eight schools selected in the department of the Bas-Rhin ( Eastern France ) with a cohort of 954 adolescents ( 92 % of the eligible students ) initially aged 11.7±0.6 y. The 6-month changes in participation in leisure organised PA ( LOPA ) , high sedentary ( SED ) behaviour ( > 3h/day ) , self-efficacy ( SELF ) and intention ( INTENT ) towards PA were analysed after controlling for baseline measures and different covariables ( age , overweight , socioprofessional occupation ) , taking into account the cluster r and omisation design . RESULTS : The proportion of intervention adolescents not engaged in organised PA was reduced by 50 % whereas it was unchanged among control students . After adjustment for baseline covariables , LOPA participation significantly increased among the intervention adolescents ( odds ratio ( 95 % confidence interval ) (OR)=3.38 ( 1.42–8.05 ) in girls ; 1.73 ( 1.12–2.66 ) in boys ) , while high SED was reduced ( OR=0.54 ( 0.38–0.77 ) in girls ; 0.52 ( 0.35–0.76 ) in boys ) . The intervention improved SELF in girls , whatever their baseline LOPA ( P ( P=0.04 ) . SELF tended to improve in boys with no baseline LOPA , without reaching statistical significance . When included in the regression , follow-up LOPA was associated with improvement of SELF in girls ( P=0.02 ) and of INTENT in girls with no baseline PA ( P of activity patterns and psychological predictors , indicating a promising approach for modifying the long-term PA level of adolescents",
"CONTEXT Some observational studies have found an association between television viewing and child and adolescent adiposity . OBJECTIVE To assess the effects of reducing television , videotape , and video game use on changes in adiposity , physical activity , and dietary intake . DESIGN R and omized controlled school-based trial conducted from September 1996 to April 1997 . SETTING Two sociodemographically and scholastically matched public elementary schools in San Jose , Calif. PARTICIPANTS Of 198 third- and fourth- grade students , who were given parental consent to participate , 192 students ( mean age , 8.9 years ) completed the study . INTERVENTION Children in 1 elementary school received an 18-lesson , 6-month classroom curriculum to reduce television , videotape , and video game use . MAIN OUTCOME MEASURES Changes in measures of height , weight , triceps skinfold thickness , waist and hip circumferences , and cardiorespiratory fitness ; self-reported media use , physical activity , and dietary behaviors ; and parental report of child and family behaviors . The primary outcome measure was body mass index , calculated as weight in kilograms divided by the square of height in meters . RESULTS Compared with controls , children in the intervention group had statistically significant relative decreases in body mass index ( intervention vs control change : 18.38 to 18.67 kg/m2 vs 18.10 to 18.81 kg/m2 , respectively ; adjusted difference -0.45 kg/m2 [ 95 % confidence interval [ CI ] , -0.73 to -0.17 ] ; P = .002 ) , triceps skinfold thickness ( intervention vs control change : 14.55 to 15.47 mm vs 13.97 to 16.46 mm , respectively ; adjusted difference , -1.47 mm [ 95 % CI , -2.41 to -0.54 ] ; P=.002 ) , waist circumference ( intervention vs control change : 60.48 to 63.57 cm vs 59.51 to 64.73 cm , respectively ; adjusted difference , -2.30 cm [ 95 % CI , -3.27 to -1.33 ] ; P waist-to-hip ratio ( intervention vs control change : 0.83 to 0.83 vs 0.82 to 0.84 , respectively ; adjusted difference , -0.02 [ 95 % CI , -0.03 to -0.01 ] ; P children 's reported television viewing and meals eaten in front of the television . There were no statistically significant differences between groups for changes in high-fat food intake , moderate-to-vigorous physical activity , and cardiorespiratory fitness . CONCLUSIONS Reducing television , videotape , and video game use may be a promising , population -based approach to prevent childhood obesity",
"BACKGROUND The aim of this research was to study the effects of overweight and leisure-time activities on maximal aerobic capacity ( VO(2)max ) in urban and rural Omani adolescents . METHODS A total of 529 ( 245 males , 284 females ) adolescents , aged 15 - 16 years were r and omly selected from segregated urban and rural schools . Maximal aerobic capacity was estimated using the multistage 20-meter shuttle-run test . RESULTS The body mass index ( BMI ) of urban boys and girls was significantly higher than that of rural boys and girls . Urban boys and girls spent significantly less weekly hours on sports activities and significantly more weekly hours on TV/computer games than their rural counterpart . Urban boys and girls achieved significantly less VO(2)max than rural boys and girls ( 44.2 and 33.0 vs. 48.3 and 38.6 mL/kg/min , respectively ) . Maximal aerobic capacity was negatively correlated with BMI in urban boys . CONCLUSION Overweight and inactivity had significant negative effects on cardiorespiratory fitness in urban boys and girls as compared to their rural counterparts . Weight gain in adolescence requires early intervention",
"OBJECTIVES To evaluate the relationship between changes in physical activity ( PA ) , sedentary behavior , and physical self-perceptions and global self-worth in 30 , 8 - 12 years old , overweight/obese children ( 13 boys , 17 girls ) . METHODS Secondary analyses from a r and omized controlled trial design ed to increase PA and reduce sedentary behavior . PA was measured by accelerometers worn by participants every day for 8 weeks . Sedentary behavior , defined as minutes per day spent in television viewing , was assessed by self-report . RESULTS Increases in PA were associated with increases in perceived physical conditioning ( r = .54 , p body satisfaction ( r = .55 , p overall physical self-worth ( r = .44 , p TV viewing were also related to increased physical and global self-worth . CONCLUSIONS Increases in PA are associated with improvements in physical self-perceptions but not global self-worth , while reductions in TV viewing are associated with increased physical and global self-worth , and these psychosocial benefits appear to be independent of changes in adiposity",
"PURPOSE To evaluate the relationship between depressive symptoms and physical activity in a geographically and ethnically diverse sample of sixth- grade adolescent girls . METHODS The Trial of Activity for Adolescent Girls ( TAAG ) baseline measurement included a r and om sample ( N = 1721 ) of sixth- grade girls in 36 schools at six field sites . Measurements were accelerometry and the 3-d Physical Activity Recall ( 3DPAR ) for physical activity , and the Center for Epidemiological Studies -Depression scale ( CES-D ) for depressive symptoms . RESULTS Girls with complete data ( N = 1397 ) , mean age 12 yr , had an average CES-D score of 14.7 ( SD = 9.25 ) and engaged in an average of about 460 min of sedentary activity , of moderate to vigorous physical activity ( MVPA ) , and min of vigorous physical activity ( VPA ) in an 18-h day . Thirty-minute segments of MVPA ranged in number from 3.9 to 1.2 , and METS for these segments ranged from > 3.0 to > 6.5 . Mixed-model regression indicated no relationship between depressive symptoms and physical activity ; however , a significant but modest inverse relationship between sedentary activity and depressive symptoms was observed . CONCLUSION A sufficient sample size , st and ardized procedures , and vali date d instruments characterized this study ; however , a relationship between depressive symptoms and physical activity was not observed for sixth- grade girls from diverse geographic locations . The average CES-D score was lower than is considered clinical ly meaningful for either adolescents or adults , and MET-minutes of sedentary activity were high . This combination of data may be different from other studies and could have contributed to the unexpected finding . This unexpected finding is informative , however , because it shows the need for additional research that includes a wider range of possible combinations of data , especially with young adolescent girls",
"Recent increases in obesity prevalence among children in developed countries are of policy concern . While significant positive associations between households ' food insecurity status and body weights have been reported for adults , it is known from the energy physiology literature that energy requirements depend on BMR , anthropometric measures and physical activity . It is therefore important to model the bi-directional relationships between body weights and households ' food insecurity scores especially for children that have evolving nutrient and energy requirements . The present paper estimated dynamic r and om effects models for children 's body weights and BMI , and households ' food insecurity scores using longitudinal data on 7635 children in the USA enrolled in 1st , 3rd and 5th grade s ( 1999 - 2003 ) of the Early Childhood Longitudinal Study -Kindergarten . The main findings were , first , physical exercise and numbers of siblings were significantly ( P with body weights , while households ' food insecurity score was not a significant predictor . Moreover , children 's body weights were significantly lower in households with higher parental education and incomes ; time spent watching television and in non-parental care were positively associated with weights . Second , models for households ' food insecurity scores showed that poverty and respondents ' poor emotional and physical health significantly increased food insecurity . Moreover , households with children who were taller and heavier for their ages faced significantly higher food insecurity levels . Overall , the results showed that household food insecurity was unlikely to exacerbate child obesity in the USA and it is important that children receive balanced school meals and perform higher physical activity",
"PURPOSE Although moderate-to-vigorous physical activity is related to premature mortality , the relationship between sedentary behaviors and mortality has not been fully explored and may represent a different paradigm than that associated with lack of exercise . We prospect ively examined sitting time and mortality in a representative sample of 17,013 Canadians 18 - 90 yr of age . METHODS Evaluation of daily sitting time ( almost none of the time , one fourth of the time , half of the time , three fourths of the time , almost all of the time ) , leisure time physical activity , smoking status , and alcohol consumption was conducted at baseline . Participants were followed prospect ively for an average of 12.0 yr for the ascertainment of mortality status . RESULTS There were 1832 deaths ( 759 of cardiovascular disease ( CVD ) and 547 of cancer ) during 204,732 person-yr of follow-up . After adjustment for potential confounders , there was a progressively higher risk of mortality across higher levels of sitting time from all causes ( hazard ratios ( HR ) : 1.00 , 1.00 , 1.11 , 1.36 , 1.54 ; P for trend Age-adjusted all-cause mortality rates per 10,000 person-yr of follow-up were 87 , 86 , 105 , 130 , and 161 ( P for trend sitting time and mortality from all causes and CVD , independent of leisure time physical activity . In addition to the promotion of moderate-to-vigorous physical activity and a healthy weight , physicians should discourage sitting for extended periods",
"OBJECTIVES . Television viewing and physical inactivity increase the risk of obesity in youth . Thus , identifying new interventions that increase physical activity and reduce television viewing would be helpful in the prevention and treatment of pediatric obesity . This study evaluated the effects of open-loop feedback plus reinforcement versus open-loop feedback alone on physical activity , targeted sedentary behavior , body composition , and energy intake in youth . METHODS . Thirty overweight or obese 8- to 12-year-old children were r and omly assigned to an intervention ( n = 14 ) or control group ( n = 16 ) . Participants wore accelerometers every day for 8 weeks and attended biweekly meetings to download the activity monitors . For children in the open-loop feedback plus reinforcement ( intervention ) group , accumulating 400 counts of physical activity on pedometers earned 1 hour of television/VCR/DVD time , which was controlled by a Token TV electronic device . Open-loop feedback control subjects wore activity monitors but had free access to targeted sedentary behavior . RESULTS . Compared with controls , the open-loop feedback plus reinforcement group demonstrated significantly greater increases in daily physical activity counts ( + 65 % vs + 16 % ) and minutes per day of moderate-to-vigorous physical activity ( + 9.4 vs + 0.3 ) and greater reductions in minutes per day spent in television viewing ( −116.1 vs + 14.3 ) . The intervention group also showed more favorable changes in body composition , dietary fat intake , and energy intake from snacks compared with controls . Reductions in sedentary behavior were directly related to reductions in BMI , fat intake , snack intake , and snack intake while watching television . CONCLUSIONS . Providing feedback of physical activity in combination with reinforcing physical activity with sedentary behavior is a simple method of modifying the home environment that may play an important role in treating and preventing child obesity",
"Background The purpose was to conduct systematic review s of the relationship between physical activity of healthy community-dwelling older ( > 65 years ) adults and outcomes of functional limitations , disability , or loss of independence . Methods Prospect i ve cohort studies with an outcome related to functional independence or to cognitive function were search ed , as well as exercise training interventions that reported a functional outcome . Electronic data base search strategies were used to identify citations which were screened ( title and abstract ) for inclusion . Included articles were review ed to complete st and ardized data extraction tables , and assess study quality . An established system of assessing the level and grade of evidence for recommendations was employed . Results Sixty-six studies met inclusion criteria for the relationship between physical activity and functional independence , and 34 were included with a cognitive function outcome . Greater physical activity of an aerobic nature ( categorized by a variety of methods ) was associated with higher functional status ( expressed by a host of outcome measures ) in older age . For functional independence , moderate ( and high ) levels of physical activity appeared effective in conferring a reduced risk ( odds ratio ~0.5 ) of functional limitations or disability . Limitation in higher level performance outcomes was reduced ( odds ratio ~0.5 ) with vigorous ( or high ) activity with an apparent dose-response of moderate through to high activity . Exercise training interventions ( including aerobic and resistance ) of older adults showed improvement in physiological and functional measures , and suggestion of longer-term reduction in incidence of mobility disability . A relatively high level of physical activity was related to better cognitive function and reduced risk of developing dementia ; however , there were mixed results of the effects of exercise interventions on cognitive function indices . Conclusions There is a consistency of findings across studies and a range of outcome measures related to functional independence ; regular aerobic activity and short-term exercise programmes confer a reduced risk of functional limitations and disability in older age . Although a precise characterization of a minimal or effective physical activity dose to maintain functional independence is difficult , it appears moderate to higher levels of activity are effective and there may be a threshold of at least moderate activity for significant outcomes",
"OBJECTIVE The aim was to develop , test , and apply an index to assess the completeness of reporting in a cohort of observational studies of conference abstract s. STUDY DESIGN AND SETTING Using rigorous methods , we reduced 245 items generated by literature review to 48 c and i date items . In a r and om sample of 30 conference abstract s of rituximab for nonHodgkin lymphoma , we developed an item impact score using a survey of abstract stakeholders combined with the prevalence of each of the 48 items . We retained 14 independent items representing completeness of reporting , the CORE-14 . Two raters determined the reliability of the instrument . We then applied the CORE-14 in another 78 studies to determine the prevalence of each feature . RESULTS Our survey response rate was 83.9 % ( 47/56 ) . Interrater reliability ( 95 % CI ) of the CORE-14 instrument was 0.56 ( 0.25 , 0.77 ) , which improved by averaging across scores provided by two raters ( 0.72 [ 0.49 , 0.86 ] ) . Applying the CORE-14 in an additional set of 78 abstract s , six items occurred > or = 85 % and four items occurred conference abstract reporting exist . This scale could guide future conference abstract su bmi ssions and aid individuals considering conference abstract data to inform clinical practice , systematic review s , guidelines , or policy",
"OBJECTIVES To examine whether children 's television viewing may be a useful indicator of risk of obesity-promoting versus healthy eating behaviours , low-level physical activity ( PA ) and overweight or obesity among children of primary school entry and exit ages . DESIGN Cross-sectional study , stratified by area-level socioeconomic status . PARTICIPANTS AND SETTING 1560 children ( 613 aged 5 - 6 years [ 50 % boys ] , and 947 aged 10 - 12 years [ 46 % boys ] ) from 24 primary schools in Melbourne , Australia , r and omly selected proportionate to school size between 1 November 2002 and 30 December 2003 . MAIN OUTCOME MEASURES Parents ' reports of the time their child spends watching television , their participation in organised physical activities ( PA ) , and their food intake ; each child 's measured height and weight and their PA levels as assessed by accelerometry for one week . RESULTS After adjusting for the age and sex of child , the parents ' level of education , clustering by school , and all other health behaviour variables , children who watched television for > 2 h/day were significantly more likely than children who watched television for serves/day of high energy drinks ( adjusted odds ratio [ AOR ] , 2.31 ; 95 % CI , 1.61 - 3.32 ) , and to have one or more serves/day of savoury snacks ( AOR , 1.50 ; 95 % CI , 1.04 - 2.17 ) . They were also less likely to have two or more serves/day of fruit ( AOR , 0.58 ; 95 % CI , 0.46 - 0.74 ) , or to participate in any organised PA ( AOR , 0.52 ; 95 % CI , 0.34 - 0.80 ) . CONCLUSIONS Health practitioners in the primary care setting may find that asking whether a child watches television for more than 2 hours daily can be a useful indicator of a child 's risk of poor diet and low physical activity level",
"Background While much cross-sectional data is available , there have been few longitudinal investigations of patterns of electronic media use in children . Further , the possibility of a bi-directional relationship between electronic media use and body mass index in children has not been considered . This study aim ed to describe longitudinal patterns of television viewing and electronic game/computer use , and investigate relationships with body mass index ( BMI ) . Methods This prospect i ve cohort study was conducted in elementary schools in Victoria , Australia . 1278 children aged 5–10 years at baseline and 8–13 years at follow-up had their BMI calculated , from measured height and weight , and transformed to z-scores based on US 2000 growth data . Weight status ( non-overweight , overweight and obese ) was based on international BMI cut-off points . Weekly television viewing and electronic game/computer use were reported by parents , these were summed to generate total weekly screen time . Children were classified as meeting electronic media use guidelines if their total screen time was ≤14 hrs/wk . Results Electronic media use increased over the course of the study ; 40 % met guidelines at baseline but only 18 % three years later . Television viewing and electronic game/computer use tracked moderately and total screen time was positively associated with adiposity cross-sectionally . While weaker relationships with adiposity were observed longitudinally , baseline z- BMI and weight status were positively associated with follow-up screen time and baseline screen time was positively associated with z- BMI and weight status at follow-up . Children who did not meet guidelines at baseline had significantly higher z- BMI and were more likely to be classified as overweight/obese at follow-up . Conclusion Electronic media use in Australian elementary school children is high , increases with age and tracks over time . There appears to be a bi-directional association suggesting that interventions targeting reductions in either screen time or adiposity may have a positive effect on both screen time and adiposity ",
"OBJECTIVE To test the hypothesis that media use mediates the relation between socioeconomic status ( SES ) and body mass index ( BMI ) . DESIGN Analysis of 2 large cross-sectional surveys , 1 from Germany and 1 from the United States . SETTING Twenty-seven public schools in northern Germany ; telephone interviews in the United States . PARTICIPANTS A total of 4810 German children and adolescents aged 10 to 17 years ( mean age , 12.8 years ) ; 4473 US children and adolescents aged 12 to 16 years ( mean age , 14.0 years ) recruited using r and om-digit-dial methods . Main Exposures Media exposure was assessed via survey questions about the presence of a television in the bedroom , television screen time , computer and video game screen time , and movie viewing . The SES was derived from type of school ( German sample ) or parental reports of their own education and family income ( US sample ) . MAIN OUTCOME MEASURES The BMI was assessed by the use of self-reports in both sample s , supplemented by parental reports ( US sample ) for height and weight . RESULTS In both sample s , SES was inversely associated with BMI , and media use was directly associated with BMI . The effect of SES on overweight was partially mediated by media exposure , which explained 35 % of the SES- BMI association in the German sample and 16 % in the US sample . In both groups , television in the bedroom and television screen time had statistically significant indirect paths , whereas video game use and movie viewing did not . CONCLUSIONS Students from low-SES background s are at higher risk for overweight in part because of higher levels of television viewing . The change of media use habits could modify this health disparity",
"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 association of television viewing and obesity in data collected during cycles II and III of the National Health Examination Survey was examined . Cycle II examined 6,965 children aged 6 to 11 years and cycle III examined 6,671 children aged 12 to 17 years . Included in the cycle III sample were 2,153 subjects previously studied during cycle II . These surveys , therefore , provided two cross-sectional sample s and one prospect i ve sample . In all three sample s , significant associations of the time spent watching television and the prevalence of obesity were observed . In 12- to 17-year-old adolescents , the prevalence of obesity increased by 2 % for each additional hour of television viewed . The associations persisted when controlled for prior obesity , region , season , population density , race , socioeconomic class , and a variety of other family variables . The consistency , temporal sequence , strength , and specificity of the associations suggest that television viewing may cause obesity in at least some children and adolescents . The potential effects of obesity on activity and the consumption of calorically dense foods are consistent with this hypothesis",
"Low levels of physical activity coupled with high levels of television viewing have been linked with obesity in children . The objective of this study was to assess the efficacy of ' Switch Off-Get Active ' , a 16-week controlled health education intervention , in increasing physical activity and reducing screen time and BMI in primary school children . A secondary objective was to compare children with high and low screen time . Participants were 312 children aged 10.2+/-0.7 years , attending nine schools in areas of social disadvantage . The 10-lesson , teacher-led intervention , conducted in spring 2003 , emphasised self-monitoring , budgeting of time and selective viewing . Differences , adjusted for baseline values by ANCOVA , existed between intervention and control children at follow-up for self-reported physical activity ( intervention + 0.84 30 min blocks/day , 95%CI 0.11 - 1.57 , p self-efficacy for physical activity ( p self-reported screen time ( intervention--0.41 blocks/day , 95%CI--0.93 - 0.12 , p=0.13 ) or BMI ( p=0.63 ) . Cross-sectional comparisons at baseline indicated lower physical activity , self-efficacy for physical activity and aerobic fitness and a higher BMI in children with high screen time . In conclusion , health education interventions can increase physical activity in primary school children but follow-ups of longer duration may be needed to demonstrate intervention effects on BMI",
"OBJECTIVE To assess the effects of reducing television viewing and computer use on children 's body mass index ( BMI ) as a risk factor for the development of overweight in young children . DESIGN R and omized controlled clinical trial . SETTING University children 's hospital . PARTICIPANTS Seventy children aged 4 to 7 years whose BMI was at or above the 75th BMI percentile for age and sex . INTERVENTIONS Children were r and omized to an intervention to reduce their television viewing and computer use by 50 % vs a monitoring control group that did not reduce television viewing or computer use . MAIN OUTCOME MEASURES Age- and sex-st and ardized BMI ( z BMI ) , television viewing , energy intake , and physical activity were monitored every 6 months during 2 years . RESULTS Children r and omized to the intervention group showed greater reductions in targeted sedentary behavior ( P z BMI ( P energy intake ( P z BMI change ( P = .01 ) , with the experimental intervention working better among families of low socioeconomic status . Changes in targeted sedentary behavior mediated changes in z BMI ( P television viewing was related to the change in energy intake ( P physical activity ( P = .37 ) . CONCLUSIONS Reducing television viewing and computer use may have an important role in preventing obesity and in lowering BMI in young children , and these changes may be related more to changes in energy intake than to changes in physical activity",
"BACKGROUND Overweight and obesity as well as weight dissatisfaction have been increasing in prevalence worldwide . Body weight dissatisfaction and fear of fatness are potential contributors to disordered eating . The present study aim ed to investigate the prevalence of self-reported overweight and weight dissatisfaction along with associations with socio-demographic characteristics , body image , health complaints , risk behaviours , physical activity and television viewing in adolescents in Palestine . METHODS The 2003/04 Palestinian Health Behaviour in School-aged Children ( HBSC ) is a cross-sectional survey of 17,817 adolescents from 405 r and omly selected schools . Students from a representative sample of grade s 6 , 8 , 10 and 12 ( aged 12 - 18 years ) self-completed a modified version of the international World Health Organization collaborative Health Behaviour in School-aged Children ( HBSC-2002 ) question naire . RESULTS Although 16.5 % of the adolescents were overweight , almost twice that number ( 32.1 % ) were dissatisfied with their weight ( i.e. dieting or perceiving a need to diet ) . Of those adolescents , two-thirds were not actually overweight ( 56.4 % boys ; 73.5 % girls ) . One-fifth of the total number of adolescents ( 16.0 % boys ; 24.0 % girls ) were not overweight but were dissatisfied with their weight . Boys reporting overweight or weight dissatisfaction were more likely to have mothers with higher education or to be from more affluent families . Among both genders , but especially among girls , weight dissatisfaction was positively associated with most of the outcome variables ( body image , health complaints , risk behaviours , and television viewing ) regardless of weight status , whereas weight status was associated with only a few of the outcome variables . CONCLUSIONS Weight dissatisfaction , independent of weight status , is associated with body image , health complaints , risk behaviours and television viewing , and represents a potential health risk factor for adolescents . Preventive interventions should focus not only on weight status , but also on body weight dissatisfaction",
"Background : Disruption of circadian rhythms has been associated with obesity in children and adolescents , and with hypertension in adults , in industrialized population s. Objective : We examined cross-sectional associations between sleep duration or television viewing and obesity and blood pressure in Brazilian adolescents . Design : The sample consisted of 4452 adolescents aged 10–12 years participating in a prospect i ve birth cohort study in Pelotas , Brazil . Sleep duration and television viewing were determined through question naires . Obesity was assessed using international cut-offs for body mass index ( BMI ) , and body fatness by skinfold thicknesses . Blood pressure was measured using a vali date d monitor . Results : Short sleep duration was associated with increased BMI , skinfolds , systolic blood pressure , activity levels and television viewing . Each hour of sleep reduced BMI by 0.16 kg/m2 ( s.e . 0.04 ) , and was associated with odds ratio for obesity of 0.86 ( s.e . 0.04 ) , both P increased BMI and skinfolds , and increased blood pressure . The effects of sleep duration and television viewing on obesity were independent of one another . Their associations with blood pressure were mediated by body fatness . Conclusions : Both short sleep duration and increased television viewing were associated with greater body fatness , obesity and higher blood pressure , independently of physical activity level . These associations were independent of maternal BMI , identified in other studies as the strongest predictor of childhood obesity . Our study shows that behavioural factors associated with metabolic risk in industrialized population s exert similar deleterious effects in a population undergoing nutritional transition and suggest options for public health interventions",
"OBJECTIVE To describe the patterns ( specifically comparing weekdays and weekends classified by intensities ) of physical activity ( PA ) measured by accelerometry in adolescent girls . RESEARCH METHODS AND PROCEDURES Healthy sixth grade girls ( n=1603 ) , 11 to 12 years old , were r and omly recruited from 36 schools participating in the Trial of Activity in Adolescent Girls . Age , ethnicity , socioeconomic status , weight , and height were taken . PA patterns were measured for 6 days using accelerometry . RESULTS Adolescent girls spend most of their time in sedentary ( 52 % to 57 % of the day ) and light activity ( 40 % to 45 % of the day ) on weekdays and weekends . In all girls , total PA comprised 44.5 % of the day ( 41.7 % light , 2.2 % moderate , and 0.7 % vigorous ) with sedentary activity comprising 55.4 % . Moderate-to-vigorous PA ( MVPA ) was higher ( p MVPA was lower in at-risk of overweight+overweight girls ( p Adolescent girls are more active at moderate and vigorous intensities on weekdays than on weekends , and at-risk of overweight and those overweight spend less time engaging in MVPA than normal-weight girls",
"OBJECTIVE : To assess the relationships between diet , body composition , physical activity , parents ’ obesity and adiposity in children at the age of 8 y and four years later . STUDY DESIGN : Prospect i ve observational study of anthropometric measures initiated in 1992 , follow-up examination in 1996 . METHODS : 112 prepubertal ( age : 8.6±1.0 y ) children were studied . Energy and nutrient intakes were assessed by diet history , body composition by anthropometry and physical activity , by a question naire . Obesity was defined as relative body mass index ( BMI ) ( rel BMI ) > 120 % , where rel BMI =( BMI / BMI at 50th centile for age and gender) × 100 . RESULTS : Prevalence of obesity was not statistically different at baseline ( 22.3 % ) than four years later ( 19.8 % ) : rel BMI at the age of 8 y was positively self-related with rel BMI at the age of 12 y ( r=0.73 , P the mother ’s BMI and TV viewing ( independent variables ) accounted for 17 % of the children ’s rel BMI variance at the age of 8 y ( R=0.42 , P rel BMI variance at the age of 12 y ( r=0.37 , P as total energy intake , nutrient intake percentage and amount of physical activity , were all rejected . An autoregressive unbalanced measures model regression analysis recognised the mother ’s and father ’s BMI s as the only variables able to predict rel BMI in the children ( mother ’s BMI coeff . 2.53 ( s.e.m . 0.26 ) , P multivariate logistic regression analysis was also performed . The children who participated in the follow-up , were divided into two groups based on the positive or negative change in the rel BMI between final and baseline measurements . Of all the variables considered , only rel BMI at baseline was selected in the final equation . Other variables such as age , gender , energy and nutrient intake , TV viewing and amount of physical activity , as well as the parents ’ BMI , were all removed . CONCLUSIONS : The parents ’ obesity was the main risk factor for obesity in this group of children . Sedentary behaviour ( TV viewing ) was independently associated with overweight at the age of 8 y. Physical activity and energy and nutrient intakes did not significantly affect the change in rel BMI over the four-year period when the parents ’ obesity was taken into account",
"The aim of this study is to examine sedentary and light activity in relation to overweight in adolescent girls . Adolescent girls were r and omly recruited from 36 schools participating in the Trial of Activity for Adolescent Girls ( TAAG ) . Assessment s included age , ethnicity , socioeconomic status , and body composition estimated from weight , height , and triceps skinfold . Sedentary and light activity was measured for 6 days using accelerometry in 6th and in 8th grade among two r and omly sample d cross-sections of girls . Sedentary activity increased from the 6th to 8th grade by 51.5 min/day . In the 8th grade , a significantly higher number of hours in sedentary activity for each of the 6-days of measurement were evident with higher tertiles of percent body fat ( 30 - 35 % , > 35 % fat ) ( P 95th percentiles ) . The increase in sedentary activity was observed on weekdays , but not on weekends for percent body fat tertiles . In the cohort of girls measured in both 6th and 8th grade s , the mean cross-sectional coefficient estimates were significant for percent body fat , but not BMI for sedentary and light activities . Adolescent girls from the 6th to 8th grade are shifting their time from light to more sedentary activity as measured by accelerometers . In addition , the increase in sedentary activity is not associated with an adverse effect on BMI or percent body fat . The eventual impact of this shift to a more sedentary lifestyle on body composition and other outcomes needs to be evaluated further",
"Childhood obesity incidence has increased substantially and it has been argued that decreasing physical activity levels , coinciding with an increase in sedentary behaviours , are responsible . Australian guidelines were published in 2004 , recommending that children participate in a minimum of 60 min of physical activity daily and spend no more than 2h a day using electronic media for entertainment . We aim ed to compare compliance with these guidelines amongst children of differing weight status . The Childhood Injury Prevention Study ( CHIPS ) collected data from a r and omly selected sample of Brisbane primary and preschool children aged 5 - 12 years . The following data were available for 518 participants : age , gender , measured height and weight and estimated time per week from a parent-completed 7 days diary in physical activity out of school and sedentary leisure activities including television viewing and computer use . Using age st and ardised body mass index estimates , approximately 20 % of the cohort were overweight . Non-compliance with guidelines was 14.7 % for out of school physical activity participation , and 30.9 % for excess electronic media entertainment use . There was a 63 % increase in the odds of overweight status amongst children who were non-compliant with the electronic entertainment recommendations than those who were compliant ( adjusted odds ratio=1.63 ; 95 % CI=1.05 - 2.54 ) . Female gender and school level socioeconomic category were also independently associated with overweight status . Non-compliance with the minimal physical activity guideline increased the odds of being overweight by 28 % , however this difference was not statistically significant . One in seven children from the Greater Brisbane area are at risk for being insufficiently active whilst a third overuse electronic media . Given that overuse of electronic entertainment was positively associated with childhood obesity , these children should be the target of public health campaigns to promote alternative leisure time activities",
"Background Previous studies examining the relationship between physical activity levels and broad-based measures of psychological wellbeing in adolescents have been limited by not controlling for potentially confounding variables . The present study examined the relationship between adolescents ’ self-reported physical activity level , sedentary behaviour and psychological wellbeing ; while controlling for a broad range of sociodemographic , health and developmental factors . Methods The study entailed a cross-sectional school-based survey in ten British towns . Two thous and six hundred and twenty three adolescents ( aged 13–16 years ) reported physical activity levels , patterns of sedentary behaviour ( TV/computer/video usage ) and completed the strengths and difficulties question naire ( SDQ ) . Results Lower levels of self-reported physical activity and higher levels of sedentary behaviour showed grade d associations with higher SDQ total difficulties scores , both for boys ( P diminished psychological wellbeing among adolescents . Longitudinal studies may provide further insights into the relationship between wellbeing and activity levels in this population . Ultimately , r and omised controlled trials are needed to evaluate the effects of increasing physical activity on psychological wellbeing among adolescents",
"OBJECTIVE To examine the relation between baseline fat mass and gain in bone area and bone mass in preschoolers studied prospect ively for 4 years , with a focus on the role of physical activity and TV viewing . STUDY DESIGN Children were part of a longitudinal study in which measures of fat , lean and bone mass , height , weight , activity , and diet were taken every 4 months from ages 3 to 7 years . Activity was measured by accelerometer and TV viewing by parent checklist . We included 214 children with total body dual energy x-ray absorptiometry ( Hologic 4500A ) scans at ages 3.5 and 7 years . RESULTS Higher baseline fat mass was associated with smaller increases in bone area and bone mass over the next 3.5 years ( P TV viewing was related to smaller gains in bone area and bone mass accounting for race , sex , and height . Activity by accelerometer was not associated with bone gains . CONCLUSIONS Adiposity and TV viewing are related to less bone accrual in preschoolers",
"BACKGROUND There are concerns that sedentariness among young people has increased and that this may be detrimental to their health . The purpose of this study was to examine the association between sedentary activities , including small-screen recreation ( SSR : watching TV/DVDs/videos , recreational computer use ) and cardiorespiratory endurance ( CRE ) in children aged 11 - 15 years . METHODS A cross-sectional representative population survey was taken of New South Wales ( Australia ) school students in Grade s 6 , 8 , and 10 ( N=2750 ) in 2004 . Sedentary activities and SSR were measured by a self-report question naire . CRE was determined by the 20-meter multi-stage shuttle run test . The optimal cut point for time spent on SSR was determined by receiver operating characteristic analysis . RESULTS Time spent in sedentary activities was inversely associated with CRE among Grade 8 students ( p=0.01 ) and Grade 10 girls ( p=0.03 ) . CRE was lower among Grade 8 students ( p 10 girls ( p or=2 hours/day on SSR compared with students who spent sensitivity ( boys : 84 % , [ 95 % CI=79 % , 87 % ] ; girls : 79 % [ 95 % CI=74 % , 84 % ] ) and low specificity ( boys : 28 % [ 95 % CI=24 % , 32 % ] ; girls : 42 % [ 95 % CI=38 % , 46 % ] ) . CONCLUSIONS Cardiorespiratory endurance did not differ consistently across quintiles of sedentariness and SSR among boys ; however , among girls there was a consistent inverse association . If confirmed in prospect i ve studies , these findings have important implication s for risk of chronic disease",
" Obese children 8 - 12 years old from 61 families were r and omized to treatment groups that targeted increased exercise , decreased sedentary behaviors , or both ( combined group ) to test the influence of reinforcing children to be more active or less sedentary on child weight change . Significant decreases in percentage overweight were observed after 4 months between the sedentary and the exercise groups ( -19.9 vs. -13.2 ) . At 1 year , the sedentary group had a greater decrease in percentage overweight than did the combined and the exercise groups ( -18.7 vs. -10.3 and -8.7 ) and greater decrease in percentage of body fat ( -4.7 vs. -1.3 ) . All groups improved fitness during treatment and follow-up . Children in the sedentary group increased their liking for high-intensity activity and reported lower caloric intake than did children in the exercise group . These results support the goal of reducing time spent in sedentary activities to improve weight loss",
"Obese children were r and omly assigned to a family-based behavioral treatment that included either stimulus control or reinforcement to reduce sedentary behaviors . Significant and equivalent decreases in sedentary behavior and high energy density foods , increases in physical activity and fruits and vegetables , and decreases in st and ardized body mass index ( z- BMI ) were observed . Children who substituted active for sedentary behaviors had significantly greater z- BMI changes at 6 ( -1.21 vs. -0.76 ) and 12 ( -1.05 vs. -0.51 ) months , respectively . Substitution of physically active for sedentary behaviors and changes in activity level predicted 6- and 12-month z- BMI changes . Results suggest stimulus control and reinforcing reduced sedentary behaviors are equivalent ways to decrease sedentary behaviors , and behavioral economic relationships in eating and activity may mediate the effects of treatment",
"BACKGROUND . The American Academy of Pediatrics recommends children ≥2 years of age limit daily media exposure to ≤1 to 2 hours and not have a television set in children 's bedrooms . However , there are limited prospect i ve studies to address how timing of media exposure influences children 's health . OBJECTIVE . Our goal was to examine relations among children 's early , concurrent , and sustained television exposure and behavioral and social skills outcomes at 5.5 years . METHODS . We analyzed data collected prospect ively from the Healthy Steps for Young Children national evaluation . Television exposure was defined as > 2 hours of daily use ( at 30–33 months and 5.5 years ) and television in child 's bedroom ( at 5.5 years ) . At 5.5 years , outcomes were assessed by using the Child Behavior Checklist and social skills using the Social Skills Rating System . Linear regression was used to estimate the effect of television exposure on behavioral and social skills outcomes . RESULTS . Sixteen percent of parents reported that their child watched > 2 hours of television daily at 30 to 33 months only , 15 % reported > 2 hours of television daily at 5.5 years only , and 20 % reported > 2 hours of television daily at both times . Forty-one percent of the children had televisions in their bedrooms at 5.5 years . In adjusted analyses , sustained television viewing was associated with behavioral outcomes . Concurrent television exposure was associated with fewer social skills . For children with heavy television viewing only in early childhood , there was no consistent relation with behavioral or social skills outcomes . Having a television in the bedroom was associated with sleep problems and less emotional reactivity at 5.5 years but was not associated with social skills . CONCLUSIONS . Sustained exposure is a risk factor for behavioral problems , whereas early exposure that is subsequently reduced presents no additional risk . For social skills , concurrent exposure was more important than sustained or early exposure . Considering the timing of media exposure is vital for underst and ing the consequences of early experiences and informing prevention strategies",
"BACKGROUND The purpose of the study was to explore the association among the following variables : physical activity , TV , videogames , and obesity . The study included a Portuguese r and om nationally representative sample of 3365 children ( 1610 girls and 1755 boys ) 7 - 9 year olds . METHODS A general question naire was completed by the parents of participating children to provide information about the hours spent per week watching television , computer use and electronic games , and the participation in physical education . Overweight and obesity were calculated by using the body mass index ( BMI ) assessment and the cut-off points for overweight ( 25 kg/m(2 ) ) and obesity ( 30 kg/m(2 ) ) . RESULTS The data from the association between BMI and the independent variables ( analysis of variance ) were only significant for time playing electronic games for boys and girls ( P between hours of watching TV and BMI was significant only for boys ( P playing electronic games is associated with obesity . Reducing childhood obesity calls for the reduction in sedentary behaviours , and the promotion of a more active lifestyle",
"OBJECTIVES To assess how trial information reported in conference abstract s differs to their subsequent full publication . METHODS R and omized trials reported at the American Society of Clinical Oncology conference ( 1992 ) were identified . CENTRAL and PubMed ( December 2002 ) were search ed to identify corresponding full publications . A checklist ( based on CONSORT ) was used to compare abstract s for 37 trials with their full publication . RESULTS Some aspects were well reported . Ninety-five percent of study objectives , 92 % of participant eligibility , 100 % of trial interventions , and 84 % of primary outcomes were the same in both abstract and full publication . Other areas were more discrepant . Forty-six percent reported the same number of participants r and omized in the abstract and full publication ; only 22 % reported the same number analyzed ( median number analyzed per trial was 96 for abstract s and 117 for full publications ) . Eighty-two percent of trials were closed to follow-up in the full publication compared to 19 % of abstract s. Lack of information was a major problem in assessing trial quality : no abstract s reported on allocation concealment , 16 % reported on blinding and 14 % reported intention to treat analysis . These figures were 49 , 19 , and 46 % , respectively , for full publications . CONCLUSION The information given for trials in conference proceedings can be unstable , especially for trials presenting early or preliminary results , and needs to be improved",
"OBJECTIVE To investigate the association of television viewing with educational and intellectual outcomes during adolescence and early adulthood . DESIGN Prospect i ve epidemiological study . SETTING Families participating in the Children in the Community Study , a prospect i ve longitudinal investigation , were interviewed at mean offspring ages 14 , 16 , and 22 years . PARTICIPANTS A community-based sample of 678 families from upstate New York . MAIN EXPOSURES Television viewing , attention difficulties , learning difficulties , and educational achievement during adolescence and early adulthood . MAIN OUTCOME MEASURES The Disorganizing Poverty Interview and age-appropriate versions of the Diagnostic Interview Schedule for Children . RESULTS Frequent television viewing during adolescence was associated with elevated risk for subsequent attention and learning difficulties after family characteristics and prior cognitive difficulties were controlled . Youths who watched 1 or more hours of television per day at mean age 14 years were at elevated risk for poor homework completion , negative attitudes toward school , poor grade s , and long-term academic failure . Youths who watched 3 or more hours of television per day were the most likely to experience these outcomes . In addition , youths who watched 3 or more hours of television per day were at elevated risk for subsequent attention problems and were the least likely to receive post secondary education . There was little evidence of bidirectionality in the association of television viewing with attention and learning difficulties . CONCLUSION Frequent television viewing during adolescence may be associated with risk for development of attention problems , learning difficulties , and adverse long-term educational outcomes"
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BACKGROUND AND PURPOSE An increasing interest in the potential benefits of cognitive motor interference ( CMI ) for stroke has recently been observed , but the efficacy of CMI for gait and balance is controversial . A systematic review and meta- analysis of r and omized controlled trials was performed to estimate the effect of CMI on gait and balance in patients with stroke . METHODS Articles in Medline , EMBASE , the Cochrane Library , Web of Science , CINAHL , PEDro and the China Biology Medicine disc were search ed from 1970 to July 2014 . Only r and omized controlled trials examining the effects of CMI for patients with stroke were included , and no language restrictions were applied . Main outcome measures included gait and balance function . RESULTS A total of 15 studies composed of 395 participants met the inclusion criteria , and 13 studies of 363 participants were used as data sources for the meta- analysis . Pooling revealed that CMI was superior to the control group for gait speed [ mean difference ( MD ) 0.19 m/s , 95 % confidence interval ( CI ) ( 0.06 , 0.31 ) , P = 0.003 ] , stride length [ MD 12.53 cm , 95 % CI ( 4.07 , 20.99 ) , P = 0.004 ] , cadence [ MD 10.44 steps/min , 95 % CI ( 4.17 , 16.71 ) , P = 0.001 ] , centre of pressure sway area [ MD -1.05 , 95 % CI ( -1.85 , -0.26 ) , P = 0.01 ] and Berg balance scale [ MD 2.87 , 95 % CI ( 0.54 , 5.21 ) , P = 0.02 ] in the short term . CONCLUSION Cognitive motor interference is effective for improving gait and balance function for stroke in the short term . However , only little evidence supports assumptions regarding CMI 's long-term benefits
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"OBJECTIVE To evaluate gait biomechanics after training with a virtual reality ( VR ) system and to eluci date underlying mechanisms that contributed to the observed functional improvement in gait speed and distance . DESIGN A single blind r and omized control study . SETTING Gait analysis laboratory in a rehabilitation hospital and the community . PARTICIPANTS Fifteen men and three women with hemiparesis caused by stroke . INTERVENTIONS Subjects trained on a six-degree of freedom force-feedback robot interfaced with a VR simulation . Subjects were r and omized to either a VR group ( n=9 ) or non-VR group ( NVR , n=9 ) . Training was performed three times a week for 4 weeks for approximately 1h each visit . MAIN OUTCOME MEASURES Kinematic and kinetic gait parameters . RESULTS Subjects in the VR group demonstrated a significantly larger increase in ankle power generation at push-off as a result of training ( p=0.036 ) . The VR group had greater change in ankle ROM post-training ( 19.5 % ) as compared to the NVR group ( 3.3 % ) . Significant differences were found in knee ROM on the affected side during stance and swing , with greater change in the VR group . No significant changes were observed in kinematics or kinetics of the hip post-training . CONCLUSIONS These findings are encouraging because they support the potential for recovery of force and power of the lower extremity for individuals with chronic hemiparesis . It is likely that the effects of training included improved motor control at the ankle , which enabled the cascade of changes that produced the functional improvements seen after training",
"Background and Purpose — Training of the lower extremity ( LE ) using a robot coupled with virtual environments has shown to transfer to improved overground locomotion . The purpose of this study was to determine whether the transfer of training of LE movements to locomotion was greater using a virtual environment coupled with a robot or with the robot alone . Methods — A single , blind , r and omized clinical trial was conducted . Eighteen individuals poststroke participated in a 4-week training protocol . One group trained with the robot virtual reality ( VR ) system and the other group trained with the robot alone . Outcome measures were temporal features of gait measured in a laboratory setting and the community . Results — Greater changes in velocity and distance walked were demonstrated for the group trained with the robotic device coupled with the VR than training with the robot alone . Similarly , significantly greater improvements in the distance walked and number of steps taken in the community were measured for the group that trained with robot coupled with the VR . These differences were maintained at 3 months ’ follow-up . Conclusions — The study is the first to demonstrate that LE training of individuals with chronic hemiparesis using a robotic device coupled with VR improved walking ability in the laboratory and the community better than robot training alone",
"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",
"BACKGROUND Falls occur mainly while walking or performing concurrent tasks . We determined whether a music-based multitask exercise program improves gait and balance and reduces fall risk in elderly individuals . METHODS We conducted a 12-month r and omized controlled trial involving 134 community-dwelling individuals older than 65 years , who are at increased risk of falling . They were r and omly assigned to an intervention group ( n = 66 ) or a delayed intervention control group scheduled to start the program 6 months later ( n = 68 ) . The intervention was a 6-month multitask exercise program performed to the rhythm of piano music . Change in gait variability under dual-task condition from baseline to 6 months was the primary end point . Secondary outcomes included changes in balance , functional performances , and fall risk . RESULTS At 6 months , there was a reduction in stride length variability ( adjusted mean difference , -1.4 % ; P Balance and functional tests improved compared with the control group . There were fewer falls in the intervention group ( incidence rate ratio , 0.46 ; 95 % confidence interval , 0.27 - 0.79 ) and a lower risk of falling ( relative risk , 0.61 ; 95 % confidence interval , 0.39 - 0.96 ) . Similar changes occurred in the delayed intervention control group during the second 6-month period with intervention . The benefit of the intervention on gait variability persisted 6 months later . CONCLUSION In community-dwelling older people at increased risk of falling , a 6-month music-based multitask exercise program improved gait under dual-task condition , improved balance , and reduced both the rate of falls and the risk of falling . Trial Registration clinical trials.gov Identifier : NCT01107288",
"Objective : The aim of this study was to evaluate the effects of virtual reality ( VR ) treadmill training on the balance skills of patients who have had a stroke . Design : A total of 14 patients with strokes were recruited and r and omly assigned to receive VR treadmill or traditional treadmill training . The outcome measures that were included for the study were center of pressure ( COP ) sway excursion , COP maximum sway in anterior-posterior direction , COP maximum sway in medial-lateral direction , COP sway area , bilateral limb-loading symmetric index , the sway excursion values for the paretic foot ( sway excursion/P ) , paretic limb stance time ( stance time/P ) , number of steps of the paretic limb ( number of steps/P ) , and contact area of the paretic foot ( contact A/P ) during quiet stance , sit-to-st and transfer , and level walking . Results : There were no significant improvements in COP-related measures and symmetric index during the quiet stance , either in the VR treadmill or traditional treadmill training group ( P > 0.05 ) . However , the difference between groups after training in COP maximum sway in medial-lateral direction during the quiet stance was significant ( P = 0.038 ) . Traditional treadmill training failed to improve sit-to-st and performance , whereas VR treadmill training improved symmetric index ( P = 0.028 ) and sway excursion ( P = 0.046 ) significantly during sit-to-st and transfer . The changes of symmetric index between groups were markedly different ( P = 0.045 ) . Finally , both groups improved significantly in stance time/P , but only VR treadmill training increased contact A/P ( P = 0.034 ) after training during level walking . The difference between groups during level walking was not significant . Conclusions : Neither traditional treadmill nor VR treadmill training had any effect on balance skill during quiet stance , but VR treadmill training improved balance skill in the medial-lateral direction better than traditional training did . VR treadmill training also improved balance skill during sit-to-st and transfers and the involvement of paretic limb in level walking more than the traditional one did",
"Using r and omized control trial methodology , we evaluated the effectiveness of a 5-week cognitive-motor dual-tasking training program developed to improve performance of a group of people with dual-tasking difficulties arising from acquired brain injury . Training involved twice-daily practice on exercises involving walking being combined with tasks which increased in cognitive dem and over the course of the intervention . A treatment group ( n = 10 ) was compared with a control group ( n = 9 ) . The primary outcome measure was a task requiring participants to walk and carry out a spoken sentence verification task simultaneously . Secondary outcome measures were measures of dual-tasking involving either two motor tasks or two cognitive tasks . A question naire measure relating to activities of daily living requiring dual-tasking was also completed . Compliance with the training program was good . We found evidence of improvement in performance on the primary outcome measure , but little evidence of generalization to other measures . There was some evidence that participants believed that their dual-tasking performance in everyday life was improved after the intervention . The study was limited in terms of sample size , was not blinded and did not control fully for therapist contact time , but has produced valuable data relating to effect sizes associated with this form of intervention . ( JINS , 2009 , 15 , 112 - 120 . )",
"PURPOSE Athletic performance dem and s simultaneous use of cognitive and postural control capabilities . Decrements to both systems have been observed following concussion . This study evaluated a dual-task methodology to establish the tenability of using this testing model in concussed athletes . METHODS Nonconcussed subjects were assessed over 2 d. Subjects were introduced to the task-switching cognitive assessment test and a NeuroCom Smart Balance Master postural control assessment protocol on day 1 . In the following session , subjects were evaluated on postural control and cognitive function tests independently ( single task ) , and then concurrently ( dual task ) . RESULTS Significant improvements were seen in three of the four balance conditions and in three of the four reaction times when the cognitive and balance task were performed simultaneously ( P balance by cognitive task interaction was revealed ( P>0.05 ) ; however , significant differences existed in reaction time based on stimulus position and increasing balance dem and s ( P healthy subjects showing improved performance when compared with individual task performance . The dual-task methodology brought about systematic changes to reaction time in relation to increasing balance dem and s. The ability of this protocol to detect changes in postural control or cognitive function following concussive injury requires further study",
"Stroke is one of the most serious healthcare problems and a major cause of impairment of cognition and physical functions . Virtual rehabilitation approaches to postural control have been used for enhancing functional recovery that may lead to a decrease in the risk of falling . In the present study , we investigated the effects of virtual reality balance training ( VRBT ) with a balance board game system on balance of chronic stroke patients . Participants were r and omly assigned to 2 groups : VRBT group ( 11 subjects including 3 women , 65.26 years old ) and control group ( 11 subjects including 5 women , 63.13 years old ) . Both groups participated in a st and ard rehabilitation program ( physical and occupational therapy ) for 60 min a day , 5 times a week for 6 weeks . In addition , the VRBT group participated in VRBT for 30 min a day , 3 times a week for 6 weeks . Static balance ( postural sway velocity with eyes open or closed ) was evaluated with the posturography . Dynamic balance was evaluated with the Berg Balance Scale ( BBS ) and Timed Up and Go test ( TUG ) that measures balance and mobility in dynamic balance . There was greater improvement on BBS ( 4.00 vs. 2.81 scores ) and TUG ( -1.33 vs. -0.52 sec ) in the VRBT group compared with the control group ( P static balance in both groups . In conclusion , we demonstrate a significant improvement in dynamic balance in chronic stroke patients with VRBT . VRBT is feasible and suitable for chronic stroke patients with balance deficit in clinical setting",
"This is a single blind r and omized controlled trial to examine the effect of virtual reality-based training on the community ambulation in individuals with stroke . Twenty subjects with stroke were assigned r and omly to either the control group ( n=9 ) or the experimental group ( n=11 ) . Subjects in the control group received the treadmill training . Subjects in the experimental group underwent the virtual reality-based treadmill training . Walking speed , community walking time , walking ability question naire ( WAQ ) , and activities-specific balance confidence ( ABC ) scale were evaluated . Subjects in the experimental group improved significantly in walking speed , community walking time , and WAQ score at posttraining and 1-month follow-up periods . Their ABC score also significantly increased at posttraining but did not maintain at follow-up period . Regarding the between-group comparisons , the experimental group improved significantly more than control group in walking speed ( P=0.03 ) and community walking time ( P=0.04 ) at posttraining period and in WAQ score ( P=0.03 ) at follow-up period . Our results support the perceived benefits of gait training programs that incorporate virtual reality to augment the community ambulation of individuals with stroke",
"Objective The purpose of this study was to investigate the effectiveness of the virtual walking training program using a real-world video recording on walking balance and spatiotemporal gait parameters in patients with chronic stroke . Design Fourteen patients with chronic stroke were r and omly assigned to either the experimental group ( n = 7 ) or the control group ( n = 7 ) . The subjects in both groups underwent a st and ard rehabilitation program ; in addition , the experimental group participated in the virtual walking training program using a real-world video recording for 30 mins a day , three times a week , for 6 wks , and the control group participated in treadmill gait training for 30 mins a day , three times a week , for 6 wks . Walking balance was measured using the Berg Balance Scale ( BBS ) and the Timed Up and Go test . Gait performance was measured using an electrical walkway system . Results In walking balance , greater improvement on the Berg Balance Scale ( experimental group : 4.14 vs. control group : 1.85 ) and the Timed Up and Go test ( −2.25 vs. −0.94 ) was observed in the experimental group compared with the control group ( P spatiotemporal gait parameters , greater improvement on velocity ( 25.40 vs. 9.74 ) and cadence ( 26.71 vs. 11.11 ) was observed in the experimental group compared with the control group ( P virtual walking training program using a real-world video recording on gait performance . These findings suggest that the virtual walking training program using a real-world video recording may be a valid approach to enhance gait performance in patients with chronic stroke",
"OBJECTIVE To examine the effectiveness of a dual-task-based exercise program on walking ability in subjects with chronic stroke . DESIGN Single-blind r and omized controlled trial . SETTING General community . PARTICIPANTS Twenty-five subjects with chronic stroke who were at least limited community ambulatory subjects ( a minimum gait velocity , 58cm/s ) . INTERVENTIONS Participants were r and omized into a control group ( n=12 ) or experimental group ( n=13 ) . Subjects in the control group did not receive any rehabilitation training . Subjects in the experimental group underwent a 4-week ball exercise program . MAIN OUTCOME MEASURES Gait performance was measured under single task ( preferred walking ) and tray-carrying task . Gait parameters of interest were walking speed , cadence , stride time , stride length , and temporal symmetry index . RESULTS The experimental group showed significant improvement in all selected gait measures except for temporal symmetry index under both task conditions . In the control group , there were no significant changes over the 4-week period for all selected measures . There was a significant difference between groups for all selected gait variables except for temporal symmetry index under both task conditions . CONCLUSIONS The dual-task-based exercise program is feasible and beneficial for improving walking ability in subjects with chronic stroke",
"Kim JH , Jang SH , Kim CS , Jung JH , You JH : Use of virtual reality to enhance balance and ambulation in chronic stroke : A double-blind , r and omized controlled study . Objective : To examine an additive effect of virtual reality on balance and gait function in patients with chronic hemiparetic stroke . Design : Twenty-four adults with hemiparetic stroke were r and omly assigned to either an experimental group ( n = 12 ) or a control group . Both groups underwent conventional physical therapy , 40 mins a day , 4 days a week for 4 wks . The experimental group received an additional 30 mins of virtual reality therapy each session . Balance performance was determined by the Balance Performance Monitor and Berg Balance Scale tests . Gait performance was determined by the 10-m walking test and Modified Motor Assessment Scale , and spatiotemporal parameters were obtained using GAITRite . Analysis of variance and correlation statistics were performed at P Berg Balance Scale scores , balance and dynamic balance angles ( ability to control weight shifting ) compared with the controls ( P velocity , Modified Motor Assessment Scale scores , cadence , step time , step length , and stride length ( P dynamic balance angles was correlated with velocity and cadence ( P adults with hemiparetic stroke when added to conventional therapy"
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Background Solutions delivered within firm sectoral boundaries are inadequate in achieving income security and better health for poor population s. Integrated microfinance and health interventions leverage networks of women to promote financial inclusion , build livelihoods , and safeguard against high cost illnesses . Our underst and ing of the effect of integrated interventions has been limited by variability in intervention , outcome , design , and method ological rigour . This systematic review synthesis es the literature through 2015 to underst and the effect of integrated microfinance and health programs . Methods We search ed PubMed , Scopus , Embase , EconLit , and Global Health data bases and source d bibliographies , identifying 964 articles exclusive of duplicates . Title , abstract , and full text review yielded 35 articles . Articles evaluated the effect of intentionally integrated microfinance and health programs on client outcomes . We rated the quality of evidence for each article . Results Most interventions combined microfinance with health education , which demonstrated positive effects on health knowledge and behaviours , though not health status . Among programs that integrated microfinance with other health components ( i.e. health micro-insurance , linkages to health providers , and access to health products ) , results were generally positive but mixed due to the smaller number and quality of studies . Interventions combining multiple health components in a given study demonstrated positive effects , though it was unclear which component was driving the effect . Most articles ( 57 % ) were moderate in quality . Discussion Integrated microfinance and health education programs were effective , though longer intervention periods are necessary to measure more complex pathways to health status . The effect of microfinance combined with other health components was less clear . Stronger r and omized research design s with multiple study arms are required to improve evidence and disentangle the effects of multiple component microfinance and health interventions . Few studies attempted to underst and changes in economic outcomes , limiting our underst and ing of the relationship between health and income effects
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"Microfinance institutions have started to bundle their basic loans with other financial services , such as health insurance . Using a r and omized control trial in Karnataka , India , we evaluate the impact on loan renewal from m and ating the purchase of actuarially-fair health insurance covering hospitalization and maternity expenses . Bundling loans with insurance led to a 16 percentage points ( 23 percent ) increase in drop-out from microfinance , as many clients preferred to give up microfinance than pay higher interest rates and receive insurance . In a Pyrrhic victory , the total absence of dem and for health insurance led to there being no adverse selection in insurance enrollment",
"Objective : To assess effects of a combined microfinance and training intervention on HIV risk behavior among young female participants in rural South Africa . Design : Secondary analysis of quantitative and qualitative data from a cluster r and omized trial , the Intervention with Microfinance for AIDS and Gender Equity study . Methods : Eight villages were pair-matched and r and omly allocated to receive the intervention . At baseline and after 2 years , HIV risk behavior was assessed among female participants aged 14–35 years . Their responses were compared with women of the same age and poverty group from control villages . Intervention effects were calculated using adjusted risk ratios employing village level summaries . Qualitative data collected during the study explored participants ' responses to the intervention including HIV risk behavior . Results : After 2 years of follow-up , when compared with controls , young participants had higher levels of HIV-related communication ( adjusted risk ratio 1.46 , 95 % confidence interval 1.01–2.12 ) , were more likely to have accessed voluntary counseling and testing ( adjusted risk ratio 1.64 , 95 % confidence interval 1.06–2.56 ) , and less likely to have had unprotected sex at last intercourse with a nonspousal partner ( adjusted risk ratio 0.76 , 95 % confidence interval 0.60–0.96 ) . Qualitative data suggest a greater acceptance of intrahousehold communication about HIV and sexuality . Although women noted challenges associated with acceptance of condoms by men , increased confidence and skills associated with participation in the intervention supported their introduction in sexual relationships . Conclusions : In addition to impacts on economic well being , women 's empowerment and intimate partner violence , interventions addressing the economic and social vulnerability of women may contribute to reductions in HIV risk behavior",
"The contribution of acute respiratory infection control project within the framework of micro-credit-based development intervention in promoting maternal knowledge of ARIs in children was assessed . Data came from a cross-sectional survey of 2814 mothers of under 5-y-old children residing in 200 r and omly selected villages in five districts in Bangladesh . Findings revealed that the ARI control project had significant positive effects in raising knowledge of clinical signs and preventive measures . When ARI control project activities were integrated with the credit-based development initiative , maternal knowledge improved even further . The study concludes that the micro-credit programme can be a catalytic agent in raising health knowledge among poor women in developing countries ",
"OBJECTIVE To explore whether adding a gender and HIV training programme to microfinance initiatives can lead to health and social benefits beyond those achieved by microfinance alone . METHODS Cross-sectional data were derived from three r and omly selected matched clusters in rural South Africa : ( i ) four villages with 2-year exposure to the Intervention with Microfinance for AIDS and Gender Equity ( IMAGE ) , a combined microfinance-health training intervention ; ( ii ) four villages with 2-year exposure to microfinance services alone ; and ( iii ) four control villages not targeted by any intervention . Adjusted risk ratios ( aRRs ) employing village-level summaries compared associations between groups in relation to indicators of economic well-being , empowerment , intimate partner violence ( IPV ) and HIV risk behaviour . The magnitude and consistency of aRRs allowed for an estimate of incremental effects . FINDINGS A total of 1409 participants were enrolled , all female , with a median age of 45 . After 2 years , both the microfinance-only group and the IMAGE group showed economic improvements relative to the control group . However , only the IMAGE group demonstrated consistent associations across all domains with regard to women 's empowerment , intimate partner violence and HIV risk behaviour . CONCLUSION The addition of a training component to group-based microfinance programmes may be critical for achieving broader health benefits . Donor agencies should encourage intersectoral partnerships that can foster synergy and broaden the health and social effects of economic interventions such as microfinance ",
"Formative research uses qualitative and quantitative methods to provide information for research ers to plan intervention programs . Gaps in the formative research literature include how to define goals , implementation plans , and research questions ; select methods ; analyze data ; and develop interventions . The National Heart , Lung , and Blood Institute funded the Trial of Activity for Adolescent Girls ( TAAG ) , a r and omized , multicenter field trial , to reduce the decline in physical activity in adolescent girls . The goals of the TAAG formative research are to ( a ) describe study communities and schools , ( b ) help design the trial ’s interventions , ( c ) develop effective recruitment and retention strategies , and ( d ) design evaluation instruments . To meet these goals , a variety of methods , including telephone interviews , surveys and checklists , semistructured interviews , and focus group discussion s , are employed . The purpose , method of development , and analyses are explained for each method",
"In northern Nigeria , interventions are urgently needed to narrow the large gap between international breastfeeding recommendations and actual breastfeeding practice s. Studies of integrated microcredit and community health interventions documented success in modifying health behaviors but typically had uncontrolled design s. We conducted a cluster-r and omized controlled trial in Bauchi State , Nigeria , with the aim of increasing early breastfeeding initiation and exclusive breastfeeding among female microcredit clients . The intervention had 3 components . Trained credit officers led monthly breastfeeding learning sessions during regularly scheduled microcredit meetings for 10 mo . Text and voice messages were sent out weekly to a cell phone provided to small groups of microcredit clients ( 5 - 7 women ) . The small groups prepared songs or dramas about the messages and presented them at the monthly microcredit meetings . The control arm continued with the regular microcredit program . R and omization occurred at the level of the monthly meeting groups . Pregnant clients were recruited at baseline and interviewed again when their infants were aged ≥6 mo . Logistic regression models accounting for clustering were used to estimate the odds of performing recommended behaviors . Among the clients who completed the final survey ( n = 390 ) , the odds of exclusive breastfeeding to 6 mo ( OR : 2.4 ; 95 % CI : 1.4 , 4.0 ) and timely breastfeeding initiation ( OR : 2.6 ; 95 % CI : 1.6 , 4.1 ) were increased in the intervention vs. control arm . Delayed introduction of water explained most of the increase in exclusive breastfeeding among clients receiving the intervention . In conclusion , a breastfeeding promotion intervention integrated into microcredit increased the likelihood that women adopted recommended breastfeeding practice s. This intervention could be scaled up in Nigeria , where local organizations provide microcredit to > 500,000 clients . Furthermore , the intervention could be adopted more widely given that > 150 million women , many of childbearing age , are involved in microfinance globally",
"Many severe health risks in developing countries could be substantially reduced with access to appropriate preventive measures . However , the associated costs are often high enough to restrict access among poor households , and free provision through public health campaigns is often not financially feasible . We describe findings from the first large-scale cluster r and omized controlled trial in a developing country context that evaluates the uptake of a health-protecting technology , insecticide-treated bednets ( ITNs ) , through micro-consumer loans , as compared to free distribution and control conditions . Numerous studies have shown that widespread , regular use of ITNs is one the most effective preventive measures against malaria . However , ownership rates remain very low in most malarious areas , including our study areas in rural Orissa ( India ) . Despite the un-subsidized price , 52 percent of sample households purchased at least one ITN , leading to 16 percent of individuals using a treated net the previous night , relative to only 2 percent in control areas where nets were not offered for sale . However , the increase fell significantly short of the 47 percent previous-night usage rate achieved with free distribution . Most strikingly , we find that neither micro-loans nor free distribution led to improvements in malaria and anemia prevalence , measured using blood tests . We examine and rule out several plausible explanations for this latter finding . We conjecture that insufficient ITN coverage is the most likely explanation , and discuss implication s for public health policy",
"BACKGROUND Women 's groups and health education by peer counsellors can improve the health of mothers and children . We assessed their effects on mortality and breastfeeding rates in rural Malawi . METHODS We did a 2 × 2 factorial , cluster-r and omised trial in 185,888 people in Mchinji district . 48 equal-sized clusters were r and omly allocated to four groups with a computer-generated number sequence . 24 facilitators guided groups through a community action cycle to tackle maternal and child health problems . 72 trained volunteer peer counsellors made home visits at five timepoints during pregnancy and after birth to support breastfeeding and infant care . Primary outcomes for the women 's group intervention were maternal , perinatal , neonatal , and infant mortality rates ( MMR , PMR , NMR , and IMR , respectively ) ; and for the peer counselling were IMR and exclusive breastfeeding ( EBF ) rates . Analysis was by intention to treat . The trial is registered as IS RCT N06477126 . FINDINGS We monitored outcomes of 26,262 births between 2005 and 2009 . In a factorial model adjusted only for clustering and the volunteer peer counselling intervention , in women 's group areas , for years 2 and 3 , we noted non-significant decreases in NMR ( odds ratio 0.93 , 0.64 - 1.35 ) and MMR ( 0.54 , 0.28 - 1.04 ) . After adjustment for parity , socioeconomic quintile , and baseline measures , effects were larger for NMR ( 0.85 , 0.59 - 1.22 ) and MMR ( 0.48 , 0.26 - 0.91 ) . Because of the interaction between the two interventions , a stratified analysis was done . For women 's groups , in adjusted analyses , MMR fell by 74 % ( 0.26 , 0.10 - 0.70 ) , and NMR by 41 % ( 0.59 , 0.40 - 0.86 ) in areas with no peer counsellors , but there was no effect in areas with counsellors ( 1.09 , 0.40 - 2.98 , and 1.38 , 0.75 - 2.54 ) . Factorial analysis for the peer counselling intervention for years 1 - 3 showed a fall in IMR of 18 % ( 0.82 , 0.67 - 1.00 ) and an improvement in EBF rates ( 2.42 , 1.48 - 3.96 ) . The results of the stratified , adjusted analysis showed a 36 % reduction in IMR ( 0.64 , 0.48 - 0.85 ) but no effect on EBF ( 1.18 , 0.63 - 2.25 ) in areas without women 's groups , and in areas with women 's groups there was no effect on IMR ( 1.05 , 0.82 - 1.36 ) and an increase in EBF ( 5.02 , 2.67 - 9.44 ) . The cost of women 's groups was US$ 114 per year of life lost ( YLL ) averted and that of peer counsellors was $ 33 per YLL averted , using stratified data from single intervention comparisons . INTERPRETATION Community mobilisation through women 's groups and volunteer peer counsellor health education are methods to improve maternal and child health outcomes in poor rural population s in Africa . FUNDING Saving Newborn Lives , UK Department for International Development , and Wellcome Trust",
"BACKGROUND Neonatal deaths in developing countries make the largest contribution to global mortality in children younger than 5 years . 90 % of deliveries in the poorest quintile of households happen at home . We postulated that a community-based participatory intervention could significantly reduce neonatal mortality rates . METHODS We pair-matched 42 geopolitical clusters in Makwanpur district , Nepal , selected 12 pairs r and omly , and r and omly assigned one of each pair to intervention or control . In each intervention cluster ( average population 7000 ) , a female facilitator convened nine women 's group meetings every month . The facilitator supported groups through an action-learning cycle in which they identified local perinatal problems and formulated strategies to address them . We monitored birth outcomes in a cohort of 28?931 women , of whom 8 % joined the groups . The primary outcome was neonatal mortality rate . Other outcomes included stillbirths and maternal deaths , uptake of antenatal and delivery services , home care practice s , infant morbidity , and health-care seeking . Analysis was by intention to treat . The study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N31137309 . FINDINGS From 2001 to 2003 , the neonatal mortality rate was 26.2 per 1000 ( 76 deaths per 2899 livebirths ) in intervention clusters compared with 36.9 per 1000 ( 119 deaths per 3226 livebirths ) in controls ( adjusted odds ratio 0.70 [ 95 % CI 0.53 - 0.94 ] ) . Stillbirth rates were similar in both groups . The maternal mortality ratio was 69 per 100000 ( two deaths per 2899 livebirths ) in intervention clusters compared with 341 per 100000 ( 11 deaths per 3226 livebirths ) in control clusters ( 0.22 [ 0.05 - 0.90 ] ) . Women in intervention clusters were more likely to have antenatal care , institutional delivery , trained birth attendance , and hygienic care than were controls . INTERPRETATION Birth outcomes in a poor rural population improved greatly through a low cost , potentially sustainable and scalable , participatory intervention with women 's groups",
"Background & Objectives : Despite remarkable progress in airborne , vector-borne and waterborne diseases in India , the morbidity associated with these diseases is still high . Many of these diseases are controllable through awareness and preventive practice . This study was an attempt to evaluate the effectiveness of a preventive care awareness campaign in enhancing knowledge related with airborne , vector-borne and waterborne diseases , carried out in 2011 in three rural communities in India ( Pratapgarh and Kanpur-Dehat in Uttar Pradesh and Vaishali in Bihar ) . Methods : Data for this analysis were collected from two surveys , one done before the campaign and the other after it , each of 300 r and omly selected households drawn from a larger sample of Self-Help Groups ( SHGs ) members invited to join community-based health insurance ( CBHI ) schemes . Results : The results showed a significant increase both in awareness ( 34 % , p preventive practice s ( 48 % , P=0.001 ) , suggesting that the awareness campaign was effective . However , average practice scores ( 0.31 ) were substantially lower than average awareness scores ( 0.47 ) , even in post campaign . Awareness and preventive practice s were less prevalent in vector-borne diseases than in airborne and waterborne diseases . Education was positively associated with both awareness and practice scores . The awareness scores were positive and significant determinants of the practice scores , both in the pre- and in the post-campaign results . Affiliation to CBHI had significant positive influence on awareness and on practice scores in the post-campaign period . Interpretation & Conclusions : The results suggest that well-crafted health educational campaigns can be effective in raising awareness and promoting health-enhancing practice s in re source -poor setting s. It also confirms that CBHI can serve as a platform to enhance awareness to risks of exposure to airborne , vector-borne and waterborne diseases , and encourage preventive practice",
"Background Poverty , lack of female empowerment , and lack of education are major risk factors for childhood illness worldwide . Microcredit programs , by offering small loans to poor individuals , attempt to address the first two of these risk factors , poverty and gender disparity . They provide clients , usually women , with a means to invest in their businesses and support their families . This study investigates the health effects of also addressing the remaining risk factor , lack of knowledge about important health issues , through r and omization of members of a microcredit organization to receive a health education module based on the World Health Organization 's Integrated Management of Childhood Illness ( IMCI ) community intervention . Methods Baseline data were collected in February 2007 from clients of a microcredit organization in Pucallpa , Peru ( n = 1,855 ) and their children ( n = 598 ) . Loan groups , consisting of 15 to 20 clients , were then r and omly assigned to receive a health education intervention involving eight monthly 30-minute sessions given by the organization 's loan officers at monthly loan group meetings . In February 2008 , follow-up data were collected , and included assessment s of sociodemographic information , knowledge of child health issues , and child health status ( including child height , weight , and blood hemoglobin levels ) . To explore the effects of treatment ( i.e. , participation in the health education sessions ) on the key outcome variables , multivariate regressions were implemented using ordinary least squares . Results Individuals in the IMCI treatment arm demonstrated more knowledge about a variety of issues related to child health , but there were no changes in anthropometric measures or reported child health status . Conclusions Microcredit clients r and omized to an IMCI educational intervention showed greater knowledge about child health , but no differences in child health outcomes compared to controls . These results imply that the intervention did not have sufficient intensity to change behavior , or that microcredit organizations may not be an appropriate setting for the administration of child health educational interventions of this type . Trial Registration This study is registered with Clinical Trials.gov , NCT01047033",
"Child labor is a common consequence of economic shocks in developing countries . We show that reducing vulnerability can affect child labor outcomes . We exploit the extension of a health and accident insurance scheme by a Pakistani microfinance institution that was set up as a r and omized controlled trial and accompanied by household panel surveys . Together with increased coverage the microfinance institution offered assistance with cl aim procedures in treatment branches . We find lower incidence of child labor , hazardous occupations and child labor earnings caused by the innovation . Boys are more often engaged in child labor in our sample , but also seem to profit more from the insurance innovation ",
"It is now well known that st and ard statistical procedures become invali date d when applied to cluster r and omized trials in which the unit of inference is the individual . A result ing consequence is that research ers conducting such trials are faced with a multitude of design choices , including selection of the primary unit of inference , the degree to which clusters should be matched or stratified by prognostic factors at baseline , and decisions related to cluster subsampling . Moreover , application of ethical principles developed for individually r and omized trials may also require modification . We discuss several topics related to these issues , with emphasis on the choices that must be made in the planning stages of a trial and on some potential pitfalls to be avoided",
"OBJECTIVE To assess the impact of health promotion programs and microcredit programs on three communities in the Dominican Republic . One community had only the health promotion program , one community had only the microcredit program , and one community had both a health promotion program and a microcredit program . This pilot project examined the hypothesis that the largest changes in 11 health indicators that were studied would be in the community with both a health promotion program and a microcredit program , that there would be intermediate changes in the community with only a health promotion program , and that the smallest changes would be in the community with only a microcredit program . METHODS The health promotion programs used community volunteers to address two major concerns : ( 1 ) the prevalent causes of mortality among children under 5 years of age and ( 2 ) women 's health ( specifically breast and cervical cancer screening ) . The microcredit program made small loans to individuals to start or exp and small businesses . Outcome measures were based on comparisons for 11 health indicators from baseline community surveys ( 27 households surveyed in each of the three communities , done in December 2000 and January 2001 ) and from follow-up surveys ( also 27 households surveyed in each of the three communities , in June and July 2002 , after the health promotion program had been operating for about 13 months ) . Households were r and omly chosen during both the baseline and follow-up surveys , without regard to their involvement in the microcredit or health promotion programs . RESULTS The health indicators improved in all three communities . However , the degree of change was different among the communities ( P microcredit and health promotion programs had the largest changes for 10 of the 11 health indicators . CONCLUSIONS Multisector development is known to be important on a macroeconomic scale . The results of this pilot project support the view that multisector development is also important on a microeconomic level , given that the parallel microcredit and health promotion programs result ed in greater change in the measured health indicators than either program alone . As far as we authors know , this is the first published study to quantify changes in health indicators related to parallel health promotion and microcredit programs as compared to control communities with only a health promotion program or a microcredit program",
"Progress towards the Millennium Development Goals ( MDGs ) has been uneven . Inequalities in child health are large and effective interventions rarely reach the most in need . Little is known about how to reduce these inequalities . We describe and explain the equity impact of a women ’s group intervention in India that strongly reduced the neonatal mortality rate ( NMR ) in a cluster-r and omised trial . We conducted secondary analyses of the trial data , obtained through prospect i ve surveillance of a population of 228 186 . The intervention effects were estimated separately , through r and om effects logistic regression , for the most and less socio-economically marginalised groups . Among the most marginalised , the NMR was 59 % lower in intervention than in control clusters in years 2 and 3 ( 70 % , year 3 ) ; among the less marginalised , the NMR was 36 % lower ( 35 % , year 3 ) . The intervention effect was stronger among the most than among the less marginalised ( P-value for difference = 0.028 , years 2 - 3 ; P-value for difference = 0.009 , year 3 ) . The stronger effect was concentrated in winter , particularly for early NMR . There was no effect on the use of health-care services in either group , and improvements in home care were comparable . Participatory community interventions can substantially reduce socio-economic inequalities in neonatal mortality and contribute to an equitable achievement of the unfinished MDG agenda",
"IMPORTANCE Community-based interventions can reduce neonatal mortality when health systems are weak . Population coverage of target groups may be an important determinant of their effect on behavior and mortality . A women 's group trial at coverage of 1 group per 1414 population in rural Bangladesh showed no effect on neonatal mortality , despite a similar intervention having a significant effect on neonatal and maternal death in comparable setting s. OBJECTIVE To assess the effect of a participatory women 's group intervention with higher population coverage on neonatal mortality in Bangladesh . DESIGN A cluster r and omized controlled trial in 9 intervention and 9 control clusters . SETTING Rural Bangladesh . PARTICIPANTS Women permanently residing in 18 unions in 3 districts and accounting for 19 301 births during the final 24 months of the intervention . INTERVENTIONS Women 's groups at a coverage of 1 per 309 population that proceed through a participatory learning and action cycle in which they prioritize issues that affected maternal and neonatal health and design and implement strategies to address these issues . MAIN OUTCOMES AND MEASURES Neonatal mortality rate . RESULTS Analysis included 19 301 births during the final 24 months of the intervention . More than one-third of newly pregnant women joined the groups . The neonatal mortality rate was significantly lower in the intervention arm ( 21.3 neonatal deaths per 1000 live births vs 30.1 per 1000 in control areas ) , a reduction in neonatal mortality of 38 % ( risk ratio , 0.62 [ 95 % CI , 0.43 - 0.89 ] ) when adjusted for socioeconomic factors . The cost-effectiveness was US $ 220 to $ 393 per year of life lost averted . Cause-specific mortality rates suggest reduced deaths due to infections and those associated with prematurity/low birth weight . Improvements were seen in hygienic home delivery practice s , newborn thermal care , and breastfeeding practice s. CONCLUSIONS AND RELEVANCE Women 's group community mobilization , delivered at adequate population coverage , is a highly cost-effective approach to improve newborn survival and health behavior indicators in rural Bangladesh . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N01805825",
"BACKGROUND HIV infection and intimate-partner violence share a common risk environment in much of southern Africa . The aim of the Intervention with Microfinance for AIDS and Gender Equity ( IMAGE ) study was to assess a structural intervention that combined a microfinance programme with a gender and HIV training curriculum . METHODS Villages in the rural Limpopo province of South Africa were pair-matched and r and omly allocated to receive the intervention at study onset ( intervention group , n=4 ) or 3 years later ( comparison group , n=4 ) . Loans were provided to poor women who enrolled in the intervention group . A participatory learning and action curriculum was integrated into loan meetings , which took place every 2 weeks . Both arms of the trial were divided into three groups : direct programme participants or matched controls ( cohort one ) , r and omly selected 14 - 35-year-old household co-residents ( cohort two ) , and r and omly selected community members ( cohort three ) . Primary outcomes were experience of intimate-partner violence -- either physical or sexual -- in the past 12 months by a spouse or other sexual intimate ( cohort one ) , unprotected sexual intercourse at last occurrence with a non-spousal partner in the past 12 months ( cohorts two and three ) , and HIV incidence ( cohort three ) . Analyses were done on a per- protocol basis . This trial is registered with Clinical Trials.gov , number NCT00242957 . FINDINGS In cohort one , experience of intimate-partner violence was reduced by 55 % ( adjusted risk ratio [ aRR ] 0.45 , 95 % CI 0.23 - 0.91 ; adjusted risk difference -7.3 % , -16.2 to 1.5 ) . The intervention did not affect the rate of unprotected sexual intercourse with a non-spousal partner in cohort two ( aRR 1.02 , 0.85 - 1.23 ) , and there was no effect on the rate of unprotected sexual intercourse at last occurrence with a non-spousal partner ( 0.89 , 0.66 - 1.19 ) or HIV incidence ( 1.06 , 0.66 - 1.69 ) in cohort three . INTERPRETATION A combined microfinance and training intervention can lead to reductions in levels of intimate-partner violence in programme participants . Social and economic development interventions have the potential to alter risk environments for HIV and intimate-partner violence in southern Africa",
"BACKGROUND Community mobilisation through participatory women 's groups might improve birth outcomes in poor rural communities . We therefore assessed this approach in a largely tribal and rural population in three districts in eastern India . METHODS From 36 clusters in Jharkh and and Orissa , with an estimated population of 228 186 , we assigned 18 clusters to intervention or control using stratified r and omisation . Women were eligible to participate if they were aged 15 - 49 years , residing in the project area , and had given birth during the study . In intervention clusters , a facilitator convened 13 groups every month to support participatory action and learning for women , and facilitated the development and implementation of strategies to address maternal and newborn health problems . The primary outcomes were reductions in neonatal mortality rate ( NMR ) and maternal depression scores . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N21817853 . FINDINGS After baseline surveillance of 4692 births , we monitored outcomes for 19 030 births during 3 years ( 2005 - 08 ) . NMRs per 1000 were 55.6 , 37.1 , and 36.3 during the first , second , and third years , respectively , in intervention clusters , and 53.4 , 59.6 , and 64.3 , respectively , in control clusters . NMR was 32 % lower in intervention clusters adjusted for clustering , stratification , and baseline differences ( odds ratio 0.68 , 95 % CI 0.59 - 0.78 ) during the 3 years , and 45 % lower in years 2 and 3 ( 0.55 , 0.46 - 0.66 ) . Although we did not note a significant effect on maternal depression overall , reduction in moderate depression was 57 % in year 3 ( 0.43 , 0.23 - 0.80 ) . INTERPRETATION This intervention could be used with or as a potential alternative to health-worker-led interventions , and presents new opportunities for policy makers to improve maternal and newborn health outcomes in poor population s. FUNDING Health Foundation , UK Department for International Development , Wellcome Trust , and the Big Lottery Fund ( UK )",
"The Sonagachi Project was initiated in Kolkata , India in 1992 as a STD/HIV intervention for sex workers . The project evolved to adopt strategies common to women 's empowerment programs globally ( i.e. , community mobilization , rights-based framing , advocacy , micro-finance ) to address common factors that support effective , evidence -based HIV/STD prevention . The Sonagachi model is now a broadly diffused evidence -based empowerment program . We previously demonstrated significant condom use increases among female sex workers in a 16 month replication trial of the Sonagachi empowerment intervention ( n=110 ) compared to a control community ( n=106 ) receiving st and ard care of STD clinic , condom promotion , and peer education in two r and omly assigned rural towns in West Bengal , India ( Basu et al. , 2004 ) . This article examines the intervention 's impacts on 21 measured variables reflecting five common factors of effective HIV/STD prevention programs to estimate the impact of empowerment strategies on HIV/STD prevention program goals . The intervention which was conducted in 2000 - 2001 significantly : 1 ) improved knowledge of STDs and condom protection from STD and HIV , and maintained STD/HIV risk perceptions despite treatment ; 2 ) provided a frame to motivate change based on reframing sex work as valid work , increasing disclosure of profession , and instilling a hopeful future orientation reflected in desire for more education or training ; 3 ) improved skills in sexual and workplace negotiations reflected in increased refusal , condom decision-making , and ability to change work contract , but not ability to take leave ; 4 ) built social support by increasing social interactions outside work , social function participation , and helping other sex workers ; and 5 ) addressed environmental barriers of economic vulnerabilities by increasing savings and alternative income , but not working in other locations , nor reduced loan taking , and did not increase voting to build social capital . This study 's results demonstrate that , compared to narrowcast clinical and prevention services alone , empowerment strategies can significantly impact a broader range of factors to reduce vulnerability to HIV/STDs",
"R and omized controlled trials ( RCTs ) are essential for evaluating the efficacy of clinical interventions , where the causal chain between the agent and the outcome is relatively short and simple and where results may be safely extrapolated to other setting s. However , causal chains in public health interventions are complex , making RCT results subject to effect modification in different population s. Both the internal and external validity of RCT findings can be greatly enhanced by observational studies using adequacy or plausibility design s. For evaluating large-scale interventions , studies with plausibility design s are often the only feasible option and may provide valid evidence of impact . There is an urgent need to develop evaluation st and ards and protocol s for use in circumstances where RCTs are not appropriate",
"A community r and omized pre-test/post-test design was used to compare the knowledge and behaviors of microfinance clients receiving malaria education ( n=213 ) to those receiving diarrhea education ( n=223 ) and to non-client controls ( n=268 ) . Comparisons assessed differences at follow-up as well as within-group changes over time . At follow-up , malaria clients had significantly better malaria knowledge than comparison groups : 48.4 % of malaria clients were able to identify groups most vulnerable to malaria compared with 39.2 % of diarrhea clients ( P=0.044 ) and 37.7 % of non-clients ( P=0.024 ) . Malaria clients were more likely than diarrhea clients ( P=0.024 ) ( P knowledge of malaria complications during pregnancy ; to own at least one bed net ; and to report at least one child or woman of reproductive age sleeping under a bed net . Malaria clients also experienced the greatest increases in ITN ownership/use ( 9 % vs. 2.9 % and 6.7 % among diarrhea clients and non-clients ) . Results indicate that , although significant barriers to malaria control remain , a malaria education program provided by microfinance institutions can effectively contribute to community and national malaria initiatives",
"The impact of community-based family planning programs and access to credit on contraceptive use , fertility , and family size preferences has not been established conclusively in the literature . We provide additional evidence on the possible effect of such programs by describing the results of a r and omized field experiment whose main purpose was to increase the use of contraceptive methods in rural areas of Ethiopia . In the experiment , administrative areas were r and omly allocated to one of three intervention groups or to a fourth control group . In the first intervention group , both credit and family planning services were provided and the credit officers also provided information on family planning . Only credit or family planning services , but not both , were provided in the other two intervention groups , while areas in the control group received neither type of service . Using pre- and post-intervention surveys , we find that neither type of program , combined or in isolation , led to an increase in contraceptive use that is significantly greater than that observed in the control group . We conjecture that the lack of impact has much to do with the mismatch between women ’s preferred contraceptive method ( injectibles ) and the contraceptives provided by community-based agents ( pills and condoms )",
"OBJECTIVES We sought to obtain evidence about the scope of women 's empowerment and the mechanisms underlying the significant reduction in intimate partner violence documented by the Intervention With Microfinance for AIDS and Gender Equity ( IMAGE ) cluster-r and omized trial in rural South Africa . METHODS The IMAGE intervention combined a microfinance program with participatory training on underst and ing HIV infection , gender norms , domestic violence , and sexuality . Outcome measures included past year 's experience of intimate partner violence and 9 indicators of women 's empowerment . Qualitative data about changes occurring within intimate relationships , loan groups , and the community were also collected . RESULTS After 2 years , the risk of past-year physical or sexual violence by an intimate partner was reduced by more than half ( adjusted risk ratio=0.45 ; 95 % confidence interval=0.23 , 0.91 ) . Improvements in all 9 indicators of empowerment were observed . Reductions in violence result ed from a range of responses enabling women to challenge the acceptability of violence , expect and receive better treatment from partners , leave abusive relationships , and raise public awareness about intimate partner violence . CONCLUSIONS Our findings , both qualitative and quantitative , indicate that economic and social empowerment of women can contribute to reductions in intimate partner violence",
"While much descriptive research has documented positive associations between social capital and a range of economic , social and health outcomes , there have been few intervention studies to assess whether social capital can be intentionally generated . We conducted an intervention in rural South Africa that combined group-based microfinance with participatory gender and HIV training in an attempt to catalyze changes in solidarity , reciprocity and social group membership as a means to reduce women 's vulnerability to intimate partner violence and HIV . A cluster r and omized trial was used to assess intervention effects among eight study villages . In this paper , we examined effects on structural and cognitive social capital among 845 participants and age and wealth matched women from households in comparison villages . This was supported by a diverse portfolio of qualitative research . After two years , adjusted effect estimates indicated higher levels of structural and cognitive social capital in the intervention group than the comparison group , although confidence intervals were wide . Qualitative research illustrated the ways in which economic and social gains enhanced participation in social groups , and the positive and negative dynamics that emerged within the program . There were numerous instances where individuals and village loan centres worked to address community concerns , both working through existing social networks , and through the establishment of new partnerships with local leadership structures , police , the health sector and NGOs . This is among the first experimental trials suggesting that social capital can be exogenously strengthened . The implication s for community interventions in public health are further explored",
"PURPOSE By adversely affecting family functioning and stability , poverty constitutes an important risk factor for children 's poor mental health functioning . This study examines the impact of a comprehensive microfinance intervention , design ed to reduce the risk of poverty , on depression among AIDS-orphaned youth . METHODS Children from 15 comparable primary schools in Rakai District of Ug and a , one of those hardest hit by HIV/AIDS in the country , were r and omly assigned to control ( n = 148 ) or treatment ( n = 138 ) conditions . Children in the treatment condition received a comprehensive microfinance intervention comprising matched savings accounts , financial management workshops , and mentorship . This was in addition to traditional services provided for all school-going orphaned adolescents ( counseling and school supplies ) . Data were collected at wave 1 ( baseline ) , wave 2 ( 10 months after intervention ) , and wave 3 ( 20 months after intervention ) . We used multilevel growth models to examine the trajectory of depression in treatment and control conditions , measured using Children 's Depression Inventory ( Kovacs ) . RESULTS Children in the treatment group exhibited a significant decrease in depression , whereas their control group counterparts showed no change in depression . CONCLUSIONS The findings indicate that over and above traditional psychosocial approaches used to address mental health functioning among orphaned children in sub-Saharan Africa , incorporating poverty alleviation-focused approaches , such as this comprehensive microfinance intervention , has the potential to improve psychosocial functioning of these children",
"Abstract Microfinance can be used to reach women and adolescent girls with HIV prevention education . We report findings from a cluster-r and omized control trial among 55 villages in West Bengal to determine the impact of non-formal education on knowledge , attitudes and behaviors for HIV prevention and savings . Multilevel regression models were used to evaluate differences between groups for key outcomes while adjusting for cluster correlation and differences in baseline characteristics . Women and girls who received HIV education showed significant gains in HIV knowledge , awareness that condoms can prevent HIV , self-efficacy for HIV prevention , and confirmed use of clean needles , as compared to the control group . Condom use was rare and did not improve for women . While HIV testing was uncommon , knowledge of HIV-testing re sources significantly increased among girls , and trended in the positive direction among women in intervention groups . Conversely , the savings education showed no impact on financial knowledge or behavior change",
"OBJECTIVES We tested whether a structural intervention combining savings-led microfinance and HIV prevention components would achieve enhanced reductions in sexual risk among women engaging in street-based sex work in Ulaanbaatar , Mongolia , compared with an HIV prevention intervention alone . METHODS Between November 2011 and August 2012 , we r and omized 107 eligible women who completed baseline assessment s to either a 4-session HIV sexual risk reduction intervention ( HIVSRR ) alone ( n=50 ) or a 34-session HIVSRR plus a savings-led microfinance intervention ( n=57 ) . At 3- and 6-month follow-up assessment s , participants reported unprotected acts of vaginal intercourse with paying partners and number of paying partners with whom they engaged in sexual intercourse in the previous 90 days . Using Poisson and zero-inflated Poisson model regressions , we examined the effects of assignment to treatment versus control condition on outcomes . RESULTS At 6-month follow-up , the HIVSRR plus microfinance participants reported significantly fewer paying sexual partners and were more likely to report zero unprotected vaginal sex acts with paying sexual partners . CONCLUSIONS Findings advance the HIV prevention repertoire for women , demonstrating that risk reduction may be achieved through a structural intervention that relies on asset building , including savings , and alternatives to income from sex work"
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BACKGROUND In the orthopaedic literature , there is a wide range of clinical outcome measurement tools that have been used in evaluating foot and ankle procedures , disorders , and outcomes , with no broadly accepted consensus as to which tools are preferred . The purpose of this study was to determine the frequency and distribution of the various outcome instruments used in the foot and ankle literature , and to identify trends for use of these instruments over time . METHODS We conducted a systematic review of all original clinical articles reporting on foot and /or ankle topics in six orthopaedic journals over a ten-year period ( 2002 to 2011 ) . All clinical patient-reported outcome rating instruments used in these articles were recorded , as were study date , study design , clinical topic , and level of evidence . RESULTS A total of 878 clinical foot and ankle articles that used at least one patient-reported outcome measure were identified among 16,513 total articles published during the ten-year period . There were 139 unique clinical outcome scales used , and the five most popular scales ( as a percentage of foot/ankle outcome articles ) were the American Orthopaedic Foot & Ankle Society ( AOFAS ) scales ( 55.9 % ) , visual analog scale ( VAS ) for pain ( 22.9 % ) , Short Form-36 ( SF-36 ) Health Survey ( 13.7 % ) , Foot Function Index ( FFI ) ( 5.5 % ) , and American Academy of Orthopaedic Surgeons ( AAOS ) outcomes instruments ( 3.3 % ) . The majority of articles described Level-IV studies ( 70.1 % ) ; only 9.4 % reported Level-I studies . CONCLUSIONS A considerable variety of outcome measurement tools are used in the foot and ankle clinical literature , with a small proportion used consistently . The AOFAS scales continue to be used at a high rate relative to other scales that have been vali date d. Data from the present study underscore the need for a paradigm shift toward the use of consistent , valid , and reliable outcome measures for studies of foot and ankle procedures and disorders . It is not clear which existing vali date d outcome instruments will emerge as widely used and clinical ly meaningful . CLINICAL RELEVANCE These data support the need for a paradigm shift toward the consistent use of valid and reliable outcome measures for foot and ankle clinical research
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"In recent years quality of life instruments have been featured as primary outcomes in many r and omized trials . One of the challenges facing the investigator using such measures is determining the significance of any differences observed , and communicating that significance to clinicians who will be applying the trial results . We have developed an approach to elucidating the significance of changes in score in quality of life instruments by comparing them to global ratings of change . Using this approach we have established a plausible range within which the minimal clinical ly important difference ( MCID ) falls . In three studies in which instruments measuring dyspnea , fatigue , and emotional function in patients with chronic heart and lung disease were applied the MCID was represented by mean change in score of approximately 0.5 per item , when responses were presented on a seven point Likert scale . Furthermore , we have established ranges for changes in question naire scores that correspond to moderate and large changes in the domains of interest . This information will be useful in interpreting question naire scores , both in individuals and in groups of patients participating in controlled trials , and in the planning of new trials",
"Background : The increasing use of computerized adaptive tests ( CATs ) to generate outcome measures during rehabilitation has prompted questions concerning score interpretation . Objective : The purpose of this study was to describe meaningful interpretations of functional status ( FS ) outcome measures estimated with a body part – specific CAT developed from the Lower-Extremity Functional Scale ( LEFS ) . Design : This investigation was a prospect i ve cohort study of 8,714 people who had hip impairments and were receiving physical therapy in 257 outpatient clinics in 31 states ( United States ) between January 2005 and June 2007 . Methods : Four approaches were used to clinical ly interpret outcome data . First , the st and ard error of the estimate was used to construct the 90 % confidence interval for each CAT-generated score estimate . Second , percentile ranks were applied to FS scores . Third , 2 threshold approaches were used to define individual subject – level change : statistically reliable change and clinical ly important change . The fourth approach was a functional staging method . Results : The precision of a single score was estimated from the FS score ±4 . On the basis of the score distribution , 25th , 50th , and 75th percentile ranks corresponded to intake FS scores of 40 , 48 , and 59 and discharge FS scores of 50 , 61 , and 75 , respectively . The reliable change index supported the conclusion that changes in FS scores of 7 or more units represented statistically reliable change , and receiver operating characteristic analyses supported the conclusion that changes in FS scores of 6 or more units represented minimal clinical ly important improvement . Participants were classified into 5 hierarchical levels of FS using a functional staging method . Limitations : Because this study was a secondary analysis of prospect ively collected data via a proprietary data base management company , generalizability of results may be limited to participating clinics . Conclusions : The results demonstrated how outcome measures generated from the hip LEFS CAT can be interpreted to improve clinical meaning . This finding might facilitate the use of patient-reported outcomes by clinicians during rehabilitation services",
"OBJECTIVES To assess responsiveness and minimally important change ( MIC ) for the Manchester-Oxford foot question naire ( MOXFQ ) using anchor and distribution-based approaches . Responsiveness and estimates of minimal clinical ly important difference ( MCID ) and minimal detectable change are compared with those from the Short-Form 36 ( SF-36 ) and American Orthopaedic Foot & Ankle Society ( AOFAS ) measures . METHODS A prospect i ve observational study of 91 consecutive patients ( 125 foot operations ) undergoing hallux valgus surgery at an orthopaedic hospital . Pre- and 12 month post-surgery , patients completed the MOXFQ and SF-36 , and foot surgeons assessed all four AOFAS scores corresponding to four regions of the foot . Transition items were asked about perceived changes compared with before surgery . RESULTS Mean changes in all domains of each instrument were statistically significant , but foot-specific MOXFQ and AOFAS domains produced much larger effect sizes ( > 1 ) than any SF-36 domains , indicating superior responsiveness . Clear associations occurred between transition items and all MOXFQ and AOFAS scores , but with only one ( physical function ) SF-36 domain . Anchor and distribution-based approaches identified generally comparable measures of MIC , which for the MOXFQ and AOFAS domains were between 1 and 2 st and ard error of measurement . In metric terms , the MCIDs were 16 , 12 , and 24 for the MOXFQ Walking/st and ing , Pain , and Social Interaction domains , respectively . CONCLUSIONS For hallux valgus surgery , the MOXFQ is highly responsive . Performance is comparable to the AOFAS and notably better than the generic SF-36 . Study estimates of MIC for the MOXFQ are useful to inform sample -size calculations for future clinical trials",
"The patient-reported outcomes measurement information system ( PROMIS ) physical function item bank v1 ( PPFIB ) contains 124 item response theory ( IRT ) calibrated items ( Rose et al. 2008 . J Clin Epidemiol 61:17–33).We report the psychometric properties of these items within an outpatient , orthopaedic patient population . In particular , we investigated whether a single unidimensional IRT scale can adequately define physical function of patients presenting with primarily upper or lower extremity orthopaedic complaints . We conducted a prospect i ve study at an orthopaedic outpatient clinic to collect data from 865 adult patients with all 124 PROMIS physical function items and seven demographic items . Items were evaluated by a Rasch model . Total variance ( 60.6 % ) across the 124 items was explained by a single Rasch dimension . The variance explained by the second dimension was 7.7 % , reflecting differential item functioning in the upper and lower extremity patients . The upper extremity physical function items had a pronounced ceiling effect . A single physical function dimension accounts for most of the item variance in the PPFIB , suggesting that the items are measuring predominantly one single construct . Separate subscales for lower versus upper extremities , especially with additional items at the upper trait level of the upper extremity subscale , may further enhance evaluation of physical function in orthopaedic patients",
"Objective . Use of item response theory ( IRT ) and , subsequently , computerized adaptive testing ( CAT ) , under the umbrella of the NIH-PROMIS initiative ( National Institutes of Health – Patient-Reported Outcomes Measurement Information System ) , to bring strong new assets to the development of more sensitive , more widely applicable , and more efficiently administered patient-reported outcome ( PRO ) instruments . We present data on current progress in 3 crucial areas : floor and ceiling effects , responsiveness to change , and interactive computer-based administration over the Internet . Methods . We examined nearly 1000 patients with rheumatoid arthritis and related diseases in a series of studies including a one-year longitudinal examination of detection of change ; compared responsiveness of the Legacy SF-36 and HAQ-DI instruments with IRT-based instruments ; performed a r and omized head-to-head trial of 4 modes of item administration ; and simulated the effect of lack of floor and ceiling items upon statistical power and sample sizes . Results . IRT-based PROMIS instruments are more sensitive to change , result ing in the potential to reduce sample size requirements substantially by up to a factor of 4 . The modes of administration tested did not differ from each other in any instance by more than one-tenth of a st and ard deviation . Floor and ceiling effects greatly reduce the number of available subjects , particularly at the ceiling . Conclusion . Failure to adequately address floor and ceiling effects , which determine the range of an instrument , can result in suboptimal assessment of many patients . Improved items , improved instruments , and computer-based administration improve PRO assessment and represent a fundamental advance in clinical outcomes research",
"Background : We examined four commonly used scores , the SF-36 , the Ankle Osteoarthritis Scale ( AOS ) , the American Orthopaedic Foot and Ankle Society ( AOFAS ) Ankle Hindfoot Score , and the Foot Function Index ( FFI ) to determine their responsiveness and validity . Methods : Patients with end stage ankle arthritis were recruited into a prospect i ve multicenter cohort study and baseline and one year outcome scores were compared . The St and ardized Response Mean and Effect Size for the AOS , AOFAS , and FFI were calculated and the three region- or disease-specific scores were compared with the SF-36 to determine their criterion validity . Results : All four scores showed acceptable responsiveness , and when using the vali date d SF-36 as the st and ard the three region or disease specific scores all showed similar criterion validity . Conclusion : All four scores are responsive and can be considered for use in this population . The objective component of the AOFAS Ankle Hindfoot Score may make it harder to perform than the other three scores which have subjective components only , and as yet its objective component has not been shown to demonstrate reliability . We recommend use of a purely subjective score such as the Ankle Osteoarthritis Scale or Foot Function Index as the region- or disease-specific score of choice in this population . As the SF-36 shows acceptable responsiveness , using it alone could also be considered . Level of Evidence : II , Prospect i ve Comparative",
"OBJECTIVES To define the minimum clinical ly important difference ( MCID ) for the visual analog scale ( VAS ) of pain severity by measuring the change in VAS associated with adequate pain control . METHODS The authors conducted a prospect i ve , observational study . Adult emergency department ( ED ) patients with acute pain ( Patients rated their pain severity on a 100-mm VAS on presentation and at discharge . Patients were asked if they would accept any analgesic , then if they would accept a parenteral analgesic before treatment . At discharge , they were asked whether they had received adequate pain control . RESULTS The authors enrolled 143 patients ( mean age , 36 years ; 54 % female ) . The mean decrease in VAS was -30.0 mm ( 95 % confidence interval [ CI ] = -36.4 to -23.6 ) for the 116 of 143 ( 81 % ) patients with adequate pain control at discharge vs. -5.7 ( 95 % CI = -11.2 to -0.3 ) for the 27 with inadequate pain control ( p mean VAS was 31.3 mm for those with adequate pain control vs. 55.1 for those without . Mean VAS for the 114 of 143 patients who would accept any analgesics initially was 64.7 vs. 47.1 for the 29 reporting no analgesic need . Initially , 77 patients would accept parenteral analgesics ( mean VAS = 72.5 mm ) . CONCLUSIONS A mean reduction in VAS of 30.0 mm represents a clinical ly important difference in pain severity that corresponds to patients ' perception of adequate pain control . Defining MCID based on adequate analgesic control rather than minimal detectable change may be more appropriate for future analgesic trials , when effective treatments for acute pain exist",
"A Foot Function Index ( FFI ) was developed to measure the impact of foot pathology on function in terms of pain , disability and activity restriction . The FFI is a self-administered index consisting of 23 items divided into 3 sub-scales . Both total and sub-scale scores are produced . The FFI was examined for test-retest reliability , internal consistency , and construct and criterion validity . A total of 87 patients with rheumatoid arthritis were used in the study . Test-retest reliability of the FFI total and sub-scale scores ranged from 0.87 to 0.69 . Internal consistency ranged from 0.96 to 0.73 . With the exception of two items , factor analysis supported the construct validity of the total index and the sub-scales . Strong correlation between the FFI total and sub-scale scores and clinical measures of foot pathology supported the criterion validity of the index . The FFI should prove useful for both clinical and research purpose",
"Orthopaedic surgeons have always based their clinical care on evidence . Surgeons use evidence to make decisions tailored to an individual patient 's needs and circumstances . The primary sources of evidence for clinicians are studies published in the medical and surgical literature , such as The Journal of Bone and Joint Surgery . In June 2000 , The Journal introduced the quarterly Evidence -Based Orthopaedics section 1 . This section introduces orthopaedic surgeons to recent r and omized trials relevant to the practice of orthopaedic surgery published in forty-two journals other than The Journal of Bone and Joint Surgery . Structured abstract s of these studies are",
"STUDY DESIGN Prospect i ve cohort study of 10 287 patients with foot/ankle impairments receiving outpatient physical therapy . OBJECTIVES To describe meaningful interpretations of functional status ( FS ) outcomes measures , estimated using a body-part-specific computerized adaptive test ( CAT ) . BACKGROUND Increased use of CATs to generate outcome measures in rehabilitation has stimulated questions concerning score interpretation . Identifying meaningful intra-individual change and reporting clinical interpretation of those generated outcomes are essential to advance the quality of rehabilitation practice . METHODS We performed 4 approaches to clinical ly interpret outcomes data . First , we used the st and ard error of the estimate to construct a 90 % confidence interval for each CAT estimated score . Second , we presented the percentile rank of FS scores . Third , we used 2 threshold approaches to define individual-patient-level change : statistically reliable change and clinical ly important change . Last , we illustrated a functional staging method . RESULTS Precision of a single score was estimated by an FS score of + /-4 . Based on score distribution , percentile ranks at 25th , 50th , and 75th percentiles corresponded to intake FS scores of 38 , 47 , and 57 , and discharge FS scores of 52 , 64 , and 77 , respectively . Minimal detectable change supported 7 or more FS change units out of 100 represented statistically reliable change , and ROC analyses supported 8 or more FS change units represented minimal clinical ly important improvement . Using a functional staging system , we established 5 hierarchical functional status levels . CONCLUSION CAT-generated outcome measures can be interpreted to improve clinical interpretation and to assist clinicians in using patient-reported outcomes during therapy practice"
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BACKGROUND Impetigo is a common clinical problem seen in general practice . Uncertainty exists as to the most effective treatment , or indeed if treatment is necessary . AIM To determine the most effective treatment for impetigo in a systemically well patient . DESIGN OF STUDY Systematic review and meta- analysis . METHOD Data bases were search ed for relevant studies . The Cochrane highly sensitive r and omised controlled trial ( RCT ) search string was employed and combined with the word ' impetigo ' as the MeSH term and keyword . The bibliographies of relevant articles were search ed for additional references . RCTs that were either double- or observer-blind , and involved systemically well patients of any age in either primary or secondary care setting s , were included . Studies that selected patients on the basis of skin swab results were excluded , as were studies that were not in English . Cure or improvement of impetigo reported at seven to 14 days from start of treatment was the primary outcome measure . Meta- analysis was performed on homogeneous studies . RESULTS Three hundred and fifty-nine studies were identified , of which 16 met the inclusion criteria . Meta- analysis demonstrated that topical antibiotics are more effective than placebo ( odds ratio [ OR ] = 2.69 , 95 % confidence interval [ CI ] = 1.49 to 4.86 ) . There is weak evidence for the superiority of topical antibiotics over some oral antibiotics , such as erythromycin ( OR = 0.48 , 95 % CI = 0.23 to 1.00 ) . There is no significant difference between the effects of mupirocin and fusidic acid ( OR = 1.76 , 95 % CI = 0.77 to 4.03 ) . CONCLUSION This review found limited high- quality evidence to inform the treatment of impetigo . From that which is available , we would recommend the use of a topical antibiotic for a period of seven days in a systemically well patient with limited disease . Further research is needed on the role of flucloxacillin and non-antibiotic treatments for impetigo
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"The efficacy and side effects of topical mupirocin ( Bactroban ) and fusidic acid ( Fucidin ) ointment were compared in a double-blind , r and omized trial in 70 patients who came to the Dermatologic Clinic of L'Enfant Jésus Hospital with primary or secondary ( or both ) skin infections . Thirty-five patients were treated with mupirocin and 35 patients were treated with fusidic acid three times a day for seven days . Clinical and bacteriologic assessment s were conducted before and after treatment . The efficacy of mupirocin , in terms of resolution and improvement of clinical signs and symptoms of infection , as well as of the elimination of infecting organisms , was similar to that of fusidic acid . Of 34 patients ( 1 could not be evaluated ) treated with mupirocin , a clinical cure was achieved in 18 , and significant improvement was demonstrated in 15 . Similarly , of 35 patients treated with fusidic acid , a clinical cure was achieved in 18 and improvement occurred in 15 . Bacteriologic cure rates were 97 % ( 30 of 31 patients evaluated ) in the mupirocin-treated group , compared with 87 % ( 27 of 31 patients evaluated ) in the fusidic acid-treated group . No side effects were observed in either treatment group . Because topical 2 % mupirocin has little or no potential for irritation , systemic side effects , or cross-resistance with other antibiotics , its efficacy is likely to make this new compound a useful agent for the treatment of superficial skin infections",
"Staphylococcus aureus has been consistently isolated from a high proportion of impetiginous lesions , and in several recent studies , it was present in the majority of the cases . Since recently a large proportion of S. aureus strains in our community showed erythromycin resistance , we undertook a prospect i ve double-blind controlled study comparing topical mupirocin with oral erythromycin to determine ( i ) the prevalence of erythromycin-resistant S. aureus strains in impetigo and ( ii ) whether an increased rate of failure of erythromycin treatment was associated with such resistance . A total of 102 patients 3 to 185 months old ( median = 49 months ) were enrolled . Culture was positive for 97 of 102 ( 95 % ) patients , and S. aureus was present in 93 % of the patients for whom cultures were positive . S. aureus was the single pathogen in 64 % of these patients . Erythromycin-resistant S. aureus strains were present in 27 of 91 ( 28 % ) patients for whom cultures were positive . In all cases but one , S. aureus was resistant to penicillin , and in all cases it was sensitive to mupirocin . A marked difference was observed in favor of mupirocin in the clinical courses of the disease . However , only patients with erythromycin-resistant S. aureus strains had unfavorable courses compared with those treated with mupirocin ( failure rate , 47 versus 2 % , respectively ) . Patients with erythromycin-susceptible S. aureus strains who received erythromycin had a failure rate of 8 % . In four patients , S. aureus strains initially susceptible to erythromycin became resistant during treatment . We conclude that erythromycin-resistant S. aureus strains are commonly isolated from impetigo in our region . ( ABSTRACT TRUNCATED AT 250 WORDS",
"Abstract Objective : The aim of this investigation was to eluci date whether the analgesic effect was due to the local aspirin or to the systemic drug . This was done by comparing skin and plasma levels of acetylsalicylic acid ( ASA ) and salicylic acid ( SA ) after topically administered ASA/diethyl ether ( ADE ) mixture in acute herpetic neuralgia ( AHN ) and postherpetic neuralgia ( PHN ) . The analgesia and the plasma and skin levels of ASA were also determined after oral administration of aspirin . Methods : Nineteen patients , 11 ( 57.9 % ) with AHN and ␣ 8 ( 42.1 % ) with PHN were given , on different days , a single 500-mg oral dose of ASA or a topical dose ( 750 mg ) of ( ADE ) daubed onto the painful skin . The analgesic effect was assessed by means of a visual analogue scale ( VAS ) . Overall pain relief was grade d as : excellent , good , fair , or poor . AHN as well as PHN patients had severe pain at baseline ( 6.83 and 5.93 ) . Levels of ASA and SA in plasma and in the stratum corneum after adhesive tape stripping of the treated area were determined by HPLC . Results : After ADE application , the analgesic effect was very rapid and VAS scores were lower than at baseline . Pain significantly decreased by 82.6 % after topical and 15.4 % after oral ASA . After ADE , 95 % of the patients had excellent or good pain relief , but after oral administration 79 % of the patients had a poor response . Pain relief was similar in the two subgroups after ADE . Skin concentrations of ASA , but not of SA , after ADE were about 80- to 100-fold those after oral administration . Levels of ASA and SA in plasma after oral administration were similar to those previously found , but after ADE were undetectable or very low . Patients with excellent pain relief showed a trend towards higher ASA skin concentrations . Conclusions : The analgesic effect can be obtained only after topical administration , because by this route the skin levels of ASA are much higher than after oral administration . The mechanism is exclusively local ; there are no active drugs in plasma after topical administration",
"Sodium fusi date ointment and mupirocin ointment were compared in 354 patients with superficial skin sepsis . The ointments were applied 3-times daily , or once daily when covered by a dressing , and the response assessed after 6 to 8 days . Both preparations proved effective clinical ly with 86 % of patients responding . There was no difference between the two preparations in cases of primary infection ( 85 % to both ointments ) , including a sub-group with impetigo ( sodium fusi date 88 % and mupirocin 84 % ) , or secondary infection ( sodium fusi date 81 % and mupirocin 89 % ) . Sodium fusi date ointment ( 98 % ) was significantly better ( p less than 0.05 ) than mupirocin ( 82 % ) in patients with other superficial infections . Both ointments were equally effective in cases where Gram-positive , Gram-negative or mixed Gram-positive/Gram-negative bacteria were isolated . Adverse effects were reported in 1.0 % of patients using sodium fusi date ointment and in 7.4 % of patients using mupirocin ointment . The majority of complaints concerned the greasiness of mupirocin ointment",
" A total of 413 eligible patients took part in an observer-blind r and omised multicentre clinical trial in order to compare the clinical and bacteriological efficacy of mupirocin ( Bactroban ) ointment with sodium fusi date ( Fucidin ) ointment for treating superficial skin infections seen in general practice . Mupirocin was applied twice daily and sodium fusi date thrice daily for a period of 7 days . Both treatments were similarly effective with 97 % patients treated with mupirocin and 93 % patients treated with sodium fusi date responding . Mupirocin was significantly more effective in the treatment of acute primary skin infections and in the treatment of a subgroup of patients with impetigo ( P less than 0.01 ) . Of the organisms detected before treatment began , 93 % were not found after treatment with mupirocin compared with 89 % after treatment with sodium fusi date . Staphylococcus aureus and /or beta-haemolytic streptococci appeared to be eliminated in significantly more patients treated with mupirocin ( 96 % ) compared with those treated with sodium fusi date ( 88 % ) , ( P = 0.03 ) . Both treatments were well tolerated",
"A total number of 104 patients with impetigo contagiosa was included in this study . They were 47 females ( 45.2 % ) and 57 males ( 54.8 % ) . Their ages ranged from one month to 40 years with a median of 4 years . This study was divided into two parts : PART I ( in vitro ) : Thirty-five patients were swabbed to determine the microbiology of impetigo contagiosa which included 33 isolates of pure S. aureus ( 94.3 % ) and 2 of a combination of S. aureus and Streptococcus pyogenes ( 5.7 % ) . The antibacterial effect of tea liquor ( lotion ) against S. aureus proved very effective . Antibiotic sensitivity was done for all bacterial isolates of S. aureus . PART II ( in vivo ) : The antibacterial effects of tea liquor and ointment were tested by treating 64 patients with impetigo contagiosa . Tea ointment was very effective with a cure rate of 81.3 % . Forty patients were taken as controls and divided into two groups . The first one was given an ointment containing Framycetin and gramicidin ( soframycin ) with a cure rate of 72.2 % ; the other group was given oral cephalexin with a cure rate of 78.6 % . To the best of our knowledge , this study was the first one which demonstrated the anti-bacterial action of crude tea in vivo , against impetigo contagiosa . Clinical data about impetigo are also included in this study",
"Because the effectiveness of topical antimicrobials in the treatment of ecthyma , impetigo , and pyoderma is not well established , the US Food and Drug Administration has recently proposed guidelines for tests of topical antimicrobial efficacy in primary skin infections . The guidelines require both comparison with the agent 's base and microbiologic documentation of efficacy . These guidelines were followed in this double-blind , eight-day evaluation of impetigo/ecthyma treated with mupirocin , a new agent that is only active topically . All cultures , before and after therapy , were taken using swabs dipped in neutralizing broth plus 10 % fetal bovine serum to minimize antimicrobial \" carry over \" to the culture plate . Staphylococcus aureus , which was isolated from 94 % of the patients before therapy , was eliminated in 88 % of the mupirocin-treated patients and 47 % of the vehicle-treated patients . Group A beta-hemolytic streptococci were eliminated in 100 % of the mupirocin-treated and 0 % of the vehicle-treated patients . To our knowledge , this is the first topical antibacterial treatment for primary skin infections proved superior to its vehicle using the proposed US Food and Drug Administration guidelines",
"The value of topical antibiotics in the treatment of pyodermas was reassessed . In a double‐blind study , the efficacy of 0.1 % gentamicin cream was tested . There was no significant statistical difference in the degree of improvement between the group of patients that received the gentamicin cream and those treated with a placebo . The response obtained was thought to be due to washing and removal of crusts . Hence , it is considered advisable to abstain from the use of topical antibiotics in pyodermas",
"In a r and omized , double-blind , parallel comparative study of 80 patients , impetigo and ecthyma were treated effectively by sulconazole nitrate 1 % cream and miconazole nitrate 2 % cream applied to lesions twice daily for 14 days . When treatment began , bacterial cultures from all pyodermal lesions yielded Group A beta-hemolytic streptococci or pathogenic staphylococci . Among the 32 sulconazole-treated impetigo patients , bacterial cultures from 26 ( 69 % ) were negative by treatment day 4 , and those from all 32 ( 100 % ) were negative by treatment day 7 ; among the 34 miconazole-treated impetigo patients , cultures from 17 ( 50 % ) were negative by treatment day 4 , cultures from 32 ( 94.1 % ) were negative by treatment day 7 , and cultures from 29 ( 97 % ) were negative by treatment day 14 . Each treatment promptly relieved the pyodermal signs ( crusts , vesicles , pustules , bullae , and exu date ) . Both agents were considered to be safe and effective medications for treating impetigo and ecthyma",
"We attempted to determine the causative bacterial pathogens of impetigo in children in our area , to compare the effectiveness of three frequently used oral antimicrobial treatment regimens , and to correlate the antimicrobial sensitivity of the bacterial isolates with clinical responses to treatment . Seventy-three children with impetigo were r and omly assigned to receive penicillin V potassium or cephalexin monohydrate , both administered in dosages of 40 to 50 mg/kg per day , or erythromycin estolate administered in a dosage of 30 to 40 mg/kg per day . All drugs were given in three divided doses for 10 days . Treatment failure was defined as persistence of lesions 8 to 10 days after initiation of drug therapy as determined by examiners blinded to the treatment therapies . Forty-five ( 62 % ) cultures showed Staphylococcus aureus only , 14 ( 19 % ) showed S aureus and group A beta-hemolytic streptococci , six ( 8 % ) showed group A beta-hemolytic streptococci only , and eight ( 11 % ) showed no growth or other organisms . Treatment failure occurred in six ( 24 % ) of 25 patients treated with penicillin V , one ( 4 % ) of 25 patients treated with erythromycin estolate , and no patients treated with cephalexin . We conclude that S aureus is the most common cause of impetigo in children in our study population , that cephalexin is the most effective treatment , that erythromycin estolate is nearly equally effective and may be preferred on a cost-effectiveness basis , and that penicillin V is inadequate for treatment of this infection",
"For the past two decades the accepted treatment of impetigo has been systemic antibiotic therapy , l The recently approved topical antibiotic mupirocin has excellent in vitro activity against Streptococcus pyogenes and Staphylococcus aureus , including multiply resistant strains . Originally called pseudomonic acid A , mupirocin is obtained from submerged fermentation of Pseudomonas fluorescens ; it acts by inhibition of bacterial protein synthesis by inactivation of isoleucyl transfer RNA synthetase . Rapidly inactivated and rapidly excreted when given systemically , mupirocin has been shown to be safe in animal and human trials.2 , 3 Double-blind studies prove mupirocin to be more effective than its polyethylene glycol vehicle for treatment of impetigo.4 , 5 Several nonblind or poorly controlled clinical trials have suggested that mupirocin 's efficacy is comparable to that of orally administered antibiotics commonly used to treat impetigo , namely , erythromycin , 6 - 1~ ampicillin , 11 and dicloxacillin . 12 We intended to vali date these findings in a double-blind , placebo-controlled study . We further hypothesized that erythromycin would cause more adverse side effects and result in poorer compliance , making mupirocin the preferred medication"
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41187fc0-06ff-11f0-808a-c43d1ab1c353
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OBJECTIVE To systematic ally review the existing literature on neurodevelopmental outcomes in children born after medically assisted reproduction compared with those of children born after spontaneous conception . DESIGN Systematic review . SETTING Not applicable . PATIENT(S ) Children born after medically assisted reproduction vs. reference groups of spontaneously conceived children . INTERVENTION(S ) Data were review ed from worldwide published articles , without restrictions as to publication year or language . A total of 80 studies included between 31 and 2,446,044 children . MAIN OUTCOME MEASURE(S ) Child neurodevelopmental outcomes categorized as cognitive , behavioral , emotional or psychomotor development , or diagnoses of mental disorders . RESULT ( S ) For infants , studies on psychomotor development showed no deficits , but few investigated cognitive or behavioral development . Studies on toddlers generally reported normal cognitive , behavioral , socio-emotional , and psychomotor development . For children in middle childhood , development seems comparable in children born after assisted reproduction and controls , although fewer studies have been conducted with follow-up to this age . Very few studies have assessed neurodevelopmental outcomes among teens , and the results are inconclusive . Studies investigating the risk of diagnoses of mental disorders are generally large , with long follow-up , but the results are inconsistent . CONCLUSION ( S ) It may tentatively be concluded that the neurodevelopment of children born after fertility treatment is overall comparable to that in children born after spontaneous conception
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"OBJECTIVE To evaluate specific effects of ovarian hyperstimulation , the in vitro procedure , and a history of subfertility on neuromotor development at 3 months of age . DESIGN Prospect i ve , cohort study . SETTING University Medical Center Groningen , The Netherl and s. PATIENT(S ) Singletons conceived after controlled ovarian hyperstimulation-IVF/intracytoplasmic sperm injection ( COH-IVF ; n = 68 ) or modified natural cycle-IVF/intracytoplasmic sperm injection ( MNC-IVF ; n = 57 ) , and naturally conceived singletons of subfertile couples ( NC ; n = 90 ) . Data from a reference population were available ( n = 450 ) . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) Quality of general movements ( GMs ) , classified as normal-optimal , normal-suboptimal , mildly abnormal , or definitely abnormal . Definitely abnormal GMs indicate brain dysfunction , mildly abnormal GMs normal but non-optimal brain function . RESULT ( S ) Mildly abnormal and definitely abnormal GMs were observed equally frequently in COH-IVF , MNC-IVF , and NC singletons . The three subfertile groups showed a reduction in GM quality , in particular more mildly abnormal GMs , in comparison with the reference population . CONCLUSION ( S ) Singletons born after IVF ( with or without ovarian hyperstimulation ) are not at increased risk for abnormal GMs compared with naturally conceived peers of subfertile parents . Mildly abnormal GMs occur more often in infants of subfertile parents than in the general population , suggesting that factors associated with subfertility rather than those related to IVF procedures may be associated with less-optimal early neurodevelopmental outcome . These results need confirmation through replication and follow-up at older ages",
"The use of a gonodotropin-releasing hormone ( Gn-RH ) agonist in an in vitro fertilization ( IVF ) program raises the question of any influence on the physical , neurologic , and mental development of the children . We compared the development of children born after long-acting Gn-RH agonist treatment with that of children born after spontaneous pregnancies . Children from singleton pregnancies and > or = 28 months of age were examined by a pediatric neurologist and a psychologist who did not know to which group the children belonged . The General Cognitive Index test was used . Each group included 30 children . Five children cooperated only partly . Physical and neurologic findings were normal in all children , except that one in the group born after in vitro fertilization had diffuse hypotonia , attention-deficit hyperactivity disorder , and hyperactivity . The General Cognitive Index for the 26 children in the study group and the 29 children in the control group who fully cooperated were 102 + /- 13.3 and 106 + /- 13.5 , respectively ( p = 0.37 ) . The verbal perception , motor , and memory indexes were not significantly different . We conclude that the long-acting Gn-RH agonist had no clinical ly identifiable influence on the development of these children",
"BACKGROUND As a continuation of two large-scale , multicentre studies on the development of 5-year-old ICSI children , we present results of the follow-up study undertaken on the cognitive and motor development of 8-year-old ICSI children . METHODS Developmental outcomes of 151 8-year-old singletons born through ICSI after 32 weeks of gestation were compared with those of 153 singletons of the same age born after spontaneous conception ( SC ) . Part of this population was seen in a cohort at the age 5 years . Outcome measures include Wechsler Intelligence Scale for Children-Revised ( WISC-R ) and Movement Assessment Battery for Children ( ABC ) . RESULTS Regarding intellectual functioning , ICSI children tend to obtain significantly higher total ( P than SC children , nevertheless remaining in similar ranges . These effects are small ( Cohen 's d maternal educational level stayed in the regression as a factor accounting for some of the variance in total IQ between the groups . In terms of motor development , no significant differences were found between ICSI and SC children regarding overall motor skills , manual , balance and ball skills . CONCLUSION In this follow-up study , ICSI and SC children show a comparable cognitive and motor development until the age of 8 years",
"OBJECTIVE To study the health of children born after ICSI and of spontaneously conceived control children at the age of 4 - 6 years . DESIGN Prospect i ve , controlled , blinded study . SETTING Tertiary-care center . PATIENT(S ) Two hundred seventy-six term-born singletons conceived by ICSI and 273 matched spontaneously conceived singletons at the age of 5.5 years . INTERVENTION(S ) Detailed physical examination , interview of the parents , and collection of data from each child 's examination booklet . MAIN OUTCOME MEASURE(S ) Biometrical data ; current health status ; acute , chronic and childhood illnesses ; hospitalizations ; and surgeries . RESULT ( S ) Detailed physical examination did not reveal any relevant differences between ICSI and spontaneously conceived children . There were no relevant differences regarding the incidence of childhood illnesses , acute or chronic illnesses , accidents , and surgeries up to the age of 5.5 years . However , a history of undescended testicles was found significantly more often in boys born after ICSI ( 5.4 % vs. 0.7 % ) , with the consequence that they had significantly more urogenital surgery ( 19.2 % vs. 8.9 % ) . Significantly more ICSI children had been hospitalized ( 37.6 % vs. 27.2 % ) , although we did not find any specific reason for the increased hospitalization rate . CONCLUSION ( S ) Other than an increased risk of undescended testicles and therefore an increase in urogenital surgeries in ICSI boys , the physical health of ICSI children was comparable to that of spontaneously conceived children at the age of 5.5 years",
"A cohort of 91 children from cryopreserved embryos and 83 control children who were conceived normally had their development assessed using the Griffiths 's scales of mental development . The controls ( 81 singletons and two twins ) of a similar age , sex , and social class were selected from siblings , cousins , and peers of the cryopreserved embryo group ( 68 singleton , 20 twins , and three triplets ) . Children from cryopreserved embryos had a lower mean birth weight and mean gestational age and a higher proportion were born by caesarean section . One child from the cryopreserved embryo group had Down 's syndrome , three had squints , and four had conductive hearing loss while in the control children , six had squints , and nine had conductive hearing loss . In both groups , including the child with Down 's syndrome , the mean Griffiths 's quotient was greater than the st and ard 100 . In the children from cryopreserved embryos , the singleton and multiple birth subgroups had statistically similar assessment results . The mean ( SD ) Griffiths 's quotient was 105.69 ( 13.55 ) in children from cryopreserved embryos and 108.18 ( 9.80 ) in controls at a chronological age of 25.08 ( 12.86 ) and 29.19 ( 14.65 ) months respectively . Overall , the development in children from cryopreserved embryos did not cause concern though formal testing had highlighted small differences compared with other children conceived normally and of a similar social class",
"Objective To investigate how pregnancy planning , time to conception , and infertility treatment influence cognitive development at ages 3 and 5 . Design Prospect i ve population based cohort study . Setting Millennium Cohort Study in the United Kingdom . Participants 18 818 children recruited at 9 months and followed up at 3 and 5 years . 11 790 singletons with available data on pregnancy , cognitive outcomes , and confounders were included in analyses at age 3 and 12 136 at age 5 . Exposure measures Mothers reported whether the pregnancy was planned , and their feelings when first pregnant ; those in whom the pregnancy was planned provided time to conception , and details of any assisted reproductive technologies . The population was divided into “ unplanned ” ( unplanned and unhappy ) , “ mistimed ” ( unplanned but happy ) , “ planned ” ( planned , time to conception “ subfertile ” ( planned , time to conception ≥12 months ) , “ induced ovulation ” ( received clomiphene citrate ) , and “ assisted reproduction ” ( in vitro fertilisation or intracytoplasmic sperm injection ) . The “ planned ” group was the comparison group in all analyses . Outcome measures Three components of the British Ability Scales ( BAS II ) . Naming vocabulary assessed verbal ability at age 3 ; this test was repeated at age 5 with the picture similarities and pattern construction subscales , which measure non-verbal and spatial abilities . Results In unadjusted analyses , the scores on all scales in children from unplanned pregnancies were significantly lower than in those from planned pregnancies — for example , the difference in mean verbal ability score at age 3 was −4.8 ( 95 % confidence interval −6.0 to −3.7 ; P in verbal ability tests ( 3.8 ( −0.2 to 7.9 ) at age 3 and 3.5 ( 0.2 to 6.8 ) at age 5 ) , which suggests that on average these children are three to four months ahead ; this difference did not completely disappear with adjustment for confounders . Children born after infertility treatment had lower mean scores in non-verbal tests ( −1.2 ( −4.1 to 1.6 ) after assisted reproduction and −1.5 ( −3.5 to 0.4 ) after induced ovulation ) and in spatial ability tests ( −2.7 ( −6.9 to 1.6 ) after assisted reproduction ) , though the differences were not significant . Conclusions Pregnancy planning , subfertility , or assisted reproduction do not adversely affect children ’s cognitive development at age 3 or 5 . The differences observed in the unadjusted analyses are almost entirely explained by marked inequalities in socioeconomic circumstances between the groups",
"Abstract Objective To compare neurological sequelae in twins born after assisted conception with singletons after assisted conception and naturally conceived twins and to assess neurological sequelae in children conceived after in vitro fertilisation ( IVF ) compared with intracytoplasmic sperm injection ( ICSI ) . Design Controlled , national register based , cohort study . Participants Twins ( n = 3393 ) and singletons ( n = 5130 ) conceived by using assisted reproductive technologies and naturally conceived twins ( n = 10 239 ) born in Denmark between 1995 and 2000 . The children 's age at time of follow up was 2 - 7 years . Data sources Children were identified by cross linkage of the national medical birth registry and the national registry for in vitro fertilisation . Neurological and psychiatric diagnoses were retrieved from the national patients ' registry and the Danish psychiatric central registry . Main outcome measures Neurological sequelae , defined as cerebral palsy , mental retardation , severe mental developmental disturbances , and retarded psychomotor development . Further we made separate analyses on the specific cerebral palsy diagnosis . Results The crude prevalence rates per 1000 of neurological sequelae in twins and singletons after assisted conception and in naturally conceived twins were 8.8 , 8.2 , and 9.6 , and of cerebral palsy 3.2 , 2.5 , and 4.0 , respectively . In twins after assisted conception compared with control twins , the odds ratios of neurological sequelae and specifically of cerebral palsy , adjusted for child sex and year of birth , were 0.9 ( 95 % confidence interval 0.6 to 1.4 ) and 0.8 ( 0.4 to 1.6 ) , respectively . The corresponding odds ratios for twins after assisted conception compared with singletons after assisted conception were 1.1 ( 0.7 to 1.7 ) for neurological sequelae and 1.3 ( 0.6 to 2.9 ) for cerebral palsy . The odds ratio of neurological sequelae in children conceived by ICSI was 0.9 ( 0.5 to 1.7 ) ν children conceived by IVF . Conclusions Twins from assisted conception have a similar risk of neurological sequelae as their naturally conceived peers and singletons from assisted conception . Children born after ICSI have the same risk of neurological sequelae as children born after IVF",
"BACKGROUND To examine the long-term child outcome after IVF until the age of 3 years in Northern Finl and , we conducted a population -based cohort study . METHODS First , a cohort of 299 IVF children born in 1990 - 1995 was compared with a cohort of 558 controls representing the general population in terms of a multiple birth rate of 1.2 % , r and omly chosen from the Finnish Medical Birth Register ( FMBR ) and matched for sex , year of birth , area of residence , parity , maternal age and social class ( full sample analyses ) . Second , IVF singletons ( n = 150 ) were compared with singleton controls ( n = 280 ) . Third , a plurality matched control cohort ( n = 100 ) for IVF twins ( n = 100 ) was r and omly chosen , matched as above , from the FMBR and analysed separately . Infant mortality rate was compared with the national rate from the FMBR . RESULTS Infant mortality in the IVF group was > 2-fold higher compared to the national rate in the general population . The risk ( OR , 95 % CI ) of low weight and height , below the lowest quartile , at 1 year of age ( 1.6 , 1.1 - 2.2 ; 1.6 , 1.1 - 2.4 ) and 2 years of age ( 1.5 , 1.1 - 2.4 ; 1.7 , 1.2 - 2.5 ) was significantly higher in the IVF group when compared with the general population control group . No statistically significant differences were found in the psychomotor development between the cohorts . Cumulative incidence of different diseases up to 3 years of age was significantly higher among IVF children in the full sample and singleton analyses ( OR , 95 % CI : 2.3 , 1.7 - 3.2 ; 2.1 , 1.3 - 3.3 respectively ) especially regarding respiratory diseases ( 3.5 , 1.9 - 6.5 ; 3.1 , 1.0 - 9.4 ) and diarrhoea ( 3.7 , 2.2 - 6.2 ; 5.7 , 2.6 - 12.7 ) , but not in twin comparisons . CONCLUSIONS The growth of IVF children was behind that of control children during the first 3 years of life , but their psychomotor development was similar . Their postnatal health was worse , probably reflecting the problems in the neonatal period",
"OBJECTIVE To study the health of children born after ovulation induction ( OI ) . DESIGN Nationwide register-based study . SETTING The OI children were followed up to the age of 4 years and compared with other children . PATIENT(S ) The OI children ( N = 4,467 ) . Two control groups : all other children ( excluding children born after IVF , N = 190,398 ) and a r and om sample of those children ( n = 26,877 ) . INTERVENTION(S ) Ovulation induction treatment in ordinary practice . MAIN OUTCOME MEASURE(S ) Mortality rates and adjusted odds ratios for perinatal outcomes , hospitalizations , health-related benefits , and long-term medication use . RESULT ( S ) A total of 12 % of OI and 2 % of control children were multiples . Even after stratifying for multiplicity and adjusting for the available confounding factors ( region , smoking , maternal age , socioeconomic position , and parity for perinatal health and mother 's socioeconomic position for other indicators ) , most indicators showed worse health among OI children compared with control children . The OI children had poorer perinatal health and more episodes of long hospitalization than the control children . Singleton OI children had more long-term illnesses in childhood , as measured by child disability allowance , long-term medication use , and hospital care episodes . CONCLUSION ( S ) Either OI treatment or the reasons for the treatment increase the risk of health problems in early childhood",
"BACKGROUND An increasing number of women are utilizing fertility treatments , but little is known about their relation to autism spectrum disorders ( ASD ) . METHODS To determine the association between maternal fertility therapy use and risk of having a child with ASD , we conducted a nested case-control study within the Nurses ' Health Study II ( n = 116,430 ) . Maternally reported diagnoses of ASD were confirmed through a supplementary question naire and , in a subgroup , the Autism Diagnostic Interview-Revised . Controls were r and omly selected by frequency matching to case children 's year of birth . Associations were examined by self-reported infertility and type of therapy using conditional logistic regression . RESULTS In all , 9 % of the 507 cases and 7 % of 2,529 controls indicated fertility therapy use for the index pregnancy . No significant associations with self-reported fertility therapies or history of infertility were seen in primary analyses . In subgroup analyses of women with maternal age ≥ 35 years ( n = 1,020 ) , artificial insemination was significantly associated with ASD ; ovulation inducing drug ( OID ) use was significantly associated in crude but not adjusted analyses ( odds ratio 1.81 , 95 % CI 0.96 - 3.42 ) . Results were similar by diagnostic subgroup , though within the advanced maternal age group , OID and artificial insemination were significantly associated with Asperger syndrome and pervasive developmental disorder not-otherwise specified , but not autistic disorder . CONCLUSION [ corrected ] Assisted reproductive therapy and history of infertility did not increase risk of having a child with ASD in this study . However , the associations observed with OID and artificial insemination among older mothers , for whom these exposures are more common , warrant further investigation",
"OBJECTIVE . The purpose of this study was to use nationwide registries to examine the health of children up to 4 years of age who were born as a result of in vitro fertilization . METHODS . Children born after in vitro fertilization ( N = 4559 ) from 1996 to 1999 were monitored until 2003 . Two control groups were selected from the Finnish Medical Birth Register as follows : all other children ( excluding children born after ovulation induction ) from the same period ( N = 190398 , for study of perinatal health and hospitalizations ) and a r and om sample of those children ( n = 26877 , for study of health-related benefits ) . Mortality rates and odds ratios for perinatal outcomes , hospitalizations , health-related benefits , and long-term medication use were calculated . RESULTS . Although the health of most in vitro fertilization children was good , such children had more health problems than other children . A total of 35.7 % of in vitro fertilization children and 2.2 % of control children were multiple births , and the health of multiple births was worse than that of singletons . Perinatal outcomes of in vitro fertilization children were worse and hospital episodes were more common than among control children . Risks for cerebral palsy and psychological and developmental disorders were increased . Among in vitro fertilization singletons , worse results for perinatal outcomes and hospitalizations , but no increased risk for specific diseases , were found . The health of in vitro fertilization multiple births was comparable to the health of control multiple births . CONCLUSIONS . Reducing the number of transferred embryos would improve the health of in vitro fertilization children . Additional studies are needed to explain the poorer health of in vitro fertilization singletons , as well as follow-up studies to examine the health of in vitro fertilization children from 4 years onward",
"We have studied from birth up to the 3rd year the psychological attitude of 33 in-vitro fertilization ( IVF ) children compared to two other groups : children born after ovarian stimulation without IVF ( n = 33 ) and children conceived naturally ( n = 33 ) during the same period . Fourteen children , born by oocyte donation , were also studied by the same methodology . In the IVF group , we found some feeding difficulties and sleep disorders in the infants at 9 months and some signs of depression in mothers . All these symptoms disappeared afterwards . The development of all the children is satisfactory and the relationship with their mother is excellent . In this preliminary study , we conclude that the method of assisted reproduction has no bad influence on the psychomotor development of these children",
"OBJECTIVE To examine infant outcome of singletons born after cryopreservation of embryos ( Cryo ) . DESIGN National population -based controlled follow-up study . SETTING Denmark , 1995 - 2007 . PATIENT(S ) The study population was 957 Cryo singletons ( Cryo-IVF , n=660 ; Cryo-ICSI , n=244 ; Cryo-IVF/-ICSI , n=53 ) . The first control group was all singletons born after fresh IVF or intracytoplasmic sperm injection ( ICSI ) during the same period ( IVF , n=6904 ; ICSI , n=3425 ) . The second control group comprised a r and om sample of non-assisted reproductive technology ( ART ) singletons ( n=4800 ) . INTERVENTION(S ) All observations were obtained from national registers . MAIN OUTCOME MEASURE(S ) Low birth weight ( LBW ; RESULT ( S ) Birth weight was higher in Cryo ( mean=3578 g , SD=625 ) versus fresh ( mean=3373 g , SD=648 ) and in Cryo versus non-ART ( mean=3537 g , SD=572 ) , and this was also the case for first birth only . Lower adjusted risk of LBW ( odds ratio [OR]=0.63 ; 95 % confidence interval [ CI ] , 0.45 - 0.87 ) and PTB ( OR=0.70 ; 95 % CI , 0.53 - 0.92 ) was observed in Cryo versus fresh . Similar LBW and PTB rates were observed when comparing Cryo with non-ART , but the perinatal mortality rate was doubled in Cryo ( 1.6 % ) compared with non-ART ( 0.8 % ) singletons , and the adjusted risks of very preterm birth ( neonatal admittance were also significantly increased . No significant differences in the prevalence rates of birth defects , neurological sequelae , malignancies , and imprinting-related diseases were observed between the Cryo and the two control groups . However higher malformation and cerebral palsy rates were observed in the total Fresh vs. non-ART group . CONCLUSION ( S ) Cryo singletons have better neonatal outcome than offspring after fresh ET but poorer compared with non-ART singletons",
"To assess the physical and mental development of infants born after in vitro fertilization ( IVF ) , we performed a general physical and developmental examination ( Bayley and Stanford-Binet scales ) on a cohort of 116 IVF children , conceived and born at our institution between February 1985 and March 1989 , and on 116 non-IVF matched controls . Study and control groups were each composed of 66 singletons , 19 pairs of twins and 4 sets of triplets , whose age at examination ranged from 12 to 45 months . The developmental indices of IVF infants were within the normal range and did not differ from those of their matched controls . The indices were positively correlated to gestational age , birth weight , head circumference at birth and at examination , and mother 's education . Mean birth weight , gestational age , and birth weight percentile of IVF infants were lower than the mean of the healthy population . Mean percentiles of weight and length at examination ( mean age 22.4 months ) were equally low but did not differ from those of the matched controls . However , mean percentiles of head circumference at birth and at examination compare well with the normal mean , both in IVF and control groups . Twins and triplets ( IVF and controls ) had significantly lower physical and mental indices as compared to singletons",
"Infertility and its treatment are increasingly viewed as public issues as well as a private concern . Treatments such as IVF draw on public re sources and pose psychological and ethical dilemmas for the community . The current paper integrates findings from a prospect i ve longitudinal study that assessed the quality of parenting in families conceiving through IVF from an attachment theory perspective . Seventy families who conceived singleton infants through IVF and a naturally conceiving control group of 63 couples were seen during pregnancy and at 4 and 12 months postpartum . Two observational procedures were used to assess maternal sensitivity to the baby , infant responsiveness and security of attachment at 4 and 12 months respectively . There were no IVF control group differences in maternal sensitivity at 4 months or in security of attachment at 12 months . Implication s of the findings for clinicians and contemporary controversies requiring further research are discussed",
"OBJECTIVE To evaluate whether children 's cognitive and psychomotor development and behavior at 2 years are affected by ovarian hyperstimulation and the IVF laboratory procedures or subfertility . DESIGN Prospect i ve longitudinal cohort study . SETTING University Medical Center Groningen , the Netherl and s. PATIENT(S ) Singletons born after controlled ovarian hyperstimulation (COH)-IVF ( n=66 ) and modified natural cycle-IVF ( n=56 ) , singletons born to subfertile couples who conceived naturally ( subfertile-naturally conceived , n=87 ) , and a reference group of 101 2-year-old singletons born to fertile couples . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) Bayley Scales of Infant Development and Achenbach Child Behavior Checklist . RESULT ( S ) Mental and psychomotor development and behavioral outcome in COH-IVF , modified natural cycle-IVF , and subfertile-natural cycle groups was not different . Developmental outcome and behavior of the subfertile groups were largely similar to those of the fertile reference group . Nevertheless , the subfertile groups scored higher on the scale of anxious-depressed behavior than the reference group . CONCLUSION ( S ) This present relatively small study found no differences in cognitive and psychomotor development and behavior at 2 years in children born after COH-IVF or modified natural cycle-IVF or naturally conceived children of subfertile parents . Replication of the study is needed before firm conclusions can be drawn . Furthermore , long-term follow-up is needed to confirm these findings in older children",
"OBJECTIVE To assess the somatic , psychomotor , and intellectual development of children conceived through intracytoplasmic single sperm injection ( ICSI ) over the whole preschool period . DESIGN Prospect i ve , controlled , cohort study . SETTING Fertility clinic in Brussels , Belgium . PATIENT(S ) Sixty-six ICSI-conceived children prospect ively compared with 52 IVF-conceived and 59 spontaneously conceived children . All children were full-term singletons . INTERVENTION(S ) Home visits by a trained psychologist . St and ardized interviews . Assessment s using the revised Brunet-Lézine scale and the revised Wechsler preschool and primary scale of intelligence . MAIN OUTCOME MEASURE(S ) Physical growth and general health . Formal developmental and intellectual assessment s. RESULT ( S ) Children conceived by ICSI were healthy : no significant differences appeared in the incidence of combined congenital malformations ( 11.3 % ) , health problems ( 44.1 % ) , surgical interventions ( 18.6 % ) , and hospitalizations ( 6.8 % ) , nor for the developmental assessment s ( mean developmental quotient at 9 months : 93.9 ; at 18 months : 102.0 ) . For the intellectual assessment s , the between-group differences disappeared when adjusted for levels of parental education ( mean intelligence quotient at 3 years : 97.0 ; at 5 years : 103.3 ) . CONCLUSION ( S ) This pilot study shows that throughout the preschool period , ICSI-conceived children have psychomotor and intellectual development similar to that of IVF-conceived and spontaneously conceived children . These conclusions need to be confirmed by multicenter studies",
"BACKGROUND Intracytoplasmic sperm injection ( ICSI ) was introduced as a new form of in-vitro fertilisation ( IVF ) in 1993 and is now accepted as the treatment of choice for severe male infertility in many centres around the world . However , there is little information about the long-term outcome of children conceived by ICSI . We aim ed to find out the medical and developmental outcome of children conceived by ICSI at age 1 year . METHODS In this prospect i ve study , we compared the medical and developmental outcome at 1 year of 89 children conceived by ICSI with 84 children conceived by routine IVF , and with 80 children conceived naturally . Formal developmental assessment was done with Bayley Scales of Infant Development ( 2nd edition ) from which a mental development index ( MDI ) was derived . FINDINGS There was no significant difference in the incidence of major congenital malformations or major health problems in the first year of life . However , the mean Bayley MDI was significantly lower for the children conceived by ICSI than for the children conceived by routine IVF or naturally ( 95.9 [ SD 10.7 ] , 101.8 [ 8.5 ] , and 102.5 [ 7.6 ] , respectively , p ICSI experienced mildly or significantly delayed development ( MDI ICSI are healthy and develop normally , there is an increased risk of mild delays in development at 1 year when compared with children conceived by routine IVF or conceived naturally . These findings support the need for ongoing developmental follow-up of children conceived by ICSI to see whether they are at increased risk of intellectual impairment or learning difficulties at school age",
"BACKGROUND Due to the growing number of children born following assisted reproduction technology , even subtle changes in the children 's health and development are of importance to society at large . The aim of the present study was to evaluate the specific effects of ovarian hyperstimulation and the in vitro procedure on neurological outcome in 4 - 18-month-old children . METHODS In this prospect i ve assessor-blinded cohort study , we included singletons born following controlled ovarian hyperstimulation in vitro fertilization ( IVF ) or intracytoplasmic sperm injection ( ICSI ) ( COH-IVF ; n = 68 ) or modified natural cycle-IVF/ICSI ( MNC-IVF ; n = 57 ) or naturally conceived singletons of subfertile couples ( NC ; n = 90 ) . Children were assessed with st and ardized , age-specific and sensitive neurological assessment s ( TINE and Hempel assessment ) at 4 , 10 and 18 months . Neurological examination result ed in a neurological optimality score ( NOS ) , a fluency score and a clinical neurological classification . Fluency of movements is easily affected by neurological dysfunction and is therefore a sensitive measure for minimal changes in neuromotor development . RESULTS The NOS and the fluency score were similar in COH-IVF , MNC-IVF and NC children . None of the children showed major neurological dysfunction and rates of minor neurological dysfunction at the three ages were not different between the three conception groups . CONCLUSIONS We found no effects of ovarian hyperstimulation or the in vitro procedure itself on neurological outcome in children aged 4 - 18 months . The findings of our study are reassuring , nevertheless it should be kept in mind that subtle neurodevelopmental disorders may emerge when children grow older . Continuation of follow-up in older and larger groups of children is therefore still needed"
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41187ff2-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND Guidelines for lifestyle and dietary modification in patients with coronary artery disease ( CAD ) are mainly supported by evidence from general population studies . CAD patients , however , differ from the general population in age ( older ) and treatment with preventive drugs . This review seeks to provide evidence for a prognostic benefit of lifestyle and dietary recommendations from studies in CAD patients . METHODS AND RESULTS A literature search was performed on the effect of lifestyle and dietary changes on mortality in CAD patients . Prospect i ve cohort studies and r and omized controlled trials of patients with established CAD were included if they reported all-causes mortality and had at least 6 months of follow-up . The effect estimates of smoking cessation ( relative risk [ RR ] , 0.64 ; 95 % CI , 0.58 to 0.71 ) , increased physical activity ( RR , 0.76 ; 95 % CI , 0.59 to 0.98 ) , and moderate alcohol use ( RR , 0.80 ; 95 % CI , 0.78 to 0.83 ) were studied most extensively . For the 6 dietary goals , data were too limited to provide reliable effect size estimates . Combinations of dietary changes were associated with reduced mortality ( RR , 0.56 ; 95 % CI , 0.42 to 0.74 ) . CONCLUSIONS Available studies show convincingly the health benefits of lifestyle changes in CAD patients . Effect estimates of combined dietary changes look promising . Future studies should confirm these findings and assess the contribution of the individual dietary factors
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"Of 22 r and omized trials of rehabilitation with exercise after myocardial infa rct ion ( MI ) , one trial had results that achieved conventional statistical significance . To determine whether or not these studies , in the aggregate , show a significant benefit of rehabilitation after myocardial infa rct ion , we performed an overview of all r and omized trials , involving 4,554 patients ; we evaluated total and cardiovascular mortality , sudden death , and fatal and nonfatal reinfa rct ion . For each endpoint , we calculated an odds ratio ( OR ) and 95 % confidence interval ( 95 % CI ) for the trials combined . After an average of 3 years of follow-up , the ORs were significantly lower in the rehabilitation than in the comparison group : specifically , total mortality ( OR = 0.80 [ 0.66 , 0.96 ] ) , cardiovascular mortality ( OR = 0.78 [ 0.63 , 0.96 ] ) , and fatal reinfa rct ion ( OR = 0.75 [ 0.59 , 0.95 ] ) . The OR for sudden death was significantly lower in the rehabilitation than in the comparison group at 1 year ( OR = 0.63 [ 0.41 , 0.97 ] ) . The data were compatible with a benefit at 2 ( OR = 0.76 [ 0.54 , 1.06 ] ) and 3 years ( OR = 0.92 [ 0.69 , 1.23 ] ) , but these findings were not statistically significant . For nonfatal reinfa rct ion , there were no significant differences between the two groups after 1 ( OR = 1.09 [ 0.76 , 1.57 ] ) , 2 ( OR = 1.10 [ 0.82 , 1.47 ] ) , or 3 years ( OR = 1.09 [ 0.88 , 1.34 ] ) of follow-up . The observed 20 % reduction in overall mortality reflects a decreased risk of cardiovascular mortality and fatal reinfa rct ion throughout at least 3 years and a reduction in sudden death during the 1st year after infa rct ion and possibly for 2 - 3 years . With respect to the independent effects of the physical exercise component of cardiac rehabilitation , the relatively small number of \" exercise only \" trials , combined with the possibility that they may have had a formal or informal nonexercise component precludes the possibility of reaching any definitive conclusion . To do so would require a r and omized trial of sufficient size to distinguish between no effect and the most plausible effect based on the results of this overview",
"Background —Our purpose was to assess the time course of the benefit of n-3 polyunsaturated fatty acids ( PUFAs ) on mortality documented by the GISSI-Prevenzione trial in patients surviving a recent ( Methods and Results —In this study , 11 323 patients were r and omly assigned to supplements of n-3 PUFAs , vitamin E ( 300 mg/d ) , both , or no treatment ( control ) on top of optimal pharmacological treatment and lifestyle advice . Intention-to-treat analysis adjusted for interaction between treatments was carried out . Early efficacy of n-3 PUFA treatment for total , cardiovascular , cardiac , coronary , and sudden death ; nonfatal myocardial infa rct ion ; total coronary heart disease ; and cerebrovascular events was assessed by right-censoring follow-up data 12 times from the first month after r and omization up to 12 months . Survival curves for n-3 PUFA treatment diverged early after r and omization , and total mortality was significantly lowered after 3 months of treatment ( relative risk [ RR ] 0.59 ; 95 % CI 0.36 to 0.97;P = 0.037 ) . The reduction in risk of sudden death was specifically relevant and statistically significant already at 4 months ( RR 0.47 ; 95 % CI 0.219 to 0.995;P = 0.048 ) . A similarly significant , although delayed , pattern after 6 to 8 months of treatment was observed for cardiovascular , cardiac , and coronary deaths . Conclusions —The early effect of low-dose ( 1 g/d ) n-3 PUFAs on total mortality and sudden death supports the hypothesis of an antiarrhythmic effect of this drug . Such a result is consistent with the wealth of evidence coming from laboratory experiments on isolated myocytes , animal models , and epidemiological and clinical studies",
"Abstract Objective To compare the hazards of cigarette smoking in men who formed their habits at different periods , and the extent of the reduction in risk when cigarette smoking is stopped at different ages . Design Prospect i ve study that has continued from 1951 to 2001 . Setting United Kingdom . Participants 34 439 male British doctors . Information about their smoking habits was obtained in 1951 , and periodically thereafter ; cause specific mortality was monitored for 50 years . Main outcome measures Overall mortality by smoking habit , considering separately men born in different periods . Results The excess mortality associated with smoking chiefly involved vascular , neoplastic , and respiratory diseases that can be caused by smoking . Men born in 1900 - 1930 who smoked only cigarettes and continued smoking died on average about 10 years younger than lifelong non-smokers . Cessation at age 60 , 50 , 40 , or 30 years gained , respectively , about 3 , 6 , 9 , or 10 years of life expectancy . The excess mortality associated with cigarette smoking was less for men born in the 19th century and was greatest for men born in the 1920s . The cigarette smoker versus non-smoker probabilities of dying in middle age ( 35 - 69 ) were 42 % ν24 % ( a twofold death rate ratio ) for those born in 1900 - 1909 , but were 43 % ν 15 % ( a threefold death rate ratio ) for those born in the 1920s . At older ages , the cigarette smoker versus non-smoker probabilities of surviving from age 70 to 90 were 10 % ν 12 % at the death rates of the 1950s ( that is , among men born around the 1870s ) but were 7 % ν 33 % ( again a threefold death rate ratio ) at the death rates of the 1990s ( that is , among men born around the 1910s ) . Conclusion A substantial progressive decrease in the mortality rates among non-smokers over the past half century ( due to prevention and improved treatment of disease ) has been wholly outweighed , among cigarette smokers , by a progressive increase in the smoker ν non-smoker death rate ratio due to earlier and more intensive use of cigarettes . Among the men born around 1920 , prolonged cigarette smoking from early adult life tripled age specific mortality rates , but cessation at age 50 halved the hazard , and cessation at age 30 avoided almost all of it",
"OBJECTIVES We sought to investigate the impact of body mass index ( BMI ) on short- and long-term outcomes after initial revascularization with percutaneous transluminal coronary angioplasty ( PTCA ) or coronary artery bypass graft surgery ( CABG ) . BACKGROUND Equivocal results exist on the impact of BMI on the risk of in-hospital complications after PTCA or CABG , and no long-term mortality data exist from a large series of revascularized patients . METHODS From the r and omized series and observational registry of the Bypass Angioplasty Revascularization Investigation ( BARI ) , 2,108 patients who had PTCA and 1,526 patients who had CABG were evaluated by taking their BMI at study entry . They were classified as follows : low ( In-hospital complications and short- and long-term mortalities were compared between levels of BMI within each mode of initial revascularization . RESULTS Among patients who had PTCA , each unit increase in BMI was associated with a 5.5 % lower adjusted risk of a major in-hospital event ( death , myocardial infa rct ion , stroke , coma ) ; among patients who had CABG , no difference in the in-hospital outcome was observed according to BMI . In contrast , BMI was not associated with five-year mortality in the PTCA group ; among the CABG group , adjusted relative risks of five-year cardiac mortality according to levels of BMI were 0.0 ( low ) , 1.0 ( normal ) , 2.02 ( overweight ) , 3.16 ( class I obese ) and 4.85 ( class II/III obese ) ( linear p short- and long-term outcomes after coronary revascularization . These results underscore the need for further research to identify factors responsible for the apparent short-term protective effect of a higher BMI in patients undergoing PTCA and to study the impact of weight reduction on the long-term survival of obese patients undergoing CABG",
"BACKGROUND Adherence to a Mediterranean diet may improve longevity , but relevant data are limited . METHODS We conducted a population -based , prospect i ve investigation involving 22,043 adults in Greece who completed an extensive , vali date d , food-frequency question naire at base line . Adherence to the traditional Mediterranean diet was assessed by a 10-point Mediterranean-diet scale that incorporated the salient characteristics of this diet ( range of scores , 0 to 9 , with higher scores indicating greater adherence ) . We used proportional-hazards regression to assess the relation between adherence to the Mediterranean diet and total mortality , as well as mortality due to coronary heart disease and mortality due to cancer , with adjustment for age , sex , body-mass index , physical-activity level , and other potential confounders . RESULTS During a median of 44 months of follow-up , there were 275 deaths . A higher degree of adherence to the Mediterranean diet was associated with a reduction in total mortality ( adjusted hazard ratio for death associated with a two-point increment in the Mediterranean-diet score , 0.75 [ 95 percent confidence interval , 0.64 to 0.87 ] ) . An inverse association with greater adherence to this diet was evident for both death due to coronary heart disease ( adjusted hazard ratio , 0.67 [ 95 percent confidence interval , 0.47 to 0.94 ] ) and death due to cancer ( adjusted hazard ratio , 0.76 [ 95 percent confidence interval , 0.59 to 0.98 ] ) . Associations between individual food groups contributing to the Mediterranean-diet score and total mortality were generally not significant . CONCLUSIONS Greater adherence to the traditional Mediterranean diet is associated with a significant reduction in total mortality",
"BACKGROUND The Lyon Diet Heart Study is a r and omized secondary prevention trial aim ed at testing whether a Mediterranean-type diet may reduce the rate of recurrence after a first myocardial infa rct ion . An intermediate analysis showed a striking protective effect after 27 months of follow-up . This report presents results of an extended follow-up ( with a mean of 46 months per patient ) and deals with the relationships of dietary patterns and traditional risk factors with recurrence . METHODS AND RESULTS Three composite outcomes ( COs ) combining either cardiac death and nonfatal myocardial infa rct ion ( CO 1 ) , or the preceding plus major secondary end points ( unstable angina , stroke , heart failure , pulmonary or peripheral embolism ) ( CO 2 ) , or the preceding plus minor events requiring hospital admission ( CO 3 ) were studied . In the Mediterranean diet group , CO 1 was reduced ( 14 events versus 44 in the prudent Western-type diet group , P=0.0001 ) , as were CO 2 ( 27 events versus 90 , P=0.0001 ) and CO 3 ( 95 events versus 180 , P=0 . 0002 ) . Adjusted risk ratios ranged from 0.28 to 0.53 . Among the traditional risk factors , total cholesterol ( 1 mmol/L being associated with an increased risk of 18 % to 28 % ) , systolic blood pressure ( 1 mm Hg being associated with an increased risk of 1 % to 2 % ) , leukocyte count ( adjusted risk ratios ranging from 1.64 to 2.86 with count > 9x10(9)/L ) , female sex ( adjusted risk ratios , 0.27 to 0 . 46 ) , and aspirin use ( adjusted risk ratios , 0.59 to 0.82 ) were each significantly and independently associated with recurrence . CONCLUSIONS The protective effect of the Mediterranean dietary pattern was maintained up to 4 years after the first infa rct ion , confirming previous intermediate analyses . Major traditional risk factors , such as high blood cholesterol and blood pressure , were shown to be independent and joint predictors of recurrence , indicating that the Mediterranean dietary pattern did not alter , at least qualitatively , the usual relationships between major risk factors and recurrence . Thus , a comprehensive strategy to decrease cardiovascular morbidity and mortality should include primarily a cardioprotective diet . It should be associated with other ( pharmacological ? ) means aim ed at reducing modifiable risk factors . Further trials combining the 2 approaches are warranted",
"BACKGROUND There is conflicting evidence on the benefits of foods rich in vitamin E ( alpha-tocopherol ) , n-3 polyunsaturated fatty acids ( PUFA ) , and their pharmacological substitutes . We investigated the effects of these substances as supplements in patients who had myocardial infa rct ion . METHODS From October , 1993 , to September , 1995 , 11,324 patients surviving recent ( were r and omly assigned supplements of n-3 PUFA ( 1 g daily , n=2836 ) , vitamin E ( 300 mg daily , n=2830 ) , both ( n=2830 ) , or none ( control , n=2828 ) for 3.5 years . The primary combined efficacy endpoint was death , non-fatal myocardial infa rct ion , and stroke . Intention-to-treat analyses were done according to a factorial design ( two-way ) and by treatment group ( four-way ) . FINDINGS Treatment with n-3 PUFA , but not vitamin E , significantly lowered the risk of the primary endpoint ( relative-risk decrease 10 % [ 95 % CI 1 - 18 ] by two-way analysis , 15 % [ 2 - 26 ] by four-way analysis ) . Benefit was attributable to a decrease in the risk of death ( 14 % [ 3 - 24 ] two-way , 20 % [ 6 - 33 ] four-way ) and cardiovascular death ( 17 % [ 3 - 29 ] two-way , 30 % [ 13 - 44 ] four-way ) . The effect of the combined treatment was similar to that for n-3 PUFA for the primary endpoint ( 14 % [ 1 - 26 ] ) and for fatal events ( 20 % [ 5 - 33 ] ) . INTERPRETATION Dietary supplementation with n-3 PUFA led to a clinical ly important and statistically significant benefit . Vitamin E had no benefit . Its effects on fatal cardiovascular events require further exploration",
"Diets rich in fruits and vegetables have been of interest because of their potential health benefits against chronic diseases such as cardiovascular disease ( CVD ) and cancer . The aim of this work was to assess the association of the dietary intake of a food group that includes fruits , berries and vegetables with all-cause , CVD-related and non-CVD-related mortality . The subjects were Finnish men aged 42 - 60 y examined in 1984 - 1989 in the prospect i ve Kuopio Ischaemic Heart Disease Risk Factor ( KIHD ) Study . Dietary intakes were assessed by 4-d food intake record during the baseline phase of the KIHD Study . The risk of all-cause and non-CVD-related deaths was studied in 2641 men and the risk of CVD-related death in 1950 men who had no history of CVD at baseline . During a mean follow-up time of 12.8 y , cardiovascular as well as noncardiovascular and all-cause mortality were lower among men with the highest consumption of fruits , berries and vegetables . After adjustment for the major CVD risk factors , the relative risk for men in the highest fifth of fruit , berry and vegetable intake for all-cause death , CVD-related and non-CVD-related death was 0.66 [ 95 % confidence interval ( CI ) 0.50 - 0.88 ] , 0.59 ( 0.33 - 1.06 ) , and 0.68 ( 0.46 - 1.00 ) , respectively , compared with men in the lowest fifth . These data show that a high fruit , berry and vegetable intake is associated with reduced risk of mortality in middle-aged Finnish men . Consequently , the findings of this work indicate that diets that are rich in plant-derived foods can promote longevity",
"BACKGROUND Prospect i ve studies suggested that substituting whole-grain products for refined-grain products lowers the risks of type 2 diabetes and cardiovascular disease ( CVD ) in women . Although breakfast cereals are a major source of whole and refined grains , little is known about their direct association with the risk of premature mortality . OBJECTIVE We prospect ively evaluated the association between whole- and refined-grain breakfast cereal intakes and total and CVD-specific mortality in a cohort of US men . DESIGN We examined 86,190 US male physicians aged 40 - 84 y in 1982 who were free of known CVD and cancer at baseline . RESULTS During 5.5 y , we documented 3114 deaths from all causes , including 1381 due to CVD ( 488 myocardial infa rct ions and 146 strokes ) . Whole-grain breakfast cereal intake was inversely associated with total and CVD-specific mortality , independent of age ; body mass index ; smoking ; alcohol intake ; physical activity ; history of diabetes , hypertension , or high cholesterol ; and use of multivitamins . Compared with men who rarely or never consumed whole-grain cereal , men in the highest category of whole-grain cereal intake ( > or = 1 serving/d ) had multivariate-estimated relative risks of total and CVD-specific mortality of 0.83 ( 95 % CI : 0.73 , 0.94 ; P for trend refined-grain breakfast cereal intakes were not significantly associated with total and CVD-specific mortality . These findings persisted in analyses stratified by history of type 2 diabetes , hypertension , and high cholesterol . CONCLUSIONS Both total mortality and CVD-specific mortality were inversely associated with whole-grain but not refined-grain breakfast cereal intake . These prospect i ve data highlight the importance of distinguishing whole-grain from refined-grain cereals in the prevention of chronic diseases",
"BACKGROUND To assess the overall influence of diet on health and disease in epidemiological studies , the habitual diet of the study participants has to be captured as a pattern rather than individual foods or nutrients . The simplest way to describe dietary preferences is to separate foods considered beneficial to health from foods considered to promote disease , and separate individuals on the basis of their regular consumption of these foods . METHODS We used data from 59 038 women participating in the prospect i ve Mammography Screening Cohort in Sweden to investigate the influence of variety of healthy and less healthy foods on all-cause and cause-specific mortality . RESULTS Women who followed a healthy diet defined as consumption of a high variety of fruits , vegetables , whole grain breads , cereals , fish , and low fat dairy products had a significantly lower mortality than women who consumed few of these foods ( 3710 deaths total ) . Women who reported regularly consuming 16 - 17 healthy foods had a 42 % lower all-cause mortality ( 95 % CI : 32 - 50 % ) compared to women reporting consumption of 0 - 8 healthy foods with any regularity ( P for trend risk of death was about 5 % lower ( 95 % CI : 4 - 6 % ) . Cardiovascular mortality was particularly low among women who reported consuming a high variety of healthy foods . A less healthy diet defined as consumption of a high variety of red meats , refined carbohydrates and sugars , and foods high in saturated or trans fats was not directly associated with a higher overall mortality . However , women who reported consuming many less healthy foods were significantly more likely to die from cancer than those who consumed few less healthy foods . CONCLUSIONS A healthy diet can affect longevity . It appears more important to increase the number of healthy foods regularly consumed than to reduce the number of less healthy foods regularly consumed",
"BACKGROUND This study examined whether a supervised exercise program improved 19-year survival in 30- to 64-year-old male myocardial infa rct ion patients . METHODS AND RESULTS The men ( n=651 ) were participants in the National Exercise and Heart Disease Project , a 3-year multicenter r and omized clinical trial conducted in the United States ( 1976 - 1979 ) . The treatment group ( n=315 ) exercised for 8 weeks in a laboratory . Thereafter , they jogged , cycled , or swam in a gymnasium/pool setting guided by an individualized target heart rate . Participants in the control group ( n=319 ) were to maintain normal routines but not participate in any regular exercise program . Participants were followed up until their death or December 31 , 1995 . Cox proportional hazards analysis revealed the all-cause mortality risk estimates ( 95 % CIs ) in the exercise group compared with controls to be 0.69 ( 0.39 to 1.25 ) after an average follow-up of 3 years , 0.84 ( 0.55 to 1.28 ) after 5 years , 0.95 ( 0.71 to 1.29 ) after 10 years , 1.02 ( 0.79 to 1.32 ) after 15 years , and 1.09 ( 0.87 to 1 . 36 ) after 19 years . Cardiovascular disease ( CVD ) mortality risk estimates ( 95 % CI ) for the same follow-up periods were 0.73 ( 0.37 to 1.43 ) , 0.98 ( 0.60 to 1.61 ) , 1.21 ( 0.79 to 1.60 ) , 1.14 ( 0.84 to 1.54 ) , and 1.16 ( 0.88 to 1.52 ) . However , each 1-MET increase in work capacity from baseline to the end of the original trial result ed in consistent reductions in all-cause and CVD mortality risk at each follow-up period , regardless of initial work-capacity level . CONCLUSIONS These findings indicate exercise-program participation result ed in nonsignificantly reduced mortality risks early in the follow-up period . Benefits diminished as time since participation increased , which suggests that the protective mechanisms associated with the program may be short term . Contamination between groups over time could also explain the diminished effects , because increased work capacity provided survival benefits up to 19 years",
"CONTEXT Most studies of diet and health care have focused on the role of single nutrients , foods , or food groups in disease prevention or promotion . Few studies have addressed the health effects of dietary patterns , which include complex mixtures of foods containing multiple nutrients and nonnutrients . OBJECTIVE To examine the association of mortality with a multifactorial diet quality index . DESIGN AND SETTING Data from phase 2 ( 1987 - 1989 ) of a prospect i ve cohort study of breast cancer screening , the Breast Cancer Detection Demonstration Project , with a median follow-up of 5.6 years . PARTICIPANTS A total of 42,254 women ( mean age , 61.1 years ) who completed the food frequency question naire portion of the survey . MAIN OUTCOME MEASURE All-cause mortality by quartile of Recommended Food Score ( RFS ; the sum of the number of foods recommended by current dietary guidelines [ fruits , vegetables , whole grains , low-fat dairy , and lean meats and poultry ] that were reported on the question naire to be consumed at least once a week , for a maximum score of 23 ) . RESULTS There were 2065 deaths due to all causes in the cohort . The RFS was inversely associated with all-cause mortality . Compared with those in the lowest quartile , subjects in the upper quartiles of the RFS had relative risks for all-cause mortality of 0.82 ( 95 % confidence interval [ CI ] , 0.73 - 0.92 ) for quartile 2 , 0.71 ( 95 % CI , 0.62 - 0.81 ) for quartile 3 , and 0.69 ( 95 % CI , 0.61 - 0.78 ) for quartile 4 adjusted for education , ethnicity , age , body mass index , smoking status , alcohol use , level of physical activity , menopausal hormone use , and history of disease ( chi2 for trend = 35.64 , P risk of mortality in women",
"OBJECTIVE To examine the effects of alcohol on risk of mortality from coronary heart disease ( CHD ) , cardiovascular disease , and all causes in men with established CHD . METHODS AND RESULTS In a population based prospect i ve study of 7169 men aged 45–64 years followed for a mean of 12.8 years , 655 men ( 9.1 % ) had a physician diagnosis of CHD ( myocardial infa rct ion 455 , angina only 200 ) . In these 655 men , there were 294 deaths from all causes including 175 CHD deaths . Ex-drinkers had the highest risk of CHD , cardiovascular mortality , and all cause mortality even after adjustment for lifestyle characteristics and pre-existing disease . Using occasional drinkers as the reference group , lifelong teetotallers , occasional drinkers , and light drinkers all showed similar risks of mortality from CHD , cardiovascular disease , and all causes . Moderate/heavy drinkers showed increased risk of mortality from CHD , cardiovascular disease , and all causes compared to occasional drinkers . The adverse effect of moderate/heavy drinking was confined to the 455 men with previous myocardial infa rct ion ( adjusted relative risk for all cause mortality 1.50 , 95 % confidence interval 1.01 to 2.23 ) . In contrast to lighter drinking , giving up smoking within five years of the start of follow up was associated with a considerable reduction in risk of all cause and cardiovascular mortality compared to those who continued to smoke . CONCLUSION Compared to occasional drinking , regular light alcohol consumption ( 1–14 units per week ) in men with established coronary heart disease is not associated with any significant benefit or deleterious effect for CHD , cardiovascular disease or all cause mortality . Higher levels of intake ( ⩾ 3 drinks per day ) are associated with increased mortality in men with previous myocardial infa rct ion . In contrast , smoking cessation in men with established CHD substantially reduces the risk of mortality",
"Objective : To see whether mortality among men with angina can be reduced by dietary advice . Design : A r and omized controlled factorial trial . Setting : Male patients of general practitioners in south Wales . Subjects : A total of 3114 men under 70 y of age with angina . Interventions : Subjects were r and omly allocated to four groups : ( 1 ) advised to eat two portions of oily fish each week , or to take three fish oil capsules daily ; ( 2 ) advised to eat more fruit , vegetables and oats ; ( 3 ) given both the above types of advice ; and ( 4 ) given no specific dietary advice . Mortality was ascertained after 3–9 y. Results : Compliance was better with the fish advice than with the fruit advice . All-cause mortality was not reduced by either form of advice , and no other effects were attributable to fruit advice . Risk of cardiac death was higher among subjects advised to take oily fish than among those not so advised ; the adjusted hazard ratio was 1.26 ( 95 % confidence interval 1.00 , 1.58 ; P=0.047 ) , and even greater for sudden cardiac death ( 1.54 ; 95 % CI 1.06 , 2.23 ; P=0.025 ) . The excess risk was largely located among the subgroup given fish oil capsules . There was no evidence that it was due to interactions with medication . Conclusion : Advice to eat more fruit was poorly complied with and had no detectable effect on mortality . Men advised to eat oily fish , and particularly those supplied with fish oil capsules , had a higher risk of cardiac death . This result is unexplained ; it may arise from risk compensation or some other effect on patients ' or doctors ' behaviour . Sponsorship : British Heart Foundation , Seven Seas Limited , Novex Pharma Limited , The Fish Foundation",
"CONTEXT The Lifestyle Heart Trial demonstrated that intensive lifestyle changes may lead to regression of coronary atherosclerosis after 1 year . OBJECTIVES To determine the feasibility of patients to sustain intensive lifestyle changes for a total of 5 years and the effects of these lifestyle changes ( without lipid-lowering drugs ) on coronary heart disease . DESIGN R and omized controlled trial conducted from 1986 to 1992 using a r and omized invitational design . PATIENTS Forty-eight patients with moderate to severe coronary heart disease were r and omized to an intensive lifestyle change group or to a usual-care control group , and 35 completed the 5-year follow-up quantitative coronary arteriography . SETTING Two tertiary care university medical centers . INTERVENTION Intensive lifestyle changes ( 10 % fat whole foods vegetarian diet , aerobic exercise , stress management training , smoking cessation , group psychosocial support ) for 5 years . MAIN OUTCOME MEASURES Adherence to intensive lifestyle changes , changes in coronary artery percent diameter stenosis , and cardiac events . RESULTS Experimental group patients ( 20 [ 71 % ] of 28 patients completed 5-year follow-up ) made and maintained comprehensive lifestyle changes for 5 years , whereas control group patients ( 15 [ 75 % ] of 20 patients completed 5-year follow-up ) made more moderate changes . In the experimental group , the average percent diameter stenosis at baseline decreased 1.75 absolute percentage points after 1 year ( a 4.5 % relative improvement ) and by 3.1 absolute percentage points after 5 years ( a 7.9 % relative improvement ) . In contrast , the average percent diameter stenosis in the control group increased by 2.3 percentage points after 1 year ( a 5.4 % relative worsening ) and by 11.8 percentage points after 5 years ( a 27.7 % relative worsening ) ( P=.001 between groups . Twenty-five cardiac events occurred in 28 experimental group patients vs 45 events in 20 control group patients during the 5-year follow-up ( risk ratio for any event for the control group , 2.47 [ 95 % confidence interval , 1.48 - 4.20 ] ) . CONCLUSIONS More regression of coronary atherosclerosis occurred after 5 years than after 1 year in the experimental group . In contrast , in the control group , coronary atherosclerosis continued to progress and more than twice as many cardiac events occurred",
"Objective : A number of long-term population -based studies have tried to study fruit and vegetable consumption in relation to cardiovascular disease , cancer and total mortality . Few of these studies are based on r and omly selected population sample s. The aim of the study was to investigate the long-term effect of fruit and vegetable consumption on mortality , cardiovascular disease , cardiovascular death , cancer morbidity and cancer death among middle-aged and elderly men . Design : Prospect i ve cohort study . Setting : General community . The Study of Men Born in 1913.Subjects : 792 men at age 54 who participated in a screening examination in 1967.Main outcome measures : A food frequency question naire was used to obtain information of the dietary habits in 730 of the men ( 92 % ) . All men were followed up with repeated examinations until the age of 80 . Results : Cardiovascular as well as total mortality was significantly lower among men with high fruit consumption in univariate analysis . There was no correlation between fruit or vegetable consumption in relation to cancer incidence , cancer death and cardiovascular disease . In multivariate survival analysis where smoking , cholesterol and hypertension were taken into account , there was a significantly lower mortality among men with a high fruit consumption during 16 y follow up until the age of 70 ( P=0.042 ) , but this finding was no longer statistically significant during 26 y follow-up at the age of 80 ( P=0.051 ) . Conclusions . Daily fruit consumption seems to have positive effect on long-term survival independently of other traditional cardiovascular risk factors like smoking , hypertension and cholesterol . Sponsorship : This study was supported by grants from the Swedish Medical Research Council ( K98 - 274 - 06276 - 17 ) King Gustav V and Queen Victoria ’s Foundation , and the Göteborg University . European Journal of Clinical Nutrition ( 2000 ) 54 ,",
"BACKGROUND The rapid emergence of coronary artery disease ( CAD ) in south Asian people is not explained by conventional risk factors . In view of cardioprotective effects of a Mediterranean style diet rich in alpha-linolenic acid , we assessed the benefits of this diet for patients at high risk of CAD . METHODS We did a r and omised , single-blind trial in 1000 patients with angina pectoris , myocardial infa rct ion , or surrogate risk factors for CAD . 499 patients were allocated to a diet rich in whole grains , fruits , vegetables , walnuts , and almonds . 501 controls consumed a local diet similar to the step I National Cholesterol Education Program ( NCEP ) prudent diet . FINDINGS The intervention group consumed more fruits , vegetables , legumes , walnuts , and almonds than did controls ( 573 g [ SD 127 ] vs 231 g [ 19 ] per day p intake of whole grains and mustard or soy bean oil . The mean intake of alpha-linolenic acid was two-fold greater in the intervention group ( 1.8 g [ SD 0.4 ] vs 0.8 g [ 0.2 ] per day , p Total cardiac end points were significantly fewer in the intervention group than the controls ( 39 vs 76 events , p Sudden cardiac deaths were also reduced ( 6 vs 16 , p=0.015 ) , as were non-fatal myocardial infa rct ions ( 21 vs 43 , p serum cholesterol concentration and other risk factors in both groups , but especially in the intervention diet group . In the treatment group , patients with pre-existing CAD had significantly greater benefits compared with such patients in the control group . INTERPRETATION An Indo-Mediterranean diet that is rich in alpha-linolenic acid might be more effective in primary and secondary prevention of CAD than the conventional step I NCEP prudent diet",
"CONTEXT Dietary sodium is positively associated with blood pressure , and ecological and animal studies both have suggested that high dietary sodium intake increases stroke mortality . OBJECTIVE To examine the risk of cardiovascular disease associated with dietary sodium intake in overweight and nonoverweight persons . DESIGN Prospect i ve cohort study . SETTING The first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study , conducted in 1982 - 1984 , 1986 , 1987 , and 1992 . PARTICIPANTS Of those aged 25 to 74 years when the survey was conducted in 1971 -1975 ( 14407 participants ) , a total of 2688 overweight and 6797 nonoverweight persons were included in the analysis . MAIN OUTCOME MEASURES Dietary sodium and energy intake were estimated at baseline using a single 24-hour dietary recall method . Incidence and mortality data for cardiovascular disease were obtained from medical records and death certificates . RESULTS For overweight and nonoverweight persons , over an average of 19 years of follow-up , the total number of documented cases were as follows : 680 stroke events ( 210 fatal ) , 1727 coronary heart disease events ( 614 fatal ) , 895 cardiovascular disease deaths , and 2486 deaths from all causes . Among overweight persons with an average energy intake of 7452 kJ , a 100 mmol higher sodium intake was associated with a 32 % increase ( relative risk [ RR ] , 1.32 ; 95 % confidence interval [ CI ] , 1.07 - 1.64 ; P = .01 ) in stroke incidence , 89 % increase ( RR , 1.89 ; 95 % CI , 1.31 - 2.74 ; P stroke mortality , 44 % increase ( RR , 1.44 ; 95 % CI , 1.14 - 1.81 ; P = .002 ) in coronary heart disease mortality , 61 % increase ( RR , 1.61 ; 95 % CI , 1.32 - 1.96 ; P cardiovascular disease mortality , and 39 % increase ( RR , 1.39 ; 95 % CI , 1.23 - 1.58 ; P mortality from all causes . Dietary sodium intake was not significantly associated with cardiovascular disease risk in nonoverweight persons . CONCLUSIONS Our analysis indicates that high sodium intake is strongly and independently associated with an increased risk of cardiovascular disease and all-cause mortality in overweight persons",
"CONTEXT The effect of age on excess mortality from all causes associated with obesity is controversial . Few studies have investigated the association between body mass index ( BMI , calculated as weight in kilograms divided by the square of height in meters ) , age , and mortality , with sufficient numbers of subjects at all levels of obesity . OBJECTIVE To assess the effect of age on the excess mortality associated with all degrees of obesity . DESIGN Prospect i ve cohort study . SETTING AND PARTICIPANTS A total of 6193 obese patients with mean ( SD ) BMI of 36.6 ( 6.1 ) kg/m2 and mean ( SD ) age of 40.4 ( 12.9 ) years who had been referred to the obesity clinic of Heinrich-Heine University , Düsseldorf , Germany , between 1961 and 1994 . Median follow-up time was 14.8 years . MAIN OUTCOME MEASURE All-cause mortality through 1994 among 6053 patients for whom follow-up data were available ( 1028 deaths ) analyzed as st and ardized mortality ratios ( SMRs ) using the male-female population of the geographic region ( North Rhine Westphalia ) as reference . RESULTS The cohort was grouped into approximate quartiles according to age ( 18 - 29 , 30 - 39 , 40 - 49 , and 50 - 74 years ) and BMI ( 25 to or = 40 kg/m2 ) at baseline . The SMRs showed a significant excess mortality with an SMR for men of 1.67 ( 95 % confidence interval , 1.51 - 1.85 ; P excess mortality associated with obesity declined with age . For men , the SMRs of the 4 age groups were 2.46 , 2.30 , 1.99 , and 1.31 , respectively ; for women , they were 1.81 , 2.10 , 1.70 , and 1.26 , respectively ( Poisson trend test , P SMRs increased with BMI but , within each BMI group , the SMRs decreased with age . The lowest SMRs ( for men , 1.01 ; for women , 0.91 ) were obtained for patients older than 50 years with BMI s of 25 to less than 32 kg/m2 . Thus , older men and women at a BMI range of 25 to less than 32 kg/m2 had no excess mortality . The highest SMRs ( for men , 4.22 ; for women , 3.79 ) were calculated for the patients aged 18 to 29 years with a BMI of 40 kg/m2 or higher . CONCLUSIONS In this large cohort of obese persons , risk of death increased with body weight , but obesity-related excess mortality declined with age at all levels of obesity",
"This study investigate the relation between fish consumption , all-cause mortality , and incidence of coronary heart disease ( CHD ) . A total of 4,513 men and 3,984 women aged 30 - 70 years , sample d r and omly from the population in Copenhagen County , Denmark , with initially examination in 1982 - 1992 was followed until 2000 for all-cause mortality and until 1997 for first admission to hospital or death from CHD . Information on fish consumption was obtained from a self-administered food-frequency question naire . Cox proportional hazard analysis gave no evidence for an inverse association between fish consumption and all-cause mortality or incident CHD after adjustment for confounders . Among subjects with a priory-defined high risk of CHD there was a nonsignificant inverse relation between fish intake and CHD morbidity ( Hazard Ratio 1.28 ( 0.92 - 1.80 ) for a consumption of fish of less than two times per month or less compared with once a week ) , but there was relatively few cases in this subgroup . These data provides no evidence for a protective effect of fish consumption on all-cause mortality or incident CHD in the population as a whole , but it can not be excluded that frequent consumption of fish benefits those at high risk for CHD",
"R and omized clinical trials of cardiac rehabilitation following myocardial infa rct ion have typically demonstrated a lower mortality in treated patients , but with a statistically significant reduction in only one trial . To overcome the problem of not being able to detect small but clinical ly important benefits in mortality in r and omized clinical trials of exercise and risk factor rehabilitation after myocardial infa rct ion with small numbers of patients , we carried out a meta- analysis on the combined results of ten r and omized clinical trials that included 4347 patients ( control , 2145 patients ; rehabilitation , 2202 patients ) . The pooled odds ratios of 0.76 ( 95 % confidence intervals , 0.63 to 0.92 ) for all-cause death and of 0.75 ( 95 % confidence intervals , 0.62 to 0.93 ) for cardiovascular death were significantly lower in the rehabilitation group than in the control group , with no significant difference for nonfatal recurrent myocardial infa rct ion . These results suggest that , for appropriately selected patients , comprehensive cardiac rehabilitation has a beneficial effect on mortality but not on nonfatal recurrent myocardial infa rct ion",
"Abstract Objective : To assess the risk of death associated20with various patterns of alcohol consumption . Design - Prospect i ve study of mortality in relation to alcohol drinking habits in 1978 , with causes of death sought over the next 13 years ( to 1991 ) . Subjects : 12 321 British male doctors born between 1900 and 1930 ( mean 1916 ) who replied to a postal question naire in 1978 . Those written to in 1978 were the survivors of a long running prospect i ve study of the effects of smoking that had begun in 195120 and was still continuing . Results - Men were divided on the basis of their response to the 1978 question naire into two groups according to whether or not they had ever had any type of vascular disease , diabetes , or “ life threatening disease ” and into seven groups according to the amount of alcohol they drank . By 1991 almost a third had died . All statistical analyses of mortality were st and ardised for age , calendar year , and smoking habit . There was a U shaped relation between all cause mortality and the average amount of alcohol reportedly drunk ; those who reported drinking 8 - 14 units of alcohol a week ( corresponding to an average of one to two units a day ) had the lowest risks . The causes of death were grouped into three main categories : “ alcohol augmented ” causes ( 6 % of all deaths : cirrhosis , liver cancer , upper aerodigestive ( mouth , oesophagus , larynx , and pharynx ) cancer , alcoholism , poisoning , or injury ) , ischaemic heart disease ( 33 % of all deaths ) , and other causes . The few deaths from alcohol augmented causes showed , at least among regular drinkers , a progressive trend , with the risk increasing with dose . In contrast , the many deaths from ischaemic heart disease showed no significant trend among regular drinkers , but there were significantly lower rates in regular drinkers than in non-drinkers . The aggregate of all other causes showed a U shaped dose-response relation similar to that for all cause mortality . Similar differences persisted irrespective of a history of previous disease , age ( under 75 or 75 and older ) , and period of follow up ( first five and last eight years ) . Some , but apparently not much , of the excess mortality in non-drinkers could be attributed to the inclusion among them of a small proportion of former drinkers . Conclusion : The consumption of alcohol appeared to reduce the risk of ischaemic heart disease , largely irrespective of amount . Among regular drinkers mortality from all causes combined increased progressively with amount drunk above 21 units a week . Among British men in middle or older age the consumption of an average of one or two units of alcohol a day is associated with significantly lower all cause mortality than is the consumption of no alcohol , or the consumption of substantial amounts . Above about three units ( two American20units ) of alcohol a day , progressively greater levels of consumption are associated with progressively higher all cause mortality",
"OBJECTIVE --To test whether a fat reduced diet rich in soluble dietary fibre , antioxidant vitamins , and minerals reduces complications and mortality after acute myocardial infa rct ion . DESIGN --R and omised , single blind , controlled trial . SETTING -- Primary and secondary care research centre for patients with myocardial infa rct ion . SUBJECTS--505 patients with suspected acute myocardial infa rct ion . Those with definite or possible acute myocardial infa rct ion and unstable angina based on World Health Organisation criteria were assigned to diet A ( n = 204 ) or diet B ( n = 202 ) within 24 - 48 hours of infa rct ion . INTERVENTIONS --Both groups were advised to follow a fat reduced diet . Group A was also advised to eat more fruit , vegetables , nuts , and grain products . MAIN OUTCOME MEASURES --Mortality from cardiac disease and other causes . Serum lipid concentrations and compliance with diet . RESULTS --Blood lipoprotein concentrations and body weight fell significantly in patients in group A compared with those in group B ( cholesterol fell by 0.74 mmol/l in group A v 0.32 mmol/l in group B , 95 % confidence interval of difference 0.14 to 0.70 , and weight by 7.1 v 3.0 kg , 0.52 to 7.68 ) . The incidence of cardiac events was significantly lower in group A than group B ( 50 v 82 patients , p less than 0.001 ) . Group A also had lower total mortality ( 21 v 38 died , p less than 0.01 ) than group B. CONCLUSIONS --Comprehensive dietary changes in conjunction with weight loss immediately after acute myocardial infa rct ion may modulate blood lipoproteins and significantly reduce complications and mortality after one year",
"A r and omised controlled trial with a factorial design was done to examine the effects of dietary intervention in the secondary prevention of myocardial infa rct ion ( MI ) . 2033 men who had recovered from MI were allocated to receive or not to receive advice on each of three dietary factors : a reduction in fat intake and an increase in the ratio of polyunsaturated to saturated fat , an increase in fatty fish intake , and an increase in cereal fibre intake . The advice on fat was not associated with any difference in mortality , perhaps because it produced only a small reduction ( 3 - 4 % ) in serum cholesterol . The subjects advised to eat fatty fish had a 29 % reduction in 2 year all-cause mortality compared with those not so advised . This effect , which was significant , was not altered by adjusting for ten potential confounding factors . Subjects given fibre advice had a slightly higher mortality than other subjects ( not significant ) . The 2 year incidence of reinfa rct ion plus death from ischaemic heart disease was not significantly affected by any of the dietary regimens . A modest intake of fatty fish ( two or three portions per week ) may reduce mortality in men who have recovered from MI",
"BACKGROUND The evidence that high salt intake increases the risk of cardiovascular disease has been challenged . We aim ed to find out whether salt intake , measured by 24 h urinary sodium excretion , is an independent risk factor for cardiovascular disease frequency and mortality , and all-cause mortality . METHODS We prospect ively followed 1173 Finnish men and 1263 women aged 25 - 64 years with complete data on 24 h urinary sodium excretion and cardiovascular risk factors . The endpoints were an incident coronary and stroke event , and death from coronary heart disease , cardiovascular disease , and any cause . Each endpoint was analysed separately with the Cox proportional hazards model . FINDINGS The hazards ratios for coronary heart disease , cardiovascular disease , and all-cause mortality , associated with a 100 mmol increase in 24 h urinary sodium excretion , were 1.51 ( 95 % CI 1.14 - 2.00 ) , 1.45 ( 1.14 - 1.84 ) , and 1.26 ( 1.06 - 1.50 ) , respectively , in both men and women . The frequency of acute coronary events , but not acute stroke events , rose significantly with increasing sodium excretion . When analyses were done separately for each sex , the risk ratios were significant in men only . There was a significant interaction between sodium excretion and body mass index for cardiovascular and total mortality ; sodium predicted mortality in men who were overweight . Correction for the regression dilution bias increased the hazards ratios markedly . INTERPRETATION High sodium intake predicted mortality and risk of coronary heart disease , independent of other cardiovascular risk factors , including blood pressure . These results provide direct evidence of the harmful effects of high salt intake in the adult population",
"In a prospect i ve , r and omised single-blinded secondary prevention trial we compared the effect of a Mediterranean alpha-linolenic acid-rich diet to the usual post-infa rct prudent diet . After a first myocardial infa rct ion , patients were r and omly assigned to the experimental ( n = 302 ) or control group ( n = 303 ) . Patients were seen again 8 weeks after r and omisation , and each year for 5 years . The experimental group consumed significantly less lipids , saturated fat , cholesterol , and linoleic acid but more oleic and alpha-linolenic acids confirmed by measurements in plasma . Serum lipids , blood pressure , and body mass index remained similar in the 2 groups . In the experimental group , plasma levels of albumin , vitamin E , and vitamin C were increased , and granulocyte count decreased . After a mean follow up of 27 months , there were 16 cardiac deaths in the control and 3 in the experimental group ; 17 non-fatal myocardial infa rct ion in the control and 5 in the experimental groups : a risk ratio for these two main endpoints combined of 0.27 ( 95 % CI 0.12 - 0.59 , p = 0.001 ) after adjustment for prognostic variables . Overall mortality was 20 in the control , 8 in the experimental group , an adjusted risk ratio of 0.30 ( 95 % CI 0.11 - 0.82 , p = 0.02 ) . An alpha-linolenic acid-rich Mediterranean diet seems to be more efficient than presently used diets in the secondary prevention of coronary events and death",
"The results of large prospect i ve epidemiologic investigations support the hypothesis that coronary disease risk depends on the quality rather than quantity of dietary fat . Whereas saturated fat and cholesterol appear to increase the risk of coronary heart disease ( CHD ) as predicted by their effects on blood lipids , strong evidence has emerged that the deleterious effects of trans unsaturated fatty acids ( trans fatty acids ) extend beyond those predicted by their well-known adverse influence on the ratio of low-density lipoprotein to high-density lipoprotein cholesterol . On the other h and , increased consumption of the polyunsaturated fats , linoleic acid and linolenic acid , appears to reduce the risk of CHD",
"BACKGROUND Alcohol consumption has both adverse and beneficial effects on survival . We examined the balance of these in a large prospect i ve study of mortality among U.S. adults . METHODS Of 490,000 men and women ( mean age , 56 years ; range , 30 to 104 ) who reported their alcohol and tobacco use in 1982 , 46,000 died during nine years of follow-up . We compared cause-specific and rates of death from all causes across categories of base-line alcohol consumption , adjusting for other risk factors , and related drinking and smoking habits to the cumulative probability of dying between the ages of 35 and 69 years . RESULTS Causes of death associated with drinking were cirrhosis and alcoholism ; cancers of the mouth , esophagus , pharynx , larynx , and liver combined ; breast cancer in women ; and injuries and other external causes in men . The mortality from breast cancer was 30 percent higher among women reporting at least one drink daily than among nondrinkers ( relative risk , 1.3 ; 95 percent confidence interval , 1.1 to 1.6 ) . The rates of death from all cardiovascular diseases were 30 to 40 percent lower among men ( relative risk , 0.7 ; 95 percent confidence interval , 0.7 to 0.8 ) and women ( relative risk , 0.6 ; 95 percent confidence interval , 0.6 to 0.7 ) reporting at least one drink daily than among nondrinkers , with little relation to the level of consumption . The overall death rates were lowest among men and women reporting about one drink daily . Mortality from all causes increased with heavier drinking , particularly among adults under age 60 with lower risk of cardiovascular disease . Alcohol consumption was associated with a small reduction in the overall risk of death in middle age ( ages 35 to 69 ) , whereas smoking approximately doubled this risk . CONCLUSIONS In this middle-aged and elderly population , moderate alcohol consumption slightly reduced overall mortality . The benefit depended in part on age and background cardiovascular risk and was far smaller than the large increase in risk produced by tobacco"
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This aim of this review is to explore the current research related to crosslinking agents used on dentine . A systematic search of publications in PubMed and Web of Science data bases was performed . Further retrieval was conducted using the search terms of specific names of crosslinkers . Review s , conference abstract s , dissertation and theses , non-English articles , studies of intrinsic crosslinking of dentine , studies of adhesives without specific crosslinker components , studies of crosslinker applications in other collagenous tissues or tooth-like structures and irrelevant studies were excluded . Manual screening was conducted on the bibliographies of remaining papers to identify other relevant articles . One hundred and one articles were included in this systematic review and full texts were retrieved . Both synthetic and naturally derived crosslinkers have been found to exhibit significant effects in biomodification of dentine via their multiple interactions with the dentine matrix . A stable matrix network or a durable hybrid layer in dentine bonding could be achieved , where the dentine collagen fibrils show improved biochemical and biomechanical properties and enzymatic biodegradation is reduced . Although no crosslinkers have been tested in clinical trials , extensive research has been conducted in laboratory studies to investigate their potential applicability for inhibition of demineralisation and /or promotion of remineralisation , caries prevention as well as improvement of bonding performance of adhesive systems . Further studies are needed to develop the feasibility for clinical use , reduce side effects as well as explore mechanisms of action and long-term effectiveness
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"The aim of this study was to evaluate the effects of a proanthocyanidin-rich grape seed extract ( GSE ) on the in vitro demineralization of root dentine . Root fragments were obtained from sound human teeth . The fragments were r and omly assigned to different treatments solutions : GSE , fluoride ( F ) , GSE+F and distilled water ( control ) . Sample s were treated daily for 30 min and subjected to a pH cycling artificial caries protocol using demineralization cycles ( 2.2 mM CaCl2 × H2O , 2.2 mM KH2PO4 , 50 mM acetic acid , pH 4.3 ) for 6 h and remineralization cycles ( 20 mM HEPES , 2.25 mM CaCl2 × H2O , 1.35 mM KH2PO4 , 130 mM KCl , pH 7.0 ) for 17.5 h. Mineral loss ( ΔZ ) and lesion depth ( LD ) were determined after 18 days of treatment/pH cycling , by transverse microradiography . GSE was able to minimize ΔZ and LD compared with the control group ( p The GSE+F and F groups showed the lowest values of ΔZ and LD ( p using GSE results in decreased rates of root demineralization and may be used in conjunction with F to prevent root caries",
"Dental caries is considered a disease of high prevalence and a constant problem in public health . Proanthocyanidins ( PAs ) are substances that have been the target of recent studies aim ing to control or treat caries . Objective The aim of this in vitro study was to evaluate the efficacy of a treatment with grape seed extract , under cariogenic challenge , to minimize or even prevent the onset of caries in the enamel and dentin . Material and Methods Blocks of enamel and dentin ( 6.0x6.0 mm ) were obtained from bovine central incisors , polished , and selected by analysis of surface microhardness ( SH ) . The blocks were r and omly divided into 3 groups ( n=15 ) , according to the following treatments : GC ( control ) , GSE ( grape seed extract ) , GF ( fluoride – 1,000 ppm ) . The blocks were subjected to 6 daily pH cycles for 8 days . Within the daily cycling , the specimens were stored in buffered solution . The blocks were then analyzed for perpendicular and surface hardness and polarized light microscopy . Results The means were subjected to statistical analysis using the ANOVA and Fisher ’s PLSD tests ( p highest hardness values . In the dentin , GF was also the one that showed higher hardness values , followed by GSE . Regarding the cross-sectional hardness values , all groups behaved similarly in both the enamel and dentin . The sample s that were treated with GSE and fluoride ( GF ) showed statistically higher values than the control . Conclusion Based on the data obtained in this in vitro study , it is suggested that grape seed extract inhibits demineralization of artificial carious lesions in both the enamel and dentin , but in a different scale in each structure and in a smaller scale when compared to fluoride",
"The aim of this study was to evaluate the effects of UVA-activated riboflavin ( UVA-RF ) on the mechanical properties of non-demineralized human dentin . Dentin specimens obtained from 20 teeth were r and omly divided into the following four groups : group 1 ( control ) : no treatment , group 2 ( low UVA-RF ) : specimens were exposed to UVA-RF for 10 min , group 3 ( medium UVA-RF ) : specimens were exposed to UVA-RF for 30 min , and group 4 ( high UVA-RF ) : specimens were exposed to UVA-RF for 60 min . Three-point flexural test and Raman spectroscopic analyses were performed . The mean flexural strengths ( MPa ) were 129.96 , 128.96 , 144.21 , and 147.54 , and the mean elastic modulus ( GPa ) were 8.59 , 8.38 , 10.21 , and 9.87 for groups 1 to 4 , respectively . Raman spectra showed chemical modifications of dental collagen under medium and high UVA-RF treatment . We conclude that medium and high UVA-RF increases the strength of non-demineralized human dentin by collagen crosslinking",
"This study was undertaken to investigate whether using a protein cross-linker , 1-ethyl-3-(3-dimethylaminopropyl ) carbodiimide ( EDC ) , improves bonding stability of fiber posts to root dentin using three resin cements . Sixty human maxillary central incisor roots were r and omly divided into six groups after endodontic treatment , according to the cements used with and without EDC pretreatment . In the etch- and -rinse group , 0.3 M EDC aqueous solution was applied on acid-etched root dentin prior to Excite DSC/Variolink II for post cementation . In the self-etch and self-adhesive groups , EDC was used on EDTA-conditioned root space prior to application of ED Primer II/Panavia F2.0 and Clearfil SA , respectively . After microslicing the root dentin , a push-out bond strength ( BS ) test was performed immediately or after one-year of water storage for each group . Data were analyzed using three-way analysis of variance and Tukey tests ( α=0.05 ) . A significant effect of cement type , time , EDC , and Time × Cement and Time × EDC interactions were observed ( p≤0.001 ) . EDC pretreatment did not affect immediate bonding of the three cements ( p>0.05 ) . Aging significantly reduced the BS in all the groups ( p≤0.001 ) , but EDC groups exhibited a higher BS compared with the respective control groups ( p decreasing the BS of fiber post to radicular dentin , EDC could diminish this effect for the three tested cements",
"ABSTRACT Objective Green tea extract has been advocated as a matrix metalloproteinase ( MMP ) inhibitor ; however , its effect on bond durability to caries-affected dentin has never been reported . Thus , the aim of this in vitro study was to evaluate the effect of two MMP inhibitors ( 2 % chlorhexidine and 2 % green tea extract ) , applied after acid etching , on bond durability of an etch- and -rinse adhesive system to caries-affected dentin . Material and Methods Occlusal enamel was removed from third molars to expose the dentin surface , and the molars were su bmi tted to a caries induction protocol for 15 days . After removal of infected dentin , specimens were conditioned with 37 % phosphoric acid ( 15 seconds ) and r and omly divided into three groups , according to the type of dentin pretreatment ( n=10 ) : NT : no treatment ; GT : 2 % green tea extract ; CLX : 2 % chlorhexidine . The etch- and -rinse adhesive system ( Adper ™ Single Bond 2 , 3 M ESPE , St. Paul , MN , USA ) was applied according to the manufacturer 's instructions , and composite resin restorations were built on the dentin . After 24 hours , at 37 ° C , the resin-tooth blocks were sectioned perpendicularly to the adhesive interface in the form of sticks ( 0.8 mm2 of adhesive area ) and r and omly subdivided into two groups according to when they were to be su bmi tted to microtensile bond strength ( μTBS ) testing : immediately or 6 months after storage in distilled water . Data were reported in MPa and su bmi tted to two-way ANOVA for completely r and omized blocks , followed by Tukey ’s test ( α=0.05 ) . Results After 24 hours , there was no significant difference in the μTBS of the groups . After 6 months , the GT group had significantly higher μTBS values . Conclusion It was concluded that the application of 2 % green tea extract was able to increase bond durability of the etch- and -rinse system to dentin . Neither the application of chlorhexidine nor non-treatment ( NT - control ) had any effect on bond strength after water storage",
"Aim : To evaluate whether the application of two simplified etch- and -rinse adhesives to biomodified dentin using ethanol-wet bonding ( EWB ) and collagen cross-linker ( CCL ) pretreatment improves their sealing ability . Material s and Methods : In 176 extracted human molars , the pulp-chambers were deroofed , and teeth were sectioned horizontally . Sample s were r and omly divided into eight groups according to four bonding techniques using two simplified etch- and -rinse adhesives ; Adper Single Bond 2 ( ASB ) and XP Bond ( XPB ) . The bonding protocol s included : ( a ) Water-wet bonding ( WWB ) ; ( b ) EWB ; ( c ) WWB and CCL application ; ( d ) EWB and CCL application . After composite resin restorations , dye leakage evaluation and scanning electron microscope analysis were done . Leakage scores were statistically analyzed using Kruskal-Wallis and Mann-Whitney U tests at a significance level of P ASB and XPB adhesives , least dye leakage was observed in EWB groups ( b and d ) ( P = 0.918 and P = 0.399 respectively ) which showed no significant difference , while maximum leakage scores were seen in WWB groups ( a and c ) . Regardless of CCL application and adhesives used , EWB technique depicted ( P = 0.003 and P = 0.004 ) significantly greater sealing ability than WWB . Conclusion : Bonding of ASB and XPB using EWB significantly improved their sealing ability . Biomodification using CCL pretreatment had no significant effect on the sealing ability of adhesives bonded with either WWB or EWB",
"PURPOSE To evaluate the effect of the inclusion of glutaraldehyde on the shear bond strength of new ethanol-based adhesives ( Gluma Comfort Bond & Desensitizer , GCBD and Gluma Comfort Bond , GCB ) versus acetone-based Gluma One Bond ( GOB ) and a conventional three-step adhesive as a control . MATERIAL S AND METHODS Forty bovine incisors were mounted in acrylic , polished to 600-grit , and r and omly assigned to four groups ( n=10 ) . Dentin was etched for 15 s using 35 % phosphoric acid , rinsed , and lightly dried . After adhesive application and curing , Charisma composite was applied in a # 5 gelatin capsule and light-cured . Specimens were loaded in shear using an Instron at 5 mm/min . Shear bond strengths were calculated by dividing failure load by bonded surface area . ANOVA showed a significant difference in means at P Mean SBS ( + /- SD , MPa ) were : GOB : 8 (4.4)ab ; GCB : 10 (4.4)ab ; GCBD : 14 (6)bc ; SBMP : 17.7 (6.4)c . Superscript letters indicate Tukey 's homogeneous subsets ( P < 0.05 )",
"This study aim ed to evaluate the bonding strength and thermal properties of demineralized dentin with and without EDC treatment . Sound human molars were r and omly divided into seven treatment groups ( n = 20 ) : control , 80 % ethanol , and five EDC ethanol solutions ( 0.01–1.0 M ) . In each group , 16 sample s were used for bond strength assessment and 4 sample s were used for scanning electron microscopy ( SEM ) analysis . A further 70 intact molars were used to obtain a fine demineralized dentin powder , treated with the same solutions and were evaluated the crosslink degree by ninhydrin test and denaturation temperature ( Td ) by differential scanning calorimetry . EDC-treated specimens ( higher bond strength , especially 0.3 and 0.5 M group , than the control counterpart . There was a significant drop in bond strength of 1.0 M EDC group . SEM revealed a homogeneous and regular interface under all treatments . EDC treatment significantly increased the demineralized dentin cross-link degree and Td compared with the control and ethanol treatments . The 0.3 and 0.5 M treatments showed the highest cross-link degree and Td . In terms of mechnical and theramal properties consideration , 0.3 and 0.5 M EDC solutions may be favorable for when applied with etch- and -rinse adhesives , but it is still needed further long-term study",
"BACKGROUND This study evaluated the synergistic effect of proanthocyanidin ( PA ) and casein phosphopeptide amorphous calcium fluoride phosphate ( CPP-ACFP ) on remineralization of artificial root caries . METHODS Demineralized root fragments ( n = 90 ) were r and omly divided into six groups based on treatments : ( 1 ) 6.5 % PA ; ( 2 ) CPP-ACP ; ( 3 ) CPP-ACFP ; ( 4 ) CPP-ACFP + 6.5 % PA ; ( 5 ) 1000 ppm fluoride ; and ( 6 ) deionized water ( control ) . Each specimen was immersed in demineralizing solution for 14 h , testing solutions/pastes for 2 h , remineralizing solution for 8 h and pH cycling was performed at 37 ° C for 8 days . Specimens were evaluated using transverse microradiography ( lesion depth and mineral loss ) , Knoop microhardness and confocal laser scanning microscopy . RESULTS Lesion depth was significantly lower in CPP-ACFP+PA and 1000 ppm fluoride groups ( p 0.05 ) . Mineral loss was the lowest in CPP-ACFP+PA group ( p 0.05 ) . Fluoride and CPP-ACFP groups showed similar mineral gain ( p > 0.05 ) . Artificial caries lesions treated with CPP-ACFP+PA showed significantly higher microhardness values at 130 μm and 150 μm from the surface ( p PA and CPP-ACFP has a synergistic effect on root caries remineralization by enhancing mineral gain and increasing hardness of artificial root caries",
"OBJECTIVES This study evaluated the effect of proanthocyanidin ( PA ) incorporation into experimental dental adhesives on resin-dentine bond strength . METHODS Four experimental hydrophilic adhesives containing different PA concentrations were prepared by combining 50wt% resin comonomer mixtures with 50wt% ethanol . Proanthocyanidin was added to the ethanol-solvated resin to yield three adhesives with PA concentrations of 1.0 , 2.0 and 3.0wt% , respectively . A PA-free adhesive served as the control . Flat dentine surfaces from 40 extracted third molars were etched with 32 % phosphoric acid . The specimens were r and omly assigned to one of the four adhesive groups . Two layers of one of the four experimental adhesives were applied to the etched dentine and light-cured for 20s . Composite build-ups were performed using Filtek Z250 ( 3 M ESPE ) . After storage in distilled water at 37 ° C for 24h , twenty-four bonded teeth were sectioned into 0.9 mm × 0.9 mm beams and stressed to failure under tension for bond strength testing . Bond strength data were evaluated by one-way ANOVA and Tukey 's test ( α=0.05 ) . Interfacial nanoleakage was examined in the remaining teeth using a field-emission scanning electron microscope and analysed using the Chi-square test ( α=0.05 ) . RESULTS No significant difference in bond strength was found amongst PA-free , 1 % and 2 % PA adhesives . However , incorporation of 3 % PA into the adhesive significantly lowered bond strength as demonstrated by a greater number of adhesive failures and more extensive nanoleakage along the bonded interface . CONCLUSION Incorporation of 2 % proanthocyanidin into dental adhesives has no adverse effect on dentine bond strength . CLINICAL SIGNIFICANCE The addition of proanthocyanidin to an experimental adhesive has no adverse effect on the immediate resin-dentine bond strength when the concentration of proanthocyanidin in the adhesive is less than or equal to 2 %",
"INTRODUCTION The aim of this study was to investigate the effects of a proanthocyanidin-rich extract ( grape seed extract [ GSE ] ) on the bond strength and stability of the adhesion of fiber posts to the root dentine using 2 adhesive systems : a total-etch and a self-etch adhesive system . METHODS Single-rooted human teeth were r and omly divided into 6 groups : G1 ( control ) , untreated + total-etch adhesive Adper Scotchbond Multi- Purpose ( 3 M ESPE , St Paul , MN ) ; G2 , 6.5 % GSE for 5 minutes + SB ; G3 , 10 % GSE for 5 minutes + SB ; and G4 to G6 groups were similar to previous ones ; however , the self-etch adhesive system Clearfil SE Bond ( Kuraray , Kurashiki , Japan ) was used . Fiber posts were cemented with RelyX ARC ( 3 M ESPE ) , and the specimens were immediately tested for push out or stored for 12 months . The bond strength means were analyzed by analysis of variance and Games-Howell post hoc tests ( α = 0.05 ) . Additionally , matrix metalloproteinase inhibition by 0.65 % , 0.065 % , and 0.0065 % GSE was examined with gelatin zymography . RESULTS The use of GSE did not affect immediate bond strength to dentin and contributed to preserve the bond strength after 12 months ( P The bond strength of SB was significantly higher than Clearfil SE Bond ( P showed reduced matrix metalloproteinase activity when recombinant enzymes were incubated with both 0.65 % and 0.065 % GSE , with complete inhibition at the highest concentration . CONCLUSIONS The pretreatment with GSE can be used as a natural alternative to improve bond strength stability of dentin-adhesive interfaces in root canals",
"Context : Resin-dentin bonds are unstable owing to hydrolytic and enzymatic degradation . Several approaches such as collagen cross-linking and ethanol-wet bonding ( EWB ) have been developed to overcome this problem . Collagen cross-linking improves the intrinsic properties of the collagen matrix . However , it leaves a water-rich collagen matrix with incomplete resin infiltration making it susceptible to fatigue degradation . Since EWB is expected to overcome the drawbacks of water-wet bonding ( WWB ) , a combination of collagen cross-linking with EWB was tested . Aim : The aim of this study was to compare the effect of pretreatment with different cross-linking agents such as ultraviolet A (UVA)-activated 0.1 % riboflavin , 1 M carbodiimide , and 6.5 wt% proanthocyanidin on the immediate and long-term bond strengths of an etch and rinse adhesive system to water- versus ethanol-saturated dentin within clinical ly relevant application time periods . Setting s and Design : Long-term in vitro study evaluating the microtensile bond strength of adhesive-dentin interface after different surface pretreatments . Subjects and Methods : Eighty freshly extracted human molars were prepared to expose dentin , etched with 37 % phosphoric acid for 15 s rinsed , and grouped r and omly . They were blot-dried and pretreated with different cross-linkers : 0.1 % riboflavin for 2 min followed by UVA activation for 2 min ; 1 M carbodiimide for 2 min ; 6.5 wt% proanthocyanidin for 2 min and rinsed . They were then bonded with Adper Single Bond Adhesive ( 3 M ESPE ) , by either WWB or EWB , followed by resin composite build-ups ( Filtek Z350 , 3 M ESPE ) . Bonded specimens in each group were then sectioned and divided into two halves . Microtensile bond strength was tested in one half after 24 h and the other after 6 months storage in artificial saliva . Statistical Analysis Used : Analysis was done using SPSS version 18 software ( SPSS Inc. , Chicago , IL , USA ) . Intergroup comparison of bond strength was done using ANOVA with post hoc Tukey 's test , and intragroup comparison was done using paired t-test . Results : The microtensile bond strength of cross-linked groups was higher compared to control group ( P bond strength values on cross-linked dentin compared to noncross-linked dentin . UVA-activated riboflavin group exhibited highest bond strengths followed by carbodiimide and proanthocyanidin groups , respectively , on both water- as well as ethanol-saturated dentin . Even after 6 months storage , cross-linked groups showed significantly higher values compared to initial bond strength values of control group ( P 0.1 % riboflavin pretreatment of dentin followed by UVA activation for 2 min exhibited highest increase in bond strength values at 24 h and least reduction in bond strength values after 6 months storage compared to other groups . Biomodification of dentin using collagen cross-linking followed by EWB exhibited a synergistic effect in improving the resin-dentin bond durability",
"OBJECTIVE This study evaluated the ability of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride ( EDC ) to improve the stability of demineralized dentin collagen matrices when subjected to mechanical cycling by means of Chewing Simulation ( CS ) . METHODS Demineralized dentin disks were r and omly assigned to four groups ( N=4 ) : ( 1 ) immersion in artificial saliva at 37 ° C for 30 days ; ( 2 ) pre-treatment with 0.5 M EDC for 60 s , then stored as in Group 1 ; ( 3 ) CS challenge ( 50 N occlusal load , 30 s occlusal time plus 30 s with no load , for 30 days ) ; ( 4 ) pre-treatment with 0.5 M EDC as in Group 2 and CS challenge as in Group 3 . Collagen degradation was evaluated by sampling storage media for ICTP and CTX telopeptides . RESULTS EDC treated specimens showed no significant telopeptides release , irrespective of the aging method . Cyclic stressing of EDC-untreated specimens caused significantly higher ICTP release at day 1 , compared to static storage , while by days 3 and 4 , the ICTP release in the cyclic group fell significantly below the static group , and then remained undetectable from 5 to 30 days . CTX release in the cyclic groups , on EDC-untreated control specimens was always lower than in the static group in days 1 - 4 , and then fell to undetectable for 30 days . SIGNIFICANCE This study showed that chewing stresses applied to control untreated demineralized dentin increased degradation of collagen in terms of CTX release , while collagen crosslinking agents may prevent dentin collagen degradation , irrespective of simulated occlusal function",
"UNLABELLED Type I collagen is a major component of the hybrid layer , and improvement of its mechanical properties may be advantageous during bonding procedures . OBJECTIVE To investigate the effect of three different cross-linking agents ( Glutaraldehyde [ GD ] , Grape seed extract [ GSE ] , and Genipin [ GE ] ) on the tensile bond strength ( TBS ) of resin-dentin bonds . MATERIAL S AND METHODS Sixty-four sound human molars were collected and their occlusal surfaces were ground flat to expose dentin . Dentin surfaces were etched using a phosphoric acid and then teeth were r and omly divided according to the dentin treatment : Control group ( no treatment ) , 5 % GD , 6.5 % GSE , or 0.5 % GE . Teeth were restored either with One Step Plus or Adper Single Bond Plus adhesive systems and resin composite . After 24 h , teeth were sectioned to produce a cross-sectional surface area of 1.0 mm(2 ) and tested for tensile bond strength . Data were statistically analyzed using ANOVA and Fisher 's PLSD tests ( p TBS ( p GD and GSE , but not GE , result ed in increased bond strength . The application of selective collagen cross-linkers during adhesive restorative procedures may be a new approach to improve dentin bond strength properties",
"BACKGROUND This study compared the effects of three flavonoids , including proanthocyanidin , naringin and quercetin on remineralization of artificial root caries . METHODS Demineralized root fragments ( n = 75 ) were r and omly divided into five groups for treatment with the remineralizing agents for 10 minutes : ( 1 ) 6.5 % proanthocyanidin ; ( 2 ) 6.5 % naringin ; ( 3 ) 6.5 % quercetin ; ( 4 ) 1000 ppm fluoride ; and ( 5 ) deionized water ( control ) . The demineralized sample s were pH-cycled through treatment solutions , acidic buffer and neutral buffer for eight days at six cycles per day . The remineralization effects were evaluated using Knoop microhardness , transverse microradiography ( lesion depth and mineral loss ) and confocal laser scanning microscopy . Microhardness at different lesion depths was analysed with two-way ANOVA and Tukey 's test , while lesion depths and mineral loss were analysed with one-way ANOVA and Tukey 's test . RESULTS Artificial caries lesions treated with fluoride and flavonoids showed significantly greater hardness than the control group ( p lesion depths and mineral loss of the flavonoid treated groups were significantly lower than the control group ( p lesion depth and mineral loss was found among the three flavonoids ( p > 0.05 ) . CONCLUSIONS All three flavonoids showed positive effects on artificial root caries remineralization , which are significantly lower than that of 1000 ppm fluoride",
"OBJECTIVE This in vitro study evaluated the shear bond strength of composite resin to deep dentin using a total etch adhesive after treatment with two collagen cross-linking agents at varying time intervals . MATERIAL S AND METHODS Thirty freshly extracted human maxillary central incisors were sectioned longitudinally into equal mesial and distal halves ( n=60 ) . The proximal deep dentin was exposed , maintaining a remaining dentin thickness ( RDT ) of approximately 1 mm . The specimens were r and omly divided into three groups based on the surface treatment of dentin prior to bonding as follows : group I ( n=12 , control ) : no prior dentin surface treatment ; group II ( n=24 ) : dentin surface pretreated with 10 % sodium ascorbate ; and group III ( n=24 ) : dentin surface pretreated with 6.5 % proanthocyanidin . Groups II and III were further subdivided into two subgroups of 12 specimens each , based on the pretreatment time of five minutes ( subgroup A ) and 10 minutes ( subgroup B ) . Shear bond strength of the specimens was tested with a universal testing machine , and the data were statistically analyzed . RESULTS Significantly higher shear bond strength to deep dentin was observed in teeth treated with 10 % sodium ascorbate ( group II ) and 6.5 % proanthocyanidin ( group III ) compared to the control group ( group I ) . Among the collagen cross-linkers used , specimens treated with proanthocyanidin showed significantly higher shear bond strength values than those treated with sodium ascorbate . No significant difference was observed between the five-minute and 10-minute pretreatment times in groups II and III . CONCLUSION It can be concluded that dentin surface pretreatment with both 10 % sodium ascorbate and 6.5 % proanthocyanidin result ed in significant improvement in bond strength of resin composite to deep dentin"
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BACKGROUND Acute psychotic illness , especially when associated with agitated or violent behaviour , can require urgent pharmacological tranquillisation or sedation . In several countries , clinicians often use benzodiazepines ( either alone or in combination with antipsychotics ) for this outcome . OBJECTIVES To estimate the effects of benzodiazepines , alone or in combination with antipsychotics , when compared with placebo or antipsychotics , alone or in combination with antihistamines , to control disturbed behaviour and reduce psychotic symptoms . SEARCH METHODS We search ed the Cochrane Schizophrenia Group 's register ( January 2012 ) , inspected reference lists of included and excluded studies and contacted authors of relevant studies . SELECTION CRITERIA We included all r and omised clinical trials ( RCTs ) comparing benzodiazepines alone or in combination with any antipsychotics , versus antipsychotics alone or in combination with any other antipsychotics , benzodiazepines or antihistamines , for people with acute psychotic illnesses . DATA COLLECTION AND ANALYSIS We reliably selected studies , quality assessed them and extracted data . For binary outcomes , we calculated st and ard estimates of relative risk ( RR ) and their 95 % confidence intervals ( CI ) using a fixed-effect model . For continuous outcomes , we calculated the mean difference ( MD ) between groups . If heterogeneity was identified , this was explored using a r and om-effects model . MAIN RESULTS We included 21 trials with a total of n = 1968 participants . There was no significant difference for most outcomes in the one trial that compared benzodiazepines with placebo , although there was a higher risk of no improvement in people receiving placebo in the medium term ( one to 48 hours ) ( n = 102 , 1 RCT , RR 0.62 , 95 % CI 0.40 to 0.97 , very low quality evidence ) . There was no difference in the number of participants who had not improved in the medium term when benzodiazepines were compared with antipsychotics ( n = 308 , 5 RCTs , RR 1.10 , 95 % CI 0.85 to 1.42 , low quality evidence ) ; however , people receiving benzodiazepines were less likely to experience extrapyramidal effects ( EPS ) in the medium term ( n = 536 , 8 RCTs , RR 0.15 , 95 % CI 0.06 to 0.39 , moderate quality of evidence ) . Data comparing combined benzodiazepines and antipsychotics versus benzodiazepines alone did not yield any significant results . When comparing combined benzodiazepines/antipsychotics ( all studies compared haloperidol ) with the same antipsychotics alone ( haloperidol ) , there was no difference between groups in improvement in the medium term ( n = 155 , 3 RCTs , RR 1.27 , 95 % CI 0.94 to 1.70 , very low quality evidence ) but sedation was more likely in people who received the combination therapy ( n = 172 , 3 RCTs , RR 1.75 , 95 % CI 1.14 to 2.67 , very low quality evidence ) . However , more participants receiving combined benzodiazepines and haloperidol had not improved by medium term when compared to participants receiving olanzapine ( n = 60,1 RCT , RR 25.00 , 95 % CI 1.55 to 403.99 , very low quality evidence ) or ziprasidone ( n = 60 , 1 RCT , RR 4.00 , 95 % CI 1.25 to 12.75very low quality evidence ) . When haloperidol and midazolam were compared with olanzapine , there was some evidence the combination was superior in terms of improvement , sedation and behaviour . AUTHORS ' CONCLUSIONS The evidence from trials for the use of benzodiazepines alone is not good . There were relatively little good data and most trials are too small to highlight differences in either positive or negative effects . Adding a benzodiazepine to other drugs does not seem to confer clear advantage and has potential for adding unnecessary adverse effects . Sole use of older antipsychotics unaccompanied by anticholinergic drugs seems difficult to justify . Much more high quality research is needed in this area
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"OBJECTIVE The authors examined the efficacy of intramuscular flunitrazepam compared with intramuscular haloperidol for the immediate control of agitated or aggressive behavior in acutely psychotic patients . METHOD Twenty-eight actively psychotic in patients , aged 20 - 60 years , who were under treatment with neuroleptic agents were selected for the study . Each was r and omly assigned on a double-blind basis to receive either 5 mg i.m . of haloperidol ( N=13 ) or 1 mg i.m . of flunitrazepam ( N=15 ) during an aggressive event . Verbal and physical aggression was measured over time with the Overt Aggression Scale . Patients were also rated with the Brief Psychiatric Rating Scale and the Clinical Global Impression scale . RESULTS Both flunitrazepam and haloperidol exhibited acute antiaggressive activity . This beneficial effect , as assessed by the Overt Aggression Scale , was obtained within 30 minutes . CONCLUSIONS Intramuscular flunitrazepam may serve as a convenient , rapid , safe , and effective adjunct to neuroleptics in reducing aggressive behavior in emergency psychiatric setting",
"OBJECTIVES To determine if midazolam is superior to lorazepam or haloperidol in the management of violent and severely agitated patients in the emergency department . Superiority would be determined if midazolam result ed in a significantly shorter time to sedation and shorter time to arousal . METHODS This was a r and omized , prospect i ve , double-blind study of a convenience sample of patients from an urban , county teaching emergency department . Participants included 111 violent and severely agitated patients . Patients were r and omized to receive intramuscular midazolam ( 5 mg ) , lorazepam ( 2 mg ) , or haloperidol ( 5 mg ) . RESULTS The mean ( + /-SD ) age was 40.7 ( + /-13 ) years . The mean ( + /-SD ) time to sedation was 18.3 ( + /-14 ) minutes for patients receiving midazolam , 28.3 ( + /-25 ) minutes for haloperidol , and 32.2 ( + /-20 ) minutes for lorazepam . Midazolam had a significantly shorter time to sedation than lorazepam and haloperidol ( p haloperidol was 9.9 minutes ( 95 % CI = 0.5 to 19.3 minutes ) . Time to arousal was 81.9 minutes for patients receiving midazolam , 126.5 minutes for haloperidol , and 217.2 minutes for lorazepam . Time to arousal for midazolam was significantly shorter than for both haloperidol and lorazepam ( p difference in time to awakening between midazolam and lorazepam was 135.3 minutes ( 95 % CI = 89 to 182 minutes ) and that between midazolam and haloperidol was 44.6 minutes ( 95 % CI = 9 to 80 minutes ) . There was no significant difference over time by repeated- measures analysis of variance between groups in regard to changes in systolic and diastolic blood pressure ( p = 0.8965 , p = 0.9581 ) , heart rate ( p = 0.5517 ) , respiratory rate ( p = 0.8191 ) , and oxygen saturation ( p = 0.8991 ) . CONCLUSIONS Midazolam has a significantly shorter time to onset of sedation and a more rapid time to arousal than lorazepam or haloperidol . The efficacies of all three drugs appear to be similar",
"The mechanisms underlying the clinical properties of atypical antipsychotics have been postulated to be mediated , in part , by interactions with the 5-HT2A receptor . Recently , it has been recognized that clinical ly effective antipsychotic drugs are 5-HT2A receptor inverse agonists rather than neutral antagonists . In the present study , which is part of the clinical development of the novel , selective 5-HT2A receptor inverse agonist ACP-103 , we applied positron emission tomography ( PET ) with the radiolig and [11C]N-methylspiperone ( [11C]NMSP ) to study the relationship between oral dose , plasma level , and uptake of ACP-103 in living human brain . The safety of drug administration was also assessed . Four healthy volunteers were examined by PET at baseline , and after the oral administration of various single doses of ACP-103 . Two subjects each received 1 , 5 , and 20 mg doses , and two subjects each received 2 , 10 , and 100 mg doses , respectively . ACP-103 was well tolerated . Detectable receptor binding was observed at very low ACP-103 serum levels . Cortical [11C]NMSP binding was found to be dose-dependent and fitted well to the law of mass action . A reduction in binding was detectable after an oral dose of ACP-103 as low as 1 mg , and reached near maximal displacement following the 10 - 20 mg dose . In conclusion , administration of ACP-103 to healthy volunteers was found to be safe and well tolerated , and single oral doses as low as 10 mg were found to fully saturate 5-HT2A receptors in human brain as determined by PET",
"OBJECTIVE While neuroleptics remain the mainstay of drug intervention in the emergency management of psychosis , a variety of agents have received study as alternatives or adjuncts to these drugs in an attempt to improve the safety and efficacy of acute treatment . The purpose s of this study were to investigate the efficacy and safety of alprazolam as a neuroleptic adjunct for schizophrenic patients in psychotic relapse and to clarify the effects of combination treatment on specific aspects of the psychotic process . METHOD Twenty-eight acutely psychotic patients with schizophrenia who were admitted to an emergency psychiatric service were r and omly assigned to treatment with either haloperidol and alprazolam or haloperidol with placebo under double-blind conditions . Drug administration lasted 72 hours . RESULTS Both groups improved significantly . The combination-treated group required significantly less medication and had 56 % fewer dystonic reactions . The addition of alprazolam was most effective for symptoms of excitement and uncooperativeness , particularly in the initial hours of treatment . CONCLUSIONS The combination of alprazolam and haloperidol seems to be the most effective for agitated patients , particularly in the first 48 hours of treatment . It may also result in fewer dystonic reactions",
"Background Agitated or violent patients constitute 10 % of all emergency psychiatric treatment . Management guidelines , the preferred treatment of clinicians and clinical practice all differ . Systematic review s show that all relevant studies are small and none are likely to have adequate power to show true differences between treatments . Worldwide , current treatment is not based on evidence from r and omised trials . In Brazil , the combination haloperidol-promethazine is frequently used , but no studies involving this mix exist . Methods TREC-Rio ( Tranquilização Rápida-Ensaio Clínico [ Translation : Rapid Tranquillisation- Clinical Trial ] ) will compare midazolam with haloperidol-promethazine mix for treatment of agitated patients in emergency psychiatric rooms of Rio de Janeiro , Brazil . TREC-Rio is a r and omised , controlled , pragmatic and open study . Primary measure of outcome is tranquillisation at 20 minutes but effects on other measures of morbidity will also be assessed . TREC-Rio will involve the collaboration of as many health care professionals based in four psychiatric emergency rooms of Rio as possible . Because the design of this trial does not substantially complicate clinical management , and in several aspects simplifies it , the study can be large , and treatments used in everyday practice can be evaluated",
"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",
"Rapid tranquilization is a routinely practice d method of calming agitated psychotic patients by use of neuroleptics , benzodiazepines , or both in combination . Although several studies have examined the efficacy of the three approaches , none have compared these treatments in a prospect i ve , r and omized , double-blind , multicenter trial . Ninety-eight psychotic , agitated , and aggressive patients ( 73 men and 25 women ) were prospect ively enrolled during an 18-month period in emergency departments in five university or general hospitals . Patients were r and omly assigned to receive intramuscular injections of lorazepam ( 2 mg ) , haloperidol ( 5 mg ) , or both in combination . Patients in each treatment group received 1 to 6 injections of the same study drug within 12 hours , based on clinical need . They were evaluated hourly after the first injection until at least 12 hours after the last . Efficacy was assessed on the Agitated Behavior Scale ( ABS ) , a modified Brief Psychiatric Rating Scale ( MBPRS ) , Clinical Global impressions ( CGI ) scale , and an Alertness Scale . Effective symptom reduction was achieved in each treatment group with significant ( P ABS ( hour 1 ) and MBPRS ( hours 2 and 3 ) suggest that tranquilization was most rapid in patients receiving the combination treatment . Study event incidence ( side effects ) did not differ significantly between treatment groups , although patients receiving haloperidol alone tended to have more extrapyramidal system symptoms . The superior results produced by the combination treatment support the use of lorazepam plus haloperidol as the treatment of choice for acute psychotic agitation",
"Background The medical management of aggressive and violent behaviour is a critical situation for which there is little evidence . In order to prepare for a r and omised trial , due to start in the psychiatric emergency rooms of Rio de Janeiro in 2001 , a survey of current practice was necessary . Methods A seven day survey of pharmacological management of aggressive people with psychosis in the emergency rooms of all four public psychiatric hospitals in Rio de Janeiro , Brazil . Results In one hospital data were not available . Of the 764 people with psychosis attending these ERs , 74 were given IM medication for rapid tranquillisation ( 9.7 % , 2.1/week/100,000 ) . A haloperidol-promethazine mix ( with or without other drugs ) was used for the majority of patients ( 83 % ) . Conclusion The haloperidol-promethazine mix , given intramuscularly for rapid tranquilization , is prevalent in Rio , where it is considered both safe and efficient . However , scientific evaluation of all pharmacological approaches to rapid tranquilization of psychotic people is inadequate or incomplete and a r and omized trial of IM haloperidol-promethazine is overdue",
"Agents currently used for acutely agitated patients such as sodium amytal and haloperidol are disadvantageous because of their adverse effects on the respiratory and extrapyramidal systems . Because of this , a rapid , safe , well-absorbed agent such as midazolam would be useful . This study compares the effectiveness of midazolam , sodium amytal , and haloperidol in agitated schizophrenic patients . Five male patients between 28 and 59 years were r and omly assigned to each group . They were administered intramuscularly either 10 mg of haloperidol , 250 mg of sodium amytal , or 5 mg of midazolam . Over a 2-hour period , patients were rated for motor agitation , hostility , auditory hallucinations , and flight of ideas . Both midazolam and sodium amytal were significantly more effective than haloperidol in controlling motor agitation . There were no treatment differences on any other symptom rated . These results indicate that further studies on the use of midazolam to achieve rapid tranquilization would be useful",
"OBJECTIVE To compare the effectiveness of intramuscular olanzapine , ziprasidone , haloperidol plus promethazine , haloperidol plus midazolam and haloperidol alone as the first medication(s ) used to treat patients with agitation and aggressive behavior . METHOD One hundred fifty patients with agitation caused by psychotic or bipolar disorder were r and omly assigned under double-blind conditions to receive olanzapine , ziprasidone , haloperidol plus midazolam , haloperidol plus promethazine or haloperidol alone . The Overt Agitation Severity Scale , Overt Aggression Scale and Ramsay Sedation Scale were applied within 12 hours after the first dosage . RESULTS All medications produced a calming effect within one hour of administration , but only olanzapine and haloperidol reduced agitation by less than 10 points , and only olanzapine reduced aggression by less than four points in the first hour . After twelve hours , only patients treated with haloperidol plus midazolam had high levels of agitation and aggression and also more side effects . Ziprasidone , olanzapine and haloperidol alone had more stable results for agitation control , while ziprasidone , haloperidol plus promethazine and olanzapine had stable results for aggression control . CONCLUSION Olanzapine , ziprasidone , haloperidol plus promethazine , haloperidol plus midazolam and haloperidol were effective in controlling agitation and aggression caused by mental illness over 12 hours . Although all the drugs had advantages and disadvantages , haloperidol plus midazolam was associated with the worst results in all the observed parameters",
"OBJECTIVES To compare the efficacy of sedation , need for rescue sedation , rates of respiratory depression , and complications of droperidol , ziprasidone , and midazolam when used for the treatment of emergency department ( ED ) patients requiring sedation for acute undifferentiated agitation . METHODS A prospect i ve , r and omized , double-blind trial of agitated ED patients requiring emergent sedation was performed . Patients were r and omized to receive droperidol 5 mg , ziprasidone 20 mg , or midazolam 5 mg intramuscularly . Interval measurements were made at 0 , 15 , 30 , 45 , 60 , and 120 minutes and included Altered Mental Status Scale ( AMS ) scores , oxygen saturations , and end-tidal carbon dioxide levels . RESULTS A total of 144 patients were enrolled ; 50 patients received droperidol , 46 received ziprasidone , and 48 received midazolam . Adequate sedation ( mean AMS score midazolam ( mean AMS score , -0.81 ) and 30 minutes for patients receiving droperidol ( mean AMS score , -1.3 ) and ziprasidone ( mean AMS score , -0.74 ) . Rescue medication for sedation was necessary in 38 of 144 patients ( droperidol , 5 of 50 ; ziprasidone , 9 of 46 ; midazolam , 24 of 48 ; p cardiac dysrhythmias were identified in any treatment group . Respiratory depression that clinical ly required treatment with supplemental oxygen occurred in 21 of 144 patients ( droperidol , 4 of 50 ; ziprasidone , 7 of 46 ; midazolam , 10 of 48 ; p = 0.20 ) . No patients required endotracheal intubation . CONCLUSIONS Acutely agitated ED patients se date d with droperidol or ziprasidone required rescue medications to achieve adequate sedation less frequently than those se date d with midazolam . The onset of adequate sedation is delayed with ziprasidone , relative to the other agents",
"BACKGROUND An intramuscular ( IM ) formulation of olanzapine has been developed because there are no rapid-acting IM atypical antipsychotic drugs currently available in the United States for treating acute agitation in patients with schizophrenia . METHODS Recently hospitalized acutely agitated patients with schizophrenia ( N = 270 ) were r and omized to receive 1 to 3 IM injections of olanzapine ( 2.5 , 5.0 , 7.5 , or 10.0 mg ) , haloperidol ( 7.5 mg ) , or placebo within 24 hours . A dose-response relationship for IM olanzapine in the reduction of agitation was assessed by measuring the reduction in Positive and Negative Syndrome Scale Excited Component ( PANSS-EC ) scores 2 hours after the first injection . Safety was assessed by recording adverse events and with extrapyramidal symptom scales and electrocardiograms at 24 hours after the first injection . RESULTS Olanzapine exhibited a dose-response relationship for reduction in agitation ( F(1,179)= 14.4 ; P Mean PANSS-EC reductions 2 hours after the first injection of olanzapine ( 2.5 mg = -5.5 ; 5.0 mg = -8.1 ; 7.5 mg = -8.7 ; 10.0 mg = -9.4 ) were superior to those with placebo ( -2.9 ; P = .01 vs olanzapine at 2.5 mg ; P haloperidol ( -7.5 ) . A dose of 5.0 , 7.5 , or 10.0 mg of olanzapine caused a greater reduction in agitation than placebo 30 minutes after the first injection . There were no differences between treatment groups for hypotension , the most frequently reported adverse event , or for clinical ly relevant changes in the QTc interval . There was a greater incidence of treatment-emergent parkinsonism during treatment with IM haloperidol ( 16.7 % ) than with 2.5 ( P = .03 ) , 5.0 ( P = .03 ) , or 7.5 mg ( P = .01 ) of IM olanzapine ( 0 % ) or with placebo ( 0 % ) ( P = .01 ) . CONCLUSIONS Intramuscular olanzapine at a dose of 2.5 to 10.0 mg per injection exhibits a dose-response relationship in the rapid treatment of acute agitation in patients with schizophrenia and demonstrates a favorable safety profile",
"The combination of haloperidol , 5 mg , and lorazepam , 4 mg , was both effective and safe for managing agitated behavior in an open trial with acutely psychotic patients . The combination also appeared to be superior to its individual components when studied in a r and omized , nonblind trial . The principle of the combined use of antipsychotics and sedative-hypnotics was further tested by comparing two new combinations : thiothixene , 5 mg , and lorazepam , 4 mg , versus haloperidol , 5 mg , and phenobarbital sodium , 130 mg . These combinations had comparable efficacy and safety , and the level of transquilization approached that produced by the haloperidol-lorazepam combination in the preceding studies",
"Two studies tested the reliability and validity of the Overt Agitation Severity Scale ( OASS ) , a new instrument developed to define and objective ly rate the severity of agitated behavior . The authors postulate that agitation should be conceptualized as vocal and motor behaviors on a continuum of expressions that extends from anxiety to aggression . Content validity through expert agreement was achieved in the development of test construction over a 2-year period . Results of two pilot studies ( n = 25 and n = 14 subjects ) established the reliability and validity of the OASS to measure agitation severity . The OASS differs from other agitation scales in that it confines its rating exclusively to observable behavioral manifestations of agitation ",
"After 2 days of drug-free observation , 20 newly admitted psychotic patients received 20 - 35 mg of haloperidol intravenously and 20 patients received 30 - 40 mg of diazepam intravenously . Posttreatment ratings at 4 and 24 hours with the Brief Psychiatric Rating Scale and the Clinical Global Impressions revealed significant improvement in both groups but no significant differences between the two treatments",
"STUDY OBJECTIVE To compare the utility of intramuscular lorazepam ( LZ ) with the combination of intramuscular haloperidol ( HDL ) and LZ to control acutely agitated behavior . DESIGN R and omized double-blind comparison . SETTING Psychiatric emergency service of a large , university-affiliated , municipal hospital . PATIENTS Twenty subjects treated on the psychiatric emergency service . INTERVENTIONS Patients received an injection of either LZ 2 mg ( 11 patients ) or HDL 5 mg plus LZ 2 mg ( 9 patients ) . The Overt Aggression Scale ( OAS ) , visual analog scales reflecting agitation and hostility , and the Clinical Global Impressions ( CGI ) severity scale were administered at baseline and 30 , 60 , 120 , and 180 minutes after the injection . MEASUREMENTS AND MAIN RESULTS Planned data comparisons included categoric assignment of patients as improved , as defined by decreases in outcome measures 60 minutes after the injection , as well as continuous variables up to 180 minutes after the injection . A significantly greater percentage of subjects receiving combined treatment improved on the specific measures 60 minutes after dosing ( p survival analyses showed significant between-group differences in survival curves plotted for the entire study period ( p serious adverse effects occurred in either treatment group . CONCLUSION Our results suggest superior efficacy for HDL-LZ over LZ alone . Categoric tests of improvement at 60 minutes provided the strongest evidence of group differences",
"There are no rapid-acting intramuscular formulations of atypical antipsychotics available for quickly calming an agitated patient with bipolar disorder . In this study , 201 agitated patients with bipolar mania were r and omly assigned to receive one to three injections of the atypical antipsychotic olanzapine ( 10 mg , first two injections ; 5 mg , third injection ) , the benzodiazepine lorazepam ( 2 mg , first two injections ; 1 mg , third injection ) , or placebo ( placebo , first two injections ; olanzapine , 10 mg , third injection ) within a 24-hour period . Agitation was measured at baseline , every 30 minutes for the first 2 hours , and at 24 hours after the first injection using the Positive and Negative Syndrome Scale – Excited Component subscale and two additional agitation scales . At 2 hours after the first injection , patients treated with olanzapine showed a significantly greater reduction in scores on all agitation scales compared with patients treated with either placebo or lorazepam . At 24 hours after the first injection , olanzapine remained statistically superior to placebo in reducing agitation in patients with acute mania , whereas patients treated with lorazepam were not significantly different from those treated with placebo or olanzapine . Furthermore , no significant differences among the three treatment groups were observed in safety measures , including treatment-emergent extrapyramidal symptoms , the incidence of acute dystonia , or QTc interval changes . These findings suggest that intramuscular olanzapine is a safe and effective treatment for reducing acute agitation in patients with bipolar mania",
"In a double-blind , prospect i ve study , 2 mg of intramuscular lorazepam and 5 mg of intramuscular haloperidol were equally effective in controlling aggression , agitation , and assaultive behavior . Although lorazepam and haloperidol produced an equivalent mean decrease in aggression , significantly more subjects who received lorazepam had a greater decrease in aggression ratings than haloperidol recipients ; this effect was independent of sedation . Lorazepam produced significantly fewer extrapyramidal symptoms . These data support the current clinical practice of using lorazepam ( alone , or in combination with a neuroleptic ) for control of acute aggressive and assaultive behavior",
"Abstract Objective To compare two widely used drug treatments for people with aggression or agitation due to mental illness . Design Pragmatic , r and omised clinical trial . Setting Three psychiatric emergency rooms in Rio de Janeiro , Brazil . Subjects 301 aggressive or agitated people . Interventions Open treatment with intramuscular midazolam or intramuscular haloperidol plus promethazine . Main outcome measures Patients tranquil or se date d at 20 minutes . Secondary outcomes : patients tranquil or asleep by 40 , 60 , and 120 minutes ; restrained or given extra drugs within 2 hours ; severe adverse events ; another episode of agitation or aggression ; needing extra visits from doctor during first 24 hours ; overall antipsychotic load in first 24 hours ; and not discharged by two weeks . Results 151 patients were r and omised to midazolam , and 150 to haloperidol-promethazine mix . Follow up for the primary outcome was available for 298 ( 99 % ) : 134/151 ( 89 % ) of patients given midazolam were tranquil or asleep after 20 minutes compared with 101/150 ( 67 % ) of those given haloperidol plus promethazine ( relative risk 1.32 ( 95 % confidence interval 1.16 to 1.49 ) ) . By 40 minutes , midazolam still had a statistically and clinical ly significant 13 % relative advantage ( 1.13 ( 1.01 to 1.26 ) ) . After 1 hour , about 90 % of both groups were tranquil or asleep . One important adverse event occurred in each group : a patient given midazolam had transient respiratory depression , and one given haloperidol-promethazine had a gr and e mal seizure . Conclusions Both treatments were effective . Midazolam was more rapidly sedating than haloperidol-promethazine , reducing the time people are exposed to aggression . Adverse effects and re sources to deal with them should be considered in the choice of the treatment",
"BACKGROUND The pharmacological management of violence in people with psychiatric disorders is under- research ed . AIMS To compare interventions commonly used for controlling agitation or violence in people with serious psychiatric disorders . METHOD We r and omised 200 people to receive intramuscular lorazepam ( 4 mg ) or intramuscular haloperidol ( 10 mg ) plus promethazine ( 25 - 50 mg mix ) . RESULTS At blinded assessment s 4 h later ( 99.5 % follow-up ) , equal numbers in both groups ( 96 % ) were tranquil or asleep . However , 76 % given the haloperidol-promethazine mix were asleep compared with 45 % of those allocated lorazepam ( RR=2.29,95 % CI 1.59 - 3.39 ; NNT=3.2,95 % CI 2.3 - 5.4 ) . The haloperidol-promethazine mix produced a faster onset of tranquillisation/sedation and more clinical improvement over the first 2 h. Neither intervention differed significantly in the need for additional intervention or physical restraints , numbers absconding , or adverse effects . CONCLUSIONS Both interventions are effective for controlling violent/agitated behaviour . If speed of sedation is required , the haloperidol-promethazine combination has advantages over lorazepam",
"Objective . To compare oral risperidone and intramuscular ( IM ) haloperidol , both in combination with IM lorazepam , in the management of acute agitation and psychosis in the medical emergency department . Methods . In this prospect i ve , r and omized , placebo-controlled , double-blind study of 30 patients presenting to the emergency department with acute agitation and /or psychosis , three groups of 10 patients received oral and IM medications : 1 ) 2 mg oral risperidone and 2 mg IM lorazepam ; 2 ) 5 mg oral haloperidol and 2 mg IM lorazepam ; 3 ) oral placebo and 2 mg IM lorazepam . Each treatment group received both an injection and a tablet to reduce treatment group variability . Patients were evaluated using the Brief Psychiatric Rating Scale ( BPRS ) and the Positive and Negative Syndrome Scale ( PANSS ) before receiving medication and at 30 and 90 minutes after medication was administered . The intergroup mean percent reductions in rating scale scores were compared using ANOVA , chi-square , and Kruskal-Wallis tests . Results . There were no statistically significant differences among the groups at any point . The two groups receiving an antipsychotic plus lorazepam showed a trend towards increased symptom reduction compared with the group receiving lorazepam alone , although this trend was not statistically significant . Conclusions . Lorazepam alone was as effective as lorazepam plus haloperidol or lorazepam plus risperidone in this small trial . While not statistically significant , a trend toward better outcomes with combined treatment warrants further study",
"STUDY OBJECTIVE We compare intravenous midazolam and droperidol for the onset of sedation of acutely agitated patients in the emergency department ( ED ) . METHODS This was a double-blind , r and omized , clinical trial set in the ED of a university teaching hospital . Subjects were adults , acutely agitated because of mental illness , intoxication , or both , who received midazolam or droperidol , 5 mg intravenously , every 5 minutes until se date d. We analyzed time to sedation using survival analysis , median times to sedation , and proportions se date d at 5 and 10 minutes . RESULTS Seventy-four patients received midazolam ; 79 patients , droperidol . Survival analysis showed no difference in time to sedation ( hazard ratio 0.86 ; 95 % confidence interval [ CI ] 0.61 to 1.23 ) , P=.42 . Median time to sedation was 6.5 minutes for midazolam ( median dose 5 mg ) and 8 minutes for droperidol ( median dose 10 mg ) , P=.075 ( effect size 1.5 minutes ; 95 % CI 0 to 4 minutes ) . At 5 minutes , 33 of 74 ( 44.6 % ) patients from the midazolam group were adequately se date d compared with 13 of 79 ( 16.5 % ) patients from the droperidol group , a difference of 28.1 % ( 95 % CI 12.9 % to 43.4 % ; P adverse events occurred in the midazolam group and 10 in the droperidol group . Three patients required active airway management ( 3 patients with assisted ventilation and 1 patient intubated ) ; all received midazolam . CONCLUSION There is no difference in onset of adequate sedation of agitated patients using midazolam or droperidol . Patients se date d with midazolam may have an increased need for active airway management",
"The efficacy of a benzodiazepine was compared with that of a neuroleptic for the rapid tranquilization of patients presenting at a psychiatric emergency room service . Thirty-seven highly agitated patients exhibiting psychotic symptoms were r and omly assigned to receive either 2 mg lorazepam or 5 mg haloperidol as needed every 30 min for 4 h. Administration route was either intramuscular injection or oral concentrate . Symptom ratings were conducted each hour using double-blind procedures . Both medications reduced symptom ratings on the Brief Psychiatric Rating Scale and Global Clinical Impression of Overall Symptom Severity Scale . Global Clinical Impression scores for the two medication groups did not differ significantly either at baseline or at 4 h after entry into the study . However , Global Clinical Impression scores of patients in the lorazepam group were less severe at intermittent ratings . The groups did not differ on the Brief Psychiatric Rating Scale at any rating time . No differences were found either in the number of doses administered or in the administration route selected . Given the potential for severe extrapyramidal symptoms developing hours or days after a single dose of haloperidol , lorazepam may provide an excellent alternative for the rapid tranquilization of the acutely agitated psychotic patient in the emergency room setting",
"Distinct calming rather than nonspecific sedation is desirable for the treatment of acute agitation . In 3 double-blind studies , acutely agitated patients with schizophrenia ( N = 311 ) , bipolar mania ( N = 201 ) , or dementia ( N = 206 ) were treated with intramuscular ( 1 - 3 injections/24 hrs ) olanzapine ( 2.5 - 10.0 mg ) , haloperidol ( 7.5 mg ) , lorazepam ( 2.0 mg ) , or placebo . The Agitation-Calmness Evaluation Scale ( ACES ; Eli Lilly and Co. ) and treatment-emergent adverse events assessed sedation . Across all studies , 1 patient ( lorazepam-treated , bipolar ) became unarousable . There were no significant between-group differences in ACES scores of deep sleep or unarousable at any time across . Excluding asleep patients , agitation remained significantly more reduced with olanzapine than placebo ( P adverse events indicative of sedation were not significantly different with olanzapine versus comparators . For the treatment of acute agitation associated with schizophrenia , bipolar mania , or dementia , intramuscular olanzapine-treated patients experienced no more sedation than haloperidol- or lorazepam-treated patients and experienced distinct calming rather than nonspecific sedation",
"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",
"OBJECTIVES Due to inherent dangers and barriers to research in emergency setting s , few data are available to guide clinicians about how best to manage behavioral emergencies . Key constructs such as agitation are poorly defined . This lack of empirical data led us to undertake a survey of expert opinion , results of which were published in the 2001 Expert Consensus Guidelines on the Treatment of Behavioral Emergencies . Several second-generation ( atypical ) antipsychotics ( SGAs ) are now available in new formulations for treating behavioral emergencies ( e.g. , intramuscular [ i.m . ] olanzapine and ziprasidone ; rapidly dissolving tablets of olanzapine and risperidone ) . Critical questions face the field . The SGAs are significantly different from the FGAs and from each other and have not been studied in unselected patients as were the FGAs . Can the SGAs can be thought of as a class , do all antipsychotics have similar anti-agitation effects in different conditions , and , if equally effective , what limits might their safety profiles impose ? Should antipsychotics be used more specifically to treat psychotic conditions , while benzodiazepines ( BNZs ) alone are used nonspecifically ? Few data are available concerning combinations of SGAs and BNZs , and findings concerning the traditional combination of haloperidol plus a BNZ may not be relevant to combinations with SGAs . The culture is also evolving with more emphasis on patient involvement in treatment decisions . An international consensus has been developing that calming rather than sedation is the appropriate endpoint of behavioral emergency interventions . We undertook a new survey of expert opinion to up date recommendations from the earlier survey . METHOD A written survey of 61 questions ( 1,020 options ) was mailed to 50 experts in the field , 48 ( 96 % ) of whom completed it . The survey sought to define level of agitation at which emergency interventions are appropriate , scope of assessment depending on urgency and patients ' ability to cooperate , guiding principles for selecting interventions , and appropriate physical and medication strategies at different levels of diagnostic confidence for a variety of provisional diagnoses and complicating conditions . A modified version of the R AND Corporation 's 9-point scale for rating appropriateness of medical decisions was used to score most options . Consensus was defined as a non-r and om distribution of scores by chi-square \" goodness-of-fit \" test . We assigned a categorical rank ( first line/preferred , second line/alternate , third line/usually inappropriate ) to each option based on the 95 % confidence interval around the mean . Ratings were used to develop guidelines for preferred strategies in key clinical situations . This study received financial support from multiple sponsors , with the panel kept blind to sponsorship to reduce possible bias . Medication ratings were based on responses of only those respondents with direct experience with each drug . In reporting practice patterns , the panel was asked to respond based on actual data rather than estimates . RESULTS The expert panel reached consensus on 78 % of the options rated on the 9-point scale . The responses suggest that physicians can make provisional diagnoses with some confidence and that pharmacological and nonpharmacological interventions are selected differentially based on diagnosis and other salient demographic and medical features . BNZs are recommended when no data are available , when there is no specific treatment ( e.g. , personality disorder ) , or when they may have specific benefits ( e.g. , intoxication ) . No single SGA emerges as a nonspecific replacement for haloperidol ; instead , different SGAs are preferred in various circumstances consistent with current evidence . To the degree that haloperidol is recommended , it is almost always in combination with a BNZ ; haloperidol alone is preferred only in the medically compromised . In contrast , the SGAs are more often recommended for use alone , and the panel would avoid combining BNZs with some SGAs . Oral risperidone alone or combined with a BNZ receives strong support in a variety of situations . Oral olanzapine was rated very similarly to risperidone , with slightly higher ratings than risperidone in situations where it has been studied ( e.g. , schizophrenia , mania ) and slightly lower ratings where it has not been studied or safety may be a concern ; there was less support for combining oral olanzapine with a BNZ . For oral treatment of agitation related to schizophrenia or mania , olanzapine alone , risperidone alone or combined with a BNZ , and haloperidol plus a BNZ are first line , with strong support also for combining divalproex with the antipsychotic for presumed mania . Oral ziprasidone and quetiapine generally received similar second-line ratings in most situations . If a parenteral agent is needed , i.m . olanzapine alone received somewhat more support than i.m . ziprasidone alone ; however , there was more support for i.m . ziprasidone alone or combined with a BNZ than for i.m . olanzapine plus a BNZ , probably reflecting safety concerns . For example , for a provisional diagnosis of schizophrenia , first-line parenteral options are i.m . olanzapine or ziprasidone alone or i.m . haloperidol or ziprasidone combined with a BNZ . Neither of the new parenteral formulations received as much support as traditional agents ( i.m . BNZs , i.m . haloperidol ) when no data are available or the diagnosis involves medical comorbidity or intoxication . When initial intervention with risperidone , ziprasidone , or haloperidol is unsuccessful , the panel recommended adding a BZD to the antipsychotic . However , when initial treatment with olanzapine or quetiapine is unsuccessful , increasing the dosage is recommended . Perphenazine was consistently rated second line and droperidol and chlorpromazine received third-line ratings throughout . CONCLUSIONS Within the limits of expert opinion and with the expectation that future research data will take precedence , these guidelines suggest that the SGAs are now preferred for agitation in the setting of primary psychiatric illnesses but that BNZs are preferred in other situations"
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Background While it is recognized that psychosocial factors are important in the development and progression of musculoskeletal pain and disability , no systematic review has specifically focused on examining the relationship between psychosocial factors and knee pain . We aim ed to systematic ally review the evidence to determine whether psychosocial factors , specifically depression , anxiety and poor mental health , are risk factors for knee pain . Methods Electronic search es of MEDLINE , EMBASE and PsycINFO were performed to identify relevant studies published up to August 2012 using MESH terms and keywords . We included studies that met a set of predefined criteria and two independent review ers assessed the method ological quality of the selected studies . Due to the heterogeneity of the studies , a best evidence synthesis was performed . Results Sixteen studies were included in the review , of which 9 were considered high quality . The study population s were heterogeneous in terms of diagnosis of knee pain . We found a strong level of evidence for a relationship between depression and knee pain , limited evidence for no relationship between anxiety and knee pain , and minimal evidence for no relationship between poor mental health and knee pain . Conclusions Despite the heterogeneity of the included studies , these data show that depression plays a significant role in knee pain , and that a biopsychosocial approach to the management of this condition is integral to optimising outcomes for knee pain
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"OBJECTIVE The combination of chronic musculoskeletal pain and depression is associated with worse clinical outcomes than either condition alone . In this study , we report the predictors of pain intensity and activity interference in primary care patients with co-morbid pain and depression . METHODS This is a secondary data analysis of the 250 persons who participated in a r and omized clinical trial design ed to test the effectiveness of 12 weeks of optimized antidepressant therapy for both depression and pain . Using multivariate linear regression analysis , we assessed the predictive value of baseline self-efficacy , fear of movement , pain beliefs , and demographic and clinical factors on 3-month Grade d Chronic Pain Scale pain intensity and activity interference outcomes . RESULTS In the full model , significant sociodemographic predictors of less activity interference included being non-white ( beta-5.8 , P = 0.04 ) and being employed ( beta-13.3 , P less pain intensity ( beta-5.6 , P = 0.01 ) . As expected , the optimized antidepressant treatment arm was associated with improved outcomes ( pain intensity : beta-3.7 , P = 0.0005 and activity interference : beta-6.4 , P = 0.01 ) . Whereas stronger perceived pain control ( beta 3.6 , P = 0.01 ) was associated with greater activity interference , higher degree of fear of movement ( or fear avoidance ) predicted greater pain intensity ( beta 0.46 , P = 0.04 ) and activity interference ( beta 0.57 , P = 0.05 ) . Neither the location ( low back vs hip/knee ) nor duration of pain were predictive of pain intensity or interference outcomes . CONCLUSION The findings are consistent with a bio-psychosocial model , implicating the need to consider the impact of sociodemographic variables and pain-related beliefs and cognition on pain-related outcomes for patients with co-morbid musculoskeletal pain and depression",
"Objective To assess the effect of lateral wedge insoles compared with flat control insoles on improving symptoms and slowing structural disease progression in medial knee osteoarthritis . Design R and omised controlled trial . Setting Community in Melbourne , Australia . Participants 200 people aged 50 or more with clinical and radiographic diagnosis of mild to moderately severe medial knee osteoarthritis . Interventions Full length 5 degree lateral wedged insoles or flat control insoles worn inside the shoes daily for 12 months . Main outcome measures Primary symptomatic outcome was change in overall knee pain ( past week ) measured on an 11 point numerical rating scale . Primary structural outcome was change in volume of medial tibial cartilage from magnetic resonance imaging scans . Secondary clinical outcomes included changes in measures of pain , function , stiffness , and health related quality of life . Secondary structural outcomes included progression of medial cartilage defects and bone marrow lesions . Results Between group differences did not differ significantly for the primary outcomes of change in overall pain ( −0.3 points , 95 % confidence intervals −1.0 to 0.3 ) and change in medial tibial cartilage volume ( −0.4 mm3 , 95 % confidence interval −15.4 to 14.6 ) , and confidence intervals did not include minimal clinical ly important differences . None of the changes in secondary outcomes showed differences between groups . Conclusion Lateral wedge insoles worn for 12 months provided no symptomatic or structural benefits compared with flat control insoles . Trial registration Australian New Zeal and Clinical Trials Registry ACTR12605000503628 and Clinical Trials.gov NCT00415259",
"OBJECTIVES To determine the effect of newly developed knee pain on general health and physical function of people > or=50 yrs living in the community . METHODS Prospect i ve cohort study of 3907 people aged 50 + registered with three general practice s in North Staffordshire , in the UK . The main outcome measures were self-reported knee pain ; general health and physical function as measured by the Short Form 36 ( SF-36 ) . RESULTS Of those with no knee pain at baseline , 24 % ( n = 501 ) reported it at follow-up . There was a steep decline in physical function in this group ( mean fall in SF-36 score at follow-up 10.3 points ) compared with the 1558 persons who had no knee pain at baseline or follow-up ( mean fall 3.3 ) . Those with knee pain at baseline whose pain had resolved at 3-yr follow-up ( n = 409 ) showed only minor improvements in physical functioning scores at follow-up ( mean improvement -1.3 ) . CONCLUSIONS The onset of knee pain is associated with a substantial and persistent reduction of physical function in older adults living in the community . Since knee pain is common , and reduced physical function in mid to older ages is a strong predictor of future disability and dependency , effective prevention or early treatment of knee pain at these ages is likely to have a major influence on healthy ageing in the population",
"BACKGROUND pain is the leading symptom of osteoarthritis ( OA ) and is often chronic in nature , leading to significant morbidity and decreased quality of life . Duloxetine , a selective serotonin norepinephrine reuptake inhibitor has been demonstrated to have a central ly acting analgesic effect . OBJECTIVES the aim of the present study was to investigate the efficacy of duloxetine in reducing pain in older adults with knee OA . METHODS totally , 288 patients aged 65 years and above with primary knee OA were enrolled in this study . Patients were r and omised 1:1 . Totally , 144 received 60 mg/day of duloxetine HCL and 144 received placebo for 16 weeks . Outcome measures included pain reduction and improvement in physical functioning scores . Pain was assessed using the visual analogue pain scale ( VAS ; 0 - 100 mm ) . The Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) scores were used to assess function . RESULTS two-hundred and seventy four of the 288 patients completed the study . There was a statistically significant reduction in pain and a significant improvement in WOMAC scores at 16 weeks in the duloxetine group versus the placebo group . No serious side effects were reported . CONCLUSIONS the findings of the present study provide evidence for the efficacy and tolerability of duloxetine in reducing pain and subsequently improving function in older adults with knee OA . TRIAL REGISTRATION NCT01425827",
"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",
"UNLABELLED Osteoarthritis pain is a significant problem for our aging population . Antidepressants that are serotonin-norepinephrine reuptake inhibitors are effective for other forms of chronic pain and may provide a new treatment option for osteoarthritis pain . We performed a single-blind , placebo run-in trial of 60 to 90 mg of duloxetine in 25 subjects with activity-limiting osteoarthritis pain . Each subject received 2 weeks of placebo followed by 10 weeks of duloxetine . The primary outcome was reduction in average pain intensity between 2 and 12 weeks for subjects completing the trial . Average pain on the Brief Pain Inventory ( BPI ) was 5.7 at baseline , 4.8 after the 2-week placebo run-in , and 3.5 at 12 weeks for the 17 patients completing the trial ( 28 % decrease between 2 and 12 weeks , P = .122 ) . Eight of 15 study completers who had nonmissing BPI results ( 53 % ) reported at least 30 % pain reduction between weeks 2 and 12 . The Western Ontario McMaster Osteoarthritis Index ( WOMAC ) pain score at baseline was 2.3 , 1.8 after 2 weeks , and 1.3 after 12 weeks ( 30 % decrease between 2 and 12 weeks , P = .018 ) . Ten of 17 patients ( 59 % ) reported at least 30 % pain relief between weeks 2 and 12 on the WOMAC . Significant improvements in self-reported physical and role function were reported but observed physical function did not improve . PERSPECTIVE Duloxetine did not significantly reduce pain intensity on the BPI but did improve pain intensity and self-reported function on the WOMAC . Duloxetine warrants further investigation as a novel treatment for osteoarthritis pain",
"OBJECTIVE To investigate the relationship between anxiety and depression and reporting of knee pain in the community . METHODS Subjects ( n = 374 ) were community volunteers aged 40 years and above who are participants in the Baltimore Longitudinal Study of Aging , a prospect i ve multidisciplinary research study of normative aging . Knee pain was defined by the First National Health and Nutrition Examination Survey question \" have you ever had pain in or around your knee on most days for at least one month ? \" ; anxiety and depression were measured by the relevant subscales of the Arthritis Impact Measurement Scales question naire . All subjects had st and ing anteroposterior radiographs , read for Kellgren and Lawrence ( K + L ) grade . RESULTS After adjustment for age , women reporting \" ever \" knee pain had significantly higher anxiety scores than those reporting \" never \" pain ( 3.06 + /- 0.26 versus 2.35 + /- 0.17 ; P = 0.025 ) . Pain reporting was related neither to anxiety scores in men , nor to depression in either sex . Analysis stratified by radiographic severity , adjusted for age and gender , showed that differences in anxiety were confined to those reporting knee pain in the absence of radiographic change ( i.e. , K + L grade 0 ) . CONCLUSIONS In the community , women reporting knee pain in the absence of radiographic osteoarthritis have higher anxiety scores than those without pain . Depression was not significantly related to knee pain in this population . Psychosocial factors may explain some of the discrepancy between reported knee pain and structural change as seen on x-ray",
"UNLABELLED Pain and depression are the most prevalent physical and psychological symptom-based disorders , respectively , and co-occur 30 to 50 % of the time . However , their reciprocal relationship and potentially causative effects on one another have been inadequately studied . Longitudinal data analysis involving 500 primary care patients with persistent back , hip , or knee pain were enrolled in the Stepped Care for Affective Disorders and Musculoskeletal Pain ( SCAMP ) study . Half of the participants had comorbid depression and were r and omized to a stepped care intervention ( n = 123 ) or treatment as usual ( n = 127 ) . Another 250 nondepressed patients with similar pain were followed in a parallel cohort . Outcomes were assessed at baseline , 3 , 6 , and 12 months . Mixed effects model repeated measures ( MMRM ) multivariable analyses were conducted to determine if change in pain severity predicted subsequent depression severity , and vice versa . Change in pain was a strong predictor of subsequent depression severity ( t-value = 6.63 , P change in depression severity was an equally strong predictor of subsequent pain severity ( t-value = 7.28 , P pain and depression have strong and similar effects on one another when assessed longitudinally over 12 months . PERSPECTIVE This study strengthens the evidence for a bidirectional and potentially causative influence of pain and depression on one another . A change in severity of either symptom predicts subsequent severity of the other symptom . Thus , recognition and management of both conditions may be warranted , particularly when treatment focused on 1 condition is not leading to an optimal response",
"BACKGROUND Previous cross-sectional studies have shown an association between pain and depression , but it is unclear which comes first . Our objectives were to determine the temporal relationship between pain and depression , and to investigate whether these two syndromes share predictors . METHODS A 2-year , population -based , prospect i ve , observational study of 3654 older adults aged 65 and above selected from the English Longitudinal Study of Ageing Waves 1 and 2 . Pain , 8-item CES-D , socio-economic variables , health indicators , and social support were assessed . RESULTS Logistic regression analyses revealed that pain at baseline was an independent predictor of becoming depressed 2 years later and depression at baseline was a predictor of developing pain at 2 years . Individuals with mobility disability and poor sight were at risk of becoming depressed as well as developing pain . Moreover , older age , poor sight and mobility disability were common predictors for pain and depression after baselines of both syndromes were adjusted . CONCLUSION Individuals who develop pain or depression are at risk for developing the other , with a spiraling risk of pain and depression . Because pain and depression share predictors , individuals who are at high risk of developing these two outcomes can be identified by aged care service practitioners",
"OBJECTIVE To examine the prevalence , correlates and prospect i ve impact of musculoskeletal pain on physical and psychological function in a population health survey of elderly Chinese men and women . STUDY DESIGN Cohort study . METHODS Four thous and men and women , aged 65 years and over , living in the community in Hong Kong took part in this study . A question naire to determine demographics , socio-economic status , medical history , smoking , alcohol intake and level of physical activity was administered by an interviewer . Participants were asked about the presence of pain in the back , neck , hip and knee in the past 12 months . They were re-interviewed after 4 years of follow-up to document physical performance measures , psychological function and occurrence of falls , fractures and mortality . RESULTS Overall , back pain was most prevalent ( 48 % ) , followed by knee ( 31 % ) , neck ( 22.5 % ) and hip ( 8.9 % ) pain ; the values was nearly twice as high in women compared with men for all sites . The presence of pain was not correlated with age , but was associated with various measures of socio-economic status as well as comorbidities . Baseline prevalence of pain was related to physical performance and quality -of-life measures , and fracture incidence after 4 years of follow-up . CONCLUSION Musculoskeletal pain is prevalent among elderly men and women , being much higher in the latter , giving rise to considerable functional and psychological impairments . Osteoporosis and osteoarthritis are likely to be the main underlying causes . The condition may be considered part of the frailty syndrome , and in this context , prevention and management represent major public health challenges",
"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",
"BACKGROUND Pain and depression are common in old age but the reciprocal relationship between pain and depression has not been established in a single study . Moreover , few studies have addressed this issue in a primary care setting . The purpose s of this study were to examine the reciprocal relationship between pain and depression and to identify whether social support , functional disability or social functioning mediated the link between pain and depression among Hong Kong Chinese elderly primary care patients . METHOD Subjects were 318 patients assessed by a trained assessor with MDS-HC at baseline and these subjects were r and omly selected from attendants of three r and omly selected elderly health centers in Hong Kong . These patients were re-assessed one year after baseline evaluation . RESULTS Multiple regression analyses revealed that pain at baseline significantly predicted depression at 12-month follow-up assessment when age , gender , martial status , education , and depression at baseline were adjusted for , but depression at baseline was not associated with pain at 12-months after baseline measure while controlling for age , gender , martial status , education , and pain at baseline . However , depression did predict the onset of pain . Moreover , social support , physical disability or social functioning did not mediate the impact of pain on depression . CONCLUSIONS These data suggest that pain is an important predictor of depression in elderly primary care patients . Therefore , aged care service practitioners must take this risk factor into consideration in their preventive intervention and treatment for psychological well-being",
"OBJECTIVE To evaluate the efficacy and safety of duloxetine in the treatment of chronic pain due to osteoarthritis of the knee . METHODS This was a 13-week , r and omized , double-blind , placebo-controlled trial in patients meeting American College of Rheumatology clinical and radiographic criteria for osteoarthritis of the knee . At baseline , patients were required to have a ≥ 4 weekly mean of the 24-hour average pain ratings . Patients were r and omized to either duloxetine 60 mg once daily ( QD ) or placebo . At week 7 , the duloxetine dosage was increased , in a blinded fashion , to 120-mg QD in patients reporting was Brief Pain Inventory ( BPI ) 24-hour average pain . Secondary efficacy measures included Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) ; Clinical Global Impressions of Severity ( CGI-S ) . Safety and tolerability was also assessed . RESULTS Of the total ( n = 256 ) patients , 111 ( 86.7 % ) in placebo group and 93 ( 72.7 % ) in duloxetine group completed the study . Patients treated with duloxetine had significantly ( P ≤ 0.001 ) greater improvement at all time points on BPI average pain and had significantly greater improvement on BPI pain severity ratings ( P ≤ 0.05 ) , WOMAC total ( P = 0.044 ) and physical functioning scores ( P = 0.016 ) , and CGI-S ( P = 0.009 ) at the study endpoint . Frequency of treatment-emergent nausea , constipation , and hyperhidrosis were significantly higher in the duloxetine group ( P ≤ 0.05 ) . Significantly more duloxetine-treated patients discontinued the trial because of adverse events ( P = 0.002 ) . CONCLUSIONS Treatment with duloxetine 60 mg to 120 mg QD was associated with significant pain reduction and improved function in patients with pain due to osteoarthritis of the knee",
"& NA ; To determine the impact of occupational psychological/social and mechanical factors on neck pain , a prospect i ve cohort study with a follow‐up period of 2 years was conducted with a sample of Norwegian employees . The following design s were tested : ( i ) cross‐sectional analyses at baseline ( n = 4569 ) and follow‐up ( n = 4122 ) , ( ii ) prospect i ve analyses with baseline predictors , ( iii ) prospect i ve analyses with average exposure over time [ ( T1 + T2)/2 ] as predictor , and ( iv ) prospect i ve analyses with measures of change in exposure from T1 to T2 as predictors . A total of 2419 employees responded to both the baseline and follow‐up question naire . Data were analyzed using ordinal logistic regression . After adjustment for age , sex , neck pain at T1 , and other exposure factors that had been estimated to be confounders , the most consistent risk factors were role conflict ( highest OR 2.97 , 99 % CI : 1.29–6.74 ) and working with arms raised to or above shoulder level ( highest OR 1.37 , 99 % CI : 1.05–1.78 ) . The most consistent protective factors were empowering leadership ( lowest OR 0.53 , 99 % CI : 0.35–0.81 ) and decision control ( lowest OR 0.60 , 99 % CI : 0.36–1.00 ) . Hence , psychological and social factors are important precursors of neck pain , along with mechanical factors . Although traditional factors such as quantitative dem and s and decision control play a part in the etiology of neck pain at work , in this study several new factors emerged as more important"
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Background Meta-analyses of short-term studies indicate favorable effects of higher protein vs. lower protein diets on health outcomes like adiposity or cardiovascular risk factors , but their long-term effects are unknown . Methods Electronic data bases ( MEDLINE , EMBASE , Cochrane Trial Register ) were search ed up to August 2012 with no restriction to language or calendar date . A r and om effect meta- analysis was performed using the Software package by the Cochrane Collaboration Review Manager 5.1 . Sensitivity analysis was performed for RCTs with a Jadad Score ≥3 , and excluding type 2 diabetic subjects ( T2D ) . Results 15 RCTs met all objectives and were included in the present meta- analysis . No significant differences were observed for weight , waist circumference , fat mass , blood lipids ( i.e. total cholesterol , LDL-cholesterol , HDL-cholesterol , triacylglycerols ) , C-reactive protein , diastolic and systolic blood pressure , fasting glucose and glycosylated hemoglobin . In contrast , improvements of fasting insulin was significantly more pronounced following high protein diets as compared to the low protein counterparts ( weighted mean difference : -0.71 μIU/ml , 95 % CI -1.36 to -0.05 , p = 0.03 ) . Sensitivity analysis of high quality RCTs confirmed the data of the primary analyses , while exclusion of studies with diabetic subjects result ed in an additional benefit of high-protein diets with respect to a more marked increase in HDL-cholesterol . Conclusion According to the present meta- analysis of long-term RCTs , high-protein diets exerted neither specific beneficial nor detrimental effects on outcome markers of obesity , cardiovascular disease or glycemic control . Thus , it seems premature to recommend high-protein diets in the management of overweight and obesity
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"CONTEXT Popular diets , particularly those low in carbohydrates , have challenged current recommendations advising a low-fat , high-carbohydrate diet for weight loss . Potential benefits and risks have not been tested adequately . OBJECTIVE To compare 4 weight-loss diets representing a spectrum of low to high carbohydrate intake for effects on weight loss and related metabolic variables . DESIGN , SETTING , AND PARTICIPANTS Twelve-month r and omized trial conducted in the United States from February 2003 to October 2005 among 311 free-living , overweight/obese ( body mass index , 27 - 40 ) nondiabetic , premenopausal women . INTERVENTION Participants were r and omly assigned to follow the Atkins ( n = 77 ) , Zone ( n = 79 ) , LEARN ( n = 79 ) , or Ornish ( n = 76 ) diets and received weekly instruction for 2 months , then an additional 10-month follow-up . MAIN OUTCOME MEASURES Weight loss at 12 months was the primary outcome . Secondary outcomes included lipid profile ( low-density lipoprotein , high-density lipoprotein , and non-high-density lipoprotein cholesterol , and triglyceride levels ) , percentage of body fat , waist-hip ratio , fasting insulin and glucose levels , and blood pressure . Outcomes were assessed at months 0 , 2 , 6 , and 12 . The Tukey studentized range test was used to adjust for multiple testing . RESULTS Weight loss was greater for women in the Atkins diet group compared with the other diet groups at 12 months , and mean 12-month weight loss was significantly different between the Atkins and Zone diets ( P 12-month weight loss was as follows : Atkins , -4.7 kg ( 95 % confidence interval [ CI ] , -6.3 to -3.1 kg ) , Zone , -1.6 kg ( 95 % CI , -2.8 to -0.4 kg ) , LEARN , -2.6 kg ( -3.8 to -1.3 kg ) , and Ornish , -2.2 kg ( -3.6 to -0.8 kg ) . Weight loss was not statistically different among the Zone , LEARN , and Ornish groups . At 12 months , secondary outcomes for the Atkins group were comparable with or more favorable than the other diet groups . CONCLUSIONS In this study , premenopausal overweight and obese women assigned to follow the Atkins diet , which had the lowest carbohydrate intake , lost more weight at 12 months than women assigned to follow the Zone diet , and had experienced comparable or more favorable metabolic effects than those assigned to the Zone , Ornish , or LEARN diets [ corrected ] While questions remain about long-term effects and mechanisms , a low-carbohydrate , high-protein , high-fat diet may be considered a feasible alternative recommendation for weight loss . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00079573",
"Aims /hypothesisTo compare the effectiveness of low-fat high-protein and low-fat high-carbohydrate dietary advice on weight loss , using group-based interventions , among overweight people with type 2 diabetes . Study design Multicentre parallel ( 1:1 ) design , blinded r and omised controlled trial . Methods Individuals with type 2 diabetes aged 30–75 years and a BMI > 27 kg/m2 were r and omised , by an independent statistician using sequentially numbered sealed envelopes , to be prescribed either a low-fat high-protein ( 30 % of energy as protein , 40 % as carbohydrate , 30 % as fat ) or a low-fat high-carbohydrate ( 15 % of energy as protein , 55 % as carbohydrate , 30 % as fat ) diet . Participants attended 18 group sessions over 12 months . Primary outcomes were change in weight and waist circumference assessed at baseline , 6 and 12 months . Secondary outcomes were body fatness , glycaemic control , lipid profile , blood pressure and renal function . A further assessment was undertaken 12 months after the intervention . Research assessors remained blinded to group allocation throughout . Intention-to-treat analysis was performed . Results A total of 419 participants were enrolled ( mean ± SD age 58 ± 9.5 years , BMI 36.6 ± 6.5 kg/m2 and HbA1c 8.1 ± 1.2 % ( 65 mmol/mol ) ) . The study was completed by 70 % ( 294/419 ) . No differences between groups were found in change in weight or waist circumference during the intervention phase or the 12-month follow-up . Both groups had lost weight ( 2–3 kg , p their waist circumference ( 2–3 cm , p weight loss for the following 12 months . By 6 months , the difference in self-reported dietary protein between groups was small ( 1.1 % total energy ; p outcomes : body fatness , HbA1c , lipids , blood pressure and renal function . There were no important adverse effects . Conclusions /interpretationIn a ‘ real-world ’ setting , prescription of an energy-reduced low-fat diet , with either increased protein or carbohydrate , results in similar modest losses in weight and waist circumference over 2 years . Trial registration : Australia New Zeal and Clinical Trials Register ACTRN12606000490572 Funding : The Health Research Council of New Zeal and ( 06/337 )",
"Cl aims about the merits or risks of carbohydrate ( CHO ) vs. protein for weight loss diets are extensive , yet the ideal ratio of dietary carbohydrate to protein for adult health and weight management remains unknown . This study examined the efficacy of two weight loss diets with modified CHO/protein ratios to change body composition and blood lipids in adult women . Women ( n = 24 ; 45 to 56 y old ) with body mass indices > 26 kg/m(2 ) were assigned to either a CHO Group consuming a diet with a CHO/protein ratio of 3.5 ( 68 g protein/d ) or a Protein Group with a ratio of 1.4 ( 125 g protein/d ) . Diets were isoenergetic , providing 7100 kJ/d , and similar amounts of fat ( approximately 50 g/d ) . After consuming the diets for 10 wk , the CHO Group lost 6.96 + /- 1.36 kg body weight and the Protein Group lost 7.53 + /- 1.44 kg . Weight loss in the Protein Group was partitioned to a significantly higher loss of fat/lean ( 6.3 + /- 1.2 g/g ) compared with the CHO Group ( 3.8 + /- 0.9 ) . Both groups had significant reductions in serum cholesterol ( approximately 10 % ) , whereas the Protein Group also had significant reductions in triacylglycerols ( TAG ) ( 21 % ) and the ratio of TAG/HDL cholesterol ( 23 % ) . Women in the CHO Group had higher insulin responses to meals and postpr and ial hypoglycemia , whereas women in the Protein Group reported greater satiety . This study demonstrates that increasing the proportion of protein to carbohydrate in the diet of adult women has positive effects on body composition , blood lipids , glucose homeostasis and satiety during weight loss",
"BACKGROUND It is not clear whether varying the protein-to-carbohydrate ratio of weight-loss diets benefits body composition or metabolism . OBJECTIVE The objective was to compare the effects of 2 weight-loss diets differing in protein-to-carbohydrate ratio on body composition , glucose and lipid metabolism , and markers of bone turnover . DESIGN A parallel design included either a high-protein diet of meat , poultry , and dairy foods ( HP diet : 27 % of energy as protein , 44 % as carbohydrate , and 29 % as fat ) or a st and ard-protein diet low in those foods ( SP diet : 16 % of energy as protein , 57 % as carbohydrate , and 27 % as fat ) during 12 wk of energy restriction ( 6 - 6.3 MJ/d ) and 4 wk of energy balance ( approximately 8.2 MJ/d ) . Fifty-seven overweight volunteers with fasting insulin concentrations > 12 mU/L completed the study . RESULTS Weight loss ( 7.9 + /- 0.5 kg ) and total fat loss ( 6.9 + /- 0.4 kg ) did not differ between diet groups . In women , total lean mass was significantly ( P = 0.02 ) better preserved with the HP diet ( -0.1 + /- 0.3 kg ) than with the SP diet ( -1.5 + /- 0.3 kg ) . Those fed the HP diet had significantly ( P glycemic response at weeks 0 and 16 than did those fed the SP diet . After weight loss , the glycemic response decreased significantly ( P serum triacylglycerol concentrations was significantly ( P HP diet group ( 23 % ) than in the SP diet group ( 10 % ) . Markers of bone turnover , calcium excretion , and systolic blood pressure were unchanged . CONCLUSION Replacing carbohydrate with protein from meat , poultry , and dairy foods has beneficial metabolic effects and no adverse effects on markers of bone turnover or calcium excretion",
"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 : To study the effect on weight loss in obese subjects by replacement of carbohydrate by protein in ad libitum consumed fat-reduced diets . DESIGN : R and omized dietary intervention study over six months comparing two ad libitum fat reduced diets ( 30 % of total energy ) strictly controlled in composition : High-carbohydrate ( HC , protein 12 % of total energy ) or high-protein ( HP , protein 25 % of total energy ) . SETTING AND PARTICIPANTS : Subjects were 65 healthy , overweight and obese subjects ( 50 women , 15 men , aged 18–55 y ) r and omly assigned to HC ( n=25 ) , HP ( n=25 ) or a control group ( C , n=15 ) . All food was provided by self- selection in a shop at the department , and compliance to the diet composition was evaluated by urinary nitrogen excretion . MAIN OUTCOME MEASURE : Change in body weight , body composition and blood lipids . RESULTS : More than 90 % completed the trial . Weight loss after six months was 5.1 kg in the HC group and 8.9 kg in the HP group ( difference 3.7 kg , 95 % confidence interval (CI)(1.3–6.2 kg ) P and fat loss was 4.3 kg and 7.6 kg , respectively ( difference 3.3 kg ( 1.1–5.5 kg ) P lost > 10 kg in the HP group ( 35 % ) than in the HC group ( 9 % ) . The HP diet only decreased fasting plasma triglycerides and free fatty acids significantly . CONCLUSIONS : Replacement of some dietary carbohydrate by protein in an ad libitum fat-reduced diet , improves weight loss and increases the proportion of subjects achieving a clinical ly relevant weight loss . More freedom to choose between protein-rich and complex carbohydrate-rich foods may allow obese subjects to choose more lean meat and dairy products , and hence improve adherence to low-fat diets in weight reduction programs",
"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 compare the long-term compliance and effects of two low-fat diets differing in carbohydrate to protein ratio on body composition and biomarkers of cardiovascular disease risk in obese subjects with hyperinsulinemia . DESIGN : Outpatient , parallel , clinical intervention study of two groups of subjects r and omly assigned to either a st and ard protein ( SP ; 15 % protein , 55 % carbohydrate ) or high-protein ( HP ; 30 % protein , 40 % carbohydrate ) diet , during 12 weeks of energy restriction ( ∼6.5 MJ/day ) and 4 weeks of energy balance ( ∼8.3 MJ/day ) . Subsequently , subjects were asked to maintain the same dietary pattern for the succeeding 52 weeks with minimal professional support . SUBJECTS : A total of 58 obese , nondietetic subjects with hyperinsulinemia ( 13 males/45 females , mean age 50.2 y , mean body mass index ( BMI ) 34.0 kg/m2 , mean fasting insulin 17.8 mU/l ) participated in the study . MEASUREMENTS : Body composition , blood pressure , blood lipids , fasting glucose , insulin , CRP and sICAM-1 were measured at baseline and at weeks 16 and 68 . Urinary urea/creatinine ratio was measured at baseline , week 16 and at 3 monthly intervals thereafter . RESULTS : In total , 43 subjects completed the study with similar dropouts in each group ( P=0.76 ) . At week 68 , there was net weight loss ( SP −2.9±3.6 % , HP −4.1±5.8 % ; P fat loss ( P significantly increased HDL cholesterol concentrations ( P and decreased fasting insulin , insulin resistance , sICAM-1 and CRP levels ( P ) . Protein intake was significantly greater in HP during the initial 16 weeks ( P achieved net weight loss and improvements in cardiovascular risk factors ",
"Objective : High-carbohydrate (HC)–high-fibre diets are recommended for weight loss and for treating and preventing diseases such as diabetes and cardiovascular disease . We report a r and omised trial comparing high-fat ( HF ) and high-protein ( HP ) diets with the conventional approach . Research design and methods : A total of 93 overweight insulin-resistant women received advice following r and omisation to HF , HP or HC dietary regimes , to achieve weight loss followed by weight maintenance over 12 months . Weight , body composition and measures of carbohydrate and lipid metabolism were investigated . Results : Retention rates were 93 % for HP and 75 % for HC and HF . Features of the metabolic syndrome improved in all groups during the first 6 months , to a greater extent on HF and HP than an HC . During the second 6 months the HF group had increases in waist circumference ( mean difference 4.4 cm ( 95 % CI 3.0 , 5.8 ) ) , fat mass ( 2.3 kg ( 1.5 , 3.1 ) ) , triglycerides ( 0.28 mmol/l ( 0.09 , 0.46 ) ) and 2 h glucose ( 0.70 mmol/l ( 0.22 , 1.18 ) ) . Overall there was substantial sustained improvement in waist circumference , triglycerides and insulin in the HP group and sustained but more modest changes on HC . Dietary compliance at 12 months was poor in all groups . Conclusions : HP and HC approaches appear to be appropriate options for insulin-resistant individuals . When recommending HP diets appropriate composition of dietary fat must be ensured . HC diet recommendations must include advice regarding appropriate high-fibre , low glycaemic index foods",
"BACKGROUND Limited evidence suggests that a higher ratio of protein to carbohydrate during weight loss has metabolic advantages . OBJECTIVE The objective was to evaluate the effects of a diet with a high ratio of protein to carbohydrate during weight loss on body composition , cardiovascular disease risk , nutritional status , and markers of bone turnover and renal function in overweight women . DESIGN The subjects were r and omly assigned to 1 of 2 isocaloric 5600-kJ dietary interventions for 12 wk according to a parallel design : a high-protein ( HP ) or a high-carbohydrate ( HC ) diet . RESULTS One hundred women with a mean ( + /-SD ) body mass index ( in kg/m(2 ) ) of 32 + /- 6 and age of 49 + /- 9 y completed the study . Weight loss was 7.3 + /- 0.3 kg with both diets . Subjects with high serum triacylglycerol ( > 1.5 mmol/L ) lost more fat mass with the HP than with the HC diet ( x + /- SEM : 6.4 + /- 0.7 and 3.4 + /- 0.7 kg , respectively ; P = 0.035 ) and had a greater decrease in triacylglycerol concentrations with the HP ( -0.59 + /- 0.19 mmol/L ) than with the HC ( -0.03 + /- 0.04 mmol/L ) diet ( P = 0.023 for diet x triacylglycerol interaction ) . Triacylglycerol concentrations decreased more with the HP ( 0.30 + /- 0.10 mmol/L ) than with the HC ( 0.10 + /- 0.06 mmol/L ) diet ( P = 0.007 ) . Fasting LDL-cholesterol , HDL-cholesterol , glucose , insulin , free fatty acid , and C-reactive protein concentrations decreased with weight loss . Serum vitamin B-12 increased 9 % with the HP diet and decreased 13 % with the HC diet ( P Folate and vitamin B-6 increased with both diets ; homocysteine did not change significantly . Bone turnover markers increased 8 - 12 % and calcium excretion decreased by 0.8 mmol/d ( P Creatinine clearance decreased from 82 + /- 3.3 to 75 + /- 3.0 mL/min ( P = 0.002 ) . CONCLUSION An energy-restricted , high-protein , low-fat diet provides nutritional and metabolic benefits that are equal to and sometimes greater than those observed with a high-carbohydrate diet",
"CONTEXT The scarcity of data addressing the health effects of popular diets is an important public health concern , especially since patients and physicians are interested in using popular diets as individualized eating strategies for disease prevention . OBJECTIVE To assess adherence rates and the effectiveness of 4 popular diets ( Atkins , Zone , Weight Watchers , and Ornish ) for weight loss and cardiac risk factor reduction . DESIGN , SETTING , AND PARTICIPANTS A single-center r and omized trial at an academic medical center in Boston , Mass , of overweight or obese ( body mass index : mean , 35 ; range , 27 - 42 ) adults aged 22 to 72 years with known hypertension , dyslipidemia , or fasting hyperglycemia . Participants were enrolled starting July 18 , 2000 , and r and omized to 4 popular diet groups until January 24 , 2002 . INTERVENTION A total of 160 participants were r and omly assigned to either Atkins ( carbohydrate restriction , n=40 ) , Zone ( macronutrient balance , n=40 ) , Weight Watchers ( calorie restriction , n=40 ) , or Ornish ( fat restriction , n=40 ) diet groups . After 2 months of maximum effort , participants selected their own levels of dietary adherence . MAIN OUTCOME MEASURES One-year changes in baseline weight and cardiac risk factors , and self-selected dietary adherence rates per self-report . RESULTS Assuming no change from baseline for participants who discontinued the study , mean ( SD ) weight loss at 1 year was 2.1 ( 4.8 ) kg for Atkins ( 21 [ 53 % ] of 40 participants completed , P = .009 ) , 3.2 ( 6.0 ) kg for Zone ( 26 [ 65 % ] of 40 completed , P = .002 ) , 3.0 ( 4.9 ) kg for Weight Watchers ( 26 [ 65 % ] of 40 completed , P low-density lipoprotein/high-density lipoprotein ( HDL ) cholesterol ratio by approximately 10 % ( all P blood pressure or glucose at 1 year . Amount of weight loss was associated with self-reported dietary adherence level ( r = 0.60 ; P total/HDL cholesterol , C-reactive protein , and insulin were significantly associated with weight loss ( mean r = 0.36 , 0.37 , and 0.39 , respectively ) with no significant difference between diets ( P = .48 , P = .57 , P = .31 , respectively ) . CONCLUSIONS Each popular diet modestly reduced body weight and several cardiac risk factors at 1 year . Overall dietary adherence rates were low , although increased adherence was associated with greater weight loss and cardiac risk factor reductions for each diet group",
"Diets with increased protein and reduced carbohydrates ( PRO ) are effective for weight loss , but the long-term effect on maintenance is unknown . This study compared changes in body weight and composition and blood lipids after short-term weight loss ( 4 mo ) followed by weight maintenance ( 8 mo ) using moderate PRO or conventional high-carbohydrate ( CHO ) diets . Participants ( age = 45.4 + /- 1.2 y ; BMI = 32.6 + /- 0.8 kg/m(2 ) ; n = 130 ) were r and omized to 2 energy-restricted diets ( -500 kcal/d or -2093 kJ/d ) : PRO with 1.6 g x kg(-1 ) x d(-1 ) protein and 0.8 g x kg(-1 ) x d(-1 ) protein , > 220 g/d carbohydrates . At 4 mo , the PRO group had lost 22 % more fat mass ( FM ) ( -5.6 + /- 0.4 kg ) than the CHO group ( -4.6 + /- 0.3 kg ) but weight loss did not differ between groups ( -8.2 + /- 0.5 kg vs. -7.0 + /- 0.5 kg ; P = 0.10 ) . At 12 mo , the PRO group had more participants complete the study ( 64 vs. 45 % , P body composition ; however , weight loss did not differ between groups ( -10.4 + /- 1.2 kg vs. -8.4 + /- 0.9 kg ; P = 0.18 ) . Using a compliance criterion of participants attaining > 10 % weight loss , the PRO group had more participants ( 31 vs. 21 % ) lose more weight ( -16.5 + /- 1.5 vs. -12.3 + /- 0.9 kg ; P FM ( -11.7 + /- 1.0 vs. -7.9 + /- 0.7 kg ; P CHO diet reduced serum cholesterol and LDL cholesterol compared with PRO ( P PRO had sustained favorable effects on serum triacylglycerol ( TAG ) , HDL cholesterol ( HDL-C ) , and TAG : HDL-C compared with CHO at 4 and 12 mo ( P FM loss and body composition improvement during initial weight loss and long-term maintenance and produced sustained reductions in TAG and increases in HDL-C compared with the CHO diet",
"Our aim was to determine whether short-term weight loss on a low-carbohydrate/low-saturated fat diet improved endothelial function compared with a conventional high-carbohydrate diet , as this diet is expected to lower both blood glucose and LDL-cholesterol . In a r and omised parallel design of two energy-restricted diets in an outpatient setting , thirty-six subjects ( BMI 33 ( sem 4 ) kg/m2 ) were r and omised to a low- or high-carbohydrate diet both low in saturated fat . Flow-mediated dilatation ( FMD ) , fasting glucose , insulin , lipids , adiponectin and adhesion molecules were measured at baseline , during weight loss and at 52 weeks . FMD did not change with either diet ( 5.2 ( sem 0.6 ) to 5.5 ( sem 0.6 ) % ) despite weight loss of 5 % and significant reductions in glucose and insulin and LDL-cholesterol and was not different after sustained weight loss of 5 % at 52 weeks . Adiponectin fell by 6 % at 12 weeks ( P = 0.1 ) with weight loss but rose by 17 % at 12 months ( P weight loss . There were no effects of diet . In contradistinction , adhesion molecules fell at 12 weeks , vascular cell adhesion molecule-1 by 14 % and intracellular adhesion molecule-1 by 13 % ( both P in HDL ( r 0.778 , P glucose ( r - 0.563 , P = 0.057 ) . In summary , weight loss does not improve FMD . Novel cardiovascular risk factors improved at 12 weeks but the improvement in adiponectin was delayed",
"BACKGROUND : We have previously reported that a fat-reduced high-protein diet had more favourable effects on body weight loss over 6 months than a medium-protein diet . OBJECTIVE : To extend this observation by a further 6–12 months less stringent intervention and a 24 months follow-up . DESIGN : A r and omised 6 months strictly controlled dietary intervention followed by 6–12 months dietary counselling period , and a subsequent 24 months follow-up , comparing an ad libitum , fat-reduced diet ( 30 % of energy ) either high in protein ( 25 % of energy , HP ) or medium in protein ( 12 % of energy , MP).SUBJECTS : A total of 50 overweight and obese subjects ( age : 19–55 y ; BMI : 26–34 kg/m2 ) . MEASUREMENTS : Change in body weight , body composition and blood parameters . RESULTS : After 6 months , the HP group ( n=23 ) achieved a greater weight loss than the MP group ( n=23 ) ( 9.4 vs 5.9 kg ) ( P the weight loss was not significantly greater among the subjects in the HP group ( 6.2 and 4.3 kg ) , but they had a 10 % greater reduction in intra-abdominal adipose tissue and more in the HP group ( 17 % ) lost > 10 kg than in the MP ( P 12 months weight loss , but more than 50 % were lost to follow-up . CONCLUSION : A fat-reduced diet high in protein seems to enhance weight loss and provide a better long-term maintenance of reduced intra-abdominal fat stores ",
"Aims /hypothesisThis study compared the long-term weight loss and health outcomes at 1-year follow-up , after a 12-week intensive intervention consisting of two low-fat , weight-loss diets , which differed in protein content . Methods We r and omly assigned 66 obese patients ( BMI : 27–40 kg/m2 ) with Type 2 diabetes to either a low-protein ( 15 % protein , 55 % carbohydrate ) or high-protein diet ( 30 % protein , 40 % carbohydrate ) for 8 weeks of energy restriction ( ~6.7 MJ/day ) and 4 weeks of energy balance . Subjects were asked to maintain the same dietary pattern for a further 12 months of follow-up . Results The study was completed by 38 of the subjects , with equal dropouts in each group . At Week 64 , weight reductions against baseline were −2.2±1.1 kg ( low protein ) and −3.7±1.0 kg ( high protein ) , p diet effect . Fat mass was not different from baseline in either group . At Week 12 , both diets reduced systolic and diastolic blood pressure by 6 and 3 mm Hg respectively , but blood pressure increased more with weight regain during follow-up in the low-protein group ( p≤0.04 ) . At Week 64 , both diets significantly increased HDL cholesterol and lowered C-reactive protein concentrations . There was no difference in the urinary urea : creatinine ratio at baseline between the two groups , but this ratio increased at Week 12 ( in the high-protein group only , p high-protein weight-reduction diet may in the long term have a more favourable cardiovascular risk profile than a low-protein diet with similar weight reduction in people with Type 2 diabetes",
"Aims /hypothesisShort-term dietary studies suggest that high-protein diets can enhance weight loss and improve glycaemic control in people with type 2 diabetes . However , the long-term effects of such diets are unknown . The aim of this study was to determine whether high-protein diets are superior to high-carbohydrate diets for improving glycaemic control in individuals with type 2 diabetes . Methods Overweight/obese individuals ( BMI 27–40 kg/m2 ) with type 2 diabetes ( HbA1c 6.5–10 % ) were recruited for a 12 month , parallel design , dietary intervention trial conducted at a diabetes specialist clinic ( Melbourne , VIC , Australia ) . Of the 108 initially r and omised , 99 received advice to follow low-fat ( 30 % total energy ) diets that were either high in protein ( 30 % total energy , n = 53 ) or high in carbohydrate ( 55 % total energy , n = 46 ) . Dietary assignment was done by a third party using computer-generated r and om numbers . The primary endpoint was change in HbA1c . Secondary endpoints included changes in weight , lipids , blood pressure , renal function and calcium loss . Study endpoints were assessed blinded to the diet group , but the statistical analysis was performed unblinded . This study used an intention-to-treat model for all participants who received dietary advice . Follow-up visits were encouraged regardless of dietary adherence and last measurements were carried forward for study non-completers . Results Ninety-nine individuals were included in the analysis ( 53 in high protein group , 46 in high carbohydrate group ) . HbA1c decreased in both groups over time , with no significant difference between groups ( mean difference of the change at 12 months ; 0.04 [ 95 % CI −0.37 , 0.46 ] ; p = 0.44 ) . Both groups also demonstrated decreases over time in weight , serum triacylglycerol and total cholesterol , and increases in HDL-cholesterol . No differences in blood pressure , renal function or calcium loss were seen . Conclusions /interpretationThese results suggest that there is no superior long-term metabolic benefit of a high-protein diet over a high-carbohydrate in the management of type 2 diabetes . Trial registration ACTRN12605000063617 ( www.anzctr.org.au ) . Funding This study was funded by a nutritional research grant from Meat and Livestock Australia ( MLA ) . J.E. Shaw is supported by NHMRC Fellowship 586623",
"OBJECTIVE The long-term health consequences of diets used for weight control are not established . We have evaluated the association of the frequently recommended low carbohydrate diets - usually characterized by concomitant increase in protein intake - with long-term mortality . DESIGN The Women 's Lifestyle and Health cohort study initiated in Sweden during 1991 - 1992 , with a 12-year almost complete follow up . SETTING The Uppsala Health Care Region . SUBJECTS 42,237 women , 30 - 49 years old at baseline , volunteers from a r and om sample , who completed an extensive question naire and were traced through linkages to national registries until 2003 . MAIN OUTCOME MEASURES We evaluated the association of mortality with : decreasing carbohydrate intake ( in deciles ) ; increasing protein intake ( in deciles ) and an additive combination of these variables ( low carbohydrate-high protein score from 2 to 20 ) , in Cox models controlling for energy intake , saturated fat intake and several nondietary covariates . RESULTS Decreasing carbohydrate or increasing protein intake by one decile were associated with increase in total mortality by 6 % ( 95 % CI : 0 - 12 % ) and 2 % ( 95 % CI : -1 to 5 % ) , respectively . For cardiovascular mortality , amongst women 40 - 49 years old at enrolment , the corresponding increases were , respectively , 13 % ( 95 % CI : -4 to 32 % ) and 16 % ( 95 % CI : 5 - 29 % ) , with the additive score being even more predictive . CONCLUSIONS A diet characterized by low carbohydrate and high protein intake was associated with increased total and particularly cardiovascular mortality amongst women . Vigilance with respect to long-term adherence to such weight control regimes is advisable",
"BACKGROUND For many people , maintenance of weight loss is elusive . Whereas high-protein ( HP ) diets have been found to be superior to high-carbohydrate ( HC ) diets for weight loss in the short term , their benefits long term are unclear , particularly for weight maintenance . Furthermore , the literature lacks consensus on the long-term effects of an HP diet on cardiovascular disease risk factors . OBJECTIVE The objective was to investigate whether macronutrient dietary composition plays a role in weight maintenance and in improvement of cardiovascular disease risk factors . DESIGN The study comprised 2 phases . Phase 1 featured a very-low-energy diet for 3 mo . In phase 2 , the subjects were r and omly assigned to an HP or an HC diet for 12 mo . The diets were isocaloric , tightly controlled , and individually prescribed for weight maintenance . The subjects were overweight or obese but otherwise healthy men and women . RESULTS The subjects lost an average of 16.5 kg during phase 1 and maintained a mean ( + /-SEM ) weight loss of 14.5 + /- 1.2 kg ( P systolic blood pressure were 14.3 + /- 2.4 mm Hg for the HP group and 7.7 + /- 2.2 mm Hg for the HC group ( P . Forty-seven percent of the 180 subjects who began the study completed both phases . CONCLUSIONS The results indicate that the protein or carbohydrate content of the diet has no effect on successful weight-loss maintenance . A general linear model analysis indicated that dietary treatment ( HP or HC ) was a significant factor in systolic blood pressure change and in favor of the HP diet . This trial was registered at www . clinical trials.gov as NCT 00625236",
"Objective : We have evaluated the effects on mortality of habitual low carbohydrate – high-protein diets that are thought to contribute to weight control . Design : Cohort investigation . Setting : Adult Greek population .Subjects methods : Follow-up was performed from 1993 to 2003 in the context of the Greek component of the European Prospect i ve Investigation into Cancer and nutrition . Participants were 22 944 healthy adults , whose diet was assessed through a vali date d question naire . Participants were distributed by increasing deciles according to protein intake or carbohydrate intake , as well as by an additive score generated by increasing decile intake of protein and decreasing decile intake of carbohydrates . Proportional hazards regression was used to assess the relation between high protein , high carbohydrate and the low carbohydrate – high protein score on the one h and and mortality on the other . Results : During 113 230 persons years of follow-up , there were 455 deaths . In models with energy adjustment , higher intake of carbohydrates was associated with significant reduction of total mortality , whereas higher intake of protein was associated with nonsignificant increase of total mortality ( per decile , mortality ratios 0.94 with 95 % CI 0.89 –0.99 , and 1.02 with 95 % CI 0.98 –1.07 respectively ) . Even more predictive of higher mortality were high values of the additive low carbohydrate – high protein score ( per 5 units , mortality ratio 1.22 with 95 % CI 1.09 –to 1.36 ) . Positive associations of this score were noted with respect to both cardiovascular and cancer mortality . Conclusion : Prolonged consumption of diets low in carbohydrates and high in protein is associated with an increase in total mortality",
"BACKGROUND AND OBJECTIVES Concerns exist about deleterious renal effects of low-carbohydrate high-protein weight loss diets . This issue was addressed in a secondary analysis of a parallel r and omized , controlled long-term trial . DESIGN , SETTING , PARTICIPANTS , AND MEASUREMENTS Between 2003 and 2007 , 307 obese adults without serious medical illnesses at three United States academic centers were r and omly assigned to a low-carbohydrate high-protein or a low-fat weight-loss diet for 24 months . Main outcomes included renal filtration ( GFR ) indices ( serum creatinine , cystatin C , creatinine clearance ) ; 24-hour urinary volume ; albumin ; calcium excretion ; and serum solutes at 3 , 12 , and 24 months . RESULTS Compared with the low-fat diet , low-carbohydrate high-protein consumption was associated with minor reductions in serum creatinine ( relative difference , -4.2 % ) and cystatin C ( -8.4 % ) at 3 months and relative increases in creatinine clearance at 3 ( 15.8 ml/min ) and 12 ( 20.8 ml/min ) months ; serum urea at 3 ( 14.4 % ) , 12 ( 9.0 % ) , and 24 ( 8.2 % ) months ; and 24-hour urinary volume at 12 ( 438 ml ) and 24 ( 268 ml ) months . Urinary calcium excretion increased at 3 ( 36.1 % ) and 12 ( 35.7 % ) months without changes in bone density or clinical presentations of new kidney stones . CONCLUSIONS In healthy obese individuals , a low-carbohydrate high-protein weight-loss diet over 2 years was not associated with noticeably harmful effects on GFR , albuminuria , or fluid and electrolyte balance compared with a low-fat diet . Further follow-up is needed to determine even longer-term effects on kidney function",
"The short-term effects on plasma lipoprotein lipids of substituting meat and dairy protein for carbohydrate in the diets of 10 free-living moderately hypercholesterolemic human subjects ( four men , six women ) were studied under closely supervised dietary control during the consumption of constant , low intakes of fat and cholesterol and the maintenance of stable body weight as well as constant fiber consumption . Subjects were r and omly allocated to either the high or low protein diets ( mean , 23 % v 11 % of energy as protein , 24 % as fat , and 53 % v 65 % as carbohydrate ) and then switched to the other diet for another 4 to 5 weeks . Mean fasting plasma high-density lipoprotein cholesterol ( HDL-C ) was significantly higher by 12 % + /- 4 % ( 0.97 + /- 0.08 v 0.89 + /- 0.08 mmol/L , P less than .01 ) , whereas mean total cholesterol ( TC ) was lower by 6.5 % + /- 1.3 % ( 5.7 + /- 0.3 v 6.1 + /- 0.3 mmol/L , P less than .001 ) , mean low-density lipoprotein-cholesterol ( LDL-C ) lower by 6.4 % + /- 2.0 % ( 4.5 + /- 0.2 v 4.8 + /- 0.2 mmol/L , P less than .02 ) , mean total triglycerides ( TG ) lower by 23 % + /- 5 % ( 1.7 + /- 0.1 v 2.4 + /- 0.3 mmol/L , P less than .02 ) , and mean high versus low protein diet . Mean values for LDL-C were significantly lower during weeks 3 to 5 of the high protein diet than during either weeks 1 to 5 or weeks 1 to 2 of the high protein diet ( 4.3 + /- 0.3 , 4.5 + /- 0.2 , and 4.7 + /- 0.3 mmol/L , respectively , P less than .05 ) and 11 % + /- 3 % lower than on low protein diet , P less than .005 . The ratio of plasma LDL-C to HDL-C was consistently lower by 17 % + /- 3 % during the high versus low protein diet ( 4.9 + /- 0.5 v 5.8 + /- 0.5 , P less than .001 ) . Lowering plasma TC and LDL-C and total TG and VLDL-TG and increasing HDL-C by chronic isocaloric substitution of dietary for carbohydrate may enhance the cardiovascular risk reduction obtained by restriction of dietary fat and cholesterol",
"BACKGROUND Data on the long-term association between low-carbohydrate diets and mortality are sparse . OBJECTIVE To examine the association of low-carbohydrate diets with mortality during 26 years of follow-up in women and 20 years in men . DESIGN Prospect i ve cohort study of women and men who were followed from 1980 ( women ) or 1986 ( men ) until 2006 . Low-carbohydrate diets , either animal-based ( emphasizing animal sources of fat and protein ) or vegetable-based ( emphasizing vegetable sources of fat and protein ) , were computed from several vali date d food-frequency question naires assessed during follow-up . SETTING Nurses ' Health Study and Health Professionals ' Follow-up Study . PARTICIPANTS 85 168 women ( aged 34 to 59 years at baseline ) and 44 548 men ( aged 40 to 75 years at baseline ) without heart disease , cancer , or diabetes . MEASUREMENTS Investigators documented 12 555 deaths ( 2458 cardiovascular-related and 5780 cancer-related ) in women and 8678 deaths ( 2746 cardiovascular-related and 2960 cancer-related ) in men . RESULTS The overall low-carbohydrate score was associated with a modest increase in overall mortality in a pooled analysis ( hazard ratio [ HR ] comparing extreme deciles , 1.12 [ 95 % CI , 1.01 to 1.24 ] ; P for trend = 0.136 ) . The animal low-carbohydrate score was associated with higher all-cause mortality ( pooled HR comparing extreme deciles , 1.23 [ CI , 1.11 to 1.37 ] ; P for trend = 0.051 ) , cardiovascular mortality ( corresponding HR , 1.14 [ CI , 1.01 to 1.29 ] ; P for trend = 0.029 ) , and cancer mortality ( corresponding HR , 1.28 [ CI , 1.02 to 1.60 ] ; P for trend = 0.089 ) . In contrast , a higher vegetable low-carbohydrate score was associated with lower all-cause mortality ( HR , 0.80 [ CI , 0.75 to 0.85 ] ; P for trend cardiovascular mortality ( HR , 0.77 [ CI , 0.68 to 0.87 ] ; P for trend Participants were not a representative sample of the U.S. population . CONCLUSION A low-carbohydrate diet based on animal sources was associated with higher all-cause mortality in both men and women , whereas a vegetable-based low-carbohydrate diet was associated with lower all-cause and cardiovascular disease mortality rates . PRIMARY FUNDING SOURCE National Institutes of Health"
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Abstract Despite being first described two thous and years ago , the varicocele remains a controversial multifaceted disease process with numerous biological consequences including infertility , hypogonadism , and chronic orchidalgia . The underlying mechanisms remain poorly understood and likely include hypoxia , oxidative stress , hyperthermia , anatomical aberrations , and genetics as primary components . Despite a high prevalence amongst asymptomatic fertile men , varicoceles paradoxically also represent the most common correctable cause for male infertility . In this systematic review we discuss the rich historical aspects of the varicocele and the contemporary data regarding its clinical manifestations . We performed a systematic literature review with the goal of comparing outcomes and complication rates of each of the major surgical approaches as they relate to infertility and pain . We performed a Preferred Reporting Items for Systematic Review s and Meta- Analysis ( PRISMA ) -compliant systematic literature review for manuscripts focused on varicocele and its biological consequences . We identified 112 studies suitable for qualitative analysis and included 56 of these for quantitative analysis , with an emphasis on infertility and chronic pain outcomes . Taken together , the clinical work to date suggests that the highest fertility rates and the lowest complication rates are associated with the microsurgical subinguinal surgical approach to varicocelectomy . In all , 26–40 % of patients undergoing varicocelectomy will successfully achieve short-term spontaneous pregnancy , and up to 90 % of all patients undergoing varicocelectomy for pain will have improvement and /or resolution of their symptoms . Taken together , the data support an ongoing role for varicocelectomy in both of these clinical arenas
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"OBJECTIVES To compare the outcomes of the different surgical techniques used in varicocelectomy . METHODS The study included 120 patients with 147 clinical ly palpable varicoceles who underwent varicocelectomy . The patients were r and omly allocated to one of three equal groups according to the varicocelectomy technique , which included the open inguinal approach , a laparoscopic approach , and subinguinal microscopic varicocelectomy . The assessment included operative and postoperative parameters , together with semen analysis and pregnancy rate . The mean follow-up was 18 months ( range 11 to 26 ) . RESULTS The operative time in the microscopic group was significantly longer than that for the other two groups . At follow-up , none of the patients of the microscopic group had developed postoperative hydrocele ; however , it was observed in 7 ( 13 % ) of 52 varicoceles in the open group and 10 ( 20 % ) of 50 in the laparoscopic group . This difference was statistically significant in favor of the microscopic group only . Only 1 patient in the microscopic group experienced recurrence of one varicocele compared with 7 and 9 patients in the open and laparoscopic groups , respectively . This difference was statistically significant in favor of the microscopic group only . Improvement in sperm motility and /or concentration was comparable and observed in 65 % , 67 % , and 76 % of the open , laparoscopic , and microscopic groups , respectively . Also , the pregnancy rate at 1 year was not significantly different and was 28 % , 30 % , and 40 % in three groups , respectively . CONCLUSIONS The findings of our study have demonstrated that , compared with open inguinal and laparoscopic varicocelectomy , subinguinal microsurgical varicocelectomy offers the best outcome",
"OBJECTIVE To compare semen parameters , pregnancy , recurrence , and complication rates after microsurgical and nonmagnified subinguinal varicocelectomy for infertile men . DESIGN Prospect i ve , r and omized study . SETTING Ghodran General Hospital , Kingdom of Saudi Arabia . PATIENT(S ) One hundred sixty-two infertile male patients with varicocele . INTERVENTION(S ) Eighty-two patients were treated by microsurgical subinguinal varicocelectomy ( MSSIV ) ( group I ) , whereas 80 patients were treated by conventional , nonmagnified subinguinal varicocelectomy ( NMSIV ) ( group II ) . MAIN OUTCOME MEASURE(S ) The patients were postoperatively evaluated by physical examination and semen analysis after 4 and 12 months . Pregnancy rate was monitored during the follow-up period . RESULT ( S ) Postoperatively , mean sperm count and motility improved significantly in both groups : 42.7 % and 67.1 % of the MSSIV group and 23.7 % and 33.8 % of the NMSIV group showed ≥50 % improvement in sperm count and motility after 1 year . Patients having bilateral varicocele showed significantly better improvement of sperm count than those with unilateral varicocele after both MSSIV and NMSIV . The pregnancy rate at the end of the follow-up period reached 37.8 % in the MSSIV group and 21.2 % in the NMSIV group . The recurrence rate was zero in the MSSIV group and 11.3 % in the NMSIV group . The rate of hydrocele formation was 1.2 % in the MSSIV group and 8.7 % in the NMSIV group . CONCLUSION ( S ) Microsurgical subinguinal varicocelectomy has a better improving effect on sperm count and motility , higher spontaneous pregnancy rates , and lower postoperative recurrence and hydrocele formation than conventional subinguinal varicocelectomy in infertile men",
"Objectives To evaluate the effect of spermatic vein ligation in patients over 30 years old and with low‐ grade left varicocele , and thus help to establish whether such patients might benefit from surgery",
"OBJECTIVE To examine the hypotheses that clinical varicoceles affect baseline serum total testosterone levels ( T ) and varicocelectomy improves T. MATERIAL S AND METHODS This prospect i ve , nonr and omized , controlled study involved 4 groups of adult men . Varicocele-infertile treatment group ( VIT ) included 66 men who underwent varicocelectomy . Thirty-three varicocele-infertile control men ( VIC ) and 33 varicocele-fertile control men ( VFC ) were only observed . Normal-control ( NC ) group included 33 fertile men without varicocele . Varicocele groups were stratified into baseline hypogonadal ( T eugonadal ( T ≥300 ng/dL ) subgroups . Main outcome measurements were between-group baseline T differences ; and within-group T changes at 6- and 12-month follow-ups of men with varicocele . P RESULTS Means ( st and ard deviations ) of baseline T in VIT , VIC , VFC , and NC were 347.4 ( 132.1 ) , 339.7 ( 125.8 ) , 396.6 ( 164.9 ) , and 504.8 ( 149.7 ) ng/dL , respectively . The baseline T levels of varicocele groups were comparable , whereas they were significantly low compared with NC group . At 6-month follow-up , VIT demonstrated significant T improvements ( mean change = 44.7 ng/dL ; 12.9 % ; P .0001 ) . T changes were more remarkable among baseline hypogonadals ( mean change = 93.7 ng/dL ; 40.1 % ; P .1223 ) . These improvements were persistent at 12-month follow-up . Contrariwise , VIC and VFC exhibited nonsignificant T changes . Postvaricocelectomy T changes correlated significantly and inversely with baseline T ( r = -0.689 ; P ; P = .013 ) . T improvements also exhibited significant positive correlations with preoperative and postoperative sperm concentrations . CONCLUSION Baseline T was significantly low in men with varicocele compared with normal men . Varicocelectomy yielded significant T improvements among hypogonadal men but insignificant changes in eugonadals . T changes correlated strongly and significantly with baseline T and sperm concentrations",
"The goal of this r and omized prospect i ve study in patients with varicocele was to evaluate the outcome following open surgery with inguinal approach versus ante grade sclerotherapy according to the Tauber procedure . From January 2002 to November 2003 , we recruited 64 patients with left varicocele for this study . All patients were clinical ly examined , before surgery and again 8 months postsurgery , by objective examination , scrotal color Doppler ultrasound , and semen analysis . These patients were r and omized in a balanced 4-block pattern : depending on r and omization , the patients underwent open surgery ( group A : 32 patients ) or ante grade sclerotherapy according to the Tauber procedure ( group B : 32 patients ) . At the current follow-up , it is possible to evaluate all the patients for whom we have preoperative and postoperative Doppler imaging and semen analysis . An analysis of seminal parameters shows a statistically significant improvement of the rate of fast progressive spermatozoa ( P reduction in immotile spermatozoa ( P . The outcomes of all other parameters ( number and morphology ) are fully comparable . Operating time is decidedly shorter for ante grade sclerotherapy ( P early or late postoperative complications . It is widely known that varicocele is a condition found in 9 % to 23 % of the male population around the world ; this percentage rises to 40 % among infertile males . The treatment of this condition not only resolves clinical symptoms but also stops continuous damage to spermatogenesis , thereby potentially improving fertility . Our experience demonstrates that sclerotherapy ( Tauber procedure ) combines shorter surgical time and faster recovery of normal daily activities with significant improvement in sperm motility",
"OBJECTIVE To study the effects of varicocele treatment on testicular function in adolescents . DESIGN A prospect i ve controlled study in 88 r and omly selected adolescents . SETTING All participants were referred to the fertility outpatient clinic of our university hospital . PARTICIPANTS All participants with a varicocele were r and omly assigned into two groups . Group 1 ( n = 33 ) was not treated , whereas group 2 ( n = 34 ) was treated . A similar group of healthy volunteers without a varicocele served as a control group ( group 3 , n = 21 ) . INTERVENTIONS Testes volumes were measured at intake and during follow-up using an orchiometer . Semen analysis was performed according to st and ard procedures both at intake and after 1 year of follow-up . Serum hormone levels were determined at intake using a radioimmunoassay . Treatment was performed by means of transcatheter embolization of the left testicular vein . MAIN OUTCOME MEASURES Testes volumes and semen quality at intake and after 1 year of follow-up were compared within and between the three groups . Hormonal parameters were determined at intake only . RESULTS Before treatment , the mean left testis volume in groups 1 ( n = 26 ) and 2 ( n = 27 ) ( 20.0 mL ; 95 % confidence interval [ CI ] : 18.2 to 21.8 and 21.6 mL ; 95 % CI : 19.4 to 23.8 , respectively ) were significantly smaller than those in the control group ( n = 19 ) ( 24.5 mL ; 95 % CI : 22.7 to 26.4 ) . During follow-up , left testis volumes of the treated group were comparable with those in the control group ( 24.2 mL ; 95 % CI : 22.2 to 26.1 and 24.8 mL ; 95 % CI : 23.0 to 26.7 respectively ) and significantly ( P ( P was observed after treatment . Semen parameters before treatment were not significantly different between the three groups . Sperm concentration increased significantly ( P semen quality in the untreated and control groups did not change . Although both testes volumes and sperm concentration improved in the treated group , these phenomena were not consistently correlated to each other . CONCLUSIONS Although not apparent in all adolescents , varicocele correction result ed in an increase in left testis volume and sperm concentration . At this moment , it is not clear if early preventive treatment of varicocele in adolescents , in time , will have a positive effect on testicular function",
"OBJECTIVES Color Doppler ultrasound ( CDU ) diagnostic criteria for varicoceles are poorly defined , and the role of CDU in diagnosing varicoceles is controversial . The purpose of this study is to assess the diagnostic accuracy of CDU for varicoceles compared to physical examination . METHODS We prospect ively studied 64 patients with CDU and collected the following data : maximum diameter of scrotal veins , the presence of a venous plexus , sum of the diameter of up to six veins of the plexus , and the duration and amplitude of flow change on Valsalva maneuver . To avoid interphysician variation , all patients were examined by one design ated senior urologist with the sonographer remaining unaware of the findings . RESULTS CDU parameters of 127 testis units in 64 patients were analyzed and compared to the physical findings . Fifty-nine testis units were positive and 57 units were negative for varicocele on physical examination . In 11 testis units , results of physical examination were inconclusive regarding the presence of varicocele . The commonly accepted CDU criterion for varicocele ( maximal vein diameter of 3 mm or greater ) had a sensitivity of 53 % and specificity of 91 % compared to physical examination . We developed a new scoring system incorporating the maximal venous diameter ( score 0 to 3 ) , the presence of a venous plexus and the sum of the diameters of veins in the plexus ( score 0 to 3 ) , and the change of flow on Valsalva maneuver ( score 0 to 3 ) . Using a total score of 4 or more to define the presence of CDU-positive varicocele , we observed a sensitivity of 93 % and a specificity of 85 % when compared to physical examination . All moderate to large varicoceles found on physical examination were positive by CDU diagnosis using the scoring system , but the same group had only a 68 % positive rate by traditional CDU diagnostic criteria . CONCLUSIONS Using the proposed new scoring system , CDU has been shown to be a reliable and accurate method of diagnosis for varicoceles compared to the current reference st and ard physical examination . CDU has the advantages of being able to objective ly examine venous plexus and measure blood flow parameters and to be less observer-dependent than physical examination",
"OBJECTIVE To evaluate mRNA expression of the HSPA2 gene in ejaculated spermatozoa in adolescents with and without varicocele . DESIGN Controlled prospect i ve study . SETTING Patients in an academic research environment . PATIENTS Adolescent patients with clinical diagnosed bilateral varicocele grade s II and III , and adolescent patients without varicocele . INTERVENTION Reverse-transcription-polymerase chain reaction ( RT-PCR ) analysis of HSPA2 gene expression in adolescents with and without varicocele . MAIN OUTCOME MEASURE Comparative RT-PCR expression analysis of HSPA2 gene mRNA , compared to the housekeeping beta-actin gene . RESULTS Sperm from adolescents with varicocele and oligozoospermia had significantly lower levels of HSPA2 gene expression than both adolescents without varicocele ( controls ) and adolescents with varicocele and normal sperm concentration ( P increase in gene expression compared to the control group . CONCLUSIONS This is the first report on HSPA2 gene expression in ejaculated spermatozoa from adolescents and its relationship with varicocele pathology . Results demonstrated that HSPA2 expression was down-regulated in adolescents with varicocele and oligozoospermia compared to controls . There was a higher , albeit nonsignificant , gene expression in adolescents with varicocele and normal sperm concentration than in controls . We speculate that expression levels of this gene might be used as a molecular marker for the acquisition of thermal tolerance in ejaculated spermatozoa",
"Introduction : The differentiation of unilateral versus bilateral varicoceles and testicular volume measurements are important in determining the need for adolescent varicocele surgery and also in following patients after varicocelectomy . The aim of this study was to prospect ively compare the findings of physical examination and color Doppler ultrasonography in the diagnosis of pediatric varicoceles and to compare the findings using the Prader orchidometer and scrotal ultrasonography in the measurement of testicular volumes . Patients and Methods : This study included 68 boys with varicoceles , ranging in age from 8 to 19 years . Varicoceles were diagnosed using both physical examination and scrotal color Doppler ultrasonography . The testicular volumes of 136 testicles were measured using the Prader orchidometer and scrotal ultrasonography . A difference of more than 10 % or 2 ml in each testicular volume was considered significant . Results : The mean age of the boys was 13.5 ± 2.3 years . On physical examination , a left unilateral varicocele was diagnosed in 46 boys ( 67.6 % ) . The other 22 boys ( 32.4 % ) had bilateral varicoceles . Color Doppler ultrasonography detected bilateral varicoceles in 4 of the 46 boys ( 8.7 % ) who were diagnosed by physical examination as having only left unilateral varicoceles ( grade 3 in 3 patients and grade 2 in 1 patient ) . A different of more than 10 % or 2 ml in testicular volume using the Prader orchidometer versus scrotal ultrasonography was detected in 3 out of 136 testicles ( 2.2 % ) . The correlation between ultrasonography and Prader orchidometer results in the measurement of testicular volumes was statistically highly significantly consistent using the intraclass correlation test ( r = 0.997 and p that color Doppler ultrasonography may be necessary in the diagnosis of bilateral varicoceles , especially in boys with high- grade left varicoceles . In contrast , scrotal ultrasonography , if considered the gold st and ard , did not show superiority over the Prader orchidometer in measuring testicular volumes",
"PURPOSE The left varicocele is usually larger in men with bilateral varicoceles . We hypothesized that most of the benefit of varicocelectomy would derive from repair of the larger varicocele . To test this hypothesis we prospect ively compared the effect of unilateral versus bilateral microsurgical varicocelectomy in men with large ( grade III ) or moderate ( II ) left varicocele associated with small but palpable ( I ) right varicocele . MATERIAL S AND METHODS A total of 91 patients were prospect ively followed and included in the study . Of the patients 65 underwent bilateral and 26 underwent unilateral left repair . All patients underwent preoperative and postoperative semen analysis . RESULTS Motile sperm concentration increased from 12.1+/-1.7 to 23.7+/-31.8 ( 95.8 % change ) in the bilateral group compared with an increase from 19.5+/-21.4 to 27.8+/-34.8 ( 42.6 % change ) in the unilateral group ( p sperm concentration increased from 23.8+/-29.5 to 48.6+/-61.3 ( 157.6 % change ) in the bilateral group compared with an increase from 41.1+/-40.9 to 59.5+/-66.7 ( 44.8 % change ) in the unilateral group ( p Bilateral varicocelectomy result ed in significantly greater improvement in post-operative seminal parameters than unilateral repair in patients with grade s II to III left varicocele associated with grade I right varicocele . Even a small , unrepaired palpable right varicocele continues to have a detrimental effect on bilateral testis function . Men with bilateral palpable varicoceles require bilateral repair",
"PURPOSE We compared the outcomes of 3 techniques of varicocelectomy in infertile patients with varicocele . MATERIAL S AND METHODS The study included 298 infertile patients ( 446 varicoceles ) who were r and omized to varicocelectomy by an open inguinal technique in 92 , laparoscopy in 94 and subinguinal microsurgery in 112 . The 3 techniques were compared regarding intraoperative , and early and late postoperative parameters , changes in semen parameters and the pregnancy rate . Patients were followed a + /- mean + /- SD of 21 + /- 9 months ( range 4 to 35 ) . RESULTS Operative time was significantly longer in the microscopic group . Early postoperative complications were comparable in the 3 groups . At followup none of the patients in the microsurgical group had hydrocele , while it was observed in 4 of 143 ( 2.8 % ) in the open group and in 8 of 148 ( 5.4 % ) in the laparoscopy group , representing a significance difference in favor of microsurgery . The incidence of recurrent varicocele was significantly lower in the microsurgical group than in the open and laparoscopy groups ( 4 of 155 patients or 2.6 % vs 16 of 143 or 11 % and 25 of 148 or 17 % , respectively ) . Compared to preoperative values in the 3 groups postoperative semen parameters showed significant improvement in sperm concentration , motility and morphology . The incidence of patients with improved sperm count and motility was significantly higher in the microsurgical group . The pregnancy rate at 1 year was not significantly different among the 3 groups . CONCLUSIONS Compared with open and laparoscopic varicocele treatment microsurgical varicocelectomy has the advantages of no hydrocele formation , a lower incidence of recurrent varicocele , and better improvement in sperm count and motility",
"The aim of this prospect i ve study was to assess long-term functional results ( spermiograms ) in subjects who underwent laparoscopic varicocelectomy via either of 2 procedures ( ligation or preservation of testicular artery ) . A total of 122 patients underwent laparoscopic varicocelectomy performed via either of the 2 different procedures : complete ligation of the spermatic vessels or preservation of the spermatic artery . After surgery when patients achieved 18 years , they were asked to undergo semen analysis . Spermiogram results were divided into 2 subgroups : \" normal \" and \" abnormal . \" We analyzed volume , sperm count per mL , percentage of motile spermatozoa , percentage of normal spermatozoa , and percentage of vitality for each group . Both groups showed the same results in terms of \" normal \" and \" abnormal \" spermiograms ( World Health Organization criteria ) , but analysis showed higher sperm concentration per mL , sperm motility , volume , vitality , and rate of morphologically normal sperm for the group with arteries preserved and \" normal \" spermiograms ( P semen quality . Therefore , we believe that surgical treatment of varicocele should be carried out using procedures involving artery preservation",
"The purpose of this study is to determine the relative advantages of laparoscopic varicocelectomy compared to the conventional open high ligation of Palomo . We studied 193 patients who presented with varicocele . While 65 patients were treated by open high ligation of the testicular veins , 128 patients had laparoscopic varicocelectomy . In addition to varicocele ligation , 14 patients ( 11 % ) had laparoscopy-assisted right orchidopexy , and 5 patients ( 4 % ) had laparoscopic repair of concomitant right inguinal hernia . The mean hospital stay was 3.5 days and 1.3 days , respectively , and the recurrence rates were 10.8 % and 3.9 % , respectively . Return to normal activity was significantly earlier in Group II ( mean 4.5 days ) compared to Group I ( mean 8.9 days ) . There was no incidence of testicular atrophy in any case in the study , regardless of whether the testicular artery was ligated or preserved during surgery . We conclude that laparoscopic varicocelectomy is safe , effective and minimally invasive . In addition to its better cosmetic results and advantage in case of bilateral disease , it allows excellent exposure and control of the affected vessels . Furthermore , the shorter hospital stay and the earlier return to normal activities are very important advantages in recommending this technique as an efficient alternative to the open surgical method",
"OBJECTIVE To determine whether high ligation is an effective treatment for infertile men with clinical varicocele . DESIGN A r and omized , controlled trial of high spermatic vein ligation was carried out . The patients were treated and observed for 3 years . SETTING Infertility treatment clinic and and rology laboratory in a hospital . PATIENTS Infertile men with abnormal semen analysis because of varicocele only . INTERVENTION High ligation 1 year postrecruitment ( group A ) and at the beginning of the study ( group B ) . RESULTS Among the 20 couples in group A , 2 pregnancies ( 10 % ) were achieved within the 1st year of observation period . During the year after high ligation , there were 8 pregnancies ( 44.4 % ) , and during the 2nd year after high ligation , there were 4 more pregnancies ( 22.2 % ) . In group B , 15 pregnancies ( 60 % ) occurred within the 1st year after operation . Three pregnancies ( 12 % ) and 1 pregnancy ( 4 % ) occurred during the 2nd and 3rd year , respectively . After operation in all patients of both groups , there was significant improvement in semen parameters , regardless of pregnancy occurrence . The difference in pregnancy rate ( PR ) between the operated group B and nonoperated group A during the 1st year of study was found to be highly significant . CONCLUSIONS It is concluded that in a population of infertile men presenting varicocele as the only demonstrable factor of infertility , the varicocele is clearly associated with infertility and reduced testicular function , and its correction by ligation improves sperm parameters and fertility rate . Furthermore , the highest PR in both groups occurred during the 1st year postoperation",
"Purpose To compare proteomic profiles of spermatozoa from patients with varicocele and poor sperm quality before and after varicocelectomy . Methods This work was design ed as a prospect i ve and observational study . The study was based on 20 men with varicocele grade 3 and poor sperm quality undergoing varicocelectomy at the Fertility Unit of Royan institute in 2009 . Two semen sample s were collected , one before varicocelectomy and the other after surgery . Protein separation was done by two-dimensional protein electrophoresis , and analyzed by gel densitometry and mass spectrometry . Differential sperm protein expression levels were measured by gel densitometry . Results Comparison of the sperm parameters showed that sperm motility and concentration were increased after varicocelectomy . At the level of protein , a total of 3 protein spots were identified whose expression was significantly lower in sperm sample s before varicocelectomy compared with after surgery including heat shock protein A5 ( HSPA5 ) , superoxide dismutase 1 ( SOD1 ) and δ-subunit of the catalytic core of mitochondrial adenosine triphosphate synthase ( ATP5D ) . Conclusions High grade varicocoele affects sperm protein expression presumably because of increasing testicular temperature . These proteins play essential roles in sperm production , DNA integrity protection , and sperm motility . This novel study demonstrates that varicocelectomy can improve both sperm quality and proteins expression",
"OBJECTIVES To compare the intraoperative results of inguinal versus subinguinal varicocelectomy using magnifying loupe , in terms of vein ligation and arterial preservation , recurrence rate , and patient tolerability . METHODS Ninety-nine patients were r and omized to undergo a varicocele repair with an inguinal or a subinguinal approach under local anesthesia . Data concerning the number of veins ligated and arterial preservation were recorded during each procedure . The amount of intraoperative and postoperative pain was assessed by means of visual analogue scale ( VAS ) scores . The recurrence rate was documented by color Doppler ultrasound examination . RESULTS The average number of ligated veins was 5.6 with a subinguinal dissection and 4.4 with the inguinal approach . Inadvertent injury of the spermatic artery occurred in 6 of 47 subinguinal and 3 of 50 inguinal dissections ; the artery could not be identified during 2 subinguinal and 1 inguinal dissection . Recurrent varicocele was detected in 8 % and 14.9 % of patients after an inguinal and a subinguinal approach , respectively . The intraoperative VAS score was significantly higher in the inguinal than in the subinguinal patients ( P = 0.008 ) . CONCLUSIONS In our h and s , the inguinal approach to the spermatic cord showed a trend toward an easier preservation of the artery and a reduced incidence of persistent pathologic vein reflux . The subinguinal approach had a lower degree of intraoperative pain . On the whole , an inguinal repair might be preferable when magnifying loupe are used for varicocelectomy",
"Background Varicocele is a condition characterized by dilated , tortuous veins within the pampiniform venous plexus of the scrotal sac . Presence of varicocele is associated with an increased risk of alteration of semen parameters . The objective of this study was to compare the current st and ard in varicocele treatment procedures : sub-inguinal microscopic ligation to percutaneous embolization in terms of semen parameters improvement , fertility , and morbidity at the university hospital of Toulouse ( France ) . Seventy six patients with clinical varicocele , alteration of semen parameters and infertility , underwent either procedure ( microsurgery in 49 case performed by a single surgeon and embolization in 27 cases ) and were prospect ively analyzed . Outcome measures were : semen parameters , spontaneous pregnancies , pain , side effects , recovery time and overall satisfaction . All patients were contacted in January 2015 in order to determine reproductive events . Results Preoperatively , there was no difference in clinical and biological items between the two groups . Postoperatively , on the overall population , there was a significant improvement of sperm concentration at 3 , 6 , 9 and 12 months ( p = and sperm motility at 6 months ( p = 0.002 ) . The sperm concentration was higher at 6 months in the percutaneous embolization group ( 13.42 , vs. 8.1 × 106/ml ; p = 0.043 ) . With a median follow-up of 4 years , 27 pregnancies occurred ( spontaneous pregnancy rate of 35.5%).There was no significant difference between procedures on the sperm quality , pregnancy rate , and the overall satisfaction . Patients undergoing percutaneous embolization reported a faster recovery time ( p = 0.002 ) and less postoperative pain ( p = 0.007 ) . Conclusion Our study shows that percutaneous embolization seems to be an equivalent alternative to sub-inguinal microscopic ligation in term of sperm quality improvement , pregnancy rate , and overall satisfaction with a slight advantage on post-operative morbidity . Résumé Context eLa varicocèle est une affection caractérisée par une dilatation et tortuosité des veines du plexus veineux pampiniforme du sac scrotal . La présence de varicocèle est associée à un risque accru d'altération des paramètres du sperme . Cette étude vise à comparer la norme actuelle des procédures de traitement par varicocèle : la ligature microscopique sous-inguinale à l'embolisation percutanée en termes d'amélioration des paramètres spermatiques , de fertilité et de morbidité dans l'hôpital universitaire de Toulouse(France ) . Soixante-seize patients atteints de varicocèle clinique , d'altération des paramètres spermatiques et d'infertilité ont subi une intervention ( microchirurgie dans 49 cas réalisées par un seul urologue et embolisation dans 27 cas ) et ont fait l'objet d'une analyse prospect i ve . Les données étudiées sont les suivantes : paramètres du sperme , grossesses spontanées , douleur , effets secondaires , temps de récupération et satisfaction globale . Tous les patients ont été contactés en janvier 2015 afin de déterminer les grossesses spontanées . RésultatsEn préopératoire , il n’existait aucune différence sur les items cliniques et biologiques entre les deux groupes . Sur la population globale , on observe une amélioration significative de la concentration spermatique à 3 , 6 , 9 et 12 mois ( p = motilité à 6 mois ( p = 0,002 ) . La concentration de spermatozoïdes était plus élevée à 6 mois dans le groupe d'embolisation percutané ( 13,42 vs 8,09 ; p = 0,043 ) . Avec un suivi médian de 4 ans , 27 grossesses sont survenues ( taux de grossesse spontanée de 35.5%).Il n'y avait pas de différence significative entre les procédures sur la qualité du sperme , le taux de grossesse et la satisfaction globale . Les patients traités par embolisation percutanée ont rapporté un temps de récupération plus rapide ( p = 0,002 ) et moins de douleur postopératoire ( p = 0,007 ) . Conclusion Notre étude montre que l'embolisation percutanée semble être une alternative équivalente à la ligature microscopique sous-inguinale en terme d'amélioration de la qualité du sperme , du taux de grossesse et de la satisfaction globale avec un léger avantage sur la morbidité post-opératoire",
"OBJECTIVES To compare and assess objective ly the postoperative outcome parameters of both microsurgical subinguinal artery sparing and retroperitoneal high ligation techniques for varicocele in infertile men . METHODS We performed a prospect i ve study that included 413 consecutive patients who presented with varicocele . Of the 413 patients , 304 underwent subinguinal varicocelectomy ( group 1 ) and 109 patients underwent high ligation varicocelectomy ( group 2 ) . Subinguinal varicocelectomies were performed under local anesthesia , with intravenous propofol sedation administered as needed . The operating microscope ( x10 to x16 ) was used to spare the arteries and lymphatics . High ligation was performed through a retroperitoneal approach . RESULTS All patients went home on the evening after surgery with minimal discomfort . No intraoperative complications occurred . The internal spermatic artery was identified in all microvaricocelectomy cases . No testicular atrophy occurred in either group . Five ( 1.6 % ) and seven ( 6.4 % ) hydroceles were identified at the 3-month postoperative visit in groups 1 and 2 , respectively . CONCLUSIONS Microvaricocelectomy is safe and effective and associated with a rapid recovery and minimal morbidity . However , it requires microsurgical training",
"OBJECTIVES To prospect ively compare sperm parameters , pregnancy and recurrence rates , and complications after r and omized high ligation surgery versus microsurgical high inguinal varicocelectomy ( MHIV ) . METHODS Varicocele was diagnosed by physical examination and color Doppler ultrasound in 468 patients who underwent one of two procedures : high ligation surgery ( n = 232 ) or MHIV ( n = 236 ) . The high ligation surgery was left unilateral in 142 and bilateral in 90 . The MHIV was left unilateral in 128 and bilateral in 108 . The patients were postoperatively evaluated by spermiograms and physical examination . The pregnancy rate was monitored for 2 years . RESULTS One year after surgery , 34.05 % in the high ligation group and 46.61 % in the MHIV group had a more than 50 % increase in their total motile sperm count ( P = 0.000 ) . The increase in sperm count was not statistically different between the two groups ( P = 0.1 ) , but the difference in the increase in sperm motility in the MHIV group was statistically significant ( P = 0.000 ) . Pregnancy rates at the end of 2 years reached 33.57 % in the high ligation group and 42.85 % in the MHIV group , not a statistically significant difference ( P = 0.0571 ) . The postoperative recurrence as detected by physical examination was markedly different between the two techniques . The recurrence rate was 15.51 % in the high ligation group and 2.11 % in the MHIV group ( P = 0.000 ) . Also , the incidence of postoperative hydrocele was significantly different between the two groups ( 9.09 % in the high ligation group and 0.69 % in the MHIV group ; P = 0.000 ) . CONCLUSIONS MHIV has lower recurrence and hydrocele rates , a higher increase in sperm motility , and results in higher pregnancy rates . Therefore , it should be the preferred technique for varicocelectomy",
"OBJECTIVES The traditional treatment for a painful varicocele consists of conservative measures followed by varicocelectomy . We report our results with microsurgical subinguinal varicocele ligation to treat pain . METHODS From 1996 to 1999 , a total of 119 men underwent subinguinal microsurgical varicocele ligation for painful varicocele . The diagnosis of varicocele was based on the findings of both physical examination and color Doppler ultrasound . Patients described pain with testicular discomfort as scrotal heaviness or a dull ache . While waiting for the operation ( range 3 to 5 weeks ) , all the patients underwent a preoperative trial of conservative management for pain . RESULTS Of 119 men , 82 ( 69 % ) were available for follow-up 3 months postoperatively . Of those 82 patients , 72 ( 88 % ) reported complete resolution of pain , 4 patients ( 5 % ) partial resolution , 5 patients ( 6 % ) no change , and 1 patient ( 1 % ) epididymal discomfort that resolved with conservative measures . Of the 9 patients with partial or no change , 2 patients had reflux recurrence as seen on color Doppler ultrasound . CONCLUSIONS Subinguinal microsurgical varicocele ligation is an effective treatment for painful varicocele when performed in selected patients",
"We compared outcome and complications of three simple varicocelectomy techniques . Groups were divided according to whether they would receive the Ivanissevich technique ( n = 55 ) , Tauber ’s technique ( n = 51 ) or subinguinal sclerotherapy ( n = 49 ) . Selection criteria were : infertility > 1 year , subnormal semen , sonographic diameter of veins > 3 mm and time of regurge > 2 s. Patients were r and omly assigned to the groups of treatment , with follow-up every 3 months for 1 year . Improvement was only in sperm count and total motility for all groups . Pregnancy rates were 20 , 13.73 and 12.24 % , respectively , with no significant difference between groups . Hydrocele occurred only in the group which received the Ivanissevich technique ( 5.5 % ) . Tauber ’s technique is simple ; however , it has the disadvantage of multiple branching of small veins",
"This prospect i ve r and omized study was performed in order to investigate the effects of interventive treatment or counselling on pregnancy rates in infertile couples in whose male partners a varicocele was diagnosed . The present report extends a previous study using the same design . A total of 125 couples were included in the current study while the previous report comprised 95 couples . Couples fulfilling the inclusion criteria were allocated r and omly either to interventive treatment ( surgical ligation or angiographic embolization of the spermatic vein ) ( n = 62 ) or to counselling as the sole treatment ( n = 63 ) . Couples were followed over the subsequent 12 months and seen at 3-monthly intervals . At the end of the 12 month period pregnancy rates , as the main outcome measure , were 29 % in the group given interventive treatment and 25.4 % in the counselled group and were not significantly different . The only significant difference found , regardless of treatment modality , was the wives ' age at admittance : the 34 wives achieving a pregnancy were 28.8 + /- 0.6 years ( mean + /- SE ) old while the 91 non-pregnant wives were 31.2 + /- 0.3 years old ( P counselling of the infertile couples is as effective as interventive treatment of varicoceles in achieving pregnancies",
"PURPOSE We review the long-term results of varicocele repair , and compare the complication rates of varicocelectomy techniques according to optical magnification use in adolescents with varicocele at a single university hospital . MATERIAL S AND METHODS We prospect ively studied 100 males 7 to 19 years old with clinical palpable varicocele . Of the patients 52 ( 52 % ) underwent left unilateral varicocelectomy and 48 ( 48 % ) underwent bilateral varicocelectomy . Varicocelectomy was performed using a microscope in 49 patients ( 79 sites ) , loupe magnification in 25 ( 35 sites ) and no magnification in 26 ( 34 sites ) using either a subinguinal or inguinal approach . Postoperative complications were compared in all patients based on technique . Preoperative and postoperative serum hormone values and semen parameters were compared in 33 patients . RESULTS Mean postoperative followup was 30.4 + /- 13.06 months ( 12 to 65 ) . Total motile sperm count increased from 22.6 million + /- 5.16 million to 64.53 million + /- 12.3 million postoperatively , which was statistically significant ( p = 0.002 ) . Postoperative recurrence rates were 0 % in cases managed by microsurgical varicocelectomy , 2.9 % in those where loupe magnification was used and 8.8 % in those where no magnification was used . Postoperative hydrocele rates in these cases were 0 % , 2.9 % and 5.9 % , respectively . The highest rates of recurrence and hydrocele were observed in cases where no magnification was used , compared to those managed by microsurgery ( p = 0.03 and p = 0.116 , respectively ) . CONCLUSIONS Adolescent varicocele repair improves semen parameters and is a safe method with low recurrence and low complication rates . Our study suggests that the postoperative complication rate significantly decreases with use of higher magnification , such as microscopy . Microsurgical varicocele repair is the best technique with the lowest postoperative rates of recurrence and hydrocele in the treatment of adolescent varicoceles"
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41188164-06ff-11f0-808a-c43d1ab1c353
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A systematic review was conducted to evaluate whether healthier dietary consumption among children and adolescents impacts executive functioning . PubMed , Education Re sources Information Center , PsychINFO and Thomson Reuters ' Web of Science data bases were search ed , and studies of executive functioning among children or adolescents aged 6 - 18 years , which examined food quality , macronutrients and /or foods , were included . Study quality was also assessed . In all , twenty-one studies met inclusion criteria . Among the twelve studies examining food quality ( n 9 ) or macronutrient intakes ( n 4 ) , studies examining longer-term diet ( n 6 ) showed positive associations between healthier overall diet quality and executive functioning , whereas the studies examining the acute impact of diet ( n 6 ) were inconsistent but suggestive of improvements in executive functioning with better food quality . Among the ten studies examining foods , overall , there was a positive association between healthier foods ( e.g. whole grains , fish , fruits and /or vegetables ) and executive function , whereas less-healthy snack foods , sugar-sweetened beverages and red/processed meats were inversely associated with executive functioning . Taken together , evidence suggests a positive association between healthy dietary consumption and executive functioning . Additional studies examining the effects of healthier food consumption , as well as macronutrients , on executive functioning are warranted . These studies should ideally be conducted in controlled environments and use vali date d cognitive tests
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"The impact of omega-3 long-chain polyunsaturated fatty acids ( LCPUFAs ) on cognition is heavily debated . In the current study , the possible association between omega-3 LCPUFAs in blood and cognitive performance of 266 typically developing adolescents aged 13–15 years is investigated . Baseline data from Food2Learn , a double-blind and r and omized placebo controlled krill oil supplementation trial in typically developing adolescents , were used for the current study . The Omega-3 Index was determined with blood from a finger prick . At baseline , participants finished a neuropsychological test battery consisting of the Letter Digit Substitution Test ( LDST ) , D2 test of attention , Digit Span Forward and Backward , Concept Shifting Test and Stroop test . Data were analyzed with multiple regression analyses with correction for covariates . The average Omega-3 Index was 3.83 % ( SD 0.60 ) . Regression analyses between the Omega-3 Index and the outcome parameters revealed significant associations with scores on two of the nine parameters . The association between the Omega-3 Index and both scores on the LDST ( β = 0.136 and p = 0.039 ) , and the number of errors of omission on the D2 ( β = −0.053 and p = 0.007 ) . This is a possible indication for a higher information processing speed and less impulsivity in those with a higher Omega-3 Index",
"The macronutrient composition of a breakfast that could facilitate performance after an overnight fast remains unclear . As glucose is the brain 's major energy source , the interest is in investigating meals differing in their blood glucose-raising potential . Findings vary due to unaccounted differences in glucoregulation , arousal and cortisol secretion . We investigated the effects of meals differing in glycaemic index ( GI ) and glycaemic load ( GL ) on cognition and mood in school children . A total of seventy-four school children were matched and r and omly allocated either to the high-GL or low-GL group . Within each GL group , children received high-GI and low-GI breakfasts . Cognitive function ( CF ) and mood were measured 95 - 140 min after breakfast . Blood glucose and salivary cortisol were measured at baseline , before and after the CF tests . Repeated- measures ANOVA was used to identify differences in CF , mood , glucose and cortisol levels between the breakfasts . Low-GI meals predicted feeling more alert and happy , and less nervous and thirsty ( P predicted feeling more confident , and less sluggish , hungry and thirsty ( P increased glucose levels 90 min after breakfast , and high-GI meals increased cortisol levels ( P baseline mood , glucose and cortisol levels were considered , low-GI meals predicted better declarative-verbal memory ( P = 0·03 ) , and high-GI meals better vigilance ( P . GI effects on cognition appear to be domain specific . On balance , it would appear that the low-GI high-GL breakfast may help to improve learning , and of potential value in informing government education policies relating to dietary recommendations and implementation concerning breakfast",
"Reliable tables of glycemic index ( GI ) compiled from the scientific literature are instrumental in improving the quality of research examining the relation between GI , glycemic load , and health . The GI has proven to be a more useful nutritional concept than is the chemical classification of carbohydrate ( as simple or complex , as sugars or starches , or as available or unavailable ) , permitting new insights into the relation between the physiologic effects of carbohydrate-rich foods and health . Several prospect i ve observational studies have shown that the chronic consumption of a diet with a high glycemic load ( GI x dietary carbohydrate content ) is independently associated with an increased risk of developing type 2 diabetes , cardiovascular disease , and certain cancers . This revised table contains almost 3 times the number of foods listed in the original table ( first published in this Journal in 1995 ) and contains nearly 1300 data entries derived from published and unpublished verified sources , representing > 750 different types of foods tested with the use of st and ard methods . The revised table also lists the glycemic load associated with the consumption of specified serving sizes of different foods",
"Twenty-nine schoolchildren were tested throughout the morning on 4 successive days , having a different breakfast each day ( either of the cereals Cheerios or Shreddies , glucose drink or No breakfast ) . A series of computerised tests of attention , working memory and episodic secondary memory was conducted prior to breakfast and again 30 , 90 , 150 and 210 min later . The glucose drink and No breakfast conditions were followed by declines in attention and memory , but the declines were significantly reduced in the two cereal conditions . This study provides objective evidence that a typical breakfast of cereal rich in complex carbohydrates can help maintain mental performance over the morning",
"Despite their potentially central role in fostering school readiness , executive function ( EF ) skills have received little explicit attention in the design and evaluation of school readiness interventions for socioeconomically disadvantaged children . The present study examined a set of five EF measures in the context of a r and omized-controlled trial of a research -based intervention integrated into Head Start programs ( Head Start REDI ) . Three hundred fifty-six 4-year-old children ( 17 % Hispanic , 25 % African American ; 54 % girls ) were followed over the course of the prekindergarten year . Initial EF predicted gains in cognitive and social-emotional skills and moderated the impact of the Head Start REDI intervention on some outcomes . The REDI intervention promoted gains on two EF measures , which partially mediated intervention effects on school readiness . We discuss the importance of further study of the neurobiological bases of school readiness , the implication s for intervention design , and the value of incorporating markers of neurobiological processes into school readiness interventions",
"Fe and n-3 long-chain PUFA ( n-3 LCPUFA ) have both been associated with cognition , but evidence remains inconclusive in well-nourished school-aged children . In the Optimal Well-Being , Development and Health for Danish Children through a Healthy New Nordic Diet ( OPUS ) School Meal Study , the 3-month intervention increased reading performance , inattention , impulsivity and dietary intake of fish and Fe . This study investigated whether the intervention influenced n-3 LCPUFA and Fe status and , if so , explored how these changes correlated with the changes in cognitive performance . The study was a cluster-r and omised cross-over trial comparing school meals with packed lunch ( control ) . At baseline and after each treatment , we measured serum ferritin , whole-blood n-3 LCPUFA and Hb , and performance in reading , mathematics and d2-test of attention . Data were analysed using mixed models ( n 726 ) and principal component analysis of test performances ( n 644 ) , which showed two main patterns : ' school performance ' and ' reading comprehension ' . The latter indicated that children with good reading comprehension were also more inattentive and impulsive ( i.e. higher d2-test error% ) . The intervention improved ' school performance ' ( P=0·015 ) , ' reading comprehension ' ( P=0·043 ) and EPA+DHA status 0·21 ( 95 % CI 0·15 , 0·27 ) w/w % ( P affect serum ferritin or Hb . At baseline , having small Fe stores was associated with poorer ' school performance ' in girls , but with better ' reading comprehension ' in both boys and girls . Both baseline EPA+DHA status and the intervention-induced increase in EPA+DHA status was positively associated with ' school performance ' , suggesting that n-3 LCPUFA could potentially explain approximately 20 % of the intervention effect . These exploratory associations indicate that increased fish intake might explain some of the increase in reading performance and inattention in the study",
"BACKGROUND Biochemical and behavioral evidence has suggested that the ratio of n-6 ( omega-6 ) to n-3 ( omega-3 ) could be an important predictor of executive function abilities in children . OBJECTIVE We determined the relation between the ratio of n-6 to n-3 and cognitive function in children . We hypothesized that children with lower ratios of n-6 to n-3 fatty acids would perform better on tests of planning and working memory . DESIGN Seventy 7- to 9-y-old children completed three 24-h diet recalls and a subset of the Cambridge Neuropsychological Test Assessment Battery . Parents provided information on their demographics and children 's diet histories . RESULTS Mean n-3 and mean n-6 intakes were related to the mean time spent on each action taken in the planning problem . The ratio of n-6 to n-3 significantly predicted performance on the working memory and planning problems . There was a significant interaction between the ratio and fatty acid intake ; when children had high ratios , a higher intake of n-3 fatty acids predicted a better performance on the planning task than when children had lower n-3 intakes . When children had low ratios , a lower intake of n-3 and lower intake of n-6 predicted better performance than when intakes were higher . CONCLUSIONS The relation between cognitive abilities and the ratio of n-6 to n-3 may be mediated by an enzymatic affinity for n-3 fatty acids . The ratio of n-6 to n-3 should be considered an important factor in the study of fatty acids and cognitive development . This trial was registered at clinical trials.gov as NCT01823419",
"BACKGROUND The aim of the study was to investigate prospect i ve associations between dietary patterns and cognitive performance during adolescence . METHODS Participants were source d from the Western Australian Pregnancy Cohort ( Raine ) Study that includes 2868 children born between 1989 and 1992 in Perth , Western Australia . When the children were 17 years old ( 2006 - 2009 ) , cognitive performance was assessed using a computerized cognitive battery of tests ( CogState ) that included six tasks . Using a food frequency question naire administered when the children were 14 years old ( 2003 - 2006 ) , ' Healthy ' and ' Western ' dietary patterns were identified by factor analysis . Associations between dietary patterns at 14 years of age and cognitive performance at 17 years of age were assessed prospect ively using multivariate regression models . RESULTS Dietary and cognitive performance data were available for 602 participants . Following adjustment for the ' Healthy ' dietary pattern , total energy intake , maternal education , family income , father 's presence in the family , family functioning and gender , we found that a longer reaction time in the detection task ( β = .016 ; 95 % CI : 0.004 ; 0.028 ; p = .009 ) and a higher number of total errors in the Groton Maze Learning Test - delayed recall task ( β = .060 ; 95 % CI : 0.006 ; 0.114 ; p = .029 ) were significantly associated with higher scores on the ' Western ' dietary pattern . The ' Western ' dietary pattern was characterized by high intakes of take-away food , red and processed meat , soft drink , fried and refined food . We also found that within the dietary patterns , high intake of fried potato , crisps and red meat had negative associations , while increased fruit and leafy green vegetable intake had positive associations with some aspects of cognitive performance . CONCLUSION Higher dietary intake of the ' Western ' dietary pattern at age 14 is associated with diminished cognitive performance 3 years later , at 17 years",
"The authors examined early psychopathology as a predictor of trajectories of drug use from ages 13 - 18 years . Six years of annual data were analyzed for 506 boys using a mixed effects polynomial growth curve model . They tested whether distinct measures of psychopathology and behavioral problems ( i.e. , attention-deficit/hyperactivity disorder , oppositional defiant disorder , conduct disorder , depression , and violence ) assessed in early adolescence could prospect ively predict level and change in alcohol and marijuana use . Higher levels of all of the types of psychopathology predicted higher levels of alcohol use , and higher levels of attention-deficit/hyperactivity disorder , conduct disorder , and violence predicted higher levels of marijuana use . Only conduct disorder predicted linear growth in alcohol use , and none of the measures predicted growth in marijuana use . The results suggest that drug use prevention programs should target youths with early symptoms of psychopathology",
"OBJECTIVE Adolescence is a stage of rapid growth , when rich nutritional supplementation is important . Maintaining optimal cognitive functioning is critical in high school students , who are under considerable academic pressure . The objectives of this study were to identify the effects of a 9-wk r and omly assigned diet of mixed grains versus a regular diet on cognitive performance and on levels of plasma brain-derived neurotrophic factor ( BDNF ) and S100B , a calcium-binding protein produced by astroglial cells , in healthy high school students ( grade s 10 and 11 ) . METHODS In this 9-wk , single-blind , controlled study , subjects were r and omly allocated to either a mixed-grain or a regular diet . Cognitive assessment s and measurements of plasma BDNF and S100B levels were performed at baseline and after the 9-wk intake of a mixed-grain or regular diet . Computerized neuropsychological tests and self-rating scales were used for the cognitive assessment s. RESULTS Significant improvements in some neuropsychological tests were found after 9 wk in both the mixed-grain and the regular-diet groups , but the changes from baseline between the two groups were not significantly different . Significant impairments on the AX-continuous performance test were observed at the endpoint in the regular-diet group , and the changes from baseline between the two groups were also significantly different for this test . A significant difference in changes in BDNF levels was observed between the two groups . CONCLUSIONS These results suggest that intake of mixed grains for 9 wk is beneficial for cognitive performance and plasma BDNF levels in high school students . These beneficial effects seem to be related to the prevention of cognitive deterioration in a mental-fatigue test with the mixed-grain diet , rather than cognitive enhancement per se"
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411881a0-06ff-11f0-808a-c43d1ab1c353
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Neurofeedback ( NF ) has gained increasing interest in the treatment of attention-deficit/hyperactivity disorder ( ADHD ) . Given learning principles underlie NF , lasting clinical treatment effects may be expected . This systematic review and meta- analysis addresses the sustainability of neurofeedback and control treatment effects by considering r and omized controlled studies that conducted follow-up ( FU ; 2–12 months ) assessment s among children with ADHD . PubMed and Scopus data bases were search ed through November 2017 . Within-group and between-group st and ardized mean differences ( SMD ) of parent behavior ratings were calculated and analyzed . Ten studies met inclusion criteria ( NF : ten studies , N = 256 ; control : nine studies , N = 250 ) . Within-group NF effects on inattention were of medium effect size ( ES ) ( SMD = 0.64 ) at post-treatment and increased to a large ES ( SMD = 0.80 ) at FU . Regarding hyperactivity/impulsivity , NF ES were medium at post-treatment ( SMD = 0.50 ) and FU ( SMD = 0.61 ) . Non-active control conditions yielded a small significant ES on inattention at post-treatment ( SMD = 0.28 ) but no significant ES at FU . Active treatments ( mainly methylpheni date ) , had large ES for inattention ( post : SMD = 1.08 ; FU : SMD = 1.06 ) and medium ES for hyperactivity/impulsivity ( post : SMD = 0.74 ; FU : SMD = 0.67 ) . Between-group analyses also revealed an advantage of NF over non-active controls [ inattention ( post : SMD = 0.38 ; FU : SMD = 0.57 ) ; hyperactivity – impulsivity ( post : SMD = 0.25 ; FU : SMD = 0.39 ) ] , and favored active controls for inattention only at pre-post ( SMD = − 0.44 ) . Compared to non-active control treatments , NF appears to have more durable treatment effects , for at least 6 months following treatment . More studies are needed for a properly powered comparison of follow-up effects between NF and active treatments and to further control for non-specific effects
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"Background : Treatment for children with attention deficit/hyperactivity disorder ( ADHD ) today is predominantly pharmacological . While it is the most common treatment , it might not always be the most appropriate one . Moreover , long term effects remain unclear . Behavior therapy ( BT ) and non-pharmacological treatments such as neurofeedback ( NF ) are promising alternatives , though there are no routine outpatient care/effectiveness studies yet that have included children with medication or changes in medication . Methods / design : This paper presents the protocol of a r and omized controlled trial to compare the effectiveness of a Slow Cortical Potential ( SCP ) NF protocol with self-management ( SM ) in a high frequent outpatient care setting . Both groups ( NF/SM ) receive a total of 30 high frequent therapy sessions . Additionally , 6 sessions are reserved for comorbid problems . The primary outcome measure is the reduction of ADHD core symptoms according to parent and teacher ratings . Preliminary Results : Untill now 58 children were included in the study ( 48 males ) , with a mean age of 8.42 ( 1.34 ) years , and a mean IQ of 110 ( 13.37 ) . Conners-3 parent and teacher ratings were used to estimate core symptom change . Since the study is still ongoing , and children are in different study stages , pre-post and follow-up results are not yet available for all children included . Preliminary results suggest overall good pre-post effects , though . For parent and teacher ratings an ANOVA with repeated measures yielded overall satisfying pre-post effects ( η2 0.175–0.513 ) . Differences between groups ( NF vs. SM ) could not yet be established ( p = 0.81 ) . Discussion : This is the first r and omized controlled trial to test the effectiveness of a NF protocol in a high frequent outpatient care setting that does not exclude children on or with changes in medication . First preliminary results show positive effects . The rationale for the trial , the design , and the strengths and limitations of the study are discussed . Trial registration : This trial is registered in www . clinical trials.gov as NCT01879644",
"Abstract Background : Different treatment approaches aim ed at reducing attention-deficit/hyperactivity disorder ( ADHD ) core symptoms are available . However , factors such as intolerance , side-effects , lack of efficacy , high new technology costs , and placebo effect have spurred on an increasing interest in alternative or complementary treatment . Aim : The aim of this study is to explore efficacy of multimodal treatment consisting of st and ard stimulant medication ( methylpheni date ) and neurofeedback ( NF ) in combination , and to compare it with the single treatment in 6-month follow-up in ADHD children and adolescents . Methods : This r and omized controlled trial with 6-month follow-up comprised three treatment arms : multimodal treatment ( NF + MED ) , MED alone , and NF alone . A total of 130 ADHD children/adolescents participated , and 62 % completed the study . ADHD core symptoms were recorded pre-/post-treatment , using parents ’ and teachers ’ forms taken from Barkley ’s Defiant Children : A Clinician ’s Manual for Assessment and Parent Training , and a self-report question naire . Results : Significant ADHD core symptom improvements were reported 6 months after treatment completion by parents , teachers , and participants in all three groups , with marked improvement in inattention in all groups . However , no significant improvements in hyperactivity or academic performance were reported by teachers or self-reported by children/adolescents , respectively , in the three groups . Changes obtained with multimodal treatment at 6-month follow-up were comparable to those with single medication treatment , as reported by all participants . Conclusions : Multimodal treatment using combined stimulant medication and NF showed 6-month efficacy in ADHD treatment . More research is needed to explore whether multimodal treatment is suitable for ADHD children and adolescents who showed a poor response to single medication treatment , and for those who want to reduce the use of stimulant medication",
"Background Estimates of the effectiveness of neurofeedback as a treatment for attention-deficit hyperactivity disorder ( ADHD ) are mixed . Aims To investigate the long-term additional effects of neurofeedback ( NFB ) compared with treatment as usual ( TAU ) for adolescents with ADHD . Method Using a multicentre parallel-r and omised controlled trial design , 60 adolescents with a DSM-IV-TR diagnosis of ADHD receiving NFB+TAU ( n=41 ) or TAU ( n=19 ) were followed up . Neurofeedback treatment consisted of approximately 37 sessions of theta/sensorimotor rhythm (SMR)-training on the vertex ( Cz ) . Outcome measures included behavioural self-reports and neurocognitive measures . Allocation to the conditions was unmasked . Results At 1-year follow-up , inattention as reported by adolescents was decreased ( range ηp2=0.23–0.36 , P ) and performance on neurocognitive tasks was faster ( range ηp2=0.20–0.67 , P NFB+TAU was as effective as TAU . Given the absence of robust additional effects of neurofeedback in the current study , results do not support the use of theta/SMR neurofeedback as a treatment for adolescents with ADHD and comorbid disorders in clinical practice . Declaration of interest None . Copyright and usage © The Royal College of Psychiatrists 2016 . This is an open access article distributed under the terms of the Creative Commons Non-Commercial , No Derivatives ( CC BY-NC-ND ) licence",
"Neurofeedback ( NF ) could help to improve attentional and self-management capabilities in children with attention-deficit/hyperactivity disorder ( ADHD ) . In a r and omised controlled trial , NF training was found to be superior to a computerised attention skills training ( AST ) ( Gevensleben et al. in J Child Psychol Psychiatry 50(7):780–789 , 2009 ) . In the present paper , treatment effects at 6-month follow-up were studied . 94 children with ADHD , aged 8–12 years , completed either 36 sessions of NF training ( n = 59 ) or a computerised AST ( n = 35 ) . Pre-training , post-training and follow-up assessment encompassed several behaviour rating scales ( e.g. , the German ADHD rating scale , FBB-HKS ) completed by parents . Follow-up information was analysed in 61 children ( ca . 65 % ) on a per- protocol basis . 17 children ( of 33 dropouts ) had started a medication after the end of the training or early in the follow-up period . Improvements in the NF group ( n = 38 ) at follow-up were superior to those of the control group ( n = 23 ) and comparable to the effects at the end of the training . For the FBB-HKS total score ( primary outcome measure ) , a medium effect size of 0.71 was obtained at follow-up . A reduction of at least 25 % in the primary outcome measure ( responder criterion ) was observed in 50 % of the children in the NF group . In conclusion , behavioural improvements induced by NF training in children with ADHD were maintained at a 6-month follow-up . Though treatment effects appear to be limited , the results confirm the notion that NF is a clinical ly efficacious module in the treatment of children with ADHD",
"OBJECTIVE To test the hypotheses that in children with attention-deficit/hyperactivity disorder ( ADHD ) ( 1 ) symptoms of ADHD , oppositional defiant disorder , and overall functioning are significantly improved by methylpheni date combined with intensive multimodal psychosocial treatment compared with methylpheni date alone and with methylpheni date plus attention control and ( 2 ) more children receiving combined treatment can be taken off methylpheni date . METHOD One hundred three children with ADHD ( ages 7 - 9 ) , free of conduct and learning disorders , who responded to short-term methylpheni date were r and omized for 2 years to ( 1 ) methylpheni date alone ; ( 2 ) methylpheni date plus psychosocial treatment that included parent training and counseling , social skills training , psychotherapy , and academic assistance , or ( 3 ) methylpheni date plus attention psychosocial control treatment . Assessment s included parent , teacher , and psychiatrist ratings , and observations in academic and gym classes . RESULTS Combination treatment did not lead to superior functioning and did not facilitate methylpheni date discontinuation . Significant improvement occurred across all treatments and continued over 2 years . CONCLUSIONS In stimulant-responsive children with ADHD , there is no support for adding ambitious long-term psychosocial intervention to improve ADHD and oppositional defiant disorder symptoms . Significant benefits from methylpheni date were stable over 2 years",
"OBJECTIVE : To evaluate sustained improvements 6 months after a 40-session , in-school computer attention training intervention using neurofeedback or cognitive training ( CT ) administered to 7- to 11-year-olds with attention-deficit/hyperactivity disorder ( ADHD ) . METHODS : One hundred four children were r and omly assigned to receive neurofeedback , CT , or a control condition and were evaluated 6 months postintervention . A 3-point growth model assessed change over time across the conditions on the Conners 3–Parent Assessment Report ( Conners 3-P ) , the Behavior Rating Inventory of Executive Function Parent Form ( BRIEF ) , and a systematic double-blinded classroom observation ( Behavioral Observation of Students in Schools ) . Analysis of variance assessed community-initiated changes in stimulant medication . RESULTS : Parent response rates were 90 % at the 6-month follow-up . Six months postintervention , neurofeedback participants maintained significant gains on Conners 3-P ( Inattention effect size [ ES ] = 0.34 , Executive Functioning ES = 0.25 , Hyperactivity/Impulsivity ES = 0.23 ) and BRIEF subscales including the Global Executive Composite ( ES = 0.31 ) , which remained significantly greater than gains found among children in CT and control conditions . Children in the CT condition showed delayed improvement over immediate postintervention ratings only on Conners 3-P Executive Functioning ( ES = 0.18 ) and 2 BRIEF subscales . At the 6-month follow-up , neurofeedback participants maintained the same stimulant medication dosage , whereas participants in both CT and control conditions showed statistically and clinical ly significant increases ( 9 mg [ P = .002 ] and 13 mg [ P Neurofeedback participants made more prompt and greater improvements in ADHD symptoms , which were sustained at the 6-month follow-up , than did CT participants or those in the control group . This finding suggests that neurofeedback is a promising attention training treatment for children with ADHD",
"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",
"Abstract To assess the long-term effects of neurofeedback ( NFB ) in children with attention deficit hyperactivity disorder ( ADHD ) , we compared behavioral and neurocognitive outcomes at a 6-month naturalistic follow-up of a r and omized controlled trial on NFB , methylpheni date ( MPH ) , and physical activity ( PA ) . Ninety-two children with a DSM-IV-TR ADHD diagnosis , aged 7–13 , receiving NFB ( n = 33 ) , MPH ( n = 28 ) , or PA ( n = 31 ) , were re-assessed 6-months after the interventions . NFB comprised theta/beta training on the vertex ( cortical zero ) . PA comprised moderate to vigorous intensity exercises . Outcome measures included parent and teacher behavioral reports , and neurocognitive measures ( auditory oddball , stop-signal , and visual spatial working memory tasks ) . At follow-up , longitudinal hierarchical multilevel model analyses revealed no significant group differences for parent reports and neurocognitive measures ( p = .058–.997 ) , except for improved inhibition in MPH compared to NFB ( p = .040 ) and faster response speed in NFB compared to PA ( p = .012 ) during the stop-signal task . These effects , however , disappeared after controlling for medication use at follow-up . Interestingly , teacher reports showed less inattention and hyperactivity/impulsivity at follow-up for NFB than PA ( p = .004–.010 ) , even after controlling for medication use ( p = .013–.036 ) . Our findings indicate that the superior results previously found for parent reports and neurocognitive outcome measures obtained with MPH compared to NFB and PA post intervention became smaller or non-significant at follow-up . Teacher reports suggested superior effects of NFB over PA ; however , some children had different teachers at follow-up . Therefore , this finding should be interpreted with caution . Clinical trial registration Train your brain and exercise your heart ? Advancing the treatment for Attention Deficit Hyperactivity Disorder ( ADHD ) , Ref . no. NCT01363544 , https:// clinical trials.gov/show/NCT01363544",
"BACKGROUND Learned self-control of slow cortical potentials ( SCPs ) may lead to behavioral improvement in attention-deficit/hyperactivity disorder ( ADHD ) . Hence , training effects should also be reflected at the neurophysiological level . METHODS Thirteen children with ADHD , aged 7 - 13 years , performed 25 SCP training sessions within 3 weeks . Before and after training , the German ADHD rating scale was completed by parents , and event-related potentials were recorded in a cued continuous performance test ( CPT ) . For a waiting-list group of nine children with ADHD , the same testing was applied . RESULTS ADHD symptomatology was reduced by approximately 25 % after SCP training . Moreover , a decrease of impulsivity errors and an increase of the contingent negative variation were observed in the CPT task . CONCLUSIONS This study provides first evidence for both positive behavioral and specific neurophysiological effects of SCP training in children with ADHD",
"One hundred children , ages 6–19 , who were diagnosed with attention-deficit/hyperactivity disorder ( ADHD ) , either inattentive or combined types , participated in a study examining the effects of Ritalin , EEG biofeedback , and parenting style on the primary symptoms of ADHD . All of the patients participated in a 1-year , multimodal , outpatient program that included Ritalin , parent counseling , and academic support at school ( either a 504 Plan or an IEP ) . Fifty-one of the participants also received EEG biofeedback therapy . Posttreatment assessment s were conducted both with and without stimulant therapy . Significant improvement was noted on the Test of Variables of Attention ( TOVA ; L. M. Greenberg , 1996 ) and the Attention Deficit Disorders Evaluation Scale ( ADDES ; S. B. McCarney , 1995 ) when participants were tested while using Ritalin . However , only those who had received EEG biofeedback sustained these gains when tested without Ritalin . The results of a Quantitative Electroencephalographic Scanning Process ( QEEG-Scan ; V. J. Monastra et al. , 1999 ) revealed significant reduction in cortical slowing only in patients who had received EEG biofeedback . Behavioral measures indicated that parenting style exerted a significant moderating effect on the expression of behavioral symptoms at home but not at school",
"The present study is a r and omized controlled trial that aims to evaluate the efficacy of Neurofeedback compared to st and ard pharmacological intervention in the treatment of attention deficit/hyperactivity disorder ( ADHD ) . The final sample consisted of 23 children with ADHD ( 11 boys and 12 girls , 7 - 14 years old ) . Participants carried out 40 theta/beta training sessions or received methylpheni date . Behavioral rating scales were completed by fathers , mothers , and teachers at pre- , post-treatment , two- , and six-month naturalistic follow-up . In both groups , similar significant reductions were reported in ADHD functional impairment by parents ; and in primary ADHD symptoms by parents and teachers . However , significant academic performance improvements were only detected in the Neurofeedback group . Our findings provide new evidence for the efficacy of Neurofeedback , and contribute to enlarge the range of non-pharmacological ADHD intervention choices . To our knowledge , this is the first r and omized controlled trial with a six-month follow-up that compares Neurofeedback and stimulant medication in ADHD",
"OBJECTIVE A double-blind , r and omized , placebo-controlled study was design ed to assess the efficacy and safety of electroencephalographic ( EEG ) neurofeedback in children with attention-deficit/hyperactivity disorder ( ADHD ) . The study started in August 2008 and ended in July 2012 and was conducted at Karakter Child and Adolescent Psychiatry University Centre in Nijmegen , The Netherl and s. METHOD Forty-one children ( aged 8 - 15 years ) with a DSM-IV-TR diagnosis of ADHD were r and omly assigned to treatment with either EEG neurofeedback ( n = 22 ) or placebo neurofeedback ( n = 19 ) for 30 sessions , given as 2 sessions per week . The children were stratified by age , electrophysiologic state of arousal , and medication use . Everyone involved in the study , except the neurofeedback therapist and the principal investigator , was blinded to treatment assignment . The primary outcome was severity of ADHD symptoms on the ADHD Rating Scale IV , scored at baseline , during treatment , and at study end . Clinical improvement as measured by the Clinical Global Impressions-Improvement scale ( CGI-I ) was a secondary outcome . RESULTS While total ADHD symptoms improved over time in both groups ( F1,39 = 26.56 , P clinical improvement as measured by the CGI-I ( P = .092 ) . No clinical ly relevant side effects were observed . Among the children and their parents , guessing treatment assignment was not better than chance level ( P = .224 for children , P = .643 for parents ) . CONCLUSION EEG neurofeedback was not superior to placebo neurofeedback in improving ADHD symptoms in children with ADHD . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00723684",
"OBJECTIVE In the Multimodal Treatment Study of ADHD ( MTA ) , the effects of medication management ( MedMgt ) and behavior modification therapy ( Beh ) and their combination ( Comb ) and usual community comparison ( CC ) in the treatment of attention-deficit/hyperactivity disorder ( ADHD ) differed at the 14-month assessment as a result of superiority of the MTA MedMgt strategy ( Comb or MedMgt ) over Beh and CC and modest additional benefits of Comb over MedMgt alone . Here we evaluate the persistence of these beneficial effects 10 months beyond the 14 months of intensive intervention . METHODS Of 579 children who entered the study , 540 ( 93 % ) participated in the first follow-up 10 months after the end of treatment . Mixed-effects regression models explored possible persisting effects of the MTA medication strategy , the incremental benefits of Comb over MedMgt alone , and the possible superiority of Beh over CC on 5 effectiveness and 4 service use domains . RESULTS The MTA medication strategy showed persisting significant superiority over Beh and CC for ADHD and oppositional-defiant symptoms at 24 months , although not as great as at 14 months . Significant additional benefits of Comb over MedMgt and of Beh over CC were not found . The groups differed significantly in mean dose ( methylpheni date equivalents 30.4 , 37.5 , 25.7 , and 24.0 mg/day , respectively ) . Continuing medication use partly mediated the persisting superiority of Comb and MedMgt . CONCLUSION The benefits of intensive MedMgt for ADHD extend 10 months beyond the intensive treatment phase only in symptom domains and diminish over time",
"OBJECTIVE Electroencephalographic ( EEG ) neurofeedback ( NF ) is considered a nonpharmacological alternative for medication in attention-deficit/hyperactivity disorder ( ADHD ) . Comparisons of the behavioral efficacy of NF and medication have produced inconsistent results . EEG measures can provide insight into treatment mechanisms , but have received little consideration . In this r and omized controlled trial ( RCT ) , effects of NF were compared with methylpheni date ( MPH ) , and physical activity ( PA ) in children with ADHD on event-related potential ( ERP ) indices of response inhibition , which are involved in ADHD psychopathology . METHODS Using a multicenter three way parallel group RCT design , 112 children with a Diagnostic and Statistical Manual of Mental Disorders , 4th ed . ( DSM-IV ) ( American Psychiatric Association 1994 ) diagnosis of ADHD , between 7 and 13 years of age , were initially included . NF training consisted of 30 sessions of theta/beta training at Cz over a 10 week period . PA training was a semiactive control group , matched in frequency and duration . MPH was titrated using a double-blind placebo controlled procedure in 6 weeks , followed by a stable dose for 4 weeks . ERP measures of response inhibition , N2 and P3 , were available for 81 children at pre- and postintervention ( n = 32 NF , n = 25 MPH , n = 24 PA ) . RESULTS Only the medication group showed a specific increase in P3 amplitude compared with NF ( partial eta-squared [ ηp(2 ) ] = 0.121 ) and PA ( ηp(2 ) = 0.283 ) , which was related to improved response inhibition . Source localization of medication effects on P3 amplitude indicated increased activation primarily in thalamic and striatal nuclei . CONCLUSIONS This is the first study that simultaneously compared NF with stimulant treatment and a semiactive control group . Only stimulant treatment demonstrated specific improvements in brain function related to response inhibition . These results are in line with recent doubts on the efficacy and specificity of NF as treatment for ADHD . CLINICAL TRIALS REGISTRATION Train Your Brain ? Exercise and Neurofeedback Intervention for ADHD , https:// clinical trials.gov/show/NCT01363544 , Ref . No. NCT01363544",
"Neurofeedback has been proposed as a potentially effective intervention for reducing Attention Deficit Hyperactivity Disorder ( ADHD ) symptoms . However , it remains unclear whether neurofeedback is of additional value to treatment as usual ( TAU ) for adolescents with clinical ADHD symptoms . Using a multicenter parallel-r and omized controlled trial design , adolescents with ADHD symptoms were r and omized to receive either a combination of TAU and neurofeedback ( NFB + TAU , n = 45 ) or TAU-only ( n = 26 ) . R and omization was computer generated and stratified for age group ( ages 12 through 16 , 16 through 20 , 20 through 24 ) . Neurofeedback treatment consisted of approximately 37 sessions of theta/sensorimotor rhythm (SMR)-training on the vertex ( Cz ) . Primary behavioral outcome measures included the ADHD-rating scale , Youth Self Report , and Child Behavior Checklist all assessed pre- and post-intervention . Behavioral problems decreased equally for both groups with medium to large effect sizes , range of partial η2 = 0.08–0.31 , p of NFB + TAU was not more effective than TAU-only on the behavioral outcome measures . In addition , reported adverse effects were similar for both groups . On behavioral outcome measures , the combination of neurofeedback and TAU was as effective as TAU-only for adolescents with ADHD symptoms . Considering the absence of additional behavioral effects in the current study , in combination with the limited knowledge of specific treatment effects , it is question able whether theta/SMR neurofeedback for adolescents with ADHD and comorbid disorders in clinical practice should be used . Further research is warranted to investigate possible working mechanisms and ( long-term ) specific treatment effects of neurofeedback ",
"PURPOSE To evaluate the efficacy of combined methylpheni date and EEG feedback treatment for children with ADHD . METHODS Forty patients with ADHD were r and omly assigned to the combination group ( methylpheni date therapy and EEG feedback training ) or control group ( methylpheni date therapy and non-feedback attention training ) in a 1:1 ratio using the double-blind method . These patients , who met the DSM-IV diagnostic criteria and were aged between 7 and 16 years , had obtained optimal therapeutic effects by titrating the methylpheni date dose prior to the trial . The patients were assessed using multiple parameters at baseline , after 20 treatment sessions , after 40 treatment sessions , and in 6-month follow-up studies . RESULTS Compared to the control group , patients in the combination group had reduced ADHD symptoms and improved in related behavioural and brain functions . CONCLUSION The combination of EEG feedback and methylpheni date treatment is more effective than methylpheni date alone . The combined therapy is especially suitable for children and adolescents with ADHD who insufficiently respond to single drug treatment or experience drug side effects",
"In a r and omized controlled trial , neurofeedback ( NF ) training was found to be superior to a computerised attention skills training concerning the reduction of ADHD symptomatology ( Gevensleben et al. , 2009 ) . The aims of this investigation were to assess the impact of different NF protocol s ( theta/beta training and training of slow cortical potentials , SCPs ) on the resting EEG and the association between distinct EEG measures and behavioral improvements . In 72 ( of initially 102 ) children with ADHD , aged 8 - 12 , EEG changes after either a NF training ( n=46 ) or the control training ( n=26 ) could be studied . The combined NF training consisted of one block of theta/beta training and one block of SCP training , each block comprising 18 units of 50 minutes ( balanced order ) . Spontaneous EEG was recorded in a two-minute resting condition before the start of the training , between the two training blocks and after the end of the training . Activity in the different EEG frequency b and s was analyzed . In contrast to the control condition , the combined NF training was accompanied by a reduction of theta activity . Protocol -specific EEG changes ( theta/beta training : decrease of posterior-midline theta activity ; SCP training : increase of central -midline alpha activity ) were associated with improvements in the German ADHD rating scale . Related EEG-based predictors were obtained . Thus , differential EEG patterns for theta/beta and SCP training provide further evidence that distinct neuronal mechanisms may contribute to similar behavioral improvements in children with ADHD",
"BACKGROUND The Multimodal Treatment Study ( MTA ) began as a 14-month r and omized clinical trial of behavioral and pharmacological treatments of 579 children ( 7 - 10 years of age ) diagnosed with attention-deficit/hyperactivity disorder (ADHD)-combined type . It transitioned into an observational long-term follow-up of 515 cases consented for continuation and 289 classmates ( 258 without ADHD ) added as a local normative comparison group ( LNCG ) , with assessment s 2 - 16 years after baseline . METHODS Primary ( symptom severity ) and secondary ( adult height ) outcomes in adulthood were specified . Treatment was monitored to age 18 , and naturalistic subgroups were formed based on three patterns of long-term use of stimulant medication ( Consistent , Inconsistent , and Negligible ) . For the follow-up , hypothesis-generating analyses were performed on outcomes in early adulthood ( at 25 years of age ) . Planned comparisons were used to estimate ADHD-LNCG differences reflecting persistence of symptoms and naturalistic subgroup differences reflecting benefit ( symptom reduction ) and cost ( height suppression ) associated with extended use of medication . RESULTS For ratings of symptom severity , the ADHD-LNCG comparison was statistically significant for the parent/self-report average ( 0.51 ± 0.04 , p symptom persistence , and for the parent/self-report difference ( 0.21 ± 0.04 , p adult height , the ADHD group was 1.29 ± 0.55 cm shorter than the LNCG ( p symptom persistence compared to local norms from the LNCG . Within naturalistic subgroups of ADHD cases , extended use of medication was associated with suppression of adult height but not with reduction of symptom severity "
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OBJECTIVE Pathomechanisms of sedentary behaviour ( SB ) are unclear . We conducted a systematic review to investigate the associations between SB and various biomarkers in older adults . METHODS Electronic data bases were search ed ( MEDLINE , EMBASE , CINAHL , AMED ) up to July 2015 to identify studies with objective or subjective measures of SB , sample size ≥50 , mean age ≥60years and accelerometer wear time ≥3days . Method ological quality was appraised with the CASP tool . The protocol was pre-specified ( PROSPERO CRD42015023731 ) . RESULTS 12701 abstract s were retrieved , 275 full text articles further explored , from which 249 were excluded . In the final sample ( 26 articles ) a total of 63 biomarkers were detected . Most investigated markers were : body mass index ( BMI , n=15 ) , waist circumference ( WC , n=15 ) , blood pressure ( n=11 ) , triglycerides ( n=12 ) and high density lipoprotein ( HDL , n=15 ) . Some inflammation markers were identified such as interleukin-6 , C-reactive protein or tumor necrosis factor alpha . There was a lack of renal , muscle or bone biomarkers . R and omized controlled trials found a positive correlation for SB with BMI , neck circumference , fat mass , HbA1C , cholesterol and insulin levels , cohort studies additionally for WC , leptin , C-peptide , ApoA1 and Low density lipoprotein and a negative correlation for HDL . CONCLUSION Most studied biomarkers associated with SB were of cardiovascular or metabolic origin . There is a suggestion of a negative impact of SB on biomarkers but still a paucity of high quality investigations exist . Longitudinal studies with objective ly measured SB are needed to further eluci date the pathophysiological pathways and possible associations of unexplored biomarkers
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"Background Age‐related endothelial dysfunction and vascular stiffening are associated with increased cardiovascular ( CV ) risk . Many groups have encouraged goals of ≥10 000 steps/day or ≥30 min/day of moderate intensity physical activity ( MPA ) to reduce age‐related CV risk . The impact of MPA on the vasculature of older adults remains unclear . Methods and Results We r and omized 114 sedentary older adults ages ≥50 to 12 weeks of either no intervention ( group 1 ) , a pedometer‐only intervention ( group 2 ) , or a pedometer with an interactive website employing strategies to increase the adoption of habitual physical activity ( PA , group 3 ) . Endothelial function by brachial flow‐mediated dilation ( FMD% ) , vascular stiffness by tonometry , step‐count by pedometer , and PA intensity/distribution by accelerometer were measured . Step‐count increased in groups 2 ( 5136±1554 to 9596±3907 , P increased MPA ≥30 min/day . Only group 3 increased MPA in continuous bouts of ≥10 minutes ( P and improved FMD% ( P=0.001 ) . Neither achievement of ≥10 000 steps/day nor ≥30 min/day of MPA result ed in improved FMD% . However , achieving ≥20 min/day in MPA bouts result ed in improved FMD% . No changes in vascular stiffness were observed . Conclusions MPA reverses age‐related endothelial dysfunction , but may require MPA to be performed in bouts of ≥10 minutes duration for ≥20 min/day to be effective . Commonly encouraged PA goals do not guarantee improved endothelial function and may not be as effective in reducing CV risk . Clinical Trial Registration URL : Clinical trials.gov . Unique identifier : NCT‐01212978",
"CONTEXT High vitamin D and physical activity ( PA ) levels are independently associated with improved body composition and muscle function in older adults . OBJECTIVE The objective of this study was to investigate the interaction of 25-hydroxyvitamin D ( 25OHD ) and PA status in maintenance of body composition and muscle function in older adults . DESIGN AND SETTING This was a 5-year prospect i ve population -based study of Australian community-dwelling older adults . PARTICIPANTS Participants in the study included 615 community-dwelling volunteers aged 50 years old or older [ 61.4 ± 6.9 ( mean ± SD ) y ; 48 % female ] r and omly selected from electoral rolls and categorized according to baseline serum 25OHD ( ≥ or follows : high 25OHD and high PA ( VitD+PA+ ) ; high 25OHD and low PA ( VitD+PA- ) ; low 25OHD and high PA ( VitD-PA+ ) ; and low 25OHD and low PA ( VitD-PA- ) . A subset of 518 participants completed accelerometer assessment s during follow-up . MAIN OUTCOME MEASURES Changes in dual-energy X-ray absorptiometry-assessed body composition and lower-limb muscle function were measured . RESULTS VitD+PA+ had significantly smaller increases in body fat over 5 years compared with other groups ( all P Higher baseline pedometer-determined PA result ed in declines in total body fat ( β = -.23 kg per 100 steps/d , P = .001 ) over 5 years for participants with high 25OHD but not those with low 25OHD ( P > .05 ) . Among participants with accelerometer data , these associations were generally mediated by higher levels of moderate/vigorous PA . CONCLUSIONS High vitamin D status appears to enhance PA-related declines in body fat during aging , but the mechanism may be greater amounts of outdoor moderate/vigorous PA rather than a direct effect of 25OHD",
"BACKGROUND Sedentary behavior is a risk factor for cardiometabolic disease . Regularly interrupting sedentary behavior with activity breaks may lower this risk . OBJECTIVE We compared the effects of prolonged sitting , continuous physical activity combined with prolonged sitting , and regular activity breaks on postpr and ial metabolism . DESIGN Seventy adults participated in a r and omized crossover study . The prolonged sitting intervention involved sitting for 9 h , the physical activity intervention involved walking for 30 min and then sitting , and the regular-activity-break intervention involved walking for 1 min 40 s every 30 min . Participants consumed a meal-replacement beverage at 60 , 240 , and 420 min . RESULTS The plasma incremental area under the curve ( iAUC ) for insulin differed between interventions ( overall P Regular activity breaks lowered values by 866.7 IU · L(-1 ) · 9 h(-1 ) ( 95 % CI : 506.0 , 1227.5 IU · L(-1 ) · 9 h(-1 ) ; P with prolonged sitting and by 542.0 IU · L(-1 ) · 9 h(-1 ) ( 95 % CI : 179.9 , 904.2 IU · L(-1 ) · 9 h(-1 ) ; P = 0.003 ) when compared with physical activity . Plasma glucose iAUC also differed between interventions ( overall P . Regular activity breaks lowered values by 18.9 mmol · L(-1 ) · 9 h(-1 ) ( 95 % CI : 10.0 , 28.0 mmol · L(-1 ) · 9 h(-1 ) ; P with prolonged sitting and by 17.4 mmol · L(-1 ) · 9 h(-1 ) ( 95 % CI : 8.4 , 26.3 mmol · L(-1 ) · 9 h(-1 ) ; P compared with physical activity . Plasma triglyceride iAUC differed between interventions ( overall P = 0.023 ) . Physical activity lowered values by 6.3 mmol · L(-1 ) · 9 h(-1 ) ( 95 % CI : 1.8 , 10.7 mmol · L(-1 ) · 9 h(-1 ) ; P = 0.006 ) when compared with regular activity breaks . CONCLUSION Regular activity breaks were more effective than continuous physical activity at decreasing postpr and ial glycemia and insulinemia in healthy , normal-weight adults . This trial was registered with the Australian New Zeal and Clinical Trials registry as ACTRN12610000953033",
"Objective : To examine whether engagement in physical activity might favorably alter the age-dependent evolution of Alzheimer disease (AD)-related brain and cognitive changes in a cohort of at-risk , late-middle-aged adults . Methods : Three hundred seventeen enrollees in the Wisconsin Registry for Alzheimer 's Prevention underwent T1 MRI ; a subset also underwent 11C-Pittsburgh compound B – PET ( n = 186 ) and 18F-fluorodeoxyglucose – PET ( n = 152 ) imaging . Participants ' responses on a self-report measure of current physical activity were used to classify them as either physically active or physically inactive based on American Heart Association guidelines . They also completed a comprehensive neuropsychological battery . Covariate-adjusted regression analyses were used to test whether the adverse effect of age on imaging and cognitive biomarkers was modified by physical activity . Results : There were significant age × physical activity interactions for β-amyloid burden ( p = 0.014 ) , glucose metabolism ( p = 0.015 ) , and hippocampal volume ( p = 0.025 ) such that , with advancing age , physically active individuals exhibited a lesser degree of biomarker alterations compared with the physically inactive . Similar age × physical activity interactions were also observed on cognitive domains of Immediate Memory ( p = 0.042 ) and Visuospatial Ability ( p = 0.016 ) . In addition , the physically active group had higher scores on Speed and Flexibility ( p = 0.002 ) compared with the inactive group . Conclusions : In a middle-aged , at-risk cohort , a physically active lifestyle is associated with an attenuation of the deleterious influence of age on key biomarkers of AD pathophysiology . However , because our observational , cross-sectional design can not establish causality , r and omized controlled trials/longitudinal studies will be necessary for determining whether midlife participation in structured physical exercise forestalls the development of AD and related disorders in later life",
"Objective : To compare the effects of behavioral interventions targeting decreased sedentary behavior versus increased moderate-to-vigorous intensity physical activity ( MVPA ) in older adults . Method : Inactive older adults ( N = 38 , 68 ± 7 years old , 71 % female ) were r and omized to 12-week interventions targeting decreased sedentary behavior ( Sit Less ) or increased MVPA ( Get Active ) . The SenseWear armb and was used to objective ly assess activity in real time . Assessment s included a blinded armb and , the Community Health Activites Model Program for Senior ( CHAMPS ) question naire , 400-meter walk , and the Short Physical Performance Battery ( SPPB ) . Results : Objective ly measured MVPA increased in Get Active ( 75 ± 22 min/week , p .001 ) ; self-reported MVPA increased in both groups ( p did not change in either group ( all p > .05 ) . Only the Sit Less group improved the SPPB score ( 0.5 ± 0.3 , p = .046 ) . Discussion : Targeting reduced sedentary behavior had a greater effect on physical function among inactive but high functioning older adults over 12 weeks . Future studies of longer duration and combining increased MVPA with reduced sedentary behavior are needed",
"Abstract Background : Physical activity guidelines recommend engaging in moderate- and vigorous-intensity physical activity to elicit health benefits . Similarly , these higher intensity ranges for activity are typically targeted in healthy living interventions ( ie , exercise prescription ) . Comparatively less attention has been focused on changing lower intensity physical activity ( ie , sedentary activity ) behaviors . The purpose of this study was to explore the effects of prescribing changes to physical activity of various intensities ( ie , sedentary through exercise ) through the primary care setting . Methods : Sixty older adults ( aged 55–75 years ; mean age 63 ± 5 years ) volunteered to participate , and were r and omly assigned to 4 groups : 3 receiving an activity prescription intervention targeting a specific intensity of physical activity ( exercise , sedentary , or both ) , and 1 control group . During the 12-week intervention period participants followed personalized activity programs at home . Basic clinical measures ( anthropometrics , blood pressure , aerobic fitness ) and blood panel for assessing cardiometabolic risk ( glucose , lipid profile ) were conducted at baseline ( week 0 ) and follow-up ( week 12 ) in a primary care office . Results : There were no differences between groups at baseline ( P > 0.05 ) . The intervention changed clinical ( F(5 , 50 ) = 20.458 , P = 0.000 , ηP2 = 0.672 ) and blood panel measures ( F(5 , 50 ) = 4.576 , P = 0.002 , ηP2 = 0.314 ) of cardiometabolic health . Post hoc analyses indicted no differences between groups ( P > 0.05 ) . Conclusion : Physical activity prescription of various intensities through the primary care setting improved cardiometabolic health status . To our knowledge , this is the first report of sedentary behavior prescription ( alone , or combined with exercise ) in primary care . The findings support the ongoing practice of fitness assessment and physical activity prescription for chronic disease management and prevention",
"BACKGROUND Sedentary behavior is regarded as a distinct risk factor for cardiometabolic morbidity and mortality , but knowledge of the efficacy of interventions targeting reductions in sedentary behavior is limited . PURPOSE To investigate the effect of an individualized face-to-face motivational counseling intervention aim ed at reducing sitting time . DESIGN A r and omized , controlled , observer-blinded , community-based trial with two parallel groups using open-end r and omization with 1:1 allocation . SETTING / PARTICIPANTS A total of 166 sedentary adults were consecutively recruited from the population -based Health2010 Study . INTERVENTION Participants were r and omized to a control ( usual lifestyle ) or intervention group with four individual theory-based counseling sessions . MAIN OUTCOME MEASURES Objective ly measured overall sitting time ( ActivPAL 3TM , 7 days ) ; secondary measures were breaks in sitting time , anthropometric measures , and cardiometabolic biomarkers , assessed at baseline and after 6 months . Data were collected in 2010 - 2012 and analyzed in 2013 - 2014 using repeated measures multiple regression analyses . RESULTS Ninety-three participants were r and omized to the intervention group and 73 to the control group , and 149 completed the study . The intervention group had a mean sitting time decrease of -0.27 hours/day , corresponding to 2.9 % of baseline sitting time ( hours/day ) ; the control group increased mean sitting time by 0.06 hours/day . The between-group difference in change , -0.32 hours/day ( 95 % CI=-0.87 , 0.24 , p=0.26 ) , was not statistically significant . Significant differences in change in fasting serum insulin of -5.9 pmol/L ( 95 % CI=-11.4 , -0.5 , p=0.03 ) ; homeostasis model assessment -estimated insulin resistance of -0.28 ( 95 % CI=-0.53 , -0.03 , p=0.03 ) ; and waist circumference of -1.42 cm ( 95 % CI=-2.54 , -0.29 , p=0.01 ) were observed in favor of the intervention group . CONCLUSIONS Although the observed decrease in sitting time was not significant , a community-based , individually tailored , theory-based intervention program aim ed at reducing sitting time may be effective for increasing st and ing and improving cardiometabolic health in sedentary adults . TRIAL REGISTRATION This study is registered at Clinical trials.gov ( NCT00289237 )",
"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",
"AIM To compare the effect of 7 h of prolonged sitting on resting blood pressure with a similar duration of sitting combined with intermittent brief bouts of light-intensity or moderate-intensity physical activity . METHODS AND RESULTS Overweight/obese adults ( n = 19 ; aged 45 - 65 years ) were recruited for a r and omized three-treatment crossover trial with a one-week washout between treatments : 1 ) uninterrupted sitting ; 2 ) sitting with 2 min bouts of light-intensity walking at 3.2 km/h every 20 min ; and , 3 ) sitting with 2 min bouts of moderate-intensity walking at between 5.8 and 6.4 km/h every 20 min . After an initial 2 h period seated , participants consumed a test meal ( 75 g carbohydrate , 50 g fat ) and completed each condition over the next 5 h. Resting blood pressure was assessed oscillometrically every hour as a single measurement , 5 min prior to each activity bout . GEE models were adjusted for sex , age , BMI , fasting blood pressure and treatment order . After adjustment for potential confounding variables , breaking up prolonged sitting with light and moderate-intensity activity breaks was associated with lower systolic blood pressure [ light : 120 ± 1 mmHg ( estimated marginal mean ± SEM ) , P = 0.002 ; moderate : 121 ± 1 mmHg , P = 0.02 ] , compared to uninterrupted sitting ( 123 ± 1 mmHg ) . Diastolic blood pressure was also significantly lower during both of the activity conditions ( light : 76 ± 1 mmHg , P = 0.006 ; moderate : 77 ± 1 mmHg , P = 0.03 ) compared to uninterrupted sitting ( 79 ± 1 mmHg ) . No significant between-condition differences were observed in mean arterial pressure or heart rate . CONCLUSION Regularly breaking up prolonged sitting may reduce systolic and diastolic blood pressure . TRIAL REGISTRATION NUMBER ACTRN12609000656235 ( http://www.anzctr.org.au ) TRIAL REGISTRATION DATE : August 4th 2009",
"OBJECTIVE To determine the efficacy of high-intensity progressive resistance training ( PRT ) on glycemic control in older adults with type 2 diabetes . RESEARCH DESIGN AND METHODS We performed a 16-week r and omized controlled trial in 62 Latino older adults ( 40 women and 22 men ; mean + /- SE age 66 + /- 8 years ) with type 2 diabetes r and omly assigned to supervised PRT or a control group . Glycemic control , metabolic syndrome abnormalities , body composition , and muscle glycogen stores were determined before and after the intervention . RESULTS Sixteen weeks of PRT ( three times per week ) result ed in reduced plasma glycosylated hemoglobin levels ( from 8.7 + /- 0.3 to 7.6 + /- 0.2 % ) , increased muscle glycogen stores ( from 60.3 + /- 3.9 to 79.1 + /- 5.0 mmol glucose/kg muscle ) , and reduced the dose of prescribed diabetes medication in 72 % of exercisers compared with the control group , P = 0.004 - 0.05 . Control subjects showed no change in glycosylated hemoglobin , a reduction in muscle glycogen ( from 61.4 + /- 7.7 to 47.2 + /- 6.7 mmol glucose/kg muscle ) , and a 42 % increase in diabetes medications . PRT subjects versus control subjects also increased lean mass ( + 1.2 + /- 0.2 vs. -0.1 + /- 0.1 kg ) , reduced systolic blood pressure ( -9.7 + /- 1.6 vs. + 7.7 + /- 1.9 mmHg ) , and decreased trunk fat mass ( -0.7 + /- 0.1 vs. + 0.8 + /- 0.1 kg ; P = 0.01 - 0.05 ) . CONCLUSIONS PRT as an adjunct to st and ard of care is feasible and effective in improving glycemic control and some of the abnormalities associated with the metabolic syndrome among high-risk older adults with type 2 diabetes",
"Objective Sedentary behaviour is increasingly recognized as an important health risk , but comparable data across Europe are scarce . The objective of this study was to explore the prevalence and correlates of self-reported sitting time in adults across and within the 28 European Union Member States . Methods This study reports data from the Special Eurobarometer 412 . In 2013 , 27,919 r and omly selected Europeans ( approximately 1000 per Member State ) were interviewed face-to-face . Sitting time on a usual day was self-reported and dichotomised into sitting less- and more than 7.5 hours per day . Uni- and multivariate odds ratios of sitting more than 7.5 hours per day were assessed by country and socio-demographic variables using binary logistic regression analyses . The analyses were stratified by country to study the socio-demographic correlates of sitting time within the different countries . Results A total of 26,617 respondents were included in the analyses . Median sitting time was five hours per day . Across Europe , 18.5 percent of the respondents reported to sit more than 7.5 hours per day , with substantial variation between countries ( ranging from 8.9 to 32.1 percent ) . In general , northern European countries reported more sitting than countries in the south of Europe . ‘ Current occupation ’ and ‘ age when stopped education ’ were found to be the strongest correlates of sitting time , both across Europe and within most Member States . Compared to manual workers , the odds ratio of sitting more than 7.5 hours per day was 5.00 for people with white collar occupations , 3.84 for students , and 3.65 for managers . Conclusions There is substantial variation in self-reported sitting time among European adults across countries as well as socio-demographic groups . While regular surveillance of ( objective ly measured ) sedentary behaviour is needed , the results of this study provide entry points for developing targeted interventions aim ed at highly sedentary population s , such as people with sedentary occupations",
"Background Epidemiological studies suggest that excessive sitting time is associated with increased health risk , independent of the performance of exercise . We hypothesized that a daily bout of exercise can not compensate the negative effects of inactivity during the rest of the day on insulin sensitivity and plasma lipids . Methodology /Principal Findings Eighteen healthy subjects , age 21±2 year , BMI 22.6±2.6 kgm−2 followed r and omly three physical activity regimes for four days . Participants were instructed to sit 14 hr/day ( sitting regime ) ; to sit 13 hr/day and to substitute 1 hr of sitting with vigorous exercise 1 hr ( exercise regime ) ; to substitute 6 hrs sitting with 4 hr walking and 2 hr st and ing ( minimal intensity physical activity ( PA ) regime ) . The sitting and exercise regime had comparable numbers of sitting hours ; the exercise and minimal intensity PA regime had the same daily energy expenditure . PA was assessed continuously by an activity monitor ( ActivPAL ) and a diary . Measurements of insulin sensitivity ( oral glucose tolerance test , OGTT ) and plasma lipids were performed in the fasting state , the morning after the 4 days of each regime . In the sitting regime , daily energy expenditure was about 500 kcal lower than in both other regimes . Area under the curve for insulin during OGTT was significantly lower after the minimal intensity PA regime compared to both sitting and exercise regimes 6727.3±4329.4 vs 7752.0±3014.4 and 8320.4±5383.7 mU•min/ml , respectively . Triglycerides , non-HDL cholesterol and apolipoprotein B plasma levels improved significantly in the minimal intensity PA regime compared to sitting and showed non-significant trends for improvement compared to exercise . Conclusions One hour of daily physical exercise can not compensate the negative effects of inactivity on insulin level and plasma lipids if the rest of the day is spent sitting . Reducing inactivity by increasing the time spent walking/st and ing is more effective than one hour of physical exercise , when energy expenditure is kept constant",
"The aim of this study is to evaluate if two different physical activity ( PA ) question naires have similar ability to rank individuals , and to examine associations with cardiovascular-metabolic risk factors , compared to an objective measure . In a r and om sample ( n=369 , age : 65±6 years ) from the population -based ‘ Malmö Diet and Cancer ’ ( MDC ) cohort , PA was measured by a leisure-time comprehensive question naire ( MDC-score ) , a simple leisure-time question naire and by accelerometer-monitoring ( CSA ) . Moderate correlations were observed between MDC-score and CSA in men and women ( r=0.35 and 0.24 , respectively ) . In men , both question naires and CSA were inversely associated with waist circumference , insulin resistance and metabolic syndrome . In women , the MDC-score was positively associated with high-density lipoprotein-cholesterol , and the simple question naire inversely associated with anthropometric indexes , but no association was seen between PA estimates and cardiovascular components . We conclude that both PA question naires distinguish health risks associated with anthropometric-metabolic risk factors , particularly in men",
"OBJECTIVE This study investigated the disparity between muscle metabolic rate and mitochondrial metabolism in human muscle of sedentary vs. active individuals . RESEARCH DESIGN AND METHODS Chronic activity level was characterized by a physical activity question naire and a triaxial accelerometer as well as a maximal oxygen uptake test . The ATP and O(2 ) fluxes and mitochondrial coupling ( ATP/O(2 ) or P/O ) in resting muscle as well as mitochondrial capacity ( ATP(max ) ) were determined in vivo in human vastus lateralis muscle using magnetic resonance and optical spectroscopy on 24 sedentary and seven active subjects . Muscle biopsies were analyzed for electron transport chain content ( using complex III as a representative marker ) and mitochondrial proteins associated with antioxidant protection . RESULTS Sedentary muscle had lower electron transport chain complex content ( 65 % of the active group ) in proportion to the reduction in ATP(max ) ( 0.69 ± 0.07 vs. 1.07 ± 0.06 mM sec(-1 ) ) as compared with active subjects . This lower ATP(max ) paired with an unchanged O(2 ) flux in resting muscle between groups result ed in a doubling of O(2 ) flux per ATP(max ) ( 3.3 ± 0.3 vs. 1.7 ± 0.2 μM O(2 ) per mM ATP ) that reflected mitochondrial uncoupling ( P/O = 1.41 ± 0.1 vs. 2.1 ± 0.3 ) and greater UCP3/complex III ( 6.0 ± 0.7 vs. 3.8 ± 0.3 ) in sedentary vs. active subjects . CONCLUSION A smaller mitochondrial pool serving the same O(2 ) flux result ed in elevated mitochondrial respiration in sedentary muscle . In addition , uncoupling contributed to this higher mitochondrial respiration . This finding resolves the paradox of stable muscle metabolism but greater mitochondrial respiration in muscle of inactive vs. active subjects",
"UNLABELLED Circadian Profile of Heart Rate Variability . INTRODUCTION Although heart rate variability ( HRV ) has been established as a tool to study cardiac autonomic activity , almost no data are available on the circadian patterns of HRV in healthy subjects aged 20 to 70 years . METHODS AND RESULTS We investigated 166 healthy volunteers ( 81 women and 85 men ; age 42 + /- 15 years , range 20 - 70 ) without evidence of cardiac disease . Time-domain HRV parameters were determined from 24-hour Holter monitoring and calculated as hourly mean values and mean 24-hour values . All volunteers were fully mobile , awoke around 7 A.M. , and had 6 to 8 hours of sleep . Circadian profiles of vagus-associated HRV parameters revealed a marked day-night pattern , with a peak at nighttime and a plateau at daytime . The characteristic nocturnal peak and the day-night amplitude diminished with aging by decade . Estimates of overall HRV ( geometric triangular index [ TI ] , SD of NN intervals [ SDNN ] ) and long-term components of HRV ( SD of the averages of NN intervals for all 5-min segments [ SDANN ] ) were low at nighttime and increased in the morning hours . There was a significant decline of 24-hour values of all HRV parameters ( P Mean 24-hour RR interval ( P SDNN , mean SD of NN intervals for all 5-minute intervals ( SDNNi ) , and SDANN ( all P . Younger men also exhibited significantly higher values for vagus-associated parameters ( root mean square successive difference [ rMSSD ] , P parasympathetic activity . The significant gender-related difference of HRV decreases with aging . These findings emphasize the need to determine age- , gender- , and nycthemeral-dependent normal ranges for HRV assessment",
"BACKGROUND A r and omized controlled trial was conducted to examine : ( a ) the effect of two physical activity modes on changes in subjective well-being ( SWB ) over the course of a 12-month period in older , formerly sedentary adults ( N = 174 , M age = 65.5 years ) and ( b ) the role played by physical activity participation and social support in changes in SWB over time . METHOD Participants were r and omized into either an aerobic activity group or a stretching and toning group . Structural equation modeling was employed to conduct multiple sample latent growth curve analyses of individual growth in measures of SWB ( happiness , satisfaction with life , and loneliness ) over time . RESULTS A curvilinear growth pattern was revealed with well-being significantly improving over the course of the intervention followed by significant declines at the 6-month follow-up . Subsequent structural analyses were conducted showing that frequency of exercise participation was a significant predictor of improvement in satisfaction with life , whereas social relations were related to increases in satisfaction with life and reductions in loneliness . Improvements in social relations and exercise frequency also helped to buffer the declines in satisfaction with life at follow-up . CONCLUSIONS It appears that social relations integral to the exercise environment are significant determinants of subjective well-being in older adults . Findings are discussed in terms of how physical activity environments might be structured to maximize improvements in more global well-being constructs such as satisfaction with life",
"BACKGROUND AND AIMS Physical activity is a cornerstone of Type 2 diabetes management but is underutilized . Physical activity consultations increase physical activity in people with Type 2 diabetes but re sources are often limited . Time2Act is a r and omized control trial to study the 12-month effectiveness of a physical activity consultation delivered by a person or in written form , in contrast to st and ard care , for people with Type 2 diabetes . METHODS A total of 134 inactive people with Type 2 diabetes in a contemplation or preparation stage were r and omized to either intervention or st and ard care . Objective ( accelerometer ) and subjective ( 7-day recall ) physical activity levels were measured over 1 week , along with physiological [ blood pressure , body mass index ( BMI ) , waist circumference ] and biochemical [ glycated haemoglobin ( HbA(1c ) ) , total and high-density lipoprotein ( HDL ) cholesterol ] measures at baseline , 6 and 12 months . RESULTS Neither a physical activity consultation delivered by a person nor in written form was better than st and ard care at increasing physical activity levels or improving health outcomes in the full study cohort . Total and HDL cholesterol , waist circumference and both systolic and diastolic blood pressure improved over 12 months in all groups , whilst HbA(1c ) improved over 6 months . In a subgroup ( baseline pedometer steps physical activity consultation delivered by a person significantly increased physical activity over 12 months and the st and ard care group significantly decreased . CONCLUSIONS More research is needed which not only investigates the most economical and effective methods to promote physical activity , but also the best setting to conduct physical activity consultations and the participant factors affecting uptake of physical activity in Type 2 diabetes",
"Objective To investigate the prospect i ve relationships between television viewing time and weight gain in the 3 years following colorectal cancer diagnosis for 1,867 colorectal cancer survivors ( body mass index ( BMI ) ≥ 18.5 kg/m2 ) . Methods BMI , television viewing time , physical activity , and socio-demographic and clinical covariates were assessed at baseline ( 5 months ) , 24 months and 36 months post-diagnosis . Multiple linear regression was used to study independent associations between baseline television viewing time and BMI at 24 and 36 months post-diagnosis . Results At both follow-up time points , there was a significant increase in mean BMI for participants reporting ≥5 h/day of television viewing compared to those watching baseline BMI , gender , age , education , marital status , smoking , cancer site , cancer disease stage , treatment mode and co-morbidities . Additional adjustment for baseline physical activity did not change results . Conclusions These findings suggest that a greater emphasis on decreasing television viewing time could help reduce weight gain among colorectal cancer survivors . This , in turn , could contribute to a risk reduction for co-morbid conditions such as type 2 diabetes and cardiovascular disease",
"Background and aims We investigated whether objective ly measured sedentary time was associated with markers of inflammation in adults with newly diagnosed type 2 diabetes . Methods and results We studied 285 adults ( 184 men , 101 women , mean age 59.0 ± 9.7 ) who had been recruited to the Early ACTivity in Diabetes ( Early ACTID ) r and omised controlled trial . C-reactive protein ( CRP ) , adiponectin , soluble intracellular adhesion molecule-1 ( sICAM-1 ) , interleukin-6 ( IL-6 ) , and accelerometer-determined sedentary time and moderate-vigorous physical activity ( MVPA ) were measured at baseline and after six-months . Linear regression analysis was used to investigate the independent cross-sectional and longitudinal associations of sedentary time with markers of inflammation . At baseline , associations between sedentary time and IL-6 were observed in men and women , an association that was attenuated following adjustment for waist circumference . After 6 months of follow-up , sedentary time was reduced by 0.4 ± 1.2 h per day in women , with the change in sedentary time predicting CRP at follow-up . Every hour decrease in sedentary time between baseline and six-months was associated with 24 % ( 1 , 48 ) lower CRP . No changes in sedentary time between baseline and 6 months were seen in men . Conclusions Higher sedentary time is associated with IL-6 in men and women with type 2 diabetes , and reducing sedentary time is associated with improved levels of CRP in women . Interventions to reduce sedentary time may help to reduce inflammation in women with type 2 diabetes",
"Background Previous studies have shown associations of sedentary behavior with cardiovascular risk , independent of moderate-to-vigorous physical activity ( MVPA ) . However , few studies have focused on older adults . This study examined the joint associations of television ( TV ) viewing time and MVPA with overweight/obesity among Japanese older adults . Methods A population -based , cross-sectional mail survey was used to collect self-reported height , weight , time spent in TV viewing , and MVPA from 1806 older adults ( age : 65–74 years , men : 51.1 % ) . Participants were classified into 4 categories according to TV viewing time ( dichotomized into high and low around the median ) and MVPA level ( dichotomized into sufficient and insufficient by the physical activity guideline level of ≥150 minutes/week ) . Odds ratios ( ORs ) for overweight/obesity ( body mass index ≥25 kg/m2 ) were calculated according to the 4 TV/MVPA categories , adjusting for potential confounders . Results Of all participants , 20.1 % were overweight/obese . The median TV viewing time ( 25th , 75th percentile ) was 840 ( 420 , 1400 ) minutes/week . As compared with the reference category ( high TV/insufficient MVPA ) , the adjusted ORs ( 95 % CI ) of overweight/obesity were 0.93 ( 0.65 , 1.34 ) for high TV/sufficient MVPA , 0.58 ( 0.37 , 0.90 ) for low TV/insufficient MVPA , and 0.67 ( 0.47 , 0.97 ) for low TV/sufficient MVPA . Conclusions In this sample of older adults , spending less time watching TV , a predominant sedentary behavior , was associated with lower risk of being overweight or obese , independent of meeting physical activity guidelines . Further studies using prospect i ve and /or intervention design s are warranted to confirm the presently observed effects of sedentary behavior , independent of physical activity , on the health of older adults",
"Higher levels of physical activity are associated with lower rates of coronary heart disease ( CHD ) . Previous studies have suggested that this is due partly to lower levels of inflammation and insulin resistance . The aim of this study was to determine whether physical activity level was associated with inflammation or insulin resistance during a 5-year period in out patients with known CHD . A total of 656 participants from the Heart and Soul Study , a prospect i ve cohort study of out patients with documented CHD , were evaluated . Self-reported physical activity frequency was assessed at baseline and after 5 years of follow-up . Participants were classified as low versus high activity at each visit , yielding 4 physical activity groups : stable low activity , decreasing activity ( high at baseline to low at year 5 ) , increasing activity ( low at baseline to high at year 5 ) , and stable high activity . Year 5 markers of inflammation ( C-reactive protein [ CRP ] , interleukin-6 , and fibrinogen ) and insulin resistance ( insulin , glucose , and glycated hemoglobin ) were compared across the 4 activity groups . After 5 years of follow-up , higher activity was associated with lower mean levels of all biomarkers . In the fully adjusted regression models , CRP , interleukin-6 , and glucose remained independently associated with physical activity frequency ( log CRP , p for trend across activity groups = 0.03 ; log interleukin-6 , p for trend = 0.01 ; log glucose , p for trend = 0.003 ) . Subjects with stable high activity typically had the lowest levels of biomarkers . In conclusion , in this novel population of out patients with known CHD followed for 5 years , higher physical activity frequency was independently associated with lower levels of CRP , interleukin-6 , and glucose"
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41188218-06ff-11f0-808a-c43d1ab1c353
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RATIONALE , AIMS AND OBJECTIVES Walking speed is an important performance variable , but information on the minimal clinical ly important difference ( MCID ) for the measure has not been consoli date d. In this review , we aim ed to summarize information on the MCID for change in comfortable gait speed measurements for patients with pathology . METHODS Relevant literature was identified by search es of four data bases ( PubMed , Web of Knowledge , CINAHL and Scopus ) , h and search es and consultation with an expert . Inclusion required that articles reported a MCID for comfortable gait speed measurements . Articles were excluded if the MCID was not determined using receiver operating characteristic ( ROC ) curve analysis . Articles were abstract ed for information on participants , interventions , gait speed documentation and the determination of MCID . Quality was assessed using a hybrid 9-item ( 0 - 18 point ) instrument . RESULTS Seven articles were selected based on inclusion and exclusion criteria . The population s studied included stroke ( n = 3 ) , hip fracture ( n = 2 ) , multiple sclerosis ( n = 1 ) and mixed ( n = 1 ) . Using 13 different anchors the studies reported MCIDs of 0.08 - 0.26 m s(-1 ) . All but three of these MCIDs were between 0.10 and 0.20 m s(-1 ) . All MCIDs for which the area under the ROC curve exceeded 0.70 were between 0.10 and 0.17 m s(-1 ) . CONCLUSIONS Changes in gait speed of 0.10 to 0.20 m s(-1 ) may be important across multiple patient groups
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"OBJECTIVES The purpose of this study was to test the value of gait speed , a clinical marker for frailty , to improve the prediction of mortality and major morbidity in elderly patients undergoing cardiac surgery . BACKGROUND It is increasingly difficult to predict the elderly patient 's risk posed by cardiac surgery because existing risk assessment tools are incomplete . METHODS A multicenter prospect i ve cohort of elderly patients undergoing cardiac surgery was assembled at 4 tertiary care hospitals between 2008 and 2009 . Patients were eligible if they were 70 years of age or older and were scheduled for coronary artery bypass and /or valve replacement or repair . The primary predictor was slow gait speed , defined as a time taken to walk 5 m of ≥ 6 s. The primary end point was a composite of in-hospital post-operative mortality or major morbidity . RESULTS The cohort consisted of 131 patients with a mean age of 75.8 ± 4.4 years ; 34 % were female patients . Sixty patients ( 46 % ) were classified as slow walkers before cardiac surgery . Slow walkers were more likely to be female ( 43 % vs. 25 % , p = 0.03 ) and diabetic ( 50 % vs. 28 % , p = 0.01 ) . Thirty patients ( 23 % ) experienced the primary composite end point of mortality or major morbidity after cardiac surgery . Slow gait speed was an independent predictor of the composite end point after adjusting for the Society of Thoracic Surgeons risk score ( odds ratio : 3.05 ; 95 % confidence interval : 1.23 to 7.54 ) . CONCLUSIONS Gait speed is a simple and effective test that may identify a subset of vulnerable elderly patients at incrementally higher risk of mortality and major morbidity after cardiac surgery",
"Background When people with stroke recover gait speed , they report improved function and reduced disability . However , the minimal amount of change in gait speed that is clinical ly meaningful and associated with an important difference in function for people poststroke has not been determined . Objective The purpose of this study was to determine the minimal clinical ly important difference ( MCID ) for comfortable gait speed ( CGS ) associated with an improvement in the modified Rankin Scale ( mRS ) score for people between 20 to 60 days poststroke . Design This was a prospect i ve , longitudinal , cohort study . Methods The participants in this study were 283 people with first-time stroke prospect ively enrolled in the ongoing Locomotor Experience Applied Post Stroke ( LEAPS ) multi-site r and omized clinical trial . Comfortable gait speed was measured and mRS scores were obtained at 20 and 60 days poststroke . Improvement of ≥1 on the mRS was used to detect meaningful change in disability level . Results Mean ( SD ) CGS was 0.18 ( 0.16 ) m/s at 20 days and 0.39 ( 0.22 ) m/s at 60 days poststroke . Among all participants , 47.3 % experienced an improvement in disability level ≥1 . The MCID was estimated as an improvement in CGS of 0.16 m/s anchored to the mRS . Limitations Because the mRS is not a gait-specific measure of disability , the estimated MCID for CGS was only 73.9 % sensitive and 57.0 % specific for detecting improvement in mRS scores . Conclusions We estimate that the MCID for gait speed among patients with subacute stroke and severe gait speed impairments is 0.16 m/s . Patients with subacute stroke who increase gait speed ≥0.16 m/s are more likely to experience a meaningful improvement in disability level than those who do not . Clinicians can use this reference value to develop goals and interpret progress in patients with subacute stroke ",
"Objective To study the relation between low walking speed and the risk of death in older people , both overall and with regard to the main causes of death . Design Prospect i ve cohort study . Setting Dijon centre ( France ) of the Three-City study . Participants 3208 men and women aged ≥65 living in the community , recruited from 1999 to 2001 , and followed for an average of 5.1 years . Main outcome measures Mortality , overall and according to the main causes of death , by thirds of baseline walking speed ( measured at maximum speed over six metres ) , adjusted for several potential confounders ; Kaplan-Meier survival curves by thirds of baseline walking speed . Vital status during follow-up . Causes of death . Results During 16 414 person years of follow-up , 209 participants died ( 99 from cancer , 59 from cardiovascular disease , 51 from other causes ) . Participants in the lowest third of baseline walking speed had an increased risk of death ( hazard ratio 1.44 , 95 % confidence interval 1.03 to 1.99 ) compared with the upper thirds . Analyses for specific causes of death showed that participants with low walking speed had about a threefold increased risk of cardiovascular death ( 2.92 , 1.46 to 5.84 ) compared with participants who walked faster . There was no relation with cancer mortality ( 1.03 , 0.65 to 1.70 ) . In stratified analyses , cardiovascular mortality was increased across various strata defined by sex , median age , median body mass index ( BMI ) , and level of physical activity . Conclusion Slow walking speed in older people is strongly associated with an increased risk of cardiovascular mortality",
"Objective Performance measures provide important information , but the meaning of change in these measures is not well known . The purpose of this research is to 1 ) examine the effect of treatment assignment on the relationship between self-report and performance ; 2 ) to estimate the magnitude of meaningful change in 400- meter walk time ( 400MWT ) , 4-meter gait speed ( 4MGS ) , and Short Physical Performance Battery ( SPPB ) and 3 ) to evaluate the effect of direction of change on estimates of magnitude . Design This is a secondary analysis of data from the LIFE-P study , a single blinded r and omized clinical trial . Using change over one year , we applied distribution-based and anchor-based methods for self-reported mobility to estimate minimally important and substantial change in 400MWT , 4MGS and SPPB . Setting Four university-based clinical research sites . Participants Sedentary adults aged 70–89 whose SPPB scores were less than 10 and who were able to complete a 400MW at baseline ( n=424 ) . Interventions A structured exercise program versus health education . Measurements 400MWT , 4MGS , SPPB . Results Relationships between self-report and performance measures were consistent between treatment arms . Minimally significant change estimates were 400MWT : 20–30 seconds , 4MGS : 0.03–0.05 m/s and SPPB : 0.3–0.8 points . Substantial changes were 400MWT : 50–60 seconds , 4MGS : 0.08 m/s , SPPB : 0.4–1.5 points . Magnitudes of change for improvement and decline were not significantly different . Conclusions The magnitude of clinical ly important change in physical performance measures is reasonably consistent using several analytic techniques and appears to be achievable in clinical trials of exercise . Due to limited power , the effect of direction of change on estimates of magnitude remains uncertain",
"OBJECTIVES To estimate meaningful improvements in gait speed observed during recovery from hip fracture and to evaluate the sensitivity and specificity of gait speed changes in detecting change in self-reported mobility . DESIGN Secondary longitudinal data analysis from two r and omized controlled trials SETTING Twelve hospitals in the Baltimore , Maryl and , area . PARTICIPANTS Two hundred seventeen women admitted with hip fracture . MEASUREMENTS Usual gait speed and self-reported mobility ( ability to walk 1 block and climb 1 flight of stairs ) measured 2 and 12 months after fracture . RESULTS Effect size-based estimates of meaningful differences were 0.03 for small differences and 0.09 for substantial differences . Depending on the anchor ( stairs vs walking ) and method ( mean difference vs regression ) , anchor-based estimates ranged from 0.10 to 0.17 m/s for small meaningful improvements and 0.17 to 0.26 m/s for substantial meaningful improvement . Optimal gait speed cutpoints yielded low sensitivity ( 0.39 - 0.62 ) and specificity ( 0.57 - 0.76 ) for improvements in self-reported mobility . CONCLUSION Results from this sample of women recovering from hip fracture provide only limited support for the 0.10-m/s cut point for substantial meaningful change previously identified in community-dwelling older adults experiencing declines in walking abilities . Anchor-based estimates and cut points derived from receiver operating characteristic curve analysis suggest that greater improvements in gait speed may be required for substantial perceived mobility improvement in female hip fracture patients . Furthermore , gait speed change performed poorly in discriminating change in self-reported mobility . Estimates of meaningful change in gait speed may differ based on the direction of change ( improvement vs decline ) or between patient population",
"Abstract Background : Limited data define what constitutes a clinical ly significant change on the Timed 25-Foot Walk ( T25FW ) in multiple sclerosis ( MS ) ; however , most studies suggest a value of ≥20 % . Analyses were undertaken to estimate the minimally important clinical difference ( MICD ) in walking speed as measured by the T25FW in patients with MS . Methods : Data from MS-F203 , a r and omized trial of dalfampridine extended release tablets , 10 mg twice daily ( prolonged-release/sustained-release fampridine outside the US ) in patients with MS , were used to calculate the MICD , as an absolute and percentage value , for the T25FW test . Both anchor- ( using the Clinician Global Impression [ CGI ] ) and distribution-based ( 2.77 × st and ard error of measurement or 0.50 st and ard deviation units ) approaches were used . Using the anchor-based estimations , the proportion of patients in the dalfampridine and placebo groups achieving at least a MICD in MS-F203 was determined . Results : A correlation between change in T25FW speed during and CGI at the end of double-blind period was found ( Spearman r = −0.39 , p mean improvement in T25FW speed of 0.36 feet/second or a 17.2 % relative change from an average baseline walking speed of 2.1 feet/second ( effect size = 0.49 ) ; values representing MICDs . MICD estimates of 0.35 and 0.37 feet/second were generated using distribution-based approaches . In MS-F203 , a greater proportion of patients receiving dalfampridine achieved ≥0.36 feet/second ( 12/72 vs. 78/224 , p = 0.007 ) and a 17.2 % ( 11/72 vs. 87/224 , p = 0.0005 ) improvement in T25FW speed compared to placebo . Limitations : MICD estimates from this analysis may not apply to patients with different disease characteristics from MS-F203 . A different anchor may result in a different MICD estimation . Conclusion : Our MICD estimate for an improvement in T25FW is close to previous estimates of 20 % change . Dalfampridine may improve walking speed in a considerable proportion of patients by a clinical ly relevant amount",
"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 ",
"Poststroke functional outcome and discharge disposition are influenced by age , lesion location and size , severity of neurological insult , prior functional ability , and social support . The effect of admission ambulation velocity on length of stay and discharge disposition has not been previously reported . Design . Prospect i ve , cohort study . Setting . Design ated acute stroke rehabilitation unit . Method . 373 patients consecutively admitted to a design ated inpatient stroke rehabilitation unit were studied . The study sample was divided into 2 groups , based on admission ambulation velocity ( meters/second ) during a 2-min timed walk test . Fast ambulators had an ambulation velocity of greater than 0.15 m/s , whereas slow ambulators had an ambulation velocity of 0.15 m/s or less , and also included nonambulators . Interventions . None . Outcome Measures . Primary outcome measures were length of stay and discharge disposition . Secondary outcome measures were change in the Functional Independence Measure ( FIM ) scores and change in ambulation velocity per week . Continuous , ordinal , and nominal variables were analyzed using the Student t test , Mann-Whitney U test , and chi-square test , respectively . Sensitivity , specificity , and positive and negative predictive values assessed admission ambulation velocity as a predictor of discharge disposition . Results . Patient variables for slow ambulators ( n = 226 ) versus fast ambulators ( n = 147 ) were as follows : age ( 68 ± 13 SD vs. 69 ± 12 , P = 0.32 ) , male-female ratio ( 100:126 vs. 78:69 , P = 0.09 ) , admission total FIM score ( 52 ± 17 vs. 77 ± 16 , P 0.0001 ) , change in total FIM score ( 20 ± 12 vs. 16 ± 12 , P 0.003 ) , change in ambulation velocity per week ( 0.05 ± 0.06 vs. 0.13 ± 0.30 , P length of stay in days ( 30 ± 28 vs. 17 ± 19 , P 0.0001 ) , and discharge disposition : home/skilled nursing facility ( 133/91 vs. 133/13 , P 0.0001 ) . Sensitivity , specificity , and positive and negative predictive values ( based on chi-square analyses ) for admission fast ambulators as a predictor of home discharge were 0.5 , 0.87 , 0.91 , and 0.41 , respectively . Admission ambulation velocity alone correctly identified discharge disposition in 78 % of the patient population , based on logistic regression analysis ( P length of stay and discharge disposition poststroke . This effect is independent of age and admission total FIM score"
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41188254-06ff-11f0-808a-c43d1ab1c353
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STUDY DESIGN Best evidence synthesis . OBJECTIVE To critically appraise and synthesize the literature on assessment of neck pain . SUMMARY OF BACKGROUND DATA The published literature on assessment of neck pain is large and of variable quality . There have been no prior systematic review s of this literature . METHODS The Bone and Joint Decade 2000 - 2010 Task Force on Neck Pain and Its Associated Disorders conducted a critical review of the literature ( published 1980 - 2006 ) on assessment tools and screening protocol s for traumatic and nontraumatic neck pain . RESULTS We found 359 articles on assessment of neck pain . After critical review , 95 ( 35 % ) were judged scientifically admissible . Screening protocol s have high predictive values to detect cervical spine fracture in alert , low-risk patients seeking emergency care after blunt neck trauma . Computerized tomography ( CT ) scans had better validity ( in adults and elderly ) than radiographs in assessing high-risk and /or multi-injured blunt trauma neck patients . In the absence of serious pathology , clinical physical examinations are more predictive at excluding than confirming structural lesions causing neurologic compression . One exception is the manual provocation test for cervical radiculopathy , which has high positive predictive value . There was no evidence that specific MRI findings are associated with neck pain , cervicogenic headache , or whiplash exposure . No evidence supports using cervical provocative discography , anesthetic facet , or medial branch blocks in evaluating neck pain . Reliable and valid self-report question naires are useful in assessing pain , function , disability , and psychosocial status in individuals with neck pain . CONCLUSION The scientific evidence supports screening protocol s in emergency care for low-risk patients ; and CT-scans for high-risk patients with blunt trauma to the neck . In nonemergency neck pain without radiculopathy , the validity of most commonly used objective tests is lacking . There is support for subjective self-report assessment in monitoring patients ' course , response to treatment , and in clinical research
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"OBJECTIVE The aim of this study was to investigate the construct validity of 6 physical performance tests that had already been shown to have acceptable repeatability . DESIGN Data were collected in a r and omized controlled multi-centre study . SUBJECTS 126 women and 105 men sick-listed for spinal pain carried out the tests and provided personal and background data at inclusion in the study . METHODS One test measured stepping up onto and down from a stool , 2 measured lifting ability and 3 walking speed . Construct validity was examined by analysing the influence of some variables on test performance . RESULTS High-rated pain behaviour and perceived high pain intensity during testing or during the previous 4 weeks were connected with low test performance . Exercise twice a week was connected with high test performance . The test with the highest ability to detect disability in the women with lumbar pain was a lumbar lifting test , while for the men , it was a cervical lifting test . The test with the highest ability to detect disability in the participants with neck pain was the cervical lifting test in addition to a gait test with burden for the women . CONCLUSION Back pain hampered the test performance more than neck pain . Impairments and activity limitations expressed by the patient should guide the choice of test",
"Background Reproducibility measurements of the range of motion are an important prerequisite for the interpretation of study results . The aim of the study is to assess the intra-rater and inter-rater reproducibility of the measurement of active Range of Motion ( ROM ) in patients with neck pain using the Cybex Electronic Digital Inclinometer-320 ( EDI-320 ) . Methods In an outpatient clinic in a primary care setting 32 patients with at least 2 weeks of pain and /or stiffness in the neck were r and omly assessed , in a test- retest design with blinded raters using a st and ardized measurement protocol . Cervical flexion-extension , lateral flexion and rotation were assessed . Results Reliability expressed by the Intraclass Correlation Coefficient ( ICC ) was 0.93 ( lateral flexion ) or higher for intra-rater reliability and 0.89 ( lateral flexion ) or higher for inter-rater reliability . The 95 % limits of agreement for intra-rater agreement , expressing the range of the differences between two ratings were -2.5 ± 11.1 ° for flexion-extension , -0.1 ± 10.4 ° for lateral flexion and -5.9 ± 13.5 ° for rotation . For inter-rater agreement the limits of agreement were 3.3 ± 17.0 ° for flexion-extension , 0.5 ± 17.0 ° for lateral flexion and -1.3 ± 24.6 ° for rotation . Conclusion In general , the intra-rater reproducibility and the inter-rater reproducibility were good . We recommend to compare the reproducibility and clinical applicability of the EDI-320 inclinometer with other cervical ROM measures in symptomatic patients",
"OBJECTIVE To assess the sensitivity to change of three algofunctional scales for neck pain . METHODS Observational , prospect i ve study . Patients with neck disorders were included . Pain and patients ' perceived h and icap assessed on visual analogue scales ( VAS Pain , VAS H and icap ) , and functional disability measures ( Neck Disability Index , Neck Pain and Disability Scale , Northwick Park Neck Pain Question naire ) were recorded twice , at baseline and at an 11-month follow-up assessment . Sensitivity to change was assessed using the effect size ( ES ) and the st and ardised response mean ( SRM ) , and the non-parametric Spearman 's rank correlation coefficient ( r ) was used to assess the correlation between quantitative variable changes and patients ' overall opinion . Analysis of variance ( ANOVA ) followed by a Tukey-test was performed to determine if the scales distinguished improved , stable , and deteriorated patients . RESULTS Seventy-one patients ( 43 women , mean age 49 years ) were included and evaluated twice at an interval of 11 + /- 2 months . The three scales showed good sensitivity to change . The ANOVA showed a group effect , and individual changes in the scales scores were statistically different in two-by-two comparisons ( improved , stable or deteriorated patients ) . Changes in NPDS scores had the highest correlation with patient 's overall assessment ( r = 0.592 ) . CONCLUSION The three scales can detect changes in patients with neck disorders . Changes in NPDS score had the best correlation with patients ' overall opinion concerning their neck disorder and this question naire should be given preference in clinical trials",
"BACKGROUND The National Emergency X-Radiography Utilization Study ( NEXUS ) recently vali date d the ability of a decision instrument to define a population with an extremely low risk of cervical spine injury ( CSI ) after blunt trauma . It is unclear whether each of the 5 individual criteria is necessary for the decision instrument to maintain its high sensitivity . METHODS NEXUS was a prospect i ve observational study at 21 emergency departments , which enrolled all patients with blunt trauma for whom cervical spine radiographs were ordered . In this sub study , we examined the NEXUS data base to determine the contribution of each of the 5 individual low-risk clinical criteria to the overall sensitivity of the decision instrument . RESULTS All but 8 of 818 patients with CSI , and all but 2 of 578 patients with significant CSI , were identified by using the decision instrument . A substantial number of patients with CSI ( 236/818 [ 29 % ] ) and patients with significant CSI ( 175/578 [ 30 % ] ) met only 1 of the 5 non -- low-risk criteria , and each of the 5 criteria was the only indicator of non -- low-risk status in at least 8 patients with CSI and at least 5 patients with significant CSI . CONCLUSION Because each of the 5 low-risk criteria was the only marker of non -- low-risk status in at least a few patients with significant CSI , modification of the overall NEXUS decision instrument by eliminating any one of the criteria would markedly reduce sensitivity and make the instrument unacceptable for clinical use",
"Abstract The aim of this study is to assess the accuracy of MRI alone in the differentiation of soft cervical disc protrusion from osteophytic compression in cervical disc disease . In a retrospective study , the MRI scans of 41 patients with cervical disc disease , who had previously undergone surgery , were presented to three independent observers , r and omly on two different occasions , to identify the accuracy of the diagnosis of the presence of hard or soft disc or both as a cause of compression . The observers ( two neurosurgeons and one neuroradiologist ) were not involved with the treatment of the cases at any stage and were unaware of the surgical findings . Their observations were compared with those of the surgeon recorded at operation . The intra-observer agreement was poor for diagnosis into three categories as hard or soft disc or both . In distinguishing between the presence or absence of hard disc , there was moderate to good ( Kappa = 0.6 ) intra observer and fair to moderate ( Kappa = 0.4 ) interobserver agreement . The sensitivity of diagnosis of a hard disc was high ( 87 % ) but specificity was low ( 44 % ) , due to the overestimation of the presence of hard disc . There was a significantly higher incidence of hard disc in the elderly age group ( 76 % over the fifth decade , P = 0.0073 ) . It is concluded that MRI alone is not a very efficient diagnostic tool in distinguishing between hard and soft disc in the cervical disc disease",
"CONTEXT High levels of variation and inefficiency exist in current clinical practice regarding use of cervical spine ( C-spine ) radiography in alert and stable trauma patients . OBJECTIVE To derive a clinical decision rule that is highly sensitive for detecting acute C-spine injury and will allow emergency department ( ED ) physicians to be more selective in use of radiography in alert and stable trauma patients . DESIGN Prospect i ve cohort study conducted from October 1996 to April 1999 , in which physicians evaluated patients for 20 st and ardized clinical findings prior to radiography . In some cases , a second physician performed independent interobserver assessment s. SETTING Ten EDs in large Canadian community and university hospitals . PATIENTS Convenience sample of 8924 adults ( mean age , 37 years ) who presented to the ED with blunt trauma to the head/neck , stable vital signs , and a Glasgow Coma Scale score of 15 . MAIN OUTCOME MEASURE Clinical ly important C-spine injury , evaluated by plain radiography , computed tomography , and a structured follow-up telephone interview . The clinical decision rule was derived using the kappa coefficient , logistic regression analysis , and chi(2 ) recursive partitioning techniques . RESULTS Among the study sample , 151 ( 1.7 % ) had important C-spine injury . The result ant model and final Canadian C-Spine Rule comprises 3 main questions : ( 1 ) is there any high-risk factor present that m and ates radiography ( ie , age > /=65 years , dangerous mechanism , or paresthesias in extremities ) ? ( 2 ) is there any low-risk factor present that allows safe assessment of range of motion ( ie , simple rear-end motor vehicle collision , sitting position in ED , ambulatory at any time since injury , delayed onset of neck pain , or absence of midline C-spine tenderness ) ? and ( 3 ) is the patient able to actively rotate neck 45 degrees to the left and right ? By cross-validation , this rule had 100 % sensitivity ( 95 % confidence interval [ CI ] , 98%-100 % ) and 42.5 % specificity ( 95 % CI , 40%-44 % ) for identifying 151 clinical ly important C-spine injuries . The potential radiography ordering rate would be 58.2 % . CONCLUSION We have derived the Canadian C-Spine Rule , a highly sensitive decision rule for use of C-spine radiography in alert and stable trauma patients . If prospect ively vali date d in other cohorts , this rule has the potential to significantly reduce practice variation and inefficiency in ED use of C-spine radiography",
"In the present study , we compared magnetic resonance imaging ( MRI ) findings of soft tissue structures in the upper cervical spine between whiplash-associated disorder ( WAD ) patients and population -based control persons , and examined whether MRI-verified abnormalities in WAD patients were related to accident-related factors hypothesized to be of importance for severity of injury . A total of 92 whiplash patients and 30 control persons , r and omly drawn , were included . Information on the accident-related factors ( i.e. , head position and impact direction ) was obtained by a question naire that was answered within 1 week after the accident . The MRI examination was performed 2 - 9 ( mean 6 ) years after the accident . Focus was on MRI abnormalities of the alar and the transverse ligaments , and the tectorial and posterior atlanto-occipital membranes , grade d 0 - 3 . For all neck structures , the whiplash patients had more high- grade lesions ( grade 2 or 3 ) than the control persons ( Chi-square test , p abnormal alar ligament was most common ( 66.3 % grade d 2 or 3 ) . Whiplash patients who had been sitting with their head/neck turned to one side at the moment of collision more often had high- grade lesions of the alar and transverse ligaments ( p Severe injuries to the transverse ligament and the posterior atlanto-occipital membrane were more common in front than in rear end collisions ( p MRI-verified lesions between WAD patients and control persons , and in particular the association with head position and impact direction at time of accident , indicate that these lesions are caused by the whiplash trauma",
"STUDY HYPOTHESIS Cervical-spine radiography does not need to be performed on selected blunt trauma patients who are awake , alert , nonintoxicated , do not complain of midline neck pain , and have no tenderness over the bony cervical spine . STUDY POPULATION One thous and consecutive patients seen in the UCLA Emergency Medicine Center with a chief complaint of blunt trauma , for whom cervical-spine films were ordered and for whom prospect i ve data question naires were completed . METHODS Clinicians completed data forms for each patient before radiograph results were known . Data items included mechanism of injury , evidence of intoxication , presence of cervical-spine pain and /or tenderness , level of alertness , presence of focal neurologic deficits , and presence of other severely painful injuries unrelated to the cervical spine . Physicians were also asked to estimate likelihood of significant cervical-spine injury . RESULTS Twenty-seven patients with cervical-spine fracture were among the 974 patients for whom data forms were completed . A number of findings were statistically more common in the group of patients with fracture than without , but no single or paired findings identified all patients with fracture . All 27 patients with fracture had at least one of the following four characteristics : midline neck tenderness , evidence of intoxication , altered level of alertness , or a severely painful injury elsewhere . Three hundred fifty-three of 947 ( 37.3 % ) patients without cervical-spine fracture had none of these findings . CONCLUSION Cervical-spine radiology may not be necessary in patients without spinous tenderness in the neck , intoxication , altered level of alertness , or other severely painful injury . A policy to limit films in such patients would have decreased film ordering by more than one third in this series , while identifying all patients with fracture",
" One hundred and seven women participated in a clinical study of an age-stratified r and om sample of sewing machine operators compared to a group of auxiliary nurses and home helpers . Four groups , according to years of being a sewing machine operator , consisted of : ( controls ) 25 ; ( 0 - 7 years ) 21 ; ( 8 - 15 years ) 25 ; and ( more than 15 years ) 36 . The numbers of the main clinical diagnoses in the four groups were : cervicobrachial fibromyalgia ( myofascial pain syndrome ) 2 , 4 , 11 , 24 ; cervical syndrome 0 , 1 , 3 , 10 ; and rotator cuff syndrome 1 , 1 , 6 , 11 . The observed exposure-response relationship between clinical outcomes and years as a sewing machine operator was maintained when adjusting for current exposure to musculoskeletal strain and other potential confounders . Muscle palpation proved to be a reproducible examination with kappa values around 0.70",
"Study Design . This was a prospect i ve study to evaluate the accuracy of magnetic resonance imaging in predicting the presence of disc material posterior to the posterior longitudinal ligament ( PLL ) , compared with the accuracy of intraoperative visual and tactile examination of the PLL . Objectives . To determine the accuracy of magnetic resonance imaging in predicting the presence of disc material posterior to the PLL . Summary of Background Data . Whether removal of the disc to the PLL is sufficient when performing an anterior cervical discectomy and fusion or it is necessary to explore the spinal canal by taking down the PLL is controversial . Methods . Fifty‐four cervical levels were examined by magnetic resonance imaging before surgery to determine whether there was disc material posterior to the PLL . During surgery , the PLL was examined and probed for disruption . The ligament was taken down , and free fragments were identified and removed . Results . Of 54 levels , 12 were correctly identified by magnetic resonance imaging as having disc material posterior to the PLL , and 26 were correctly identified as not having disc material posterior to the PLL . Surgery confirmed that at 26 levels there was disc material posterior to the PLL . Of these 26 , 23 ( 88.5 % ) had visual or palpable disruption of the PLL . Magnetic resonance imaging failed to predict disc material posterior to the PLL in 14 of the cases in which its presence was confirmed during surgery . Magnetic resonance imaging had 46.2 % sensitivity and 92.9 % specificity rates . Conclusions . Because of low sensitivity , magnetic resonance imaging should be used cautiously for predicting free disc material posterior to the PLL . Visual or palpable examination of the PLL during surgery is more accurate for this prediction",
"OBJECTIVES Clearing the cervical spine in a time-sensitive fashion is difficult . We hypothesized that admission computed tomographic scan of the occiput to T1 ( CTS ) with multiplanar reformatted images will replace five-view ( odontoid , anteroposterior , lateral , and oblique ) plain films of the cervical spine ( CSX ) in the initial evaluation of blunt trauma patients with altered mental status . METHODS Between January and July 2001 , all patients aged 16 years or older with altered mental status undergoing both CTS and CSX were prospect ively entered into the study group . Attending physician interpretation defined the presence of cervical spine injury . Unstable fractures were defined as requiring surgical or halo stabilization . RESULTS One thous and six patients met study criteria . One hundred sixteen patients had 172 cervical spine injuries ( CSIs ) ( fracture and subluxation ) . CSX missed 90 of 172 ( 52.3 % ) CSIs in 65 of 172 ( 56.0 % ) patients . Anatomically , CSX failed to identify 14 of 15 occipital fractures ( 93.3 % ) , 17 of 36 ( 47.2 % ) C1 - 3 fractures , and 59 of 121 ( 48.8 % ) C4-T1 CSIs . CSX failed to identify 5 of 29 ( 17.2 % ) patients with unstable CSIs . CTS failed to diagnose 3 of 172 ( 1.7 % ) CSIs that were stable ( spinous process fractures at C6 - 7 ) . Two patients exhibited spinal cord injury without radiologic abnormality missed by both modalities . CTS had a sensitivity of 97.4 % , a specificity of 100 % , a prevalence of 11.5 % , a positive predictive value of 100 % , and a negative predictive value of 99.7 % . CSX had a sensitivity of 44.0 % , a specificity of 100 % , a prevalence of 11.5 % , a positive predictive value of 100 % , and a negative predictive value of 93.2 % . CONCLUSION CTS outperformed five-view CSX in a group of patients with altered mental status or distracting injuries . Five-view CSX failed to diagnose 52.3 % of cervical spine fractures identified by CTS . Five-view CSX failed to diagnose five patients with unstable cervical fractures and failed to identify 93.3 % of patients with occipital condyle fractures",
"PURPOSE To assess whether a single enhanced T1-weighted gradient echo volume sequence , with the appropriate reformatted images , could be equivalent to a more conventional 2D set of MR sequences for the evaluation of cervical extradural degenerative disk disease ( bony canal and foraminal stenosis ; disk herniation ) . MATERIAL S AND METHODS Sixty-one patients evaluated for extradural degenerative disease by MR were imaged with a \" st and ard \" MR examination ( Sagittal T1-weighted spin echo , axial low flip angle gradient echo ) , were then given 0.1 mmol/kg Gd-DTPA intravenously , and reimaged with either a 3D FLASH ( fast low angle shot ) , TR 40/TE 7/1 excitation ) , 40 degree flip angle , acquired as 64 , 2-mm sagittal partitions , or a 3D turbo FLASH ( MP RAGE-magnetization prepared rapid acquisition gradient echo ) ( 10/4/1 ) , 10 degree flip angle acquired as 128 , 2-mm coronal partitions . The volume sequences were reconstructed in the axial plane , and right and left 45 degree oblique coronal planes . The two sets of examinations ( st and ard vs volume ) were prospect ively interpreted by two neuroradiologists for quality of examination , and location , type , and severity of extradural degenerative disease in a r and om , blinded , independent fashion . RESULTS There was no significant difference between the st and ard examination and the 3D MP RAGE for central extradural disease . The 3D FLASH examination was significantly worse than the st and ard examination in identification of central extradural disease , with an average of 21 herniations not identified , or underestimated in size . Neither the 3D FLASH , nor the 3D MP RAGE examinations showed any significant improvement compared to the routine 2D examination for the location and severity of foraminal disease . CONCLUSION If extradural degenerative disk disease is being evaluated , then a single enhanced 3D T1-weighted imaging sequence taking 6 minutes can be equivalent to a routine set of mixed 2D spin echo and low flip angle gradient echo sequences",
"BACKGROUND CONTEXT In a small prospect i ve study assessing 10 symptomatic and 10 asymptomatic subjects , Schellhas et al. compared cervical discography to magnetic resonance imaging . Within that study he reported on the distribution of pain for the C3-C4 to C6-C7 levels . Four years later , Grubb and Ellis reported retrospective data from his 12-year experience using cervical discography from C2-C3 to C7-T1 in 173 patients . To date , no large prospect i ve study defining pain referral patterns for each cervical disc has been performed . PURPOSE To conduct a prospect i ve visual and statistical descriptive study of pain provocation of a cohort of subjects undergoing cervical discography . STUDY DESIGN / SETTING Prospect i ve multicenter descriptive study . METHODS Pain referral maps were generated for each disc level from patients undergoing cervical discography with at least two levels assessed . If concordant pain was reproduced in a morphologically abnormal disc , the subject immediately completed a pain diagram . An independent observer interviewed the subject and recorded the location of provoked symptoms . Visual data were compiled using a body sector bit map , which consisted of 48 clinical ly relevant body regions . Visual maps with graduated color codes and frequencies of symptom location at each cervical disc level were generated . RESULTS A total of 101 symptom provocation maps were recorded during cervical discography on 41 subjects . There were 10 at C2-C3 , 19 at C3-C4 , 27 at C4-C5 , 27 at C5-C6 , 16 at C6-C7 and 2 at C7-T1 . Predominantly unilateral symptoms were provoked just as often as bilateral symptoms . The C2-C3 disc referred pain to the neck , subocciput and face . The C3-C4 disc referred pain to the neck , subocciput , trapezius , anterior neck , face , shoulder , interscapular and limb . The C4-C5 disc referred pain to the neck , shoulder , interscapular , trapezius , extremity , face , chest and subocciput . The C5-C6 disc referred pain to the neck , trapezius , interscapular , suboccipital , anterior neck , chest and face . The C6-C7 disc referred pain to the neck , interscapular , trapezius , shoulder , extremity and subocciput . At C7-T1 we produced neck and interscapular pain . Visual maps with graduated color codes and frequencies of symptom location at each cervical disc level were generated . CONCLUSIONS In conclusion , these results confirm the observations of prior investigators that cervical internal disc disruption can elicit axial and peripheral symptoms . The particular patterns of pain generation allow the discographer to preprocedurally anticipate disc levels to assess . With these data , the number of disc punctures that are required can be limited rather than routinely assessing all cervical discs",
"BACKGROUND Because clinicians fear missing occult cervical-spine injuries , they obtain cervical radiographs for nearly all patients who present with blunt trauma . Previous research suggests that a set of clinical criteria ( decision instrument ) can identify patients who have an extremely low probability of injury and who consequently have no need for imaging studies . METHODS We conducted a prospect i ve , observational study of such a decision instrument at 21 centers across the United States . The decision instrument required patients to meet five criteria in order to be classified as having a low probability of injury : no midline cervical tenderness , no focal neurologic deficit , normal alertness , no intoxication , and no painful , distracting injury . We examined the performance of the decision rule in 34,069 patients who underwent radiography of the cervical spine after blunt trauma . RESULTS The decision instrument identified all but 8 of the 818 patients who had cervical-spine injury ( sensitivity , 99.0 percent [ 95 percent confidence interval , 98.0 to 99.6 percent ] ) . The negative predictive value was 99.8 percent ( 95 percent confidence interval , 99.6 to 100 percent ) , the specificity was 12.9 percent , and the positive predictive value was 2.7 percent . Only two of the patients classified as unlikely to have an injury according to the decision instrument met the preset definition of a clinical ly significant injury ( sensitivity , 99.6 percent [ 95 percent confidence interval , 98.6 to 100 percent ] ; negative predictive value , 99.9 percent [ 95 percent confidence interval , 99.8 to 100 percent ] ; specificity , 12.9 percent ; positive predictive value , 1.9 percent ) , and only one of these two patients received surgical treatment . According to the results of assessment with the decision instrument , radiographic imaging could have been avoided in the cases of 4309 ( 12.6 percent ) of the 34,069 evaluated patients . CONCLUSIONS A simple decision instrument based on clinical criteria can help physicians to identify reliably the patients who need radiography of the cervical spine after blunt trauma . Application of this instrument could reduce the use of imaging in such patients",
"The human sufferings and socioeconomic burden due to whiplash-associated disorders ( WAD ) are obvious but the pathogenesis of WAD is obscure . The possible involvement of the immune system during the disease process in WAD is not known . Effector molecules including chemokines and their receptors could play a role in WAD . In a prospect i ve study using flow cytometry , we examined percentages of blood mononuclear cells ( MNC ) expressing the chemokines RANTES , MCP-1 , MIP-1α , MIP-1β , and IL-8 , the chemokine receptor CCR-5 , the T cell activation marker CD25 , and the T cell chemoattractant IL-16 in patients with WAD and , for reference , in healthy controls . Higher percentages of RANTES-expressing blood MNC and T cells were observed in patients with WAD examined within 3 days compared to 14 days after the whiplash injury and , likewise , compared with healthy controls . The patients with WAD examined within 3 days after the accident also had higher percentages of CCR-5-expressing blood MNC , T cells , and CD45RO+ T cells compared to healthy controls . In contrast , there were no differences for any of these variables between patients with WAD examined 14 days after injury and healthy controls . In conclusion , WAD is associated with a systemic but transient dysregulation in percentages of RANTES and CCR-5 expressing MNC and T cells ",
"BACKGROUND Current literature supports the use of the three-view plain-radiograph series supplemented , when necessary , with helical computed tomography to evaluate the cervical spine in patients who have sustained trauma injury . The purpose of this study was to determine if helical computed tomography alone can be used to evaluate the cervical spine for acute osseous injury following high-energy trauma , thus eliminating the need to make radiographs . METHODS Patients were prospect ively evaluated with helical computed tomography scanning of the cervical spine and st and ard three-view plain radiography . At a later date , the plain radiographs and computed tomography scans were independently review ed by two radiologists who were blinded to both the initial interpretation and the interpretation of the corresponding study . The radiologists documented whether the plain radiographs were adequate and whether they showed an acute process . The findings in the study were compared with the initial findings and , when necessary , with the discharge summaries to determine if an injury had been identified . The accuracy of the plain radiographs , of the plain radiographs that had been deemed adequate , and of helical computed tomography used alone was ascertained . RESULTS Plain radiographs and helical computed tomography scans were made for 407 patients , and traumatic injuries were identified in fifty-eight of them . Plain radiographs alone were adequate for 194 ( 48 % ) of the 407 patients . Plain radiographs had a sensitivity of 45 % , a specificity of 97 % , a positive predictive value of 74 % , and a negative predictive value of 91 % . Adequate plain radiographs had a sensitivity of 52 % , a specificity of 98 % , a positive predictive value of 81 % , and a negative predictive value of 93 % . Helical computed tomography had a sensitivity and specificity of 98 % , a positive predictive value of 89 % , and a negative predictive value of > 99 % . The sensitivity , positive predictive value , and negative predictive value of adequate plain radiographs differed significantly from those of helical computed tomography alone ( p computed tomography missed that injury . Helical computed tomography alone missed one ( 2 % ) of the fifty-eight injuries . CONCLUSIONS Although helical computed tomography has a limited ability to detect pure ligamentous injury , it can be safely used without plain radiographs to evaluate the cervical spine for osseous abnormalities such as fractures and dislocations after high-energy trauma",
"Previous investigations with plain radiography , myelography , and computed tomography have shown that degenerative disease of the cervical spine frequently occurs in the absence of clinical symptoms . We studied the magnetic resonance-imaging scans of sixty-three volunteers who had no history of symptoms indicative of cervical disease . The scans were mixed r and omly with thirty-seven scans of patients who had a symptomatic lesion of the cervical spine , and all of the scans were interpreted independently by three neuroradiologists . The scans were interpreted as demonstrating an abnormality in 19 per cent of the asymptomatic subjects : 14 per cent of those who were less than forty years old and 28 per cent of those who were older than forty . Of the subjects who were less than forty , 10 per cent had a herniated nucleus pulposus and 4 per cent had foraminal stenosis . Of the subjects who were older than forty , 5 per cent had a herniated nucleus pulposus ; 3 per cent , bulging of the disc ; and 20 per cent , foraminal stenosis . Narrowing of a disc space , degeneration of a disc , spurs , or compression of the cord were also recorded . The disc was degenerated or narrowed at one level or more in 25 per cent of the subjects who were less than forty years old and in almost 60 per cent of those who were older than forty . The prevalence of abnormal magnetic-resonance images of the cervical spine as related to age in asymptomatic individuals emphasizes the dangers of predicating operative decisions on diagnostic tests without precisely matching those findings with clinical signs and symptoms",
"Study Design . A prospect i ve observational study was conducted on the use of the Chinese version of the Northwick Park Neck Pain Question naire . Objective . To examine the reliability , validity , and responsiveness of the Chinese version of the Northwick Park Neck Pain Question naire in Chinese patients with neck pain in Hong Kong . Summary of Background Data . There is increasing recognition that patient perspectives are essential both in making medical decisions and in judging the treatment outcomes . A valid Chinese version of a neck disability index question naire is urgently needed for effective and reliable evaluation of the treatment outcomes for patients with neck pain . Methods . Two sample s with 532 consecutive adult patients with neck pain from seven physiotherapy outpatient departments in Hong Kong who completed the Northwick Park Neck Pain Question naire were observed and measured at different intervals : at the beginning of physiotherapy , at 7 days , at 3 weeks , and 6 weeks after physiotherapy . Results . The question naire had good content validity , very good test – retest reliability , and internal consistency ( intraclass correlation coefficient , 0.95 ; Cronbach ’s alpha , 0.87 ) . It also had good validity ( Spearman correlation coefficient of 0.59 when the score was correlated with that of a generic 42-item Chinese health question naire ) and good responsiveness ( effect size of 1.11 at week 6 after treatment began ) . Conclusions . The Chinese version of the Northwick Park Neck Pain Question naire has been shown to demonstrate very good content validity , a high degree of test – retest reliability , and internal consistency . It also exhibited good construct validity and high sensitivity to changes in severity over time",
"STUDY OBJECTIVE Flexion-extension ( F/E ) radiographs of the cervical spine are often used in patients with blunt trauma when the evaluating physician remains concerned about bony or ligamentous injuries despite negative or nondiagnostic st and ard radiographs . The use of this approach has never been addressed in a large prospect i ve study . We sought to determine the clinical factors associated with ordering F/E views and the incidence of diagnostic F/E films in patients with a normal 3-view cervical spine series . METHODS Patients with blunt trauma selected for radiographic cervical spine imaging at 21 participating institutions in the National Emergency X-Radiography Utilization Study project underwent st and ard 3-view ( cross-table lateral , anteroposterior , and odontoid views ) series , as well as any other imaging deemed necessary by their physicians . Injuries detected by means of screening radiography were then compared with final injury status for each patient , as determined by review of all radiographic studies . Patients who underwent F/E views were analyzed separately . RESULTS Of 818 patients ultimately found to have cervical spine injury , 86 ( 10.5 % ) underwent F/E testing . Two patients sustained stable bony injuries detected only on F/E views . Four other patients had a subluxation detected only on F/E views , but all had other injuries apparent on routine cervical spine imaging . CONCLUSION F/E imaging adds little to the acute evaluation of patients with blunt trauma . Other approaches , including magnetic resonance imaging , computed tomography , or delayed F/E , in the presence of specific clinical concerns would seem to provide a more reasonable approach to adjunctive imaging",
"OBJECTIVE To investigate the reliability and discriminative ability of a new test design ed to detect accuracy of neck movements . DESIGN Repeated- measures . Case-control . SETTING University musculoskeletal research clinic in Icel and . PARTICIPANTS Twenty women ( mean age + /- st and ard deviation [ SD ] , 30.8+/-9.1 y ; range , 18 - 49 y ) with chronic whiplash-associated disorders ( WAD ) grade s I and II ( duration , 6 mo-6 y ) , with current pain score on a visual analog scale of 46.8+/-21.8 , and a disability score on the Northwick Park Neck Pain Disability Index of 45%+/-14 % . Twenty asymptomatic women ( mean age + /- SD , 29.3+/-8.6 y ; range , 18 - 48 y ) with no history of whiplash or insidious onset neck pain served as controls . INTERVENTION A slowly moving object appeared on a computer screen and traced an unpredictable movement path that the subjects were required to follow by moving their heads . Three r and omly ordered movement patterns were tested . MAIN OUTCOME MEASURE A new software program connected to a 3Space Fastrak system was used to measure the mean absolute error ( in millimeters ) of 3 trials in each movement pattern . RESULTS The mean differences ( + /-2 SD ) between days 1 and 2 were.01+/-.64 mm for the asymptomatic group and .33+/-1.80 mm for the WAD group . The between-day intraclass correlation coefficients were between.60 and .77 for the asymptomatic group and .79 and .86 for the WAD group . Repeated- measures analysis of variance revealed a significant difference between groups ( P=.02 ) . The Tukey post hoc test showed significant between-group differences for each movement pattern ( P reliability was detected for the asymptomatic group than for the WAD group . The test could discriminate between the asymptomatic group versus the chronic WAD group",
"Objective : To examine the reliability , validity and responsiveness of the generic Current Perceived Health 42 ( CPH42 ) Profile in Chinese patients with neck pain in Hong Kong . Design : A prospect i ve observational study . Setting : Physiotherapy outpatient departments . Subjects : Two sample s with 472 consecutive adult patients with neck pain from seven physiotherapy outpatient departments in Hong Kong . Methods : Subjects were requested to complete the CPH42 Profile , and their pain intensity was measured using the 11-point numerical rating scale ( NRS ) . They were observed and measured at the beginning of physiotherapy , at seven days , at week 3 and at week 6 after treatment began . Results : The CPH42 Profile had very good test – retest reliability and internal consistency ( intraclass correlation coefficient 0.91 , Cronbach 's alpha 0.90 ) . Validity was confirmed by a moderate correlation with the NRS at the beginning of treatment and week 6 ( rank correlation 0.41–0.53 ) . Moreover , a significant difference in scores was found between those who had sought medical consultation and /or had taken medication because of neck pain than those who did not . The responsiveness measured from the beginning of treatment to week 3 and week 6 ( st and ard response means of 0.33 and 0.36 ) was comparable to the respective changes in pain intensity . Conclusion : The CPH42 Profile has been shown to demonstrate good reliability and validity , and it is sensitive to changes in severity over time . It is suitable for use as an outcome measure for evaluation of patients with neck pain",
"The present study was undertaken to evaluate if MRI within 2 days of a motor vehicle accident could reveal pathology of importance for underst and ing long-term disability after whiplash neck-sprain injuries . As part of a prospect i ve study cervical and cerebral MRI was performed on 40 neck sprain patients with whiplash injury after car accidents . The imaging was done within 2 days of the injury to make sure that any neck muscle bleeding , oedema or other soft tissue injuries could be detected . The MRI findings from the patients were both correlated to reported symptoms 6 months after the accident and compared to a control group of 20 volunteers . The MRI of both brain and neck revealed no significant differences between the patients and the control group . When the patients were grouped according to the main MRI findings at intake and compared according to the development of subjective symptoms reported by the patients , the only significant difference was more headaches at 6 months in the groups with disk pathology or spondylosis when compared to the group with no pathology . In conclusion , MRI within 2 days of the whiplash neck-sprain injury could not detect pathology connected to the injury nor predict symptom development and outcome",
"BACKGROUND The National Emergency X-Radiography Utilization Study defined five criteria for obtaining cervical spine radiographic investigations in blunt trauma patients . Distracting injury was given as the indication for more than 30 % of all x-ray studies ordered . The hypothesis of this study was that upper and lower torso injuries would have different effects on clinical cervical spine assessment . METHODS This is a single-center , prospect i ve , observational study of admitted , alert , adult blunt-trauma patients . All patients underwent cervical spine plain-film radiography . Data were collected on all injuries , physical examination findings , narcotic administration , and radiograph results . Patients with upper and lower torso injuries were compared in their ability complain of pain or midline tenderness relative to a cervical spine fracture . RESULTS In all , 406 patients participated . All patients received narcotic analgesics before examination . Forty patients ( 9.9 % ) had cervical spine fractures , of whom seven had a nontender neck examination . All seven patients with a nontender cervical spine and a neck fracture had at least one upper torso injury . None of the 99 patients with injuries isolated to the lower torso and a nontender neck had a cervical spine fracture ( p frequency of cervical spine fracture among patients with cervical spine tenderness was 19.8 % ( n = 33 ) . CONCLUSIONS The National Emergency X-Radiography Utilization Study definition of a distracting injury may be narrowed . Upper torso injuries may be sufficiently painful to distract from a reliable cervical spine examination . Patients may detect spine tenderness in the presence of isolated painful lower torso injuries . Patients with spine tenderness warrant imaging",
"Abstract This cross-sectional study aim ed at investigating the influence of occupational exposure to static and highly repetitive work involving the neck and shoulder muscles , myalgia of and tender point in the trapezius muscle on biomechanical output , and electromyogram ( EMG ) variables ( mean frequency MNF , signal amplitude and ability to relax ) during maximal forward flexions of the shoulder muscles . Groups of 25 cleaners suffering from chronic myalgia of the trapezius muscle , 25 cleaners free from myalgia of the trapezius muscle and 21 teachers performed 150 forward flexions using an isokinetic dynamometer . Perception of fatigue was reported and surface EMG was recorded from four muscles during the endurance test . The cleaners were stronger than the teachers . Myalgia was associated with lower levels of endurance and a high degree of perceived fatigue . The ability to relax the trapezius muscle decreased with age and was even lower in cleaners with and without myalgia . Higher MNF of the deltoid muscle but not of the trapezius muscle was found in the group suffering from myalgia compared to the groups free from myalgia . This cross-sectional study indicated that myalgia of the trapezius muscle did not influence the strength but did influence the endurance of the forward flexor muscles of cleaners . The observed decrease in the ability to relax the trapezius muscle in cleaners compared to healthy teachers might be indicative of a future insufficiency in the muscle . Prospect i ve studies are needed to define the significance of the results presented here",
"OBJECTIVE To develop and assess the reliability of a group of cervical nonorganic physical signs to be used as a simple screening tool for identifying patients with low neck pain who exhibit abnormal illness behavior . DESIGN Survey , consecutive sample . DATA SET Double masked . SETTING Functional restoration program . PATIENTS Twenty-six consecutive patients with complaints of chronic neck pain ( greater than 4 months duration ) . Each patient was evaluated by a physician and then again by either a physical or occupational therapist , for the presence of specific cervical nonorganic signs . Both of the evaluations occurred on the same day . MAIN OUTCOME MEASURES Five categories consisting of eight tests were appraised : ( 1 ) tenderness , ( 2 ) simulation , ( 3 ) range of motion , ( 4 ) regional disturbance , and ( 5 ) overreaction . RESULTS The percent agreement between raters ranged from a high of 100 % for regional sensory disturbance , to a low of 68 % for one of the simulation tests . The average agreement between raters across all of the nonorganic test signs was 84.6 % . Likewise , kappa coefficients ranged from 1.00 to .16 , reflecting differences in strength of agreement . CONCLUSION For many years , the lumbar nonorganic signs ( developed by Waddell and colleagues ) have been a useful screening tool in the assessment of abnormal illness behavior in the low back pain population . For the first time , a group of cervical nonorganic signs have been developed , st and ardized , and proven reliable",
"Study Design This study compared the ambulatory electromyogram activity of persons reporting pain in the shoulder and cervical regions with an equal group of persons not reporting such pain . Ambulatory electromyogram data were obtained over 3‐day periods . In addition , all participants completed several st and ard psychological question naires . Objectives The results were analyzed with inferential statistics to determine whether subjects reporting significant pain in the shoulder and cervical regions had greater ambulatory electromyogram activity than an equal number of subjects not reporting pain . Summary of Background Data Considerable controversy exists regarding the role of muscle activity in the etiology and maintenance of muscle pain disorders . Given the availability of ambulatory recording devices that can provide a detailed record of muscle activity over an extended period of time , the present research was conducted to determine whether persons reporting shoulder and cervical pain could be differentiated from a group of normal subjects . Methods All subjects ( N = 20 ) completed a battery of tests with st and ardized psychometric instruments and then were fitted with ambulatory electromyogram monitors to record electromyographic activity of the upper trapezius region of the dominant side ; the time , duration , and amplitude of electromyogram activity greater than 2 μV was recorded . The monitors were worn during normal working hours ( mean , 6.2 hours per day ) over 3 consecutive days . In addition to wearing the monitors , all subjects completed hourly self‐ratings of perceived muscle tension during the recording periods . Results As expected , subjects with muscle pain reported significantly more pain ( mean , 4.9 ) than did the normal control subjects ( mean , 0.9 ) , t(15 ) = 3.29 , P greater average electromyogram activity ( mean , 6.4 μV ) over the 3‐day period as compared to the normal controls ( mean , 7.1 μV ) , t(18 ) = ‐0.25 , P 0.80 . Self‐monitoring of perceived muscle tension also did not reveal differences between pain subjects and the normal control subjects ( P measurements of electromyogram activity did not differentiate persons reporting upper trapezius or cervical pain from those that did not report such pain . Persons reporting pain are also not distinguishable from normal control subjects on a variety of self‐report measures . These results raise questions regarding the role of ambulatory electromyogram recordings in the evaluation and treatment of muscle pain disorders",
"Objective : To determine the false-positive rate of anesthetic blocks of the medial branches of the cervical dorsal rami in the diagnosis of cervical zygapophysial joint pain . Design : Comparison between single diagnostic blocks , and a criterion st and ard of double-blind , controlled , differential anesthetic blocks . Setting : Tertiary referral center . Patients : The first 55 consecutive patients with neck pain for > 3 months after and attributable to a motor vehicle accident , and who had completed a second diagnostic block after an initial positive response . A total of 60 joints was studied , with five patients providing two joints each . The mean age was 41 years : 61 % were female . Methods : Each patient had been investigated with radiologically controlled blocks of the medial branches of the cervical dorsal rami to anesthetize the target cervical zygapophysial joint . The initial block was performed using either 0.5 % bupivacaine or 2 % lignocaine , r and omly selected . The duration of pain relief was assessed in a double-blind fashion . The procedure was repeated with the complementary anesthetic . Only patients experiencing a longer period of pain relief from bupivacaine were considered to have true-positive responses . Results : The second block failed to relieve pain in two of the tested joints . In a further 14 joints , the control blocks relieved pain , but the patient failed to correctly discriminate the longer acting anesthetic . The remaining 44 joints met the criteria for true-positive responses . The false-positive rate of single blocks was 16 of 60 or 27 % ( 95 % confidence interval 15 % , 38 % ) . Conclusion : Uncontrolled diagnostic blocks are compromised by a significant false-positive rate that seriously detracts from the specificity of the test",
"Study Design . Double-blind , r and omized , placebo-controlled trial . Objectives . To evaluate the effect of manual endplay assessment on neck pain and stiffness outcomes in neck pain patients receiving spinal manipulation . Summary of the Background Data . There have been no studies on the efficacy of palpation used as an indicator for manipulation in the management of back and neck pain . Methods . Neck pain patients ( n = 104 ) were r and omly assigned to two groups . The study group received manipulation targeted to individual cervical vertebrae according to endplay restriction noted by the examining clinician . The control group received manipulation determined by sham , computer-generated examination findings ; endplay examination was ignored and served as a placebo assessment . Treatment was rendered on a single occasion by a chiropractor . Outcomes were neck pain and stiffness assessed before and after manipulation and at least 5 hours following treatment . Results . The study and control groups showed clinical ly important improvement in neck pain and stiffness . However , there were no clinical ly important or statistically significant differences between the study and control groups in terms of pain or stiffness outcomes . Findings were robust across patient , complaint , and treatment characteristics . Conclusions . Endplay assessment in and of itself did not contribute to the same-day pain and stiffness relief observed in neck pain patients receiving spinal manipulation . The impact on a longer course of treatment remains to be investigated . The data suggest that pain modulation may not be limited to mechanisms associated with manipulation of putative motion restrictions",
"Study Design . A blinded , prospect i ve diagnostic test study was conducted . Objectives . To assess the reliability and accuracy of individual clinical examination items and self-report instruments for the diagnosis of cervical radiculopathy , and to identify and assess the accuracy of an optimum test-item cluster for the diagnosis of cervical radiculopathy . Summary of Background Data . Although cervical radiculopathy remains largely a clinical diagnosis , the reliability and diagnostic accuracy of clinical examination items , individually or in combination , for cervical radiculopathy is largely unknown . Methods . Patients with suspected cervical radiculopathy or carpal tunnel syndrome received st and ardized electrophysiologic examination of the symptomatic upper quarter followed by a st and ardized clinical examination by physical therapist examiners blinded to diagnosis . Diagnostic properties were assessed using a neural impairment reference criterion st and ard . Results . The study involved 82 patients . More than two thirds of 34 clinical examination items had reliability coefficients rated at least fair or better , and 13 items had likelihood ratio point estimates above 2 or below 0.50 . A single diagnostic test item cluster of four variables was identified and produced a positive likelihood ratio point estimate of 30.3 . The 95 % confidence intervals for all likelihood ratio point estimates in this study were wide . Conclusions . Many items of the clinical examination were found to be reliable and to have acceptable diagnostic properties , but the test item cluster identified was more useful for indicating cervical radiculopathy than any single test item . Upper limb tension Test A was the most useful test for ruling out cervical radiculopathy . Further investigation is required both to vali date the test item cluster and to improve point estimate precision",
"STUDY OBJECTIVE We evaluate the accuracy , reliability , and potential impact of the National Emergency X-Radiography Utilization Study ( NEXUS ) low-risk criteria for cervical spine radiography , when applied in Canadian emergency departments ( EDs ) . METHODS The Canadian C-Spine Rule derivation study was a prospect i ve cohort study conducted in 10 Canadian EDs that recruited alert and stable adult trauma patients . Physicians completed a 20-item data form for each patient and performed interobserver assessment s when feasible . The prospect i ve assessment s included the 5 individual NEXUS criteria but not an explicit interpretation of the overall need for radiography according to the criteria . Patients underwent plain radiography , flexion-extension views , and computed tomography at the discretion of the treating physician . Patients who did not have radiography were followed up with a structured outcome assessment by telephone to determine clinical ly important cervical spine injury , a previously vali date d outcome measurement . Analyses included sensitivity and specificity with 95 % confidence interval ( CI ) , kappa coefficient , and potential radiography rates . RESULTS Among 8,924 patients , 151 ( 1.7 % ) patients had an important cervical spine injury . The combined NEXUS criteria identified important cervical spine injury with a sensitivity of 92.7 % ( 95 % CI 87 % to 96 % ) and a specificity of 37.8 % ( 95 % CI 37 % to 39 % ) . Application of the NEXUS criteria would have potentially reduced cervical spine radiography rates by 6.1 % from the actual rate of 68.9 % to 62.8 % . Of 11 patients with important injuries not identified , 2 were treated with internal fixation and 3 with a halo . CONCLUSION This retrospective validation found the NEXUS low-risk criteria to be less sensitive than previously reported . The NEXUS low-risk criteria should be further explicitly and prospect ively evaluated for accuracy and reliability before widespread clinical use outside of the United States",
"Abstract . Several work-related , psychosocial and individual factors have been verified as being related to neck and shoulder pain , but the role of pathology visualized by magnetic resonance imaging ( MRI ) remains unclear . In this study , the relationship between neck and shoulder pain and cervical high-field MRI findings was investigated in a sample of persons in a longitudinal survey . The study aim ed to determine whether subjects with persistent or recurrent neck and shoulder pain were more likely to have abnormal MRI findings of cervical spine than those without neck and shoulder pain . A r and om sample of 826 high-school students was investigated initially when the students were 17–19 years , and again when they had reached 24–26 years of age . Eighty-seven percent participated in the first survey in 1989 , of whom 76 % took part in the second survey , in 1996 . The vali date d Nordic Musculoskeletal Question naire was used to collect data about neck and shoulder symptoms . Two groups were chosen for the MRI study : the first group ( n=15 ) consisted of the participants who had reported no neck and shoulder symptoms in either of the inquiries , while the second group ( n=16 ) comprised those who were suffering from neck and shoulder symptoms once a week or more often at the time of both surveys . The degrees of disc degeneration , anular tear , disc herniation and protrusion were assessed by two radiologists . The differences between the two study groups were evaluated . The study found that abnormal MRI findings were common in both study groups . Disc herniation was the only MRI finding that was significantly associated with neck pain . These findings indicate that pathophysiological changes of cervical spine verified on MRI seem to explain only part of the occurrence of neck and shoulder pain in young adults ",
"Study Design . A cross-sectional study was conducted to analyze a convenience sample of patients seeking treatment for cervical spine conditions . Objective . To develop and evaluate the psychometric properties of a comprehensive , disease-specific question naire for characterizing complaints of neck pain and evaluating the outcomes of treatments for these complaints . Summary of Background Data . There currently are a number of generic and disease-specific instruments for assessing complaints of neck pain . None comprehensively cover the wide range of factors considered essential in evaluating treatment outcomes . Methods . The authors developed a comprehensive , disease-specific question naire for characterizing complaints of neck pain and evaluating the outcomes of treatments for these complaints . In this study , 216 patients who underwent surgery for cervical spine disorders completed the Cervical Spine Outcomes Question naire before treatment , then at 3 and 6 months after treatment . The data were used to evaluate the reliability , validity , and responsiveness of the question naire . Results . The authors have shown that the Cervical Spine Outcomes Question naire has high test – retest reliability , good construct validity , and responsiveness to change after treatment . Conclusions . The Cervical Spine Outcomes Question naire is a comprehensive , disease-specific instrument for assessing complaints of neck pain and evaluating the outcomes of treatments for these complaints . It provides information on demographics , pain severity , functional disability , psychological distress , physical symptoms , health care utilization , and satisfaction . It appears to be acceptable to patients , easy to administer , highly reliable , valid , and responsive . It should be considered for use in monitoring patients with cervical spine conditions and in studies of cervical spine disorders and their treatments",
"& NA ; The utility of r and omised , double‐blind , controlled , comparative local anaesthetic blocks for the diagnosis of cervical , zygapophysial joint pain was studied in 47 patients with chronic neck pain following whiplash injury . Each patient was investigated with radiologically controlled blocks of the medial branches of the cervical , dorsal rami to anaesthetise the target cervical , zygapophysial joint . The blocks were performed using either lignocaine or bupivacaine , r and omly allocated , and the patients ' responses were assessed in a double‐blind fashion . Any positive response was subsequently assessed by repeating the block with the complementary anaesthetic . Only those patients experiencing a longer period of pain relief from the bupivacaine were considered to have true‐positive responses . Forty‐four patients had pain relief from two blocks at a single level , of whom 34 had longer pain relief from bupivacaine . This result is unlikely to have occurred by chance ( P = 0.0002 ) . The duration s of pain relief obtained from the anaesthetics were consistent with the known characteristics of these drugs with bupivacaine lasting significantly longer than lignocaine ( P = 0.0003 ) . A subgroup of 13 patients were identified with unexpected , prolonged responses to one or both of the anaesthetics . Comparative , diagnostic blocks are a valid technique in the identification of painful zygapophysial joints , and constitute an implementable alternative to normal saline controls",
"The cervical curvature of 488 patients with acute whiplash injury was prospect ively studied by comparison with 495 asymptomatic healthy volunteers . Plain radiography of the cervical spine in the neutral position was evaluated qualitatively . No significant difference was noted in frequencies of non-lordotic cervical curvature and local angular kyphosis between acute whiplash injury patients and asymptomatic subjects . No significant association was apparent between clinical symptoms and cervical curvature . These results suggest that non-lordotic cervical curvature and angular kyphosis in acute whiplash injury patients constitute normal variants rather than pathological findings",
"Iohexol , a new water-soluble nonionic contrast medium , was evaluated in clinical trials in Europe and North America for lumbar , thoracic , and cervical myelography using direct C1 - 2 or lumbar puncture . Iohexol was administered at 180 , 240 , or 300 mg I/ml to 677 adult patients for visualization of the lumbar subarachnoid space , and to 368 adult patients for evaluation of the cervical area . Compared with metrizamide , use of iohexol result ed in equivalent opacification but significantly reduced patient morbidity ( headache , nausea , vomiting , dizziness ) . No epileptogenic activity was recorded in over 370 patients receiving iohexol . No mental or psycho-organic syndrome manifestations were observed in any of the 1,045 patients receiving iohexol . Adverse reactions occurring after iohexol injection were not related to the concentration or site used or to total dose administered . Iohexol has , thus far , proven superior to metrizamide for myelography",
"BACKGROUND There are numerous clinical tests used in the evaluation of patients with symptoms arising from the cervical spine . It is necessary to use clinical tests with high validity and reliability . Previous studies of reliability of clinical tests used in the evaluation of the cervical spine have come to various conclusions , most of which suggest low reliability . This might be explained by differences between examiners in performance and where the limit of normality is placed . OBJECTIVE To evaluate the interexaminer reliability of clinical tests used in everyday clinical work , where the examiners base their evaluations on a comparison between left and right sides . STUDY DESIGN A total of 50 volunteers were examined by two physiotherapists . The interexaminer reliability of clinical tests included in the physical examination of patients with symptoms from the cervical spine was evaluated . METHODS Two physiotherapists independently examined volunteers . RESULTS An acceptable reliability was found for two of 10 clinical tests . CONCLUSION When it is possible to compare left and right sides , it is possible to show acceptable reliability for some clinical tests . Reliability studies most often find low reliability , perhaps because of bias ; clinical tests are not st and ardized . In future studies , greater efforts should be taken to reduce bias",
"Criteria for excluding cervical spine injury in patients who have sustained blunt head or neck trauma were prospect ively studied at four hospitals in the Chicago area . The authors attempted to define a subset of these adult patients who , based on clinical criteria , could reliably be excluded from cervical spine radiography , thus avoiding unnecessary radiation and saving considerable time and money in their evaluation . Patients fell into four groups : ( 1 ) patients who were awake , alert , and had no complaint of neck pain or tenderness on physical examination ; ( 2 ) patients who were awake , alert , but had complaint of neck pain or tenderness on physical examination laterally over the trapezius muscle only ; ( 3 ) patients who were awake , alert , but had complaint of central neck pain or tenderness on physical examination over the cervical spine or center of the neck ; and ( 4 ) patients who were not fully awake or alert , were clinical ly intoxicated , had other painful or distracting injuries , or had focal neurologic findings . Patients in group 4 had significantly more fractures ( 21/387 ) when compared with all other patients ( 7/478 ) . Patients with central neck pain or tenderness ( group 3 ) had significantly more fractures ( 7/237 ) than patients without pain or tenderness or with these findings limited to the trapezius area ( 0/236 ) . It is clear that patients who have altered mental status , abnormal examination findings , distracting injury , or pain or tenderness over the cervical spine must have cervical spine radiographs . ( ABSTRACT TRUNCATED AT 250 WORDS",
"Study Design . A survey of the prevalence of cervical zygapophysial jooint pain was conducted . Objectives . To determine the prevalence of cervical zygapophysial joint pain in patients with chronic neck pain after whiplash . Summary of Backgound Data . In a significant porportion of patients with whiplash , chronic , refractory neck pain develops . Provisional data suggests many of these patients have zygapophysial joint pain , but the diagnosis has been established by single , uncontrolled diagnostic blocks . Methods . Fifty consecutive , referred patients with chronic neck pain after whiplash injury were studid using double-blind , controlled , diagnotic blocks of the cervical zygapophysial joints . On separate occasions , the joint was blocked with either lignocaine or bupivacaine in r and om order . Results . A positive diagnosis was made only if both blocks relieved the patient 's pain and bupivacaine provided longer relief , Painful joints were identified in 54 % of the patients ( 95 % confidence interval , 40 % to 68 % ) . Conclusion . In this population , cervical zygapophysial joint pain was the most common source of chronic neck pain after whiplash",
"Objective To assess whether the introduction of the National Emergency X-ray Utilization Study guidelines in a UK emergency department reduced the number of patients having cervical spine radiographs and altered the accuracy of diagnosis of cervical spine injury . Methods This was a prospect i ve , observational study . The number of patients with recent neck injury who had cervical spine radiographs taken was assessed for 3 months before and three months after the introduction of the National Emergency X-ray Utilization Study guidelines to an urban emergency department in the UK . The number of injuries missed by emergency department doctors during the two 3-month periods was also recorded . Results Prior to using the guidelines , 252 of 715 patients ( 35 % ) were X-rayed and when using the guidelines , 268 of 706 patients ( 38 % ) were X-rayed . No significant difference was observed between the rates of X-ray in the two groups ( P=0.288 ) . No injuries were missed by emergency department doctors either before or after the introduction of the guidelines . Conclusion Introduction of the National Emergency X-ray Utilization Study guidelines to a UK emergency department did not reduce the number of patients having cervical spine radiographs after neck trauma and had no effect on the pick-up rate for cervical spine injuries ",
"OBJECTIVE Reliable and valid measures of pain are needed to advance research initiatives on appropriate and effective use of analgesia in the emergency department ( ED ) . The reliability of visual analog scale ( VAS ) scores has not been demonstrated in the acute setting where pain fluctuation might be greater than for chronic pain . The objective of the study was to assess the reliability of the VAS for measurement of acute pain . METHODS This was a prospect i ve convenience sample of adults with acute pain presenting to two EDs . Intraclass correlation coefficients ( ICCs ) with 95 % confidence intervals ( 95 % CIs ) and a Bl and -Altman analysis were used to assess reliability of paired VAS measurements obtained 1 minute apart every 30 minutes over two hours . RESULTS The summary ICC for all paired VAS scores was 0.97 [ 95 % CI = 0.96 to 0.98 ] . The Bl and -Altman analysis showed that 50 % of the paired measurements were within 2 mm of one another , 90 % were within 9 mm , and 95 % were within 16 mm . The paired measurements were more reproducible at the extremes of pain intensity than at moderate levels of pain . CONCLUSIONS Reliability of the VAS for acute pain measurement as assessed by the ICC appears to be high . Ninety percent of the pain ratings were reproducible within 9 mm . These data suggest that the VAS is sufficiently reliable to be used to assess acute pain",
"STUDY OBJECTIVES A decision instrument based on 5 clinical criteria has been shown to be highly sensitive in selecting patients who require cervical spine imaging after blunt trauma , while simultaneously reducing overall imaging . We examine the performance of this instrument in the elderly and explore some of the common features of geriatric cervical spine injury ( CSI ) . METHODS The National Emergency X-radiography Utilization Study ( NEXUS ) was a prospect i ve , observational , multicenter study conducted at 21 geographically diverse centers . We analyzed the performance of the NEXUS decision instrument among patients at least 65 years of age . RESULTS The study group consisted of 2,943 ( 8.6 % ) geriatric patients , representing 8.6 % of the entire NEXUS sample . The rate of CSI was twice as great in these patients as it was in nongeriatric patients ( 4.59 % versus 2.19 % ) . Odontoid fractures were particularly common in geriatric patients , accounting for 20 % of geriatric fractures compared with 5 % of nongeriatric fractures . The frequency of patients meeting NEXUS criteria was similar in the 2 groups , with 14 % of geriatric patients and 12.5 % of nongeriatric patient classified as low risk . CSI occurred in only 2 low-risk geriatric patients , and these patients ' injuries met our preset definition of a clinical ly insignificant injury . The sensitivity of the NEXUS decision instrument for clinical ly significant injury in the geriatric group was therefore 100 % ( 95 % confidence interval 97.1 % to 100 % ) . CONCLUSION The prevalence of CSI , and especially odontoid fracture , is relatively increased among geriatric patients with blunt trauma . The NEXUS decision instrument can be applied safely to these patients , with an expected reduction in cervical imaging comparable with that achieved in nongeriatric patients",
"The purpose of the present study was to assess five manual tests for pain provocation of the neck to determine their suitability for epidemiological investigations . To 75 r and omly selected men , five manual pain-provoking tests were applied in a single-blind design . Prevalence of reported neck dysfunction , sensitivity , specificity , and positive and negative predicted value for each test were calculated . 22 of the 75 reported present neck pain , while the remainder reported freedom from neck pain for at least one year . Palpation over the facet joints in the cervical spine was found to be the most appropriate screening test to corroborate the replies in self-reported question naires on dysfunctions of the neck . The outcome of this test was quite consistent with the reported neck pain . The test of the formina intervertebralia and the upper limb tension test caused pain in almost all subjects with reported neck dysfunctions , though not causing referred pain in the arm as an indication of neurogenous tissue origin , as it was aim ed to . Neither the neck rotation test nor the active flexion/extension test was sufficiently provocative to confirm the reported neck pain in these subjects , as both were insufficiently sensitive",
"This is the second in a series of five articles Considerable effort has been expended at the interface between clinical medicine and scientific methods to achieve the maximum validity and usefulness of diagnostic tests . This article focuses on the specific kinds of questions that arise in diagnostic research and the study architectures ( the conversions of these clinical questions into appropriate research design s ) used to answer them . As an example we shall take shall take assessment of the value of the plasma concentration of B-type natriuretic peptide ( BNP ) in the diagnosis of left ventricular dysfunction.1 R and omised controlled trials are dealt with elsewhere . As in other forms of clinical research , there are several different ways study ing the potential or real diagnostic value of a physical sign or laboratory test , and each is appropriate to one kind of question and inappropriate for others . Among the possible questions about the relation between a putative diagnostic test and a target disorder ( for example , the concentration of BNP and left ventricular dysfunction ) , four are most relevant . # # # # Summary points Diagnostic studies should match methods to diagnostic questions The keys to validity in diagnostic test studies are Both specificity and sensitivity may change as the same diagnostic test is applied in primary ,",
"Background : The development of target-specific local anesthetic blocks has enabled pain physicians to explore the anatomical source of chronic spinal pain . However , such blocks rely on subjective responses and may be subject to the placebo effect . Comparative local anesthetic blocks have been advocated as a means of identifying true-positive cases and excluding placebo responders . This paradigm employs two local anesthetics with different duration s of action ; only patients who obtain reproducible relief and correctly identify the longer-acting agent are considered positive . Objective : Our objective was to evaluate the reliability of comparative blocks of the medial branches of the cervical dorsal rami in the diagnosis of cervical zygapophysial joint pain . Design : We compared comparative blocks and the criterion-st and ard of r and omized , double-blind , placebo-controlled blocks . Setting : The study was conducted at a tertiary referral center . Patients : We studied the first 50 consecutive patients referred for assessment of chronic neck pain ( > 3 months ' duration ) after a motor vehicle accident , who completed a series of placebo-controlled blocks after an initial positive response . Patients were 41 ± 11 years ( mean ± SD ) old with a male/female ratio of 1:2 . Methods : Patients underwent three blocks using three different agents— lignocaine , bupivacaine , and normal saline — administered on separate occasions , in r and om order and under double-blind conditions . The diagnostic decision based on comparative blocks alone was compared with that based on placebo-controlled blocks . Results : Comparative blocks were found to have a specificity of 88 % , but only marginal sensitivity ( 54 % ) . Although comparative blocks result in few false-positive diagnoses , their liability is that they result in a high proportion of false-negative diagnoses . Exp and ing the comparative blocks diagnostic criteria to include all patients with reproducible relief , irrespective of duration , increases sensitivity to 100 % but lowers specificity to 65 % . Conclusions : Whether physicians use comparative or placebo-controlled blocks depends upon the implication s of their results . If innocuous therapy will be prescribed , comparative blocks might suffice . However , when diagnostic certainty is critical , such as in a medicolegal context or when surgical intervention is contemplated , placebo-controlled blocks are recommended",
"STUDY OBJECTIVE We determine whether the use of an emergency medical services ( EMS ) protocol for selective spine immobilization would result in appropriate immobilization without spinal cord injury associated with nonimmobilization . METHODS A 4-year prospect i ve study examined EMS and hospital records for patients after the implementation of an EMS protocol for selective spine immobilization . EMS personnel were trained to perform and document a spine injury assessment for out-of-hospital trauma patients with a mechanism of injury judged sufficient to cause a spine injury . The assessment included these clinical criteria : altered mental status , evidence of intoxication , neurologic deficit , suspected extremity fracture , and spine pain or tenderness . The protocol required immobilization for patients with a positive assessment on any of those criteria . Outcome characteristics included the presence or absence of spine injury and spine injury management . RESULTS The study collected data on 13,483 patients ; 126 of the patients were subsequently excluded from the study because of incomplete data , leaving a study sample of 13,357 patients with complete data . Spine injuries were confirmed in the hospital records for 3 % ( n=415 ) of patients , including 50 patients with cord injuries and 128 patients with cervical injuries . Sensitivity of the EMS protocol was 92 % ( 95 % confidence interval [ CI ] 89.4 to 94.6 % ) result ing in nonimmobilization of 8 % of the patients with spine injuries ( 33 of 415 ) . None of the nonimmobilized patients sustained cord injuries . The specificity was 40 % ( 95 % CI 38.9 to 40.5 % ) . CONCLUSION The use of our selective immobilization protocol result ed in spine immobilization for most patients with spine injury without causing harm in cases in which spine immobilization was withheld",
"Abstract Grading pain intensity scales into simple categories provides useful information for both clinicians and epidemiologists and methods to classify pain severity for numerical rating scales have been recommended . However , the establishment of cut‐points is still in its infancy and little is known as to whether cut‐points are affected by age or gender . The objectives of this paper were to establish optimal cut‐points in pain severity in individuals with neck pain ( NP ) and to investigate if the cut‐points were influenced by gender , age , and NP duration . Data from the population ‐based ‘ Funen Neck and Chest Pain Study ’ was used . Univariate and multivariate analyses of variance were performed to calculate optimal single and double cut‐points for three different pain intensity scores within the past 2 weeks relative to two neck disability scales ( ‘ global assessment of NP ’ and the ‘ Copenhagen Neck Functional Disability Scale ’ ) . The two disability scales showed small differences in optimal cut‐points . Furthermore , cut‐points changed for each of the three pain intensity scales . Only small gender differences in cut‐points were seen and no specific trend was noted in either single or double cut‐points in different age groups . The cut‐points were almost identical for acute , subacute , and chronic NP . This paper has implication s for underst and ing the impact of using different pain intensity scales and provides reference cut‐points in NP for use in future clinical and epidemiological research"
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41188290-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND & AIMS Inflammatory bowel disease has considerable effects on work-related outcomes and leads to high societal costs due to sick leave and disability pension . The aims of this study were to systematic ally review evidence on work-related outcomes that are relevant to productivity losses and to evaluate whether medical or surgical interventions have a positive impact on patients ' work ability . METHODS A systematic literature search in PubMed was conducted in June 2013 . Abstract s were screened by two independent review ers , and full-text articles describing the frequency of work-related outcomes were retrieved . Two independent review ers extracted data according to the PRISMA Statement for Reporting Systematic Review s and Meta-Analyses . Findings were organized by study design ( non-interventional/interventional ) . Non-interventional studies were structured according to whether they presented data in comparison to control groups or not and interventional studies were summarized according to type of intervention . RESULTS This review included 30 non-interventional ( 15 with comparison groups and 15 without comparison group ) and 17 interventional studies ( 9 surgical and 8 medical ) . The majority of the studies reported a high burden of work-related outcomes among inflammatory bowel disease patients regardless of the methodology used . While biologic agents showed positive effect on work absenteeism and presenteeism in r and omized clinical trials , the impact of surgical interventions needs further evaluation . CONCLUSIONS Inflammatory bowel disease patients experience a high burden in work-related outcomes . Additional data on productivity losses and the long-term impact of interventions is needed to help inform decision-makers about treatment options and their benefits in reducing productivity losses in inflammatory bowel disease patients
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"Introduction The aim of this prospect i ve study was to analyze the impact of different surgical techniques on patients undergoing intestinal surgery for Crohn ’s disease ( CD ) in terms of recovery , quality of life , and direct and indirect costs . Patients and methods Forty-seven consecutive patients admitted for intestinal surgery for CD were enrolled in this prospect i ve study . Surgical procedures were evaluated as possible predictors of outcome in terms of disability status ( Barthel ’s Index ) , quality of life ( Clevel and Global Quality of Life score ) , body image , disease activity ( Harvey – Bradshaw Activity Index ) , and costs ( calculated in 2008 Euros ) . Univariate and multivariate analyses were performed . Results Significant predictors of a long postoperative hospital stay were the creation of a stoma , postoperative complications , disability status on the third post-operative day , and surgical access ( R2 = 0.59 , p Barthel ’s index at discharge was independently predicted by laparoscopic-assisted approach , ileal CD , and colonic CD ( R2 = 0.53 , p disability status at admission showed to be an independent predictor of quality of life score at follow-up . The overall cost for intestinal surgery for CD was 12,037 ( 10,117–15,795 ) euro per patient and stoma creation revealed to be its only predictor ( p = 0.006 ) . Conclusions Laparoscopy was associated with a shorter postoperative length of stay ; stoma creation was associated with a long and expensive postoperative hospital stay , and stricturoplasty was associated with a slower recovery of bowel function",
"Aliment Pharmacol Ther 2010 ; 32 : 1228–1239",
" One hundred and twenty-two r and omly selected patients with ulcerative colitis ( 28 of whom had undergone colectomy ) were interviewed to obtain data on the quality of their family , emotional , social , and professional lives . They were compared with an age- and sex-matched group of patients with acute conditions from the same area . The two groups were similar in marital status , the frequency of severe family or sexual problems , leisure activities , physical and earning capacity , the incidence of mental disorders before the interview , and intake of alcohol and psychopharmacological drugs . A higher proportion of the patients with colitis had had a higher education and belonged to higher socioeconomic groups than the controls , and this difference had been present at the time of diagnosis . These results show that patients with ulcerative colitis seem to adapt themselves well to their condition and suffer few social or professional disabilities",
" Seventy young adults ( 50 with Crohn 's disease ( CD ) and 20 with ulcerative colitis ( UC ) ( from a geographically derived cohort of patients with juvenile onset inflammatory bowel disease were interviewed and examined at a mean of 14 ( range 5.2 - 29.5 ) years after diagnosis . Details of education and employment were collected as part of a structured clinical interview . Although 57 % had had periods of absence from school of two months or more , their school examination pass rates were similar to those of the healthy population . The achievements of CD patients were consistently better than those of the UC group . In 15 patients , relapses of inflammatory bowel disease had adversely affected examination performance or prevented them from sitting school examinations . Extra tuition in hospital had been provided for only four patients , and three others had had privately arranged tuition at home . Fifty per cent proceeded to full time higher education . At the time of review , seven patients were full time students , one was a university research fellow , 47 were in full time and three in part time employment , one was self employed , four were housewives , and only six were involuntarily unemployed . All four unemployed CD patients attributed this to inflammatory bowel disease , but other factors were relevant in the unemployed UC patients . Few had direct evidence of rejection by employers on health grounds , though some did not declare their illness to prospect i ve employers",
"A r and om sample of 170 patients ( 88 men ) with chronic inflammatory bowel disease ( 75 ulcerative colitis ) were first interviewed in 1978 about their employment status , problems at work , and influence of surgery . Surgery had been carried out on 120 and 53 had an ileostomy . After six years 144 ( 92 % ) of the 156 survivors replied to a follow up postal question naire . Of the initial sample , 122 ( 72 % ) were working and there were only three ( 1 % ) registered unemployed . After six years a similar proportion were working and only seven ( 5 % ) were unemployed . Continuity of employment was good with 57 % in the same job . Changes in work because of health had been made by 72 patients mainly caused by bowel disease . After surgery 10 % completely changed and 22 % modified their work while a few had to retrain or retire . Panproctocolectomy and ileostomy result ed in more changes and longer time off work after surgery than colectomy and ileorectal anastomosis , with 35 % and 17 % respectively off work after one year . Problems at work , in particular general malaise and arthritis were experienced by 34 ( 28 % ) patients . Fewer problems were experienced by patients with a stoma who also had less sickness absence than those without a stoma . Colleagues and employers were usually supportive although some patients encountered discrimination especially those with a stoma or working in the food industry . Few patients had been counselled on their work . In general employment prospect s and time off work were good and employers should be encouraged to take an optimistic and supportive role . Doctors should consider that convalescence after surgery may be longer than they perceive and must provide better counselling for patients",
"Objective To compare the work disability ( WD ) rate in inflammatory bowel disease ( IBD ) patients 10 years after disease onset , with the WD rate in the background population , and to assess whether clinical or demographic factors in the early disease course could predict WD after 10 years disease . Design A large , population -based inception cohort ( the Inflammatory Bowel in South Eastern Norway cohort ) was prospect ively followed up at 1 , 5 and 10 years after diagnosis . At the 10-year follow-up data on WD were collected . Data on disability pension ( DP ) in the background population were retrieved from public data bases . We calculated overall and age-st and ardised relative risks ( RR ) for DP . Logistic regression analysis was used to examine predictive factors . Results A total of 518 patients completed the 10-year follow-up ( response rate 83.5 % ) . The overall disability rate in the IBD population was 18.8 % , and the RR was 1.8 ( 95 % CI 1.4 to 2.3 ) for ulcerative colitis ( UC ) and 2.0 ( 95 % CI 1.4 to 2.7 ) for Crohn 's disease ( CD ) . The RR for DP was highest in patients aged below 40 years while patients aged over 60 years had no increased RR . Steroid treatment at the 1-year follow-up predicted WD after 10 years disease in both CD and UC . In UC , increased C-reactive protein ( CRP ) or erythrocyte sedimentation rate ( ESR ) at diagnosis , early colectomy , and more than two relapses during the first year of the disease also predicted WD . Conclusion Ten years after disease onset IBD patients had an increased RR for DP as compared with the background population . The youngest patients had the highest RR . Markers of severe disease course predicted WD",
"BACKGROUND Crohn 's disease ( CD ) is a chronic inflammatory bowel disease usually diagnosed in early adult life and characterized by unpredictable flares and debilitating symptoms such as diarrhea , abdominal pain , and fever , which can interfere with a patient 's ability to work and perform daily activities . OBJECTIVE The aim of this study was to assess the validity , reliability , and responsiveness of the Work Productivity and Activity Impairment question naire in CD ( WPAI : CD ) . METHODS The WPAI : CD was tested in CD patients enrolled in a 26-week r and omized clinical trial of cer-tolizumab pegol versus placebo . Discriminative validity of WPAI : CD absenteeism , presenteeism(reduced on-the-job effectiveness ) , overall work productivity loss ( absenteeism + presenteeism ) , and activity impairment scores was assessed relative to 5 measures of disease severity and health status : CD Activity Index ( CDAI ) , Short Form-36 physical component summary ( PCS ) and mental health component summary ( MCS ) scores , Inflammatory Bowel Disease Question naire ( IBDQ ) , and the 5-dimensional EuroQoL health-related quality -of-life visual analog scale ( EQ-VAS ) . Responsiveness was assessed by comparing changes in WPAI : CD scores from baseline to week 26 for patients in remission ( CDAI A total of 662 patients ( mean [ range ] age , 37.4 [ 18 - 77 ] years ; male , 288 [ 43.5 % ] ; white , 629 [ 95.0 % ] ) were enrolled in the study . Patients with CD of the worst severity ( CDAI > median ) showed significantly higher impairment in work ( + 10.5 % ) and activities ( + 10.4 % ) versus patients with \" best health \" ( no problems ) ( both , P worst \" IBDQ , PCS , MCS , and EQ-VAS scores also showed significantly higher impairments in work ( IBDQ , VAS -24.2 % ; PCS , -24.1 % ; MCS , -15.9 % ; EQ-VAS , -16.5 % ) and activities ( IBDQ , -23.3 % ; PCS , -21.8 % ; MCS , -16.5 % ; EQ-VAS , -17.2 % ) versus \" best \" scores ( all , P WPAI : CD impairment scores for patients in remission versus patients failing to achieve remission ( P SRMs were small ( ie , 0.5 ) for patients in remission . CONCLUSIONS The discriminative validity , reliability , and responsiveness of the WPAI : CD were demonstrated . The WPAI : CD may be useful for evaluating drug impact on CD",
"OBJECTIVES : Hospitalization , surgery , work loss , and impaired quality of life contribute to the cost and burden of care for patients with Crohn 's disease . We examined the impact of remission on patients ' employment , quality of life , and hospitalization and surgery in a clinical trial to vali date clinical remission , as defined by the Crohn 's disease activity index ( CDAI ) , as the key treatment goal in managing Crohn 's disease . METHODS : ACCENT I evaluated the efficacy and safety of long-term dosing of infliximab compared to a single dose of infliximab in 573 patients with moderately-to-severely active Crohn 's disease . At wk 54 , employment status was compared between patients in CDAI remission and those not in CDAI remission , for those not employed at baseline . Physical component summary ( PCS ) and mental component summary ( MCS ) scores of the SF-36 question naire were also compared between these two groups . The numbers of Crohn's-related hospitalizations and surgeries were compared among four groups of patients who spent 0–25 % , 25–50 % , 50–75 % , and 75–100 % of time , respectively , in CDAI remission during the study . RESULTS : At baseline , patients had a severely impaired quality of life and a high unemployment rate ( 38.4 % ) . Among the group of patients who were unemployed at baseline , 31 % of those patients who achieved CDAI remission ( CDAI ) . PCS and MCS scores of patients in CDAI remission at wk 54 were significantly higher ( p population . Hospitalization and surgery rates decreased as the percentage of time patients were in CDAI remission increased ( p reduced hospitalizations and surgeries , increased employment , and normalized quality of life . Sustained CDAI remission should be the key therapeutic goal in managing Crohn 's disease",
"OBJECTIVE To evaluate open-label adalimumab therapy for clinical effectiveness , fistula healing , patient-reported outcomes and safety in Canadian patients with moderate to severe Crohn 's disease ( CD ) who were either naive to or previously exposed to antitumour necrosis factor ( anti-TNF ) therapy . METHODS Patients with moderate to severe CD ( CD activity index [ CDAI ] score of greater than 220 , or Harvey-Bradshaw index [ HBI ] of 7 or greater ) were eligible . Patients received open-label adalimumab as induction ( 160 mg and 80 mg subcutaneously [ sc ] ) at weeks 0 and 2 , respectively and maintenance ( 40 mg sc every other week ) therapy . At or after eight weeks , patients with flare or nonresponse could have their dosage increased to 40 mg sc weekly . Patients were followed for a minimum of six months or until adalimumab was commercially available in Canada . RESULTS Of the 304 patients enrolled , 160 were infliximab experienced , while 144 were anti-TNF naive . HBI remission ( HBI score of 4 or lower ) at week 24 was achieved by 53 % of anti-TNF-naive and 36 % of infliximab-experienced patients ( P Fistula healing rates at week 12 were 48 % for anti-TNF-naive patients , and 26 % for infliximab-experienced patients . At week 24 , fistula healing rates were significantly greater for the anti-TNF-naive group ( 60 % versus 28 % ; P Improvements in quality of life and work productivity were sustained from week 4 to week 24 for all patients . Serious infections occurred in 2 % of patients . CONCLUSIONS Adalimumab therapy induced and sustained steroidfree remission in both infliximab-experienced and anti-TNF-naive patients with moderate to severe CD . Clinical ly meaningful rates of fistula healing were also observed . Improvements in patient-reported outcomes were sustained throughout the 24-week study period",
"Abstract Introduction : Inflammatory bowel disease ( IBD ) is a chronic condition that afflicts young adults in their economically productive years . The goal of this study was to determine the costs of IBD in Germany from a societal perspective , using cost diaries . Methods : Members of the German Crohn ’s Disease and Ulcerative Colitis Association who had IBD were recruited by post , and those who agreed to participate documented their IBD-associated costs prospect ively in a diary over 4 weeks . They documented their use of healthcare facilities , medications , sick leave and out-of-pocket expenditures , as well as general demographic information , the status and history of their IBD , and long-term disability . Item costs were calculated according to national sources . Cost data were calculated using non-parametric bootstrapping and presented as mean costs ( year 2004 ) over 4 weeks . Results : The cost diaries were returned by 483 subjects ( Crohn ’s disease : n = 241 , ulcerative colitis : n = 242 ) with a mean age of 42 years and an average disease duration of 13 years ( SD ± 8.09 ) . The cost diaries were regarded as ‘ easy to complete ’ by 89 % of participants . The mean 4-week costs per subject were € 1425 ( 95 % CI 1201 , 1689 ) for Crohn ’s disease and € 1015 ( 95 % CI 832 , 1258 ) for ulcerative colitis . Of the total costs for Crohn ’s disease , 64 % were due to indirect costs such as early retirement or sick leave and 32 % were due to direct medical costs . In contrast , of the total costs for ulcerative colitis , 41 % were due to direct medical costs and 54 % to indirect costs . Conclusions : This is the first comprehensive cost study for Crohn ’s disease and ulcerative colitis in Germany . The most important economic factors that influenced the cost profiles of both diseases were the long-term productivity losses due to an ongoing inability to work and the cost of medications . Results indicate significant cost differences between Crohn ’s disease and ulcerative colitis . This data provides initial cost estimates that can be analysed further with respect to cost determinants and disease-specific costs in the future",
"OBJECTIVE To find out whether a threefold increase in follow up ( median 108 compared with 36 months ) influenced major morbidity and functional outcome between the first 32 and the last 32 patients consecutively operated on with J-pouch ileoanal anastomosis for ulcerative colitis from 1984 to 1997 . DESIGN Retrospective and prospect i ve study . SETTING University hospital , Norway . PATIENTS 64 patients with ulcerative colitis who had proctocolectomy and ileal pouch-anal anastomoses . INTERVENTIONS The pouches were mainly h and anastomosed ( n = 61 ) to the dentate line after mucosectomy or anastomosed by double stapling technique without mucosectomy ( n = 3 ) . The 58 patients who still had their pouches responded to a question naire on functional outcome and satisfaction . MAIN OUTCOME MEASURES Morbidity , functional outcome , and patients ' satisfaction . RESULTS Major morbidity in these 64 patients comprised pelvic sepsis in 3 ( 5 % ) , operation for intestinal obstruction in 5 ( 8 % ) , pouchitis in 12 ( 19 % ) , fistulas in 7 ( 11 % ) and pouch excision in 6 ( 9 % ) . Thirteen patients ( 20 % ) had 35 reoperations and 11 patients ( 17 % ) had 22 re-laparotomies . There were more complications among the first 32 patients with the longest follow up than among the last 32 patients , but this difference was significant only concerning the rate of reoperations ( 31 % compared with 9 % ) because of the higher number of pouch excisions ( 5 compared with 1 ) in this group . There were no significant differences in the functional outcome and degree of patient satisfaction between the first 29 and the last 29 patients . Respective values for 24 hour median stool freqency were 7.0 and 6.3 , leakage of stool 48 % and 38 % , ability to defer defaecation 86 % and 97 % , perineal irritation 59 % and 48 % , use of antidiarrhoeal medication 55 % and 52 % , and wearing of pad 28 % and 38 % . Sexual life ( n = 57 ) was improved in 11 ( 19 % ) and reduced in 7 ( 12 % ) . Potency was reduced in 5 ( 15 % ) and ejaculation in 4 ( 12 % ) , one of whom ( 3 % ) had retro grade ejaculation . Three ( 5 % ) received disability pensions and five ( 9 % ) had reduced workload . After the pouch operation 48 ( 91 % ) felt better and 3 ( 6 % ) felt worse because of frequent bowel emptying , perineal eczema , or pouch fistula . CONCLUSION Continence-preserving proctocolectomy carries considerable morbidity , but the long term functional outcome is satisfactory and does not seem to deteriorate substantially",
"Background : Impairment of health‐related quality of life , employment , and productivity has been documented in patients with moderate to severe ulcerative colitis . Methods : Using prospect ively collected data from the Active Ulcerative Colitis Trials 1 and 2 , we examined the impact of clinical response or remission , as defined using the Mayo score , on health‐related quality of life , employment , disability , productivity , and hours worked per week . These analyses were based on observed data and included all 728 patients , regardless of their r and omized treatment group ( i.e. , placebo and infliximab patients were grouped for analysis ) . Changes in Inflammatory Bowel Disease Question naire ( IBDQ ) and Medical Outcomes Study 36‐Item Short Form ( SF‐36 ) scores among nonresponders , responders , and patients in remission were compared . In addition , changes in employment , disability status , productivity , and hours worked per week of patients in clinical remission and patients not in clinical remission were compared . Results : Ulcerative colitis patients in clinical response or remission had significantly improved IBDQ and SF‐36 scores at week 30 compared with those of nonresponders ( P receiving disability compensation ( 58.8 % ) than were those not in remission ( 8.3 % and 20.0 % , respectively ; P improvements from baseline in productivity and both actual and fully productive hours worked per week were greater for patients in remission compared with those not in remission ( P < 0.05 for all three comparisons ) . Conclusions : These results confirm the validity of response and remission as defined using the Mayo score",
"Goals : Unemployment and disability rates in Crohn 's disease patients from the ACCENT I trial were assessed . Factors associated with employment and disability status were explored . Background : Limited data regarding unemployment and disability status in patients with active Crohn 's disease are available . Study : Baseline data were used to assess unemployment and disability rates . Logistic regression analysis examined factors that were associated with employment and disability status . Analysis of variance was used to compare quality of life . Results : The baseline full- and part-time employment rates were 48 % and 13 % , respectively , with 39 % of patients unemployed and 25 % receiving disability compensation . Only 14 % of 225 unemployed patients felt well enough to work if a job were available . Younger age , female gender , shorter disease duration , and prior bowel resection predicted a higher likelihood of unemployment . Younger age and female gender also predicted a higher likelihood of not being employed full-time . Prior bowel resection predicted a higher likelihood of receiving disability compensation . Quality of life ( Inflammatory Bowel Disease Question naire , Short Form-36 ) scores were significantly higher in employed patients . Conclusions : Patients with moderately to severely active Crohn 's disease had low employment and high disability rates . Given their economic importance , assessment of these outcomes should be integrated into future evaluations of therapy , including clinical trials",
"BACKGROUND AND AIMS Crohn 's disease negatively affects patients ' quality of life and ability to work . We investigated the impact of adalimumab on work productivity , daily activities , and quality of life in an open-label trial ( N=945 ) . The population comprised both infliximab-naïve and -exposed patients , including infliximab primary non-responders . METHODS Patients received adalimumab induction therapy ( 160 mg/80 mg at Weeks 0/2 ) , followed by adalimumab 40 mg every other week for up to 20 weeks ( patients with flares/non-response could receive 40 mg weekly at/after Week 12 ) . The Work Productivity and Activity Impairment Question naire and Short Inflammatory Bowel Disease Question naire were assessed . Indirect cost savings were estimated based on the average work productivity improvements at Week 20 . RESULTS Mean baseline scores indicated severe productivity impairment and poor quality of life . At Week 20 , 60 % of infliximab-naïve and 47 % of infliximab primary non-responders achieved clinical ly important improvements ( ≥9 points ) on the Short Inflammatory Bowel Disease Question naire , and 51 % and 43 % , respectively , achieved the minimum clinical ly important difference ( improvement ≥7 percentage points ) for total work productivity impairment ( non-responder imputation ) . At Week 20 , 64 % of infliximab-naïve and 55 % of infliximab primary non-responders achieved clinical ly important improvements in total activity impairment . Estimated 20-week total indirect productivity-related cost savings were € 3070 per infliximab-naïve patient and € 2059 per infliximab-exposed patient . CONCLUSIONS Adalimumab therapy significantly improved work productivity and disease-specific quality of life for patients with moderate to severe Crohn 's disease . Patients who failed prior infliximab therapy and patients naïve to infliximab benefited from adalimumab , with potentially greater benefits for infliximab-naïve patients ( NCT00409617 )",
" Abstract 442 patients with ulcerative colitis were su bmi tted to an operative programme of ileostomy and removal of the large bowel , between the years 1947 and 1965 ; of the 85 deaths , 46 were due to operation . Of the 39 late deaths , carcinoma ( 15 cases ) and liver failure ( 7 cases ) were the most common causes . Only 2 of the late deaths were attributable to surgical treatment and were due to obstruction . Initially emergency operation predominated over elective . During the period this position was reversed . A r and om group of 100 patients ( 38 men and 62 women ) were brought to hospital for review five or more years after surgery . Although the ability to work and enjoy leisure and the state of nutrition was satisfactory in this group an increased infertility was observed in females and sexual disability was noted in the males . A further 62 men were interviewed . The cause of sexual disability seems to be technical failure in removal of the rectum . With experience this should be avoidable . Cancer is a serious risk in patients with disease persisting for ten years . It remains a risk if any part of the large intestine is retained"
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411882cc-06ff-11f0-808a-c43d1ab1c353
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In observational studies , vegetarians generally have lower body weights compared with omnivores . However , weight changes that occur when vegetarian diets are prescribed have not been well quantified . We estimated the effect on body weight when vegetarian diets are prescribed . We search ed PubMed , EMBASE , and the Cochrane Central Register of Controlled Trials for articles through December 31 , 2013 . Additional articles were identified from reference lists . We included intervention trials in which participants were adults , interventions included vegetarian diets of ≥4 weeks ' duration without energy intake limitations , and effects on body weight were reported . Two investigators independently extracted data using predetermined fields . Estimates of body weight change , comparing intervention groups to untreated control groups , were derived using a r and om effects model to estimate the weighted mean difference . To quantify effects on body weight of baseline weight , sex , age , study duration , study goals , type of diet , and study authors hip , additional analyses examined within-group changes for all studies reporting variance data . We identified 15 trials ( 17 intervention groups ) , of which 4 included untreated controls . Prescription of vegetarian diets was associated with a mean weight change of -3.4 kg ( 95 % CI -4.4 to -2.4 ; P Greater weight loss was reported in studies with higher baseline weights , smaller proportions of female participants , older participants , or longer duration s , and in studies in which weight loss was a goal . Using baseline data for missing values , I(2 ) equaled 52.3 ( P=0.10 ) , indicating moderate heterogeneity . When missing data were omitted , I(2 ) equaled 0 ( P=0.65 ) , indicating low heterogeneity . Studies are relatively few , with variable quality . The prescription of vegetarian diets reduces mean body weight , suggesting potential value for prevention and management of weight-related conditions
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"BACKGROUND The results of previous studies indicated that energy density , independent of fat content , influences energy intake . In most studies , however , both fat content and energy density were lower than in typical American diets . OBJECTIVE We examined the influence of energy density on intake when fat content was above , below , or similar to the amount of fat typically consumed and when energy density was closer to that of American diets . DESIGN Lean ( n = 19 ) and obese ( n = 17 ) women consumed all meals daily in our laboratory during 6 experimental sessions . The main entrées , consumed ad libitum , were formulated to vary in fat content ( 25 % , 35 % , and 45 % of energy ) and energy density ( 5.23 kJ/g , or low energy density , and 7.32 kJ/g , or high energy density ) but to have similar palatability . RESULTS Energy density influenced energy intake across all fat contents in both lean and obese women ( P consumed less energy in the low ( 7531 kJ ) than in the high ( 9414 kJ ) energy density condition . Despite this 20 % lower energy intake , there were only small differences in hunger ( 7 % ) and fullness ( 5 % ) . Women consumed a similar volume , but not weight , of food daily across conditions . Differences in intake by weight , but not volume , occurred because for some versions of manipulated foods , weight and volume were not directly proportional . CONCLUSIONS Energy density affected energy intake across different fat contents and at levels of energy density comparable with those in typical diets . Furthermore , our findings suggest that cues related to the amount of food consumed have a greater influence on short-term intake than does the amount of energy consumed",
"BACKGROUND A vegetarian diet may lead to numerous health benefits , including weight loss . OBJECTIVE We examined the joint effects of personal preference of dietary treatment and a calorie-restricted , low-fat lactoovovegetarian diet ( LOV-D ) compared with a st and ard calorie-restricted , low-fat omnivorous diet ( STD-D ) on changes in weight , total cholesterol , ratio of LDL to HDL cholesterol ( LDL : HDL cholesterol ) , triacylglycerols , insulin resistance , and macronutrient intake during an 18-mo study . DESIGN This was a r and omized clinical trial of 176 overweight and obese adults who were recruited and r and omly assigned first to 1 of 2 preference conditions ( yes or no ) . If assigned to Preference-No , they were r and omly assigned to 1 of the 2 diet conditions ( STD-D or LOV-D ) . If assigned to Preference-Yes , they were assigned to the diet they indicated as preferred at screening . The 12-mo intervention was followed by a 6-mo maintenance phase . RESULTS Participants were mainly women ( 86.9 % ) and white ( 70.5 % ) ; 75 % completed the 18-mo study . A significant interaction between preference and dietary treatment was not observed for any of the outcome variables . However , participants in the Preference-No groups significantly decreased their triacylglycerols ( P = 0.04 ) . The only effect observed for diet was a borderline significant decrease in LDL : HDL cholesterol for the LOV-D group ( P = 0.06 ) . Within the LOV-D groups , those who were 100 % adherent to the LOV-D had significant and marginally significant reductions in monounsaturated fat ( P = 0.02 ) and total fat ( P = 0.05 ) intakes at 18 mo . CONCLUSIONS Our findings suggest that neither prescribing a vegetarian diet nor allowing persons to choose their preferred diet had a significant effect on outcome measures . However , all participants had a significant reduction in total energy and fat intakes and an increase in energy expenditure , which was reflected in reduced body weight . This clinical trial was registered at www . clinical trials.gov as NCT00330629",
"BACKGROUND 3-Hydroxy-3-methyl-glutaryl-coenzyme A ( HMG-CoA ) reductase inhibitors reduce serum cholesterol and are increasingly advocated in primary prevention to achieve reductions in LDL cholesterol . Newer dietary approaches combining cholesterol-lowering foods may offer another option , but these approaches have not been compared directly with statins in the same persons . OBJECTIVE The objective was to compare , in the same subjects , the cholesterol-lowering potential of a dietary portfolio with that of a statin . DESIGN Thirty-four hyperlipidemic participants underwent all three 1-mo treatments in r and om order as out patients : a very-low-saturated-fat diet ( control diet ) , the same diet plus 20 mg lovastatin ( statin diet ) , and a diet high in plant sterols ( 1.0 g/1000 kcal ) , soy-protein foods ( including soy milks and soy burgers , 21.4 g/1000 kcal ) , almonds ( 14 g/1000 kcal ) , and viscous fibers from oats , barley , psyllium , and the vegetables okra and eggplant ( 10 g/1000 kcal ) ( portfolio diets ) . Fasting blood sample s were obtained at 0 , 2 , and 4 wk . RESULTS LDL-cholesterol concentrations decreased by 8.5+/-1.9 % , 33.3+/-1.9 % , and 29.6+/-1.3 % after 4 wk of the control , statin , and portfolio diets , respectively . Although the absolute difference between the statin and the portfolio treatments was significant at 4 wk ( P=0.013 ) , 9 participants ( 26 % ) achieved their lowest LDL-cholesterol concentrations with the portfolio diet . Moreover , the statin ( n=27 ) and the portfolio ( n=24 ) diets did not differ significantly ( P=0.288 ) in their ability to reduce LDL cholesterol below the 3.4-mmol/L primary prevention cutoff . CONCLUSIONS Dietary combinations may not differ in potency from first-generation statins in achieving current lipid goals for primary prevention . They may , therefore , bridge the treatment gap between current therapeutic diets and newer statins",
"Background / objectives : To determine the effects of a low-fat plant-based diet program on anthropometric and biochemical measures in a multicenter corporate setting .Subjects/ methods : Employees from 10 sites of a major US company with body mass index ⩾25 kg/m2 and /or previous diagnosis of type 2 diabetes were r and omized to either follow a low-fat vegan diet , with weekly group support and work cafeteria options available , or make no diet changes for 18 weeks . Dietary intake , body weight , plasma lipid concentrations , blood pressure and glycated hemoglobin ( HbA1C ) were determined at baseline and 18 weeks . Results : Mean body weight fell 2.9 kg and 0.06 kg in the intervention and control groups , respectively ( P fell 8.0 and 8.1 mg/dl in the intervention group and 0.01 and 0.9 mg/dl in the control group ( P HbA1C fell 0.6 percentage point and 0.08 percentage point in the intervention and control group , respectively (P , mean changes in body weight were −4.3 kg and −0.08 kg in the intervention and control groups , respectively ( P fell 13.7 and 13.0 mg/dl in the intervention group and 1.3 and 1.7 mg/dl in the control group ( P HbA1C levels decreased 0.7 percentage point and 0.1 percentage point in the intervention and control group , respectively ( P dietary intervention using a low-fat plant-based diet in a corporate setting improves body weight , plasma lipids , and , in individuals with diabetes , glycemic control",
"OBJECTIVE : To compare body mass index ( BMI ) in four diet groups ( meat-eaters , fish-eaters , vegetarians and vegans ) in the Oxford cohort of the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC-Oxford ) and to investigate lifestyle and dietary factors associated with any observed differences . DESIGN : Cross-sectional analysis of self-reported dietary , anthropometric and lifestyle data . PARTICIPANTS : A total of 37 875 healthy men and women aged 20–97 y participating in EPIC-Oxford . RESULTS : Age-adjusted mean BMI was significantly different between the four diet groups , being highest in the meat-eaters ( 24.41 kg/m2 in men , 23.52 kg/m2 in women ) and lowest in the vegans ( 22.49 kg/m2 in men , 21.98 kg/m2 in women ) . Fish-eaters and vegetarians had similar , intermediate mean BMI . Differences in lifestyle factors including smoking , physical activity and education level accounted for less than 5 % of the difference in mean age-adjusted BMI between meat-eaters and vegans , whereas differences in macronutrient intake accounted for about half of the difference . High protein ( as percent energy ) and low fibre intakes were the dietary factors most strongly and consistently associated with increasing BMI both between and within the diet groups . CONCLUSIONS : Fish-eaters , vegetarians and especially vegans had lower BMI than meat-eaters . Differences in macronutrient intakes accounted for about half the difference in mean BMI between vegans and meat-eaters . High protein and low fibre intakes were the factors most strongly associated with increasing BMI",
"BACKGROUND Low-fat vegetarian and vegan diets are associated with weight loss , increased insulin sensitivity , and improved cardiovascular health . OBJECTIVE We compared the effects of a low-fat vegan diet and conventional diabetes diet recommendations on glycemia , weight , and plasma lipids . DESIGN Free-living individuals with type 2 diabetes were r and omly assigned to a low-fat vegan diet ( n = 49 ) or a diet following 2003 American Diabetes Association guidelines ( conventional , n = 50 ) for 74 wk . Glycated hemoglobin ( Hb A(1c ) ) and plasma lipids were assessed at weeks 0 , 11 , 22 , 35 , 48 , 61 , and 74 . Weight was measured at weeks 0 , 22 , and 74 . RESULTS Weight loss was significant within each diet group but not significantly different between groups ( -4.4 kg in the vegan group and -3.0 kg in the conventional diet group , P = 0.25 ) and related significantly to Hb A(1c ) changes ( r = 0.50 , P = 0.001 ) . Hb A(1c ) changes from baseline to 74 wk or last available values were -0.34 and -0.14 for vegan and conventional diets , respectively ( P = 0.43 ) . Hb A(1c ) changes from baseline to last available value or last value before any medication adjustment were -0.40 and 0.01 for vegan and conventional diets , respectively ( P = 0.03 ) . In analyses before alterations in lipid-lowering medications , total cholesterol decreased by 20.4 and 6.8 mg/dL in the vegan and conventional diet groups , respectively ( P = 0.01 ) ; LDL cholesterol decreased by 13.5 and 3.4 mg/dL in the vegan and conventional groups , respectively ( P = 0.03 ) . CONCLUSIONS Both diets were associated with sustained reductions in weight and plasma lipid concentrations . In an analysis controlling for medication changes , a low-fat vegan diet appeared to improve glycemia and plasma lipids more than did conventional diabetes diet recommendations . Whether the observed differences provide clinical benefit for the macro- or microvascular complications of diabetes remains to be established . This trial was registered at clinical trials.gov as NCT00276939",
"CONTEXT The Lifestyle Heart Trial demonstrated that intensive lifestyle changes may lead to regression of coronary atherosclerosis after 1 year . OBJECTIVES To determine the feasibility of patients to sustain intensive lifestyle changes for a total of 5 years and the effects of these lifestyle changes ( without lipid-lowering drugs ) on coronary heart disease . DESIGN R and omized controlled trial conducted from 1986 to 1992 using a r and omized invitational design . PATIENTS Forty-eight patients with moderate to severe coronary heart disease were r and omized to an intensive lifestyle change group or to a usual-care control group , and 35 completed the 5-year follow-up quantitative coronary arteriography . SETTING Two tertiary care university medical centers . INTERVENTION Intensive lifestyle changes ( 10 % fat whole foods vegetarian diet , aerobic exercise , stress management training , smoking cessation , group psychosocial support ) for 5 years . MAIN OUTCOME MEASURES Adherence to intensive lifestyle changes , changes in coronary artery percent diameter stenosis , and cardiac events . RESULTS Experimental group patients ( 20 [ 71 % ] of 28 patients completed 5-year follow-up ) made and maintained comprehensive lifestyle changes for 5 years , whereas control group patients ( 15 [ 75 % ] of 20 patients completed 5-year follow-up ) made more moderate changes . In the experimental group , the average percent diameter stenosis at baseline decreased 1.75 absolute percentage points after 1 year ( a 4.5 % relative improvement ) and by 3.1 absolute percentage points after 5 years ( a 7.9 % relative improvement ) . In contrast , the average percent diameter stenosis in the control group increased by 2.3 percentage points after 1 year ( a 5.4 % relative worsening ) and by 11.8 percentage points after 5 years ( a 27.7 % relative worsening ) ( P=.001 between groups . Twenty-five cardiac events occurred in 28 experimental group patients vs 45 events in 20 control group patients during the 5-year follow-up ( risk ratio for any event for the control group , 2.47 [ 95 % confidence interval , 1.48 - 4.20 ] ) . CONCLUSIONS More regression of coronary atherosclerosis occurred after 5 years than after 1 year in the experimental group . In contrast , in the control group , coronary atherosclerosis continued to progress and more than twice as many cardiac events occurred",
"Purpose . To determine whether a multicomponent nutrition intervention program at a corporate site reduces body weight and improves other cardiovascular risk factors in overweight individuals . Design . Prospect i ve clinical intervention study . Subjects/ Setting . Employees of the Government Employees Insurance Company ( GEICO ) ( N = 113 ) , aged 21 to 65 years , with a body mass index ≥ 25 kg/m2 and /or previous diagnosis of type 2 diabetes . Intervention . A 22-week intervention including a low-fat , vegan diet . Measures . Changes in body weight , anthropometric measures , blood pressure , lipid profile , and dietary intake . Analysis . Multivariate analyses of variance were calculated for clinical and nutrient measures , followed by univariate analyses of variance , to determine the significance of differences between groups in changes over time . Results . Intervention-group participants experienced greater weight changes compared with control-group participants ( mean , – 5.1 [ SE , .6 ] kg vs. + .1 [ SE , .6 ] kg , p greater changes in waist circumference ( mean , – 4.7 [ SE , .6 ] cm vs. + .8 [ SE , .6 ] cm , p ( mean , – .006 [ SE , .003 ] vs. + .014 [ SE , .005 ] , p = .0007 ) . Weight loss of 5 % of body weight was more frequently observed in the intervention group ( 48.5 % ) compared with the control group ( 11.1 % ) ( χ2[1 , N= 113 ] = 16.99 , p individuals volunteering for a 22-week worksite research study , an intervention using a low-fat , vegan diet effectively reduced body weight and waist circumference ",
"The effect on blood pressure of an ovo-lacto-vegetarian ( OLV ) diet was assessed in a r and omized controlled crossover trial . Fifty-eight mild untreated hypertensive subjects recruited from the Perth Centre for the 1983 National Heart Foundation ( NHF ) Risk Factor Prevalence Survey were r and omly allocated to one of three groups : the first maintained their usual diet throughout 12 weeks ; the other two were given an OLV diet for either the first or second 6 weeks of the 12-week trial . A significant fall in systolic blood pressure , on average of the order of 5 mmHg , was associated with eating an OLV diet . Blood pressure change was unrelated to change in urinary sodium , potassium or body weight , but was related to initial blood pressures . Although an OLV diet may have an adjunctive role in control of mild hypertension , in view of likely problems with acceptability the dietary components responsible for the blood pressure changes need to be identified",
"Fasting is an effective treatment for rheumatoid arthritis , but most patients relapse on re introduction of food . The effect of fasting followed by one year of a vegetarian diet was assessed in a r and omised , single-blind controlled trial . 27 patients were allocated to a four-week stay at a health farm . After an initial 7 - 10 day subtotal fast , they were put on an individually adjusted gluten-free vegan diet for 3.5 months . The food was then gradually changed to a lactovegetarian diet for the remainder of the study . A control group of 26 patients stayed for four weeks at a convalescent home , but ate an ordinary diet throughout the whole study period . After four weeks at the health farm the diet group showed a significant improvement in number of tender joints , Ritchie 's articular index , number of swollen joints , pain score , duration of morning stiffness , grip strength , erythrocyte sedimentation rate , C-reactive protein , white blood cell count , and a health assessment question naire score . In the control group , only pain score improved score . In the control group , only pain score improved significantly . The benefits in the diet group were still present after one year , and evaluation of the whole course showed significant advantages for the diet group in all measured indices . This dietary regimen seems to be a useful supplement to conventional medical treatment of rheumatoid arthritis",
"OBJECTIVE To investigate whether glycemic and lipid control in patients with non-insulin-dependent diabetes ( NIDDM ) can be significantly improved using a low-fat , vegetarian ( vegan ) diet in the absence of recommendations regarding exercise or other lifestyle changes . METHODS Eleven subjects with NIDDM recruited from the Georgetown University Medical Center or the local community were r and omly assigned to a low-fat vegan diet ( seven subjects ) or a conventional low-fat diet ( four subjects ) . Two additional subjects assigned to the control group failed to complete the study . The diets were not design ed to be isocaloric . Fasting serum glucose , body weight , medication use , and blood pressure were assessed at baseline and biweekly thereafter for 12 weeks . Serum lipids , glycosylated hemoglobin , urinary albumin , and dietary macronutrients were assessed at baseline and 12 weeks . RESULTS Although the sample was intentionally small in accordance with the pilot study design , the 28 % mean reduction in fasting serum glucose of the experimental group , from 10.7 to 7.75 mmol/L ( 195 to 141 mg/dl ) , was significantly greater than the 12 % decrease , from 9.86 to 8.64 mmol/L ( 179 to 157 mg/dl ) , for the control group ( P mean weight loss was 7.2 kg in the experimental group , compared to 3 . 8 kg for the control group ( P Insulin was reduced in both experimental group patients on insulin . No patient in the control group reduced medication use . Differences between the diet groups in the reductions of serum cholesterol and 24-h microalbuminuria did not reach statistical significance ; however , high-density lipoprotein concentration fell more sharply ( 0.20 mmol/L ) in the experimental group than in the control group ( 0.02 mmol/L ) ( P low-fat , vegetarian diet in patients with NIDDM was associated with significant reductions in fasting serum glucose concentration and body weight in the absence of recommendations for exercise . A larger study is needed for confirmation",
"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 :",
"Few controlled trials have studied cholesterol-lowering diets in premenopausal women . None has examined the cholesterol-lowering effect of a low-fat vegetarian diet , which , in other population groups , leads to marked reductions in serum cholesterol concentrations and , in combination with other life-style changes , a regression of atherosclerosis . We tested the hypothesis that a low-fat , vegetarian diet significantly reduces serum total and low-density lipoprotein ( LDL ) cholesterol concentrations in premenopausal women . In a crossover design , 35 women , aged 22 to 48 , followed a low-fat vegetarian diet deriving approximately 10 % of energy from fat for 2 menstrual cycles . For 2 additional cycles , they followed their customary diet while also taking a \" supplement \" ( placebo ) pill . Serum lipid concentrations were assessed at baseline and during each intervention phase . Mean serum LDL , high-density lipoprotein ( HDL ) , and total cholesterol concentrations decreased 16 . 9 % , 16.5 % , and 13.2 % , respectively , from baseline to the intervention diet phase ( p mean serum triacylglycerol concentration increased 18.7 % ( p LDL/HDL ratio remained unchanged . Thus , in healthy premenopausal women , a low-fat vegetarian diet led to rapid and sizable reductions in serum total , LDL , and HDL cholesterol concentrations",
"BACKGROUND Although therapeutic diets are critical to diabetes management , their acceptability to patients is largely unstudied . OBJECTIVE To quantify adherence and acceptability for two types of diets for diabetes . DESIGN Controlled trial conducted between 2004 and 2006 . SUBJECTS/ SETTING Individuals with type 2 diabetes ( n=99 ) at a community-based research facility . Participants were r and omly assigned to a diet following 2003 American Diabetes Association guidelines or a low-fat , vegan diet for 74 weeks . MAIN OUTCOME MEASURES Attrition , adherence , dietary behavior , diet acceptability , and cravings . STATISTICAL ANALYSES For nutrient intake and question naire scores , t tests determined between-group differences . For diet-acceptability measures , the related sample s Wilcoxon sum rank test assessed within-group changes ; the independent sample s Mann-Whitney U test compared the diet groups . Changes in reported symptoms among the groups was compared using chi(2 ) for independent sample s. RESULTS All participants completed the initial 22 weeks ; 90 % ( 45/50 ) of American Diabetes Association guidelines diet group and 86 % ( 42/49 ) of the vegan diet group participants completed 74 weeks . Fat and cholesterol intake fell more and carbohydrate and fiber intake increased more in the vegan group . At 22 weeks , group-specific diet adherence criteria were met by 44 % ( 22/50 ) of members of the American Diabetes Association diet group and 67 % ( 33/49 ) of vegan-group participants ( P=0.019 ) ; the American Diabetes Association guidelines diet group reported a greater increase in dietary restraint ; this difference was not significant at 74 weeks . Both groups reported reduced hunger and reduced disinhibition . Question naire responses rated both diets as satisfactory , with no significant differences between groups , except for ease of preparation , for which the 22-week ratings marginally favored the American Diabetes Association guideline group . Cravings for fatty foods diminished more in the vegan group at 22 weeks , with no significant difference at 74 weeks . CONCLUSIONS Despite its greater influence on macronutrient intake , a low-fat , vegan diet has an acceptability similar to that of a more conventional diabetes diet . Acceptability appears to be no barrier to its use in medical nutrition therapy",
"We tested the effects of an uncooked vegan diet , rich in lactobacilli , in rheumatoid patients r and omized into diet and control groups . The intervention group experienced subjective relief of rheumatic symptoms during intervention . A return to an omnivorous diet aggravated symptoms . Half of the patients experienced adverse effects ( nausea , diarrhoea ) during the diet and stopped the experiment prematurely . Indicators of rheumatic disease activity did not differ statistically between groups . The positive subjective effect experienced by the patients was not discernible in the more objective measures of disease activity ( Health Assessment Question naire , duration of morning stiffness , pain at rest and pain on movement ) . However , a composite index showed a higher number of patients with 3 - 5 improved disease activity measures in the intervention group . Stepwise regression analysis associated a decrease in the disease activity ( measured as change in the Disease Activity Score , DAS ) with lactobacilli-rich and chlorophyll-rich drinks , increase in fibre intake , and no need for gold , methotrexate or steroid medication ( R2=0.48 , P=0.02 ) . The results showed that an uncooked vegan diet , rich in lactobacilli , decreased subjective symptoms of rheumatoid arthritis . Large amounts of living lactobacilli consumed daily may also have positive effects on objective measures of rheumatoid arthritis",
"59 healthy , omnivorous subjects aged 25 - 63 years were r and omly allocated to a control group , which ate an omnivorous diet for 14 weeks , or to one of two experimental groups , whose members ate an omnivorous diet for the first 2 weeks and a lacto-ovo-vegetarian diet for one of two 6-week experimental periods . Mean systolic and diastolic blood pressures did not change in the control group but fell significantly in both experimental groups during the vegetarian diet and rose significantly in the experimental group which reverted to the omnivorous diet . Adjustment of the blood-pressure changes for age , obesity , heart rate , weight change , and blood pressure before dietary change indicated a diet-related fall of some 5 - 6 mm Hg systolic and 2 - 3 mm Hg diastolic . Although the nutrient(s ) causing these blood-pressure changes are unknown , the effects were apparently not mediated by changes in sodium or potassium intake",
"OBJECTIVE The objective was to assess the effect of a low-fat , vegan diet compared with the National Cholesterol Education Program ( NCEP ) diet on weight loss maintenance at 1 and 2 years . RESEARCH METHODS AND PROCEDURES Sixty-four overweight , postmenopausal women were r and omly assigned to a vegan or NCEP diet for 14 weeks , and 62 women began the study . The study was done in two replications . Participants in the first replication ( N = 28 ) received no follow-up support after the 14 weeks , and those in the second replication ( N = 34 ) were offered group support meetings for 1 year . Weight and diet adherence were measured at 1 and 2 years for all participants . Weight loss is reported as median ( interquartile range ) and is the difference from baseline weight at years 1 and 2 . RESULTS Individuals in the vegan group lost more weight than those in the NCEP group at 1 year [ -4.9 ( -0.5 , -8.0 ) kg vs. -1.8 ( 0.8 , -4.3 ) ; p lost more weight at 1 year ( p improved weight loss at 1 year ( p vegan diet was associated with significantly greater weight loss than the NCEP diet at 1 and 2 years . Both group support and meeting attendance were associated with significant weight loss at follow-up",
"UNLABELLED The effect of eliminating all animal ( meat and fish ) products except eggs and milk products from the current Spanish-Mediterranean diet was studied in 14 healthy subjects . This dietary manipulation decreased saturated and monounsaturated fat , protein , and cholesterol intakes . During the 2-month intervention period , a decrease in total plasma cholesterol concentrations ( 4.53 + /- 0.13 vs. 4.29 + /- 0.13 mmol/l , p high-density lipoprotein cholesterol levels ( 1.66 + /- 0.08 vs. 1.47 + /- 0.08 mmol/l , p low-density lipoprotein cholesterol levels ( 2.51 + /- 0.15 vs. 2.43 + /- 0.13 mmol/l ) did not reach statistical significance . Nevertheless , there was a significant association between the decrease in cholesterol intake and the decrease in low-density lipoprotein cholesterol levels ( r = 0.719 , p protein intake was also correlated with the decrease in total cholesterol levels ( r = 0.629 , p Body weight and lean body mass were not modified during the study . Maximal aerobic power and maximal oxygen consumption were not significantly affected by the diet manipulation . IN CONCLUSION a 2-month change from the current Spanish-Mediterranean diet to an ovolactovegetarian diet in young healthy persons decreases total plasma cholesterol levels , but mainly due to a decrease in high-density lipoprotein cholesterol levels"
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BACKGROUND Health services often manage agitated or violent people and for emergency psychiatric services such behaviour is particularly prevalent ( 10 % ) . The drugs used in this situation should ensure that the person swiftly and safely becomes calm . OBJECTIVES To examine whether haloperidol plus promethazine is an effective treatment for psychosis induced agitation/aggression . SEARCH STRATEGY We search ed the Cochrane Schizophrenia Group 's Register ( July 2004 ) . SELECTION CRITERIA We included all r and omised clinical trials involving aggressive people with psychosis for which haloperidol plus promethazine was being used . DATA COLLECTION AND ANALYSIS We reliably selected , quality assessed and extracted data from all relevant studies . For binary outcomes we calculated st and ard estimations of risk ratio ( RR ) and their 95 % confidence intervals ( CI ) . Where possible we estimated weighted number needed to treat or harm ( NNT/H ) . MAIN RESULTS We identified two relevant high quality studies . One compared the haloperidol plus promethazine mix with midazolam ( n=301 ) and one with lorazepam ( n=200 ) . The combined results were largely heterogeneous . In Brazil , haloperidol plus promethazine was an effective means of tranquillisation with over two thirds of people being tranquil or se date d by 30 minutes , but midazolam was more swift ( n=301 , RR 2.9 CI 1.75 to 4.80 , NNH 5 CI 3 to 12 ) . In India , however , 95 % of people were tranquil or se date d by 30 minutes if allocated to the combination treatment ( vs lorazepam , n=200 , RR 0.26 CI 0.10 to 0.68 , NNT 8 CI 6 to 17 ) . Over the next few hours of treatment reported differences are negligible . One person given midazolam had respiratory depression ( reversed by flumazenil ) , one given lorazepam had respiratory difficulty . A single person given haloperidol plus promethazine had an epileptic fit . Once the initial tranquillisation was administered , few needed additional medications for continued agitation ( n=501 , 2 RCTs , RR needing additional tranquillising drugs by four hours 1.67 CI 0.62 to 4.54 , 4 % vs 2 % , I squared 50 % ) and there were no differences in the low levels of use of restraints . About 28 % of people in Brazil in both groups had another episode of aggression in the first day after the initial injection ( n=301 , RR 0.89 CI 0.62 to 1.29 ) . About half of all people in the Indian study were discharged by four hours ( n=200 , RR 1.13 CI 0.85 to 1.50 ) and a similar proportion in Brazil by 15 days ( n=301 , RR 1.05 CI 0.84 to 1.29 ) . Both studies attained 99 % follow up for their primary outcomes . Even by two weeks only 4 % of people could not be accounted for ( n=501 , 2 RCTs , RR 0.91 CI 0.38 to 2.17 ) . AUTHORS ' CONCLUSIONS This review suggests that both benzodiazepines work , but that midazolam has a faster onset and thereby reduces the risk of exposure to violence . Both benzodiazepines have the potential to cause respiratory depression , probably midazolam more so than lorazepam , and we would question the use of this group of drugs outside of those services fully confident of observing for and managing the consequences of respiratory distress . Most evidence , however , exists for the haloperidol plus promethazine mix , with currently more than 400 people r and omised to the combination . The onset of action is swift and faster than lorazepam . The combination also seems safe with no clear longer term consequences . We would expect policy makers recommending other drug managements to have equally compelling evidence to support their guidance and hope that this would not be founded in conjecture or consensus , which may be more difficult to defend than evidence from high quality studies
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"We have investigated the action of pimozide in tardive dyskinesia induced by prolonged administration of phenothiazines . Improvement was recorded in a double blind study of 18 patients treated with maximum tolerated dosage ( mean 18.8 mg/day ) for 6 weeks . There was no deterioration in the therapeutic action of pimozide over this time . Parkinsonism and sedation were the main adverse effects . They were corrected by reduction of the dose of pimozide , but often recurred so that further adjustments of dosage were necessary . Our findings support the view that tardive dyskinesia is produced by a disturbance in the balance of central transmitters such that dopaminergic transmission is increased",
"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",
"Background Agitated or violent patients constitute 10 % of all emergency psychiatric treatment . Management guidelines , the preferred treatment of clinicians and clinical practice all differ . Systematic review s show that all relevant studies are small and none are likely to have adequate power to show true differences between treatments . Worldwide , current treatment is not based on evidence from r and omised trials . In Brazil , the combination haloperidol-promethazine is frequently used , but no studies involving this mix exist . Methods TREC-Rio ( Tranquilização Rápida-Ensaio Clínico [ Translation : Rapid Tranquillisation- Clinical Trial ] ) will compare midazolam with haloperidol-promethazine mix for treatment of agitated patients in emergency psychiatric rooms of Rio de Janeiro , Brazil . TREC-Rio is a r and omised , controlled , pragmatic and open study . Primary measure of outcome is tranquillisation at 20 minutes but effects on other measures of morbidity will also be assessed . TREC-Rio will involve the collaboration of as many health care professionals based in four psychiatric emergency rooms of Rio as possible . Because the design of this trial does not substantially complicate clinical management , and in several aspects simplifies it , the study can be large , and treatments used in everyday practice can be evaluated",
"OBJECTIVE To determine the incidence and causes of agitation states in patients presenting at the Rouen University Hospital emergency room and to analyze the management scheme . PATIENTS AND METHOD A prospect i ve study was conducted over a 9 month period in 100 consecutive patients presenting a state of agitation assessed using the Overt Aggression Scale . A pre-planned management protocol was applied . RESULTS The incidence of states of agitation was 0.56 % . There were 43 women and 57 men , mean age 33 years . Most of the agitated patients were admitted between 6 p.m. and 4 a.m. ( 69 % ) . Over the 9 month period , 2 patients were admitted twice for agitation and 2 absconded . Low glucose level was the cause of agitation in 4 cases . Alcohol and /or drug use concerned 73 % of the agitated patients and was the most frequently observed triggering factor ( 17 % ) . Only 6 % of the patients had a regular employment . Physical restraining measures and sedation were required in 86 % and 84 % of the cases respectively . Among 67 patients given loxapine for sedation , 2 developed acute dyskinesia and 9 low blood pressure . One out of 4 patients were referred to a psychiatric unit . CONCLUSION Patients in a state of agitation are young , often female , and in a difficult socio-economic situation . Hypoglycemia is the main differential diagnosis . A triggering factor can often be identified . A state of agitation is not a repetitive condition but occurs as a short-lived episode in the patientís history . Such patients need rapid care to avoid further aggravation and disruption of the emergency room activity , and to prevent the patient from fleeing . Loxapine provides effective sedation but requires regular monitoring of blood pressure and can provoke acute dyskinesia in young subjects",
"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",
"Background The medical management of aggressive and violent behaviour is a critical situation for which there is little evidence . In order to prepare for a r and omised trial , due to start in the psychiatric emergency rooms of Rio de Janeiro in 2001 , a survey of current practice was necessary . Methods A seven day survey of pharmacological management of aggressive people with psychosis in the emergency rooms of all four public psychiatric hospitals in Rio de Janeiro , Brazil . Results In one hospital data were not available . Of the 764 people with psychosis attending these ERs , 74 were given IM medication for rapid tranquillisation ( 9.7 % , 2.1/week/100,000 ) . A haloperidol-promethazine mix ( with or without other drugs ) was used for the majority of patients ( 83 % ) . Conclusion The haloperidol-promethazine mix , given intramuscularly for rapid tranquilization , is prevalent in Rio , where it is considered both safe and efficient . However , scientific evaluation of all pharmacological approaches to rapid tranquilization of psychotic people is inadequate or incomplete and a r and omized trial of IM haloperidol-promethazine is overdue",
"SINCE THE discovery of rapid eye movements ( REMs ) associated with a desynchronized electroencephalogram ( EEG ) during behavioral sleep 1 and the correlation of this sleep stage with dreaming , 2 considerable investigation of REM sleep has been instituted to assess its significance in normal man and in various psychiatric illnesses . The similarity between mentation during dreaming in normal people and thought patterns in schizophrenia has led to many investigations of REM sleep in this disease . These studies have not consistently demonstrated marked differences in REM sleep between schizophrenics and normal subjects . 3 Similarly , REM sleep does not appear to be markedly altered in mental illness characterized primarily by depression . 3 Several recent studies have suggested , however , that Stage 4 or delta sleep may be decreased in schizophrenia 4 and depressive psychosis . 5,6 Various drugs used in the treatment of mental illness have",
"BACKGROUND An intramuscular ( IM ) formulation of olanzapine has been developed because there are no rapid-acting IM atypical antipsychotic drugs currently available in the United States for treating acute agitation in patients with schizophrenia . METHODS Recently hospitalized acutely agitated patients with schizophrenia ( N = 270 ) were r and omized to receive 1 to 3 IM injections of olanzapine ( 2.5 , 5.0 , 7.5 , or 10.0 mg ) , haloperidol ( 7.5 mg ) , or placebo within 24 hours . A dose-response relationship for IM olanzapine in the reduction of agitation was assessed by measuring the reduction in Positive and Negative Syndrome Scale Excited Component ( PANSS-EC ) scores 2 hours after the first injection . Safety was assessed by recording adverse events and with extrapyramidal symptom scales and electrocardiograms at 24 hours after the first injection . RESULTS Olanzapine exhibited a dose-response relationship for reduction in agitation ( F(1,179)= 14.4 ; P Mean PANSS-EC reductions 2 hours after the first injection of olanzapine ( 2.5 mg = -5.5 ; 5.0 mg = -8.1 ; 7.5 mg = -8.7 ; 10.0 mg = -9.4 ) were superior to those with placebo ( -2.9 ; P = .01 vs olanzapine at 2.5 mg ; P haloperidol ( -7.5 ) . A dose of 5.0 , 7.5 , or 10.0 mg of olanzapine caused a greater reduction in agitation than placebo 30 minutes after the first injection . There were no differences between treatment groups for hypotension , the most frequently reported adverse event , or for clinical ly relevant changes in the QTc interval . There was a greater incidence of treatment-emergent parkinsonism during treatment with IM haloperidol ( 16.7 % ) than with 2.5 ( P = .03 ) , 5.0 ( P = .03 ) , or 7.5 mg ( P = .01 ) of IM olanzapine ( 0 % ) or with placebo ( 0 % ) ( P = .01 ) . CONCLUSIONS Intramuscular olanzapine at a dose of 2.5 to 10.0 mg per injection exhibits a dose-response relationship in the rapid treatment of acute agitation in patients with schizophrenia and demonstrates a favorable safety profile",
"BACKGROUND The aim of this study was to examine differences in the improvement of clinical psychopathology and in fine motor functions at 2 doses of risperidone in first-episode , acutely psychotic patients . METHOD In a double-blind , fixed-dose study , 49 acutely psychotic , neuroleptic-naive patients who were admitted for the first time and who met DSM-IV criteria for schizophrenia , schizophreniform disorder , or schizoaffective disorder were r and omly assigned to 2 or 4 mg/day of risperidone . Treatment efficacy was measured using the Brief Psychiatric Rating Scale , the Scale for the Assessment of Negative Symptoms , The Clinical Global Impressions scale , and the Social and Occupational Functioning Assessment Scale . Fine motor functions were assessed using a computerized device ( the Vienna Test System ) and were compared with those of a control group of 20 healthy subjects who were matched for age , gender , and educational level . RESULTS Treatment with doses of 2 and 4 mg of risperidone daily significantly reduced positive ( p .0001 ) and negative ( p .01 ) symptoms at 8 weeks . Although there were no significant differences in motor movements as measured using the Barnes Akathisia Scale and the Simpson-Angus Scale , computerized fine motor assessment showed significantly less motor dysfunction in the 2-mg/day group at 8 weeks . No significant correlations to plasma concentration of active moiety were found for data on psychopathology and fine motor functions . CONCLUSION The 2 doses of risperidone did not differ in terms of clinical improvement , but the 2-mg/day dose produced fewer fine motor dysfunctions . These results suggest that a dose as low as 2 mg/day of risperidone may be effective for patients with first-episode psychosis",
"Two studies tested the reliability and validity of the Overt Agitation Severity Scale ( OASS ) , a new instrument developed to define and objective ly rate the severity of agitated behavior . The authors postulate that agitation should be conceptualized as vocal and motor behaviors on a continuum of expressions that extends from anxiety to aggression . Content validity through expert agreement was achieved in the development of test construction over a 2-year period . Results of two pilot studies ( n = 25 and n = 14 subjects ) established the reliability and validity of the OASS to measure agitation severity . The OASS differs from other agitation scales in that it confines its rating exclusively to observable behavioral manifestations of agitation ",
"Objective To determine whether haloperidol alone results in swifter and safer tranquillisation and sedation than haloperidol plus promethazine . Design Pragmatic r and omised open trial ( January-July 2004 ) . Setting Psychiatric emergency room , Rio de Janeiro , Brazil . Participants 316 patients who needed urgent intramuscular sedation because of agitation , dangerous behaviour , or both . Interventions Open treatment with intramuscular haloperidol 5 - 10 mg or intramuscular haloperidol 5 - 10 mg plus intramuscular promethazine up to 50 mg ; doses were at the discretion of the prescribing clinician . Main outcome measures The primary outcome was proportion tranquil or asleep by 20 minutes . Secondary outcomes were asleep by 20 minutes ; tranquil or asleep by 40 , 60 , and 120 minutes ; physically restrained or given additional drugs within 2 hours ; severe adverse events ; another episode of agitation or aggression ; additional visit from the doctor during the subsequent 24 hours ; overall antipsychotic load in the first 24 hours ; and still in hospital after 2 weeks . Results Primary outcome data were available for 311 ( 98.4 % ) people , 77 % of whom were thought to have a psychotic illness . Patients allocated haloperidol plus promethazine were more likely to be tranquil or asleep by 20 minutes than those who received intramuscular haloperidol alone ( relative risk 1.30 , 95 % confidence interval 1.10 to 1.55 ; number needed to treat 6 , 95 % confidence interval 4 to 16 ; P=0.002 ) . No differences were found after 20 minutes . However , 10 cases of acute dystonia occurred , all in the haloperidol alone group . Conclusions Haloperidol plus promethazine is a better option than haloperidol alone in terms of speed of onset of action and safety . Enough data are now available to change guidelines that continue to recommend treatments that leave people exposed to longer periods of aggression than necessary and patients vulnerable to distressing and unsafe adverse effects . Trial registration Current Controlled Trials IS RCT N83261243",
"Abstract Objective To compare two widely used drug treatments for people with aggression or agitation due to mental illness . Design Pragmatic , r and omised clinical trial . Setting Three psychiatric emergency rooms in Rio de Janeiro , Brazil . Subjects 301 aggressive or agitated people . Interventions Open treatment with intramuscular midazolam or intramuscular haloperidol plus promethazine . Main outcome measures Patients tranquil or se date d at 20 minutes . Secondary outcomes : patients tranquil or asleep by 40 , 60 , and 120 minutes ; restrained or given extra drugs within 2 hours ; severe adverse events ; another episode of agitation or aggression ; needing extra visits from doctor during first 24 hours ; overall antipsychotic load in first 24 hours ; and not discharged by two weeks . Results 151 patients were r and omised to midazolam , and 150 to haloperidol-promethazine mix . Follow up for the primary outcome was available for 298 ( 99 % ) : 134/151 ( 89 % ) of patients given midazolam were tranquil or asleep after 20 minutes compared with 101/150 ( 67 % ) of those given haloperidol plus promethazine ( relative risk 1.32 ( 95 % confidence interval 1.16 to 1.49 ) ) . By 40 minutes , midazolam still had a statistically and clinical ly significant 13 % relative advantage ( 1.13 ( 1.01 to 1.26 ) ) . After 1 hour , about 90 % of both groups were tranquil or asleep . One important adverse event occurred in each group : a patient given midazolam had transient respiratory depression , and one given haloperidol-promethazine had a gr and e mal seizure . Conclusions Both treatments were effective . Midazolam was more rapidly sedating than haloperidol-promethazine , reducing the time people are exposed to aggression . Adverse effects and re sources to deal with them should be considered in the choice of the treatment",
"BACKGROUND The pharmacological management of violence in people with psychiatric disorders is under- research ed . AIMS To compare interventions commonly used for controlling agitation or violence in people with serious psychiatric disorders . METHOD We r and omised 200 people to receive intramuscular lorazepam ( 4 mg ) or intramuscular haloperidol ( 10 mg ) plus promethazine ( 25 - 50 mg mix ) . RESULTS At blinded assessment s 4 h later ( 99.5 % follow-up ) , equal numbers in both groups ( 96 % ) were tranquil or asleep . However , 76 % given the haloperidol-promethazine mix were asleep compared with 45 % of those allocated lorazepam ( RR=2.29,95 % CI 1.59 - 3.39 ; NNT=3.2,95 % CI 2.3 - 5.4 ) . The haloperidol-promethazine mix produced a faster onset of tranquillisation/sedation and more clinical improvement over the first 2 h. Neither intervention differed significantly in the need for additional intervention or physical restraints , numbers absconding , or adverse effects . CONCLUSIONS Both interventions are effective for controlling violent/agitated behaviour . If speed of sedation is required , the haloperidol-promethazine combination has advantages over lorazepam",
"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 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",
"BACKGROUND The tricyclic antidepressant trimipramine exhibits several features ( e. g. , dopaminergic effect , molecular structure similar to a neuroleptic , receptor-binding profile similar to clozapine ) that suggest its potential as an antipsychotic medication . The aim of the study was to investigate the antipsychotic potential of trimipramine in a controlled clinical trial comparing its antipsychotic efficacy with that of a neuroleptic . METHOD In a German multi-center , r and omized , double-blind trial , the antipsychotic efficacy of trimipramine was compared with that of the phenothiazine neuroleptic perazine , using the Brief Psychiatric Rating Scale ( BPRS ) , the Positive and Negative Syndrome Scale ( PANSS ) , and Clinical Global Impressions ( CGI ) . Antidepressant efficacy of both agents was measured by use of the Bech-Rafaelsen Melancholia Scale ( BRMES ) . Ninety-five patients with acute schizophrenia ( DSM-III-R ) and a BPRS total score > 40 at baseline were treated with either 300 - 400 mg trimipramine or 450 - 600 mg perazine for 5 weeks . RESULTS Therapeutic equivalence of both treatments ( in the dosages used ) could not be demonstrated ( change in BPRS total score , per- protocol [ PP ] analysis , one-sided equivalence testing ) . However , intention-to-treat ( ITT ) as well as PP analysis showed a statistically significant decrease in the BPRS total scores in both treatment groups ( PP : trimipramine , 56.5 + /- 9.8 to 44.1 + /- 17.9 ; perazine , 56.4 + /- 10.8 to 37.9 + /- 12.9 ) . Significant decreases in all BPRS and PANSS subscores as well as CGI results and response rate support the antipsychotic efficacy of trimipramine . The BRMES total scores significantly decreased in both treatment groups without showing a significant difference between the two agents . Trimipramine was better tolerated than perazine and did not elicit extrapyramidal symptoms . CONCLUSION Trimipramine failed to exhibit therapeutic equivalence to perazine in the dosages used . However , there was evidence of a substantial antipsychotic effect of trimipramine . It may be a useful medication if depressive symptoms in psychotic patients require antidepressant treatment or if other antipsychotics can not be administered",
"The authors administered haloperidol 4.5 mg t.i.d . to 33 drug-free schizophrenic patients . Ten patients did not receive anything else ( group HPL ) , while ten patients received procyclidine 5 mg t.i.d . , and 13 patients were given promethazine 25 mg t.i.d . ( groups HPRC and HPRM respectively ) in addition . Seven patients dropped out of the HPL group and three out of the HPRM group , but none out of the HPRC group . These drop outs were due to the development of early extrapyramidal side effects , which were absent in the HPRC group . The findings suggest that antiparkinson prophylaxis is useful during commencement of therapy with high-potency neuroleptic agents"
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41188344-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND This is the second substantive up date of this review . It was originally published in 1998 and was previously up date d in 2009 . Elevated blood pressure ( known as ' hypertension ' ) increases with age - most rapidly over age 60 . Systolic hypertension is more strongly associated with cardiovascular disease than is diastolic hypertension , and it occurs more commonly in older people . It is important to know the benefits and harms of antihypertensive treatment for hypertension in this age group , as well as separately for people 60 to 79 years old and people 80 years or older . OBJECTIVES Primary objective • To quantify the effects of antihypertensive drug treatment as compared with placebo or no treatment on all-cause mortality in people 60 years and older with mild to moderate systolic or diastolic hypertension Secondary objectives • To quantify the effects of antihypertensive drug treatment as compared with placebo or no treatment on cardiovascular-specific morbidity and mortality in people 60 years and older with mild to moderate systolic or diastolic hypertension• To quantify the rate of withdrawal due to adverse effects of antihypertensive drug treatment as compared with placebo or no treatment in people 60 years and older with mild to moderate systolic or diastolic hypertension SEARCH METHODS : The Cochrane Hypertension Information Specialist search ed the following data bases for r and omised controlled trials up to 24 November 2017 : the Cochrane Hypertension Specialised Register , the Cochrane Central Register of Controlled Trials ( CENTRAL ) , MEDLINE Ovid ( 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 omised controlled trials of at least one year 's duration comparing antihypertensive drug therapy versus placebo or no treatment and providing morbidity and mortality data for adult patients ( ≥ 60 years old ) with hypertension defined as blood pressure greater than 140/90 mmHg . DATA COLLECTION AND ANALYSIS Outcomes assessed were all-cause mortality ; cardiovascular morbidity and mortality ; cerebrovascular morbidity and mortality ; coronary heart disease morbidity and mortality ; and withdrawal due to adverse effects . We modified the definition of cardiovascular mortality and morbidity to exclude transient ischaemic attacks when possible . MAIN RESULTS This up date includes one additional trial ( MRC-TMH 1985 ) . Sixteen trials ( N = 26,795 ) in healthy ambulatory adults 60 years or older ( mean age 73.4 years ) from western industrialised countries with moderate to severe systolic and /or diastolic hypertension ( average 182/95 mmHg ) met the inclusion criteria . Most of these trials evaluated first-line thiazide diuretic therapy for a mean treatment duration of 3.8 years . Antihypertensive drug treatment reduced all-cause mortality ( high-certainty evidence ; 11 % with control vs 10.0 % with treatment ; risk ratio ( RR ) 0.91 , 95 % confidence interval ( CI ) 0.85 to 0.97 ; cardiovascular morbidity and mortality ( moderate-certainty evidence ; 13.6 % with control vs 9.8 % with treatment ; RR 0.72 , 95 % CI 0.68 to 0.77 ; cerebrovascular mortality and morbidity ( moderate-certainty evidence ; 5.2 % with control vs 3.4 % with treatment ; RR 0.66 , 95 % CI 0.59 to 0.74 ; and coronary heart disease mortality and morbidity ( moderate-certainty evidence ; 4.8 % with control vs 3.7 % with treatment ; RR 0.78 , 95 % CI 0.69 to 0.88 . Withdrawals due to adverse effects were increased with treatment ( low-certainty evidence ; 5.4 % with control vs 15.7 % with treatment ; RR 2.91 , 95 % CI 2.56 to 3.30 . In the three trials restricted to persons with isolated systolic hypertension , reported benefits were similar . This comprehensive systematic review provides additional evidence that the reduction in mortality observed was due mostly to reduction in the 60- to 79-year-old patient subgroup ( high-certainty evidence ; RR 0.86 , 95 % CI 0.79 to 0.95 ) . Although cardiovascular mortality and morbidity was significantly reduced in both subgroups 60 to 79 years old ( moderate-certainty evidence ; RR 0.71 , 95 % CI 0.65 to 0.77 ) and 80 years or older ( moderate-certainty evidence ; RR 0.75 , 95 % CI 0.65 to 0.87 ) , the magnitude of absolute risk reduction was probably higher among 60- to 79-year-old patients ( 3.8 % vs 2.9 % ) . The reduction in cardiovascular mortality and morbidity was primarily due to a reduction in cerebrovascular mortality and morbidity . AUTHORS ' CONCLUSIONS Treating healthy adults 60 years or older with moderate to severe systolic and /or diastolic hypertension with antihypertensive drug therapy reduced all-cause mortality , cardiovascular mortality and morbidity , cerebrovascular mortality and morbidity , and coronary heart disease mortality and morbidity . Most evidence of benefit pertains to a primary prevention population using a thiazide as first-line treatment
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"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",
"CONTEXT The Systolic Hypertension in the Elderly Program ( SHEP ) demonstrated that treating isolated systolic hypertension in older patients decreased incidence of total stroke , but whether all types of stroke were reduced was not evaluated . OBJECTIVE To investigate antihypertensive drug treatment effects on incidence of stroke by type and subtype , timing of strokes , case-fatality rates , stroke residual effects , and relationship of attained systolic blood pressure to stroke incidence . DESIGN The SHEP study , a r and omized , double-blind , placebo-controlled trial began March 1 , 1985 , and had an average follow-up of 4.5 years . SETTING AND PARTICIPANTS A total of 4736 men and women aged 60 years or older with isolated systolic hypertension at 16 clinical centers in the United States . INTERVENTIONS Patients were r and omly assigned to receive treatment with 12.5 mg/d of chlorthalidone ( step 1 ) ; either 25 mg/d of atenolol or 0.05 mg/d of reserpine ( step 2 ) could be added ( n = 2365 ) ; or placebo ( n = 2371 ) . MAIN OUTCOME MEASURES Occurrence , type and subtype , and timing of first strokes and stroke fatalities ; and change in stroke incidence for participants ( whether in active treatment or placebo groups ) reaching study -specific systolic blood pressure goal ( decrease of at least 20 mm Hg from baseline to below 160 mm Hg ) compared with participants not reaching goal . RESULTS A total of 85 and 132 participants in the active treatment and placebo groups , respectively , had ischemic strokes ( adjusted relative risk [ RR ] , 0.63 ; 95 % confidence interval [ CI ] , 0.48 - 0.82 ) ; 9 and 19 had hemorrhagic strokes ( adjusted RR , 0.46 ; 95 % CI , 0.21 - 1.02 ) ; and 9 and 8 had strokes of unknown type ( adjusted RR , 1.05 ; 95 % CI , 0.40 - 2 . 73 ) , respectively . Four subtypes of ischemic stroke were observed in active treatment and placebo group participants , respectively , as follows : for lacunar , n = 23 and n = 43 ( adjusted RR , 0.53 ; 95 % CI , 0.32 - 0.88 ) ; for embolic , n = 9 and n = 16 ( adjusted RR , 0.56 ; 95 % CI , 0.25 - 1.27 ) ; for atherosclerotic , n = 13 and n = 13 ( adjusted RR , 0 . 99 ; 95 % CI , 0.46 - 2.15 ) ; and for unknown subtype , n = 40 and n = 60 ( adjusted RR , 0.64 ; 95 % CI , 0.43 - 0.96 ) . Treatment effect was observed within 1 year for hemorrhagic strokes but was not seen until the second year for ischemic strokes . Stroke incidence significantly decreased in participants attaining study -specific systolic blood pressure goals . CONCLUSIONS In this study , antihypertensive drug treatment reduced the incidence of both hemorrhagic and ischemic ( including lacunar ) strokes . Reduction in stroke incidence occurred when specific systolic blood pressure goals were attained . JAMA . 2000;284:465 -",
"Background — Early after coronary artery bypass surgery ( CABG ) , activation of numerous neurohumoral and endogenous vasodilator systems occurs that could be influenced favorably by angiotensin-converting enzyme inhibitors . Methods and Results — The Ischemia Management with Accupril post – bypass Graft via Inhibition of the coNverting Enzyme ( IMAGINE ) trial tested whether early initiation ( ≤7 days ) of an angiotensin-converting enzyme inhibitor after CABG reduced cardiovascular events in stable patients with left ventricular ejection fraction ≥40 % . The trial was a double-blind , placebo-controlled study of 2553 patients r and omly assigned to quinapril , target dose 40 mg/d , or placebo , who were followed up to a maximum of 43 months . The mean ( SD ) age was 61 ( 10 ) years . The incidence of the primary composite end point ( cardiovascular death , resuscitated cardiac arrest , nonfatal myocardial infa rct ion , coronary revascularization , unstable angina or heart failure requiring hospitalization , documented angina , and stroke ) was 13.7 % in the quinapril group and 12.2 % in the placebo group ( hazard ratio 1.15 , 95 % confidence interval 0.92 to 1.42 , P=0.212 ) over a median follow-up of 2.95 years . The incidence of the primary composite end point increased significantly in the first 3 months after CABG in the quinapril group ( hazard ratio 1.52 , 95 % confidence interval 1.03 to 2.26 , P=0.0356 ) . Adverse events also increased in the quinapril group , particularly during the first 3 months after CABG . Conclusions — In patients at low risk of cardiovascular events after CABG , routine early initiation of angiotensin-converting enzyme inhibitor therapy does not appear to improve clinical outcome up to 3 years after CABG ; however , it increases the incidence of adverse events , particularly early after CABG . Thus , early after CABG , initiation of angiotensin-converting enzyme inhibitor therapy should be individualized and continually reassessed over time according to risk",
"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",
"OBJECTIVE --To investigate the relation between mortality and treated systolic and diastolic blood pressures . DESIGN --R and omised double blind placebo controlled trial . Mortality in the two treatment groups was examined in thirds of treated systolic and diastolic blood pressures . PATIENTS --339 And 352 patients allocated to placebo and active treatment , respectively . The groups were similar at r and omisation in sex ratio ( 70 % women ) , mean age ( 71.5 years ) , blood pressure ( 182/101 mm Hg ) , and proportion of patients with cardiovascular complications ( 35 % ) . MEASUREMENTS AND MAIN RESULTS --In the placebo group total mortality rose with increasing systolic pressure whereas it had a U shaped relation with diastolic pressure , the total lowest mortality being in patients in the middle third of the distribution of diastolic pressure . In the group given active treatment total mortality showed a U shaped relation with systolic pressure and an inverse association with treated diastolic pressure . In both groups cardiovascular and non-cardiovascular mortality followed the same trends as total mortality . The increased mortality in the lowest thirds of pressure was not associated with an increased proportion of patients with cardiovascular complications at r and omisation or with a fall in diastolic pressure exceeding the median fall in pressure in each group . In contrast , patients in the lowest thirds of pressure showed greater decreases in body weight and haemoglobin concentration than those in the middle and upper thirds of pressure . CONCLUSIONS --In patients taking active treatment total mortality was increased in the lowest thirds of treated systolic and diastolic blood pressures . This increased mortality is not necessarily explained by an exaggerated reduction in pressure induced by drugs as for diastolic pressure a U shaped relation also existed during treatment with placebo . In addition , patients in the lowest thirds of systolic and diastolic pressures were characterised by decreases in body weight and haemoglobin concentration , and the patients in the lowest thirds of diastolic pressure taking active treatment also by an increased non-cardiovascular mortality , suggesting some deterioration of general health",
"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",
"The Systolic Hypertension in the Elderly Program ( SHEP ) , a r and omized , double-masked , placebo-controlled trial of 4736 persons , was design ed to assess the efficacy of antihypertensive drug treatment to reduce the risk of fatal and nonfatal strokes among people age 60 and over with isolated systolic hypertension . The statistical method used in interim monitoring of results was conditional power ( or stochastic curtailment ) . The findings did not become conclusive until near the completion of the trial , and therefore SHEP was continued to its scheduled closing date . The trial demonstrated a 36 % reduction in the incidence of stroke in the active treatment group ( P = .0003 ) . In addition to evaluating overall efficacy of treatment , the monitoring process considered such other issues as nonstroke outcomes , lag time between first report of stroke and final confirmation of stroke diagnosis , consistency of results across subgroups , and completeness of follow-up . The purpose of this article is to review these factors with primary emphasis on the statistical aspects",
"Hypertensive patients over the age of 60 years were admitted to a double-blind placebo-controlled trial . Patients in the actively treated group received a combined potassium-losing and -sparing diuretic ( triamterene 50 mg plus hydrochlorothiazide 25 mg ; n = 416 ) ; this dose could be doubled and methyldopa ( up to 2 g , daily ) was added in 35 % of patients when blood pressure remained high . The placebo group ( n = 424 ) received matching capsules and tablets . Adverse effects were assessed in the double-blind period of the trial by calculating the incidence of abnormal biochemical results , investigator reports of diseases and prescriptions of concomitant therapy and a self-administered symptom question naire completed by patients . In 1000 hypertensive subjects over 60 years of age , 1 year of active treatment would prevent 11 fatal cardiac events , 6 fatal and 11 non-fatal strokes and 8 cases of severe congestive heart failure . No unexpected adverse treatment effects were observed . A significant excess incidence rate ( per 1000 person years ) was found in the active group compared with placebo for : ( 1 ) impaired renal function , a serum creatinine greater than 180 mumol/l ( 2.0 mg/dl ) ; ( 2 ) mild hypokalaemia , a serum potassium less than 3.5 mmol/l ; ( 3 ) reports of gout ; and ( 4 ) an elevated serum uric acid greater than 0.52 mmol/l in men or greater than 0.46 in women . Elevated blood sugar and prescriptions for hypoglycaemic drugs tended to be more frequent in the actively treated group , but this difference was not statistically significant . In both groups , there was a low incidence ( less than 7 per 1000 person years ) of anaemia and depression and diseases of the liver , gall bladder or pancreas . ( ABSTRACT TRUNCATED AT 250 WORDS",
"BACKGROUND There are scant data on the effect of body mass index ( BMI ) ( calculated as weight in kilograms divided by the square of height in meters ) on cardiovascular events and death in older patients with hypertension . OBJECTIVE To determine if low body mass in older patients with hypertension confers an increased risk of death or stroke . PATIENTS Participants were 3975 men and women ( mean age , 71 years ) enrolled in 17 US centers in the Systolic Hypertension in the Elderly Program trial , a r and omized , double-blind , placebo-controlled clinical trial of lowdose antihypertensive therapy , with follow-up for 5 years . MAIN OUTCOME MEASURES Five-year adjusted mortality and stroke rates from Cox proportional hazards analyses . RESULTS There was no statistically significant relation of death or stroke with BMI in the placebo group ( P = .47 ) , and there was a U- or J-shaped relation in the treatment group . The J-shaped relation of death with BMI in the treated group ( P = .03 ) showed that the lowest probability of death for men was associated with a BMI of 26.0 and for women with a BMI of 29.6 ; the curve was quite flat for women across a wide range of BMI s. For stroke , men and women did not differ , and the BMI nadir for both sexes combined was 29 , with risk increasing steeply at BMI s below 24 . Those in active treatment , however , had lower death and stroke rates compared with those taking placebo . CONCLUSIONS Among older patients with hypertension , a wide range of BMI s was associated with a similar risk of death and stroke ; a low BMI was associated with increased risk . Lean , older patients with hypertension in treatment should be monitored carefully for additional risk factors",
"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 ",
"BACKGROUND Although nonpharmacologic interventions are widely recommended in the therapy of high blood pressure in older adults , surprisingly little data exist to confirm the efficacy of these interventions in older persons . METHODS We conducted a r and omized , controlled clinical trial in persons aged 60 to 85 years with a diastolic blood pressure of 85 to 100 mm Hg . The experimental arm was a nonpharmacologic intervention combining weight reduction , sodium restriction , and increased physical activity . The nonpharmacologic intervention consisted of eight weekly group and two individual sessions during the intensive phase , followed by four monthly group sessions during the maintenance phase . The control group received no treatment during the study . Blood pressure was assessed by certified technicians ( blinded to group assignment ) using r and om zero sphygmomanometers . RESULTS Of 56 participants r and omized , 47 completed the entire 6-month trial ( 21 in the intervention group and 26 in the control group ) . Attendance at the intervention sessions was excellent . The intervention group lost more weight ( -2.1 kg ) over 6 months than the control group ( + 0.3 kg ) . Trends for decreasing 24-hour urine sodium excretion in both the intervention and control groups , with greater trend in the intervention group , were not statistically significant . The intervention group experienced more reduction in systolic and diastolic blood pressure than did the control group ( mean differences between groups at 6 months , 4.2/4.9 mm Hg , respectively ) . CONCLUSIONS Our data indicate that a nonpharmacologic intervention will lower systolic and diastolic blood pressure levels in older people with borderline or mild elevations of diastolic blood pressure",
"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 The risk of cardiovascular events among patients with atrial fibrillation is high . We evaluated whether irbesartan , an angiotensin-receptor blocker , would reduce this risk . METHODS We r and omly assigned patients with a history of risk factors for stroke and a systolic blood pressure of at least 110 mm Hg to receive either irbesartan at a target dose of 300 mg once daily or double-blind placebo . These patients were already enrolled in one of two trials ( of clopidogrel plus aspirin versus aspirin alone or versus oral anticoagulants ) . The first co primary outcome was stroke , myocardial infa rct ion , or death from vascular causes ; the second was this composite outcome plus hospitalization for heart failure . RESULTS A total of 9016 patients were enrolled and followed for a mean of 4.1 years . The mean reduction in systolic blood pressure was 2.9 mm Hg greater in the irbesartan group than in the placebo group , and the mean reduction in diastolic blood pressure was 1.9 mm Hg greater . The first co primary outcome occurred at a rate of 5.4 % per 100 person-years in both groups ( hazard ratio with irbesartan , 0.99 ; 95 % confidence interval [ CI ] , 0.91 to 1.08 ; P=0.85 ) . The second co primary outcome occurred at a rate of 7.3 % per 100 person-years among patients receiving irbesartan and 7.7 % per 100 person-years among patients receiving placebo ( hazard ratio , 0.94 ; 95 % CI , 0.87 to 1.02 ; P=0.12 ) . The rates of first hospitalization for heart failure ( a prespecified secondary outcome ) were 2.7 % per 100 person-years among patients receiving irbesartan and 3.2 % per 100 person-years among patients receiving placebo ( hazard ratio , 0.86 ; 95 % CI , 0.76 to 0.98 ) . Among patients who were in sinus rhythm at baseline , there was no benefit of irbesartan in preventing hospitalization for atrial fibrillation or atrial fibrillation recorded on 12-lead electrocardiography , nor was there a benefit in a subgroup that underwent transtelephonic monitoring . More patients in the irbesartan group than in the placebo group had symptomatic hypotension ( 127 vs. 64 ) and renal dysfunction ( 43 vs. 24 ) . CONCLUSIONS Irbesartan did not reduce cardiovascular events in patients with atrial fibrillation . ( Funded by Bristol-Myers Squibb and Sanofi-Aventis ; Clinical Trials.gov number , NCT00249795 . )",
"Syst-Eur is a multicenter placebo-controlled outcome trial design ed by the European Working Party on High Blood Pressure in the Elderly to investigate the effect of antihypertensive treatment on the incidence of stroke in elderly patients with isolated systolic hypertension ( ISH ) . Eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160 - 219 mm Hg with a diastolic blood pressure less than 95 mm Hg . The present paper is an interim report on the first 316 patients r and omized into this trial . The placebo ( n = 170 ) and active treatment ( n = 146 ) groups were similar at r and omization with respect to age ( 73 + /- 8 years ; mean + /- SD ) , sitting blood pressure ( 178 + /- 12 mm Hg systolic ; 85 + /- 7 mm Hg diastolic ) , percentage of men ( 34 % ) , and percentage of patients with cardiovascular complications ( 29 % ) . After r and omization blood pressure fell more ( p less than 0.001 ) in patients on active treatment than in those in the placebo group ( 19 + /- 20 mm Hg systolic ; 6 + /- 10 mm Hg diastolic vs. 7 + /- 19 and 1 + /- 10 mm Hg for sitting blood pressure ) . This first interim report on the Syst-Eur trial demonstrates that a multinational trial in elderly patients with ISH is feasible and that a significant blood pressure difference between the two treatment groups can be achieved and maintained . New centers are being recruited in order to r and omize a total of 3,000 patients",
"OBJECTIVE To assess variability in the use of coronary artery bypass grafting ( CABG ) and percutaneous transluminal angioplasty ( PTCA ) in the Systolic Hypertension in the Elderly Program ( SHEP ) cohort with incident coronary heart disease ( CHD ) by age , sex , and race . DESIGN Retrospective analysis of a multicenter prospect i ve cohort study . SETTING Community-based ambulatory population in academic centers . PATIENTS Among 4736 subjects initially enrolled in SHEP , there were 432 incident cases of CHD , excluding those patients who experienced rapid or sudden cardiac death . MAIN OUTCOME MEASURE Incident cases of CHD who underwent CABG or PTCA . RESULTS Of those participants > or = 60 and age , 7.3 % underwent PTCA , compared with 3.9 % of those > or = 75 years ( P = 0.14 ) . 15.4 % of those CABG surgery , compared with 7.8 % of those 75 and older ( P = 0.018 ) . When both of these endpoints , CABG and PTCA , were combined , 22.4 % of those CABG or PTCA ( P use of procedures in participants Race , activity limitations , number of comorbid conditions , education level , marital status , employment status , and social support were not significantly associated with CABG or PTCA use . When the variables studied were entered into a logistic regression model , increased age and female sex remained independently associated with decreased CABG and PTCA use . CONCLUSION In the SHEP trial older patients and women , regardless of comorbid conditions , socioeconomic status , and social support , underwent less intensive cardiovascular interventions than did younger patients and men when they developed CHD",
"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 )",
"BACKGROUND Previous studies have suggested that blockade of the renin-angiotensin system may prevent diabetes in people with cardiovascular disease or hypertension . METHODS In a double-blind , r and omized clinical trial with a 2-by-2 factorial design , we r and omly assigned 5269 participants without cardiovascular disease but with impaired fasting glucose levels ( after an 8-hour fast ) or impaired glucose tolerance to receive ramipril ( up to 15 mg per day ) or placebo ( and rosiglitazone or placebo ) and followed them for a median of 3 years . We studied the effects of ramipril on the development of diabetes or death , whichever came first ( the primary outcome ) , and on secondary outcomes , including regression to normoglycemia . RESULTS The incidence of the primary outcome did not differ significantly between the ramipril group ( 18.1 % ) and the placebo group ( 19.5 % ; hazard ratio for the ramipril group , 0.91 ; 95 % confidence interval [ CI ] , 0.81 to 1.03 ; P=0.15 ) . Participants receiving ramipril were more likely to have regression to normoglycemia than those receiving placebo ( hazard ratio , 1.16 ; 95 % CI , 1.07 to 1.27 ; P=0.001 ) . At the end of the study , the median fasting plasma glucose level was not significantly lower in the ramipril group ( 102.7 mg per deciliter [ 5.70 mmol per liter ] ) than in the placebo group ( 103.4 mg per deciliter [ 5.74 mmol per liter ] , P=0.07 ) , though plasma glucose levels 2 hours after an oral glucose load were significantly lower in the ramipril group ( 135.1 mg per deciliter [ 7.50 mmol per liter ] vs. 140.5 mg per deciliter [ 7.80 mmol per liter ] , P=0.01 ) . CONCLUSIONS Among persons with impaired fasting glucose levels or impaired glucose tolerance , the use of ramipril for 3 years does not significantly reduce the incidence of diabetes or death but does significantly increase regression to normoglycemia . ( Clinical Trials.gov number , NCT00095654 [ Clinical Trials.gov ] . )",
"BACKGROUND The multicenter double-blind , r and omized Bergamo Nephrologic Diabetes Complications Trial ( BENEDICT ) was design ed to assess whether angiotensin-converting-enzyme inhibitors and non-dihydropyridine calcium-channel blockers , alone or in combination , prevent microalbuminuria in subjects with hypertension , type 2 diabetes mellitus , and normal urinary albumin excretion . METHODS We studied 1204 subjects , who were r and omly assigned to receive at least three years of treatment with tr and olapril ( at a dose of 2 mg per day ) plus verapamil ( sustained-release formulation , 180 mg per day ) , tr and olapril alone ( 2 mg per day ) , verapamil alone ( sustained-release formulation , 240 mg per day ) , or placebo . The target blood pressure was 120/80 mm Hg . The primary end point was the development of persistent microalbuminuria ( overnight albumin excretion , > or = 20 microg per minute at two consecutive visits ) . RESULTS The primary outcome was reached in 5.7 percent of the subjects receiving tr and olapril plus verapamil , 6.0 percent of the subjects receiving tr and olapril , 11.9 percent of the subjects receiving verapamil , and 10.0 percent of control subjects receiving placebo . The estimated acceleration factor ( which quantifies the effect of one treatment relative to another in accelerating or slowing disease progression ) adjusted for predefined baseline characteristics was 0.39 for the comparison between verapamil plus tr and olapril and placebo ( P=0.01 ) , 0.47 for the comparison between tr and olapril and placebo ( P=0.01 ) , and 0.83 for the comparison between verapamil and placebo ( P=0.54 ) . Tr and olapril plus verapamil and tr and olapril alone delayed the onset of microalbuminuria by factors of 2.6 and 2.1 , respectively . Serious adverse events were similar in all treatment groups . CONCLUSIONS In subjects with type 2 diabetes and hypertension but with normoalbuminuria , the use of tr and olapril plus verapamil and tr and olapril alone decreased the incidence of microalbuminuria to a similar extent . The effect of verapamil alone was similar to that of placebo",
"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",
"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",
"Aims Angiotensin-converting enzyme ( ACE ) inhibitors improve left ventricular ( LV ) remodelling and outcome in heart failure and hypertensive heart disease . They may be similarly beneficial in patients with aortic stenosis ( AS ) , but historical safety concerns have limited their use , and no prospect i ve clinical trials exist . Methods and results We conducted a prospect i ve , r and omized , double-blind , placebo-controlled trial in 100 patients with moderate or severe asymptomatic AS to examine the physiological effects of ramipril , particularly LV mass ( LVM ) regression . Subjects were r and omized to ramipril 10 mg daily ( n = 50 ) or placebo ( n = 50 ) for 1 year , and underwent cardiac magnetic resonance , echocardiography , and exercise testing at 0 , 6 , and 12 months , with follow-up data available in 77 patients . There was a modest but progressive reduction in LVM ( the primary end point ) in the ramipril group vs. the placebo group ( mean change −3.9 vs. + 4.5 g , respectively , P = 0.0057 ) . There were also trends towards improvements in myocardial physiology : the ramipril group showed preserved tissue Doppler systolic velocity compared with placebo ( + 0.0 vs. −0.5 cm/s , P = 0.04 ) , and a slower rate of progression of the AS ( valve area 0.0 cm2 in the ramipril group vs. −0.2 cm2 in the placebo arm , P = 0.067 ) . There were no significant differences in major adverse cardiac events . Conclusion ACE inhibition leads to a modest , but progressive reduction in LVM in asymptomatic patients with moderate – severe AS compared with placebo , with trends towards improvements in myocardial physiology and slower progression of valvular stenosis . A larger clinical outcome trial to confirm these findings and explore their clinical relevance is required",
"Abstract Objective To investigate whether a low dose of the angiotensin converting enzyme ( ACE ) inhibitor ramipril lowers cardiovascular and renal events in patients with type 2 diabetes who have microalbuminuria or proteinuria . Design R and omised , double blind , parallel group trial comparing ramipril ( 1.25 mg/day ) with placebo ( on top of usual treatment ) for cardiovascular and renal outcomes for at least three years . Setting Multicentre , primary care study conducted mostly by general practitioners in 16 European and north African countries . Participants 4912 patients with type 2 diabetes aged > 50 years who use oral antidiabetic drugs and have persistent microalbuminuria or proteinuria ( urinary albumin excretion 20 mg/l in two consecutive sample s ) , and serum creatinine ≤ 150 μmol/l . Main outcome measures The primary outcome measure was the combined incidence of cardiovascular death , non-fatal myocardial infa rct ion , stroke , heart failure leading to hospital admission , and end stage renal failure . Results Participants were followed for 3 to 6 ( median 4 ) years . There were 362 primary events among the 2443 participants taking ramipril ( 37.8 per 1000 patient years ) and 377 events among the 2469 participants taking placebo ( 38.8 per 1000 patient years ; hazard ratio 1.03 ( 95 % confidence interval 0.89 to 1.20 , P = 0.65 ) ) . None of the components of the primary outcome was reduced . Ramipril lowered systolic and diastolic blood pressures ( by 2.43 and 1.06 mm Hg respectively after two years ) and favoured regression from microalbuminuria ( 20 - 200 mg/l ) or proteinuria ( > 200mg/l ) to normal level ( ) in 1868 participants who completed the study . Conclusions Low dose ( 1.25 mg ) ramipril once daily has no effect on cardiovascular and renal outcomes of patients with type 2 diabetes and albuminuria , despite a slight decrease in blood pressure and urinary albumin . The cardiovascular benefits of a daily higher dose ( 10 mg ) ramipril observed elsewhere are not found with an eightfold lower daily dose",
"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 Microalbuminuria is an early predictor of diabetic nephropathy and premature cardiovascular disease . We investigated whether treatment with an angiotensin-receptor blocker ( ARB ) would delay or prevent the occurrence of microalbuminuria in patients with type 2 diabetes and normoalbuminuria . METHODS In a r and omized , double-blind , multicenter , controlled trial , we assigned 4447 patients with type 2 diabetes to receive olmesartan ( at a dose of 40 mg once daily ) or placebo for a median of 3.2 years . Additional antihypertensive drugs ( except angiotensin-converting-enzyme inhibitors or ARBs ) were used as needed to lower blood pressure to less than 130/80 mm Hg . The primary outcome was the time to the first onset of microalbuminuria . The times to the onset of renal and cardiovascular events were analyzed as secondary end points . RESULTS The target blood pressure ( olmesartan and 71 % taking placebo ; blood pressure measured in the clinic was lower by 3.1/1.9 mm Hg in the olmesartan group than in the placebo group . Microalbuminuria developed in 8.2 % of the patients in the olmesartan group ( 178 of 2160 patients who could be evaluated ) and 9.8 % in the placebo group ( 210 of 2139 ) ; the time to the onset of microalbuminuria was increased by 23 % with olmesartan ( hazard ratio for onset of microalbuminuria , 0.77 ; 95 % confidence interval , 0.63 to 0.94 ; P=0.01 ) . The serum creatinine level doubled in 1 % of the patients in each group . Slightly fewer patients in the olmesartan group than in the placebo group had nonfatal cardiovascular events--81 of 2232 patients ( 3.6 % ) as compared with 91 of 2215 patients ( 4.1 % ) (P=0.37)--but a greater number had fatal cardiovascular events--15 patients ( 0.7 % ) as compared with 3 patients ( 0.1 % ) ( P=0.01 ) , a difference that was attributable in part to a higher rate of death from cardiovascular causes in the olmesartan group than in the placebo group among patients with preexisting coronary heart disease ( 11 of 564 patients [ 2.0 % ] vs. 1 of 540 [ 0.2 % ] , P=0.02 ) . CONCLUSIONS Olmesartan was associated with a delayed onset of microalbuminuria , even though blood-pressure control in both groups was excellent according to current st and ards . The higher rate of fatal cardiovascular events with olmesartan among patients with preexisting coronary heart disease is of concern . ( Funded by Daiichi Sankyo ; Clinical Trials.gov number , NCT00185159 . )",
"AIMS Major guidelines recommend lowering systolic blood pressure ( SBP ) to hypertensives , but evidence is missing whether this is beneficial in ( i ) uncomplicated hypertensives , ( ii ) grade 1 hypertensives , and ( iii ) elderly hypertensives . Providing this missing evidence is important to justify efforts and costs of aggressive therapy in all hypertensives . METHODS AND RESULTS Felodipine Event Reduction ( FEVER ) was a double-blind , r and omized trial on 9711 Chinese hypertensives , in whom cardiovascular outcomes were significantly reduced by more intense therapy ( low-dose hydrochlorothiazide and low-dose felodipine ) achieving a mean of 138 mmHg SBP compared with less-intense therapy ( low-dose hydrochlorothiazide and placebo ) achieving a mean of 142 mmHg . FEVER included older and younger patients , and patients with and without diabetes or cardiovascular disease . In the analyses here reported , Cox regression models assessed outcome differences between more and less-intense treatments in groups of patients with different baseline characteristics . Significant reductions in stroke were found in uncomplicated hypertensives ( -39 % , P = 0.002 ) , in hypertensives with r and omization SBP SBP was lowered by more intense treatment . Significant reductions ( between -29 and -47 % , P = 0.02 to all cardiovascular events and all deaths . Achieving mean SBP values cardiovascular events every 100 patients treated for 3.3 years . CONCLUSIONS These analyses provide strong support , missing so far , to guidelines recommending goal SBP < 140 mmHg in uncomplicated hypertensives , individuals with moderately elevated BP and elderly hypertensives",
"BACKGROUND It is not known whether drugs that block the renin-angiotensin system reduce the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance . METHODS In this double-blind , r and omized clinical trial with a 2-by-2 factorial design , we assigned 9306 patients with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors to receive valsartan ( up to 160 mg daily ) or placebo ( and nateglinide or placebo ) in addition to lifestyle modification . We then followed the patients for a median of 5.0 years for the development of diabetes ( 6.5 years for vital status ) . We studied the effects of valsartan on the occurrence of three co primary outcomes : the development of diabetes ; an extended composite outcome of death from cardiovascular causes , nonfatal myocardial infa rct ion , nonfatal stroke , hospitalization for heart failure , arterial revascularization , or hospitalization for unstable angina ; and a core composite outcome that excluded unstable angina and revascularization . RESULTS The cumulative incidence of diabetes was 33.1 % in the valsartan group , as compared with 36.8 % in the placebo group ( hazard ratio in the valsartan group , 0.86 ; 95 % confidence interval [ CI ] , 0.80 to 0.92 ; P Valsartan , as compared with placebo , did not significantly reduce the incidence of either the extended cardiovascular outcome ( 14.5 % vs. 14.8 % ; hazard ratio , 0.96 ; 95 % CI , 0.86 to 1.07 ; P=0.43 ) or the core cardiovascular outcome ( 8.1 % vs. 8.1 % ; hazard ratio , 0.99 ; 95 % CI , 0.86 to 1.14 ; P=0.85 ) . CONCLUSIONS Among patients with impaired glucose tolerance and cardiovascular disease or risk factors , the use of valsartan for 5 years , along with lifestyle modification , led to a relative reduction of 14 % in the incidence of diabetes but did not reduce the rate of cardiovascular events . ( Clinical Trials.gov number , NCT00097786 .",
"Assessing the compliance of people over 60 years of age and older with an antihypertensive treatment regimen was a major objective of the Systolic Hypertension in the Elderly Program ( SHEP ) pilot study . The study r and omized 551 men and women over the age of 60 ( mean age = 72 years ) to a stepped care treatment that included chlorthalidone or placebo in a double-blind trial . Three measures of compliance to treatment protocol --pill count , self-report , and a urine chlorthalidone assay -- all indicated high levels of compliance in 80 to 90 % of participants at 3 months and 1 year after r and omization . Pill-taking compliance was similar in the active and placebo groups , although the rate of discontinuance from study medications at 1 year was higher in the placebo than in the active group . Compliance was high in all age categories , including those over age 80 . These data suggest that elderly patients can achieve high levels of compliance with antihypertensive medications",
"The Systolic Hypertension in the Elderly Program ( SHEP ) is a r and omized double-blind placebo-controlled trial to determine if antihypertensive treatment of isolated systolic hypertension ( ISH ) [ systolic blood pressure ( SBP ) greater than or equal to 160 mmHg , diastolic blood pressure ( DBP ) less than 90 mmHg ] reduces the 5 year incidence of fatal and nonfatal stroke . Between March 1 , 1985 and January 15 , 1988 , 4736 persons ( target 4800 ) with ISH , age 60 years and over , were enrolled . Potential participants met blood pressure ( BP ) and age criteria . Those on antihypertensive medication prior to enrollment without documented diastolic hypertension had their medication tapered and discontinued , and then met BP criteria ( 33 % of cohort ) . Stepped-care therapy with chlorthalidone and atenolol ( alternative , reserpine ) or matching placebos was initiated as first and second steps . At baseline the trial population was 43.1 % male , 56.9 % female ; 13.9 % black , 86.1 % non-black . Also , the mean age was 71.6 years ; the mean SBP was 170.3 mmHg and the mean DBP was 76.6 mmHg ; 59.8 % had codeable resting electrocardiographic abnormalities . The trial is now in follow-up phase with scheduled termination in 1991",
"OBJECTIVES The primary objective of this study was to investigate the effects of the angiotensin-converting enzyme ( ACE ) inhibitor , ramipril , on carotid atherosclerosis in patients with coronary , cerebrovascular or peripheral vascular disease . BACKGROUND Angiotensin-converting enzyme inhibitors have been shown to reduce the risk of coronary events in various patient groups and to prevent the development of atherosclerosis in animal models . It has been hypothesized that the clinical benefits of ACE inhibitors may , therefore , be mediated by effects on atherosclerosis . METHODS Six hundred seventeen patients were r and omized in equal proportions to ramipril ( 5 - 10 mg daily ) or placebo . At baseline , two years and four years , carotid atherosclerosis was assessed by B-mode ultrasound , and left ventricular mass was assessed by M-mode echocardiography . RESULTS Blood pressure ( BP ) was reduced by a mean of 6 mm Hg systolic and 4 mm Hg diastolic in the ramipril group compared with the placebo group ( p common carotid artery wall thickness ( p = 0.58 ) or in carotid plaque ( p = 0.93 ) . Left ventricular mass index decreased by 3.8 g/m2 ( 4 % ) in the ramipril group compared with the placebo group ( 2p = 0.04 ) . CONCLUSIONS The results provide no support for the hypothesis that reduced atherosclerosis is responsible for the beneficial effects of ACE inhibitors on major coronary events . It is more likely that the benefits are due to lower BP , reduced left ventricular mass or other factors such as reversal of endothelial dysfunction",
"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",
"BACKGROUND There is a pressing clinical requirement for an early simple test of severity in acute pancreatitis . We investigated the use of an assay of trypsinogen activation peptide ( TAP ) . METHODS We undertook a multicentre study in 246 patients ( 172 with acute pancreatitis [ 35 with severe disease ] , 74 controls ) . We assessed the predictive value of urinary TAP concentrations measured by a vali date d competitive immunoassay . We compared the results with those for plasma C-reactive protein and three clinicobiochemical scoring systems . TAP and C-reactive protein concentrations were analysed at set times after symptom onset and compared with the clinicobiochemical systems scores at key times during hospital stay . FINDINGS At 24 h after symptom onset , the median urinary TAP concentration was 37 nmol/L ( IQR 17 - 110 ) for severe and 15 nmol/L ( 5 - 35 ) for mild disease ( p plasma C-reactive protein were 24 mg/L ( 3 - 34 ) and 25 mg/L ( 6 - 75 ; p=0.208 ) . The sensitivity , specificity , positive predictive , and negative predictive values of the test to show severe acute pancreatitis compared with mild acute pancreatitis at 24 h were : for TAP ( > 35 nmol/L ) , 58 % , 73 % , 39 % , and 86 % , respectively , and for C-reactive protein ( > 150 mg/L ) , 0 % , 90 % , 0 % , and 75 % . 48 h after admission the values for the clinicobiochemical scoring systems were : APACHE II ( > or = 8) , 56 % , 64 % , 30 % , and 85 % ; Ranson score ( > or = 3 ) , 89 % , 64 % , 38 % , and 96 % ; and Glasgow score ( > or = 3 ) , 77 % , 75 % , 44 % , and 93 % . At 48 h , the values for C-reactive protein were 86 % , 61 % , 37 % , and 94 % and for TAP were 83 % , 72 % , 44 % , and 94 % . Combined testing of C-reactive protein and TAP was not superior to TAP alone for accuracy . INTERPRETATION Urinary TAP provided accurate severity prediction 24 h after onset of symptoms . This single marker of severity in acute pancreatitis deserves routine clinical application",
"OBJECTIVE The objective of this study was to examine the prevalence and correlates of postural hypotension ( defined as a drop in systolic blood pressure of greater than or equal to 20 mm Hg ) in a cohort of elderly persons with isolated systolic hypertension ( ISH ) . DESIGN Baseline cross-sectional analysis of the 4,736 persons r and omized in the Systolic Hypertension in the Elderly Program ( SHEP ) . SETTING A r and omized multi-center double-blind outpatient clinical trial of the impact of treating ISH . PARTICIPANTS Men and women age greater than or equal to 60 years with the systolic blood pressure ( SBP ) greater than or equal to 160 mm Hg and diastolic blood pressure ( DBP ) less than 90 mm Hg . MEASURES Medical histories were obtained using interviewer-administered , st and ardized clinical history forms . At entry into the study , seated and st and ing BP was measured by certified BP technicians using a r and om zero sphygmomanometer . Postural hypotension ( PH ) was assessed at 1 and 3 minutes after the participant arose from a seated position . MAIN RESULTS PH was found in 10.4 % of participants at 1 minute and in 12.0 % of participants at 3 minutes . 5.3 % of participants demonstrated PH at both time intervals while 17.3 % demonstrated PH at either or both of the time intervals . Factors significantly ( P less than 0.05 ) associated with the presence of PH were higher mean SBP and a lower mean body mass index . CONCLUSIONS Somewhat different persons were defined as having PH based upon the 1 minute and 3 minute st and ing measures of BP , and prevalence estimates of PH can vary depending on whether one or more intervals of measurement are used . Cross-sectional data analysis indicated that PH , in healthy community-dwelling older persons with ISH , may not be associated with a history of disorders or problems usually thought to be related to PH . However , prospect i ve data are needed to determine the prognostic significance of PH , and whether one or multiple measurements carry more significance",
"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",
"Background The Sc and inavian C and esartan Acute Stroke Trial ( SCAST ) showed no beneficial clinical effects of blood pressure lowering with the angiotensin receptor blocker c and esartan in the acute phase of stroke . In the present analysis we wanted to see if the effects of blood pressure lowering are harmful in the subgroup of patients with carotid artery stenosis . Methods SCAST was a r and omized- and placebo-controlled , double-masked trial of 2029 patients with acute stroke and high systolic blood pressure ( ≥140 mmHg ) . Of 1733 patients with ischemic stroke 993 underwent carotid artery imaging , and the degree of stenosis was categorized as no/insignificant ( 0–49 % , n = 806 ) , moderate ( 50–69 % , n = 97 ) or severe ( = 70 % , n = 90 ) . The trial 's two co- primary effect variables were the composite end-point of vascular death , stroke or myocardial infa rct ion , and functional outcome at six-months , according to the modified Rankin Scale . Results Among patients with moderate or severe carotid artery stenosis the vascular end-point occurred in 9 of 87 patients ( 10·3 % ) treated with c and esartan and in 17 of 100 controls ( 17·0 % ) , and there was no evidence of a different risk in patients with severe stenosis ( adjusted hazard ratio 0·74 , 95 % confidence interval 0·28–1·96 , P = 0·54 ) . For functional outcome there was also no clear difference , although in patients with severe stenosis the risk of a poor outcome was somewhat higher than in any of the other groups ( adjusted odds ratio 2·24 , 95 % confidence interval 0·71–7·09 , P = 0·16 ) . Progressive stroke also occurred more often in patients with carotid artery stenosis treated with c and esartan ( 10 of 87 patients ( 11·5 % ) vs. 4 of 100 patients ( 4·0 % ) ) , with a trend towards an increased risk with increasing severity of stenosis ( P-value for linear trend = 0·04 ) . Conclusions There is no clear evidence that the effect of c and esartan is qualitatively different in patients with carotid artery stenosis , but there are signals that patients with severe stenosis are at particularly high risk of stroke progression and poor functional outcome",
"The Renoprotection of Optimal Antiproteinuric Doses ( ROAD ) study was performed to determine whether titration of benazepril or losartan to optimal antiproteinuric doses would safely improve the renal outcome in chronic renal insufficiency . A total of 360 patients who did not have diabetes and had proteinuria and chronic renal insufficiency were r and omly assigned to four groups . Patients received open-label treatment with a conventional dosage of benazepril ( 10 mg/d ) , individual uptitration of benazepril ( median 20 mg/d ; range 10 to 40 ) , a conventional dosage of losartan ( 50 mg/d ) , or individual uptitration of losartan ( median 100 mg/d ; range 50 to 200 ) . Uptitration was performed to optimal antiproteinuric and tolerated dosages , and then these dosages were maintained . Median follow-up was 3.7 yr . The primary end point was time to the composite of a doubling of the serum creatinine , ESRD , or death . Secondary end points included changes in the level of proteinuria and the rate of progression of renal disease . Compared with the conventional dosages , optimal antiproteinuric dosages of benazepril and losartan that were achieved through uptitration were associated with a 51 and 53 % reduction in the risk for the primary end point ( P = 0.028 and 0.022 , respectively ) . Optimal antiproteinuric dosages of benazepril and losartan , at comparable BP control , achieved a greater reduction in both proteinuria and the rate of decline in renal function compared with their conventional dosages . There was no significant difference for the overall incidence of major adverse events between groups that were given conventional and optimal dosages in both arms . It is concluded that uptitration of benazepril or losartan against proteinuria conferred further benefit on renal outcome in patients who did not have diabetes and had proteinuria and renal insufficiency",
"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",
"BACKGROUND Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke . In addition , inhibition of the renin-angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events , including stroke . However , the effect of lowering of blood pressure with a renin-angiotensin system inhibitor soon after a stroke has not been clearly established . We evaluated the effects of therapy with an angiotensin-receptor blocker , telmisartan , initiated early after a stroke . METHODS In a multicenter trial involving 20,332 patients who recently had an ischemic stroke , we r and omly assigned 10,146 to receive telmisartan ( 80 mg daily ) and 10,186 to receive placebo . The primary outcome was recurrent stroke . Secondary outcomes were major cardiovascular events ( death from cardiovascular causes , recurrent stroke , myocardial infa rct ion , or new or worsening heart failure ) and new-onset diabetes . RESULTS The median interval from stroke to r and omization was 15 days . During a mean follow-up of 2.5 years , the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group . A total of 880 patients ( 8.7 % ) in the telmisartan group and 934 patients ( 9.2 % ) in the placebo group had a subsequent stroke ( hazard ratio in the telmisartan group , 0.95 ; 95 % confidence interval [ CI ] , 0.86 to 1.04 ; P=0.23 ) . Major cardiovascular events occurred in 1367 patients ( 13.5 % ) in the telmisartan group and 1463 patients ( 14.4 % ) in the placebo group ( hazard ratio , 0.94 ; 95 % CI , 0.87 to 1.01 ; P=0.11 ) . New-onset diabetes occurred in 1.7 % of the telmisartan group and 2.1 % of the placebo group ( hazard ratio , 0.82 ; 95 % CI , 0.65 to 1.04 ; P=0.10 ) . CONCLUSIONS Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke , major cardiovascular events , or diabetes . ( Clinical Trials.gov number , NCT00153062 .",
"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 ",
"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",
"We have tested the concept that fewer patients are needed in trials of antihypertensive treatment if blood pressure is measured by ambulatory monitoring rather than by conventional sphygmomanometry . 233 patients ( > or = 60 years old ) with isolated systolic hypertension were r and omly allocated placebo ( n = 119 ) or active treatment ( n = 114 ) . Blood pressure measurements were compared by Wilcoxon 's test and blood pressure profiles by ANOVA . With either method of measurement , the same number of patients ( 40 in each treatment group ) was required to show a reduction after 1 year in clinic ( 13/8 mm Hg ) or average blood pressure over 24 h ( 9/5 mm Hg ) . To detect that the decrease in systolic pressure was not steadily maintained through the day , 40 patients in each treatment group were needed for blood pressure profiles made up of 4-hourly or 2-hourly means and 60 for profiles of 1-hourly means . For diastolic pressure , the corresponding numbers were 80 , 100 , and more than the number of available patients , respectively . We conclude that parallel-group trials focusing on the average blood pressure over 24 h , rather than on conventionally measured blood pressure , can not economise on sample size . Moreover , trials study ing the full course of blood pressure throughout the day , require more -- not fewer-- patients than studies of only the conventional or average 24 h blood pressure",
"BACKGROUND Little information has been published on the impact of antihypertensive medications on quality of life in older persons . Particular concern has existed that lowering systolic blood pressure in older persons might have adverse consequences on cognition , mood , or leisure activities . METHODS A multicenter double-blind r and omized controlled trial was conducted over an average of 5 years ' followup involving 16 academic clinical trial clinics . Participants consisted of 4736 persons ( 1.06 % ) selected from 447,921 screenees aged 60 years and older . Systolic blood pressure at baseline ranged from 160 to 219 mm Hg , while diastolic blood pressure was less than 90 mm Hg . Participants were r and omized to active antihypertensive drug therapy or matching placebo . Active treatment consisted of 12.5 to 25 mg of chlorthalidone for step 1 , while step 2 consisted of 25 to 50 mg of atenolol . If atenolol was contraindicated , 0.05 to 0.10 mg of reserpine could be used for the second-step drug . The impact of drug treatment on measures of cognitive , emotional , and physical function and leisure activities was assessed . RESULTS Our analyses demonstrate that active treatment of isolated systolic hypertension in the Systolic Hypertension in the Elderly Program cohort had no measured negative effects and , for some measures , a slight positive effect on cognitive , physical , and leisure function . The positive findings in favor of the treatment group were small . There was no effect on measures related to emotional state . Measures of cognitive and emotional function were stable in both groups for the duration of the study . Both treatment groups showed a modest trend toward deterioration of some measures of physical and leisure function over the study period . CONCLUSIONS The overall study cohort exhibited decline over time in activities of daily living , particularly the more strenuous ones , and some decline in certain leisure activities . However , mood , cognitive function , basic self-care , and moderate leisure activity were remarkably stable for both the active and the placebo groups throughout the entire study . Results of this study support the inference that medical treatment of isolated systolic hypertension does not cause deterioration in measures of cognition , emotional state , physical function , or leisure activities",
"Adverse treatment effects were assessed in 840 elderly hypertensive patients r and omly assigned to active treatment ( a combination of triamterene and hydrochlorothiazide ) or placebo ; methyldopa was added to the regimen in one third of the treated patients . Symptoms of dry mouth , nasal stuffiness , and diarrhea were reported by significantly more treated patients than placebo control subjects . More patients receiving diuretics plus methyldopa than diuretics alone reported dry mouth and diarrhea . Significantly more treated patients than control subjects showed evidence of a high serum creatinine level , mild hypokalemia , and gout . More treated patients tended to have diabetes . The benefits of treatment outweighed these adverse treatment effects",
"Long-term effects of antihypertensive treatment on various electrocardiogram ( ECG ) voltages and the association between ECG findings at r and omization and subsequent mortality were evaluated in the double-blind , placebo-controlled trial of elderly hypertensive patients , conducted by the European Working Party on High Blood Pressure in the Elderly ( EWPHE ) . Patients were treated with a combination of hydrochlorothiazide and triamterene or matching placebo ; methyldopa or placebo was added if blood pressures remained high . RaVL and SV1 + RV5 at r and omization were related to systolic blood pressure ( SBP ) and RaVL was also related to diastolic blood pressure ( DBP ) , after adjustment for age , gender , and body mass index ( BMI ) . When adjusted for age and body mass index , the decreases in RaVL and SV1 + RV5 were not correlated with the changes in SBP after 1 year of active treatment but the decreases in SV1 + RV5 were positively related to the fall in DBP . After 4 years of active treatment , the fall in SBP was associated with decreases in RaVL and in SV1 + RV5 , after adjustment for age and changes in BMI",
"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",
"This study compares blood pressure ( BP ) changes during active antihypertensive treatment and placebo as assessed by conventional and ambulatory BP measurement . Older patients ( > or = 60 years , n=337 ) with isolated systolic hypertension by conventional sphygmomanometry at the clinic were r and omized to placebo or active treatment consisting of nitrendipine ( 10 to 40 mg/d ) , with the possible addition of enalapril ( 5 to 20 mg/d ) and /or hydrochlorothiazide ( 12.5 to 25 mg/d ) . At baseline , clinic systolic/diastolic BP averaged 175/86 mm Hg and 24-hour and daytime ambulatory BPs averaged 148/80 and 154/85 mm Hg , respectively . After 13 months ( median ) of active treatment , clinic BP had dropped by 22.7/7.0 mm Hg and 24-hour and daytime BPs by 10.5/4.5 and 9.7/4.3 mm Hg , respectively ( P mm Hg ) , 24-hour ( 2.1/1.1 mm Hg ) , and daytime ( 2.9/1.0 mm Hg ) BPs decreased also during placebo ( P daytime diastolic BP ) ; these decreases represented 43%/23 % , 20%/24 % , and 30%/23 % of the corresponding BP fall during active treatment . After subtraction of placebo effects , the net BP reductions during active treatment averaged only 12.9/5.4 , 8.3/3.4 , and 6.8/3.2 mm Hg for clinic , 24-hour , and daytime BPs , respectively . The effect of active treatment was also subject to diurnal variation ( P hourly systolic and diastolic BP means amounted to ( median ) 21 % ( range , -1 % to 42 % ) and 25 % ( -3 % to 72 % ) , respectively , of the corresponding changes during active treatment . In conclusion , expressed in millimeters of mercury , the effect of antihypertensive treatment on BP is larger with conventional than with ambulatory measurement . Regardless of whether BP is measured by conventional sphygmomanometry or ambulatory monitoring , a substantial proportion of the long-term BP changes observed during active treatment may be attributed to placebo effects . Thus , ambulatory monitoring uncorrected for placebo or control observations , like conventional sphygmomanometry , overestimates BP responses in clinical trials of long duration ",
"Context Previously published results of this r and omized , double-blind trial showed that high-risk patients with type 2 diabetic nephropathy had better renal protection if they were treated with irbesartan rather than amlodipine in addition to conventional antihypertensive therapy . Contribution These detailed analyses showed no differences in overall cardiovascular outcomes between patients given irbesartan or amlodipine . Fewer patients given irbesartan had heart failure and fewer patients given amlodipine had heart attacks . Caution s The trial had limited power to detect important differences between groups in mortality or strokes , and most patients received several antihypertensive agents . The Editors Patients with diabetes have an increased risk for cardiovascular complications and death ( 1 ) . Studies that analyzed the effects of inhibition of the reninangiotensin system on the risk for cardiovascular complications included a substantial number of patients with diabetes ( 2 - 5 ) or were done exclusively in patients with diabetes ( 6 - 8 ) . The meta- analysis of these studies ( 9 ) , the analysis of the diabetic cohorts in the Heart Outcomes Prevention Evaluation ( HOPE ) study ( 2 ) , and the Losartan Intervention for Endpoint Reduction in Hypertension ( LIFE ) trial ( 5 ) demonstrated that angiotensin-converting enzyme ( ACE ) inhibitors ( 2 , 9 ) and angiotensin-receptor blockers ( 5 ) had a statistically significant advantage over placebo or alternative agents in decreasing the risk for several cardiovascular events . These studies r and omly assigned few patients with renal involvement and overt proteinuria . Overt proteinuria occurred in fewer than 20 % of the 470 patients in the Appropriate Blood Pressure Control in Diabetes ( ABCD ) trial ( 6 ) , and only 11 % of the 1195 patients in the LIFE trial ( 5 ) . The Captopril Prevention Project ( CAPP ) ( 3 ) and the Swedish Trial in Old Patients with Hypertension-2 ( STOP Hypertension-2 ) ( 4 ) did not state the number of patients with diabetes and overt proteinuria . There were no such patients in the Fosinopril versus Amlodipine Cardiovascular Events Trial ( FACET ) ( 7 ) , and patients with dipstick-positive albuminuria were excluded from the HOPE trial ( 2 ) . Since proteinuria is an independent risk factor for cardiovascular disease ( 10 , 11 ) , the data obtained in the aforementioned trials can not be extrapolated to patients with type 2 diabetes and overt nephropathy . Trials performed in such patients have reported a blood pressureindependent effect of two different angiotensin-receptor blocker agents to protect against nephropathy ( 12 , 13 ) without a change in all-cause mortality . Apart from studies in heart failure , few cardiovascular data exist for receptor blockers compared with either placebo or calcium-channel blockers . We report on the analysis of the cardiovascular end points that were monitored as secondary end points in the Irbesartan Diabetic Nephropathy Trial ( IDNT ) ( 12 ) and assess whether an angiotensin II receptor blocker or a calcium-channel blocker alters the risk for cardiovascular events beyond those observed by blood pressure reduction alone without such agents . Methods Patients The IDNT was a r and omized , double-blind study on the effect of treatment with irbesartan or amlodipine compared with placebo in patients with type 2 diabetic nephropathy . The protocol of this study has been published ( 12 , 14 ) . Entry criteria required that patients be between 30 and 70 years of age and have type 2 diabetes mellitus and overt nephropathy , as evidence d by current treatment for hypertension or by a protein excretion rate of 900 mg/d or greater , serum creatinine level of 89 mol/L ( 1.0 mg/dL ) to 266 mol/L ( 3.0 mg/dL ) in women or of 106 mol/L ( 1.2 mg/dL ) to 266 mol/L ( 3.0 mg/dL ) in men , and baseline seated blood pressure greater than 135/85 mm Hg . The institutional review boards of each center approved the protocol . All patients gave written informed consent . Treatment and R and omization Patients were r and omly assigned central ly by computer to receive treatment with irbesartan , 300 mg/d ( Avapro , Bristol-Myers Squibb , Princeton , New Jersey ) ; amlodipine , 10 mg/d ( Norvasc , Pfizer , New York ) ; or matched placebo . To minimize any center effect , r and omization was blocked by center . All patients had blood pressure controlled to the same blood pressure goal of less than 135/85 mm Hg by using antihypertensive agents other than ACE inhibitors , angiotensin II receptor blocking agents , or calcium-channel blockers . For the analysis of cardiovascular end points , patients were followed to initiation of treatment for end-stage renal failure ( dialysis or renal transplantation ) , reaching a serum creatinine level of 530.4 mol/L ( 6.0 mg/dL ) or higher , death , or administrative censoring in December 2000 . Outcomes We prospect ively established cardiovascular outcomes , defined in the Appendix Table . Appendix Table . Classification for Fatal and Nonfatal Cardiovascular Events Ascertainment of Cardiovascular Events Information about hospitalizations and adverse events were screened at Bristol-Myers Squibb , Princeton , New Jersey , by trained , blinded clinical research associates to identify potential cardiovascular events . Investigators used study forms to report and characterize all cardiovascular outcomes . For all potential events , records , including laboratory values , electrocardiograms , and radiographic reports were obtained for clarification . Since myocardial infa rct ions may go unrecognized , a central electrocardiogram reading center was established at Brigham and Women 's Hospital , Boston , Massachusetts , where two cardiologists review ed every electrocardiogram . Electrocardiography was performed at baseline , 6 months , 12 months , and annually thereafter . A total of 5698 electrocardiograms were review ed at the center . When a new Q-wave infa rct ion was found , the cardiologists asked whether a clinical myocardial infa rct ion was reported . Even when myocardial infa rct ions were not clinical ly reported , these Q-wave infa rct ions were adjudicated as myocardial infa rct ions . Adjudication of Cardiovascular Events Investigators at each center reported cardiovascular events , defined in the Appendix Table . The information on all potential events was referred to one member of the Outcomes Confirmation and Classification Committee ( Appendix ) . If the committee member agreed with the judgment of the center investigator , their combined judgment was accepted . If the center investigator and the committee member differed , the case material was review ed by the membership of the committee , whose decision was accepted . Deaths were adjudicated by a Mortality Committee ( Appendix ) . Each death was review ed by two members of the committee and presented to the membership , whose decision was accepted as final . Statistical Analysis For graphical presentation ( Figure ) and overall testing for statistically significant differences among the three treatment groups , time to the first occurrence of either a specific cardiovascular outcome or one of the composite outcomes was analyzed by product-limit survival curves and the log-rank test ( 15 ) . We used proportional hazards modeling to determine hazard ratios . For the cardiovascular death outcome , which could occur only once , we used the st and ard proportional hazards model ( 16 ) , with treatment assignment as the only independent covariate . For other cardiovascular outcomes , which could occur more than once , we used the And ersonGill formulation of the proportional hazards model ( 17 ) , in which patients are considered at risk for the first event from r and omization to the first event , at risk for the second event from the day following the first event to the second event , and so forth , permitting use of all the data . In accordance with the method of Lee and colleagues ( 18 ) , we used a robust variance estimate that accounts for the possibility of correlation of risk for several events within a patient . We believed that occurrence of a first event of a given type increases the likelihood of a subsequent similar event . Therefore , both treatment assignment and a time-dependent covariate indicating whether the event was the first of its type or a subsequent event were included in these analyses . The time-dependent covariate was statistically significant in each case , confirming the above assumption . There was no statistically significant interaction between treatment and the time-dependent covariatethe effects of treatment assignment were similar for first and subsequent events and inclusion of the time-dependent covariate did not change either the estimates of the treatment effect or their statistical significance s. Figure . Time to first cardiovascular composite event as a function of treatment assignment . P Data management and computations were done by using SAS software for Windows , version 8 ( SAS Institute , Inc. , Cary , North Carolina ) , or S-Plus for Windows , version 6.0 ( Insightful Corp. , Seattle , Washington ) . Statistical tests were two sided . A P value of 0.05 or less , unadjusted for the multiple comparisons , was considered statistically significant . Role of the Funding Sources The funding sources were involved in the data collection but not in the analysis or interpretation or the decision to su bmi t the manuscript for publication . Results The baseline characteristics of the three groups are shown in Table 1 . A flow diagram of the study is shown in the Appendix Figure . Table 1 . Baseline Characteristics Appendix Figure . Flow diagram for the Irbesartan Diabetic Nephropathy Trial . Clinical Management During the study , the blood pressure decreased from the baseline values to 140/77 mm Hg in the irbesartan group , 141/77 mm Hg in the amlodipine group , and 144/80 mm Hg in the placebo group . Blood pressure in the two active treatment groups did not differ ; values in both groups were statistically significantly lower than in the placebo group ( P = 0.001 ) . The distribution of non study drugs used to achieve the target blood pressure was similar",
"Because many r and omized clinical trials study more than one important outcome variable , evaluation of efficacy is often difficult and not completely satisfactory . This paper considers the use of a procedure for endpoint determination described by Follmann et al. , that allows raters to integrate subjectively all relevant information about an individual 's clinical course into a single univariate assessment . To explore the method 's feasibility , we tested the procedure with data from a completed clinical trial , the Systolic Hypertension in the Elderly Program ( SHEP ) . We provided raters blinded to treatment assignment with cards that schematically represent the clinical trajectories of SHEP study participants . The raters independently ranked these trajectories . The method combined ranks across raters to determine a single rank for each study participant ; we used a rank procedure to test treatment effect . The major findings were : ( i ) the raters showed a high level of concordance of rankings ; ( ii ) tests of treatment effect were highly statistically significant ; ( iii ) three statistical methods were effective for implementing the ranking in the large study size case . These methods were use of : ( a ) scoring rules ; ( b ) incomplete block design s , and ( c ) categorical ranking",
"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",
"Summary The Hypertension in the Very Elderly Trial ( HYVET ) is a multicentre , open , r and omised , controlled trial . The aim of this trial is to investigate the effect of active treatment on stroke incidence in hypertensive patients over the age of 80 years . Secondary end-points include total cardiovascular mortality and morbidity . Entry criteria include a sustained sitting systolic blood pressure of 160 to 219 mm Hg plus a sustained sitting diastolic pressure of 95 to 109 mm Hg . Also required is a st and ing systolic blood pressure of at least 140 mm Hg . Patients must give their informed consent , and be free of congestive heart failure requiring treatment , gout , renal failure or a recent cerebral haemorrhage . Patients are to be r and omised to 3 groups — ( i ) no treatment ; ( ii ) treatment with a diuretic [ bendroflumethiazide ( bendrofluazide ) ] ; or ( iii ) treatment with an angiotensin converting enzyme ( ACE ) inhibitor (lisinopril).Starting dosage for bendroflumethiazide and lisinopril is 2.5 mg/day . In order to achieve goal sitting systolic and diastolic blood pressures ( diltiazem ( 120 mg/day increasing to 240 mg/day if required ) may be added to the medication of the actively treated groups . These drugs have been chosen as inexpensive and appropriate representatives of their therapeutic classes.700 patients in each group ( a total of 2100 ) will be sufficient to detect a 40 % difference in cerebrovascular events between no treatment and active treatment ( α = 0.01 , 1−β = 0.90 ) . These numbers will also detect a difference in total mortality of 25 % and in cardiovascular mortality of 35%.The pilot phase of the trial has been started with support from the British Heart Foundation . Centres which are interested in taking part should contact C. J. Bulpitt or any of the other authors",
"Background : Earlier angiographic studies have suggested that calcium antagonists may prevent the formation of new coronary lesions and the progression of minimal lesions . Conversely , a meta- analysis suggested that these drugs may increase cardiovascular mortality and morbidity in patients with coronary heart disease . Objective : To investigate whether nisoldipine retards the progression of coronary atherosclerosis or reduces the occurrence of clinical events . Design and setting : The NICOLE study ( NIsoldipine in COronary artery disease in LEuven ) is a single centre , r and omised , double blind , placebo controlled trial with coronary angiography at baseline , six months , and three years of follow up . Patients : 826 patients who had undergone successful coronary angioplasty were r and omised to nisoldipine 40 mg once daily or placebo . The intention to treat and per protocol population consisted of 819 and 578 patients , respectively . Results : In the per protocol population , 625 of the nisoldipine treated and 655 of the placebo treated patients ( NS ) showed angiographic progression in at least one coronary arterial segment , defined as an increase in diameter stenosis of ≥ 13 % . The average minimum luminal diameter of the non-dilated lesions decreased by 0.163 mm and 0.167 mm in the nisoldipine and placebo groups , respectively ( NS ) . The respective numbers of new lesions detected were 7 and 13 ( NS ) . In the intention to treat population , the rates of death , stroke , and acute myocardial infa rct ion were similar in both treatment groups . However , nisoldipine use was associated with fewer revascularisation procedures and thus the percentage of patients with any clinical event was lower ( 44.6 % v 52.6 % , p = 0.02 ) . Conclusions : Nisoldipine has no demonstrable effect on the angiographic progression of coronary atherosclerosis or the risk of major cardiovascular events but its use is associated with fewer revascularisation procedures ",
"Results of the European Working Party on High Blood Pressure in the Elderly ( EWPHE ) trial have been analysed in relation to age , sex , blood pressure , and previous cardiovascular disease . Cardiovascular mortality and the cardiovascular study -terminating events were significantly and independently related to treatment , age , cardiovascular complications at r and omisation , and systolic but not diastolic blood pressure . The benefits of treatment observed in the trial seemed to be independent of entry blood pressure and the presence or absence of cardiovascular complications at entry . There was some evidence that treatment effect decreases with advancing age . Little or no benefit from treatment could be demonstrated in patients over the age of 80 years , the great majority of whom were women",
"This report from the double-blind placebo-controlled SYST-EUR trial investigated whether modern antihypertensive drugs are suitable for maintaining long-term BP control in older ( > or = 60 years of age ) subjects with isolated systolic hypertension ( SBP 160 - 219 mmHg and DBP Active treatment consisted of nitredipine ( 10 - 40 mg/day ) with the possible addition of enalapril ( 5 - 20 mg/day ) and hydrochlorothiazide ( 12.5 - 25 mg/day ) , if necessary to reduce SBP to or = 20 mmHg . Matching placebos were used in the control group . This analysis was restricted to 18 months of follow-up . The placebo ( n = 456 ) and active treatment ( n = 485 ) groups had similar characteristics at r and omisation ( sitting pressure 176/85 mmHg ; age 73 years ) . SBP fell ( P placebo and DBP 4 mmHg more . Fewer patients remained on monotherapy in the placebo than in the active treatment group ( P placebo the second and third line medications were started earlier ( P Nitrendipine tablets were discontinued in nine patients on placebo and in 29 patients assigned to active treatment ( P significant BP reduction can be achieved and maintained in older patients with isolated systolic hypertension treated with a calcium antagonist ( associated with a converting-enzyme inhibitor and a thiazide , where necessary ) . Whether this BP reduction results in a clinical ly meaningful decrease of cardiovascular complications is under investigation",
"The relation between serum cholesterol and mortality was investigated in 822 elderly hypertensive patients r and omly assigned to treatment with diuretics , with or without methyldopa , or placebo . Cox 's proportional hazards model showed that pretreatment serum total cholesterol levels were independently and inversely correlated with total mortality ( p = 0.03 ) , noncardiovascular mortality ( p = 0.02 ) , and cancer mortality ( p = 0.04 ) during treatment . Total and noncardiovascular mortality were also negatively correlated with pretreatment hemoglobin levels and body weight . All factors being equal , an increase in total serum cholesterol of 2.3 mmol/L was associated with a one-year prolongation of survival . After adjustment for gender , age , pretreatment cardiovascular complications , and systolic pressure , the correlations between serum cholesterol and cardiovascular and cardiac mortality were not significant",
"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 association of serum lipids with coronary heart disease has been studied extensively in middle-aged men and , to a lesser extent , in similar women . Less well defined are lipid variables predictive of CHD in individuals of age > or = 60 years . METHODS AND RESULTS The Systolic Hypertension in the Elderly Program recruited 4736 persons ( mean age , 72 years ; 14 % were black ; and 43 % were men ) . Mean systolic and diastolic blood pressures were 170 and 77 mm Hg , respectively . Baseline mean total cholesterol was 6.11 mmol/L ( 236 mg/dL ) ; HDL cholesterol , 1.39 mmol/L ( 54 mg/dL ) ; and non-HDL cholesterol , 4.72 mmol/L ( 182 mg/dL ) . Triglyceride levels were 1.62 mmol/L ( 144 mg/dL ) for fasting participants and 1.78 mmol/L for the total group . LDL cholesterol , estimated in fasting sample s with triglycerides of baseline total , non-HDL , and LDL cholesterol levels and the ratios of total , non-HDL , and LDL to HDL cholesterol were significantly related to CHD incidence . HDL cholesterol and triglycerides were not significant in these analyses . In fasting participants with triglyceride levels of total , non-HDL , or LDL cholesterol was associated with a 30 % to 35 % higher CHD event rate . CONCLUSIONS The results of this study support the concept that serum lipids are CHD risk factors in older Americans",
"BACKGROUND Treatment with angiotensin-converting-enzyme ( ACE ) inhibitors reduces the rate of cardiovascular events among patients with left-ventricular dysfunction and those at high risk of such events . We assessed whether the ACE inhibitor perindopril reduced cardiovascular risk in a low-risk population with stable coronary heart disease and no apparent heart failure . METHODS We recruited patients from October , 1997 , to June , 2000 . 13655 patients were registered with previous myocardial infa rct ion ( 64 % ) , angiographic evidence of coronary artery disease ( 61 % ) , coronary revascularisation ( 55 % ) , or a positive stress test only ( 5 % ) . After a run-in period of 4 weeks , in which all patients received perindopril , 12218 patients were r and omly assigned perindopril 8 mg once daily ( n=6110 ) , or matching placebo ( n=6108 ) . The mean follow-up was 4.2 years , and the primary endpoint was cardiovascular death , myocardial infa rct ion , or cardiac arrest . Analysis was by intention to treat . FINDINGS Mean age of patients was 60 years ( SD 9 ) , 85 % were male , 92 % were taking platelet inhibitors , 62 % beta blockers , and 58 % lipid-lowering therapy . 603 ( 10 % ) placebo and 488 ( 8 % ) perindopril patients experienced the primary endpoint , which yields a 20 % relative risk reduction ( 95 % CI 9 - 29 , p=0.0003 ) with perindopril . These benefits were consistent in all predefined subgroups and secondary endpoints . Perindopril was well tolerated . INTERPRETATION Among patients with stable coronary heart disease without apparent heart failure , perindopril can significantly improve outcome . About 50 patients need to be treated for a period of 4 years to prevent one major cardiovascular event . Treatment with perindopril , on top of other preventive medications , should be considered in all patients with coronary heart disease",
"Ventricular ectopic activity was recorded at baseline in 5.6 % of the 12-lead electrocardiograms and 8.2 % of the 2-minute rhythm strips of 4674 subjects with isolated systolic hypertension ( systolic blood pressure 160 to 219 mm Hg , diastolic blood pressure In this study 1.3 % had 6 to 10 ventricular premature beats ( VPB ) , and 0.7 % had > 10 VPB on the 2-minute rhythm strip . Correlates of VPB presence on the 12-lead ECG were older-age male sex , presence of Q/QS pattern and higher heart rate . Participants with serum potassium prevalence of VPB . Similarly , the number of VPB on the 2-minute rhythm strip was associated with male sex , increasing age , with lower serum potassium , history of palpitations , and presence of Q/QS patterns",
"The Systolic Hypertension in the Elderly Program ( SHEP ) Pilot Study was conducted to determine the feasibility of conducting a long-term placebo-controlled r and omized clinical trial in elderly subjects . Enrolled in the study were 551 men and women between the ages of 60 and 90 years with isolated systolic hypertension ( SBP greater than or equal to 160 mmHg and DBP less than 90 mmHg ) . The study showed that it is possible to recruit old and very old subjects into a clinical trial ; the elderly are good compliers ( drugs and follow-up visits ) , with some decline after the age of 80 ; control of blood pressure was accomplished in the large majority of patients ; evaluation of side effects represents a potential problem as varied complaints increase with age thus creating difficulties in distinguishing those attributed to the study drug ; and finally , cause-specific mortality is probably preferable to all-cause mortality as an end-point in prevention trials of antihypertensive regimens",
"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",
"BACKGROUND Angiotensin-converting-enzyme ( ACE ) inhibitors are effective in reducing the risk of heart failure , myocardial infa rct ion , and death from cardiovascular causes in patients with left ventricular systolic dysfunction or heart failure . ACE inhibitors have also been shown to reduce atherosclerotic complications in patients who have vascular disease without heart failure . METHODS In the Prevention of Events with Angiotensin Converting Enzyme Inhibition ( PEACE ) Trial , we tested the hypothesis that patients with stable coronary artery disease and normal or slightly reduced left ventricular function derive therapeutic benefit from the addition of ACE inhibitors to modern conventional therapy . The trial was a double-blind , placebo-controlled study in which 8290 patients were r and omly assigned to receive either tr and olapril at a target dose of 4 mg per day ( 4158 patients ) or matching placebo ( 4132 patients ) . RESULTS The mean ( + /-SD ) age of the patients was 64+/-8 years , the mean blood pressure 133+/-17/78+/-10 mm Hg , and the mean left ventricular ejection fraction 58+/-9 percent . The patients received intensive treatment , with 72 percent having previously undergone coronary revascularization and 70 percent receiving lipid-lowering drugs . The incidence of the primary end point -- death from cardiovascular causes , myocardial infa rct ion , or coronary revascularization -- was 21.9 percent in the tr and olapril group , as compared with 22.5 percent in the placebo group ( hazard ratio in the tr and olapril group , 0.96 ; 95 percent confidence interval , 0.88 to 1.06 ; P=0.43 ) over a median follow-up period of 4.8 years . CONCLUSIONS In patients with stable coronary heart disease and preserved left ventricular function who are receiving \" current st and ard \" therapy and in whom the rate of cardiovascular events is lower than in previous trials of ACE inhibitors in patients with vascular disease , there is no evidence that the addition of an ACE inhibitor provides further benefit in terms of death from cardiovascular causes , myocardial infa rct ion , or coronary revascularization",
"Syst-Eur is a multicentre placebo-controlled outcome trial , design ed by the European Working Party on High Blood Pressure in the Elderly ( EWPHE ) , to investigate the effect of antihypertensive treatment on the incidence of stroke in elderly patients with isolated systolic hypertension ( ISH ) . Eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160 - 219 mmHg with a diastolic blood pressure less than 95 mmHg . The present paper in an interim report on the first 316 patients r and omized into this trial . The placebo ( N = 170 ) and active treatment ( N = 146 ) groups were similar at r and omization with respect to age ( 73 + /- 8 years ; mean + /- st and ard deviation ) , sitting blood pressure ( 178 + /- 12/85 + /- 7 mmHg ) , percentage men ( 34 % ) and percentage of patients with cardiovascular complications ( 29 % ) . After r and omization blood pressure fell more ( p sitting blood pressure ) . This first interim report on the Syst-Eur trial demonstrates that a multinational trial in elderly patients with ISH is feasible and that a significant blood pressure difference between the 2 treatment groups can be achieved and maintained . New centres are being recruited in order to r and omize a total of 3,000 patients",
" Elderly hypertensive patients were r and omly assigned to treatment with diuretics and methyldopa ( n = 352 ) or placebo ( n = 339 ) , and divided into three groups , each according to their blood pressures , after nine months of treatment . Subsequently , 65 placebo patients and 56 treated patients died . A U-shaped relation was seen in treated patients between mortality and systolic blood pressure , and in placebo patients between mortality and diastolic blood pressure . Whereas in treated patients , the highest mortality was seen in patients with the lowest diastolic pressure , the lowest mortality was seen in the group with the highest diastolic pressure . The increased mortality in treated patients with the lowest blood pressure may not be drug-induced , but an expression of deterioration in general health , as indicated by the decreases in body weight and hemoglobin levels found in patients with the lowest blood pressures in previous analyses of these data",
"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",
" Orthostatic fall in blood pressure in the very elderly hypertensive : results from the Hypertension in the Very Elderly Trial ( HYVET ) —",
"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",
"BACKGROUND In 1989 , the European Working Party on High Blood Pressure in the Elderly started the double-blind , placebo-controlled , Systolic Hypertension in Europe Trial to test the hypothesis that antihypertensive drug treatment would reduce the incidence of fatal and nonfatal stroke in older patients with isolated systolic hypertension . This report addresses whether the benefit of antihypertensive treatment varied according to sex , previous cardiovascular complications , age , initial blood pressure ( BP ) , and smoking or drinking habits in an intention-to-treat analysis and explores whether the morbidity and mortality results were consistent in a per- protocol analysis . METHODS After stratification for center , sex , and cardiovascular complications , 4695 patients 60 years of age or older with a systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg were r and omized . Active treatment consisted of nitrendipine ( 10 - 40 mg/d ) , with the possible addition of enalapril maleate ( 5 - 20 mg/d ) and /or hydrochlorothiazide ( 12.5 - 25 mg/d ) , titrated or combined to reduce the sitting systolic BP by at least 20 mm Hg , to below 150 mm Hg . In the control group , matching placebo tablets were employed similarly . RESULTS In the intention-to-treat analysis , male sex , previous cardiovascular complications , older age , higher systolic BP , and smoking at r and omization were positively and independently correlated with cardiovascular risk . Furthermore , for total ( P = .009 ) and cardiovascular ( P = .09 ) mortality , the benefit of antihypertensive drug treatment weakened with advancing age ; for total mortality ( P = .05 ) , the benefit increased with higher systolic BP at entry , while for fatal and nonfatal stroke ( P = .01 ) , it was most evident in nonsmokers ( 92.5 % of all patients ) . In the per protocol analysis , active treatment reduced total mortality by 24 % ( P = .05 ) , reduced all fatal and nonfatal cardiovascular end points by 32 % ( P all strokes by 44 % ( P = .004 ) , reduced nonfatal strokes by 48 % ( P = .005 ) , and reduced all cardiac end points , including sudden death , by 26 % ( P = .05 ) . CONCLUSIONS In elderly patients with isolated systolic hypertension , stepwise antihypertensive drug treatment , starting with the dihydropyridine calcium channel blocker nitrendipine , improves prognosis . The per- protocol analysis suggested that treating 1000 patients for 5 years would prevent 24 deaths , 54 major cardiovascular end points , 29 strokes , or 25 cardiac end points . The effects of antihypertensive drug treatment on total and cardiovascular mortality may be attenuated in very old patients",
"Five hundred and seven elderly hypertensive patients were followed for 1 year , 371 for 2 years and 270 for 3 years in a double-blind , r and omized , controlled trial in which they received either placebo or 25 - 50 mg hydrochlorothiazide and 50 - 100 mg of triamterene daily . One third of the active treatment group also received 250 mg to 2 g methyldopa daily . After 1 year the active treatment group had an average increase in fasting blood sugar of 2.5 mg/dl compared with an average fall of 1.4 mg/dl in the placebo group ( P = 0.01 ) . The increase in blood sugar 1 hour and 2 hours after 50 g oral glucose tended to be greater in the actively treated group but these increases did not achieve statistical significance . The effects of diuretic treatment were established after one year and did not increase further over the next 2 years . Overall there was an increase in fasting blood sugar of 5 mg/dl in the active treatment group which occurred mainly in the first year . The hyperglycaemic effect of diuretics appeared to be partly or wholly related to potassium loss since , in both groups , impairment of glucose tolerance was most marked in those in whom serum potassium decreased . The measures of blood sugar were also positively related to systolic pressure before and after treatment",
"OBJECTIVES To assess the risk of total and cardiovascular mortality in older adults with systolic hypertension and with a low ankle-arm index ( AAI ) as a marker of sub clinical peripheral arterial disease ( PAD ) . DESIGN Prospect i ve observational study PARTICIPANTS A subgroup of 1537 participants in the Systolic Hypertension in the Elderly Program ( SHEP ) were screened for lower extremity arterial disease using the AAI . Participants were evaluated at 4 years to determine vital status and cause of death . Total and cardiovascular disease ( CVD ) mortality rates were assessed in relationship to clinical CVD at baseline , cardiovascular risk factors and the presence of a low AAI ( sub clinical PAD ) . RESULTS Total mortality rates increased as the AAI decreased in those with and without clinical CVD at baseline . In those without clinical CVD at baseline , the presence of an AAI total mortality in men and 2.67 in women . Results were similar for CVD mortality and persisted after adjustment for cardiovascular risk factors including the presence of an abnormal electrocardiogram . CONCLUSIONS A low ankle arm-index predicted a two to three-fold increase in total and cardiovascular mortality in older adults with systolic hypertension of risk for incident cardiovascular disease . In this study of older adults with systolic hypertension , 19.7 % of the participants had sub clinical PAD . Risk factor modification could be targeted to older adults based on markers of asymptomatic atherosclerosis",
"Objective This long-term study investigated the widely accepted hypothesis that ambulatory pressure does not decrease in patients given placebo . Methods : One hundred and twelve older ( ±60 years ) out patients with isolated systolic hypertension were recruited . Treatment consisted of a placebo during a 3-month baseline period and long-term follow-up . Results : At baseline , on placebo treatment , clinic systolic/diastolic ( SBP/DBP ) blood pressure ( ±SD ) averaged 176±12/86±7 mmHg and 24-h SBP/DBP 151 ± 15/81 ± 10mmHg . These pressures were unaltered in 51 patients in whom the baseline measurements were repeated after a further month on placebo . After the 112 patients had received placebo for 1 year ( median ) , clinic SBP/DBP fell by 6.6±15.9 ( P (P=0.06)mmHg and 24-h SBP by 2.4±10.7mmHg ( P whereas 24-h DBP did not change significantly . The 24-h SBP decreased more with higher baseline level and longer follow-up ( 5–21 months ) . Conclusions : These findings in older patients with isolated systolic hypertension suggest that in long-term studies the ambulatory pressure may slightly but significantly decrease on a placebo . Like those using conventional sphygmomano-metry , long-term studies using non-invasive ambulatory monitoring require a placebo-controlled design",
"The Australian Therapeutic Trial in Mild Hypertension was a controlled trial in which mildly hypertensive patients , aged between 35 and 65 years ( diastolic blood pressure 95 - 109 ) were r and omly assigned to take antihypertensive drugs or matched placebos for periods of up to 6 years . The overall data showed that the treated group had a lower incidence of both death and of nonfatal cardiovascular events . The differences in the incidence of noncardiovascular deaths did not differ significantly between the two groups . Univariate analysis of possible prognostic factors at the time of entry into the study showed a higher incidence of trial endpoints -- mostly events due to ischemic heart disease and cerebrovascular disease -- in older subjects , men , cigarette smokers and those with higher systolic blood pressures , and in thinner subjects than in others . There was a lower incidence of these events in actively treated persons than in control subjects at each level of incidence of each covariate measured . Treatment benefit was greatest in persons with lower systolic blood pressures and lower serum cholesterol levels . Multivariate regression analyses confirmed that the incidence of trial endpoints increased with age and with systolic blood pressures . There was a higher incidence in smokers than in nonsmokers , especially in those with low body weights . Treatment benefited thin smokers most , and the effects of treatment seemed to be reduced in those with higher serum cholesterol levels . There was a substantial fall in blood pressure in many of the placebo group",
"BACKGROUND Renal function declines progressively in patients who have diabetic nephropathy , and the decline may be slowed by antihypertensive drugs . The purpose of this study was to determine whether captopril has kidney-protecting properties independent of its effect on blood pressure in diabetic nephropathy . METHODS We performed a r and omized , controlled trial comparing captopril with placebo in patients with insulin-dependent diabetes mellitus in whom urinary protein excretion was > or = 500 mg per day and the serum creatinine concentration was Blood-pressure goals were defined to achieve control during a median follow-up of three years . The primary end point was a doubling of the base-line serum creatinine concentration . RESULTS Two hundred seven patients received captopril , and 202 placebo . Serum creatinine concentrations doubled in 25 patients in the captopril group , as compared with 43 patients in the placebo group ( P = 0.007 ) . The associated reductions in risk of a doubling of the serum creatinine concentration were 48 percent in the captopril group as a whole , 76 percent in the subgroup with a baseline serum creatinine concentration of 2.0 mg per deciliter ( 177 mumol per liter ) , 55 percent in the subgroup with a concentration of 1.5 mg per deciliter ( 133 mumol per liter ) , and 17 percent in the subgroup with a concentration of 1.0 mg per deciliter ( 88.4 mumol per liter ) . The mean ( + /- SD ) rate of decline in creatinine clearance was 11 + /- 21 percent per year in the captopril group and 17 + /- 20 percent per year in the placebo group ( P = 0.03 ) . Among the patients whose base-line serum creatinine concentration was > or = 1.5 mg per deciliter , creatinine clearance declined at a rate of 23 + /- 25 percent per year in the captopril group and at a rate of 37 + /- 25 percent per year in the placebo group ( P = 0.01 ) . Captopril treatment was associated with a 50 percent reduction in the risk of the combined end points of death , dialysis , and transplantation that was independent of the small disparity in blood pressure between the groups . CONCLUSIONS Captopril protects against deterioration in renal function in insulin-dependent diabetic nephropathy and is significantly more effective than blood-pressure control alone",
"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",
"Abstract Aims /hypothesisThe renal and cardiovascular protective effects of angiotensin receptor blocker ( ARB ) remain controversial in type 2 diabetic patients treated with a contemporary regimen including an angiotensin converting enzyme inhibitor ( ACEI ) . Methods We examined the effects of olmesartan , an ARB , on primary composite outcome of doubling of serum creatinine , endstage renal disease and death in type 2 diabetic patients with overt nephropathy . Secondary outcome included composite cardiovascular outcomes , changes in renal function and proteinuria . R and omisation and allocation to trial group were carried out by a central computer system . Participants , caregivers , the people carrying out examinations and people assessing the outcomes were blinded to group assignment . Results Five hundred and seventy-seven ( 377 Japanese , 200 Chinese ) patients treated with antihypertensive therapy ( 73.5 % [ n = 424 ] received concomitant ACEI ) , were given either once-daily olmesartan ( 10–40 mg ) ( n = 288 ) or placebo ( n = 289 ) over 3.2 ± 0.6 years ( mean±SD ) . In the olmesartan group , 116 developed the primary outcome ( 41.1 % ) compared with 129 ( 45.4 % ) in the placebo group ( HR 0.97 , 95 % CI 0.75 , 1.24 ; p = 0.791 ) . Olmesartan significantly decreased blood pressure , proteinuria and rate of change of reciprocal serum creatinine . Cardiovascular death was higher in the olmesartan group than the placebo group ( ten vs three cases ) , whereas major adverse cardiovascular events ( cardiovascular death plus non-fatal stroke and myocardial infa rct ion ) and all-cause death were similar between the two groups ( major adverse cardiovascular events 18 vs 21 cases , all-cause deaths ; 19 vs 20 cases ) . Hyperkalaemia was more frequent in the olmesartan group than the placebo group ( 9.2 % vs 5.3 % ) . Conclusions /interpretationOlmesartan was well tolerated but did not improve renal outcome on top of ACEI . Trial registration : Clinical Trials.gov NCT00141453 Funding : The ORIENT study was supported by a research grant from Daiichi Sankyo",
"OBJECTIVES The purpose of this study was to investigate the effects of angiotensin II receptor blockers on the prevention of cardiovascular events in patients with coronary artery disease ( CAD ) . BACKGROUND Angiotensin II may contribute to the pathogenesis of CAD . Long-term clinical trials have shown that blockade of the renin-angiotensin system can reduce cardiovascular events in patients with acute myocardial infa rct ion complicated by heart failure . METHODS Patients with a history of coronary intervention and no significant coronary stenosis on follow-up angiography 6 months after intervention were r and omly assigned into a c and esartan group ( n = 203 ; baseline treatment plus c and esartan 4 mg/d ) or a control group ( n = 203 ; baseline treatment alone ) . The primary end point was a composite of revascularization , nonfatal myocardial infa rct ion , or cardiovascular death . The secondary end point was hospitalization for cardiovascular causes . RESULTS There were no changes in blood pressure and in other coronary risk factors in either group during a mean follow-up of 24 months . Primary end point risk was significantly lower in the c and esartan group ( n = 12 ) than in control group patients ( n = 25 ) ( P = .03 ) . C and esartan treatment reduced primary end point risk ( 5.9 % vs 12.3 % for control subjects ; relative risk , 0.47 ; 95 % CI , 0.24 to 0.93 ) . The incidence of all events including secondary end points and noncardiovascular death was significantly lower in the c and esartan group than in control group patients ( 23 vs 40 cases ) ( P = .02 ) . CONCLUSIONS Relatively low-dose c and esartan , which did not alter blood pressure levels , reduces cardiovascular risk in high-risk patients with CAD",
"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",
"& 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 One third of patients treated for hypertension attain adequate blood pressure ( BP ) control , and multidrug regimens are often required . Given the lifelong nature of hypertension , there is a need to evaluate the long-term efficacy and tolerability of higher doses of combination anti-hypertensive therapies . OBJECTIVE This study investigated the efficacy and tolerability of valsartan ( VAL ) or hydrochlorothiazide (HCTZ)-monotherapy and higher-dose combinations in patients with essential hypertension . METHODS The first part of this study was an 8-week , multicenter , r and omized , double-blind , placebo controlled , parallel-group trial . Patients with essential hypertension ( mean sitting diastolic BP [ MSDBP ] , > or = 95 mm Hg and were r and omized to 1 of 8 treatment groups : VAL 160 or 320 mg ; HCTZ 12.5 or 25 mg ; VAL/HCTZ 160/12.5 , 320/12.5 , or 320/25 mg ; or placebo . Mean changes in MSDBP and mean sitting systolic BP ( MSSBP ) were analyzed at the 8-week core study end point . VAL/HCTZ 320/12.5 and 320/25 mg were further investigated in a 54-week , open-label extension . Response was defined as MSDBP or = 10 mm Hg decrease compared to baseline . Control was defined as MSDBP Tolerability was assessed by monitoring adverse events at r and omization and all subsequent study visits and regular evaluation of hematology and blood chemistry . RESULTS A total of 1346 patients were r and omized into the 8-week core study ( 734 men , 612 women ; 924 white , 291 black , 23 Asian , 108 other ; mean age , 52.7 years ; mean weight , 92.6 kg ) . All active treatments were associated with significantly reduced MSSBP and MSDBP during the core 8-week study , with each monotherapy significantly contributing to the overall effect of combination therapy ( VAL and HCTZ , P reductions in MSSBP and MSDBP compared with the monotherapies and placebo ( all , P mean reduction in MSSBP/MSDBP with VAL/HCTZ 320/25 mg was 24.7/16.6 mm Hg , compared with 5.9/7.0 mm Hg with placebo . The reduction in MSSBP was significantly greater with VAL/HCTZ 320/25 mg compared with VAL/HCTZ 160/12.5 mg ( P Rates of response and BP control were significantly higher in the groups that received combination treatment compared with those that received monotherapy . The incidence of hypokalemia was lower with VAL/HCTZ combinations ( 1.8%-6.1 % ) than with HCTZ monotherapies ( 7.1%-13.3 % ) . The majority of adverse events in the core study were of mild to moderate severity . The efficacy and tolerability of VAL/HCTZ combinations were maintained during the extension ( 797 patients ) . CONCLUSIONS In this study population , combination therapies with VAL/HCTZ were associated with significantly greater BP reductions compared with either monotherapy , were well tolerated , and were associated with less hypokalemia than HCTZ alone",
"Summary 1 . A total of 450 hypertensive patients above the age of 60 years have entered the double-blind multicentre trial of the European Working Party on High blood pressure in Elderly ( EWPHE ) . After stratification and r and omization half were treated with one capsule daily containing 25 mg of hydrochlorothiazide and 50 mg of triamterene and half were given placebo . In those receiving active treatment , if blood pressure control was not adequate they were given a second capsule and if necessary up to 2 g of methyldopalday . 2 . No significant differences between the groups were present before r and omization . A significant blood pressure difference of 25/10 mmHg was obtained between the groups and maintained during 4 years of follow-up . No major disturbances in serum potassium or serum sodium were noted with the present drug combination . 3 . During the initial phase an increase in serum creatinine and serum uric acid was noted in the actively treated group , which was maintained during the later years . This increase in serum creatinine in the actively treated group was related ( P = 0.003 and r = -0.247 ) to the decrease in sitting systolic blood pressure . Changes in serum uric acid were ( r = 0.3 and P = 0 - 003 ) correlated with the changes in serum creatinine both in the placebo and in the actively treated group , but Correspondence : Professor Dr A. Amery , Hypertension and Cardiovascular Rehabilitation Unit , Academic Hospital , St Raphael , Kapucijnenvoer 35 , B-3000 Leuven , Belgium . independent of the change in creatinine ; the serum uric acid was on average 1 mg higher in the actively treated than in the placebo group . 4 . Fasting blood glucose did not change significantly in the placebo-treated group but in the active treatment group the rise was statistically signficant . 5 . A favourable influence on prognosis by active treatment can be expected on the basis of the blood pressure reduction and in the absence of major electrolytes disturbances . However , the balance between this decreased risk and the increased risk produced by the rise in blood glucose and the other treatment effects remains to be determined . Therefore the trial continues and more patients are being admitted",
"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",
"OBJECTIVE To determine the relationship between increasing depressive symptoms and cardiovascular events or mortality . DESIGN Cohort analytic study of data from r and omized placebo-controlled double-blind clinical trial of antihypertensive therapy . Depressive symptoms were assessed semi-annually with the Center for Epidemiological Studies -Depression ( CES-D ) scale during an average follow-up of 4.5 years . SETTING Ambulatory patients in 16 clinical centers of the Systolic Hypertension in the Elderly Program . PATIENTS Generally healthy men and women aged 60 years or older r and omized to active antihypertensive drug therapy or placebo who were 70 % white and 53 % women and had follow-up CES-D scores and no outcome events during the first 6 months ( N=4367 ) . MAIN OUTCOME MEASURES All-cause mortality , fatal or nonfatal stroke , or myocardial infa rct ion . RESULTS Baseline depressive symptoms were not related to subsequent events ; however , an increase in depression was prognostic . Cox proportional hazards regression analyses with the CES-D scale as a time-dependent variable , controlling for multiple covariates , indicated a 25 % increased risk of death per 5-unit increase in the CES-D score ( relative risk [ RR ] , 1.25;95 % confidence interval [ CI ] , 1.15 to 1.36 ) . The RR for stroke or myocardial infa rct ion was 1.18(95%CI,1.08 to 1.30 ) . Increase in CES-D score was an independent predictor in both placebo and active drug groups , and it was strongest as a risk factor for stroke among women ( RR,1.29;95%CI,1.07 to 1.34 ) . CONCLUSIONS Among elderly persons , a significant and substantial excess risk of death and stroke or myocardial infa rct ion was associated with an increase in depressive symptoms over time , which may be a marker for subsequent major disease events and warrants the attention of physicians to such mood changes . However , further studies of casual pathways are needed before wide-spread screening for depression in clinical practice is to be recommended",
"The Systolic Hypertension in the Elderly ( SHEP ) pilot trial was a five-center study in which 551 persons aged 60 years or older with isolated systolic hypertension were given antihypertensive drugs or placebos in order to determine the effects on blood pressure control and possible side effects of therapy . A life events inventory was administered to the cohort one year into the study . Results of this inventory were then compared to blood pressure and changes in blood pressure in the placebo and active therapy groups . One or more of the life events assessed were present in about 65 % of the population . Although the sample was too small to detect very subtle effects , there was no evidence in this study that either individual or groups of life events play a major role in blood pressure regulation of persons with isolated systolic hypertension",
"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",
"Objective To assess longitudinally the association of serum uric acid and its change due to diuretic treatment with cardiovascular events in hypertensive patients . Design Cohort study in a r and omized trial . Setting Cohort of hypertensive patients . Participants A total of 4327 men and women , aged ≥ 60 years , with isolated systolic hypertension , r and omized to placebo or chlorthalidone , with the addition of atenolol or reserpine if needed , were observed for 5 years . Main outcome measures Major cardiovascular events , coronary events , stroke and all-cause mortality . Results Cardiovascular event rates for quartiles of baseline serum uric acid were : I , 32.7 per 1000 person-years ; II , 34.5 per 1000 person-years ; III , 38.1 per 1000 person-years ; and IV , 41.4 per 1000 person-years ( P for trend = 0.02 ) . The adjusted hazard ratio ( HR ) , of cardiovascular events for the highest quartile of serum uric acid versus the lowest quartile was 1.32 ( 95 % CI , 1.03–1.69 ) . The benefit of active treatment was not affected by baseline serum uric acid . After r and omization , an increase of serum uric acid with a HR of 0.58 ( 0.37–0.92 ) for coronary events compared with those with a serum uric acid increase ≥ 0.06 mmol/l . This difference was not explained by blood pressure effects . Those with a serum uric acid increase ≥ 0.06 mmol/l in the active treatment group had a similar risk of coronary events as the placebo group . Conclusions Serum uric acid independently predicts cardiovascular events in older persons with isolated systolic hypertension . Monitoring serum uric acid change during diuretic treatment may help to identify patients who will most benefit from treatment",
"Despite the clear-cut result of the Australian Therapeutic Trial in Mild Hypertension , which demonstrated prospect ively the benefit of treatment of diastolic blood pressure in the range of 95 to 109 mm Hg , a retrospective analysis that classified subjects by the average diastolic pressure level attained during the trial purported to show an absence of treatment benefit at lower average diastolic pressures and a negative treatment effect at higher levels . However , the method of classification by average attained diastolic pressure introduced substantial selection bias , invalidating the retrospective analysis and rendering as spurious both the deleterious treatment effect and its lack of efficacy at lower diastolic levels",
"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",
"Background and objective . This interim report from the Syst-Eur trial investigated the level of blood pressure control achieved during the double-blind period in patients followed in general practice s. Methods . In the Syst-Eur trial elderly patients ( 60 years or older ) with isolated systolic hypertension were r and omized to either active or placebo treatment . Active treatment consisted of nitrendipine combined with enalapril and /or hydrochlorothiazide to reduce systolic pressure to Results . This analysis was restricted to patients of general practitioners who had been followed for at least 12 months . The placebo ( N = 204 ) and active treatment ( N = 217 ) groups had similar characteristics at r and omization . At one year , the difference in sitting pressure between the two treatment groups was 10 mmHg systolic and 4 mmHg diastolic . Fewer patients remained on monotherapy in the placebo than in the active treatment group and on placebo the second and third line medications were started earlier . Nitrendipine tablets were discontinued in 10 patients on placebo and in 21 patients assigned to active treatment ( P Conclusions . A significant blood pressure reduction can be achieved and maintained in older patients with isolated systolic hypertension followed by general practitioners . Whether this blood pressure reduction results in a clinical ly meaningful decrease of cardiovascular complications is under investigation . Keywords . Antihypertensive treatment , general practice , isolated systolic hypertension , r and omized clinical 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",
"In an ancillary study of the Systolic Hypertension in the Elderly Program ( SHEP ) , the effects of diuretics on ventricular ectopic activity were investigated in 186 patients with isolated systolic hypertension . Ventricular premature complexes ( VPCs ) were examined as the number of VPCs/24 hours , presence of > or = 1 VPC , presence of > or = 10 VPCs/24 hours , and presence of VPC pairs or ventricular tachycardia . Significant changes in VPCs were not observed either in the 92 patients r and omized to chlorthalidone stepped-care ( 12.5 and 25 mg/day ) or in the 94 placebo-treated patients ( p > 0.1 for all VPC definitions and both groups ) . Serum potassium decreased from 4.4 + /- 0.5 to 4.1 + /- 0.5 mEq/liter ( p = 0.002 ) in the chlorthalidone group and did not change ( 4.4 + /- 0.5 to 4.5 + /- 0.4 mEq/liter ) in the placebo group . Potassium was prescribed routinely for confirmed hypokalemia serum potassium and VPC or change in serum potassium and change in VPC was not observed in the chlorthalidone group . In summary , in patients with isolated systolic hypertension , chlorthalidone in doses that are effective in decreasing stroke and cardiovascular event rates ( 12.5 or 25 mg/day ) , did not increase VPCs",
"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",
"Obesity and hypertension are often found in the same patients , particularly in elderly women . However , few data on the joint impact of these two conditions in women and the elderly are available . In the current study of 800 elderly hypertensive patients r and omly assigned to active treatment or placebo , the initial mean body mass index ( BMI ) was 26.7 kg/m2 in 560 women and 25.7 kg/m2 in 240 men . During the trial , total mortality and cardiovascular and noncardiovascular terminating events were highest in the patients at the leanest BMI quintile . The association between BMI and cardiovascular end points was U-shaped , whereas noncardiovascular mortality decreased with increasing BMI . The results in the women were similar to those in the total group . The U-shaped relation was confirmed with Cox 's proportional hazards model , controlling for age , gender , systolic blood pressure , hemoglobin , serum cholesterol , blood glucose , and cardiovascular complications at entry . The BMI level with the lowest risk was 28 to 29 kg/m2 for total mortality and cardiovascular terminating events , 26 to 27 kg/m2 for cardiovascular mortality , and 31 to 32 kg/m2 for noncardiovascular mortality . BMI did not modify the favorable effects of drug treatment . There was no evidence that obesity would protect elderly hypertensive men or women from cardiovascular complications",
"The Systolic Hypertension in the Elderly Program ( SHEP ) is a r and omized , blinded test of the efficacy of antihypertensive drug treatment . In a large feasibility trial , 551 men and women who had isolated systolic hypertension and were at least 60 years old received chlorthalidone ( 25 to 50 mg/day ) or matching placebo as the step I drug . After 1 year , 83 % of the chlorthalidone group and 80 % of the placebo group were still taking SHEP medications . Of those still taking chlorthalidone , 88 % had reached goal blood pressure ( BP ) without requiring a step II drug , and most had responded to the lower dose ( 25 mg/day ) . The BP response was similar in all age , sex and race subgroups , with an overall mean difference between r and omized groups of 17 mm Hg for systolic BP ( p less than 0.001 ) and 6 mm Hg for diastolic BP ( p less than 0.001 ) . The only common adverse effects were asymptomatic changes in the serum levels of potassium ( 0.5 mEq/liter lower in the chlorthalidone group , p less than 0.001 ) , uric acid ( 0.9 mg/dl higher , p less than 0.001 ) and creatinine ( 0.08 mg/dl higher , p = 0.02 ) . This study indicates that chlorthalidone is effective for lowering BP in elderly patients with systolic hypertension and sets the stage for a larger trial of the effects of such treatment on the incidence of cardiovascular disease",
"BACKGROUND Diabetic nephropathy is the leading cause of end-stage renal disease . Interruption of the renin-angiotensin system slows the progression of renal disease in patients with type 1 diabetes , but similar data are not available for patients with type 2 , the most common form of diabetes . We assessed the role of the angiotensin-II-receptor antagonist losartan in patients with type 2 diabetes and nephropathy . METHODS A total of 1513 patients were enrolled in this r and omized , double-blind study comparing losartan ( 50 to 100 mg once daily ) with placebo , both taken in addition to conventional antihypertensive treatment ( calcium-channel antagonists , diuretics , alpha-blockers , beta-blockers , and central ly acting agents ) , for a mean of 3.4 years . The primary outcome was the composite of a doubling of the base-line serum creatinine concentration , end-stage renal disease , or death . Secondary end points included a composite of morbidity and mortality from cardiovascular causes , proteinuria , and the rate of progression of renal disease . RESULTS A total of 327 patients in the losartan group reached the primary end point , as compared with 359 in the placebo group ( risk reduction , 16 percent ; P=0.02 ) . Losartan reduced the incidence of a doubling of the serum creatinine concentration ( risk reduction , 25 percent ; P=0.006 ) and end-stage renal disease ( risk reduction , 28 percent ; P=0.002 ) but had no effect on the rate of death . The benefit exceeded that attributable to changes in blood pressure . The composite of morbidity and mortality from cardiovascular causes was similar in the two groups , although the rate of first hospitalization for heart failure was significantly lower with losartan ( risk reduction , 32 percent ; P=0.005 ) . The level of proteinuria declined by 35 percent with losartan ( P patients with type 2 diabetes and nephropathy , and it was generally well tolerated",
"A study protocol for a double-blind r and omised control trial of hypotensive treatment in elderly hypertensive patients has been tested in a number of pilot centres throughout Europe . It was shown that this study is possible from the logistic point of view . In these elderly patients , hydrochlorothiazide + triamterene treatment with or without methyldopa , maintained a significant hypotensive effect in the absence of major electrolyte disturbances . The initiation of hypotensive therapy did not provoke an excess of cardiovascular complications . The influence of hypotensive therapy on the general well-being and on the morbidity and the mortality of elderly patients with high blood pressure , is thereby being assessed . The study will continue for 5 years and other centres are invited to join",
"BACKGROUND Angiotensin-converting enzyme ( ACE ) inhibitors reduce major cardiovascular events , but are not tolerated by about 20 % of patients . We therefore assessed whether the angiotensin-receptor blocker telmisartan would be effective in patients intolerant to ACE inhibitors with cardiovascular disease or diabetes with end-organ damage . METHODS After a 3-week run-in period , 5926 patients , many of whom were receiving concomitant proven therapies , were r and omised to receive telmisartan 80 mg/day ( n=2954 ) or placebo ( n=2972 ) by use of a central automated r and omisation system . R and omisation was stratified by hospital . The primary outcome was the composite of cardiovascular death , myocardial infa rct ion , stroke , or hospitalisation for heart failure . Analyses were done by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00153101 . FINDINGS The median duration of follow-up was 56 ( IQR 51 - 64 ) months . All r and omised patients were included in the efficacy analyses . Mean blood pressure was lower in the telmisartan group than in the placebo group throughout the study ( weighted mean difference between groups 4.0/2.2 [ SD 19.6/12.0 ] mm Hg ) . 465 ( 15.7 % ) patients experienced the primary outcome in the telmisartan group compared with 504 ( 17.0 % ) in the placebo group ( hazard ratio 0.92 , 95 % CI 0.81 - 1.05 , p=0.216 ) . One of the secondary outcomes -a composite of cardiovascular death , myocardial infa rct ion , or stroke-occurred in 384 ( 13.0 % ) patients on telmisartan compared with 440 ( 14.8 % ) on placebo ( 0.87 , 0.76 - 1.00 , p=0.048 unadjusted ; p=0.068 after adjustment for multiplicity of comparisons and overlap with primary outcome ) . 894 ( 30.3 % ) patients receiving telmisartan were hospitalised for a cardiovascular reason , compared with 980 ( 33.0 % ) on placebo ( relative risk 0.92 , 95 % CI 0.85 - 0.99 ; p=0.025 ) . Fewer patients permanently discontinued study medication in the telmisartan group than in the placebo group ( 639 [ 21.6 % ] vs 705 [ 23.8 % ] ; p=0.055 ) ; the most common reason for permanent discontinuation was hypotensive symptoms ( 29 [ 0.98 % ] in the telmisartan group vs 16 [ 0.54 % ] in the placebo group ) . INTERPRETATION Telmisartan was well tolerated in patients unable to tolerate ACE inhibitors . Although the drug had no significant effect on the primary outcome of this study , which included hospitalisations for heart failure , it modestly reduced the risk of the composite outcome of cardiovascular death , myocardial infa rct ion , or stroke . FUNDING Boehringer Ingelheim",
"BACKGROUND Antihypertensive therapy reduces the risk of cardiovascular events among high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher , but its role in persons at intermediate risk and with lower blood pressure is unclear . METHODS In one comparison from a 2-by-2 factorial trial , we r and omly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to receive either c and esartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo . The first co primary outcome was the composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke ; the second co primary outcome additionally included resuscitated cardiac arrest , heart failure , and revascularization . The median follow-up was 5.6 years . RESULTS The mean blood pressure of the participants at baseline was 138.1/81.9 mm Hg ; the decrease in blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in the placebo group . The first co primary outcome occurred in 260 participants ( 4.1 % ) in the active-treatment group and in 279 ( 4.4 % ) in the placebo group ( hazard ratio , 0.93 ; 95 % confidence interval [ CI ] , 0.79 to 1.10 ; P=0.40 ) ; the second co primary outcome occurred in 312 participants ( 4.9 % ) and 328 participants ( 5.2 % ) , respectively ( hazard ratio , 0.95 ; 95 % CI , 0.81 to 1.11 ; P=0.51 ) . In one of the three prespecified hypothesis-based subgroups , participants in the subgroup for the upper third of systolic blood pressure ( > 143.5 mm Hg ) who were in the active-treatment group had significantly lower rates of the first and second co primary outcomes than those in the placebo group ; effects were neutral in the middle and lower thirds ( P=0.02 and P=0.009 , respectively , for trend in the two outcomes ) . CONCLUSIONS Therapy with c and esartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day was not associated with a lower rate of major cardiovascular events than placebo among persons at intermediate risk who did not have cardiovascular disease . ( Funded by the Canadian Institutes of Health Research and AstraZeneca ; Clinical Trials.gov number , NCT00468923 . )"
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This systematic review and meta- analysis examined the associations between obesity and puberty timing based on scientific evidence . Eight electronic data bases were search ed up to February 2017 for eligible studies , and two review ers screened the articles and extracted the data independently . A total of 11 cohort studies with 4841 subjects met the inclusion criteria . Compared with the group of normal-weight girls , the obese group had more girls with menarche ( RR : 1.87 , 95 % CI : 1.59 - 2.19 , 2 studies ) . The number of girls with early puberty was significantly higher in the obese group than the normal weight group ( RR : 2.44 , 95 % CI : 1.32 - 4.52 , 5 studies ) . However , no differences were detected between girls who were obese or normal weight at age of menarche ( WMD : -0.53 years , 95 % CI : -1.24 - 0.19 , 2 studies ) . There is no consistent result in the relationship between obesity and timing of pubertal onset in boys . Obesity may contribute to early onset of puberty in girls , while in boys , there is insufficient data . Given the limited number of cohort studies included in this meta- analysis , high- quality studies with strong markers of puberty onset , as well as st and ardized criteria for defining obesity are needed
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"PURPOSE The purpose of the article was to examine the association of early life growth with age at menarche . METHODS Using data from a prospect i ve birth cohort ( n = 1134 women , 290 sibling sets ) , we assessed the association between postnatal growth at 4 months , 1 year , and 4 years and age at menarche , using generalized estimating equations and generalized linear r and om effects models . RESULTS Overall , 18 % of the cohort experienced early menarche ( years ) . After accounting for postnatal growth in length , faster postnatal change in weight ( per 10-percentile increase ) in all three periods was associated with an increase ( range 9%-20 % ) in the likelihood of having an early menarche . In adjusted linear models , faster weight gains in infancy and childhood were associated with an average age at menarche that was 1.1 - 1.3 months earlier compared with stable growth . The overall results were consistent for percentile and conditional growth models . Girls who experienced rapid growth ( defined as increasing across two major Centers for Disease Control and Prevention growth percentiles ) in early infancy had an average age at menarche that was 4.6 months earlier than girls whose growth was stable . CONCLUSIONS Faster postnatal weight gains in infancy and early childhood before the age of 4 years are associated with earlier age at menarche",
"Background : Given global trends toward earlier onset of puberty and the adverse psychosocial consequences of early puberty , it is important to underst and the childhood predictors of pubertal timing and tempo . Objective : We examined the association between early growth and the timing and tempo of puberty in adolescents in South Africa . Methods : We analyzed prospect ively collected data from 1060 boys and 1135 girls participating in the Birth-to-Twenty cohort in Soweto , South Africa . Height-for-age z scores ( HAZs ) and body mass index – for-age z scores ( BMI Zs ) were calculated based on height ( centimeters ) and body mass index ( kilograms per meter squared ) at ages 5 y and 8 y. The development of genitals , breasts , and pubic hair was recorded annually from 9 to 16 y of age with the use of the Tanner sexual maturation scale ( SMS ) . We used latent class growth analysis to identify pubertal trajectory classes and also characterized children as fast or slow developers based on the SMS score at 12 y of age . We used multinomial logistic regression to estimate associations of HAZ and BMI Z at ages 5 and 8 y with pubertal development . Results : We identified 3 classes for pubic hair development ( for both girls and boys ) and 4 classes for breast ( for girls ) and genital ( for boys ) development . In girls , both HAZ and BMI Z at age 5 y were positively associated with pubic hair development [ relative risk ratio ( RRR ) : 1.57 , P BMI at age 8 y ( RRR : 2.06 , P = 0.03 ) ; similar findings were observed for breast development . In boys , HAZ and BMI Z at age 5 y were positively associated with pubic hair development ( RRR : 1.78 , P HAZ at age 5 y was associated with development of genitals ( RRR : 2.19 , P : In boys and girls , both height and body mass index in early childhood predicted the trajectory of pubertal development . This may provide a tool to identify children at risk of early pubertal onset",
"OBJECTIVE The objective of this study was to determine the influence of birth weight and postnatal weight gain on age at menarche . DESIGN , SETTING , AND PARTICIPANTS This was a prospect i ve cohort study where girls from the West Australian Pregnancy ( Raine ) Cohort Study were followed prospect ively from fetal life ( 18 wk of pregnancy ) to adolescence ( 12 - 14 yr ) . MAIN OUTCOME MEASURE Age at menarche was the main outcome measure . RESULTS Growth status at birth was judged by expected birth weight ratio ( EBW ; a ratio of observed infant 's birth weight over median birth weight appropriate for maternal age , weight , height , parity , infant sex , and gestational age ) . Postnatal growth status was judged by body mass index ( BMI ) . Both EBW ( P = 0.020 ) and BMI in childhood ( 8 yr of age ) ( P age at menarche . Menarche occurred earlier in girls with lower EBW and higher BMI . CONCLUSIONS We have demonstrated for the first time that both birth weight and weight gain in childhood are associated with age at menarche . Weight gain before birth and subsequent weight gain up to the age of 8 yr were found to have opposing influences on the timing of menarche . Lower EBW combined with higher BMI during childhood predicted early age at menarche , and this relationship existed across normal birth weight and BMI ranges",
"Aims /hypothesisEarlier age at menarche is associated with increased BMI and obesity risk from early childhood through to adulthood . We hypothesised that earlier age at menarche would also predict subsequent diabetes risk . Methods This was a population -based prospect i ve cohort study of 13,308 women , who were aged 40 to 75 years between 1993 and 1997 and participating in the Norfolk cohort of the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC-Norfolk ) . We used data on age at menarche and ascertained diabetes incidence to 2005 . Results There were 734 cases of diabetes ( 363 incident and 371 prevalent cases ) . Mean age at menarche was lower in women with diabetes than in non-diabetic women ( 12.8 vs 13.0 years , p = 0.008 ) . Compared with the earliest quintile ( menarche at 8–11 years ) , women in the oldest quintile ( menarche at 15–18 years ) had lower BMI ( 25.5 vs 27.4 kg/m2 , p reduced risk of diabetes ( OR 0.66 [ 95 % CI 0.51–0.86 ] adjusted for age , family history , physical activity , smoking , occupational social class , parity and use of hormonal preparations ) . The association between age at menarche and diabetes was linear ( adjusted OR 0.91 [ 95 % CI 0.87–0.96 ] per 1 year later menarche ) and appeared to be completely mediated by adult BMI or waist circumference ( OR 0.98 [ 95 % CI 0.93–1.03 ] , further adjusted for BMI at age 40–75 years ) . Conclusions /interpretationEarlier age at menarche increases the risk of diabetes in women and this association appears to be mediated by increased adiposity . History of earlier menarche may help to identify women with increased subsequent risk of diabetes",
"Background Lack of appropriate reporting of method ological details has previously been shown to distort risk of bias assessment s in r and omized controlled trials . The same might be true for observational studies . The goal of this study was to compare the Newcastle-Ottawa Scale ( NOS ) assessment for risk of bias between review ers and authors of cohort studies included in a published systematic review on risk factors for severe outcomes in patients infected with influenza . Methods Cohort studies included in the systematic review and published between 2008–2011 were included . The corresponding or first authors completed a survey covering all NOS items . Results were compared with the NOS assessment applied by review ers of the systematic review . Inter-rater reliability was calculated using kappa ( K ) statistics . Results Authors of 65/182 ( 36 % ) studies completed the survey . The overall NOS score was significantly higher ( p . Inter-rater reliability by item ranged from slight ( K = 0.15 , 95 % confidence interval [ CI ] = −0.19 , 0.48 ) to poor ( K = −0.06 , 95 % CI = −0.22 , 0.10 ) . Reliability for the overall score was poor ( K = −0.004 , 95 % CI = −0.11 , 0.11 ) . Conclusions Differences in assessment and low agreement between review ers and authors suggest the need to contact authors for information not published in studies when applying the NOS in systematic review",
"CONTEXT Adult women with polycystic ovary syndrome ( PCOS ) have decreased GnRH pulse generator sensitivity to progesterone (P)-mediated slowing . This defect is and rogen mediated because it is reversed with and rogen receptor blockade . Adolescent hyper and rogenism often precedes PCOS . OBJECTIVE The aim of the study was to evaluate GnRH pulse generator sensitivity to P-mediated slowing in normal and hyper and rogenic girls . DESIGN We conducted a controlled interventional study . SETTING The study was conducted in a general clinical research center . PARTICIPANTS A total of 26 normal control ( NC ) and 26 hyper and rogenic ( HA ) girls were studied . INTERVENTION Frequent blood sampling was performed for 11 h to assess LH pulse frequency before and after 7 d of oral estradiol and P. MAIN OUTCOME MEASURE We measured the slope of the percentage reduction in LH pulse frequency as a function of d 7 P ( slope ) . RESULTS Overall , Tanner 3 - 5 HA subjects were less sensitive to P-mediated slowing than Tanner 3 - 5 NC ( slope , 4.7 + /- 3.4 vs. 10.3 + /- 7.7 ; P = 0.006 ) . However , there was variability in the responses of HA subjects ; 15 had P sensitivities within the range seen in NC , whereas nine were relatively P insensitive . The two groups had similar testosterone levels . Fasting insulin levels were higher in P-insensitive HA girls ( 39.6 + /- 30.6 vs. 22.2 + /- 13.9 microIU/ml ; P = 0.02 ) , and there was an inverse relationship between fasting insulin and P sensitivity in HA girls ( P = 0.02 ) . Tanner 1 - 2 NC had lower testosterone levels and were more P sensitive than Tanner 3 - 5 NC ( slope , 19.3 + /- 5.8 ; P = 0.04 ) . CONCLUSIONS Hyper and rogenism is variably associated with reduced GnRH pulse generator sensitivity to P-mediated slowing during adolescence . In addition to and rogen levels , insulin resistance may modulate P sensitivity",
"CONTEXT Rapid postnatal weight gain has been associated with subsequent increased childhood adiposity . However , the contribution of rapid weight gain during specific infancy periods is not clear . OBJECTIVE We aim ed to determine which periods of infancy weight gain are related to childhood adiposity and also to age at menarche in UK girls . DESIGN , SETTING , AND PARTICIPANTS A total of 2715 girls from a prospect i ve UK birth cohort study participated in the study . MAIN OUTCOME MEASURES Routinely measured weights and lengths at ages 2 , 9 , and 19 months were extracted from the local child health computer data base . Body composition was assessed by dual-energy x-ray absorptiometry at age 10 yr , and age at menarche was assessed by question naire ( categorized into three groups : 13.0 yr ) . RESULTS Faster early infancy weight gain between 0 and 2 months and also 2 to 9 months were associated with increased body fat mass relative to lean mass at age 10 yr and also with earlier age at menarche . Each + 1 unit gain in weight sd score between 0 and 9 months was associated with an odds ratio ( 95 % confidence interval ) = 1.48 ( 1.27 - 1.60 ) for overweight ( body mass index > 85th centile ) at 10 yr , and 1.34 ( 1.21 - 1.49 ) for menarche at less than 12 yr . In contrast , subsequent weight gain between 9 and 19 months was not associated with later adiposity or age at menarche . CONCLUSIONS In developed setting s , rapid weight gain during the first 9 months of life is a risk factor for both increased childhood adiposity and early menarche in girls",
"STUDY OBJECTIVE To analyze age at menarche and its association with excess weight and body fat percentage . DESIGN School-based cross-sectional survey . SETTING Southwestern region of the Brazilian Amazon . PARTICIPANTS The sample was made up of 727 girls , in the 8- to 16-year age range , divided into 3 groups : early , normal , and late menarche , from public and private schools , selected through proportional stratified r and om sampling . INTERVENTIONS AND MAIN OUTCOME MEASURES Bioimpedance was used to measure body fat percentage and body mass index , applying the Global School-Based Student Health Survey question naire to categorize behavior variables . Age at menarche was determined using the status quo method . Sexual maturity was assessed through self- assessment according to criteria described by Tanner . RESULTS Overall age at menarche was 11.52 ( ±1.35 ) , early 10.48 ( ±0.78 ) , normal 12.39 ( ±0.50 ) and late 14.27 ( ±0.51 ) years . Prevalence of excess weight and body fat was 28.3 % ( 206/727 ) and 44.3 % ( 322/727 ) , among those with menarche . There was a positive association between excess weight and body fat with age at early menarche ( P = .000 and .015 ) . CONCLUSION Age at menarche among girls from the Amazon region is similar to that of industrialized countries . Prevalence of excess weight and body fat was high , and there was evidence of an association between age with early menarche and excess weight . Trends in age at menarche and stage of sexual maturation should be monitored with related factors , to adopt obesity control strategies from an early age",
"BACKGROUND Higher body mass index ( BMI ) has been associated with earlier pubertal development . OBJECTIVE The aim of this longitudinal study was to determine menarcheal age in a Spanish cohort and to assess its association with anthropometric variables at birth , childhood and adolescence . We also analyse whether the tracking of weight between different ages could affect the timing of menarche . METHODS The sample population included 195 r and omly selected 6 - 8-year-old girls who participated in the baseline of the Four Provinces Study and in the follow-up of this study at 13 - 16 years old . Anthropometrical variables were measured and BMI and BMI z-score were calculated . Information regarding birth weight and menarche was obtained by means of self-report question naire . RESULTS Correlation analysis showed a significant negative association of age at menarche with weight , BMI and BMI z-score in the baseline and follow-up groups but not with weight at birth . Fat mass at adolescence is related to a significantly earlier menarcheal age . When comparing weight categories , earliest menarcheal age is associated with an increase of BMI between 6 - 8-year-old and 13 - 16-year-old girls . CONCLUSION In our study , high weight in girls is associated with the earliest age at menarche . This becomes a major influence when weight gain occurs between pre-pubertal school age and adolescence",
"OBJECTIVE To examine the association between body mass index ( BMI [ calculated as weight in kilograms divided by height in meters squared ] ) and timing of pubertal onset in a population -based sample of US boys . DESIGN Longitudinal prospect i ve study . SETTING Ten US sites that participated in the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development . PARTICIPANTS Of 705 boys initially enrolled in the study , information about height and weight measures and pubertal stage by age 11.5 years was available for 401 boys . MAIN EXPOSURE The BMI trajectory created from measured heights and weights at ages 2 , 3 , 4.5 , 7 , 9 , 9.5 , 10.5 , and 11.5 years . MAIN OUTCOME MEASURE Onset of puberty at age 11.5 years as measured by Tanner genitalia staging . RESULTS Boys in the highest BMI trajectory ( mean BMI z score at age 11.5 years , 1.84 ) had a greater relative risk of being prepubertal compared with boys in the lowest BMI trajectory ( mean BMI z score at age 11.5 years , -0.76 ) ( adjusted relative risk = 2.63 ; 95 % confidence interval , 1.05 - 6.61 ; P = .04 ) . CONCLUSIONS The relationship between body fat and timing of pubertal onset is not the same in boys as it is in girls . Further studies are needed to better underst and the physiological link between body fat and timing of pubertal onset in both sexes"
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411883bc-06ff-11f0-808a-c43d1ab1c353
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Studies related to vitamin D deficiency and lower respiratory tract infections ( LRTI ) in children have inconsistent findings . The objective of this systematic review was to assess the prevalence of vitamin D deficiency in children with LRTI , and to evaluate the correlation between vitamin D levels and the incidence and severity of LRTI . A total of 12 studies enrolling 2279 participants were included in our analysis . Children with LRTI were found to have significantly lower mean vitamin D levels as compared to controls There was likewise a correlation between vitamin D levels and incidence and severity of LRTI . Large r and omised controlled trials are needed to evaluate effect of vitamin D supplementation for LRTI
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"Background : Calcium absorption is generally considered to be impaired under conditions of vitamin D deficiency , but the vitamin D status that fully normalizes absorption is not known for humans . Objective : To quantify calcium absorption at two levels of vitamin D repletion , using pharmacokinetic methods and commercially marketed calcium supplements . Design : Two experiments performed in the spring of the year , one year apart . In the first , in which participants were pretreated with 25-hydroxyvitamin D ( 25OHD ) , mean serum 25OHD concentration was 86.5 nmol/L ; and in the other , with no pretreatment , mean serum concentration was 50.2 nmol/L. Participants received 500 mg oral calcium loads as a part of a st and ard low calcium breakfast . A low calcium lunch was provided at mid-day . Blood was obtained fasting and at frequent intervals for 10 to 12 hours thereafter . Methods : Relative calcium absorption at the two 25OHD concentrations was estimated from the area under the curve ( AUC ) for the load-induced increment in serum total calcium . Results : AUC9 ( ± SEM ) , was 3.63 mg hr/dL ± 0.234 in participants pretreated with 25OHD and 2.20 ± 0.240 in those not pretreated ( P brief , absorption was 65 % higher at serum 25OHD levels averaging 86.5 nmol/L than at levels averaging 50 nmol/L ( both values within the nominal reference range for this analyte ) . Conclusions : Despite the fact that the mean serum 25OHD level in the experiment without supplementation was within the current reference ranges , calcium absorptive performance at 50 nmol/L was significantly reduced relative to that at a mean 25OHD level of 86 nmol/L. Thus , individuals with serum 25-hydroxyvitamin D levels at the low end of the current reference ranges may not be getting the full benefit from their calcium intake . We conclude that the lower end of the current reference range is set too low",
"OBJECTIVE : Observational studies suggest that serum levels of 25-hydroxyvitamin D ( 25[OH]D ) are inversely associated with acute respiratory infections ( ARIs ) . We hypothesized that vitamin D supplementation of children with vitamin D deficiency would lower the risk of ARIs . METHODS : By using cluster r and omization , classrooms of 744 Mongolian schoolchildren were r and omly assigned to different treatments in winter ( January – March ) . This analysis focused on a subset of 247 children who were assigned to daily ingestion of unfortified regular milk ( control ; n = 104 ) or milk fortified with 300 IU of vitamin D3 ( n = 143 ) . This comparison was double-blinded . The primary outcome was the number of parent-reported ARIs over the past 3 months . RESULTS : At baseline , the median serum 25(OH)D level was 7 ng/mL ( interquartile range : 5–10 ng/mL ) . At the end of the trial , follow-up was 99 % ( n = 244 ) , and the median 25(OH)D levels of children in the control versus vitamin D groups was significantly different ( 7 vs 19 ng/mL ; P receiving vitamin D reported significantly fewer ARIs during the study period ( mean : 0.80 vs 0.45 ; P = .047 ) , with a rate ratio of 0.52 ( 95 % confidence interval : 0.31–0.89 ) . Adjusting for age , gender , and history of wheezing , vitamin D continued to halve the risk of ARI ( rate ratio : 0.50 [ 95 % confidence interval : 0.28–0.88 ] ) . Similar results were found among children either below or above the median 25(OH)D level at baseline ( rate ratio : 0.41 vs 0.57 ; Pinteraction = .27 ) . CONCLUSIONS : Vitamin D supplementation significantly reduced the risk of ARIs in winter among Mongolian children with vitamin D deficiency",
"Summary Background Vitamin D has a role in regulating immune function , and its deficiency is a suggested risk factor for childhood pneumonia . Our aim was to assess whether oral supplementation of vitamin D3 ( cholecalciferol ) will reduce the incidence and severity of pneumonia in a high-risk infant population . Methods We did a r and omised placebo-controlled trial to compare oral 100 000 IU ( 2·5 mg ) vitamin D3 with placebo given to children aged 1–11 months in Kabul , Afghanistan . R and omisation was by use of a computer-generated list . Vitamin D or placebo was given by fieldworkers once every 3 months for 18 months . Children presenting at the study hospital with signs of pneumonia had their diagnosis confirmed radiographically . Our primary outcome was the first or only episode of radiologically confirmed pneumonia . Our analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00548379 . Findings 1524 children were assigned to receive vitamin D3 and 1522 placebo . There was no significant difference between the incidence of first or only pneumonia between the vitamin D ( 0·145 per child per year , 95 % CI 0·129–0·164 ) and the placebo group ( 0.137 , 0·121–0·155 ) ; the incidence rate ratio was 1·06 ( 95 % CI 0·89–1·27 ) . From 652 children during five separate periods of testing serum calcifediol , only one child in each of two testing periods had results greater than 375 nmol/L in the intervention group — a toxic level . Interpretations Quarterly bolus doses of oral vitamin D3 supplementation to infants are not an effective intervention to reduce the incidence of pneumonia in infants in this setting . Funding Wellcome Trust and British Council",
"BACKGROUND Respiratory syncytial virus ( RSV ) is a common cause of severe lower respiratory tract infection in infants . Only a proportion of children infected with RSV require hospitalization . Because known risk factors for severe disease , such as premature birth , can not fully explain differences in disease severity , genetic factors have been implicated . METHODS To study the complexity of RSV susceptibility and to identify the genes and biological pathways involved in its development , we performed a genetic association study involving 470 children hospitalized for RSV bronchiolitis , their parents , and 1008 r and om , population controls . We analyzed 384 single-nucleotide polymorphisms ( SNPs ) in 220 c and i date genes involved in airway mucosal responses , innate immunity , chemotaxis , adaptive immunity , and allergic asthma . RESULTS SNPs in the innate immune genes VDR ( rs10735810 ; P=.0017 ) , JUN ( rs11688 ; P=.0093 ) , IFNA5 ( rs10757212 ; P=.0093 ) , and NOS2 ( rs1060826 ; P=.0031 ) demonstrated the strongest association with bronchiolitis . Apart from association at the allele level , these 4 SNPs also demonstrated association at the genotype level ( P=.0056 , P=.0285 , P=.0372 , and P=.0117 for the SNPs in VDR , JUN , IFNA5 , and NOS2 , respectively ) . The role of innate immunity as a process was reinforced by association of the whole group of innate immune SNPs when the global test for groups of genes was applied ( P=.046 ) . CONCLUSION SNPs in innate immune genes are important in determining susceptibility to RSV bronchiolitis",
"OBJECTIVES To determine whether ( i ) supplementation of oral 100,000 iu of vitamin D(3 ) ( cholecalciferol ) along with antibiotics will reduce the duration of illness in children with pneumonia ; ( ii ) supplementation will reduce the risk of repeat episodes . METHODS Double-blind individually r and omised placebo-controlled trial in an inner-city hospital in Kabul , of 453 children aged 1 - 36 months , diagnosed with non-severe or severe pneumonia at the outpatient clinic . Children with rickets , other concurrent severe diseases , very severe pneumonia or wheeze , were excluded . Children were given vitamin D(3 ) or placebo drops additional to routine pneumonia treatment . RESULTS Two hundred and twenty-four children received vitamin D(3 ; ) and 229 received placebo . There was no significant difference in the mean number of days to recovery between the vitamin D(3 ) ( 4.74 days ; SD 2.22 ) and placebo arms ( 4.98 days ; SD 2.89 ; P = 0.17 ) . The risk of a repeat episode of pneumonia within 90 days of supplementation was lower in the intervention ( 92/204 ; 45 % ) than the placebo group [ 122/211 ; ( 58 % ; relative risk 0.78 ; 95 % CI 0.64 , 0.94 ; P = 0.01 ] . Children in the vitamin D(3 ) group survived longer without experiencing a repeat episode ( 72 days vs. 59 days ; HR 0.71 ; 95 % CI 0.53 - 0.95 ; P = 0.02 ) . CONCLUSION A single high-dose oral vitamin D(3 ) supplementation to young children along with antibiotic treatment for pneumonia could reduce the occurrence of repeat episodes of pneumonia",
" Two hundred and fifty children with clinical , biochemical and radiological evidence of vitamin-D-deficiency rickets were studied over a period of 5 years . Their ages ranged from 1 month to 2 years . Breastfed infants formed 63 % of total cases . Intramuscular therapy with vitamin D in a dose of 600,000 IU , deep intramuscular , proved to be safe and effective . In contrast , oral vitamin D did not provide such satisfactory results , presumably owing to poor patient/parental compliance . This report reveals that vitamin-D-deficieny rickets is common in Kuwait in spite of abundant sunlight all through the year because children are wrapped up and kept indoors . Insufficient intake of vitamin D is another important factor in the pathogenesis of vitamin-D-deficiency rickets in Kuwait",
"BACKGROUND The association of rickets and vitamin D deficiency ( VDD ) with pneumonia is well documented , but not with its outcomes . OBJECTIVES To investigate whether rickets and VDD predict the outcomes in very severe pneumonia ( VSP ) . DESIGN A prospect i ve cohort study conducted at Al-Sabeen hospital in Sana'a , Yemen . A total of 152 children aged 2 - 59 months with WHO-defined VSP were enrolled , managed , and followed for up to 30 days . Treatment outcome was either successful or failure ( antibiotic modification for clinical worsening , death , relapse after 10-day antibiotics , or development of complications ) . Serum vitamin D ( 25OHD ) was measured in 79 cases . A concentration of VDD . MAIN OUTCOME MEASURES Association of rickets with treatment outcome ; and VDD with the circulating neutrophils ( PMNs ) , and oxygen saturation% ( SpO(2)% ) , respectively . RESULTS Treatment failure occurred in 24 ( 15.8 % ) , all aged 2 - 12 months , and 21 ( 87.5 % ) were rachitic . Of the 79 subset , 29 had VDD of which 23 ( 79.3 % ) had rickets . Treatment failure was significantly higher in the rachitic compared to non-rachitic [ 20.6 % ( 21/102 ) vs. 6 % ( 3/50 ) ; OR 1.38 ( 95 % CI 1.13 - 1.69 ) , P = 0.031 ] . In multivariate regression , rickets significantly predict a reduced successful treatment compared with non-rachitic [ 79.4 % ( 81/102 ) vs. 94 % ( 47/50 ) ; Adjusted OR 0.41 ( 95 % CI 0.20 - 0.85 ) ; P = 0.02 ] . VDD was strongly associated with reduced PMNs% [ Mean ( SD ) 37 ( 17 ) vs. 47 ( 17 ) ; Adjusted OR 0.71 ( 95 % CI 0.53 - 0.95 ) , P = 0.02 ] , and reduced SpO(2)% [ Mean ( SD ) 85.9 ( 7.9 ) vs. 89.8 ( 7.1 ) ; OR 0.96 ( 95 % CI 0.93 - 0.99 ) , P = 0.021 ] . CONCLUSIONS In VSP , rickets was significantly associated with treatment outcome and VDD significantly predict both reduced circulating PMNs , and Day-5 hypoxemia ( SpO(2)% , < 88 % )",
"BACKGROUND : Respiratory syncytial virus ( RSV ) is the most important pathogen causing severe lower respiratory tract infection ( LRTI ) in infants . Epidemiologic and basic studies suggest that vitamin D may protect against RSV LRTI . OBJECTIVE : To determine the association between plasma vitamin D concentrations at birth and the subsequent risk of RSV LRTI . DESIGN : A prospect i ve birth cohort study was performed in healthy term neonates . Concentrations of 25-hydroxyvitamin D ( 25-OHD ) in cord blood plasma were related to RSV LRTI in the first year of life , defined as parent-reported LRTI symptoms in a daily log and simultaneous presence of RSV RNA in a nose-throat specimen . RESULTS : The study population included 156 neonates . Eighteen ( 12 % ) developed RSV LRTI . The mean plasma 25-OHD concentration was 82 nmol/L. Overall , 27 % of neonates had 25-OHD concentrations Cord blood 25-OHD concentrations were strongly associated with maternal vitamin D3 supplementation during pregnancy . Concentrations of 25-OHD were lower in neonates who subsequently developed RSV LRTI compared with those who did not ( 65 nmol/L versus 84 nmol/L , P = .009 ) . Neonates born with 25-OHD concentrations risk of RSV LRTI in the first year of life compared with those with 25-OHD concentrations ≥75 nmol/L. CONCLUSIONS : Vitamin D deficiency in healthy neonates is associated with increased risk of RSV LRTI in the first year of life . Intensified routine vitamin D supplementation during pregnancy may be a useful strategy to prevent RSV LRTI during infancy",
"Objective To determine the role of oral vitamin D supplementation for resolution of severe pneumonia in under-five children . Design R and omized , double blind , placebo-controlled trial . Setting In patients from a tertiary care hospital . Participants Two hundred children [ mean ( SD ) age : 13.9 ( 11.7 ) months ; boys : 120 ] between 2 months to 5 years with severe pneumonia . Pneumonia was diagnosed in the presence of fever , cough , tachypnea ( as per WHO cut-offs ) and crepitations . Children with pneumonia and chest indrawing or at least one of the danger sign ( inability to feed , lethargy , cyanosis ) were diagnosed as having severe pneumonia . The two groups were comparable for baseline characteristics including age , anthropometry , socio-demographic profile , and clinical and laboratory parameters . InterventionOral vitamin D ( 1000 IU for 1 year ) ( n=100 ) or placebo ( lactose ) ( n=100 ) once a day for 5 days , from enrolment . Both the groups received antibiotics as per the Indian Academy of Pediatrics guidelines , and supportive care ( oxygen , intravenous fluids and monitoring ) . Outcome variables Primary : time to resolution of severe pneumonia . Secondary : duration of hospitalization and time to resolution of tachypnea , chest retractions and inability to feed . Results Median duration ( SE , 95 % CI ) of resolution of severe pneumonia was similar in the two groups [ vitamin D : 72 ( 3.7 , 64.7–79.3 ) hours ; placebo : 64 ( 4.5 , 55.2–72.8 ) hours ] . Duration of hospitalization and time to resolution of tachypnea , chest retractions , and inability to feed were also comparable between the two groups . ConclusionS hort-term supplementation with oral vitamin D ( 1000–2000 IU per day for 5 days ) has no beneficial effect on resolution of severe pneumonia in under-five children . Further studies need to be conducted with higher dose of Vitamin D or longer duration of supplementation to corroborate these findings"
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The aim of this network meta- analysis ( NMA ) is to compare the effects of different oils/solid fats on blood lipids . Literature search es were performed until March 2018 . Inclusion criteria were as follows : i ) r and omized trial ( 3 weeks study length ) comparing at least two of the following oils/solid fats : safflower , sunflower , rapeseed , hempseed , flaxseed , corn , olive , soybean , palm , and coconut oil , and lard , beef-fat , and butter ; ii ) outcomes LDL-cholesterol ( LDL-C ) , total cholesterol ( TC ) , HDL-cholesterol ( HDL-C ) , and triacylglycerols ( TGs ) . A r and om dose-response ( per 10 % isocaloric exchange ) NMA was performed and surface under the cumulative ranking curve ( SUCRA ) was estimated . Fifty-four trials were included in the NMA . Safflower oil had the highest SUCRA value for LDL-C ( 82 % ) and TC ( 90 % ) , followed by rapeseed oil ( 76 % for LDL-C , 85 % for TC ) ; whereas , palm oil ( 74 % ) had the highest SUCRA value for TG , and coconut oil ( 88 % ) for HDL-C. Safflower , sunflower , rapeseed , flaxseed , corn , olive , soybean , palm , and coconut oil as well beef fat were more effective in reducing LDL-C ( -0.42 to -0.23 mmol/l ) as compared with butter . Despite limitations in these data , our NMA findings are in line with existing evidence on the metabolic effects of fat and support current recommendations to replace high saturated-fat food with unsaturated oils
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"Abstract Purpose The aim of the study was to investigate the influence of foods enriched with vegetable oils varying in their n-3 polyunsaturated fatty acids profile on cardiovascular risk factors for hypertriglyceridemic subjects . Methods Fifty-nine hypertriglyceridemic subjects ( triglycerides ≥ 1.5 mmol/L ) were included in the r and omized , double-blind , placebo-controlled , crossover study . The placebo group received sunflower oil [ linoleic acid ( LA ) group ; 10 g LA/day ] . The intervention groups received linseed oil [ α-linolenic acid ( ALA ) group ; 7 g ALA/day ] , echium oil [ stearidonic acid ( SDA ) group ; 2 g SDA/day ] or microalgae oil [ docosahexaenoic acid ( DHA ) group ; 2 g DHA/day ] over 10 weeks . Blood sample s were collected at baseline and at the end of each period . Results Total cholesterol ( TC ) and low-density-lipoprotein cholesterol decreased significantly in the LA and ALA groups ( LA : P ≤ 0.01 , ALA : P ≤ 0.05 ) . No changes in blood lipids were observed in the SDA group . Significant increases in TC and high-density-lipoprotein cholesterol occurred in the DHA group ( P ≤ 0.05 ) . In the ALA and SDA groups , the content of eicosapentaenoic acid in erythrocyte lipids increased significantly ( P ≤ 0.05 ) after 10 weeks ( ALA group : 38 ± 37 % , SDA group : 73 ± 59 % ) . Conclusion Foods enriched with different vegetable oils rich in ALA or SDA are able to increase the n-3 long-chain polyunsaturated fatty acids content in erythrocyte lipids ; echium oil is more potent in comparison with linseed oil . Blood lipids were beneficially modified through the consumption of food products enriched with sunflower , linseed and microalgae oils , whereas echium oil did not affect blood lipids . Clinical Trials.gov : NCT01437930",
"Consumption of diets high in hydrogenated fat/trans fatty acids has been shown to have an adverse affect on lipoprotein profiles with respect to cardiovascular disease risk . Dietary fat and cholesterol play an important role in the regulation of immune and inflammatory responses shown to be involved in atherogenesis . We investigated the effects of diets containing hydrogenated fat on cellular immune response and production of inflammatory cytokines in human subjects with moderately elevated cholesterol levels ( LDL cholesterol > 130 mg/dl ) . In a double blind cross-over study , 19 subjects consumed three diets , 30 % of calories as fat , of which two thirds were provided as soybean oil , soybean oil-based stick margarine , or butter for 32 days , each in a r and omized order . Production of proinflammatory mediators , prostagl and in (PG)E(2 ) , interleukin (IL)-1beta , IL-6 , and tumor necrosis factor alpha ( TNF-alpha ) ; delayed type hypersensitivity ( DTH ) response , in vitro lymphocyte proliferation , and production of IL-2 were determined . Production of IL-6 and TNF-alpha was significantly higher after consumption of stick margarine diet compared with soybean oil diet . IL-1beta and TNF-alpha production correlated positively with ratios of total cholesterol to HDL cholesterol ( r = 0.499 , P DTH response , lymphocyte proliferation , or levels of IL-2 and PGE(2 ) produced among three groups . Our results indicate that consumption of a diet high in hydrogenated fat does not adversely affect cellular immunity but increases production of inflammatory cytokines that have been associated with the pathophysiology of atherosclerosis",
"The effects of dietary supplementation with coconut oil on the biochemical and anthropometric profiles of women presenting waist circumferences ( WC ) > 88 cm ( abdominal obesity ) were investigated . The r and omised , double-blind , clinical trial involved 40 women aged 20–40 years . Groups received daily dietary supplements comprising 30 mL of either soy bean oil ( group S ; n = 20 ) or coconut oil ( group C ; n = 20 ) over a 12-week period , during which all subjects were instructed to follow a balanced hypocaloric diet and to walk for 50 min per day . Data were collected 1 week before ( T1 ) and 1 week after ( T2 ) dietary intervention . Energy intake and amount of carbohydrate ingested by both groups diminished over the trial , whereas the consumption of protein and fibre increased and lipid ingestion remained unchanged . At T1 there were no differences in biochemical or anthropometric characteristics between the groups , whereas at T2 group C presented a higher level of HDL ( 48.7 ± 2.4 vs. 45.00 ± 5.6 ; P = 0.01 ) and a lower LDL : HDL ratio ( 2.41 ± 0.8 vs. 3.1 ± 0.8 ; P = 0.04 ) . Reductions in BMI were observed in both groups at T2 ( P reduction in WC ( P = 0.005 ) . Group S presented an increase ( P 0.05 ) in total cholesterol , LDL and LDL : HDL ratio , whilst HDL diminished ( P = 0.03 ) . Such alterations were not observed in group C. It appears that dietetic supplementation with coconut oil does not cause dyslipidemia and seems to promote a reduction in abdominal obesity ",
"Introduction High dietary saturated fat intake is associated with higher blood concentrations of low-density lipoprotein cholesterol ( LDL-C ) , an established risk factor for coronary heart disease . However , there is increasing interest in whether various dietary oils or fats with different fatty acid profiles such as extra virgin coconut oil may have different metabolic effects but trials have reported inconsistent results . We aim ed to compare changes in blood lipid profile , weight , fat distribution and metabolic markers after four weeks consumption of 50 g daily of one of three different dietary fats , extra virgin coconut oil , butter or extra virgin olive oil , in healthy men and women in the general population . Design R and omised clinical trial conducted over June and July 2017 . Setting General community in Cambridgeshire , UK . Participants Volunteer adults were recruited by the British Broadcasting Corporation through their websites . Eligibility criteria were men and women aged 50–75 years , with no known history of cancer , cardiovascular disease or diabetes , not on lipid lowering medication , no contraindications to a high-fat diet and willingness to be r and omised to consume one of the three dietary fats for 4 weeks . Of 160 individuals initially expressing an interest and assessed for eligibility , 96 were r and omised to one of three interventions ; 2 individuals subsequently withdrew and 94 men and women attended a baseline assessment . Their mean age was 60 years , 67 % were women and 98 % were European Caucasian . Of these , 91 men and women attended a follow-up assessment 4 weeks later . Intervention Participants were r and omised to extra virgin coconut oil , extra virgin olive oil or unsalted butter and asked to consume 50 g daily of one of these fats for 4 weeks , which they could incorporate into their usual diet or consume as a supplement . Main outcomes and measures The primary outcome was change in serum LDL-C ; secondary outcomes were change in total and high-density lipoprotein cholesterol ( TC and HDL-C ) , TC/HDL-C ratio and non-HDL-C ; change in weight , body mass index ( BMI ) , waist circumference , per cent body fat , systolic and diastolic blood pressure , fasting plasma glucose and C reactive protein . Results LDL-C concentrations were significantly increased on butter compared with coconut oil ( + 0.42 , 95 % CI 0.19 to 0.65 mmol/L , P of LDL-C in coconut oil compared with olive oil ( −0.04 , 95 % CI −0.27 to 0.19 mmol/L , P=0.74 ) . Coconut oil significantly increased HDL-C compared with butter ( + 0.18 , 95 % CI 0.06 to 0.30 mmol/L ) or olive oil ( + 0.16 , 95 % CI 0.03 to 0.28 mmol/L ) . Butter significantly increased TC/HDL-C ratio and non-HDL-C compared with coconut oil but coconut oil did not significantly differ from olive oil for TC/HDL-C and non-HDL-C. There were no significant differences in changes in weight , BMI , central adiposity , fasting blood glucose , systolic or diastolic blood pressure among any of the three intervention groups . Conclusions and relevance Two different dietary fats ( butter and coconut oil ) which are predominantly saturated fats , appear to have different effects on blood lipids compared with olive oil , a predominantly monounsaturated fat with coconut oil more comparable to olive oil with respect to LDL-C. The effects of different dietary fats on lipid profiles , metabolic markers and health outcomes may vary not just according to the general classification of their main component fatty acids as saturated or unsaturated but possibly according to different profiles in individual fatty acids , processing methods as well as the foods in which they are consumed or dietary patterns . These findings do not alter current dietary recommendations to reduce saturated fat intake in general but highlight the need for further elucidation of the more nuanced relationships between different dietary fats and health . Trial registration number NCT03105947 ; Results",
"Purpose Despite the fact that extra virgin olive oil ( EVOO ) is widely used in obese individuals to treat cardiovascular diseases , the role of EVOO on weight/fat reduction remains unclear . We investigated the effects of energy-restricted diet containing EVOO on body composition and metabolic disruptions related to obesity . Methods This is a r and omized , double-blinded , placebo-controlled clinical trial in which 41 adult women with excess body fat ( mean ± SD 27.0 ± 0.9 year old , 46.8 ± 0.6 % of total body fat ) received daily high-fat breakfasts containing 25 mL of soybean oil ( control group , n = 20 ) or EVOO ( EVOO group , n = 21 ) during nine consecutive weeks . Breakfasts were part of an energy-restricted normal-fat diets ( −2090 kJ , ~32%E from fat ) . Anthropometric and dual-energy X-ray absorptiometry were assessed , and fasting blood was collected on the first and last day of the experiment . Results Fat loss was ~80 % higher on EVOO compared to the control group ( mean ± SE : −2.4 ± 0.3 kg vs. −1.3 ± 0.4 kg , P = 0.037 ) . EVOO also reduced diastolic blood pressure when compared to control ( –5.1 ± 1.6 mmHg vs. + 0.3 ± 1.2 mmHg , P = 0.011 ) . Within-group differences ( P for HDL-c ( −2.9 ± 1.2 mmol/L ) and IL-10 ( + 0.9 ± 0.1 pg/mL ) in control group , and for serum creatinine ( + 0.04 ± 0.01 µmol/L ) and alkaline phosphatase ( −3.3 ± 1.8 IU/L ) in the EVOO group . There was also a trend for IL-1β EVOO reduction ( −0.3 ± 0.1 pg/mL , P = 0.060 ) . Conclusion EVOO consumption reduced body fat and improved blood pressure . Our results indicate that EVOO should be included into energy-restricted programs for obesity treatment",
"Knowledge about the effects of dietary fats on sub clinical inflammation and cardiovascular disease risk are mainly derived from studies conducted in Western population s. Little information is available on South East Asian countries . This current study investigated the chronic effects on serum inflammatory markers , lipids , and lipoproteins of three vegetable oils . Healthy , normolipidemic subjects ( n = 41 ; 33 females , 8 males ) completed a r and omized , single-blind , crossover study . The subjects consumed high oleic palm olein ( HOPO diet : 15 % of energy 18:1n-9 , 9 % of energy 16:0 ) , partially hydrogenated soybean oil ( PHSO diet : 7 % of energy 18:1n-9 , 10 % of energy 18:1 trans ) and an unhydrogenated palm stearin ( PST diet : 11 % of energy 18:1n-9 , 14 % of energy 16:0 ) . Each dietary period lasted 5 weeks with a 7 days washout period . The PHSO diet significantly increased serum concentrations of high sensitivity C-reactive protein compared to HOPO and PST diets ( by 26 , 23 % , respectively ; P decreased interleukin-8 ( IL-8 ) compared to PST diet ( by 12 % ; P PHSO diet , and also PST diet , significantly increased total : HDL cholesterol ratio compared to HOPO diet ( by 23 , 13 % , respectively ; P PST diet having a lesser effect than the PHSO diet ( by 8 % ; P < 0.05 ) . The use of vegetable oils in their natural state might be preferred over one that undergoes the process of hydrogenation in modulating blood lipids and inflammation",
"BACKGROUND Dietary behenic acid ( 22:0 ) is poorly absorbed . Because of its low bioavailability compared with other fatty acids and because of its very long chain length , the effect of dietary behenic acid ( behenate ) on serum lipid concentrations in humans is assumed to be neutral . OBJECTIVE The objective was to establish the cholesterol-raising potential of behenic acid by comparing the effects on lipid and lipoprotein concentrations of a specially formulated fat enriched with behenic acid with those of palm oil ( rich in palmitic acid ; 16:0 ) and high-oleic acid sunflower oil ( rich in cis oleic acid ; 18:1 ) . DESIGN In a r and omized , crossover , metabolic-ward study , 7 mildly hypercholesterolemic men were fed 3 natural-food diets supplemented with behenate oil , palm oil , or high-oleic acid sunflower oil . Mean serum lipid and lipoprotein concentrations and plasma triacylglycerol fatty acid composition were determined from fasting blood drawn during the final 4 d of each 3-wk diet period . RESULTS Behenate oil produced mean concentrations of total cholesterol ( 5.87+/-0.8 mmol/L ) and LDL cholesterol ( 4.40+/-0.8 mmol/L ) not significantly different from those produced by palm oil ( 5.84+/-0.7 and 4.42+/-0.7 mmol/L , respectively ) but significantly higher than those produced by high-oleic acid sunflower oil ( 5.12+/-0.5 and 3.70+/-0.6 mmol/L , respectively ) . There were no significant differences in triacylglycerol or HDL-cholesterol concentrations . CONCLUSIONS Despite its low bioavailability compared with oleic acid , behenic acid is a cholesterol-raising fatty acid in humans and is therefore not a suitable substitute for palmitic acid in manufactured triacylglycerols",
"Twenty-one healthy normocholesterolemic young adults , men and women , completed a r and omized 30-d/30-d crossover comparison of the effect of palmolein and olive oil on plasma lipids . The subjects were free-living volunteers who changed to low-fat diets to which one of the test oils was added ( used as a spread , for baking , or for frying ) in turn . Complete food records were kept throughout : the test oils were compared at 17 % of total dietary energy . Under the conditions of this experiment plasma total and low-density-lipoprotein ( LDL ) cholesterol were almost identical with the two oils , so that when the palmitic acid ( 16:0 ) in palm oil replaced oleic acid ( 18:1 ) in olive oil the expected increase in LDL cholesterol was not seen . These results indicate that 16:0 , though saturated , is not always a plasma cholesterol-raising fatty acid . Palmolein is rich in vitamin E , alpha-tocopherol , and especially tocotrienols , but the latter were barely detectable in plasma",
"This study 's purpose was to evaluate the fasting human plasma lipid and lipoprotein responses to dietary beef fat ( BF ) by comparison with coconut oil ( CO ) and safflower oil ( SO ) , fats customarily classified as saturated and polyunsaturated . Nineteen free-living normolipidemic men aged 25.6 + /- 3.5 yr consumed central ly-prepared lunches and dinners of common foods having 35 % fat calories , 60 % of which was the test fat . The test fats were isocalorically substituted , and each fed for five weeks in r and om sequences with intervening five weeks of habitual diets . Plasma total cholesterol ( TC ) , high-density lipoprotein cholesterol ( HDL-C ) , and low-density lipoprotein cholesterol ( LDL-C ) concentrations among individuals follows the same relative rank regardless of diet . Triglycerides ( TG ) concentrations among individuals also maintain their relative rank regardless of diet but in a different order from that of the cholesterols . Plasma TC , HDL-C , and LDL-C responses to BF were significantly lower and TG higher than to CO . As compared to SO , BF produced equivalent levels of TG , HDL-C , and LDL-C and marginally higher TC . Thus , the customary consideration of BF as \" saturated \" and grouping it with CO appears unwarranted",
"Activities of low-fat diets with olive oil or corn oil on lipids and platelets were studied in 23 middle-aged patients with high atherosclerosis risk for 8 wk . The olive oil diet had a polyunsaturated-saturated ratio of 0.33 vs 1.28 for the corn oil diet . Plasma total cholesterol was reduced with corn oil , but high-density lipoprotein cholesterol levels were lower with corn oil and unchanged or raised by olive . Plasma apolipoprotein B levels were equally reduced by both diets ; apolipoprotein AI and the apo AI : B ratio rose only with olive oil . Plasma-glucose levels were lowered significantly with olive oil . Changes in platelet function were characterized by a reduced sensitivity to arachidonic acid ( particularly with corn oil ) and to collagen ( particularly with olive ) . An olive oil diet with a moderate fat intake ( about 30 % of total calories ) leads to favorable plasma lipoprotein and platelet changes",
"This r and omized blind crossover study compared serum lipid and apolipoprotein concentrations in 20 men consuming 37 - 43 % of energy as fat from diets based on corn oil , high-oleic acid sunflower oil , and butter . Each phase of the crossover design included 2 wk of butter-based diet followed by 5 wk of design ated vegetable-oil-based diet with a 7-wk washout period between phases . Compared with values for the butter-based diet , the vegetable-oil-based diets reduced serum total cholesterol by 16 - 21 % ( p less than 0.001 ) , LDL cholesterol by 21 - 26 % ( p less than 0.001 ) , triglycerides by 10 - 21 % ( p less than 0.01 for the higher figure ) , and apolipoprotein B-100 by 22 - 29 % ( p less than 0.001 ) . When values fell , they fell further on the corn-oil-based diet . There were no significant changes in serum HDL cholesterol or apolipoprotein A-1 . These data suggest that when men on diets high in saturated fatty acids reduce their saturated fatty acid intake but not their total fat intake , many can still experience a significant lowering in serum total cholesterol",
"To evaluate which dietary fat may provide the best response in terms of plasma lipids and lipoproteins and also of platelet aggregability and superoxide formation by white blood cells , 12 type II patients were r and omly allocated to three different diets , which provided polyunsaturated fatty acids ( corn oil ) , monounsaturated fatty acids ( olive oil ) , and a supplementation of ethyl esters of n-3 fatty acids to a prudent diet . Olive oil and , more significantly , n-3 ethyl esters lowered total cholesterol best ( -2.2 % and -5.8 % , respectively ) ; the latter diet , as expected , also significantly lowered triglyceridemia ( -21.4 % ) . The corn-oil diet exerted a small , statistically significant reduction of high-density-lipoprotein cholesterol ( HDL ) ( -4.3 % ) , and it also lowered plasma total apo B concentrations ( -3.8 % ) . n-3 ethyl esters significantly raised both total ( + 3.1 % ) and particularly HDL2 cholesterol ( + 24 % ) . Platelet reactivity was insignificantly reduced by the three regimens , but all three significantly reduced thrombin-stimulated formation of thromboxane B2 . Finally , only the n-3 fatty acid supplementation significantly reduced O2- generation by adherent monocytes . Dietary unsaturated fatty acids are generally effective on the plasma lipid and lipoproteins in type II patients , but significant differences may be found between the three tested regimens",
"Increased HDL-cholesterol levels have been associated with lower coronary heart disease ( CHD ) risk . However , HDL are heterogeneous lipoproteins , and particles enriched in apolipoprotein ( Apo ) AII have been associated with increased CHD risk . We examined the effect of dietary intervention on HDL composition in 14 postmenopausal women subjected to two consecutive diet periods , i.e. , an oleic acid sunflower oil diet followed by a palmolein diet , each lasting 4 wk . The linoleic acid was kept at 4 % total energy and the cholesterol intake at 400 mg/d . The palmolein diet increased serum total cholesterol ( TC ) ( P phospholipids ( P Apo AII ( P HDL cholesterol ( P HDL lipids ( P HDL proteins ( P HDL total mass ( P HDL cholesterol/Apo AI ratio was increased 22.0 % ( P HDL cholesterol/Apo AII and the Apo AI/Apo AII ratios were decreased 19.4 % ( P cholesterolemia status ( 6.2 mmol/L ) , the most significant changes ( P Apo AII levels . Moreover , a significant dietary oil by cholesterol level interaction was found for Apo AII and the HDL cholesterol/Apo AII ratio . In summary , a palmolein diet increased TC and HDL cholesterol compared with oleic acid sunflower oil diet ; however , the increase in Apo AII but not in Apo AI suggests the impairment of reverse cholesterol transport and potentially an increase in CHD risk . This effect was more marked in women with serum TC > 6.2",
"The effects on plasma lipid concentrations of two oleic acid-rich diets , prepared with two different plant oils -- olive oil and sunflower oil high in monounsaturated fatty acids (MUFAs)-- were compared with a National Cholesterol Education Program ( NCEP ) I diet . Twenty-one healthy , normolipidemic , young males consumed an NCEP-I diet ( 30 % of energy as fat ) during a 25-d period . Subjects were then assigned to two 4-wk study periods , according to a r and omized , crossover design . Group one was placed on an olive oil-enriched diet ( 40 % fat , 22 % MUFAs ) , followed by a 4-wk period of a sunflower oil-enriched diet ( 40 % fat , 22 % MUFAs ) . In group two , the order of the diets was reversed . Both MUFA dietary periods result ed in an increase in high-density-lipoprotein ( HDL ) cholesterol ( 7 % for the olive oil diet and 4 % for the sunflower oil diet ) and in apolipoprotein ( apo ) A-I ( 9 % for both ) compared with the NCEP-I diet . Low-density-lipoprotein ( LDL ) cholesterol and apo B concentrations ( x + /- SEM ) were lower ( P oil diet ( 2.40 + /- 0.11 mmol/L , 0.85 + /- 0.04 mg/L ) than during the olive oil diet ( 2.64 + /- 0.15 mmol/L , 0.93 + /- 0.05 mg/L ) . No significant differences were observed in these variables between the sunflower oil and NCEP-I ( 2.48 + /- 0.13 mmol/L , 0.89 + /- 0.04 mg/L ) diets . ( ABSTRACT TRUNCATED AT 250 WORDS",
"The effects on serum lipids of palm oil ( PA ) used in Chinese diets were compared with those of soybean oil ( SO ) , peanut oil ( PE ) and lard ( LA ) in normocholesterolemic subjects and with that of PE in hypercholesterolemic subjects . Normocholesterolemic subjects [ 120 men , 18 - 25 y , total cholesterol ( TC ) 2.8 - 5.0 mmol/L ] were assigned to four groups to consume test diets for six consecutive weeks after a run-in period of 3 wk . About 30 % of dietary energy was derived from fat , 75 - 80 % of which came from test oils . In comparison with the entry level , the average serum TC and LDL cholesterol ( LDL-C ) were 6.7 and 13.1 % lower , respectively , in the PA group and 22.8 and 30.7 % higher , respectively , ( P serum TC , LDL-C and the ratio of TC/HDL cholesterol ( HDL-C ) in the PA group were significantly lower than those of the LA group . Hypercholesterolemic subjects ( 31 men , 20 women , 32 - 68 y , TC 5.5 - 7.0 mmol/L ) were divided into two groups . For 6 wk , one group ( 15 men , 10 women ) consumed the PA diet ; another group ( 16 men , 9 women ) consumed the PE diet . After a 3-wk interval , the two groups interchanged diets for another 6 wk . The test diets again contained about 30 % energy from fat , 60 - 65 % of which came from test oils . Compared with entry values , the PA diet caused significant reductions in serum TC , LDL-C and TC/HDL-C during the first 6 wk and also a significant reduction in TC/HDL-C during the second 6 wk . The PE diet had no significant influence on serum lipids in either experimental period",
"We compared plasma lipid changes due to the polyunsaturated fatty acids ( PUFAs ) in partially hydrogenated soybean oil , corn oil , and sunflower oil fed in reduced-fat diets ( 22 - 26 % of total energy ) . Each oil was the dominant fat in isoenergetic diets of central ly prepared foods consumed by 26 male and 35 female normolipidemic , free-living individuals . Test diets were consumed double-blind , alternating with self-selected diets for 5 wk each . The ranges of proportions of total fat were : 4.7 - 9.7 % polyunsaturated fat , 8.9 - 14.2 % monounsaturated fat and 5.4 - 7.4 % saturated fat . All three diets lowered ( P total cholesterol ( 11 % ) , LDL cholesterol ( 13 % ) , and HDL cholesterol ( 10 % ) , without triglyceride changes . We conclude that PUFAs at approximately 6 % of total energy result in clinical ly relevant plasma cholesterol-lowering and that the proportion of polyunsaturated fat must be an important consideration when planning reduced-fat , reduced-saturated-fat diets",
"Although medium-chain triacylglycerols ( MCTs , composed of medium-chain fatty acids 8:0 and 10:0 ) have long been described as having neutral effects on serum cholesterol concentrations , experimental evidence supporting this cl aim is limited . In a r and omized , crossover , metabolic-ward study , we compared the lipid effects of a natural food diet supplemented with either MCTs , palm oil , or high oleic acid sunflower oil in nine middle-aged men with mild hypercholesterolemia . Rather than having a neutral effect , MCT oil produced total cholesterol concentrations that were not significantly different from those produced by palm oil ( MCT oil : 5.87 + /- 0.75 mmol/L ; palm oil : 5.79 + /- 0.72 mmol/L ) but significantly higher than that produced by high oleic acid sunflower oil ( 5.22 + /- 0.52 mmol/L ) . Low-density-lipoprotein (LDL)-cholesterol concentrations paralleled those of total cholesterol . MCT oil tended to result in higher triacylglycerol concentrations than either palm oil or high oleic acid sunflower oil , but this difference was not significant . There were no differences in high-density-lipoprotein cholesterol concentrations . The palmitic acid and total saturated fatty acid content of plasma triacylglycerols in the MCT-oil diet was not significantly different from that in the palm oil diet . On the basis of percentage of energy , this study suggests that medium-chain fatty acids have one-half the potency that palmitic acid has at raising total and LDL-cholesterol concentrations",
"BACKGROUND Restricted intakes of saturated and trans-fatty acids is emphasized in heart-healthy diets , and replacement with poly- and monounsaturated fatty acids is encouraged . OBJECTIVE To compare the effects of polyunsaturated fatty acid-rich corn oil ( CO ) and monounsaturated fatty acid-rich extra-virgin olive oil ( EVOO ) on plasma lipids in men and women ( N = 54 ) with fasting low-density lipoprotein cholesterol ( LDL-C ) ≥130 mg/dL and METHODS In a double-blind , r and omized , crossover design ( 21-day treatments , 21-day washout between ) , 4 tablespoons/day CO or EVOO were provided in 3 servings study product/day ( muffin , roll , yogurt ) as part of a weight-maintenance diet ( ∼35 % fat , ate breakfast at the clinic every weekday throughout the study . Lunches , dinners , and snacks ( and breakfasts on weekends ) were provided for consumption away from the clinic . RESULTS Baseline mean ( st and ard error ) lipids in mg/dL were : LDL-C 153.3 ( 3.5 ) , total cholesterol ( total-C ) 225.7 ( 3.9 ) , non-high-density lipoprotein (non-HDL)-C 178.3 ( 3.7 ) , HDL-C 47.4 ( 1.7 ) , total-C/HDL-C 5.0 ( 0.2 ) , and TG 124.8 ( 7.2 ) . CO result ed in significantly larger least-squares mean % changes ( all P baseline in LDL-C -10.9 vs -3.5 , total-C -8.2 vs -1.8 , non-HDL-C -9.3 vs -1.6 , and total-C/HDL-C -4.4 vs 0.5 . TG rose a smaller amount with CO , 3.5 vs 13.0 % with EVOO ( P = .007 ) . HDL-C responses were not significantly different between conditions ( -3.4 vs -1.7 % ) . CONCLUSION Consumption of CO in a weight-maintenance , low saturated fat and cholesterol diet result ed in more favorable changes in LDL-C and other atherogenic lipids vs EVOO",
"BACKGROUND Metabolic studies suggest that fatty acids containing at least one double bond in the trans configuration , which are found in hydrogenated fat , have a detrimental effect on serum lipoprotein cholesterol levels as compared with unsaturated fatty acids containing double bonds only in the cis configuration . We compared the effects of diets with a broad range of trans fatty acids on serum lipoprotein cholesterol levels . METHODS Eighteen women and 18 men consumed each of six diets in r and om order for 35-day periods . The foods were identical in each diet , and each diet provided 30 percent of calories as fat , with two thirds of the fat contributed as soybean oil ( semiliquid margarine ( soft margarine ( 7.4 g per 100 g ) , shortening ( 9.9 g per 100 g ) , or stick margarine ( 20.1 g per 100 g ) . The effects of those diets on serum lipoprotein cholesterol , triglyceride , and apolipoprotein levels were compared with those of a diet enriched with butter , which has a high content of saturated fat . RESULTS The mean ( + /-SD ) serum low-density lipoprotein ( LDL ) cholesterol level was 177+/-32 mg per deciliter ( 4.58+/-0.85 mmol per liter ) and the mean high-density lipoprotein ( HDL ) cholesterol level was 45+/-10 mg per deciliter ( 1.2+/-0.26 mmol per liter ) after subjects consumed the butter-enriched diet . The LDL cholesterol level was reduced on average by 12 percent , 11 percent , 9 percent , 7 percent , and 5 percent , respectively , after subjects consumed the diets enriched with soybean oil , semiliquid margarine , soft margarine , shortening , and stick margarine ; the HDL cholesterol level was reduced by 3 percent , 4 percent , 4 percent , 4 percent , and 6 percent , respectively . Ratios of total cholesterol to HDL cholesterol were lowest after the consumption of the soybean-oil diet and semiliquid-margarine diet and highest after the stick-margarine diet . CONCLUSIONS Our findings indicate that the consumption of products that are low in trans fatty acids and saturated fat has beneficial effects on serum lipoprotein cholesterol levels",
"OBJECTIVE To evaluate the effects of a trans fat-free monounsaturated fatty acid-rich vegetable oil ( NuSun sunflower oil , National Sunflower Association , Bismark , ND ) that is a good source of polyunsaturated fatty acids ( PUFA ) and low in saturated fatty acids on lipid and lipoprotein levels and oxidative stress . DESIGN A double-blinded , r and omized , three period crossover , controlled feeding study . SUBJECTS/ SETTING Thirty-one men ( n=12 ) and women ( n=19 ) with moderate hypercholesterolemia who were 25 to 64 years of age . INTERVENTION Experimental diets provided 30 % fat ( olive oil or NuSun sunflower oil contributed one half of the total fat ) , 8.3 % vs 7.9 % saturated fatty acid , 17.2 % vs 14.2 % monounsaturated fatty acid , and 4.3 % vs. 7.7 % PUFA ( olive oil and NuSun sunflower oil , respectively ) , and 294 mg cholesterol . The control diet was an average American diet ( 34 % fat , 11.2 % saturated fatty acid , 14.9 % monounsaturated fatty acid , 7.8 % PUFA ) . Subjects consumed each diet for 4 weeks with a 2-week compliance break before crossing over to another diet . MAIN OUTCOME MEASURES Lipid and lipoprotein levels were measured , and measures of oxidative stress , including lag time , rate of oxidation , total dienes , and lipid hydroperoxides , were assessed . STATISTICAL ANALYSIS The mixed model procedure was used to test for main effects of diet , feeding period , and order of diets . Tukey-Kramer adjusted P values were used to determine diet effects . RESULTS The NuSun sunflower oil diet decreased both total and low-density lipoprotein cholesterol levels compared with the average American diet and the olive oil diet . There was no effect of the olive oil diet compared with the average American diet . Total cholesterol decreased 4.7 % and low-density lipoprotein cholesterol decreased 5.8 % on the NuSun sunflower oil diet vs the average American diet . There was no effect of the experimental diets on triglyceride levels , rate of oxidation , total dienes , lipid hydroperoxides , or alpha-tocopherol . Lag time was the longest following the olive oil diet and shortest following the NuSun sunflower oil diet . CONCLUSIONS The higher PUFA content appeared to account for the greater total and low-density lipoprotein cholesterol lowering and reduction in lag time of the NuSun sunflower oil diet . However , the fact that there were no differences in the result ing oxidation products suggests there were no adverse effects on low-density lipoprotein oxidation . Since PUFAs are important for cholesterol lowering , foods that replace saturated fatty acids should include a balance of unsaturated fatty acids",
"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",
"BACKGROUND Current dietary guidelines recommend the replacement of saturated fatty acids ( SAFAs ) with carbohydrates or monounsaturated fatty acids ( MUFAs ) based on evidence on lipid profile alone , the chronic effects of the mentioned replacements on insulin secretion and insulin sensitivity are however unclear . OBJECTIVE To assess the chronic effects of the substitution of refined carbohydrate or MUFA for SAFA on insulin secretion and insulin sensitivity in central ly obese subjects . METHODS Using a crossover design , r and omized controlled trial in abdominally overweight men and women , we compared the effects of substitution of 7 % energy as carbohydrate or MUFA for SAFA for a period of 6 weeks each . Fasting and postpr and ial blood sample s in response to corresponding SAFA , carbohydrate , or MUFA-enriched meal-challenges were collected after 6 weeks on each diet treatment for the assessment of outcomes . RESULTS As expected , postpr and ial nonesterified fatty acid suppression and elevation of C-peptide , insulin and glucose secretion were the greatest with high-carbohydrate ( CARB ) meal . Interestingly , CARB meal attenuated postpr and ial insulin secretion corrected for glucose response ; however , the insulin sensitivity and disposition index were not affected . SAFA and MUFA had similar effects on all markers except for fasting glucose-dependent insulinotropic peptide concentrations , which increased after MUFA but not SAFA when compared with CARB . CONCLUSION In conclusion , a 6-week lower-fat/higher-carbohydrate ( increased by 7 % refined carbohydrate ) diet may have greater adverse effect on insulin secretion corrected for glucose compared with isocaloric higher-fat diets . In contrast , exchanging MUFA for SAFA at 7 % energy had no appreciable adverse impact on insulin secretion",
"BACKGROUND Despite the high content of palmitic acid , palm olein has been shown to have a neutral effect on plasma cholesterol concentrations when compared with olive oil , which is suggested to be attributable to palmitic acid in the sn-1 and sn-3 position . In contrast , palmitic acid is in the sn-2 position in lard . OBJECTIVE The objective was to investigate the effects of a diet rich in palm olein , fractionated palm oil , olive oil , and lard on plasma blood lipids , inflammatory markers , glucose , and insulin . DESIGN A controlled double-blinded , r and omized 3 × 3 wk crossover dietary intervention study included 32 healthy men who daily replaced part of their habitual dietary fat intake with ~ 17 % of energy from palm olein , olive oil , or lard , respectively . RESULTS Compared with intake of olive oil , palm olein and lard increased total cholesterol and LDL cholesterol ( P ) . Palm olein result ed in a lower plasma triacylglycerol concentration than did olive oil ( P in plasma HDL-cholesterol , high-sensitivity C-reactive protein , plasminogen activator-1 , insulin , and glucose concentrations . CONCLUSIONS The current study did not support the previous finding that the effect of palm olein on total plasma cholesterol and LDL cholesterol in healthy individuals with normal plasma cholesterol concentrations is neutral compared with that of olive oil . Thus , sn-positioning was not confirmed to be important with regard to the effect on plasma cholesterol . The relatively lower plasma triacylglycerol concentration after the palm olein diet than after the olive oil diet was unexpected . This trial is registered at clinical trials.gov as NCT00743301",
"OBJECTIVE We investigated the effects of dietary intervention with canola or olive oil in comparison with commonly used refined oil in Asian Indians with nonalcoholic fatty liver disease ( NAFLD ) . SUBJECTS AND METHODS This was a 6-month intervention study including 93 males with NAFLD , matched for age and body mass index ( BMI ) . Subjects were r and omized into three groups to receive olive oil ( n=30 ) , canola oil ( n=33 ) , and commonly used soyabean/safflower oil ( control ; n=30 ) as cooking medium ( not exceeding 20 g/day ) along with counseling for therapeutic lifestyle changes . The BMI , fasting blood glucose ( FBG ) and insulin levels , lipids , homeostasis model of assessment for insulin resistance ( HOMA-IR ) , HOMA denoting β-cell function ( HOMA-βCF ) , and disposition index ( DI ) were measured at pre- and post-intervention . Data were analyzed with one-way analysis of variance ( ANOVA ) and Tukey 's Honestly Significant Difference multiple comparison test procedures . RESULTS Olive oil intervention led to a significant decrease in weight and BMI ( ANOVA , P=0.01 ) compared with the control oil group . In a comparison of olive and canola oil , a significant decrease in fasting insulin level , HOMA-IR , HOMA-βCF , and DI ( P in high-density lipoprotein level ( P=0.004 ) in the olive oil group and a significant decrease in FBG ( P=0.03 ) and triglyceride ( P=0.02 ) levels in the canola oil group . The pre- and post-intervention difference in liver span was significant only in the olive ( 1.14 ± 2 cm ; P and canola ( 0.66 ± 0.33 cm ; P In the olive and canola oil groups , post-intervention grading of fatty liver was reduced significantly ( grade I , from 73.3 % to 23.3 % and from 60.5 % to 20 % , respectively [ P grading of fatty liver , liver span , measures of insulin resistance , and lipids with use of canola and olive oil compared with control oils in Asian Indians with NAFLD",
"We investigated the effect of olive oil , rapeseed oil , and sunflower oil on blood lipids and lipoproteins including number and lipid composition of lipoprotein subclasses . Eighteen young , healthy men participated in a double-blinded r and omized cross-over study ( 3-week intervention period ) with 50 g of oil per 10 MJ incorporated into a constant diet . Plasma cholesterol , triacylglycerol , apolipoprotein B , and very low density lipoprotein ( VLDL ) , intermediate density lipoprotein ( IDL ) , and low density lipoprotein ( LDL ) cholesterol concentrations were 10;-20 % higher after consumption of the olive oil diet compared with the rapeseed oil and sunflower oil diets [ analysis of variance ( ANOVA ) , P size of IDL , VLDL , and LDL subfractions did not differ between the diets , whereas a significantly higher number ( apolipoprotein B concentration ) and lipid content of the larger and medium-sized LDL subfractions were observed after the olive oil diet compared with the rapeseed oil and sunflower oil diets ( ANOVA , P Total HDL cholesterol concentration did not differ significantly , but HDL(2a ) cholesterol was higher after olive oil and rapeseed oil compared with sunflower oil ( ANOVA , P rapeseed oil and sunflower oil had more favorable effects on blood lipids and plasma apolipoproteins as well as on the number and lipid content of LDL subfractions compared with olive oil . Some of the differences may be attributed to differences in the squalene and phytosterol contents of the oils",
"This r and omized crossover study compared the impact of virgin coconut oil ( VCO ) to safflower oil ( SO ) on body composition and cardiovascular risk factors . Twelve postmenopausal women ( 58.8 ± 3.7 year ) consumed 30 mL VCO or SO for 28 days , with a 28-day washout . Anthropometrics included body weight and hip and waist circumference . Fat percent for total body , and roid and gynoid , fat mass , and lean mass were measured using dual-energy X-ray absorptiometry . Women maintained their typical diet recording 28 days of food records during the study . Results were analyzed with SPSS v24 with significance at P ≤ .05 . Comparisons are reported as paired t-test since no intervention sequence effect was observed . VCO significantly raised total cholesterol , TC ( + 18.2 ± 22.8 mg/dL ) , low-density lipoprotein ( + 13.5 ± 16.0 mg/dL ) , and high-density lipoprotein , HDL ( + 6.6 ± 7.5 mg/dL ) . SO did not significantly change lipid values . TC and HDL were significantly different between test oils . The TC/HDL ratio change showed a neutral effect of both VCO and SO . One person had adverse reactions to VCO and increased inflammation . VCO decreased IL-1β for each person who had a detected sample . The impact of VCO and SO on other cytokines varied on an individual basis . This was the first study evaluating the impact of VCO on body composition in Caucasian postmenopausal women living in the United States . Results are suggestive that individuals wishing to use coconut oil in their diets can do so safely , but more studies need to be conducted with larger sample sizes , diverse population s , and more specific clinical markers such as particle size",
"The study deals with 412 men , aged 30 to 64 years , r and omized 1 to 2 years after a first myocardial infa rct ion . For the experimental group a diet low in saturated fats and cholesterol , and high in polyunsaturated fats was recommended . After 5 years , as reported previously , the incidence of fatal and nonfatal myocardial reinfa rct ion was found to be significantly reduced . “ Sudden death ” was uninfluenced . Major coronary heart disease ( CHD ) relapses , including fatal and nonfatal events ( MI ) , were significantly reduced ( P = 0.05).After 11 years , death from all causes had occurred in 101 of the original dieters and 108 controls . A significantly reduced myocardial infa rct ion mortality in the original diet group was found ( 32 versus 57 , P = 0.004 ) . The total number of coronary deaths ( fatal myocardial infa rct ion and sudden death ) was 79 in the diet group and 94 in the control group ( P = 0.097).The CHD mortality was correlated with age , serum cholesterol level , blood pressure , body weight , smoking habits , and a combination of these risk factors",
"Background / objectives : Dietary triacylglycerols containing palmitic acid in the sn-2 position might impair insulin release and increase plasma glucose . Subjects/ Methods : We used a cross-over design ed feeding trial in 53 healthy Asian men and women ( 20–50 years ) to test this hypothesis by exchanging 20 % energy of palm olein ( PO ; control ) with r and omly interesterified PO ( IPO ) or high oleic acid sunflower oil ( HOS ) . After a 2-week run-in period on PO , participants were fed PO , IPO and HOS for 6 week consecutively in r and omly allocated sequences . Fasting ( midpoint and endpoint ) and postpr and ial blood at the endpoint following a test meal ( 3.54 MJ , 14 g protein , 85 g carbohydrate and 50 g fat as PO ) were collected for the measurement of C-peptide , insulin , glucose , plasma glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 , lipids and apolipoproteins ; pre-specified primary and secondary outcomes were postpr and ial changes in C-peptide and plasma glucose . Results : Low density lipoprotein cholesterol was 0.3 mmol/l ( 95 % confidence interval ( 95 % CI ) ) 0.1 , 0.5 ; P 10 male and 31 female completers in the incremental area under the curve ( 0–2 h ) for C-peptide in nmol.120 min/l : GM ( 95 % CI ) were PO 220 ( 196 , 245 ) , IPO 212 ( 190 , 235 ) and HOS 224 ( 204 , 244 ) . Plasma glucose was 8 % lower at 2 h on IPO vs PO and HOS ( both P<0.05 ) . Conclusion : Palmitic acid in the sn-2 position does not adversely impair insulin secretion and glucose homeostasis",
"To assess whether the type of fat ingested at breakfast can modify the plasma lipid profile and other cardiovascular risk variables in postmenopausal women at risk of cardiovascular disease , a longitudinal , r and omized , and crossover study was carried out with postmenopausal women at risk of CVD . They were r and omly assigned to eat each type of breakfast during one month : 6 study periods ( breakfast with the same composition plus butter/margarine/virgin olive oil ) separated by two washout periods . On the first and last days of each study period , weight , arterial blood pressure , heart rate , and body mass index were recorded in fasting conditions and a blood sample was collected to measure plasma lipid profile . When comparing final values to baseline values , we only found out statistically significant differences on plasma lipid profiles . Butter-based breakfast increased total cholesterol and HDL , while margarine-based breakfast decreased total cholesterol and LDL and increased HDL . After the olive oil-based breakfast intake , a tendency towards a decrease of total cholesterol and LDL levels and an increase of HDL levels was observed . No statistically significant differences were observed in triglycerides levels , BMI , and arterial pressure in any breakfast type . The margarine-based breakfast was the only one which significantly increased the percentage of volunteers with optimal lipid profiles . The polyunsaturated fat at breakfast has improved the plasma lipid profile in the analyzed sample population , suggesting that PUFA-based breakfast can be advisable in women at risk of CVD",
"Background Dietary trans-rich and interesterified fats were compared to an unmodified saturated fat for their relative impact on blood lipids and plasma glucose . Each fat had melting characteristics , plasticity and solids fat content suitable for use as hardstock in margarine and other solid fat formulations . Methods Thirty human volunteers were fed complete , whole food diets during 4 wk periods , where total fat ( ~31 % daily energy , > 70 % from the test fats ) and fatty acid composition were tightly controlled . A crossover design was used with 3 r and omly-assigned diet rotations and repeated- measures analysis . One test fat rotation was based on palm olein ( POL ) and provided 12.0 percent of energy ( % en ) as palmitic acid ( 16:0 ) ; a second contained trans-rich partially hydrogenated soybean oil ( PHSO ) and provided 3.2 % en as trans fatty acids plus 6.5 % en as 16:0 , while the third used an interesterified fat ( IE ) and provided 12.5 % en as stearic acid ( 18:0 ) . After 4 wk the plasma lipoproteins , fatty acid profile , as well as fasting glucose and insulin were assessed . In addition , after 2 wk into each period an 8 h postpr and ial challenge was initiated in a subset of 19 subjects who consumed a meal containing 53 g of test fat . Results After 4 wk , both PHSO and IE fats significantly elevated both the LDL/HDL ratio and fasting blood glucose , the latter almost 20 % in the IE group relative to POL . Fasting 4 wk insulin was 10 % lower after PHSO ( p > 0.05 ) and 22 % lower after IE ( p the glucose incremental area under the curve ( IAUC ) following the IE meal was 40 % greater than after either other meal ( p depressed insulin and C-peptide ( p PHSO and IE fats altered the metabolism of lipoproteins and glucose relative to an unmodified saturated fat when fed to humans under identical circumstances",
"Background The effects of alpha-linolenic acid ( ALA ) on cardiovascular risk factors considerably vary between published reports . Therefore , we investigated the effects of 12-week supplementation with flaxseed oil ( FO ) , which is a rich source of ALA , on cardiovascular risk factors such as serum small dense low-density lipoprotein ( sd-LDL ) concentrations . Methods In a r and omized , double blind , crossover study , 15 subjects ingested 10 g of FO or corn oil ( CO ) , containing 5.49 g and 0.09 g of ALA , respectively , once daily with dinner . Blood sample s were collected at 0 , 4 and 12 weeks , and were used for analysis of serum lipid , lipid-related proteins , serum fatty acids and serum sd-LDL cholesterol . Differences during the test period were identified using a repeated- measures analysis of variance ( ANOVA ) for within-group effects . Group differences were identified using paired t-test at each blood sampling time point . Results ALA and eicosapentaenoic acid concentrations were significantly higher in the FO period at 4 and 12 weeks than in the CO period . No significant differences in docosahexaenoic acid concentrations were observed between two periods , and cholesteryl ester transfer protein and apolipoprotein B concentrations were significantly lower in the FO period than in the CO period at 12 weeks . FO supplementation was associated with a significant decrease in sd-LDL concentrations at 4 and 12 weeks , and CO supplementation had no effect . Moreover , sd-LDL concentrations were significantly lower in the FO period than in the CO period at 4 weeks . Among subjects with triglyceride ( TG ) concentrations of > 100 mg/dl , FO supplementation markedly reduced sd-LDL concentrations at 4 and 12 weeks compared with baseline . Sd-LDL concentrations significantly differed between the periods at both 4 and 12 weeks . Conclusion This study indicates that the FO , which is a rich source of ALA , leads to lower sd-LDL cholesterol concentrations",
"The effect of rice bran oil , and oil not commonly consumed in the United States , on plasma lipid and apolipoprotein concentrations was studied within the context of a National Cholesterol Education Panel ( NCEP ) Step 2 diet and compared with the effects of canola , corn , and olive oils . The study subjects were 15 middle-aged and elderly subjects ( 8 postmenopausal women and 7 men ; age range , 44 to 78 years ) with elevated low-density lipoprotein ( LDL ) cholesterol ( C ) concentrations ( range , 133 to 219 mg/dL ) . Diets enriched in each of the test oils were consumed by each subject for 32-day periods in a double-blind fashion and were ordered in a Latin square design . All food and drink were provided by the metabolic research unit . Diet components were identical ( 17 % of calories as protein , 53 % as carbohydrate , 30 % as fat [ rice bran , canola , corn , or olive oil . Mean + /- SD plasma total cholesterol concentrations were 192 + /- 19 , 194 + /- 20 , 194 + /- 19 , and 205 + /- 19 mg/dL , and LDL-C concentrations were 109 + /- 30 , 109 + /- 26 , 108 + /- 31 , and 112 + /- 29 mg/dL after consumption of the rice bran , canola , corn , and olive oil-enriched diets , respectively . Plasma cholesterol and LDL-C concentrations were similar and statistically indistinguishable when the subjects consumed the rice bran , canola , and corn oil-enriched diets and lower than when they consumed the olive oil-enriched diet . ( ABSTRACT TRUNCATED AT 250 WORDS",
"Background Dietary alpha-linolenic acid ( ALA ) has been associated with reduced risk of development of atherosclerosis . Adiponectin is a hormone specifically secreted by adipocytes and considered to have anti-atherogenic properties . Aim of the study We examined the effect of increased dietary intake of ALA on plasma concentration of adiponectin . Methods Thirty-five non-diabetic , dyslipidemic men , 38–71 years old , were r and omly allocated to take either 15 ml of flaxseed oil rich in ALA ( 8.1 g/day ; n = 18 ) , or 15 ml of safflower oil per day , containing the equivalent n-6 fatty acid ( 11.2 g/day linoleic acid , LA ; n = 17 ) ( control group ) . The intervention period lasted for 12 weeks . Results Plasma levels of adiponectin did not change after the increase in dietary intake of ALA in the flaxseed oil supplementation group , compared to the control group . No changes in body mass index , serum lipid concentrations , LDL density , or plasma TNF-α were found in the flaxseed oil versus the control group . Conclusions Dietary ALA has no effect on plasma adiponectin concentration in dyslipidemic men",
"BACKGROUND Inflammation plays an important role in the pathogenesis of coronary artery disease . We examined whether dietary supplementation with alpha-linolenic acid ( ALA , 18:3n-3 ) affects the levels of inflammatory markers in dyslipidaemic patients . METHODS We recruited 76 male dyslipidaemic patients ( mean age=51+/-8 years ) following a typical Greek diet . They were r and omly assigned either to 15 ml of linseed oil ( rich in ALA ) per day ( n=50 ) or to 15 ml of safflower oil ( rich in linoleic acid ( LA , 18:2n-6 ) ) per day ( n=26 ) . The ratio of n-6:n-3 in linseed oil supplemented group was 1.3:1 and in safflower oil supplemented group 13.2:1 . Dietary intervention lasted for 3 months . Blood lipids and C-reactive protein ( CRP ) , serum amyloid A ( SAA ) , and interleukin-6 ( IL-6 ) levels were determined prior and after intervention . CRP and SAA were measured by nephelometry and IL-6 by immunoassay . RESULTS Dietary supplementation with ALA decreased significantly CRP , SAA and IL-6 levels . The median decrease of CRP was 38 % ( 1.24 vs. 0.93 mg/l , P=0.0008 ) , of SAA 23.1 % ( 3.24 vs. 2.39 mg/l , P=0.0001 ) and of IL-6 10.5 % ( 2.18 vs. 1.7 pg/ml , P=0.01 ) . The decrease of inflammatory markers was independent of lipid changes . Dietary supplementation with LA did not affect significantly CRP , SAA and IL-6 concentrations but decreased cholesterol levels . CONCLUSIONS Dietary supplementation with ALA for 3 months decreases significantly CRP , SAA and IL-6 levels in dyslipidaemic patients . This anti-inflammatory effect may provide a possible additional mechanism for the beneficial effect of plant n-3 polyunsaturated fatty acids in primary and secondary prevention of coronary artery disease",
"BACKGROUND Hypolipidemic effects of vegetable oils have been demonstrated in a number of studies , but there is no study , which compares the effects of canola oil ( CO ) and rice bran oil ( RBO ) on diabetic patient . We aim ed to compare the effects of CO and RBO consumption on blood lipids in women with type 2 diabetes . METHODS Seventy-five postmenopausal women with type 2 diabetes participated in this single-center , r and omized , controlled , parallel-group trial in Shiraz , Iran . Participants were r and omly allocated to three groups including a control group ( balance diet + 30 g/d sunflower oil ) and two intervention groups ( balance diet + 30 g/day CO or RBO ) . At baseline and after 8 weeks , serum total cholesterol ( TC ) , triglyceride ( TG ) , low-density lipoprotein cholesterol ( LDL-C ) , and high-density lipoprotein cholesterol ( HDL-C ) were measured . RESULTS At 8 weeks , mean of serum levels of TG ( mg/dL ) , TC ( mg/dL ) , and LDL-C ( mg/dL ) significantly decreased in the CO group ( -23.66 , P RBO group ( -38.62 , P changes of TG , LDL-C , and non-HDL-C levels were significantly more in the RBO group ( P = .007 , P = .012 , and P = .011 , respectively ) . Levels of serum HDL-C remained unchanged in all groups at the end of study . CONCLUSIONS Substitution of RBO or CO for sunflower oil could attenuate lipid disorders in type 2 diabetes women . Moreover , RBO could improve lipid profile more efficiently than CO",
"Little is known about the physiological effects of red palm olein ( RPO ) . The effects of red palm olein and palm olein ( POL ) compared to sunflower oil ( SFO ) , on lipids , haemostatic factors and fibrin network characteristics in hyperfibrinogenaemic volunteers were investigated . Fifty-nine free-living , hyperfibrinogenaemic volunteers participated in this r and omized , controlled , single blind parallel study . After a 4-week run-in , during which subjects received sunflower oil products , they were paired and r and omly assigned to one of three intervention groups receiving products containing 25 g/day ( approximately 12 % of total energy intake ) of either red palm olein , palm olein or sunflower oil for another 4 weeks . Anthropometric measurements , blood sample s and dietary intakes were measured before run-in , and before and after intervention . The differences in changes in total serum cholesterol response between palm olein and red palm olein ( + 0.59 vs. + 0.18 mmol/l ; p=0.053 ) , and between palm olein and sunflower oil ( + 0.59 vs. -0.003 mmol/l ; p low-density lipoprotein cholesterol ( LDLC ) response in the palm olein- and sunflower oil-groups also differed significantly ( + 0.42 vs. -0.11 mmol/l ; p Tissue plasminogen activator antigen ( tPA(ag ) ) decreased significantly in the red palm olein group compared to the palm olein- and sunflower oil-groups . No effects were found in other haemostatic variables . Palm olein and red palm olein had no independent effect on fibrin network characteristics . In conclusion , compared to palm olein , red palm olein had less detrimental effects on the lipid profile and decreased tissue plasminogen activator antigen . Studies in larger groups are advised for confirmation of results , elucidation of mechanisms and effects of nonglyceride constituents of red palm oil ( PO )",
"Summary Background Both hempseed oil ( HO ) and flaxseed oil ( FO ) contain high amounts of essential fatty acids ( FAs ) ; i.e. linoleic acid ( LA , 18:2n-6 ) and alpha-linolenic acid ( ALA , 18:3n-3 ) , but almost in opposite ratios . An excessive intake of one essential FA over the other may interfere with the metabolism of the other while the metabolisms of LA and ALA compete for the same enzymes . It is not known whether there is a difference between n-3 and n-6 FA of plant origin in the effects on serum lipid profile . Aim of the study To compare the effects of HO and FO on the profile of serum lipids and fasting concentrations of serum total and lipoprotein lipids , plasma glucose and insulin , and haemostatic factors in healthy humans . Methods Fourteen healthy volunteers participated in the study . A r and omised , double-blind crossover design was used . The volunteers consumed HO and FO ( 30 ml/day ) for 4 weeks each . The periods were separated by a 4-week washout period . Results The HO period result ed in higher proportions of both LA and gamma-linolenic acid in serum cholesteryl esters ( CE ) and triglycerides ( TG ) as compared with the FO period ( P ALA in both serum CE and TG as compared with the HO period ( P proportion of arachidonic acid in CE was lower after the FO period than after the HO period ( P total-to-HDL cholesterol ratio compared with the FO period ( P = 0.065 ) . No significant differences were found between the periods in measured values of fasting serum total or lipoprotein lipids , plasma glucose , insulin or hemostatic factors . Conclusions The effects of HO and FO on the profile of serum lipids differed significantly , with only minor effects on concentrations of fasting serum total or lipoprotein lipids , and no significant changes in concentrations of plasma glucose or insulin or in haemostatic factors",
"BACKGROUND & AIMS Hypertension is one of the most important risk factors for coronary heart disease . Recent studies have pointed out the possibility that virgin olive oil ( VOO ) may lower blood pressure in hypertensive ( HT ) subjects . However , until the date there is scarce information regarding elderly people . The present study was design ed to assess the effect of dietary VOO on blood pressure in medically treated hypertensive elderly patients . METHODS 31 medically treated HT elderly patients and 31 normotensive ( NT ) elderly volunteers participated in a r and omized sequential dietary intervention . Subjects consumed diets enriched in sunflower oil ( SO ) or VOO for 4 weeks each with a 4-week washout period between them . RESULTS VOO reduced total and LDL-cholesterol in NT but not in HT ( P levels of tocopherols among the groups studied . Iron-induced oxidation of LDL result ed in a complete loss of monoacylglycerols ( MG ) and diacylglycerols ( DG ) and a reduction in triacylglycerols ( TG ) ( 60 - 80 % ) , which was found to be greater in HT ( P systolic pressure in the HT group ( 136 + /- 10 mmHg ) compared to SO ( 150 + /- 8 mmHg ) . CONCLUSION Dietary VOO proved to be helpful in reducing the systolic pressure of treated HT elderly subjects . However , a greater resistance to the lowering effect of VOO of total and LDL-cholesterol and a greater susceptibility to TG oxidation was detected in these patients",
"BACKGROUND & AIMS The aim of this study was to compare the in vivo effects of a diet rich in virgin olive oil or sunflower oil on the lipid profile and on LDL susceptibility to oxidative modification in free-living Spanish male patients with peripheral vascular disease . METHODS A total of 20 Spanish male subjects diagnosed with peripheral vascular disease were r and omly divided into two groups ( n = 10 ) receiving different supplements , virgin olive oil and sunflower oil for 4 months . RESULTS The adaptation of patients to the experimental supplements was demonstrated since plasma and LDL fatty acids composition reflected dietary fatty acids . No differences in triglycerides , total cholesterol , LDL-cholesterol or HDL-cholesterol concentrations were found between the groups of patients . A significantly higher LDL susceptibility to oxidation was observed after sunflower oil intake in comparison with virgin olive oil , in spite of an increase in LDL alpha-tocopherol concentration in sunflower oil group . CONCLUSIONS The results of the present study provide further evidence that sunflower-oil-enriched diets does not protect LDL against oxidation as virgin olive oil does in patients with peripheral vascular disease",
"BACKGROUND Butter is known to have a cholesterol-raising effect and , therefore , has often been included as a negative control in dietary studies , whereas the effect of moderate butter intake has not been eluci date d to our knowledge . OBJECTIVE We compared the effects of moderate butter intake , moderate olive oil intake , and a habitual diet on blood lipids , high-sensitivity C-reactive protein ( hsCRP ) , glucose , and insulin . DESIGN The study was a controlled , double-blinded , r and omized 2 × 5-wk crossover dietary intervention study with a 14-d run-in period during which subjects consumed their habitual diets . The study included 47 healthy men and women ( mean ± SD total cholesterol : 5.22 ± 0.90 mmol/L ) who substituted a part of their habitual diets with 4.5 % of energy from butter or refined olive oil . RESULTS Study subjects were 70 % women with a mean age and body mass index ( in kg/m² ) of 40.4 y and 23.5 , respectively . Butter intake increased total cholesterol and LDL cholesterol more than did olive oil intake ( P increased HDL cholesterol compared with the run-in period ( P for triacylglycerol , hsCRP , insulin , and glucose concentrations . The intake of saturated fatty acids was significantly higher in the butter period than in the olive oil and run-in periods ( P of butter result ed in increases in total cholesterol and LDL cholesterol compared with the effects of olive oil intake and a habitual diet ( run-in period ) . Furthermore , moderate butter intake was also followed by an increase in HDL cholesterol compared with the habitual diet . We conclude that hypercholesterolemic people should keep their consumption of butter to a minimum , whereas moderate butter intake may be considered part of the diet in the normocholesterolemic population",
"OBJECTIVE Compared to vegetable oils in their unmodified state , partially-hydrogenated fat is associated with less favorable effects on cardiovascular disease ( CVD ) risk factors . Acceptable alternatives must be adjudicated . Our objective was to assess the effect of a recent commercial fat substitution , corn oil for partially-hydrogenated soybean oil . METHODS Using a double-blind cross-over design , 30 postmenopausal women > or=50 years with LDL-cholesterol concentrations > or=120 mg/dL were r and omly assigned to each of two 35-day phases ; all food and beverage was provided to maintain body weight . Corn or partially-hydrogenated soybean oil was incorporated throughout the diet and contributed two-thirds of fat . Primary outcomes included fasting and non-fasting lipid , lipoprotein , apolipoprotein , and fasting high sensitivity C-reactive protein ( hsCRP ) concentrations ; secondary outcomes included fasting small dense LDL (sdLDL)-cholesterol , remnant lipoprotein cholesterol ( RemLC ) , glycated albumin , adiponectin and immunoreactive insulin concentrations , and endogenous cholesteryl ester transfer protein ( CETP ) and lecithin : cholesterol acyl transferase ( LCAT ) activities . RESULTS Relative to the partially-hydrogenated soybean oil enriched diet , the corn oil enriched diet result ed in lower fasting total cholesterol ( 7 % ; P LDL-cholesterol ( 10 % ; P VLDL-cholesterol ( 7 % ; P=0.052 ) , apo B ( 9 % ; P lipoprotein ( a ) [ Lp(a ) ] ( 5 % ; P=0.024 ) , sdLDL-cholesterol ( 17 % ; P=0.001 ) , and RemLC ( 20 % ; P=0.007 ) concentrations , and no significant effect on the other outcomes . Changes in postpr and ial ( 4-h post-meal ) lipid , lipoprotein and apolipoprotein concentrations were similar to the fasting state . CONCLUSION The replacement of partially-hydrogenated soybean oil with corn oil favorably affects a range of CVD risk factors and is an appropriate option to decrease cardiovascular disease risk factors in moderately hypercholesterolemic individuals",
"The present studies were conducted to evaluate the cholesterolemic effects of whole-food diets high in stearic acid . In study no. 1 , normocholesterolemic young men were fed diets high in stearic acid provided by cocoa butter ( CB ) ; oleic acid provided by olive oil ( OO ) ; linoleic acid provided by soybean oil ( SO ) ; and myristic acid ( and lauric acid ) provided by dairy butter ( B ) . In study no. 2 , different subjects with similar baseline characteristics were fed diets high in stearic acid provided by milk chocolate ( C ) , CB , CB+B ( 4:1 , MIX ) , and myristic ( and lauric ) acid provided by B. Both studies used a r and omized , crossover , double-blind experimental design , and experimental subjects ( n = 18 for study no. 1 and n = 15 for study no. 2 ) in each study consumed every diet for 26 days with a 1-month wash-out period between each experimental period . The diets provided 37 % of calories from fat , of which 81 % was provided by the test fat . Ten ounces ( 280 g ) C was provided daily by the C diet . In study no. 1 , the B diet was hypercholesterolemic , whereas the SO diet was hypocholesterolemic , compared with the other diets . The OO and SO diets were hypocholesterolemic compared with the CB diet . Low-density lipoprotein ( LDL ) cholesterol levels , in general , paralleled the changes in plasma total cholesterol levels . SO significantly decreased apolipoprotein ( apo ) B levels compared with the other diets . Plasma very-low density lipoprotein ( VLDL ) cholesterol , high-density lipoprotein ( HDL ) cholesterol , and apo A-I levels were unaffected by the experimental diets . ( ABSTRACT TRUNCATED AT 250 WORDS",
"OBJECTIVE Olive oil ( OO ) is a rich source of monounsaturated fat and bioactive components that exert strong anti-oxidant and anti-inflammatory properties . Flaxseed oil ( FO ) is rich in α-linolenic n-3 fatty acid ( ALA ) , which also exhibits anti-inflammatory effects . This r and omized , cross-over study aim ed at exploring whether diet 's enrichment with FO could beneficially alter inflammatory markers and lipid profile , compared to OO , in a sample of normal weight , apparently healthy young adults . MATERIAL S AND METHODS Participants were supplied with 15 mL/day of either FO or OO . Each intervention and the wash-out period lasted 6 weeks . Dietary , anthropometric and physical activity variables were recorded at the beginning and the end of each intervention . Serum biochemical and inflammatory markers were measured . Compliance to the intervention was evaluated by fatty acid analysis in erythrocytes . Repeated Measures ANOVA was used to assess the effect of the treatment . RESULTS Thirty seven participants completed the study . No difference between the two interventions was observed in adiponectin , TNF-α , high sensitivity-CRP or glucose levels and lipid profile . At the end of the FO period , participants exhibited significant reductions in total ( -5.0 % ) and LDL-cholesterol ( -6.7 % ) levels ( all P period serum adiponectin changes were significantly correlated with changes in erythrocyte % ALA ( rs=0.34 , P=0.007 ) and in erythrocyte % EPA ( r(s)=0.47 , P=0.01 ) , respectively . CONCLUSIONS Daily consumption of FO did not confer any benefit in inflammatory or biochemical markers in normal weight young adults , who traditionally use olive oil as the main edible oil",
"BACKGROUND Dietary fat type is known to modulate the plasma lipid profile , but its effects on plasma homocysteine and inflammatory markers are unclear . OBJECTIVE We investigated the effects of high-protein Malaysian diets prepared with palm olein , coconut oil ( CO ) , or virgin olive oil on plasma homocysteine and selected markers of inflammation and cardiovascular disease ( CVD ) in healthy adults . DESIGN A r and omized-crossover intervention with 3 dietary sequences of 5 wk each was conducted in 45 healthy subjects . The 3 test fats , namely palmitic acid (16:0)-rich palm olein ( PO ) , lauric and myristic acid ( 12:0 + 14:0)-rich CO , and oleic acid (18:1)-rich virgin olive oil ( OO ) , were incorporated at two-thirds of 30 % fat calories into high-protein Malaysian diets . RESULTS No significant differences were observed in the effects of the 3 diets on plasma total homocysteine ( tHcy ) and the inflammatory markers TNF-α , IL-1β , IL-6 , and IL-8 , high-sensitivity C-reactive protein , and interferon-γ . Diets prepared with PO and OO had comparable nonhypercholesterolemic effects ; the postpr and ial total cholesterol for both diets and all fasting lipid indexes for the OO diet were significantly lower ( P decrease postpr and ial lipoprotein(a ) . CONCLUSION Diets that were rich in saturated fatty acids prepared with either PO or CO , and an OO diet that was high in oleic acid , did not alter postpr and ial or fasting plasma concentrations of tHcy and selected inflammatory markers . This trial was registered at clinical trials.gov as NCT00941837",
"Camelina sativa-derived oil ( camelina oil ) is a good source of alpha-linolenic acid . The proportion of alpha-linolenic acid in serum fatty acids is associated with the risk of cardiovascular diseases . We studied the effects of camelina oil on serum lipids and on the fatty acid composition of total lipids in comparison to rapeseed and olive oils in a parallel , double-blind setting . Sixty-eight hypercholesterolemic subjects aged 28 to 65 years were r and omly assigned after a 2-week pretrial period to 1 of 3 oil groups : camelina oil , olive oil , and rapeseed oil . Subjects consumed daily 30 g ( actual intake , approximately 33 mL ) of test oils for 6 weeks . In the camelina group , the proportion of alpha-linolenic acid in fatty acids of serum lipids was significantly higher ( P rapeseed oil group and 4 times higher compared to the olive oil group . Respectively the proportions of 2 metabolites of alpha-linolenic acid ( eicosapentaenoic and docosapentaenoic acids ) increased and differed significantly in the camelina group from those in other groups . During the intervention , the serum low-density lipoprotein ( LDL ) cholesterol concentration decreased significantly by 12.2 % in the camelina oil group , 5.4 % in the rapeseed oil group , and 7.7 % in the olive oil group . In conclusion , camelina oil significantly elevated the proportions of alpha-linolenic acid and its metabolites in serum of mildly or moderately hypercholesterolemic subjects . Camelina oil 's serum cholesterol-lowering effect was comparable to that of rapeseed and olive oils",
"The effects of a diet containing soybean oil ( SBO ) , rice bran oil ( RBO ) , palm oil ( PO ) or a RBO/PO ( 3:1 ) mixture on the composition and oxidation of small dense low-density lipoproteins ( sdLDL ) in 16 hypercholesterolaemic women were investigated . During the 8-week control period , participants consumed a free-choice weight-maintaining diet comprising carbohydrate ( 55 % energy ) , protein ( 15 % energy ) and fat ( 30 % energy ) with During each 10-week study period , participants consumed this same diet but with the addition of one of the three test oils or the RBO/PO mixture . Total cholesterol and low-density lipoprotein (LDL)-cholesterol levels were significantly reduced during SBO , RBO and RBO/PO consumption , while high-density lipoprotein cholesterol was significantly decreased by SBO consumption . There was a significant reduction in sdLDL-cholesterol levels only after using SBO and it tended to be reduced during RBO/PO consumption , whereas it was significantly increased following PO consumption . The sdLDL oxidation lag time was significantly increased during PO , RBO/PO and RBO consumption , but significantly reduced following SBO . The results for the RBO/PO mixture suggest that this oil mixture might further reduce the risk of atherosclerosis",
"In a prospect i ve , r and omised single-blinded secondary prevention trial we compared the effect of a Mediterranean alpha-linolenic acid-rich diet to the usual post-infa rct prudent diet . After a first myocardial infa rct ion , patients were r and omly assigned to the experimental ( n = 302 ) or control group ( n = 303 ) . Patients were seen again 8 weeks after r and omisation , and each year for 5 years . The experimental group consumed significantly less lipids , saturated fat , cholesterol , and linoleic acid but more oleic and alpha-linolenic acids confirmed by measurements in plasma . Serum lipids , blood pressure , and body mass index remained similar in the 2 groups . In the experimental group , plasma levels of albumin , vitamin E , and vitamin C were increased , and granulocyte count decreased . After a mean follow up of 27 months , there were 16 cardiac deaths in the control and 3 in the experimental group ; 17 non-fatal myocardial infa rct ion in the control and 5 in the experimental groups : a risk ratio for these two main endpoints combined of 0.27 ( 95 % CI 0.12 - 0.59 , p = 0.001 ) after adjustment for prognostic variables . Overall mortality was 20 in the control , 8 in the experimental group , an adjusted risk ratio of 0.30 ( 95 % CI 0.11 - 0.82 , p = 0.02 ) . An alpha-linolenic acid-rich Mediterranean diet seems to be more efficient than presently used diets in the secondary prevention of coronary events and death",
"Background Observational cohort studies and a secondary prevention trial have shown inverse associations between adherence to the Mediterranean diet and cardiovascular risk . Methods In a multicenter trial in Spain , we assigned 7447 participants ( 55 to 80 years of age , 57 % women ) who were at high cardiovascular risk , but with no cardiovascular disease at enrollment , to one of three diets : a Mediterranean diet supplemented with extra‐virgin olive oil , a Mediterranean diet supplemented with mixed nuts , or a control diet ( advice to reduce dietary fat ) . Participants received quarterly educational sessions and , depending on group assignment , free provision of extra‐virgin olive oil , mixed nuts , or small nonfood gifts . The primary end point was a major cardiovascular event ( myocardial infa rct ion , stroke , or death from cardiovascular causes ) . After a median follow‐up of 4.8 years , the trial was stopped on the basis of a prespecified interim analysis . In 2013 , we reported the results for the primary end point in the Journal . We subsequently identified protocol deviations , including enrollment of household members without r and omization , assignment to a study group without r and omization of some participants at 1 of 11 study sites , and apparent inconsistent use of r and omization tables at another site . We have withdrawn our previously published report and now report revised effect estimates based on analyses that do not rely exclusively on the assumption that all the participants were r and omly assigned . Results A primary end‐point event occurred in 288 participants ; there were 96 events in the group assigned to a Mediterranean diet with extra‐virgin olive oil ( 3.8 % ) , 83 in the group assigned to a Mediterranean diet with nuts ( 3.4 % ) , and 109 in the control group ( 4.4 % ) . In the intention‐to‐treat analysis including all the participants and adjusting for baseline characteristics and propensity scores , the hazard ratio was 0.69 ( 95 % confidence interval [ CI ] , 0.53 to 0.91 ) for a Mediterranean diet with extra‐virgin olive oil and 0.72 ( 95 % CI , 0.54 to 0.95 ) for a Mediterranean diet with nuts , as compared with the control diet . Results were similar after the omission of 1588 participants whose study ‐group assignments were known or suspected to have departed from the protocol . Conclusions In this study involving persons at high cardiovascular risk , the incidence of major cardiovascular events was lower among those assigned to a Mediterranean diet supplemented with extra‐virgin olive oil or nuts than among those assigned to a reduced‐fat diet . ( Funded by Instituto de Salud Carlos III , Spanish Ministry of Health , and others ; Current Controlled Trials number , IS RCT N35739639 .",
"This study examines , for the first time , the effect of hybrid Elaeis oleifera × E. guineensis palm oil supplementation on human plasma lipids related to CVD risk factors . One hundred sixty eligible participants were r and omized and assigned to one of the two treatments : 25 mL hybrid palm oil ( HPO group ) or 25 mL extra virgin olive oil ( EVOO group ) daily for 3 months . Fasting venous sample s were obtained at baseline and after 1 , 2 and 3 months for measurement of plasma lipids ( TC , LDL-C , HDL-C and TAGs ) . Changes in body mass index and waist circumference were also assessed . Although there was an overall reduction in TC ( 7.4 % , p LDL-C ( 15.6 % , p TC ( p = 0.0525 ) , LDL-C ( p = 0.2356 ) , HDL-C ( p = 0.8293 ) or TAGs ( p = 0.3749 ) . Furthermore , HPO consumption had similar effects on plasma lipids to EVOO , thus providing additional support for the concept that hybrid Elaeis oleifera × E. guineensis palm oil can be seen as a \" tropical equivalent of olive oil \""
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BACKGROUND Seasonal affective disorder ( SAD ) consists of recurrent major depressive episodes in the fall/winter with remissions in spring/summer . METHOD A Medline search was conducted to identify studies relating to clinical management of SAD using the Medical Subject Heading , seasonal affective disorder , and key words , depress * and season * , focusing on studies published in the past 10 years . The Cochrane library of systematic review s was also search ed for relevant studies . RESULTS A careful history is important to make the diagnosis and differentiate SAD from other similar conditions such as subsyndromal SAD and atypical depression . Seasonal patterns with winter worsening are also recognized in " nonseasonal " depression as well as many other psychiatric conditions , and comorbidity with SAD is common . The pathophysiology of SAD seems to be heterogeneous as research on circadian , neurotransmitter function and genetic hypotheses have shown discrepant results . A dual vulnerability model with differential loading on separate seasonal and depression factors has been proposed to explain these findings . Recent systematic review s have shown that light therapy is an efficacious and well-tolerated treatment for SAD . There is also evidence for efficacy of pharmacotherapy to treat and prevent SAD . Clinical studies show equal effectiveness with light and antidepressants , so patient preference should be considered in the selection of initial treatment . Dawn stimulation , negative air ions , exercise and cognitve behaviour therapy are under investigation and may also be helpful treatments for SAD . CONCLUSIONS SAD is a common condition with significant psychosocial impairment . Clinicians should be vigilant in recognizing seasonal patterns of depressive episodes because there are effective , evidence -based treatments for SAD
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"Rationale Seasonal affective disorder ( SAD ) is a relatively common cyclical depressive illness characterized by seasonal depressions during winter . The disorder is commonly responsive to light therapy , but antidepressant drug efficacy has not been definitely established . Serotonin selective re-uptake inhibitors are potentially efficacious treatments for SAD . Objectives The objective of this study was to evaluate the efficacy , tolerability and safety of sertraline treatment for SAD . Methods One hundred and eighty seven out patients with seasonal pattern recurrent winter depression ( DSM-III-R defined ) and a minimum 29-item Hamilton depression scale ( SIGH-SAD version ) score of 22 were r and omized to 8 weeks treatment with either sertraline or placebo in a double-blind , multi-country , multi-center , parallel-group , flexible dose ( 50–200 mg once daily ) study . Efficacy was investigated using physician and patient-rated scales measuring depression , anxiety and symptoms characteristic of seasonal affective disorder . Results Sertraline produced a significantly greater response than placebo at endpoint as measured by changes in the 29-item and 21-item Hamilton depression scales , the clinical global impression ( CGI ) severity scale , the Hamilton anxiety scale , and the hospital anxiety and depression scale . The proportion of sertraline-treated subjects achieving a response on the CGI improvement rating ( ratings of 1 or 2 ) at endpoint ( last observation carried forward ) was significantly greater than that of the placebo group . Overall sertraline was well tolerated with the most frequent placebo adjusted adverse events , being nausea , diarrhea , insomnia and dry mouth . Adverse events were mostly mild to moderate and transient . Conclusions Sertraline pharmacotherapy has been demonstrated to be an effective and well-tolerated therapy for out patients with SAD . As such , sertraline offers an important pharmacological option in the clinical management of this condition",
"OBJECTIVE In DSM-IV , winter seasonal affective disorder ( SAD ) is classified as a seasonal pattern of recurrent major depressive episodes in winter with full remission of symptoms in summer . However , other groups with \" winter depression \" have been identified , including patients with incomplete summer remission ( ISR ) and subsyndromal SAD ( sub-SAD , winter depressive symptoms that do not meet criteria for major depression ) . In this study , we compare the clinical characteristics of these three seasonal groups and their response to light therapy . METHOD 558 patients assessed at a specialized SAD Clinic were diagnosed using DSM-III-R or DSM-IV criteria . Clinical information was recorded using a checklist at index assessment . A subset of patients ( N=192 ) were treated with an open , 2 week trial of light therapy using a 10000 lux fluorescent light box for 30 min per day in the early morning . Patients were assessed before and after treatment with the 29 item modified Hamilton Depression Rating Scale and clinical response was defined as greater than 50 % improvement in scores . RESULTS The rates of some melancholic symptoms , anxiety , panic , suicidal ideation , and family history of mood disorder were lowest in the sub-SAD group . The clinical response rates to light therapy were highest in the sub-SAD group ( N=32 , 78 % ) , intermediate in the SAD group ( N=113 , 66 % ) , and lowest in the ISR group ( N=47 , 51 % ) . LIMITATIONS This was a retrospective study of patients seen in a specialty clinic , although information was obtained in a st and ardized format . The light therapy trial had an open design so that placebo response could not be determined . CONCLUSIONS There are differences in both the patterns of clinical symptoms and the response to light therapy in these three groups with winter depression . These results are consistent with a dual vulnerability hypothesis that considers these groups to result from interaction of separate factors for seasonality and depression",
" In patients with winter seasonal affective disorder ( SAD ) the onset of a depressive episode is probably associated with the decreasing amount of light during the autumn . A highly predictable onset of a recurrent depressive episode with seasonal pattern provides a rationale for testing the efficacy of bright-light treatment as a preventive measure . Twelve out- patients with winter SAD were assigned to start bright light treatment either when they were well , or not to start it until the first symptoms of depression had already emerged . The severity of depressive symptoms was prospect ively rated for a parallel r and omized comparison . Bright light given well in advance of the emerging symptoms prevented a depressive episode . Clinical remission was significantly more frequent in the former subgroup of the patients in January and in March . To sum up , bright light can be successfully administered as prophylactic treatment for the prevention of winter SAD",
"Seasonal affective disorder ( SAD ) is a syndrome characterized by recurrent depressions that occur annually at the same time each year . We describe 29 patients with SAD ; most of them had a bipolar affective disorder , especially bipolar II , and their depressions were generally characterized by hypersomnia , overeating , and carbohydrate craving and seemed to respond to changes in climate and latitude . Sleep recordings in nine depressed patients confirmed the presence of hypersomnia and showed increased sleep latency and reduced slow-wave ( delta ) sleep . Preliminary studies in 11 patients suggest that extending the photoperiod with bright artificial light has an antidepressant effect ",
" Of a total of 581 consecutive depressed subjects attending psychiatric services of 6 centres in Finl and , 183 patients were eligible and completed a 6-week r and omised double-blind trial with either moclobemide or fluoxetine . Of these , 32 ( 17.5 % ) patients met the DSM-III-R criteria for mood disorder with a seasonal ( winter ) pattern and 19 patients ( 10.5 % ) met the original criteria for seasonal affective disorder ( SAD ) . There were no significant difference in the antidepressive response to the treatment between the patients with SAD and other depressive disorder . The treatment of 6 weeks with either moclobemide ( 300 - 450 mg daily ) or fluoxetine ( 20 - 40 mg daily ) result ed in a full remission in 15 ( 52 % ) patients with SAD and in 44 ( 37 % ) patients with other depressive disorder . Altogether , 23 ( 79 % ) and 83 ( 70 % ) patients , respectively , got significant benefit from the treatment . The improvement in the health-related quality of life in terms of ability to work was significantly more extensive in the patients with SAD assigned to receive moclobemide compared with the other depressive patients allocated to the same medication . Subjects who in addition met the operational criteria for atypical depression were equally distributed into the SAD and other depressive patient groups",
"Background : This study sought to determine whether the prevalence of the seasonal subtype of major depression ( SAD ) in the community varied as a function of latitude . Methods : R and om telephone numbers were generated across 8 degrees of latitude ( 41.5 ° N to 49.5 ° N ) for the province of Ontario . Eight strata of 1 degree each were sample d equally throughout a 12-month period . Using a vali date d and structured diagnostic interview , we interviewed by telephone respondents over 20 years of age who had lived in the region for 3 years or more . We evaluated patterns of symptom change across seasons to establish a diagnosis of SAD according to DSM-IV criteria . Results : Of the 2078 households that were assessed for eligibility , 1605 ( 77 % ) completed the interview . The crude prevalence of lifetime SAD was 2.6 % ( 95 % CI , 1.9 to 3.5 ) . There was no impact of latitude on prevalence of either major depression or the seasonal subtype across the 8 strata , although the global measure of the severity of seasonal change in mood was significantly negatively correlated with latitude . Conclusions : SAD is a common subtype of major depression in Ontario , but there is no evidence to support an increase in prevalence with increasing latitude . Context e : Cette étude visait à déterminer si la prévalence du caractère saisonnier de la dépression majeure ( DMS ) dans la communauté variait selon la latitude . Méthodes : Des numéros de téléphone aléatoires ont été fournis sur 8 degrés de latitude ( de 41,5 ° N. à 49,5 ° N. ) dans la province de l'Ontario . Huit b and es de 1 degré chacune ont été échantillonnées également sur une période de 12 mois . À l'aide d'une entrevue diagnostique validée et structurée , nous avons interviewé par téléphone des répondants âgés de plus de 20 ans qui habitaient la région depuis 3 ans ou plus . Nous avons évalué les changements des modèles de symptômes selon les saisons pour établir un diagnostic de DMS selon les critères du DSM-IV . Résultats : Sur les 2 078 ménages admissibles , 1 605 ( 77 % ) ont terminé l'entrevue . La prévalence brute de la DMS à vie était de 2,6 % ( 95 % IC , 1,9 à 3,5 ) . La latitude n'influait pas sur la prévalence de la dépression majeure ou du caractère saisonnier dans les 8 b and es , bien que la mesure globale de la sévérité du changement saisonnier de l'humeur ait indiqué une corrélation négative significative à la latitude . Conclusions : La dépression majeure saisonnière est un sous-type rép and u de la dépression majeure en Ontario , mais aucune preuve ne soutient une augmentation de la prévalence parallèle à l'accroissement de la latitude",
"OBJECTIVE Previous reports of side effects from light therapy were mostly based on administration of 2,500-lux treatments . It has become common practice to use brighter , 10,000-lux exposure when treating seasonal affective disorder . The authors studied side effects produced by short-term 10,000-lux light therapy . METHOD Seventy subjects with seasonal affective disorder who underwent brief 10,000-lux light therapy were asked to report side effects . RESULTS Of the 70 subjects , 32 ( 45.7 % ) experienced side effects , and nine ( 12.9 % ) reported two or more apiece . Headaches and eye or vision problems were the most common . Almost all were mild , were transient , and did not interfere with treatment . CONCLUSIONS Short-term 10,000-lux light therapy often produces side effects early in treatment . These are not serious or prolonged , however , confirming findings from earlier studies that used dimmer light",
"The effects of two non-drug treatments ( physical exercise and bright light ) on mood , body weight and oxygen consumption were compared in age-matched groups of female subjects with winter depression , non-seasonal depression or without depression . It was found that oxygen consumption in the pre-treatment condition was similar in non-depressed subjects ( n=18 ) and depressed non-seasonals ( n=18 ) , while comparatively lower values were obtained in winter depression ( n=27 ) . Neither mood nor metabolic parameters changed significantly in the group of nine untreated winter depressives . One week of physical exercise ( 1-h pedaling on a bicycle ergometer between 13.00 and 14.00 h ) increased oxygen consumption in the group of nine winter depressives and lowered oxygen consumption in nine-subject groups of depressed and non-depressed non-seasonals . One week of bright light treatment ( 2-h exposure to 2500 lux between 14.00 and 16.00 h ) increased oxygen consumption in nine winter depressives and nine non-depressed subjects , while no significant change in oxygen consumption was found in nine subjects with non-seasonal depression . Weight loss was observed in the groups treated with physical exercise and in the group of light-treated winter depressives . Winter depression responded equally well to exercising and light , while a significant therapeutic difference in favor of exercising was found in non-seasonal depression . Overall , the results of the study suggest that energy-regulating systems are implicated in the antidepressant action of the non-drug treatments",
"OBJECTIVE Light therapy and antidepressants have shown comparable efficacy in separate studies of seasonal affective disorder treatment , but few studies have directly compared the two treatments . This study compared the effectiveness of light therapy and an antidepressant within a single trial . METHOD This double-blind , r and omized , controlled trial was conducted in four Canadian centers over three winter seasons . Patients met DSM-IV criteria for major depressive disorder with a seasonal ( winter ) pattern and had scores > or = 23 on the 24-item Hamilton Depression Rating Scale . After a baseline observation week , eligible patients were r and omly assigned to 8 weeks of double-blind treatment with either 1 ) 10,000-lux light treatment and a placebo capsule , or 2 ) 100-lux light treatment ( placebo light ) and fluoxetine , 20 mg/day . Light treatment was applied for 30 minutes/day in the morning with a fluorescent white-light box ; placebo light boxes used neutral density filters . RESULTS A total of 96 patients were r and omly assigned to a treatment condition . Intent-to-treat analysis showed overall improvement with time , with no differences between treatments . There were also no differences between the light and fluoxetine treatment groups in clinical response rates ( 67 % for each group ) or remission rates ( 50 % and 54 % , respectively ) . Post hoc testing found that light-treated patients had greater improvement at 1 week but not at other time points . Fluoxetine was associated with greater treatment-emergent adverse events ( agitation , sleep disturbance , palpitations ) , but both treatments were generally well-tolerated with no differences in overall number of adverse effects . CONCLUSIONS Light treatment showed earlier response onset and lower rate of some adverse events relative to fluoxetine , but there were no other significant differences in outcome between light therapy and antidepressant medication . Although limited by lack of a double-placebo condition , this study supports the effectiveness and tolerability of both treatments for seasonal affective disorder and suggests that other clinical factors , including patient preference , should guide selection of first-line treatment",
"PURPOSE We assessed the potential ocular hazards of bright light therapy for patients with seasonal affective disorder , after both short- and long-term treatment , and identified prospect i ve patients with pre-existing ocular abnormalities . METHODS Fifty patients with seasonal affective disorder received daily exposure to artificial light in the morning or evening for 30 minutes at an illuminance level of 10,000 lux ( irradiant dose , 0.016 J/cm2 ) . Ophthalmologic examinations were performed before and after short-term treatment ( two to eight weeks ) and after three to six years of use during the fall and winter months . Over the four years of patient intake , the eye examination included subsets of the following tests : visual acuity , intraocular pressure , slit-lamp biomicroscopy , direct and indirect ophthalmoscopy , color vision , visual field , fundus photography , Amsler grid , ocular motility , pupillary reactions , contrast sensitivity , stereopsis , and the macular stress test . RESULTS No ocular changes were detected after short-term treatment . Long-term treatment ( three to six years ) of 17 patients , with cumulative exposure duration s of 60 to 1,250 hours , also result ed in no ocular abnormalities . CONCLUSIONS Light therapy yields about 75 % clinical remissions . It is effective as an antidepressant and appears safe for the eyes . Current knowledge is insufficient to specify any definite ocular contraindications for bright light therapy , although we recommend that patients with preexisting ocular abnormalities and those using photosensitizing drugs undergo treatment only with periodic ophthalmologic examination",
"BACKGROUND The need to develop supplementary or alternative treatments for seasonal affective disorder ( SAD ) is underscored by the significant minority ( 47 % ) of SAD patients that is refractory to light therapy , the persistence of residual symptoms despite light treatment , and poor long-term compliance with light use . Because preliminary studies suggest that cognitive and behavioral factors are involved in SAD , cognitive-behavioral therapy ( CBT ) warrants investigation as a possible treatment option . METHODS We piloted a 6-week r and omized clinical trial to compare a st and ard light therapy protocol ; a novel , SAD-tailored , group CBT intervention ; and their combination in ameliorating and remitting a current SAD episode and as prophylaxis against episode recurrence . Depressive symptom severity and remission rates were assessed at post-treatment and at a 1-year follow-up visit to examine long-term treatment durability . RESULTS CBT , light therapy , and their combination all demonstrated significant reductions in depressive symptoms on two different outcome measures . Remission rates varied by measure , but did not reach statistical significance . During the subsequent winter , CBT , particularly in combination with light therapy , appeared to improve long-term outcome regarding symptom severity , remission rates , and relapse rates . No CBT-treated participant , with or without light , experienced a full SAD relapse compared to over 60 % of those treated with light alone . LIMITATIONS These results should be viewed as preliminary and are limited by the small sample size ( n=23 ) and lack of a control group . CONCLUSIONS The nearly half of SAD patients who do not remit with light alone may benefit from CBT as an adjunct or alternative treatment , especially as a prophylaxis against episode recurrence",
"BACKGROUND Artificial bright light presents a promising nonpharmacological treatment for seasonal affective disorder . Past studies , however , have lacked adequate placebo controls or sufficient power to detect group differences . The importance of time of day of treatment -- specifically , morning light superiority -- has remained controversial . METHODS This study used a morning x evening light crossover design balanced by parallel-group controls , in addition to a nonphotic control , negative air ionization . Subjects with seasonal affective disorder ( N = 158 ) were r and omly assigned to 6 groups for 2 consecutive treatment periods , each 10 to 14 days . Light treatment sequences were morning-evening , evening-morning , morning-morning , and evening-evening ( 10,000 lux , 30 min/d ) . Ion density was 2.7 x 10(6 ) ( high ) or 1.0 x 10(4 ) ( low ) ions per cubic centimeter ( high-high and low-low sequences , 30 min/d in the morning ) . RESULTS Analysis of depression scale percentage change scores showed low-density ion response to be inferior to all other groups , with no other group differences . Response to evening light was reduced when preceded by treatment with morning light , the sole sequence effect . Stringent remission criteria , however , showed significantly higher response to morning than evening light , regardless of treatment sequence . CONCLUSIONS Bright light and high-density negative air ionization both appear to act as specific antidepressants in patients with seasonal affective disorder . Whether clinical improvement would be further enhanced by their use in combination , or as adjuvants to medication , awaits investigation",
"BACKGROUND This r and omized controlled trial investigates the efficacy of two non-pharmacologic treatments , bright light and high-density negative air ions for non-seasonal chronic depression . Both methods have shown clinical success for seasonal affective disorder ( SAD ) . METHOD Patients were 24 ( 75 % ) women and 8 ( 25 % ) men , ages 22 - 65 years ( mean age + /- S.D. , 43.7 + /- 12.4 years ) , with Major Depressive Disorder , Single Episode ( DSM-IV code , 296.2 ) , Chronic ( episode duration > or = 2 years ) . Patients were entered throughout the year and r and omly assigned to exposure to bright light ( 10 000 lux , n = 10 ) , or high-density ( 4.5 x 10(14 ) ions/s flow rate , n = 12 ) or low-density ( 1.7 x 10(11 ) ions/s , n = 10 , placebo control ) negative air ions . Home treatment sessions occurred for 1 h upon awakening for 5 weeks . Blinded raters assessed symptom severity weekly with the Structured Interview Guide for the Hamilton Depression Rating Scale -- Seasonal Affective Disorder ( SIGH-SAD ) version . Evening saliva sample s were obtained before and after treatment for ascertainment of circadian melatonin rhythm phase . RESULTS SIGH-SAD score improvement was 53.7 % for bright light and 51.1 % for high-density ions v. 17.0 % for low-density ions . Remission rates were 50 % , 50 % and 0 % respectively . The presence or severity of atypical symptoms did not predict response to either treatment modality , nor were phase advances to light associated with positive response . CONCLUSIONS Both bright light and negative air ions are effective for treatment of chronic depression . Remission rates are similar to those for SAD , but without a seasonal dependency or apparent mediation by circadian rhythm phase shifts . Combination treatment with antidepressant drugs may further enhance clinical response",
"Patterns of seasonal changes in mood and behavior in Montgomery County , Maryl and , were evaluated in r and omly selected household sample s by lay interviewers using a telephone version of the Seasonal Pattern Assessment Question naire . The method for selecting the sample unit was r and om-digit dialing . We found that 92 % of the survey subjects noticed seasonal changes of mood and behavior to varying degrees . For 27 % of the sample seasonal changes were a problem and 4.3 % to 10 % of subjects , depending on the case-finding definition , rated a degree of seasonal impairment equivalent to that of patients with seasonal affective disorder . The seasonal pattern of \" feeling worst \" exhibited a bimodal distribution with a greater winter and a substantially lower summer peak ( ratio , 4.5:1 ) . Younger women who have a problem with seasonal changes and who feel worse on short days tended to exhibit the highest seasonality scores . It is apparent from our study that seasonal affective disorder represents the extreme end of the spectrum of seasonality that affects a large percentage of the general population . The influence of environmental factors on mood disorders and mood changes in the general population might provide valuable insight into pathogenesis , treatment , and prevention of affective illness",
"BACKGROUND Disturbances of serotonergic neurotransmission appear to be particularly important for the pathophysiology of winter depression . This study investigated whether fluoxetine has antidepressant effects comparable to bright light in the treatment of seasonal affective disorder ( winter type ) . METHOD A r and omized , parallel design was used with rater and patients blind to treatment conditions . One week of placebo ( phase I ) was followed by 5 weeks of treatment ( phase II ) with fluoxetine ( 20 mg per day ) and a placebo light condition versus bright light ( 3000 lux , 2 h per day ) and a placebo drug . There were 40 patients ( 20 in each treatment condition ) suffering from seasonal affective disorder ( SAD ) according to DSM-III-R who had a total score on the Hamilton Depression Scale of at least 16 . RESULTS Forty patients entered phase II and 35 completed it ( one drop-out in the fluoxetine group and four in the bright light group ) . Fourteen ( 70 % ) of the patients treated with bright light and 13 ( 65 % ) of those treated with fluoxetine were responders ( NS ) . The remission rate in the bright light group tended to be superior ( bright light 50 % , fluoxetine 25 % ; P = 0.10 ) . Light therapy improved HDRS scores significantly faster , while fluoxetine had a faster effect on atypical symptoms . Light treatment in the morning produced a significantly faster onset of improvement , but at the end of treatment the time of light application seemed not to be crucial . CONCLUSION Both treatments produced a good antidepressant effect and were well tolerated . An apparently better response to bright light requires confirmation in a larger sample",
"BACKGROUND Bright light therapy has been established for treatment of winter depression , or seasonal affective disorder ( SAD ) . Analysis of side effects most often have focused on a narrow set of suspected symptoms , based on clinical observation ( e.g. , headache , eyestrain , nausea , insomnia , and hyperactivity ) . This study broadens the purview to a set of 88 physical and subjective symptoms that might emerge , remit , or remain unchanged relative to baseline , thus reducing bias toward assessment of presumed side effects . METHOD Eighty-three patients with SAD ( DSM-III-R criteria for mood disorders with seasonal pattern [ winter type ] and National Institute of Mental Health criteria for SAD ) received bright light therapy at 10,000 lux for 30 minutes daily in the morning or evening for 10 to 14 days . They completed a question naire ( Systematic Assessment for Treatment Emergent Effects ) , rating symptom severity before and after treatment . Results were compared for morning or evening treatment and for responders and nonresponders . RESULTS Several side effects emerged -- mostly mildly -- including jumpiness/jitteriness ( 8.8 % ) , headache ( 8.4 % ) , and nausea ( 15.9 % ) , mirroring findings of past studies with a less inclusive scope . In most cases , remission rate equalled or exceeded emergence rate . Several nondepressive symptoms also showed large improvement , including poor vision and skin rash/itch/irritation . Being overactive/excited/elated showed greater emergence under morning light and greater remission under evening light . Emergence of nausea was greater than remission in responders . CONCLUSION The dominant effect of light treatment was improvement in bothersome symptoms . Although patients should be advised of side effects and guided in dose manipulations to reduce them , attention also should be drawn to the substantial benefit-to-risk ratio . Improvement of symptoms outside the depressive cluster , seen in both responders and nonresponders , may point to new therapeutic uses of light therapy",
"BACKGROUND Hypersomnia is a cardinal symptom of seasonal affective disorder/winter depression . This open-label pilot study assessed modafinil , a novel wake-promoting agent , as treatment for seasonal affective disorder/winter depression . METHODS Total daily modafinil dose was 100 mg ( all patients week 1 ) , and 100 mg or 200 mg split dose ( weeks 2 - 8 ) . Efficacy assessment s ( weeks 1 , 2 , 5 , and 8) included the Structured Interview Guide for the Hamilton Depression ( HAM-D ) Rating Scale , Seasonal Affective Disorder Version ( SIGH-SAD ) , Montgomery-Asberg Depression Rating Scale ( MADRS ) , Clinical Global Impression of Change ( CGI-C ) , Fatigue Severity Scale ( FSS ) , and Epworth Sleepiness Scale ( ESS ) . RESULTS Thirteen patients ( 11 women ; mean age , 41 years ) were enrolled , 12 were evaluable for efficacy ( 100 mg dose , five patients ; 200 mg dose , seven patients ) , and nine completed treatment . Modafinil significantly improved winter depression as shown by reductions from baseline in mean SIGH-SAD at week 1 ( P MADRS total scores from week 2 through week 8 ( P mean SIGH-SAD total score was 17.1 ( versus 37.2 at baseline , P MADRS total score was 13.3 ( versus 26.9 at baseline , P overall clinical condition at all time points ( P SIGH-SAD ( 29 item ) , HAM-D ( 21 item ) , and MADRS , and 100 % on eight atypical SIGH-SAD items . Modafinil significantly reduced fatigue ( FSS ) and improved wakefulness ( ESS ) from weeks 2 through 8 ( P tolerated . LIMITATIONS This was an open-label , single site study . CONCLUSIONS Modafinil may be an effective and well-tolerated treatment in patients with seasonal affective disorder/winter depression",
"Seasonal affective disorder ( SAD ) represents a subgroup of major depression with a regular occurrence of symptoms in autumn/winter and full remission in spring/summer . Light therapy ( LT ) has become the st and ard treatment of this type of depression . Apart from this , pharmacotherapy with antidepressants also seems to provide an improvement of SAD symptoms . The aim of this controlled , single-blind study was to evaluate if hypericum , a plant extract , could be beneficial in treating SAD patients and whether the combination with LT would be additionally advantageous . Patients who fulfilled DSM-III-R criteria for major depression with seasonal pattern were r and omized in a 4-week treatment study with 900 mg of hypericum per day combined with either bright ( 3000 lux , n = 10 ) or dim ( was applied for 2 hours daily . We found a significant ( MANOVA , P Hamilton Depression Scale score in both groups but no significant difference between the two groups . Our data suggest that pharmacologic treatment with hypericum may be an efficient therapy in patients with seasonal affective disorder",
"BACKGROUND Seasonal affective disorder ( SAD ) can cause significant distress and impairment . No antidepressant studies have previously attempted to prevent the onset of autumn-winter depression . METHODS Three prospect i ve , r and omized , placebo-controlled prevention trials were conducted on 1042 SAD patients , enrolled in autumn and treated while still well , across the northern US and Canada . Patients received either bupropion XL 150 - 300 mg or placebo daily by mouth from enrollment until spring and were then followed off medications for 8 additional weeks . Primary efficacy variables were end-of-treatment depression-free rates and survival distributions of depressive recurrence . RESULTS Despite a reported average of 13 previous seasonal depressive episodes , almost 60 % of patients had never previously been treated for depression . Major depression recurrence rates during the three studies for bupropion XL and placebo groups were 19 % versus 30 % ( p = 0.026 ) , 13 % versus 21 % ( p = 0.049 ) , and 16 % versus 31 % ; yielding a relative risk reduction across the three studies of 44 % for patients taking bupropion XL . Survival analyses for depression onset also favored bupropion XL over placebo ( p = .081 , .057 , and recurrence of seasonal major depressive episodes by beginning bupropion treatment early in the season while patients are still well",
"Noradrenergic and dopaminergic mechanisms have been proposed for the pathophysiology of seasonal affective disorder ( SAD ) . We investigated the effects of catecholamine depletion using α-methyl-para-tyrosine ( AMPT ) , an inhibitor of tyrosine hydroxylase , in patients with SAD in natural summer remission . Nine drug-free patients with SAD by DSM-IV criteria , in summer remission for at least eight weeks , completed a double-blind , crossover study . Behavioral ratings and serum HVA and MHPG levels were obtained for 3-day sessions during which patients took AMPT or an active control drug , diphenhydramine . The active AMPT session significantly reduced serum levels of HVA and MHPG compared with the control diphenhydramine session . The AMPT session result ed in higher depression ratings with all nine patients having significant clinical relapse , compared with two patients during the diphenhydramine session . All patients returned to baseline scores after drug discontinuation . Catecholamine depletion results in significant clinical relapse in patients with SAD in the untreated , summer-remitted state . AMPT-induced depressive relapse may be a trait marker for SAD , and /or brain catecholamines may play a direct role in the pathogenesis of SAD",
"OBJECTIVE The authors investigated the efficacy and safety of fluoxetine in the treatment of winter seasonal affective disorder . METHOD Sixty-eight out patients who met the DSM-III-R criteria for recurrent major depressive episodes , seasonal ( winter ) pattern , were r and omly assigned to 5 weeks of treatment with fluoxetine , 20 mg/day ( N = 36 ) , or placebo ( N = 32 ) . The outcome measures included the 29-item modified Hamilton Depression Rating Scale , administered by experienced clinicians , and the self-rated Beck Depression Inventory ; adverse events and safety data were also recorded . Clinical response was defined as a greater than 50 % reduction in depression score between baseline and study termination . RESULTS Both groups showed significant improvement . The fluoxetine group had lower depression scores at termination than the placebo group , but these differences did not achieve statistical significance . However , the rate of clinical response in the fluoxetine group ( 59 % ) was superior to that in the placebo group ( 34 % ) . Post hoc analyses showed that the greatest fluoxetine responses were in the most markedly depressed patients and that overall response was greater for patients studied later in the season . Fluoxetine was well tolerated , and few subjects dropped out because of adverse events . CONCLUSIONS On the basis of clinical response rate , fluoxetine appears to be an effective , well-tolerated treatment for seasonal affective disorder . Because the differences between fluoxetine and placebo in the continuous outcome measures did not reach statistical significance , further studies with larger study groups and longer treatment periods are required to conclusively demonstrate efficacy of fluoxetine for seasonal affective disorder",
"Objective : To examine estimates of lifetime prevalence of seasonal affective disorder ( SAD ) in Toronto , Ontario . Method R and om telephone numbers were generated for the city of Toronto , and 781 respondents completed a telephone interview . Trained nonphysician interviewers conducted all interviews , which involved structured questions for diagnosing major depression . Patterns of symptom change across seasons were evaluated to establish a diagnosis of SAD according to DSM-III-R criteria . Results Correcting for sex and age , the prevalence of SAD defined by DSM-III-R criteria was 2.9 % ( 95%CI , 1.7 % to 4.0 % ) , and the overall lifetime prevalence of major depression in the sample was 26.4 % ( 95%CI , 23.3 % to 29.4 % ) . Some subjects were contacted for a follow-up interview conducted in person ; the positive predictive value for the diagnosis of major depression for the telephone interview was 100 % , and the negative predictive value was 93 % . Conclusions The seasonal subtype of depression represents 11 % of all subjects with major depression , suggesting that SAD is a significant public health concern . The telephone interview demonstrated adequate reliability , indicating that it is appropriate for epidemiological surveys of this nature",
"BACKGROUND A dysfunction of the serotonin system may play a major role in the pathogenesis of seasonal affective disorder . Bright light therapy has been shown to be effective in the treatment of winter depression in patients with seasonal affective disorder . Light therapy-induced remission from depression may be associated with changes in brain serotonin function . METHODS After at least 2 weeks of clinical remission , 12 drug-free patients who had had depression with seasonal affective disorder underwent tryptophan depletion in a double-blind , placebo-controlled , balanced cross-over design study . RESULTS Short-term tryptophan depletion induced a significant decrease in plasma free and total tryptophan levels ( P transient depressive relapse , which was most pronounced on the day after the tryptophan-depletion testing . No clinical ly relevant mood changes were observed in the control testing . CONCLUSIONS The maintenance of light therapy-induced remission from depression in patients with seasonal mood cycles seems to depend on the functional integrity of the brain serotonin system . Our results suggest that the serotonin system might be involved in the mechanism of action of light therapy",
"Objective : We have tested the relapse‐preventive effect of citalopram when compared with placebo in 282 patients with Seasonal Affective Disorder ( SAD ) responding to 1 week of light therapy",
"BACKGROUND Previous studies show that rapid tryptophan depletion reverses the effects of therapy with serotonergic , but not noradrenergic , antidepressant drugs in patients with remitted nonseasonal depression . The objective of this study was to investigate the effects of rapid tryptophan depletion in patients with seasonal affective disorder ( SAD ) that was in clinical remission after light therapy . METHODS Patients who met DSM-III-R criteria for recurrent major depressive episodes , seasonal ( winter ) pattern ( equivalent to SAD ) , were treated with a st and ard course of light therapy . Ten patients with SAD in clinical remission after light therapy underwent rapid tryptophan depletion in a placebo-controlled , double-blind crossover study . Behavioral ratings and plasma tryptophan levels were obtained before and after rapid tryptophan depletion . RESULTS Plasma total and free tryptophan levels were significantly reduced to 20 % of normal levels by the rapid tryptophan depletion . The depletion session result ed in significant increases in depression scores compared with the sham control session . Six of 10 patients had a clinical ly significant relapse of their depression following the tryptophan depletion session . CONCLUSIONS Rapid tryptophan depletion appears to reverse the antidepressant effect of bright light therapy in patients with SAD . This suggests that the therapeutic effects of bright light in SAD may involve a serotonergic mechanism",
" Sixty-one winter depressive patients were evaluated for evidence of bipolar illness . Using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version and the General Behavior Inventory , only nine ( 15 % ) could be considered bipolar . On prospect i ve evaluation of patients during the summer following winter depression , few showed signs of manic or hypomanic symptoms . Also , few patients had a family history of bipolar illness . When patients were asked to evaluate symptoms of winter depression , lack of energy was found to be the most prominent feature of the syndrome",
"Seasonal affective disorder ( SAD ) , winter type , is a condition characterized by the annual recurrence of depressive episodes during fall/winter , alternating with spring/summer euthymia or hypomania . Various neurotransmitters have been implicated in the etiology of SAD , the strongest evidence involving serotonin . Recently , increasing attention has been paid to the potential role of catecholaminergic pathways in the pathophysiology of SAD . We investigated the efficacy and tolerability of reboxetine , a selective noradrenaline inhibitor , in patients with SAD . Eleven out of sixteen patients who were included in a 6-week drug surveillance during winter season experienced full remission of depressive symptoms . Nine patients reported a rapid relief of preexistent severe atypical depressive symptoms within the first treatment week . Reboxetine might therefore be an effective and well-tolerated treatment option for SAD patients . In conclusion , our preliminary results are in line with evidence from recent studies suggesting that catecholaminergic systems might also be involved in the pathophysiology of SAD",
" Thirty‐four patients with seasonal affective disorder , winter depression type ( WD ) were r and omly distributed to receive the selective monoamine oxidase‐A inhibitor moclobemide ( 400 mg daily ) or placebo in a double‐blind , parallel group study lasting for up to 14 weeks . Severity measures were the Montgomery‐Åsberg Depression Rating Scale ( MADRS ) extended with characteristic symptoms of WD ; summed score of the “ atypical ” symptoms hypersomnia , hyperphagia and carbohydrate craving ; and Clinical Global Impressions ( CGI ) . After 3 weeks , patients with unsatisfactory response were switched to open moclobemide . Three patients on placebo dropped out before 3 weeks . Extended MADRS and CGI showed no significant difference between the groups at 3 weeks , whereas the atypical score was reduced significantly more on moclobemide than on placebo already after one week . Nonresponders after 3 weeks ( 9 of 16 on moclobemide and 7 of 15 on placebo ) improved rapidly after being given open moclobemide . Predictor analysis showed a remarkably high negative correlation between improvement at 3 weeks ( extended MADRS ) and age in the placebo group and a strong , nonsignificant trend in the same direction in the moclobemide group . Dichotomizing the patients according to the median age ( 45 years ) result ed in a somewhat better effect of moclobemide than placebo in the older age group . There were no significant differences in side effects between moclobemide and placebo",
"The following test of the circadian phase-shift hypothesis for patients with winter depression ( seasonal affective disorder , or SAD ) uses low-dose melatonin administration in the morning or afternoon/evening to induce phase delays or phase advances , respectively , without causing sleepiness . Correlations between depression ratings and circadian phase revealed a therapeutic window for optimal alignment of circadian rhythms that also appears to be useful for phase-typing SAD patients for the purpose of administering treatment at the correct time . These analyses also provide estimates of the circadian component of SAD that may apply to the antidepressant mechanism of action of appropriately timed bright light exposure , the treatment of choice . SAD may be the first psychiatric disorder in which a physiological marker correlates with symptom severity before , and in the course of , treatment in the same patients . The findings support the phase-shift hypothesis for SAD , as well as suggest a way to assess the circadian component of other psychiatric , sleep , and chronobiologic disorders"
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Background The pathophysiology of functional dyspepsia ( FD ) has not been eluci date d precisely ; accordingly , effective management of FD has not yet been found . Until now , treatment with antianxiety or antidepressive agents has been empirically applied ; however , the efficacy of these treatments has not been established . We carried out this study to estimate the efficacy of these treatment approaches by systematic ally review ing the literature concerning trials with agents that are efficacious against anxiety , neurosis , or depression . Methods Articles were search ed from the MEDLINE data base up to October 2003 , using the terms , “ antianxiety agents ” , “ antidepressants ” , and “ dyspepsia ” , and from reference lists of published articles . Finally , studies in which the effectiveness of drugs was clearly stated were selected from the retrieved articles . Results Thirteen articles , on 1717 patients , were selected from among 90 articles retrieved through our literature search . In 11 of the 13 studies , dyspeptic symptoms were improved significantly by treatment . Statistical analysis of 4 trials showed a significant benefit of treatment with antianxiety or antidepressive agents ( pooled relative risk , 0.55 ; 95 % confidence interval [ CI ] , 0.36–0.85 ) , although funnel plots were asymmetric . Conclusions Antianxiety or antidepressive agents may be effective in the treatment of FD patients , though further clinical trials are necessary
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"BACKGROUND / AIMS Although antidepressants have been used for decades in treating patients with functional abdominal syndromes , how they influence gastrointestinal motility remains unclear . We aim ed to assess the role of depression in functional dyspepsia , and the effect of antidepressants on the functional dyspepsia patients ' symptoms and gastric myoelectrical activity . METHODOLOGY We conducted an open clinical trial with 40 functional dyspepsia patients . Zung self-rating depression scale was used in evaluating the patients ' depression . Cutaneous electrogastrography and evaluation of upper gastrointestinal symptoms were performed before and after administration of a one-month course of fluoxetine . RESULTS In the baseline study , the depressed functional dyspepsia patients had higher symptom scores than non-depressed patients ( P tachygastria than healthy controls ( P electrogastrography parameters of depressed and non-depressed functional dyspepsia patients were not different . After one-month fluoxetine treatment , the symptom scores improved significantly in the depressed functional dyspepsia patients ( P Electrogastrography did not improve in either group . CONCLUSIONS Depressive functional dyspepsia patients had higher symptom scores and responded well to fluoxetine treatment . However , electrogastrography did not improve after the treatment . These findings suggest that depression is significant in the presentation of functional dyspepsia symptoms , but not correlated with gastric myoelectrical activity",
"The reduction of pain by two antidepressants , clomipramine and mianserin , was , in this study on 253 patients with chronic idiopathic pain syndrome , found to be not better than a placebo when all patients were compared independently of the classification of pain . The improvement rate was around 40 % after 6 weeks of treatment when using a 50 % or better reduction in pain level . However , in patients who fulfilled a checklist definition of minor to major depression ( 30 % of the total patient material ) clomipramine was superior to mianserin and placebo with an improvement rate of 75 % after 6 weeks . Using pain curves over time as outcome measure in the various clinical pain categories it was found that both mianserin and clomipramine seemed superior to placebo in patients with tension headache , but in patients with low back pain syndrome placebo was superior to the two antidepressants . No difference among the three treatments was found in patients with burning mouth syndrome or in patients with abdominal pain . These differences underline the importance of study ing specific pain syndromes rather than composite groups of patients with idiopathic pain . The clinical significance of these pain curves needs further placebo controlled investigations",
"Summary : In a double-blind cross-over clinical trial conducted on 30 out- patients , a significant preference emerged for medazepam against a placebo preparation when patients compared the efficacy of the two agents in relieving several major symptom complexes associated with functional bowel disease . The results suggest that medazepam can rationally be used in the treatment of aerophagy , nervous dyspepsia and functional gastro-intestinal pain . No significant side effects emerged during the study",
"Objectives Levosulpiride is the levo-enantiomer of sulpiride , a well-known antiemetic , antidyspeptic and antipsychotic drug . This study was undertaken to investigate the effects of levosulpiride on dyspeptic symptoms and gastric motor function in a group of patients with functional dyspepsia showing delayed gastric emptying . Method Forty two eligible patients were entered into a 3 week , double-blind r and omized comparison of 25 mg of levosulpiride or placebo t.i.d .. Symptom assessment and gastric scintigraphy following the intake of scrambled egg s and wich , were performed in each patient before and after treatment . Results The improvement of symptom score in levosulpiride group was higher than the placebo group ( p global efficacy , which was excellent in 1 ( 6 % ) , good 11 ( 65 % ) , fair 4 ( 24 % ) , nil 1 ( 6 % ) of those receiving levosulpiride , and fair 9(60 % ) , nil 5 ( 33 % ) , poor 1 ( 6 % ) of those receiving placebo . Levosulpiride tended to be more effective than placebo in relieving the dyspeptic symptoms especially in the subgroups of dysmotility-like ( p reduction of gastric emptying time after levosulpiride treatment was more marked than Placebo group ( p symptom score and gastric emptying time ( r=0.47 , p=0.01 . No serious adverse effects were reported after administration of either levosulpiride or placebo . Only two patients reported mild somnolence during levosulpiride administration . Conclusions Levosulpiride is effective and well tolerated in patients with functional dyspepsia accompanied by delayed gastric emptying . Its efficacy may be related to its action on the gastric motor function by improving the delayed gastric emptying",
"BACKGROUND This paper reports the 3-month prevalence rates of gastrointestinal ( GI ) symptoms from the Domestic/International Gastroenterology Surveillance Study ( DIGEST ) , and their relationship with demographic factors ; namely age , gender and body mass index ( BMI ) . METHODS Subjects were recruited from 10 international sites by a total of 5581 face-to-face interviews conducted with r and omly selected members of the general population aged 18 years and over ( 50.6 % female ; mean age 44 years ) . The sample was divided according to whether subjects reported 1 or more of 14 GI symptoms , or no GI symptoms . Those with any of 11 upper GI symptoms were then subdivided according to their most bothersome symptom : gastro-oesophageal reflux (GORD)-like symptoms , ulcer-like symptoms or dysmotility-like symptoms . Symptoms were classified as relevant if they were of at least moderate severity and /or occurred at least once a week . RESULTS A mean of 46.4 % of subjects reported experiencing one or more of the 14 GI symptoms , with 28.1 % experiencing upper GI symptoms classified as relevant . Significant differences between the prevalences of relevant symptoms were evident between sampling sites . The estimated prevalence of GORD-like symptoms for the pooled sample was 7.7 % . For ulcer-like symptoms , prevalence was 4.1 % , and for dysmotility-like symptoms 15.5 % . Significant differences were observed in the prevalence rates of symptom groups between countries . Women were significantly more likely than men to experience relevant symptoms , with gender differences also observed in the rates of GORD-like and dysmotility-like symptoms . The proportion of those with relevant symptoms experiencing GORD-like symptoms increased significantly with age ; ulcer-like symptoms showed no significant relationship with age ; and dysmotility-like symptoms decreased significantly with age . The prevalence of relevant symptoms increased with increasing BMI . CONCLUSIONS In conclusion , the DIGEST has provided valuable data on the cross-country prevalence of upper GI symptoms , and their association with biological factors",
"Altered visceral perception is common in functional dyspepsia ( FD ) . Dopaminergic pathways control gastrointestinal motility , but whether they modulate visceral sensitivity is unknown",
"Nonulcer dyspepsia ( NUD ) is a common syndrome , but the optimal treatments have yet to be established . This study was performed to determine the most effectivetreatment for NUD . Subjects were recruited through the Department of General InternalMedicine at the Kyushu University Hospital because oftheir somatic symptoms . When no organic lesions werefound , the patients were directed to consult ourdepartment ( Psychosomatic Medicine ) ; 194 consecutive NUD patients were studied . All subjects were assessedpsychiatrically with the Structured Clinical Interviewfor DSM-III-R(SCID ) . Patients with serious NUD were hospitalized , and r and omly divided into control(N = 42 ) and experimental groups ( N = 86 ) . The controlswere treated with physical treatment alone . Theexperimental group received psychiatric treatment inaddition , based on the results of SCID . The experimentalgroup showed a significant improvement compared with thecontrols ( P < 0.0001 ) . The treatment for NUD takinginto consideration both the physical and psychiatric conditions is highly effective",
"A double‐blind group comparison study of L‐sulpiride and amitriptyline was carried out in 30 bipolar out patients on maintenance treatment with lithium suffering from a major depressive recurrence . L‐sulpiride showed equivalent antidepressant activity to amitriptyline at 4 weeks using the Hamilton Rating Scale for Depression . However , the onset of action was faster in the L‐sulpiride group , showing a significant improvement at 1 week in both anxiety‐somatization and specific depression items , including depressed mood , feelings of guilt , work & activities and retardation . The incidence of anticholinergic side effects was significantly higher in the amitriptyline treatment group",
"AIM To investigate the prevalence of functional dyspepsia and Helicobacter pylori infection and their relationship in a Japanese population . METHODS Two thous and five hundred people who visited Shimane Institute of Health Science for their annual medical check-up from September 1998 to August 1999 were prospect ively enrolled in the study . After routine medical examination , including an upper gastrointestinal study and an ultrasonographic examination , all subjects were asked st and ard questions to check for the presence of any symptoms that suggested dyspepsia . Helicobacter pylori infection was determined by using a serum IgG antibody concentration with an ELISA . RESULTS Of the 2,500 persons investigated , 2,263 showed no abnormal finding in any medical examination . The presence or absence of symptoms and H. pylori infection was investigated in these 2,263 cases . Of these , 201 people ( 8.9 % ) experienced nausea , fullness and /or early satiety and were diagnosed as having dysmotility-like dyspepsia , while 118 people ( 5.2 % ) experienced pain localized to the epigastrium and were diagnosed as having ulcer-like dyspepsia . The frequency of these symptoms had a tendency to decline with age , although this was not statistically significant . In contrast , the rate of H. pylori infection increased with age . There was no significant relationship between H. pylori infection and any type of functional dyspepsia . CONCLUSIONS Helicobacter pylori infection does not influence the prevalence of the dysmotility-like and ulcer-like dyspeptic symptoms",
"It remains controversial whether the cure of H. pylori infection improves NUD symptoms .",
"The efficacy and tolerability of fluvoxamine ( 100 - 300 mg/day ) and clomipramine ( 100 - 250 mg/day ) were compared in a r and omized , double-blind , parallel-group study of 79 patients with obsessive-compulsive disorder ( OCD ) without coexisting major depression . After a 2-week placebo lead-in period , patients were r and omized to fluvoxamine ( 37 patients ) or clomipramine ( 42 patients ) for 10 weeks . Efficacy was evaluated with the Yale-Brown Obsessive-Compulsive Scale ( Y-BOCS ) , the National Institute of Mental Health Obsessive-Compulsive scale , and Patient and Clinical Global Improvement scales . Hamilton Rating Scale for Depression scores and somatic symptoms were also assessed . Seventy-eight percent of fluvoxamine patients and 64 % of clomipramine patients completed the study . At the end of treatment , 56 % of fluvoxamine patients were classified as responders ( > or = 25 % decrease in Y-BOCS score ) , compared with 54 % of clomipramine patients . Both groups showed steady improvement throughout the study ; no statistically significant differences were observed between the groups for any efficacy variable at any time . A similar percentage of patients in both groups withdrew because of adverse events . No serious adverse events related to drug occurred with either drug . Insomnia , nervousness , and dyspepsia were more statistically frequent with fluvoxamine ; dry mouth and postural hypotension were more frequent with clomipramine . In this study , fluvoxamine and clomipramine were equally effective in reducing OCD symptoms over a 10-week treatment period but displayed different side effect profiles",
"Abnormalities in gastrointestinal motility have been reported in a substantial proportion of patients with functional dyspepsia , supporting the use of prokinetic drugs for treatment of dyspeptic symptoms . To evaluate efficacy and safety of levosulpiride in short-term treatment , 1298 patients were enrolled in a double-blind multicentric study carried out in 45 Italian Gastroenterology Departments . Patients were r and omly assigned to either levosulpiride ( 25 mg tid ) , domperidone ( 10 mg tid ) , metoclopramide ( 10 mg tid ) or placebo ( 1 tablet tid ) for 4 weeks . Patients were selected on the basis of : a ) occurrence in the last 4 weeks of at least 5/10 selected symptoms ( anorexia , nausea , vomiting , upper abdominal pain , postpr and ial bloating , abdominal fullness , early satiety , belching , heartburn , regurgitation ) , severity of which should reach/exceed a total score of 8 , as assessed by a specific scale ranging from 0 ( absent ) to 3 ( severe ) ; b ) normal results of routine biochemical , ultrasound and endoscopic examinations . In addition , each patient subjectively evaluated efficacy of treatment by a visual analogue scale . Significant improvement was recorded for all symptoms at days 10 and 28 in all groups ( p levosulpiride was significantly ( p , metoclopramide and placebo both in the overall clinical improvement scale as well as in a subgroup of symptoms ( postpr and ial bloating , epigastric pain , heartburn ) . Active treatments and placebo were comparable as far as concerns occurrence of side-effects ( 12 - 20 % ) including galactorrhoea , breast tenderness and menstrual changes",
"Diagnosis of functional gastrointestinal disorder with significant anxiety overlay was the basis for selecting 52 subjects for a double-blind study of adjunctive administration of diazepam versus placebo , conjointly with propantheline bromide . R and om division of subjects result ed in well matched groups with respect to age , sex , weight and initial symptomatology . Greater relief of anxiety and related symptoms was obtained from treatment with diazepam than with placebo . Mean global ratings indicated progressive improvement in all patients , with greater effects among diazepam-treated subjects by the end of the first week of test medication . The most commonly encountered side effects were dryness of mouth ( attributed to the anticholinergic agent ) and drowsiness ( affecting 8 subjects on diazepam and 1 on placebo ) ; in no case was a side effect so severe that trial medication had to be discontinued",
"Background : 50 % of patients with functional dyspepsia have delayed gastric emptying . Levosulpiride is an orthopramide drug that stimulates gastrointestinal motility . Aim of our study was to evaluate the effect of levosulpiride on symptoms and gastric and gall‐bladder emptying , in dyspeptic patients",
"BACKGROUND Fluvoxamine and paroxetine , both serotonin selective reuptake inhibitors ( SSRIs ) , were compared at two centers in a 7-week double-blind study in out patients with major depression , diagnosed by DSM-III-R criteria . METHOD Sixty patients were r and omly assigned to receive dosage titrated upward to between 50 - 150 mg/day of fluvoxamine ( N = 30 ) or 20 - 50 mg/day of paroxetine ( N = 30 ) . The mean + /- SD daily dose administered at the last assessment was 102 + /- 44 mg/day for fluvoxamine and 36 + /- 13 mg/day for paroxetine . Sixteen ( 53 % ) fluvoxamine-treated patients and 10 ( 33 % ) paroxetine-treated patients were titrated to the maximum permissible dosage of either drug . Sample size was calculated to provide at least 85 % power at 5 % level of significance to detect at least a 1.00-point difference in mean severity of adverse events , assuming a st and ard deviation of 1.0 . RESULTS Fluvoxamine and paroxetine were similarly effective in ameliorating depression as demonstrated by mean total scores of 10.9 + /- 7.3 ( p Hamilton Rating Scale for Depression ( HAM-D ) . Adverse events were mostly mild to moderate in severity . The most common events were headache ( N = 17 , 57 % ) , nausea ( N = 14 , 47 % ) , sweating ( N = 10 , 33 % ) , somnolence ( N = 9 , 30 % ) , diarrhea ( N = 9 , 30 % ) , dry mouth ( N = 8 , 27 % ) , dizziness ( N = 8 , 27 % ) , and , among males , impotence ( N = 3 , 21 % ) and ejaculatory abnormality ( N = 3 , 21 % ) in the paroxetine group , and headache ( N = 12 , 40 % ) , somnolence ( N = 12 , 40 % ) , nausea ( N = 11 , 37 % ) , dry mouth ( N = 11 , 37 % ) , insomnia ( N = 9 , 30 % ) , asthenia ( N = 7 , 23 % ) , and dyspepsia ( N = 7 , 23 % ) in the fluvoxamine group . The only statistically significant difference between treatment groups was for sweating ( 33 % paroxetine vs. 10 % fluvoxamine , p = .028 ) . CONCLUSION Observed differences in some side effects , although not statistically significant , indicate that when a patient has difficulty tolerating one SSRI , the clinician may choose to change to a different agent within the same class",
"BACKGROUND The efficacy of unselected monoamine reuptake inhibitors ( tricyclic antidepressants ) in the treatment of patients with functional gastrointestinal disorders ( FGD ) has not been convincingly demonstrated . We investigated the efficacy of an antidepressant ( mianserin ) with a different receptor profile ( combined 5-hydroxytryptamine-2 + 3 and alpha-2 antagonist ) in FGD . METHODS After excluding patients with psychopathology and initial placebo responders from the study , eligible patients ( n = 49 ) were r and omized to 7 weeks of double-blind treatment with either mianserin , 120 mg/day , or placebo . Efficacy was assessed by using observer-completed ratings , the Global Improvement Scale , and patient self-ratings , Visual Analog Scale , and Disability Scales . RESULTS Patients taking mianserin reported less abdominal pain , symptoms of abdominal distress , and functional disability than those given placebo ( p efficacy was significant across different lengths of illness periods and types of functional disorder . There was no major change 4 weeks after tapering . CONCLUSION Mianserin may be an effective and well-tolerated pharmacologic short-term treatment for functional gastrointestinal disorders in patients with no clinical evidence of psychopathology",
"OBJECTIVE Tricyclic antidepressants in low doses are widely used in the therapy of patients with functional gastrointestinal disorders , yet the mechanism(s ) of action of these drugs in these disorders is not known . In the current study , we sought to determine in a group of patients with functional dyspepsia and associated poor sleep how amitryptiline affects digestive symptoms , perceptual responses to gastric distension , and subjective and objective measures of sleep . METHODS Patients were r and omized to 4 wk of amitryptiline 50 mg taken at bedtime versus placebo . There was a 3-wk washout phase , followed by a cross-over to the alternate treatment . Perceptual sensitivity to gastric distention and sleep EEG were recorded at the end of each treatment period . Diaries of symptoms were maintained throughout . RESULTS Seven of seven patients reported significantly less severe gastrointestinal symptoms after 4 wk on amitryptiline compared to placebo . Five of seven patients had evidence for altered perception of gastric balloon distension during placebo . However , the subjective symptom improvement on amitryptiline was not associated with a normalization of the perceptual responses to gastric distension . Baseline sleep dysfunction in the form of reduced sleep efficiency , increased arousal , or abnormal amounts of REM sleep was found in all seven patients . Amitryptiline significantly reduced absolute and relative amounts of REM sleep , but had no effect on sleep parameters related to nonregenerative sleep . CONCLUSION The beneficial effect of low dose amitryptiline seen in functional dyspepsia is not related to changes in perception of gastric distension , or to measures of arousal from sleep . An increased tolerance to aversive visceral sensations may play a role in the therapeutic effect",
"The efficacy of H2‐receptor antagonists in functional dyspepsia is equivocal and the therapeutic place of proton pump inhibitors in functional dyspepsia is unknown",
"The efficacy of several prokinetic drugs on dyspeptic symptoms and on gastric emptying rates are well‐established in patients with functional dyspepsia , but formal studies comparing different prokinetic drugs are lacking"
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411884ac-06ff-11f0-808a-c43d1ab1c353
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Study Design . The Oswestry Disability Index ( ODI ) has become one of the principal condition-specific outcome measures used in the management of spinal disorders . This review is based on publications using the ODI identified from the authors ’ personal data bases , the Science Citation Index , and h and search es of Spine and current textbooks of spinal disorders . Objectives . To review the versions of this instrument , document methods by which it has been vali date d , collate data from scores found in normal and back pain population s , provide curves for power calculations in studies using the ODI , and maintain the ODI as a gold st and ard outcome measure . Summary of Background Data . It has now been 20 years since its original publication . More than 200 citations exist in the Science Citation Index . The authors have a large correspondence file relating to the ODI , that is cited in most of the large textbooks related to spinal disorders . Methods . All the published versions of the question naire were identified . A systematic review of this literature was made . The various reports of validation were collated and related to a version . Results . Four versions of the ODI are available in English and nine in other language s. Some published versions contain misprints , and many omit the scoring system . At least 114 studies contain usable data . These data provide both validation and st and ards for other users and indicate the power of the instrument for detecting change in sample population s. Conclusions . The ODI remains a valid and vigorous measure and has been a worthwhile outcome measure . The process of using the ODI is review ed and should be the subject of further research . The receiver operating characteristics should be explored in a population with higher self-report disabilities . The behavior of the instrument is incompletely understood , particularly in sensitivity to real change .
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"Abstract The inability to predict outcome in patients with low back/neck pain leads to inappropriate or unnecessary treatment . The aims of the study were to identify prognostic factors for disability at 1‐year follow‐up in patients with back pain visiting primary care , and to compare the effect of these in two treatment strategies – chiropractic and physiotherapy . Data were taken from a r and omised trial on patients with back/neck pain visiting the general practitioner , in which patients were allocated to chiropractic and physiotherapy as primary management . Three hundred and twenty‐three patients , aged 18–60 years , who had no contraindications to manipulation and who had not been treated within the previous month were included in the study . Multiple regression analysis was used to identify prognostic factors . Dependent variables were mean Oswestry score and mean change in Oswestry score at 12‐month follow‐up . The multiple regression analysis revealed five significant ( P ; duration of current episode , Oswestry score at entry , expectations of treatment , number of localisations , and well‐being . Besides , the regression coefficients for the significant factors were compared between the two treatment strategies . No significant difference in effect or regression coefficients for the prognostic factors were seen between the two treatment strategies . Twelve per cent of the patients had poor prognostic factors ( duration ≥1 month , more than one localisation , low expectations of treatment and low well‐being ) at entry . These patients had a mean Oswestry score above 20 % at 1‐year follow‐up . Clinical decision models for the management of patients with back pain visiting primary care that consider prognostic factors need to be implemented and prospect ively evaluated",
"In clinical measurement comparison of a new measurement technique with an established one is often needed to see whether they agree sufficiently for the new to replace the old . Such investigations are often analysed inappropriately , notably by using correlation coefficients . The use of correlation is misleading . An alternative approach , based on graphical techniques and simple calculations , is described , together with the relation between this analysis and the assessment of repeatability",
"In a study that indicates more definitive investigation is needed , 118 patients with chronic back problems seeking treatment for acute attacks of pain were included in a 4-week r and omised double-blinded study on the safety and effectiveness of an extract of Harpagophytum procumbens . Both , the treatment and the placebo were administered in the form of two tablets taken three times per day ; the treatment group had a daily consumption equal to 6,000 mg of crude preparation ( 50 mg harpagoside , the putative active ingredient ) . The treatment and placebo groups were well matched in physical characteristics ; in the severity , duration , nature and accompaniments of their pain ; and in laboratory indices of organ system function . 109 patients completed the study . The study was originally design ed to measure Harpagophytum 's effectiveness by measuring the use of supplementary pain-killer Tramadol over its final 3 weeks . However , this did not differ between the Harpagophytum and placebo groups nor was the consumption closely related to the amount of pain . Further analysis , though , revealed that 9 out of 51 patients who received the extract were pain free at the end of treatment compared to only 1 out of 54 patients who received placebo . A modification of the Arhus index was used as an additional measure , covering the more global impact . The percentage change was greater in those patients who received Harpagophytum extract than in those who received placebo , but inferential testing ( Mann Whitney ) allowed only 94 % degree of confidence that this had not arisen by chance . The Arhus index reduction was based on improvement in pain . This indication of effectiveness , and the absence of demonstrable adverse effects show that more definite clinical studies of Harpagophytum extract will be worthwhile",
"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",
"BACKGROUND Although epidural corticosteroid injections are commonly used for sciatica , their efficacy has not been established . METHODS In a r and omized , double-blind trial , we administered up to three epidural injections of methylprednisolone acetate ( 80 mg in 8 ml of isotonic saline ) or isotonic saline ( 1 ml ) to 158 patients with sciatica due to a herniated nucleus pulposus . All patients had Oswestry disability scores higher than 20 ( on a scale of 1 to 100 , with scores of 20 or less indicating minimal disability , and higher scores greater disability ) . RESULTS At three weeks , the Oswestry score had improved by a mean of -8.0 in the methylprednisolone group and -5.5 in the placebo group ( 95 percent confidence interval for the difference , -7.1 to 2.2 ) . Differences in improvements between the groups were not significant , except for improvements in the finger-to-floor distance ( P=0.006 ) and sensory deficits ( P=0.03 ) , which were greater in the methylprednisolone group . After six weeks , the only significant difference was the improvement in leg pain , which was greater in the methylprednisolone group ( P=0.03 ) . After three months , there were no significant differences between the groups . The Oswestry score had improved by a mean of -17.3 in the methylprednisolone group and -15.4 in the placebo group ( 95 percent confidence interval for the difference , -9.3 to 5.4 ) . At 12 months , the cumulative probability of back surgery was 25.8 percent in the methylprednisolone group and 24.8 percent in the placebo group ( P=0.90 ) . CONCLUSIONS Although epidural injections of methylprednisolone may afford short-term improvement in leg pain and sensory deficits in patients with sciatica due to a herniated nucleus pulposus , this treatment offers no significant functional benefit , nor does it reduce the need for surgery",
"BACKGROUND AND PURPOSE The Rol and -Morris Question naire ( RMQ ) is a self-administered disability measure in which greater levels of disability are reflected by higher numbers on a 24-point scale . The RMQ has been shown to yield reliable measurements , which are valid for inferring the level of disability , and to be sensitive to change over time for groups of patients with low back pain . Little is known about the usefulness of this instrument in aiding decision making regarding individual patients . The purpose of this study was to determine the minimum level of detectable change when the RMQ is applied to individual patients . SUBJECTS The study sample consisted of 60 out patients with low back pain . METHODS The RMQ was administered at the subjects ' initial visit and again 4 to 6 weeks later . Conditional st and ard errors of measurement ( CSEMs ) were computed for initial and follow-up RMQ scores , and these values were used to estimate the minimum level of detectable change . Results . Minimum levels of detectable change at the 90 % confidence level varied from 4 to 5 RMQ points . CONCLUSION AND DISCUSSION The magnitude of CSEMs is sufficiently small to detect change in patients with initial scores in the central portion of the scale ( 4 - 20 RMQ points ) ; however , the magnitude is too large to detect improvement in patients with scores of less than 4 and deterioration in patients who have scores greater than 20",
"McKenzie 's methods for evaluating and treating low back pain are used often but studied little . When using the McKenzie system , it is important to observe signs of symptom movement to a central location ( central ization ) . This study investigated the relationships between central ization of low back pain and /or radiculopathy and the subjects ' rating of functional outcome . Thirty-six subjects with low back pain volunteered to participate and were evaluated and treated by six research ers . Subjects were tested initially and again 14 days after initiation of treatment using the Oswestry Low Back Pain Disability Question naire and the Performance Assessment and Capacity Testing Spinal Function Sort ( SFS ) . Symptoms were monitored for the occurrence of \" complete central ization . \" Of the 36 subjects , 25 showed complete central ization within 14 days . The SFS score changes were significantly higher for subjects who completely central ized ( p = 0.015 ) . The results supported the hypothesis that subjects who central ize will have improved functional outcome and , thus , quality of life . However , shorter time to occurrence of complete central ization does not necessarily correlate with improved outcome",
"Study Design . Population ‐based r and omized clinical trial . Objectives . To develop and test a model of management of subacute back pain , to prevent prolonged disability . Summary of Background Data . The present management of back pain seems inadequate , and development of innovative models has been urged . Methods . A model for the treatment of subacute work‐related back pain has been developed and evaluated in a population ‐based r and omized clinical trial . Workers ( n = 130 ) from eligible workplaces in the Sherbrooke area ( N = 31 ) , who had been absent from work for more than 4 weeks for back pain , were r and omized , based on their workplace , in one of four treatment groups : usual care , clinical intervention , occupational intervention , and full intervention ( a combination of the last two ) . The duration of absence from regular work and from any work was evaluated using survival analysis . Functional status and pain were compared at study entry and after 1 year of follow‐up . Results . The full intervention group returned to regular work 2.41 times faster than the usual care intervention group ( 95 % confidence interval 1.19‐4.89 ; P = 0.01 ) . The specific effect of the occupational intervention accounted for the most important part of this result , with a rate ratio of return to regular work of 1.91 ( 95 % confidence interval = 1.18‐3.10 ; P demonstrated either a statistically significant reduction or a trend toward reduction in the three intervention groups , compared with the trend in the usual care intervention group . Conclusions . Close association of occupational intervention with clinical care is of primary importance in impeding progression toward chronicity of low back pain",
"OBJECTIVE To evaluate a progressive fitness programme for patients with chronic low back pain . DESIGN Single blind r and omised controlled trial . Assessment s were carried out before and after treatment by an observer blinded to the study and included a battery of vali date d measures . All patients were followed up by postal question naire six months after treatment . SETTING Physiotherapy department of orthopaedic hospital . SUBJECTS 81 patients with chronic low back pain referred from orthopaedic consultants for physiotherapy . The patients were r and omly allocated to a fitness programme or control group . INTERVENTION Both groups were taught specific exercises to carry out at home and referred to a back-school for education in back care . Patients allocated to the fitness class attended eight exercise classes over four weeks in addition to the home programme and backschool . RESULTS Significant differences between the groups were shown in the changes before and after treatment in scores on the Oswestry low back pain disability index ( P pain reports ( sensory P self efficacy reports ( P walking distance ( P general health question naire or question naire on pain locus of control . A benefit of about 6 percentage points on the disability index was maintained by patients in the fitness group at six months . CONCLUSION There is a role for supervised fitness programmes in the management of moderately disabled patients with chronic low back pain . Further clinical trials , however , need to be established in other centres to confirm these findings",
"Reprinted with permission from the British Medical Journal 300:1431 - 1437.1990 . Objective - To compare chiropractic and hospital outpatient treatment for managing low back pain of mechanical origin . Design - R and omized controlled trial . Allocation to chiropractic or hospital management by minimization to establish groups for analysis of results according to initial referral clinic , length of current episode , history , and severity of back pain . Patients were followed up for up to two years . Setting - Chiropractic and hospital outpatient clinics in 11 centers . Patients - 741 patients aged 18 - 65 who had no contraindications to manipulation and who had not been treated within the past month . Interventions - Treatment at the discretion of the chiropractors , who used chiropractic manipulation in most patients , or of the hospital staff , who most commonly used Maitl and mobilization or manipulation , or both . Main outcome measures - Changes in the score on the Oswestry pain disability question naire and in the results of tests of straight leg raising and lumbar flexion . Results - Chiropractic treatment was more effective than hospital outpatient management , mainly for patients with chronic or severe back pain . A benefit of about 7 percent points on the Oswestry scale was seen at two years . The benefit of chiropractic treatment became more evident throughout the follow-up period . Secondary outcome measures also showed that chiropractic was more beneficial . Conclusions - For patients with low back pain in whom manipulation is not contraindicated , chiropractic almost certainly confers worthwhile , long-term benefit in comparison with hospital outpatient management . The benefit is seen mainly in those with chronic or severe pain . Introducing chiropractic into NHS practice should be considered . J Orthop Sports Phys Ther 1991;13(6):278 - 287",
"External transpedicular fixation was applied to the lower lumbar spine in a prospect i ve study on 42 patients with chronic low back pain combined with suspected instability of the lumbar segments ; the diagnosis was failed disk surgery , spondylolisthesis , and degenerative disk disease . The aim was to realign the involved segments , to restore disk height , and to record changes in pain and performance during the external fixation test . Pain was recorded on a visual analog scale , and performance was assessed using the Oswestry disability score . As independent observer assessed the test and treatment results . Twenty-nine patients experienced relief of pain and performed better in the fixator ; they were subjected to anterior interbody fusion , the external frame being kept as a stabilizing device for an additional four months . Twenty-two patients have had follow-up evaluations for two years . One and two years after successful lumbar fusion , significantly ( p pain and performance scores were recorded ; the results of lumbar fusion corresponded to the preoperative fixation test . A temporary external fixation test may be a useful procedure in patients considered for subsequent spondylodesis",
"Study Design . Open , prospect i ve trial with patients participating in an active back restoration program . Objectives . To compare the concentrations of biochemical indicators of Type I and III collagen synthesis and Type I collagen degradation in the serum of patients with chronic low back pain and healthy control subjects and to evaluate the effect of active back rehabilitation based on vigorous exercise on collagen metabolism . Summary of Background Data . The aim of active back rehabilitation is to restore the physical function of low back pain patients falling into the so-called \" deconditioning syndrome . \" The changes in functional muscle strength measurements during the restoration rehabilitation program always depend on motivation , learning phenomena , and fear of pain and injury , so that even more objective ways of showing changes in physical activity are needed . Methods . Specific radioimmunoassays for the amino-terminal ( PINP ) and carboxy-terminal ( PICP ) propeptides of Type I procollagen , the amino-terminal propeptide of Type III procollagen ( PIIINP ) , and the cross-linked carboxy-terminal telopeptide of Type I collagen ( ICTP ) were used for serum sample s obtained from 41 patients before , during , and after an active back restoration program and from 16 age- and sex-matched healthy control subjects . Results . The circulating concentrations of PINP and PICP were initially lower in the patients ( [ mean ± SD ] 35.3 ± 12.5 μg/L and 119.0 ± 32.6 μg/L , respectively ) than in the control subjects ( 47.9 ± 18.0 μg/L and 136.7 ± 47.7 μg/L , respectively ; P active back rehabilitation program , both PINP and PICP increased in the patients ( P circulating PICP concentration increasing earlier than that of PINP . In the intervention group , the PIIINP concentration also increased ( P ICTP concentration remained unchanged , with a tendency to decrease . No changes occurred in the control subjects . Conclusions . Active back rehabilitation based on vigorous exercise increases Type I collagen synthesis in patients with chronic low back pain ; this may provide a means of objective ly verifying the effects of such rehabilitation",
"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",
"& NA ; Chronic pain adversely affects individuals ' physical as well as emotional well‐being . A cognitive‐behavioral model has been proposed to explain the role of cognitive appraisal variables in mediating the development of emotional distress following pain of long duration . There is little evidence linking the prevalence of depression in chronic pain patients to life stage , but there are suggestions in the literature that the link between medical illness and depression may be stronger in elderly patients . One purpose of this study was to replicate the efficacy of a previous study of the cognitive‐behavioral mediation model in explaining the association between pain and depressed affect . A second purpose of this study was to extend the cognitive‐behavioral model to evaluate relationships among pain , cognitive appraisal variables , and depressive affect in the elderly chronic pain population . One hundred chronic pain patients were divided into two age groups ( ≤ 69 years and ≥ 70 years ) . A path analysis conducted for the total sample supported the cognitive‐behavioral mediation model of depression in chronic pain , in which cognitive appraisal variables mediate the pain‐depression relationship . Correlations among variables in each of the two age groups , however , revealed different patterns of association . Consistent with the cognitive‐behavioral model , the younger patients demonstrated a low and non‐significant correlation between pain severity and depression ( r = 0.01 ) . Conversely , a strong direct association was observed in the older patients between these variables ( r = 0.51 ) . These results suggest that the relationship between pain and depression varies substantially depending upon age cohort",
"Our purpose , in this prospect i ve clinical study , was to identify the best predictors of 2-month return to work or retraining for a group of low back injured subjects ( n = 40 ) who completed at least 8 weeks of a community-based rehabilitation program that combined aerobic and flexibility exercise conducted in the water ( aquafitness ) with muscle strength and endurance training . Baseline demographic characteristics and changes in physical fitness , pain , disability , and psychological well-being during the course of program participation were compared between two groups of low back injured subjects : those who returned to work ( RTW ) [ n = 24 ] , and those who did not ( N-RTW ) [ n = 16 ] . Subjects in both groups showed comparable improvement in measures of physical fitness at 8 weeks . However , multivariate analyses showed significant between-group differences in self-report measures . The RTW group showed significant improvement in measures of pain , disability , anxiety , and vigor while self-esteem and affect remained stable . The N-RTW group displayed no change in pain and disability variables and had significant deterioration in mean overall psychological well-being over time . The best predictors of return to work using logistic regression analyses were a first injury rather than a repeat injury to the lower back , and stability in self-esteem . Suggestions are offered for further research to examine the benefits of aquafit exercise for the low back injured , for additional interventions for those with a reinjury , and for maintaining or enhancing self-esteem as a treatment goal",
"OBJECTIVE To determine the relationship between overall disability in daily activities , assessed with the Pain Disability Index ( PDI ) and the Oswestry Disability Question naire ( ODQ ) , and impaired performance on three physical tests in patients with chronic low-back pain . DESIGN AND SUBJECTS The PDI and ODQ were administered in a cross-sectional study , before beginning a back rehabilitation program , to 45 patients with low-back pain of > or = 3 months ' duration , with or without radiation to the legs . All patients also performed repetitive sit-up , arch-up , and squatting tests . SETTING Tertiary care center . RESULTS Modestly significant ( p PDI and ODQ ( Wilcoxon 's two- sample test : p performance on all physical tests ( p self-perceived disability , and impaired performance on repetitive squatting , arch-up , and sit-up tests , as measures of physical capability , show some overlap in low-back-pain patients . Both types of disability measures are clearly influenced by the patient 's work status",
"The prevailing opinion seems to accept that the natural course of lumbar spinal stenosis is one of progressive worsening , and that only surgery can check this development . In fact , the choice of treatment for lumbar spinal stenosis is still an open question . The aim of this study was to compare in the matched-pair format the outcome of surgically and non-surgically treated patients with lumbar spinal stenosis . The surgically treated group consisted of 496 patients who were operated on during the period 1974 - 1987 and 440 of whom were re-examined an average of 4.1 years after surgery . The non-surgically treated group consisted of 57 patients who were treated conservatively during the period 1980 - 1987 and were re-examined an average of 4.3 years after the start of treatment . The matching criteria were sex , age , myelographic findings , major symptom and duration of symptoms . We were able to form 54 similar matched-pairs from the surgically and non-surgically treated patients . Subjective disability was assessed using the Oswestry question naire and functional status was evaluated during the clinical examination . For statistical analysis the McNemar test and the paired Student 's t-test were used . The overall results showed no statistical difference in outcome between the matched-pair groups , but the operated men fared significantly better than the non-operated men . The functional status was very good in both groups and for both sexes . In conclusion , conservative treatment of lumbar spinal stenosis should be considered for the patients with moderate stenosis . Controlled , prospect i ve and r and omized trials are needed to clarify better the choice of treatment in patients with lumbar stenosis",
"Study Design . A r and omized , controlled trial , test‐retest design , with a 3‐ , 6‐ , and 30‐month postal question naire follow‐up . Objective . To determine the efficacy of a specific exercise intervention in the treatment of patients with chronic low back pain and a radiologic diagnosis of spondylolysis or spondylolisthesis . Summary of Background Data . A recent focus in the physiotherapy management of patients with back pain has been the specific training of muscles surrounding the spine ( deep abdominal muscles and lumbar multifidus ) , considered to provide dynamic stability and fine control to the lumbar spine . In no study have research ers evaluated the efficacy of this intervention in a population with chronic low back pain where the anatomic stability of the spine was compromised . Methods . Forty‐four patients with this condition were assigned r and omly to two treatment groups . The first group underwent a 10‐week specific exercise treatment program involving the specific training of the deep abdominal muscles , with co‐activation of the lumbar multifidus proximal to the pars defects . The activation of these muscles was incorporated into previously aggravating static postures and functional tasks . The control group underwent treatment as directed by their treating practitioner . Results . After intervention , the specific exercise group showed a statistically significant reduction in pain intensity and functional disability levels , which was maintained at a 30‐month follow‐up . The control group showed no significant change in these parameters after intervention or at follow‐up . Summary . A \" specific exercise \" treatment approach appears more effective than other commonly prescribed conservative treatment programs in patients with chronically symptomatic spondylolysis or spondylolisthesis",
"OBJECTIVE To assess the efficacy of a back school program for patients with a first episode of acute work-related low back pain requiring compensation . DESIGN A r and omized single-blind controlled trial . SETTING A private physiatrics outpatient clinic . PATIENTS The mean duration of low back pain was 15 days . INTERVENTION Eligible patients were r and omized to a st and ard treatment program that included daily physiotherapy ( n = 86 ) or the same program with the addition of back school ( n = 82 ) . The back school program consisted of three 90-minute sessions given by a single trained instructor at 0 , 1 , and 8 weeks . MAIN OUTCOME MEASURES The primary outcomes were the time off work for the presenting episode of back pain and the number and duration of recurrences in the year following the study onset . Secondary outcomes included the level of pain , spinal mobility , active straight-leg raising , and functional disability assessed by the Oswestry and Rol and -Morris scales . RESULTS Those r and omized to the back school group gained significantly more knowledge , based on the multiple choice examination ( p = .0001 ) and performed the exercise program significantly better ( p = .0001 ) than the st and ard care group . There were no differences between the two treatment groups for either of the primary outcomes . The median time to return to work from r and omization was 33 days for both the back school and the st and ard care groups ( p = .48 ) . The number of compensated recurrences of low back pain over 1 year was similar ( back school = 14 , st and ard care = 10 , p = .16 ) , as was the median duration of these episodes ( back school = 25 days , st and ard care = 70 days , p = .21 ) . There were no significant differences favoring the back school group for any of the secondary outcomes at the posttreatment , 6-month , or 12-month assessment s. CONCLUSION A back school intervention in addition to st and ard care result ed in no reduction in the time to return to work or the number or duration of recurrences of low back pain requiring compensation over a period of one year",
"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",
"Summary A total of 15 patients suffering from chronic low back pain were treated with an intradiscal injection of either 1 ml of 50 % glycerol or 2 ml of 0.5 % bupivacaine . Most ( 60 % ) of the patients had previously undergone spinal surgery for lumbar disc herniation or spinal stenosis and 73 % showed clinical signs and symptoms of segmental instability of the lumbar spine . According to self-evaluation question naires , immediate response to both treatments was mainly good . Of the 9 patients who received glycerol , 56 % showed subjective improvement on the first day after the injection and after two weeks , 45 % of the patients still felt improvement . After one month , however , the pain had reappeared in all except one ( 11 % ) patient . The corresponding numbers for the 6 with bupivacaine treated patients were 83 % , 67 % , and 17 % . Based on the very short duration of response to the treatment , we did not find intradiscal injections with these agents to be cost-effective . In our department , this therapeutic approach is no longer employed in patients with chronic discogenic pain",
"BACKGROUND AND PURPOSE The efficacy of a physical therapy outpatient program with multiple interventions to treat low back pain in subjects receiving workers ' compensation was examined . The primary purpose of the study was to describe the level of disability , physical impairment , and rate of return to work for compensated patients . SUBJECTS One hundred thirty-eight patients ( 84 male , 54 female ) , aged 17 to 63 years ( mean = 38 , SD = 10 ) , were evaluated prospect ively . METHODS Subjects were assessed initially ( INA ) and were reevaluated 1 month later ( 1MO ) and again at the time of discharge ( DC ) . The Oswestry disability score , fingertip-to-floor distance during forward bending , maximal isometric lift , and work status were described as outcomes . Subjects were grouped based on compliance , chronicity , and leg symptoms . Each disability/impairment outcome was analyzed with paired t tests ( INA versus 1MO and INA versus DC ) . The frequency of subjects returning to work across groups was evaluated with a chi-square analysis corrected for unequal group sizes . RESULTS Overall , there was improvement in each dependent measure at 1MO and DC compared with the INA . Subjects with high compliance had a 10 % reduction in mean disability at 1MO and a 12 % reduction in mean disability at DC compared with the INA . The low-compliance group , in contrast , showed less than a 5 % reduction in mean disability at both the 1MO and DC assessment s compared with the INA . The magnitude of improvement in disability status , forward bending , and maximal lift was approximately two to three times greater for subjects with acute symptoms compared with those with chronic symptoms . The increase in mean forward bending for subjects without leg symptoms was over twice as large as the increase in forward bending for subjects with leg symptoms . Seventy-five percent of the subjects followed at DC ( 30 out of 40 ) were released to work in some capacity . There was no association between compliance or presence of leg symptoms and work status at DC . Eighty percent of the subjects with acute symptoms , however , were working at the time of DC compared with 44 % of those with chronic symptoms . CONCLUSION AND DISCUSSION Compliance , chronicity , and leg symptoms are all factors that can affect the outcome of physical therapy . The positive outcomes for subjects who complied with therapy suggest that a physical therapy program with multiple interventions may decrease disability and impairment",
"& 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",
"Study Design . A r and omized trial was conducted in which patients with back and neck pain , visiting a general practitioner , were allocated to chiropractic or physiotherapy . Objectives . To compare outcome and costs of chiropractic and physiotherapy as primary treatment for patients with back and neck pain , with special reference to subgroups , recurrence rate , and additional health care use at follow‐up evaluation 12 months after treatment . Summary of Background Data . Earlier studies on the effect of spinal manipulation have shown inconsistent results . Mostly they include only short‐term follow‐up periods , and few cost‐effectiveness analyses have been made . Methods . A group of 323 patients aged 18‐60 years who had no contraindications to manipulation and who had not been treated within the previous month were included . Outcome measures were changes in Oswestry scores , pain intensity , and general health ; recurrence rate ; and direct and indirect costs . Results . No differences were detected in health improvement , costs , or recurrence rate between the two groups . According to Oswestry score , chiropractic was more favorable for patients with a current pain episode of less than 1 week ( 5 % ) and physiotherapy for patients with a current pain episode of greater than 1 month ( 6.8 % ) . Nearly 60 % of the patients reported two or more recurrences . More patients in the chiropractic group ( 59 % ) than in the physiotherapy group ( 41 % ) sought additional health care . Costs varied considerably among individuals and subgroups ; the direct costs were lower for physiotherapy in a few subgroups . Conclusions . Effectiveness and costs of chiropractic or physiotherapy as primary treatment were similar for the total population , but some differences were seen according to subgroups . Back problems often recurred , and additional health care was common . Implication s of the result are that treatment policy and clinical decision models must consider subgroups and that the problem often is recurrent . Models must be implemented and tested",
"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",
"Study Design . A multicenter , r and omized , single‐blinded controlled trial with 1‐year follow‐up . Objectives . To evaluate the efficiency of progressively grade d medical exercise therapy , conventional physiotherapy , and self‐exercise by walking in patients with chronic low back pain . Summary and Background Data . Varieties of medical exercise therapy and conventional physiotherapy are considered to reduce symptoms , improve function , and decrease sickness absence , but this opinion is controversial . Methods . Patients with chronic low back pain or radicular pain sick‐listed for more than 8 weeks and less than 52 weeks ( Sickness Certificate II ) were included . The treatment lasted 3 months ( 36 treatments ) . Pain intensity , functional ability , patient satisfaction , return to work , number of days on sick leave , and costs were recorded . Results . Of the 208 patients included in this study , 71 were r and omly assigned to medical exercise therapy , 67 to conventional physiotherapy , and 70 to self‐exercise . Thirty‐three ( 15.8 % ) patients dropped out during the treatment period . No difference was observed between the medical exercise therapy and conventional physiotherapy groups , but both were significantly better than self‐exercise group . Patient satisfaction was highest for medical exercise therapy . Return to work rates were equal for all 3 intervention groups at assessment 15 months after therapy was started , with 123 patients were back to work . In terms of costs for days on sick leave , the medical exercise therapy group saved 906,732 Norwegian Kroner ( NOK ) ( $ 122,531.00 ) , and the conventional physiotherapy group saved NOK 1,882,560 ( $ 254,200.00 ) , compared with the self‐exercise group . Conclusions . The efficiency of medical exercise therapy and conventional physiotherapy is shown . Leaving patients with chronic low back pain untampered poses a risk of worsening the disability , result ing in longer periods of sick leave",
"Aspects of validity are investigated with a brief functional assessment measure among out patients undergoing rehabilitation for musculoskeletal problems . The Medical Rehabilitation Follow Along measure ( MRFA ) currently has screening , musculoskeletal , neurologic , and multiple sclerosis forms . In this study , the 31-item musculoskeletal form of the MRFA is compared with and contrasted to a measure of general health status , the Medical Outcomes Trust SF-36 . Content , construct , and criterion validity are addressed using scale scores before ( n = 94 ) and after ( n = 48 ) outpatient rehabilitation . Scale scores are compared with therapists ' ratings of improvement . The results provide support for the validity of inferences made from scale scores of the MRFA for persons with musculoskeletal problems . Applications of the MRFA , including screening , monitoring , and outcome assessment are discussed for clinical management , measuring treatment effectiveness , and program evaluation",
"There are only few publications about the effect of music therapy on pain relief . The intention of this prospect i ve study is to demonstrate the influence of the Nordoff/Robbins method of active music therapy in a group of 12 patients with fibromyalgia , myofascial pain syndromes and polyarthritis on pain reduction , life quality and coping . The clinical parameters of each patient were related to the observations in the audio- and video-documented music therapy setting s and to the self-reported changes in pain intensity and pain behaviour . There was a significant reduction of pain intensity and pain-related disability in the music group compared to a control group , but no change in the depression and anxiety score . The influence of music therapy could be even better demonstrated in the systematic analysis of the single cases by individual profiles . Active music therapy affects especially the communicative and emotional dimension of chronic pain . Psychophysiological and psychodynamic models are presented to explain the effectiveness of music therapy on pain reduction . Clinical studies on music therapy as well as on other \" art therapies \" should relate the analysis of clinical parameters to the descriptive-phenomenological documentation of the therapeutic process to demonstrate systematic ally the influence of music and art in the individual case",
"Cognitive behavioral treatment has been incorporated into st and ard medical treatment procedures in German pain centers . Acceptance of the treatment by patients and outcome in terms of pain , coping , and disability was investigated . Components of the psychological treatment are education , relaxation and imagery , modifying thoughts and feelings , enhancement of pleasant activities , and training of good postural habits . The program was conducted in a group setting in accordance with a treatment manual and consists of 12 weekly 2.5-h sessions . A two-factor experiment with repeated measures on one factor was applied . Ninety-four consecutive patients with low-back pain were r and omly assigned to an experimental group having a combined medical and cognitive-behavioral treatment , or to a control group with medical treatment only . Assessment s were taken pre-treatment , post-treatment , and --in the treated group only -- at a 6-months follow-up . At each assessment , patients kept a pain diary over a period of 4 weeks , and filled in self-report question naires . The sample consisted of 36 experimental and 40 control subjects at post-treatment . Experimental subjects reported less pain , better control over pain , more pleasurable activities and feelings , less avoidance and less catastrophizing . In addition , disability was reduced in terms of social roles , physical functions and mental performance . The results were maintained at follow-up . Patients who only received medical treatment showed little improvement . Data indicate that the program meets the needs of the patients and should be continued",
"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",
"BACKGROUND Bed rest and back-extension exercises are often prescribed for patients with acute low back pain , but the effectiveness of these two competing treatments remains controversial . METHODS We conducted a controlled trial among employees of the city of Helsinki , Finl and , who presented to an occupational health care center with acute , nonspecific low back pain . The patients were r and omly assigned to one of three treatments : bed rest for two days ( 67 patients ) , back-mobilizing exercises ( 52 patients ) , or the continuation of ordinary activities as tolerated ( the control group ; 67 patients ) . Outcomes and costs were assessed after 3 and 12 weeks . RESULTS After 3 and 12 weeks , the patients in the control group had better recovery than those prescribed either bed rest or exercises . There were statistically significant differences favoring the control group in the duration of pain , pain intensity , lumbar flexion , ability to work as measured subjectively , the Oswestry back-disability index , and number of days absent from work . Recovery was slowest among the patients assigned to bed rest . The overall costs of care did not differ significantly among the three groups . CONCLUSIONS Among patients with acute low back pain , continuing ordinary activities within the limits permitted by the pain leads to more rapid recovery than either bed rest or back-mobilizing exercises",
"Study Design A prospect ively design ed study was performed to assess the influence of employment status and a compensation cl aim on patients experiencing low back pain . Objectives To determine the factor that most influences disability arising from low back pain , unemployment or a compensation cl aim . Summary of Background Data Two hundred sixtynine consecutive patients were assessed from a low back pain clinic . Methods Disability was assessed using the Oswestry Disability Score , and employment , and compensation status were recorded . Results Both unemployment and patients involved in compensation had higher disability scores . However , by controlling the data for employment and assessing only the compensation group it was found that those cl aim ing compensation , but still working had significantly less disability than those cl aim ing compensation who were unemployed . Conclusions Both unemployment and compensation cl aims influence disability , but employment status is the most important factor",
"Study Design This prospect i ve , multicenter study was design ed to investigate the efficacy and outcome of spinal cord stimulation using a variety of clinical and psychosocial outcome measures . Data were collected before implantation and at regular intervals after implantation . This report focuses on 70 patients who had undergone 1 year of follow‐up treatment at the time of data analysis . Objectives To provide a more generalizable assessment of long‐term spinal cord stimulation outcome by comparing a variety of pain and functional/ quality ‐of‐life measures before and after management . This report details results after 1 year of stimulation . Summary of Background Data The historically diverse methods , patient selection criteria , and outcome measures reported in the spinal cord stimulation literature have made interpretation and comparison of results difficult . Although short‐term outcomes are generally consistent , long‐term outcomes of spinal cord stimulation , as determined by prospect i ve studies that assess multidimensional aspects of the pain complaint among a relatively homogeneous population , are not well established . Methods Two hundred nineteen patients were entered at six centers throughout the United States . All patients underwent a trial of stimulation before implant of the permanent system . Most were psychologically screened . One hundred eighty‐two patients were implanted with a permanent stimulating system . At the time of this report , complete 1‐year follow‐up data were available on 70 patients , 86 % of whom reported pain in the back or lower extremities . Patient evaluation of pain and functional levels was completed before implantation and 3 , 6 , 12 , and 24 months after implantation . Complications , medication usage , and work status also were monitored . Results All pain and quality ‐of‐life measures showed statistically significant improvement during the treatment year . These included the average pain visual analogue scale , the McGill Pain Question naire , the Oswestry Disability Question naire , the Sickness Impact Profile , and the Beck Depression Inventory . Overall success of the therapy was defined as at least 50 % pain relief and patient assessment of the procedure as fully or partially beneficial and worthwhile . Using this definition , spinal cord stimulation successfully managed pain in 55 % of patients on whom 1‐year follow‐up is available . Complications requiring surgical intervention were reported by 17 % ( 12 of 70 ) of patients . Medication usage and work status were not changed significantly . Conclusions This prospect i ve , multicenter study confirms that spinal cord stimulation can be an effective therapy for management of chronic low back and extremity pain . Significant improvements in many aspects of the pain condition were measured , and complications were minimal",
"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",
"Intradevice reliability of isokinetic trunk strength measurements has been studied frequently , but no evidence is available on interdevice reliability . This motivated the present study , in which two isokinetic devices , the Ariel 5000 and Lido Multi-Joint II , were compared in a sample of 41 subjects ( 20 healthy and 21 low back pain subjects ) . The measurements were made in a r and om order with both machines . The results showed that the two isokinetic machines gave quite different results in trunk flexion-extension strength measurements . A statistically significant difference was present in the average peak torques between the two devices , with the exception of flexion at low angular velocity ( 60 degrees/s ) , and the correlations between the two measurements were low . The results were assumed to be more of a reflection of the interdevice variations ( hardware and software , attachment of the subject ) than of learning effects or other phenomena . We conclude that isokinetic trunk-muscle strength test results with the Ariel and Lido are device specific , and one can not automatically compare results obtained from different devices with each other",
"In a prospect i ve study 122 patients with herniated lumbar disc pre-operatively completed psychological question naires . Surgical outcome was evaluated 12 months post-operatively mainly by a composite clinical overall score ( COS ) , and by its separate elements . Anxiety ( HAD-A scale ) and psychosomatic symptoms ( MSPQ ) had predictive value : fewer symptoms favoured a satisfactory overall outcome , and vice versa . The HAD-A Scale had a predictive power of poor ( ppp ) and satisfactory ( pps ) outcome of 28 and 81 % , respectively . Correspondingly , for the MSPQ , the ppp and pps were 42 and 85 % . Anamnestic and biological variables ( including fibrinolytic variables : ECLT and PAI-1 ) predicted 20 % of the outcome . By adding all psychological variables the prediction increased only to 24 % , but the HAD-A Scale and the MSPQ were still significant . The results suggest that in order to further improve prediction of outcome , future studies should combine biological variables sensitive to the mental state of the patient , with psychometric assessment",
"Study Design . A r and omized , clinical trial was conducted in which patients with back/neck problems , visiting a general practitioner , were allocated to chiropractic or physiotherapy as primary management . Objectives . To compare outcome and costs of chiropractic and physiotherapy in managing patients with low back or neck pain . Summary of Background Data . Earlier studies on the treatment of back pain by spinal manipulation have shown inconsistent results . When a \" new \" strategy ‐chiropractic‐in the treatment of back pain was introduced in public health care in Sweden , there was a need to compare the effects and costs of chiropractic with the established physiotherapy . Methods . Three hundred twenty‐three patients aged 18 to 60 years who had no contraindications to manipulation and who had not been treated within the previous month were included in the study . Treatment was carried out at the discretion of the therapist . Outcome measures were primarily changes in pain intensity and general health , both assessed with visual analog scale and Oswestry pain disability question naire . Direct and indirect costs were measured . Results . For patients with low back or neck pain visiting the general practitioner in primary care , both chiropractic and physiotherapy as primary treatment reduced the symptoms . No difference in outcome or direct or indirect costs between the two groups could be seen , nor in subgroups defined as duration , history , or severity . Conclusions . The effectiveness and total costs of chiropractic or physiotherapy as primary treatment were similar to reach the same result after treatment and after 6 months"
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411884e8-06ff-11f0-808a-c43d1ab1c353
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Background Gastric cancer is a major health problem , and frailty and sarcopenia will affect the postoperative outcomes in older people . However , there is still no systematic review to determine the role of frailty and sarcopenia in predicting postoperative outcomes among older patients with gastric cancer who undergo gastrectomy surgery . Methods We search ed Embase , Medline through the Ovid interface and PubMed websites to identify potential studies . All the search strategies were run on August 24 , 2016 . We search ed the Google website for unpublished studies on June 1 , 2017 . The data related to the endpoints of gastrectomy surgery were extracted . Odds ratios ( ORs ) and their 95 % confidence intervals ( CIs ) were pooled to estimate the association between sarcopenia and adverse postoperative outcomes by using Stata version 11.0 . PRISMA guidelines for systematic review s were followed . Results After screening 500 records , we identified eight studies , including three prospect i ve cohort studies and five retrospective cohort studies . Only one study described frailty , and the remaining seven studies described sarcopenia . Frailty was statistically significant for predicting hospital mortality ( OR 3.96 ; 95 % CI : 1.12–14.09 , P = 0.03 ) . Sarcopenia was also associated with postoperative outcomes ( pooled OR 3.12 ; 95 % CI : 2.23–4.37 ) . No significant heterogeneity was observed across these pooled studies ( Chi2 = 3.10 , I2 = 0 % , P = 0.685 ) . ConclusionS arcopenia and frailty seem to have significant adverse impacts on the occurrence of postoperative outcomes . Well- design ed prospect i ve cohort studies focusing on frailty and quality of life with a sufficient sample are needed
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[
"BACKGROUND Selecting elderly persons who need geriatric interventions and making accurate treatment decisions are recurring challenges in geriatrics . Chronological age , although often used , does not seem to be the best selection criterion . Instead , the concept of frailty , which indicates several concurrent losses in re sources , can be used . METHODS The predictive values of chronological age and frailty were investigated in a large community sample of persons aged 65 years and older , r and omly drawn from the register of six municipalities in the northern regions of the Netherl and s ( 45 % of the original addressees ) . The participants ' generative capacity to sustain well-being ( i.e. , self-management abilities ) was used as the main outcome measure . RESULTS When using chronological age instead of frailty , both too many and too few persons were selected . Furthermore , frailty related more strongly ( with beta values ranging from -.25 to -.39 ) to a decline in the participants ' self-management abilities than did chronological age ( with beta values ranging from -.06 to -.14 ) . Chronological age added very little to the explained variances of all outcomes once frailty was included . CONCLUSIONS Using frailty as the criterion to select older persons at risk for interventions may be better than selecting persons based only on their chronological age",
"Abstract Currently , the association between sarcopenia and long-term prognosis after gastric cancer surgery has not been investigated . Moreover , the association between sarcopenia and postoperative complications remains controversial . This large-scale retrospective study aims to ascertain the prevalence of sarcopenia and assess its impact on postoperative complications and long-term survival in patients undergoing radical gastrectomy for gastric cancer . From December 2008 to April 2013 , the clinical data of all patients who underwent elective radical gastrectomy for gastric cancer were collected prospect ively . Only patients with available preoperative abdominal CT scan within 30 days of surgery were considered for analysis . Skeletal muscle mass was determined by abdominal ( computed tomography ) CT scan , and sarcopenia was diagnosed by the cut-off values obtained by means of optimum stratification . Univariate and multivariate analyses evaluating risk factors of postoperative complications and long-term survival were performed . A total of 937 patients were included in this study , and 389 ( 41.5 % ) patients were sarcopenic based on the diagnostic cut-off values ( 34.9 cm2/m2 for women and 40.8 cm2/m2 for men ) . Sarcopenia was an independent risk factor for severe postoperative complications ( OR = 3.010 , P total complications . However , sarcopenia did not show significant association with operative mortality . Moreover , sarcopenia was an independent predictor for poorer overall survival ( HR = 1.653 , P disease-free survival ( HR = 1.620 , P sarcopenia remained an independent risk factor for overall survival and disease-free survival in patients with TNM stage II and III , but not in patients with TNM stage I.Sarcopenia is an independent predictive factor of severe postoperative complications after radical gastrectomy for gastric cancer . Moreover , sarcopenia is independently associated with overall and disease-free survival in patients with TNM stage II and III , but not in patients with TNM stage",
"BACKGROUND Preoperative risk assessment is important yet inexact in older patients because physiologic reserves are difficult to measure . Frailty is thought to estimate physiologic reserves , although its use has not been evaluated in surgical patients . We design ed a study to determine if frailty predicts surgical complications and enhances current perioperative risk models . STUDY DESIGN We prospect ively measured frailty in 594 patients ( age 65 years or older ) presenting to a university hospital for elective surgery between July 2005 and July 2006 . Frailty was classified using a vali date d scale ( 0 to 5 ) that included weakness , weight loss , exhaustion , low physical activity , and slowed walking speed . Patients scoring 4 to 5 were classified as frail , 2 to 3 were intermediately frail , and 0 to 1 were nonfrail . Main outcomes measures were 30-day surgical complications , length of stay , and discharge disposition . Multiple logistic regression ( complications and discharge ) and negative binomial regression ( length of stay ) were done to analyze frailty and postoperative outcomes associations . RESULTS Preoperative frailty was associated with an increased risk for postoperative complications ( intermediately frail : odds ratio [ OR ] 2.06 ; 95 % CI 1.18 - 3.60 ; frail : OR 2.54 ; 95 % CI 1.12 - 5.77 ) , length of stay ( intermediately frail : incidence rate ratio 1.49 ; 95 % CI 1.24 - 1.80 ; frail : incidence rate ratio 1.69 ; 95 % CI 1.28 - 2.23 ) , and discharge to a skilled or assisted-living facility after previously living at home ( intermediately frail : OR 3.16 ; 95 % CI 1.0 - 9.99 ; frail : OR 20.48 ; 95 % CI 5.54 - 75.68 ) . Frailty improved predictive power ( p risk index ( ie , American Society of Anesthesiologists , Lee , and Eagle scores ) . CONCLUSIONS Frailty independently predicts postoperative complications , length of stay , and discharge to a skilled or assisted-living facility in older surgical patients and enhances conventional risk models . Assessing frailty using a st and ardized definition can help patients and physicians make more informed decisions",
"Background Sarcopenia is a decrease in both muscle mass and strength . It remains unclear whether sarcopenia is associated with morbidity after gastric cancer surgery . This study evaluated the impact of sarcopenia on the morbidity of gastric cancer surgery . Methods A total of 293 gastric cancer patients who underwent curative surgery between May 2011 and June 2013 were retrospectively examined . Patients with performance status 3 or 4 were excluded . Preoperative lean body mass ( LBM ) was evaluated by bioelectrical impedance analysis and expressed as LBM index . Preoperative muscle function was measured by h and grip strength ( HGS ) . The cutoff values were the gender-specific lowest 20 % . Grade 2 or higher morbidities , as retrospectively evaluated by the Clavien – Dindo classification , were obtained from the patient record . The risk factors for morbidity were examined by univariate and multivariate analyses . Results Morbidity was observed in 39 patients ( 13.3 % ) , including 7 with pancreatic leakage , 12 with anastomotic leakage , and 4 with intraabdominal abscesses , but no mortality was observed . The univariate analysis showed that male gender , total gastrectomy , splenectomy , and a low HGS were significant risk factors for morbidity . A low LBM was not a significant risk factor . A low HGS , male gender , and total gastrectomy remained significant in the multivariate analysis . Conclusions A low h and grip strength was a significant risk factor for morbidity after gastric cancer surgery . The importance of the h and grip strength as a risk factor should be examined in future prospect i ve studies",
"Objectives : ( 1 ) Determine the relationship of geriatric assessment markers to 6-month postoperative mortality in elderly patients . ( 2 ) Create a clinical prediction rule using geriatric markers from preoperative assessment . Background : Geriatric surgery patients have unique physiologic vulnerability requiring preoperative assessment beyond the traditional evaluation of older adults . The constellation of frailty , disability and comorbidity predict poor outcomes in elderly hospitalized patients . Methods : Prospect ively , subjects ≥65 years undergoing a major operation requiring postoperative intensive care unit admission were enrolled . Preoperative geriatric assessment s included : Mini-Cog Test ( cognition ) , albumin , having fallen in the past 6-months , hematocrit , Katz Score ( function ) , and Charlson Index ( comorbidities ) . Outcome measures included 6-month mortality ( primary ) and postdischarge institutionalization ( secondary ) . Results : One hundred ten subjects ( age 74 ± 6 years ) were studied . Six-month mortality was 15 % ( 16/110 ) . Preoperative markers related to 6-month mortality included : impaired cognition ( P recent falls ( P lower albumin ( P greater anemia ( P functional dependence ( P increased comorbidities ( P functional dependence ( odds ratio 13.9 ) as the strongest predictor of 6-month mortality . Four or more markers in any one patient predicted 6-month mortality with a sensitivity of 81 % ( 13/16 ) and specificity of 86 % ( 81/94 ) . Conclusions : Geriatric assessment markers for frailty , disability and comorbidity predict 6-month postoperative mortality and postdischarge institutionalization . The preoperative presence of ≥4 geriatric-specific markers has high sensitivity and specificity for 6-month mortality . Preoperative assessment using geriatric-specific markers is a substantial paradigm shift from the traditional preoperative evaluation of older adults",
"Background Sarcopenia is characterized by decreased skeletal muscle plus low muscle strength and /or physical performance . This study was performed to determine the association of sarcopenia with short-term postoperative outcomes after gastrectomy for gastric cancer . Methods We conducted a prospect i ve study of 255 consecutive patients with gastric cancer who underwent curative gastrectomy . The sarcopenia elements , including lumbar skeletal muscle index , h and grip strength , and gait speed , were measured before surgery . Patients were followed up after gastrectomy to gain the actual clinical outcomes . Factors contributing to postoperative complications were analyzed by univariate and multivariate analysis . Results Sarcopenia was present in 32 of 255 patients ( 12.5 % ) , and was significantly correlated with advance age , lower body mass index , higher nutritional risk screening ( NRS ) 2002 score , and lower preoperative serum albumin and hemoglobin . Compared with non-sarcopenic patients , sarcopenic patients had a higher risk of postoperative complications , longer postoperative hospital stay , and more hospital costs . In univariate analysis , sarcopenia ( p , nutritional risk ( NRS 2002 score ≥3 ; p = 0.003 ) , advanced age ( ≥75 years ; p = 0.014 ) , anemia ( p = 0.012 ) , hypoalbuminemia ( p = 0.029 ) , and diabetes ( p = 0.014 ) were associated with postoperative complications . Multivariable analysis revealed that sarcopenia ( p Sarcopenia is an independent predictor of postoperative complications in patients with gastric cancer after gastrectomy"
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41188524-06ff-11f0-808a-c43d1ab1c353
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Context Although a recent meta- analysis of r and omized controlled trials showed that adoption of a vegetarian diet reduces plasma lipids , the association between vegetarian diets and long-term effects on plasma lipids has not been subjected to meta- analysis . Objective The aim was to conduct a systematic review and meta- analysis of observational studies and clinical trials that have examined associations between plant-based diets and plasma lipids . Data Sources MEDLINE , Web of Science , and the Cochrane Central Register of Controlled Trials were search ed for articles published in English until June 2015 . Study Selection The literature was search ed for controlled trials and observational studies that investigated the effects of at least 4 weeks of a vegetarian diet on plasma lipids . Data Extraction Two review ers independently extracted the study methodology and sample size , the baseline characteristics of the study population , and the concentrations and variance measures of plasma lipids . Mean differences in concentrations of plasma lipids between vegetarian and comparison diet groups were calculated . Data were pooled using a r and om-effects model . Results Of the 8385 studies identified , 30 observational studies and 19 clinical trials met the inclusion criteria ( N = 1484 ; mean age , 48.6 years ) . Consumption of vegetarian diets was associated with lower mean concentrations of total cholesterol ( -29.2 and -12.5 mg/dL , P low-density lipoprotein cholesterol ( -22.9 and -12.2 mg/dL , P high-density lipoprotein cholesterol ( -3.6 and -3.4 mg/dL , P Triglyceride differences were -6.5 ( P = 0.092 ) in observational studies and 5.8 mg/dL ( P = 0.090 ) in intervention trials . Conclusions Plant-based diets are associated with decreased total cholesterol , low-density lipoprotein cholesterol , and high-density lipoprotein cholesterol , but not with decreased triglycerides . Systematic Review Registration PROSPERO number CRD42015023783 . Available at : https://www.crd.york.ac.uk/ PROSPERO /display_record.asp?ID = CRD42015023783
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"CONTEXT To enhance the effectiveness of diet in lowering cholesterol , recommendations of the Adult Treatment Panel III of the National Cholesterol Education Program emphasize diets low in saturated fat together with plant sterols and viscous fibers , and the American Heart Association supports the use of soy protein and nuts . OBJECTIVE To determine whether a diet containing all of these recommended food components leads to cholesterol reduction comparable with that of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) . DESIGN R and omized controlled trial conducted between October and December 2002 . SETTING AND PARTICIPANTS Forty-six healthy , hyperlipidemic adults ( 25 men and 21 postmenopausal women ) with a mean ( SE ) age of 59 ( 1 ) years and body mass index of 27.6 ( 0.5 ) , recruited from a Canadian hospital-affiliated nutrition research center and the community . INTERVENTIONS Participants were r and omly assigned to undergo 1 of 3 interventions on an outpatient basis for 1 month : a diet very low in saturated fat , based on milled whole-wheat cereals and low-fat dairy foods ( n = 16 ; control ) ; the same diet plus lovastatin , 20 mg/d ( n = 14 ) ; or a diet high in plant sterols ( 1.0 g/1000 kcal ) , soy protein ( 21.4 g/1000 kcal ) , viscous fibers ( 9.8 g/1000 kcal ) , and almonds ( 14 g/1000 kcal ) ( n = 16 ; dietary portfolio ) . MAIN OUTCOME MEASURES Lipid and C-reactive protein levels , obtained from fasting blood sample s ; blood pressure ; and body weight ; measured at weeks 0 , 2 , and 4 and compared among the 3 treatment groups . RESULTS The control , statin , and dietary portfolio groups had mean ( SE ) decreases in low-density lipoprotein cholesterol of 8.0 % ( 2.1 % ) ( P = .002 ) , 30.9 % ( 3.6 % ) ( P reductions in C-reactive protein were 10.0 % ( 8.6 % ) ( P = .27 ) , 33.3 % ( 8.3 % ) ( P = .002 ) , and 28.2 % ( 10.8 % ) ( P = .02 ) . The significant reductions in the statin and dietary portfolio groups were all significantly different from changes in the control group . There were no significant differences in efficacy between the statin and dietary portfolio treatments . CONCLUSION In this study , diversifying cholesterol-lowering components in the same dietary portfolio increased the effectiveness of diet as a treatment of hypercholesterolemia",
"Introduction The purpose of this study was to investigate the effects of vegan diet in patients with rheumatoid arthritis ( RA ) on blood lipids oxidized low-density lipoprotein ( oxLDL ) and natural atheroprotective antibodies against phosphorylcholine ( anti-PCs ) . Methods Sixty-six patients with active RA were r and omly assigned to either a vegan diet free of gluten ( 38 patients ) or a well-balanced non-vegan diet ( 28 patients ) for 1 year . Thirty patients in the vegan group completed more than 3 months on the diet regimen . Blood lipids were analyzed by routine methods , and oxLDL and anti-PCs were analyzed by enzyme-linked immunosorbent assay . Data and serum sample s were obtained at baseline and after 3 and 12 months . Results Mean ages were 50.0 years for the vegan group and 50.8 years for controls . Gluten-free vegan diet induced lower body mass index ( BMI ) and low-density lipoprotein ( LDL ) and higher anti-PC IgM than control diet ( p BMI , LDL , and cholesterol decreased after both 3 and 12 months ( p Triglycerides and high-density lipoprotein did not change . IgA anti-PC levels increased after 3 months ( p = 0.027 ) and IgM anti-PC levels increased trendwise after 12 months ( p = 0.057 ) . There was no difference in IgG anti-PC levels . In the control diet group , IgM anti-PC levels decreased both after 3 and 12 months ( p vegan patients into clinical responders and non-responders at 12 months , the effects on oxLDL and anti-PC IgA were seen only in responders ( p gluten-free vegan diet in RA induces changes that are potentially atheroprotective and anti-inflammatory , including decreased LDL and oxLDL levels and raised anti-PC IgM and IgA levels",
"BACKGROUND Replacement of red meat in the diet with chicken has reduced the urinary albumin excretion rate ( UAER ) and serum cholesterol in microalbuminuric type 2 diabetes patients . The effects of withdrawing red meat are unknown in the more advanced stages of diabetic nephropathy . OBJECTIVE Our objective was to assess the effects of replacing red meat in the usual diet ( UD ) with chicken ( CD ) and of consuming a lactovegetarian low-protein diet ( LPD ) on renal function , fatty acid , and lipid profile in macroalbuminuric type 2 diabetes patients . DESIGN A crossover controlled trial was conducted in 17 type 2 diabetes patients with macroalbuminuria ( 24-h UAER > or = 200 microg/min ) . Each patient followed the UD , CD , and LPD in a r and om order for 4 wk . After each diet , glomerular filtration rate , UAER , serum fatty acid , lipid profile , glycemic control , anthropometric indexes , and blood pressure were measured . RESULTS UAER [ median CD : 269.4 ( range : 111 - 1128 ) microg/min ; LPD : 229.3 ( 76.6 - 999.3 ) microg/min ; UD : 312.8 ( 223.7 - 1223.7 ) microg/min ; P mean ( + /-SD ) non-HDL cholesterol ( CD : 3.92 + /- 0.99 mmol/L ; LPD : 3.92 + /- 0.93 mmol/L ; UD : 4.23 + /- 1.06 mmol/L ; P = 0.042 ) were lower after CD and LPD than after UD . Compared with the UD , an increase in serum total polyunsaturated fatty acids was also observed ( CD : 39.8 + /- 2.6 % ; LPD : 39.7 + /- 4.4 % ; UD : 37.3 + /- 3.1 % ; P = 0.029 ) . CONCLUSION In macroalbuminuric patients with type 2 diabetes , withdrawing red meat from the diet reduces the UAER",
"BACKGROUND A vegetarian diet may lead to numerous health benefits , including weight loss . OBJECTIVE We examined the joint effects of personal preference of dietary treatment and a calorie-restricted , low-fat lactoovovegetarian diet ( LOV-D ) compared with a st and ard calorie-restricted , low-fat omnivorous diet ( STD-D ) on changes in weight , total cholesterol , ratio of LDL to HDL cholesterol ( LDL : HDL cholesterol ) , triacylglycerols , insulin resistance , and macronutrient intake during an 18-mo study . DESIGN This was a r and omized clinical trial of 176 overweight and obese adults who were recruited and r and omly assigned first to 1 of 2 preference conditions ( yes or no ) . If assigned to Preference-No , they were r and omly assigned to 1 of the 2 diet conditions ( STD-D or LOV-D ) . If assigned to Preference-Yes , they were assigned to the diet they indicated as preferred at screening . The 12-mo intervention was followed by a 6-mo maintenance phase . RESULTS Participants were mainly women ( 86.9 % ) and white ( 70.5 % ) ; 75 % completed the 18-mo study . A significant interaction between preference and dietary treatment was not observed for any of the outcome variables . However , participants in the Preference-No groups significantly decreased their triacylglycerols ( P = 0.04 ) . The only effect observed for diet was a borderline significant decrease in LDL : HDL cholesterol for the LOV-D group ( P = 0.06 ) . Within the LOV-D groups , those who were 100 % adherent to the LOV-D had significant and marginally significant reductions in monounsaturated fat ( P = 0.02 ) and total fat ( P = 0.05 ) intakes at 18 mo . CONCLUSIONS Our findings suggest that neither prescribing a vegetarian diet nor allowing persons to choose their preferred diet had a significant effect on outcome measures . However , all participants had a significant reduction in total energy and fat intakes and an increase in energy expenditure , which was reflected in reduced body weight . This clinical trial was registered at www . clinical trials.gov as NCT00330629",
"In general , vegetarians have lower serum lipids and blood pressures than omnivores have . We tested the blood pressure and serum lipid lowering effects of two fat-modified diets differing primarily in their source of protein . Twenty-six men were r and omized in an incomplete block design to two of three diets : a high-fat diet , a fat-modified lactoovovegetarian diet ( LOV ) and a diet in which 60 % of plant protein in the LOV was replaced with lean meat ( LM ) . Compared with the high-fat diet both prudent diets significantly lowered blood pressure , serum total cholesterol ( TC ) , and LDL cholesterol but significantly increased serum triglycerides . The LOV diet had a significantly greater cholesterol-lowering effect than did the LM diet ( 10 % vs 5 % decrease ) but blood pressure reductions were similar . The partial substitution of lean meat for plant protein in a fat-modified diet did not negate the overall cardiovascular-risk lowering of the lactoovovegetarian diet",
"CONTEXT Low levels of high-density lipoprotein ( HDL ) cholesterol are inversely related to cardiovascular risk . Whether this is a causal effect is unclear . OBJECTIVE To determine whether genetically reduced HDL cholesterol due to heterozygosity for 4 loss-of-function mutations in ABCA1 cause increased risk of ischemic heart disease ( IHD ) . DESIGN , SETTING , AND PARTICIPANTS Three studies of white individuals from Copenhagen , Denmark , were used : the Copenhagen City Heart Study ( CCHS ) , a 31-year prospect i ve general population study ( n = 9022 ; 28 heterozygotes ) ; the Copenhagen General Population Study ( CGPS ) , a cross-sectional general population study ( n = 31,241 ; 76 heterozygotes ) ; and the Copenhagen Ischemic Heart Disease Study ( CIHDS ) , a case-control study ( n = 16,623 ; 44 heterozygotes ) . End points in all 3 studies were recorded during the period of January 1 , 1976 , through July 9 , 2007 . MAIN OUTCOME MEASURES Levels of HDL cholesterol in the general population , cellular cholesterol efflux , and the association between IHD and HDL cholesterol and genotype . RESULTS Heterozygotes vs noncarriers for 4 ABCA1 mutations ( P1065S , G1216V , N1800H , R2144X ) had HDL cholesterol levels of 41 mg/dL ( interquartile range , 31 - 50 mg/dL ) vs 58 mg/dL ( interquartile range , 46 - 73 mg/dL ) , corresponding to a reduction in HDL cholesterol of 17 mg/dL ( P HDL cholesterol level in the CCHS was associated with a multifactorially adjusted hazard ratio for IHD of 1.70 ( 95 % confidence interval [ CI ] , 1.57 - 1.85 ) . However , for IHD in heterozygotes vs noncarriers , the multifactorially adjusted hazard ratio was 0.67 ( 95 % CI , 0.28 - 1.61 ; 1741 IHD events ) in the CCHS , the multifactorially adjusted odds ratio was 0.82 ( 95 % CI , 0.34 - 1.96 ; 2427 IHD events ) in the CGPS , and the multifactorially adjusted odds ratio was 0.86 ( 95 % CI , 0.32 - 2.32 ; 2498 IHD cases ) in the CIHDS . The corresponding odds ratio for IHD in heterozygotes vs noncarriers for the combined studies ( n = 41,961 ; 6666 cases ; 109 heterozygotes ) was 0.93 ( 95 % CI , 0.53 - 1.62 ) . CONCLUSION Lower plasma levels of HDL cholesterol due to heterozygosity for loss-of-function mutations in ABCA1 were not associated with an increased risk of IHD",
"BACKGROUND AND AIMS : Fatty acids are important cellular constituents that may affect many metabolic processes relevant for the development of diabetes and its complications . We showed previously that vegetarian diet leads to greater increase in metabolic clearance rate of glucose ( MCR ) than conventional hypocaloric diet . The aim of this secondary analysis was to explore the role of changes in fatty acid composition of serum phospholipids in diet- and exercise-induced changes in MCR in subjects with type 2 diabetes ( T2D ) . METHODS : Subjects with T2D ( n=74 ) were r and omly assigned into a vegetarian group ( VG , n=37 ) following vegetarian diet or a control group ( CG , n=37 ) following a conventional diet . Both diets were calorie restricted ( −500 kcal day–1 ) . Participants were examined at baseline , 12 weeks of diet intervention and 24 weeks ( subsequent 12 weeks of diet were combined with aerobic exercise ) . The fatty acid composition of serum phospholipids was measured by gas liquid chromatography . MCR was measured by hyperinsulinemic isoglycemic clamp . Visceral fat ( VF ) was measured by magnetic resonance imaging . RESULTS : Linoleic acid ( LA ; 18:2n6 ) increased in VG ( P=0.04 ) , whereas it decreased in CG ( P=0.04 ) in response to dietary interventions . It did not change significantly after the addition of exercise in either group ( group × time P changes in 18:2n6 correlated positively with changes in MCR ( r=+0.22 ; P=0.04 ) and negatively with changes in VF ( r=−0.43 ; P=0.01 ) . After adjustment for changes in body mass index , the association between 18:2n6 and MCR was no longer significant . The addition of exercise result ed in greater changes of phospholipid fatty acids composition in VG than in CG . CONCLUSION : We demonstrated that the insulin-sensitizing effect of a vegetarian diet might be related to the increased proportion of LA in serum phospholipids",
"The effects of a strict uncooked vegan diet on serum lipid and sterol concentrations were studied in patients with rheumatoid arthritis . The subjects were r and omized into a vegan diet group ( n 16 ) , who consumed a vegan diet for 2 - 3 months , or into a control group ( n 13 ) , who continued their usual omnivorous diets . Serum total and LDL-cholesterol and -phospholipid concentrations were significantly decreased by the vegan diet . The levels of serum cholestanol and lathosterol also decreased , but serum cholestanol : total cholesterol and lathosterol : total cholesterol did not change . The effect of a vegan diet on serum plant sterols was divergent as the concentration of campesterol decreased while that of sitosterol increased . This effect result ed in a significantly greater sitosterol : campesterol value in the vegan diet group than in the control group ( 1.48 ( SD 0.39 ) v. 0.72 ( SD 0.14 ) ; P concentration of campesterol compared with sitosterol is normal in omnivorous subjects and can be explained by lower absorption and esterification rates of sitosterol . Our results suggest that a strict uncooked vegan diet changes the relative absorption rates of these sterols and /or their biliary clearance",
"Background / objectives : To determine the effects of a low-fat plant-based diet program on anthropometric and biochemical measures in a multicenter corporate setting .Subjects/ methods : Employees from 10 sites of a major US company with body mass index ⩾25 kg/m2 and /or previous diagnosis of type 2 diabetes were r and omized to either follow a low-fat vegan diet , with weekly group support and work cafeteria options available , or make no diet changes for 18 weeks . Dietary intake , body weight , plasma lipid concentrations , blood pressure and glycated hemoglobin ( HbA1C ) were determined at baseline and 18 weeks . Results : Mean body weight fell 2.9 kg and 0.06 kg in the intervention and control groups , respectively ( P fell 8.0 and 8.1 mg/dl in the intervention group and 0.01 and 0.9 mg/dl in the control group ( P HbA1C fell 0.6 percentage point and 0.08 percentage point in the intervention and control group , respectively (P , mean changes in body weight were −4.3 kg and −0.08 kg in the intervention and control groups , respectively ( P fell 13.7 and 13.0 mg/dl in the intervention group and 1.3 and 1.7 mg/dl in the control group ( P HbA1C levels decreased 0.7 percentage point and 0.1 percentage point in the intervention and control group , respectively ( P dietary intervention using a low-fat plant-based diet in a corporate setting improves body weight , plasma lipids , and , in individuals with diabetes , glycemic control",
"Background Limited evidence suggests that dietary interventions may offer a promising approach for migraine . The purpose of this study was to determine the effects of a low-fat plant-based diet intervention on migraine severity and frequency . Methods Forty-two adult migraine sufferers were recruited from the general community in Washington , DC , and divided r and omly into two groups . This 36-week crossover study included two treatments : dietary instruction and placebo supplement . Each treatment period was 16 weeks , with a 4-week washout between . During the diet period , a low-fat vegan diet was prescribed for 4 weeks , after which an elimination diet was used . Participants were assessed at the beginning , midpoint , and end of each period . Significance was determined using student ’s t-tests . Results Worst headache pain in last 2 weeks , as measured by visual analog scale , was initially 6.4/10 cm ( SD 2.1 cm ) , and declined 2.1 cm during the diet period and 0.7 cm during the supplement period ( p=0.03 ) . Average headache intensity ( 0–10 scale ) was initially 4.2 ( SD 1.4 ) per week , and this declined by 1.0 during the diet period and by 0.5 during the supplement period ( p=0.20 ) . Average headache frequency was initially 2.3 ( SD 1.8 ) per week , and this declined by 0.3 during the diet period and by 0.4 during the supplement period ( p=0.61 ) . The Patient ’s Global Impression of Change showed greater improvement in pain during the diet period ( p nutritional approach may be a useful part of migraine treatment , but that method ologic issues necessitate further research .Trial registration Clinical trials.gov , NCT01699009 and NCT01547494",
"BACKGROUND Low-fat vegetarian and vegan diets are associated with weight loss , increased insulin sensitivity , and improved cardiovascular health . OBJECTIVE We compared the effects of a low-fat vegan diet and conventional diabetes diet recommendations on glycemia , weight , and plasma lipids . DESIGN Free-living individuals with type 2 diabetes were r and omly assigned to a low-fat vegan diet ( n = 49 ) or a diet following 2003 American Diabetes Association guidelines ( conventional , n = 50 ) for 74 wk . Glycated hemoglobin ( Hb A(1c ) ) and plasma lipids were assessed at weeks 0 , 11 , 22 , 35 , 48 , 61 , and 74 . Weight was measured at weeks 0 , 22 , and 74 . RESULTS Weight loss was significant within each diet group but not significantly different between groups ( -4.4 kg in the vegan group and -3.0 kg in the conventional diet group , P = 0.25 ) and related significantly to Hb A(1c ) changes ( r = 0.50 , P = 0.001 ) . Hb A(1c ) changes from baseline to 74 wk or last available values were -0.34 and -0.14 for vegan and conventional diets , respectively ( P = 0.43 ) . Hb A(1c ) changes from baseline to last available value or last value before any medication adjustment were -0.40 and 0.01 for vegan and conventional diets , respectively ( P = 0.03 ) . In analyses before alterations in lipid-lowering medications , total cholesterol decreased by 20.4 and 6.8 mg/dL in the vegan and conventional diet groups , respectively ( P = 0.01 ) ; LDL cholesterol decreased by 13.5 and 3.4 mg/dL in the vegan and conventional groups , respectively ( P = 0.03 ) . CONCLUSIONS Both diets were associated with sustained reductions in weight and plasma lipid concentrations . In an analysis controlling for medication changes , a low-fat vegan diet appeared to improve glycemia and plasma lipids more than did conventional diabetes diet recommendations . Whether the observed differences provide clinical benefit for the macro- or microvascular complications of diabetes remains to be established . This trial was registered at clinical trials.gov as NCT00276939",
"Purpose . This study evaluated the effect of the Dr. Dean Ornish Program for Reversing Heart Disease on cardiovascular disease as measured by the intima-media thickness of the common carotid artery and compared this effect to outcomes from patients participating in traditional cardiac rehabilitation . Design . R and omized clinical trial . Setting . SwedishAmerican Health System . Subjects . Ninety three patients with clinical ly confirmed coronary artery disease were r and omly assigned to the intervention ( n = 46 ) or traditional cardiac rehabilitation ( n = 47 ) . Intervention . Dr. Dean Ornish Program for Reversing Heart Disease . Measures . Ultrasound of the carotid artery and other cardiovascular risk factors were measured at baseline , 6 , and 12 months . Analysis . Intent-to-treat analysis . Results . There was no significant reduction in the carotid intima-media thickness of the carotid artery in the Ornish group or the cardiac rehabilitation group . Ornish Program participants had significantly improved dietary habits ( p weight ( p body mass index ( p number of patients with angina from baseline to 12 months was 44 % in Ornish and 12 % in cardiac rehabilitation . Conclusions . The Ornish Program appears to causes improvements in cardiovascular risk factors but does not appear to change the atherosclerotic process as it affects the carotid artery",
"CONTEXT The Lifestyle Heart Trial demonstrated that intensive lifestyle changes may lead to regression of coronary atherosclerosis after 1 year . OBJECTIVES To determine the feasibility of patients to sustain intensive lifestyle changes for a total of 5 years and the effects of these lifestyle changes ( without lipid-lowering drugs ) on coronary heart disease . DESIGN R and omized controlled trial conducted from 1986 to 1992 using a r and omized invitational design . PATIENTS Forty-eight patients with moderate to severe coronary heart disease were r and omized to an intensive lifestyle change group or to a usual-care control group , and 35 completed the 5-year follow-up quantitative coronary arteriography . SETTING Two tertiary care university medical centers . INTERVENTION Intensive lifestyle changes ( 10 % fat whole foods vegetarian diet , aerobic exercise , stress management training , smoking cessation , group psychosocial support ) for 5 years . MAIN OUTCOME MEASURES Adherence to intensive lifestyle changes , changes in coronary artery percent diameter stenosis , and cardiac events . RESULTS Experimental group patients ( 20 [ 71 % ] of 28 patients completed 5-year follow-up ) made and maintained comprehensive lifestyle changes for 5 years , whereas control group patients ( 15 [ 75 % ] of 20 patients completed 5-year follow-up ) made more moderate changes . In the experimental group , the average percent diameter stenosis at baseline decreased 1.75 absolute percentage points after 1 year ( a 4.5 % relative improvement ) and by 3.1 absolute percentage points after 5 years ( a 7.9 % relative improvement ) . In contrast , the average percent diameter stenosis in the control group increased by 2.3 percentage points after 1 year ( a 5.4 % relative worsening ) and by 11.8 percentage points after 5 years ( a 27.7 % relative worsening ) ( P=.001 between groups . Twenty-five cardiac events occurred in 28 experimental group patients vs 45 events in 20 control group patients during the 5-year follow-up ( risk ratio for any event for the control group , 2.47 [ 95 % confidence interval , 1.48 - 4.20 ] ) . CONCLUSIONS More regression of coronary atherosclerosis occurred after 5 years than after 1 year in the experimental group . In contrast , in the control group , coronary atherosclerosis continued to progress and more than twice as many cardiac events occurred",
"Purpose . To determine whether a multicomponent nutrition intervention program at a corporate site reduces body weight and improves other cardiovascular risk factors in overweight individuals . Design . Prospect i ve clinical intervention study . Subjects/ Setting . Employees of the Government Employees Insurance Company ( GEICO ) ( N = 113 ) , aged 21 to 65 years , with a body mass index ≥ 25 kg/m2 and /or previous diagnosis of type 2 diabetes . Intervention . A 22-week intervention including a low-fat , vegan diet . Measures . Changes in body weight , anthropometric measures , blood pressure , lipid profile , and dietary intake . Analysis . Multivariate analyses of variance were calculated for clinical and nutrient measures , followed by univariate analyses of variance , to determine the significance of differences between groups in changes over time . Results . Intervention-group participants experienced greater weight changes compared with control-group participants ( mean , – 5.1 [ SE , .6 ] kg vs. + .1 [ SE , .6 ] kg , p greater changes in waist circumference ( mean , – 4.7 [ SE , .6 ] cm vs. + .8 [ SE , .6 ] cm , p ( mean , – .006 [ SE , .003 ] vs. + .014 [ SE , .005 ] , p = .0007 ) . Weight loss of 5 % of body weight was more frequently observed in the intervention group ( 48.5 % ) compared with the control group ( 11.1 % ) ( χ2[1 , N= 113 ] = 16.99 , p individuals volunteering for a 22-week worksite research study , an intervention using a low-fat , vegan diet effectively reduced body weight and waist circumference ",
"Objective : To examine the serum fatty acid and lipid profiles and dietary intake of Hong Kong Chinese omnivores and vegetarians with respect to cardiovascular health . Design : R and om population survey stratified by age and sex . Subjects : One-hundred and ninety-four omnivore subjects ( 81 men , 113 women ) age 25–70 y , and 60 ovo-lacto-vegetarian adults ( 15 men , 45 women ) age 30–55 y. Measurements : Nutrient quantitation was by a food frequency method . Serum fatty acids were analysed by gas chromatography , and serum lipid by st and ard laboratory methods . Results : Compared with omnivores , vegetarians had higher serum concentrations of polyunsaturated ( PUFA ) and monosaturated fatty acids ( MUFA ) , and lower saturated fatty acids ( SFA ) , long chain omega-3 and trans fatty acids ( TFA ) . They also had lower serum cholesterol and higher apoA-I concentrations , but the LDL/HDL ratio was not different . The ratio of polyunsaturated to saturated fatty acids intake was higher in vegetarians . Compared with results from population s with higher incidences of coronary heart disease , while lower myristic and palmitic acid concentrations and higher eicosapentaneoic ( EPA ) and docosahexanoic acid ( DHA ) may partly account for the difference in incidence , linoleic acid concentration was higher . Although the Chinese vegetarian diet may be beneficial for heart health in that antioxidant and fibre intakes are higher and saturated fat lower , the low EPA and DHA due to omission from dietary source and suppressed formation by high linoleic acid level , and the presence of TFA in the diet , may exert an opposite effect . Conclusion : There are some favourable features in the serum fatty acid profile in the Hong Kong Chinese population with respect to cardiovascular health , but the consumption of TFA is of concern . The Chinese vegetarian diet also contains some adverse features . Sponsorship : This study is partly sponsored by the Hong Kong Health Services Research Grant . European Journal Of Clinical Nutrition ( 2000 ) 24 ,",
"OBJECTIVE To investigate whether glycemic and lipid control in patients with non-insulin-dependent diabetes ( NIDDM ) can be significantly improved using a low-fat , vegetarian ( vegan ) diet in the absence of recommendations regarding exercise or other lifestyle changes . METHODS Eleven subjects with NIDDM recruited from the Georgetown University Medical Center or the local community were r and omly assigned to a low-fat vegan diet ( seven subjects ) or a conventional low-fat diet ( four subjects ) . Two additional subjects assigned to the control group failed to complete the study . The diets were not design ed to be isocaloric . Fasting serum glucose , body weight , medication use , and blood pressure were assessed at baseline and biweekly thereafter for 12 weeks . Serum lipids , glycosylated hemoglobin , urinary albumin , and dietary macronutrients were assessed at baseline and 12 weeks . RESULTS Although the sample was intentionally small in accordance with the pilot study design , the 28 % mean reduction in fasting serum glucose of the experimental group , from 10.7 to 7.75 mmol/L ( 195 to 141 mg/dl ) , was significantly greater than the 12 % decrease , from 9.86 to 8.64 mmol/L ( 179 to 157 mg/dl ) , for the control group ( P mean weight loss was 7.2 kg in the experimental group , compared to 3 . 8 kg for the control group ( P Insulin was reduced in both experimental group patients on insulin . No patient in the control group reduced medication use . Differences between the diet groups in the reductions of serum cholesterol and 24-h microalbuminuria did not reach statistical significance ; however , high-density lipoprotein concentration fell more sharply ( 0.20 mmol/L ) in the experimental group than in the control group ( 0.02 mmol/L ) ( P low-fat , vegetarian diet in patients with NIDDM was associated with significant reductions in fasting serum glucose concentration and body weight in the absence of recommendations for exercise . A larger study is needed for confirmation",
"Few controlled trials have studied cholesterol-lowering diets in premenopausal women . None has examined the cholesterol-lowering effect of a low-fat vegetarian diet , which , in other population groups , leads to marked reductions in serum cholesterol concentrations and , in combination with other life-style changes , a regression of atherosclerosis . We tested the hypothesis that a low-fat , vegetarian diet significantly reduces serum total and low-density lipoprotein ( LDL ) cholesterol concentrations in premenopausal women . In a crossover design , 35 women , aged 22 to 48 , followed a low-fat vegetarian diet deriving approximately 10 % of energy from fat for 2 menstrual cycles . For 2 additional cycles , they followed their customary diet while also taking a \" supplement \" ( placebo ) pill . Serum lipid concentrations were assessed at baseline and during each intervention phase . Mean serum LDL , high-density lipoprotein ( HDL ) , and total cholesterol concentrations decreased 16 . 9 % , 16.5 % , and 13.2 % , respectively , from baseline to the intervention diet phase ( p mean serum triacylglycerol concentration increased 18.7 % ( p LDL/HDL ratio remained unchanged . Thus , in healthy premenopausal women , a low-fat vegetarian diet led to rapid and sizable reductions in serum total , LDL , and HDL cholesterol concentrations",
"The possible effect of diet on plasma lipids was investigated in a group of vegetarians . Seventy-three men and 43 women who had adhered to a vegetarian diet for an average of three years were studied in the fasting state and compared with a r and omly selected group of controls matched for age and sex . Mean cholesterol levels in milligrams per deciliter for vegetarians and controls , respectively , were 126 and 184 ; low-density lipoprotein , 73 and 118 ; very-low-density lipoprotein , 11.8 and 17.2 ; high-density lipoproteins , 42 and 49 ; and mean triglyceride levels 59 and 86 . Mean weight and subscapular skinfold thicknesses were 58 kg and 6 mm for vegetarians and 73 kg and 17 mm for controls . Similar differences in lipid levels were found between subgroups of 42 vegetarians and controls with identical mean weights . Multiple regression analyses showed that consumption of dairy foods and eggs , but not body weight , was associated with the lipoprotein and cholesterol findings",
"Context People can achieve recommended fat intake while consuming high or low amounts of vegetables , fruits , legumes , and whole grains . Contribution This 4-week r and omized trial compared 2 diets with different vegetable , fruit , legume , and whole-grain content but identical total fat , saturated fat , protein , carbohydrate , and cholesterol content . The 59 adults who consumed high amounts of vegetables , fruits , legumes , and whole grains had greater improvements in total and low-density lipoprotein cholesterol levels than the 61 adults who ate low amounts of these foods . Implication s At least over the short term , greater improvements in low-density lipoprotein and total cholesterol are an additional benefit of diets high in vegetables , fruits , legumes , and whole grains . The Editors It is well established that elevated low-density lipoprotein ( LDL ) cholesterol concentrations are a risk factor for cardiovascular diseases and that dietary modification is considered a first approach to their treatment and control ( 1 , 2 ) . For several decades , dietary modification for lipid management traditionally focused on avoiding saturated fat and cholesterol ( 3 - 5 ) . Previous examples of dietary interventions targeting LDL cholesterol level often reported only modest lipid improvements , leading some to consider diet a relatively ineffective therapy ( 6 ) . However , recent developments have suggested that the traditional focus of lipid management may have been overly simplistic and that diets might be more effective if more attention was focused on including certain foods or factors rather than just avoiding saturated fat and cholesterol . Effective refinements of dietary strategies for lipid management could decrease the gap in effectiveness between dietary approaches and drug therapy . Several dietary factors or foods , including soy protein , soy isoflavones , plant sterols , soluble fiber , oats , nuts , and garlic , have established or potential lipid benefits ( 7 - 13 ) . Each is derived from plant food sources , and it is inclusion of these factors , rather than avoidance , that is reported to confer benefits . However , given that most plant foods contain low or negligible amounts of saturated fat and that all plant foods are devoid of cholesterol , it follows that a plant-based diet is inherently low in saturated fat and cholesterol . Therefore , it is difficult to distinguish between plasma lipid benefits derived from the actual plant-based dietary components and those derived from avoidance of saturated fat and cholesterol . Several studies have been design ed to test the effects on plasma lipids of diets with identical saturated fat and cholesterol intake but varied amounts of 1 or 2 additional dietary components ( 14 - 16 ) . Data are more limited on dietary approaches that hold saturated fat and cholesterol intake constant while modifying multiple other dietary components simultaneously ( 17 ) . Modifying multiple dietary components simultaneously ( for example , increasing intake of vegetables , fruits , and low-fat dairy ) while holding sodium intake constant has been shown to effectively lower elevated blood pressure in the Dietary Approaches to Stop Hypertension trials ( DASH I and II ) ( 18 , 19 ) . Testing a parallel approach to refining dietary intervention for lipid management is warranted . In 2000 , the American Heart Association ( AHA ) reported revised dietary guidelines that substantially modified its 1993 and 1996 guidelines ( 2 , 4 , 5 ) . All 3 versions of the guidelines recommended keeping saturated fat intake at less than 10 % of energy and cholesterol intake below 300 mg/d . A notable modification of the 2000 guidelines was to emphasize foods and overall eating patterns , including increased intakes of vegetables and whole grains ( in general , a plant-based diet ) . It was our hypothesis that a plant-based diet consistent with the revised AHA 2000 guidelines would increase the LDL cholesterol-lowering benefits of the previous AHA Step I guidelines . We theorized that this improvement would be independent of the plant-based diet 's saturated fat and cholesterol content . Therefore , we design ed 2 diets that had identical levels of total fat ( 30 % of energy ) , saturated fat ( 10 % of energy ) , and cholesterol ( LDL cholesterol-lowering benefits among adults with moderately elevated cholesterol levels would be greater under weight-stable conditions with a plant-based low-fat diet than with a more typical , convenience-oriented low-fat diet that was identical in intake of total fat , saturated fat , and cholesterol . Methods Participants Participants were recruited from the local community , primarily through newspaper advertisements , letters to previous study participants , and flyers sent to university employees . Men and women were invited to enroll if they were 30 to 65 years of age with fasting plasma LDL cholesterol levels of 3.3 to 4.8 mmol/L ( 130 to 190 mg/dL ) , fasting plasma triglyceride levels less than 2.83 mmol/L ( During the recruitment phase , 1096 individuals were screened by telephone interview and 345 who met the initial inclusion criteria were considered eligible for cholesterol testing . Of these 345 persons , 188 who were found to have eligible concentrations of LDL cholesterol and triglycerides attended an orientation meeting . Fifty-one persons decided not to participate ( primarily because of the time commitment ) , and an additional 12 potential participants were excluded after a 3-day food record showed that their estimated average intake of saturated fat was already less than 10 % of energy . One hundred twenty-five participants were r and omly assigned to 1 of the 2 diet groups . The Stanford University Human Subjects Committee review ed and approved the investigation , all participants signed an informed consent form before enrollment , and the study was performed according to Declaration of Helsinki guidelines ( 20 ) . Design The trial used a parallel design . We r and omly assigned participants in blocks of 20 by selecting , without replacement , from a set of indistinguishable envelopes containing 10 assignments to each of the 2 diet groups . R and omization of the envelopes was done by h and , without a computer algorithm . No stratification criteria were used . Each participant was provided with meals , snacks , and beverages on an outpatient basis for 28 days , as described later . Diets Both study diets were design ed to provide 30 % of energy from total fat , 10 % of energy from saturated fat , and approximately 100 mg of cholesterol per 1000 kcal per day . During the menu- design ing stage of the study , the nutrient composition of the diets was determined by using the data base of Food Processor software , version 7.0 ( ESHA Research , Salem , Oregon ) . Menus were design ed by using commonly available foods from local markets . The Low-Fat diet was design ed to include many reduced-fat prepared-food items ( for example , reduced-fat cheeses , low-fat frozen lasagna , and low-fat and sugar-rich snack foods ) . In contrast , the Low-Fat Plus diet was design ed to include considerably more vegetables , legumes , whole grains , and fruits . Butter , cheese , and eggs were added to the daily menus for the Low-Fat Plus diet , increasing the saturated fat and cholesterol content to match the Low-Fat diet . A 7-day menu cycle was design ed for each of the 2 study diets ; therefore , each menu was repeated 4 times during the 28 days . The diets included breakfast , lunch , dinner , beverages , and snacks for each day . Each weekday , the participants ate either lunch or dinner at the dining facility of the Stanford General Clinical Research Center . After their on-site meal , they were given coolers that contained meals and snacks to be consumed off-site . On Fridays , participants received weekend meals to be consumed off-site . Appendix Table 1 and Appendix Table 2 list the daily menus . One free-choice evening meal was allowed each weekend . For this meal , participants were given guidelines for choosing low-fat meals consistent with their diet assignments and were required to keep a record of foods consumed . These records were analyzed for nutritional content and were used to determine the impact of the free-choice meals on the overall study diets . Adherence was measured by using daily log sheets kept by participants that tracked incomplete consumption of study foods or consumption of any non study foods . The 28 daily food logs for each participant were examined for deviations from the diets . The energy contribution of each deviation was determined and then totaled for the entire 28-day protocol period . Each of the 14 daily menus ( 7-day cycle 2 diets ) was analyzed chemically for nutrient content before the study and then again during the study ( Covance Laboratories , Madison , Wisconsin ) . The chemical analyses performed before the study confirmed that the average composition of the daily menus provided 30 % of energy from total fat , 10 % of energy from saturated fat , and approximately 100 mg of cholesterol per 1000 kcal per day . When the 2 diets were first design ed , we attempted to match their mono- and polyunsaturated fat content . However , the data base used in the design phase was missing values for these nutrients for approximately 20 % of the foods . In addition , many of the specific products purchased locally for the study provided incomplete information for the content of these unsaturated fats . The first round of chemical analyses of the diets , performed before enrollment began , indicated a modest discrepancy"
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BACKGROUND Medium-chain triglycerides ( MCTs ) may result in negative energy balance and weight loss through increased energy expenditure and lipid oxidation . However , results from human intervention studies investigating the weight reducing potential of MCTs , have been mixed . OBJECTIVE To conduct a systematic review and meta- analysis of r and omized controlled trials comparing the effects of MCTs , specifically C8:0 and C10:0 , to long-chain triglycerides ( LCTs ) on weight loss and body composition in adults . Changes in blood lipid levels were secondary outcomes . METHODS R and omized controlled trials > 3 weeks ' duration conducted in healthy adults were identified search ing Web of Knowledge , Discover , PubMed , Scopus , New Zeal and Science , and Cochrane CENTRAL until March 2014 with no language restriction . Identified trials were assessed for bias . Mean differences were pooled and analyzed using inverse variance models with fixed effects . Heterogeneity between studies was calculated using I(2 ) statistic . An I(2)>50 % or P Thirteen trials ( n=749 ) were identified . Compared with LCTs , MCTs decreased body weight ( -0.51 kg [ 95 % CI-0.80 to -0.23 kg ] ; P waist circumference ( -1.46 cm [ 95 % CI -2.04 to -0.87 cm ] ; P hip circumference ( -0.79 cm [ 95 % CI -1.27 to -0.30 cm ] ; P=0.002 ; I(2)=0 % ) , total body fat ( st and ard mean difference -0.39 [ 95 % CI -0.57 to -0.22 ] ; P total subcutaneous fat ( st and ard mean difference -0.46 [ 95 % CI -0.64 to -0.27 ] ; P visceral fat ( st and ard mean difference -0.55 [ 95 % CI -0.75 to -0.34 ] ; P blood lipid levels . Many trials lacked sufficient information for a complete quality assessment , and commercial bias was detected . Although heterogeneity was absent , study design s varied with regard to duration , dose , and control of energy intake . CONCLUSIONS Replacement of LCTs with MCTs in the diet could potentially induce modest reductions in body weight and composition without adversely affecting lipid profiles . However , further research is required by independent research groups using large , well- design ed studies to confirm the efficacy of MCT and to determine the dosage needed for the management of a healthy body weight and composition
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"A double blind clinical trial was carried out to clarify the effects of oil with medium- and long-chain triglyceride ( MLCT ) on body fat and blood lipid profiles in hypertriglyceridemic subjects . One-hundred- and -twelve subjects were enrolled and divided into two groups ; those that consumed MLCT oil and those that consumed long-chain triglyceride ( LCT ) oil for 8 weeks . All subjects were requested to consume 25 - 30 g of the oils daily and maintain a fixed level of energy intake and exercise . Anthropometric and blood biochemical parameters were measured when the study was initiated and completed . The LCT group consisted of 50 subjects ( 34 men and 16 women ) , while the MLCT group consisted of 51 subjects ( 33 men and 18 women ) who completed the study . Larger decreases in body weight , body mass index , waist circumference , body fat , total fat area and subcutaneous fat area in the abdomen and serum triglycerides , low-density lipoprotein cholesterol , apolipoprotein B , C2 , C3 and E were observed in male subjects in the MLCT group than those in the LCT group . However , no significant differences in these parameters between the female subjects in the two groups were observed . Data from this study indicate that consumption of medium- and long-chain triglycerides can reduce body weight and body fat and improve blood lipid profiles in male hypertriglyceridemic subjects",
"OBJECTIVE The objectives of this study were to compare the effects of diets rich in medium-chain triglycerides ( MCTs ) or long-chain triglycerides ( LCTs ) on body composition , energy expenditure , substrate oxidation , subjective appetite , and ad libitum energy intake in overweight men . RESEARCH METHODS AND PROCEDURES Twenty-four healthy , overweight men with body mass indexes between 25 and 31 kg/m(2 ) consumed diets rich in MCT or LCT for 28 days each in a crossover r and omized controlled trial . At baseline and after 4 weeks of each dietary intervention , energy expenditure was measured using indirect calorimetry , and body composition was analyzed using magnetic resonance imaging . RESULTS Upper body adipose tissue ( AT ) decreased to a greater extent ( p olive oil ( OL ) consumption ( -0.67 + /- 0.26 kg and -0.02 + /- 0.19 kg , respectively ) . There was a trend toward greater loss of whole-body subcutaneous AT volume ( p = 0.087 ) with FctO compared with OL consumption . Average energy expenditure was 0.04 + /- 0.02 kcal/min greater ( p average fat oxidation was greater ( p = 0.052 ) with FctO compared with OL intake on day 2 but not day 28 . DISCUSSION Consumption of a diet rich in MCTs results in greater loss of AT compared with LCTs , perhaps due to increased energy expenditure and fat oxidation observed with MCT intake . Thus , MCTs may be considered as agents that aid in the prevention of obesity or potentially stimulate weight loss",
"Objectives : To investigate the effects of medium- and long-chain triacylglycerol ( MLCT ) on blood triglyceride ( TG ) in Chinese hypertriglyceridemic subjects . Methods : A double-blind controlled clinical trial was carried out , in which 112 subjects with hypertriglyceridemia were r and omly divided into two dietary oil groups : ( 1 ) long-chain triacylglycerol ( LCT ) and ( 2 ) MLCT . All subjects were requested to ingest fixed energy and to continue their normal activity levels , and to consume LCT or MLCT oil at 25–30 g daily during the study period . Anthropometric measurements of body weight , body mass index ( BMI ) , body fat , body fat percentage , waist and hip circumference ( WC and HC ) , areas of subcutaneous and visceral fat by computed tomography scanning and blood biochemical markers were measured at the beginning and end of the study . Results : There were 50 and 51 subjects left in LCT and MLCT groups , respectively . There were no significant differences in daily intake of energy , protein , fat and carbohydrate , as well as the daily physical activity between the two groups during the study . After 8 weeks , MLCT group showed a significant decrease in body weight , BMI , WC , HC , ratio of WC and HC , body fat , body fat percentage and subcutaneous fat when compared with the initial values . The decrease in body weight , BMI , WC , body fat and subcutaneous and visceral fat was significantly greater in MLCT group than that in the LCT group . Furthermore , the serum concentrations of TG in MLCT group were significantly lower than those in the LCT group . Conclusions : Consumption of MLCT may reduce body weight , body fat and blood TG in hypertriglyceridemic subjects under an appropriate dietary regime",
"We investigated whether a structured medium- and long-chain triacylglycerols ( MLCT ) diet could decrease accumulation of body fat in healthy humans . The study was conducted under a double-blind r and omized design . Ninety-three subjects participated in this study . However , 10 subjects could not consume the specified meal , and one subject wished to opt out . Consequently , the study included 82 subjects . The experimental subjects consumed the test bread , which was made with 14 g of MLCT containing 1.7 g MCFA , daily at breakfast during the study period of 12 weeks , and the control subjects consumed bread made with long-chain triacylglycerols ( LCT ) . All subjects consumed the same st and ard packaged meals . Body composition parameters were body weight , total body fat and abdominal fat , and blood analyses included serum cholesterol , triacylglycerols and phospholipids . Significant decreases of body weight , the amount of body fat , subcutaneous and visceral fat were noted in the MLCT group as compared with those of the LCT group for 12 weeks ( P serum total cholesterol was noted in the MLCT group as compared with that of the LCT group at 8 weeks ( P serum parameters were not different between the MLCT and LCT groups . The results suggest that the daily intake of MLCT diet could result in a reduction in body weight and in accumulation of body fat , and , moreover , it could reduce serum total cholesterol",
"The effects of dietary supplementation with coconut oil on the biochemical and anthropometric profiles of women presenting waist circumferences ( WC ) > 88 cm ( abdominal obesity ) were investigated . The r and omised , double-blind , clinical trial involved 40 women aged 20–40 years . Groups received daily dietary supplements comprising 30 mL of either soy bean oil ( group S ; n = 20 ) or coconut oil ( group C ; n = 20 ) over a 12-week period , during which all subjects were instructed to follow a balanced hypocaloric diet and to walk for 50 min per day . Data were collected 1 week before ( T1 ) and 1 week after ( T2 ) dietary intervention . Energy intake and amount of carbohydrate ingested by both groups diminished over the trial , whereas the consumption of protein and fibre increased and lipid ingestion remained unchanged . At T1 there were no differences in biochemical or anthropometric characteristics between the groups , whereas at T2 group C presented a higher level of HDL ( 48.7 ± 2.4 vs. 45.00 ± 5.6 ; P = 0.01 ) and a lower LDL : HDL ratio ( 2.41 ± 0.8 vs. 3.1 ± 0.8 ; P = 0.04 ) . Reductions in BMI were observed in both groups at T2 ( P reduction in WC ( P = 0.005 ) . Group S presented an increase ( P 0.05 ) in total cholesterol , LDL and LDL : HDL ratio , whilst HDL diminished ( P = 0.03 ) . Such alterations were not observed in group C. It appears that dietetic supplementation with coconut oil does not cause dyslipidemia and seems to promote a reduction in abdominal obesity ",
"BACKGROUND Dietary fatty acids that are more prone to oxidation than to storage may be less likely to lead to obesity . OBJECTIVE The aim of this study was to determine the effect of chain length , degree of unsaturation , and stereoisomeric effects of unsaturation on the oxidation of individual fatty acids in normal-weight men . DESIGN Fatty acid oxidation was examined in men consuming a weight-maintenance diet containing 40 % of energy as fat . After consuming the diet for 1 wk , subjects were fed fatty acids labeled with (13)C in the methyl or carboxyl position ( 10 mg/kg body wt ) . The fatty acids fed in r and om order were laurate , palmitate , stearate , oleate , elai date ( the trans isomer of oleate ) , linoleate , and linolenate blended in a hot liquid meal . Breath sample s were collected for the next 9 h and the oxidation of each fatty acid was assessed by examining liberated (13)CO(2 ) in breath . RESULTS Cumulative oxidation over the 9-h test ranged from a high of 41 % of the dose for laurate to a low of 13 % of the dose for stearate . Of the 18-carbon fatty acids , linolenate was the most highly oxidized and linoleate appeared to be somewhat conserved . (13)C recovery in breath from the methyl-labeled fatty acids was approximately 30 % less than that from the carboxyl-labeled fatty acids . CONCLUSIONS In summary , lauric acid is highly oxidized , whereas the polyunsaturated and monounsaturated fatty acids are fairly well oxidized . Oxidation of the long-chain , saturated fatty acids decreases with increasing carbon number",
"In contrast to the consumption of long-chain triacylglycerols ( LCT ) , consumption of medium- and long-chain triacylglycerols ( MLCT ) reduces the body fat and blood triacylglycerols ( TAG ) level in hypertriacylglycerolemic Chinese individuals . These responses may be affected by BMI because of obesity-induced insulin resistance . We aim ed to compare the effects of consuming MLCT or LCT on reducing body fat and blood TAG level in hypertriacylglycerolemic Chinese subjects with different ranges of BMI . Employing a double-blind , r and omized and controlled protocol , 101 hypertriacylglycerolemic subjects ( including 67 men and 34 women ) were r and omly allocated to ingest 25–30 g/day MLCT or LCT oil as the only cooking oil for 8 consecutive weeks . Anthropometric measurements of body weight , BMI , body fat , WC , HC , blood biochemical variables , and subcutaneous fat area and visceral fat area in the abdomen were measured at week 0 and 8 . As compared to subjects with BMI 24–28 kg/m2 in the LCT group , corresponding subjects in the MLCT group showed significantly greater decrease in body weight , BMI , body fat , WC , ratio of WC to HC , total fat area and subcutaneous fat area in the abdomen , as well as blood TAG and LDL-C levels at week 8 . Based upon our results , consumption of MLCT oil may reduce body weight , body fat , and blood TAG and LDL-C levels in overweight hypertriacylglycerolemic Chinese subjects but may not induce these changes in normal or obese hypertriacylglycerolemic subjects",
"We investigated the effect of long-term ingestion of dietary medium-chain triacylglycerols ( MCT ) on body weight and fat in humans . Using a double-blind , controlled protocol , we assessed the potential health benefits of MCT compared with long-chain triacylglycerols ( LCT ) in 78 healthy men and women [ body mass index ( BMI ) > or = 23 kg/m(2 ) : n = 26 ( MCT ) , n = 30 ( LCT ) ; BMI Changes in anthropometric variables , body weight and body fat during the 12-wk MCT treatment period were compared with those in subjects consuming the LCT diet . The subjects were asked to consume 9218 kJ/d and 60 g/d of total fat . The energy , fat , protein and carbohydrate intakes did not differ significantly between the groups . Body weight and body fat in both groups had decreased by wk 4 , 8 and 12 of the study . However , in the subjects with BMI > or = 23 kg/m(2 ) , the extent of the decrease in body weight was significantly greater in the MCT group than in the LCT group . In subjects with BMI > or = 23 kg/m(2 ) , the loss of body fat in the MCT group ( -3.86 + /- 0.3 kg ) was significantly greater than that in the LCT group ( -2.75 + /- 0.2 kg ) at 8 wk . In addition , in subjects with BMI > or = 23 kg/m(2 ) , the decrease in the area of subcutaneous fat in the MCT group was significantly greater than that in the LCT group at wk 4 , 8 and 12 . These results suggest that the MCT diet may reduce body weight and fat in individuals ( BMI > or = 23 kg/m(2 ) ) more than the LCT diet",
"Medium-chain triglycerides ( MCT ) have been proposed as weight-lowering agents , although there is some concern regarding their hyperlipidemic effect . This study evaluates the effects of a combination of MCT oil , phytosterols and flaxseed oil [ functional oil ( FctO ) ] on plasma lipid concentrations and LDL particle size . Twenty-four healthy overweight men ( body mass index 28.2 + /- 0.4 kg/m(2 ) ) consumed controlled diets design ed to maintain weight for two periods of 29 d each . Diets contained 40 % of energy as fat , 75 % of which was added fat , either FctO or olive oil ( OL ) . Body composition and blood sample s were analyzed at the baseline and the endpoint of each period . Total cholesterol concentration decreased 12.5 % ( -0.68 mmol/L ; P FctO and 4.7 % when they consumed OL . Similarly , FctO consumption lowered LDL cholesterol concentrations by 13.9 % , whereas OL consumption did not . There was no difference in absolute change in LDL-cholesterol between FctO and OL consumption . Peak LDL particle size was greater in those who consumed FctO than in those who consumed OL ( P FctO have a better lipid profile than those who consume a diet rich in OL , which also leads to a larger lipoprotein particle size . Functional oil consumption can therefore help reduce the risk of cardiovascular disease",
"Although medium-chain triacylglycerols ( MCTs , composed of medium-chain fatty acids 8:0 and 10:0 ) have long been described as having neutral effects on serum cholesterol concentrations , experimental evidence supporting this cl aim is limited . In a r and omized , crossover , metabolic-ward study , we compared the lipid effects of a natural food diet supplemented with either MCTs , palm oil , or high oleic acid sunflower oil in nine middle-aged men with mild hypercholesterolemia . Rather than having a neutral effect , MCT oil produced total cholesterol concentrations that were not significantly different from those produced by palm oil ( MCT oil : 5.87 + /- 0.75 mmol/L ; palm oil : 5.79 + /- 0.72 mmol/L ) but significantly higher than that produced by high oleic acid sunflower oil ( 5.22 + /- 0.52 mmol/L ) . Low-density-lipoprotein (LDL)-cholesterol concentrations paralleled those of total cholesterol . MCT oil tended to result in higher triacylglycerol concentrations than either palm oil or high oleic acid sunflower oil , but this difference was not significant . There were no differences in high-density-lipoprotein cholesterol concentrations . The palmitic acid and total saturated fatty acid content of plasma triacylglycerols in the MCT-oil diet was not significantly different from that in the palm oil diet . On the basis of percentage of energy , this study suggests that medium-chain fatty acids have one-half the potency that palmitic acid has at raising total and LDL-cholesterol concentrations",
"BACKGROUND Different dietary fats are metabolized differently in humans and may influence energy expenditure , substrate oxidation , appetite regulation , and body weight regulation . OBJECTIVE We examined the short-term effects of 4 triacylglycerols ( test fats ) on subjective appetite , ad libitum energy intake , meal-induced thermogenesis , and postpr and ial substrate oxidation . DESIGN Eleven healthy , normal-weight men ( mean age : 25.1 + /- 0.5 y ) consumed 4 different test fats [ conventional fat ( rapeseed oil ) and 3 modified fats ( lipase-structured fat , chemically structured fat , and physically mixed fat ) ] in a r and omized , double-blind , crossover design . RESULTS No significant differences in appetite sensations or ad libitum energy intakes were observed between the 4 test fats . Overall , the 4 fats exerted different effects on energy expenditure ( meal effect : P substrate oxidation ( interaction between meal and time : P postpr and ial energy expenditure and fat oxidation than did the conventional fat ( P short-term postpr and ial appetite sensations or ad libitum energy intakes but do result in higher postpr and ial energy expenditure and fat oxidation than do conventional fats and hence promote negative energy and fat balance . In humans , a physically mixed fat ( trioctanoate + rapeseed oil ) is metabolized as quickly as are structured fats . The position of medium-chain fatty acids on the glycerol backbone of triacylglycerols does not seem to affect energy expenditure or appetite",
"A r and omised crossover study of eight overweight or obese men ( aged 24 - 49 years , BMI 25.5 - 31.3 kg/m(2 ) ) , who followed two diets for 4 weeks each , was performed to determine whether substitution of saturated fat with monounsaturated fat affects body weight and composition . Subjects were provided with all food and beverages as modules ( selected ad libitum ) of constant macronutrient composition , but differing energy content . The % total energy from saturated fat , monounsaturated fat and polyunsaturated fat was 24 , 13 and 3 % respectively on the saturated fatty acid (SFA)-rich diet and 11 , 22 and 7 % respectively on the monounsaturated fatty acid (MUFA)-rich diet . MUFA accounted for about 80 % of the unsaturated fats consumed on both diets . Body composition , blood pressure , energy expenditure ( resting and postpr and ial metabolic rates , substrate oxidation rate , physical activity ) , serum lipids , the fatty acid profile of serum cholesteryl esters and plasma glucose and insulin concentrations were measured before and after each diet period . Significant ( P total cholesterol and the fatty acid composition of serum cholesteryl esters provided evidence of dietary adherence . The men had a lower weight ( -2.1 ( SE 0.4 ) kg , P=0.0015 ) and fat mass ( -2.6 ( SE 0.6 ) kg , P=0.0034 ) at the end of the MUFA-rich diet as compared with values at the end of the SFA-rich diet . No significant differences were detected in energy or fat intake , energy expenditure , substrate oxidation rates or self-reported physical activity . Substituting dietary saturated with unsaturated fat , predominantly MUFA , can induce a small but significant loss of body weight and fat mass without a significant change in total energy or fat intake",
"BACKGROUND : Medium chain triglycerides ( MCT ) are energetically less dense , highly ketogenic , and more easily oxidised than long chain triglycerides ( LCT ) . MCT also differ from LCT in their digestive and metabolic pathways . OBJECTIVE : To test the effects of MCT supplementation during a very low calorie diet (VLCD).SUBJECTS AND METHODS : Three groups of tightly matched obese women with body mass index ( BMI ) > 30 kg/m2 received an isoenergetic ( 578.5 kcal ) VLCD ( Adinax ® , Novo Vital , Sweden ) enriched with MCT or LCT ( 8.0 and 9.9 g/100 g Adinax ® respectively ) or a low-fat ( 3 g/100 g ) and high-carbohydrate regimen . The diets were administered over 4 weeks . Body composition was measured with DEXA and appetite/satiety-according to Blundell . Beta hydroxybutyric acid concentration in plasma and nitrogen excretion in urine was measured during consecutive days of VLCD . The study was performed in a r and omised double-blind manner . RESULTS : The MCT group showed a significantly greater decrease in body weight during the first 2 weeks . The contribution of body fat to the total weight loss was higher while the contribution of fat-free mass ( FFM ) was lower . The MCT group had a higher concentration of ketone bodies in plasma and a lower nitrogen excretion in urine . Hunger feelings were less intense while satiety was higher . These differences were observed during the first 2 weeks of treatment and gradually declined during the third and fourth weeks . CONCLUSIONS : Replacement of LCT by MCT in the VLCD increased the rate of decrease of body fat and body weight and has a sparing effect on FFM . The intensity of hunger feelings was lower and paralleled the higher increase of ketone bodies . These effects gradually declined , indicating subsequent metabolic adaptation . Further studies are required to confirm the protein-sparing and appetite-suppressing effects of MCT supplementation during the first 2 weeks of VLCD treatment",
"OBJECTIVE : To determine the effects of long-term consumption of medium chain ( MCT ) versus long chain triglycerides ( LCT ) on energy expenditure ( EE ) , substrate oxidation and body composition . HYPOTHESIS : MCT consumption will not result in greater EE , substrate oxidation , and body weight loss compared with LCT consumption . RESEARCH METHODS AND PROCEDURES : Seventeen healthy obese women participated in this r and omized , crossover inpatient trial . Meals were prepared and consumed on site for two periods of 27 days . Diets containing 40 % of energy as fat , with treatment fat comprising 75 % of the total fat , were design ed to supply each subject with their individual weight-maintaining energy needs . The MCT diet contained 67 % of treatment fat as MCT oil ( 49 % octanoate , 50 % decanoate ) whereas the LCT diet contained exclusively beef tallow as treatment fat . Body composition was assessed by magnetic resonance imaging ( MRI ) on day 1 and 28 of each phase while energy expenditure was measured on day 2 and 27 . RESULTS : Changes in total and subcutaneous adipose tissue volumes following consumption of MCT and LCT were not different ( −0.61±0.38 l vs −0.54±0.48 l and −0.58±0.35 l vs −0.48±0.40 l , respectively ) . Average EE and fat oxidation were greater ( P during MCT than LCT consumption ( 0.95±0.019 vs 0.90±0.024 kcal/min , respectively , for EE and 0.080±0.0026 vs 0.075±0.0022 g/min , respectively for fat oxidation ) . DISCUSSION : These results show that long-term consumption of MCT enhances EE and fat oxidation in obese women , when compared to LCT consumption . The difference in body composition change between MCT and LCT consumption , although not statistically different , was consistent with differences predicted by the shifts in EE . It can be concluded that substitution of MCT for LCT in a targeted energy balance diet may prevent long-term weight gain via increased EE",
"We found previously that the ingestion of margarine containing medium-chain triacylglycerols ( MCT ) result ed in a significant increase in postpr and ial thermogenesis when compared with long-chain triacylglycerols ( LCT ) . Diets that included margarine containing MCT and LCT were compared for 12 weeks in 73 subjects to investigate the effects on body weight , body fat , areas of subcutaneous and visceral fat , serum total cholesterols , triglycerides , lipoproteins , plasma glucose , serum insulin , total ketone bodies , and the activities of aspartate aminotransferase , alanine aminotransferase , and gamma-glutamyltranspeptidase . We conducted a double-blind , controlled study and used blended rapeseed oil and soybean oil ( LCT ) as a comparison . Two groups ingested 2100 - 2400 kcal/day of energy , 65 - 73 g/day of total fat , and 14 g/day of test margarine ( 5 g/day of MCT or LCT ) . The subjects on the MCT diet demonstrated significant decreases in body fat weight ( - 3.8 + /- 2.4 kg vs - 2.4 + /- 1.7 kg ; MCT vs LCT , mean + /- SD ) , subcutaneous fat ( - 38.2 + /- 29.9 cm(2 ) vs - 22.6 + /- 19.3 cm(2 ) ) , and visceral fat ( - 12.2 + /- 11.2 cm(2 ) vs - 1.6 + /- 12.8 cm(2 ) ) after 12 weeks . There were no clinical differences in measured blood parameters . We suggest that the postpr and ial increase in thermogenesis and control of postpr and ial triglyceride levels may explain these results",
"Prior studies of medium-chain triglyceride ( MCT ) suggest that MCT might be a useful tool for body fat mass management in obese nondiabetic humans . We now report a pilot study that tests if MCT is beneficial for moderately overweight subjects with type 2 diabetes mellitus . The study was conducted in a group of 40 free-living subjects in an urban area of China . The subjects were r and omized into 2 test groups , with one given MCT and the other corn oil as control for long-chain triglycerides ( LCTs ) . The test oil ( 18 g/d ) was administered as part of daily food intake for 90 days . All subjects completed the study with self-reported full compliance . Body weight , waist circumference ( WC ) , and serum sample s were analyzed on days 0 , 45 , and 90 . The MCT group showed an across-time reduction in body weight and WC , an increase in serum C-peptide concentration , a reduction in homeostasis model assessment of insulin resistance , and a decrease in serum cholesterol concentration ( P No significant across-time difference for the above parameters was detected for the LCT group . These changes were associated with an involuntary reduction in energy intake in the MCT group ( P reduced body weight , WC , and homeostasis model assessment of insulin resistance in the MCT group compared with the LCT group at the end of the study . Collectively , our results suggest a link between moderate consumption of MCT and improved risk factors in moderately overweight humans in a low-cost , free-living setting",
"In this study we investigated the effects on lipoproteins of medium chain fatty acids ( MCFA ) and myristic acid relative to those of oleic acid . Thirty-seven women and 23 men consumed a 3-wk run-in diet enriched in oleic acid followed by a 6-wk test diet rich in MCFA ( n = 21 ) , myristic ( n = 20 ) , or oleic acid ( n = 19 ) . Experimental fats were incorporated into solid foods . Total fat intake was 40 En% fat . The dietary compositions were the same except for 10 En% , which was provided by MCFA , myristic , or oleic acids , respectively . With the myristic acid diet , low density lipoprotein ( LDL ) cholesterol was 0.37 mmol/L higher compared with the oleic acid diet ( P = 0.0064 for difference in changes ) . The MCFA diet increased LDL cholesterol , though not significantly , with 0.23 mmol/L relative to the oleic acid diet ( P = 0.0752 ) . Compared with the oleic acid diet , HDL cholesterol concentrations increased with the myristic acid diet by 0.10 mmol/L ( P = 0.0273 ) but not with the MCFA diet . The MCFA diet slightly elevated triacylglycerol concentrations , but responses did not significantly differ between the diets . The MCFA diet significantly decreased the apoA-I to apoB ratio compared with both other diets ( P LDL cholesterol concentrations slightly and affect the apoA-I to apoB ratio unfavorably compared with oleic acid . Myristic acid is hypercholesterolemic , although less than predicted earlier , and raises both LDL and HDL cholesterol concentrations compared with oleic acid",
"Medium chain triacylglycerols ( MCT ) have been suggested as efficacious in weight management because they possess greater thermogenic qualities relative to long chain triacylglycerols ; however , MCT may also increase circulating lipid concentrations , possibly increasing risk of cardiovascular disease ( CVD ) . The present objective was to examine the effect of a diet supplemented with a functional oil ( FctO ) composed of energy expenditure-enhancing MCT ( 50 % of fat ) , cholesterol-lowering phytosterols ( 22 mg/kg body weight ) , and triacylglycerol-suppressing n-3 fatty acids ( 5 % of fat ) , versus a beef tallow-based diet ( BT ) , on plasma lipid and aminothiol concentrations . In a r and omized , single-blind , crossover design , partially-inpatient trial , 17 overweight women consumed each oil as part of a controlled , supervised , targeted energy balance diet for 27 days , with 4 or 8 weeks of washout between phases . Mean plasma total cholesterol concentration was lower ( P Mean plasma low-density lipoprotein ( LDL ) cholesterol was also lower ( P High-density lipoprotein ( HDL ) cholesterol and circulating triacylglycerol concentrations remained unaffected by treatment . Ratios of HDL : LDL and HDL : total cholesterol were higher ( P Plasma total homocysteine remained unchanged with FctO , but decreased ( P FctO ( 6.95 + /- 0.33 micromol/L ) versus BT ( 6.27 + /- 0.28 micromol/L ) . Plasma glutathione increased ( P homocysteine levels , consumption of a functional oil composed of MCT , phytosterols , and n-3 fatty acids for 27 days improves the overall cardiovascular risk profile of overweight women",
"Although medium chain triglyceride ( MCT ) is less calorically dense than long chain triglyceride ( LCT ) , it produces a greater thermic effect following ingestion . We hypothesized that the previously observed high rate of thermogenesis produced by MCT overfeeding was due to hepatic de novo synthesis of long chain fatty acids ( LCFA ) from the excess medium chain fatty acids ( MCFA ) . To study this , we compared the effects of overfeeding MCT- and LCT-containing diets on blood lipid profiles . Ten in-patient , nonobese males were overfed ( 150 % of estimated energy requirements ) two formula diets for 6 days each , in a r and omized crossover design . Diets differed only in the composition of the fat and contained either 40 % of energy as MCT or LCT ( soybean oil ) . The major differences between diets in the result ing pattern of blood lipids were : 1 ) a reduction in fasting serum total cholesterol concentrations with the LCT , but not the MCT diet ; and 2 ) a threefold increase in fasting serum triglyceride concentrations with MCT , but not LCT , diet . Moreover , 10 % of the fasting triglyceride fatty acids were medium chain and 40 % were 16:0 with the MCT diet . This compared to 1 % and 20 % for medium chain and 16:0 , respectively , with the LCT diet . In addition , there were increases in 16:1 , 18:0 , and 18:1 in the triglycerides during MCT feeding . The changes in fatty acids in triglycerides with MCT feeding are consistent with the hypothesis that excess dietary MCT cause a significant increase in the hepatic synthesis of these fatty acids from MCFA through de novo synthesis and /or chain elongation and desaturation . These processes could account for the higher rate of postpr and ial thermogenesis with MCT as compared to LCT",
"OBJECTIVE : Medium-chain triglyceride ( MCT ) consumption has been shown to increase energy expenditure ( EE ) and lead to greater losses of the adipose tissue in animals and humans . The objective of this research was to examine the relationship between body composition and thermogenic responsiveness to MCT treatment . DESIGN : R and omized , crossover , controlled feeding trial , with diets rich in either MCT or long-chain triglyceride ( LCT ) ( as olive oil ) for periods of 4 weeks each . SUBJECTS : A total of 19 healthy overweight men aged ( x±s.e.m . ) 44.5±2.5 y with a body mass index of 27.8±0.5 kg/m2 . MEASUREMENTS : EE and body composition were measured using indirect calorimetry and magnetic resonance imaging , respectively , at the baseline and end point of each feeding period . EE was measured for 30 min before consumption of a st and ard meal and for 5.5 h following the meal . RESULTS : Body weight ( BW ) decreased ( P in average EE between MCT and LCT consumptions was related to initial BW , such that men with lower initial BW had a greater rise in EE with MCT consumption relative to LCT on day 28 ( r=−0.472 , P=0.04 ) but not day 2 ( r=−0.368 , P=0.12 ) . Similar results were obtained with fat oxidation on day 28 ( r=−0.553 , P=0.01 ) . The greater rise in fat oxidation with MCT compared to LCT consumption on day 2 tended to be related to greater loss of BW after MCT vs LCT consumption ( r=−0.4075 , P=0.08 ) . CONCLUSION : These data suggest that shunting of dietary fat towards oxidation results in diminished fat storage , as reflected by the loss of BW and subcutaneous adipose tissue . Furthermore , MCT consumption may stimulate EE and fat oxidation to a lower extent in men of greater BW compared to men of lower BW , indicative of the lower responsiveness to a rapidly oxidized fat by overweight men",
"BACKGROUND Medium chain triglycerides ( MCT ) have been suggested as modulators of human energy expenditure ( EE ) and thus may influence total and regional body fat distribution . OBJECTIVE To investigate in overweight men the effects of structured medium and long chain triglycerides on EE , substrate oxidation and body adiposity , compared to extra virgin olive oil ( OO ) . METHODS In a 6 week single-blind crossover study , 23 overweight men were r and omly assigned to consume a st and ard high-fat diet of which 75 % total fat was provided as either structured medium and long chain triglycerides referred to as structured oil ( StO ) , or OO . EE and body composition were measured using indirect calorimetry and magnetic resonance imaging , respectively , at weeks 1 and 6 of each phase . RESULTS Body weight decreased ( p body composition among treatment groups . No differences between diets for EE measurements were reported . Fat oxidation rates did not differ between oils , but were reduced ( p carbohydrate oxidation rate were noted across diets or time . CONCLUSION The present structured medium and long chain triglyceride oil increases short-term fat oxidation but fails to modulate body weight or adiposity through a change in EE",
"High-fat diets are associated with obesity , and the weak satiety response elicited in response to dietary lipids is likely to play a role . Preliminary evidence from studies of medium ( MCT ) and long chain triglycerides ( LCT ) supports greater appetite suppression on high-MCT diets , possibly a consequence of direct portal access , more rapid oxidation and muted lipaemia . No data is as yet available on high-SCT diets which also have direct hepatic access . In this study SCT- ( dairy fats ) , MCT- ( coconut oil ) and LCT-enriched ( beef tallow ) test breakfasts ( 3.3 MJ ) containing 52 g lipid ( 58 en% fat ) were investigated in a r and omized , cross-over study in 18 lean men . All participants were required to complete the 3 study days in r and omised order . Participants rated appetite sensations using visual analogue scales ( VAS ) , and energy intake ( EI ) was measured by covert weighing of an ad libitum lunch meal 3.5 h postpr and ially . Blood sample s were collected by venous cannulation . There were no detectable differences between breakfasts in perceived pleasantness , visual appearance , smell , taste , aftertaste and palatability ( P>0.05 ) . There was no significant effect of fatty acid chain length on ratings of hunger , fullness , satisfaction or current thoughts of food , nor did energy ( mean , sem : SCT : 4406 , 366 kJ ; MCT : 4422 , 306 kJ ; LCT : 4490 , 324 kJ ; P>0.05 ) or macronutrient intake at lunch differ between diets . The maximum difference in EI between diets was less than 2 % . Postpr and ial lipaemia also did not differ significantly . We conclude that there was no evidence that fatty acid chain length has an effect on measures of appetite and food intake when assessed following a single high-fat test meal in lean participants",
"BACKGROUND Treatment of obesity with strict reducing diets is as a rule associated with the development of energetic efficiency manifested among others also by a decline of energy expenditure . The objective of the trial was to test whether addition of oils containing triacylglycerols with medium-chain fatty acid can prevent this decline and whether their administration can affect the lipid spectrum . METHODS AND RESULTS Sixty obese patients were served for a four-week period of hospitalization at the obesitology unit a low-energy diet REDITA ( Promil Co. , N. Bydzov ) providing 1596 kJ , 37 g protein , 50 g carbohydrate and 3 g fat . Part of the treatment was regular aerobic exercise , behavioural therapy to teach correct dietary habits and physical activity ; physical activity was monitored by means of pedometers . From this group during the 3rd and 4th week 11 patients with similar characteristics were separated ( age , body weight , BMI and energy expenditure at rest ) as in the basic group . These patients were given daily 15 ml oil containing triacylglycerols with medium-chain fatty acids , MCT OIL ( Mead Johnson , Evansville ) , providing 545 kJ. The resting energy expenditure was assessed in all patients every morning on fasting , immediately after awakening , using indirect calorimetry and it was corrected with regard to the respiratory quotient and excretion of catabolic nitrogen . The body composition was assessed at the beginning and at the end of the trial by hydrostatic weighing . Administration of oil containing triacylglycerols with medium-chain fatty acids ( MCT OIL ) prevented the decline of the resting energy expenditure ( 130.0 + /- 9.2 kJ/kg lean body mass/day , as compared with 126.5 + /- 7.2 kJ/kg lean body mass/day in the basic group : the difference is statistically not significant ) . Although addition of oil increased the energy intake by 545 kJ/day , the drop of body weight and BMI was comparable with that in the group of obese patients who did not receive the oil ( 10.3 + /- 1.1 kg vs. 10.6 + /- 0.5 kg ) . While during administration of the oil the resting energy expenditure did not change ( 5.97 + /- 0.30 kJ/min . vs. 5.24 + /- 0.58 kJ/min . ) , in obese patients who were only on the strict reducing diet it declined from 5.45 + /- 0.18 kJ/min . to 4.44 + /- 0.22 kJ/min . ( p total cholesterol achieved by dietotherapy alone ( 5.41 + /- 0.21 mmol/l vs. 6.26 0.20 mmol/l before treatment ) was not affected by administration of oil ( 4.86 + /- 0.28 mmol/l vs. 5.69 + /- 0.35 mmol/l before treatment ) . HDL-cholesterol , on the other h and , declined only in obese patients with dietotherapy ( 1.40 + /- 0.04 mmol/vs . 1.22 + /- 0.04 mmol/l after treatment , p triacylglycerol values declined significantly in both groups ( p diet-induced energetic efficiency and can improve the long-term success of dietotherapy of obese patients",
"OBJECTIVE To determine whether medium-chain triglycerides , in low-to-moderate amounts consumed with meals ( at breakfast , lunch and dinner ) , can increase daily energy expenditure ( EE ) and 24-h urinary excretion of catecholamines in humans . DESIGN Dose-response study conducted under double-blind r and omised design . SETTING Respiratory chamber at the Faculty of Medicine , University of Geneva . SUBJECTS Eight healthy young men were recruited from the student population by advertisement in our Faculty . METHODS 24-h EE and urinary catecholamines were measured in each subject during stay in a respiratory chamber on four separate occasions . These were r and omised between four different combinations of medium-chain triglycerides ( MCT ) and long-chain triglycerides ( LCT ) , a total 30g/day , which was consumed with their habitual diet in three equal parts ( 10 g each ) at breakfast , lunch , and dinner in the following ratio of MCT : LCT ( g/g ) 0:30 , 5:25 , 15:15 and 30:0 . RESULTS 24-h EE increased significantly with increasing MCT : LCT ratio ( ANOVA , P EE by 5 % : this corresponds to a mean absolute increase in daily EE of approximately 500kJ , with individual values varying between 268 kJ and 756 kJ. No significant differences were observed in respiratory quotient nor in urinary nitrogen losses across diets , but 24-h urinary noradrenaline was significantly increased ( ANOVA , P adrenaline and dopamine were unaltered . CONCLUSIONS This study suggests that relatively low-to-moderate intake of MCT ( 15 - 30 g per day ) as part of habitual diet may play a role in the control of human body composition by enhancing daily EE , and that this effect is mediated at least in part through activation of the sympathetic nervous system",
"Phytosterols ( PSs ) have been recently added to various mediums . Nevertheless , matrices with functional properties , such as medium-chain triglycerides ( MCTs ) , should be precisely examined for supplementary advantages . The objective of this study was to identify the existence of combined biological actions of a functional oil enriched in PSs within MCTs and high-oleic canola ( HOC ) , relative to a control ( olive oil ) , in overweight , hyperlipidemic men using a rigorously controlled dietary intervention . Twenty-three overweight , hyperlipidemic men consumed both types of oil in a r and omized , crossover trial for 6 weeks each . Fasted plasma sample s were collected on the first and last 2 days of each study period . Body weight decreased -1.22 + /- 0.35 kg ( P = .0019 ) and -1.68 + /- 0.47 kg ( P = .0016 ) after the 6-week study period in the olive oil and functional oil groups , respectively . The end points for total cholesterol and low-density lipoprotein cholesterol ( LDL-C ) in the functional oil group ( P = .0006 ) were lower than in the olive oil group ( P = .0002 ) . Total cholesterol values decreased from comparable baseline to end point of 4.71 + /- 0.16 mmol/L ( P LDL-C demonstrated a similar drop , to an end point of 3.12 + /- 0.16 mmol/L ( P High-density lipoprotein cholesterol levels did not change in either treatment . Triacylglycerol end points decreased in functional oil and olive oil groups ( P = .0195 and .0105 , respectively ) to the same extent from baseline . Results indicate that PSs mixed within an MCT- and HOC-rich matrix lower plasma LDL-C , without significantly changing the high-density lipoprotein cholesterol concentrations , in hyperlipidemic , overweight men , and may therefore decrease the risk of cardiovascular events",
"Objective : To compare postpr and ial whole-body fat oxidation rates in humans , following high-fat ( 43 % of total energy ) mixed breakfast meals , of fixed energy and macronutrient composition , rich in either monounsaturated fat ( MUFA ) from extra virgin olive oil or saturated fat ( SFA ) from cream . Design : Paired comparison of resting metabolic rate ( RMR ) , thermic effect of a meal and substrate oxidation rates following consumption of isocaloric breakfast meals , differing only in the type of fat , administered in r and om order 1–2 weeks apart . Subjects : Fourteen male volunteers , body mass index ( BMI ) in the range 20–32 kg/m2 , aged 24–49 y and resident in Melbourne , Australia , were recruited by advertisement in the local media or by personal contact . Measurements : Body size and composition was determined by anthropometry and dual energy X-ray absorptiometry ( DEXA ) . Indirect calorimetry was used to measure RMR , thermic effect of a meal , post-meal total energy expenditure and substrate oxidation rate . Blood pressure and pulse rates were measured with an automated oscillometric system . Fasting and 2 h postpr and ial glucose and insulin concentrations and the fasting lipid profile were also determined . Results : In the 5 h following the MUFA breakfast , there was a significantly greater postpr and ial fat oxidation rate ( 3.08±4.58 g/5 h , P=0.017 ) , and lower postpr and ial carbohydrate oxidation rate ( P=0.025 ) , than after the SFA breakfast . Thermic effect of a meal was significantly higher ( 55 kJ/5 h , P=0.034 ) after the MUFA breakfast , in subjects with a high waist circumference ( HWC≥99 cm ) than those with a low waist circumference ( LWC following the SFA breakfast ( P=0.910 ) . Conclusion : If postpr and ial fat oxidation rates are higher after high MUFA , rather than SFA meals , then a simple change to the type of dietary fat consumed might have beneficial effects in curbing weight gain in men consuming a relatively high-fat diet . This may be particularly evident in men with a large waist circumference",
"Two groups of Chinese hypertriacylglycerolemic subjects were recruited and r and omized to medium- and long-chain triacylglycerols ( MLCT ) oil or long-chain triacylglycerols ( LCT ) oil . Two subgroups were divided by age at less or more 60 years in both groups . Both oils were consumed at 25–30 g daily for 8 weeks . Anthropometry , blood biochemicals , and computed tomography ( CT ) scanning were done at the initial and final times . In subjects of age less than 60 years on MLCT , the body weight , body mass index ( BMI ) , waist circumference ( WC ) , hip circumference ( HC ) , waist-hip ratio ( WHR ) , body fat , total fat area , and subcutaneous fat area were significantly lower than those of the initial values , and the change values in these indicators and visceral fat area lowered significantly as compared with those on LCT . The levels of apoB , apoA2 , apoC2 , and apoC3 decreased significantly , and the change in values in the levels of triglyceride ( TG ) , low-density lipoprotein cholesterol ( LDL-C ) , apoA1 , apoB , apoA2 , apoC2 , apoC3 were significantly lower on MLCT of age under 60 years as compared with those on LCT",
"The effects of a liquid-formula diet supplement containing structured medium- and long-chain triacylglycerols ( SMLCT ) composed of medium- ( 10 % ) and long-chain ( 90 % ) fatty acids were compared with those of long-chain triacylglycerols ( LCT ) on bodyfat accumulation in 13 healthy male volunteers aged 18 - 20 years . The subjects were r and omly assigned the SMLCT or LCT group . The subjects in each group received a liquid-formula diet supplement of the SMLCT or LCT , which provided 1040 kJ plus daily energy intake for 12 weeks . Mean energy intake containing liquid diet throughout the 12-week period did not differ between the SMLCT and LCT groups . Bodyweight of subjects in both groups increased slightly from the baseline throughout the 12-week period , but the differences were not significant . Rates of variation of bodyfat percentage were significantly lower in the SMLCT group than in the LCT group throughout the 12-week period . Comparisons between the SMLCT and LCT groups at baseline and 12 weeks showed no significant differences in any of the biochemical blood parameters . These results suggest that replacing LCT with SMLCT over long periods of time could produce bodyfat loss in the absence of reduced energy intake",
"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"
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The aim of this systematic review was to establish whether the clinical debonding ( failure ) rates of orthodontic brackets bonded either with resin-modified glass ionomer ( RM-GIC ) or with composite resin adhesive are the same . Five data bases were search ed for articles up to 18 November 2010 . Inclusion criteria were titles/ abstract s relevant to the review question and two or more arm clinical trial . Exclusion criteria were the following : no computable data recorded and subjects of both groups not followed up in the same way . From the accepted trials , data sets were analysed concerning clinical precision and internal validity . Eleven trials were accepted . From these , 15 dichotomous data sets were extracted . Relative risk with 95 % confidence interval of nine data sets showed no statistically significant differences in outcome between the treatment and control group after 6 months–1.32 years . Five showed a statistically significant difference ( p resin composite bonding after 12 and 18 months . One favoured RM-GIC after 10 months . Meta- analysis found no difference in the failure rate between the two treatment groups after 12 months ( RR , 1.11 ; 95 % CI , 0.87–1.42 ; p = 0.40 ) and found in favour of composite resin adhesive after > 14 months ( RR , 2.25 ; 95 % CI , 1.60–3.17 ; p internal validity due to selection and detection/performance bias risk . The current evidence suggests no difference between the types of material s after 12 months but favours composite resin adhesives after a > 14-month period . However , its risk of selection and detection/performance bias are high , and all results need to be regarded with caution . Further high quality r and omised control trials addressing this topic are needed . The clinical relevance of this study is that RM-GIC may have the same clinical debonding ( failure ) rate as composite resin adhesives after 1 year when used for bonding of orthodontic brackets
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"Glass ionomer orthodontic adhesives cause less enamel demineralization during fixed orthodontic appliance treatment than do traditional resin-based products . An in vivo r and omized clinical trial was performed comparing the clinical performance of a resin-modified glass ionomer ( RMGI ) adhesive with a no-mix , resin-based ( the control ) adhesive over a 12-month period . The split-mouth technique was used to analyze bracket retention , bracket failure causes , and mode of failure for both adhesives in 61 patients . Bracket-failure rates were 10 % for the RMGI and 4 % for the resin-based adhesive . Both adhesives had 4 times more bracket failures when opposing occlusion was present . The resin-based product demonstrated a higher proportion of resin-to-enamel adhesive failures than did the RMGI . Compared with the resin-based adhesive , the RMGI-bracketed teeth showed improved clinical performance , no enamel surface loss , less enamel demineralization , and faster adhesive removal . However , the RMGI had a 2.6 times greater bracket-failure rate than did the resin-based product ",
"OBJECTIVE Pumicing of the enamel prior to direct bonding with conventional diacrylate bonding agents has been shown to be unnecessary . It is not known whether this is also the case with resin-modified glass poly(alkenoate ) cements . The aims of this study were two-fold : ( a ) . to determine whether pumicing prior to bonding has an effect on the in vivo failure of brackets bonded with either Right-On or Fuji II LC ; ( b ) . to determine whether there is a difference in the in vivo failure of brackets bonded with either Right-On or Fuji II LC . Design A cross-mouth controlled clinical trial was performed on a total of 60 patients in which the variables under test were pumicing or not pumicing of the enamel prior to bonding using two different bonding agents . MAIN OUTCOME MEASURES The measurement variable was bond failure over an 18-month period . RESULTS AND CONCLUSIONS Prior pumicing of the enamel has no effect on in vivo failure when using either a conventional diacrylate or a resin modified glass poly(alkenoate ) cement . A greater number of bonds failed with the resin-modified glass poly(alkenoate ) cement",
"The objectives of this study were ( 1 ) to compare the in vivo survival rates of orthodontic brackets bonded with a resin-modified glass ionomer adhesive ( Fuji Ortho LC ; GC America , Alsip , Ill ) after conditioning with 10 % polyacrylic acid and a conventional resin adhesive ( Light Bond ; Reliance Orthodontic Products , Itasca , Ill ) bonded with 37 % phosphoric acid , ( 2 ) to compare the in vitro bond shear/peel bond strength between the 2 adhesives , ( 3 ) to determine the mode of bracket failure in the in vivo and in vitro tests according to the adhesive remnant index ( ARI ) , and ( 4 ) to compare the changes in surface morphology of enamel surface after etching or conditioning with 10 % polyacrylic acid , with scanning electron microscopy . In the in vitro study , 50 extracted premolars were r and omly divided into 4 groups : brackets bonded with Fuji Ortho LC or Light Bond adhesive that were debonded after either 30 minutes or 24 hours . Bond strengths were determined with a testing machine at a crosshead speed of 1 mm/min . Data were analyzed with analysis of variance and a paired Student t test . The in vivo study consisted of 398 teeth that were r and omly bonded with Fuji Ortho LC or Light Bond adhesive in 22 subjects with the split-mouth technique . Bracket survival rates and distribution were followed for 1.3 years . Data were analyzed with Kaplan-Meier product-limit estimates of survivorship function . The in vitro study results showed significant differences ( P debond times . Light Bond had significantly greater bond strengths than Fuji Ortho LC at 24 hours ( 18.46 + /- 2.95 MPa vs 9.56 + /- 1.85 MPa ) and 30 minutes ( 16.19 + /- 2.04 MPa vs 6.93 + /- 1.93 MPa ) . Mean ARI scores showed that Fuji Ortho LC had significantly greater incidences of enamel/adhesive failure than Light Bond adhesive ( 4.9 vs 4.1 ) . For the in vivo study , no significant differences in failure rate , sex , or location in dental arch or ARI ratings were found between the 2 adhesives . These results suggest that , compared with conventional resin , brackets bonded with resin-modified glass ionomer adhesive had significantly less shear bond strength in vitro . However , similar survival rates of the 2 material s studied after 1.3 years indicate that resin-reinforced glass ionomers can provide adequate bond strengths clinical ly . The weaker chemical bonding between the adhesive and the enamel might make it easier for clinicians to clean up adhesives on the enamel surface after debonding",
"The aim of this investigation was to compare the clinical performance of a glass ionomer cement ( GIC ) with a composite resin when used for direct bonding of st and ard edgewise orthodontic brackets . Fourteen patients ( 10 females , four males ) , in whom 242 teeth were bonded with brackets , were divided into two groups : GIC ( 121 teeth ) and composite ( 121 teeth ) . The brackets were allocated to alternate quadrants and first-time failures were recorded over a period of 24 months . Data were analysed statistically ( non-parametric chi-squared test ) . The results demonstrated a significantly lower unp review ed debonding index ( UDI ) ( 15.7 per cent ) for the composite than for the GIC ( 28.1 per cent ) ( P = 0.042 ) . The use of heavy archwires was largely responsible for this difference . No difference was observed when light and medium archwires were used . GIC may be a viable alternative to composite for use with light archwires and with limited treatment objectives",
"Decalcification during orthodontic treatment is a serious problem . A glass ionomer agent is now available to bond orthodontic brackets as an alternative to composite resins . This prospect i ve study was a clinical trial to determine if a glass ionomer bonding system ( Fuji Ortho LC ) decreases the incidence of decalcification without increasing the amount of bonding failures . A prospect i ve clinical trial with 16 patients encompassing a total of 298 teeth was conducted . The 149 control teeth were bonded with a light-cured composite resin ( Reliance Light Bond ) whereas the 149 experimental teeth were bonded with the light-cured glass ionomer agent . Patients were followed for a period of 12 to 14 months . All teeth were evaluated for breakage ( bonding failure rate ) , and all maxillary anterior teeth ( 96 ) were evaluated for decalcification on a grade d scale . The glass ionomer failure rate was 24.8 % , and was higher than the composite resin failure rate of 7.4 % ( P glass ionomer bond failures in 12 of 16 patients ( P Enamel decalcification was similar in the 2 bonding systems",
"The purpose s of this investigation were to compare the clinical performance of a resin-reinforced self-cured glass ionomer cement to a st and ard composite resin in the direct bonding of orthodontic brackets when bonded onto : a ) dry teeth and b ) teeth soaked with saliva . The two bonding agents were compared using a split-mouth design . In that , both systems were used for direct bonding of stainless steel brackets in every patient . Thirty-eight consecutive patients with fixed appliances were followed for a period of 12 months . The patients were r and omly divided into two groups : group A ( 11 patients ) and group B ( 27 patients ) . In group A , the performance of 220 stainless steel brackets was evaluated : 110 brackets were bonded with GC Fuji Ortho glass ionomer cement ( GC Industrial Co. , Tokyo , Japan ) onto dry teeth , and 110 bonded with System 1 + composite resin ( Ormco Corp. , Glendora , CA ) . In group B , the performance of 540 stainless steel brackets was evaluated : 270 brackets were bonded with GC Fuji Ortho onto teeth soaked with saliva , and 270 bonded with System 1 + . In group A , GC Fuji Ortho recorded an overall failure rate ( 34.5 % ) significantly higher ( p 0.05 ) between the failure rates of the two bonding agents were found when GC Fuji Ortho was used on teeth soaked with saliva . It was concluded , therefore , that GC Fuji Ortho shows clinical ly acceptable bond strengths when bonded onto moist teeth , but not when used on dry enamel . Both bonding agents failed mostly at the enamel/adhesive interface , without causing any enamel damage",
"The purpose of this study was to compare the clinical performance of a resin-reinforced self-cured glass ionomer cement to a st and ard composite resin in a split mouth design , by using both systems for direct bonding of orthodontic stainless steel brackets in every patient . Forty eight patients ( 34 females and 14 males , of which 29 were adults > 18 years of age ) with fixed appliances were followed for a mean period of 10 months ( range 4 - 16 months ) . The performance of 864 stainless steel brackets was evaluated : 404 brackets were bonded with GC Fuji Ortho glass ionomer cement ( GC Industrial , Tokyo , Japan ) onto teeth soaked with water , and 460 were bonded with System 1 + composite resin ( Ormco , Glendora , CA ) . System 1 + recorded an overall failure rate ( 18.2 % ) significantly higher ( p GC Fuji Ortho ( 7.9 % ) . There were no statistically significant differences ( p > 0.05 ) between the failure rates in the upper and lower arches with either material . Both in the upper and lower arches , System 1 + exhibited a failure rate significantly higher ( p GC Fuji Ortho . When the bonding performance of the six anterior teeth was compared with first and second premolars , no statistically significant differences were found ( p > 0.05 ) between bonding agents in either arch . System 1 + exhibited a failure rate significantly higher ( p GC Fuji Ortho , both in the anterior and posterior segments . Both bonding agents failed mainly at the enamel-adhesive interface , without causing any damage to the enamel",
"A new self-curing ( chemically cured ) resin-modified glass-ionomer cement , Fuji Ortho ( GC International ) , is based on the technology of hybrid glass-ionomer restorative material s and features chemical adhesion to tooth structure and long-term fluoride release . This article describes a 12-month clinical evaluation of Fuji Ortho for the direct bonding of orthodontic ( metal ) brackets with System 1 + ( Ormco Corp. ) as a control . Three failures of Fuji Ortho occurred from a sample of 60 ( 5 % ) , with five failures of the composite resin from a sample of 60 ( 8.3 % ) . No statistical significance was seen between these results . Fuji Ortho is a satisfactory adhesive for the direct bonding of orthodontic brackets where there are no occlusal interferences",
"The clinical performance of a glass ionomer cement for direct bonding of orthodontic brackets was compared with a composite resin routinely used in this procedure . Brackets were bonded , using both material s , in alternate quadrants of 16 patients of the Orthodontic Clinic of the State University of Rio de Janeiro . A total of 225 teeth , 112 in the glass ionomer cement group and 113 in the composite group , were tested . Bond failure frequencies were recorded for 12 months , and chi-square statistical test was carried out comparing the failure rates of the material s. The composite showed a statistically significant lower failure rate ( 7.96 % ) than the glass ionomer cement ( 50.89 % ) , regardless of the dental arch tested . Although the glass ionomer cement presents important properties not observed in the composite , it is necessary to increase its cohesive strength to permit its clinical use for direct bonding of orthodontic brackets",
"Since the last comprehensive review of anticoagulation in acute myocardial infa rct ion four additional r and omized control trials have been reported . The overwhelming majority of all trials favored anticoagulation . Rates of thromboembolism were higher in the control , and hemorrhagic complications in the anticoagulated group . Pooling of all r and omized control trials gives mean case fatality rates of 19.6 % for the control and 15.4 % for the anticoagulated group , a relative reduction of 21 % ( P less than 0.05 or less than 0.001 , depending on the analytic method ) . Five of six r and omized control trials reported \" no effect \" because the difference favoring anticoagulation was not statistically significant . However , sample sizes in these \" negative \" papers were too small to protect against missing a 21 % reduction in true case fatality rate due to anticoagulation ( beta greater than 0.10 ) . All patients who present no specific contraindication should receive anticoagulants during hospitalization for infa rct ion ",
" One hundred and twelve first molar b and s and 614 directly bonded brackets on incisor , canine , and premolar teeth were included in a clinical trail to investigate the importance of omission of pumice prophylaxis at the time of b and ing and bonding , on their possible subsequent failure . Half of the sample were selected for the non-pumiced test groups using a r and om number allocation method , the remaining pumiced teeth acting as control groups . Two etch times were used for the direct bonding part of the study , 15 and 60 seconds , with non-pumiced test and pumiced control groups included within both etch-time groups . Results showed no statistical difference in the failure rate of attachments in either test or control groups during the course of treatment . The different etch times had no significant effects in the direct bonding part of the study",
"The aim of this study was to investigate the in vivo bonding of orthodontic brackets using two resin-modified glass poly(alkenoate ) cements and to compare them with a conventional light-cured diacrylate bonding agent . Twenty consecutive patients attending for bond up appointments took part in this r and omized cross-mouth control study . Alternate quadrants were bonded with either Fuji Ortho LC or 3 M Multi-Cure . Transbond [ Adhesive Pre-Coated Brackets ( APC ) ] acted as the control in the other quadrants . Failed brackets were rebonded with the same material . Bond failure rates were collected over a 1-year period . The bond failure rates over 1 year were 7.2 per cent for Transbond ( APC ) , 5.9 per cent for 3 M Multi-Cure , and 5.8 per cent for Fuji Ortho LC . Statistically , there was no significant difference between the bond failure rates of the material s and there was no effect of time . This clinical investigation confirmed the suitability of the resin-modified glass poly(alkenoate ) cements under test as orthodontic bonding agents",
"The objective of this in vitro study was to compare resistance to enamel demineralization after b and ing with 3 orthodontic cements . The 3 orthodontic cement groups and the nonb and ed control group were evaluated for cariopreventive potential . One hundred twenty extracted human molars were selected for b and ing , embedded in resin blocks , and r and omly assigned to the following 4 groups : zinc phosphate cement , zinc polycarboxylate cement , resin-modified glass ionomer ( RMGI ) , and nonb and ed control . Orthodontic b and s were placed and cemented ; specimens were stored in artificial saliva at 37 degrees C for 30 days , thermocycled for 24 hours , and then deb and ed with a customized b and -removal device attached to a universal testing machine . The cement was h and removed , and 2 coats of nail varnish were applied to the teeth , leaving a 2 x 2-mm window exposed on the buccal surface of the mesiobuccal cusp . The teeth were stored in lactic acid-gelatin solution for 4 weeks at 37 degrees C to develop simulated white spot decalcification in the window . The teeth were subjected to dye ( 10 % methylene blue ) for 24 hours and then sectioned through the window . The depth of dye penetration was determined and used as a measure of the cariopreventive effect of the b and ing cement . Data were analyzed with a 1-way ANOVA and a Tukey test for the multiple comparisons . Dye penetration occurred as follows : the zinc phosphate and control groups were about the same ; there was less dye penetration with the zinc polycarboxylate , and the least with the resin-modified glass ionomer . The 2 fluoride-releasing cements ( zinc polycarboxylate and RMGI ) demonstrated less demineralization than the zinc phosphate in vitro and might provide greater protection from demineralization around a b and periphery in clinical setting",
"The purpose of this study was to compare the debonding force of orthodontic brackets bonded with two conventional resin adhesives ( Resilience L3 and Light Bond ) and a resin-reinforced glass ionomer cement ( Fuji Ortho LC ) . For the in vitro part of the study , 80 extracted premolars were r and omly divided into four groups . In groups A and B , brackets were bonded to unetched enamel using Fuji Ortho LC cement in wet and dry conditions , respectively . In groups C and D , brackets were bonded to etched enamel using Resilience L3 and Light Bond , respectively . Debonding force was determined using a servohydraulic testing machine at a crosshead speed of 1 mm/min . Data was analyzed using the ANOVA and Tukey-Kramer multiple comparison test at p debonding force between unetched Fuji Ortho LC and the two conventional resins . There was no significant difference between the two conventional resins or between unetched resin-reinforced glass ionomer in the wet and dry conditions . For the in vivo part of the study , 30 patients were r and omly assigned to one of the three bonding material groups . Bracket survival rates and distributions were obtained by following these patients for 1.2 years . Data was analyzed using the Kaplan-Meier product-limit estimates of survivorship function . Bond failure interface was determined using a modified adhesive remnant index ( ARI ) . These results showed no significant difference between survival rates and distributions among the three bonding material s with respect to the type of malocclusion , type of orthodontic treatment , or location of bracket . There were significant differences between survival distributions of males and females in the unetched Fuji Ortho LC group and among type of teeth in the conventional resin groups . The predominant mode of bracket failure for the unetched Fuji Ortho LC cement was at the enamel-adhesive interface , and for conventional resins , the enamel-adhesive interface and the bracket-adhesive interface . These results suggest that resin-reinforced glass ionomer cement can withst and occlusal and orthodontic forces despite having a bond strength lower than that of conventional resin adhesives",
"Glass polyalkenoate cements have the unique properties of physicochemically bonding to enamel and base metals and to leach fluoride over prolonged periods . These cements have been modified to provide a dual setting with both light activation and chemical cure to produce a more rapid set . This article reports a 12-month clinical trial of a light-activated glass polyalkenoate cement for the direct bonding of orthodontic brackets , compared with a st and ard composite bonding adhesive . There was no significant difference in failure rates of direct bonded orthodontic brackets cemented with Fuji II LC light-activated glass polyalkenoate cement ( GC Industrial Co. , Tokyo , Japan ) ( 3.3 % ) compared with System I+ composite bonding resin ( Ormco Corp. , Glendora , Calif. ) ( 1.6 % )",
"This study evaluated the clinical performance of a new resin modified glass ionomer cement , Geristore ( Den-Mat Corp. , Santa Maria , Calif. ) , for the bonding of orthodontic brackets and its effect on certain caries-associated microorganisms . This cement has been shown to possess increased mechanical properties and long-term fluoride release . There were 716 brackets bonded in 40 patients ( 17 males and 23 females ) , with a split-mouth technique and a composite resin , Phase II ( Reliance , Itasca , III . ) , as a control . Bond failures were recorded up to 1 year . Plaque scores and plaque sample s were taken from the area of the bonding adhesive in 20 patients , before , at 1 week , and 5 months after the placement of brackets . The plaque sample s were investigated for the presence of Streptococcus mutans and lactobacilli . The overall bond failure rate was found to be 8.9 % for Geristore and 3.1 % for Phase II ( p 0.05 ) in bond failure rate : 3.8 % for Geristore and 1.7 % for Phase II . The proportions of S. mutans and lactobacilli in plaque taken from around Geristore cement were reduced at 1 week and 5 months , when compared with Phase II resin , and this reduction was statistically significant ( p Geristore may be of use in the labial segments , especially in caries prone patients , in whom demineralization at debond may present an esthetic and restorative problem several years after treatment",
"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"
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INTRODUCTION There are different parameters to express the loss of weight in the treatment of overweight and obesity : absolute loss , percentage of loss , decrease in BMI , etc . OBJECTIVE To determine the magnitudes more used in the bibliography in order to establish criteria for uniformity in the expression of those results . METHODS a systematic review of the last five years has made at Proquest , CINHAL , Scopus , with descriptors " body fat distribution " and " diet " and " diet , reducing " and " weight loss " . Articles published in English , French and Spanish were selected . Inclusion criteria were used : articles only dietary treatment of overweight in humans , and exclusion criteria : not dietary treatments , metabolic diseases , less than 50 patients and less than 8 weeks of treatment . Title , summary , methodology , results and discussion have been analysed by two research ers independently . RESULTS AND DISCUSSION 854 items found , only 61 met the criteria . These were grouped into 5 subgroups , as they expressed the weight loss ( weight or fat loss in kg ; weight and fat loss in kg ; weight or fat loss in % ; weight loss in % and fat loss in kg or vice versa ; weight and far loss in% ) . The results show a lack of homogeneity in the loss , being the percentage the most used expression . CONCLUSIONS There is great heterogeneity in the expression of results of the treatments for weight loss ; the diet is one of the least used tools ; the analysis of clinical trials of intervention reflects a high quality in subjects older than 18 years , highlighting the lack of this type of research lines in children under 18 years . Therefore , it should st and ardize the magnitudes of expression of the success of these treatments and increase the lines of research on this topic
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[
"Limited data on sex differences in body composition changes in response to higher protein diets ( PRO ) compared to higher carbohydrate diets ( CARB ) suggest that a PRO diet helps preserve lean mass ( LM ) in women more so than in men . Objective To compare male and female body composition responses to weight loss diets differing in macronutrient content . Design Twelve month r and omized clinical trial with 4mo of weight loss and 8mo weight maintenance . SubjectsOverweight ( N = 130 ; 58 male ( M ) , 72 female ( F ) ; BMI = 32.5 ± 0.5 kg/m2 ) middle-aged subjects were r and omized to energy-restricted ( deficit ~500 kcal/d ) diets providing protein at 1.6 g.kg-1.d-1 ( PRO ) or 0.8 g.kg-1.d-1 ( CARB ) . LM and fat mass ( FM ) were measured using dual X-ray absorptiometry . Body composition outcomes were tested in a repeated measures ANOVA controlling for sex , diet , time and their two- and three-way interactions at 0 , 4 , 8 and 12mo . Results When expressed as percent change from baseline , males and females lost similar amounts of weight at 12mo ( M:-11.2 ± 7.1 % , F:-9.9 ± 6.0 % ) , as did diet groups ( PRO:-10.7 ± 6.8 % , CARB:-10.1 ± 6.2 % ) , with no interaction of gender and diet . A similar pattern emerged for fat mass and lean mass , however percent body fat was significantly influenced by both gender ( M:-18.0 ± 12.8 % , F:-7.3 ± 8.1 % , p ( PRO:-14.3 ± 11.8 % , CARB:-9.3 ± 11.1 % , p 0.9 % of their total body fat in the trunk ( P reduced trunk fat during weight loss more than women ( M:-3.0 ± 0.5 % , F:-1.8 ± 0.3 % , p 0.9 % more total body fat in the legs , but loss of total body fat in legs was similar in men and women . Conclusion PRO was more effective in reducing percent body fat vs. CARB over 12mo weight loss and maintenance . Men lost percent total body fat and trunk fat more effectively than women . No interactive effects of protein intake and gender are evident",
"Background The aim of this study was to determine the physiological effects of an high-intensity circuit training ( HICT ) on several cardiovascular disease risk factors in healthy , overweight middle-aged subjects , and to compare the effects of HICT to traditional endurance training ( ET ) and low-intensity circuit training ( LICT ) . Methods Fifty-eight participants ( ages 61±3.3 yrs , BMI 29.8±0.9 ) were r and omly assigned to one of the three exercise treatment groups : HICT , LICT and ET . The three groups exercised three times per week , 50 min per session for 12 weeks . Baseline and after intervention anthropometric characteristics : body weight ( BW ) , fat mass ( FM ) ; blood pressure : diastolic ( DBP ) and systolic ( SBP ) , blood parameters ; CHOL-t ( total cholesterol ) , LDL-C ( low density lipoprotein-cholesterol ) , HDL-C ( high density lipoprotein-cholesterol ) , TG ( triglycerides ) , ApoB and ratio ApoB/ApoA1 were measured . Results Compared to other groups , HICT showed significantly higher reductions in FM , DBP , CHOLt , LDL-C , TG , ApoB and significantly greater increases in high density HDL-C. LICT result ed in the greatest reduction in SBP . All groups showed a significant improvement of BW without any significant differences between groups . Conclusions Our findings indicate that high-intensity circuit training is more effective in improving blood pressure , lipoproteins and triglycerides than endurance training alone or lower intensity circuit training",
"Background The prevalence of childhood obesity has increased worldwide , which is a serious concern as obesity is associated with many negative immediate and long-term health consequences . Therefore , the treatment of overweight and obesity in children and adolescents is strongly recommended . Inpatient weight-loss programs have shown to be effective particularly regarding short-term weight-loss , whilst little is known both on the long-term effects of this treatment and the determinants of successful weight-loss and subsequent weight maintenance . The purpose of this study is to evaluate the short , middle and long-term effects of an inpatient weight-loss program for children and adolescents and to investigate the likely determinants of weight changes , whereby the primary focus lies on the potential role of differences in polymorphisms of adiposity-relevant genes . Methods / Design The study involves overweight and obese children and adolescents aged 6 to 19 years , who participate in an inpatient weight-loss program for 4 to 6 weeks . It started in 2006 and it is planned to include 1,500 participants by 2013 . The intervention focuses on diet , physical activity and behavior therapy . Measurements are taken at the start and the end of the intervention and comprise blood analyses ( DNA , lipid and glucose metabolism , adipokines and inflammatory markers ) , anthropometry ( body weight , height and waist circumference ) , blood pressure , pubertal stage , and exercise capacity . Physical activity , dietary habits , quality of life , and family background are assessed by question naires . Follow-up assessment s are performed 6 months , 1 , 2 , 5 and 10 years after the intervention : Children will complete the same question naires at all time points and visit their general practitioner for examination of anthropometric parameters , blood pressure and assessment of pubertal stage . At the 5 and 10 year follow-ups , blood parameters and exercise capacity will be additionally measured . Discussion Apart from illustrating the short , middle and long-term effects of an inpatient weight-loss program , this study will contribute to a better underst and ing of inter-individual differences in the regulation of body weight , taking into account the role of genetic predisposition and lifestyle factors . Trial Registration NCT01067157",
"Purpose The maintenance of an obtained lower weight level is often found to be difficult . The aim of this study was to determine weight maintenance after an initial weight loss by consumption of a meal replacement with a vegetable-oil emulsion associated with prolonged satiety . Methods After a 6-week weight loss period with very low calorie diet ( VLCD ) , subjects with > 5 % body weight ( BW ) loss were r and omized to a 12-week weight maintenance follow-up period , comparing a partial meal replacement diet containing a vegetable-oil emulsion ( test ) or dairy fat ( control ) . Anthropometric data and safety variables were collected at baseline and after 4 , 8 and 12 weeks . Results A significant weight loss was observed during the 12-week weight maintenance diet in the test and control group , respectively ; 1.0 ± 2.1 kg ( p groups . Body fat mass ( BFM ) decreased significantly ( p a vegetable-oil emulsion to a meal replacement weight maintenance program after an initial weight loss using VLCD was associated with decreased BFM by 0.9 % without any change in BW between the two groups",
"The purpose of this study was to determine whether physical activity , with and without lower body pressure , leads to increased regional fat loss in the lower extremities of overweight females . Eighty-six obese women with a female phenotype were r and omly assigned into four groups : control group ( C ) , diet only ( D ) , diet plus exercise ( DE ) or diet , exercise and lower body pressure intervention ( DEP ) . The three treatment groups followed the same diet , the two exercise groups ( DE and DEP ) additionally followed an endurance training program of 30 min of cycling at 50%VO2max three times per week with or without lower body pressure . Body composition and fat distribution were assessed by DXA . Body size circumference measurements were recorded as well as subjective ratings of cellulite and skin appearance . As expected , all test groups ( D , DE , DEP ) showed a significant decrease ( p total body mass and fat mass . DXA revealed significant differences between the experimental groups and C. The DEP group also lost significantly more body mass and fat mass when compared with D , while no significant difference was observed between the other groups . A similar pattern was seen for circumference measurement data . A significant perceived improvement was made by the DEP group when compared with C , D and DE groups for skin condition and also between the DEP versus C and D groups for cellulite . The combination of diet and exercise is successful for weight reduction . The additional application of lower body pressure especially affects skin appearance",
"BACKGROUND Some evidence has suggested that a diet with a higher ratio of protein to carbohydrates has metabolic advantages in the treatment of polycystic ovary syndrome ( PCOS ) . OBJECTIVE The objective of this study was to compare the effect of a high-protein ( HP ) diet to a st and ard-protein ( SP ) diet in women with PCOS . DESIGN A controlled , 6-mo trial was conducted in 57 PCOS women . The women were assigned through rank minimization to one of the following 2 diets without caloric restriction : an HP diet ( > 40 % of energy from protein and 30 % of energy from fat ) or an SP diet ( The women received monthly dietary counseling . At baseline and 3 and 6 mo , anthropometric measurements were performed , and blood sample s were collected . RESULTS Seven women dropped out because of pregnancy , 23 women dropped out because of other reasons , and 27 women completed the study . The HP diet produced a greater weight loss ( mean : 4.4 kg ; 95 % CI : 0.3 , 8.6 kg ) and body fat loss ( mean : 4.3 kg ; 95 % CI : 0.9 , 7.6 kg ) than the SP diet after 6 mo . Waist circumference was reduced more by the HP diet than by the SP diet . The HP diet produced greater decreases in glucose than did the SP diet , which persisted after adjustment for weight changes . There were no differences in testosterone , sex hormone-binding globulin , and blood lipids between the groups after 6 mo . However , adjustment for weight changes led to significantly lower testosterone concentrations in the SP-diet group than in the HP-diet group . CONCLUSION Replacement of carbohydrates with protein in ad libitum diets improves weight loss and improves glucose metabolism by an effect that seems to be independent of the weight loss and , thus , seems to offer an improved dietary treatment of PCOS women",
"The aim of the present study was to compare the long-term effects of two dietary approaches on changes in dietary intakes , eating behaviours and body weight : ( 1 ) approach using restrictive messages to limit high-fat foods ( low-fat intake ; LOFAT ) ; ( 2 ) approach emphasising non-restrictive messages directed towards the inclusion of fruits and vegetables ( high intake of fruits and vegetables ; HIFV ) . A total of sixty-eight overweight or obese postmenopausal women were r and omly assigned to one of the two dietary approaches . The 6-month dietary intervention included three group sessions and ten individual sessions with a dietitian . Dietary intakes , eating behaviours and anthropometrics were measured at baseline , at the end of the dietary intervention ( T = 6 ) and 6 months and 12 months after the end of the intervention ( T = 12 and T = 18 ) . In the LOFAT group , energy and fat intakes were lower at T = 6 when compared with baseline and remained lower at T = 12 and T = 18 . In the HIFV group , fruit and vegetable intakes increased significantly at T = 6 but were no longer significantly different from baseline at T = 12 and T = 18 . Dietary restraint increased at T = 6 and remained higher than baseline at T = 18 in the LOFAT group while no significant change was observed in the HIFV group . At T = 6 , body weight was significantly lower than baseline in both groups ( LOFAT : - 3.7 ( SD 2.8 ) kg ; HIFV : - 1.8 ( SD 3.0 ) kg ) and no significant difference in body-weight change from baseline was found between groups at T = 18 . We concluded that weight loss was similar at 1-year follow-up in both dietary approaches . Despite relatively good improvements in the short term , the adherence to a 6-month dietary intervention promoting high intakes of fruits and vegetables was difficult to maintain",
"Background : Regular consumption of diets with increased protein or fibre intakes may benefit body weight and composition and cardiovascular disease risk factors . Lupin flour is a novel food ingredient high in protein and fibre . Objective : To investigate the effects of a lupin-enriched diet , during and following energy restriction , on body weight and composition and cardiovascular disease risk factors in overweight individuals . Design : Participants ( n=131 ) were recruited to a 12-month parallel- design trial . They were r and omly assigned to consume lupin-enriched foods or matching high-carbohydrate control foods . All participants underwent 3 months of weight loss , 1 month of weight stabilization and 8 months of weight maintenance . Body weight and composition and cardiovascular disease risk factors were assessed at baseline , 4 and 12 months . Results : Lupin , relative to control , did not significantly influence ( mean difference ( 95 % CI ) ) weight loss at 4 months ( 0.1 kg ( −1.2 , 1.4 ) ) and 12 months ( −0.6 kg ( −2.0 , 0.8 ) ) , maintenance of weight loss from 4 to 12 months ( −0.7 kg ( −1.83 , 0.48 ) ) or measures of body fat and fat-free mass . Relative to control , 24-h ambulatory systolic ( −1.3 mm Hg ( −2.4 , −0.3 ) , P=0.016 ) and diastolic ( −1.0 mm Hg ( −1.9 , −0.2 ) , P=0.021 ) blood pressures were lower at 12 months but not at 4 months ; fasting insulin concentrations and homeostasis model assessment ( HOMA ) scores were significantly lower at 4 months ( −1.2 mU l–1 ( −1.3 , −1.1 ) , P=0.004 and −0.6 units ( −1.0 , −0.19 ) , P=0.004 ) and 12 months ( −1.3 mU l–1 ( −1.4 , −1.1 ) , P from lupin-enriched foods does not enhance weight loss or improve the maintenance of weight loss . However , such a diet may provide cardiovascular health benefits in terms of insulin sensitivity and blood pressure",
"This study tested the efficacy of two school-based programs for prevention of body weight/fat gain in comparison to a control group , in all participants and in overweight children . The Louisiana ( LA ) Health study utilized a longitudinal , cluster r and omized 3-arm controlled design , with 28 months of follow-up . Children ( N=2060 ; M age = 10.5 years , SD = 1.2 ) from rural communities in Grade s 4 to 6 participated in the study . 17 school clusters ( M = 123 children/cluster ) were r and omly assigned to one of three prevention arms : 1 ) Primary Prevention ( PP ) , an environmental modification program , 2 ) Primary + Secondary Prevention ( PP+SP ) , the environmental program with an added classroom and internet education component , or 3 ) Control ( C ) . Primary outcomes were changes in percent body fat and body mass index z scores . Secondary outcomes were changes in behaviors related to energy balance . Comparisons of PP , PP+SP , and C on changes in body fat and BMI z scores found no differences . PP and PP+SP study arms were combined to create an environmental modification arm ( EM ) . Relative to C , EM decreased body fat for boys ( −1.7 % ± 0.38 % versus −0.14 % ± 0.69 % ) and attenuated fat gain for girls ( 2.9 % ± 0.22 % versus 3.93 % ± 0.37 % ) , but st and ardized effect sizes were relatively small ( this school-based environmental modification programs had modest beneficial effects on changes in percent body fat . Addition of a classroom/internet program to the environmental program did not enhance weight/fat gain prevention , but did impact physical activity and social support in overweight children",
"A 12-week r and omized controlled multi-center clinical trial was conducted in 106 overweight and obese adults . Diets were design ed to produce a 2,093 kJ/day energy deficit with either low calcium ( LC ; ~600 mg/day ) , high calcium ( HC ; ~1,400 mg/day ) , or high dairy ( HD ; three dairy servings , diet totaling ~1,400 mg/day ) . Ninety-three subjects completed the trial , and 68 met all a priori weekly compliance criteria . Both HC and HD contained comparable levels of calcium , but HC was only ~30 % as effective as HD in suppressing 1,25-(OH)2D and exerted no significant effects on weight loss or body composition compared to LC . In the group that met compliance criteria , HD result ed in ~two-fold augmentation of fat loss compared to LC and HC ( HD : -4.43 ± 0.53 kg ; LC : -2.69 ± 0.0.53 kg ; HC : -2.23 ± 0.73 kg , p augmentated central ( trunk ) fat loss ( HD : -2.38 ± 0.30 kg ; HC : -1.42 ± 0.30 kg ; LC : -1.36 ± 0.42 kg , p and waist circumference ( HD : -7.65 ± 0.75 cm ; LC : -4.92 ± 0.74 cm ; LC : -4.95 ± 1.05 cm , p that dairy-rich diets augment weight loss by targeting the fat compartment during energy restriction",
"Diets with increased protein and reduced carbohydrates ( PRO ) are effective for weight loss , but the long-term effect on maintenance is unknown . This study compared changes in body weight and composition and blood lipids after short-term weight loss ( 4 mo ) followed by weight maintenance ( 8 mo ) using moderate PRO or conventional high-carbohydrate ( CHO ) diets . Participants ( age = 45.4 + /- 1.2 y ; BMI = 32.6 + /- 0.8 kg/m(2 ) ; n = 130 ) were r and omized to 2 energy-restricted diets ( -500 kcal/d or -2093 kJ/d ) : PRO with 1.6 g x kg(-1 ) x d(-1 ) protein and 0.8 g x kg(-1 ) x d(-1 ) protein , > 220 g/d carbohydrates . At 4 mo , the PRO group had lost 22 % more fat mass ( FM ) ( -5.6 + /- 0.4 kg ) than the CHO group ( -4.6 + /- 0.3 kg ) but weight loss did not differ between groups ( -8.2 + /- 0.5 kg vs. -7.0 + /- 0.5 kg ; P = 0.10 ) . At 12 mo , the PRO group had more participants complete the study ( 64 vs. 45 % , P body composition ; however , weight loss did not differ between groups ( -10.4 + /- 1.2 kg vs. -8.4 + /- 0.9 kg ; P = 0.18 ) . Using a compliance criterion of participants attaining > 10 % weight loss , the PRO group had more participants ( 31 vs. 21 % ) lose more weight ( -16.5 + /- 1.5 vs. -12.3 + /- 0.9 kg ; P FM ( -11.7 + /- 1.0 vs. -7.9 + /- 0.7 kg ; P CHO diet reduced serum cholesterol and LDL cholesterol compared with PRO ( P PRO had sustained favorable effects on serum triacylglycerol ( TAG ) , HDL cholesterol ( HDL-C ) , and TAG : HDL-C compared with CHO at 4 and 12 mo ( P FM loss and body composition improvement during initial weight loss and long-term maintenance and produced sustained reductions in TAG and increases in HDL-C compared with the CHO diet",
"Background Despite record rates of childhood obesity , effective evidence -based treatments remain elusive . While prolonged tertiary specialist clinical input has some individual impact , these services are only available to very few children . Effective treatments that are easily accessible for all overweight and obese children in the community are urgently required . General practitioners are logical care providers for obese children but high- quality trials indicate that , even with substantial training and support , general practitioner care alone will not suffice to improve body mass index ( BMI ) trajectories . HopSCOTCH ( the Shared Care Obesity Trial in Children ) will determine whether a shared-care model , in which paediatric obesity specialists co-manage obesity with general practitioners , can improve adiposity in obese children . Design R and omised controlled trial nested within a cross-sectional BMI survey conducted across 22 general practice s in Melbourne , Australia . Participants Children aged 3–10 years identified as obese by Centers for Disease Control criteria at their family practice , and r and omised to either a shared-care intervention or usual care . InterventionA single multidisciplinary obesity clinic appointment at Melbourne ’s Royal Children ’s Hospital , followed by regular appointments with the child ’s general practitioner over a 12 month period . To support both specialist and general practice consultations , web-based shared-care software was developed to record assessment , set goals and actions , provide information to caregivers , facilitate communication between the two professional groups , and jointly track progress . Outcomes Primary - change in BMI z-score . Secondary - change in percentage fat and waist circumference ; health status , body satisfaction and global self-worth . Discussion This will be the first efficacy trial of a general-practitioner based , shared-care model of childhood obesity management . If effective , it could greatly improve access to care for obese children . Trial Registration Australian New Zeal and Clinical Trials Registry",
"Background Physical inactivity and overweight are two known risk factors for postmenopausal breast cancer . Former exercise intervention studies showed that physical activity influences sex hormone levels , known to be related to postmenopausal breast cancer , mainly when concordant loss of body weight was achieved . The question remains whether there is an additional beneficial effect of physical activity when weight loss is reached . The aim of this study is to investigate the effect attributable to exercise on postmenopausal breast cancer risk biomarkers , when equivalent weight loss is achieved compared with diet-induced weight loss . Design The SHAPE-2 study is a three-armed , multicentre trial . 243 sedentary , postmenopausal women who are overweight or obese ( BMI 25–35 kg/m2 ) are enrolled . After a 4 - 6 week run-in period , wherein a baseline diet is prescribed , women are r and omly allocated to ( 1 ) a diet group , ( 2 ) an exercise group or ( 3 ) a control group . The aim of both intervention groups is to lose an amount of 5–6 kg body weight in 10–14 weeks . The diet group follows an energy restricted diet and maintains the habitual physical activity level . The exercise group participates in a 16-week endurance and strength training programme of 4 hours per week . Furthermore , they are prescribed a moderate caloric restriction . The control group is asked to maintain body weight and continue the run-in baseline diet . Measurements include blood sampling , question naires , anthropometrics ( weight , height , waist and hip circumference ) , maximal cycle exercise test ( VO2peak ) , DEXA-scan ( body composition ) and abdominal MRI ( subcutaneous and visceral fat ) . Primary outcomes are serum levels of oestradiol , oestrone , testosterone and sex hormone binding globulin ( SHBG ) . Discussion This study will give insight in the potential attributable effect of physical activity on breast cancer risk biomarkers and whether this effect is mediated by changes in body composition , in postmenopausal women . Eventually this may lead to the design of specific lifestyle guidelines for prevention of breast cancer . Trial registration The SHAPE-2 study is registered in the register of clinical trials.gov , Identifier : NCT01511276",
"Background Obesity is a major public health problem in many poor countries where micronutrient deficiencies are prevalent . A partial meal replacement may be an effective strategy to decrease obesity and increase micronutrient intake in such population s. The objective was to evaluate the efficacy of a partial meal replacement with and without inulin on weight reduction , blood lipids and micronutrients intake in obese Mexican women . Methods In a r and omized controlled clinical trial 144 women ( 18–50 y ) with BMI ≥ 25 kg/m2 , were allocated into one of the following treatments during 3 months : 1 ) Two doses/d of a partial meal replacement ( PMR ) , 2 ) Two doses/d of PMR with inulin ( PMR + I ) , 3 ) Two doses/d of 5 g of inulin ( INU ) and 4 ) Control group ( CON ) . All groups received a low calorie diet ( LCD ) . Weight , height , hip and waist circumference were measured every 2 weeks and body composition , lipids and glucose concentration and nutrient intake were assessed at baseline and after 3 months . Results All groups significantly reduced weight , BMI , waist and hip circumference . Differences between groups were only observed in BMI and weight adjusted changes : At 45 days PMR group lost more weight than INU and CON groups by 0.9 and 1.2Kg , respectively . At 60 days , PMR + I and PMR groups lost more weight than in INU by 0.7 and 1Kg , respectively . Subjects in PMR , PMR + I and INU significantly decreased triglycerides . Energy intake was reduced in all groups . Fiber intake increased in PMR + I and INU groups . Some minerals and vitamins intakes were higher in PMR and PMR + I compared with INU and CON groups . Conclusion Inclusion of PMR with and without inulin to a LCD had no additional effect on weight reduction than a LCD alone but reduced triglycerides and improved intake of micronutrients during caloric restriction . PMR could be a good alternative for obese population s with micronutrient deficiencies . Clinical Trials . Gov",
"Objective : We examined the effects of an aerobic exercise intervention on adiposity outcomes that may be involved in the association between physical activity and breast cancer risk . Design : This study was a two-centre , two-armed , r and omized controlled trial . The 1-year-long exercise intervention included 45 min of moderate-to-vigorous aerobic exercise five times per week , with at least three of the sessions being facility based . The control group was asked not to change their activity and both groups were asked not to change their diet . Subjects : A total of 320 postmenopausal , sedentary , normal weight-to-obese women aged 50–74 years who were cancer-free , nondiabetic and nonhormone replacement therapy users were included in this study . Measurements : Anthropometric measurements of height , weight and waist and hip circumferences ; dual energy X-ray absorptiometry measurements of total body fat ; and computerized tomography measurements of abdominal adiposity were carried out . Results : Women in the exercise group exercised a mean of 3.6 days ( s.d.=1.3 ) per week and 178.5 min ( s.d.=76.1 ) per week . Changes in all measures of adiposity favored exercisers relative to controls ( P abdominal fat area . A linear trend of greater body fat loss with increasing volume of exercise was also observed . Conclusion : A 1-year aerobic exercise program consistent with current public health guidelines result ed in reduced adiposity levels in previously sedentary postmenopausal women at higher risk of breast cancer",
"Objective . To investigate effects of weight loss on adipokines and health measures in obese older adults with symptomatic knee osteoarthritis . Methods . Participants were r and omly assigned to either weight loss ( WL ) ( men : 12 , women : 14 ) or weight stable ( WS ) group ( men : 12 , women : 13 ) . WL intervention included meal replacements and structured exercise training . Measurements of leptin , adiponectin , soluble leptin receptor , lifestyle behaviors , and body composition were collected at baseline and 6 months . Univariate analysis of covariance was performed on 6 month variables , and Spearman and partial correlations were made between variables . Results . Weight loss was 13.0 % and 6.7 % in WL for men and women , respectively . Women in WL had lower whole body and trunk fat than WS . The leptin : adiponectin ratio was lower for women in WL than WS at 6 months , with no group differences in adipokines for men . Leptin and free leptin index correlated with body fat in both genders at baseline . Interestingly , only women showed reductions in leptin ( P free leptin index with total fat and trunk fat . Partial correlations between 6 month adipokines after adjustments for covariates and group/time period show potential multivariate influences . Conclusions . In the presence of an effective weight loss intervention in older obese adults , there are significant relationships between weight and fat loss and leptin in women , but not men , suggesting gender-specific features of adipokine metabolism in this age group",
"Objective To determine the safety and efficacy of altering the ratio of carbohydrate and protein in low-energy diets in conjunction with a popular exercise program in obese women . Design Matched , prospect i ve clinical intervention study to assess efficacy of varying ratios of carbohydrate and protein intake in conjunction with a regular exercise program . Participants One-hundred sixty one sedentary , obese , pre-menopausal women ( 38.5 ± 8.5 yrs , 164.2 ± 6.7 cm , 94.2 ± 18.8 kg , 34.9 ± 6.4 kg·m-2 , 43.8 ± 4.2 % ) participated in this study . Participants were weight stable and not participating in additional weight loss programs . Methods Participants were assigned to either a no exercise + no diet control ( CON ) , a no diet + exercise group ( ND ) , or one of four diet + exercise groups ( presented as kcals ; % carbohydrate : protein : fat ) : 1 ) a high energy , high carbohydrate , low protein diet ( HED ) [ 2,600 ; 55:15:30 % ] , 2 ) a very low carbohydrate , high protein diet ( VLCHP ) [ 1,200 kcals ; 63:7:30 % ] , 3 ) a low carbohydrate , moderate protein diet ( LCMP ) [ 1,200 kcals ; 50:20:30 % ] and 4 ) a high carbohydrate , low protein diet ( HCLP ) [ 1,200 kcals ; 55:15:30 % ] . Participants in exercise groups ( all but CON ) performed a pneumatic resistance-based , circuit training program under supervision three times per week . Measurements Anthropometric , body composition , resting energy expenditure ( REE ) , fasting blood sample s and muscular fitness assessment s were examined at baseline and weeks 2 , 10 and 14 . Results All groups except CON experienced significant reductions ( P over 14 weeks . VLCHP , LCHP and LPHC participants experienced similar but significant ( P – 0.001 ) reductions in body mass when compared to other groups . Delta responses indicated that fat loss after 14 weeks was significantly greatest in VLCHP ( 95 % CI : -5.2 , -3.2 kg ) , LCMP ( -4.0 , -1.9 kg ) and HCLP ( -3.8 , -2.1 kg ) when compared to other groups . Subsequent reductions in % body fat were significantly greater in VLCHP , LCMP and HCLP participants . Initial dieting decreased ( P muscular fitness , but these improvements were not different among groups . Favorable but non-significant mean changes occurred in lipid panels , glucose and HOMA-IR . Leptin levels decreased ( P quality of life and body image . Conclusion Exercise alone ( ND ) appears to have minimal impact on measured outcomes with positive outcomes apparent when exercise is combined with a hypoenergetic diet . Greater improvements in waist circumference and body composition occurred when carbohydrate is replaced in the diet with protein . Weight loss in all diet groups ( VLCHP , LCMP and HCLP ) was primarily fat and stimulated improvements in markers of cardiovascular disease risk , body composition , energy expenditure and psychosocial parameters",
"Background : New technology offers increased opportunities for weight control . However , it is not clear whether older people with less computer training can make use of this tool . Our objective was to examine how members above the age of 65 years performed in an internet-based behavioral weight loss program , compared to younger members . Methods : Data from members ( n = 23,233 ) of an internet-based behavioral weight loss program were analyzed . We restricted our study to active participants accessing the weight club , during a 6-month period ( n = 4,440 ) . The number of logins , food intake , and weight records were examined . Participants were divided into age tertiles separately for men and women . The oldest tertile was further subdivided into two groups : above and below the age of 65 years . Results : Participants aged 65 or older were more likely to remain active in the weight club for at least 6 months compared to younger age groups . They had the highest frequency of recordings of food intake and current weight . Among women , those older than 65 years had on average the highest percentage of weight loss ( 5.6 kg , 6.8 % ) . Men above 65 years of age had the highest number of logins , on average 161 times during the 6-month period . Conclusion : Older participants are performing equally well or even better in an internet-based behavioral weight loss program than younger participants . Internet-based programs could be a promising and attractive option for older adults requiring assistance in losing weight",
"Background / Objective : Imaging methods by magnetic resonance imaging are being increasingly used to quantify visceral adipose tissue ( VAT ) , but there is no clear consensus as to a st and ardized protocol . We compared the ability of two commonly used imaging protocol s ( multiple slice versus single slice ) to detect changes in VAT with diet or exercise . Subjects/ Methods : We utilized data from the participants who completed our diet ( n=22 ) or exercise ( n=35 ) based weight-loss interventions . The intervention mainly comprised of weekly dietary modification sessions or aerobic exercise sessions over 12 weeks . Multiple-slice images obtained from T9 to S1 and a single-slice image at L4–L5 were compared using the effect size of the VAT change . In addition , we calculated the sample size needed to compare the two imaging protocol s ’ ability to detect significant changes in VAT . Results : VAT and subcutaneous adipose tissue volumes and areas , and other anthropometry decreased significantly after both the diet and exercise interventions . For VAT , a single-slice image had a lower effect size ( diet : 1.23 ; exercise : 0.49 ) than the multiple-slice images ( diet : 1.81 ; exercise : 0.90 ) . The sample size required for multiple slice was substantially lower than for the single-slice with both weight-loss interventions . Conclusions : The different image protocol s may lead to different results in relative VAT changes . Furthermore , single-slice imaging required a substantially larger sample size than multiple-slice imaging , and for research ers to detect smaller changes in VAT with single-slice imaging , a larger sample size would be needed . Thus , multiple-slice imaging has advantages for assessing VAT change in future clinical research",
"BACKGROUND AND AIMS Recent studies suggest that calcium metabolism and perhaps other components of dairy products may contribute to shifting the energy balance and thus play a role in weight regulation . We compared the effects of cows ' milk , calcium fortified soy milk and calcium supplement on weight and body fat reduction in premenopausal overweight and obese women . METHODS AND RESULTS In this clinical trial , 100 healthy overweight or obese premenopausal women were r and omized to one of the following dietary regimens for 8 weeks : ( 1 ) a control diet providing a 500kcal/day deficit , with 500 - 600mg/day dietary calcium ; ( 2 ) a calcium-supplemented diet identical to the control diet with 800mg/day of calcium as calcium carbonate ; ( 3 ) a milk diet providing a 500kcal/day deficit and containing three servings of low-fat milk ; ( 4 ) a soy milk diet providing a 500kcal/day deficit and containing three servings of calcium fortified soy milk . At baseline and after 8 weeks , weight , waist circumference , and hip circumference were measured . Three 24-h dietary records and physical activity records were also taken . Comparing the mean differences in weight , waist circumference , body mass index ( BMI ) and waist-to-hip ratio ( WHR ) using repeated measure of variance analysis showed that changes in waist circumference and WHR were significant among the four groups ( p=0.029 and p=0.015 , respectively ) . After adjustment for baseline values , changes in weight and BMI were also significant ( p=0.017 and p=0.019 , respectively ) . Weight reductions in high milk , soy milk , calcium supplement and control groups were 4.43±1.93(kg ) , 3.46±1.28(kg ) , 3.89±2.40(kg ) and 2.87±1.55(kg ) , respectively . The greatest changes were seen in the high dairy group in all variables . CONCLUSION Increasing low fat milk consumption significantly reduces the general and central obesity beyond a low calorie diet",
"AIM The prevalence of obesity is rising . Because obesity is positively associated with many health related risks and negatively associated with life expectancy this is a threat to public health . Physical exercise is a well known method to lose fat mass . Due to shame of their appearance , bad general condition and social isolation , starting and continuing physical exercise tends to be problematic for obese adults . A supervised training program could be useful to overcome such negative factors . In this study we hypothesized that offering a supervised exercise program for obese adults would lead to greater benefits in body fat and total body mass reduction than a non-specific oral advice to increase their physical activity . METHODS Thirty-four participants were r and omised to a supervised exercise program group ( N.=17 ) and a control group ( N.=17 ) . Fifteen c and i date s in the intervention group and 12 in the control group appeared for baseline measurements and bought an all inclusive sports pass to a health club for Euro 10 , per month . The control group just received the oral advice to increase their physical activity at their convenience . The supervised exercise group received biweekly exercise sessions of 2 hours with an estimated energy expenditure of 2 500 kJ per hour . Both groups received no dietary advice . RESULTS After 4 months the overall decrease in body mass in the intervention group was 8.0 kg ( SD 6.2 ) and the decrease in body fat was 6.2 kg ( SD 4.5 ) . The control group lost 2.8 kg overall ( SD 4.2 ) and the decrease in body fat was 1.7 kg ( SD 3.1 ) . Correction for differences between groups in gender and age by multiple linear regression analysis showed significantly greater loss of total body mass ( P = 0.001 ) and fat mass ( P = 0.002 ) in the intervention group compared with the control group . CONCLUSIONS Stimulation of physical activity alone seems to result in a slight short term body mass and fat mass reduction in obese adults who are eager to lose weight . Supervised exercise under supervision of a qualified fitness instructor leads to a larger decrease",
"UNLABELLED Obesity-related hepatic steatosis is a major risk factor for metabolic and cardiovascular disease . Fat reduced hypocaloric diets are able to relieve the liver from ectopically stored lipids . We hypothesized that the widely used low carbohydrate hypocaloric diets are similarly effective in this regard . A total of 170 overweight and obese , otherwise healthy subjects were r and omized to either reduced carbohydrate ( n = 84 ) or reduced fat ( n = 86 ) , total energy restricted diet ( -30 % of energy intake before diet ) for 6 months . Body composition was estimated by bioimpedance analyses and abdominal fat distribution by magnetic resonance tomography . Subjects were also su bmi tted to fat spectroscopy of liver and oral glucose tolerance testing . In all , 102 subjects completed the diet intervention with measurements of intrahepatic lipid content . Both hypocaloric diets decreased body weight , total body fat , visceral fat , and intrahepatic lipid content . Subjects with high baseline intrahepatic lipids ( > 5.56 % ) lost ≈7-fold more intrahepatic lipids compared with those with low baseline values ( contrast , changes in visceral fat mass and insulin sensitivity were similar between subgroups , with low and high baseline intrahepatic lipids . CONCLUSION A prolonged hypocaloric diet low in carbohydrates and high in fat has the same beneficial effects on intrahepatic lipid accumulation as the traditional low-fat hypocaloric diet . The decrease in intrahepatic lipids appears to be independent of visceral fat loss and is not tightly coupled with changes in whole body insulin sensitivity during 6 months of an energy restricted diet",
"Weight loss can have substantial health benefits for overweight or obese persons ; however , the ratio of fat : lean tissue loss may be more important . We aim ed to determine how daily exercise ( resistance and /or aerobic ) and a hypoenergetic diet varying in protein and calcium content from dairy foods would affect the composition of weight lost in otherwise healthy , premenopausal , overweight , and obese women . Ninety participants were r and omized to 3 groups ( n = 30/group ) : high protein , high dairy ( HPHD ) , adequate protein , medium dairy ( APMD ) , and adequate protein , low dairy ( APLD ) differing in the quantity of total dietary protein and dairy food- source protein consumed : 30 and 15 % , 15 and 7.5 % , or 15 and Body composition was measured by DXA at 0 , 8 , and 16 wk and MRI ( n = 39 ) to assess visceral adipose tissue ( VAT ) volume at 0 and 16 wk . All groups lost body weight ( P fat ( P fat loss during wk 8–16 was greater in the HPHD group than in the APMD and APLD groups ( P gained lean tissue with a greater increase during 8–16 wk than the APMD group , which maintained lean mass and the APLD group , which lost lean mass ( P VAT as assessed by MRI ( P trunk fat as assessed by DXA ( P reduction in VAT in all groups was correlated with intakes of calcium ( r = 0.40 ; P total and visceral fat loss and lean mass gain ",
"To evaluate the efficacy of adding cognitive behavioural treatment ( CBT ) to either a low-carbohydrate ( LC ) diet or a low-fat ( LF ) diet in the treatment of weight loss of obese women , a r and omised clinical intervention study was performed . A total of 105 healthy non-pregnant obese women ( average age and BMI of 45.4 ( sd 10.4 ) years and 36 ( sd 4.3 ) kg/m2 ) were r and omly allocated to the CBT or control ( C ) groups ; within each group , women were r and omly selected to receive either the LC or LF diet during 6 months . The pre-planned primary trial end-point was the weight loss . Differences between the groups were assessed using one-way ANOVA . There were three women ( 2.8 % ) who dropped out , all of them in the CBT group . No differences in the anthropometric and laboratory characteristics at baseline were noted between women in the CBT ( n 52 ) and control groups ( n 50 ) . Intention-to-treat analysis showed that weight loss in the CBT-LC ( 90 ( sd 12.3 ) to 82.1 ( sd 12.1 ) kg ) and C-LC ( 89.4 ( sd 10.0 ) to 85.8 ( sd 9.8 ) kg ) groups reached 8.7 and 4.0 % , respectively ( P Weight loss was higher in the CBT-LF group than in the CBT-LC groups ( P = 0.049 ) . The present results showed that adding CBT to either the LF or LC diet produced significantly greater short-term weight loss in obese women compared with diet alone . These finding support the efficacy of CBT in breaking previous dietary patterns and in developing healthier attitudes that reinforce a healthier lifestyle",
"BACKGROUND A number of diet and exercise programs purport to help promote and maintain weight loss . However , few studies have compared the efficacy of different methods . OBJECTIVE To determine whether adherence to a meal-replacement-based diet program ( MRP ) with encouragement to increase physical activity is as effective as following a more structured meal-plan-based diet and supervised exercise program ( SDE ) in sedentary obese women . DESIGN R and omized comparative effectiveness trial . PARTICIPANTS / SETTING From July 2007 to October 2008 , 90 obese and apparently healthy women completed a 10-week university-based weight loss trial while 77 women from this cohort also completed a 24-week weight maintenance phase . INTERVENTION Participants were matched and r and omized to participate in an MRP or SDE program . MAIN OUTCOME MEASURES Weight loss , health , and fitness-related data were assessed at 0 and 10 weeks on all subjects as well as at 14 , 22 , and 34 weeks on participants who completed the weight maintenance phase . STATISTICAL ANALYSES PERFORMED Data were analyzed by multivariate analysis of variance for repeated measures . RESULTS During the 10-week weight loss phase , moderate and vigorous physical activity levels were significantly higher in the SDE group with no differences observed between groups in daily energy intake . The SDE group lost more weight ( -3.1 ± 3.7 vs -1.6 ± 2.5 kg ; P = 0.03 ) ; fat mass ( -2.3 ± 3.5 vs -0.9 ± 1.6 kg ; P = 0.02 ) ; centimeters from the hips ( -4.6 ± 7 vs -0.2 ± 6 cm ; P = 0.002 ) and waist ( -2.9 ± 6 vs -0.6 ± 5 cm ; P = 0.05 ) ; and , experienced a greater increase in peak aerobic capacity than participants in the MRP group . During the 24-week maintenance phase , participants in the SDE group maintained greater moderate and vigorous physical activity levels , weight loss , fat loss , and saw greater improvement in maximal aerobic capacity and strength . CONCLUSIONS In sedentary and obese women , an SDE-based program appears to be more efficacious in promoting and maintaining weight loss and improvements in markers of health and fitness compared to an MRP type program with encouragement to increase physical activity",
"BACKGROUND It has been reported that adequate calcium intake decreases body fat and appropriate intakes of magnesium suppress the development of the metabolic syndrome . Furthermore , lactulose increases the absorption of calcium and magnesium . An optimal combination of calcium , magnesium and lactulose may therefore reduce body fat mass . METHODS An open-label r and omized controlled trial was conducted to investigate the body fat-reducing effects of a test food containing 300 mg calcium , 150 mg magnesium , and 4.0 g lactulose . Body composition parameters and blood hormone and urine mineral concentrations were measured at baseline and at 6 and 12 months thereafter . Whole-body fat mass was measured with dual-energy x-ray absorptiometry . RESULTS Seventy-six middle-aged Japanese women ( 47.5±4.7 years ) were r and omized to the intake group ( n=48 ) or the non-intake control group ( n=28 ) . At 12 months the difference in body fat mass change between the two groups ( intake group - control group ) was -0.8 kg ( 95 % CI : -1.5 - 0.0 kg , p=0.046 ) , although there were no differences in anthropometric data between the two groups . Body fat percentage at 12 months tended to be lower in the intake group , but the difference was not significant ( p=0.09 ) . CONCLUSIONS These findings may suggest that calcium in combination with magnesium and lactulose can reduce body fat mass in middle-aged Japanese women . However , the contribution of magnesium and lactulose are unclear in this study . Further studies are needed to clarify these contributions",
"BACKGROUND Exercise intensity may affect the selective loss of abdominal adipose tissue . OBJECTIVE This study showed whether aerobic exercise intensity affects the loss of abdominal fat and improvement in cardiovascular disease risk factors under conditions of equal energy deficit in women with abdominal obesity . DESIGN This was a r and omized trial in 112 overweight and obese [ body mass index ( in kg/m(2 ) ) : 25 - 40 ; waist circumference > 88 cm ] , postmenopausal women assigned to one of three 20-wk interventions of equal energy deficit : calorie restriction ( CR only ) , CR plus moderate-intensity aerobic exercise ( CR + moderate-intensity ) , or CR plus vigorous-intensity exercise ( CR + vigorous-intensity ) . The diet was a controlled program of underfeeding during which meals were provided at individual calorie levels ( approximately 400 kcal/d ) . Exercise ( 3 d/wk ) involved treadmill walking at an intensity of 45 - 50 % ( moderate-intensity ) or 70 - 75 % ( vigorous-intensity ) of heart rate reserve . The primary outcome was abdominal visceral fat volume . RESULTS Average weight loss for the 95 women who completed the study was 12.1 kg ( + /-4.5 kg ) and was not significantly different across groups . Maximal oxygen uptake ( O(2)max ) increased more in the CR + vigorous-intensity group than in either of the other groups ( P lean mass than did either exercise group ( P abdominal visceral fat ( approximately 25 % ; P visceral fat were inversely related to increases in O(2)max ( P Changes in lipids , fasting glucose or insulin , and 2-h glucose and insulin areas during the oral-glucose-tolerance test were similar across treatment groups . CONCLUSION With a similar amount of total weight loss , lean mass is preserved , but there is not a preferential loss of abdominal fat when either moderate- or vigorous-intensity aerobic exercise is performed during caloric restriction . This trial was registered at ( Clinical Trials.gov ) as : NCT00664729",
"Background / objectives : Weight loss in obesity can reduce morbidity and mortality and benefits persist as long as weight loss is maintained . Weight maintenance is difficult in the long term and new strategies need to be developed to achieve this goal . We aim ed to evaluate the efficacy of substituting a low-calorie diet formula for a meal in a weight loss program during the maintenance phase . Methods : R and omized paralleled clinical trial including 62 adult patients with at least a 5 % weight loss with diet alone for 6 months , r and omized to two groups : daily replacement of one meal with a low-calorie diet formula , or dieting alone for another 6 months ( weight maintenance phase ) . Results : Weight maintenance or further weight loss occurred in 83.9 % of patients in the intervention group , whereas only in 58.1 % in the control group ( P=0.025 ) . As a whole , patients in the intervention group lost a further 3.2±3.7 % of initial weight compared with a 1.3±3.6 % in the control group ( P=0.030 ) . Body fat mass diminished in both groups , with no differences between them ( 1.6±3.5 vs 1.0±9.3 kg , respectively , P=0.239 ) , and the same happened with free fat mass ( 0.9±3.3 vs 0.4±6.7 kg , respectively , P=0.471 ) . A multivariate logistic regression analysis ( R 2=0.114 , P=0.023 ) retained only the intervention as a predictor of the achievement of weight maintenance with an odds ratio ( 95 % confidence interval ) of 3.756 ( 1.138–12.391 ) . Conclusions : Substitution of a low-calorie diet formula for a meal is an effective measure for weight loss maintenance compared with dieting alone",
"UNLABELLED Clinical research on weight management in young women is limited . This r and omized controlled trial compared the efficacy of two iso-energetically restricted ( 5600 kJ ) diets [ higher protein ( HP ) : 32 % protein , 41 % carbohydrate , 25 % fat or higher carbohydrate ( HC ) : 20 , 58 , 21 % , respectively ] in 71 ( HP : n = 36 ; HC : n = 35 ) young healthy women ( 18 - 25 years ; body mass index ≥ 27.5 kg/m2 ) for weight ( kg ; percent weight loss ) , body composition , metabolic and iron changes assessed at baseline , 6 and 12 months . DATA mean ( 95 % CI ) . In HP completers at 6 months , percent weight loss was higher [ HP : 9.3 ( 5.6 - 13.1 ) ; HC : 5.1 (2.3 - 7.9)% ; p = 0.06 ] ; although , this did not reach statistical significance . Absolute weight [ HP : 8.9 ( 5.3 - 12.5 ) ; HC : 4.6 ( 2.2 - 7.0 ) kg ; p = 0.034 ] and fat loss [ HP : 8.0 ( 4.4 - 11.5 ) ; HC : 3.4 ( 1.3 - 5.6 ) kg ; p = 0.022 ] were significantly greater . No significant between-diet differences were observed at 12 months . Biochemistry remained within normal ranges with HP showing superior preservation of ferritin at 6 months [ HP : 53 ( 40 - 66 ) ; HC : 46 ( 30 - 61 ) µg/l ; p = 0.029 ] . Both diets supported clinical ly meaningful weight loss with HP tending to be more effective in the medium-term",
"BACKGROUND Weight loss reduces body fat and lean mass , but whether these changes are influenced by macronutrient composition of the diet is unclear . OBJECTIVE We determined whether energy-reduced diets that emphasize fat , protein , or carbohydrate differentially reduce total , visceral , or hepatic fat or preserve lean mass . DESIGN In a subset of participants in a r and omized trial of 4 weight-loss diets , body fat and lean mass ( n = 424 ; by using dual-energy X-ray absorptiometry ) and abdominal and hepatic fat ( n = 165 ; by using computed tomography ) were measured after 6 mo and 2 y. Changes from baseline were compared between assigned amounts of protein ( 25 % compared with 15 % ) and fat ( 40 % compared with 20 % ) and across 4 carbohydrate amounts ( 35 % through 65 % ) . RESULTS At 6 mo , participants lost a mean ( ±SEM ) of 4.2 ± 0.3 kg ( 12.4 % ) fat and 2.1 ± 0.3 kg ( 3.5 % ) lean mass ( both P ) abdominal fat : 1.5 ± 0.2 kg ( 13.6 % ) subcutaneous fat and 0.9 ± 0.1 kg ( 16.1 % ) visceral fat ( all P Women lost more visceral fat than did men relative to total-body fat loss . Participants regained ~40 % of these losses by 2 y , with no differences between diets ( P ≥ 0.23 ) . Weight loss reduced hepatic fat , but there were no differences between groups ( P ≥ 0.28 ) . Dietary goals were not fully met ; self-reported contrasts were closer to 2 % protein , 8 % fat , and 14 % carbohydrate at 6 mo and 1 % , 7 % , and 10 % , respectively , at 2 y. CONCLUSION Participants lost more fat than lean mass after consumption of all diets , with no differences in changes in body composition , abdominal fat , or hepatic fat between assigned macronutrient amounts . This trial was registered at clinical trials.gov as NCT00072995",
"BACKGROUND Family and friend participation may provide culturally salient social support for weight loss in African American adults . METHODS SHARE ( Supporting Healthy Activity and eating Right Everyday ) was a 2-year trial of a culturally specific weight loss program . African American women and men who enrolled alone ( individual stratum , 63 index participants ) or together with 1 or 2 family members or friends ( family stratum , 130 index participants ) were r and omized , within strata , to high or low social support treatments ; 90 % were female . RESULTS At 6 months , the family index participants lost approximately 5 to 6 kg ; the individual index participants lost approximately 3 to 4 kg . The mean weight change was not different in high vs low social support in either stratum and generally not when high or low support treatments were compared across strata . The overall intention-to-treat mean weight change at 24 months was -2.4 kg ( 95 % confidence interval , -3.3 kg to -1.5 kg ) . The family index participant weight loss was greater among the participants whose partners attended more personally tailored counseling sessions at 6 months in the high-support group and at 6 , 12 , and 24 months in the low-support group ( all P percentage of weight loss of the family index participants was greater if partners lost at least 5 % vs less than 5 % of their baseline weight ( respectively , -6.1 % vs -2.9 % [ P = .004 ] , high support ; and -6.1 % vs -3.1 % [ P = .01 ] , low support ) . CONCLUSIONS Being assigned to participate with family members , friends , or other group members had no effect on weight change . Enrolling with others was associated with greater weight loss only when partners participated more and lost more weight . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00146081"
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BACKGROUND Aspirin is the prophylactic antiplatelet drug of choice for people with cardiovascular disease . Adding a second antiplatelet drug to aspirin may produce additional benefit for people at high risk and people with established cardiovascular disease . This is an up date to a previously published review from 2011 . OBJECTIVES To review the benefit and harm of adding clopidogrel to aspirin therapy for preventing cardiovascular events in people who have coronary disease , ischaemic cerebrovascular disease , peripheral arterial disease , or were at high risk of atherothrombotic disease , but did not have a coronary stent . SEARCH METHODS We up date d the search es of CENTRAL ( 2017 , Issue 6 ) , MEDLINE ( Ovid , 1946 to 4 July 2017 ) and Embase ( Ovid , 1947 to 3 July 2017 ) on 4 July 2017 . We also search ed Clinical Trials.gov and the WHO ICTRP portal , and h and search ed reference lists . We applied no language restrictions . SELECTION CRITERIA We included all r and omised controlled trials comparing over 30 days use of aspirin plus clopidogrel with aspirin plus placebo or aspirin alone in people with coronary disease , ischaemic cerebrovascular disease , peripheral arterial disease , or at high risk of atherothrombotic disease . We excluded studies including only people with coronary drug-eluting stent ( DES ) or non-DES , or both . DATA COLLECTION AND ANALYSIS We collected data on mortality from cardiovascular causes , all-cause mortality , fatal and non-fatal myocardial infa rct ion , fatal and non-fatal ischaemic stroke , major and minor bleeding . The overall treatment effect was estimated by the pooled risk ratio ( RR ) with 95 % confidence interval ( CI ) , using a fixed-effect model ( Mantel-Haenszel ) ; we used a r and om-effects model in cases of moderate or severe heterogeneity ( I2 ≥ 30 % ) . We assessed the quality of the evidence using the GRADE approach . We used GRADE profiler ( GRADE Pro ) to import data from Review Manager to create a ' Summary of findings ' table . MAIN RESULTS The search identified 13 studies in addition to the two studies in the previous version of our systematic review . Overall , we included data from 15 trials with 33,970 people . We completed a ' Risk of bias ' assessment for all studies . The risk of bias was low in four trials because they were at low risk of bias for all key domains ( r and om sequence generation , allocation concealment , blinding , selective outcome reporting and incomplete outcome data ) , even if some of them were funded by the pharmaceutical industry . Analysis showed no difference in the effectiveness of aspirin plus clopidogrel in preventing cardiovascular mortality ( RR 0.98 , 95 % CI 0.88 to 1.10 ; participants = 31,903 ; studies = 7 ; moderate quality evidence ) , and no evidence of a difference in all-cause mortality ( RR 1.05 , 95 % CI 0.87 to 1.25 ; participants = 32,908 ; studies = 9 ; low quality evidence ) .There was a lower risk of fatal and non-fatal myocardial infa rct ion with clopidogrel plus aspirin compared with aspirin plus placebo or aspirin alone ( RR 0.78 , 95 % CI 0.69 to 0.90 ; participants = 16,175 ; studies = 6 ; moderate quality evidence ) . There was a reduction in the risk of fatal and non-fatal ischaemic stroke ( RR 0.73 , 95 % CI 0.59 to 0.91 ; participants = 4006 ; studies = 5 ; moderate quality evidence ) .However , there was a higher risk of major bleeding with clopidogrel plus aspirin compared with aspirin plus placebo or aspirin alone ( RR 1.44 , 95 % CI 1.25 to 1.64 ; participants = 33,300 ; studies = 10 ; moderate quality evidence ) and of minor bleeding ( RR 2.03 , 95 % CI 1.75 to 2.36 ; participants = 14,731 ; studies = 8 ; moderate quality evidence ) .Overall , we would expect 13 myocardial infa rct ions and 23 ischaemic strokes be prevented for every 1000 patients treated with the combination in a median follow-up period of 12 months , but 9 major bleeds and 33 minor bleeds would be caused during a median follow-up period of 10.5 and 6 months , respectively . AUTHORS ' CONCLUSIONS The available evidence demonstrates that the use of clopidogrel plus aspirin in people at high risk of cardiovascular disease and people with established cardiovascular disease without a coronary stent is associated with a reduction in the risk of myocardial infa rct ion and ischaemic stroke , and an increased risk of major and minor bleeding compared with aspirin alone . According to GRADE criteria , the quality of evidence was moderate for all outcomes except all-cause mortality ( low quality evidence ) and adverse events ( very low quality evidence )
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"BACKGROUND Patients with transient ischaemic attack ( TIA ) or minor stroke are at high immediate risk of stroke . The optimum early treatment options for these patients are not known . METHODS Within 24 h of symptom onset , we r and omly assigned , in a factorial design , 392 patients with TIA or minor stroke to clopidogrel ( 300 mg loading dose then 75 mg daily ; 198 patients ) or placebo ( 194 patients ) , and simvastatin ( 40 mg daily ; 199 patients ) or placebo ( 193 patients ) . All patients were also given aspirin and were followed for 90 days . Descriptive analyses were done by intention to treat . The primary outcome was total stroke ( ischaemic and haemorrhagic ) within 90 days . Safety outcomes included haemorrhage related to clopidogrel and myositis related to simvastatin . This study is registered as an International St and ard R and omised Controlled Trial ( number 35624812 ) and with Clinical Trials.gov ( NCT00109382 ) . FINDINGS The median time to stroke outcome was 1 day ( range 0 - 62 days ) . The trial was stopped early due to a failure to recruit patients at the prespecified minimum enrolment rate because of increased use of statins . 14 ( 7.1 % ) patients on clopidogrel had a stroke within 90 days compared with 21 ( 10.8 % ) patients on placebo ( risk ratio 0.7 [ 95 % CI 0.3 - 1.2 ] ; absolute risk reduction -3.8 % [ 95 % CI -9.4 to 1.9 ] ; p=0.19 ) . 21 ( 10.6 % ) patients on simvastatin had a stroke within 90 days compared with 14 ( 7.3 % ) patients on placebo ( risk ratio 1.3 [ 0.7 - 2.4 ] ; absolute risk increase 3.3 % [ -2.3 to 8.9 ] ; p=0.25 ) . The interaction between clopidogrel and simvastatin was not significant ( p=0.64 ) . Two patients on clopidogrel had intracranial haemorrhage compared with none on placebo ( absolute risk increase 1.0 % [ -0.4 to 2.4 ] ; p=0.5 ) . There was no difference between groups for the simvastatin safety outcomes . INTERPRETATION Immediately after TIA or minor stroke , patients are at high risk of stroke , which might be reduced by using clopidogrel in addition to aspirin . The haemorrhagic risks of the combination of aspirin and clopidogrel do not seem to offset this potential benefit . We were unable to provide evidence of benefit of simvastatin in this setting . This aggressive prevention approach merits further study",
"BACKGROUND Clopidogrel therapy has recently been shown to reduce cardiovascular events in patients with stable vascular disease . This benefit may be due to effects not exclusively related to platelet aggregation . The aim of this study was to evaluate the effect of clopidogrel therapy on microvascular endothelial function in subjects with stable coronary artery disease ( CAD ) . METHODS AND RESULTS Forty subjects with stable CAD were r and omised to clopidogrel therapy ( 75mg/day ) or control . Blood and endothelial function testing occurred at baseline , one week and three months following r and omisation . Microvascular endothelial function was assessed via reactive hyperaemic index ( RHI ) . Platelet function was assessed by adenosine diphosphate (ADP)-induced whole blood aggregation and the VerifyNow ™ system . Plasma markers of endothelial function ( asymmetric dimethylarginine , ADMA ) and oxidative stress ( myeloperoxidase , MPO ) were also tested . The primary endpoint was endothelial function assessment ( RHI ) at three months . At one week RHI increased by 20±10 % in the clopidogrel group ; this effect was maintained at three months ( 21±9 % increase from baseline ; P decrease in ADP-induced platelet aggregation and P2Y12 reaction units was observed in the clopidogrel therapy group ( P between endothelial function and platelet function testing in the clopidogrel therapy group . CONCLUSION Clopidogrel therapy is associated with improved microvascular endothelial function in patients with stable CAD . This effect is independent of its effects on ADP-induced platelet reactivity",
"Background The aim of this study was to analyze the benefits and safety associated with the combination therapy of clopidogrel and aspirin among minor stroke or transient ischemic attack patients treated within 12 hours . Methods and Results This was a sub analysis of the CHANCE ( Clopidogrel in High‐Risk Patients with Acute Nondisabling Cerebrovascular Events ) trial , mainly limited to the prespecified group of patients r and omized within 12 hours to either the combination of clopidogrel plus aspirin or aspirin alone . The primary outcome was ischemic stroke during 90‐day follow‐up . Recurrent ischemic stroke and progressive ischemic stroke were analyzed . Multivariable Cox modeling showed that r and omization within 12 hours was an independent predictor of ischemic stroke events ( hazard ratio [ 95 % CI ] 1.25 [ 1.04–1.49 ] , P=0.02 ) . Among 2573 patients r and omized within 12 hours , 282 ( 10.96 % ) patients had ischemic stroke events . Among them , 158 ( 12.34 % ) of 1280 patients taking aspirin experienced ischemic stroke compared with 124 ( 9.59 % ) of 1293 patients taking clopidogrel – aspirin ( P=0.02 ) . The dual antiplatelet was more effective than aspirin alone in reducing the risk of recurrent ischemic stroke ( 6.57 % versus 8.91 % , P=0.03 ) but not progressive ischemic stroke ( 3.02 % versus 3.43 % , P=0.28 ) . There was no significant difference in hemorrhagic events ( P=0.39 ) . Conclusions Among patients treated within 12 hours , the combination of clopidogrel and aspirin was more effective than aspirin alone in reducing the risk of recurrent ischemic stroke during the 90‐day follow‐up and did not increase the hemorrhagic risk . Clinical Trial Registration URL : https://www . clinical trials.gov/. Unique identifier : NCT00979589",
"OBJECTIVES We prospect ively assessed cardiac and pulmonary function in patients with stable coronary artery disease ( CAD ) treated with ticagrelor , clopidogrel , or placebo in the ONSET/OFFSET ( A Multi-Centre R and omised , Double-Blind , Double-Dummy Parallel Group Study of the Onset and Offset of Antiplatelet Effects of AZD6140 Compared With Clopidogrel and Placebo With Aspirin as Background Therapy in Patients With Stable Coronary Artery Disease ) study . BACKGROUND Ticagrelor reduces cardiovascular events more effectively than clopidogrel in patients with acute coronary syndromes . Dyspnea develops in some patients treated with ticagrelor , and it is not known whether this is associated with changes in cardiac or pulmonary function . METHODS In all , 123 stable aspirin-treated CAD patients r and omly received either ticagrelor ( 180 mg load , then 90 mg twice daily ; n=57 ) , clopidogrel ( 600 mg load , then 75 mg daily ; n=54 ) , or placebo ( n=12 ) for 6 weeks in a double-blind , double-dummy design . Electrocardiography , echocardiography , serum N-terminal pro-brain natriuretic peptide , and pulmonary function tests were performed before ( baseline ) and 6 weeks after drug administration and /or after development of dyspnea . RESULTS After drug administration , dyspnea was reported by 38.6 % , 9.3 % , and 8.3 % of patients in the ticagrelor , clopidogrel , and placebo groups , respectively ( p cardiac or pulmonary function parameters . CONCLUSIONS Dyspnea is commonly associated with ticagrelor therapy , but was not associated in this study with any adverse change in cardiac or pulmonary function . ( A Multi-Centre R and omised , Double-Blind , Double-Dummy Parallel Group Study of the Onset and Offset of Antiplatelet Effects of AZD6140 Compared With Clopidogrel and Placebo With Aspirin as Background Therapy in Patients With Stable Coronary Artery Disease [ ONSET/OFFSET ] ; NCT00528411 )",
"Background — The Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events ( CHANCE ) trial showed that the combined treatment of clopidogrel and aspirin decreases the 90-day risk of stroke without increasing hemorrhage in comparison with aspirin alone , but provided insufficient data to establish whether the benefit persisted over a longer period of time beyond the trial termination . We report the 1-year follow-up outcomes of this trial . Methods and Results — The trial was a r and omized , double-blind , placebo-controlled trial conducted at 114 centers in China . We r and omly assigned 5170 patients within 24 hours after onset of minor stroke or high-risk transient ischemic attack to clopidogrel-aspirin therapy ( loading dose of 300 mg of clopidogrel on day 1 , followed by 75 mg of clopidogrel per day for 90 days , plus 75 mg of aspirin per day for the first 21 days ) or to the aspirin-alone group ( 75 mg/d for 90 days ) . The primary outcome was stroke event ( ischemic or hemorrhagic ) during 1-year follow-up . Differences in outcomes between groups were assessed by using the Cox proportional hazards model . Stroke occurred in 275 ( 10.6 % ) patients in the clopidogrel-aspirin group , in comparison with 362 ( 14.0 % ) patients in the aspirin group ( hazard ratio , 0.78 ; 95 % confidence interval , 0.65–0.93 ; P=0.006 ) . Moderate or severe hemorrhage occurred in 7 ( 0.3 % ) patients in the clopidogrel-aspirin group and in 9 ( 0.4 % ) patients in the aspirin group ( P=0.44 ) . Conclusions — The early benefit of clopidogrel-aspirin treatment in reducing the risk of subsequent stroke persisted for the duration of 1-year of follow-up . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00979589",
"Background — The effects of dual antiplatelet therapy with aspirin and clopidogrel on the progression of native coronary artery disease after coronary artery bypass grafting are unknown . Methods and Results — In the Clopidogrel After Surgery for Coronary Artery DiseasE ( CASCADE ) trial , a total of 113 patients were r and omized to receive aspirin plus clopidogrel or aspirin plus placebo for 1 year after coronary artery bypass grafting . In this secondary analysis , the 92 patients who underwent preoperative and 1-year postoperative angiograms at 2 centers had each of their coronary stenoses grade d serially by using 6 thresholds ( grade 0 [ 0%–24 % ] , grade 1 [ 25%–37 % ] , grade 2 [ 38%–62 % ] , grade 3 [ 63%–82 % ] , grade 4 [ 83%–98 % ] , and grade 5 [ 99%–100 % ] ) . We compared the incidence and degree of evolving coronary artery disease between the 2 treatment groups . A total of 543 preoperative stenoses and occlusions were quantified and followed . At 1-year postoperatively , there were 103 evolving ( 94 worsened , 9 improved ) and 22 new lesions . The right coronary artery territory and sites proximal to a graft were more commonly associated with worsening coronary artery disease ( P⩽0.02 ) . There were no differences in clinical events between treatment groups , and the proportion of patients with evolving or new lesions was also similar ( 70 % versus 74 % , aspirin – clopidogrel versus aspirin – placebo , respectively ; P=0.8 ) . However , in evolving or new lesions , the mean grade change ( 1.1±1.0 versus 1.6±1.1 , respectively ; P=0.01 ) and the proportion of new occlusions ( 7 % versus 22 % ; P=0.02 ) were lower in the aspirin – clopidogrel group . Conclusions — The addition of clopidogrel to aspirin correlates with less worsening of native coronary artery disease 1 year after coronary artery bypass grafting . These findings may help guide post – coronary artery bypass grafting antiplatelet therapy . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00228423",
"Context The optimal aspirin dose for prevention of cardiovascular events is unknown . Contribution This post hoc analysis of CHARISMA trial data suggests no overall differences in efficacy or safety by aspirin dose . However , in the subgroup of patients r and omly assigned to clopidogrel , there was a hint of reduced efficacy and increased harm with higher doses . Caution Patients were not r and omly assigned to aspirin dose . Implication Lower aspirin doses ( 75 to 81 mg/d ) may optimize efficacy and safety for patients requiring aspirin for long-term prevention , especially those taking clopidogrel . The Editors Aspirin is the most widely used drug worldwide for the prevention of thrombotic cardiovascular events . Of note , the doses of aspirin used most often clinical ly or recommended in guidelines are based not on the results of trials design ed to identify the most efficacious or safest dose , but on a combination of historical precedents and trials in which specific doses of aspirin were m and ated by protocol . This practice has led to a wide range in aspirin doses ( 75 to 325 mg/d ) recommended by the U.S. Food and Drug Administration ( 1 ) for the management of cardiovascular disease in various population s. Although as little as 30 mg of aspirin daily is needed to fully inhibit platelet thromboxane production ( 2 ) , doses more than 10 times higher than this are routinely used in long-term prevention of cardiovascular disease . Because aspirin has been used clinical ly for more than a century and is a mainstay of therapy for patients who have or are at risk for atherosclerotic disease and other common ailments , its risks are often underappreciated . However , given that more than one third of U.S. adults are estimated to take aspirin daily for cardiovascular disease ( 3 ) , even a very small incidence of hemorrhagic complications places a large number of people at risk . Consistent with this is a recent analysis of hospitalizations for adverse drug effects that found aspirin to be one of the most common causal agents ( 4 ) . The gastrointestinal tract is the leading source of bleeding events in aspirin-treated patients because of inhibition of gastroprotective prostacyclins , with an excess risk for upper gastrointestinal complications of 5 cases per 1000 aspirin users per year ( 5 ) . Prospect i ve evaluation of aspirin-treated patients with coronary artery disease identified an incidence of upper gastrointestinal bleeding of 1.5 % per year , with substantial associated morbidity ( 6 ) . Because inhibition of gastric prostacyclin is dose-dependent and not maximal until a daily dose of about 1300 mg is reached ( 4 ) , minimizing the dose of aspirin to that needed to fully inhibit platelet thromboxane production would probably offer the greatest potential benefit with the lowest possible risk . In several observational studies of large prospect i ve trials , lower doses of aspirin ( bleeding events ( 8) . These favorable trends in efficacy and safety were confirmed in the CURE ( Clopidogrel in Unstable angina to prevent Recurrent Events ) trial ( 9 ) of dual antiplatelet therapy with clopidogrel plus aspirin versus placebo plus aspirin . On the basis of these results , the design of the CHARISMA ( Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization , Management and Avoidance ) trial ( 10 ) , which r and omly assigned 15603 patients at high risk for atherothrombotic events to clopidogrel or placebo in conjunction with aspirin , m and ated a daily aspirin dose of 75 to 162 mg . We performed a post hoc analysis of associations between investigator-determined daily aspirin dose and thrombotic and hemorrhagic outcomes in the prospect i ve CHARISMA trial . Methods The design , methods , and primary results of the CHARISMA study are reported elsewhere ( 10 ) . In brief , CHARISMA was a multicenter , double-blind , r and omized , placebo-controlled trial of long-term clopidogrel ( 75 mg/d ) treatment versus placebo in patients 45 years or older who had established atherosclerotic disease or were asymptomatic but at high risk because of a combination of risk factors . All patients also received low-dose aspirin therapy , which was limited by protocol to between 75 and 162 mg/d . Patients were excluded if they had an established indication for clopidogrel therapy , such as a recent acute coronary syndrome or stent implantation . Clinical follow-up was done at 1 , 3 , and 6 months and every 6 months thereafter until the end of the trial . The actual dose of aspirin being taken was confirmed at each evaluation . The ethics committee at each of the 768 participating hospitals worldwide , as well as the appropriate national ethics committee for each of the 32 participating countries , review ed and approved the study protocol . All patients provided written informed consent before enrollment . The primary efficacy end point was the first occurrence of myocardial infa rct ion , stroke , or cardiovascular death . The primary safety end point was severe or life-threatening bleeding according to the GUSTO-I ( Global Utilization of Streptokinase and TPA for Occluded coronary arteries ) criteria ( 11 ) : intracerebral bleeding or bleeding result ing in substantial hemodynamic compromise requiring treatment . A secondary safety end point was the combined incidence of severe or life-threatening bleeding or moderate bleeding by the GUSTO-I criteria , with moderate defined as bleeding requiring transfusion but not result ing in hemodynamic compromise ( 11 ) . Of note , patients believed to be at high risk for bleeding were excluded from enrollment . Aspirin dose was not r and omized ; rather , it was selected at the discretion of the treating physician . We prospect ively divided patients into 3 major groups according to clear demarcations in aspirin dose at baseline : less than 100 mg/d , represented almost entirely by doses of either 75 or 81 mg/d ; 100 mg/d ; and greater than 100 mg/d , represented by either 150 or 162 mg/d . We evaluated the relative efficacy and safety of the different doses of aspirin among all patients , and we evaluated the efficacy and safety end points between the treatment ( clopidogrel ) versus placebo groups by aspirin dose category . Statistical Analysis We performed all data analyses on the intention-to-treat population . We performed hypothesis tests by using 2-sided tests at the 5 % significance level . Baseline characteristics were compared by using chi-square tests for discrete variables and t tests for continuous variables . We calculated cumulative KaplanMeier estimates of the event rates and assessed differences in the unadjusted rates of primary efficacy and safety end points across the aspirin groups by using a 2-sided log-rank test . We used log-rank weights to compute a test for trend across aspirin dose categories . We estimated the treatment effect , measured by the hazard ratio and its 95 % CI , by using the Cox proportional hazards model . Multivariable modeling was performed to determine whether aspirin dose was independently associated with the primary efficacy and safety outcomes after controlling for potentially confounding factors . Because patients could have had more than 1 efficacy or safety event , we defined the time to the primary efficacy end point as the first occurrence of myocardial infa rct ion , stroke , or cardiovascular death . We defined the time to the primary safety end point as the first occurrence of severe or life-threatening bleeding according to the GUSTO-I criteria ( 11 ) . We selected variables for inclusion in the models on the basis of differences in baseline characteristics among patients in the 3 aspirin dose categories or their clinical relevance to the outcomes . Covariates included in the multivariable model for the primary efficacy end point were the continuous variables of age , weight , and systolic blood pressure and the categorical variables of sex ; race or ethnicity ( white or Hispanic vs. other ) ; hypertension ; hypercholesterolemia ; history of congestive heart failure ; previous myocardial infa rct ion ; previous stroke ; previous transient ischemic attack ; diabetes mellitus ; atrial fibrillation ; peripheral arterial disease ; diabetic nephropathy ; current smoking ; primary ( vs. secondary ) prevention and past use of statins , nitrates , and antiplatelet agents other than aspirin . We developed models with and without inclusion of interaction terms for r and omized treatment assignment by aspirin dose category . Adjustment variables in the multivariable model for the primary safety end point ( GUSTO-I severe or life-threatening bleeding ) included age and weight as continuous variables and the categorical variables of stable angina with multivessel disease , sex , race or ethnicity ( white or Hispanic vs. other ) , history of congestive heart failure , previous myocardial infa rct ion , previous stroke , previous transient ischemic attack , diabetes mellitus , atrial fibrillation , peripheral arterial disease , diabetic nephropathy , hypertension , hypercholesterolemia , primary prevention ( vs. secondary ) , and current smoking . We developed models with and without inclusion of interaction terms for r and omized treatment assignment by daily aspirin dose category . To adjust for geographical region without estimating its effect , we used region ( categorized as United States , Canada , Western Europe , Eastern Europe , Latin America , Asia and Australia , or Africa ) as a stratification variable in models for both end points . We assessed the interaction of aspirin dose and r and omized treatment in both models . We calculated and tested the difference between the maximum likelihood ratios with and without 2 interaction terms ( r and omized treatment assignment by daily aspirin dose of 100 mg and greater than 100 mg ) . We assessed proportional hazards by multiplying each covariate by the log of the time to the event . A Wald test was performed to test the linear hypotheses of the regression coefficients . The proportional",
"Background : Aspirin plus clopidogrel ( A+C ) may be more effective than aspirin only ( AO ) acutely after TIA and minor stroke , but the risk of bleeding in the acute phase is uncertain . We determined this risk , focusing particularly on aspirin-naïve patients . Methods : We studied consecutive referrals to the EXPRESS study clinic from 1/4/02 to 31/3/08 . A 30- to 90-day course of A+C was given to patients presenting acutely . Bleeding events were identified by face-to-face follow-up , diagnostic coding , and blood transfusion data . Unpublished data from the FASTER pilot trial were also studied . Results : Among 633 EXPRESS patients treated with aspirin ( + /– clopidogrel ) , there were 12 spontaneous bleeds ( 6 minor , 6 major/life-threatening ) within 90 days after assessment , with a higher risk for A+C vs. AO ( 8/247 vs. 4/386 , p = 0.047 overall ; 5/247 vs. 1/386 , p = 0.03 for major/life-threatening bleeds ) . The excess of major/life-threatening bleeds on A+C vs. AO was seen in aspirin-naïve patients , ( 4/137 vs. 0/273 , p = 0.01 ) , but not in prior-aspirin patients ( 1/110 vs. 1/113 , p = 0.98 ) . All symptomatic bleeds in the FASTER pilot also occurred in aspirin-naïve patients r and omized to A+C ( 6/104 vs. 0/94 , p = 0.03 ) . In a pooled analysis , major/life-threatening bleeding on A+C occurred in 9/241 aspirin-naïve patients ( 90-day risk = 4.8 % , 1.6–8.0 ) versus 1/204 prior-aspirin patients ( p = 0.009 ) . Conclusion : Although based on relatively few outcomes , the high risk of major bleeding on A+C acutely after TIA or minor stroke in aspirin-naïve patients is a cause for concern . The potential risk to patients is sufficient to m and ate detailed monitoring of bleeding risk in ongoing trials and stratify results by whether patients were aspirin-naïve",
"BACKGROUND Despite the use of aspirin , there is still a risk of ischaemic events after percutaneous coronary intervention ( PCI ) . We aim ed to find out whether , in addition to aspirin , pretreatment with clopidogrel followed by long-term therapy after PCI is superior to a strategy of no pretreatment and short-term therapy for only 4 weeks after PCI . METHODS 2658 patients with non-ST-elevation acute coronary syndrome undergoing PCI in the CURE study had been r and omly assigned double-blind treatment with clopidogrel ( n=1313 ) or placebo ( n=1345 ) . Patients were pretreated with aspirin and study drug for a median of 6 days before PCI during the initial hospital admission , and for a median of 10 days overall . After PCI , most patients ( > 80 % ) in both groups received open-label thienopyridine for about 4 weeks , after which study drug was restarted for a mean of 8 months . The primary endpoint was a composite of cardiovascular death , myocardial infa rct ion , or urgent target-vessel revascularisation within 30 days of PCI . The main analysis was by intention to treat . FINDINGS There were no drop-outs . 59 ( 4.5 % ) patients in the clopidogrel group had the primary endpoint , compared with 86 ( 6.4 % ) in the placebo group ( relative risk 0.70 [ 95 % CI 0.50 - 0.97 ] , p=0.03 ) . Long-term administration of clopidogrel after PCI was associated with a lower rate of cardiovascular death , myocardial infa rct ion , or any revascularisation ( p=0.03 ) , and of cardiovascular death or myocardial infa rct ion ( p=0.047 ) . Overall ( including events before and after PCI ) there was a 31 % reduction cardiovascular death or myocardial infa rct ion ( p=0.002 ) . There was less use of glycoprotein IIb/IIIa inhibitor in the clopidogrel group ( p=0.001 ) . At follow-up , there was no significant difference in major bleeding between the groups ( p=0.64 ) . INTERPRETATION In patients with acute coronary syndrome receiving aspirin , a strategy of clopidogrel pretreatment followed by long-term therapy is beneficial in reducing major cardiovascular events , compared with placebo",
"Purpose To present the 12-month results of a trial investigating the effects of dual antiplatelet therapy on target lesion revascularization ( TLR ) after balloon angioplasty ± stenting in the femoropopliteal segment . Methods A prospect i ve , r and omized , single-center , double-blinded and placebo-controlled clinical trial r and omly assigned 40 patients to receive pre- and postinterventional therapy with aspirin and clopidogrel . Another 40 patients received the same doses of aspirin and placebo instead of clopidogrel . Clopidogrel and placebo were stopped after 6 months , and patients remained on aspirin only . At 12 months after the intervention , 36 clopidogrel patients and 37 placebo patients were reevaluated . Results At 6 months , clopidogrel patients had significantly lower rates of TLR compared to placebo patients [ 2 ( 5 % ) vs. 8 ( 20 % ) , p=0.04 ] . After stopping clopidogrel/placebo after 6 months , there was no significant difference in TLR at 12 months after treatment [ 9 ( 25 % ) clopidogrel vs. 12 ( 32.4 % ) placebo , p=0.35 ] . Mortality was 0 vs. 1 in the placebo group at 6 months ( p=0.32 ) and 0 vs. 3 at 12 months ( p=0.08 ) . Conclusion In contrast to the first report of a reduction in the TLR at 6 months , this advantage of dual antiplatelet therapy does not persist after stopping clopidogrel . Prolonged dual therapy ( > 6 months ) should be considered in patients who are at high risk for restenosis",
"Background Despite the use of anti-platelet agents such as acetylsalicylic acid ( ASA ) and clopidogrel in coronary heart disease , some patients continue to suffer from atherothrombosis . This has stimulated development of platelet function assays to monitor treatment effects . However , it is still not recommended to change treatment based on results from platelet function assays . This study aim ed to evaluate the capacity of a static platelet adhesion assay to detect platelet inhibiting effects of ASA and clopidogrel . The adhesion assay measures several aspects of platelet adhesion simultaneously , which increases the probability of finding conditions sensitive for anti-platelet treatment . Methods With a r and omised cross-over design we evaluated the anti-platelet effects of ASA combined with clopidogrel as well as monotherapy with either drug alone in 29 patients with a recent acute coronary syndrome . Also , 29 matched healthy controls were included to evaluate intra-individual variability over time . Platelet function was measured by flow cytometry , serum thromboxane B2 (TXB2)-levels and by static platelet adhesion to different protein surfaces . The results were subjected to Principal Component Analysis followed by ANOVA , t-tests and linear regression analysis . Results The majority of platelet adhesion measures were reproducible in controls over time denoting that the assay can monitor platelet activity . Adenosine 5'-diphosphate (ADP)-induced platelet adhesion decreased significantly upon treatment with clopidogrel compared to ASA . Flow cytometric measurements showed the same pattern ( r2 = 0.49 ) . In opposite , TXB2-levels decreased with ASA compared to clopidogrel . Serum TXB2 and ADP-induced platelet activation could both be regarded as direct measures of the pharmacodynamic effects of ASA and clopidogrel respectively . Indirect pharmacodynamic measures such as adhesion to albumin induced by various soluble activators as well as SFLLRN-induced activation measured by flow cytometry were lower for clopidogrel compared to ASA . Furthermore , adhesion to collagen was lower for ASA and clopidogrel combined compared with either drug alone . Conclusion The indirect pharmacodynamic measures of the effects of ASA and clopidogrel might be used together with ADP-induced activation and serum TXB2 for evaluation of anti-platelet treatment . This should be further evaluated in future clinical studies where screening opportunities with the adhesion assay will be optimised towards increased sensitivity to anti-platelet treatment",
"The optimal duration of treatment with clopidogrel after percutaneous coronary intervention ( PCI ) with stent placement remains controversial . The R and omized Argentine Clopidogrel Stent ( RACS ) trial was a prospect i ve , r and omized , nonblinded study of 1,004 patients undergoing PCI who were r and omized after successful bare metal stent placement to 30 versus 180 days of clopidogrel ; all patients also received aspirin . Patients were eligible regardless of whether they had presented with ST-elevation myocardial infa rct ion ( MI ) , acute coronary syndrome , or stable angina . The primary end point was a composite of death , MI , and stroke at 180 days . Baseline clinical characteristics showed no differences between groups in terms of age , gender , history , risk factors , or incidence of diabetes ; 72 % presented with an acute coronary syndrome and 15 % had MI as the indication for PCI . At hospital discharge and 30 days , when the 2 groups received the same treatment , there were no significant differences between groups in frequency of death , MI , or stroke . However , from 30 days to 6 months , patients assigned to 6 months of clopidogrel reached the primary end point of death , MI , and stroke less frequently ( 4.99 % vs 1.74 % , p = 0.010 , relative risk decrease 65 % ) . No significant between-group differences were found in frequency of total bleeding ( 0.64 % vs 1.52 % , p = 0.34 ) for the control and study groups . In conclusion , after successful placement of a bare metal stent in a coronary artery , patients treated with 6 months of clopidogrel showed a trend toward fewer adverse events compared with those treated for 30 days",
"Background : There are limited data on the effect of dual antiplatelet treatment with clopidogrel plus aspirin in patients with ischemic cerebrovascular disease and intracranial and extracranial arteriostenosis . The aim of our study was to evaluate the efficacy and safety of aspirin plus clopidogrel in the treatment of ischemic cerebrovascular disease with intracranial and extracranial arteriostenosis . Methods : Patients with clinical ly evident acute cerebral infa rct ion or transient ischemic attack combined with intracranial and extracranial arteriostenosis ( greater than 50 % ) who were unsuitable or reluctance to perform stent implantation were enrolled in this study . We r and omly assigned these patients to receive clopidogrel ( 75 or 50 mg ) plus aspirin ( 100 mg ) or aspirin ( 100 mg ) once daily through 90 days , and followed them for 90 days . We examined the main endpoints including the recurrence of stroke , death from cardiovascular causes , and bleeding events . Results : In all , 200 patients were recruited and followed for 90 days . Ischemic stroke occurred in 6 patients ( 9.1 % ) treated with 50 mg clopidogrel and aspirin , 6 patients ( 9.1 % ) receiving 75 mg clopidogrel and aspirin , whereas 19 patients ( 27.9 % ) in the aspirin group ( aspirin alone vs copidogrel 50 mg plus aspirin ; 95 % confidence intervals 1.704–23.779 , P aspirin alone vs copidogrel 75 mg plus aspirin ; 95 % confidence intervals 1.190–13.240 , P hemorrhagic events among recipients ( 3 patients [ 2.3 % ] ) in the copidogrel plus aspirin group than aspirin recipients ( 0 patient [ 0 % ] ) , including 1 subcutaneous hemorrhage in the group of 50 mg clopidogrel and aspirin , doubling the number of nasal and gum bleeding in the group of 75 mg clopidogrel and aspirin ( P > 0.05 ) . No intracranial hemorrhage and gastro-intestinal hemorrhage occurred in these 3 groups . Conclusion : Accordingly , 50 mg clopidogrel plus aspirin , and 75 mg clopidogrel plus aspirin were all superior to aspirin alone as stroke prevention in patients with cerebral infa rct ion or transient ischemic attack combined with intracranial and extracranial arteriostenosis . The effect of secondary stroke prevention was similar between 50 mg clopidogrel plus aspirin and 75 mg clopidogrel plus aspirin . The therapy of 75 mg clopidogrel plus aspirin result ed in a worrisome tread in bleeding events",
"BACKGROUND Few r and omised clinical trials have investigated the use of antithrombotic drugs for early secondary prevention of stroke or transient ischaemic attack in patients with intracranial atherosclerotic stenosis . Microembolic signals , detected by transcranial doppler , are a surrogate marker of future stroke risk and have been used to show treatment efficacy in patients with extracranial carotid stenosis . We aim ed to investigate whether treatment with clopidogrel plus aspirin reduced the number of microembolic signals detected with transcranial doppler ultrasound compared with aspirin alone in patients with recent stroke . METHODS The clopidogrel plus aspirin for infa rct ion reduction in acute stroke or transient ischaemic attack patients with large artery stenosis and microembolic signals ( CLAIR ) trial was a r and omised , open-label , blinded-endpoint trial . Between Oct 28 , 2003 , and Nov 19 , 2008 , patients with acute ischaemic stroke or transient ischaemic attack who had symptomatic large artery stenosis in the cerebral or carotid arteries and in whom microembolic signals were present on transcranial doppler were r and omly assigned within 7 days of symptom onset to receive clopidogrel ( 300 mg for the first day , then 75 mg daily ) plus aspirin ( 75 - 160 mg daily ) or aspirin alone ( 75 - 160 mg daily ) for 7 days . Patients were r and omly assigned in blocks of four or six by use of a r and omisation website . Monitoring of microembolic signals on transcranial doppler was done on days 2 and 7 . The primary endpoint was the proportion of patients who had microembolic signals on day 2 . Analysis was by modified intention to treat . All analyses were done by an investigator masked to both patient identity and the day the recording was taken . This trial is registered with the Centre for Clinical Trials , Chinese University of Hong Kong , number CUHK_CCT00164 . FINDINGS 100 patients were r and omly assigned to clopidogrel plus aspirin ( n=47 ) or aspirin monotherapy ( n=53 ) . 93 of 100 patients had symptomatic intracranial stenosis in either the intracranial internal carotid artery or the middle cerebral artery : 45 of 46 in the dual therapy group and 48 of 52 in the monotherapy group . At day 2 , 14 of 45 patients in the dual therapy group and 27 of 50 patients in the monotherapy group for whom data were available had at least one microembolic signal on transcranial doppler ( relative risk reduction 42.4 % , 95 % CI 4.6 - 65.2 ; p=0.025 ) . Adverse events were similar in the two groups . No patients had intracranial or severe systemic haemorrhage , but two patients in the dual therapy group had minor haemorrhages . INTERPRETATION Combination therapy with clopidogrel and aspirin is more effective than aspirin alone in reducing microembolic signals in patients with predominantly intracranial symptomatic stenosis . Clinical trials are now warranted to investigate whether this combination treatment also results in a reduction in stroke incidence",
"Background Short course of dual antiplatelet therapy for early secondary prevention is a promising treatment for patients with minor stroke or transient ischemic attack at high risk of recurrence . Methods We examined the efficacy and safety of dual antiplatelets in patients with transient ischemic attack or minor stroke , defined as National Institute of Health Stroke Scale scores 0–3 , in a subgroup analysis of Clopidogrel plus aspirin versus Aspirin alone for Reducing embolization in patients with acute symptomatic cerebral or carotid artery stenosis ( CLAIR ) study . Microembolic signals on transcranial Doppler monitoring was used as surrogate marker for recurrent stroke risk . Patients with ≥1 microembolic signals at baseline were r and omized to receive dual therapy ( aspirin 75–160 mg daily and clopidogrel 300 mg day 1 then 75 mg daily ) or monotherapy ( aspirin 75–160 mg daily ) for seven-days . Results Sixty-five of 100 patients recruited had transient ischemic attack or minor stroke : 30 received dual therapy and 35 received monotherapy . Mean onset-to-r and omization was 2·3 days in dual therapy group and 3·2 days in monotherapy group ( P = 0·03 ) . At day 7 , the proportion of patients with ≥1 microembolic signals was 9 of 29 patients in dual therapy group and 18 of 34 patients in monotherapy group ( adjusted relative risk reduction 41·4 % , 95 % CI 29·8–51·1 , P 0·001 ) . The median number of microembolic signals on day 7 was 0 in dual therapy group and 1·0 in monotherapy group ( P = 0·046 ) . No patients had intracranial or severe systemic hemorrhage . Conclusions Early dual therapy with clopidogrel and aspirin reduces microembolic signals in patients with minor ischemic stroke or transient ischemic attack , without causing significant bleeding complications",
"Background — The optimal duration of dual-antiplatelet therapy and the risk-benefit ratio for long-term dual-antiplatelet therapy after coronary stenting remain poorly defined . We evaluated the impact of up to 6 versus 24 months of dual-antiplatelet therapy in a broad all-comers patient population receiving a balanced proportion of Food and Drug Administration – approved drug-eluting or bare-metal stents . Methods and Results — We r and omly assigned 2013 patients to receive bare-metal , zotarolimus-eluting , paclitaxel-eluting , or everolimus-eluting stent implantation . At 30 days , patients in each stent group were r and omly allocated to receive up to 6 or 24 months of clopidogrel therapy in addition to aspirin . The primary end point was a composite of death of any cause , myocardial infa rct ion , or cerebrovascular accident . The cumulative risk of the primary outcome at 2 years was 10.1 % with 24-month dual-antiplatelet therapy compared with 10.0 % with 6-month dual-antiplatelet therapy ( hazard ratio , 0.98 ; 95 % confidence interval , 0.74–1.29 ; P=0.91 ) . The individual risks of death , myocardial infa rct ion , cerebrovascular accident , or stent thrombosis did not differ between the study groups ; however , there was a consistently greater risk of hemorrhage in the 24-month clopidogrel group according to all prespecified bleeding definitions , including the recently proposed Bleeding Academic Research Consortium classification . Conclusions — A regimen of 24 months of clopidogrel therapy in patients who had received a balanced mixture of drug-eluting or bare-metal stents was not significantly more effective than a 6-month clopidogrel regimen in reducing the composite of death due to any cause , myocardial infa rct ion , or cerebrovascular accident . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00611286",
"Background — Evidence for efficacy of dual antiplatelet therapy in stroke is limited . Symptomatic carotid stenosis patients are at high risk of early recurrent stroke . In this group , asymptomatic microembolic signals ( MES ) , detected by transcranial Doppler ultrasound ( TCD ) , are markers of future stroke and transient ischemic attack ( TIA ) risk . They offer a surrogate marker to evaluate antiplatelet therapy , but no multicenter study has evaluated the feasibility of this approach . Methods and Results —Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis ( CARESS ) is a r and omized , double-blind study in subjects with recently symptomatic ≥50 % carotid stenosis . Patients were screened with TCD , and if MES were detected , they were r and omized to clopidogrel and aspirin or aspirin monotherapy . Repeated TCD recordings were made on days 2 and 7 . MES were detected in 110 of 230 patients by online analysis at baseline , of whom 107 were r and omized . Intention-to-treat analysis revealed a significant reduction in the primary end point : 43.8 % of dual-therapy patients were MES positive on day 7 , as compared with 72.7 % of monotherapy patients ( relative risk reduction 39.8 % ; 95 % CI , 13.8 to 58.0 ; P=0.0046 ) . The secondary end point of MES frequency per hour was reduced ( compared with baseline ) by 61.4 % ( 95 % CI , 31.6 to 78.2 ; P=0.0013 ) in the dual-therapy group at day 7 and by 61.6 % ( 95 % CI , 34.9 to 77.4 ; P=0.0005 ) on day 2 . There were 4 recurrent strokes and 7 TIAs in the monotherapy group versus no stroke and 4 TIAs in the dual-therapy group that were treatment emergent and ipsilateral to the qualifying carotid stenosis ; 2 additional ipsilateral TIAs occurred before treatment started . MES frequency was greater in the 17 patients with recurrent ipsilateral events compared with the 90 without ( mean±SD : 24.4±27.7 versus 8.9±11.5 per hour ; P=0.0003 ) . Conclusions —In patients with recently symptomatic carotid stenosis , combination therapy with clopidogrel and aspirin is more effective than aspirin alone in reducing asymptomatic embolization . Doppler MES detection is a feasible method to evaluate the efficacy of antiplatelet therapy in multicenter studies",
"Background — The optimal duration of dual antiplatelet therapy ( DAPT ) after implantation of drug-eluting coronary stents remains undetermined . We aim ed to test whether 6-month DAPT would be noninferior to 12-month DAPT after implantation of drug-eluting stents . Methods and Results — We r and omly assigned 1443 patients undergoing implantation of drug-eluting stents to receive 6- or 12-month DAPT ( in a 1:1 ratio ) . The primary end point was a target vessel failure , defined as the composite of cardiac death , myocardial infa rct ion , or ischemia-driven target vessel revascularization at 12 months . Rates of target vessel failure at 12 months were 4.8 % in the 6-month DAPT group and 4.3 % in the 12-month DAPT group ( the upper limit of 1-sided 95 % confidence interval , 2.4 % ; P=0.001 for noninferiority with a predefined noninferiority margin of 4.0 % ) . Although stent thrombosis tended to occur more frequently in the 6-month DAPT group than in the 12-month group ( 0.9 % versus 0.1 % ; hazard ratio , 6.02 ; 95 % confidence interval , 0.72–49.96 ; P=0.10 ) , the risk of death or myocardial infa rct ion did not differ in the 2 groups ( 2.4 % versus 1.9 % ; hazard ratio , 1.21 ; 95 % confidence interval , 0.60–2.47 ; P=0.58 ) . In the prespecified subgroup analysis , target vessel failure occurred more frequently in the 6-month DAPT group than in the 12-month group ( hazard ratio , 3.16 ; 95 % confidence interval , 1.42–7.03 ; P=0.005 ) among diabetic patients . Conclusions — Six-month DAPT did not increase the risk of target vessel failure at 12 months after implantation of drug-eluting stents compared with 12-month DAPT . However , the noninferiority margin was wide , and the study was underpowered for death or myocardial infa rct ion . Our results need to be confirmed in larger trials . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00698607",
"BACKGROUND Clopidogrel was superior to aspirin in patients with previous manifestations of atherothrombotic disease in the CAPRIE study and its benefit was amplified in some high-risk subgroups of patients . We aim ed to assess whether addition of aspirin to clopidogrel could have a greater benefit than clopidogrel alone in prevention of vascular events with potentially higher bleeding risk . METHODS We did a r and omised , double-blind , placebo-controlled trial to compare aspirin ( 75 mg/day ) with placebo in 7599 high-risk patients with recent ischaemic stroke or transient ischaemic attack and at least one additional vascular risk factor who were already receiving clopidogrel 75 mg/day . Duration of treatment and follow-up was 18 months . The primary endpoint was a composite of ischaemic stroke , myocardial infa rct ion , vascular death , or rehospitalisation for acute ischaemia ( including rehospitalisation for transient ischaemic attack , angina pectoris , or worsening of peripheral arterial disease ) . Analysis was by intention to treat , using logrank test and a Cox 's proportional-hazards model . FINDINGS 596 ( 15.7 % ) patients reached the primary endpoint in the group receiving aspirin and clopidogrel compared with 636 ( 16.7 % ) in the clopidogrel alone group ( relative risk reduction 6.4 % , [ 95 % CI -4.6 to 16.3 ] ; absolute risk reduction 1 % [ -0.6 to 2.7 ] ) . Life-threatening bleedings were higher in the group receiving aspirin and clopidogrel versus clopidogrel alone ( 96 [ 2.6 % ] vs 49 [ 1.3 % ] ; absolute risk increase 1.3 % [ 95 % CI 0.6 to 1.9 ] ) . Major bleedings were also increased in the group receiving aspirin and clopidogrel but no difference was recorded in mortality . INTERPRETATION Adding aspirin to clopidogrel in high-risk patients with recent ischaemic stroke or transient ischaemic attack is associated with a non-significant difference in reducing major vascular events . However , the risk of life-threatening or major bleeding is increased by the addition of aspirin",
"Background —Antiplatelet therapy and antithrombin therapy have been demonstrated to reduce the risk of cardiac events in patients presenting with acute coronary syndrome , yet all effective therapies also increase the risk of bleeding . Methods and Results —In the Clopidogrel in Unstable angina to prevent Recurrent ischemic Events ( CURE ) trial , 12 562 patients were r and omized to clopidogrel or placebo in addition to aspirin , and the primary outcome was cardiovascular ( CV ) death , myocardial infa rct ion ( MI ) , or stroke . The benefits were consistent among those undergoing percutaneous coronary intervention ( PCI ) [ 9.6 % for clopidogrel , 13.2 % for placebo ; relative risk ( RR ) , 0.72 ; 95 % CI , 0.57 to 0.90 ] , coronary artery bypass grafting ( CABG ) surgery ( 14.5 % for clopidogrel 16.2 % for placebo ; RR , 0.89 ; 95 % CI , 0.71 to 1.11 ) , and medical therapy only ( 8.1 % for clopidogrel , 10.0 % for placebo ; RR , 0.80 ; 95 % CI , 0.69 to 0.92 ; test for interaction among strata , 0.53 ) . For CABG during the initial hospitalization ( 530 for placebo , 485 for clopidogrel ) , the frequency of CV death , MI or stroke before CABG was 4.7 % for placebo and 2.9 % for clopidogrel ( RR , 0.56 ; 95 % CI , 0.29 to 1.08 ) . For the entire study , there was a 1 % excess of major bleeding but no significant excess of life-threatening bleeding . Among patients undergoing CABG , the rates of life-threatening bleeding were 5.6 % for clopidogrel and 4.2 % for placebo ( RR , 1.30 ; 95 % CI , 0.91 to 1.95 ; both nonsignificant ) . Conclusions —The benefits versus risks of early and long-term clopidogrel therapy ( freedom from CV death , MI , stroke , or life-threatening bleeding ) are similar in those undergoing revascularization ( CABG or PCI ) and in the study population as a whole . Overall , the benefits of starting clopidogrel on admission appear to outweigh the risks , even among those who proceed to CABG during the initial hospitalization",
"Objective The purpose of this study was to evaluate the long term effect of clopidogrel-based antiplatelet therapy on neointimal formation . Methods This study comprised 78 patients with typical stable angina pectoris or documented myocardial ischaemia , and with only one angiographic lesion in one native coronary artery undergoing successful stent implantation without predilatation with C-reactive protein levels ≤5 mg/l at 72 h after the procedure . All patients received dual antiplatelet therapy with 75 mg/day clopidogrel and 300 mg/day aspirin for four weeks . Clopidogrel was switched to isochronous placebo in half of the patients ( n=39 ) at the end of the fourth week . This allocation was maintained for 20 weeks , and at week 24 of the study , coronary angiography and intravascular ultrasound imaging were performed again in all cases in order to evaluate the changes that had occurred in the in-stent neointimal formation ; rates of restenosis were also recorded Results At the end of the follow-up period , angiographic stenosis diameter and restenosis rates were smaller in the clopidogrel group than in the placebo group ( 23.3 % versus 35.6 % , p=0.05 and 5.12 % versus 10.25 % ; p=0.03 respectively ) ; the intravascular ultrasonographic neointimal cross sectional area was also smaller in the clopidogrel group ( 3.6±2.7 mm2 versus 5.2±2.5 mm2 , p=0.03 ) . Conclusions Long-term clopidogrel administration significantly reduced neointimal formation at the stent site as well as reducing major clinical events in patients who did not develop high-risk systemic inflammatory response after percutaneous coronary intervention",
"UNLABELLED In general , obesity is associated with better outcome in patients undergoing percutaneous coronary interventions ( PCI ) . One small study has suggested that these patients do not achieve adequate platelet inhibition with clopidogrel and that this may shape clinical outcomes . We evaluated the relationship between body mass index ( BMI ) and clinical outcomes at 1 year following PCI in patients r and omized to clopidogrel or placebo in the CREDO trial . METHODS AND RESULTS BMI , baseline clinical characteristics and clopidogrel regimen were assessed in 2,116 patients . The primary study endpoint was the 1-year composite of death , MI or stroke . A total of 342 patients had low or normal BMI ( Obese patients were more likely to be young males with diabetes , hypertension and hyperlipidemia ( p Bleeding complications occurred in 38 % of low BMI , 32 % of overweight/obese , and 25 % of very obese patients ( p = 0.03 ) . R and omization to clopidogrel was associated with a 25 % risk reduction in 1-year death , MI or stroke events , as BMI increased by every 5 kg per m2 ( p = 0.009 ) . CONCLUSION In general , increasing BMI was associated with better efficacy and bleeding outcomes at 1 year in this nonurgent PCI population . R and omization to early- and long-term clopidogrel was associated with even further improvements in those with increasing BMI",
"OBJECTIVES The goal of this study was to evaluate shorter duration ( 3 months ) dual antiplatelet therapy ( DAPT ) after drug-eluting stent ( DES ) implantation . BACKGROUND There have been few published reports of prospect i ve r and omized clinical studies comparing the safety and efficacy of shorter duration DAPT after DES implantation . METHODS We r and omly assigned 2,117 patients with coronary artery stenosis into 2 groups according to DAPT duration and stent type : 3-month DAPT following Endeavor zotarolimus-eluting stent ( E-ZES ) implantation ( E-ZES+3-month DAPT , n=1,059 ) versus 12-month DAPT following the other DES implantation ( st and ard therapy , n=1,058 ) . We hypothesized that the E-ZES+3-month DAPT would be noninferior to the st and ard therapy for the primary composite endpoint ( cardiovascular death , myocardial infa rct ion , stent thrombosis , target\\vessel revascularization , or bleeding ) at 1 year . RESULTS The primary endpoint occurred in 40 ( 4.7 % ) patients assigned to E-ZES+3-month DAPT compared with 41 ( 4.7 % ) patients assigned to the st and ard therapy ( difference : 0.0 % ; 95 % confidence interval [ CI ] : -2.5 to 2.5 ; p=0.84 ; p composite rates of any death , myocardial infa rct ion , or stent thrombosis were 0.8 % and 1.3 % , respectively ( difference : -0.5 % ; 95 % CI : -1.5 to 0.5 ; p=0.48 ) . The rates of stent thrombosis were 0.2 % and 0.3 % , respectively ( difference : -0.1 % ; 95 % CI : -0.5 to 0.3 ; p=0.65 ) without its further occurrence after cessation of clopidogrel in the E-ZES+3-month DAPT group . The rates of target vessel revascularization were 3.9 % and 3.7 % , respectively ( difference : 0.2 % ; 95 % CI : -2.3 to 2.6 ; p=0.70 ) . CONCLUSIONS E-ZES+3-month DAPT was noninferior to the st and ard therapy with respect to the occurrence of the primary endpoint . ( REal Safety and Efficacy of a 3-month dual antiplatelet Therapy following E-ZES implantation [ RESET ] ; NCT01145079 )",
"BACKGROUND Clopidogrel resinate is a resinate complex of (+)-clopidogrel optical isomer , wherein the (+)-clopidogrel isomer binds to a water-soluble cation exchange resin via sulfonic acid groups . It was approved by the Korean Food and Drug Administration on the basis of a Phase I study that demonstrated the bioequivalence of clopidogrel resinate and clopidogrel bisulfate . However , there are no available data regarding efficacy and tolerability in patients with vascular disease . OBJECTIVE The goal of this study was to investigate the antiplatelet efficacy and tolerability of clopidogrel resinate in patients with coronary heart disease ( CHD ) or CHD-equivalent risks . METHODS This study was a Phase IV , r and omized , double-blind , double-dummy , parallel-group , noninferiority trial . We prospect ively recruited patients in 10 centers between March 2008 and July 2008 . Patients who had documented CHD or CHD-equivalent risks were r and omly assigned to 1 of 3 groups : group A , aspirin ( 100 mg ) + clopidogrel bisulfate placebo + clopidogrel resinate placebo ; group B , aspirin ( 100 mg ) + clopidogrel bisulfate placebo + clopidogrel resinate ( 75 mg ) ; or group C , aspirin ( 100 mg ) + clopidogrel bisulfate ( 75 mg ) + clopidogrel resinate placebo . The primary outcome was the percent P2Y(12 ) inhibition after medication , assessed by using a point-of-care assay . If the 1-sided 90 % upper confidence limit for the difference was less than the prespecified delta value ( -5.7 ) , clopidogrel resinate would be considered noninferior to clopidogrel bisulfate . The secondary outcome , the prevalence of adverse events ( AEs ) associated with study medications , was assessed at each visit by direct interview . RESULTS A total of 314 patients ( mean [ SD ] age , 62.2 [ 9.0 ] years ; male 63.7 % ; weight , 67.3 [ 13.6 ] kg [ range , 45 - 102 kg ] ; all Asian ) were enrolled , and 287 patients finished the study ( group A , n = 97 ; group B , n = 90 ; and group C , n = 100 ) . Eight patients took no study medications and were excluded from the tolerability and efficacy analyses . Nineteen patients discontinued the study because of protocol violation ( n = 15 ) , adverse events ( n = 3 ) , or voluntary withdrawal ( n = 1 ) and were excluded from the efficacy analysis . There were no significant differences in baseline clinical characteristics among the groups except for the frequency of a history of CHD ( group A , 85.4 % ; group B , 73.0 % ; and group C , 88.3 % ; P = 0.01 ) . Patients treated with either type of clopidogrel showed significant inhibition ( mean [ SD ] ) of P2Y(12 ) ( group A , -5.9 % [ 15.1 % ] ; group B , 23.4 % [ 21.9 % ] ; and group C , 19.5 % [ 23.8 % ] ; P clopidogrel resinate and clopidogrel bisulfate in the inhibition of P2Y(12 ) did not exceed the predetermined value for inferiority ( P for noninferiority , 0.02 ; 90 % CI , -0.9 to 10.3 ) . In the tolerability analysis , there was no mortality during the study period and no significant differences between groups in the frequency of AEs and serious AEs ( AEs : group A , 33.0 % ; group B , 26.0 % ; and group C , 23.3 % [ P = 0.27 ] ; serious AEs : group A , 1.0 % ; group B , 3.0 % ; and group C , 1.0 % [ P = 0.42 ] ) . One patient in group B underwent coronary stent implantation for treatment of stable angina . CONCLUSIONS In this small , selected Asian patient population , differences in the platelet inhibition efficacies of clopidogrel resinate and clopidogrel bisulfate did not exceed the predetermined limits for noninferiority . The differences in tolerability between the 2 drugs did not reach statistical significance",
"BACKGROUND Despite improvements in the emergency treatment of myocardial infa rct ion ( MI ) , early mortality and morbidity remain high . The antiplatelet agent clopidogrel adds to the benefit of aspirin in acute coronary syndromes without ST-segment elevation , but its effects in patients with ST-elevation MI were unclear . METHODS 45,852 patients admitted to 1250 hospitals within 24 h of suspected acute MI onset were r and omly allocated clopidogrel 75 mg daily ( n=22,961 ) or matching placebo ( n=22,891 ) in addition to aspirin 162 mg daily . 93 % had ST-segment elevation or bundle branch block , and 7 % had ST-segment depression . Treatment was to continue until discharge or up to 4 weeks in hospital ( mean 15 days in survivors ) and 93 % of patients completed it . The two prespecified co- primary outcomes were : ( 1 ) the composite of death , reinfa rct ion , or stroke ; and ( 2 ) death from any cause during the scheduled treatment period . Comparisons were by intention to treat , and used the log-rank method . This trial is registered with Clinical Trials.gov , number NCT00222573 . FINDINGS Allocation to clopidogrel produced a highly significant 9 % ( 95 % CI 3 - 14 ) proportional reduction in death , reinfa rct ion , or stroke ( 2121 [ 9.2 % ] clopidogrel vs 2310 [ 10.1 % ] placebo ; p=0.002 ) , corresponding to nine ( SE 3 ) fewer events per 1000 patients treated for about 2 weeks . There was also a significant 7 % ( 1 - 13 ) proportional reduction in any death ( 1726 [ 7.5 % ] vs 1845 [ 8.1 % ] ; p=0.03 ) . These effects on death , reinfa rct ion , and stroke seemed consistent across a wide range of patients and independent of other treatments being used . Considering all fatal , transfused , or cerebral bleeds together , no significant excess risk was noted with clopidogrel , either overall ( 134 [ 0.58 % ] vs 125 [ 0.55 % ] ; p=0.59 ) , or in patients aged older than 70 years or in those given fibrinolytic therapy . INTERPRETATION In a wide range of patients with acute MI , adding clopidogrel 75 mg daily to aspirin and other st and ard treatments ( such as fibrinolytic therapy ) safely reduces mortality and major vascular events in hospital , and should be considered routinely",
"BACKGROUND A substantial proportion of patients receiving fibrinolytic therapy for myocardial infa rct ion with ST-segment elevation have inadequate reperfusion or reocclusion of the infa rct -related artery , leading to an increased risk of complications and death . METHODS We enrolled 3491 patients , 18 to 75 years of age , who presented within 12 hours after the onset of an ST-elevation myocardial infa rct ion and r and omly assigned them to receive clopidogrel ( 300-mg loading dose , followed by 75 mg once daily ) or placebo . Patients received a fibrinolytic agent , aspirin , and when appropriate , heparin ( dispensed according to body weight ) and were scheduled to undergo angiography 48 to 192 hours after the start of study medication . The primary efficacy end point was a composite of an occluded infa rct -related artery ( defined by a Thrombolysis in Myocardial Infa rct ion flow grade of 0 or 1 ) on angiography or death or recurrent myocardial infa rct ion before angiography . RESULTS The rates of the primary efficacy end point were 21.7 percent in the placebo group and 15.0 percent in the clopidogrel group , representing an absolute reduction of 6.7 percentage points in the rate and a 36 percent reduction in the odds of the end point with clopidogrel therapy ( 95 percent confidence interval , 24 to 47 percent ; P end point of death from cardiovascular causes , recurrent myocardial infa rct ion , or recurrent ischemia leading to the need for urgent revascularization by 20 percent ( from 14.1 to 11.6 percent , P=0.03 ) . The rates of major bleeding and intracranial hemorrhage were similar in the two groups . CONCLUSIONS In patients 75 years of age or younger who have myocardial infa rct ion with ST-segment elevation and who receive aspirin and a st and ard fibrinolytic regimen , the addition of clopidogrel improves the patency rate of the infa rct -related artery and reduces ischemic complications",
"BACKGROUND The potential benefits and risks of the use of dual antiplatelet therapy beyond a 12-month period in patients receiving drug-eluting stents have not been clearly established . METHODS In two trials , we r and omly assigned a total of 2701 patients who had received drug-eluting stents and had been free of major adverse cardiac or cerebrovascular events and major bleeding for a period of at least 12 months to receive clopidogrel plus aspirin or aspirin alone . The primary end point was a composite of myocardial infa rct ion or death from cardiac causes . Data from the two trials were merged for analysis . RESULTS The median duration of follow-up was 19.2 months . The cumulative risk of the primary outcome at 2 years was 1.8 % with dual antiplatelet therapy , as compared with 1.2 % with aspirin monotherapy ( hazard ratio , 1.65 ; 95 % confidence interval [ CI ] , 0.80 to 3.36 ; P=0.17 ) . The individual risks of myocardial infa rct ion , stroke , stent thrombosis , need for repeat revascularization , major bleeding , and death from any cause did not differ significantly between the two groups . However , in the dual-therapy group as compared with the aspirin-alone group , there was a nonsignificant increase in the composite risk of myocardial infa rct ion , stroke , or death from any cause ( hazard ratio , 1.73 ; 95 % CI , 0.99 to 3.00 ; P=0.051 ) and in the composite risk of myocardial infa rct ion , stroke , or death from cardiac causes ( hazard ratio , 1.84 ; 95 % CI , 0.99 to 3.45 ; P=0.06 ) . CONCLUSIONS The use of dual antiplatelet therapy for a period longer than 12 months in patients who had received drug-eluting stents was not significantly more effective than aspirin monotherapy in reducing the rate of myocardial infa rct ion or death from cardiac causes . These findings should be confirmed or refuted through larger , r and omized clinical trials with longer-term follow-up . ( Clinical Trials.gov numbers , NCT00484926 and NCT00590174 .",
"Background — Clopidogrel inhibits intimal hyperplasia in animal studies and therefore may reduce saphenous vein graft ( SVG ) intimal hyperplasia after coronary artery bypass grafting . The Clopidogrel After Surgery for Coronary Artery DiseasE ( CASCADE ) study was undertaken to evaluate whether the addition of clopidogrel to aspirin inhibits SVG disease after coronary artery bypass grafting , as assessed at 1 year by intravascular ultrasound . Methods and Results — In this double-blind phase II trial , 113 patients undergoing coronary artery bypass grafting with SVGs were r and omized to receive aspirin 162 mg plus clopidogrel 75 mg daily or aspirin 162 mg plus placebo daily for 1 year . The primary outcome was SVG intimal hyperplasia ( mean intimal area ) as determined by intravascular ultrasound at 1 year . Secondary outcomes were graft patency , major adverse cardiovascular events , and major bleeding . One-year intravascular ultrasound and coronary angiography were performed in 92 patients ( 81.4 % ) . At 1 year , SVG intimal area did not differ significantly between the 2 groups ( 4.1±2.0 versus 4.5±2.1 mm2 , aspirin-clopidogrel versus aspirin-placebo , P=0.44 ) . Overall 1-year graft patency was 95.2 % in the aspirin-clopidogrel group compared with 95.5 % in the aspirin-placebo group ( P=0.90 ) , and SVG patency was 94.3 % in the aspirin-clopidogrel group versus 93.2 % in the aspirin-placebo group ( P=0.69 ) . Freedom from major adverse cardiovascular events at 1 year was 92.9±3.4 % in the aspirin-clopidogrel group and 91.1±3.8 % in the aspirin-placebo group ( P=0.76 ) . The incidence of major bleeding at 1 year was similar for the 2 groups ( 1.8 % versus 0 % , aspirin-clopidogrel versus aspirin-placebo , P=0.50 ) . Conclusions — Compared with aspirin monotherapy , the combination of aspirin plus clopidogrel did not significantly reduce the process of SVG intimal hyperplasia 1 year after coronary artery bypass grafting . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00228423",
"BACKGROUND Antiplatelet drugs are recommended for patients with acute noncardioembolic stroke . However , few r and omized clinical trials have investigated the safety and efficacy of dual antiplatelet therapy for these patients . The aim of this study was to evaluate the effects of treatment with clopidogrel and aspirin ( combination therapy ) and aspirin alone ( monotherapy ) on neurologic deterioration , platelet activation , and other short-term outcomes in patients with acute large-artery atherosclerosis stroke . MATERIAL S AND METHODS Altogether 574 patients with acute ( ≤2 days ) large-artery atherosclerosis stroke were r and omly assigned to receive either combined clopidogrel and aspirin or aspirin alone . Platelet aggregation and platelet-leukocyte aggregation studies were performed at days 1 and 30 . Primary outcomes including recurrent ischemic stroke , neurologic deterioration , periphery vascular events , and myocardial infa rct ion were monitored . Safety endpoints were hemorrhagic episodes and death . RESULTS The prevalence of neurologic deterioration and recurrent ischemic stroke were lower in patients in the combination therapy group than in those of the monotherapy group ( 3.52 % versus 9.78 % and 1.76 % versus 6.29 % , respectively ) . At day 30 of treatment , the platelet aggregations and platelet-leukocyte aggregates were lower in patients who were treated with clopidogrel and aspirin than in patients given aspirin alone ( P patients with acute large-artery atherosclerosis stroke , treatment with clopidogrel and aspirin for 1 month provided significantly greater inhibition of platelet activity than aspirin alone . Thus , dual therapy can be safer and more effective in reducing ischemic stroke recurrence and neurologic deterioration ",
"BACKGROUND Reactive thrombocytosis has been reported in 20 % of patients after coronary artery bypass grafting ( CABG ) , a frequency that might be related to the high incidence of thrombotic complications . The present study was planned to investigate the effect of combined treatment with clopidogrel and acetylsalicylic acid ( ASA ) on post-CABG reactive thrombocytosis . METHODS Included in this prospect i ve , r and omized study were 60 patients who underwent CABG operation with a 6-month follow-up . Three study groups were defined : group 1 ( n = 20 ) , a control group of patients who have not developed reactive thrombocytosis after CABG surgery ; group 2 ( n = 20 ) , patients who have developed reactive thrombocytosis and continue taking ASA ( 300 mg/day ) ; and group 3 ( n = 20 ) , patients who have developed reactive thrombocytosis and continue taking ASA ( 300 mg/day ) with the addition of clopidogrel ( 75 mg/day ) . RESULTS The mean ages and sex distributions of the patient groups were similar . There were no significant differences between the groups regarding cardiovascular risk factors , baseline laboratory findings , or intraoperative characteristics . Thrombocytosis disappeared within the first month after the operation in both treatment groups . An evaluation of graft patency in the sixth postoperative month revealed that group 2 had significantly more patients with a \" positive \" result in the exercise test than group 3 and that group 3 had a lower incidence of graft occlusion than group 2 ( P Combination antiplatelet therapy with ASA and clopidogrel seems to be more effective than ASA alone for maintaining graft patency in patients with reactive thrombocytosis",
"Background —We studied the benefits and risks of adding clopidogrel to different doses of aspirin in the treatment of patients with acute coronary syndrome ( ACS ) . Methods and Results —In the Clopidogrel in Unstable angina to prevent Recurrent Events ( CURE ) trial , 12 562 patients with ACS using aspirin , 75 to 325 mg daily , were r and omized to clopidogrel or placebo for up to 1 year . In this analysis , patients were divided into the following 3 aspirin dose groups : ≤100 mg , 101 through 199 mg , and ≥200 mg . The combined incidence of cardiovascular death , myocardial infa rct ion , or stroke was reduced by clopidogrel regardless of aspirin dose , as follows : ≤100 mg , 10.5 % versus 8.6 % ( relative risk [ RR ] , 0.81 [ 95 % CI , 0.68 to 0.97 ] ) ; 101 to 199 mg , 9.8 % versus 9.5 % ( RR , 0.97 [ 95 % CI 0.77 to 1.22 ] ) ; and ≥200 mg , 13.6 % versus 9.8 % ( RR , 0.71 [ 95 % CI , 0.59 to 0.85 ] ) . The incidence of major bleeding increased with increasing aspirin dose both in the placebo group ( 1.9 % , 2.8 % , and 3.7 % , respectively ; P = 0.0001 ) and the clopidogrel group ( 3.0 % , 3.4 % , and 4.9 % , respectively ; P = 0.0009 ) ; thus , the excess risk with clopidogrel was 1.1 % , 1.2 % , and 1.2 % , respectively . The adjusted hazard ratio for major bleeding for the highest versus the lowest dose of aspirin was 1.9 ( 95 % CI 1.29 to 2.72 ) in the placebo group , 1.6 ( 95 % CI 1.19 to 2.23 ) in the clopidogrel group , and 1.7 ( 95 % CI 1.36 to 2.20 ) in the combined group . Conclusions —In patients with ACS , adding clopidogrel to aspirin is beneficial regardless of aspirin dose . Bleeding risks increase with increasing aspirin dose , with or without clopidogrel , without any increase in efficacy . Our findings suggest that the optimal daily dose of aspirin may be between 75 and 100 mg , with or without clopidogrel ",
"BACKGROUND Despite current treatments , patients who have acute coronary syndromes without ST-segment elevation have high rates of major vascular events . We evaluated the efficacy and safety of the antiplatelet agent clopidogrel when given with aspirin in such patients . METHODS We r and omly assigned 12,562 patients who had presented within 24 hours after the onset of symptoms to receive clopidogrel ( 300 mg immediately , followed by 75 mg once daily ) ( 6259 patients ) or placebo ( 6303 patients ) in addition to aspirin for 3 to 12 months . RESULTS The first primary outcome --a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , or stroke -- occurred in 9.3 percent of the patients in the clopidogrel group and 11.4 percent of the patients in the placebo group ( relative risk with clopidogrel as compared with placebo , 0.80 ; 95 percent confidence interval , 0.72 to 0.90 ; P --the first primary outcome or refractory ischemia -- occurred in 16.5 percent of the patients in the clopidogrel group and 18.8 percent of the patients in the placebo group ( relative risk , 0.86 ; 95 percent confidence interval , 0.79 to 0.94 ; P patients with in-hospital refractory or severe ischemia , heart failure , and revascularization procedures were also significantly lower with clopidogrel . There were significantly more patients with major bleeding in the clopidogrel group than in the placebo group ( 3.7 percent vs. 2.7 percent ; relative risk , 1.38 ; P=0.001 ) , but there were not significantly more patients with episodes of life-threatening bleeding ( 2.2 percent [ corrected ] vs. 1.8 percent ; P=0.13 ) or hemorrhagic strokes ( 0.1 percent vs. 0.1 percent ) . CONCLUSIONS The antiplatelet agent clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation . However , the risk of major bleeding is increased among patients treated with clopidogrel",
"BACKGROUND The hemoglobin threshold for transfusion of red cells in patients with acute gastrointestinal bleeding is controversial . We compared the efficacy and safety of a restrictive transfusion strategy with those of a liberal transfusion strategy . METHODS We enrolled 921 patients with severe acute upper gastrointestinal bleeding and r and omly assigned 461 of them to a restrictive strategy ( transfusion when the hemoglobin level fell below 7 g per deciliter ) and 460 to a liberal strategy ( transfusion when the hemoglobin fell below 9 g per deciliter ) . R and omization was stratified according to the presence or absence of liver cirrhosis . RESULTS A total of 225 patients assigned to the restrictive strategy ( 51 % ) , as compared with 61 assigned to the liberal strategy ( 14 % ) , did not receive transfusions ( P probability of survival at 6 weeks was higher in the restrictive- strategy group than in the liberal- strategy group ( 95 % vs. 91 % ; hazard ratio for death with restrictive strategy , 0.55 ; 95 % confidence interval [ CI ] , 0.33 to 0.92 ; P=0.02 ) . Further bleeding occurred in 10 % of the patients in the restrictive- strategy group as compared with 16 % of the patients in the liberal- strategy group ( P=0.01 ) , and adverse events occurred in 40 % as compared with 48 % ( P=0.02 ) . The probability of survival was slightly higher with the restrictive strategy than with the liberal strategy in the subgroup of patients who had bleeding associated with a peptic ulcer ( hazard ratio , 0.70 ; 95 % CI , 0.26 to 1.25 ) and was significantly higher in the subgroup of patients with cirrhosis and Child-Pugh class A or B disease ( hazard ratio , 0.30 ; 95 % CI , 0.11 to 0.85 ) , but not in those with cirrhosis and Child-Pugh class C disease ( hazard ratio , 1.04 ; 95 % CI , 0.45 to 2.37 ) . Within the first 5 days , the portal-pressure gradient increased significantly in patients assigned to the liberal strategy ( P=0.03 ) but not in those assigned to the restrictive strategy . CONCLUSIONS As compared with a liberal transfusion strategy , a restrictive strategy significantly improved outcomes in patients with acute upper gastrointestinal bleeding . ( Funded by Fundació Investigació Sant Pau ; Clinical Trials.gov number , NCT00414713 . )",
"Background —The risk of ischemic events is high , both early and late after acute coronary syndromes ( ACS ) . We examine the benefits and risks associated with the use of adding clopidogrel to aspirin within the first 30 days and later ( 31 days to 12 months ) in 12 562 patients with ACS . Methods and Results —A total of 12 562 ACS patients were r and omized to receive clopidogrel ( 300 mg initially followed by 75 mg/d ) or placebo for 3 to 12 months . The proportion of patients experiencing cardiovascular death , myocardial infa rct ion , or strokes ( primary outcome ) at 30 days was 5.4 % in the placebo group and 4.3 % in the active group ( relative risk 0.79 , 95 % CI 0.67 to 0.92 ) . Beyond 30 days , the corresponding rates were 6.3 % versus 5.2 % ( relative risk 0.82 , 95 % CI 0.70 to 0.95 ) . There was no significant excess in life-threatening bleeds in each period ( 0.97 % versus 1.28 % , relative risk 1.32 , 95 % CI 0.95 to 1.84 for 0 to 30 days ; 0.83 % versus 0.91 % , relative risk 1.09 , 95 % CI 0.75 to 1.59 for 31 days to 12 months ) . Further subdivision of the early data indicates benefits within 24 hours with consistently lower rates of the primary outcome in combination with refractory or severe ischemia . Conclusions —Clopidogrel reduces the risk of ischemic vascular events , with the benefits emerging within 24 hours of initiation of treatment and continuing throughout the 12 months ( mean 9 months ) of the study",
"Background —The Clopidogrel in Unstable angina to prevent Recurrent Events ( CURE ) trial demonstrated that clopidogrel , given early and continued long term , was superior to placebo in patients with non-ST – elevation acute coronary syndromes receiving aspirin . The purpose of the present analysis was to estimate the treatment effect Zof clopidogrel in patients who were stratified according to their risk of future cardiovascular events . Methods and Results — Patients ( n=12 562 ) who presented within 24 hours after the onset of symptoms were r and omized to receive clopidogrel ( 300 mg followed by 75 mg daily ) or placebo in addition to aspirin for 3 to 12 months . Treatment effect was analyzed in various risk groups according to the Thrombolysis in Myocardial Infa rct ion ( TIMI ) risk score . The TIMI risk model was vali date d in the CURE population ( C statistic , 0.634 ) . The primary composite outcome of cardiovascular death , myocardial infa rct ion , or stroke increased proportionally with increasing risk according to the TIMI risk score . The impact of clopidogrel versus placebo on the rate of the primary outcome was as follows : low-risk group ( TIMI score 0 to 2 ) , 4.1 % versus 5.7 % ( relative risk [ RR ] , 0.71 ; 95 % confidence interval [ CI ] , 0.52 to 0.97;P clopidogrel demonstrated in the CURE trial is consistent in low- , intermediate- , and high-risk patients with acute coronary syndromes ( as stratified by TIMI risk score ) , thus supporting its use in all patients with documented non – ST elevation acute coronary syndromes",
"OBJECTIVES This study sought to determine the optimal timing of a 300-mg clopidogrel loading dose before percutaneous coronary intervention ( PCI ) in patients enrolled in the Clopidogrel for the Reduction of Events During Observation ( CREDO ) trial . BACKGROUND A loading dose of clopidogrel before a PCI has become relatively commonplace , although the data supporting this practice are limited and sometimes conflicting . METHODS Patients were r and omized to receive either 300 mg clopidogrel or a matching placebo administered a minimum of 3 h and a maximum of 24 h before PCI . The primary 28-day combined end point was death , myocardial infa rct ion , or urgent target vessel revascularization . Linear splines were used to summarize the effect of the time of pre-treatment as a continuous variable . RESULTS A total of 1,762 patients were evaluated . For patients r and omized to placebo , there was no relationship between the duration of pre-treatment and the occurrence of the primary end point , whereas longer duration s of pre-treatment in patients r and omized to clopidogrel were associated with improved outcomes . The event rates diverged maximally at 24 h. The difference in outcomes between placebo and clopidogrel pre-treated patients was not significant until > or = 15 h pre-treatment , with a 58.8 % ( p = 0.028 ) reduction in the primary end point in patients pre-treated with clopidogrel > or = 15 h compared with placebo . CONCLUSIONS When a 300-mg loading dose of clopidogrel is used , little benefit is obtained compared with just 75 mg at the time of the PCI when the treatment duration is < 12 h. In patients pre-treated for longer duration s , the optimal duration seems to approach 24",
"OBJECTIVES We sought to evaluate the effect of aspirin plus clopidogrel versus aspirin alone on saphenous vein graft occlusion at 3 months after coronary artery bypass grafting ( CABG ) . BACKGROUND Prevalence of graft occlusion is high after CABG . Aggressive antiplatelet therapy is expected to improve early post-operative graft patency . METHODS From December 2007 through December 2008 , 249 consecutive patients undergoing elective CABG at Fuwai Hospital were r and omly assigned to 2 groups : 124 received aspirin ( 100 mg ) plus clopidogrel ( 75 mg ) daily ( AC group ) , and 125 received aspirin ( 100 mg ) alone daily ( A group ) . Antiplatelet therapies were initiated when post-operative chest tube drainage was ≤ 30 cc/h for 2 h. All participants were invited for clinical follow-up and 64-slice multislice computed tomography angiography ( MSCTA ) analysis at 3 months post-operatively . Generalized estimating equations analysis was used to determine predictors of graft patency . RESULTS One participant , from group A , died before 3-month follow-up . Of the remaining 248 patients , 224 ( 90.3 % ) underwent MSCTA . Participants had similar pre-operative and intraoperative characteristics at baseline . No significant differences were observed in intraoperative transit-time flow measurement findings or major adverse cardiac-related events . Three-month MSCTA follow-up revealed that saphenous vein graft patency was 91.6 % ( 219 of 239 ) in the AC group versus 85.7 % ( 198 of 231 ) in the A group ( p = 0.043 ) . In multivariate analysis , combined antiplatelet therapy independently increased venous graft patency ( p = 0.045 ) . CONCLUSIONS Aspirin plus clopidogrel is more effective in venous graft patency than aspirin alone in the short term after CABG , but further , long-term study is needed . ( The Clopidogrel and Aspirin After Surgery for Coronary Artery Disease ; NCT00776477 )",
"BACKGROUND The relative efficacy of streptokinase and tissue plasminogen activator and the roles of intravenous as compared with subcutaneous heparin as adjunctive therapy in acute myocardial infa rct ion are unresolved questions . The current trial was design ed to compare new , aggressive thrombolytic strategies with st and ard thrombolytic regimens in the treatment of acute myocardial infa rct ion . Our hypothesis was that newer thrombolytic strategies that produce earlier and sustained reperfusion would improve survival . METHODS In 15 countries and 1081 hospitals , 41,021 patients with evolving myocardial infa rct ion were r and omly assigned to four different thrombolytic strategies , consisting of the use of streptokinase and subcutaneous heparin , streptokinase and intravenous heparin , accelerated tissue plasminogen activator ( t-PA ) and intravenous heparin , or a combination of streptokinase plus t-PA with intravenous heparin . ( \" Accelerated \" refers to the administration of t-PA over a period of 1 1/2 hours -- with two thirds of the dose given in the first 30 minutes -- rather than the conventional period of 3 hours . ) The primary end point was 30-day mortality . RESULTS The mortality rates in the four treatment groups were as follows : streptokinase and subcutaneous heparin , 7.2 percent ; streptokinase and intravenous heparin , 7.4 percent ; accelerated t-PA and intravenous heparin , 6.3 percent , and the combination of both thrombolytic agents with intravenous heparin , 7.0 percent . This represented a 14 percent reduction ( 95 percent confidence interval , 5.9 to 21.3 percent ) in mortality for accelerated t-PA as compared with the two streptokinase-only strategies ( P = 0.001 ) . The rates of hemorrhagic stroke were 0.49 percent , 0.54 percent , 0.72 percent , and 0.94 percent in the four groups , respectively , which represented a significant excess of hemorrhagic strokes for accelerated t-PA ( P = 0.03 ) and for the combination strategy ( P death or disabling stroke was significantly lower in the accelerated-tPA group than in the streptokinase-only groups ( 6.9 percent vs. 7.8 percent , P = 0.006 ) . CONCLUSIONS The findings of this large-scale trial indicate that accelerated t-PA given with intravenous heparin provides a survival benefit over previous st and ard thrombolytic regimens",
"BACKGROUND Lacunar infa rcts are a frequent type of stroke caused mainly by cerebral small-vessel disease . The effectiveness of antiplatelet therapy for secondary prevention has not been defined . METHODS We conducted a double-blind , multicenter trial involving 3020 patients with recent symptomatic lacunar infa rcts identified by magnetic resonance imaging . Patients were r and omly assigned to receive 75 mg of clopidogrel or placebo daily ; patients in both groups received 325 mg of aspirin daily . The primary outcome was any recurrent stroke , including ischemic stroke and intracranial hemorrhage . RESULTS The participants had a mean age of 63 years , and 63 % were men . After a mean follow-up of 3.4 years , the risk of recurrent stroke was not significantly reduced with aspirin and clopidogrel ( dual antiplatelet therapy ) ( 125 strokes ; rate , 2.5 % per year ) as compared with aspirin alone ( 138 strokes , 2.7 % per year ) ( hazard ratio , 0.92 ; 95 % confidence interval [ CI ] , 0.72 to 1.16 ) , nor was the risk of recurrent ischemic stroke ( hazard ratio , 0.82 ; 95 % CI , 0.63 to 1.09 ) or disabling or fatal stroke ( hazard ratio , 1.06 ; 95 % CI , 0.69 to 1.64 ) . The risk of major hemorrhage was almost doubled with dual antiplatelet therapy ( 105 hemorrhages , 2.1 % per year ) as compared with aspirin alone ( 56 , 1.1 % per year ) ( hazard ratio , 1.97 ; 95 % CI , 1.41 to 2.71 ; P All-cause mortality was increased among patients assigned to receive dual antiplatelet therapy ( 77 deaths in the group receiving aspirin alone vs. 113 in the group receiving dual antiplatelet therapy ) ( hazard ratio , 1.52 ; 95 % CI , 1.14 to 2.04 ; P=0.004 ) ; this difference was not accounted for by fatal hemorrhages ( 9 in the group receiving dual antiplatelet therapy vs. 4 in the group receiving aspirin alone ) . CONCLUSIONS Among patients with recent lacunar strokes , the addition of clopidogrel to aspirin did not significantly reduce the risk of recurrent stroke and did significantly increase the risk of bleeding and death . ( Funded by the National Institute of Neurological Disorders and Stroke and others ; SPS3 Clinical Trials.gov number , NCT00059306 . )",
"Objective The purpose of this r and omized study was to evaluate the effect on graft patency by adding clopidogrel to aspirin in off-pump coronary artery bypass ( OPCAB ) grafting and the possible side effects of such therapy . Methods Twenty patients who underwent st and ard OPCAB through median sternotomy were r and omized immediately after surgery in two groups . Patients in group A ( n = 10 ) received 100 mg of aspirin starting preoperatively , continuing indefinitely . Patients in group B received 100 mg of aspirin and , in addition , 75 mg of clopidogrel starting immediately after the operation and for 3 months . Postoperative bleeding and other perioperative parameters were compared . Angiography was repeated 3 months after surgery to determine the patency and quality of grafts . Results Preoperative risk factors were similar in the two groups . There was no significant difference in average number of distal anastomosis ( P = 0.572 ) , operation time ( P = 0.686 ) , postoperative bleeding ( P = 0.256 ) , ventilation time ( P = 0.635 ) , and intensive care unit stay ( P = 0.065 ) . Length of stay was shorter in group B ( P = 0.024 ) . There was no postoperative complication in either groups . Eight of 27 grafts in group A and 2 of 29 grafts in group B ( P = 0.037 ) were occluded at the time of control angiography . Conclusions Early administration of a combined regimen of clopidogrel and aspirin after OPCAB grafting is not associated with increased postoperative bleeding or other major complications . Despite the small number of patients in this study and small number of examined grafts , the results suggest that the addition of clopidogrel may increase graft patency after OPCAB grafting",
"There is a high risk of reocclusion after successful lower limb angioplasty . Platelets play a central role in this process . The aim of this study was to investigate the antiplatelet effect of a combination of aspirin and clopidogrel compared with aspirin alone in patients with claudication undergoing endovascular revascularization",
"Dual antiplatelet therapy ( DAPT ) with clopidogrel and aspirin is a widely accepted strategy in patients undergoing transcatheter aortic valve implantation ( TAVI ) , but this approach is not evidence based . The goal of the present study was to determine whether DAPT in patients undergoing TAVI is associated with improved outcomes compared to aspirin alone . From May 2009 to August 2010 , consecutive patients were r and omized to receive a 300-mg loading dose of clopidogrel on the day before TAVI followed by a 3-month maintenance daily dose of 75 mg plus aspirin 100 mg lifelong ( DAPT group ) or aspirin 100 mg alone ( ASA group ) . The primary end point was the composite of major adverse cardiac and cerebrovascular events , defined as death from any cause , myocardial infa rct ion , major stroke , urgent or emergency conversion to surgery , or life-threatening bleeding . The cumulative incidence of major adverse cardiac and cerebrovascular events at 30 days and 6 months was 14 % and 16 % , respectively . No significant differences between the DAPT and ASA groups were noted at both 30 days ( 13 % vs 15 % , p = 0.71 ) and 6 months ( 18 % vs 15 % ; p = 0.85 ) . In conclusion , the strategy of adding clopidogrel to aspirin for 3 months after TAVI was not found to be superior to aspirin alone . These results must be confirmed in a larger r and omized trial",
"Background The Clopidogrel for High Atherothrombotic Risk and Ischaemic Stabilisation , Management and Avoidance ( CHARISMA ) trial reported no statistically significant benefit of adding clopidogrel to acetylsalicylic acid in the long-term management of a broad population of patients with stable vascular disease . However , a sub analysis raised the hypothesis that dual antiplatelet therapy with clopidogrel plus acetylsalicylic acid may be more effective than aspirin in patients with prior ischaemic stroke , myocardial infa rct ion of symptomatic peripheral arterial disease . We aim ed to determine whether the possible benefits of clopidogrel plus acetylsalicylic acid in patients with transient ischaemic attack and ischaemic stroke may be ‘ front-loaded ’ , and maximal within the first 30-days of r and omisation , without being unduly hazardous . Methods This was a sub analysis of a r and omised , double-blind , placebo-controlled trial of clopidogrel vs. placebo , in addition to background therapy with low-dose acetylsalicylic acid ( CHARISMA trial ) , restricted to all patients with transient ischaemic attack or ischaemic stroke . The primary efficacy outcome was stroke , and safety outcome severe bleeding , during the follow-up period . Results Among all transient ischaemic attack and ischaemic stroke patients r and omised to placebo ( n=2163 ) , 131 ( 6·1 % ) experienced a stroke during follow-up compared with 105 ( 4·9 % ) of 2157 patients assigned clopidogrel ( hazard ratio : 0·80 , 95 % confidence intervals : 0·62–1·03 ) . There was no significant difference in severe bleeding ( 1·7 % placebo vs. 1·9 % clopidogrel , hazard ratio : 1·11 , 95 % confidence intervals : 0·71–1·73 ) . Among all patients r and omised within 30-days of their qualifying transient ischaemic attack or ischaemic stroke to placebo ( n=667 ) , 46 ( 6·9 % ) experienced a stroke compared with 34 ( 5·1 % ) of 664 patients assigned clopidogrel ( hazard ratio : 0·74 , 0·46–1·16 ) . There was no significant difference in severe bleeding ( 1·6 % placebo vs. 1·4 % clopidogrel , hazard ratio : 0·83 , 95 % confidence intervals : 0·34–2·01 ) . Conclusion The data are consistent with , but do not prove the hypothesis that early addition of clopidogrel to acetylsalicylic acid in patients with transient ischaemic attack and ischaemic stroke of arterial origin may be more effective and acceptably safe compared with acetylsalicylic acid alone . Adequately powered clinical trials that are dedicated to exploring this hypothesis are needed",
"OBJECTIVE Dual antiplatelet therapy with clopidogrel plus acetylsalicylic acid ( ASA ) is superior to ASA alone in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention . We sought to determine whether clopidogrel plus ASA conferred benefit on limb outcomes over ASA alone in patients undergoing below-knee bypass grafting . METHODS Patients undergoing unilateral , below-knee bypass graft for atherosclerotic peripheral arterial disease ( PAD ) were enrolled 2 to 4 days after surgery and were r and omly assigned to clopidogrel 75 mg/day plus ASA 75 to 100 mg/day or placebo plus ASA 75 to 100 mg/day for 6 to 24 months . The primary efficacy endpoint was a composite of index-graft occlusion or revascularization , above-ankle amputation of the affected limb , or death . The primary safety endpoint was severe bleeding ( Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries [ GUSTO ] classification ) . RESULTS In the overall population , the primary endpoint occurred in 149 of 425 patients in the clopidogrel group vs 151 of 426 patients in the placebo ( plus ASA ) group ( hazard ratio [ HR ] , 0.98 ; 95 % confidence interval [ CI ] , 0.78 - 1.23 ) . In a prespecified subgroup analysis , the primary endpoint was significantly reduced by clopidogrel in prosthetic graft patients ( HR , 0.65 ; 95 % CI , 0.45 - 0.95 ; P = .025 ) but not in venous graft patients ( HR , 1.25 ; 95 % CI , 0.94 - 1.67 , not significant [ NS ] ) . A significant statistical interaction between treatment effect and graft type was observed ( P(interaction ) = .008 ) . Although total bleeds were more frequent with clopidogrel , there was no significant difference between the rates of severe bleeding in the clopidogrel and placebo ( plus ASA ) groups ( 2.1 % vs 1.2 % ) . CONCLUSION The combination of clopidogrel plus ASA did not improve limb or systemic outcomes in the overall population of PAD patients requiring below-knee bypass grafting . Subgroup analysis suggests that clopidogrel plus ASA confers benefit in patients receiving prosthetic grafts without significantly increasing major bleeding risk",
"BACKGROUND Antiplatelet therapy with clopidogrel decreases ischemic complication especially in patients with acute coronary syndromes or after percutaneous coronary interventions . Our study was design ed to test the effects of clopidogrel on soluble CD40 lig and ( sCD40l ) and on high-sensitivity C-reactive protein ( hs-CRP ) in patients with stable coronary artery disease ( CAD ) . METHODS This is a r and omized , double-blind , placebo-controlled study . A total of 73 patients with stable CAD for > 6 months were r and omized to receive either clopidogrel ( loading dose 300 mg followed by 75 mg/d ) for 8 weeks or placebo . Soluble CD40 lig and and hs-CRP were measured at baseline and at completion of the study . RESULTS All patients were on aspirin therapy , and 74 % were on statins . Median and interquartile ranges ( IQR ) of sCD40l decreased from 64 pg/mL ( 43 - 99 ) at baseline to 53 pg/mL ( 35 - 77 ) at 8 weeks ( P = .03 ) in the clopidogrel group and remained unchanged in the placebo group ( 59 pg/mL , IQR 35 - 77 vs 55 pg/mL , IQR 35 - 78 ) ( P = non significant ) . Levels of hs-CRP were not affected by therapy and remained unchanged in both groups . CONCLUSIONS In patients with stable CAD , clopidogrel inhibits the release of sCD40l by platelets , which may contribute to the clinical benefit provided by this drug . This , however , does not translate in a reduction of sub clinical inflammation , as measured by hs-CRP",
"BACKGROUND Data on the effects of oral antiplatelet agents on blood coagulation in vivo are conflicting . The platelet glycoprotein ( GP ) IIIa PlA2 allele has been suggested to modulate antithrombotic actions of clopidogrel . AIM We investigated whether clopidogrel combined with aspirin affects local thrombin formation and platelet activation triggered by vascular injury . METHOD We studied patients with stable coronary artery disease on chronic aspirin therapy r and omised to addition of clopidogrel 75 mg/d ( n = 30 ) or continuation of aspirin 100 mg/d ( n = 30 ) for 4 weeks . Markers of thrombin generation [ thrombin-antithrombin complexes ( TAT ) and prothrombin 1.2 fragments ( F1.2 ) ] and markers of platelet activation [ soluble CD40 lig and ( sCD40L ) and P-selectin ] were determined in the supernatant of blood sample s obtained from a microvascular injury site . RESULTS Total amounts of thrombin markers produced at the site of injury were similar before and after addition of clopidogrel , whereas platelet release of sCD40L and P-selectin was lower during treatment with aspirin + clopidogrel by 33.8 % and 27.8 % ( p reduction in platelet activation had previous myocardial infa rct ion and peripheral arterial disease and released the highest amounts of sCD40L and P-selectin at baseline . TAT and F1.2 generation as well as sCD40L or P-selectin release were not influenced by the presence of the PlA2 allele . CONCLUSION Our study shows that clopidogrel combined with aspirin does not reduce thrombin formation following vascular injury , but attenuates platelet sCD40L and P-selectin release",
"BACKGROUND The CURE study demonstrated the benefit of clopidogrel in patients with non-ST elevation ( NSTE ) acute coronary syndromes ( ACSs ) , including those undergoing percutaneous coronary intervention ( PCI ) . It did not report the relation between clopidogrel and timing of PCI or , more specifically , the role of clopidogrel in patients managed with an early interventional strategy , the current preferred treatment option for patients with NSTE ACSs . In the present study , we examined the relation between clopidogrel therapy , timing of PCI , and cardiovascular ( CV ) events in patients participating in the CURE study . METHODS A total of 12562 patients with NSTE ACSs was r and omized in double-blind fashion to clopidogrel or placebo ( 300 mg loading dose , then 75 mg/d ) in addition to aspirin for up to 1 year . We analyzed the data of the 2658 CURE patients undergoing PCI and related the incidence of outcome events ( CV death/myocardial infa rct ion [ MI ] ) to timing of PCI after r and omization : early ( or = 48 hours to initial hospital discharge , median 6.8 days , n = 1360 ) , and late ( after initial hospital discharge , median 47.6 days , n = 928 ) . RESULTS Clopidogrel showed consistent treatment benefit over the 12-month ( mean 9 months ) follow-up period irrespective of timing of PCI ( relative risk [ RR ] 0.53 for the early group , RR 0.72 for the intermediate group , RR 0.70 for the late group ) . After adjustment for propensity to undergo PCI , the greatest treatment benefit of clopidogrel was observed in patients undergoing PCI event rate ( 6.7 % CV death/MI ) was observed in patients treated with clopidogrel and undergoing PCI within 48 hours . There was no increased risk of major bleeding in the early PCI group . CONCLUSIONS The benefit of therapy with clopidogrel in addition to aspirin in patients presenting with NSTE ACSs was significant irrespective of the timing of PCI . The combination of clopidogrel and an early ( rates for CV death/nonfatal MI",
"In this study , we aim ed to disclose the net effect of long-term ( 6-month ) clopidogrel treatment as compared to that of short-term ( 1-month ) treatment in the poststenting period . A total of 278 patients with successful stent implantation were involved in the study . After preloading with 300 mg of clopidogrel orally ( p.o . ) 24 h prior to the procedure , r and omly selected patients were given either 75 mg p.o . for 1 month ( group A ) or 75 mg p.o . for 6 months ( group B ) . The patients were followed up clinical ly and underwent control angiography at 6 months regardless of their clinical status to delineate the coronary anatomy and assess quantitative computer-assisted ( QCA ) analysis . In 140 ( 50.4 % ) patients ( group A ) , 244 ( 50.6 % ) stents were used to treat 237 coronary lesions , and in 138 patients ( group B ) , 238 ( 49.4 % ) stents were used to treat 238 coronary lesions . There was no difference between the groups with respect to any of the clinical characteristics , intracoronary thrombus , antiaggregant therapy , the type of lesion , vessel score index , and baseline QCA parameters . In 62 patients binary in-stent restenosis ( ISR ) was determined with no statistical difference between the groups ( group A : 20.7 % vs group B : 23.9 % , P = not significance ) . There was also no difference between the two groups at 6 months regarding QCA parameters . Thirty-seven of the 62 patients with restenosis have developed major adverse coronary events such as death , myocardial infa rct ion , and target vessel revascularization ( group A : 12.9 % vs group B : 13.8 % , P = not significant ) . In patients with chronic coronary syndrome , in the poststenting period , 6-month clopidogrel use as an adjunct to aspirin has shown no benefit over 1 month use with respect to clinical outcome and angiographic outcome , such as restenosis rate , follow-up , minimal luminal diameter , late loss , lost index , and net gain",
"BACKGROUND Dual antiplatelet therapy with clopidogrel plus low-dose aspirin has not been studied in a broad population of patients at high risk for atherothrombotic events . METHODS We r and omly assigned 15,603 patients with either clinical ly evident cardiovascular disease or multiple risk factors to receive clopidogrel ( 75 mg per day ) plus low-dose aspirin ( 75 to 162 mg per day ) or placebo plus low-dose aspirin and followed them for a median of 28 months . The primary efficacy end point was a composite of myocardial infa rct ion , stroke , or death from cardiovascular causes . RESULTS The rate of the primary efficacy end point was 6.8 percent with clopidogrel plus aspirin and 7.3 percent with placebo plus aspirin ( relative risk , 0.93 ; 95 percent confidence interval , 0.83 to 1.05 ; P=0.22 ) . The respective rate of the principal secondary efficacy end point , which included hospitalizations for ischemic events , was 16.7 percent and 17.9 percent ( relative risk , 0.92 ; 95 percent confidence interval , 0.86 to 0.995 ; P=0.04 ) , and the rate of severe bleeding was 1.7 percent and 1.3 percent ( relative risk , 1.25 ; 95 percent confidence interval , 0.97 to 1.61 percent ; P=0.09 ) . The rate of the primary end point among patients with multiple risk factors was 6.6 percent with clopidogrel and 5.5 percent with placebo ( relative risk , 1.2 ; 95 percent confidence interval , 0.91 to 1.59 ; P=0.20 ) and the rate of death from cardiovascular causes also was higher with clopidogrel ( 3.9 percent vs. 2.2 percent , P=0.01 ) . In the subgroup with clinical ly evident atherothrombosis , the rate was 6.9 percent with clopidogrel and 7.9 percent with placebo ( relative risk , 0.88 ; 95 percent confidence interval , 0.77 to 0.998 ; P=0.046 ) . CONCLUSIONS In this trial , there was a suggestion of benefit with clopidogrel treatment in patients with symptomatic atherothrombosis and a suggestion of harm in patients with multiple risk factors . Overall , clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infa rct ion , stroke , or death from cardiovascular causes . ( Clinical Trials.gov number , NCT00050817 . )",
"BACKGROUND Stroke is common during the first few weeks after a transient ischemic attack ( TIA ) or minor ischemic stroke . Combination therapy with clopidogrel and aspirin may provide greater protection against subsequent stroke than aspirin alone . METHODS In a r and omized , double-blind , placebo-controlled trial conducted at 114 centers in China , we r and omly assigned 5170 patients within 24 hours after the onset of minor ischemic stroke or high-risk TIA to combination therapy with clopidogrel and aspirin ( clopidogrel at an initial dose of 300 mg , followed by 75 mg per day for 90 days , plus aspirin at a dose of 75 mg per day for the first 21 days ) or to placebo plus aspirin ( 75 mg per day for 90 days ) . All participants received open-label aspirin at a clinician-determined dose of 75 to 300 mg on day 1 . The primary outcome was stroke ( ischemic or hemorrhagic ) during 90 days of follow-up in an intention-to-treat analysis . Treatment differences were assessed with the use of a Cox proportional-hazards model , with study center as a r and om effect . RESULTS Stroke occurred in 8.2 % of patients in the clopidogrel-aspirin group , as compared with 11.7 % of those in the aspirin group ( hazard ratio , 0.68 ; 95 % confidence interval , 0.57 to 0.81 ; P Moderate or severe hemorrhage occurred in seven patients ( 0.3 % ) in the clopidogrel-aspirin group and in eight ( 0.3 % ) in the aspirin group ( P=0.73 ) ; the rate of hemorrhagic stroke was 0.3 % in each group . CONCLUSIONS Among patients with TIA or minor stroke who can be treated within 24 hours after the onset of symptoms , the combination of clopidogrel and aspirin is superior to aspirin alone for reducing the risk of stroke in the first 90 days and does not increase the risk of hemorrhage . ( Funded by the Ministry of Science and Technology of the People 's Republic of China ; CHANCE Clinical Trials.gov number , NCT00979589 . )",
"The purpose of this study was to compare the effect of dual antiplatelet therapy [ clopidogrel + aspirin ( ASA ) ] with respect to ASA on the protein expression of platelets from controlled type-2 diabetic patients with stable coronary ischemia . Patients had been taking ASA ( 100 mg day ) and they were r and omized to receive ( n = 29 ) or not ( n = 28 ) 75 mg day clopidogrel for 12 ± 2 weeks in a blind form . Protein expression was analyzed by two-dimensional electrophoresis and mass spectrometry . The protein expression of a limited number of proteins such as actin-binding protein isotypes 2 and 5 , lactate dehydrogenase , serotransferrin isotype 4 , protein disulfide isomerase-A3 isotype 1 , fibrinogen beta chain isotype 5 , Ras-related protein Rab-7b isotypes 1 and 6 , and immunoglobulin heavy chain was changed after dual antiplatelet therapy . Plasma level of platelet factor 4 ( PF4 ) , an in vivo marker of platelet activity , was not different between both groups . These changes suggest lower platelet reactivity after dual antiplatelet therapy in the studied patients . However , the variation in platelet proteome was lower than it would be initially expected , taking into account the apparent clinical beneficial effects of dual antiplatelet therapy . PF4 plasma level was not further decreased in the platelets treated for a longer time than 9 - 12 months with ASA + clopidogrel , as compared with ASA alone",
"Advances in antithrombotic therapy , along with an early invasive strategy , have reduced the incidence of recurrent ischemic events and death in patients with acute coronary syndromes ( ACS ; unstable angina , non – ST-segment – elevation myocardial infa rct ion [ MI ] , and ST-segment – elevation MI).1,–,4 However , the combination of multiple pharmacotherapies , including aspirin , platelet P2Y12 inhibitors , heparin plus glycoprotein IIb/IIIa inhibitors , direct thrombin inhibitors , and the increasing use of invasive procedures , has also been associated with an increased risk of bleeding . Editorial see p 2664 Bleeding complications have been associated with an increased risk of subsequent adverse outcomes , including MI , stroke , stent thrombosis , and death , in patients with ACS and in those undergoing percutaneous coronary intervention (PCI),5,–,10 as well as in the long-term antithrombotic setting .11,12 Thus , balancing the anti-ischemic benefits against the bleeding risk of antithrombotic agents and interventions is of paramount importance in assessing new therapies and in managing patients . Prior r and omized trials comparing antithrombotic agents suggest that a reduction in bleeding events is associated with improved survival.13,14 Because prevention of major bleeding may represent an important step in improving outcomes by balancing safety and efficacy in the contemporary treatment of ACS , bleeding events have been systematic ally identified as a crucial end point for the assessment of the safety of drugs during the course of r and omized clinical trials , and are an important aspect of the evaluation of new devices and interventional therapies.15 Unlike ischemic clinical events ( eg , cardiac death , MI , stent thrombosis ) , for which there is now general consensus on end-point definitions,16,17 there is substantial heterogeneity among the many bleeding definitions currently in use . Lack of st and ardization makes it difficult to optimally organize key clinical trial processes such as adjudication , and even more difficult to interpret relative",
"Objective To determine the individual variability in the response to aspirin and /or clopidogrel and its impact on graft patency after off-pump coronary artery bypass grafting . Design A single-centre prospect i ve r and omised controlled study design ed according to the Consoli date d St and ards of Reporting Trials statement . R and omisation was obtained by a computer-generated algorithm . Setting University medical school in Italy . Patients 300 patients who underwent off-pump coronary artery bypass grafting were r and omised to receive aspirin ( n=150 ) or aspirin plus clopidogrel ( n=150 ) . Intervention Aspirin 100 mg or aspirin 100 mg plus clopidogrel 75 mg daily was initiated when postoperative chest tube drainage was ≤50 ml/h for 2 h and patients were followed up for 12 months . Main outcome measures Qualitative and quantitative assessment of platelet function , angiographic evaluation of coronary revascularisation by 64-slice CT and clinical outcome . Results In the aspirin group , 49 patients ( 32.6 % ) were aspirin resistant and , in the aspirin-clopidogrel group , 19 patients ( 12.6 % ) were aspirin and clopidogrel resistant . The platelet response to aspirin was similar in all aspirin responders despite the study arm ( Aspirin Reaction Units 313.2±44.8 vs 323.6±53.6 ; p=0.07 ) . The platelet response to clopidogrel was enhanced by aspirin in patients responsive to both aspirin and clopidogrel ( synergistic effect ) compared with responders to clopidogrel only ( P2Y12 Reaction Units 139.9±15.5 vs 179.4±18.5 ; p with a reduced vein graft occlusion rate ( 7.4 % vs 13.1 % ; p=0.04 ) . Antiplatelet resistance was a predictor of graft occlusion ( RR 3.6 , 95 % CI 2.5 to 6.9 ; p ) . Synergistic aspirin and clopidogrel activity was a strong predictor of vein graft patency ( RR 5.1 , 95 % CI 1.4 to 16.3 ; p Combined clopidogrel and aspirin overcome single drug resistances , are safe for bleeding and improve venous graft patency ",
"BACKGROUND Microembolic signals ( MESs ) are direct markers of unstable large artery atherosclerotic plaques . In a previous study , we found that the number of MESs is associated with stroke recurrence and that clopidogrel plus aspirin more effectively reduce the number of MESs than does aspirin alone . Stroke recurrence is associated with not only the number of MESs but also the size of the MES , which can theoretically be estimated by monitoring the MES intensity via transcranial doppler ( TCD ) . Thus , we compared the effects of clopidogrel and aspirin with aspirin alone on MES intensity using TCD . METHODS We recruited 100 patients who experienced acute ischemic stroke or transient ischemic attack ( TIA ) within 7days of symptom onset . All patients also had large artery stenosis in the cerebral or carotid arteries and the presence of MES as revealed by TCD . The patients were r and omized to receive either aspirin or clopidogrel and aspirin for 7days . MES monitoring was performed on days 2 and 7 . RESULTS Intent-to-treat ( ITT ) analysis ( 46 patients in the dual therapy group , 52 patients in the monotherapy group ) and per- protocol ( PP ) analysis ( 25 patients in the dual therapy group , 31 patients in the monotherapy group ) were performed on 98 patients . The primary finding was that the MES intensity was dramatically reduced in the dual therapy group . ITT analysis of the dual therapy group revealed that the MES intensity was 8.04 ( 0 - 16 ) dB before treatment , 0.00 ( 0 - 17 ) dB on day 2 , and 0.00 ( 0 - 12 ) dB on day 7 ( P=0.000 ) . In the monotherapy group , the MES intensity was 9.00 ( 0 - 20 ) dB before treatment , 8.25 ( 0 - 17 ) dB on day 2 , and 7.0 ( 0 - 18 ) dB on day 7 ( P=0.577 ) . PP analysis revealed similar results . No severe hemorrhagic complications were detected . The two patients in this study who experienced stroke recurrence were in the monotherapy group . CONCLUSIONS Clopidogrel and aspirin more effectively decrease the MES intensity than aspirin alone in patients with large artery stenotic minor stroke or TIA",
"BACKGROUND The superiority of clopidogrel and aspirin versus aspirin alone for up to 1 year in patients who undergo percutaneous coronary intervention ( PCI ) after presenting with acute coronary syndromes without ST-segment elevation was demonstrated in the PCI-CURE study . We evaluated the long-term cost-effectiveness of clopidogrel use for up to 1 year using patient-level outcomes and re source use from PCI-CURE , and estimates of life expectancy gains based on external sources . METHODS PCI-CURE involved 2658 patients who underwent PCI between 1998 and 2000 after being r and omized in the CURE trial to clopidogrel ( n = 1313 ) or placebo ( n = 1345 ) . Roughly two thirds ( clopidogrel n = 821 , placebo n = 909 ) underwent PCI during the initial hospitalization ( early PCI ) . Costs were applied to hospitalizations according to diagnosis-related group . Clopidogrel was assigned the average wholesale price of 3.22 dollars per day . Life expectancy gains result ing from the prevention of major clinical events were estimated using external sources . RESULTS Average total costs were higher with clopidogrel ( difference [ based on costing method ] 253 dollars-423 dollars ) . For patients who underwent PCI during the initial hospitalization , the difference ranged from 155 dollars lower to 90 dollars higher with clopidogrel . The estimated life expectancy gain with clopidogrel was 0.0885 years , whereas it was 0.0962 years for the early PCI subgroup . Incremental cost per year of life gained with clopidogrel ranges from 2856 dollars to 4775 dollars overall and from dominant ( life expectancy benefit with cost savings ) to 935 dollars for the early PCI subgroup . CONCLUSIONS Clopidogrel given for up to 1 year in patients undergoing PCI after presentation with acute coronary syndromes is a highly cost-effective treatment strategy",
"Background Dual antiplatelet therapy with clopidogrel and aspirin reduces the presence and number of microembolic signals in patients with large artery disease . However , whether it is effective in patients with intracranial disease alone remains uncertain . We performed a subgroup analysis of the The CLopidogrel plus Aspirin for Infa rct ion Reduction ( CLAIR in acute stroke or transient ischemic attack patients with large artery stenosis and microembolic signals ) study of only patients with intracranial occlusive disease , excluding those with extra cranial disease . Methods CLAIR was a r and omized-controlled , open-label , multicenter clinical trial with blinded outcome evaluation , which recruited patients with symptoms of ischemic stroke or transient ischemic attack within seven-days of onset , with large artery stenosis verified by transcranial Doppler and carotid ultrasound , and with microembolic signals detected by transcranial Doppler recording . All patients were r and omized to receive clopidogrel plus aspirin daily for seven-days ( dual treatment ) , or aspirin alone for seven-days ( monotherapy ) . Repeated transcranial Doppler recordings for microembolic signals were made on day one , two , and seven . This subgroup study only analyzed the patients with purely intracranial large artery disease and excluded those with extra cranial stenosis . Results There were 70 patients recruited with purely intracranial stenosis , 34 in the dual treatment group and 36 in the monotherapy group . The proportion of the patients with positive emboli at day seven in the dual treatment group was significantly lower than that in the monotherapy group ( relative risk reduction 56·5 % , 95 % confidence interval 2·5–80·6 ; P = 0·029 ) . The number of emboli in the dual treatment group decreased significantly at day two ( P = 0·043 ) and day seven ( P = 0·018 ) compared with the monotherapy group . After adjustment for the number of emboli at day one , the effect of dual treatment was still significant for the reduction of presence ( relative risk reduction 56·0 % ; 95 % confidence interval 5·4–79·6 ; P = 0·036 ) and number ( adjusted mean difference −0·9 ; 95 % confidence interval −1·5 to −0·3 ; P = 0·004 ) of positive emboli at day seven . Conclusions Dual treatment with clopidogrel and aspirin for seven-days is more effective than aspirin alone to reduce microembolic signals in patients with intracranial arterial stenosis",
"OBJECTIVE In peripheral arterial disease ( PAD ) patients , a limiting factor in the success of percutaneous transluminal angioplasty ( PTA ) is the development of restenosis secondary to vascular smooth muscle cell ( SMC ) proliferation . Following endothelial damage and platelet activation , there is release of factors and adhesion molecules which affect SMC proliferation . The aim of this study was to determine the effect of combination antiplatelet therapy ( clopidogrel and aspirin compared with aspirin and placebo ) on the ability of plasma from PAD patients undergoing PTA to stimulate SMCs in vitro . We further aim ed to investigate the effect of combination treatment on the levels of circulating adhesion molecules and factors , which are known to mediate SMC proliferation in experimental models . METHODS Fifty patients were r and omized to receive blinded clopidogrel or placebo , for thirty days , in addition to their daily 75 mg aspirin . To measure proliferative capacity , diluted plasma was incubated for 15 minutes with 24 hour-growth-arrested rat vascular smooth muscle cells , and extracellular regulated kinase (ERK)1/2 activation was analyzed by Western blotting at baseline , one hour pre-PTA , one hour , 24 hours and 30 days post-PTA . Plasma platelet-derived growth factor ( PDGF ) , sE-selectin , intracellular adhesion molecule-1 ( sICAM-1 ) , and von Willebr and factor ( vWF ) were measured by ELISA , at the same five timepoints . Platelet activation was measured by flow cytometry of ADP-stimulated platelet fibrinogen binding at baseline and one hour post-PTA . RESULTS ADP-stimulated platelet fibrinogen binding was significantly inhibited by clopidogrel before and after PTA . ERK 1/2 activation was significantly increased post-PTA in both the aspirin/clopidogrel and aspirin/placebo groups ( P PDGF ( P = .004 ) , and increase in vWF ( P = .026 ) , following loading with clopidogrel . sICAM-1 levels significantly decreased ( P = .016 ) in the aspirin/placebo group following PTA . There were no other significant changes and also there was no statistically significant difference between the two treatment groups for each of ERK 1/2 , sICAM-1 , sE-selectin , or vWF . CONCLUSIONS This is the first study to show in-vitro ERK 1/2 activation ( a surrogate marker of SMC proliferation ) increases post-PTA . Combination antiplatelet therapy had no significant effect on this , although it did reduce PDGF . Further work is required to evaluate potential therapeutic treatments , which may reduce peripheral PTA-induced smooth muscle cell activation . CLINICAL RELEVANCE High rates of restenosis remain the major limitation of peripheral arterial angioplasty and stenting . The restenotic lesion occurs secondary to platelet activation , released circulating factors , and subsequent smooth musclecell proliferation and migration into the intima . Methods to limit the restenotic lesion are poorly understood . This paperinvestigates the effect of PTA on smooth muscle cell activation and the release of factors in plasma which mediate SMCproliferation . It also examines the effect of combination antiplatelet therapy as a potential therapeutic strategy",
"BACKGROUND High-sensitivity C-reactive protein ( hsCRP ) and soluble cluster of differentiation 40 lig and ( sCD40L ) have been established as effective markers of inflammation in predicting the risk for adverse outcomes in patients with acute coronary syndromes ( ACSs ) . Activated platelets secrete certain inflammatory mediators such as P-selectin and sCD40L , which play a role in the pathogenesis of ACSs . Although acetylsalicylic acid ( ASA ) has been found to be an effective treatment of ACSs , the addition of clopidogrel bisulfate has been found tofurther improve clinical outcomes as a result of additional antiplatelet and anti-inflammatory action . Few data exist concerning the effects of dual antiplatelet therapy on these markers in patients with ACSs . OBJECTIVE The aim of this study was to assess the effectiveness and clinical significance of clopidogrel administration in patients with ACSs without ST segment elevation treated with ASA . METHODS This r and omized , single-blind , controlled trial was conducted at the First Department of Cardiology , Hippokration Hospital , Athens , Greece . In patients aged > or=21 years with ACSs without ST segment elevation were r and omly assigned to 1 of 2 groups : ASA 325 mg/d for 1 week , followed by ASA ( 100 mg/d ) plus clopidogrel ( 300-mg loading dose followed by 100 mg/d ) for 36 weeks ( ASA+Clop group ) or ASA alone ( 325 mg/d for 1 week , followed by 75 mg/d for 36 weeks ) ( ASA group ) . Levels of serum sCD40L , hsCRP , and P-selectin were determined on admission and at 8 hours , 48 hours , and 6 days of treatment . By means of clinical follow-up , Kaplan-Meier free-of-major adverse cardiovascular events ( MACES ) plots were used to assess the prevalence of MACES , including cardiovascular-related death , in patients with and without high levels of hsCRP ( > or=3 mg/L ) and sCD40L ( > or=5 microg/L ) for 52 weeks . RESULTS A total of 86 patients were enrolled ( 71 men , 15 women ; mean [ SD ] age , 68 [ 3 ] years ; mean [ SD ] weight , 86 [ 18 ] kg ; white race , 86 [ 100 % ] ; 43 patients per group ) . Both groups had similar initial clinical characteristics and P-selectin levels . Baseline hsCRP and sCD40L levels were correlated with baseline P-selectin levels ( hsCRP , r2=0.099 CONCLUSIONS The results of this small study suggest that early activation of platelets , as measured using P-selectin levels , was effectively inhibited by the addition of clopidogrel to a regimen of ASA in the subgroup of patients with ACSs and intense activation of platelets ( defined as high hsCRP and sCD40L levels ) . In patients without high hsCRP and sCD40L levels , the addition of clopidogrel did not have a significant effect on P-selectin levels ",
"Abstract Objectives : To study whether Clopidogrel – Aspirin combined treatment for high risk transient ischaemic attack ( TIA ) or minor stroke results in increased number of lesions associated with anti-thrombotic cerebral haemorrhage or cerebral micro-bleeds ( CMB ) than aspirin alone treatment . Methods : The patients recruited in CHANCE test in our hospital participated in this study . We made a comparison between treatments Aspirin – Clopidogrel combined group and the Aspirin alone group in the numbers of CMB and subsequent cerebral haemorrhages . In addition , we analysed the association between the increased numbers of CMB and subsequent intracerebral haemorrhages . All 129 patients with high risk TIA with microbleeds or minor stroke within 24 hours after the onset ( average age 65.9 ± 9.3 , 48.7 % were male patients ) were divided r and omly into two groups : ( 1 ) 67 patients were given combination therapy with clopidogrel and aspirin ( clopidogrel at an initial dose of 300 mg , then 75 mg per day for 90 days , plus aspirin at a dose of 75 mg per day for the first 21 days);(2 ) the rest patients were given aspirin treatment ( 75 mg per day for 90 days ) . All participants received open-label aspirin at a clinician-determined dose of 75–300 mg on the first day . Results : The CMB were found in 52.7 % of all patients in both groups . There was no siginificant difference between the Aspirin group and the Aspirin – clopidogrel treated group , though the latter showed some slight increase in CMB ( Odds ratios ( OR ) = 1.16 , 95 % confidence intervals ( CI ) = 0.54–2.47 , P = 0.71 ) . But the numbers of CMB were remarkably associated with the number of primary existing CMB ( OR = 6.46 , 95%CI 2.57–16.23 , P numbers of CMB associated with primary CMB lesions , which located in corticosubcortical area ( CSC ) ( OR = 4.69 , 95%CI 1.51–14.53 , P = 0.007 ) . Conclusions : For the treatment of high-risk TIA or minor stroke patients , the clopidogrel – aspirin treatment did not increase the number of CMB than Aspirin alone . It appears that the extent of CMB was associated with the extent of existing CMB occurred in previous stroke , which was mostly located in cortical , subcortical zone",
"Peripheral arterial disease ( PAD ) is associated with platelet hyperactivity . Aspirin and clopidogrel , two platelet inhibitors , act by different mechanisms . Aspirin inhibits thromboxane A2 synthesis and clopidogrel acts on the P2Y12 platelet ADP receptor . We evaluated the effect of clopidogrel ( 75 mg/day ) , aspirin ( 75 mg/day ) and then both drugs on several platelet function indices in patients with PAD ( n = 20 ) . There was a significant ( P = 0.0001 ) decrease in ADP-induced aggregation , after clopidogrel but not after taking aspirin . Clopidogrel plus aspirin significantly decreased spontaneous platelet aggregation ( SPA ) ( P = 0.01 to P = 0.002 ) but SPA was not significantly altered by either aspirin or clopidogrel monotherapy . Similarly , monotherapy did not inhibit serotonin (5HT)-induced aggregation but there was a significant inhibition ( P = 0.03 to P therapy . ADP ( 0.8 μM)-induced platelet shape change ( PSC ) was significantly inhibited by clopidogrel ( P = 0.004 ) or aspirin ( P = 0.01 ) . This was also true for 5HT-induced PSC ( clopidogrel , P = 0.01 ; aspirin , P = 0.03 ) . Soluble P-selectin decreased significantly ( from 32 ± 24 to 25 ± 17 ng/ml , P = 0.04 ) with combination therapy . Plasma platelet-derived growth factor and intraplatelet 5HT levels were not altered by combination therapy . In PAD , clopidogrel is a more potent inhibitor of ADP-induced platelet activation than aspirin ; combination therapy is more effective than clopidogrel or aspirin monotherapy . These potentially clinical ly relevant findings should be evaluated in appropriately design ed trials",
"Objective : To assess the effectiveness of long term treatment with clopidogrel of patients with extracardiac vascular disease ( ECVD ) ( a history of either peripheral arterial disease or cerebrovascular disease ) . Design : Subgroup analysis of a prospect i ve r and omised clinical trial . Setting : The CREDO ( clopidogrel for the reduction of events during observation ) trial was a r and omised , double blind , placebo controlled trial conducted at 99 centres in North America from June 1999 through April 2001 . Patients : 2116 patients who were to undergo elective coronary intervention or were deemed at high likelihood of undergoing percutaneous coronary intervention were enrolled in the CREDO trial . The current study sample consisted of 272 patients with ECVD . Main outcome measure : One year incidence of the composite of death , myocardial infa rct ion , or stroke in the intent to treat population . Results : Patients with ECVD had a more than twofold greater relative risk reduction with clopidogrel for the primary end point compared with patients without ECVD ( 47.9 % , 95 % confidence interval ( CI ) −4.2 % to 73.9 % , v 18.2 % , 95 % CI −10.5 % to 39.5 % , respectively ) . Conclusions : Longer term clopidogrel treatment provides added protection against thrombotic events throughout the arterial vasculature , not limited to the coronary arteries , and may be especially effective for patients with more diffuse atherosclerosis such as ECVD",
"Aims : To evaluate the effects of treatments with clopidogrel plus aspirin ( dual therapy ) on early neurological deterioration ( END ) and outcomes at 6 months in patients with acute large artery atherosclerosis ( LAA ) stroke . Methods : A total of 574 patients with LAA stroke were r and omly assigned to receive either dual therapy or aspirin alone ( monotherapy ) . The primary outcome was END . Secondary outcomes included recurrent ischemic stroke ( RIS ) and outcomes at 6 months . Results : The prevalence of END and RIS was lower in patients on dual therapy than in those on monotherapy during the 30 days . At 6 months , dual therapy improved outcomes among older patients and those with symptomatic stenosis in the posterior circulation and basilar artery . Conclusion : Clopidogrel plus aspirin is superior to aspirin alone for reducing END and RIS within 30 days and improves outcomes in certain subgroups at 6 months",
"Coronary artery bypass grafting is pivotal in the contemporary management of complex coronary artery disease . Interpatient variability to antiplatelet agents , however , harbors the potential to compromise the revascularization benefit by increasing the incidence of adverse events . This study was design ed to define the impact of dual antiplatelet therapy ( dAPT ) on clinical outcomes among aspirin-resistant patients who underwent coronary artery surgery . We r and omly assigned 219 aspirin-resistant patients according to multiple electrode aggregometry to receive clopidogrel ( 75 mg ) plus aspirin ( 300 mg ) or aspirin-monotherapy ( 300 mg ) . The primary end point was a composite outcome of all-cause death , nonfatal myocardial infa rct ion , stroke , or cardiovascular hospitalization assessed at 6 months postoperatively . The primary end point occurred in 6 % of patients assigned to dAPT and 10 % of patients r and omized to aspirin-monotherapy ( relative risk 0.61 , 95 % confidence interval 0.25 to 1.51 , p = 0.33 ) . No significant treatment effect was noted in the occurrence of the safety end point . The total incidence of bleeding events was 25 % and 19 % in the dAPT and aspirin-monotherapy groups , respectively ( relative risk 1.34 , 95 % confidence interval 0.80 to 2.23 , p = 0.33 ) . In the subgroup analysis , dAPT led to lower rates of adverse events in patients with a body mass index > 30 kg/m(2 ) ( 0 % vs 18 % , p clopidogrel in patients found to be aspirin resistant after coronary artery bypass grafting did not reduce the incidence of adverse events , nor did it increase the number of recorded bleeding events . dAPT did , however , lower the incidence of the primary end point in obese patients and those ",
"Abstract A hypercoagulable state has , in observational studies , been associated with increased risk of thromboembolic events . The aim of this trial was to study whether dual antiplatelet therapy ( DAPT ) with clopidogrel in addition to aspirin could reduce the rate of graft occlusions , thromboembolic events , and death compared to aspirin monotherapy in hypercoagulable patients undergoing coronary artery bypass surgery . A total of 1683 patients were screened for eligibility , among which 165 patients were r and omized and 133 patients underwent multislice computed tomography scan to evaluate their grafts . Thrombelastography ( TEG ) and multiplate aggregometry were performed before and after surgery , and again at three months follow up . TEG hypercoagulability was defined as the maximum amplitude above 69 mm . At three months follow up , 17 out of 66 ( 25.7 % ) DAPT patients and 15 of 67 ( 22.4 % ) aspirin patients had significant graft stenosis or occlusions ( p = 0.839 ) . Saphenous vein grafts ( SVGs ) were stenosed or occluded in 15 ( 22.7 % ) patients in the DAPT group and 7 ( 10.4 % ) in the aspirin group ( p = 0.167 ) . Thromboembolic events and death after the second postoperative day ( when clopidogrel was started ) were numerically , but not statistically , lower in the DAPT group , 3 ( 3.8 % ) vs. 8 ( 9.9 % ) , p = 0.211 . In univariate logistic regression analysis , only postoperative day 4 platelet response to aspirin measured with multiplate was correlated with graft occlusion , OR 1.020 [ 1.002–1.039 ] , p = 0.033 . This is the first trial to test the hypothesis of intensified antiplatelet therapy in hypercoagulable patients . Due to the low enrollment and high loss to follow up , our results can only be viewed as hypothesis generating . We found a high rate of graft occlusions in this patient population . Our results were not suggestive of that DAPT improved saphenous vein graft patency . A trend was observed in patients on DAPT toward fewer MI and deaths . Postoperative response to aspirin therapy was found to be associated with early SVG occlusion",
"Background and Purpose — In patients with acute ischemic stroke caused by large artery atherosclerosis , clopidogrel plus aspirin versus aspirin alone might be more effective to prevent recurrent cerebral ischemia . However , there is no clear evidence . Methods — In this multicenter , double-blind , placebo-controlled trial , we r and omized 358 patients with acute ischemic stroke of presumed large artery atherosclerosis origin within 48 hours of onset to clopidogrel ( 75 mg/d without loading dose ) plus aspirin ( 300-mg loading followed by 100 mg/d ) or to aspirin alone ( 300-mg loading followed by 100 mg/d ) for 30 days . The primary outcome was new symptomatic or asymptomatic ischemic lesion on magnetic resonance imaging within 30 days . Secondary outcomes were 30-day functional disability , clinical stroke recurrence , and composite of major vascular events . Safety outcome was any bleeding . Results — Of 358 patients enrolled , 334 ( 167 in each group ) completed follow-up magnetic resonance imaging . The 30-day new ischemic lesion recurrence rate was comparable between the clopidogrel plus aspirin and the aspirin monotherapy groups ( 36.5 % versus 35.9 % ; relative risk , 1.02 ; 95 % confidence interval , 0.77–1.35 ; P=0.91 ) . Of the recurrent ischemic lesions , 94.2 % were clinical ly asymptomatic . There were no differences in secondary outcomes between the 2 groups . Any bleeding were more frequent in the combination group than in the aspirin monotherapy group , but the difference was not significant ( 16.7 % versus 10.7 % ; P=0.11 ) . One hemorrhagic stroke occurred in the clopidogrel plus aspirin group . Conclusions — Clopidogrel plus aspirin might not be superior to aspirin alone for preventing new ischemic lesion and clinical vascular events in patients with acute ischemic stroke caused by large artery atherosclerosis . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00814268",
"Background — Uncertainty exists about the frequency , correlates , and clinical significance of bleeding with dual antiplatelet therapy ( DAPT ) , particularly over an extended period in a stable population . We sought to determine the frequency and time course of bleeding with DAPT in patients with established vascular disease or risk factors only ; identify correlates of bleeding ; and determine whether bleeding is associated with mortality . Methods and Results — We analyzed 15 603 patients enrolled in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization , Management , and Avoidance ( CHARISMA ) trial , a double-blind , placebo-controlled , r and omized trial comparing long-term clopidogrel 75 mg/d versus placebo ; all patients received aspirin ( 75 to 162 mg ) daily . Patients had either established stable vascular disease or multiple risk factors for vascular disease without established disease . Median follow-up was 28 months . Bleeding was assessed with the use of the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries ( GUSTO ) criteria . Severe bleeding occurred in 1.7 % of the clopidogrel group versus 1.3 % on placebo ( P=0.087 ) ; moderate bleeding occurred in 2.1 % versus 1.3 % , respectively ( P risk of bleeding was greatest the first year . Patients without moderate or severe bleeding during the first year were no more likely than placebo-treated patients to have bleeding thereafter . The frequency of bleeding was similar in patients with established disease and risk factors only . In multivariable analysis , the relationship between moderate bleeding and all-cause mortality was strong ( hazard ratio , 2.55 ; 95 % confidence interval , 1.71 to 3.80 ; P stroke ( hazard ratio , 4.20 ; 95 % confidence interval , 3.05 to 5.77 ; P risk of bleeding with long-term clopidogrel . The incremental risk of bleeding was greatest in the first year and similar thereafter . Moderate bleeding was strongly associated with mortality . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00050817"
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Aims Investigations on the possible effect of the Nordic diet ( ND ) on the glycemic control and the risk of diabetes have led to inconsistent results . The present study tried to determine the effect of the ND on the markers of blood glucose control using a systematic review and meta- analysis of r and omized controlled clinical trials ( RCTs ) . Methods Predefined keywords were used to search PubMed , ISI Web of Science , Scopus and Google Scholar up to April 2019 . The r and om effects model was used to compute the overall estimates . Results In total , six RCTs with 618 participants ( 6–26 weeks of follow-up period ) were included in the present study . The meta- analysis revealed that the ND might not have a considerable effect on fasting blood glucose levels [ weighted mean difference ( WMD ) = −0.05 mmol/l , 95 % CI − 0.13 , 0.01 , P = 0.112 ] . In contrast , the analyses showed that the ND significantly reduces serum insulin concentrations ( WMD = −1.12 mU/l , 95 % CI − 1.84 , − 0.39 , P = 0.002 ) and the homeostasis model assessment for insulin resistance ( HOMA-IR ) ( WMD = − 0.34 , 95 % CI − 0.53 , − 0.14 , P = 0.001 ) compared to control diets . The effect on serum insulin levels was sensitive to one of the included studies . This dietary pattern did not significantly affect 2-h post-pr and ial blood glucose and Matsuda index . Conclusions Adherence to the ND might improve serum insulin and HOMA-IR levels ; however , this effect was not confirmed for other markers of blood glucose control . Future well- design ed and long-term clinical trials are highly recommended
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"OBJECTIVE To test whether a weight loss program promotes greater weight loss , glycemic control , and improved cardiovascular disease risk factors compared with control conditions and whether there is a differential response to higher versus lower carbohydrate intake . RESEARCH DESIGN AND METHODS This r and omized controlled trial at two university medical centers enrolled 227 overweight or obese adults with type 2 diabetes and assigned them to parallel in-person diet and exercise counseling , with prepackaged foods in a planned menu during the initial phase , or to usual care ( UC ; two weight loss counseling sessions and monthly contacts ) . RESULTS Relative weight loss was 7.4 % ( 95 % CI 5.7–9.2 % ) , 9.0 % ( 7.1–10.9 % ) , and 2.5 % ( 1.3–3.8 % ) for the lower fat , lower carbohydrate , and UC groups ( P . Glycemic control markers and triglyceride levels were lower in the intervention groups compared with UC group at 1 year ( fasting glucose 141 [ 95 % CI 133–149 ] vs. 159 [ 144–174 ] mg/dL , P = 0.023 ; hemoglobin A1c 6.9 % [ 6.6–7.1 % ] vs. 7.5 % [ 7.1–7.9 % ] or 52 [ 49–54 ] vs. 58 [ 54–63 ] mmol/mol , P = 0.001 ; triglycerides 148 [ 134–163 ] vs. 204 [ 173–234 ] mg/dL , P lower hemoglobin A1c ( 6.6 % [ 95 % CI 6.3–6.8 % ] vs. 7.2 % [ 6.8–7.5 % ] or 49 [ 45–51 ] vs. 55 [ 51–58 ] mmol/mol ) at 1 year ( P = 0.008 ) . CONCLUSIONS The weight loss program result ed in greater weight loss and improved glycemic control in type 2 diabetes",
"We served a low-fat ( 28 % of energy ) , high-fiber ( 3.3 g/MJ ) diet according to Nordic nutrition recommendations ( Rec diet ) , and a high-fat diet ( 39 % of energy ) corresponding to the average Danish diet ( Dane diet ) for periods of 2 wk in a r and omized crossover study of 21 healthy middle-aged individuals . The Rec diet result ed in lower serum concentrations of low-density-lipoprotein ( LDL ) cholesterol ( medians : 2.77 vs 3.04 mmol/L , P high-density-lipoprotein ( HDL ) cholesterol ( 1.08 vs 1.24 mmol/L , P higher fasting triglycerides ( 1.11 vs 0.86 mmol/L , P = 0.04 ) than did the Dane diet . Furthermore , the Rec diet lowered plasma factor VII coagulant activity ( FVIIc ) ( 88 % vs 96 % , P = 0.002 ) and raised plasma fibrinolytic activity . Our observations indicate that a low-fat , high-fiber diet may not only reduce the atherogenic but also the thrombogenic tendency of an individual compared with a diet corresponding to the average Danish diet",
"BACKGROUND Ad libitum , low-carbohydrate diets decrease caloric intake and cause weight loss . It is unclear whether these effects are due to the reduced carbohydrate content of such diets or to their associated increase in protein intake . OBJECTIVE We tested the hypothesis that increasing the protein content while maintaining the carbohydrate content of the diet lowers body weight by decreasing appetite and spontaneous caloric intake . DESIGN Appetite , caloric intake , body weight , and fat mass were measured in 19 subjects placed sequentially on the following diets : a weight-maintaining diet ( 15 % protein , 35 % fat , and 50 % carbohydrate ) for 2 wk , an isocaloric diet ( 30 % protein , 20 % fat , and 50 % carbohydrate ) for 2 wk , and an ad libitum diet ( 30 % protein , 20 % fat , and 50 % carbohydrate ) for 12 wk . Blood was sample d frequently at the end of each diet phase to measure the area under the plasma concentration versus time curve ( AUC ) for insulin , leptin , and ghrelin . RESULTS Satiety was markedly increased with the isocaloric high-protein diet despite an unchanged leptin AUC . Mean ( + /-SE ) spontaneous energy intake decreased by 441 + /- 63 kcal/d , body weight decreased by 4.9 + /- 0.5 kg , and fat mass decreased by 3.7 + /- 0.4 kg with the ad libitum , high-protein diet , despite a significantly decreased leptin AUC and increased ghrelin AUC . CONCLUSIONS An increase in dietary protein from 15 % to 30 % of energy at a constant carbohydrate intake produces a sustained decrease in ad libitum caloric intake that may be mediated by increased central nervous system leptin sensitivity and results in significant weight loss . This anorexic effect of protein may contribute to the weight loss produced by low-carbohydrate diets",
"BACKGROUND The regional Mediterranean Diet has been associated with lower risk of disease . OBJECTIVE We tested the health effects of the New Nordic Diet ( NND ) , which is a gastronomically driven regional , organic , and environmentally friendly diet , in a carefully controlled but free-living setting . DESIGN A total of 181 central ly obese men and women , with a mean ( range ) age of 42 y ( 20 - 66 y ) , body mass index ( in kg/m(2 ) ) of 30.2 ( 22.6 - 47.3 ) , and waist circumference of 100 cm ( 80 - 138 cm ) were r and omly assigned to receive either the NND ( high in fruit , vegetables , whole grains , and fish ) or an average Danish diet ( ADD ) for 26 wk . Participants received cookbooks and all foods ad libitum and free of charge by using a shop model . The primary endpoint was the weight change analyzed by both completer and intention-to-treat analyses . RESULTS A total of 147 subjects [ 81 % ( NND 81 % ; ADD 82 % ) ] completed the intervention . A high dietary compliance was achieved , with significant differences in dietary intakes between groups . The mean ( ±SEM ) weight change was -4.7 ± 0.5 kg for the NND compared with -1.5 ± 0.5 kg for the ADD ( adjusted difference : -3.2 kg ; 95 % CI : -4.6 , -1.8 kg ; P greater reductions in systolic blood pressure ( adjusted difference : -5.1 mm Hg ; 95 % CI : -8.2 , -2.1 mm Hg ) and diastolic blood pressure ( adjusted difference : -3.2 mm Hg ; 95 % CI : -5.7 , -0.8 mm Hg ) than did the ADD . CONCLUSION An ad libitum NND produces weight loss and blood pressure reduction in central ly obese individuals . This trial was registered at www . clinical trials.gov as NCT01195610",
"OBJECTIVE To investigate the long-term associations of magnesium intake with incidence of diabetes , systemic inflammation , and insulin resistance among young American adults . RESEARCH DESIGN AND METHODS A total of 4,497 Americans , aged 18–30 years , who had no diabetes at baseline , were prospect ively examined for incident diabetes based on quintiles of magnesium intake . We also investigated the associations between magnesium intake and inflammatory markers , i.e. , high-sensitivity C-reactive protein ( hs-CRP ) , interleukin-6 ( IL-6 ) , and fibrinogen , and the homeostasis model assessment of insulin resistance ( HOMA-IR ) . RESULTS During the 20-year follow-up , 330 incident cases of diabetes were identified . Magnesium intake was inversely associated with incidence of diabetes after adjustment for potential confounders . The multivariable-adjusted hazard ratio of diabetes for participants in the highest quintile of magnesium intake was 0.53 ( 95 % CI , 0.32–0.86 ; Ptrend magnesium intake was significantly inversely associated with hs-CRP , IL-6 , fibrinogen , and HOMA-IR , and serum magnesium levels were inversely correlated with hs-CRP and HOMA-IR . CONCLUSIONS Magnesium intake was inversely longitudinally associated with incidence of diabetes in young American adults . This inverse association may be explained , at least in part , by the inverse correlations of magnesium intake with systemic inflammation and insulin resistance ",
"Children 's vitamin D intake and status can be optimised to meet recommendations . We investigated if nutritionally balanced school meals with weekly fish servings affected serum 25-hydroxyvitamin D ( 25(OH)D ) and markers related to bone in 8- to 11-year-old Danish children . We conducted an explorative secondary outcome analysis on data from 784 children from the OPUS School Meal Study , a cluster-r and omised cross-over trial where children received school meals for 3 months and habitual lunch for 3 months . At baseline , and at the end of each dietary period , 25(OH)D , parathyroid hormone ( PTH ) , osteocalcin ( OC ) , insulin-like growth factor-1 ( IGF-1 ) , bone mineral content ( BMC ) , bone area ( BA ) , bone mineral density ( BMD ) , dietary intake and physical activity were assessed . School meals increased vitamin D intake by 0·9 ( 95 % CI 0·7 , 1·1 ) μg/d . No consistent effects were found on 25(OH)D , BMC , BA , BMD , IGF-1 or OC . However , season-modified effects were observed with 25(OH)D , i.e. children completing the school meal period in January/February had higher 25(OH)D status ( 5·5 ( 95 % CI 1·8 , 9·2 ) nmol/l ; P = 0·004 ) than children completing the control period in these months . A similar tendency was indicated in November/December ( 4·1 ( 95 % CI –0·12 , 8·3 ) nmol/l ; P = 0·057 ) . However , the effect was opposite in March/April ( –4·0 ( 95 % CI –7·0 , –0·9 ) nmol/l ; P = 0·010 ) , and no difference was found in May/June ( P = 0·214 ) . Unexpectedly , the school meals slightly increased PTH ( 0·18 ( 95 % CI 0·07 , 0·29 ) pmol/l ) compared with habitual lunch . Small increases in dietary vitamin D might hold potential to mitigate the winter nadir in Danish children 's 25(OH)D status while higher increases appear necessary to affect status throughout the year . More trials on effects of vitamin D intake from natural foods are needed",
"It is widely assumed that nutrition can improve school performance in children ; however , evidence remains limited and inconclusive . In the present study , we investigated whether serving healthy school meals influenced concentration and school performance of 8- to 11-year-old Danish children . The OPUS ( Optimal well-being , development and health for Danish children through a healthy New Nordic Diet ) School Meal Study was a cluster-r and omised , controlled , cross-over trial comparing a healthy school meal programme with the usual packed lunch from home ( control ) each for 3 months ( NCT 01457794 ) . The d2 test of attention , the Learning Rating Scale ( LRS ) and st and ard tests on reading and mathematics proficiency were administered at baseline and at the end of each study period . Intervention effects were evaluated using hierarchical mixed models . The school meal intervention did not influence concentration performance ( CP ; primary outcome , n 693 ) or processing speed ; however , the decrease in error percentage was 0·18 points smaller ( P increased reading speed ( 0·7 sentence , P=0·009 ) and the number of correct sentences ( 1·8 sentences , P The percentage of correct sentences also improved ( P the number correct improved relatively more than reading speed . There was no effect on overall math performance or outcomes from the LRS . In conclusion , school meals did not affect CP , but improved reading performance , which is a complex cognitive activity that involves inference , and increased errors related to impulsivity and inattention . These findings are worth examining in future trials",
"The aim of the present study was to compare total food intake , total and relative edible plate waste and self-reported food likings between school lunch based on the new Nordic diet ( NND ) and packed lunch from home . In two 3-month periods in a cluster-r and omised controlled unblinded cross-over study 3rd- and 4th- grade children ( n 187 ) from two municipal schools received lunch meals based on NND principles and their usual packed lunch ( control ) . Food intake and plate waste ( n 1558 ) were calculated after weighing lunch plates before and after the meal for five consecutive days and self-reported likings ( n 905 ) assessed by a web-based question naire . Average food intake was 6 % higher for the NND period compared with the packed lunch period . The quantity of NND intake varied with the menu ( P self-reported likings . The edible plate waste was 88 ( sd 80 ) g for the NND period and 43 ( sd 60 ) g for the packed lunch period whereas the relative edible plate waste was no different between periods for meals having waste ( n 1050 ) . Edible plate waste differed between menus ( P period . Self-reported likings were negatively associated with percentage plate waste ( P reduction of plate waste , children 's likings and nutritious school meals are crucial from both a nutritional , economic and environmental point of view",
"Objective : It has been suggested that overweight is negatively associated with cognitive functions . The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women . Methods : 20 overweight postmenopausal women were r and omized to either a modified paleolithic diet or a st and ard diet adhering to the Nordic Nutrition Recommendations for 6 months . We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions . Results : Episodic memory performance improved significantly ( p = 0.010 ) after the dietary interventions . Concomitantly , brain activity increased in the anterior part of the right hippocampus during memory encoding , without differences between diets . This was associated with decreased levels of plasma free fatty acids ( FFA ) . Brain activity increased in pre-frontal cortex and superior/middle temporal gyri . The magnitude of increase correlated with waist circumference reduction . During episodic retrieval , brain activity decreased in inferior and middle frontal gyri , and increased in middle/superior temporal gyri . Conclusions : Diet-induced weight loss , associated with decreased levels of plasma FFA , improves episodic memory linked to increased hippocampal activity",
"The OPUS ( Optimal well-being , development and health for Danish children through a healthy New Nordic Diet ( NND ) ) School Meal Study investigated the effects on the intake of foods and nutrients of introducing school meals based on the principles of the NND covering lunch and all snacks during the school day in a cluster-r and omised cross-over design . For two 3-month periods , 834 Danish children aged 8 - 11 years from forty-six school classes at nine schools received NND school meals or their usual packed lunches brought from home ( control ) in r and om order . The whole diet of the children was recorded over seven consecutive days using a vali date d Web-based Dietary Assessment Software for Children . The NND result ed in higher intakes of potatoes ( 130 % , 95 % CI 2·07 , 2·58 ) , fish ( 48 % , 95 % CI 1·33 , 1·65 ) , cheese ( 25 % , 95 % CI 1·15 , 1·36 ) , vegetables ( 16 % , 95 % CI 1·10 , 1·21 ) , eggs ( 10 % , 95 % CI 1·01 , 1·19 ) and beverages ( 6 % , 95 % CI 1·02 , 1·09 ) , and lower intakes of bread ( 13 % , 95 % CI 0·84 , 0·89 ) and fats ( 6 % , 95 % CI 0·90 , 0·98 ) were found among the children during the NND period than in the control period ( all , P found in mean energy intake ( P= 0·4 ) , but on average children reported 0·9 % less energy intake from fat and 0·9 % higher energy intake from protein during the NND period than in the control period . For micronutrient intakes , the largest differences were found for vitamin D ( 42 % , 95 % CI 1·32 , 1·53 ) and iodine ( 11 % , 95 % CI 1·08 , 1·15 ) due to the higher fish intake . In conclusion , the present study showed that the overall dietary intake at the food and nutrient levels was improved among children aged 8 - 11 years when their habitual packed lunches were replaced by school meals following the principles of the NND",
"Background : Type-2 diabetes ( T2D ) prevalence is rapidly increasing worldwide . Lifestyle factors , in particular obesity , diet , and physical activity play a significant role in the etiology of the disease . Of dietary patterns , particularly the Mediterranean diet has been studied , and generally a protective association has been identified . However , other regional diets are less explored . Objective : The aim of the present study was to investigate the association between adherence to a healthy Nordic food index and the risk of T2D . The index consists of six food items : fish , cabbage , rye bread , oatmeal , apples and pears , and root vegetables . Methods : Data was obtained from a prospect i ve cohort study of 57,053 Danish men and women aged 50–64 years , at baseline , of whom 7366 developed T2D ( median follow-up : 15.3 years ) . The Cox proportional hazards model was used to assess the association between the healthy Nordic food index and risk of T2D , adjusted for potential confounders . Results : Greater adherence to the healthy Nordic food index was significantly associated with lower risk of T2D after adjusting for potential confounders . An index score of 5−6 points ( high adherence ) was associated with a statistically significantly 25 % lower T2D risk in women ( HR : 0.75 , 95%CI : 0.61–0.92 ) and 38 % in men ( HR : 0.62 ; 95%CI : 0.53–0.71 ) compared to those with an index score of 0 points ( poor adherence ) . Conclusion : Adherence to a healthy Nordic food index was found to be inversely associated with risk of T2D , suggesting that regional diets other than the Mediterranean may also be recommended for prevention of T2D",
"Background / Objectives : Few studies have used biomarkers of whole-grain intake to study its relation to glucose metabolism . We aim ed to investigate the association between plasma alkylresorcinols ( AR ) , a biomarker of whole-grain rye and wheat intake , and glucose metabolism in individuals with metabolic syndrome (MetS).Subjects/ Methods : Participants were 30–65 years of age , with body mass index 27–40 kg/m2 and had MetS without diabetes . Individuals were recruited through six centers in the Nordic countries and r and omized to a healthy Nordic diet ( ND , n=96 ) , rich in whole-grain rye and wheat , or a control diet ( n=70 ) , for 18–24 weeks . In addition , associations between total plasma AR concentration and C17:0/C21:0 homolog ratio as an indication of the relative whole-grain rye intake , and glucose metabolism measures from oral glucose tolerance tests were investigated in pooled ( ND+control ) regression analyses at 18/24 weeks . Results : ND did not improve glucose metabolism compared with control diet , but the AR C17:0/C21:0 ratio was inversely associated with fasting insulin concentrations ( P=0.002 ) and positively associated with the insulin sensitivity indices Matsuda ISI ( P=0.026 ) and disposition index ( P=0.022 ) in pooled analyses at 18/24 weeks , even after adjustment for confounders . The AR C17:0/C21:0 ratio was not significantly associated with insulin secretion indices . Total plasma AR concentration was not related to fasting plasma glucose or fasting insulin at 18/24 weeks . Conclusions : The AR C17:0/C21:0 ratio , an indicator of relative whole-grain rye intake , is associated with increased insulin sensitivity in a population with",
"BACKGROUND In the 2.8 years of the Diabetes Prevention Program ( DPP ) r and omised clinical trial , diabetes incidence in high-risk adults was reduced by 58 % with intensive lifestyle intervention and by 31 % with metformin , compared with placebo . We investigated the persistence of these effects in the long term . METHODS All active DPP participants were eligible for continued follow-up . 2766 of 3150 ( 88 % ) enrolled for a median additional follow-up of 5.7 years ( IQR 5.5 - 5.8 ) . 910 participants were from the lifestyle , 924 from the metformin , and 932 were from the original placebo groups . On the basis of the benefits from the intensive lifestyle intervention in the DPP , all three groups were offered group-implemented lifestyle intervention . Metformin treatment was continued in the original metformin group ( 850 mg twice daily as tolerated ) , with participants unmasked to assignment , and the original lifestyle intervention group was offered additional lifestyle support . The primary outcome was development of diabetes according to American Diabetes Association criteria . Analysis was by intention-to-treat . This study is registered with Clinical Trials.gov , number NCT00038727 . FINDINGS During the 10.0-year ( IQR 9.0 - 10.5 ) follow-up since r and omisation to DPP , the original lifestyle group lost , then partly regained weight . The modest weight loss with metformin was maintained . Diabetes incidence rates during the DPP were 4.8 cases per 100 person-years ( 95 % CI 4.1 - 5.7 ) in the intensive lifestyle intervention group , 7.8 ( 6.8 - 8.8 ) in the metformin group , and 11.0 ( 9.8 - 12.3 ) in the placebo group . Diabetes incidence rates in this follow-up study were similar between treatment groups : 5.9 per 100 person-years ( 5.1 - 6.8 ) for lifestyle , 4.9 ( 4.2 - 5.7 ) for metformin , and 5.6 ( 4.8 - 6.5 ) for placebo . Diabetes incidence in the 10 years since DPP r and omisation was reduced by 34 % ( 24 - 42 ) in the lifestyle group and 18 % ( 7 - 28 ) in the metformin group compared with placebo . INTERPRETATION During follow-up after DPP , incidences in the former placebo and metformin groups fell to equal those in the former lifestyle group , but the cumulative incidence of diabetes remained lowest in the lifestyle group . Prevention or delay of diabetes with lifestyle intervention or metformin can persist for at least 10 years . FUNDING National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK )",
"Background Increased circulating cathepsin S levels have been linked to increased risk of cardiometabolic diseases and cancer . However , whether cathepsin S is a modifiable risk factor is unclear . We aim ed to investigate the effects of a prudent diet on plasma cathepsin S levels in healthy individuals . Findings Explorative analyses of a r and omized study were performed in 88 normal to slightly overweight and hyperlipidemic men and women ( aged 25 to 65 ) that were r and omly assigned to ad libitum prudent diet , i.e. healthy Nordic diet ( ND ) or a control group ( habitual Western diet ) for 6 weeks . Whereas all foods in the ND were provided , the control group was advised to consume their habitual diet throughout the study . The ND was in line with dietary recommendations , e.g. low in saturated fats , sugars and salt , but high in plant-based foods rich in fibre and unsaturated fats . The ND significantly decreased cathepsin S levels ( from 20.1 ( + /-4.0 SD ) to 19.7 μg/L ( + /-4.3 SD ) ) compared with control group ( from 18.2 ( + /-2.9 SD ) to 19.1 μg/L ( + /-3.8 SD ) ) . This difference remained after adjusting for sex and change in insulin sensitivity ( P = 0.03 ) , and near significant after adjusting for baseline cathepsin S levels ( P = 0.06 ) , but not for change in weight or LDL-C. Changes in cathepsin S levels were directly correlated with change in LDL-C. Conclusions Compared with a habitual control diet , a provided ad libitum healthy Nordic diet decreased cathepsin S levels in healthy individuals , possibly mediated by weight loss or lowered LDL-C. These differences between groups in cathepsin S were however not robust and therefore need further investigation",
"Fe and n-3 long-chain PUFA ( n-3 LCPUFA ) have both been associated with cognition , but evidence remains inconclusive in well-nourished school-aged children . In the Optimal Well-Being , Development and Health for Danish Children through a Healthy New Nordic Diet ( OPUS ) School Meal Study , the 3-month intervention increased reading performance , inattention , impulsivity and dietary intake of fish and Fe . This study investigated whether the intervention influenced n-3 LCPUFA and Fe status and , if so , explored how these changes correlated with the changes in cognitive performance . The study was a cluster-r and omised cross-over trial comparing school meals with packed lunch ( control ) . At baseline and after each treatment , we measured serum ferritin , whole-blood n-3 LCPUFA and Hb , and performance in reading , mathematics and d2-test of attention . Data were analysed using mixed models ( n 726 ) and principal component analysis of test performances ( n 644 ) , which showed two main patterns : ' school performance ' and ' reading comprehension ' . The latter indicated that children with good reading comprehension were also more inattentive and impulsive ( i.e. higher d2-test error% ) . The intervention improved ' school performance ' ( P=0·015 ) , ' reading comprehension ' ( P=0·043 ) and EPA+DHA status 0·21 ( 95 % CI 0·15 , 0·27 ) w/w % ( P affect serum ferritin or Hb . At baseline , having small Fe stores was associated with poorer ' school performance ' in girls , but with better ' reading comprehension ' in both boys and girls . Both baseline EPA+DHA status and the intervention-induced increase in EPA+DHA status was positively associated with ' school performance ' , suggesting that n-3 LCPUFA could potentially explain approximately 20 % of the intervention effect . These exploratory associations indicate that increased fish intake might explain some of the increase in reading performance and inattention in the study",
"The aim of this study is to review recent data on dietary fiber ( DF ) and the glycemic index ( GI ) , with special focus on studies from the Nordic countries regarding cardiometabolic risk factors , type 2 diabetes , cardiovascular disease , cancer , and total mortality . In this study , recent guidelines and scientific background papers or up date s on older reports on DF and GI published between 2000 and 2011 from the US , EU , WHO , and the World Cancer Research Fund were review ed , as well as prospect i ve cohort and intervention studies carried out in the Nordic countries . All of the reports support the role for fiber-rich foods and DF as an important part of a healthy diet . All of the five identified Nordic papers found protective associations between high intake of DF and health outcomes ; lower risk of cardiovascular disease , type 2 diabetes , colorectal and breast cancer . None of the reports and few of the Nordic papers found clear evidence for the GI in prevention of risk factors or diseases in healthy population s , although association was found in sub-groups , e.g. overweight and obese individuals and suggestive for prevention of type 2 diabetes . It was concluded that DF is associated with decreased risk of different chronic diseases and metabolic conditions . There is not enough evidence that choosing foods with low GI will decrease the risk of chronic diseases in the population overall . However , there is suggestive evidence that ranking food based on their GI might be of use for overweight and obese individuals . Issues regarding methodology , validity and practicality of the GI remain to be clarified",
"A New Nordic Diet ( NND ) was developed in the context of the Danish OPUS Study ( Optimal well-being , development and health for Danish children through a healthy New Nordic Diet ) . Health , gastronomic potential , sustainability and Nordic identity were crucial principles of the NND . The aim of the present study was to investigate the effects of serving NND school meals compared with the usual packed lunches on the dietary intake of NND signature foods . For two 3-month periods , 834 Danish children aged 8 - 11 years received NND school meals or their usual packed lunches brought from home ( control ) in r and om order . The entire diet was recorded over 7 consecutive days using a vali date d Web-based Dietary Assessment Software for Children . The NND result ed in higher intakes during the entire week ( % increase ) of root vegetables ( 116 ( 95 % CI 1·93 , 2·42 ) ) , cabbage ( 26 ( 95 % CI 1·08 , 1·47 ) ) , legumes ( 22 ( 95 % CI 1·06 , 1·40 ) ) , herbs ( 175 ( 95 % CI 2·36 , 3·20 ) ) , fresh berries ( 48 ( 95 % CI 1·13 , 1·94 ) ) , nuts and seeds ( 18 ( 95 % CI 1·02 , 1·38 ) ) , lean fish and fish products ( 47 ( 95 % CI 1·31 , 1·66 ) ) , fat fish and fish products ( 18 ( 95 % CI 1·02 , 1·37 ) ) and potatoes ( 129 ( 95 % CI 2·05 , 2·56 ) ) . Furthermore , there was a decrease in the number of children with zero intakes when their habitual packed lunches were replaced by NND school meals . In conclusion , this study showed that the children increased their intake of NND signature foods , and , furthermore , there was a decrease in the number of children with zero intakes of NND signature foods when their habitual packed lunches were replaced by school meals following the NND principles",
"OBJECTIVE —The excess risk of macrovascular disease and death associated with diabetes seems higher in women than in men . The pathogenesis for this risk difference has not been fully eluci date d. We investigated whether female sex was associated with macrovascular disease and death , independently of known risk factors related to type 2 diabetes , nephropathy , or retinopathy in normotensive patients with type 2 diabetes and microalbuminuria . RESEARCH DESIGN AND METHODS —We conducted a prospect i ve , prolonged follow-up study of a subgroup of 67 diabetic patients ( 46 men and 21 women ) without established cardiovascular disease who participated in a larger clinical trial . Data were collected on current and past health , medication use , blood pressure , renal function , and HbA1c during the follow-up period of 4.7 ± 0.8 ( means ± SE ) years . The end point was a composite of death , cardiovascular disease , cerebrovascular events , and peripheral artery disease . RESULTS —Of the women , eight ( 38.1 % ) met the end point compared with six ( 13.4 % ) of the men ( P = 0.02 for difference in event-free survival ) . The hazard ratio of women relative to men was 3.19 ( 95 % CI 1.11–9.21 ) , which further increased after adjusting for age , systolic blood pressure , BMI , smoking , total-to-HDL cholesterol ratio , urinary albumin excretion , and retinopathy . CONCLUSIONS —In our study population of normotensive patients with type 2 diabetes and microalbuminuria , female sex was associated with increased risk of fatal and nonfatal cardiovascular disease , independent of the classical cardiovascular risk factors , the severity of nephropathy or presence of retinopathy , or health care utilization",
"BACKGROUND Type 2 diabetes mellitus is increasingly common , primarily because of increases in the prevalence of a sedentary lifestyle and obesity . Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known . METHODS We r and omly assigned 522 middle-aged , overweight subjects ( 172 men and 350 women ; mean age , 55 years ; mean body-mass index [ weight in kilograms divided by the square of the height in meters ] , 31 ) with impaired glucose tolerance to either the intervention group or the control group . Each subject in the intervention group received individualized counseling aim ed at reducing weight , total intake of fat , and intake of saturated fat and increasing intake of fiber and physical activity . An oral glucose-tolerance test was performed annually ; the diagnosis of diabetes was confirmed by a second test . The mean duration of follow-up was 3.2 years . RESULTS The mean ( + /-SD ) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group ; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group ( P cumulative incidence of diabetes after four years was 11 percent ( 95 percent confidence interval , 6 to 15 percent ) in the intervention group and 23 percent ( 95 percent confidence interval , 17 to 29 percent ) in the control group . During the trial , the risk of diabetes was reduced by 58 percent ( P the incidence of diabetes was directly associated with changes in lifestyle . CONCLUSIONS Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects",
"OBJECTIVE Higher intake of magnesium appears to improve glucose and insulin homeostasis ; however , there are sparse prospect i ve data on the association between magnesium intake and incidence of type 2 diabetes . RESEARCH DESIGN AND METHODS In the Women 's Health Study , a cohort of 39,345 U.S. women aged > /=45 years with no previous history of cardiovascular disease , cancer , or type 2 diabetes completed vali date d semiquantitative food frequency question naires in 1993 and were followed for an average of 6 years . We used Cox proportional hazard models to estimate multivariate relative risks ( RRs ) of type 2 diabetes across quintiles of magnesium intake compared with the lowest quintile . In a sample of 349 apparently healthy women from this study , we measured plasma fasting insulin levels to examine their relation to magnesium intake . RESULTS During 222,523 person-years of follow-up , we documented 918 confirmed incident cases of type 2 diabetes . There was a significant inverse association between magnesium intake and risk of type 2 diabetes , independent of age and BMI ( P = 0.007 for trend ) . After further adjustment for physical activity , alcohol intake , smoking , family history of diabetes , and total calorie intake , the multivariate-adjusted RRs of diabetes from the lowest to highest quintiles of magnesium intake were attenuated at 1.0 , 1.06 , 0.81 , 0.86 , and 0.89 ( P = 0.05 for trend ) . Among women with BMI > /=25 kg/m2 , the inverse trend was significant ; multivariate-adjusted RRs were 1.0 , 0.96 , 0.76 , 0.84 , and 0.78 ( P = 0.02 for trend ) . Multivariate-adjusted geometric mean insulin levels for overweight women in the lowest quartile of magnesium intake was 53.5 compared with 41.5 pmol/l among those at the highest quartile ( P = 0.03 for trend ) . CONCLUSIONS These findings support a protective role of higher intake of magnesium in reducing the risk of developing type 2 diabetes , especially in overweight women",
"BACKGROUND Accumulation of myocardial triglycerides ( MTG ) is associated with impaired left ventricular ( LV ) remodelling and function in obese and diabetic subjects . The role of MTG accumulation in development of heart failure in this group of patients is unknown . Short-term studies suggest that diets that lead to weight loss could mobilize MTG , with a favourable effect on cardiac remodelling . In a 24-month , r and omized , investigator-blinded study , we assessed the effect of two different diets and subsequent weight loss on cardiac function and MTG in postmenopausal women . METHODS Sixty-eight healthy postmenopausal women with body mass index [ BMI ] ≥27kg/m(2 ) were r and omized to an ad libitum Palaeolithic diet ( PD ) or a Nordic Nutrition Recommendation ( NNR ) diet for 24months . Morphology , cardiac function , and MTG levels were measured using magnetic resonance ( MR ) scanning , including proton spectroscopy at baseline and 6 and 24months . RESULTS Despite mean weight losses of 4.9 ( 1.0 ) kg ( NNR ) and 7.8 ( 1.1 ) kg ( PD ) , the MTG content did not change over time ( p=0.98 in the NNR and p=0.11 in the PD group at 24months ) . Reduced left ventricular mass was observed in both diet groups over 24months . Blood pressure was reduced at 6months , but returned to baseline levels at 24months . End diastolic volume , stroke volume , and cardiac output decreased over time . No differences between diet groups were observed . CONCLUSIONS Diet intervention and moderate weight loss over 24months improved LV remodelling but did not alter MTG levels in overweight/obese postmenopausal women",
"Background The fatty acid ( FA ) composition of serum lipids is related to the quality of dietary fat intake . Objective To investigate the effects of a healthy Nordic diet ( ND ) on the FA composition of serum cholesterol esters ( CE-FA ) and assess the associations between changes in the serum CE-FA composition and blood lipoproteins during a controlled dietary intervention . Design The NORDIET trial was a 6-week r and omised , controlled , parallel-group dietary intervention study that included 86 adults ( 53±8 years ) with elevated low-density lipoprotein cholesterol ( LDL-C ) . Serum CE-FA composition was measured using gas chromatography . Diet history interviews were conducted , and daily intake was assessed using checklists . Results Food and nutrient intake data indicated that there was a reduction in the intake of fat from dairy and meat products and an increase in the consumption of fatty fish with the ND . The levels of saturated fatty acids in cholesterol esters ( CE-SFA ) 14:0 , 15:0 , and 18:0 , but not 16:0 , showed a significant decrease after intake of ND compared to the control diet ( p increase in serum 22:6n – 3 was observed compared with the control diet ( p changes in CE-SFA 14:0 , 15:0 , and 18:0 correlated positively with changes in LDL-C , HDL-C , LDL-C/HDL-C , ApoA1 , and ApoB ( p the changes in polyunsaturated fatty acids in cholesterol esters ( CE-PUFA ) 22:6n – 3 were negatively correlated with changes in the corresponding serum lipids . Conclusions The decreased intake of saturated fat and increased intake of n-3 PUFA in a healthy ND is partly reflected by changes in the serum CE-FA composition , which are associated with an improved serum lipoprotein pattern",
"Bias in self-reported dietary intake is important when evaluating the effect of dietary interventions , particularly for intervention foods . However , few have investigated this in children , and none have investigated the reporting accuracy of fish intake in children using biomarkers . In a Danish school meal study , 8- to 11-year-old children ( n 834 ) were served the New Nordic Diet ( NND ) for lunch . The present study examined the accuracy of self-reported intake of signature foods ( berries , cabbage , root vegetables , legumes , herbs , potatoes , wild plants , mushrooms , nuts and fish ) characterising the NND . Children , assisted by parents , self-reported their diet in a Web-based Dietary Assessment Software for Children during the intervention and control ( packed lunch ) periods . The reported fish intake by children was compared with their ranking according to fasting whole-blood EPA and DHA concentration and weight percentage using the Spearman correlations and cross-classification . Direct observation of school lunch intake ( n 193 ) was used to score the accuracy of food-reporting as matches , intrusions , omissions and faults . The reporting of all lunch foods had higher percentage of matches compared with the reporting of signature foods in both periods , and the accuracy was higher during the control period compared with the intervention period . Both Spearman 's rank correlations and linear mixed models demonstrated positive associations between EPA+DHA and reported fish intake . The direct observations showed that both reported and real intake of signature foods did increase during the intervention period . In conclusion , the self-reported data represented a true increase in the intake of signature foods and can be used to examine dietary intervention effects",
"BACKGROUND Intensive lifestyle interventions can reduce the incidence of type 2 diabetes in people with impaired glucose tolerance , but how long these benefits extend beyond the period of active intervention , and whether such interventions reduce the risk of cardiovascular disease ( CVD ) and mortality , is unclear . We aim ed to assess whether intensive lifestyle interventions have a long-term effect on the risk of diabetes , diabetes-related macrovascular and microvascular complications , and mortality . METHODS In 1986 , 577 adults with impaired glucose tolerance from 33 clinics in China were r and omly assigned to either the control group or to one of three lifestyle intervention groups ( diet , exercise , or diet plus exercise ) . Active intervention took place over 6 years until 1992 . In 2006 , study participants were followed-up to assess the long-term effect of the interventions . The primary outcomes were diabetes incidence , CVD incidence and mortality , and all-cause mortality . FINDINGS Compared with control participants , those in the combined lifestyle intervention groups had a 51 % lower incidence of diabetes ( hazard rate ratio [ HRR ] 0.49 ; 95 % CI 0.33 - 0.73 ) during the active intervention period and a 43 % lower incidence ( 0.57 ; 0.41 - 0.81 ) over the 20 year period , controlled for age and clustering by clinic . The average annual incidence of diabetes was 7 % for intervention participants versus 11 % in control participants , with 20-year cumulative incidence of 80 % in the intervention groups and 93 % in the control group . Participants in the intervention group spent an average of 3.6 fewer years with diabetes than those in the control group . There was no significant difference between the intervention and control groups in the rate of first CVD events ( HRR 0.98 ; 95 % CI 0.71 - 1.37 ) , CVD mortality ( 0.83 ; 0.48 - 1.40 ) , and all-cause mortality ( 0.96 ; 0.65 - 1.41 ) , but our study had limited statistical power to detect differences for these outcomes . INTERPRETATION Group-based lifestyle interventions over 6 years can prevent or delay diabetes for up to 14 years after the active intervention . However , whether lifestyle intervention also leads to reduced CVD and mortality remains unclear",
"The healthy Nordic diet has been previously shown to have health beneficial effects among subjects at risk of CVD . However , the extent of food changes needed to achieve these effects is less explored . The aim of the present study was to investigate the effects of exchanging a few commercially available , regularly consumed key food items ( e.g. spread on bread , fat for cooking , cheese , bread and cereals ) with improved fat quality on total cholesterol , LDL-cholesterol and inflammatory markers in a double-blind r and omised , controlled trial . In total , 115 moderately hypercholesterolaemic , non-statin-treated adults ( 25 - 70 years ) were r and omly assigned to an experimental diet group ( Ex-diet group ) or control diet group ( C-diet group ) for 8 weeks with commercially available food items with different fatty acid composition ( replacing SFA with mostly n-6 PUFA ) . In the Ex-diet group , serum total cholesterol ( P and LDL-cholesterol ( P -11 % in total cholesterol and LDL-cholesterol , respectively . No difference in change in plasma levels of inflammatory markers ( high-sensitive C-reactive protein , IL-6 , soluble TNF receptor 1 and interferon-γ ) was observed between the groups . In conclusion , exchanging a few regularly consumed food items with improved fat quality reduces total cholesterol , with no negative effect on levels of inflammatory markers . This shows that an exchange of a few commercially available food items was easy and manageable and led to clinical ly relevant cholesterol reduction , potentially affecting future CVD risk",
"The effects on blood lipids and blood pressure of a diet corresponding to present Nordic Nutrition Recommendations , i.e. less than 30 % of energy from fat and with a fibre content exceeding 3 g/MJ , were studied in 18 men and 12 women ( mean age , 24 years ) under strict dietary control over 8 months . Blood sampling , blood pressure and body weight measurement were performed at four occasions on their habitual diet and once a month during the intervention period . An age-matched control group ( 17 men , 8 women ) was followed with monthly measurements parallel to the intervention group . The habitual diets , assessed by 7-day records , showed an average fat content corresponding to 36 % of energy . Initial levels of total cholesterol and HDL cholesterol ( X + /- SD ) were 4.21 + /- 0.61 and 1.23 + /- 0.23 mmol/l for the men in the intervention group ; 4.35 + /- 0.79 and 1.21 + /- 0.26 mmol/l for the male controls ; 4.61 + /- 0.59 and 1.46 + /- 0.31 mmol/l for the women in the intervention group and 4.48 + /- 0.64 and 1.48 + /- 0.29 mmol/l for the female controls . Significantly decreased levels of total cholesterol and HDL cholesterol throughout the experimental period were seen for both sexes in the intervention group . Total cholesterol fell 0.49 mmol/l ( 95 % CI : 0.41 - 0.56 ) in the male subjects and 0.49 mmol/l ( 95 % CI : 0.39 - 0.59 ) in the female subjects . The fall in HDL cholesterol was 0.16 mmol/l ( 95 % C : 0.13 - 0.18 ) and 0.18 mmol/l ( 95 % CI : 0.12 - 0.23 ) , respectively . Total cholesterol changes were independent of initial values . All subjects were normotensive at the start of the study with an average blood pressure of 122/68 mmHg for men and 112/68 mmHg for the women . Systolic blood pressure dropped gradually and significantly in the male subjects of the intervention group . A minimum of 6 mmHg below initial values was noted after six months of dietary intervention . No significant changes in dietary intake and blood lipids were observed in the control group . Thus , changes of present dietary habits of young healthy Danish subjects to an intake in accordance with the Nordic Nutrition Recommendations 1989 will favourably affect suggested risk factors for disease",
"BACKGROUND Experimental studies in animals and cross-sectional studies in humans have suggested that low serum magnesium levels might lead to type 2 diabetes ; however , this association has not been examined prospect ively . METHODS We assessed the risk for type 2 diabetes associated with low serum magnesium level and low dietary magnesium intake in a cohort of nondiabetic middle-aged adults ( N = 12,128 ) from the Atherosclerosis Risk in Communities Study during 6 years of follow-up . Fasting serum magnesium level , categorized into 6 levels , and dietary magnesium intake , categorized into quartiles , were measured at the baseline examination . Incident type 2 diabetes was defined by self-report of physician diagnosis , use of diabetic medication , fasting glucose level of at least 7.0 mmol/L ( 126 mg/dL ) , or nonfasting glucose level of at least 11.1 mmol/L ( 200 mg/dL ) . RESULTS Among white participants , a grade d inverse relationship between serum magnesium levels and incident type 2 diabetes was observed . From the highest to the lowest serum magnesium levels , there was an approximate 2-fold increase in incidence rate ( 11.1 , 12.2 , 13.6 , 12.8 , 15.8 , and 22.8 per 1000 person-years ; P = .001 ) . This grade d association remained significant after simultaneous adjustment for potential confounders , including diuretic use . Compared with individuals with serum magnesium levels of 0.95 mmol/L ( 1.90 mEq/L ) or greater , the adjusted relative odds of incident type 2 diabetes rose progressively across the following lower magnesium categories : 1.13 ( 95 % CI , 0.79 - 1.61 ) , 1.20 ( 95 % CI , 0.86 - 1.68 ) , 1.11 ( 95 % CI , 0.80 - 1.56 ) , 1.24 ( 95 % CI , 0.86 - 1.78 ) , and 1.76 ( 95 % CI , 1.18 - 2.61 ) ( for trend , P = .01 ) . In contrast , little or no association was observed in black participants . No association was detected between dietary magnesium intake and the risk for incident type 2 diabetes in black or white participants . CONCLUSIONS Among white participants , low serum magnesium level is a strong , independent predictor of incident type 2 diabetes . That low dietary magnesium intake does not confer risk for type 2 diabetes implies that compartmentalization and renal h and ling of magnesium may be important in the relationship between low serum magnesium levels and the risk for type 2 diabetes",
"BACKGROUND The effect of increasing the intake of dietary fiber on glycemic control in patients with type 2 diabetes mellitus is controversial . METHODS In a r and omized , crossover study , we assigned 13 patients with type 2 diabetes mellitus to follow two diets , each for six weeks : a diet containing moderate amounts of fiber ( total , 24 g ; 8 g of soluble fiber and 16 g of insoluble fiber ) , as recommended by the American Diabetes Association ( ADA ) , and a high-fiber diet ( total , 50 g ; 25 g of soluble fiber and 25 g of insoluble fiber ) , containing foods not fortified with fiber ( unfortified foods ) . Both diets , prepared in a research kitchen , had the same macronutrient and energy content . We compared the effects of the two diets on glycemic control and plasma lipid concentrations . RESULTS Compliance with the diets was excellent . During the sixth week , the high-fiber diet , as compared with the the sixth week of the ADA diet , mean daily prepr and ial plasma glucose concentrations were 13 mg per deciliter [ 0.7 mmol per liter ] lower ( 95 percent confidence interval , 1 to 24 mg per deciliter [ 0.1 to 1.3 mmol per liter ] ; P=0.04 ) and mean median difference , daily urinary glucose excretion 1.3 g ( 0.23 ; 95 percent confidence interval , 0.03 to 1.83 g ; P= 0.008 ) . The high-fiber diet also lowered the area under the curve for 24-hour plasma glucose and insulin concentrations , which were measured every two hours , by 10 percent ( P=0.02 ) and 12 percent ( P=0.05 ) , respectively . The high-fiber diet reduced plasma total cholesterol concentrations by 6.7 percent ( P=0.02 ) , triglyceride concentrations by 10.2 percent ( P=0.02 ) , and very-low-density lipoprotein cholesterol concentrations by 12.5 percent ( P=0.01 ) . CONCLUSIONS A high intake of dietary fiber , particularly of the soluble type , above the level recommended by the ADA , improves glycemic control , decreases hyperinsulinemia , and lowers plasma lipid concentrations in patients with type 2 diabetes",
"Background / Objectives : Short-term studies have suggested beneficial effects of a Palaeolithic-type diet ( PD ) on body weight and metabolic balance . We now report the long-term effects of a PD on anthropometric measurements and metabolic balance in obese postmenopausal women , in comparison with a diet according to the Nordic Nutrition Recommendations (NNR).Subjects/ Methods : Seventy obese postmenopausal women ( mean age 60 years , body mass index 33 kg/m2 ) were assigned to an ad libitum PD or NNR diet in a 2-year r and omized controlled trial . The primary outcome was change in fat mass as measured by dual-energy X-ray absorptiometry . Results : Both groups significantly decreased total fat mass at 6 months ( −6.5 and −2.6 kg ) and 24 months ( −4.6 and −2.9 kg ) , with a more pronounced fat loss in the PD group at 6 months ( P ) . Waist circumference and sagittal diameter also decreased in both the groups , with a more pronounced decrease in the PD group at 6 months ( −11.1 vs−5.8 cm , P=0.001 and −3.7 vs−2.0 cm , P respectively ) . Triglyceride levels decreased significantly more at 6 and 24 months in the PD group than in the NNR group ( P P=0.004 ) . Nitrogen excretion did not differ between the groups . Conclusions : A PD has greater beneficial effects vs an NNR diet regarding fat mass , abdominal obesity and triglyceride levels in obese postmenopausal women ; effects not sustained for anthropometric measurements at 24 months . Adherence to protein intake was poor in the PD group . The long-term consequences of these changes remain to be studied",
"We served a low-fat ( 28 % of energy ) high-fibre ( 3.3 g/MJ ) diet according to Nordic Nutrition Recommendations ( REC diet ) , and a high-fat diet ( 39 % of energy ) corresponding to the average Danish diet ( DANE diet ) to 21 healthy middle-aged individuals in a two times two weeks cross-over study . The REC diet result ed in lower serum concentrations of low density lipoprotein ( LDL ) cholesterol ( medians : 2.77 vs 3.04 mmol/l , p high-density lipoprotein ( HDL ) cholesterol ( 1.08 vs 1.24 mmol/l , p higher fasting triglycerides ( 1.11 vs 0.86 mmol/l , p = 0.04 ) than the DANE diet . Furthermore , the REC diet lowered plasma factor VII coagulant activity ( FVIIc ) ( 88 vs 96 % , p = 0.002 ) and raised plasma fibrinolytic activity . Our observations indicate that a low-fat high-fibre diet may not only reduce the atherogenic , but also the thrombogenic tendency of an individual compared with a diet corresponding to the average Danish diet",
"Introduction : Danish children consume too much sugar and not enough whole grain , fish , fruit , and vegetables . The Nordic region is rich in such foods with a strong health-promoting potential . We lack r and omised controlled trials that investigate the developmental and health impact of serving school meals based on Nordic foods . Aim : This paper describes the rationale , design , study population , and potential implication s of the Optimal well-being , development and health for Danish children through a healthy New Nordic Diet ( OPUS ) School Meal Study . Methods : In a cluster-r and omised cross-over design , 1021 children from 3rd and 4th grade s ( 8–11 years old ) at nine Danish municipal schools were invited to participate . Classes were assigned to two 3-month periods with free school meals based on the New Nordic Diet ( NND ) or their usual packed lunch ( control ) . Dietary intake , nutrient status , physical activity , cardiorespiratory fitness , sleep , growth , body composition , early metabolic and cardiovascular risk markers , illness , absence from school , wellbeing , cognitive function , social and cultural features , food acceptance , waste , and cost were assessed . Results : In total , 834 children ( 82 % of those invited ) participated . Although their parents were slightly better educated than the background population , children from various socioeconomic background s were included . The proportion of overweight and obese children ( 14 % ) resembled that of earlier examinations of Danish school children . Drop out was 8.3 % . Conclusions : A high inclusion rate and low drop out rate was achieved . This study will be the first to determine whether school meals based on the NND improve children ’s diet , health , growth , cognitive performance , and early disease risk markers",
"OBJECTIVE the aim of this study was to investigate the effects of a healthy Nordic diet ( ND ) on cardiovascular risk factors . DESIGN AND SUBJECTS in a r and omized controlled trial ( NORDIET ) conducted in Sweden , 88 mildly hypercholesterolaemic subjects were r and omly assigned to an ad libitum ND or control diet ( subjects ' usual Western diet ) for 6 weeks . Participants in the ND group were provided with all meals and foods . Primary outcome measurements were low-density lipoprotein ( LDL ) cholesterol , and secondary outcomes were blood pressure ( BP ) and insulin sensitivity ( fasting insulin and homeostatic model assessment -insulin resistance ) . The ND was rich in high-fibre plant foods , fruits , berries , vegetables , whole grains , rapeseed oil , nuts , fish and low-fat milk products , but low in salt , added sugars and saturated fats . RESULTS the ND contained 27 % , 52 % , 19 % and 2 % of energy from fat , carbohydrate , protein and alcohol , respectively . In total , 86 of 88 subjects r and omly assigned to diet completed the study . Compared with controls , there was a decrease in plasma cholesterol ( -16 % , P , LDL cholesterol ( -21 % , P , high-density lipoprotein ( HDL ) cholesterol ( -5 % , P , LDL/HDL ( -14 % , P and apolipoprotein (apo)B/apoA1 ( -1 % , P reduced insulin ( -9 % , P = 0.01 ) and systolic BP by -6.6 ± 13.2 mmHg ( -5 % , P body weight decreased after 6 weeks in the ND compared with the control group ( -4 % , P for blood lipids , but not for insulin sensitivity or BP . There were no significant differences in diastolic BP or triglyceride or glucose concentrations . CONCLUSIONS a healthy ND improves blood lipid profile and insulin sensitivity and lowers blood pressure at clinical ly relevant levels in hypercholesterolaemic subjects",
"Background / Objectives : Our objective was to investigate changes in liver fat and insulin sensitivity during a 2-year diet intervention . An ad libitum Paleolithic diet ( PD ) was compared with a conventional low-fat diet (LFD).Subjects/ Methods : Seventy healthy , obese , postmenopausal women were r and omized to either a PD or a conventional LFD . Diet intakes were ad libitum . Liver fat was measured with proton magnetic resonance spectroscopy . Insulin sensitivity was evaluated with oral glucose tolerance tests and calculated as homeostasis model assessment -insulin resistance (HOMA-IR)/liver insulin resistance ( Liver IR ) index for hepatic insulin sensitivity and oral glucose insulin sensitivity (OGIS)/Matsuda for peripheral insulin sensitivity . All measurements were performed at 0 , 6 and 24 months . Forty-one women completed the examinations for liver fat and were included . Results : Liver fat decreased after 6 months by 64 % ( 95 % confidence interval : 54–74 % ) in the PD group and by 43 % ( 27–59 % ) in the LFD group ( P months , liver fat decreased 50 % ( 25–75 % ) in the PD group and 49 % ( 27–71 % ) in the LFD group . Weight reduction between baseline and 6 months was correlated to liver fat improvement in the LFD group ( rs=0.66 , P Hepatic insulin sensitivity improved during the first 6 months in the PD group ( P A PD with ad libitum intake had a significant and persistent effect on liver fat and differed significantly from a conventional LFD at 6 months . This difference may be due to food quality , for example , a higher content of mono- and polyunsaturated fatty acids in the PD . Changes in liver fat did not associate with alterations in insulin sensitivity ",
"OBJECTIVE Abdominal fat accumulation after menopause is associated with low- grade inflammation and increased risk of metabolic disorders . Effective long-term lifestyle treatment is therefore needed . METHODS Seventy healthy postmenopausal women ( age 60 ± 5.6 years ) with BMI 32.5 ± 5.5 were r and omized to a Paleolithic-type diet ( PD ) or a prudent control diet ( CD ) for 24 months . Blood sample s and fat biopsies were collected at baseline , 6 months , and 24 months to analyze inflammation-related parameters . RESULTS And roid fat decreased significantly more in the PD group ( P = 0.009 ) during the first 6 months with weight maintenance at 24 months in both groups . Long-term significant effects ( P adipose gene expression were found for toll-like receptor 4 ( decreased at 24 months ) and macrophage migration inhibitory factor ( increased at 24 months ) in both groups . Serum interleukin 6 ( IL-6 ) and tumor necrosis factor α levels were decreased at 24 months in both groups ( P P = 0.022 ) . High-sensitivity C-reactive protein was decreased in the PD group at 24 months ( P = 0.001 ) . CONCLUSIONS A reduction of abdominal obesity in postmenopausal women is linked to specific changes in inflammation-related adipose gene expression",
"Biomarkers of dietary intake can be important tools in nutrition research . Our aim was to assess whether plasma alkylresorcinol ( AR ) and β-carotene concentrations could be used as dietary biomarkers for whole-grain , fruits and vegetables in a healthy Nordic diet ( ND ) . Participants ( n = 166 ) , 30 - 65 y with a body mass index of 27 - 40 kg/m(2 ) and two more features of metabolic syndrome ( International Diabetes Federation definition , slightly modified ) , were recruited through six centers in the Nordic countries and r and omly assigned to an ND or control diet for 18 or 24 wk , depending on study center . Plasma AR and β-carotene were analyzed and nutrient intake calculated from 4-d food records . Median fiber intake increased in the ND group from 2.5 g/MJ at baseline to 4.1 g/MJ ( P 24 ) , and median ( IQR ) fasting plasma total AR concentration increased from 73 ( 88 ) to 106 ( 108 ) nmol/L , or 45 % , from baseline to end point ( P 0.001 ) . The AR concentration was significantly higher in the ND group ( P at end point . β-Carotene intake tended to increase in the ND group ( P = 0.07 ) , but the plasma β-carotene concentration did not change significantly throughout the study and did not differ between the groups at follow-up . In conclusion , an ND result ed in higher dietary fiber intake and increased plasma total AR concentration compared with the control diet , showing that the total AR concentration might be a valid biomarker for an ND in which whole-grain wheat and rye are important components . No significant difference in plasma β-carotene concentrations was observed between the ND and control groups , suggesting that β-carotene may not be a sensitive enough biomarker of the ND"
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41188696-06ff-11f0-808a-c43d1ab1c353
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The aim of this study was to assess the effects of different dietary approaches on low-density lipoprotein ( LDL ) cholesterol , high-density lipoprotein ( HDL ) cholesterol , and triglyceride ( TG ) levels in patients with type 2 diabetes ( T2D ) by applying network meta- analysis ( NMA ) . Systematic electronic and h and search es were conducted until January 2018 . R and omized controlled trials ( RCTs ) with an intervention period of ≥ 12 weeks , focussing on adults with T2D , and comparing dietary approaches regarding LDL , HDL or TGs , were included . For each outcome measure , r and om effects NMA was performed in order to determine the effect of each dietary approach compared to every other dietary intervention . Mean differences ( MDs ) and 95 % confidence intervals ( 95 % CIs ) were calculated , and for the ranking , the surface under the cumulative ranking curves ( SUCRA ) was determined . Additionally , the credibility of evidence was evaluated . 52 RCTs ( 44 for LDL , 48 for HDL and 52 for TGs ) comparing nine dietary approaches ( low fat , vegetarian , Mediterranean , high protein , moderate carbohydrate , low carbohydrate , control , low glycaemic index/glycaemic load and Palaeolithic diet ) enrolling 5360 T2D patients were included . The vegetarian diet most effectively reduced LDL levels [ MD ( 95 % CI ) : − 0.33 ( − 0.55 , − 0.12 ) mmol/L ; compared to the control diet ] . The Mediterranean diet beneficially raised HDL [ MD ( 95 % CI ) : 0.09 ( 0.04 , 0.15 ) mmol/L ] and decreased TG levels [ MD ( 95 % CI ) : − 0.41 ( − 0.72 , − 0.10 ) mmol/L ] compared to the control diet . The Mediterranean diet was the most effective dietary approach to manage diabetic dyslipidaemia altogether ( SUCRA : 79 % ) . The overall findings are mainly limited by low credibility of evidence
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"OBJECTIVE To test whether a weight loss program promotes greater weight loss , glycemic control , and improved cardiovascular disease risk factors compared with control conditions and whether there is a differential response to higher versus lower carbohydrate intake . RESEARCH DESIGN AND METHODS This r and omized controlled trial at two university medical centers enrolled 227 overweight or obese adults with type 2 diabetes and assigned them to parallel in-person diet and exercise counseling , with prepackaged foods in a planned menu during the initial phase , or to usual care ( UC ; two weight loss counseling sessions and monthly contacts ) . RESULTS Relative weight loss was 7.4 % ( 95 % CI 5.7–9.2 % ) , 9.0 % ( 7.1–10.9 % ) , and 2.5 % ( 1.3–3.8 % ) for the lower fat , lower carbohydrate , and UC groups ( P . Glycemic control markers and triglyceride levels were lower in the intervention groups compared with UC group at 1 year ( fasting glucose 141 [ 95 % CI 133–149 ] vs. 159 [ 144–174 ] mg/dL , P = 0.023 ; hemoglobin A1c 6.9 % [ 6.6–7.1 % ] vs. 7.5 % [ 7.1–7.9 % ] or 52 [ 49–54 ] vs. 58 [ 54–63 ] mmol/mol , P = 0.001 ; triglycerides 148 [ 134–163 ] vs. 204 [ 173–234 ] mg/dL , P lower hemoglobin A1c ( 6.6 % [ 95 % CI 6.3–6.8 % ] vs. 7.2 % [ 6.8–7.5 % ] or 49 [ 45–51 ] vs. 55 [ 51–58 ] mmol/mol ) at 1 year ( P = 0.008 ) . CONCLUSIONS The weight loss program result ed in greater weight loss and improved glycemic control in type 2 diabetes",
"Aims /hypothesisThe study aim ed to compare the effects of a 2 year intervention with a low-fat diet ( LFD ) or a low-carbohydrate diet ( LCD ) , based on four group meetings to achieve compliance . Methods This was a prospect i ve r and omised parallel trial involving 61 adults with type 2 diabetes consecutively recruited in primary care and r and omised by drawing ballots . Patients that did not speak Swedish could not be recruited . The primary outcomes in this non-blinded study were weight and HbA1c . Patients on the LFD aim ed for 55–60 energy per cent ( E% ) and those on LCD for 20 E% from carbohydrate . Results The mean BMI and HbA1c of the participants were 32.7 ± 5.4 kg/m2 and 57.0 ± 9.2 mmol/mol , respectively . No patients were lost to follow-up . Weight loss did not differ between groups and was maximal at 6 months : LFD −3.99 ± 4.1 kg ( n = 31 ) ; LCD −4.31 ± 3.6 kg ( n = 30 ) ; p 0.020 within groups , respectively ) . HbA1c fell in the LCD group only ( LCD at 6 months −4.8 ± 8.3 mmol/mol , p = 0.004 , at 12 months −2.2 ± 7.7 mmol/mol , p = 0.12 ; LFD at 6 months −0.9 ± 8.8 mmol/mol , p = 0.56 ) . At 6 months , HDL-cholesterol had increased with the LCD ( from 1.13 ± 0.33 mmol/l to 1.25 ± 0.47 mmol/l , p = 0.018 ) while LDL-cholesterol did not differ between groups . Insulin doses were reduced in the LCD group ( 0 months , LCD 42 ± 65 E , LFD 39 ± 51 E ; 6 months , LCD 30 ± 47 E , LFD 38 ± 48 E ; p = 0.046 for between-group change ) . Conclusions /interpretationWeight changes did not differ between the diet groups , while insulin doses were reduced significantly more with the LCD at 6 months , when compliance was good . Thus , aim ing for 20 % of energy intake from carbohydrates is safe with respect to cardiovascular risk compared with the traditional LFD and this approach could constitute a treatment alternative . Trial registration : Clinical Trials.gov NCT01005498 Funding : University Hospital of Linköping Research Funds , Linköping University , the County Council of Östergötl and , and the Diabetes Research Centre of Linköping",
"AIMS To compare the effects of lifestyle modification programs that prescribe low-glycemic load ( GL ) vs. low-fat diets in a r and omized trial . METHODS Seventy-nine obese adults with type 2 diabetes received low-fat or low-GL dietary instruction , delivered in 40-week lifestyle modification programs with identical goals for calorie intake and physical activity . Changes in weight , HbA(1c ) , and other metabolic parameters were compared at weeks 20 and 40 . RESULTS Weight loss did not differ between groups at week 20 ( low-fat : -5.7±3.7 % ; low-GL : -6.7±4.4 % , p=.26 ) or week 40 ( low-fat : -4.5±7.5 % ; low-GL : -6.4±8.2 % , p=.28 ) . Adjusting for changes in antidiabetic medications , subjects on the low-GL diet had larger reductions in HbA(1c ) than those on the low-fat diet at week 20 ( low-fat : -0.3±0.6 % ; low-GL : -0.7±0.6 % , p=.01 ) , and week 40 ( low-fat : -0.1±1.2 % ; low-GL : -0.8±1.3 % ; p=.01 ) . Groups did not differ significantly on any other metabolic outcomes ( p≥.06 ) . CONCLUSIONS Results suggest that targeting GL , rather than dietary fat , in a low-calorie diet can significantly enhance the effect of weight loss on HbA(1c ) in patients with type 2 diabetes",
"BACKGROUND & AIMS The usefulness of low-carbohydrate diet ( LCD ) for Japanese patients with type 2 diabetes mellitus ( T2DM ) has not been fully investigated . Therefore , we compared the effectiveness and safety of LCD with calorie restricted diet ( CRD ) . METHODS This prospect i ve , r and omized , open-label , comparative study included 66 T2DM patients with HbA1c > 7.5 % even after receiving repeated education programs on CRD . They were r and omly allocated to either the 130g/day LCD group ( n = 33 ) or CRD group ( n = 33 ) . Patients received personal nutrition education of CRD or LCD for 30 min at baseline , 1 , 2 , 4 , and 6 months . Patients of the CRD group were advised to maintain the intake of calories and balance of macronutrients ( 28 × ideal body weight calories per day ) . Patients of the LCD group were advised to maintain the intake of 130 g/day carbohydrate without other specific restrictions . Several parameters were assessed at baseline and 6 months after each intervention . The primary endpoint was a change in HbA1c level from baseline to the end of the study . RESULTS At baseline , BMI and HbA1c were 26.5 ( 24.6 - 30.1 ) and 8.3 ( 8.0 - 9.3 ) , and 26.7 ( 25.0 - 30.0 ) kg/m2 and 8.0 ( 7.6 - 8.9 ) % , in the CRD and LCD , respectively . At the end of the study , HbA1c decreased by -0.65 ( -1.53 to -0.10 ) % in the LCD group , compared with 0.00 ( -0.68 to 0.40 ) % in the CRD group ( p decrease in BMI in the LCD group [ -0.58 ( -1.51 to -0.16 ) kg/m2 ] exceeded that observed in the CRD group ( p = 0.03 ) . CONCLUSIONS Our study demonstrated that 6-month 130 g/day LCD reduced HbA1c and BMI in poorly controlled Japanese patients with T2DM . LCD is a potentially useful nutrition therapy for Japanese patients who can not adhere to CRD . This trial was registered at http://www.umin.ac.jp/english/ ( University Hospital Medical Information Network : study ID number 000010663 )",
"BACKGROUND The appropriate dietary intervention for overweight persons with type 2 diabetes mellitus ( DM2 ) is unclear . Trials comparing the effectiveness of diets are frequently limited by short follow-up times and high dropout rates . AIM The effects of a low carbohydrate Mediterranean ( LCM ) , a traditional Mediterranean ( TM ) , and the 2003 American Diabetic Association ( ADA ) diet were compared , on health parameters during a 12-month period . METHODS In this 12-month trial , 259 overweight diabetic patients ( mean age 55 years , mean body mass index 31.4 kg/m(2 ) ) were r and omly assigned to one of the three diets . The primary end-points were reduction of fasting plasma glucose , HbA1c and triglyceride ( TG ) levels . RESULTS 194 patients out of 259 ( 74.9 % ) completed follow-up . After 12 months , the mean weight loss for all patients was 8.3 kg : 7.7 kg for ADA , 7.4 kg for TM and 10.1 kg for LCM diets . The reduction in HbA1c was significantly greater in the LCM diet than in the ADA diet ( -2.0 and -1.6 % , respectively , p HDL cholesterol increased ( 0.1 mmol/l + /- 0.02 ) only on the LCM ( p reduction in serum TG was greater in the LCM ( -1.3 mmol/l ) and TM ( -1.5 mmol/l ) than in the ADA ( -0.7 mmol/l ) , p = 0.001 . CONCLUSIONS An intensive 12-month dietary intervention in a community-based setting was effective in improving most modifiable cardiovascular risk factors in all the dietary groups . Only the LCM improved HDL levels and was superior to both the ADA and TM in improving glycaemic control",
"Background Our aim was to compare the effects of a Paleolithic ( ' Old Stone Age ' ) diet and a diabetes diet as generally recommended on risk factors for cardiovascular disease in patients with type 2 diabetes not treated with insulin . Methods In a r and omized cross-over study , 13 patients with type 2 diabetes , 3 women and 10 men , were instructed to eat a Paleolithic diet based on lean meat , fish , fruits , vegetables , root vegetables , eggs and nuts ; and a Diabetes diet design ed in accordance with dietary guidelines during two consecutive 3-month periods . Outcome variables included changes in weight , waist circumference , serum lipids , C-reactive protein , blood pressure , glycated haemoglobin ( HbA1c ) , and areas under the curve for plasma glucose and plasma insulin in the 75 g oral glucose tolerance test . Dietary intake was evaluated by use of 4-day weighed food records . Results Study participants had on average a diabetes duration of 9 years , a mean HbA1c of 6,6 % units by Mono-S st and ard and were usually treated with metformin alone ( 3 subjects ) or metformin in combination with a sulfonylurea ( 3 subjects ) or a thiazolidinedione ( 3 subjects ) . Mean average dose of metformin was 1031 mg per day . Compared to the diabetes diet , the Paleolithic diet result ed in lower mean values of HbA1c ( -0.4 % units , p = 0.01 ) , triacylglycerol ( -0.4 mmol/L , p = 0.003 ) , diastolic blood pressure ( -4 mmHg , p = 0.03 ) , weight ( -3 kg , p = 0.01 ) , BMI ( -1 kg/m2 , p = 0.04 ) and waist circumference ( -4 cm , p = 0.02 ) , and higher mean values of high density lipoprotein cholesterol ( + 0.08 mmol/L , p = 0.03 ) . The Paleolithic diet was mainly lower in cereals and dairy products , and higher in fruits , vegetables , meat and eggs , as compared with the Diabetes diet . Further , the Paleolithic diet was lower in total energy , energy density , carbohydrate , dietary glycemic load , saturated fatty acids and calcium , and higher in unsaturated fatty acids , dietary cholesterol and several vitamins . Dietary GI was slightly lower in the Paleolithic diet ( GI = 50 ) than in the Diabetic diet ( GI = 55 ) . Conclusion Over a 3-month study period , a Paleolithic diet improved glycemic control and several cardiovascular risk factors compared to a Diabetes diet in patients with type 2 diabetes . Trial registration Clinical Trials.gov NCT00435240",
"BACKGROUND AND AIM Diets where carbohydrate has been partially exchanged for protein have shown beneficial changes in persons with type 2 diabetes but no studies have enrolled people with albuminuria . We aim to determine if a high protein to carbohydrate ratio ( HPD ) in an energy reduced diet has a beneficial effect on metabolic control and cardiovascular risk factors without negatively affecting renal function . METHOD AND RESULTS Adult , overweight participants with type 2 diabetes , with albuminuria ( 30 - 600 mg/24 h or an albumin-to-creatinine ratio of 3.0 - 60 mg/mmol ) , and estimated GFR of > 40 ml/min/1.73 m(2 ) were enrolled . Participants were r and omized to an HPD or an SPD . Protein : fat : carbohydrate ratio was 30:30:40 % of energy for the HPD and 20:30:50 % for the SPD . Main outcomes were renal function , weight loss , blood pressure , serum lipids and glycaemic control . We recruited 76 volunteers and 45 ( 35 men and 10 women ) finished . There were no overall changes in renal function at 12 months and no significant differences in weight loss between groups ( 9.7 ± 2.9 kg and 6.6 ± 1.4 kg HPD and SPD group respectively ; p = 0.32 ) . Fasting blood glucose decreased significantly with no treatment effect . The decrease in HbA1c differed between treatments at 6 months ( HPD -0.9 vs. SPD -0.3 % ; p = 0.039 ) but not at 12 months . HDL increased significantly with no treatment effects . There were no changes in LDL or blood pressure overall but DBP was lower in the HPD group ( p = 0.024 ) at 12 months . CONCLUSION Weight loss improved overall metabolic control in this group of well controlled participants with type 2 diabetes regardless of diet composition",
"BACKGROUND Adherence to a Mediterranean diet may improve longevity , but relevant data are limited . METHODS We conducted a population -based , prospect i ve investigation involving 22,043 adults in Greece who completed an extensive , vali date d , food-frequency question naire at base line . Adherence to the traditional Mediterranean diet was assessed by a 10-point Mediterranean-diet scale that incorporated the salient characteristics of this diet ( range of scores , 0 to 9 , with higher scores indicating greater adherence ) . We used proportional-hazards regression to assess the relation between adherence to the Mediterranean diet and total mortality , as well as mortality due to coronary heart disease and mortality due to cancer , with adjustment for age , sex , body-mass index , physical-activity level , and other potential confounders . RESULTS During a median of 44 months of follow-up , there were 275 deaths . A higher degree of adherence to the Mediterranean diet was associated with a reduction in total mortality ( adjusted hazard ratio for death associated with a two-point increment in the Mediterranean-diet score , 0.75 [ 95 percent confidence interval , 0.64 to 0.87 ] ) . An inverse association with greater adherence to this diet was evident for both death due to coronary heart disease ( adjusted hazard ratio , 0.67 [ 95 percent confidence interval , 0.47 to 0.94 ] ) and death due to cancer ( adjusted hazard ratio , 0.76 [ 95 percent confidence interval , 0.59 to 0.98 ] ) . Associations between individual food groups contributing to the Mediterranean-diet score and total mortality were generally not significant . CONCLUSIONS Greater adherence to the traditional Mediterranean diet is associated with a significant reduction in total mortality",
"AIMS The aim of this study is to compare the efficacy of low glycaemic index ( GI ) vs. conventional carbohydrate exchange ( CCE ) dietary advice on glycaemic control and metabolic parameters in patients with type 2 diabetes . METHODS A total of 104 patients with type 2 diabetes were r and omly assigned to either a low GI ( GI ) or CCE dietary advice over a 12-week period . The primary end-point was glycaemic control as assessed by glycated haemoglobin A1c ( HbA1c ) , fructosamine level and plasma glucose . The secondary end-points were anthropometric measurements and metabolic parameters that include blood pressure , lipid profile and insulin levels . The oral antidiabetic medications remained unchanged throughout the duration of the study . RESULTS A low-GI diet was associated with significant changes in the fructosamine level ( DeltaGI = -0.20 + /- 0.03 ; DeltaCCE = -0.08 + /- 0.03 mmol/l , p waist circumference ( DeltaGI group = -1.88 + /- 0.30 cm ; DeltaCCE group : -0.36 + /- 0.4 cm , p in fasting glucose ( DeltaGI = -0.03 + /- 0.3 ; DeltaCCE = 0.7 + /- 0.3 mmol/l ; p waist circumference ( DeltaGI = -2.35 + /- 0.47 cm ; DeltaCCE group = -0.66 + /- 0.46 cm ; p changes in postpr and ial glycaemia at time 0 , 60 , 150 and 180 min after consuming the st and ard test meal was lower than with the CCE diet ( p low-GI diet result ed in significant changes of serum fructosamine level , plasma glucose and waist circumference in Asian patients with type 2 diabetes over a 12-week period compared with those following a CCE diet . The effect on HbA1c and other metabolic parameters was not significantly different between the two study groups but the improvement within the GI group was more pronounced and of clinical benefit",
"OBJECTIVE —The purpose of this study was to compare the effects of high – monounsaturated fatty acid ( MUFA ) and high-carbohydrate ( CHO ) diets on body weight and glycemic control in men and women with type 2 diabetes . RESEARCH DESIGN AND METHODS —Overweight/obese participants with type 2 diabetes ( n = 124 , age = 56.5 ± 0.8 years , BMI = 35.9 ± 0.3 kg/m2 , and A1C = 7.3 ± 0.1 % ) were r and omly assigned to 1 year of a high-MUFA or high-CHO diet . Anthropometric and metabolic parameters were assessed at baseline and after 4 , 8 , and 12 months of dieting . RESULTS —Baseline characteristics were similar between the treatment groups . The overall retention rate for 1 year was 77 % ( 69 % for the high-MUFA group and 84 % for the high-CHO group ; P = 0.06 ) . Based on food records , both groups had similar energy intake but a significant difference in MUFA intake . Both groups had similar weight loss over 1 year ( −4.0 ± 0.8 vs. −3.8 ± 0.6 kg ) and comparable improvement in body fat , waist circumference , diastolic blood pressure , HDL cholesterol , A1C , and fasting glucose and insulin . There were no differences in these parameters between the groups . A follow-up assessment of a subset of participants ( n = 36 ) was conducted 18 months after completion of the 52-week diet . These participants maintained their weight loss and A1C during the follow-up period . CONCLUSIONS —In individuals with type 2 diabetes , high-MUFA diets are an alternative to conventional lower-fat , high-CHO diets with comparable beneficial effects on body weight , body composition , cardiovascular risk factors , and glycemic control",
"OBJECTIVE Despite their independent cardiovascular disease ( CVD ) advantages , effects of α-linolenic acid ( ALA ) , monounsaturated fatty acid ( MUFA ) , and low-glycemic-load ( GL ) diets have not been assessed in combination . We therefore determined the combined effect of ALA , MUFA , and low GL on glycemic control and CVD risk factors in type 2 diabetes . RESEARCH DESIGN AND METHODS The study was a parallel design , r and omized trial wherein each 3-month treatment was conducted in a Canadian academic center between March 2011 and September 2012 and involved 141 participants with type 2 diabetes ( HbA1c 6.5%–8.5 % [ 48–69 mmol/mol ] ) treated with oral antihyperglycemic agents . Participants were provided with dietary advice on either a low-GL diet with ALA and MUFA given as a canola oil – enriched bread supplement ( 31 g canola oil per 2,000 kcal ) ( test ) or a whole-grain diet with a whole-wheat bread supplement ( control ) . The primary outcome was HbA1c change . Secondary outcomes included calculated Framingham CVD risk score and reactive hyperemia index ( RHI ) ratio . RESULTS Seventy-nine percent of the test group and 90 % of the control group completed the trial . The test diet reduction in HbA1c units of −0.47 % ( −5.15 mmol/mol ) ( 95 % CI −0.54 % to −0.40 % [ −5.92 to −4.38 mmol/mol ] ) was greater than that for the control diet ( −0.31 % [ −3.44 mmol/mol ] [ 95 % CI −0.38 % to −0.25 % ( −4.17 to −2.71 mmol/mol ) ] , P = 0.002 ) , with the greatest benefit observed in those with higher systolic blood pressure ( SBP ) . Greater reductions were seen in CVD risk score for the test diet , whereas the RHI ratio increased for the control diet . CONCLUSIONS A canola oil – enriched low-GL diet improved glycemic control in type 2 diabetes , particularly in participants with raised SBP , whereas whole grains improved vascular reactivity",
"Aims /hypothesisTo compare the effectiveness of low-fat high-protein and low-fat high-carbohydrate dietary advice on weight loss , using group-based interventions , among overweight people with type 2 diabetes . Study design Multicentre parallel ( 1:1 ) design , blinded r and omised controlled trial . Methods Individuals with type 2 diabetes aged 30–75 years and a BMI > 27 kg/m2 were r and omised , by an independent statistician using sequentially numbered sealed envelopes , to be prescribed either a low-fat high-protein ( 30 % of energy as protein , 40 % as carbohydrate , 30 % as fat ) or a low-fat high-carbohydrate ( 15 % of energy as protein , 55 % as carbohydrate , 30 % as fat ) diet . Participants attended 18 group sessions over 12 months . Primary outcomes were change in weight and waist circumference assessed at baseline , 6 and 12 months . Secondary outcomes were body fatness , glycaemic control , lipid profile , blood pressure and renal function . A further assessment was undertaken 12 months after the intervention . Research assessors remained blinded to group allocation throughout . Intention-to-treat analysis was performed . Results A total of 419 participants were enrolled ( mean ± SD age 58 ± 9.5 years , BMI 36.6 ± 6.5 kg/m2 and HbA1c 8.1 ± 1.2 % ( 65 mmol/mol ) ) . The study was completed by 70 % ( 294/419 ) . No differences between groups were found in change in weight or waist circumference during the intervention phase or the 12-month follow-up . Both groups had lost weight ( 2–3 kg , p their waist circumference ( 2–3 cm , p weight loss for the following 12 months . By 6 months , the difference in self-reported dietary protein between groups was small ( 1.1 % total energy ; p outcomes : body fatness , HbA1c , lipids , blood pressure and renal function . There were no important adverse effects . Conclusions /interpretationIn a ‘ real-world ’ setting , prescription of an energy-reduced low-fat diet , with either increased protein or carbohydrate , results in similar modest losses in weight and waist circumference over 2 years . Trial registration : Australia New Zeal and Clinical Trials Register ACTRN12606000490572 Funding : The Health Research Council of New Zeal and ( 06/337 )",
"BACKGROUND The optimal source and amount of dietary carbohydrate for managing type 2 diabetes ( T2DM ) are unknown . OBJECTIVE We aim ed to compare the effects of altering the glycemic index or the amount of carbohydrate on glycated hemoglobin ( HbA1c ) , plasma glucose , lipids , and C-reactive protein ( CRP ) in T2DM patients . DESIGN Subjects with T2DM managed by diet alone ( n=162 ) were r and omly assigned to receive high-carbohydrate , high-glycemic-index ( high-GI ) , high-carbohydrate , low-glycemic-index ( low-GI ) , or low-carbohydrate , high-monounsaturated-fat ( low-CHO ) diets for 1 y. RESULTS The high-GI , low-GI , and low-CHO diets contained , respectively , 47 % , 52 % , and 39 % of energy as carbohydrate and 31 % , 27 % , and 40 % of energy as fat ; they had GIs of 63 , 55 , and 59 , respectively . Body weight and HbA1c did not differ significantly between diets . Fasting glucose was higher ( P=0.041 ) , but 2-h postload glucose was lower ( P=0.010 ) after 12 mo of the low-GI diet . With the low-GI diet , overall mean triacylglycerol was 12 % higher and HDL cholesterol 4 % lower than with the low-CHO diet ( P ratio of total to HDL cholesterol disappeared by 6 mo ( time x diet interaction , P=0.044 ) . Overall mean CRP with the low-GI diet , 1.95 mg/L , was 30 % less than that with the high-GI diet , 2.75 mg/L ( P=0.0078 ) ; the concentration with the low-CHO diet , 2.35 mg/L , was intermediate . CONCLUSIONS In subjects with T2DM managed by diet alone with optimal glycemic control , long-term HbA1c was not affected by altering the GI or the amount of dietary carbohydrate . Differences in total : HDL cholesterol among diets had disappeared by 6 mo . However , because of sustained reductions in postpr and ial glucose and CRP , a low-GI diet may be preferred for the dietary management of T2DM",
"BACKGROUND Few well-controlled studies have comprehensively examined the effects of very-low-carbohydrate diets on type 2 diabetes ( T2D ) . OBJECTIVE We compared the effects of a very-low-carbohydrate , high-unsaturated fat , low-saturated fat ( LC ) diet with a high-carbohydrate , low-fat ( HC ) diet on glycemic control and cardiovascular disease risk factors in T2D after 52 wk . DESIGN In this r and omized controlled trial that was conducted in an outpatient research clinic , 115 obese adults with T2D [ mean ± SD age : 58 ± 7 y ; body mass index ( in kg/m(2 ) ) : 34.6 ± 4.3 ; glycated hemoglobin ( HbA1c ) : 7.3 ± 1.1 % ; duration of diabetes : 8 ± 6 y ] were r and omly assigned to consume either a hypocaloric LC diet [ 14 % of energy as carbohydrate ( carbohydrate ] or an energy-matched HC diet [ 53 % of energy as carbohydrate , 17 % of energy as protein , and 30 % of energy as fat ( 10 % saturated fat ) ] combined with supervised aerobic and resistance exercise ( 60 min ; 3 d/wk ) . Outcomes were glycemic control assessed with use of measurements of HbA1c , fasting blood glucose , glycemic variability assessed with use of 48-h continuous glucose monitoring , diabetes medication , weight , blood pressure , and lipids assessed at baseline , 24 , and 52 wk . RESULTS Both groups achieved similar completion rates ( LC diet : 71 % ; HC diet : 65 % ) and mean ( 95 % CI ) reductions in weight [ LC diet : -9.8 kg ( -11.7 , -7.9 kg ) ; HC diet : -10.1 kg ( -12.0 , -8.2 kg ) ] , blood pressure [ LC diet : -7.1 ( -10.6 , -3.7)/-6.2 ( -8.2 , -4.1 ) mm Hg ; HC diet : -5.8 ( -9.4 , -2.2)/-6.4 ( -8.4 , -4.3 ) mm Hg ] , HbA1c [ LC diet : -1.0 % ( -1.2 % , -0.7 % ) ; HC diet : -1.0 % ( -1.3 % , -0.8 % ) ] , fasting glucose [ LC diet : -0.7 mmol/L ( -1.3 , -0.1 mmol/L ) ; HC diet : -1.5 mmol/L ( -2.1 , -0.8 mmol/L ) ] , and LDL cholesterol [ LC diet : -0.1 mmol/L ( -0.3 , 0.1 mmol/L ) ; HC diet : -0.2 mmol/L ( -0.4 , 0.03 mmol/L ) ] ( P-diet effect ≥ 0.10 ) . Compared with the HC-diet group , the LC-diet group achieved greater mean ( 95 % CI ) reductions in the diabetes medication score [ LC diet : -0.5 arbitrary units ( -0.7 , -0.4 arbitrary units ) ; HC diet : -0.2 arbitrary units ( -0.4 , -0.06 arbitrary units ) ; P = 0.02 ] , glycemic variability assessed by measuring the continuous overall net glycemic action-1 [ LC diet : -0.5 mmol/L ( -0.6 , -0.3 mmol/L ) ; HC diet : -0.05 mmol/L ( -0.2 , -0.1 mmol/L ) ; P = 0.003 ] , and triglycerides [ LC diet : -0.4 mmol/L ( -0.5 , -0.2 mmol/L ) ; HC diet : -0.01 mmol/L ( -0.2 , 0.2 mmol/L ) ; P = 0.001 ] and greater mean ( 95 % CI ) increases in HDL cholesterol [ LC diet : 0.1 mmol/L ( 0.1 , 0.2 mmol/L ) ; HC diet : 0.06 mmol/L ( -0.01 , 0.1 mmol/L ) ; P = 0.002 ] . CONCLUSIONS Both diets achieved substantial weight loss and reduced HbA1c and fasting glucose . The LC diet , which was high in unsaturated fat and low in saturated fat , achieved greater improvements in the lipid profile , blood glucose stability , and reductions in diabetes medication requirements , suggesting an effective strategy for the optimization of T2D management . This trial was registered at www.anzctr.org.au as ACTRN12612000369820",
"AIM To describe for the first time the direct costs of Type 2 diabetes treatment by analysing nationwide routine data from statutory health insurance in Germany . METHODS This cost-of-illness- study was based on a 6.8 % r and om sample of all German people with statutory health insurance ( 4.3 out of 70 million people ) . The healthcare expenses show direct per capita costs from the payer perspective . Healthcare expenses for physicians , dentists , pharmacies , hospitals , sick benefits and other healthcare costs were considered . Per capita costs , cost ratios for people with Type 2 diabetes and without diabetes as well as diabetes-attributable costs were calculated . RESULTS Per capita costs for people with Type 2 diabetes amounted to € 4,957 in 2009 and € 5,146 in 2010 . People with Type 2 diabetes had 1.7-fold higher health expenses than people without diabetes . The largest differences in health expenses were found for prescribed medication from pharmacies ( cost ratio diabetes/no diabetes : 2.2 ) and inpatient treatment ( 1.8 ) . Ten percent of the total statutory health insurance expense , in total € 16.1 billion , was attributable to the medical care of people with Type 2 diabetes . CONCLUSIONS This nationwide study indicates that one in 10 Euros of healthcare expenses is spent on people with Type 2 diabetes in Germany . In the future , national statutory health insurance data can be used to quantify time trends of costs in the healthcare system",
"Aims The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance , visceral fat and oxidative stress markers in subjects with Type 2 diabetes . Methods A 24-week , r and omized , open , parallel design was used . Seventy-four patients with Type 2 diabetes were r and omly assigned to either the experimental group ( n = 37 ) , which received a vegetarian diet , or the control group ( n = 37 ) , which received a conventional diabetic diet . Both diets were isocaloric , calorie restricted ( -500 kcal/day ) . All meals during the study were provided . The second 12 weeks of the diet were combined with aerobic exercise . Participants were examined at baseline , 12 weeks and 24 weeks . Primary outcomes were : insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp ; volume of visceral and subcutaneous fat measured by magnetic resonance imaging ; and oxidative stress measured by thiobarbituric acid reactive substances . Analyses were by intention to treat . Results Forty-three per cent of participants in the experimental group and 5 % of participants in the control group reduced diabetes medication ( P decreased more in the experimental group than in the control group [ –6.2 kg ( 95 % CI –6.6 to –5.3 ) vs. –3.2 kg ( 95 % CI –3.7 to –2.5 ) ; interaction group × time P = 0.001 ] . An increase in insulin sensitivity was significantly greater in the experimental group than in the control group [ 30 % ( 95 % CI 24.5–39 ) vs. 20 % ( 95 % CI 14–25 ) , P = 0.04 ] . A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group ( P = 0.007 and P = 0.02 , respectively ) . Plasma adiponectin increased ( P = 0.02 ) and leptin decreased ( P = 0.02 ) in the experimental group , with no change in the control group . Vitamin C , superoxide dismutase and reduced glutathione increased in the experimental group ( P = 0.002 , P exercise training . Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat . Conclusions A calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks . The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance . The addition of exercise training further augmented the improved outcomes with the vegetarian diet",
"OBJECTIVE Although caloric restriction is a widely used intervention to reduce body weight and insulin resistance , many patients are unable to comply with such dietary therapy for long periods . The clinical effectiveness of low-carbohydrate diets was recently described in a position statement of Diabetes UK and a scientific review conducted by the American Diabetes Association . However , r and omised trials of dietary interventions in Japanese patients with type 2 diabetes are scarce . Therefore , the aim of this study was to examine the effects of a non-calorie-restricted , low-carbohydrate diet in Japanese patients unable to adhere to a calorie-restricted diet . METHODS The enrolled patients were r and omly allocated to receive a conventional calorie-restricted diet or low-carbohydrate diet . The patients received consultations every two months from a registered dietician for six months . We compared the effects of the two dietary interventions on glycaemic control and metabolic profiles . RESULTS The HbA1c levels decreased significantly from baseline to six months in the low-carbohydrate diet group ( baseline 7.6±0.4 % , six months 7.0±0.7 % , p=0.03 ) but not in the calorie-restricted group ( baseline 7.7±0.6 % , six months 7.5±1.0 % , n.s . ) , ( between-group comparison , p=0.03 ) . The patients in the former group also experienced improvements in their triglyceride levels , without experiencing any major adverse effects or a decline in the quality of life . CONCLUSION Our findings suggest that a low-carbohydrate diet is effective in lowering the HbA1c and triglyceride levels in patients with type 2 diabetes who are unable to adhere to a calorie-restricted diet",
"BACKGROUND Lifestyle changes soon after diagnosis might improve outcomes in patients with type 2 diabetes mellitus , but no large trials have compared interventions . We investigated the effects of diet and physical activity on blood pressure and glucose concentrations . METHODS We did a r and omised , controlled trial in southwest Engl and in adults aged 30 - 80 years in whom type 2 diabetes had been diagnosed 5 - 8 months previously . Participants were assigned usual care ( initial dietary consultation and follow-up every 6 months ; control group ) , an intensive diet intervention ( dietary consultation every 3 months with monthly nurse support ) , or the latter plus a pedometer-based activity programme , in a 2:5:5 ratio . The primary endpoint was improvement in glycated haemoglobin A(1c)(HbA(1c ) ) concentration and blood pressure at 6 months . Analysis was done by intention to treat . This study is registered , number IS RCT N92162869 . FINDINGS Of 593 eligible individuals , 99 were assigned usual care , 248 the diet regimen , and 246 diet plus activity . Outcome data were available for 587 ( 99 % ) and 579 ( 98 % ) participants at 6 and 12 months , respectively . At 6 months , glycaemic control had worsened in the control group ( mean baseline HbA(1c ) percentage 6·72 , SD 1·02 , and at 6 months 6·86 , 1·02 ) but improved in the diet group ( baseline-adjusted difference in percentage of HbA(1c ) -0·28 % , 95 % CI -0·46 to -0·10 ; p=0·005 ) and diet plus activity group ( -0·33 % , -0·51 to -0·14 ; p seen in bodyweight and insulin resistance between the intervention and control groups . Blood pressure was similar in all groups . INTERPRETATION An intensive diet intervention soon after diagnosis can improve glycaemic control . The addition of an activity intervention conferred no additional benefit . FUNDING Diabetes UK and the UK Department of Health",
"Background / objectives : To determine the effects of a low-fat plant-based diet program on anthropometric and biochemical measures in a multicenter corporate setting .Subjects/ methods : Employees from 10 sites of a major US company with body mass index ⩾25 kg/m2 and /or previous diagnosis of type 2 diabetes were r and omized to either follow a low-fat vegan diet , with weekly group support and work cafeteria options available , or make no diet changes for 18 weeks . Dietary intake , body weight , plasma lipid concentrations , blood pressure and glycated hemoglobin ( HbA1C ) were determined at baseline and 18 weeks . Results : Mean body weight fell 2.9 kg and 0.06 kg in the intervention and control groups , respectively ( P fell 8.0 and 8.1 mg/dl in the intervention group and 0.01 and 0.9 mg/dl in the control group ( P HbA1C fell 0.6 percentage point and 0.08 percentage point in the intervention and control group , respectively (P , mean changes in body weight were −4.3 kg and −0.08 kg in the intervention and control groups , respectively ( P fell 13.7 and 13.0 mg/dl in the intervention group and 1.3 and 1.7 mg/dl in the control group ( P HbA1C levels decreased 0.7 percentage point and 0.1 percentage point in the intervention and control group , respectively ( P dietary intervention using a low-fat plant-based diet in a corporate setting improves body weight , plasma lipids , and , in individuals with diabetes , glycemic control",
"Background We found marked improvement of glycemic control and several cardiovascular risk factors in patients with type 2 diabetes given advice to follow a Paleolithic diet , as compared to a diabetes diet . We now report findings on subjective ratings of satiety at meal times and participants ’ other experiences of the two diets from the same study . Methods In a r and omized cross-over study , 13 patients with type 2 diabetes ( 3 women and 10 men ) , were instructed to eat a Paleolithic diet based on lean meat , fish , fruits , vegetables , root vegetables , eggs and nuts , and a diabetes diet design ed in accordance with dietary guidelines , during two consecutive 3-month periods . In parallel with a four-day weighed food record , the participants recorded their subjective rating of satiety . Satiety quotients were calculated as the intra-meal quotient of change in satiety during a meal and consumed energy or weight of food and drink for that specific meal . All participants answered the same three open-ended questions in a survey following each diet : “ What thoughts do you have about this diet ? ” , “ Describe your positive and negative experiences with this diet ” and “ How do you think this diet has affected your health ? ” . Results The participants were equally satiated on both diets . The Paleolithic diet result ed in greater satiety quotients for energy per meal ( p = 0.004 ) , energy density per meal ( p = 0.01 ) and glycemic load per meal ( p = 0.02 ) . The distribution of positive and negative comments from the survey did not differ between the two diets , and the comments were mostly positive . Among comments relating to recurring topics , there was no difference in distribution between the two diets for comments relating to tastelessness , but there was a trend towards more comments on the Paleolithic diet being satiating and improving blood sugar values , and significantly more comments on weight loss and difficulty adhering to the Paleolithic diet . Conclusions A Paleolithic diet is more satiating per calorie than a diabetes diet in patients with type 2 diabetes . The Paleolithic diet was seen as instrumental in weight loss , albeit it was difficult to adhere to . Trial registration Clinical Trials.gov :",
"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 In this r and omized controlled trial we evaluated the effect of registered dietitian – led management of diabetes on glycemic control and macronutrient intake in type 2 diabetic patients in primary care clinics in Taiwan and studied the association between changes in macronutrient intake and glycemic measures . RESEARCH DESIGN AND METHODS We recruited 154 adult patients with type 2 diabetes and r and omly assigned them to a routine care control group ( n = 79 ) or a registered dietitian – led intervention group ( n = 75 ) who received on-site diabetic self-management education every 3 months over 12 months . RESULTS Over the 1-year period , neither the intervention group ( n = 75 ) nor the control group ( n = 79 ) had significant changes in A1C , whereas the intervention patients with poorly controlled baseline A1C ( ≥7 % ) ( n = 56 ) had significantly greater improvements in A1C and fasting plasma glucose than the control subjects ( n = 60 ) ( −0.7 vs. −0.2 % , P = 0.034 ; −13.4 vs. 16.9 mg/dl , P = 0.007 ) during the same period . We also found significant net intervention-control group differences in overall energy intake ( −229.06 ± 309.16 vs. 56.10 ± 309.41 kcal/day ) and carbohydrate intake ( −31.24 ± 61.53 vs. 7.15 ± 54.09 g/day ) ( P between changes in carbohydrate intake and A1C in the intervention group ( n = 56 ; β = 0.10 , SEM = 0.033 , P = 0.004 ) . CONCLUSIONS On-site registered dietitian – led management of diabetes can improve glycemic control in patients with poorly managed type 2 diabetes in primary care clinics in Taiwan . A reduction in carbohydrate intake may improve glycemic status ",
"OBJECTIVE To evaluate the effects of two low-fat hypocaloric diets differing in the carbohydrate-to-protein ratio , with and without resistance exercise training ( RT ) , on weight loss , body composition , and cardiovascular disease ( CVD ) risk outcomes in overweight/obese patients with type 2 diabetes . RESEARCH DESIGN AND METHODS A total of 83 men and women with type 2 diabetes ( aged 56.1 ± 7.5 years , BMI 35.4 ± 4.6 kg/m2 ) were r and omly assigned to an isocaloric , energy-restricted diet ( female subjects 6 MJ/day , male subjects 7 MJ/day ) of either st and ard carbohydrate ( CON ; carbohydrate : protein : fat 53:19:26 ) or high protein ( HP ; 43:33:22 ) , with or without supervised RT ( 3 days/week ) for 16 weeks . Body weight and composition , waist circumference ( WC ) , and cardiometabolic risk markers were assessed . RESULTS Fifty-nine participants completed the study . There was a significant group effect ( P ≤ 0.04 ) for body weight , fat mass , and WC with the greatest reductions occuring in HP+RT ( weight [ CON : −8.6 ± 4.6 kg , HP : −9.0 ± 4.8 kg , CON+RT : −10.5 ± 5.1 kg , HP+RT : −13.8 ± 6.0 kg ] , fat mass [ CON : −6.4 ± 3.4 kg , HP : −6.7 ± 4.0 kg , CON+RT : −7.9 ± 3.7 kg , HP+RT : −11.1 ± 3.7 kg ] , and WC [ CON : −8.2 ± 4.6 cm , HP : −8.9 ± 3.9 cm , CON+RT : −11.3 ± 4.6 cm , HP+RT : −13.7 ± 4.6 cm ] ) . There was an overall reduction ( P mass ( −2.0 ± 2.3 kg ) , blood pressure ( −15/8 ± 10/6 mmHg ) , glucose ( −2.1 ± 2.2 mmol/l ) , insulin ( −4.7 ± 5.4 mU/l ) , A1C ( −1.25 ± 0.94 % ) , triglycerides ( −0.47 ± 0.81 mmol/l ) , total cholesterol ( −0.67 ± 0.69 mmol/l ) , and LDL cholesterol ( −0.37 ± 0.53 mmol/l ) , with no difference between groups ( P ≥ 0.17 ) . CONCLUSIONS An energy-restricted HP diet combined with RT achieved greater weight loss and more favorable changes in body composition . All treatments had similar improvements in glycemic control and CVD risk markers ",
"OBJECTIVE To compare three sets of dietary guidelines for the treatment of non-insulin-dependent diabetes ( NIDDM ) in free-living individuals and to observe the effects on metabolic control over an 18-month period . RESEARCH DESIGN AND METHODS Seventy volunteer subjects with NIDDM were r and omly assigned to one of three diets , a weight-management diet , a high-carbohydrate/fiber diet , or a modified-lipid diet and followed for 18 months . Nutrient intakes , weight , blood lipids , and glycemic control were measured . RESULTS In all diet groups , glycated hemoglobin ( HbA1 ) fell significantly before diet intervention began , remaining lower throughout the study and at follow-up 9 months later . Low-density lipoprotein ( LDL ) cholesterol showed a sustained fall in all groups after diet intervention . Apart from transient changes in high-density lipoprotein ( HDL ) cholesterol and triglyceride ( TG ) in the diet groups with the higher carbohydrate intake , no lasting differences were found between the three diet groups . CONCLUSIONS In the long term , there were few differences in the outcome of the three dietary prescriptions . Even with intensive instruction , participants found it difficult to meet recommended nutrient intakes ; however , specific dietary advice did result in an improvement in LDL cholesterol . Adverse changes in HDL cholesterol and TG because of diet intervention were transient . The significant improvement in glycemic control during the recruitment phase may have been the result of particpants ' previous dietary knowledge and the increased attention that they received during the intervention",
"BACKGROUND Legumes , including beans , chickpeas , and lentils , are among the lowest glycemic index ( GI ) foods and have been recommended in national diabetes mellitus ( DM ) guidelines . Yet , to our knowledge , they have never been used specifically to lower the GI of the diet . We have therefore undertaken a study of low-GI foods in type 2 DM with a focus on legumes in the intervention . METHODS A total of 121 participants with type 2 DM were r and omized to either a low-GI legume diet that encouraged participants to increase legume intake by at least 1 cup per day , or to increase insoluble fiber by consumption of whole wheat products , for 3 months . The primary outcome was change in hemoglobin A1c ( HbA1c ) values with calculated coronary heart disease ( CHD ) risk score as a secondary outcome . RESULTS The low-GI legume diet reduced HbA1c values by -0.5 % ( 95 % CI , -0.6 % to -0.4 % ) and the high wheat fiber diet reduced HbA1c values by -0.3 % ( 95 % CI , -0.4 % to -0.2 % ) . The relative reduction in HbA1c values after the low-GI legume diet was greater than after the high wheat fiber diet by -0.2 % ( 95 % CI , -0.3 % to -0.1 % ; P CHD risk reduction on the low-GI legume diet was -0.8 % ( 95 % CI , -1.4 % to -0.3 % ; P = .003 ) , largely owing to a greater relative reduction in systolic blood pressure on the low-GI legume diet compared with the high wheat fiber diet ( -4.5 mm Hg ; 95 % CI , -7.0 to -2.1 mm Hg ; P glycemic control and reduced calculated CHD risk score in type 2 DM",
"Background In type 2 diabetes , acute hyperglycemia worsens endothelial function and inflammation , while resistance to GLP-1 action occurs . All these phenomena seem to be related to the generation of oxidative stress . A Mediterranean diet , supplemented with olive oil , increases plasma antioxidant capacity , suggesting that its implementation can have a favorable effect on the aforementioned phenomena . In the present study , we test the hypothesis that a Mediterranean diet using olive oil can counteract the effects of acute hyperglycemia and can improve the resistance of the endothelium to GLP-1 action . Methods Two groups of type 2 diabetic patients , each consisting of twelve subjects , participated in a r and omized trial for three months , following a Mediterranean diet using olive oil or a control low-fat diet . Plasma antioxidant capacity , endothelial function , nitrotyrosine , 8-iso-PGF2a , IL-6 and ICAM-1 levels were evaluated at baseline and at the end of the study . The effect of GLP-1 during a hyperglycemic clamp , was also studied at baseline and at the end of the study . Results Compared to the control diet , the Mediterranean diet increased plasma antioxidant capacity and improved basal endothelial function , nitrotyrosine , 8-iso-PGF2a , IL-6 and ICAM-1 levels . The Mediterranean diet also reduced the negative effects of acute hyperglycemia , induced by a hyperglycemic clamp , on endothelial function , nitrotyrosine , 8-iso-PGF2a , IL-6 and ICAM-1 levels . Furthermore , the Mediterranean diet improved the protective action of GLP-1 on endothelial function , nitrotyrosine , 8-iso-PGF2a , IL-6 and ICAM-1 levels , also increasing GLP-1-induced insulin secretion . Conclusions These data suggest that the Mediterranean diet , using olive oil , prevents the acute hyperglycemia effect on endothelial function , inflammation and oxidative stress , and improves the action of GLP-1 , which may have a favorable effect on the management of type 2 diabetes , particularly for the prevention of cardiovascular disease",
"Objective Several intervention studies have suggested that vegetarian or vegan diets have clinical benefits , particularly in terms of glycemic control , in patients with type 2 diabetes ( T2D ) ; however , no r and omized controlled trial has been conducted in Asians who more commonly depend on plant-based foods , as compared to Western population s. Here , we aim ed to compare the effect of a vegan diet and conventional diabetic diet on glycemic control among Korean individuals . Material s and Methods Participants diagnosed with T2D were r and omly assigned to follow either a vegan diet ( excluding animal-based food including fish ; n = 46 ) or a conventional diet recommended by the Korean Diabetes Association 2011 ( n = 47 ) for 12 weeks . HbA1c levels were measured at weeks 0 , 4 , and 12 , and the primary study endpoint was the change in HbA1c levels over 12 weeks . Results The mean HbA1c levels at weeks 0 , 4 , and 12 were 7.7 % , 7.2 % , and 7.1 % in the vegan group , and 7.4 % , 7.2 % , and 7.2 % in the conventional group , respectively . Although both groups showed significant reductions in HbA1C levels , the reductions were larger in the vegan group than in the conventional group ( -0.5 % vs. -0.2 % ; p-for-interaction = 0.017 ) . When only considering participants with high compliance , the difference in HbA1c level reduction between the groups was found to be larger ( -0.9 % vs. -0.3 % ) . The beneficial effect of vegan diets was noted even after adjusting for changes in total energy intake or waist circumference over the 12 weeks . Conclusion Both diets led to reductions in HbA1c levels ; however , glycemic control was better with the vegan diet than with the conventional diet . Thus , the dietary guidelines for patients with T2D should include a vegan diet for the better management and treatment . However , further studies are needed to evaluate the long-term effects of a vegan diet , and to identify potential explanations of the underlying mechanisms . Trial Registration CRiS",
"We compared the effects of two diets on glycated hemoglobin ( HbA1c ) and other health-related outcomes in overweight or obese adults with type 2 diabetes or prediabetes ( HbA1c>6 % ) . We r and omized participants to either a medium carbohydrate , low fat , calorie-restricted , carbohydrate counting diet ( MCCR ) consistent with guidelines from the American Diabetes Association ( n = 18 ) or a very low carbohydrate , high fat , non calorie-restricted diet whose goal was to induce nutritional ketosis ( LCK , n = 16 ) . We excluded participants receiving insulin ; 74 % were taking oral diabetes medications . Groups met for 13 sessions over 3 months and were taught diet information and psychological skills to promote behavior change and maintenance . At 3 months , mean HbA1c level was unchanged from baseline in the MCCR diet group , while it decreased 0.6 % in the LCK group ; there was a significant between group difference in HbA1c change favoring the LCK group ( −0.6 % , 95 % CI , −1.1 % to −0.03 % , p = 0.04 ) . Forty-four percent of the LCK group discontinued one or more diabetes medications , compared to 11 % of the MCCR group ( p = 0.03 ) ; 31 % discontinued sulfonylureas in the LCK group , compared to 5 % in the MCCR group ( p = 0.05 ) . The LCK group lost 5.5 kg vs. 2.6 kg lost in MCCR group ( p = 0.09 ) . Our results suggest that a very low carbohydrate diet coupled with skills to promote behavior change may improve glycemic control in type 2 diabetes while allowing decreases in diabetes medications . This clinical trial was registered with Clinical Trials.gov , number NCT01713764",
"Objective Dietary carbohydrate is the major determinant of postpr and ial glucose levels , and several clinical studies have shown that low-carbohydrate diets improve glycemic control . In this study , we tested the hypothesis that a diet lower in carbohydrate would lead to greater improvement in glycemic control over a 24-week period in patients with obesity and type 2 diabetes mellitus . Research design and methods Eighty-four community volunteers with obesity and type 2 diabetes were r and omized to either a low-carbohydrate , ketogenic diet ( LCKD ) or a low-glycemic , reduced-calorie diet ( 500 kcal/day deficit from weight maintenance diet ; LGID ) . Both groups received group meetings , nutritional supplementation , and an exercise recommendation . The main outcome was glycemic control , measured by hemoglobin A1c . Results Forty-nine ( 58.3 % ) participants completed the study . Both interventions led to improvements in hemoglobin A1c , fasting glucose , fasting insulin , and weight loss . The LCKD group had greater improvements in hemoglobin A1c ( -1.5 % vs. -0.5 % , p = 0.03 ) , body weight ( -11.1 kg vs. -6.9 kg , p = 0.008 ) , and high density lipoprotein cholesterol ( + 5.6 mg/dL vs. 0 mg/dL , p Diabetes medications were reduced or eliminated in 95.2 % of LCKD vs. 62 % of LGID participants ( p Dietary modification led to improvements in glycemic control and medication reduction/elimination in motivated volunteers with type 2 diabetes . The diet lower in carbohydrate led to greater improvements in glycemic control , and more frequent medication reduction/elimination than the low glycemic index diet . Lifestyle modification using low carbohydrate interventions is effective for improving and reversing type 2 diabetes",
"OBJECTIVE To compare the effects of a 1-year intervention with a low-carbohydrate and a low-fat diet on weight loss and glycemic control in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS This study is a r and omized clinical trial of 105 overweight adults with type 2 diabetes . Primary outcomes were weight and A1C . Secondary outcomes included blood pressure and lipids . Outcome measures were obtained at 3 , 6 , and 12 months . RESULTS The greatest reduction in weight and A1C occurred within the first 3 months . Weight loss occurred faster in the low-carbohydrate group than in the low-fat group ( P = 0.005 ) , but at 1 year a similar 3.4 % weight reduction was seen in both dietary groups . There was no significant change in A1C in either group at 1 year . There was no change in blood pressure , but a greater increase in HDL was observed in the low-carbohydrate group ( P = 0.002 ) . CONCLUSIONS Among patients with type 2 diabetes , after 1 year a low-carbohydrate diet had effects on weight and A1C similar to those seen with a low-fat diet . There was no significant effect on blood pressure , but the low-carbohydrate diet produced a greater increase in HDL cholesterol",
"BACKGROUND Low-fat vegetarian and vegan diets are associated with weight loss , increased insulin sensitivity , and improved cardiovascular health . OBJECTIVE We compared the effects of a low-fat vegan diet and conventional diabetes diet recommendations on glycemia , weight , and plasma lipids . DESIGN Free-living individuals with type 2 diabetes were r and omly assigned to a low-fat vegan diet ( n = 49 ) or a diet following 2003 American Diabetes Association guidelines ( conventional , n = 50 ) for 74 wk . Glycated hemoglobin ( Hb A(1c ) ) and plasma lipids were assessed at weeks 0 , 11 , 22 , 35 , 48 , 61 , and 74 . Weight was measured at weeks 0 , 22 , and 74 . RESULTS Weight loss was significant within each diet group but not significantly different between groups ( -4.4 kg in the vegan group and -3.0 kg in the conventional diet group , P = 0.25 ) and related significantly to Hb A(1c ) changes ( r = 0.50 , P = 0.001 ) . Hb A(1c ) changes from baseline to 74 wk or last available values were -0.34 and -0.14 for vegan and conventional diets , respectively ( P = 0.43 ) . Hb A(1c ) changes from baseline to last available value or last value before any medication adjustment were -0.40 and 0.01 for vegan and conventional diets , respectively ( P = 0.03 ) . In analyses before alterations in lipid-lowering medications , total cholesterol decreased by 20.4 and 6.8 mg/dL in the vegan and conventional diet groups , respectively ( P = 0.01 ) ; LDL cholesterol decreased by 13.5 and 3.4 mg/dL in the vegan and conventional groups , respectively ( P = 0.03 ) . CONCLUSIONS Both diets were associated with sustained reductions in weight and plasma lipid concentrations . In an analysis controlling for medication changes , a low-fat vegan diet appeared to improve glycemia and plasma lipids more than did conventional diabetes diet recommendations . Whether the observed differences provide clinical benefit for the macro- or microvascular complications of diabetes remains to be established . This trial was registered at clinical trials.gov as NCT00276939",
"OBJECTIVE To determine the effect of a high-protein ( HP ) weight loss diet compared with a lower-protein ( LP ) diet on fat and lean tissue and fasting and postpr and ial glucose and insulin concentrations . RESEARCH DESIGN AND METHODS Replacing dietary protein for carbohydrate ( CHO ) during energy restriction and weight loss has been effective in sparing lean mass and improving insulin sensitivity in obese subjects but has not been tested in subjects with type 2 diabetes . We compared an HP diet ( 28 % protein , 42 % CHO , 28 % fat [ 8 % saturated fatty acids , 12 % monounsaturated fatty acids , 5 % polyunsaturated fatty acids ] ) with an LP diet ( 16 % protein , 55 % CHO , 26 % fat [ 8 % saturated fatty acids , 11 % monounsaturated fatty acids , 5 % polyunsaturated fatty acids ] ) in 54 obese men and women with type 2 diabetes during 8 weeks of energy restriction ( 1,600 kcal ) and 4 weeks of energy balance . Body composition was determined by dual-energy X-ray absorptiometry at weeks 0 and 12 . RESULTS Overall , weight loss of 5.2 + /- 1.8 kg was achieved independently of diet composition . However , women on the HP diet lost significantly more total ( 5.3 vs. 2.8 kg , P=0.009 ) and abdominal ( 1.3 vs. 0.7 kg , P=0.006 ) fat compared with the women on the LP diet , whereas , in men , there was no difference in fat loss between diets ( 3.9 vs. 5.1 kg ) . Total lean mass decreased in all subjects independently of diet composition . LDL cholesterol reduction was significantly greater on the HP diet ( 5.7 % ) than on the LP diet ( 2.7 % ) ( P cardiovascular disease ( CVD ) risk profile as a consequence of weight loss . However , the greater reductions in total and abdominal fat mass in women and greater LDL cholesterol reduction observed in both sexes on the HP diet suggest that it is a valid diet choice for reducing CVD risk in type 2 diabetes",
"Aims /hypothesisThis study compared the long-term weight loss and health outcomes at 1-year follow-up , after a 12-week intensive intervention consisting of two low-fat , weight-loss diets , which differed in protein content . Methods We r and omly assigned 66 obese patients ( BMI : 27–40 kg/m2 ) with Type 2 diabetes to either a low-protein ( 15 % protein , 55 % carbohydrate ) or high-protein diet ( 30 % protein , 40 % carbohydrate ) for 8 weeks of energy restriction ( ~6.7 MJ/day ) and 4 weeks of energy balance . Subjects were asked to maintain the same dietary pattern for a further 12 months of follow-up . Results The study was completed by 38 of the subjects , with equal dropouts in each group . At Week 64 , weight reductions against baseline were −2.2±1.1 kg ( low protein ) and −3.7±1.0 kg ( high protein ) , p diet effect . Fat mass was not different from baseline in either group . At Week 12 , both diets reduced systolic and diastolic blood pressure by 6 and 3 mm Hg respectively , but blood pressure increased more with weight regain during follow-up in the low-protein group ( p≤0.04 ) . At Week 64 , both diets significantly increased HDL cholesterol and lowered C-reactive protein concentrations . There was no difference in the urinary urea : creatinine ratio at baseline between the two groups , but this ratio increased at Week 12 ( in the high-protein group only , p high-protein weight-reduction diet may in the long term have a more favourable cardiovascular risk profile than a low-protein diet with similar weight reduction in people with Type 2 diabetes",
"BACKGROUND AND AIMS Type 2 diabetes is one of the most important risk factor for the development of chronic kidney disease ( CKD ) . Recently , it has been shown that lower high-density lipoprotein cholesterol ( HDL-C ) levels predicted the development of microalbuminuria in type 2 diabetic individuals . We have prospect ively assessed the effects of plasma HDL-C levels on the incidence of CKD in a large cohort of type 2 diabetic patients . METHODS AND RESULTS We followed 1987 type 2 diabetic out patients with normal or near-normal kidney function at baseline for 5 years for the occurrence of incident CKD defined as glomerular filtration rate plasma HDL-C levels and incident CKD . During a median follow-up of 5 years , 11.8 % ( n=234 ) of participants developed incident CKD . In multivariate regression analysis , higher HDL-C levels were associated with a lower risk of incident CKD ( multiple-adjusted hazard ratio 0.76 ; 95 % coefficient intervals 0.61 - 0.96 ; p=0.025 ) independently of age , gender , body mass index , hypertension , smoking history , diabetes duration , hemoglobin A1c , plasma triglycerides , LDL-cholesterol , presence of diabetic retinopathy , baseline albuminuria , and current use of medications ( anti-hypertensive , anti-platelet , lipid-lowering and hypoglycemic drugs ) . CONCLUSIONS Higher plasma levels of HDL-C are associated with a lower risk of incident CKD in a large cohort of type 2 diabetic adults independently of numerous confounding factors",
"OBJECTIVE To examine the effects of a high-carbohydrate low-fat ( HCLF ) and a modified-fat ( MF ) diet on body weight and metabolic control in subjects with non-insulin-dependent diabetes mellitus ( NIDDM ) living at home . RESEARCH DESIGN AND METHODS Twenty-four NIDDM patients followed HCLF and MF diets alternately and in r and om order for a 3-month period while at home , with a 1-month baseline and washout between diets . Before and after each diet , fasting glucose and lipids , HbAlc , blood pressure , and body weight were measured . Dietary preferences were assessed by question naire . RESULTS Subjects consumed 50 % of energy as carbohydrate and 23 % as fat on the HCLF diet and 40 % of energy as carbohydrate and 36 % as fat ( over half of which was monounsaturated fat ) on the MF diet . Subjects lost weight on both HCLF and MF diets ( mean loss 0.7 and 1.3 kg , respectively ) . Although the MF diet result ed in a small decrease in fasting glucose levels , there was no significant change in HbA1c . Similarly , there was no significant difference between the diets in changes in blood pressure or fasting blood lipids . Most subjects ( 65 % ) preferred the MF diet . CONCLUSIONS Although the MF diet is not a low-fat diet , it did not appear to facilitate weight gain in subjects with NIDDM living at home . The MF diet provides an alternative for individuals unable to comply with HCLF diets",
"OBJECTIVE Diabetes mellitus requires lifelong treatment , most of which is accomplished in family and community setting s. The present study was design ed to identify the effectiveness of nutrition intervention provided by public dietitian on glycemic control in a community setting in China . METHODS Two communities were selected and r and omly assigned to a routine care group ( 59 subjects ) and a public dietitian-led intervention group ( 58 subjects ) who received diabetic nutrition management for one year . The main measures included fasting plasma glucose , HbA1c , weight , body mass index ( BMI ) , lipid profile , and blood pressure . RESULTS In the intervention group , there was significant improvement in fasting plasma glucose , HbA1c , cholesterol , and triglyceride levels relative to the control subjects ( p energy intake , including reductions in absolute amounts ( grams ) of protein and fat in the intervention group . The energy percent values of carbohydrate , protein , and fat were 50.7 % , 17.0 % , and 32.3 % , respectively , at baseline and 53.0 % , 17.1 % , and 29.9 % ( within the recommended range ) after the intervention . There were significant improvements in total energy , absolute amounts of fat and protein , and the energy percent values of carbohydrates and fat . In the control group , however , these values were similar before and after the intervention , and the energy percent values of fat were still above the recommended range . CONCLUSIONS In a community setting , a diabetes nutrition intervention led by a public dietitian significantly improved the glycemic control of type 2 diabetic patients",
"Aims /hypothesisShort-term dietary studies suggest that high-protein diets can enhance weight loss and improve glycaemic control in people with type 2 diabetes . However , the long-term effects of such diets are unknown . The aim of this study was to determine whether high-protein diets are superior to high-carbohydrate diets for improving glycaemic control in individuals with type 2 diabetes . Methods Overweight/obese individuals ( BMI 27–40 kg/m2 ) with type 2 diabetes ( HbA1c 6.5–10 % ) were recruited for a 12 month , parallel design , dietary intervention trial conducted at a diabetes specialist clinic ( Melbourne , VIC , Australia ) . Of the 108 initially r and omised , 99 received advice to follow low-fat ( 30 % total energy ) diets that were either high in protein ( 30 % total energy , n = 53 ) or high in carbohydrate ( 55 % total energy , n = 46 ) . Dietary assignment was done by a third party using computer-generated r and om numbers . The primary endpoint was change in HbA1c . Secondary endpoints included changes in weight , lipids , blood pressure , renal function and calcium loss . Study endpoints were assessed blinded to the diet group , but the statistical analysis was performed unblinded . This study used an intention-to-treat model for all participants who received dietary advice . Follow-up visits were encouraged regardless of dietary adherence and last measurements were carried forward for study non-completers . Results Ninety-nine individuals were included in the analysis ( 53 in high protein group , 46 in high carbohydrate group ) . HbA1c decreased in both groups over time , with no significant difference between groups ( mean difference of the change at 12 months ; 0.04 [ 95 % CI −0.37 , 0.46 ] ; p = 0.44 ) . Both groups also demonstrated decreases over time in weight , serum triacylglycerol and total cholesterol , and increases in HDL-cholesterol . No differences in blood pressure , renal function or calcium loss were seen . Conclusions /interpretationThese results suggest that there is no superior long-term metabolic benefit of a high-protein diet over a high-carbohydrate in the management of type 2 diabetes . Trial registration ACTRN12605000063617 ( www.anzctr.org.au ) . Funding This study was funded by a nutritional research grant from Meat and Livestock Australia ( MLA ) . J.E. Shaw is supported by NHMRC Fellowship 586623",
"OBJECTIVE We compared the effects of a low glycemic index ( GI ) diet with the American Diabetes Association ( ADA ) diet on glycosylated hemoglobin ( HbA1c ) among individuals with type 2 diabetes . METHODS Forty individuals with poorly controlled type 2 diabetes were r and omized to a low-GI or an ADA diet . The intervention , consisting of eight educational sessions ( monthly for the first 6 mo and then at months 8 and 10 ) , focused on a low-GI or an ADA diet . Data on demographics , diet , physical activity , psychosocial factors , and diabetes medication use were assessed at baseline and 6 and 12 mo . Generalized linear mixed models were used to compare the two groups on HbA1c , diabetic medication use , blood lipids , weight , diet , and physical activity . RESULTS Participants ( 53 % female , mean age 53.5 y ) were predominantly white with a mean body mass index of 35.8 kg/m(2 ) . Although both interventions achieved similar reductions in mean HbA1c at 6 mo and 12 mo , the low-GI diet group was less likely to add or increase dosage of diabetic medications ( odds ratio 0.26 , P = 0.01 ) . Improvements in high-density lipoprotein cholesterol , triacylglycerols , and weight loss were similar between groups . CONCLUSION Compared with the ADA diet , the low-GI diet achieved equivalent control of HbA1c using less diabetic medication . Despite its limited size , this trial suggests that a low-GI diet is a viable alternative to the ADA diet . Findings should be evaluated in a larger r and omized controlled trial",
"Summary Type 2 ( insulin independent ) diabetic women were r and omly allocated to receive advice for low fat diets or low carbohydrate diets . By 24 h weighed dietary intakes before and after a mean interval of six months , patients in the low fat group had reduced their fat intake from 41 % to 31 % of total energy , while carbohydrate percentage of total energy intake increased from 38 % to 46 % . Percentage energy intake from fat and carbohydrate in the control group remained unchanged . Body weight fell in both groups , especially for patients in the low fat group who were obese ( weight/height2 ⩾ 28 kg/m2 ) . Mean plasma glucose , HbA1 , and triglycerides were unchanged . Mean plasma total cholesterol fell significantly in the low fat group compared with the controls ( p reduction of high density lipoprotein cholesterol observed in both groups . Thus , adherence to low fat diets occurred without deterioration of diabetes and with benefit for weight and total cholesterol ",
"1 . A prospect i ve r and omized study of two dietary regimens has been started in newly-diagnosed diabetics to determine their effect on circulating metabolites and on diabetic complications . 2 . During the first year of treatment the fasting plasma glucose concentrations on both the low-carbohydrate diet and the high-carbohydrate , modified-fat ( MF ) diet showed a similar decrease . 3 . Plasma cholesterol showed a sustained decrease only in patients recommended a MF diet . Transient changes in plasma triglyceride concentrations occurred in patients on both dietary regimens . 4 . Increased plasma cholesterol levels are associated with atheromatous disease which is common in diabetics in Europe and North America . A MF diet may therefore have an advantage in that it lowers the plasma cholesterol as well as being effective in lowering the plasma glucose",
"OBJECTIVE To investigate whether glycemic and lipid control in patients with non-insulin-dependent diabetes ( NIDDM ) can be significantly improved using a low-fat , vegetarian ( vegan ) diet in the absence of recommendations regarding exercise or other lifestyle changes . METHODS Eleven subjects with NIDDM recruited from the Georgetown University Medical Center or the local community were r and omly assigned to a low-fat vegan diet ( seven subjects ) or a conventional low-fat diet ( four subjects ) . Two additional subjects assigned to the control group failed to complete the study . The diets were not design ed to be isocaloric . Fasting serum glucose , body weight , medication use , and blood pressure were assessed at baseline and biweekly thereafter for 12 weeks . Serum lipids , glycosylated hemoglobin , urinary albumin , and dietary macronutrients were assessed at baseline and 12 weeks . RESULTS Although the sample was intentionally small in accordance with the pilot study design , the 28 % mean reduction in fasting serum glucose of the experimental group , from 10.7 to 7.75 mmol/L ( 195 to 141 mg/dl ) , was significantly greater than the 12 % decrease , from 9.86 to 8.64 mmol/L ( 179 to 157 mg/dl ) , for the control group ( P mean weight loss was 7.2 kg in the experimental group , compared to 3 . 8 kg for the control group ( P Insulin was reduced in both experimental group patients on insulin . No patient in the control group reduced medication use . Differences between the diet groups in the reductions of serum cholesterol and 24-h microalbuminuria did not reach statistical significance ; however , high-density lipoprotein concentration fell more sharply ( 0.20 mmol/L ) in the experimental group than in the control group ( 0.02 mmol/L ) ( P low-fat , vegetarian diet in patients with NIDDM was associated with significant reductions in fasting serum glucose concentration and body weight in the absence of recommendations for exercise . A larger study is needed for confirmation",
"Few controlled trials have studied cholesterol-lowering diets in premenopausal women . None has examined the cholesterol-lowering effect of a low-fat vegetarian diet , which , in other population groups , leads to marked reductions in serum cholesterol concentrations and , in combination with other life-style changes , a regression of atherosclerosis . We tested the hypothesis that a low-fat , vegetarian diet significantly reduces serum total and low-density lipoprotein ( LDL ) cholesterol concentrations in premenopausal women . In a crossover design , 35 women , aged 22 to 48 , followed a low-fat vegetarian diet deriving approximately 10 % of energy from fat for 2 menstrual cycles . For 2 additional cycles , they followed their customary diet while also taking a \" supplement \" ( placebo ) pill . Serum lipid concentrations were assessed at baseline and during each intervention phase . Mean serum LDL , high-density lipoprotein ( HDL ) , and total cholesterol concentrations decreased 16 . 9 % , 16.5 % , and 13.2 % , respectively , from baseline to the intervention diet phase ( p mean serum triacylglycerol concentration increased 18.7 % ( p LDL/HDL ratio remained unchanged . Thus , in healthy premenopausal women , a low-fat vegetarian diet led to rapid and sizable reductions in serum total , LDL , and HDL cholesterol concentrations",
"OBJECTIVE To determine the optimal diet for improving glucose and lipid profiles in obese patients with type 2 diabetes during moderate energy restriction . RESEARCH DESIGN AND METHODS A total of 35 free-living obese patients with type 2 diabetes were assigned to one of three 1,600 kcal/day diets for 12 weeks . The diets were high carbohydrate ( 10 % fat , 4 % saturated ) , high monounsaturated fat ( MUFA ) ( 32 % fat , 7 % saturated ) , or high saturated fat ( SFA ) ( 32 % fat , 17 % saturated ) . RESULTS Diet composition did not affect the magnitude of weight loss , with subjects losing an average of 6.6 + /- 0.9 kg . Energy restriction and weight loss result ed in reductions in fasting plasma glucose ( -14 % ) , insulin ( -27 % ) , GHb ( -14 % ) , and systolic ( -7 % ) and diastolic blood pressure ( -10 % ) levels and the glucose response area ( -17 % ) independent of diet composition . Diet composition did affect the lipoprotein profile . LDL was 10 % and 17 % lower with the high-carbohydrate and high-MUFA diets , respectively , whereas no change was observed with the high-SFA diet ( P HDL was transiently reduced on the high-carbohydrate diet at weeks 1 , 4 , and 8 , whereas higher fat consumption maintained these levels . The total cholesterol : HDL ratio , although significantly reduced on the high-MUFA diet ( P glycemic control ; however , reducing SFA intake by replacing SFA with carbohydrate or MUFA reduces LDL maximally during weight loss and to a greater degree than has been shown in weight-stable studies",
"OBJECTIVE This study sought to examine the effects of a 3-month programme of dietary advice to restrict carbohydrate intake compared with reduced-portion , low-fat advice in obese subjects with poorly controlled Type 2 diabetes . RESEARCH DESIGN AND METHODS One hundred and two patients with Type 2 diabetes were recruited across three centres and r and omly allocated to receive group education and individual dietary advice . Weight , glycaemic control , lipids and blood pressure were assessed at baseline and 3 months . Dietary quality was assessed at the end of study . RESULTS Weight loss was greater in the low-carbohydrate ( LC ) group ( -3.55 + /- 0.63 , mean + /- sem ) vs. -0.92 + /- 0.40 kg , P = 0.001 ) and cholesterol : high-density lipoprotein ( HDL ) ratio improved ( -0.48 + /- 0.11 vs. -0.10 + /- 0.10 , P = 0.01 ) . However , relative saturated fat intake was greater ( 13.9 + /- 0.71 vs. 11.0 + /- 0.47 % of dietary intake , P short-term weight loss compared with st and ard advice , but this was at the expense of an increase in relative saturated fat intake",
"Background Adherence to the Mediterranean diet is associated with lower mortality in a general population but limited evidence exists on the effect of a Mediterranean diet on mortality in subjects with diabetes . We aim to examine the association between the Mediterranean diet and mortality in diabetic individuals . Design Prospect i ve cohort study on 1995 type 2 diabetic subjects recruited within the MOLI-SANI study . Methods : Food intake was recorded by the European Project Investigation into Cancer and Nutrition food frequency question naire . Adherence to the Mediterranean diet was appraised by the Greek Mediterranean diet score . Hazard ratios were calculated using multivariable Cox-proportional hazard models . Results During follow-up ( median 4.0 years ) , 109 all-cause including 51 cardiovascular deaths occurred . A 2-unit increase in Mediterranean diet score was associated with 37 % ( 19%–51 % ) lower overall mortality . Data remained unchanged when restricted to those being on a hypoglycaemic diet or on antidiabetic drug treatment . A similar reduction was observed when cardiovascular mortality only was considered ( hazard ratio = 0.66 ; 0.46–0.95 ) . A Mediterranean diet-like pattern , originated from principal factor analysis , indicated a reduced risk of overall death ( hazard ratio = 0.81 ; 0.62–1.07 ) . The effect of Mediterranean diet score was mainly contributed by moderate alcohol drinking ( 14.7 % in the reduction of the effect ) , high intake of cereals ( 12.2 % ) , vegetables ( 5.8 % ) and reduced consumption of dairy and meat products ( 13.4 % and 3.4 % respectively ) . Conclusions The traditional Mediterranean diet was associated with reduced risk of both total and cardiovascular mortality in diabetic subjects , independently of the severity of the disease . Major contributions were offered by moderate alcohol intake , high consumption of cereals , fruits and nuts and reduced intake of dairy and meat products",
"Approximately 80 % of patients with type 2 diabetes are overweight/obese ( 1 ) , and weight loss is the mainstay of treatment for these individuals . However , there is growing controversy as to whether reduced-fat or reduced-carbohydrate diets are best suited for this purpose , and results ( 2–8 ) in nondiabetic subjects suggest that lower carbohydrate diets are similarly or more efficacious in improving weight , triglycerides , and HDL cholesterol . There are no published r and omized studies evaluating the role of dietary macronutrients with respect to weight loss and cardiovascular risk improvement in patients with type 2 diabetes . Thus , we r and omized diet-treated patients with type 2 diabetes to hypocaloric diets , moderately restricted in either carbohydrate or fat , to determine whether weight loss or metabolic improvement differed as a function of macronutrient composition . A total of 29 patients with diet-treated type 2 diabetes were recruited from the San Francisco Bay area . All subjects gave written informed consent . Inclusion criteria included BMI 27–36 kg/m2 , fasting plasma glucose concentration 7.2–8.3 mmol/l , no use of antihyperglycemic medications , and stable weight for 3 months . Subjects on anti-hypertensive or cholesterol-lowering drugs or aspirin were allowed to continue their medications . Insulin-mediated glucose uptake was quantified by a modification ( 9 ) of the insulin suppression test as originally described ( 10 ) and vali date d ( 11 ) . In this test , a 180-min infusion of somatostatin ( 0.27 μg/m2 per min ) , insulin ( 25 mU/m2 per min ) ,",
"High-density lipoprotein ( HDL ) plays an important role in the process of reverse cholesterol transport , which may become suboptimal with increasing body fatness . HDL cholesterol that is reduced in obese subjects paradoxically decreases during weight reduction . To determine how weight reduction affects HDL subclasses that are involved in reverse cholesterol transport , we studied HDL from obese diabetic subjects before and after energy restriction within background diets high in either carbohydrate or monounsaturated fatty acids ( MUFAs ) . Body weight , blood glucose , total cholesterol , and LDL cholesterol decreased after 8 and 12 weeks of weight reduction . With the very-low-fat diet , HDL cholesterol decreased significantly at 8 weeks , but recovered to initial levels after 12 weeks as body weight began to stabilize . Plasma apolipoprotein A-I ( apo A-I ) decreased substantially and significantly at 8 and 12 weeks with both diets , and was reflected in the reduction of apo A-I in HDL subclasses alpha1 , alpha2 , pre-beta1 , and pre-beta2 + pre-beta3 . The calculation of the percentage distribution of apo A-I among HDL species showed that only the proportion of pre-beta1-HDL decreased , whereas alpha2-HDL increased . This led to a significant increase in the alpha1 + alpha2/pre-beta ratio , ie , the ratio of the large cholesterol \" storage \" or \" sink \" HDL to the HDL \" shuttle \" fraction considered to be the initial acceptor of cell cholesterol . These data suggest that despite the reduction in HDL cholesterol and apo A-I , the redistribution of apo A-I in pre-beta1-HDL and alpha-HDL observed with weight reduction appears to revert to the pattern that we have previously reported in lean as opposed to overweight subjects",
"Objective To determine the extent to which intensive dietary intervention can influence glycaemic control and risk factors for cardiovascular disease in patients with type 2 diabetes who are hyperglycaemic despite optimised drug treatment . Design R and omised controlled trial . Setting Dunedin , New Zeal and . Participants 93 participants aged less than 70 years with type 2 diabetes and a glycated haemoglobin ( HbA1c ) of more than 7 % despite optimised drug treatments plus at least two of overweight or obesity , hypertension , and dyslipidaemia . Intervention Intensive individualised dietary advice ( according to the nutritional recommendations of the European Association for the Study of Diabetes ) for six months ; both the intervention and control participants continued with their usual medical surveillance . Main outcome measures HbA1c was the primary outcome . Secondary outcomes included measures of adiposity , blood pressure , and lipid profile . Results After adjustment for age , sex , and baseline measurements , the difference in HbA1c between the intervention and control groups at six months ( −0.4 % , 95 % confidence interval −0.7 % to −0.1 % ) was highly statistically significant ( P=0.007 ) , as were the decreases in weight ( −1.3 kg , −2.4 to −0.1 kg ; P=0.032 ) , body mass index ( −0.5 , −0.9 to −0.1 ; P=0.026 ) , and waist circumference ( −1.6 cm , −2.7 to −0.5 cm ; P=0.005 ) . A decrease in saturated fat ( −1.9 % total energy , −3.3 % to −0.6 % ; P=0.006 ) and an increase in protein ( 1.6 % total energy , 0.04 % to 3.1 % ; P=0.045 ) in the intervention group were the most striking differences in nutritional intake between the two groups . Conclusions Intensive dietary advice has the potential to appreciably improve glycaemic control and anthropometric measures in patients with type 2 diabetes and unsatisfactory HbA1c despite optimised hypoglycaemic drug treatment . Trial registration Clinical trials NCT00124553",
"Low-carbohydrate diets have been associated with significant reductions in weight and HbA(1c ) in obese , diabetic participants who received high-intensity lifestyle modification for 6 or 12 months . This investigation sought to determine whether comparable results to those of short-term , intensive interventions could be achieved over a 24-month study period using a low-intensity intervention that approximates what is feasible in outpatient practice . A total of 144 obese , diabetic participants were r and omly assigned to a low-carbohydrate diet ( a low fat diet ( . Participants were provided weekly group nutrition education sessions for the first month , and monthly sessions thereafter through the end of 24 months . Weight , HbA(1c ) , glucose , and lipids were measured at baseline and 6 , 12 , and 24 months . Of the 144 enrolled participants , 68 returned for the month 24 assessment visit . Weights were retrieved from electronic medical records for an additional 57 participants ( total , 125 participants ) at month 24 . All participants with a baseline measurement and at least one of the three other measurements were included in the mixed-model analyses ( n = 138 ) . The low-intensity intervention result ed in modest weight loss in both groups at month 24 . At this time , participants in the low-carbohydrate group lost 1.5 kg , compared to 0.2 kg in the low-fat group ( P = 0.147 ) . Lipids , glycemic indexes , and dietary intake did not differ between groups at month 24 ( or at months 6 or 12 ) ( Clinical Trials.gov number , NCT00108459 )",
"BACKGROUND Low-carbohydrate diets are effective for weight reduction in people without diabetes , but there is limited evidence for people with Type 2 diabetes . Aims To assess the impact of a low-carbohydrate diet on body weight , glycated haemoglobin ( HbA(1c ) ) , ketone and lipid levels in diabetic and non-diabetic subjects . METHODS Thirteen Type 2 diabetic subjects ( on diet or metformin ) and 13 non-diabetic subjects were r and omly allocated to either a low-carbohydrate diet ( or = 40 g carbohydrate/day ) or a healthy-eating diet following Diabetes UK nutritional recommendations and were seen monthly for 3 months . Subjects ( 25 % male ) were ( mean + /- sd ) age 52 + /- 9 years , weight 96.3 + /- 16.6 kg , body mass index 35.1 kg/m(2 ) , HbA(1c ) 6.6 + /- 1.1 % , total cholesterol 5.1 + /- 1.1 mmol/l , high-density lipoprotein cholesterol 1.3 + /- 0.4 mmol/l , low-density lipoprotein cholesterol 3.1 + /- 0.9 mmol/l , triglycerides ( geometric mean ) 1.55 ( 1.10 , 2.35 ) mmol/l and ketones range 0.0 - 0.2 mmol/l . RESULTS Analysis was by intention to treat with last observation carried forward . Twenty-two of the participants ( 85 % ) completed the study . Weight loss was greater ( 6.9 vs. 2.1 kg , P = 0.003 ) in the low-carbohydrate group , with no difference in changes in HbA(1c ) , ketone or lipid levels . CONCLUSIONS The diet was equally effective in those with and without diabetes",
"Abstract Objective To determine the effects of diets varying in carbohydrate to fat ratio on total energy expenditure . Design R and omized trial . Setting Multicenter collaboration at US two sites , August 2014 to May 2017 . Participants 164 adults aged 18 - 65 years with a body mass index of 25 or more . Interventions After 12 % ( within 2 % ) weight loss on a run-in diet , participants were r and omly assigned to one of three test diets according to carbohydrate content ( high , 60 % , n=54 ; moderate , 40 % , n=53 ; or low , 20 % , n=57 ) for 20 weeks . Test diets were controlled for protein and were energy adjusted to maintain weight loss within 2 kg . To test for effect modification predicted by the carbohydrate-insulin model , the sample was divided into thirds of pre-weight loss insulin secretion ( insulin concentration 30 minutes after oral glucose ) . Main outcome measures The primary outcome was total energy expenditure , measured with doubly labeled water , by intention-to-treat analysis . Per protocol analysis included participants who maintained target weight loss , potentially providing a more precise effect estimate . Secondary outcomes were resting energy expenditure , measures of physical activity , and levels of the metabolic hormones leptin and ghrelin . Results Total energy expenditure differed by diet in the intention-to-treat analysis ( n=162 , P=0.002 ) , with a linear trend of 52 kcal/d ( 95 % confidence interval 23 to 82 ) for every 10 % decrease in the contribution of carbohydrate to total energy intake ( 1 kcal=4.18 kJ=0.00418 MJ ) . Change in total energy expenditure was 91 kcal/d ( 95 % confidence interval −29 to 210 ) greater in participants assigned to the moderate carbohydrate diet and 209 kcal/d ( 91 to 326 ) greater in those assigned to the low carbohydrate diet compared with the high carbohydrate diet . In the per protocol analysis ( n=120 , P pre-weight loss insulin secretion , the difference between the low and high carbohydrate diet was 308 kcal/d in the intention-to-treat analysis and 478 kcal/d in the per protocol analysis ( P was significantly lower in participants assigned to the low carbohydrate diet compared with those assigned to the high carbohydrate diet ( both analyses ) . Leptin was also significantly lower in participants assigned to the low carbohydrate diet ( per protocol ) . Conclusions Consistent with the carbohydrate-insulin model , lowering dietary carbohydrate increased energy expenditure during weight loss maintenance . This metabolic effect may improve the success of obesity treatment , especially among those with high insulin secretion . Trial registration Clinical Trials.gov NCT02068885",
"CONTEXT Clinical trials using antihyperglycemic medications to improve glycemic control have not demonstrated the anticipated cardiovascular benefits . Low-glycemic index diets may improve both glycemic control and cardiovascular risk factors for patients with type 2 diabetes but debate over their effectiveness continues due to trial limitations . OBJECTIVE To test the effects of low-glycemic index diets on glycemic control and cardiovascular risk factors in patients with type 2 diabetes . DESIGN , SETTING , AND PARTICIPANTS A r and omized , parallel study design at a Canadian university hospital research center of 210 participants with type 2 diabetes treated with antihyperglycemic medications who were recruited by newspaper advertisement and r and omly assigned to receive 1 of 2 diet treatments each for 6 months between September 16 , 2004 , and May 22 , 2007 . INTERVENTION High-cereal fiber or low-glycemic index dietary advice . MAIN OUTCOME MEASURES Absolute change in glycated hemoglobin A(1c ) ( HbA(1c ) ) , with fasting blood glucose and cardiovascular disease risk factors as secondary measures . RESULTS In the intention-to-treat analysis , HbA(1c ) decreased by -0.18 % absolute HbA(1c ) units ( 95 % confidence interval [ CI ] , -0.29 % to -0.07 % ) in the high-cereal fiber diet compared with -0.50 % absolute HbA(1c ) units ( 95 % CI , -0.61 % to -0.39 % ) in the low-glycemic index diet ( P high-density lipoprotein cholesterol in the low-glycemic index diet by 1.7 mg/dL ( 95 % CI , 0.8 - 2.6 mg/dL ) compared with a decrease of high-density lipoprotein cholesterol by -0.2 mg/dL ( 95 % CI , -0.9 to 0.5 mg/dL ) in the high-cereal fiber diet ( P = .005 ) . The reduction in dietary glycemic index related positively to the reduction in HbA(1c ) concentration ( r = 0.35 , P high-density lipoprotein cholesterol ( r = -0.19 , P = .009 ) . CONCLUSION In patients with type 2 diabetes , 6-month treatment with a low-glycemic index diet result ed in moderately lower HbA(1c ) levels compared with a high-cereal fiber diet . Trial Registration clinical trials.gov identifier : NCT00438698",
"BACKGROUND AND AIMS To investigate the impact of a diet modeled on the traditional Cretan Mediterranean diet on metabolic control and vascular risk in type 2 diabetes . METHODS AND RESULTS Twenty-seven subjects ( 47 - 77 yrs ) with type 2 diabetes were r and omly assigned to consume either the intervention diet ad libitum or their usual diet for 12 weeks and then cross over to the alternate diet . Most of the meals and staple foods for the intervention diet were provided . Lipids , glycemic variables , blood pressure , homocysteine , C-reactive protein , plasma carotenoids and body composition ( anthropometry and dual energy X-ray absorptiometry ) were assessed at baseline , and at the end of both diet periods . Dietary adherence was monitored using plasma carotenoid and fatty acid ( FA ) analysis , complemented by diet diaries . Compared with usual diet , on the ad libitum Mediterranean intervention diet glycosylated haemoglobin fell from 7.1 % ( 95 % CI : 6.5 - 7.7 ) to 6.8 % ( 95 % CI : 6.3 - 7.3 ) ( p=0.012 ) and diet quality improved significantly [ plant : animal ( g/day ) food ratio increased from 1.3 ( 95 % CI : 1.1 - 1.5 ) to 5.4 ( 95 % CI : 4.3 - 6.6 ) ( p plasma lycopene and lutein/zeaxanthin increased ( 36 % and 25 % , respectively ) , plasma saturated and trans FAs decreased , and monounsaturated FAs increased . CONCLUSION A traditional moderate-fat Mediterranean diet improves glycemic control and diet quality in men and women with well-controlled type 2 diabetes , without adverse effects on weight"
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OBJECTIVE This systematic review aim ed to inform research ers and policymakers about what vali date d outcome measures are available to evaluate clinical genetics services ( CGS ) and the need for new measures . METHODS Vali date d outcome measures used to evaluate CGS were identified from a systematic literature review . Subjective outcome measures were assumed to have been vali date d only if some form of psychometric assessment was reported . RESULTS A total of 1688 titles and abstract s were identified , and 61 articles met the inclusion criteria for the final review , which covered 67 vali date d outcome measures . There were 37 nongenetics-specific and 30 genetics-specific measures identified . No single vali date d outcome measure encompassed all potential patient benefits from using a CGS . A variety of different domains were identified , including anxiety and depression , coping , decision-making , distress , family environment , health status , knowledge , mood , perception of risk , perceived personal control , psychological impact , quality of life , satisfaction and expectations , self-esteem , spiritual well-being , and worry . Some important aspects of patient benefit from CGS are not covered by existing outcome measures . CONCLUSIONS New research is necessary to develop the array of outcome measures required to quantify the benefits CGS offer patients living with the effects of genetic conditions . These need to be suitable for use in prospect i ve evaluation studies to provide robust evidence for decision-makers to inform service development and commissioning . This includes prioritization of the existing vali date d outcome measures in terms of their usefulness and relevance to the measurement and valuation of patient benefits from a CGS
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"ABSTRACT Despite increased interest among the public in breast cancer genetic risk and genetic testing , there are limited services to help women make informed decisions about genetic testing . This study , conducted with female callers ( N = 279 ) to the National Cancer Institute 's ( NCI 's ) Atlantic Region Cancer Information Service ( CIS ) , developed and evaluated a theory-based , educational intervention design ed to increase callers ' underst and ing of the following : ( a ) the kinds of information required to determine inherited risk ; ( b ) their own personal family history of cancer ; and ( c ) the benefits and limitations of genetic testing . Callers requesting information about breast/ovarian cancer risk , risk assessment services , and genetic testing were r and omized to either : ( 1 ) st and ard care or ( 2 ) an educational intervention . Results show that the educational intervention reduced intention to obtain genetic testing among women at average risk and increased intention among high-risk women at 6 months . In addition , high monitors , who typically attend to and seek information , demonstrated greater increases in knowledge and perceived risk over the 6-month interval than low monitors , who typically are distracted from information . These findings suggest that theoretically design ed interventions can be effective in helping women underst and their cancer risk and appropriate risk assessment options and can be implemented successfully within a service program like the CIS",
"OBJECTIVE --To assess the efficiency , reliability , and ease of use of DNA diagnosis for Duchenne and Becker muscular dystrophies ( DMD/BMD ) using the polymerase chain reaction ( PCR ) . DESIGN --DNA from the patients was screened for deletion mutations using multiplex PCR , and the results were compared with those obtained by Southern blot analysis . The PCR multiplex reaction detects nine specific \" hot-spot \" exons in the dystrophin gene while the Southern analysis detects 66 specific dystrophin gene restriction fragments . The multiplex reaction requires 50-fold less DNA than Southern analysis and thus is considerably more sensitive . SETTING --Fourteen university-affiliated and private genetic disease diagnostic laboratories . PATIENTS --Male patients with clinical signs of DMD/BMD . Cases were selected for analysis r and omly , without knowledge of whether a deletion was present within the dystrophin gene . MAIN OUTCOME MEASURES --The percentage of cases that were detectable by multiplex PCR in comparison with Southern analysis , the frequency , extent , and location of the detected deletion mutations . In some cases , duplication mutations were monitored . RESULTS --The accuracy of a single PCR multiplex amplification ( nine exons ) was compared with Southern analysis with 10 cDNA probes that cover the full length of the gene . The multiplex PCR analytic method detected 82 % of those deletions detected by Southern analysis methods . In one of 745 analyses , the multiplex method suggested a single exon deletion , which was not confirmed by Southern analysis , representing a false-positive rate of 0.013 % . CONCLUSIONS --Multiplex PCR represents a sensitive and accurate method for deletion detection of 46 % of all cases of DMD/BMD . The method requires 1 day for analysis , is easy to perform , and does not use radioactive tracers . As such , multiplex PCR represents an efficient and rapid method for prenatal or postnatal diagnosis of DMD/BMD",
"Patient satisfaction measures have previously addressed satisfaction with medical care , satisfaction with providers , and satisfaction with outcomes , but not satisfaction with the health care decision itself . As patients become more involved in health care decisions , it is important to underst and specific dynamics of the decision itself The Satisfaction with Decision ( SWD ) scale measures satisfaction with health care decisions . It was developed in the context of postmenopausal hormone-replacement therapy decisions The six-item scale has excellent reliability ( Cronbach 's alpha = 0.86 ) . Discriminant validity , tested by performing principal- components analysis of items pooled from the SWD scale and two conceptually related measures , was good . Correlation of the SWD scale with measures of satisfaction with other aspects of the decision-making process showed the SWD scale was correlated most highly ( 0.64 ) with \" decisional confidence , \" and least with \" desire to participate in health care de cisions \" and \" satisfaction with provider \" The SWD scale predicts decision certainty in this study . Use in an independent study showed that the SWD scale was correlated with the likelihood of patients ' intentions to get a flu shot . Further investigation in relation to other health decisions will establish the utility of the SWD scale as an outcome measure Key words : patient satisfaction ; medical decision making ; decision support ( Med Decis Making 1996;16:58 - 64",
"Most UK genetics centres offering predictive testing for hereditary non‐polyposis colorectal cancer ( HNPCC ) use an extended counselling protocol originally developed for Huntington 's disease . Shortened counselling may be more appropriate in the context of treatable genetic conditions such as HNPCC . Twenty‐six high‐risk individuals were r and omized to extended genetic counselling ( two sessions of education and reflection held 1 month apart ) or shortened genetic counselling ( a single educational session ) prior to HNPCC testing . Prospect i ve question naires , interviews and transcripts of counselling sessions were analysed . Participants were unsure what to expect prior to genetic counselling and had already decided to undergo genetic testing . There was no evidence of psychological harm caused by shortened genetic counselling , with a high level of satisfaction with the counselling received in both groups . Reflective counselling occurred in both groups but was framed in terms of practical action and information . Participants expressed differing preferences for the level of information received . This exploratory study indicates that shortened genetic counselling may be an appropriate means of supporting decisions already made by individuals about HNPCC testing . However , participants would benefit from preparatory information to help them reflect on issues not previously considered , which can then be explored more fully as part of a tailored counselling approach",
"OBJECTIVE Previous research has indicated low rates of adherence to monthly breast self-examination ( BSE ) in women with a family history of breast cancer , and anxiety has been identified as a major factor that may interfere with regular self-examination . However , the direction of the relationship between anxiety and BSE frequency remains unclear , with some studies indicating that high anxiety promotes adherence and others indicating that it leads to avoidance . The aim of the present study was to clarify the relationship between anxiety and adherence to breast self-examination by comparing the impact of general anxiety with that of cancer-specific anxiety on BSE frequency . METHODS A sample of at-risk women ( N=833 ) completed a question naire regarding BSE frequency , general anxiety , breast cancer worries , perceived risk of breast cancer , and family history of breast cancer . Women who self-examined infrequently ( N=211 ) , appropriately ( N=462 ) , or excessively ( N=156 ) were compared on these variables . RESULTS Statistical analyses indicated that general anxiety differentiated only between excessive self-examiners and less frequent self-examiners , with excessive self-examiners reporting significantly higher general anxiety . Breast cancer worries differentiated between all three groups in a linear fashion , with increasing cancer worries associated with higher levels of BSE . CONCLUSIONS In some at-risk women , high cancer anxiety may lead to high general anxiety and precipitate hypervigilant breast self-examination rather than avoidance . These findings are discussed in relation to psychoeducational interventions and genetic counseling services for women with a family history of breast cancer",
"BACKGROUND Because of the growing dem and for genetic assessment , there is an urgent need for information about what services are appropriate for women with a family history of breast cancer . Our purpose was to compare the psychologic impact and costs of a multidisciplinary genetic and surgical assessment service with those of current service provisions . METHODS We carried out a prospect i ve r and omized trial of surgical consultation with ( the trial group ) and without ( the control group ) genetic assessment in 1000 women with a family history of breast cancer . All P : values are from two-sided tests . RESULTS Although statistically significantly greater improvement in knowledge about breast cancer was found in the trial group ( P : = .05 ) , differences between groups in other psychologic outcomes were not statistically significant . Women in both groups experienced statistically significant reductions in anxiety and found attending the clinics to be highly satisfying . An initial specialist genetic assessment cost pound 14.27 ( U.S. $ 22.55 ) more than a consultation with a breast surgeon . Counseling and genetic testing of affected relatives , plus subsequent testing of family members of affected relatives identified as mutation carriers , raised the total extra direct and indirect costs per woman in the trial group to pound 60.98 ( U.S. $ 96.35 ) over costs for the control subjects . CONCLUSIONS There may be little benefit in providing specialist genetics services to all women with a family history of breast cancer . Further investigation of factors that may mediate the impact of genetic assessment is in progress and may reveal subgroups of women who would benefit from specialist genetics services",
"OBJECTIVES To evaluate women 's reasons for having an invasive procedure , their knowledge , how information was obtained , their satisfaction with this information , their concerns about complications and psychological reactions and distress evoked by the procedure . METHODS Ninety-four pregnant women undergoing early amniocentesis or chorionic villus sampling ( CVS ) at 10 - 13 weeks ' gestation participated in a question naire study . The women could choose between early amniocentesis ( n = 38 ) and CVS ( n = 31 ) , or to be r and omized to either of them ( n = 25 ) . RESULTS Apart from two items , no differences were found between the groups . Age was the main reason for testing , and anxiety was stated as a reason by 38.3 % . The women knew more about methods for fetal karyotyping , what the tests can reveal and how they are performed , than about the risks and reliability of the tests . The main source of information had been doctors and midwives at the antenatal care center . For a majority of women ( 64.9 % ) the decision to have the test was made together with their partner . The women 's concerns were focused on worry about fetal injury , miscarriage and waiting for the result . The test did not have a major psychological impact on the women in general , but a substantial minority reacted with anxiety and distress . CONCLUSIONS Knowledge of factors important to women and their concerns is essential for professionals working with genetic counselling and performance of invasive procedures",
"Purpose : A r and omized trial was conducted to test the effects of two counseling methods ( genetic counseling and group counseling ) against a control no-intervention condition on interest in genetic testing in lower risk women . Methods : After completing baseline surveys , women ( N = 357 ) were r and omized to one of three conditions : to receive individual genetic risk counseling , to receive a group psychosocial group counseling , or to serve as a control group . Participants completed follow-up question naires 6 months after r and omization . Results : All participants had some familial history of breast cancer , but none had a family history indicative of autosomal dominant genetic mutation . At baseline over three fourths of the sample judged themselves to be appropriate c and i date s for testing . By the end of the survey , two thirds ( 70 % ) of the women in the counseling group still judged themselves to be appropriate c and i date s for testing . Findings were similar for interest in genetic testing . Changes in beliefs about genetic testing ( e.g. , beliefs about potential stigma associated with testing ) altered the effects of counseling . Conclusion : These results indicate that counseling can change interest in genetic testing only slightly and that changing women ’s beliefs about the properties of testing might be one mechanism of doing so",
"This paper reports on the development of a unidimensional genetic knowledge index that has been tested and vali date d in a general population sample . The Index is intended to provide the basis for a st and ard measure of basic genetic knowledge that can be applied across diverse population s and research setting s. The study group was composed of 330 European Americans selected r and omly in the Louisville , KY , metropolitan area . The final version of the Genetic Knowledge Index ( GKI ) consisted of five items identified by principle components analysis , correlation coefficients , and the alpha measure of internal consistency . Construct validity of the GKI was determined by appropriate statistical correlations with educational attainment and attitudes toward genetic discrimination . The Index provides a numerical ranking of subjects ' knowledge of practical genetics . Implication s for research are discussed",
"OBJECTIVE To assess the outcome of accelerated patient surveillance in patients at high risk for inherited breast or ovarian cancer . METHODS Using stringent inclusion criteria , 57 high-risk patients ( 7 positive for BRCA1/2 mutations , 39 mutation negative , and 11 unaffected ) were recruited from a genetic testing protocol for inherited breast/ovarian cancer and were followed for 5 years ( 192.5 total patient years ) . Patients received twice annual physical examinations , imaging studies , measurement of CA125 and CA15 - 3 , psychometric measurements , and unstructured interviews by a psychologist . RESULTS When mutation ( + ) and mutation ( - ) patients were compared , there were no significant differences in the development of disease metastasis , recurrence , or new cancers . No unaffected patients developed cancer . Management of osteoporosis , sexual function , and psychological distress were major concerns . CONCLUSIONS Our data suggest that all patients with remarkable family history , regardless of their mutation status , may be at substantially increased risk for disease progression and development of new cancers , which is often not ovarian or recurrent breast cancer . Although prophylactic surgery is important in decreasing cancer recurrence in mutation carriers , increased surveillance with physical examinations and psychological support is also valuable and acceptable to such high-risk patients",
"OBJECTIVES To identify predictors of utilization of breast-ovarian cancer susceptibility ( BRCA1 gene ) testing and to evaluate outcomes of participation in a testing program . DESIGN Prospect i ve cohort study with baseline interview assessment of predictor variables ( eg , sociodemographic factors , knowledge about hereditary cancer and genetic testing , perceptions of testing benefits , limitations , and risks ) . BRCA1 test results were offered after an education and counseling session in a research setting . Outcome variables ( including depression , functional health status , and prophylactic surgery plans [ follow-up only ] ) were assessed at baseline and 1-month follow-up interviews . PARTICIPANTS Adult male and female members ( n=279 ) of families with BRCA1-linked hereditary breast-ovarian cancer ( HBOC ) . RESULTS Of subjects who completed a baseline interview ( n=192 ) , 60 % requested BRCA1 test results ( 43 % of all study subjects requested results ) . Requests for results were more frequent for persons with health insurance ( odds ration [ OR ] , 3.74 ; 95 % confidence interval [ CI ] , 2.06 - 6.80 ) ; more first-degree relatives affected with breast cancer ( OR , 1.59 ; 95 % CI , 1.16 - 2.16 ) ; more knowledge about BRCA1 testing ( OR , 1.85 ; 95 % CI , 1.36 - 2.50 ) ; and indicating that test benefits are important ( OR , 1.45 ; 95 % CI , 1.13 - 1.86 ) . At follow-up , noncarriers of BRCA1 mutations showed statistically significant reductions in depressive symptoms and functional impairment compared with carriers and nontested individuals . Individuals identified as mutation carriers did not exhibit increases in depression and functional impairment . Among unaffected women with no prior prophylactic surgery , 17 % of carriers ( 2/12 ) intended to have mastectomies and 33 % ( 4/12 ) to have oophorectomies . CONCLUSIONS Only a subset of HBOC family members are likely to request BRCA1 testing when available . Rates of test use may be higher in persons of a higher socioeconomic status and those with more relatives affected with breast cancer . For some high-risk individuals who receive test results in a research setting that includes counseling , there may be psychological benefits . More research is needed to assess the generalizability of these results and evaluate the long-term consequences of BRCA1 testing",
"STUDY OBJECTIVE To assess the need for and ability to apply a postnatal assessment protocol ( PNAP ) , consisting of clinical examination , photographs , radiographs , chromosomal analysis and postmortems , of fetuses from mid-pregnancy genetic terminations of pregnancy . DESIGN Prospect i ve hospital-based study . SETTING The maternity unit at the Pretoria Academic Hospital . MAIN RESULTS Fifty consecutively delivered fetuses were assessed by means of the PNAP after genetic termination of pregnancy . A definitive prenatal diagnosis was available in 17 ( 34 % ) cases . In 33 ( 66 % ) cases the termination was undertaken on the basis of a provisional prenatal diagnosis which was confirmed postnatally in 12 ( 24 % ) cases ; a definitive postnatal diagnosis could not be confirmed in 5 ( 10 % ) cases . In the remaining 16 ( 32 % ) cases a totally different postnatal diagnosis was obtained . The definitive postnatal diagnoses in the 28 cases with provisional prenatal diagnoses were confirmed by clinical examination in 13 ( 26 % ) , by chromosomal analysis in 7 ( 14 % ) , by postmortem in 5 ( 10 % ) and with radiographs in 3 ( 6 % ) . On retrospective analysis , 22 of the 33 provisional prenatal diagnoses could have been confirmed using available radiographs , chromosome results and photographs only . CONCLUSIONS Genetic terminations of pregnancy are a subgroup of stillbirths for which a PNAP is essential to ensure that appropriate postnatal genetic counselling can be given to the parent(s )",
"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"
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4118870e-06ff-11f0-808a-c43d1ab1c353
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AIM To synthesize the effects of theory-based self-management educational interventions on patients with type 2 diabetes ( T2DM ) in r and omized controlled trials . BACKGROUND Type 2 diabetes is a common chronic disease causing complications that put a heavy burden on society and reduce the quality of life of patients . Good self-management of diabetes can prevent complications and improve the quality of life of T2DM patients . DESIGN Systematic review with meta- analysis of r and omized controlled trials following Cochrane methods . DATA RE SOURCES A literature search was carried out in the MEDLINE , EMBASE , CINAHL , PSYCINFO , and Web of Science data bases ( 1980-April 2015 ) . REVIEW METHODS The risk of bias of these eligible studies was assessed independently by two authors using the Cochrane Collaboration 's tool . The Publication bias of the main outcomes was examined . Statistical heterogeneity and r and om-effects model were used for meta- analysis . RESULTS Twenty studies with 5802 participants met the inclusion criteria . The interventions in the studies were based on one or more theories which mostly belong to mid-range theories . The pooled main outcomes by r and om-effects model showed significant improvements in HbA1c , self-efficacy , and diabetes knowledge , but not in BMI . As for quality of life , no conclusions can be drawn as the pooled outcome became the opposite with reduced heterogeneity after one study was excluded . No significant publication bias was found in the main outcomes . CONCLUSION To get theory-based interventions to produce more effects , the role of patients should be more involved and stronger and the education team should be trained beyond the primary preparation for the self-management education program
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"OBJECTIVE To test whether a theory-based , literacy , and culturally tailored self-management intervention , Latinos en Control , improves glycemic control among low-income Latinos with type 2 diabetes . RESEARCH DESIGN AND METHODS A total of 252 patients recruited from community health centers were r and omized to the Latinos en Control intervention or to usual care . The primarily group-based intervention consisted of 12 weekly and 8 monthly sessions and targeted knowledge , attitudes , and self-management behaviors . The primary outcome was HbA1c . Secondary outcomes included diet , physical activity , blood glucose self-monitoring , diabetes knowledge and self-efficacy , and other physiological factors ( e.g. , lipids , blood pressure , and weight ) . Measures were collected at baseline and at 4- and 12-month follow-up . Change in outcomes over time between the groups and the association between HbA1c and possible mediators were estimated using mixed-effects models and an intention-to-treat approach . RESULTS A significant difference in HbA1c change between the groups was observed at 4 months ( intervention −0.88 [ −1.15 to −0.60 ] versus control −0.35 [ −0.62 to 0.07 ] , P differences in diabetes knowledge at 12 months ( P = 0.001 ) , self-efficacy ( P = 0.001 ) , blood glucose self-monitoring ( P = 0.02 ) , and diet , including dietary quality ( P = 0.01 ) , kilocalories consumed ( P , percentage of fat ( P = 0.003 ) , and percentage of saturated fat ( P = 0.04 ) . These changes were in turn significantly associated with HbA1c change at 12 months . CONCLUSIONS Literacy-sensitive , culturally tailored interventions can improve diabetes control among low-income Latinos ; however , strategies to sustain improvements are needed",
"PURPOSE The purpose of this r and omized controlled trial is to determine the effectiveness of an intervention led by promotoras ( community lay workers ) on the glycemic control , diabetes knowledge , and diabetes health beliefs of Mexican Americans with type 2 diabetes living in a major city on the Texas-Mexico border . METHODS One hundred fifty Mexican American participants were recruited at a Catholic faith-based clinic and r and omized into 2 groups . Personal characteristics , acculturation , baseline A1C level , diabetes knowledge , and diabetes health beliefs were measured . The intervention was culturally specific and consisted of participative group education , telephone contact , and follow-up using inspirational faith-based health behavior change postcards . The A1C levels , diabetes knowledge , and diabetes health beliefs were measured 3 and 6 months postbaseline , and the mean change between the groups was analyzed . RESULTS The 80 % female sample , with a mean age of 58 years , demonstrated low acculturation , income , education , health insurance coverage , and strong Catholicism . No significant changes were noted at the 3-month assessment , but the mean change of the A1C levels , F(1 , 148 ) = 10.28 , P diabetes knowledge scores , F(1 , 148 ) = 9.0 , P health belief scores decreased in both groups . CONCLUSIONS The intervention result ed in decreased A1C levels and increased diabetes knowledge , suggesting that using promotoras as part of an interdisciplinary team can result in positive outcomes for Mexican Americans who have type 2 diabetes . Clinical implication s and recommendations for future research are suggested",
"Background Dealing with heterogeneity in meta-analyses is often tricky , and there is only limited advice for authors on what to do . We investigated how authors addressed different degrees of heterogeneity , in particular whether they used a fixed effect model , which assumes that all the included studies are estimating the same true effect , or a r and om effects model where this is not assumed . Methods We sample d r and omly 60 Cochrane review s from 2008 , which presented a result in its first meta- analysis with substantial heterogeneity ( I2 greater than 50 % , i.e. more than 50 % of the variation is due to heterogeneity rather than chance ) . We extracted information on choice of statistical model , how the authors had h and led the heterogeneity , and assessed the method ological quality of the review s in relation to this . Results The distribution of heterogeneity was rather uniform in the whole I2 interval , 50 - 100 % . A fixed effect model was used in 33 review s ( 55 % ) , but there was no correlation between I2 and choice of model ( P = 0.79 ) . We considered that 20 review s ( 33 % ) , 16 of which had used a fixed effect model , had major problems . The most common problems were : use of a fixed effect model and lack of rationale for choice of that model , lack of comment on even severe heterogeneity and of reservations and explanations of its likely causes . The problematic review s had significantly fewer included trials than other review s ( 4.3 vs. 8.0 , P = 0.024 ) . The problems became less pronounced with time , as those review s that were most recently up date d more often used a r and om effects model . Conclusion One-third of Cochrane review s with substantial heterogeneity had major problems in relation to their h and ling of heterogeneity . More attention is needed to this issue , as the problems we identified can be essential for the conclusions of the review",
"Uncontrolled diabetes is a major health problem in Thail and . The objective of this study was to determine the effects of a diabetes self-management program on glycemic control , coronary heart disease ( CHD ) risk , and quality of life in 147 diabetic patients ( aged 56.8 + /- 10.2 years ) . Type 2 diabetic patients who met the research criteria were r and omized into two groups for a period of 6 months : the experimental group received the diabetes self-management program and the control group received the usual nursing care . The findings indicated that the experimental group demonstrated a significant decrease in the hemoglobin A(1c ) level and CHD risk , with an increase in quality of life ( QOL ) compared to the control group . The diabetes self-management program was effective for improving metabolic control and the QOL for individuals with diabetes . Further studies should be replicated using larger groups over a longer time frame",
"Background Multiple-risk-factor interventions offer a promising means for addressing the complex interactions between lifestyle behaviors , psychosocial factors , and the social environment . This report examines the long-term effects of a multiple-risk-factor intervention . Methods Postmenopausal women ( N = 279 ) with type 2 diabetes participated in the Mediterranean Lifestyle Program ( MLP ) , a r and omized , comprehensive lifestyle intervention study . The intervention targeted healthful eating , physical activity , stress management , smoking cessation , and social support . Outcomes included lifestyle behaviors ( i.e. , dietary intake , physical activity , stress management , smoking cessation ) , psychosocial variables ( e.g. , social support , problem solving , self-efficacy , depression , quality of life ) , and cost analyses at baseline , and 6 , 12 , and 24 months . Results MLP participants showed significant 12- and 24-month improvements in all targeted lifestyle behaviors with one exception ( there were too few smokers to analyze tobacco use effects ) , and in psychosocial measures of use of supportive re sources , problem solving , self-efficacy , and quality of life . Conclusion The MLP was more effective than usual care over 24 months in producing improvements on behavioral and psychosocial outcomes . Directions for future research include replication with other population",
"AIMS To determine the effects of the Diabetes Manual on glycaemic control , diabetes-related distress and confidence to self-care of patients with Type 2 diabetes . METHODS A cluster r and omized , controlled trial of an intervention group vs. a 6-month delayed-intervention control group with a nested qualitative study . Participants were 48 urban general practice s in the West Midl and s , UK , with high population deprivation levels and 245 adults with Type 2 diabetes with a mean age of 62 years recruited pre-r and omization . The Diabetes Manual is 1:1 structured education design ed for delivery by practice nurses . Measured outcomes were HbA(1c ) , cardiovascular risk factors , diabetes-related distress measured by the Problem Areas in Diabetes Scale and confidence to self-care measured by the Diabetes Management Self-Efficacy Scale . Outcomes were assessed at baseline and 26 weeks . RESULTS There was no significant difference in HbA(1c ) between the intervention group and the control group [ difference -0.08 % , 95 % confidence interval ( CI ) -0.28 , 0.11 ] . Diabetes-related distress scores were lower in the intervention group compared with the control group ( difference -4.5 , 95 % CI -8.1 , -1.0 ) . Confidence to self-care Scores were 11.2 points higher ( 95 % CI 4.4 , 18.0 ) in the intervention group compared with the control group . The patient response rate was 18.5 % . CONCLUSIONS In this population , the Diabetes Manual achieved a small improvement in patient diabetes-related distress and confidence to self-care over 26 weeks , without a change in glycaemic control . Further study is needed to optimize the intervention and characterize those for whom it is more clinical ly and psychologically effective to support its use in primary care",
"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 measure whether the benefits of a single education and self management structured programme for people with newly diagnosed type 2 diabetes mellitus are sustained at three years . Design Three year follow-up of a multicentre cluster r and omised controlled trial in primary care , with r and omisation at practice level . Setting 207 general practice s in 13 primary care sites in the United Kingdom . Participants 731 of the 824 participants included in the original trial were eligible for follow-up . Biomedical data were collected on 604 ( 82.6 % ) and question naire data on 513 ( 70.1 % ) participants . Intervention A structured group education programme for six hours delivered in the community by two trained healthcare professional educators compared with usual care . Main outcome measures The primary outcome was glycated haemoglobin ( HbA1c ) levels . The secondary outcomes were blood pressure , weight , blood lipid levels , smoking status , physical activity , quality of life , beliefs about illness , depression , emotional impact of diabetes , and drug use at three years . Results HbA1c levels at three years had decreased in both groups . After adjusting for baseline and cluster the difference was not significant ( difference −0.02 , 95 % confidence interval −0.22 to 0.17 ) . The groups did not differ for the other biomedical and lifestyle outcomes and drug use . The significant benefits in the intervention group across four out of five health beliefs seen at 12 months were sustained at three years ( P life did not differ at three years . Conclusion A single programme for people with newly diagnosed type 2 diabetes mellitus showed no difference in biomedical or lifestyle outcomes at three years although there were sustained improvements in some illness beliefs . Trial registration Current Controlled Trials IS RCT N17844016",
"AIM Patient education that enhances one 's self-management ability is of utmost importance for improving patient outcomes in chronic diseases . We developed a 12 month self-management education program for type 2 diabetes , based on a previous 6 month program , and examined its efficacy . METHODS A r and omized controlled trial was carried out on out patients with type 2 diabetes from two hospitals who met the criteria and gave consent to participate . They were r and omly divided into an intervention group that followed the program and a control group that followed usual clinical practise . The intervention group received based on the program 's textbook and biweekly telephone calls from a nurse educator throughout the 12 months . RESULTS Of the 50 participants in the intervention group and the 25 participants in the control group , 42 and 23 , respectively , completed the program ( a completion rate of 84.0 % ) . The body weight , HbA1c , self-efficacy , dietary and exercise stages , quality of life , diastolic blood pressure , and total cholesterol level were significant by two-way repeated- measures anova . As for changes over time within the groups , only the intervention group showed significant differences by Friedman 's test . The complication prevention behaviors showed a high implementation rate in the intervention group . The overall evaluation of this program by the participants was very high and , therefore , they highly recognized the need for this type of program . CONCLUSIONS Self-management education works successfully in relation to patients ' behavior modification skills , degree of goal attainment , and self-efficacy , consequently improving their health outcomes",
"The aim of the present study was to evaluate the impact of empowerment group education on type 2 diabetes patients ' confidence in diabetes knowledge , self-efficacy , satisfaction with daily life , BMI and glycaemic control compared with the impact of routine diabetes care on the same factors at a 1-year follow-up . In this r and omized controlled trial , conducted at 7 primary care centres in central Sweden , 101 patients were r and omly assigned either to empowerment group education ( intervention group ) or to routine diabetes care ( control group ) . Out of these , 42 patients in the intervention group and 46 in the control group completed the 1-year follow-up . Before the intervention and at the 1-year follow-up , the patients answered a 27-item question naire , and weight , BMI and HbA1c were measured . The question naire comprised three domains : confidence in diabetes knowledge , self-efficacy and satisfaction with daily life . At 1-year follow-up , the level of confidence in diabetes knowledge was significantly higher in the intervention group than in the control group ( p self-efficacy , satisfaction with daily life , BMI and HbA1c between the intervention and control group . The empowerment group education did improve patients ' confidence in diabetes knowledge with maintained glycaemic control despite the progressive nature of the disease",
"Objective To improve glycaemic control among Type 2 diabetics using patient-physician consultations guided by the Stages of Change ( SOC ) model . Design and Methods A r and omised trial was conducted . After ensuring concealment of allocation , Type 2 diabetics were r and omly assigned to receive the intervention or the control . The intervention consisted of identifying each patient 's Stage of Change for managing their diabetes by diet , exercise and medications , and applying personalised , stage-specific care during the patient-physician consultations based on the SOC model . Patients in the control group received routine care . The variables of interest were effect on glycaemic control ( measured by the difference in HbA1c levels ) and patients ' readiness to change ( measured by identifying patients ' SOC for managing their diabetes by diet , exercise and medications ) . Results Participants were primarily over age 50 , male and Indo-Trinidadian . Most had received only a primary school education and over 65 % had a monthly income of $ 320 USD/month or less . Sixty-one Type 2 diabetics participated in each arm . Three patients were lost to follow-up in the intervention arm . After 48 weeks , there was an overall increase in HbA1c of 0.52 % ( SE 0.17 ) and 1.09 % ( SE 0.18 ) for both the intervention and control groups respectively . There was a relative reduction in HbA1c of 0.57 % ( 95 % CI 0.07 , 1.07 ) with the intervention group compared to the control ( p = 0.025 ) . For exercise and diet there was an overall tendency for participants in the intervention arm to move to a more favourable SOC , but little change was noted with regards medication use . Conclusions The result suggests a tendency to a worsening of glycaemic control in this population despite adopting more favourable SOC for diet and exercise . We hypothesized that harsh social conditions prevailing at the time of the study overrode the clinical intervention",
"OBJECTIVE Few multiple lifestyle behavior change programs have been design ed to reduce the risk of coronary heart disease in postmenopausal women with type 2 diabetes . This study tested the effectiveness of the Mediterranean Lifestyle Program ( MLP ) , a comprehensive lifestyle self-management program ( Mediterranean low-saturated fat diet , stress management training , exercise , group support , and smoking cessation ) , in reducing cardiovascular risk factors in postmenopausal women with type 2 diabetes . RESEARCH DESIGN AND METHODS Postmenopausal women with type 2 diabetes ( n = 279 ) were r and omized to either usual care ( control ) or treatment ( MLP ) conditions . MLP participants took part in an initial 3-day retreat , followed by 6 months of weekly meetings , to learn and practice program components . Biological end points were changes in HbA(1c ) , lipid profiles , BMI , blood pressure , plasma fatty acids , and flexibility . Impact on quality of life was assessed . RESULTS Multivariate ANCOVAs revealed significantly greater improvements in the MLP condition compared with the usual care group on HbA(1c ) , BMI , plasma fatty acids , and quality of life at the 6-month follow-up . Patterns favoring intervention were seen in lipids , blood pressure , and flexibility but did not reach statistical significance . CONCLUSIONS These results demonstrate that postmenopausal women with type 2 diabetes can make comprehensive lifestyle changes that may lead to clinical ly significant improvements in glycemic control , some coronary heart disease risk factors , and quality of life",
"Background Type II diabetes and its complications impose a large economic burden on health care systems . This study aims to assess the effectiveness of educational intervention based on extended health belief model on type 2 diabetic patients . Methods 120 patients with type II diabetes referring to r and omly selected hospitals of Tehran University of Medical Sciences were enrolled in this educational intervention study . Patients were r and omly divided into two groups ( intervention and control ) . Data were collected using a question naire including demographic information and extended health belief model constructs . Two face to face educational sessions were conducted for each patient . Data were collected in two groups at three stages of the study ; before the educational sessions and at 3 months and 6 months intervals . Analysis was performed by SPSS ( 17.0 ) and STATA ( 11.0 ) using independent T-test , Chi-square , Fisher ’s exact test , analysis of covariance and Generalized Estimating Equation . A p value of less than 0.05 was regarded as statistically significant . Results The educational program had a positive and significant impact ( p extended health model belief constructs ( including perceived susceptibility , perceived intensity , perceived benefits , perceived barriers and self-efficacy ) in experimental group , 3 and 6 months after the intervention . Conclusions The results of this study showed the importance of extended health belief model based education in improving the model constructs and increasing self-efficacy in patients with type-2 diabetes",
"Self-management has been described as the cornerstone of care for diabetes . Many self-management studies are limited by poor methodology and poor descriptions of the intervention . The current study developed a theoretically based self-management programme for patients with type 2 diabetes , which was evaluated via a r and omized controlled trial . At immediate post-intervention and three-month follow-up the intervention group showed significant improvement relative to controls on self-management behaviours , quality of life and illness beliefs . A trend towards improved HbA1c was also observed . Documentation in a manual and development of a training programme for facilitators ensures the programme is replicable",
"The purpose of this study was to test the extent that constructs from two theoretical models ( self-regulatory theory and social cognitive theory ) mediated change in outcomes following a self-management intervention . One hundred and twenty four individuals with type 2 diabetes who had participated in a r and omised controlled trial of a diabetes self-management programme were analysed for the extent that illness beliefs and self-efficacy mediated change in self-management behaviours and illness specific quality of life . Exercise specific self-efficacy significantly mediated change in exercise at three months ( B = .03 ; .01 , p monitoring specific self-efficacy mediated change in monitoring behaviour at both three ( B = .04 ; .01 , p ) . Belief in control over diabetes mediated change in illness specific quality of life at three months ( B = −.07 ; .28 , p change in exercise behaviour at immediately post-intervention ( B = −.12 ; .17 , p may have a stronger role in mediating self-management behaviours than illness beliefs ; however , belief in control over diabetes may be important to manipulate for change in quality of life . This suggests different theoretical constructs may mediate change dependent on outcome",
"This study examines the effectiveness of a brief self-management intervention to support patients recently diagnosed with type-2 diabetes to achieve sustained improvements in their self-care behaviours . Based on proactive coping , the intervention emphasizes the crucial role of anticipation and planning in maintaining self-care behaviours . In a r and omised controlled trial among recent screen-detected patients , participants who received the intervention were compared with usual-care controls , examining changes in proximal outcomes ( intentions , self-efficacy and proactive coping ) , self-care behaviour ( diet , physical activity and medication ) and weight over time ( 0 , 3 and 12 months ) . Subsequently , the contribution of proactive coping in predicting maintenance of behavioural change was analysed using stepwise hierarchical regression analyses , controlling for baseline self-care behaviour , patient characteristics , and intentions and self-efficacy as measured after the course . The intervention was effective in improving proximal outcomes and behaviour with regard to diet and physical activity , result ing in significant weight loss at 12 months . Furthermore , proactive coping was a better predictor of long-term self-management than either intentions or self-efficacy . Proactive coping thus offers new insights into behavioural maintenance theory and can be used to develop effective self-management interventions ",
"Objective To evaluate the effectiveness of a structured group education programme on biomedical , psychosocial , and lifestyle measures in people with newly diagnosed type 2 diabetes . Design Multicentre cluster r and omised controlled trial in primary care with r and omisation at practice level . Setting 207 general practice s in 13 primary care sites in the United Kingdom . Participants 824 adults ( 55 % men , mean age 59.5 years ) . Intervention A structured group education programme for six hours delivered in the community by two trained healthcare professional educators compared with usual care . Main outcome measures Haemoglobin A1c levels , blood pressure , weight , blood lipid levels , smoking status , physical activity , quality of life , beliefs about illness , depression , and emotional impact of diabetes at baseline and up to 12 months . Main results Haemoglobin A1c levels at 12 months had decreased by 1.49 % in the intervention group compared with 1.21 % in the control group . After adjusting for baseline and cluster , the difference was not significant : 0.05 % ( 95 % confidence interval −0.10 % to 0.20 % ) . The intervention group showed a greater weight loss : −2.98 kg ( 95 % confidence interval −3.54 to −2.41 ) compared with 1.86 kg ( −2.44 to −1.28 ) , P=0.027 at 12 months . The odds of not smoking were 3.56 ( 95 % confidence interval 1.11 to 11.45 ) , P=0.033 higher in the intervention group at 12 months . The intervention group showed significantly greater changes in illness belief scores ( P=0.001 ) ; directions of change were positive indicating greater underst and ing of diabetes . The intervention group had a lower depression score at 12 months : mean difference was −0.50 ( 95 % confidence interval −0.96 to −0.04 ) ; P=0.032 . A positive association was found between change in perceived personal responsibility and weight loss at 12 months ( β=0.12 ; P=0.008 ) . Conclusion A structured group education programme for patients with newly diagnosed type 2 diabetes result ed in greater improvements in weight loss and smoking cessation and positive improvements in beliefs about illness but no difference in haemoglobin A1c levels up to 12 months after diagnosis . Trial registration Current Controlled Trials IS RCT N17844016",
"Living with Type 2 diabetes requires that patients develop a range of competencies that allow them to take greater control over the treatment of their disease . This requires education that promotes health whilst respecting individuals ' self-perceived needs and voluntary choices . Whilst such a concept is not new in the field of diabetes , health professionals are still struggling with how to administer it successfully . This paper presents the findings of a research trial of a theoretically constructed educational intervention . It focuses on the patients ' perspectives of what they valued about the intervention which was found to be clinical ly effective over a short-term period only . Limitations to maintaining effects were associated with a number of factors . The study found that whilst patients can be educated toward greater autonomy , not all health professionals are ready to work in partnership with them . It highlighted the importance of clinical staff not only gaining a better underst and ing of diabetes management , but also of the theoretical principles underlying patient empowerment . This paper outlines these principles and shows how they were synthesized to produce a framework for informing practice . Patients ' views are utilized to provide guidelines for improving the outcomes of patient education",
"BACKGROUND Type 2 diabetes is a serious and growing problem in Taiwan where it is the fifth leading cause of death , and health care costs are 4.3 times higher than for people without diabetes . OBJECTIVES The purpose of this study was to determine whether participation in a motivational interview for people with type 2 diabetes would improve their self-management , psychological and glycemic outcomes . DESIGN A r and omized controlled trial to assess the effects of the motivational interviewing intervention . SETTING S Participants were drawn from the diabetes outpatient clinic of a large teaching hospital in South Taiwan . PARTICIPANTS A sample of 250 type 2 diabetes people . METHODS Type 2 diabetes people were r and omly allocated into either the motivational interview group or the usual care group from baseline to 3 months follow-up . The intervention was based on motivational interviewing which encompassed a variety of interviewing techniques , and reflected each person 's readiness stage to change . The control group was provided with usual care by nursing staff . RESULTS A total of 250 type 2 diabetic participants were r and omized . The retention rate in the intervention group was 83 % ( n=104 ) . The motivational interview did improve participants significantly in self-management , self-efficacy , quality of life , and HbA1c among diabetes people with appropriate baseline value ( 7.62 , respectively ) but not in depression , anxiety and stress ( F=0.13 , p=0.72 ) compared to the control group at 3 months follow-up . CONCLUSION The findings provided important evidence concerning the positive effect of motivational interventions in self-management , psychological and glycemic outcomes . This research provided evidence for future clinical practice s in diabetes care",
"The aim of this study was to examine the effects of a self-efficacy program for persons with type 2 diabetes in Taiwan . A r and omized controlled trial was design ed ( n = 145 ) , with 72 participants in the intervention group and 73 in the control group . The participants were pretested to establish a baseline and then post-tests were undertaken 3 and 6 months after the baseline data were collected . The participants in the intervention group received the st and ard diabetes education program and an additional self-efficacy program . The scores for efficacy expectations , outcome expectations , and self-care activities had significantly increased in the intervention group at the 3 and 6 month follow-ups , when compared to those of the control group . A smaller proportion of the participants in the intervention group had been hospitalized or had visited an emergency room than in the control group at the 6 month follow-up . This study revealed that a self-efficacy program for diabetes was acceptable and effective in the short term in the self-management of persons with type 2 diabetes",
"CONTEXT Patients with depression and poorly controlled diabetes mellitus , coronary heart disease ( CHD ) , or both have higher medical complication rates and higher health care costs , suggesting that more effective care management of psychiatric and medical disease control might also reduce medical service use and enhance quality of life . OBJECTIVE To evaluate the cost-effectiveness of a multicondition collaborative treatment program ( TEAMcare ) compared with usual primary care ( UC ) in out patients with depression and poorly controlled diabetes or CHD . DESIGN R and omized controlled trial of a systematic care management program aim ed at improving depression scores and hemoglobin A(1c ) ( HbA(1c ) ) , systolic blood pressure ( SBP ) , and low-density lipoprotein cholesterol ( LDL-C ) levels . SETTING Fourteen primary care clinics of an integrated health care system . PATIENTS Population -based screening identified 214 adults with depressive disorder and poorly controlled diabetes or CHD . INTERVENTION Physician-supervised nurses collaborated with primary care physicians to provide treatment of multiple disease risk factors . MAIN OUTCOME MEASURES Blinded assessment s evaluated depressive symptoms , SBP , and HbA(1c ) at baseline and at 6 , 12 , 18 , and 24 months . Fasting LDL-C concentration was assessed at baseline and at 12 and 24 months . Health plan accounting records were used to assess medical service costs . Quality -adjusted life-years ( QALYs ) were assessed using a previously developed regression model based on intervention vs UC differences in HbA(1c ) , LDL-C , and SBP levels over 24 months . RESULTS Over 24 months , compared with UC controls , intervention patients had a mean of 114 ( 95 % CI , 79 to 149 ) additional depression-free days and an estimated 0.335 ( 95 % CI , -0.18 to 0.85 ) additional QALYs . Intervention patients also had lower mean outpatient health costs of $ 594 per patient ( 95 % CI , -$3241 to $ 2053 ) relative to UC patients . CONCLUSIONS For adults with depression and poorly controlled diabetes , CHD , or both , a systematic intervention program aim ed at improving depression scores and HbA(1c ) , SBP , and LDL-C levels seemed to be a high-value program that for no or modest additional cost markedly improved QALYs . TRIAL REGISTRATION clinical trials.gov Identifier :",
"OBJECTIVE To assess the effectiveness of a culturally sensitive , structured education programme ( CSSEP ) on biomedical , knowledge , attitude and practice measures among Arabs with type two diabetes . RESEARCH DESIGN S AND METHODS A total of 430 patients with type II diabetes mellitus living in Doha , Qatar were enrolled in the study . They were r and omized to either intervention ( n = 215 ) or a control group ( n = 215 ) . A baseline and one-year interval levels of biomedical variables including HbA1C , lipid profile , urine for microalbuminuria ; in addition to knowledge , attitude and practice ( KAP ) scores were prospect ively measured . The intervention was based on theory of empowerment , health belief models and was culturally sensitive in relation to language ( Arabic ) , food habits and health beliefs . It consisted of four educational sessions for each group of patients ( 10 - 20 patients per session ) , lasting for 3 - 4 h. The first session discussed diabetes pathophysiology and complications ; while the second session discussed healthy life style incorporating the Idaho plate method ; and the third session dealt with exercise benefits and goal setting and the fourth session concentrated enhancing attitude and practice using counselling techniques . Outcomes were assessed at base line and 12 months after intervention . RESULTS After 12 months participation in the intervention was shown to have led to a statistically significant reduction in HbA1C in the ( CSSEP ) group ( -0.55 mmol/L , P = 0.012 ) , fasting blood sugar ( -0.92 mmol/L , P = 0.022 ) , body mass index ( 1.70 , P = 0.001 ) and albumin/creatinine ratio ( -3.09 , P Diabetes knowledge ( 5.9 % , P attitude ( 6.56 % , P practice ( 6.52 % , P = 0.0001 ) . CONCLUSION This study demonstrates the effectiveness of culturally sensitive , structured , group-based diabetes education in enhancing biomedical and behavioural outcomes in Diabetic patients",
"Purpose The purpose of the study was to assess the value of reinforcing diabetes self-management for improving glycemia and self-care among adults with type 2 diabetes who had at least 3 hours of prior diabetes education . Methods In this r and omized controlled trial , 134 participants ( 75 % white , 51 % female , 59 ± 9 years old , 13 ± 8 years with diabetes , A1C = 8.4 % ± 1.2 % ) were r and omized to either a group map-based program ( intervention ) or group education on cholesterol and blood pressure ( control ) . Participants were assessed for A1C levels , diabetes self-care behaviors ( 3-day pedometer readings , 6-minute walk test , blood glucose checks , frequency of self-care ) , and psychosocial factors ( distress , frustration , quality of life ) at baseline , 3 , 6 , and 12 months post intervention and health literacy at baseline . Results Groups did not differ on baseline characteristics including A1C levels , health literacy , or self-care ; however , the intervention group had more years of education than controls . Intervention arm participants modestly improved A1C levels at 3 months post intervention but did not maintain that improvement at 6 and 12 months while control patients did not improve A1C levels at any time during follow-up . Importantly , frequency of self-reported self-care , diabetes quality of life , diabetes-related distress , and frustration with diabetes self-care improved in both groups over time . Conclusions Reinforcing self-care with diabetes education for patients who have not met glycemic targets helps improve A1C and could be considered a necessary component of ongoing diabetes care . The best method to accomplish reinforcement needs to be established"
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BACKGROUND Growing expenditures on prescription medicines represent a major challenge to many health systems . Cap and co-payment policies are intended as an incentive to deter unnecessary or marginal utilisation , and to reduce third-party payer expenditures by shifting parts of the financial burden from insurers to patients , thus increasing their financial responsibility for prescription medicines . Direct patient payment policies include caps ( maximum numbers of prescriptions or medicines that are reimbursed ) , fixed co-payments ( patients pay a fixed amount per prescription or medicine ) , co-insurance ( patients pay a percentage of the price ) , ceilings ( patients pay the full price or part of the cost up to a ceiling , after which medicines are free or are available at reduced cost ) and tier co-payments ( differential co-payments usually assigned to generic and br and medicines ) . This is the first up date of the original review . OBJECTIVES To determine the effects of cap and co-payment ( cost-sharing ) policies on use of medicines , healthcare utilisation , health outcomes and costs ( expenditures ) . SEARCH METHODS For this up date , we search ed the following data bases and websites : The Cochrane Central Register of Controlled Trials ( CENTRAL ) ( including the Cochrane Effective Practice and Organisation of Care ( EPOC ) Group Specialised Register , Cochrane Library ; MEDLINE , Ovid ; EMBASE , Ovid ; IPSA , EBSCO ; EconLit , ProQuest ; Worldwide Political Science Abstract s , ProQuest ; PAIS International , ProQuest ; INRUD Bibliography ; WHOLIS , WHO ; LILACS ) , VHL ; Global Health Library WHO ; PubMed , NHL ; SCOPUS ; SciELO , BIREME ; OpenGrey ; JOLIS Library Network ; OECD Library ; World Bank e-Library ; World Health Organization , WHO ; World Bank Documents & Reports ; International Clinical Trials Registry Platform ( ICTRP ) , WHO ; Clinical Trials.gov , NIH . We search ed all data bases during January and February 2013 , apart from SciELO , which we search ed in January 2012 , and ICTRP and Clinical Trials.gov , which we search ed in March 2014 . SELECTION CRITERIA We defined policies in this review as laws , rules or financial or administrative orders made by governments , non-government organisations or private insurers . We included r and omised controlled trials , non-r and omised controlled trials , interrupted time series studies , repeated measures studies and controlled before-after studies of cap or co-payment policies for a large jurisdiction or system of care . To be included , a study had to include an objective measure of at least one of the following outcomes : medicine use , healthcare utilisation , health outcomes or costs ( expenditures ) . DATA COLLECTION AND ANALYSIS Two review authors independently extracted data and assessed study limitations . We reanalysed time series data for studies with sufficient data , if appropriate analyses were not reported . MAIN RESULTS We included 32 full-text articles ( 17 new ) reporting evaluations of 39 different interventions ( one study - Newhouse 1993 - comprises five papers ) . We excluded from this up date eight controlled before-after studies included in the previous version of this review , because they included only one site in their intervention or control groups . Five papers evaluated caps , and six evaluated a cap with co-insurance and a ceiling . Six evaluated fixed co-payment , two evaluated tiered fixed co-payment , 10 evaluated a ceiling with fixed co-payment and 10 evaluated a ceiling with co-insurance . Only one evaluation was a r and omised trial . The certainty of the evidence was found to be generally low to very low . Increasing the amount of money that people pay for medicines may reduce insurers ' medicine expenditures and may reduce patients ' medicine use . This may include reductions in the use of life-sustaining medicines as well as medicines that are important in treating chronic conditions and medicines for asymptomatic conditions . These types of interventions may lead to small decreases in or uncertain effects on healthcare utilisation . We found no studies that reliably reported the effects of these types of interventions on health outcomes . AUTHORS ' CONCLUSIONS The diversity of interventions and outcomes addressed across studies and differences in setting s , population s and comparisons made it difficult to summarise results across studies . Cap and co-payment polices may reduce the use of medicines and reduce medicine expenditures for health insurers . However , they may also reduce the use of life-sustaining medicines or medicines that are important in treating chronic , including symptomatic , conditions and , consequently , could increase the use of healthcare services . Fixed co-payment with a ceiling and tiered fixed co-payment may be less likely to reduce the use of essential medicines or to increase the use of healthcare services
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"This paper examines changes in drug utilization following Taiwan 's newly implemented National Health Insurance ( NHI ) outpatient prescription drug cost-sharing program for persons over 65 years old . The study is a hospital outpatient prescription level analysis that adopts a pretest-posttest control group experiment design . Selected measures of outpatient prescription drug utilization are examined for cost-sharing and non cost-sharing groups in cost-sharing periods and pre cost-sharing periods . Additional analyses were conducted comparing older patients with and without chronic diseases and differences for essential and non-essential drugs . Patients over age 65 were drawn from 21 hospitals in the Taipei area using a stratified r and om sampling method . This paper yields several interesting findings . First , average prescription cost and prescription period increased for both the cost-sharing and non cost-sharing groups . However , the rate of increase was significantly less in the cost-sharing group when compared with the non cost-sharing group . Second , the elderly with non-chronic diseases were more sensitive ( i.e. , reducing drug utilization ) to the drug cost-sharing program when compared with those with chronic diseases . Third , for the elderly with non-chronic diseases average drug cost per prescription experienced a smaller decrease in essential drugs but a moderate increase in non-essential drugs for the cost-sharing group . By contrast , for the non cost-sharing group , average drug cost per prescription increased sharply in non-essential drugs as well as essential drugs . Finally , there was a significant increase in the number of prescriptions as well as drug costs above the upper bound of the cost-sharing schedule . The outpatient drug cost-sharing program implemented by the NHI in Taiwan did not reverse the trend of prescription drug cost increases in hospitals . The significant increase in the number of prescriptions above the upper bound of the cost-sharing schedule implies that the NHI should increase the upper bound . Further analysis needs to evaluate any adverse clinical impact for older patients result ing from policy changes",
"CONTEXT Rising costs of medications and inequities in access have sparked calls for drug policy reform in the United States and Canada . Control of drug expenditures by prescription cost-sharing for elderly persons and poor persons is a contentious issue because little is known about the health impact in these subgroups . OBJECTIVES To determine ( 1 ) the impact of introducing prescription drug cost-sharing on use of essential and less essential drugs among elderly persons and welfare recipients and ( 2 ) rates of emergency department ( ED ) visits and serious adverse events associated with reductions in drug use before and after policy implementation . DESIGN AND SETTING Interrupted time-series analysis of data from 32 months before and 17 months after introduction of a prescription coinsurance and deductible cost-sharing policy in Quebec in 1996 . Separate 10-month prepolicy control and postpolicy cohort studies were conducted to estimate the impact of the drug reform on adverse events . PARTICIPANTS A r and om sample of 93 950 elderly persons and 55 333 adult welfare medication recipients . MAIN OUTCOME MEASURES Mean daily number of essential and less essential drugs used per month , ED visits , and serious adverse events ( hospitalization , nursing home admission , and mortality ) before and after policy introduction . RESULTS After cost-sharing was introduced , use of essential drugs decreased by 9.12 % ( 95 % confidence interval [ CI ] , 8.7%-9.6 % ) in elderly persons and by 14.42 % ( 95 % CI , 13.3%-15.6 % ) in welfare recipients ; use of less essential drugs decreased by 15.14 % ( 95 % CI , 14.4%-15.9 % ) and 22.39 % ( 95 % CI , 20.9%-23.9 % ) , respectively . The rate ( per 10 000 person-months ) of serious adverse events associated with reductions in use of essential drugs increased from 5.8 in the prepolicy control cohort to 12.6 in the postpolicy cohort in elderly persons ( a net increase of 6.8 [ 95 % CI , 5.6 - 8.0 ] ) and from 14.7 to 27.6 in welfare recipients ( a net increase of 12.9 [ 95 % CI , 10.2 - 15.5 ] ) . Emergency department visit rates related to reductions in the use of essential drugs also increased by 14.2 ( 95 % CI , 8.5 - 19.9 ) per 10 000 person-months in elderly persons ( prepolicy control cohort , 32.9 ; postpolicy cohort , 47.1 ) and by 54.2 ( 95 % CI , 33.5 - 74.8 ) among welfare recipients ( prepolicy control cohort , 69.6 ; postpolicy cohort , 123.8 ) . These increases were primarily due to an increase in the proportion of recipients who reduced their use of essential drugs . Reductions in the use of less essential drugs were not associated with an increase in risk of adverse events or ED visits . CONCLUSIONS In our study , increased cost-sharing for prescription drugs in elderly persons and welfare recipients was followed by reductions in use of essential drugs and a higher rate of serious adverse events and ED visits associated with these reductions",
"Abstract Objective To compare the results of a r and omised and an observational evaluation of the same policy that restricted reimbursement for nebulised respiratory medications in adult patients in a community setting . Design s Cluster r and omised controlled trial and observational time series with historical controls . Setting Pharmacare , the government funded drug benefits plan for elderly people and patients receiving social assistance in British Columbia , Canada . Participants In the r and omised controlled trial 104 clusters of medical practice s , pair matched by geography and approximately by practice size , were r and omised to the intervention group ( 449 patients affected by the policy on 1 March 1999 ) , and the control group ( offered a six month exemption , affecting 386 patients ) . The observational analysis included all Pharmacare beneficiaries ( excluding the 386 exempt patients ) who had used any nebulised drugs six months before the policy ( 4624 patients ) . Intervention Pharmacare restricted reimbursement for nebulised bronchodilators , steroids , and cromoglycate to patients whose doctors applied for an individual patient 's exemption , giving an appropriate clinical reason . Main outcome measures Number of contacts with doctors and services , emergency admissions to hospital , and utilisation of and expenditure for respiratory drugs in data bases of British Columbia 's Ministry of Health . Results Contacts with doctors or emergency admissions to hospital did not increase in association with the restriction , regardless of the analytical approach . In the observational analysis , we found a reduction of $ C24 per patient month in all nebulised drug use ( 95 % confidence interval 19 to 29 ) and an increase of $ C3 per patient month in all expenditure for inhalers ( 1.4 to 4.5 ) . The r and omised evaluation found savings of $ C8 per patient month for nebulisers ( P = 0.24 ) and no increase in spending on inhalers ( P = 0.79 ) . Correcting for 60 % non-compliance by exempt doctors in a sensitivity analysis yielded similar results as the observational evaluation . Conclusions Observational as well as r and omised analyses found moderate net savings and no increase in unintended healthcare outcomes after restricting reimbursement for nebulised respiratory drugs . R and omised policy trials are feasible and , if carefully implemented , likely to be concordant with observational evaluations",
"BACKGROUND Medication nonadherence is a major public health problem , especially for patients with coronary artery disease . The cost of prescription drugs is a central reason for nonadherence , even for patients with drug insurance . Removing patient out-of-pocket drug costs may increase adherence , improve clinical outcomes , and even reduce overall health costs for high-risk patients . The existing data are inadequate to assess whether this strategy is effective . TRIAL DESIGN The Post-Myocardial Infa rct ion Free Rx and Economic Evaluation ( Post-MI FREEE ) trial aims to evaluate the effect of providing full prescription drug coverage ( ie , no copays , coinsurance , or deductibles ) for statins , beta-blockers , angiotensin-converting enzyme inhibitors , and angiotensin II receptor blockers to patients after being recently discharged from the hospital . Potentially eligible patients will be those individuals who receive their health and pharmacy benefits through Aetna , Inc. Patients enrolled in a Health Savings Account plan , who are > or = 65 years of age , whose plan sponsor ( ie , the employer , union , government , or association that sponsors the particular benefits package ) has opted out of participating in the study , and who do not receive both medical services and pharmacy coverage through Aetna will be excluded . The plan sponsor of each eligible patient will be block r and omized to either full drug coverage or current levels of pharmacy benefit , and all subsequently eligible patients of that same plan sponsor will be assigned to the same benefits group . The primary outcome of the trial is a composite clinical outcome of readmission for acute MI , unstable angina , stroke , congestive heart failure , revascularization , or inhospital cardiovascular death . Secondary outcomes include medication adherence and health care costs . All patients will be followed up for a minimum of 1 year . CONCLUSION The Post-MI FREEE trial will be the first r and omized study to evaluate the impact of reducing cost-sharing for essential cardiac medications in high-risk patients on clinical and economic outcomes",
"OBJECTIVE To evaluate the impact of the final Centers for Medicare & Medicaid Services ' ( CMS ) \" short-fill \" rule regarding the appropriate dispensing of prescription drugs in long-term care facilities . DESIGN A prospect i ve study to determine rates of unconsumed medication and the net-cost impact on Medicare Part D prescription drug plans based on the proposed and final CMS rule and other scenarios under consideration by CMS . SETTING Four hundred twenty-five long-term care facilities in six states . PATIENTS Residents covered by Medicare Part D. MAIN OUTCOME MEASURES Rates of unconsumed medication , average dispensing fees , potential reduction in unconsumed medication , incremental fills , incremental dispensing fees , net cost or savings to Medicare Part D plans , and percentage increase in fills . RESULTS Total estimates of the cost of unconsumed medication charged to Medicare Part D plans for residents in long-term care facilities are $ 87 million for br and products and $ 39 million for generics annually . Based on current dispensing fees , it is likely that implementation of the final rule will result in incremental costs to CMS plans in the range of $ 30 million annually . The number of Medicare Part D prescription fills will increase by about 20 % . A seven-day fill requirement on br and products would raise incremental costs to more than $ 150 million annually , and inclusion of generic products in a seven-day fill requirement would result in incremental costs in the range of $ 850 million annually . CONCLUSION The final CMS rule on short-fills is unlikely to result in savings to Medicare Part D plans . Shorter fill times and inclusion of generic products would significantly raise costs to these plans",
"OBJECTIVE To examine the effect of Part D on 65 - 78-year-old noninstitutionalized dual eligibles ' prescription utilization and expenditures . DATA SOURCE R and om sample of unique pharmacy customers of a national retail pharmacy chain who filled at least one prescription during both 2005 and 2006 . For each subject , we obtained cl aims data for every prescription filled between January 1 , 2005 , and April 31 , 2007 . STUDY DESIGN Generalized estimating equations were used to examine the experience of a \" treatment \" group ( dual eligibles between 65 and 78 years on January 1 , 2005 ) with that of a \" control \" group ( near-elderly patients with Medicaid coverage between 60 and 63 years on January 1 , 2005 ) during the first 18 months after Part D implementation . PRINCIPAL FINDINGS Expenditures for the treatment and control groups tracked each other closely in the pre-Part D period . Immediately following the implementation of Part D , expenditures for both groups decreased and then leveled off . There were no significant changes in trends in the dual eligibles ' out-of-pocket expenditures , total monthly expenditures , pill-days , or total number of prescriptions due to Part D. CONCLUSIONS We find no evidence that Part D adversely affected pharmaceutical utilization or out-of-pocket expenditures of dual eligibles during the transition period , nor during the 16 months subsequent to Part D implementation",
"Objectives : In February 2002 , the Department of Veterans Affairs ( VA ) raised medication copayments from $ 2 to $ 7 per 30-day supply of medication for certain veteran groups . We examined the impact of the copayment increase on medication acquisition from VA . Methods : This was a retrospective cohort study using data from national VA data bases from February 2001 through February 2003 . We took a r and om sample of over 5 % of male VA users in 2001 . Of 149,107 veterans sample d , 19,504 ( 13 % ) had copayments for no drugs , 101,410 ( 68 % ) had copayments for some drugs , and 28,193 ( 19 % ) had copayments for all drugs . We used multivariable count models to examine changes in the number of 30-day medication supplies after the increase . Results : After the copayment increase , veterans subject to copayments for all drugs received 8 % fewer 30-day supplies of medication annually relative to veterans with no copayments ( P effect of the copayment increased as the number of different medications veterans received increased . Among veterans subject to copayments for all drugs , acquisition of lower-cost drugs fell by 36 % , higher-cost medications fell by 6 % , over-the-counter medications fell by 40 % , and prescription-only medications fell by 4 % relative to veterans with no drug copayments . Conclusions : The number of medications veterans obtained from VA decreased after the copayment increase . There were relatively larger impacts on veterans with higher medication use and on lower-cost and over-the-counter medications",
"Objectives . This study uses variance cost analysis and regression analysis as tools for investigating the initial effects of Taiwan ’s outpatient prescription drug copayment program in the elderly . Under its new National Health Insurance program , Taiwan implemented a prescription drug cost-sharing program August 1 , 1999 . We compare an elderly population ’s prescription drug use after the policy was implemented with an elderly population ’s prescription drug use before the policy change to describe initial and general consequences of the drug cost-sharing program . Methods . Approximately 240,000 patients aged 65 and over representing 1,600,000 outpatient prescriptions were drawn from 21 hospitals in the Taipei area for the study using a stratified r and om sampling method . Variance analysis , as used primarily in accounting , was applied to decompose overall cost variance of the policy into the sum of variances of several specific factors that are important to policymakers . The cost variances of each specific factor can be further decomposed into sublevels of analyses . Regression analysis is then applied to better underst and covariates that might influence drug cost variances of significant magnitude . Results . The initial effects of the policy change did not reverse the trend of drug cost increases . Instead , there was a significant increase in total prescription drug costs in the cost-sharing group ( approximately 12.86 % ) and an even higher increase rate in the non-cost-sharing group ( approximately 51.42 % ) . The main reason for the drug cost increase for the cost-sharing group was attributed to an increase in average drug costs per prescription ( explaining 69.20 % of the variance ) . We found physicians seemed to prescribe more expensive drugs and extend prescription duration , especially when drug costs exceed the upper bound of the cost-sharing schedule . By contrast , the main factor contributing to the increase in drug costs for the non-cost-sharing group was an increase in average prescription duration ( explaining 64.98 % of the variance ) . The increase mainly results from the effect of extended prescriptions for chronic diseases that were design ed to reduce unnecessary visits for refills . Discussion . The significant increase in average drug price per prescription indicates that many prescriptions could move above the upper bound of the cost-sharing schedule . The results suggest that the Bureau of National Health Insurance should increase the upper bound . We do not think these effects are unique to Taiwan . Rather , these effects should be considered as countries change their outpatient drug benefit programs . We also found a decrease in utilization of essential drugs with an increase in utilization of nonessential drugs for patients subject to copayments . The results suggest potential adverse effects on patients ’ health outcome",
"This study examined the prescription drug costs of Medicare beneficiaries participating in a Medicaid home- and community-based services ( HCBS ) program and discussed possible implication s of providing a prescription drug benefit under Medicare . The study examined Medicaid pharmaceutical cl aims data using two r and om sample s ( n=766 ) of dually eligible Medicare beneficiaries in a HCBS program from four regions in Georgia . The average total monthly Medicaid prescription drug expenditure was determined . Annual prescription expenditures for this group averaged more than 1,500 dollars per person . Prescription drugs intended for the treatment of cancer and circulatory disorders combined to account for 61 % of total program drug expenditures . Multivariate analysis found that drug expenditures were higher for those who died during the observation period , the young-old , Caucasians , and those who self-selected into the program . Higher drug expenditures for the self-selected group , even after frailty adjustments , suggest the presence of adverse selection . Medicare prescription drug benefit proposals that rely on voluntary enrollment may also experience adverse selection from frail , low-income beneficiaries",
"This paper estimates how cost-sharing affects the use of prescription drugs . The data for this analysis are derived from the R and Health Insurance Experiment ( HIE ) , a r and omized controlled trial that r and omly assigned participants to insurance plans with varying coinsurance rates and deductibles . Therefore , the cost-sharing they faced was independent of their health and demographic characteristics . The paper used HIE data from four sites to estimate how drug expenditures vary by insurance plan , and to compare the plan response for drugs with that for all ambulatory expenses . The findings show that : ( 1 ) individuals with more generous insurance buy more prescription drugs ; ( 2 ) the cost-sharing response for drugs is similar to the response for all ambulatory medical services ; ( 3 ) the Dayton , Ohio site had significantly greater drug expenditures per capita than the other sites studied and a significantly higher proportion of drugs sold by physicians ; and ( 4 ) the proportion of br and -name drugs among all drugs purchased in pharmacies was not a function of insurance plan . In the Dayton , Ohio site , a significantly higher proportion of the drugs purchased in pharmacies were br and -name rather than generic",
"Little is known about how generosity of insurance and population characteristics affect quantity or appropriateness of antibiotic use . Using insurance cl aims for antibiotics from 5765 non-elderly people who lived in six sites in the United States and were r and omly assigned to insurance plans varying by level of cost-sharing , we describe how antibiotic use varies by insurance plan , diagnosis and health status , geographic area , and demographic characteristics . People with free medical care used 85 % more antibiotics than those required to pay some portion of their medical bills ( controlling for all other variables ) . Antibiotic use was significantly more common among women , the very young , patients with poorer health , and persons with higher income . Use of antibiotics for viral , viral-bacterial , and bacterial conditions did not differ between free and cost-sharing insurance plans , given antibiotics were the treatment of choice . Cost sharing reduced inappropriate and appropriate antibiotic use to a similar degree",
"We studied the effect of insurance coverage on the use of emergency department services , using data from a national trial of cost sharing in health insurance . A total of 3973 persons below the age of 62 years were r and omly assigned to fee-for-service health insurance plans with coinsurance rates of 0 , 25 , 50 , or 95 per cent , subject to an income-related upper limit on out-of-pocket expenses . Persons with no cost sharing had emergency department expenses that were 42 per cent higher than those for persons on the 95 per cent plan ( P less than 0.01 ) and about 16 per cent higher than those for persons with smaller amounts of cost sharing . Without cost sharing , emergency department visits for less serious diagnoses ( e.g. , abrasions ) increased three times as much as did visits for more serious diagnoses ( e.g. , lacerations ) . After control for insurance , persons in the lower third of the income distribution had emergency department expenses that were 64 per cent higher than those in the upper third ( P less than 0.001 ) and received a greater proportion of their ambulatory care in the emergency department . We conclude that the absence of cost sharing results in significantly greater emergency department use than does insurance with cost sharing . A disproportionate amount of the increased use involves less serious conditions",
"Objective : This is the first study to compare total Medicare Part D ( MPD ) st and -alone prescription drug plan ( PDP ) estimated annual costs ( EAC ) between 2007 and 2008 in all MPD regions of the US using a patient cohort of Medicare-eligible patients . Methods : A total of 50 patients were selected at r and om from a data base of Medicare-eligible patients . Each patient profile , based on pharmacy cl aims data , was entered into the Medicare website and the EAC of each PDP in each of the 34 MPD regions was obtained . The lowest , 25th percentile , median and highest EAC plans were obtained for each patient in each region for 2007 and 2008 . Pair-wise , within-region , between-year comparisons were made using the Wilcoxon Signed-Ranks test . Results : Annual trends were variable between MPD regions . Only the highest EAC showed significant decreases in some regions , while all other comparisons showed no change or an increase in regional costs . Conclusions : Out-of-pocket Medicare prescription drug costs increased from 2007 to 2008 . Increases in plan costs highlight the need for annual re-evaluation of PDP costs so that the patient is able to obtain the lowest cost plan each year . The decrease in the highest cost plan may suggest improvements in formulary coverage",
"BACKGROUND Mental health disorders represent one of the most common problems facing adults in the labor force . It is estimated that within a 12-month period nearly 30 % of the US population experiences some diagnosable mental health or addictive disorder . This study examines the impact that corporate benefit policies can have on mental health treatment costs . AIMS To measure the effects of a change in mental health benefit design on treatment expenditures for employees of a large US-based company . METHODS Data came from mental health treatment administrative cl aims and eligibility information provided by the company and a comparable set of cl aims for a r and omly selected control group for the years 1995 - 1998 . We measure the effect of a change in mental health benefits consisting of three major elements : a company-wide effort to destigmatize mental illness ; reduced cost-sharing for mental health treatment ; and the implementation of a provider network that emphasized access to non-physician mental health specialists . We use a two-part regression model within a difference in differences framework to examine outpatient , pharmaceutical , and combined outpatient and pharmaceutical expenditures between the treatment company and the control group . RESULTS We find that the program led to a statistically significant dollar 17 increase in outpatient costs ( excluding pharmaceutical costs ) per employee . Similar to outpatient care we find that the benefit change was associated with a statistically significant increase in pharmaceutical costs of about dollar 15 . DISCUSSION The results reveal that the mental health benefit expansion at the company led to a significant increase in aggregate mental health expenditures among employees . However , the aggregate increase in cost masks a number of interesting underlying trends in mental health utilization . First , conditional upon any mental health treatment , mental health costs were virtually unchanged before and after the benefit change . Conditional on any use , outpatient and pharmaceutical expenditures went in opposite directions , with outpatient expenditures falling and pharmaceutical expenditures increasing . IMPLICATION S FOR HEALTH CARE PROVISION AND USE Private sector initiatives can increase use of mental health care treatment through decreased cost-sharing , improved access to specialty providers , and destigmatization of mental disorders . IMPLICATION S FOR HEALTH CARE POLICY FORMULATION : Given that the vast majority of people in the US get their health insurance through employer-sponsored health insurance , efforts on the part of the private sector to recognize and treat serious chronic illnesses such as mental disorder in a proactive manner should be encouraged . IMPLICATION S FOR FUTURE RESEARCH While the aggregate cost of corporate initiatives to improve access to quality mental health care is frequently examined , it is also important to decompose the aggregate cost changes into effects from a change in the rate of initiation and changes in utilization conditional upon initiation",
"Context In 2006 , Medicare inaugurated a drug benefit for older adults . Contribution Using data from a r and om sample of pharmacy customers who were beneficiaries of the program after the enrollment deadline , the authors estimate that the drug benefit saved people about $ 9 a month and gave them an extra 14 days of pills , on average . Caution The authors did not examine effects of the doughnut hole and did not look at specific drugs or drug classes . Implication The Medicare drug benefit has led to modest decreases in expense and increases in drug use for older adults . The Editors The Medicare Modernization Act Prescription Drug Benefit ( Part D ) established a prescription drug benefit for all 43 million Medicare beneficiaries in the United States . This is the largest change to Medicare since the program began several decades ago ( 1 ) . The prescription benefit has increased the proportion of Medicare enrollees with prescription drug coverage ( 2 ) , and the Centers for Medicaid & Medicare Services report that among seniors eligible for Medicare , Part D enrollees save on out-of-pocket expenses compared with those not enrolled in Part D ( 3 , 4 ) . Previous reports also have examined enrollment and used surveys to examine beneficiaries ' beliefs and experiences ( 57 ) . Although these reports and others ( 8 , 9 ) point to positive effects of the Part D benefit , several questions remain unanswered about its overall effect on prescription utilization and expenditures . This is because studies have tended to focus only on beneficiaries who have enrolled in a Medicare Part D plan . Changes in drug utilization or expenditures measured in these studies could represent Part D coverage , trends in prescription drug use unrelated to Part D , or differences between beneficiaries who enrolled in Part D and those who did not . A 2004 projection suggested that the Medicare drug benefit would reduce average out-of-pocket expenditures by about 14 % among elderly persons with Medicare coverage and by about 47 % among elderly persons without preexisting drug coverage , result ing in an overall increase in total drug spending of about 6 % ( 10 ) . This prediction was mainly driven by the fact that almost three fourths of elderly persons in the United States already had some kind of drug coverage and that Medicare Part D would have a small effect on their expenditures and utilization . Yet with the exception of 1 recent study ( 11 ) , little work has been done to empirically estimate the effect of the Part D benefit on prescription drug utilization and expenditures . We sought to address these limitations by analyzing pharmacy cl aims from a national pharmacy chain accounting for approximately one eighth of the market share of prescription medicines in the United States . Although this sample may not be nationally representative , it offers an opportunity to study the effect of Part D on a broad and heterogeneous population that accounts for a substantial portion of the entire Medicare population . Our analyses compare the effect of Part D on prescription drug utilization and expenditures among persons eligible for the benefit who enrolled in a Part D plan , persons eligible for the benefit who did not enroll , and noneligible persons . We also distinguish between the overall effect of Part D during the penalty-free enrollment period and the postpenalty-free period , when enrollment was stable , to determine the steady-state effect of Part D , independent of enrollment dynamics . Methods Sample and Measurements We selected a 5 % r and om sample of unique pharmacy customers who filled at least 1 prescription during both the 2005 and the 2006 calendar years through the Walgreens pharmacy chain , whether at a retail store or by mail order . For each person in our sample , we obtained cl aims data for every prescription filled between 1 September 2004 and 31 April 2007 . For each prescription cl aim , we obtained data on the cl aim ant 's demographic characteristics ( age , sex , language preference , ZIP code of residence ) , insurance characteristics ( whether the cl aim was paid through a prescription drug plan , method of payment ) , pharmacy characteristics ( ZIP code location ) , prescription characteristics ( National Drug Code , therapeutic class , drug dose , number of treatment days , date dispensed , number of refills ) , and expenditures ( amount paid out of pocket , amount paid by third party ) . We used data on cl aim ants ' ZIP code of residence ( the residence recorded at the person 's first pharmacy cl aim in 2005 ) to link the pharmacy cl aims data to data from the 2000 U.S. Census , including information on the total population , median household income , income per capita , proportion of urban residents , proportion of African-American persons , unemployment rate , and poverty rate within the ZIP code of residence ( 12 , 13 ) . We also used data from the Behavioral Risk Factor Surveillance System ( BRFSS ) to compare the characteristics of our sample with those of all Medicare beneficiaries . We used simple descriptive statistics to compare the age and sex distribution of our sample with those of persons age 60 to 63 years and 66 to 79 years in the BRFSS . We also linked BRFSS data to 2000 U.S. Census data to examine whether the ZIP codelevel demographic characteristics of our pharmacy sample were similar to those of the nationally representative BRFSS sample in the same age groups , and whether the characteristics of our sample were similar to those of only BRFSS respondents who lived in the same geographic areas as our pharmacy sample . We excluded persons 80 years of age or older because the proportion of persons in nursing homes is higher among this age group and because changes in the Medicare Modernization Act regarding persons receiving nursing home care and long-term care ( 14 ) do not extend to the majority of the Medicare population . Outcomes Our 2 outcomes were monthly average out-of-pocket prescription costs and prescription utilization , as measured by the quantity of a prescription medicine sufficient for 1 day of therapy ( pill-day ) . Each person in our sample contributed 32 observations corresponding to 32 months of data . We divided the 32 months into 3 periods : the prePart D period ( September 2004 to December 2005 ) ; the ramp-up postPart D period , during which seniors could enroll in Part D plans without penalty ( January 2006 to May 2006 ) ; and the stable postPart D period , after the deadline for penalty-free Part D enrollment ( June 2006 to April 2007 ) . Because we aim ed to estimate the effect of Part D , we sought to compare observed trends in out-of-pocket costs and utilization among seniors eligible for the benefit ( the Part Deligible group , consisting of persons age 66 to 79 years as of 1 January 2006 ) with predicted counterfactual trends for the same group of seniors had Part D not been enacted . Thus , we sought to estimate the effect of Part D on expenditures and utilization netting out contemporaneous changes to the outcome variable due to factors unrelated to Part D ( 15 , 16 ) . To estimate counterfactual trends , we used the contemporaneous time profile of the corresponding outcomes in a control group of persons age 60 to 63 years who were not yet eligible for the benefit ( the Part Dineligible group ) . We dropped persons ages 64 and 65 years as of 1 January 2006 from the sample because they had partial-year Medicare eligibility during the study period . We first confirmed that the trends in outcomes in persons 60 to 63 years of age provided an adequate control for persons in the eligible group during the prePart D era ( September 2004 to December 2005 ) by examining both the statistical significance and magnitude of the coefficients in our regression model that represented the differential trends between the Part Deligible and Part Dineligible groups during the prePart D era . We then used the counterfactual control trends in the ramp-up period and in the stable enrollment period after the Part D enrollment deadline in May 2006 to represent the counterfactual trends in outcomes for the Part Deligible group assuming Part D had not been enacted . Statistical Analysis We estimated trends and generated predictions by using generalized estimating equations ( GEEs ) . We adjusted for sample demographic characteristics ( sex , English-speaking status , Medicaid coverage , age ) , ZIP codelevel characteristics ( total population , median household income , per-capita income , proportion of urban residents , proportion of African-American persons , unemployment rate , poverty rate ) , fixed effects for calendar months ( January to December ) , study period ( prePart D , ramp-up postPart D , and stable postPart D ) , and Part Deligible group . Moreover , we explored a variety of splines for representing differential time trends between periods ; we ultimately used cubic splines because they produced the best fit for both the prePart D and the stable postPart D periods . A linear spline was used for the ramp-up postPart D period because this period was short . We added up to 3-way interactions between study period and Part Deligible group fixed effects and the splines over time . We assessed overall model fit by using a variety of goodness-of-test criteria . We used gamma distribution to model out-of-pocket expenditures and negative binomial distribution to model pill-days . All estimators used log-link models . In addition , we explored the correlation structure between monthly observations within participants and used a first-order autoregressive correlation structure for out-of-pocket costs and an unstructured correlation matrix for pill-days . We had 2 main goals . First , we sought to estimate the policy effect of Part D coverage during both the ramp-up and stable postPart D periods . These effects represent the mean differences in the monthly outcomes between the observed factual trends and predicted counterfactual trends if Part D had not been enacted over these 2 periods . The Appendix Figure provides details about the specifications of these models and how the",
"BACKGROUND Prior studies of the Medicare Part D coverage gap are limited in generalizability and scope . OBJECTIVE To determine the effect of the coverage gap on drugs used for asymptomatic ( antihypertensive and lipid-lowering drugs ) and symptomatic ( pain relievers , acid suppressants , and antidepressants ) conditions in elderly patients with hypertension and hyperlipidemia . DESIGN Quasi-experimental study using pre-post design and contemporaneous control group . SETTING Medicare cl aims files from 2005 and 2006 for 5 % r and om sample of Medicare beneficiaries . PATIENTS Part D plan enrollees with hypertension or hyperlipidemia aged 65 years or older who had no coverage , generic-only coverage , or both br and -name and generic coverage during the gap in 2006 . Patients who were fully eligible for the low-income subsidy served as the control group . MEASUREMENTS Monthly 30-day supply prescriptions available , medication adherence , and continuous medication gaps of 30 days or more for antihypertensive or lipid-lowering drugs ; monthly 30-day supply prescriptions available for pain relievers , acid suppressants , or antidepressants before and after coverage gap entry . RESULTS Patients with no gap coverage had a decrease in monthly antihypertensive and lipid-lowering drug prescriptions during the coverage gap . Nonadherence also increased in this group ( antihypertensives : odds ratio [ OR ] , 1.60 [ 95 % CI , 1.50 to 1.71 ] ; lipid-lowering drugs : OR , 1.59 [ CI , 1.50 to 1.68 ] ) . The proportion of patients with no gap coverage who had continuous medication gaps in lipid-lowering medication use and antihypertensive use increased by an absolute 7.3 % ( OR , 1.38 [ CI , 1.29 to 1.46 ] ) and 3.2 % ( OR , 1.35 [ CI , 1.25 to 1.45 ] ) , respectively , because of the coverage gap . Decreases in use were smaller for pain relievers and antidepressants and larger for acid suppressants in patients with no gap coverage . Patients with generic-only coverage had decreased use of cardiovascular medications but no change in use of drugs for symptomatic conditions . No measures changed in the br and -name and generic coverage groups . Results of sensitivity analyses were consistent with the main findings . LIMITATION Because this study was nonr and omized , unobserved differences may still exist between study groups . CONCLUSION The Part D coverage gap was associated with decreased use of medications for hypertension and hyperlipidemia in patients with no gap coverage and generic-only gap coverage . The proposed phasing out of the gap by 2020 will benefit such patients ; however , use of low-value medications may also increase . PRIMARY FUNDING SOURCE Penn-Pfizer Alliance and American Heart Association"
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41188786-06ff-11f0-808a-c43d1ab1c353
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