target
stringlengths 55
10.5k
| src_docs
listlengths 1
305
| id
stringlengths 36
36
|
|---|---|---|
Background The aging process is associated with a progressive decline of neuromuscular function , increased risk of falls and fractures , impaired functional performance , and loss of independence . Plyometric training may mitigate or even reverse such age-related deterioration ; however , little research on the effects of plyometric exercises has been performed in older adults . Objective The objective of this systematic review was to evaluate the safety and efficacy of plyometric training in older adults . Methods Papers reporting on r and omized trials of plyometric training in older adults ( ≥ 60 years ) and published up to December 2017 were sought in the PubMed , SPORTD iscus , Scopus , and EMBASE data bases , and their method ological quality was assessed using the Physiotherapy Evidence Data base ( PEDro ) scale . A narrative synthesis of the findings is presented in this systematic review . Results Of the 2236 identified papers , 18 were included in the review , reporting on 12 different studies with a mean PEDro score of 6.0 ( range 4–7 ) . Altogether , 289 subjects ( 176 females and 113 males ) were included in 15 intervention groups with plyometric components ( n = 8–36 per group ) ; their mean age ranged from 58.4 to 79.4 years . The plyometric training lasted from 4 weeks to 12 months . Muscular strength , bone health , body composition , postural stability , and jump and physical performance were the most often reported outcomes . No study reported increased occurrence of injuries or other adverse events related to plyometric exercises . Conclusion Plyometric training is a feasible and safe training option with potential for improving various performance , functional , and health-related outcomes in older persons
|
[
"In animal studies , bone adaptation has been initiated successfully without the transient force spike associated with high impact exercises . Consequently , a 12-week bilateral hopping on the balls of the feet intervention was conducted . 25 elderly men ( age 72(SD4 ) years , height 171(6 ) cm , weight 75(9 ) kg ) were r and omly assigned into exercise and control groups . Ten subjects in each group completed the study . Carboxyterminal propeptide of type I collagen ( CICP ) , bone-specific alkaline phosphatase ( bALP ) and carboxyterminal telopeptide of type I collagen ( CTx ) were measured from venous blood sample s at baseline , at 2 weeks and at the end of the intervention . Maximal ground reaction force ( GRF ) , osteogenic index ( OI ) and jump height ( JH ) were determined from bilateral hopping test and balance was assessed with velocity of center of pressure ( COPvelocity ) while st and ing on the preferred leg with eyes open . The intervention consisted of 5–7 sets of 10 s timed bilateral hopping exercise at 75–90 % intensity three times/week . There was no significant group × time interaction for GRF , OI and JH ( P = 0.065 ) . GRF ( 11 % change from baseline vs. 4 % ) , OI ( 15 vs. 6 % ) and COPvelocity ( −10 vs. −1 % ) were not influenced by the intervention ( P > 0.170 ) , while the control group improved JH ( P = 0.031 ) ( 2 vs. 18 % ) . For the biomarkers , no effect was observed in MANOVA ( P = 0.536 ) or in univariate analyses ( P = 0.082 to P = 0.820 ) ( CICP −2 vs. −3 % , CTx 8 vs. −12 % , bALP 0 vs. −3.7 % ) . Allowing transient impact force spikes may be necessary to initiate a bone response in elderly men as the intervention was ineffective",
"Objective This study aim ed to compare the effects of two frequencies of high-speed resistance training ( HSRT ) on physical performance and quality of life of older women . Methods A total of 24 older women participated in a 12-week HSRT program composed of either two or three sessions/week ( equated for volume and intensity ) . Women were r and omized into three arms : a control group ( CG , n=8 ) , a resistance training group performing two sessions/week ( RT2 , n=8 ) , and a resistance training group performing three sessions/week ( RT3 , n=8 ) . The training program for both experimental groups included exercises that required high-speed concentric muscle actions . Results No baseline differences were observed among groups . Compared with the CG , both training groups showed similar small to moderate improvements ( P muscle strength , power , functional performance , balance , and quality of life . Conclusion These results suggest that equated for volume and intensity , two and three training sessions/week of HSRT are equally effective for improving physical performance and quality of life of older women",
"Purpose This study compared the effect of periodised versus non-periodised ( NP ) resistance training on neuromuscular adaptions in older adults . Methods Forty-one apparently healthy untrained older adults ( female = 21 , male = 20 ; 70.9 ± 5.1 years ; 166.3 ± 8.2 cm ; 72.9 ± 13.4 kg ) were recruited and r and omly stratified to an NP , block periodised ( BP ) , or daily undulating periodised ( DUP ) training group . Outcome measures were assessed at baseline and following a 22-week resistance training intervention ( 3 day week−1 ) , including : muscle cross-sectional area ( CSA ) , vertical jump performance , isometric and isokinetic peak torque , isometric rate of force development ( RFD ) , and muscle activation . Thirty-three participants satisfied all study requirements and were included in analyses ( female = 17 , male = 16 ; 71.3 ± 5.4 years ; 166.3 ± 8.5 cm ; 72.5 ± 13.7 kg ) . Results Block periodisation , DUP , and NP resistance training induced statistically significant improvements in muscle CSA , vertical jump peak velocity , peak power and jump height , and peak isometric and isokinetic torque of the knee extensors at 60 and 180 ° s−1 , with no between-group differences . Muscle activity and absolute RFD measures were statistically unchanged following resistance training across the entire cohort . Conclusions Periodised resistance training , specifically BP and DUP , and NP resistance training are equally effective for promoting increases in muscular hypertrophy , strength , and power among untrained older adults . Consequently , periodisation strategies are not essential for optimising neuromuscular adaptations during the initial stages of resistance training in the aging population",
"BACKGROUND AND PURPOSE The interpretation of patient scores on clinical tests of physical mobility is limited by a lack of data describing the range of performance among people without disabilities . The purpose of this study was to provide data for 4 common clinical tests in a sample of community-dwelling older adults . SUBJECTS Ninety-six community-dwelling elderly people ( 61 - 89 years of age ) with independent functioning performed 4 clinical tests . METHODS Data were collected on the Six-Minute Walk Test ( 6MW ) , Berg Balance Scale ( BBS ) , and Timed Up & Go Test ( TUG ) and during comfortable- and fast-speed walking ( CGS and FGS ) . Intraclass correlation coefficients ( ICCs ) were used to determine the test-retest reliability for the 6MW , TUG , CGS , and FGS measurements . Data were analyzed by gender and age ( 60 - 69 , 70 - 79 , and 80 - 89 years ) cohorts , similar to previous studies . Means , st and ard deviations , and 95 % confidence intervals for each measurement were calculated for each cohort . RESULTS The 6MW , TUG , CGS , and FGS measurements showed high test-retest reliability ( ICC [2,1]=.95-.97 ) . Mean test scores showed a trend of age-related declines for the 6MW , BBS , TUG , CGS , and FGS for both male and female subjects . DISCUSSION AND CONCLUSION Preliminary descriptive data suggest that physical therapists should use age-related data when interpreting patient data obtained for the 6MW , BBS , TUG , CGS and FGS . Further data on these clinical tests with larger sample sizes are needed to serve as a reference for patient comparisons",
"The purpose s of this study were to analyze the impact of 24 weeks of vibratory and multicomponent training ( MT ) and to determine what type of training creates greater adaptations on body composition and isokinetic strength of the knee and ankle joints in postmenopausal women . Thirty-eight women ( 60.0 ± 6.3 years ) were r and omly assigned to whole body vibration group ( WBVG ) , multicomponent training group ( MTG ) , or a control group . A significant decrease in total fat mass was observed in experimental groups . There were no changes in total lean mass and total bone mineral density in both groups . WBVG and MTG showed significant increases in isokinetic strength for knee extensors at 60 ° /s and at 270 ° /s . Regarding the ankle joint , there were significant increments in strength for plantar flexion at 60 ° /s in WBVG and at 120 ° /s in the two trainings groups . MTG showed a significant increase in strength for dorsiflexion at 60 ° /s . With respect to eversion and inversion , WBVG and MTG improved strength at 60 ° /s . Also , the WBVG showed increased strength in the ankle evertors at 120 ° /s and both groups showed increased strength in the ankle invertors at 120 ° /s . Twenty-four weeks of whole body vibration or MTs result in positive modifications in total fat mass . These trainings are effective in improving knee extension and stabilizer muscles of the ankle joint strength ",
"Summary This study showed that combination of strength , balance , agility and jumping training prevented functional decline and bone fragility in home-dwelling elderly women . The finding supports the idea that it is possible to maintain good physical functioning by multi-component exercise program and thus postpone the age-related functional problems . Introduction This 1-year r and omized , controlled exercise intervention trial assessed the effects of two different training programs and their combination on physical functioning and bone in home-dwelling elderly women . Methods One hundred and forty-nine healthy women aged 70–78 years were r and omly assigned into : group 1—resistance training ( RES ) , group 2—balance-jumping training ( BAL ) , group 3—combination of resistance and balance-jumping training ( COMB ) , and group 4—controls ( CON ) . Self-rated physical functioning , leg extensor force , dynamic balance , and bone mass and structure were measured . Results Self-rated physical functioning improved in the COMB group , but was reduced in the CON group ; the mean inter-group difference was 10 % ( 95 % CI : 0–22 % ) . Mean increase in the leg extensor force was higher in the RES ( 14 % ; 4–25 % ) and COMB ( 13 % ; 3–25 % ) compared with the CON groups . Dynamic balance improved in the BAL ( 6 % ; 1–11 % ) and in the COMB ( 8 % ; 3–12 % ) groups . There were no inter-group differences in BMC at the proximal femur . In those COMB women who trained at least twice a week , the tibial shaft structure weakened 2 % ( 0–4 % ) less than those in the CON group . Conclusions Strength , balance , agility , and jumping training ( especially in combination ) prevented functional decline in home-dwelling elderly women . In addition , positive effects seen in the structure of the loaded tibia indicated that exercise may also play a role in preventing bone fragility",
"Summary This study showed that about a half of the exercise-induced gain in dynamic balance and bone strength was maintained one year after cessation of the supervised high-intensity training of home-dwelling elderly women . However , to maintain exercise-induced gains in lower limb muscle force and physical functioning , continued training seems necessary . Introduction Maintenance of exercise-induced benefits in physical functioning and bone structure was assessed one year after cessation of 12-month r and omized controlled exercise intervention . Methods Originally 149 healthy women 70–78 years of age participated in the 12-month exercise RCT and 120 ( 81 % ) of them completed the follow-up study . Self-rated physical functioning , dynamic balance , leg extensor force , and bone structure were assessed . Results During the intervention , exercise increased dynamic balance by 7 % in the combination resistance and balance-jumping training group ( COMB ) . At the follow-up , a 4 % ( 95 % CI : 1–8 % ) gain compared with the controls was still seen , while the exercise-induced isometric leg extension force and self-rated physical functioning benefits had disappeared . During the intervention , at least twice a week trained COMB subjects obtained a significant 2 % benefit in tibial shaft bone strength index compared to the controls . A half of this benefit seemed to be maintained at the follow-up . Conclusions Exercise-induced benefits in dynamic balance and rigidity in the tibial shaft may partly be maintained one year after cessation of a supervised 12-month multi-component training in initially healthy elderly women . However , to maintain the achieved gains in muscle force and physical functioning , continued training seems necessary",
"This r and omized , controlled trial evaluated the effects of exercise on health-related quality of life ( HRQoL ) and fear of falling ( FoF ) among 149 home-dwelling older women . The 12-mo exercise program was intended to reduce the risk of falls and fractures . HRQoL was assessed by the R AND -36 Survey , and FoF , with a visual analog scale , at baseline , 12 mo , and 24 mo . On all R AND -36 scales , the scores indicated better health and well-being . The exercise had hardly any effect on HRQoL ; only the general health score improved slightly compared with controls at 12 mo ( p = .019 ) , but this gain was lost at 24 mo . FoF decreased in both groups during the intervention with no between-groups difference at 12 or 24 mo . In conclusion , despite beneficial physiological changes , the exercise intervention showed rather limited effects on HRQoL and FoF among relatively high-functioning older women . This modest result may be partly because of insufficient responsiveness of the assessment instruments used",
"Stretching of an activated muscle prior to its shortening enhances its performance during the concentric contraction . This phenomenon has been interpreted to be primarily due to the utilization of elastic energy stored in the series elastic elements of the muscle during the stretch . However , reflex potential has also been suggested as an additional cause for performance increase . To examine this hypothesis five subjects performed maximal vertical jumps on a force platform from two different starting positions : ( a ) maximal plantar flexion from a static position ( SJ ) ( pure concentric contraction ) , ( b ) a toe-st and ing position with preliminary counter-movement ( CMJ ) . In this condition the calf muscles were actively stretched before concentric work . In both conditions the knee and hip joints were fixed . The results indicated that the utilization of the stretch-shortening cycle enhanced the performance over that of the pure concentric contraction ( P less than 0.001 ) . Similarly , the EMG recording demonstrated that in all five subjects the myoelectrical activity of the calf muscles ( mm . gastrocnemius and soleus ) was potentiated during the concentric phase in CMJ when compared to SJ ( P less than 0.001 ) . Therefore , the increase in performance was attributed to a combination of utilization of elastic energy and myoelectrical potentiation of muscle activation",
"Background : Regular exercise has been recommended as a potential strategy to counteract the age-related bone loss experienced by men ; however , the optimal exercise prescription is not known . Objective : To perform a pilot study to examine the osteogenic effect , safety and feasibility of a combined program of upper body resistance exercise and two doses of impact-loading exercise on bone mineral density ( BMD ) of middle-aged and older men . Methods : Forty-two community-dwelling men aged 50 - 74 years were r and omly assigned to either an exercise program of combined upper body resistance exercise and either high-dose impact-loading ( HI ; 80 jumps per session ) or moderate-dose impact-loading ( MOD ; 40 jumps per session ) or a control ( CON ) group . The 9-month intervention involved 4 sessions each week : 2 supervised clinic-based and 2 home-based . BMD of the lumbar spine , femoral neck , total hip , trochanter and whole body as well as lean and fat mass were assessed at baseline and 9 months by dual-energy X-ray absorptiometry . Bone turnover markers , hormone levels , physical function and muscle strength were also assessed . Results : Following 9 months of training , significant differences in BMD among groups were found at the total hip ( p = 0.010 ) and trochanter ( p = 0.047 ) with BMD in the MOD group decreasing relative to the HI group . Although not significant , the HI group consistently preserved BMD , whereas BMD of the MOD and CON groups declined at the hip sites . Mean change for all groups at all skeletal sites was approximately within ±1 % . There was no change in bone turnover markers . There were no adverse events as a result of the intervention ; however , overall attendance for the HI and MOD groups was 53 % ( clinic : 68 % , home : 38 % ) and 65 % ( clinic : 74 % , home : 55 % ) , respectively . Conclusions : This study indicates that while impact-loading exercise can be safely undertaken in middle-aged and older men , the current combined program did not elicit significant improvements in BMD",
"BACKGROUND The authors ' objective was to evaluate the efficacy of a 6-month Tai Chi intervention for decreasing the number of falls and the risk for falling in older persons . METHODS This r and omized controlled trial involved a sample of 256 physically inactive , community-dwelling adults aged 70 to 92 ( mean age , 77.48 years ; st and ard deviation , 4.95 years ) who were recruited through a patient data base in Portl and , Oregon . Participants were r and omized to participate in a three-times-per-week Tai Chi group or to a stretching control group for 6 months . The primary outcome measure was the number of falls ; the secondary outcome measures included functional balance ( Berg Balance Scale , Dynamic Gait Index , Functional Reach , and single-leg st and ing ) , physical performance ( 50-foot speed walk , Up&Go ) , and fear of falling , assessed at baseline , 3 months , 6 months ( intervention termination ) , and at a 6-month postintervention follow-up . RESULTS At the end of the 6-month intervention , significantly fewer falls ( n=38 vs 73 ; p=.007 ) , lower proportions of fallers ( 28 % vs 46 % ; p=.01 ) , and fewer injurious falls ( 7 % vs 18 % ; p=.03 ) were observed in the Tai Chi group compared with the stretching control group . After adjusting for baseline covariates , the risk for multiple falls in the Tai Chi group was 55 % lower than that of the stretching control group ( risk ratio,.45 ; 95 % confidence interval , 0.30 to 0.70 ) . Compared with the stretching control participants , the Tai Chi participants showed significant improvements ( p functional balance , physical performance , and reduced fear of falling . Intervention gains in these measures were maintained at a 6-month postintervention follow-up in the Tai Chi group . CONCLUSIONS A three-times-per-week , 6-month Tai Chi program is effective in decreasing the number of falls , the risk for falling , and the fear of falling , and it improves functional balance and physical performance in physically inactive persons aged 70 years or older",
"Abstract Purpose The present study examined the effects of repetitive hopping training on muscle activation profiles and fascicle – tendon interaction in the elderly . Methods 20 physically active elderly men were r and omly assigned for training ( TG ) and control groups ( CG ) . TG performed supervised bilateral short contact hopping training with progressively increasing training volume . Measurements were performed before the training period ( BEF ) as well as after 2 weeks ( 2 W ) and 11 weeks ( 11 W ) of training . During measurements , the gastrocnemius medialis – muscle ( GaM ) fascicle and its outer Achilles tendon length changes during hopping were examined by ultrasonography together with electromyographic ( EMG ) activities of calf muscles , kinematics , and kinetics . Results At 2 W , the ankle joint stiffness was increased by 21.0 ± 19.3 % and contact time decreased by 9.4 ± 7.8 % in TG . Thereafter , from 2–11 W the jumping height increased 56.2 ± 18.1 % in TG . Simultaneously , tendon forces increased 24.3 ± 19.0 % but tendon stiffness did not change . GaM fascicles shifted to shorter operating lengths after training without any changes in their length modifications during the contact phase of hopping . Normalized EMG amplitudes during hopping did not change with training . Conclusions The present study shows that 11 W of hopping training improves the performance of physically active elderly men . This improvement is achieved with shorter GaM operating lengths and , therefore , increased fascicle stiffness and improved tendon utilization after training . Based on these results , hopping training could be recommended for healthy fit elderly to retain and improve rapid force production capacity",
"BACKGROUND AND OBJECTIVE previously , a r and omised controlled exercise intervention study ( RCT ) showed that combined resistance and balance-jumping training ( COMB ) improved physical functioning and bone strength . The purpose of this follow-up study was to assess whether this exercise intervention had long-lasting effects in reducing injurious falls and fractures . DESIGN five-year health-care register-based follow-up study after a 1-year , four-arm RCT . SETTING community-dwelling older women in Finl and . SUBJECTS one hundred and forty-five of the original 149 RCT participants ; women aged 70 - 78 years at the beginning . METHODS participants ' health-care visits were collected from computerised patient register . An injurious fall was defined as an event in which the subject contacted the health-care professionals or was taken to a hospital , due to a fall . The rate of injured fallers was assessed by Cox proportional hazards model ( hazard ratio , HR ) , and the rate of injurious falls and fractures by Poisson regression ( risk ratio , RR ) . RESULTS eighty-one injurious falls including 26 fractures occurred during the follow-up . The rate of injured fallers was 62 % lower in COMB group compared with the controls ( HR 0.38 , 95 % CI 0.17 to 0.85 ) . In addition , COMB group had 51 % less injurious falls ( RR 0.49 , 95 % CI 0.25 to 0.98 ) and 74 % less fractures ( RR 0.26 , 95 % CI 0.07 to 0.97 ) . CONCLUSIONS home-dwelling older women who participated in a 12-month intensive multi-component exercise training showed a reduced incidence for injurious falls during 5-year post-intervention period . Reduction in fractures was also evident . These long-term effects need to be confirmed in future studies",
" Thomas , K , French , D , and Hayes , PR . The effect of two plyometric training techniques on muscular power and agility in youth soccer players . J Strength Cond Res 23(1 ) : 332 - 335 , 2009-The aim of this study was to compare the effects of two plyometric training techniques on power and agility in youth soccer players . Twelve males from a semiprofessional football club 's academy ( age = 17.3 ± 0.4 years , stature = 177.9 ± 5.1 cm , mass = 68.7 ± 5.6 kg ) were r and omly assigned to 6 weeks of depth jump ( DJ ) or countermovement jump ( CMJ ) training twice weekly . Participants in the DJ group performed drop jumps with instructions to minimize ground-contact time while maximizing height . Participants in the CMJ group performed jumps from a st and ing start position with instructions to gain maximum jump height . Posttraining , both groups experienced improvements in vertical jump height ( p 0.05 ) and agility time ( p and no change in sprint performance ( p > 0.05 ) . There were no differences between the treatment groups ( p > 0.05 ) . The study concludes that both DJ and CMJ plyometrics are worthwhile training activities for improving power and agility in youth soccer players",
"AIM The objective of this study was to determine whether regular combined exercise program , which consists strength , stretching and aerobic exercises and additional jumping training , improve balance , fall risk , quality of life and depression status of older people living in a residential care . METHODS A total of 168 residents who live in a long term care facility were screened . The trial began with 78 eligible participants and they were r and omly grouped as combined exercises program ( COM ) group that includes stretching , strength and aerobic exercises , and COM plus jumping ( COMpJ ) group . 66 of the participants finished the trial . The groups were convened three times a week for six weeks . Each group had a warm-up , effective training and a cooling down periods . The total exercising time was no longer than 45 minutes in each group . Berg balance test and Biodex Balance System for the assessment of the dynamic balance and fall risk , short form 36 ( SF 36 ) for the health related quality of life and Geriatric Depression Scale ( GDS ) for evaluation of the depression status were used . RESULTS The balance improvement and fall risk reduction were observed in both of the groups at the end of the trial ; however , the improvements were statistically better in jumping combined group . Also health related quality of life improved in both groups . CONCLUSION Regular group exercise in a long term care facility have several beneficial effects on the elderly residents in regard to balance improvement , fall risk reduction and quality of life . The addition of jumping to strength , stretching and aerobic exercises provides important contributions to balance improvement and fall risk reduction",
"Abstract Campillo , RR , And rade , DC , and Izquierdo , M. Effects of plyometric training volume and training surface on explosive strength . J Strength Cond Res 27(10 ) : 2714–2722 , 2013—The purpose of this study is to examine the effects of different volume and training surfaces during a short-term plyometric training program on neuromuscular performance . Twenty-nine subjects were r and omly assigned to 4 groups : control group ( CG , n = 5 ) , moderate volume group ( MVG , n = 9 , 780 jumps ) , moderate volume hard surface group ( MVGHS , n = 8 , 780 jumps ) , and high volume group ( HVG , n = 7 , 1,560 jumps ) . A series of tests were performed by the subjects before and after 7 weeks of plyometric training . These tests were measurement of maximum strength ( 5 maximum repetitions [ 5RMs ] ) , drop jumps ( DJs ) of varying heights ( 20 , 40 , and 60 cm ) , squat and countermovement jumps ( SJ and CMJ , respectively ) , timed 20-m sprint , agility , body weight , and height . The results of the present study suggest that high training volume leads to a significant increase in explosive performance that requires fast stretch-shortening cycle ( SSC ) actions ( such as DJ and sprint ) in comparison to what is observed after a moderate training volume regimen . Second , when plyometric training is performed on a hard training surface ( high-impact reaction force ) , a moderate training volume induces optimal stimulus to increase explosive performance requiring fast SSC actions ( e.g. , DJ ) , maximal dynamic strength enhancement , and higher training efficiency . Thus , a finding of interest in the study was that after 7 weeks of plyometric training , performance enhancement in maximal strength and in actions requiring fast SSC ( such as DJ and sprint ) were dependent on the volume of training and the surface on which it was performed . This must be taken into account when using plyometric training on different surfaces",
"Objective : To evaluate the feasibility of jump training for nearly ambulatory patients after stroke . Design : Case series . Setting : A rehabilitation centre for adult people with neurological disorders . Subjects : Six subacute , nearly ambulatory patients with hemiparesis due to stroke . Interventions : A modified form of jump training performed over a period of six weeks . Measures : Impairments : We used the Motricity Index to measure strength , the Fugl-Meyer subtest passive joint motion/pain for range of motion and pain and the modified Tardieu Scale to measure spasticity at baseline and after six weeks . Activity level : To assess walking ability we used the Functional Ambulation Category , to measure walking quality we used 10-m gait velocity , stride length and Rivermead Visual Gait Index and to assess walking capacity we used the six-minute walk test . Results : No severe adverse events were observed during the study period . Motricity Index sum score of the affected leg increased from 38±11 points ( mean±SD ) to 56±15 points ; P = 0.028 . Modified Tardieu Scale and Fugl-Meyer subtest passive joint motion/pain remained unchanged over time ( P=1.0 ; P=0.157 , respectively ) . All patients were able to walk at the end of training ( median Functional Ambulation Category grade five , P=0.023 ) . Gait quality improved as shown in increased gait velocity ( from 0.3±0.1 to 1.1±0.5 m/s ; P = 0.028 ) , improved stride length ( from 0.3±0.1 to 0.6±0.2 m ; P = 0.028 ) and improved Rivermead Visual Gait Index score ( from 38.7±5.6 points to 24.8±7.0 points ; P = 0.027 ) . All patient increased gait capacity ( from 97±33 m to 289±134 m ; P = 0.028 ) . Conclusion : Jump exercises are feasible for selected subacute stroke patients with hemiparesis",
" Abstract A group of 32 healthy men ( M ) divided into three different age groups , i.e. M20 years [ mean 21 ( SD 1 ) ; n = 12 ] , M40 [ mean 40 ( SD 2 ) ; n = 10 ] and M70 [ mean 71 ( SD 5 ) ; n = 10 ] volunteered as subjects for examination of maximal and explosive force production of leg extensor muscles in both isometric and dynamic actions ( squat jump , SJ and counter movement jump , CMJ , and st and ing long-jump , SLJ ) . The balance test was performed on a force platform in both isometric and dynamic actions . Maximal bilateral isometric force value in M70 was lower ( P maximal rate of force development ( RFD ) on the force-time curve was in M70 lower ( P The heights in SJ and CMJ and the distance in SLJ in M70 were lower ( P response time in reaching the lit centre ( TT ) and remained 20%–34 % ( P individual values of isometric RFD correlated significantly ( P TT and TC . The present results would suggest that the capacity for explosive force production declines drastically with increasing age , even more than maximal muscle strength . Aging may also lead to impaired balance with a decrease in event detection and speed of postural adjustments . The decreased ability to develop force rapidly in older people seems to be associated with a lower capacity for neuromuscular response in controlling postural sway",
"PURPOSE This study compared the effect of periodized versus nonperiodized ( NP ) resistance training ( RT ) on physical function and health outcomes in older adults . METHODS Forty-one apparently healthy untrained older adults ( women = 21 , men = 20 ; 70.9 ± 5.1 yr ; 166.3 ± 8.2 cm ; 72.9 ± 13.4 kg ) were recruited and r and omly stratified to a NP , block periodized , or daily undulating periodized training group . Outcome measures were assessed at baseline and after a 22-wk × 3 d·wk RT intervention , including ; anthropometrics , body composition , blood pressure and biomarkers , maximal strength , functional capacity , balance confidence , and quality of life . RESULTS Thirty-three subjects satisfied all study requirements and were included in analyses ( women = 17 , men = 16 ; 71.3 ± 5.4 yr ; 166.3 ± 8.5 cm ; 72.5 ± 13.7 kg ) . The main finding was that all three RT models produced significant improvements in several physical function and physiological health outcomes , including ; systolic blood pressure , blood biomarkers , body composition , maximal strength , functional capacity and balance confidence , with no between-group differences . CONCLUSIONS Periodized RT , specifically block periodization and daily undulating periodized , and NP RT are equally effective for promoting significant improvements in physical function and health outcomes among apparently healthy untrained older adults . Therefore , periodization strategies do not appear to be necessary during the initial stages of RT in this population . Practitioners should work toward increasing RT participation in the age via feasible and efficacious interventions targeting long-term adherence in minimally supervised setting",
"The effects of a vertical jumping exercise regime on bone mineral density ( BMD ) have been assessed using r and omized controlled trials in both pre- and postmenopausal women , the latter stratified for hormone replacement therapy ( HRT ) . Women were screened for contraindications or medication likely to influence bone . The premenopausal women were at least 12 months postpartum and not lactating ; the postmenopausal women had been stable on , or off , HRT for the previous 12 months and throughout the study . BMD was measured blind using dual-energy X-ray absorptiometry at the spine ( L2-L4 ) and the proximal femur . The exercise consisted of 50 vertical jumps on 6 days/week of mean height 8.5 cm , which produced mean ground reactions of 3.0 times body weight in the young women and 4.0 times in the older women . In the premenopausal women , the exercise result ed in a significant increase of 2.8 % in femoral BMD after 5 months ( p postmenopausal women , there was no significant difference between the exercise and control groups after 12 months ( total n = 123 ) nor after 18 months ( total n = 38 ) . HRT status did not affect this outcome , at least up to 12 months . It appears that premenopausal women respond positively to this brief high-impact exercise but postmenopausal women do not",
"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 .",
"INTRODUCTION There is little evidence as to whether exercise can increase BMD in older men with no investigation of high impact exercise . Lifestyle changes and individual variability may confound exercise trials but can be minimised using a within-subject unilateral design ( exercise leg [ EL ] vs. control leg [ CL ] ) that has high statistical power . PURPOSE This study investigated the influence of a 12month high impact unilateral exercise intervention on femoral neck BMD in older men . METHODS Fifty , healthy , community-dwelling older men commenced a 12month high impact unilateral exercise intervention which increased to 50 multidirectional hops , 7days a week on one r and omly allocated leg . BMD of both femurs was measured using dual energy X-ray absorptiometry ( DXA ) before and after 12months of exercise , by an observer blind to the leg allocation . Repeated measures ANOVA with post hoc tests was used to detect significant effects of time , leg and interaction . RESULTS Thirty-five men ( mean±SD , age 69.9±4.0years ) exercised for 12months and intervention adherence was 90.5±9.1 % ( 304±31 sessions completed out of 336 prescribed sessions ) . Fourteen men did not complete the 12month exercise intervention due to : health problems or injuries unrelated to the intervention ( n=9 ) , time commitments ( n=2 ) , or discomfort during exercise ( n=3 ) , whilst BMD data were missing for one man . Femoral neck BMD , BMC and cross-sectional area all increased in the EL ( + 0.7 , + 0.9 and + 1.2 % respectively ) compared to the CL ( -0.9 , -0.4 and -1.2 % ) ; interaction effect P0.05 ) , there were significant main effects of time for section modulus ( P=0.044 ) and minimum neck width ( P=0.006 ) . Section modulus increased significantly in the EL ( P=0.016 ) but not in the CL ( P=0.465 ) ; mean change + 2.3 % and + 0.7 % respectively , whereas minimum neck width increased significantly in the CL ( P=0.004 ) but not in the EL ( P=0.166 ) ; mean changes being + 0.7 % and + 0.3 % respectively . CONCLUSION A 12month high impact unilateral exercise intervention was feasible and effective for improving femoral neck BMD , BMC and geometry in older men . Carefully targeted high impact exercises may be suitable for incorporation into exercise interventions aim ed at preventing fractures in healthy community-dwelling older men",
"The objective of the present study was to evaluate and compare the neuromuscular , morphological and functional adaptations of older women subjected to 3 different types of strength training . 58 , healthy women ( 67 ± 5 year ) were r and omized to experimental ( EG , n=41 ) and control groups ( CG , n=17 ) during the first 6 weeks when the EG group performed traditional resistance exercise for the lower extremity . Afterwards , EG was divided into three specific strength training groups ; a traditional group ( TG , n=14 ) , a power group ( PG , n=13 ) that performed the concentric phase of contraction at high speed and a rapid strength group ( RG , n=14 ) that performed a lateral box jump exercise emphasizing the stretch-shortening-cycle ( SSC ) . Subjects trained 2 days per week through the entire 12 weeks . Following 6 weeks of generalized strength training , significant improvements occurred in EG for knee extension one-repetition ( 1RM ) maximum strength ( + 19 % ) , knee extensor muscle thickness ( MT , + 15 % ) , maximal muscle activation ( + 44 % average ) and onset latency ( -31 % average ) for vastus lateralis ( VL ) , vastus medialis ( VM ) and rectus femoris ( RF ) compared to CG ( p specific strength training , the 1RM increased significantly and similarly between groups ( average of + 21 % ) , as did muscle thickness of the VL ( + 25 % ) , and activation of VL ( + 44 % ) and VM ( + 26 % ) . The onset latency of RF ( TG=285 ± 109 ms , PG=252 ± 76 ms , RG=203 ± 43 ms ) , reaction time ( TG=366 ± 99 ms , PG=274 ± 76 ms , RG=201 ± 41 ms ) , 30-s chair st and ( TG=18 ± 3 , PG=18 ± 1 , RG=21 ± 2 ) and counter movement jump ( TG=8 ± 2 cm , PG=10 ± 3 cm , RG=13 ± 2 cm ) was significantly improved only in RG ( p training , the rate of force development ( RFD ) over 150 ms ( TG=2.3 ± 9.8 N·s(-1 ) , PG=3.3 ± 3.2 N·s(-1 ) , RG=3.8 ± 6.8 N·s(-1 ) , CG=2.3 ± 7.0 N·s(-1 ) ) was significantly greater in RG and PG than in TG and CG ( p conclusion , rapid strength training is more effective for the development of rapid force production of muscle than other specific types of strength training and by consequence , better develops the functional capabilities of older women",
"Objective : To compare the effects of 12 weeks of high‐speed resistance training on functional performance and quality of life in elderly women when using either a traditional‐set ( TS ) or a cluster‐set ( CS ) configuration for inter‐set rest . Methods : Three groups of subjects were formed by block‐ design r and omization as follows : ( i ) control group ( CG , n = 17 ; age , 66.5 ± 5.4 years ) ; ( ii ) 12‐week high‐speed resistance training group under a CS configuration ( CSG , n = 15 ; age , 67.6 ± 5.4 years ) ; and ( iii ) 12‐week high‐speed resistance training group under a TS configuration ( TSG , n = 20 ; age , 68.0 ± 5.3 years ) . Training was undertaken three times per week , including high‐speed resistance training exercises . The main difference between the training groups was the recovery set structure . In the TSG , women rested for 150 s after each set of eight repetitions , whereas the CSG used an interest rest redistribution , such that after two consecutive repetitions , a 30‐s rest was allowed . Results : Group × test interactions were observed for a 10‐m walking speed test , an 8‐foot up‐ and ‐go test , a sit‐to‐st and test , and physical quality of life ( p improve functional performance and quality of life , however , the CS configuration induced significantly greater improvements in functional performance and quality of life than the TS configuration . Conclusion : These results should be considered when design ing appropriate and better resistance training programs for older adults . HighlightsFunctional performance and quality of life may be hindered during aging . High‐speed resistance‐training may increase functional performance and quality of life . High‐speed resistance‐training may be particularly effective using a cluster training sets configuration",
"OBJECTIVES This study aim ed to determine the efficacy of an exercise program for post-menopausal women with osteopenia undertaken in community exercise facilities . DESIGN R and omised , single-blind controlled trial . METHODS Thirty-nine community volunteers with hip osteopenia and not taking bone-enhancing medication were r and omly allocated to an exercise ( EX ) or control ( CON ) group . EX participants attended an exercise facility in Melbourne , Australia , three times/week for 52 weeks ( with a 2 week break ) for partially supervised exercises targeting hip bone strength , muscle strength and balance . They also performed daily jumping exercises at home . CON participants continued with their usual care . All participants were given calcium supplementation . Assessment at baseline and 52 weeks measured bone mineral density ( BMD ) at the proximal femur and lumbar spine . Health-related quality of life ( QOL ) and objective measures of strength and balance were also collected . RESULTS ANCOVA adjusting for baseline values revealed a small benefit of exercise in mean total hip BMD ( the primary outcome ) with a significant mean difference in change between groups of -0.012 g/cm(2 ) ( 95 % CI -0.022 to -0.002 g/cm(2 ) ) . EX participants improved 0.5 % compared with a 0.9 % loss for CON participants . The only other between-group differences were in QOL and a test of trunk and upper limb endurance , which both favoured the EX group . CONCLUSIONS This exercise program appears to have modest benefits for post-menopausal women with osteopenia who are not taking bone-enhancing medication . This mode of exercise delivery has adherence and progression limitations but may be appropriate to recommend for some people"
] |
4116b4d8-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND Many antihypertensive agents exist today for the treatment of primary hypertension ( systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg , or both ) . R and omised controlled trials ( RCTs ) have been carried out to investigate the evidence for these agents . There is , for example , strong RCT evidence that thiazides reduce mortality and morbidity . Some of those trials used reserpine as a second-line therapy . However , the dose-related blood pressure reduction with this agent is not known . OBJECTIVES The primary objective of this review was to quantify the dose-related efficacy of reserpine versus placebo or no treatment in reducing systolic blood pressure ( SBP ) or diastolic blood pressure ( DBP ) , or both . We also aim ed to evaluate the dose-related effects of reserpine on mean arterial blood pressure ( MAP ) and heart rate ( HR ) , as well as the dose-related effects on withdrawals due to adverse events . SEARCH METHODS We search ed the Cochrane Hypertension Group Specialised Register ( January 1946 to October 2016 ) , CENTRAL ( 2016 , Issue 10 ) , MEDLINE ( January 1946 to October 2016 ) , Embase ( January 1974 to October 2016 ) , and Clinical Trials.gov ( all date s to October 2016 ) . We also traced citations in the reference sections of the retrieved studies . SELECTION CRITERIA Included studies were truly r and omised controlled trials ( RCTs ) comparing reserpine monotherapy to placebo or no treatment in participants with primary hypertension . DATA COLLECTION AND ANALYSIS We assessed methods of r and omisation and concealment . We extracted and analysed data on blood pressure reduction , heart rate , and withdrawal due to adverse effects . MAIN RESULTS We found four RCTs ( with a total of 237 participants ) that met the inclusion criteria , none of which we found through the 2016 up date search . The overall pooled effect demonstrates a statistically significant systolic blood pressure ( SBP ) reduction in participants taking reserpine compared with placebo ( weighted mean difference ( WMD ) -7.92 , 95 % confidence interval ( CI ) -14.05 to -1.78 ) . Because of significant heterogeneity across the trials , a significant effect in diastolic blood pressure ( DBP ) , mean arterial pressure ( MAP ) , and heart rate ( HR ) could not be found . A dose of reserpine 0.5 mg/day or greater achieved the SBP effects . However , we could not determine the dose-response pattern because of the small number of trials . We did not combine data from the trial that investigated Rauwiloid against placebo with reserpine data from the remaining three trials . This is because Rauwiloid is a different alkaloid extract of the plant Rauwolfia serpentina , and the dose used is not comparable to reserpine . None of the included trials reported withdrawals due to adverse effects . AUTHORS ' CONCLUSIONS Reserpine is effective in reducing SBP roughly to the same degree as other first-line antihypertensive drugs . However , we could not make definite conclusions regarding the dose-response pattern because of the small number of included trials . More RCTs are needed to assess the effects of reserpine on blood pressure and to determine the dose-related safety profile before the role of this drug in the treatment of primary hypertension can be established
|
[
"The relative benefits and risks of reserpine and guanethidine were compared in patients with thiazide-treated mild to moderate hypertension ( diastolic pressure 95–115 mm Hg ) . Fortynine ambulant patients ( 30 men , 19 women ) were treated throughout the study with hydrochlorothiazide , 50 mg/day . In this double blind crossover study each drug was added in grade d increments until a predetermined therapeutic response was obtained , blood pressure measurements and side effect scores were evaluated biweekly . Major conclusions of the study were : 1 ) guanethidine , as well as reserpine , will reduce mild to moderate blood pressures to normal ; 2 ) in most cases , side effects which did occur while taking guanethidine or reserpine were well tolerated and neither drug was clearly superior . Side effects associated with larger doses of guanethidine employed in severe hypertension were absent or only slightly bothersome . Thus , guanethidine appears to have a good benefit-to-risk ratio in the therapy of mild to moderate hypertension and offers a number of advantages over drugs commonly used in this syndrome . This study refutes the common belief that guanethidine must be reserved only for the treatment of more severe degrees of hypertension",
"We compared the efficacy and adverse effects of antihypertensive drug regimens in 690 men past age 60 with diastolic blood pressure 90 - 114 mm Hg and systolic blood pressure less than 240 mm Hg . They received either a low ( 25 - 50 mg ) or high ( 50 - 100 mg ) dose of hydrochlorothiazide daily . Of 644 patients who completed the hydrochlorothiazide titration , 375 ( 58.2 % ) were responders ( diastolic blood pressure less than 90 and less than or equal to 5 mm Hg below baseline ) and 92.8 % of these completed a 6-month maintenance period . Blood pressure was reduced from 157.6/98.5 mm Hg by 18.3/9.5 mm Hg with low dose hydrochlorothiazide and by 20.4/9.6 mm Hg with high dose hydrochlorothiazide ; more patients achieved goal blood pressure with the high dose . Whites and blacks responded equally . Serum potassium less than 3.5 mmol/l occurred in 104 of 321 ( 32.3 % ) of the high dose versus 62 of 333 ( 18.6 % ) of the low dose hydrochlorothiazide patients . The 269 nonresponders to hydrochlorothiazide were r and omly assigned in a double-blind study to receive hydralazine , methyldopa , metoprolol , or reserpine in addition to hydrochlorothiazide ; 79.2 % responded to the addition of the second drug and 87.3 % of these completed a 6-month maintenance phase . Overall , there were no significant efficacy differences among the step 2 regimens . We conclude that the lower dose of hydrochlorothiazide was nearly as effective as the higher dose , and the addition of a second drug was effective and generally well tolerated in elderly patients",
"Fifty patients ( 25 Blacks and 25 Indians ) suffering from mild-to-moderate hypertension ( supine diastolic blood pressure 100 - 105 mmHg ) were studied in order to compare the antihypertensive effect of a combination of a beta-blocker ( sotalol hydrochloride 160 mg/d ) plus a thiazide derivative ( hydrochlorothiazide 25 mg/d ) ( Sotazide ; B-M ) with that of a combination of reserpine 0,1 mg/d ( Serpasil ; Ciba ) plus hydrochlorothiazide 25 mg/d ( Dichlotride ; Frosst MSD ) . The combination of reserpine plus hydrochlorothiazide was found to be as effective as that of sotalol plus hydrochlorothiazide in lowering the blood pressure in both the Black and the Indian patients . Two patients taking the combination containing reserpine developed side-effects , but this did not occur in any of those taking the combination containing sotalol . We feel that in developing countries , where the cost of therapy is important , reserpine in a dosage of less than 0,1 mg/d plus a thiazide derivative in low dosage is preferable to a beta-blocker plus a thiazide derivative in the treatment of hypertension",
"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",
"The efficacy of thiazide-like chlorthalidone , 50 mg , plus reserpine , 0.25 mg , was compared with that of hydrochlorothiazide , 50 mg , plus reserpine , 0.125 mg , in a six-week double-blind study of 57 patients with essential hypertension unresponsive to diet control and diuretic ( step 1 ) therapy . An average decrease in diastolic pressure of 17.0 mm Hg was attained at the end of week 6 by the chlorthalidone/reserpine group ; the average drop in the hydrochlorothiazide/reserpine group was 18.6 mm Hg . Both treatment groups displayed greater blood pressure control each week than the preceding week ; and , at the end of week 6 , both groups attained control of at least 5 mm Hg below the diastolic goal pressure of 90 mm Hg . The chlorthalidone/reserpine-treated group required fewer titrations than the hydrochlorothiazide/reserpine-treated group . There were no reports of frequent or severe side effects with either drug",
"In a double-blind study to investigate the antihypertensive effect of a fixed triple combination with 0.05 mg reserpine , 2.5 mg clopamide and 0.4 mg dihydroergocristine in comparison to a fixed double combination with 0.05 mg reserpine and 2.5 mg clopamide , a patient subgroup of 34 patients followed a unicenter ( central unit , ' institute ' ) as well as a multicenter ( established physicians ) study design . The patients visited both investigation units on the day of admission to the study ( week 0 ) , after four weeks and after eight weeks of therapy ( after the morning intake of the drugs ) . The paper in h and looks at the results of this subgroup with respect to the conformity of blood pressure values in the two investigative units . The analyses confirm the already published results of the entire study : Both combinations proved to be highly effective antihypertensive drugs . The triple combination showed therapeutical advantages for systolic blood pressure after four weeks , for diastolic pressure after eight weeks of therapy at the ' institute ' as well as , although less distinct , in the medical offices . A comparison of the individual values did not show a convincing coherence of the measurements between institute and offices . All investigated possible systematic sources of error ( different methods of measurement , days or times of measurement ) could be excluded by correlation statistics as a reason for the divergences . The results show the necessity -- particularly in multicenter studies --of a careful documentation of all accompanying data ( e.g. method or time of measurement ) as well as a greatest possible st and ardization of investigation ( e.g. identical measuring apparatus and investigator .",
"A single-blind clinical trial compared step 2 combination therapy consisting of 50 or 100 mg of hydroflumethiazide plus either 0.125 to 0.250 mg of reserpine , 500 to 2,000 mg of methyldopa , or 80 to 320 mg of propranolol hydrochloride , in 59 patients whose elevated blood pressure ( BP ) failed to respond adequately to the thiazide alone . After nine weeks of treatment , diastolic BP was reduced below 90 mm Hg in all 20 patients treated with the reserpine-hydroflumethiazide combination , in 13 of the 19 patients treated with methyldopa and hydroflumethiazide , and in 16 of the 20 patients treated with propranolol and hydroflumethiazide . Changes in laboratory values were not substantial ; adverse reactions occurred only in the methyldopa group . Although the three treatment regimens were similar with respect to safety and efficacy , the reserpine-hydroflumethiazide combination offers the advantages of more convenient dosage at lower cost",
"In a double-blind , parallel , 12-week trial , antihypertensive effects of diltiazem and reserpine were compared in 107 patients with essential hypertension . Diltiazem reduced blood pressure from 176/100 mmHg to 154/86 mmHg after 12 weeks , and reserpine reduced blood pressure from 171/96 mmHg to 155/85 mmHg . The difference between diltiazem and reserpine was not statistically significant . However , among a subset of patients given 180 mg/day of diltiazem , a significantly better antihypertensive effect was achieved than among a subset given 0.3 mg of reserpine . The incidence of side effects and complications in the diltiazem group was about one half that in the reserpine group ( 12.3 % and 27.1 % , respectively ) . Side effects of diltiazem were mild , and the drug was extremely well tolerated . These results show that diltiazem is an effective antihypertensive drug for the treatment of mild to moderate essential hypertension",
"Low-dose combination therapy has been proposed as a rational first-line approach to hypertension treatment . We compared the efficacy and tolerability of the fixed combination of reserpine ( 0.1 mg ) plus the thiazide clopamid ( 5 mg ) with its single components and the calcium-antagonist nitrendipine ( 20 mg ) in a r and omized , double-blind , parallel study of 273 hypertensive patients with diastolic blood pressure ( BP ) between 100 and 114 mm Hg . The four groups did not differ regarding baseline characteristics ( mean age , 58 years ; 51 % men ; mean BP after a 2-week placebo period , 158 to 160/103 to 104 mm Hg ) . After 6 weeks of treatment with one capsule daily , mean reductions in sitting BP from baseline at 24 hours after dosing in the reserpine-clopamid combination , reserpine , clopamid , and nitrendipine groups were -23.0/-17.1 , -14.0/-11.7 , -13.6/-11.9 , and -11.6/-12.3 mm Hg , respectively ( 2P normalization rates ( diastolic BP mean BP reductions were -25.7/-18.1 , -14.6/-12.2 , -17.7/-13.4 , and -14.9/-15.3 mm Hg in the four groups , respectively ( 2P normalization rates were 69 % , 35 % , 39 % , and 45 % ( 2P reserpine and clopamid combined acted more than additively . As regards tolerability , adverse experiences were observed in 27 % , 28 % , 29 % , and 48 % of patients , respectively ( 2P rates of premature discontinuation because of adverse effects were 3 % , 3 % , 7 % , and 13 % ( 2P = .06 ) . In conclusion , a low-dose combination of reserpine and clopamid lowered BP significantly more than both the components alone and nitrendipine . Moreover , the combination was tolerated as well as its components and significantly better than nitrendipine . Thus , the use of this low-dose reserpine-thiazide combination appears to be a rational alternative to conventional monotherapy in the first-line treatment of hypertension",
" In a series of 450 patients with mild essential hypertension , propranolol alone ( P ) , propranolol plus hydrochlorothiazide ( P+T ) , propranolol plus hydralazine ( P+H ) , and propranolol plus hydrochlorothiazide plus hydralazine ( P+T+H ) were compared to reserpine plus hydrochlorothiazide ( R+T ) . Comparison was based on reduction of diastolic blood pressures ( BP ) to below 90 mm Hg and at least 5 mm Hg less than initial BP after six months of treatment . This was achieved in 92 % of patients who received P+T+H , 88 % taking R+T , 81 % receiving P+T , 72 % on P+H and 52 % taking P alone . The number of drop-outs , morbid events , and terminating side effects were insignificantly different among the various regimens . In this study , P and P+H were less effective , while P+T and P+T+H were as effective as the st and ard regimen",
"1 . The changes in plasma volume , haemodynamic variables , plasma renin activity and plasma aldosterone were studied in forty-one hypertensive patients after administration of adrenergic-blocking agents . Four drugs were used : alpha-methyldopa ( fourteen patients ) , guanethidine ( ten patients ) , clonidine ( nine patients ) and reserpine ( eight patients ) . Drugs were administered orally during 7 days ' hospitalization on a normal sodium diet ( 110 mmol/day ) . 2 . The four drugs had similar effects : a significant decrease in blood pressure , a significant increase in plasma volume and no change in stroke volume . 3 . With alpha-methyldopa and guanethidine , heart rate , plasma renin activity and plasma aldosterone were unchanged . 4 . With reserpine and clonidine , heart rate and plasma renin activity were significantly decreased , whereas plasma aldosterone did not change significantly . 5 . This study suggests that the decrease in plasma renin activity was related to the lowering of the heart rate rather than to sodium retention and that adrenergic-blocking agents can impair the normal relationship between stroke index and plasma volume , between plasma volume and plasma renin activity , and between plasma renin activity and plasma aldosterone",
"OBJECTIVE To compare the effectiveness of the combination of hydrochlorothiazide ( HCT ) plus sustained-release nifedipine with the combination of HCT plus reserpine in lowering high blood pressure ( BP ) unresponsive to HCT monotherapy . DESIGN An open , r and omised crossover drug trial . SETTING Out patients ' clinic in Parirenyatwa Hospital , Harare , a tertiary referral centre . SUBJECTS 32 Black patients of both sexes with newly diagnosed or previously treated hypertension aged between 21 and 65 years who had a BP > 140/95 after receiving HCT 25 mg daily for four weeks were studied . INTERVENTION Patients were kept on HCT 25 mg daily and were r and omised to receive either reserpine 0.25 mg daily or nifedipine ( Adalat Retard ) 20 mg bd for four weeks . This was followed by a two week washout period during which patients received HCT 25 mg daily only . After the washout period patients were crossed over to the alternative treatment for four weeks . Patients were kept on HCT 25 mg daily throughout the trial . MAIN OUTCOME MEASURES The main outcome measure was the fall in BP which was taken as the difference between the BP at baseline and the BP at the end of each treatment period . Both systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) measurements were taken . RESULTS Both second line drugs were effective in lowering SBP and DBP and there was no significant difference between them . Nifedipine reduced SBP by 18.9 mmHg ( 95 % CI 12.1 to 25.7 ) and DBP by 9.6 mmHg ( 95 % CI 7.2 to 12.0 ) . Reserpine reduced SBP by 15.9 mmHg ( 95 % CI 8.4 to 23.4 ) and DBP by 11.1 mmHg ( 95 % CI 7.5 to 14.6 ) . However , only two patients attained the target DBP of SBP and DBP and reserpine is much cheaper than nifedipine , it is recommended that for a developing country like Zimbabwe , the combination of HCT and reserpine at the above doses should be used as the first step to treat mild to moderate hypertension without evidence of end organ damage . However , further trials should compare BP lowering effects as well as end organ protection offered by the trial drugs",
"A sample of 20 patients suffering hypertension ( with a moderate rise in blood pressure ) was r and omly divided into two treatment groups of equal size . The patients of one group received antihypertension treatment with the combination drug Briserin ¿ ( containing 0.1 mg reserpine , 5 mg clopamide , 0.5 mg dihydroergocristin/per tablet ) ; the other patients who served as control group , received a matched placebo . After a fortnight 's treatment , the responsiveness of both groups to five different psychologically stressing situations ( those with cognitive and /or emotional overload ) was tested . Analysis of covariance revealed clinical ly significant differences in the mean systolic and diastolic pressure scores of the two groups . The scores of the treatment group were lower not only under stress but also at rest . There was in interaction between rise of blood pressure under stress and kind of stress in the two groups , i.e. , in situations with heavy emotional and /or cognitive load the differences in the pressure scores of the two groups were less substantial than in situations with a low or medium load . The treatment had no systematic effect on heart rate in this sample . In the treatment group reaction time , perceptual speed , and short-term memory were impaired as compared with the control group ; but these differences did not reach a level of significance",
"Brinerdin ( S and oz ) , a combination of a diuretic ( clopamide 5 mg ) , a vasodilator ( dihydro-ergocristine 0.5 mg ) and reserpine ( 0.1 mg ) ( CDR ) was compared with methyldopa ( MD ) plus hydrochlorothiazide ( HCT ) for antihypertensive effect , adverse reactions , compliance and patient preference in an open cross-over trial . Eighteen patients completed both arms of the trial and 5 patients who completed the CDR arm were withdrawn while on the MD arm because of adverse effects in 4 and poor control in 1 . On HCT 50 mg daily the mean baseline systolic blood pressure was 163.9 + /- 16.3 mmHg and the diastolic blood pressure was 105.9 + /- 6.7 mmHg . On CDR these were reduced to systolic blood pressure 140.3 + /- 15.1 mmHg and diastolic blood pressure 87.8 + /- 9.3 mmHg . On MD + HCT the systolic blood pressure was reduced to 138.5 + /- 16.9 mmHg and the diastolic blood pressure to 88.9 + /- 10.3 mmHg . The differences between the two treatment periods in systolic blood pressure ( 1.8 mmHg ; 95 % confidence interval ( CI ) - 4.1 + 7.7 mmHg ) and diastolic blood pressure ( 1.1 mmHg ; 95 % CI - 4.6 + 2.4 mmHg ) were not significant with P values of 0.6 and 0.7 respectively . Compliance was 98.2 % for CDR and 94.7 % for MD + HCT ( P = 0.02 ) . Unusual sleepiness occurred more frequently in the MD arm ( P less than 0.01 ) . Thirteen patients chose to continue on CDR , 2 on MD + HCT and 3 had no preference ( P = 0.005 ) . CDR is similar in antihypertensive effect to MD + HCT but is better tolerated with fewer withdrawals , fewer adverse effects , better compliance and has more patients electing to continue taking it",
"The concept of initiating treatment of mild-to-moderate hypertension with a low-dose combination of reserpine and the thiazide clopamide in comparison to monotherapy with an ACE inhibitor was investigated . A total of 127 adult out patients with diastolic blood pressure between 100 and 114 mmHg were r and omized into this double-blind , parallel group study . After a 2-week wash-out period and a subsequent 2-week placebo run-in period , they were allocated to once-daily treatment with 0.1 mg reserpine plus 5 mg clopamide ( R/C ) , or 5 mg enalapril . If diastolic blood pressure was not normalized after 3 weeks of therapy ( i.e. DBP change from baseline in mean sitting diastolic and systolic blood pressure ( DBP/SBP ) after 3 weeks of therapy . Secondary variables included the change in DBP and SBP after 6 weeks of therapy , the BP normalization rates at 3 and 6 weeks and , concerning tolerability , the rates of adverse events after 6 weeks of therapy . An intent-to-treat analysis was performed . The reserpine/ clopamide and enalapril groups did not differ with regard to demographic and baseline characteristics ( mean age 57 or 58 years , respectively ; 63 % or 56 % males , respectively ; mean SBP/DBP after the 2-week placebo period = 156 mmHg/104 mmHg in both groups ) . After 3 weeks of treatment with one capsule daily , mean SBP/DBP reduction from baseline ( 24 h after last medication intake ) in the R/C combination group was -19.6/ -17.0 mmHg , in the enalapril group -6.1/ -9.5 mmHg ( between-group comparison : 2p normalization rates for DBP ( ) ( 2p Adverse events that were considered possibly or definitely drug-related by the investigator were noted in 11 patients ( 17.2 % ) in the R/C group and in 9 patients ( 14.3 % ) in the enalapril group ( NS ) . Two patients in the enalapril group discontinued the study prematurely due to adverse events ( cough ; skin eruption ) . In the treatment of mild-to-moderate hypertension , a low-dose combination of reserpine and clopamide once a day is considerably more effective than , and as tolerable as , 5 - 10 mg of enalapril once a day . These findings suggest that treatment with a combination of different antihypertensives with different modes of action in low doses is a rational alternative to conventional monotherapy in the first-line treatment of hypertension . Besides , the \" old \" reserpine-diuretic regimen also in these days appears to be a rational alternative to \" modern \" monotherapies",
"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",
"BACKGROUND It is expected that the treatment of hypertension in patients with renal disease decreases the risk of cardiovascular events , but the evidence in these patients is lacking . OBJECTIVE To assess the effect of diuretic-based treatment on cardiovascular events in patients with isolated systolic hypertension and renal dysfunction . METHODS A total of 4336 persons aged 60 years and older with systolic blood pressures of 160 mm Hg and higher and diastolic blood pressures of less than 90 mm Hg were r and omly assigned to receive either placebo or chlorthalidone ( 12.5 - 25.0 mg/d ) , with the addition of atenolol ( 25 - 50 mg/d ) or reserpine ( 0.05 - 0.10 mg/d ) if needed , and observed for 5 years . The risk of first-occurring cardiovascular events , including stroke , transient ischemic attack , myocardial infa rct ion , heart failure , coronary artery bypass surgery , angioplasty , aneurysm , endarterectomy , sudden death , or rapid death , was stratified according to baseline serum creatinine levels ( 35.4 - 84.0 , 84.1 - 101.6 , 101.7 - 119.3 , and 119.4 - 212.2 micromol/L [ 0.4 - 0.9 , 1.0 - 1.1 , 1.2 - 1.3 , and 1.4 - 2.4 mg/dL ] ) . RESULTS Systolic blood pressure reduction was not affected by baseline serum creatinine levels . Active treatment did not affect the risk of serum creatinine levels becoming elevated during follow-up . The risk of hypokalemia with active treatment decreased significantly with increasing baseline serum creatinine levels . In the 4 baseline serum creatinine groups , the relative risk ( 95 % confidence interval ) of cardiovascular events developing with active treatment was 0.73 ( 0.54 - 0.97 ) , 0.63 ( 0.49 - 0.82 ) , 0.62 ( 0.44 - 0.87 ) , and 0.59 ( 0.38 - 0.91 ) . The results were similar for the outcomes of stroke or coronary artery events and in analyses stratified by sex or age . CONCLUSION Diuretic-based treatment of patients with isolated systolic hypertension prevents the development of cardiovascular events in older persons with mild renal dysfunction",
"To compare findings in a hospital trial of hypotensive drugs with those in a general practice trial several patients with mild hypertension were studied at the same time in hospital and in general practice . They received bendrofluazide and potassium chloride or bendrofluazide , potassium chloride , and reserpine according to a double-blind crossover protocol , and blood biochemical values were studied over eight weeks and six months . When reserpine was withdrawn from nine women they followed a modified protocol comparing bendrofluazide and potassium chloride with potassium chloride alone . The blood pressure values measured by the general practitioners were similar to those measured in hospital . Both the diuretic alone and the diuretic with reserpine produced significant falls in blood pressures . Although plasma renin activity increased on diuretic treatment , continued treatment did not produce a further increase , and levels gradually declined towards normal",
"Abstract Morbidity , mortality , and target organ function have been followed in a double-blind study of a predominantly Negro clinic population with mild to moderately severe hypertension over a 2-year period . Patients were placed r and omly on either hypotensive drug therapy ( reserpine , thiazide , guanethedine ) or matched placebos . There were 6 treatment failures among 45 patients in the treatment group and 19 failures among 42 patients in the placebo group . All but one of the failures in the placebo group improved or cleared upon early institution of appropriate hypertensive and supportive therapy . Abnormalities in carbohydrate metabolism and serum uric acid levels were found in patients receiving long-term thiazide therapy . Hypertensive disease in the Negro population of Baltimore is a serious , life-threatening condition . Our study provides evidence of the need for continuous close supervision , and the provision of organized teams devoted to the care , of such a population",
"The effect of atenolol and reserpine on incidence of strokes , coronary heart disease ( CHD ) , cardiovascular disease ( CVD ) , and mortality was assessed in 4736 persons aged 60 years and older with isolated systolic hypertension . Participants were r and omized to either chlorthalidone ( 2371 ) , with step-up to atenolol , or reserpine if needed , or placebo ( 2365 ) . The average baseline SBP/DBP was 170/77 mm Hg . In the active treatment group , step 1 , dose 1 was chlorthalidone , 12.5 mg/day ; dose 2 was 25 mg/day . For step 2 , dose 1 was atenolol 25 mg/day ( or reserpine 0.05 mg/day if atenolol was contraindicated ) ; dose 2 was 50 mg/day ( reserpine , 0.10 mg/day ) . During 4.5 years average follow-up , 32 % ( 757 ) of the active treatment group were on atenolol , with an average exposure of two years and 8 % ( 193 ) were on reserpine with an average exposure of 1.7 years . Overall there were 96 strokes , 140 CHD events and 289 CVD events among the 2365 active group participants . Using time-dependent lifetable regression with adjustment for several variables , the addition of either atenolol or reserpine to chlorthalidone did not substantially alter the risk ratios for chlorthalidone alone . The relative risk for CHD events for atenolol versus no atenolol was 1.04 ( 95 % confidence interval : 0.58 , 1.86 ) and for reserpine versus no reserpine was 0.93 ( 95 % confidence interval : 0.29 , 2.96 ) . The relative risk for atenolol were 0.84 ( 95 % confidence interval : 0.54 , 1.30 ) for death , 1.34 ( 95 % confidence interval : 0.80 , 2.28 ) for stroke , and 1.07 ( 95 % confidence interval : 0.71 , 1.61 ) for CVD . For reserpine , the corresponding relative risks and confidence intervals were 0.65 ( 0.26 , 1.59 ) for death , 0.27 ( 0.04 , 2.26 ) for stroke , and 0.55 ( 0.20 , 1.49 ) for CVD . Thus , the beneficial effects in several outcomes in Systolic Hypertension in the Elderly Program ( SHEP ) were due to the treatment regimen of lowering blood pressure based on low-dose chlorthalidone ( plus atenolol or reserpine as required to meet blood pressure criteria ) . Additional ( independent ) benefits attributable to atenolol or to reserpine were not identified . However , a greater number of patients might have been necessary to adequately evaluate potential differential effects of these drugs , especially for reserpine",
"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",
"To compare the antihypertensive effect of a Rauwolfia whole root‐chlorothiazide combination with reserpine plus chlorothiazide , subjects were selected who had average diastolic pressures of 90 mm . Hg or more at home , in the sitting position . In a double‐blind study providing 3 months on each regimen with a 6 week placebo period intervening , no significant difference in antihypertensive effect was demonstrated between the whole root Rauwolfia‐chlorothiazide combination and the reserpine plus chlorothiazide",
"Abstract By a double‐blind crossover method , the hypotensive effects and side effects of cryptenamine were studied in 22 patients with Group 1 or 2 essential hypertension . The dosage administered was 2.5 mg . of methyclothiazide alone and a combination of 2.5 mg . of methyclothiazide and : ( a ) 2.0 mg . of cryptenamine , ( b ) 0.1 mg . of reserpine , and ( c ) 1.0 mg . of cryptenamine and 0.1 mg . of reserpine . Each preparation was administered four times each day for 8 weeks . The mean decrease in diastolic blood pressure with methyclothiazide alone was 10.5 mm . Hg ; with methyclothiazide and cryptenamine , 15 mm . Hg ; with methyclothiazide and reserpine , 21.6 mm . Hg ; and with methyclothiazide , reserpine , and cryptenanmine , 23.5 mm . Hg . Two patients receiving methyclothiazide and cryptenamine were unable to complete the study because of nausea or depression . Mild side effects were more frequent with the combinations . Hypokalemia was noted in 50 % of the patients , and small increases in levels of uric acid , urea , and blood sugar were without complication"
] |
4116b51e-06ff-11f0-808a-c43d1ab1c353
|
Background The measurement properties of instruments used to assess functional capacity , physical activity and muscle strength in participants with non-small cell lung cancer ( NSCLC ) have not been systematic ally review ed . Method Objectives : To identify outcome measures used to assess these outcomes in participants with NSCLC ; and to evaluate , synthesis e and compare the measurement properties of the outcome measures identified . Data Sources : A systematic review of articles using electronic data bases MEDLINE ( 1950–2012 ) , CINAHL ( 1982–2012 ) , EMBASE ( 1980–2012 ) , Cochrane Library ( 2012 ) , Exp and ed Academic ASAP ( 1994–2012 ) , Health Collection Informit ( 1995–2012 ) and PEDRO ( 1999–2012 ) . Additional studies were identified by search ing personal files and cross referencing . Eligibility Criteria for Study Selection : Search one : studies which assessed functional capacity , physical activity or muscle strength in participants with NSCLC using non-laboratory objective tests were included . Search two : studies which evaluated a measurement property ( inter- or intra-rater reliability ; measurement error ; criterion or construct validity ; or responsiveness ) in NSCLC for one of the outcome measures identified in search one . Studies published in English from 1980 were eligible . Data Extraction and Method ological Quality Assessment : data collection form was developed and data extracted . Method ological quality of studies was assessed by two independent review ers using the 4-point COSMIN checklist . Results Thirteen outcome measures were identified . Thirty-one studies evaluating measurement properties of the outcome measures in participants with NSCLC were included . Functional capacity was assessed using the six- and twelve-minute walk tests ; incremental- and endurance-shuttle walk tests ; and the stair-climbing test . Criterion validity for three of these measures was established in NSCLC but not the reliability or responsiveness . Physical activity was measured using accelerometers and pedometers . Only the construct validity for accelerometers and pedometers was reported . Muscle strength was measured using h and -held dynamometry , h and -grip dynamometry , manual muscle test , one-repetition maximum and the chair-st and test , however only two studies reported reliability and measurement error and one study reported construct validity . Conclusion Currently there is a gap in the literature regarding the measurement properties of commonly used outcome measures in NSCLC participants , particularly reliability , measurement error and responsiveness . Further research needs to be conducted to determine the most suitable outcome measures for use in trials involving NSCLC participants
|
[
"BACKGROUND Lung resections determine a variable functional reduction depending on the extent of the resection and the time elapsed from the operation . The objectives of this study were to prospect ively investigate the postoperative changes in FEV(1 ) , carbon monoxide lung diffusion capacity ( Dlco ) , and exercise tolerance after major lung resection at repeated evaluation times . METHODS FEV(1 ) , Dlco , and peak oxygen consumption ( Vo(2)peak ) calculated using the stair climbing test were measured in 200 patients preoperatively , at discharge , and 1 month and 3 months after lobectomy or pneumonectomy . Preoperative and repeated postoperative measures were compared , and a time-series , cross-sectional regression analysis was performed to identify factors associated with postoperative Vo(2)peak . RESULTS One month after lobectomy , FEV(1 ) , Dlco , and Vo(2)peak values were 79.5 % , 81.5 % , and 96 % of preoperative values and recovered up to 84 % , 88.5 % , and 97 % after 3 months , respectively . One month after pneumonectomy , FEV(1 ) percentage of predicted , Dlco percentage of predicted , and Vo(2)peak values were 65 % , 75 % , and 87 % of preoperative values , and were 66 % , 80 % , and 89 % after 3 months , respectively . Three months after lobectomy , 27 % of patients with COPD had improved FEV(1 ) , 34 % had improved Dlco , and 43 % had improved Vo(2)peak compared to preoperative values . The time-series , cross-sectional regression analysis showed that postoperative Vo(2)peak values were directly associated with preoperative values of Vo(2)peak , and postoperative values of FEV(1 ) and Dlco , and were inversely associated with age and body mass index . CONCLUSIONS Our findings may be used during preoperative counseling and for deciding eligibility for operation along with other more traditional measures of outcome",
"OBJECTIVE To identify predictors of postoperative exercise oxygen desaturation ( EOD ) in patients su bmi tted to lobectomy or pneumonectomy for lung carcinoma . PATIENTS AND METHODS A consecutive series of 227 patients with non-small cell lung cancer su bmi tted to lobectomy or pneumonectomy from January 2000 through October 2002 were prospect ively analyzed . Maximal stair-climbing tests were performed preoperatively ( the day before the operation ) and postoperatively ( on average , 9.2 days after operation ) in room air for all patients . A fall in oxygen saturation during the exercise below 90 % was termed ' desaturation ' . Univariate and multivariate analyses were performed to identify predictors of postoperative EOD . RESULTS Thirty-five patients ( 15.4 % ) developed postoperative EOD . After multivariate analysis , the only independent predictor of postoperative EOD result ed a reduction in oxygen saturation during the preoperative exercise ( P=0.0004 ) . CONCLUSIONS Patients with a reduction in oxygen saturation during the preoperative exercise test are at increased risk to develop a postoperative EOD below 90 % . A postoperative exercise test should be performed in all these patients . Should EOD be confirmed , an intermittent home oxygen therapy is recommended in order to facilitate recovery from operation and improve the quality of life",
"Background : The lower limb muscle strength is an important determinant of physical function in older people . However , measurement in clinical and epidemiological setting s has been limited because of the requirement for large-scale equipment . A protocol using a novel , versatile h and -held dynamometer ( HHD ) has been developed to measure the quadriceps strength in a supine position . Objective : The objective of this study was to assess the validity of this new methodology for measuring the lower limb muscle strength compared to the gold st and ard Biodex dynamometer . Methods : The supine quadriceps strength was measured twice with each of the Biodex and the HHD in 20 men and women , aged 61–81 years , on their non-dominant leg . The agreement between the peak torques obtained by Biodex and HHD was analyzed . Results : The mean peak Biodex and HHD results were 83.4 ± ( SD ) 28.0 Nm and 68.9 ± 19.6 Nm , respectively . The HHD undermeasured the quadriceps strength by an average of 14.5 Nm ( 95 % CI 8.5 , 20.6 ) compared to the Biodex , and this effect was most marked in the strongest participants . Nevertheless , there was a good correlation between the measures ( r = 0.91 , p of muscle strength showed good agreement between the two methods ( Kappa = 0.69 , p muscle strength for use in healthy older people . It underestimates the absolute quadriceps strength compared to the Biodex particularly in stronger people , but is a useful tool for ranking muscle strength of older people in epidemiological studies . It may also be of value for quick and objective assessment of physical function in the clinical setting",
"BACKGROUND The objective of this study was to assess the role of a modified stair climbing test in predicting postoperative cardiopulmonary complications . METHODS A consecutive series of 150 patients who had undergone pulmonary resection for lung carcinoma formed the prospect i ve data base of this study . All patients performed a preoperative modified stair climbing test . Univariate and multivariate analyses were performed to identify predictors of postoperative cardiopulmonary complications . RESULTS With univariate analysis , the patients with complications had a lower pre-exercise and postexercise percentage of oxygen saturation . PaO ( 2 ) levels were found to be lower and a greater change in oxygen desaturation during exercise was noted . Logistic regression analysis showed that the percent of oxygen saturation pre-exercise and the change in percent of oxygen desaturation during exercise were independent and reliable predictors of cardiopulmonary morbidity . CONCLUSIONS A modified stair climbing test is a safe , economical and simple test capable of predicting cardiopulmonary complications",
"Abstract Background . Patients with lung cancer are often burdened by dyspnoea , fatigue , decreased physical ability and loss of weight . Earlier studies of physical exercise of patients with COPD have shown promising results . The aim of this study was to investigate , if a well-documented COPD rehabilitation protocol can improve physical fitness and quality of life ( QoL ) in patients with lung cancer . Material and methods . Forty-five patients , with a minimum walking distance of 50 meters , absence of cognitive deficits or severe heart disease and motivated for physical training were invited to an exercise intervention . The intervention consisted of seven weeks of twice weekly training , focusing on walking training , circuit training , h and ling of dyspnoea and instructions in daily diary-based training at home . Prior to , and after the intervention , Incremental- and Endurance Shuttle Walk Test ( ISWT and ESWT ) were performed , and pulmonary function as well as self-reported QoL ( EORTC-QLQ-C30 and LC13 ) were measured . Results . Fourteen subjects dropped out before commencement of the intervention . Seven were excluded after physiotherapeutic evaluation . Of the remaining 24 , three were excluded because of insufficient attendance ( thus 21 patients completed the intervention . For 17 patients with complete pre- and post intervention data , ISWT increased 9 % ( −77 to 39 % ) ( median and range ) ( p = 0.021 ) , while ESWT increased 109 % ( −70 to 432 % ) ( p = 0.002 ) . Twelve of 17 improved in ISWT , while 15 improved in ESWT . No changes in pulmonary function and improvements in QoL were observed . Conclusion . Patients with pulmonary cancer can achieve significant improvements in physical fitness measured with ISWT and ESWT after completion of the intervention program . No changes in pulmonary function and QoL were observed . In addition , we found that a large number of patients dropped out before intervention and that the patients , who succeeded , often discontinued training at home",
"OBJECTIVES Maximum oxygen consumption per min ( VO(₂max ) ) is currently considered the most accurate test for the preoperative risk assessment in patients scheduled for pulmonary resection . Due to its high-technology requirements and cost , VO(₂max ) is performed less frequently than is desired . The objective of this investigation is to determine if the measurement of the basal daily ambulatory activity of the patients , with a pedometer , can be used to predict VO(₂max ) values . METHODS This is a prospect i ve study on 38 patients referred for scheduled lobectomy or pneumonectomy . Daily basal preoperative activity of the patients was measured 3 weeks before surgery by means of an OMROM HJ-72OIT-E2 pedometer . Before surgery , VO(₂max ) ( dependent variable ) was calculated using a Master Screen CPX module of Jaeger-Vyasis-Healthcare . The following independent variables were studied : age , sex , preoperative forced expiratory volume in 1s percentage ( FEV1 % ) and carbon monoxide diffusing capacity percentage ( DLCO% ) , mean number of steps per day ( aerobic and non-aerobic ) , mean daily time of aerobic activity ( in min ) and mean daily walked distance ( in km ) . Two linear regression models with bootstrap robust estimation of the st and ard error of the coefficients were adjusted and the estimated values of VO(₂max ) were kept as a new variable for comparison . To avoid collinearity problems , only one of the pedometer records entered the regression model . RESULTS Data of the series ( mean ± SD ) : age 62.8 ± 10.14 years ; FEV1 % 90.1 ± 21.8 ; DLCO% 82.8 ± 20.1 . After collinearity analysis , mean daily walked distance was chosen as the most representative variable . In the first regression model , ' Distance ' ( p = 0.000 ) was highly correlated to the dependent variable ( adjusted R² : 0.812 ) . The second model improved the predictive value of the first one adding DLCO% to the model . In this model , DLCO% ( p = 0.000 ) and ' Distance ' ( p = 0.002 ) were correlated to the dependent variable . The adjusted R² of the second lineal model was 0.935 . CONCLUSION These preliminary data show that a combination of the measured daily ambulatory activity using a pedometer , especially the mean daily walked distance in km , and the DLCO% of the patient could predict the VO(₂max ) value . Larger data series are needed for conclusive results",
"CONTEXT AND OBJECTIVE There is increasing involvement of health professionals in organizing protocol s to determine the impact of lung surgery on functional state and activities of daily living , with the aim of improving quality of life ( QoL ) . The objective of this study was to investigate predictors of QoL improvement among patients undergoing parenchyma resection due to lung cancer . DESIGN AND SETTING Prospect i ve study , at teaching hospital of Universidade Estadual de Campinas ( Unicamp ) . METHODS 36 patients with lung cancer diagnosis were assessed before surgery and on the 30th , 90th and 180th days after surgery . The Short-Form Health Survey ( SF-36 ) was used as the dependent variable . The independent variables were the Hospital Anxiety and Depression ( HAD ) scale , a six-minute walking test ( 6-MWT ) , a visual analogue scale for pain , forced vital capacity ( FVC ) , type of surgery and use of radiotherapy and chemotherapy . Generalized estimation equations ( GEE ) were utilized . RESULTS The median age for these 20 men and 16 women was 55.5 + /- 13.4 years . Both FVC and 6-MWT were predictors of improvement in the physical dimensions of QoL ( p = 0.011 and 0.0003 , respectively ) , as was smaller extent of surgical resection ( p = 0.04 ) . The social component of QoL had improved by the third postoperative month ( p = 0.0005 ) . CONCLUSION The predictors that affected QoL positively were better FVC and 6-MWT results and less extensive lung resection . Three months after the surgery , an improvement in social life was already seen",
"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 Surgery remains the treatment of choice in patients with potentially resectable lung carcinoma . Both the British Thoracic Society and American Chest Physician guidelines for the selection of patients with lung cancer surgery suggest the use of a shuttle walk test to predict outcome in patients with borderline lung function . The guidelines suggest that if the patient is unable to walk 250 m during a shuttle walk test , they are high risk for surgery . However , there is no published evidence to support this recommendation . Therefore , we undertook a prospect i ve study to examine the relationship between shuttle walk test and surgical outcome in 139 patients undergoing assessment for possible lung cancer surgery . METHODS The shuttle walk test was performed in 139 potentially resectable patients , recruited over a 2 year period , prior to surgery . One hundred and eleven patients underwent surgery . Outcome of surgery , including duration of hospital stay , complication and mortality rates was recorded . Student 's t-test was used to compare the shuttle walk distance in patients with good and poor outcome from surgery . RESULTS Mean age of patients undergoing surgery was 69 years ( 42 - 85 ) . Mean shuttle walk distance was 395 m ( 145 - 780 ) , with a mean oxygen desaturation of 4 % ( 0 - 14 ) during the test . Sixty nine patients had a good surgical outcome and 34 had a poor outcome . The shuttle walk distance was not statistically different in the two outcome groups . CONCLUSION Shuttle walk distance should not be used to predict poor surgical outcome in lung cancer patients , contrary to current recommendations . It is therefore advisable to perform a formal cardiopulmonary exercise test if at all possible . The usefulness of a shuttle walk test might be improved . It could be compared to a predicted value , as for a formal cardiopulmonary exercise test",
"AIM To test the predictive value of stairs climbing test for the development of postoperative complications in lung cancer patients with forced expiratory volume in one second (FEV1) METHODS The prospect i ve study was conducted in 101 consecutive patients with an FEV1 Preoperative examination included medical history and physical examination , lung function testing , electrocardiography , laboratory testing , and chest radiography . All patients underwent stairs climbing with pulse oximetry before the operation with the number of steps climbed and the time to complete the test recorded . Oxygen saturation and pulse rate were measured every 20 steps . Data on postoperative complications including oxygen use , prolonged mechanical ventilation , and early postoperative mortality were collected . RESULTS Eighty-seven of 101 patients ( 86 % ) had at least one postoperative complication . The type of surgery was significantly associated with postoperative complications ( 25.5 % patients with lobectomy had no early postoperative complications ) , while age , gender , smoking status , postoperative oxygenation , and artificial ventilation were not . There were more postoperative complications in more extensive and serious types of surgery ( P stairs climbing test produced a significant decrease in oxygen saturation ( -1 % ) and increase in pulse rate ( by 10/min ) for every 20 steps climbed . The stairs climbing test was predictive for postoperative complications only in lobectomy group , with the best predictive parameter being the quotient of oxygen saturation after 40 steps and test duration ( positive likelihood ratio [ LR ] , 2.4 ; 95 % confidence interval [ CI ] , 1.71 - 3.38 ; negative LR , 0.53 ; 95 % CI , 0.38 - 0.76 ) . In patients with other types of surgery the only significant predictive parameter for incident severe postoperative complications was the number of days on artificial ventilation ( P=0.006 ) . CONCLUSION Stairs climbing test should be done in routine clinical practice as a st and ard test for risk assessment and prediction of the development of postoperative complications in lung cancer patients selected for elective surgery ( lobectomy ) . Comparative to spirometry , it detects serious disorders in oxygen transport that are a baseline for a later development of cardiopulmonary postoperative complications and mortality in this subgroup of patients",
"Background : Algorithms for the pre-operative evaluation of lung resection c and i date s with impaired lung function invariably include maximum oxygen uptake ( v̇O2MAX ) as a critical parameter of functional reserves , with a v̇O2MAX ≧20 ml/kg/min generally considered sufficient for pneumonectomy . Stair climbing is a low-cost alternative to assess exercise capacity . Objectives : As stair climbing is not st and ardised , we aim ed to compare the altitude reached and the speed of ascent with v̇O2MAX measured by cycle ergometry . Methods : We prospect ively enrolled 44 pulmonary resection c and i date s ( mean age : 47.6 ± 12.5 years ) with an FEV1 Patients were asked to climb as high and as fast as they could , to a maximum elevation of 20 m. The altitude reached and the average speed of ascent were compared to v̇O2MAX . Results : Forty-three patients reached a 20-metre elevation . Thirteen of them , as well as the patient who did not reach this height , had a v̇O2MAX between speed of ascent and v̇O2MAX/kg ( R2 = 0.67 ) , but not between altitude and v̇O2MAX/kg . All 24 patients with a speed ≧15 m/min had a v̇O2MAX ≧20 ml/kg/min . Thirty-nine of 40 patients with a speed ≧12 m/min had a v̇O2MAX ≧15 ml/kg/min . Conclusions : The average speed of ascent during stair climbing was an accurate semiquantitative predictor of v̇O2MAX/kg , whereas altitude was not . We were able to identify potential cut-off values for lobectomy or pneumonectomy . Pending validation with clinical endpoints , stair climbing may replace formal exercise testing at much lower costs in a large proportion of lung resection c and i date",
"BACKGROUND The objective of this study was to assess the role of a symptom-limited stair climbing test in predicting postoperative cardiopulmonary complications in elderly c and i date s for lung resection . METHODS A consecutive series of 109 patients more than 70 years of age who underwent pulmonary lobectomy for lung carcinoma from January 2000 through May 2003 formed the prospect i ve data base of this study . All patients in the analysis performed a preoperative symptom-limited stair climbing test . Univariate and multivariate analyses were performed to identify predictors of postoperative cardiopulmonary complications . RESULTS At univariate analysis , the patients with complications had a lower forced expiratory capacity percentage of predicted ( p = 0.048 ) , predicted postoperative forced expiratory volume in 1 second percentage of predicted ( p = 0.049 ) , climbed a lower height at preoperative stair climbing test ( p = 0.0004 ) , and presented a greater proportion of cardiac comorbiditiy with respect to the patients without complications ( p = 0.02 ) . After logistic regression analysis , significant predictors of postoperative complications result ed in the presence of a concomitant cardiac disease ( p = 0.04 ) and a low height climbed preoperatively ( p = 0.0015 ) . CONCLUSIONS A symptom-limited stair climbing test was a safe and simple instrument capable of predicting cardiopulmonary complications in the elderly after lung resection",
"Background : The relationship between the shuttle walk test and peak oxygen consumption in patients with lung cancer has not previously been reported . A study was undertaken to examine this relationship in patients referred for lung cancer surgery to test the hypothesis that the shuttle walk test would be useful in this clinical setting . Methods : 125 consecutive patients with potentially operable lung cancer were prospect ively recruited . Each performed same day shuttle walking and treadmill walking tests . Results : Shuttle walk distances ranged from 104 m to 1020 m and peak oxygen consumption ranged from 9 to 35 ml/kg/min . The shuttle walk distance significantly correlated with peak oxygen consumption ( r = 0.67 , p peak oxygen consumption of at least 15 ml/kg/min . Seventy of 125 patients failed to achieve 400 m on the shuttle walk test ; in 22 of these the peak oxygen consumption was less than 15 ml/kg/min . Nine of 17 patients who achieved less than 250 m had a peak oxygen consumption of more than 15 ml/kg/min . Conclusion : The shuttle walk is a useful exercise test to assess potentially operable lung cancer patients with borderline lung function . However , it tends to underestimate exercise capacity at the lower range compared with peak oxygen consumption . Our data suggest that patients achieving 400 m on the shuttle walk test do not require formal measurement of oxygen consumption . In patients failing to achieve this distance we recommend assessment of peak oxygen consumption , particularly in those unable to walk 250 m , because a considerable proportion would still qualify for surgery as they had an acceptable peak oxygen consumption",
"PURPOSE To assess the 6-minute walk test ( 6MWT ) as a predictor of radiation therapy-induced lung injury ( RTLI ) . METHODS AND MATERIAL S The 6MWT is a simple , economical , and reproducible test that measures both how far a person can walk in 6 min and any associated changes in vital signs . As part of a prospect i ve trial to study RTLI , a pre-RT 6MWT was performed in 41 patients . The predictive capacities of pre-RT 6MWT , forced expiratory volume in 1 s ( FEV1 ) , and single-breath diffusing capacity for carbon monoxide ( DLCO ) for the development of RTLI were assessed with receiver operating curve ( ROC ) techniques . To evaluate the 6MWT , alone or with mean lung dose ( MLD ) of radiation , as a predictor of RTLI , the rates of RTLI in patient subgroups defined by 6MWT results were compared by using Fisher 's exact test . RESULTS Thirty-one patients with > or =3 months ' follow-up were evaluable . The median baseline 6MWT result was 1400 ft . Of 31 patients , 7 developed Grade > or = 2 RTLI . Of 15 patients with an MLD > 18 Gy ( the median ) , 5 developed RTLI , compared with 2 of 16 with MLD RTLI rates were 0 of 8 and 2 of 8 for 6MWT results > or = 1400 ft or ROC area under the curve for individual metrics was as follows : FEV1 0.66 , MLD 0.70 , DLCO 0.61 , and 6MWT 0.47 . Combining FEV1 with 6MWT increased the ROC to 0.71 , suggesting that the ratio might be a better predictor than the individual values . Patients with a high 6MWT/FEV1 ratio had a lower rate of RTLI than those with a relatively low ratio . CONCLUSIONS The 6MWT might provide prognostic information beyond pulmonary function tests and dosimetric parameters in predicting RTLI . Additional work is needed to better assess the utility of these functional metrics",
"Studies evaluating predictors of operative outcome for lung resection have focused on physiological measures of cardiorespiratory impairment , but these have proved inadequate . This study evaluated the predictive abilities of six preoperative variables : the global quality of life ( QL ) , social function ( SF ) , and emotional function ( EF ) scales of the European Organization for the Research and Treatment of Cancer 's ( EORTC ) QLQ-C30 question naire , 6-min walk distance ( 6MWD ) , forced expiratory volume ( FEV1 ) , and diffusion capacity ( DLco ) . Operative outcome was represented by the surrogate measure length of stay out of hospital within the first 30 days ( LOSOH ) . A single-centre prospect i ve cohort study evaluating 70 subjects was conducted using multiple regression . LOSOH was bimodally distributed , therefore analysis was undertaken for the entire sample and for two separate groups ( A and B ) . Group B ( n = 4 ) experienced severe complications ( LOSOH = 0–5 days ) and was too small for statistical analysis . Group A ( n = 66 ) suffered fewer and less severe complications ( LOSOH = 14–26 days ) . For the entire sample , age was the sole predictor of LOSOH ( R2 = 0.123 , p = 0.003 ) . In Group A , the strongest predictors of LOSOH were global QL score and 6MWD ( R2 = 0.224 , p with complications . While it remains difficult to predict severe complications in this population , within Group A , health status measures demonstrated a limited ability to predict LOSOH",
"STUDY OBJECTIVE To evaluate the capability of the stair climbing test to predict cardiopulmonary complications after lung resection for lung cancer . DESIGN A prospect i ve cohort of c and i date s for lung resection . Spirometric assessment and the stair climbing test were performed the day before operation . Univariate and multivariate analyses were performed to identify predictors of postoperative complications . SETTING Tertiary referral center . PATIENTS A consecutive series of 160 c and i date s for lung resection with lung carcinoma from January 2000 through March 2001 . RESULTS At univariate analysis , the patients with complications were significantly older ( p = 0.02 ) , had a significantly lower FEV(1 ) percentage ( p = 0.007 ) and predicted postoperative FEV(1 ) percentage ( p = 0.01 ) , had a greater incidence of a concomitant cardiac disease ( p = 0.02 ) , climbed a lower altitude at the stair climbing test ( p calculated maximum oxygen consumption ( O(2)max ) [ p = 0.03 ] and predicted postoperative O(2)max ( p = 0.006 ) compared to the patients without complications . At multivariate analysis , the altitude reached at the stair climbing test remained the only significant independent predictor of complications . CONCLUSIONS The stair climbing test is a safe and economical exercise test , and it was the best predictor of cardiopulmonary complications after lung resection",
"BACKGROUND This investigation evaluated whether the performance at a preoperative symptom-limited stair-climbing test was a prognostic factor in resected pathologic stage I non-small cell lung cancer ( NSCLC ) . METHODS Observational analysis was performed on a prospect i ve data base that included 296 patients who underwent pulmonary lobectomy for pathologic stage T1 N0 or T2 N0 NSCLC ( 2000 to 2008 ) . Patients who received induction chemotherapy were excluded . Survival was calculated by the Kaplan-Meyer method . The log-rank test was used to assess differences in survival between groups . The relationships between survival and baseline and clinical variables were determined by Cox multivariate analyses . RESULTS Median follow-up was 43 months . The best cutoff associated with prognosis was an 18-meter stair climb . Median ( months ) survival and 5-year survival of patients who climbed more than 18 meters were significantly longer than those who climbed less than 18 meters ( 97 vs 74 ; 77 % vs 54 % , p=0.001 ) . Cox regression model ( hazard ratio ) showed that climbing more than 18 meters ( 0.5 ; p=0.003 ) , diffusion capacity of the lung for carbon monoxide ( 0.98 ; p=0.02 ) , and pT stage ( 1.8 ; p=0.02 ) were independent prognostic factors . Patients who climbed less than 18 meters had increased deaths from cancer ( 24 % vs 15 % , p=0.1 ) or other causes ( 19 % vs 9 % , p=0.02 ) . CONCLUSIONS Preoperative cardiopulmonary fitness is a significant prognostic factor in patients after resection for early-stage NSCLC . Interventions aim ed at improving exercise tolerance can be useful to improve long-term prognosis after NSCLC operations",
"Patients with lung cancer experience muscle wasting and weakness . Therapeutic exercise may be beneficial but is not always practical . An alternative approach may be neuromuscular electrical stimulation ( NMES ) of the quadriceps muscles , but this has not been formally examined in patients with cancer . Thus , we have undertaken this pilot study to assess feasibility and inform the design of future studies . Sixteen patients were r and omized to receive usual care ( control group ) or usual care plus NMES for four weeks . NMES consisted of daily stimulation to both thighs for up to 30minutes ( frequency 50Hz , \" on \" cycle 11%-25 % ) . Adherence was assessed by a self-report diary and a semistructured evaluation form . Quadriceps muscle strength , exercise endurance , and free-living physical activity were assessed using a Cybex NORM dynamometer , an endurance shuttle walk test , and an ActivPAL accelerometer ( mean daily step count ) , respectively . Changes in outcome from baseline were compared between groups by mean differences and their 95 % confidence intervals using independent t-test ( P=0.05 ) . Median ( range ) adherence to the program was 80 % ( 69%-100 % ) . All patients found the NMES device easy to use . Changes in outcome favored the NMES group , with mean differences of 9.4 Nm ( 21 % ) in quadriceps muscle strength , 768 steps ( 15 % ) in free-living activity , and 138 m ( 8 % ) in exercise endurance , but none of the differences were statistically significant . In conclusion , NMES warrants further study in patients with lung cancer",
"BACKGROUND We wanted to determine if cardiopulmonary exercise testing could better identify the threshold where physiologic function is irreparably impaired for patients with borderline pulmonary function who are being considered for lung cancer resection . METHODS We performed an open , prospect i ve preoperative trial and a postoperative outcome evaluation with a combined medical , surgical , and exercise physiology evaluation at three university hospitals . All eligible patients had spirometry , lung volume determination , and quantitative perfusion scanning and performed a cardiopulmonary stress test , stair climbing , and a 12-minute walk for distance . Functional status was determined with an Eastern Cooperative Oncology Group score , a dyspnea score , and a cardiopulmonary risk index . RESULTS We identified 12 patients who met strict criteria for borderline pulmonary function during a 1-year study period . The mean forced expiratory volume in 1 second ( FEV1 ) was 1.38 L ( 48 % of predicted ) . The mean predicted postoperative FEV1 based on pneumonectomy was 700 mL. Eleven of the patients did the stair climb and 10 passed . All 12 patients achieved a maximum oxygen consumption greater than or equal to 10 mL x kg(-1 ) x min(-1 ) ( mean value , 13.8 mL x kg(-1 ) x min(-1 ) ) . Thirteen operations were performed on the 12 patients . Nine complications occurred in 7 patients . CONCLUSIONS Patients with borderline pulmonary function can undergo resection safely if they have an FEV1 equal to or greater than 1.6 L or 40 % of its predicted value , a predicted postoperative FEV1 of 700 mL or more , a maximum oxygen consumption of 10 mL x kg(-1 ) x min(-1 ) or greater , or stair climbing of three flights or more . Cardiopulmonary stress testing and stair climbing add valuable clinical information for patients with an FEV1 of less than 1.6",
"Background : The stair-climbing test is commonly used in the preoperative evaluation of lung resection c and i date s , but it is difficult to st and ardize and provides little physiologic information on the performance . Objective : To verify the association between the altitude and the VO2peak measured during the stair-climbing test . Methods : 109 consecutive c and i date s for lung resection performed a symptom-limited stair-climbing test with direct breath-by-breath measurement of VO2peak by a portable gas analyzer . Stepwise logistic regression and bootstrap analyses were used to verify the association of several perioperative variables with a VO2peak VO2peak from stair-climbing parameters and other patient-related variables . Results : 56 % of patients climbing VO2peak 22 m had a VO2peak > 15 ml/kg/min . The altitude reached at stair-climbing test result ed in the only significant predictor of a VO2peak estimate VO2peak factoring altitude ( p speed of ascent ( p = 0.005 ) and body mass index ( p = 0.0008 ) . Conclusions : There was an association between altitude and VO2peak measured during the stair-climbing test . Most of the patients climbing more than 22 m are able to generate high values of VO2peak and can proceed to surgery without any additional tests . All others need to be referred for a formal cardiopulmonary exercise test . In addition , we were able to generate an equation to estimate VO2peak , which could assist in streamlining the preoperative workup and could be used across different setting s to st and ardize this test",
"PURPOSE To assess the utility of the 6-minute walk test ( 6MWT ) as a predictor of symptomatic radiation-induced pneumonitis ( RP ) . METHODS As part of a prospect i ve trial to study radiation-induced lung injury , 53 patients receiving thoracic radiotherapy ( RT ) underwent a pre-RT 6MWT , pulmonary function tests ( PFTs ) , and had > or=3-month follow-up for prospect i ve assessment of Grade 2 or worse RP ( requiring medications or worse ) . Dosimetric parameters ( e.g. , the percentage of lung receiving > or=30 Gy ) were extracted from the lung dose-volume histogram . The correlations between the 6MWT and PFT results were assessed using Pearson 's correlation . The receiver operating characteristic technique was used in patient subgroups to evaluate the predictive capacities for RP of the dosimetric parameters , 6MWT results , and PFT results , or the combination ( using discriminant analysis ) of all three metrics . ROCKIT software was used to compare the receiver operating characteristic areas between each predictive model . The association of the decline in 6MWT with the development of RP was evaluated using Fisher 's exact test . RESULTS The pre-RT PFT and 6MWT results correlated weakly ( r = 0.44 - 0.57 , p RP . The dose-volume histogram-based dosimetric parameters were the best single-metric model for predicting RP ( e.g. , percentage of lung receiving > or=30 Gy , receiver operating characteristic area 0.73 , p = 0.03 ) . Including the PFT or 6MWT results with the percentage of lung receiving > or=30 Gy did not improve the predictions . The predictive abilities of dosimetric-based models improved when the analysis was restricted to those patients whose tumors were not causing regional lung dysfunction . No correlation was found between the decline in the 6MWT result and the RP rate ( p = 0.6 ) . CONCLUSION Although the PFTs and 6MWT are related to each other , the correlation coefficients were weak , suggesting that they could be measuring different physiologic functions . In the present data set , the addition of the PFTs or 6MWT did not increase the ability of the dosimetric parameters to predict for acute symptomatic RP . Additional work is needed to better underst and the interaction among the PFT results , exercise tolerance ( 6MWT ) , and the risk of RT-induced lung dysfunction "
] |
4116b564-06ff-11f0-808a-c43d1ab1c353
|
Background It is well known that physical exercise is important to promote physical and cognitive health in older population . However , inconsistent research findings were shown regarding exercise intensity , particularly on whether low-intensity exercise ( 1.5 metabolic equivalent tasks ( METs ) to 3.0 METs ) can improve physical and cognitive health of older adults . This systematic review aim ed to fill this research gap . The objective of this study is to conduct a systematic review of the effectiveness of low-intensity exercise interventions on physical and cognitive health of older adults . Methods Published research was identified in various data bases including CINAHL , MEDLINE , PEDro , PubMed , Science Direct , SPORTD iscus , and Web of Science . Research studies published from January 01 , 1994 to February 01 , 2015 were selected for examination . Studies were included if they were published in an academic peer- review ed journal , published in English , conducted as r and omized controlled trial ( RCT ) or quasi-experimental studies with appropriate comparison groups , targeted participants aged 65 or above , and prescribed with low-intensity exercise in at least one study arm . Two review ers independently extracted the data ( study , design , participants , intervention , and results ) and assessed the quality of the selected studies . Fifteen studies met the inclusion criteria . Quality index ranged from 15 to 18 mean = 18.3 with a full score of 28 , indicating a moderate quality . Most of the outcomes reported in these studied were lower limb muscle strength ( n = 9 ) , balancing ( n = 7 ) , flexibility ( n = 4 ) , and depressive symptoms ( n = 3 ) . Results Out of the 15 selected studies , 11 reported improvement in flexibility , balancing , lower limb muscle strength , or depressive symptoms by low-intensity exercises . Conclusions The current literature suggests the effectiveness of low-intensity exercise on improved physical and cognitive health for older adults . It may be a desired intensity level in promoting health among older adults with better compliance , lower risk of injuries , and long-term sustainability
|
[
"Background Depression is a disabling , prevalent condition . Physical activity programs may assist depression management in older people , ameliorate co-morbid conditions and reduce the need for antidepressants . The UPLIFT pilot study assessed the feasibility of older depressed people attending a community-based progressive resistance training ( PRT ) program . The study also aim ed to determine whether PRT improves depressive status in older depressed patients . Methods A r and omised controlled trial was conducted . People aged ≥ 65 years with depressive symptoms were recruited via general practice s. Following baseline assessment , subjects were r and omly allocated to attend a local PRT program three times per week for 10 weeks or a brief advice control group . Follow-up assessment of depressive status , physical and psychological health , functional and quality of life status occurred post intervention and at six months . Results Three hundred and forty six people responded to the study invitation , of whom 22 % had depressive symptoms ( Geriatric Depression Scale , GDS-30 score ≥ 11 ) . Thirty two people entered the trial . There were no significant group differences on the GDS at follow-up . At six months there was a trend for the PRT intervention group to have lower GDS scores than the comparison group , but this finding did not reach significance ( p = 0.08 ) . More of the PRT group ( 57 % ) had a reduction in depressive symptoms post program , compared to 44 % of the control group . It was not possible to discern which specific components of the program influenced its impact , but in post hoc analyses , improvement in depressive status appeared to be associated with the number of exercise sessions completed ( r = -0.8 , p older people with depression can be successfully recruited to a community based PRT program . The program can be offered by existing community-based facilities , enabling its ongoing implementation for the potential benefit of other older people",
"BACKGROUND Although exercise has been shown to relieve depression , little is known about its mechanism or dose-response characteristics . We hypothesized that high intensity progressive resistance training ( PRT ) would be more effective than either low intensity PRT or st and ard care by a general practitioner ( GP ) in depressed elderly persons , and that high intensity PRT would provide superior benefits in quality of life , sleep quality , and self-efficacy . METHODS Sixty community-dwelling adults > 60 years with major or minor depression were r and omized to supervised high intensity PRT ( 80 % maximum load ) or low intensity PRT ( 20 % maximum load ) 3 days per week for 8 weeks , or GP care . RESULTS A 50 % reduction in the Hamilton Rating Scale of Depression score was achieved in 61 % of the high intensity , 29 % of the low intensity , and 21 % of the GP care group ( p = .03 ) . Strength gain was directly associated with reduction in depressive symptoms ( r = 0.40 , p = .004 ) , as was baseline social support network type ( F = 3.52 , p = .015 ) , whereas personality type , self-efficacy , and locus of control were unrelated to the antidepressant effect . Vitality quality -of-life scale improved more in the high intensity group than in the others ( p = .04 ) . Sleep quality improved significantly in all participants ( p PRT is more effective than is low intensity PRT or GP care for the treatment of older depressed patients",
"BACKGROUND Falls in elderly people are a common presenting complaint to accident and emergency departments . Current practice commonly focuses on the injury , with little systematic assessment of the underlying cause , functional consequences , and possibilities for future prevention . We undertook a r and omised controlled study to assess the benefit of a structured inderdisciplinary assessment of people who have fallen in terms of further falls . METHODS Eligible patients were aged 65 years and older , lived in the community , and presented to an accident and emergency department with a fall . Patients assigned to the intervention group ( n=184 ) underwent a detailed medical and occupational-therapy assessment with referral to relevant services if indicated ; those assigned to the control group ( n=213 ) received usual care only . The analyses were by intention to treat . Follow-up data were collected every 4 months for 1 year . FINDINGS At 12-month follow-up , 77 % of both groups remained in the study . The total reported number of falls during this period was 183 in the intervention group compared with 510 in the control group ( p=0.0002 ) . The risk of falling was significantly reduced in the intervention group ( odds ratio 0.39 [ 95 % CI 0.23 - 0.66 ] ) as was the risk of recurrent falls ( 0.33 [ 0.16 - 0.68 ] ) . In addition , the odds of admission to hospital were lower in the intervention group ( 0.61 [ 0.35 - 1.05 ] ) whereas the decline in Barthel score with time was greater in the control group ( p high-risk population can significantly decrease the risk of further falls and limit functional impairment",
"OBJECTIVES This r and omized controlled trial studied the effects of a low- to moderate-intensity group exercise program on strength , endurance , mobility , and fall rates in fall-prone elderly men with chronic impairments . METHODS Fifty-nine community-living men ( mean age = 74 years ) with specific fall risk factors ( i.e. , leg weakness , impaired gait or balance , previous falls ) were r and omly assigned to a control group ( n = 28 ) or to a 12-week group exercise program ( n = 31 ) . Exercise sessions ( 90 minutes , three times per week ) focused on increasing strength and endurance and improving mobility and balance . Outcome measures included isokinetic strength and endurance , five physical performance measures , and self-reported physical functioning , health perception , activity level , and falls . RESULTS Exercisers showed significant improvement in measures of endurance and gait . Isokinetic endurance increased 21 % for right knee flexion and 26 % for extension . Exercisers had a 10 % increase ( p distance walked in six minutes , and improved ( p observational gait scale . Isokinetic strength improved only for right knee flexion . Exercise achieved no significant effect on hip or ankle strength , balance , self-reported physical functioning , or number of falls . Activity level increased within the exercise group . When fall rates were adjusted for activity level , the exercisers had a lower 3-month fall rate than controls ( 6 falls/1000 hours of activity vs 16.2 falls/1000 hours , p exercise can improve endurance , strength , gait , and function in chronically impaired , fall-prone elderly persons . In addition , increased physical activity was associated with reduced fall rates when adjusted for level of activity",
"We examined the effects of two physical activity modes on depressive symptoms over a 5-year period among older adults and change in physical self-esteem as a mediator of changes in depressive symptoms . Formerly sedentary , older adults ( N = 174 ) were r and omly assigned into 6-month conditions of either walking or low-intensity resistance/flexibility training . Depressive symptoms and physical self-esteem were measured before and after the 6-month intervention , and 12 and 60 months after intervention initiation . Depressive symptoms scores were decreased immediately after the intervention , followed by a sustained reduction for 12 and 60 months after intervention initiation ; there was no differential pattern of change between the physical activity modes . Change in physical self-esteem predicted change in depressive symptoms . This study supports the effectiveness of an exercise intervention for the sustained reduction of depressive symptoms among sedentary older adults and physical self-esteem as a potential mediator of this effect",
"BACKGROUND Previous observational and interventional studies have suggested that regular physical exercise may be associated with reduced symptoms of depression . However , the extent to which exercise training may reduce depressive symptoms in older patients with major depressive disorder ( MDD ) has not been systematic ally evaluated . OBJECTIVE To assess the effectiveness of an aerobic exercise program compared with st and ard medication ( ie , antidepressants ) for treatment of MDD in older patients , we conducted a 16-week r and omized controlled trial . METHODS One hundred fifty-six men and women with MDD ( age , > or = 50 years ) were assigned r and omly to a program of aerobic exercise , antidepressants ( sertraline hydrochloride ) , or combined exercise and medication . Subjects underwent comprehensive evaluations of depression , including the presence and severity of MDD using Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria and Hamilton Rating Scale for Depression ( HAM-D ) and Beck Depression Inventory ( BDI ) scores before and after treatment . Secondary outcome measures included aerobic capacity , life satisfaction , self-esteem , anxiety , and dysfunctional cognitions . RESULTS After 16 weeks of treatment , the groups did not differ statistically on HAM-D or BDI scores ( P = .67 ) ; adjustment for baseline levels of depression yielded an essentially identical result . Growth curve models revealed that all groups exhibited statistically and clinical ly significant reductions on HAM-D and BDI scores . However , patients receiving medication alone exhibited the fastest initial response ; among patients receiving combination therapy , those with less severe depressive symptoms initially showed a more rapid response than those with initially more severe depressive symptoms . CONCLUSIONS An exercise training program may be considered an alternative to antidepressants for treatment of depression in older persons . Although antidepressants may facilitate a more rapid initial therapeutic response than exercise , after 16 weeks of treatment exercise was equally effective in reducing depression among patients with MDD",
"OBJECTIVES We reported the interim findings of a r and omized controlled trial ( RCT ) to examine the effects of a mind body physical exercise ( Tai Chi ) on cognitive function in Chinese subjects at risk of cognitive decline . SUBJECTS 389 Chinese older persons with either a Clinical Dementia Rating ( CDR 0.5 ) or amnestic-MCI participated in an exercise program . The exercise intervention lasted for 1 year ; 171 subjects were trained with 24 forms simplified Tai Chi ( Intervention , I ) and 218 were trained with stretching and toning exercise ( Control , C ) . The exercise comprised of advised exercise sessions of at least three times per week . RESULTS At 5th months ( 2 months after completion of training ) , both I and C subjects showed an improvement in global cognitive function , delayed recall and subjective cognitive complaints ( paired t-tests , p visual spans and CDR sum of boxes scores were observed in I group ( paired t-tests , p to dementia ( Pearson chi square = 8.71 , OR = 5.34 , 95 % CI 1.56 - 18.29 ) . Logistic regression analysis controlled for baseline group differences in education and cognitive function suggested I group was associated with stable CDR ( OR = 0.14 , 95%CI = 0.03 - 0.71 , p = 0.02 ) . CONCLUSIONS Our interim findings showed that Chinese style mind body ( Tai Chi ) exercise may offer specific benefits to cognition , potential clinical interests should be further explored with longer observation period",
"Background : Falls in the elderly are a major health problem . Although exercise programs have been shown to reduce the risk of falls , the optimal exercise components , as well as the working mechanisms that underlie the effectiveness of these programs , have not yet been established . Objective : To test whether the Nijmegen Falls Prevention Program was effective in reducing falls and improving st and ing balance , balance confidence , and obstacle avoidance performance in community-dwelling elderly people . Methods : A total of 113 elderly with a history of falls participated in this study ( exercise group , n = 79 ; control group , n = 28 ; dropouts before r and omization , n = 6 ) . Exercise sessions were held twice weekly for 5 weeks . Pre- and post-intervention fall monitoring and quantitative motor control assessment s were performed . The outcome measures were the number of falls , st and ing balance and obstacle avoidance performance , and balance confidence scores . Results : The number of falls in the exercise group decreased by 46 % ( incidence rate ratio ( IRR ) 0.54 , 95 % confidence interval ( CI ) 0.36–0.79 ) compared to the number of falls during the baseline period and by 46 % ( IRR 0.54 , 95 % CI 0.34–0.86 ) compared to the control group . Obstacle avoidance success rates improved significantly more in the exercise group ( on average 12 % ) compared to the control group ( on average 6 % ) . Quiet stance and weight-shifting measures did not show significant effects of exercise . The exercise group also had a 6 % increase of balance confidence scores . Conclusion : The Nijmegen Falls Prevention Program was effective in reducing the incidence of falls in otherwise healthy elderly . There was no evidence of improved control of posture as a mechanism underlying this result . In contrast , an obstacle avoidance task indicated that subjects improved their performance . Laboratory obstacle avoidance tests may therefore be better instruments to evaluate future fall prevention studies than posturographic balance assessment",
"Context How common is mild cognitive impairment in older adults ? Contribution This study of 856 individuals from the national Health and Retirement Study found that 22 % of adults age 71 or older had cognitive impairment that did not reach the threshold for dementia . Annually , about 8 % of those with cognitive impairment without dementia died and about 12 % progressed to dementia . Caution Criteria that differentiate mild impairment from dementia are imperfect . Only 856 of 1770 and 180 of 241 selected individuals completed baseline and follow-up cognitive examinations , respectively . Implication Cognitive impairment without dementia probably affects a large segment of the elderly population . The Editors Cognitive impairment that does not reach the threshold for dementia diagnosis is associated with increased risk for progression to dementia in most studies , with progression rates of 10 % to 15 % per year compared with 1 % to 2.5 % among cognitively healthy older adults ( 13 ) . However , even among those without dementia , cognitive impairment contributes to decreased quality of life , increased neuropsychiatric symptoms , and increased disability ( 4 , 5 ) , as well as increased health care costs ( 6 , 7 ) . All of these negative outcomes make accurate national estimates of the prevalence of cognitive impairment without dementia essential for determining the full societal impact of cognitive impairment on patients , families , and health care programs . However , previous estimates of the prevalence of this condition from regional and non-U.S. sample s have varied from 3 % to 29 % ( 810 ) , a range that is most likely due to differences in diagnostic criteria and sample characteristics . Estimates of the total number of people with cognitive impairment without dementia in the United States are not available . We conducted ADAMS ( Aging , Demographics , and Memory Study ) to determine the national prevalence of dementia and cognitive impairment without dementia in the United States . We previously ( 11 ) reported our estimates of the prevalence of dementia . In this article , we report prevalence rates from what we believe to be the first population -based study of cognitive impairment without dementia to include individuals from all regions of the country , as well as rates of progression from cognitive impairment without dementia to dementia and death . Methods Participants We drew the ADAMS sample from the larger HRS ( Health and Retirement Study ) , an ongoing nationally representative cohort study of individuals born before 1954 that was design ed to investigate the health , social , and economic implication s of aging in the U.S. population ( 1214 ) . The HRS began in 1992 , and the current sample includes approximately 22000 participants . The ADAMS sample began with a stratified r and om sub sample of 1770 individuals age 70 years or older from 5 cognitive strata based on participants ' scores on a self-reported or proxy-reported cognitive measure ( 15 ) from the most recent HRS interview ( either 2000 or 2002 ) . We further stratified the 3 highest cognitive strata by age ( age 70 to 79 years vs. 80 years ) and sex to ensure adequate numbers in each subgroup . Full details of the ADAMS sample design and selection procedures are described elsewhere ( 16 , 17 ) . The ADAMS initial assessment s occurred between July 2001 and December 2003 , on average , 13.3 months ( SD , 6.9 ) after the HRS interview . Thus , participants were 71 years of age or older at the initial assessment . As part of the ADAMS assessment , proxies ( usually a spouse or adult child ) provided information about the participant 's cognitive and functional decline , neuropsychiatric symptoms , and medical history . Use of proxies to collect this information is preferred , because self-reporting of this type of information may not be reliable , particularly among cognitively impaired individuals . The Figure summarizes the number of participants at each phase of the study ; additional details on participation rates are reported elsewhere ( 17 ) . A total of 856 individuals , 56 % of the nondeceased target sample , participated in all phases of the dementia assessment . A major concern in ADAMS , as in similar population -based studies , is the potential for selective nonparticipation to bias prevalence estimates . However , because the ADAMS sample was derived from the HRS sample , a wide range of health and social information was available to assess and correct for potential selection bias due to nonparticipation in our sample . Using logistic regression , we modeled the probability that a sample individual participated in the ADAMS assessment as a function of covariates , such as age , sex , education , marital status , HRS cognition scores , nursing home residency , and indicators of past or existing major health conditions . We used the results of this response propensity analysis to develop nonresponse adjustments to the ADAMS sample selection weights ( 18 ) . We then constructed population sample weights to take into account the probabilities of selection in the stratified sample design and to adjust for differential nonparticipation in ADAMS ( 16 ) . Figure . Study flow diagram . ADAMS = Aging , Demographics , and Memory Study . The ADAMS data are publicly available and can be obtained from the HRS Web site ( hrsonline.isr.umich.edu ) . The institutional review boards at Duke University Medical Center and the University of Michigan approved all study procedures , and study participants or their surrogates provided informed consent . Measurements A nurse and a neuropsychology technician assessed all participants at their residence for cognitive impairment . The full details of the assessment and diagnostic procedures are described elsewhere ( 17 ) . In brief , the following information about the participant was collected from a knowledgeable informant : chronological history of cognitive symptoms , medical history , current medications , current neuropsychiatric symptoms , measures of severity of cognitive and functional impairment , and family history of memory problems . During the assessment , the participant completed a battery of neuropsychological measures ; a self-reported depression measure ; a st and ardized neurologic examination ; a blood pressure measurement ; collection of buccal DNA sample s for apolipoprotein E ( APOE ) genotyping ; and a 7-minute , videotaped segment covering portions of the cognitive status and neurologic examinations . Specific assessment measures reported here are the Mini-Mental State Examination ( 19 ) and the Dementia Severity Rating Scale ( 20 ) . The Dementia Severity Rating Scale is completed by an informant and assesses the presence and severity of impairment in 12 cognitive and functional domains . Scores range from 0 to 54 , with higher scores reflecting more impairment . We also sought medical record releases to obtain relevant neuroimaging and laboratory results from participants ' physicians . A consensus expert panel of neuropsychologists , neurologists , geropsychiatrists , and internists review ed all information collected during the in-home assessment and assigned final diagnoses . The consensus panel review ed each case and assigned a diagnosis in 2 stages , first without and then with medical records . For most cases , the consensus panel reached agreement with little discussion ; however , diagnostic agreement was more challenging for participants with little or no education or with substantial sensory or physical impairment . The medical records often provided the necessary neuroimaging results to change a diagnosis from possible Alzheimer disease or vascular dementia to probable Alzheimer disease or vascular dementia . Except for these situations , the diagnoses seldom changed after the consensus panel review ed the additional information in the medical records . Diagnoses were divided within the 3 general categories : normal cognitive function , cognitive impairment without dementia , and dementia . The consensus panel used clinical judgment to assign the final diagnosis , based on the following criteria . Dementia diagnosis was based on guidelines from the Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition ( 21 ) , and the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ( 22 ) ; diagnoses of Alzheimer disease and other types of dementia were based on currently accepted criteria ( 2326 ) . The definition of cognitive impairment without dementia and its subtypes has been developed over 17 years , primarily on the basis of the accumulated clinical experience of a group of research ers common to ADAMS and 3 other epidemiologic studies of dementia ( 2729 ) . Before ADAMS , we operationalized the definition for cognitive impairment without dementia on the basis of analyses of both neuropsychological data and an objective measure of daily function from participants with this diagnosis in our other studies ( 27 , 28 ) . We defined cognitive impairment without dementia as mild cognitive or functional impairment , reported by the participant or informant , that did not meet criteria for dementia ( that is , Dementia Severity Rating Scale score of 6 to 11 ) , or performance on neuropsychological measures that was both below expectation and at least 1.5 SDs below published norms on any test . To reflect the variation in clinical presentation and potential differences in the cause of the impairment we used 12 diagnostic subcategories for cognitive impairment without dementia , unspecified cognitive impairment without dementia : prodromal Alzheimer disease , amnestic mild cognitive impairment ( 30 , 31 ) , vascular cognitive impairment without dementia , stroke , medical conditions or sensory impairment , neurologic conditions , depression , other psychiatric disorders , low baseline intellect or learning disorder , past alcohol abuse , and current alcohol abuse ( Appendix Table 1 ) . In population -based sample s , few individuals meet the criteria typically used for amnestic mild cognitive impairment ( 30 , 31 ) . For this reason , we used the additional category of",
"BACKGROUND recent studies have found that moderate intensity exercise is an effective intervention strategy for preventing falls in older people . However , research is required to determine whether supervised group exercise programmes , conducted in community setting s with at-risk older people referred by their health care practitioner are also effective in improving physical functioning and preventing falls in this group . OBJECTIVES to determine whether participation in a weekly group exercise programme with ancillary home exercises over one year improves balance , muscle strength , reaction time , physical functioning , health status and prevents falls in at-risk community-dwelling older people . METHODS the sample comprised 163 people aged over 65 years identified as at risk of falling using a st and ardised assessment screen by their general practitioner or hospital-based physiotherapist , residing in South Western Sydney , Australia . Subjects were r and omised into either an exercise intervention group or a control group . Physical performance and general health measures were assessed at baseline and repeated 6-months into the trial . Falls were measured over a 12-month follow-up period using monthly postal surveys . RESULTS at baseline both groups were well matched in their physical performance , health and activity levels . The intervention subjects attended a median of 23 exercise classes over the year , and most undertook the home exercise sessions at least weekly . At retest , the exercise group performed significantly better than the controls in three of six balance measures ; postural sway on the floor with eyes open and eyes closed and coordinated stability . The groups did not differ at retest in measures of strength , reaction time and walking speed or on Short-Form 36 , Physical Activity Scale for the Elderly or fear of falling scales . Within the 12-month trial period , the rate of falls in the intervention group was 40 % lower than that of the control group ( IRR=0.60 , 95 % CI 0.36 - 0.99 ) . CONCLUSIONS these findings indicate that participation in a weekly group exercise programme with ancillary home exercises can improve balance and reduce the rate of falling in at-risk community dwelling older people",
"At 16 senior centers , we studied the effectiveness of exercise and cognitive-behavioral programs , compared with a discussion control program , in reducing falls and injuries among 230 older adults . After 1 year of the programs , we observed no significant difference in time to first fall . Even though a relatively high percentage ( 38.6 % ) suffered at least one fall , only 7.8 % of these community-residing elderly required medical attention . Secondary outcome measures such as strength , balance , fear of falling , and perceived health did not significantly change",
"BACKGROUND People with osteoarthritis ( OA ) of the knee experience pain and deconditioning that lead to disability . This study challenged the clinical belief that repetitive lower extremity exercise is not indicated in persons with knee OA . The effects of high-intensity and low-intensity stationary cycling on functional status , gait , overall and acute pain , and aerobic capacity were examined . METHODS Thirty-nine adults ( 71+/-6.9 years old ) with complaints of knee pain and diagnosis of OA were r and omized to either a high-intensity ( 70 % heart rate reserve [ HRR ] ) or low-intensity ( 40 % HRR ) exercise group for 10 weeks of stationary cycling . Participants cycled for 25 minutes , 3 times per week . Before and after the exercise intervention they completed the Arthritis Impact Measurement Scale 2 for overall pain assessment , underwent timed chair rise , 6-minute walk test , gait , and grade d exercise treadmill tests . Acute pain was reported daily with a visual analog scale and the Western Ontario and McMaster Universities Osteoarthritis Index scale . RESULTS Analysis of variance revealed that participants in both groups significantly improved in the timed chair rise , in the 6-minute walk test , in the range of walking speeds , in the amount of overall pain relief , and in aerobic capacity . No differences between groups were found . Daily pain reports suggested that cycling did not increase acute pain in either group . CONCLUSIONS Cycling may be considered as an alternative exercise modality for patients with knee OA . Low-intensity cycling was as effective as high-intensity cycling in improving function and gait , decreasing pain , and increasing aerobic capacity",
"OBJECTIVE To determine the effect on balance and strength of 3 months of intensive balance and /or weight training followed by 6 months of low intensity Tai Chi training for maintenance of gains . DESIGN R and omized control intervention . Four groups in 2 x 2 design : Control , Balance , Strength , Balance + Strength , using blinded testers . SETTING Exercise and balance laboratory at University of Connecticut Health Center . PARTICIPANTS Subjects were 110 healthy community dwellers ( mean age 80 ) who were free of dementia , neurological disease , and serious cardiovascular or musculoskeletal conditions . INTERVENTIONS Short-term training ( 3 months ) occurred 3 times/week ( 45 minutes Balance and Strength , 90 minutes Balance + Strength ) . Balance training included equilibrium control exercises of firm and foam surfaces and center-of-pressure biofeedback . Strengthening consisted of lower extremity weight-lifting . All subjects than received long-term group Tai Chi instruction ( 6 months , 1 hour , 1 time/week ) . MEASUREMENTS Losses of balance during Sensory Organization Testing ( LOB ) , single stance time ( SST ) , voluntary limits of stability ( FBOS ) , summed isokinetic torque of eight lower extremity movements ( ISOK ) , and usual gait velocity ( GVU ) . RESULTS AND CONCLUSIONS Balance training meaningfully improved all balance measures by restoring performance to a level analogous to an individual 3 to 10 years younger : LOB = -2.0 + /- 0.3 ( adjusted paired differences , P ISOK by 1.1 + /- 0.1 Nm kg-1 ( P Tai Chi , although there was some decrement",
"BACKGROUND Among elderly persons , falls account for 87 % of all fractures and are contributing factors in many nursing home admissions . This study evaluated the effect of an easily implemented , low-intensity exercise program on the incidence of falls and the time to first fall among a clinical ly defined population of elderly men and women . METHODS This community-based , r and omized trial compared the exercise intervention with a no-intervention control . The participants were 294 men and women , aged 60 years or older , who had either a hospital admission or bed rest for 2 days or more within the previous month . Exercise participants were scheduled to attend exercise sessions lasting 45 minutes , including warm-up and cool-down , 3 times a week for 8 weeks ( 24 sessions ) . Assessment s included gait and balance measures , self-reported physical function , the number of medications being taking at baseline , participant age , sex , and history of falling . Falls were tracked for 1 year after each participant 's baseline assessment . RESULTS 29 % of the study participants reported a fall during the study period . The effect of exercise in preventing falls varied significantly by baseline physical function level ( p risk for falls decreased for exercise participants with low baseline physical functioning ( hazard ratio,.51 ) but increased for exercise participants with high baseline physical functioning ( hazard ratio , 3.51 ) . CONCLUSIONS This easily implemented , low-intensity exercise program appears to reduce the risk for falls among elderly men and women recovering from recent hospitalizations , bed rest , or both who have low levels of physical functioning",
"BACKGROUND The authors ' objective was to evaluate the efficacy of a 6-month Tai Chi intervention for decreasing the number of falls and the risk for falling in older persons . METHODS This r and omized controlled trial involved a sample of 256 physically inactive , community-dwelling adults aged 70 to 92 ( mean age , 77.48 years ; st and ard deviation , 4.95 years ) who were recruited through a patient data base in Portl and , Oregon . Participants were r and omized to participate in a three-times-per-week Tai Chi group or to a stretching control group for 6 months . The primary outcome measure was the number of falls ; the secondary outcome measures included functional balance ( Berg Balance Scale , Dynamic Gait Index , Functional Reach , and single-leg st and ing ) , physical performance ( 50-foot speed walk , Up&Go ) , and fear of falling , assessed at baseline , 3 months , 6 months ( intervention termination ) , and at a 6-month postintervention follow-up . RESULTS At the end of the 6-month intervention , significantly fewer falls ( n=38 vs 73 ; p=.007 ) , lower proportions of fallers ( 28 % vs 46 % ; p=.01 ) , and fewer injurious falls ( 7 % vs 18 % ; p=.03 ) were observed in the Tai Chi group compared with the stretching control group . After adjusting for baseline covariates , the risk for multiple falls in the Tai Chi group was 55 % lower than that of the stretching control group ( risk ratio,.45 ; 95 % confidence interval , 0.30 to 0.70 ) . Compared with the stretching control participants , the Tai Chi participants showed significant improvements ( p functional balance , physical performance , and reduced fear of falling . Intervention gains in these measures were maintained at a 6-month postintervention follow-up in the Tai Chi group . CONCLUSIONS A three-times-per-week , 6-month Tai Chi program is effective in decreasing the number of falls , the risk for falling , and the fear of falling , and it improves functional balance and physical performance in physically inactive persons aged 70 years or older",
"BACKGROUND The purpose of this efficacy study was to measure the dose-response effect of a free weight-based resistance training program by comparing the effects of two training intensities ( low-moderate and high ) of the knee extensor ( KE ) muscles on muscle function , functional limitations , and self-reported disability . METHODS The authors conducted a single-blinded , r and omized , placebo-controlled trial . Twenty-two institutionalized elders ( mean age , 81.5 years ) were assigned to either high-intensity strength training ( HI ; n = 8) , low-moderate intensity strength training ( LI ; n = 6 ) , or weight-free placebo-control training ( PC ; n = 8) . The HI group trained at 80 % of their 1-repetition maximum and the LI group trained at 40 % . All groups performed 3 sets of 8 repetitions , 3 times per week for 10 weeks . Outcome measures included KE maximal strength , KE endurance , and functional performance as assessed by 6-minute walking , chair-rising , and stair-climbing tests , and by self-reported disability . RESULTS KE strength and endurance , stair-climbing power , and chair-rising time improved significantly in the HI and LI groups compared with the PC group . Six-minute walking distance improved significantly in the HI group but not in the LI group compared with the PC group . Changes observed in HI were significantly different from those observed in the LI group for KE strength and endurance and the 6-minute walking test , with a trend in the same direction for chair-rising and stair-climbing . Changes in strength were significantly related to changes in functional outcomes , explaining 37 % to 61 % of the variance . CONCLUSIONS These results show strong dose-response relationships between resistance training intensity and strength gains , and between strength gains and functional improvements after resistance training . Low-moderate intensity resistance training of the KE muscles may not be sufficiently robust from a physiologic perspective to achieve optimal improvement of functional performance . Supervised HI , free weight-based training for frail elders appears to be as safe as lower intensity training but is more effective physiologically and functionally",
"OBJECTIVE To test the hypothesis that increased gait variability predicts falls among community-living older adults attending an outpatient clinic . DESIGN Prospect i ve , cohort study . SETTING Three outpatient geriatric clinics . PARTICIPANTS Fifty-two community-living , ambulatory men and women aged > or = 70 years . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Subjects walked at a normal pace for up to 6 minutes wearing force-sensitive insoles that measured the gait rhythm on a stride-to-stride basis . Afterward , subjects reported fall status on a weekly basis for 1 year . The primary outcomes were the association between measures of the stride-to-stride fluctuations in gait rhythm and ( 1 ) subsequent falls during a 12-month follow-up period and ( 2 ) potential contributing factors . RESULTS Almost 40 % of the subjects reported falling during the 12-month follow-up period . Stride time variability was 106 + /- 30 ms in subjects who subsequently fell ( n = 20 ) and 49 + /- 4 ms in those who did not experience a fall ( n = 32 ) during the 12-month follow-up period ( p stride time variability predicted falls ( p Stride time variability correlated significantly with multiple factors including strength , balance , gait speed , functional status , and even mental health , but these other measures did not discriminate future fallers from nonfallers . CONCLUSIONS These findings show both the feasibility of obtaining stride-to-stride measures of gait timing in the ambulatory setting and the potential use of gait variability measures in augmenting the prospect i ve evaluation of fall risk in community-living older adults",
"Context Some studies suggest that people with high levels of physical activity are less likely to develop dementia . Content All 1740 participants in this cohort study were 65 years of age or older and were cognitively intact at baseline . Over 6.2 years , the rate of dementia was 13.0 per 1000 person-years in those who exercised 3 or more times per week and 19.7 per 1000 person-years in those who exercised less than 3 times per week . Limitations The only measure of exercise intensity was self-reported frequency . The cohort was largely white and well-educated . Implication s This study adds to the evidence that regular exercise is associated with a lower risk for dementia . However , the existing evidence does not prove that regular exercise is associated with a lower dementia risk . The Editors Alzheimer disease and other dementing illnesses are major sources of morbidity and mortality ( 1 - 3 ) that affect millions of persons in the increasingly aging society of the United States . Research design ed to discover strategies to delay onset and progression of these potentially devastating illnesses is ongoing worldwide . Effective prevention strategies would result in substantial benefits through improved quality of life , prolonged independent life expectancy , and reduced economic cost and social burdens . Regular physical exercise is an important element in overall health promotion ( 4 ) and might also be an effective strategy to delay onset of dementia ( 5 ) . A biological basis for how physical exercise might preserve brain function includes improved cerebral blood flow and oxygen delivery ( 6 ) and inducing fibroblast growth factor in the hippocampus ( 7 ) . More recent evidence suggests that reduced loss of hippocampal brain tissue in the aging brain is related to level of physical fitness ( 8) . Evidence from some longitudinal studies and r and omized trials suggests that physical exercise enhances cognitive function in older adults ( 9 - 15 ) , whereas other studies have failed to observe the benefits of physical exercise in preserving cognitive function ( 16 - 19 ) . Many people regard Alzheimer disease as one of the most dreaded consequences of aging . If regular physical exercise were shown to be effective in reducing the risk or delaying the onset of dementing illnesses , it would be another compelling reason to promote physical exercise . Few population -based longitudinal studies have examined the role of physical exercise on the risk for dementia in elderly persons . One recent longitudinal study showed that physical exercise was associated with decreased risk for decline in cognitive function ( odds ratio [ OR ] , 0.58 ) , Alzheimer disease ( OR , 0.50 ) , and any dementia ( OR , 0.63 ) ( 11 ) , whereas another longitudinal study showed no association between physical exercise and dementia ( 16 ) . More recent studies showed that walking was associated with a reduced risk for dementia and Alzheimer disease in a cohort of Japanese-American men ( 20 ) and that engaging in more diverse physical activities was associated with a reduced risk for dementia in the Cardiovascular Health Study ( 21 ) . The purpose of this study was 2-fold : 1 ) to determine whether regular exercise is associated with a reduced risk for incidence of dementia ( in particular , Alzheimer disease ) in a cohort followed biennially over 6 years and 2 ) to examine whether the association of physical exercise with incident dementia is modulated by other potential risk factors , such as depression , cardiovascular and cerebrovascular disease , diabetes , apolipoprotein E 4 allele , cognitive function , physical function , self-rated health , and lifestyle characteristics . Methods Study Sample The Adult Changes in Thought ( ACT ) study is a population -based , longitudinal study of aging and dementia . The ACT study was design ed to determine the incidence of Alzheimer disease , other types of dementia , and cognitive impairment as well as to determine risk factors for these conditions . The details of the ACT study have been described elsewhere ( 22 , 23 ) . Briefly , a r and om sample of 6782 individuals was drawn from Seattle-area members of Group Health Cooperative ( GHC ) , a consumer-governed health maintenance organization . The participants were 65 years of age and older when the study began in 1994 to 1996 . Those who had an existing diagnosis of dementia , were current residents of a nursing home , or were participating in other studies were ineligible ( n= 1360 ) . Of 5422 eligible persons , 2581 participated and 2841 declined participation . Age , sex , and ethnicity of the remaining 2581 participants did not differ significantly from those who were excluded . Nonresponse has been described elsewhere ( 22 ) . Declining to participate was more common among the oldest age group ( > 85 years ) , women , and African-American and minority groups ( 22 ) . Additional details regarding the incident rates of dementia and Alzheimer disease from the ACT study have been published elsewhere and are consistent with rates reported in U.S. and European cohort studies ( 22 ) . The institutional review boards of the University of Washington and Group Health Cooperative approved the ACT study . Participants received the Cognitive Ability Screening Instrument ( CASI ) ( 24 ) as initial screening for cognitive function and were interviewed with structured question naires to obtain data , including demographic characteristics , medical history , memory and general functioning , and potential epidemiologic risk factors . Persons scoring 86 or higher on the CASI were entered directly into the ACT cohort as being cognitively intact . ( The CASI scores range from 0 to 100 ; a score of 86 corresponds to a Mini-Mental State Examination score of 25 to 26 . ) Persons with a score lower than 86 had additional medical record review and st and ardized clinical and neuropsychological evaluation for dementia . Persons who did not meet established criteria for dementia ( 25 ) were included in the ACT cohort . The current study sample was selected from the 2581 ACT participants to examine the temporal relationship of physical exercise preceding development of dementia . By design , we selected the 1895 persons whose CASI scores were above the 25th percentileCASI scores 91 to 100 . We excluded 686 persons whose CASI scores were in the lowest quartileCASI scores 62 to 90because the lowest quartile group might include persons who had mild cognitive impairment or impending dementia ( 26 ) . We did not collect information about the history of exercise before the participants entered the study . Therefore , in the group with low CASI scores , we could not be certain whether a reported low level of physical exercise preceded the development of dementia or was a consequence of the development of cognitive impairment or dementia . Of 1895 participants selected , 155 withdrew after the baseline visit and did not have a follow-up examination and were thus excluded from the analyses , leaving the analytic sample of 1740 persons . Incident Dementia We conducted biennial examinations to identify cases of incident dementia , when participants were rescreened with the CASI . Those who scored 86 or higher on the CASI remained in the ACT cohort . Scores on the CASI that were less than 86 at follow-up prompted a full st and ardized clinical examination . The results of rescreening by the CASI and by the clinical and neuropsychological examinations were review ed at a consensus diagnosis conference that included at least the examining physician , a neuropsychologist , another study physician , and the study nurse . Persons who did not meet the criteria for dementia were considered as not having dementia and were followed in the ACT cohort ( 22 , 23 ) . Persons who met the Diagnostic and Statistical Manual of Mental Disorders , fourth edition ( DSM-IV ) , criteria ( 25 ) for dementia were considered to have incident dementia . Dementia type was determined by the National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer 's Disease and Related Disorders Association ( NINCDS-ADRDA ) criteria ( 27 ) for Alzheimer disease and by the DSM-IV criteria ( 25 ) for other types of dementia . Level of physical activity was not considered at the consensus conference . Physical Exercise Physical exercise was assessed at baseline by asking participants the number of days per week they did each of the following activities for at least 15 minutes at a time during the past year : walking , hiking , bicycling , aerobics or calisthenics , swimming , water aerobics , weight training or stretching , or other exercise . The frequency of exercise was calculated by the times per week that participants engaged in any of these forms of exercise . In this study , persons who exercised at least 3 times a week , above the lowest quartile , were classified as exercising regularly . Baseline Variables as Potential Confounders Numerous factors may influence the relationship between exercise and risk for dementia , including physical functioning , cognitive function , depression , health conditions , and lifestyle characteristics . Physical function was assessed by a performance-based physical function ( PPF ) test ( 23 ) , which consisted of 4 performance tests : 10-foot timed walk , time to st and from a seated position in a chair to a st and ing position 5 times , balance test , and grip strength in the dominant h and . Each test was scored from 0 to 4 points . The final PPF score was the sum of the scores for the 4 performance tests and ranged from 0 to 16 ; higher scores indicated better physical function . Details of the PPF test have been reported elsewhere ( 23 ) . Cognitive function was assessed by using the CASI , which provides quantitative assessment of attention , concentration , orientation , short-term memory , long-term memory , language ability , visual construction , list-generating fluency , abstract ion , and judgment ( 24 ) . At baseline , depression was measured by using the 11-item Center for Epidemiologic Studies Depression ( CES-D ) scale ( 28 ) . The CES-D scores ranged from 0 to 33 , with higher scores",
"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",
"Background / Aims : Inconsistencies in the relationship between depression and cognitive decline may exist because the expected cognitive domains at risk have not been specified in previous study design s. We aim ed to examine the relationship between depressive symptoms and verbal episodic memory functioning over time . Methods : Data from a prospect i ve cohort study ( Health and Retirement Study ; 1998–2004 ; n = 18,465 ) , a multistage national probability sample of older adults in the United States , were analyzed . Verbal learning and memory of a 10-word list learning task were the main outcomes . Depressive symptoms ( Center for Epidemiologic Studies – Depression Scale ) constituted the main predictor . Results : Depressive symptoms were associated with significantly lower immediate ( –0.05 ; p and delayed ( –0.06 ; p after controlling for demographics and baseline and time-varying cardiovascular disease risks and diseases . Conclusions : In this US national study of older adults , elevated depressive symptoms were associated with declines in episodic learning and memory over time . These associations were little affected by the demographic or medical conditions considered in this study . The results suggest that learning and memory decline may be a long-term feature associated with depressive symptoms among the nation ’s older adult population",
"OBJECTIVES To determine whether an intervention that combines low-intensity exercise and incontinence care offsets some of its costs by reducing the incidence of selected health conditions in nursing home residents . DESIGN R and omized , controlled trial with the incidence and costs of selected , acute conditions compared between a 6-month baseline and an 8-month intervention phase . SETTING Four nursing homes . PARTICIPANTS One hundred ninety incontinent , long-stay nursing home residents . INTERVENTION Low-intensity , functionally oriented exercise and incontinence care were provided every 2 hours from 8:00 a.m. to 4:00 p.m. for 5 days a week for 8 months . MEASUREMENTS Predefined acute conditions hypothesized to be related to physical inactivity , incontinence , or immobility were abstract ed from residents ' medical records by blinded observers during a 6-month baseline period and throughout the 8-month intervention . Conditions included those in the dermatological , genitourinary , gastrointestinal , respiratory and cardiovascular systems ; falls ; pain ; and psychiatric and nutritional disturbances . Costs were determined using Current Procedural Terminology Center and Medicare allowable cost reimbursement at a rate of 80 % . RESULTS The intervention group had significantly better functional outcomes than the control group ( strength , mobility endurance , urinary and fecal incontinence ) and a reduction of 10 % in the incidence of the acute conditions , which was not significant . There were no significant differences between groups in the cost of assessing and treating these acute conditions between baseline and intervention . CONCLUSION The intervention , which is consistent with federal and clinical practice guidelines , significantly improved functional outcomes but did not reduce the incidence and costs of selected acute health conditions . The cost of implementing these labor-intensive interventions for frail nursing home residents will have to be justified based on functional and quality -of-life outcomes and are unlikely to be offset by savings in medical care costs in this population",
"OBJECTIVES To identify the characteristics of elderly persons who develop a fear of falling after experiencing a fall and to investigate the association of this fear with changes in health status over time . DESIGN A prospect i ve study of falls over a 2-year period ( 1991 - 92 ) . Falls were ascertained using bimonthly postcards plus telephone interview with a st and ardized ( World Health Organisation ) question naire for circumstances , fear of falling and consequences of each reported fall . Each participant underwent a physical exam and subjective health assessment each year form 1990 to 1993 . SETTING New-Mexico Aging Process Study , USA . SUBJECTS 487 elderly subjects ( > 60 years ) living independently in the community . MAIN OUTCOME MEASURES Fear of falling after experiencing a fall . RESULTS 70 ( 32 % ) of 219 subjects who experienced a fall during the 2 year study period reported a fear of falling . Women were more likely than men to report fear of falling ( 74 % vs 26 % ) . Fallers who were afraid of falling again had significantly ore balance ( 31.9 % vs 12.8 % ) and gait disorders ( 31.9 % vs 7.4 % ) at entry in the study in 1990 . Among sex , age , mental status , balance and gait abnormalities , economic re source and physical health , logistic regression analysis show gait abnormalities and poor self-perception of physical health , cognitive status and economic re sources to be significantly associated with fear of falling . Subjects who reported a fear of falling experienced a greater increase in balance ( P = 0.08 ) , gait ( P cognitive disorders ( P = 0.09 ) over time , result ing in a decrease in mobility level . CONCLUSION The study indicated that about one-third of elderly people develop a fear of falling after an incident fall and this issue should be specifically addressed in any rehabilitation programme",
"The terminal decline hypothesis states that in the proximity of death , an individual 's decline in cognitive abilities accelerates . We aim ed at estimating the onset of faster rate of decline in global cognition using Mini Mental State Examination ( MMSE ) scores from participants of the Cambridge City over 75 Cohort Study ( CC75C ) , a U.K. population -based longitudinal study of aging where almost all participants have died . The r and om change point model fitted to MMSE scores structured as a function of distance to death allowed us to identify a potentially different onset of change in rate of decline before death for each individual in the sample . Differences in rate of change before and after the onset of change in rate of decline by sociodemographic variables were investigated . On average , the onset of a faster rate of change occurred about 7.7 years before death and varied across individuals . Our results show that most individuals experience a period of slight decline followed by a much sharper decline . Education , age at death , and cognitive impairment at study entry were identified as modifiers of rate of change before and after change in rate of decline . Gender differences were found in rate of decline in the final stages of life . Our study suggests that terminal decline is a heterogeneous process , with its onset varying between individuals",
"BACKGROUND Depression is common in later life . AIMS To determine whether exercise is effective as an adjunct to antidepressant therapy in reducing depressive symptoms in older people . METHOD Patients were r and omised to attend either exercise classes or health education talks for 10 weeks . Assessment s were made \" blind \" at baseline , and at 10 and 34 weeks . The primary outcome was seen with the 17-item Hamilton Rating Scale for Depression ( HRSD ) . Secondary outcomes were seen with the Geriatric Depression Scale , Clinical Global Impression and Patient Global Impression . RESULTS At 10 weeks a significantly higher proportion of the exercise group ( 55 % v. 33 % ) experienced a greater than 30 % decline in depression according to HRSD ( OR=2.51 , P=0.05 , 95 % CI 1.00 - 6.38 ) . CONCLUSIONS Because exercise was associated with a modest improvement in depressive symptoms at 10 weeks , older people with poorly responsive depressive disorder should be encouraged to attend group exercise activities",
"BACKGROUND The role of walking , as compared with vigorous exercise , in the prevention of coronary heart disease remains controversial , and data for women on this topic are sparse . METHODS We prospect ively examined the associations between the score for total physical activity , walking , and vigorous exercise and the incidence of coronary events among 72,488 female nurses who were 40 to 65 years old in 1986 . Participants were free of diagnosed cardiovascular disease or cancer at the time of entry and completed serial detailed question naires about physical activity . During eight years of follow-up , we documented 645 incident coronary events ( nonfatal myocardial infa rct ion or death from coronary disease ) . RESULTS There was a strong , grade d inverse association between physical activity and the risk of coronary events . As compared with women in the lowest quintile group for energy expenditure ( expressed as the metabolic-equivalent [ MET ] score ) , women in increasing quintile groups had age-adjusted relative risks of 0.77 , 0.65 , 0.54 , and 0.46 for coronary events ( P for trend risk of coronary events ; women in the highest quintile group for walking , who walked the equivalent of three or more hours per week at a brisk pace , had a multivariate relative risk of 0.65 ( 95 percent confidence interval , 0.47 to 0.91 ) as compared with women who walked infrequently . Regular vigorous exercise ( > or = 6 MET ) was associated with similar risk reductions ( 30 to 40 percent ) . Sedentary women who became active in middle adulthood or later had a lower risk of coronary events than their counterparts who remained sedentary . CONCLUSIONS These prospect i ve data indicate that brisk walking and vigorous exercise are associated with substantial and similar reductions in the incidence of coronary events among women",
"To study risk factors for falling , we conducted a one-year prospect i ve investigation , using a sample of 336 persons at least 75 years of age who were living in the community . All subjects underwent detailed clinical evaluation , including st and ardized measures of mental status , strength , reflexes , balance , and gait ; in addition , we inspected their homes for environmental hazards . Falls and their circumstances were identified during bimonthly telephone calls . During one year of follow-up , 108 subjects ( 32 percent ) fell at least once ; 24 percent of those who fell had serious injuries and 6 percent had fractures . Predisposing factors for falls were identified in linear-logistic models . The adjusted odds ratio for sedative use was 28.3 ; for cognitive impairment , 5.0 ; for disability of the lower extremities , 3.8 ; for palmomental reflex , 3.0 ; for abnormalities of balance and gait , 1.9 ; and for foot problems , 1.8 ; the lower bounds of the 95 percent confidence intervals were 1 or more for all variables . The risk of falling increased linearly with the number of risk factors , from 8 percent with none to 78 percent with four or more risk factors ( P less than 0.0001 ) . About 10 percent of the falls occurred during acute illness , 5 percent during hazardous activity , and 44 percent in the presence of environmental hazards . We conclude that falls among older persons living in the community are common and that a simple clinical assessment can identify the elderly persons who are at the greatest risk of falling",
"OBJECTIVE The role of exercise in the prevention of falls and fall-related injuries among elderly persons is unclear . The objective of this study was to assess the response to an exercise-based rehabilitation program intended to improve balance and mobility and reduce or prevent falls . DESIGN Pretest-posttest experimental design with repeated measures at baseline , immediately postintervention , and 6 months postintervention . To assess the effect of repeated exposure to our main outcome measure ( the obstacle course ) , half of the participants ( r and omly selected ) were allowed to practice on the obstacle course . SETTING A veterans affairs medical center . PARTICIPANTS Elderly , ambulatory , community-dwelling volunteers recruited from among local out patients at our medical center . INTERVENTION Sixty-five volunteers completed a 6-week supervised low to moderate intensity program of stretching , postural control , endurance walking , and coordination exercises design ed to improve balance and mobility . Participants were divided into 2 groups : 34 participants who did not practice on the obstacle course during their exercise program and 31 participants who practice d on the obstacle course in addition to their otherwise identical exercise program . MAIN OUTCOME MEASURES Performance on a functionally oriented obstacle course and self-reported falls and fall-related injuries . RESULTS No significant performance differences were found between the two groups . After intervention , mean qualitative obstacle course scores improved modestly ( 5 % ) and mean obstacle course completion time decreased by 15 % from baseline . These postintervention pairwise performance differences were clinical ly important but not statistically significant . Relative to baseline levels , postintervention falls and injuries did not change significantly . CONCLUSIONS Our exercise intervention may have the potential to improve functional performance . However , some modifications are necessary to enhance efficacy . The obstacle course may be a useful tool in the evaluation of elderly persons with balance and mobility impairment in the rehabilitation setting",
"This study looked at the effect of a single session of mild exercise in a group of cognitively unimpaired institutionalized elderly patients , aged 70 + , on tests of cognitive performance . Results indicate that mild exercise , such as range-of-motion , does improve the ability to recall and that the effect lasts for at least half an hour . Mild exercise programmes appear to be a practical , low-cost nursing intervention that can enhance memory and independence . Programmes that are design ed to meet individual needs and that are incorporated into daily routine and activities without imposing extra effort or inconvenience are more appealing to elderly patients . Exercise can be easily learned and implemented by nurses , personal care attendants or nurse aides . This is an extremely important consideration in a health care system that dem and s low-cost quality care",
"OBJECTIVE Because of the rapid aging of the population and inconsistent findings of previous epidemiological studies in Hong Kong , a prevalence study of depression among older adults was timely . The authors assessed the prevalence of depression among older adults and identified factors associated with it . METHODS The authors interviewed a r and om representative sample of 917 community-dwelling Chinese adults age 60 and over . The 15-item Chinese Geriatric Depression Scale with a cutoff of > or = 8 was used to identify clinical ly significant depression in the older adults . RESULTS The authors found that 11.0 % and 14.5 % of older Chinese men and women , respectively , scored above the cutoff , a prevalence rate similar to those found in other countries , including the United States , Engl and , and Finl and . Factors that were associated with an increased likelihood of depression among older adults included poor self-rated health , long-term pain , vision problems , higher level of impairment in activities of daily living , residing in Hong Kong less than 20 years , financial strain , and having less social support . CONCLUSIONS The prevalence rate of depression among older Chinese adults in Hong Kong is more or less similar to rates found in Western countries . The data suggest that older adults who receive less social support are more likely to be depressed",
"CONTEXT Five-year survival rates for early stage colorectal , breast , and prostate cancer currently exceed 90 % and are increasing . Cancer survivors are at greater risk for second malignancies , other comorbidities , and accelerated functional decline . Lifestyle interventions may provide benefit , but it is unknown whether long-term cancer survivors can modify their lifestyle behaviors sufficiently to improve functional status . OBJECTIVE To determine whether a telephone counseling and mailed print material -based diet and exercise intervention is effective in reorienting functional decline in older , overweight cancer survivors . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial of 641 overweight ( body mass index > or = 25 and or = 5 years ) survivors ( aged 65 - 91 years ) of colorectal , breast , and prostate cancer , who were r and omly assigned to an intervention group ( n = 319 ) or delayed intervention ( control ) group ( n = 322 ) in Canada , the United Kingdom , and 21 US states . Individuals were recruited for the Reach out to Enhance Wellness ( RENEW ) trial from July 1 , 2005 , through May 17 , 2007 . INTERVENTION A 12-month , home-based tailored program of telephone counseling and mailed material s promoting exercise , improved diet quality , and modest weight loss . The control group was wait-listed for 12 months . MAIN OUTCOME MEASURES Change in self-reported physical function on the Short-Form 36 physical function subscale ( score range , 0 - 100 ; a high score indicates better functioning ) from baseline to 12 months was the primary end point . Secondary outcomes included changes in function on the basic and advanced lower extremity function subscales of the Late Life Function and Disability Index ( score range , 0 - 100 ) , physical activity , body mass index , and overall health-related quality of life . RESULTS The mean baseline Short-Form 36 physical function score was 75.7 . At the 12-month follow-up , the mean function scores declined less rapidly in the intervention group ( -2.15 ; 95 % confidence interval [ CI ] , -0.36 to -3.93 ) compared with the control group ( -4.84 ; 95 % CI , -3.04 to -6.63 ) ( P = .03 ) . The mean baseline basic lower extremity function score was 78.2 . The mean changes in basic lower extremity function were 0.34 ( 95 % CI , -0.84 to 1.52 ) in the intervention group compared with -1.89 ( 95 % CI , -0.70 to -3.09 ) in the control group ( P = .005 ) . Physical activity , dietary behaviors , and overall quality of life increased significantly in the intervention group compared with the control group , and weight loss also was greater ( 2.06 kg [ 95 % CI , 1.69 to 2.43 kg ] vs 0.92 kg [ 95 % CI , 0.51 to 1.33 kg ] , respectively ; P Among older , long-term survivors of colorectal , breast , and prostate cancer , a diet and exercise intervention reduced the rate of self-reported functional decline compared with no intervention . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00303875",
"BACKGROUND Pharmacological treatment of depression in geriatric patients is often difficult . Although unsupervised exercise has been shown to benefit younger depressed patients , there is no evidence that unsupervised exercise can be used as a maintenance treatment for depression in elderly patients . Our aim was to test the feasibility and efficacy of unsupervised exercise as a long-term treatment for clinical depression in elderly patients . METHODS We studied 32 subjects ( 71.3 + /- 1.2 years of age , mean + /- SE ) in a 20-week , r and omized , controlled trial , with follow-up at 26 months . Subjects were community-dwelling patients with major or minor depression or dysthymia . Exercisers engaged in 10 weeks of supervised weight-lifting exercise followed by 10 weeks of unsupervised exercise . Controls attended lectures for 10 weeks . No contact was made with either group after 20 weeks until final follow-up . Blinded assessment was made with the Beck Depression Inventory ( BDI ) , the Philadelphia Geriatric Morale Scale , and Ewart 's Self Efficacy Scale at 20 weeks and with the BDI and physical activity question naire at 26 months . RESULTS Patients r and omized to the exercise condition completed 18 + /- 2 sessions of unsupervised exercise during Weeks 10 to 20 . The BDI was significantly reduced at both 20 weeks and 26 months of follow-up in exercisers compared with controls ( p weight lifting , versus 0 % of controls ( p Unsupervised weight-lifting exercise maintains its antidepressant effectiveness at 20 weeks in depressed elderly patients . Long-term changes in exercise behavior are possible in some patients even without supervision",
"PURPOSE To compare the effects of functional home exercise of repeated sit-to-st and s with low-intensity progressive resistance training , on performance measures in mobility-limited adults over 80 years of age . SETTING Participants ' homes . DESIGN Community-dwelling older adults > or = 80 years of age were invited to participate in a r and omised controlled clinical trial . Baseline and outcome measures were : comfortable gait velocity , 30-s chair-st and test , 15-s step test , Berg Balance Scale , Modified Falls Efficacy Scale and the Late-Life Function and Disability Instrument-function component . Participants r and omised to the intervention group performed repeated sit-to-st and s using a Gr and St and System ; a biofeedback device that recorded and displayed the number of repetitions performed . Participants r and omised to the control group performed knee extensions using ankle cuff weights . Both groups performed the exercises daily for 6 weeks . RESULTS Sixty-six older adults took part . The intervention group had a statistically significant improvement in Berg Balance Scale mean score , 1.67 + /- 2.64 points , P = 0.001 ( control group 0.73 + /- 3.63 points , P = 0.258 ) , indicating an improvement in balance over the 6-week exercise period . There was no statistically significant effect of either intervention on the other outcome measures . CONCLUSIONS In a highly variable population of older adults with mobility limitations , low-intensity functional home exercise of repeated sit-to-st and s using the Gr and St and System improved Berg Balance Scale score while low-intensity progressive resistance training did not . While statistically significant , the improvement in Berg Balance Scale score was modest raising the issue of what extent of change in score is clinical ly significant in this population",
"Background : Falls are among the leading causes of injuries and deaths . Results from a number of studies have suggested that a community-based exercise program may be effective in improving lower body strength , although some have shown only limited improvements . However , the impact of these programs on gait and balance are equivocal . Further , studies that have specifically targeted deconditioned elderly individuals , rather than individuals drawn from the general community , either showed limited or no improvements in gait and balance . Objective : This study examined the effectiveness of a community-based , short-term , low-intensity exercise intervention strategy on measures of mobility skills , gait and balance , and muscle strength for a clinical ly targeted group of elderly individuals at high risk of falls . Methods : 245 men and women aged 60 years or older were r and omized into either an intervention or control group and received a baseline ( T1 ) assessment . Subjects in the intervention group received up to 24 sessions ( 45 min long ) of low-intensity st and ard exercise modalities tailored to the individual patient over an 8- to 10-week period . At the conclusion of the program , the participants in the intervention group were instructed to continue performing the exercises at home until 1 year after T1 . Measures of physical function and performance were collected for all subjects at three different points of study enrollment . Results : Of the subjects assessed at baseline , 138 ( 56 % ) also had a postintervention assessment ( T2 ) , 128 ( 52 % ) had a 6-month follow-up assessment ( T3 ) , and 105 subjects had assessment s at all time points . Primary analyses were based on the 105 subjects who had assessment s at all time points . Intervention and control subjects did not differ in any of the physical function or performance measures at baseline . Between T1 and T2 , the intervention subjects showed significantly greater improvement than the control subjects on all outcomes , with improvements plateauing for most measures between T2 and T3 . Gait and balance scores continued to improve throughout the study period for both groups of subjects . Conclusions : This easily implemented , low-intensity exercise program may lead to improvements in physical functioning that are retained over the long term and effectively targets a clinical ly defined population of deconditioned elders at high risk of falling and sustaining serious injury",
"OBJECTIVE To examine the effects of a 3-month low-intensity exercise program on physical frailty . DESIGN R and omized clinical trial . SETTING Regional tertiary-care hospital and academic medical center with an outpatient rehabilitation fitness center . PARTICIPANTS Eighty-four physically frail older adults ( mean age , 83 + /- 4 yrs ) . INTERVENTION Three-month low-intensity supervised exercise ( n = 48 ) versus unsupervised home-based flexibility activities ( n = 36 ) . MAIN OUTCOME MEASURES Physical performance test , measures of balance , strength , flexibility , coordination , speed of reaction , peripheral sensation . RESULTS Significant improvement was made by the exercise group on our primary indicator of frailty , a physical performance test ( PPT ) ( 29 + /- 4 vs 31 + /- 4 out of a possible 36 points ) , as well as many of the risk factors previously identified as contributors to frailty ; eg , reductions in flexibility , strength , gait speed , and poor balance . Although the home exercise control group showed increases in range of motion , the improvements in flexibility did not translate into improvements in physical performance capacity as assessed by the PPT . CONCLUSIONS Our results suggest that physical frailty is modifiable with a program of modest activities that can be performed by virtually all older adults . They also indicate that exercise programs consisting primarily of flexibility activities are not likely to reverse or attenuate physical frailty . Although results suggest that frailty is modifiable , it is not likely to be eliminated with exercise , and efforts should be directed toward preventing the condition",
"INTRODUCTION An important mechanism by which physical activity reduces the risk of cardiovascular disease is through regulating plasma lipids . We investigated whether low-intensity exercise modulates lipid metabolism and the transcription factors peroxisome proliferator-activated receptor gamma ( PPARgamma ) and liver X receptor alpha ( LXRalpha ) responsible for controlling reverse cholesterol transport ( RCT ) . METHODS Thirty-four sedentary adults , mean age 45.6 + /- 11.1 yr , participated in an 8-wk low-intensity exercise program consisting of walking 10,000 steps , three times a week . Subjects were r and omly allocated to either an exercise group or a sedentary control group , and serum lipid or lipoprotein concentrations were determined . RESULTS Compared with controls , there was a significant decrease in total cholesterol ( preexercise , 5.73 + /- 1.39 mmol x L ; postexercise , 5.32 + /- 1.28 mmol x L ) and a significant increase in HDL ( preexercise , 1.46 + /- 0.47 mmol x L ; postexercise , 1.56 + /- 0.50 mmol x L ) after the exercise program . There was a significant increase in serum oxidized LDL ( oxLDL ) concentrations in the exercise group before and after exercise ( 0 wk , 554 + /- 107 ng x mL ; 4 wk , 698 + /- 134 ng x mL ; 8 wk , 588 + /- 145 ng x mL ) . A significant increase in leukocyte mRNA expression for PPARgamma ( 4 wk , 1.8 + /- 0.9-fold ; 8 wk , 4.3 + /- 1.9-fold ) was observed , which was reinforced by increased PPARgamma DNA-binding activity postexercise ( preexercise , 0.22 + /- 0.09 OD units ; postexercise , 1.13 + /- 0.29 OD units ) . A significant increase in gene expression was observed for the oxLDL scavenger receptor CD36 ( 4 wk , 3.8 + /- 0.6-fold ; 8 wk , 2.7 + /- 0.5-fold ) and LXRalpha ( 8 wk , 3.5 + /- 0.8-fold ) . Two LXRalpha-regulated genes involved in RCT , namely , ATP-binding cassette transporters A1 and GI ( ABCA1 and ABCG1 , respectively ) , were significantly up-regulated postexercise ( 8 wk : ABCA1 , 3.46 + /- 0.56-fold ; ABCG1 , 3.06 + /- 0.47-fold ) . CONCLUSION We propose that the net effect of these changes may be to increase oxLDL uptake , to stimulate RCT , and thus to promote clearance of proatherogenic lipids from the vasculature , ultimately contributing to the cardiovascular benefits of low-intensity aerobic exercise",
"Thirty community-dwelling , moderately depressed elderly were r and omly assigned to 1 of 3 interventions : experimenter-accompanied exercise in the form of walking , a social contact control condition , and a wait-list control . Exercise and social contact both result ed in significant reductions in both the total and the psychological subscale of the Beck Depression Inventory ( BDI ) . The exercise condition , however , unlike the control conditions , result ed in decreased somatic symptoms of the BDI . These results indicate that , at least in the short term , exercise has a broader effect compared with control conditions in reducing depressive symptoms in the moderately depressed elderly",
"BACKGROUND This study , conducted between 1998 and 2001 and analyzed in 2002 and 2003 , was design ed to test ( 1 ) whether exercise is an efficacious treatment for mild to moderate major depressive disorder ( MDD ) , and ( 2 ) the dose-response relation of exercise and reduction in depressive symptoms . DESIGN The study was a r and omized 2x2 factorial design , plus placebo control . SETTING / PARTICIPANTS All exercise was performed in a supervised laboratory setting with adults ( n = 80 ) aged 20 to 45 years diagnosed with mild to moderate MDD . INTERVENTION Participants were r and omized to one of four aerobic exercise treatment groups that varied total energy expenditure ( 7.0 kcal/kg/week or 17.5 kcal/kg/week ) and frequency ( 3 days/week or 5 days/week ) or to exercise placebo control ( 3 days/week flexibility exercise ) . The 17.5-kcal/kg/week dose is consistent with public health recommendations for physical activity and was termed \" public health dose \" ( PHD ) . The 7.0-kcal/kg/week dose was termed \" low dose \" ( LD ) . MAIN OUTCOME MEASURES The primary outcome was the score on the 17-item Hamilton Rating Scale for Depression ( HRSD(17 ) ) . RESULTS The main effect of energy expenditure in reducing HRSD(17 ) scores at 12 weeks was significant . Adjusted mean HRSD(17 ) scores at 12 weeks were reduced 47 % from baseline for PHD , compared with 30 % for LD and 29 % for control . There was no main effect of exercise frequency at 12 weeks . CONCLUSIONS Aerobic exercise at a dose consistent with public health recommendations is an effective treatment for MDD of mild to moderate severity . A lower dose is comparable to placebo effect"
] |
4116b5aa-06ff-11f0-808a-c43d1ab1c353
|
Objectives The aim of this review was to assess the effect of different adhesive systems and tooth preparation on the retention of tooth-colored restorative material s placed in non-carious cervical lesions ( NCCLs ) . Methods R and omized clinical trials with a minimum of 3 years of follow-up that evaluated the effectiveness of tooth-colored material s , adhesive systems , and preparation techniques for the restoration of NCCLs were selected . The Cochrane Central Register of Controlled Trials ( CENTRAL ) , EMBASE ( OVID ) , the Latin American and Caribbean Health Sciences Literature data base ( LILACS ) , and Medline ( OVID ) electronic data bases were search ed from 1990 to 2013 . Results Twenty-seven r and omized clinical trials were included and review ed . Meta- analysis was used to determine the relative risk of loss of tooth-colored NCCL restorations between different categories of adhesive systems . The effect of tooth preparation could not be similarly analyzed . Conclusion The current best evidence indicates that a glass ionomer cement has a significantly lower risk of loss of a NCCL restoration compared to either a three-step etch- and -rinse or a two-step etch- and -rinse adhesive system ; a three-step etch- and -rinse adhesive system has a significantly lower risk of loss of a NCCL restoration compared to a two-step etch- and -rinse adhesive system . No significant difference could be observed in the risk of loss of a tooth-colored NCCL restoration between a three-step etch- and -rinse adhesive system and either a two-step self-etch or a one-step self-etch adhesive system
|
[
"OBJECTIVE This controlled clinical trial evaluated the 5-year clinical performance of a self-etching primer system including selective enamel-etching with phosphoric acid and a one-bottle adhesive system . METHODS Seventy-two non-carious cervical lesions in 8 patients ( 4 male and 4 female ) with a mean age of 61.3 years ( range 45 - 78 ) participated in the study . An enamel bevel was placed and dentin lightly ground , and cavities restored with clearfil liner bond II ( LB ) or single bond ( SB ) in conjunction with a hybrid resin composite ( Clearfil AP-X ) . In the case of 27 cavities for LB , the enamel was pretreated with 37 % phosphoric acid for 10 s. Each patient received both types of restoration , which were distributed on a r and om basis . All restorations ( 37 restorations for LB and 35 restorations for SB ) were placed by one dentist . The restorations were evaluated blind after 5 years using modified USPHS criteria . The data were statistically analyzed using the Fisher 's exact test . RESULTS All but one restoration ( which was replaced by a crown after the 2-year recall ) were evaluated after 5 years . 100 % retention rates were recorded for both restorative groups . No caries was detected in association with any restorations . The only minor problem was marginal discoloration ; superficial and localized marginal discoloration occurred around 18 % of the restorations , and mainly at the dentin margin . There were no significant differences in the marginal integrity between the LB and SB groups . CONCLUSIONS Restorative material s used in this study demonstrated a good clinical effectiveness in the restoration of non-carious cervical lesions for 5 years",
"PURPOSE To study the clinical performance of two c and i date s for improvement of the original Gluma bonding system . MATERIAL S AND METHODS Eight teeth with cervical buccal abrasion/erosion lesions were identified in 40 patients . The lesions were conditioned with an oxalic acid solution followed by either a HEMA-glutaraldehyde bonding agent or a formamide-containing bonding agent . The lesions were restored with a hybrid composite . Each patient received the same number of restorations with the two different bonding formulations . All restorations were made by the same operator ( JK ) . Evaluations were based on the USPHS system . RESULTS No difference between the two groups as to retention , marginal adaptation and discoloration was observed after 3 years . Eight restorations were lost and a slight increase in marginal discoloration was seen during the observation period",
"BACKGROUND A new restorative called a \" giomer composite \" has been introduced . The authors conducted a study to determine retention , anatomical form , caries , staining , marginal discoloration , marginal adaptation , surface roughness and sensitivity of giomer compared with those of a microfilled composite . METHODS The authors placed 40 sets of restorations r and omly in canines and premolars in vivo . They used a giomer composite and a microfilled composite in erosion/abrasion/abfraction Class V lesions that were not altered with rotary instruments . They placed the restorations according to manufacturer 's recommendations , and two calibrated examiners evaluated the restorations independently using modified U.S. Public Health Service criteria at baseline and at six , 18 and 36 months . The lesions receiving the restorations did not differ from each other in the amount of circumferential enamel present , the percentage of the surface area of dentin or lesion type . RESULTS There were no differences in the restorations at baseline , an evaluation made two weeks after placement . At 36 months , the giomer and microfilled composite restorations were not significantly different from one another in any of the eight criteria evaluated . The percentage agreement between examiners was at least 83 percent for each criterion in each evaluation period . CONCLUSIONS Both the giomer and the microfilled composite used in this study meet the clinical portion of the Acceptance Program Guidelines for Dentin and Enamel Adhesives Material s established by the American Dental Association . CLINICAL IMPLICATION S Both the giomer and the microfilled composite used in this study can be used with confidence in Class V lesions",
"PURPOSE To compare the clinical performance of a resin composite and a polyacid-modified resin composite ( compomer ) in non-carious cervical lesions using a one-step self-etch adhesive . METHODS Thirty patients , each with two non-carious cervical lesions ( 60 restorations ) , received one composite ( Pertac-II ) restoration and one compomer ( Hytac ) restoration , both used in conjunction with a self-etch adhesive ( Prompt L-Pop ) and placed following the manufacturer 's instructions . Evaluations were at baseline , 6 , 12 and 36 months after placement for retention , margin adaptation , marginal discoloration , anatomic form , secondary caries and postoperative sensitivity . Statistical analysis with the Pearson Chi-square test was undertaken . RESULTS Retention rates were 86.6 % for composite and 86.7 % for compomer at 36 months . 3.3 % of composite and 6.7 % of compomer restorations showed a deficiency in marginal adaptation . Both material s showed a slight marginal discoloration of 7.7 % . More deterioration in anatomic form occurred with the compomer ( 11.5 % ) than the composite ( 3.8 % ) . None of the restorations exhibited secondary caries or postoperative sensitivity problems . There was no significant difference in performance between the material s in any of the categories evaluated",
"Three restorative material s used for cervical erosion /abrasion lesions were evaluated clinical ly after 10 years . Thirty adult patients with at least four cervical lesions received one restoration of each of Ketac-Fil , finished immediately , Ketac-Fil , finished after a delay , Chelon-FIl ( all glass-ionomer cements ) , and Cervident ( a resin composite ) . Restorations were placed without any tooth preparations . Eighteen patients returned for their 10-year examinations . Two experienced examiners provided the periodic evaluations . Complete retention at 10 years was 83 % for Ketac-Fil , finished immediately ; 78 % for Ketac-Fil , finished after a delay ; 67 % for Chelon-Fil ; and 17 % for Cervident . All three glass-ionomer restorative material s exhibited statistically significantly greater retention that did Cervident . When a noninvasive procedure is desired , glass-ionomer material s are the restorative material of choice for abrasion/erosion lesions because of their long-term retention values",
"One hundred non-carious , non-undercut cervical lesions were restored with Silux Plus or Estio LC and bonded with Fuji Bond LC . The restorations were evaluated yearly for retention and marginal discoloration . After five years , the overall retention rate was 96 % . Of the 41 restorations examined at five years , five had clinical ly evident marginal discoloration",
"OBJECTIVES This r and omized controlled clinical trial evaluated the 3-year clinical performance of a hybrid ( Clearfil AP-X ; AP ) and a flowable ( Clearfil Flow FX ; FX ) resin composite in 98 non-carious cervical lesions . METHODS Twenty-two patients , 11 males and 11 females ( mean age : 61.9 years , range : 29 - 78 years ) regularly visiting the Nagasaki University Hospital , participated in the study . Each patient received both material s r and omly . All restorations ( 48 restorations for AP and 50 restorations for FX ) were placed in conjunction with an all-in-one system ( Clearfil S(3 ) Bond ) by one dentist . The restorations were blindly evaluated by two examiners at baseline , 6 months , 1 , 2 and 3 years using modified USPHS criteria . The data were statistically analyzed using the Cochran 's Q-test and Fisher 's exact test . RESULTS All the patients were examined at each recall . However , five restorations could not be evaluated at 3-year recall as two teeth had been extracted and three restorations had been lost . The only minor problem was the integrity of the enamel margin . The incidence and extent of marginal staining increased with time , but it was still superficial . Marginal staining occurred adjacent to 11 restorations for AP and 12 restorations for FX after 3 years . Neither lesion size nor depth had influence on marginal staining adjacent to each type of resin composite . There were no significant differences in the clinical performances between AP and FX for each variable . CONCLUSIONS Under the protocol used in this study , both types of resin composite in conjunction with S(3 ) Bond demonstrated an acceptable clinical performance up to 3 years",
"This r and omized clinical trial compared the performance of an all-in-one adhesive ( iBond ) applied in sclerotic and non-sclerotic non-carious cervical lesions with that of a three-step etch-prime-bond adhesive ( Gluma Solid Bond , SB ) . One-hundred and five lesions were r and omly assigned to four groups according to adhesive , sclerosis scale and technique : 1 ) SB applied to lesions with sclerosis scale 1 and 2 ( n=26 ) ; 2 ) iBond applied to lesions with sclerosis scale 1 and 2 ( n=28 ) ; 3 ) iBond applied to lesions with sclerosis scale 3 and 4 ( n=25 ) and 4 ) iBond applied with prior acid-etching to lesions with sclerosis scale 3 and 4 ( n=26 ) . A microfilled composite ( Durafill VS ) was used as the restorative material . The restorations were evaluated for retention , color match , marginal adaptation , anatomic form , cavosurface margin discoloration , secondary caries , pre- and post-operative sensitivity , surface texture and fracture at insertion ( baseline ) , 6 , 18 months and at 3 years using modified USPHS evaluation criteria ( Alfa = excellent ; Bravo= clinical ly acceptable ; Charlie= clinical ly unacceptable ) . There was a high percentage of Bravo scores for marginal adaptation ( 4%-32 % ) and marginal discoloration ( 18%-60 % ) in Groups 2 , 3 and 4 , but all groups had Charlie scores at 6 months and Charlie scores at 18 months for retention and marginal discoloration , respectively . However , it should be noted that 13 % of the restorations in Group 4 were not retained at three years",
"OBJECTIVES The objective of this r and omized controlled clinical trial was to evaluate the 8-year clinical performance of a mild 2-step self-etch adhesive in non-carious Class-V lesions with and without prior selective phosphoric acid-etching of the enamel cavity margins . METHODS A total of 100 non-carious Class-V lesions in 29 patients were restored with Clearfil AP-X ( Kuraray ) . The composite restorations were bonded following two different approaches : ( 1 ) application of Clearfil SE ( Kuraray ) following a self-etch approach ( control group ; C-SE non-etch ) , ( 2 ) selective phosphoric acid-etching of the enamel cavity margins before application of Clearfil SE ( experimental group ; C-SE etch ) . The restorations were evaluated after 6 months , 1 , 2 , 3 , 5 and 8 years of clinical service regarding their retention , marginal integrity and discoloration , caries occurrence , preservation of tooth vitality and post-operative sensitivity . RESULTS The recall rate at 8 years was 76 % . Only two restorations , one of the C-SE non-etch group and one of the C-SE etch group , were clinical ly unacceptable due to loss of retention leading to a retention rate and a clinical success rate of 97 % in both groups . Aging of the restorations was characterized by an increase in the percentage of restorations with a small but clinical ly acceptable marginal defect ( C-SE non-etch : 92 % ; C-SE etch : 84 % ) and /or a superficial marginal discoloration ( C-SE non-etch : 44 % ; C-SE etch : 28 % ) . At the enamel side , the presence of small marginal defects ( C-SE non-etch : 86 % ; C-SE etch : 65 % ) and superficial marginal discoloration ( C-SE non-etch : 11 % ; C-SE etch% ) was more frequently noticed in the control group than in the experimental group . The difference , however , was only statistically significant for the presence of superficial marginal discoloration ( McNemar , p=0.01 ) . SIGNIFICANCE After 8 years of clinical functioning , the clinical effectiveness of Clearfil SE remained excellent , with selective acid-etching of the enamel cavity margins only having some minor positive effect on marginal integrity and absence of marginal discoloration at enamel",
"Objective To assess 1 ) the quality of reporting r and omised clinical trials in dental ( RCT -Ds ) and medical research ( RCT -Ms ) , 2 ) the quality of RCT reports in relation to the journal impact factor , 3 ) the source of funding , and 4 ) the quality of RCT -Ds in different areas of dental research . Design R and om sample s of 100 RCT -Ds and 100 RCT -Ms published in 1999 were evaluated for quality of reporting under blinded conditions with the Jadad quality assessment scale . In addition , correlation between the quality scores and journal impact factor or source of funding , as well as area of dental research were analysed . Results The quality of RCT -Ds and RCT -Ms published in 1999 was generally inadequate . The quality was largely equivalent in RCT -Ds and RCT -Ms . There was no correlation between the quality scores and the journal impact factor or the source of funding . Some differences were found in the quality scores between different areas of dental research . Conclusions The results from these RCT -Ds and RCT -Ms show that most of them were imperfect in the reporting of methodology and trial conduct . There is a clear need to improve the quality of trial reporting in dental and medical research",
"PURPOSE To place four restorative material s , including two resin-based composites ( Pertac III and Synergy ) , an improved resin-modified glass-ionomer ( Fuji II LC Improved ) , and a compomer ( Dyract AP ) , in Class 5 non-carious cervical lesions and to evaluate and compare those restorations for marginal discoloration , anatomic form , surface texture , secondary caries , retention , and marginal adaptation at baseline and annually for 3 years . METHODS The tested material s were used to restore moderate-size Class 5 non-carious cervical lesions . All material s were used following the manufacturers ' directions for etching , bonding , curing , and finishing . Thirty restorations of each material were placed . After rubber-dam isolation , a bevel was placed on the occlusal margin of all preparations except the Fuji II LC Improved , and all preparations were cleaned with pumice . Each restorative material was placed and cured in increments except Fuji II LC Improved . All restorations were evaluated at baseline , 6 months , 1 , 2 , and 3-year recalls using a modified USPHS scale . RESULTS Analysis with Chi Square and Logit Analysis revealed that , at 3 years , Pertac III and Fuji II LC Improved were significantly rougher than all other material s. Pertac III had significantly poorer marginal adaptation than all other material s. All other comparisons were not significant . At 3-year recall , most restorations were satisfactory",
"PURPOSE To evaluate the retention and marginal staining of restorations placed in non-carious cervical lesions using the all-in-one self-etching system , One-Up Bond F and Palfique Estelite resin composite . METHODS Fifty-one non-undercut non-carious cervical lesions received restorations with One-Up Bond F and Palfique Estelite in 15 subjects ( mean age 57.7 years ) by one operator . Teeth were cleaned with pumice and water , restored following the manufacturer 's instructions and evaluated at 6 months , 1 , 2 , 4 and 5 years for retention and presence of marginal staining . RESULTS At 1 year , 42 restorations were evaluated , and all were intact with three restorations showing slight marginal staining . At 2 years , 37 restorations were evaluated from 11 subjects , and all were intact . Marginal staining was observed around nine restorations . At 4 years , 27 restorations and at 5 years , 24 restorations could be evaluated . Marginal staining showed a significant increase at the enamel and cervical margins over the 5 years of the study , with two restorations showing severe , nine mild and 13 no staining . Although a number of restorations could not be evaluated , the retention rate of 92 % at 5 years showed One-Up Bond F/Palfique Estelite resin composite for the restoration of non-carious cervical lesions produced an excellent outcome . Marginal staining was limited to a small number of subjects and is unlikely to be a problem if margins are refurbished at recall visits",
"This 13-year r and omized clinical trial compared the clinical effectiveness of two three-step etch- and -rinse adhesives in combination with a hybrid , stiffer composite versus a micro-filled , more flexible composite . The influence of composite stiffness on the clinical performance of one of the adhesives was assessed as well . One hundred and forty-two non-carious cervical lesions were restored with composites with contrasting stiffness . Seventy-one patients r and omly received two cervical restorations placed following two out of three adhesive procedures : ( 1 ) the three-step etch- and -rinse adhesive Permaquick applied with the stiff micro-hybrid composite Amelogen Hybrid ( PMQ-H , Ultradent ) , ( 2 ) Permaquick applied with the more flexible micro-filled Amelogen Microfill ( PMQ-M , Ultradent ) , or ( 3 ) the “ gold-st and ard ” three-step etch- and -rinse adhesive Optibond FL applied with the micro-hybrid composite Prodigy ( OFL-P , Kerr ) . The restorations were evaluated after 6 months , 1 , 2 , 3 , 5 , 7 , and 13 years of clinical service regarding their retention , marginal integrity and discoloration , caries occurrence , preservation of tooth vitality , and post-operative sensitivity . Retention loss , severe marginal defects , and /or discoloration that needed intervention ( repair or replacement ) and the occurrence of caries were considered as clinical failures . The recall rate at 13 years was 77 % . Bond degradation after 13 years was mainly characterized by a further increase in the presence of small but clinical ly acceptable marginal defects and superficial marginal discoloration . Twelve percent of the OFL-P restorations were clinical ly unacceptable . In the PMQ group , 22 % of the PMQ-M restorations and 26 % of the PMQ-H restorations needed repair or replacement . Regarding the clinical failure rate , Optibond FL scored significantly better than Permaquick ( McNemar ; p = 0.015 ) . No statistically significant differences were found between the micro-filled and the hybrid composite for each of the parameters evaluated ( McNemar , p > 0.05 ) . After 13 years of clinical functioning , the clinical effectiveness of the three adhesive/composite combinations remained highly acceptable",
"AIM To comparatively assess the 5-year clinical performance of a 1-bottle adhesive and resin composite system with a resin-modified glass ionomer restorative in non-carious cervical lesions . METHOD AND MATERIAL S One operator placed 70 restorations ( 35 resin modified glass ionomer restorations and 35 resin composite restorations ) in 30 patients under rubber dam isolation without mechanical preparation . The restorations were directly assessed by 2 independent examiners , using modified USPHS criteria at baseline and 6 , 12 , 24 and 60 months . RESULTS Twenty-two patients were available for recall after 5 years ( 73.3 % recall rate ) and 55 out of 70 restorations were evaluated . Excellent agreement was registered for all criteria between examiners ( kappa > or = 0.85 ) . Sixteen composite restorations were dislodged ( 51.5 % retention ) and 1 ionomer restoration was lost ( 96.4 % retention ) . The McNemar test detected significant differences in resin composite restorations between baseline and 5-year recall for marginal integrity ( p retention ( p=0.004 ) . For resin modified glass ionomer restorations , no significant differences were identified for all criteria ( p>0.05 ) . When comparing both material s , the Fisher exact test pointed out significant differences in retention ( p=0.002 ) after 5 years of clinical service . CONCLUSIONS After 5 years of evaluation , the clinical performance of resin modified glass ionomer restorations was superior to resin composite restorations",
"This study evaluated the effect of the elastic modulus and margin configuration on the clinical performance of resin-based composite restorations in Class V non-carious defects . One hundred and five cervical non-carious defects on buccal surfaces of canines and premolars were included in this study . Defects were r and omly divided into three Groups and restored according to the following techniques : Group 1 - -no enamel bevel was placed and the defect was restored with a microfilled resin-based composite ( Durafill VS ) ; Group 2 - -the enamel margin was beveled and the defect restored as in Group 1 ; Group 3-the enamel margin was beveled and the defect was restored with a flowable resin-based composite ( Natural Flow ) . Each group comprised 35 lesions . A total-etch , one-bottle adhesive ( One-Step ) was used in all groups . Retention rate , pre- and post-operative sensitivity , marginal discoloration and secondary caries were determined over a three-year period and the data were analyzed statistically . At six months post-insertion , the restorations placed with beveled enamel margins result ed in 100 % retention regardless of the composite used compared to a 66 % retention of the non-beveled margins . At two and three years , no significant difference in retention rate was found among the three groups . Post-operative sensitivity , marginal discoloration and secondary caries were not affected by enamel beveling and restorative material . Beveled enamel margins result ed in significantly better clinical retention in the first six months only . Enamel beveling and composite viscosity appeared to not significantly affect the clinical performance of Class V non-retentive composite restorations after three years",
"The use of adhesive material s to restore non-carious cervical lesions ( NCCL ) has become the st and ard practice . Until recently , the most reliable material for restoring NCCL is glass ionomer cement , but the esthetics can be problematic . This study compared the retention of a self-etching adhesive , Clearfil SE Bond , with Clearfil ST resin composite ( SE ) , with the phosphoric acid-etch single bottle adhesive Single Bond with A110 resin composite ( SB ) and a resin-modified glass ionomer cement , Fuji II LC , ( FJ ) . Ninety-two restorations in 20 patients ( mean age 61 years ) were placed . The teeth were restored r and omly and manufacturers ' instructions were followed . Patients were recalled at 6 months , 1 , 2 and 3 years and the restorations were evaluated for marginal staining . The restorations were photographed at baseline and at recall periods . At one year , 80 restorations were available for evaluation ; at 2 years , 65 restorations were evaluated and at 3 years , 55 restorations were evaluated . The cumulative retention rates at 1 year , 2 years and 3 years , respectively , were SE : 97 % , 93 % , 90 % ; SB : 86 % , 77 % , 77 % ; FJ : 100 % , 100 % , 97 % . At 3 years , RM-GIC performed the best , followed by Clearfil SE Bond/Clearfil ST . Single Bond/A110 's performance was significantly less than the other 2 material s ( p = 0.012 )",
"OBJECTIVES The aim of this study was to evaluate the clinical long-term retention to dentin of seven adhesive systems . METHODS A total of 270 Class V restorations of four etch- and -rinse , one self-etch adhesive system and a resin-modified glass ionomer cement were placed in non-carious cervical lesions without intentional enamel involvement . The restorations were evaluated at baseline , 6 , 12 , 18 , and 24 months and then every year during a 13-year follow-up . Dentin bonding efficiency was determined by the percentage of lost restorations . RESULTS During the 13 years , 215 restorations could be evaluated . The cumulative loss rate at 13 years was 53.0 % , with significant different failures rates for the different systems varying between 35.6 and 86.8 % . Four systems fulfilled the ADA 18-month full acceptance retention criteria . Two systems showed at 18 months and earlier high debonding rates . The annual failure rates for the etch- and -rinse systems were Optibond 3.1 % , Permagen 13.0 % , Scotchbond MP 4.8 % , Syntac classic 2.8 % ; for the self-etch system P&S 4.4 % ; and the resin-modified glass ionomer cement Vitremer 2.7 % . CONCLUSION It can be concluded that all systems showed a continuous degradation of the bond with a wide variation , which was independent of the adhesion strategy . Three bonding systems showed a cumulative failure rate after 13 years between 36 and 41 % with the best retention for the resin-modified glass ionomer cement and a four-step etch- and -rinse system",
"PURPOSE To evaluate the 5-yr clinical performance of a resin-modified glass-ionomer cement and a polyacid-modified resin composite in restoring non-carious cervical lesions . MATERIAL S AND METHODS Non-carious cervical lesions in 46 incisors , canines , and premolars were restored either with Fuji II LC ( n=18 ) or with Dyract ( n=28 ) in 16 healthy patients . The lesions were restored without cavity preparation strictly according to the manufacturer 's instructions . The restorations were clinical ly evaluated single blind after 5 yrs using modified USPHS criteria . RESULTS The percentage of Alfa ratings were as follows ( Dyract/Fuji II LC ) : color match 81.3%/28.6 % , surface texture 93.8%/21.4 % , anatomic form 75.0%/28.6 % , marginal integrity ( enamel ) 62.5%/42.9 % , marginal integrity ( dentin ) 68.8%/28.6 % , marginal discoloration ( enamel ) 56.3%/42.9 % , marginal discoloration ( dentin ) 68.8%/21.5 % . Five-yr data revealed a significant difference between the clinical ratings of Dyract and Fuji II LC for all criteria except marginal integrity and marginal discoloration in enamel . A total of five Dyract restorations and four Fuji II LC restorations failed within the study period . CLINICAL SIGNIFICANCE A considerably high and almost similar overall failure rate was found for both restorative material s in restoring non-carious cervical lesions . However , retained Dyract restorations presented superior clinical performance compared to Fuji II LC restorations",
"Laboratory testing of dentin adhesive systems still requires corroboration by long-term clinical trials for their ultimate clinical effectiveness to be vali date d. The objective of this clinical investigation was to evaluate , retrospectively , the clinical effectiveness of earlier-investigated dentin adhesive systems ( Scotchbond , Gluma , Clearf il New Bond , Scotchbond 2 , Tenure , and Tripton ) , and to compare their clinical results with those obtained with four modern total-etch adhesive systems ( Bayer exp . 1 and 2 , Clearfil Liner Bond System , and Scotchbond Multi- Purpose ) . In total , 1177 Class V cervical lesions in the teeth of 346 patients were restored following two cavity design s : In Group A , enamel was neither beveled nor intentionally etched , as per ADA guidelines ; in Group B , adjacent enamel was beveled and conditioned . Clinical retention rates definitely indicated the improved clinical efficacy of the newest dentin adhesives over the earlier systems . With regard to adhesion strategy , adhesive systems that removed the smear layer and concurrently demineralized the dentin surface layer performed clinical ly better than systems that modified the disorderly layer of smear debris without complete removal . Hybridization by resin interdiffusion into the exposed dentinal collagen layer , combined with attachment of resin tags into the opened dentin tubules , appeared to be essential for reliable dentin bonding but might be insufficient by itself . The additional formation of an elastic bonding area as a polymerization shrinkage absorber and the use of a microfine restorative composite apparently guaranteed an efficient clinical result . The perfect one-year retention recorded for Clearfil Liner Bond System and Scotchbond Multi- Purpose must be confirmed at later recalls",
"The present study aim ed at the determination of changes of tooth-colored cervical restorations in vivo using an optical 3-dimensional laser scanning device . The study was performed on 197 cervical restorations placed on incisors , canines , and premolars . Four different tooth-colored restoration material s , a composite , a polyacid-modified resin composite , and two resin-modified glass ionomer cements , were used for the restoration of the lesions . For the determination of changes , images were taken at baseline and 15 , 24 and 36 months after the placement of the fillings using a 3D-laser scanning device . The images were superimposed automatically , and digital subtraction was made by a specially developed image analysis software . The total substance loss on the entire filling surface at 36 months for the resin-modified glass ionomer Photac-Fil was 44 ( + /-23 ) microm , for Fuji II LC 45 ( + /-26 ) microm , for Dyract 71 ( + /-47 ) microm and for Tetric 18 ( + /-12 ) microm . Differentiating between the class of lesion , a higher wear rate was observed at 36 months on restorations which had been placed in erosion/non-carious cervical cavities ( 66 ( + /-33 ) microm ) . In conclusion , the composite material demonstrated a distinctly lower surface wear rate over time in comparison to the resin-modified glass ionomer cements and the polyacid-modified resin composite",
"Abstract The aim of this study was to compare the treatment results using four different types of tooth colored material s for restoring class V lesions . A total of 197 class V restorations ( n=197 ) were placed by one dentist in 37 patients on incisors , canines and premolars . The fillings were placed due to different indications : erosion/non-carious cervical defects ( n=69 ) , primary carious lesions ( n=57 ) , and for replacing defective existing fillings ( n=71 ) . The teeth were assigned on a r and om basis to four groups for restoration with either a composite ( group 1 : n=36 ; Tetric , Vivadent ) , or a polyacid-modified resin composite ( group 2 : n=79 ; Dyract , Dentsply ) , or one of two different resin-modified glass ionomer cements ( group 3 : n=51 , Fuji II LC , GC ; group 4 : n=31 , Photac-Fil , Espe ) . The restorations were evaluated by a single-blind design , according to a modified USPHS system 36 months following placement . Statistical analysis was completed with the Pearson Chi-square test for comparing the results of the four groups ( P survival rates were analyzed with the Kaplan-Meier estimator and the Log-rank test ( P shade match ( 86%/77%/58%/40 % ) , surface texture ( 81%/83%/16%/9 % ) , marginal integrity ( enamel ) ( 73%/67%/61%/61 % ) , marginal integrity ( dentin ) ( 86%/70%/55%/61 % ) , marginal discoloration ( enamel ) ( 59%/44%/58%/52 % ) , marginal discoloration ( dentin ) ( 82%/84%/71%/48 % ) , anatomic contours ( 91%/83%/39%/ 35 % ) . One Tetric restoration , five Dyract restorations , two Fuji II LC restorations and three Photac restorations were dislodged within the study period . The retention of the restorations showed no significant difference among the four material s. However , the clinical performance of the restorations retained over the 3-year period showed distinct differences for the four material s. The best clinical performance was observed for the resin composite , whereas the quality of the Dyract restorations without enamel etching was worse . The poorest results were obtained for the restorations with the resin-modified glass ionomers",
"Recently a calcium aluminate cement ( Doxa Certex , Uppsala , Sweden ) has been developed intended to be used as direct restorative filling material . The aim of this study was to evaluate intra-individually the experimental calcium aluminate cement ( CAC ) and a resin composite ( RC;Tetric Ceram ) in Class V restorations . Each of 46 participants received at least one pair of restorations of the same size , one CAC and one RC . The 119 restorations were evaluated clinical ly , according to slightly modified USPHS criteria , at baseline , after 6 mths , 1 , 2 and 3 yrs . None of the patients reported post-operative sensitivity . At 3 yrs , 111 restorations were evaluated . Significantly better clinical durability was shown for RC . Two non-acceptable CAC restorations were observed at 6 months , 3 CAC and 1 RC at 12 months , 5 CAC and 2 RC at 24 months , and 8 CAC at 36 months . This result ed in a cumulative failure frequency of 32 % for the CAC material and 5 % for the RC material . Main reason for failure for the CAC was total or partial lost restorations , and for the RC lost restorations . It can be concluded that the CAC showed a non-acceptable clinical failure rate for Class V restorations",
"PURPOSE The aim of this double-blind r and omized study was to compare the clinical performance of a resin-modified glass ionomer ( Vitremer , 3 M ) and a polyacid-modified resin ( Dyract , Dentsply DeTrey ) in noncarious Class V restorations after 5 years . MATERIAL S AND METHODS Twelve patients , having at least one pair of equal-sized noncarious cervical lesions under occlusion and a mean age of 40 years ( range 19 to 63 years ; median 41 ) , were enrolled in this study . A total of 32 restorations ( 16 with each material ) were placed according to the manufacturers ' instructions by two calibrated operators . Two other independent examiners evaluated the restorations at baseline and after 5 years according to the USPHS criteria . The assessment criteria were : retention , anatomical form , marginal adaptation and marginal discoloration , color match , surface texture , and secondary caries . Statistical analysis was conducted using Fisher 's exact test ( alpha = 0.05 ) . RESULTS No secondary caries was detected with either material . The retention rate for Vitremer ( 93 % ) and for Dyract ( 78.5 % ) did not differ significantly ( p > 0.05 ) . Regarding anatomical form , only two restorations of each material were recorded as bravo . In terms of marginal adaptation , 38.5 % of Dyract restorations were rated alpha and 61.5 % bravo , while 84.6 % of Vitremer restorations were rated alpha and only 15.4 % bravo ( p marginal discoloration , 18.2 % of Dyract restorations and 84.6 % of Vitremer restorations were rated alpha , with the remaining rated bravo . 86 % of Vitremer restorations were rated as bravo and 23 % alpha for both surface texture and color match . All Dyract restorations were classified as alpha regarding surface texture , and only two Dyract restorations ( 18.2 % ) were classified as bravo in the color match item . CONCLUSION The marginal adaptation of the RMGIC ( Vitremer ) was significantly better , the marginal discoloration lower , and the retention rate higher ( though not significantly ) than that of the PMRC ( Dyract ) after 5 years in situ . Dyract performed better in terms of surface texture and color match in noncarious Class V restorations after 5 years",
"UNLABELLED This double-blind r and omized clinical trial compared different ethanol/water and acetone-based systems in non-carious cervical lesions over 36 months . MATERIAL S AND METHODS Eighty-four patients having at least one non-carious cervical lesion [ NCCL ] under occlusion were enrolled in this study . A total of 84 restorations were placed , half for each group ( Adper Single Bond [ SB ] + FiltekA110 or One Step [ OS ] + MicroNew ) . All the material s were placed by two calibrated operators . Two other independent examiners evaluated the restorations at baseline , 6 , 12 , 18 and 36 months , according to slightly modified USPHS criteria . Statistical analysis between material s in each period was conducted using the Fisher 's exact test ( alpha=0.05 ) , and performance of the material s in the baseline in comparison to each period was evaluated by McNemar 's test ( alpha=0.05 ) . RESULTS The 12- , 18- and 36-month retention rates for SB were 95.2 % ( 12 and 18 months ) and 92.3 % ( 36 months ) . For OS , the retention rates were 83.3 % , 73.8 % and 56.4 % , respectively , for each recall period . After 36 months , 10 OS restorations ( 25.7 % ) and seven SB restorations ( 17.9 % ) were rated as Bravo in the marginal discoloration item . CONCLUSIONS The ethanol/water-based adhesive ( Single Bond ) that was evaluated showed a higher retention rate than the acetone-based system ( One Step ) after 36 months of clinical service",
"OBJECTIVE The purpose of this study was to compare the esthetics of 3 resin-modified glass-ionomer material s and 1 polyacid-modified resin composite to the esthetics of a conventional glass-ionomer control material . METHOD AND MATERIAL S One hundred eighty-seven Class V cervical restorations were observed clinical ly over 18 months . The esthetic index system that was used evaluated color match , translucency or opacity , and surface roughness . RESULTS The tested material s behaved very dissimilarly and inconsistently . In general , the esthetic results of the resin-modified glass-ionomer material s and the polyacid-modified resin composite were far from optimal . The esthetic appearance of restorations seriously deteriorated during clinical service , mainly because of discoloration of margins , changes in translucency and opacity , and rapidly appearing roughness or dullness on the surface . Both the resin-modified glass-ionomer material s and the polyacid-modified resin composite evaluated in this study performed better esthetically than did the conventional glass-ionomer material . CONCLUSION Indications for these combination material s are limited to areas where esthetics is not a primary concern but where their ease of application may guarantee a more durable functional result",
"One hundred fifty-nine noncarious cervical lesions were restored with glass-ionomer cement , resin composite used with a dentinal bonding agent , or the laminate ( s and wich ) restoration , which combines both these material s. These restorations were evaluated at baseline , 1 year , and 3 years for color match , cavosurface marginal discoloration , anatomic form , marginal adaptation , and retention . There was a general deterioration of the restorations with time . Lesions restored with resin composite and a dentinal bonding agent exhibited the highest percentage of lost restorations",
"One hundred cervical \" abrasion/erosion \" lesions were restored in groups of twenty with All-Bond , Photobond , Denthesive , and Pertac dentin adhesives with resin composite , and Geristore resin-based material . The mean patient age was 63 years . All but seven restoration sites were examined for up to approximately 14 months , and the cumulative retention rates of restorations calculated . At the end of the observation period , the percentage of restorations retained was ; All-Bond 69.6 % , Photobond 78.2 % , Denthesive 42.8 % , Pertac 7.5 % , Geristore 71.8 % , which was in approximate quantitative agreement with laboratory bond strength studies . The relationship of laboratory bond strength tests to clinical performance , and the influence of patient age on the clinical results , are discussed",
"BACKGROUND The authors conducted an in vivo investigation to compare the clinical performance of two commercial one-bottle adhesives and a two-bottle adhesive for restoration of noncarious cervical lesions ( NCCLs ) . METHOD The patient pool consisted of 57 patients and 171 teeth ( three teeth per patient ) , with one NCCL per tooth . Each patient received three resin-based composite restorations , each with a different adhesive : one tooth with a two-bottle , water-based adhesive as the control ; another tooth with a one-bottle , ethanol-based adhesive ; and a third tooth with a one-bottle , solvent-free adhesive . The authors assessed restorations in terms of retention , marginal integrity , margin discoloration and air sensitivity at baseline , six months , one year , two years and three years after initial placement . RESULTS The retention rates at 36 months were 88 percent for the first adhesive , 81 percent for the second adhesive and 90 percent for the third adhesive . No statistically significant differences in retention rates could be shown , with 86 percent of restorations retained overall . Measures of marginal integrity , marginal discoloration and sensitivity also had no statistically significant differences between the three adhesives ( P > .05 ) . CONCLUSIONS All three adhesives performed with acceptable outcomes after a 36-month period , with small differences between the one- and two-bottle systems and between the various solvents . Retention rate was moderately high and air sensitivity was markedly reduced ; however , superficial marginal discoloration and marginal degradation was notable . Certain lesion , tooth and patient characteristics may predispose restorations to retention failure . CLINICAL IMPLICATION S The type of solvent may not be a major factor in retention of Class V restorations in NCCLs . Both single-bottle adhesives and conventional two-bottle adhesives performed acceptably",
"PURPOSE To clinical ly evaluate the 3-year performance of a one-bottle dentin adhesive in the restoration of non-carious cervical lesions ( NCCLs ) with resin composite . MATERIAL S AND METHODS 105 NCCLs were restored with either AElite Flow , Bisco Glaze ( both flowable resin-based composites ) or Silux ( a microfilled resin-based composite ) , using One-Step dentin adhesive . The cavities were cleaned with pumice and water slurry , the dentin lightly roughened with a fine diamond bur , and the restorations placed according to the manufacturer 's instructions . Patients were recalled at 6 months , 1 year , 2 years and 3 years , and restoration integrity and marginal discoloration assessed . RESULTS The overall retention rates were : 6 months , 100 % ; 1 year , 95 % ; 2 years , 87 % ; 3 years , 75 % . Marginal discoloration was negligible , and there was no significant difference among the material s , although there was a trend for it to be greater around the Bisco Glaze restorations",
"Despite the fact that one-step adhesives are currently used routinely in clinical practice , long-term studies on their clinical performance are scarce . The objective of this r and omized controlled clinical trial was to test the hypothesis that a 2-hydroxyethyl methacrylate (HEMA)-free one-step self-etch adhesive performs worse than a conventional multistep etch- and -rinse adhesive . Two-hundred and seventy-six non-carious cervical lesions in 52 patients were restored with a micro-hybrid composite ( Gradia Direct ; GC ) . These restorations were bonded in r and om order either with the HEMA-free one-step adhesive G-Bond ( GC ) or with the ' gold-st and ard ' ( control ) three-step adhesive Optibond FL ( Kerr ) . The restorations were evaluated after 6 , 12 , 24 , and 36 months of clinical service regarding retention , marginal adaptation , microleakage , caries occurrence , and sensitivity . After a medium-long period of 3 yr , similar success in clinical performance was observed for the simplified all-in-one adhesive and the conventional three-step adhesive . However , the one-step adhesive exhibited significantly more incisal marginal defects and discolorations . Whereas marginal degradation appeared to arrest for the multistep etch- and -rinse adhesive after 12 months , the enamel margins of the restorations bonded with the one-step self-etch adhesive continued to deteriorate . These incisal marginal defects were , however , small and could easily be removed by polishing . For both adhesives , large and sclerosed lesions appeared to be at higher risk of retention loss",
"OBJECTIVE To assess the quality of the reporting of r and omised controlled trials ( RCTs ) in dental public health journals . METHOD Electronic and h and search es were used to search for RCTs published in the following three journals over the period 1993 - 2008 : Community Dental Health , Community Dentistry & Oral Epidemiology and the Journal of Public Health Dentistry . Exclusion criteria were applied . Each of the result ing papers was review ed and scored , according to 56 criteria , based on the CONSORT statement . RESULTS The search identified 48 papers . The average number of criteria present per article was 27.0 ( SD = 6.9 ) , with variation between journals as follows : Community Dental Health ( 27.7 ) ; Community Dentistry & Oral Epidemiology ( 27.4 ) ; Journal of Public Health Dentistry ( 23.2 ) . The average number of criteria present per article increased over the time period used . CONCLUSION There were inadequacies in the reporting of trials in dental public health journals . The quality of the reporting could be improved if the CONSORT statement was followed more closely",
"To optimize the bonding of glass polyalkenoate ( ionomer ) cement to dentin , different conditioning methods have been suggested . The effect of two easily applied conditioning methods , a 10 - 15 seconds cleaning with a 10 % polyacrylic acid or rinsing with copious amounts of water , was compared in class V abrasion/erosion lesions . The cervical lesions were restored , without any form of mechanical cavity preparation , with an anhydrous glass ionomer cement . During a 4-yr period , 137 restorations were evaluated every 6 months . Cumulative loss rates after 4 yr were 15.6 % for the polyacrylic acid group and 21.9 % for the water rinsing group . The difference was not significant . No secondary caries was registered",
"About 35 years ago , Ryge provided a practical approach to evaluation of clinical performance of restorative material s. This systematic approach was soon universally accepted . While that methodology has served us well , a large number of scientific method ologies and more detailed questions have arisen that require more rigor . Current restorative material s have vastly improved clinical performance and any changes over time are not easily detected by the limited sensitivity of the Ryge criteria in short term clinical investigations . However , the clinical evaluation of restorations not only involves the restorative material per se but also different operative techniques . For instance , a composite resin may show good longevity data when applied in conventional cavities but not in modified operative approaches . Insensitivity , combined with the continually evolving and non-st and ard investigator modifications of the categories , scales , and reporting methods , has created a body of literature that is extremely difficult to meaningfully interpret . In many cases , the insensitivity of the original Ryge methods is misinterpreted as good clinical performance . While there are many good features of the original system , it is now time to move to a more contemporary one . The current review approaches this challenge in two ways : ( 1 ) a proposal for a modern clinical testing protocol for controlled clinical trials , and ( 2 ) an in-depth discussion of relevant clinical evaluation parameters , providing 84 references that are primarily related to issues or problems for clinical research trials . Together , these two parts offer a st and ard for the clinical testing of restorative material s/ procedures and provide significant guidance for research teams in the design and conduct of contemporary clinical trials . Part 1 of the review considers the recruitment of subjects , restorations per subject , clinical events , validity versus bias , legal and regulatory aspects , rationale s for clinical trial design s , guidelines for design , r and omization , number of subjects , characteristics of participants , clinical assessment , st and ards and calibration , categories for assessment , criteria for evaluation , and supplemental documentation . Part 2 of the review considers categories of assessment for esthetic evaluation , functional assessment , biological responses to restorative material s , and statistical analysis of results . The overall review represents a considerable effort to include a range of clinical research interests over the past years . As part of the recognition of the importance of these suggestions , the review is being published simultaneously in identical form in both the “ Journal of Adhesive Dentistry ” and the “ Clinical Oral Investigations . ” Additionally an extended abstract will be published in the “ International Dental Journal ” giving a link to the web full version . This should help to introduce these considerations more quickly to the scientific community",
"OBJECTIVES The purpose of this study was to evaluate the clinical retention of a new resin-modified glass ionomer cement based adhesive combined with a hybrid resin composite or a poly-acid modified resin composite in non-carious cervical lesions during a 6-year period . METHODS The resin-modified glass ionomer adhesive ( Fuji Bond LC ) , was placed in 73 cervical lesions , 36 with a universal hybrid resin composite ( Tetric Ceram ) and 37 with a poly-acid modified resin composite ( Hytac ) . Fifty-one in lesions with sclerotic dentin and 22 in non-sclerotic ones . Of the sclerotic lesions 38 were slightly roughened with a diamond bur before conditioning . The restorations were evaluated with slightly modified USPHS criteria every six months during a 6-year period . RESULTS All except six restorations were evaluated during the 6 years . Twelve ( 17.9 % ) were lost , four Tetric Ceram ( 11.8 % ) and eight Hytac ( 24.2 % ) ( p non-sclerotic lesions ( 20.0 % ) and eight in sclerotic lesions ( 17.0 % ) . The differences between the sclerotic and non-sclerotic and the roughened and non-roughened lesions were not significant . CONCLUSIONS The resin-modified glass adhesive showed a superior clinical retention combined with the resin composite material , with an annual failure rate of 2 %",
"The dentinal adhesive Scotchbond 2 was evaluated with the microfilled composite resin Silux in cervical and root caries lesions for up to 3 years . Clinical criteria evaluated included retention , marginal integrity , marginal discoloration , color match , anatomic form , recurrent caries , gingival response , and postoperative sensitivity . Overall , the adhesive demonstrated improved performance over earlier dentinal adhesive systems . Retention was greatest at 3 years when available enamel margins had been etched ( 93 % ) and when root caries lesions ( 97 % ) had been restored . Other criteria were reported as generally favorable . Early findings suggest that the level of development of sclerotic dentin may influence behavior of the adhesive . The greatest difficulty was noted in lesions presenting with heavy sclerotic dentin",
"The aim of this study was to clinical ly evaluate a polyacid-modified resin composite ( Dyract ; Dentsply deTrey ) . Forty-one Dyract restorations were placed ( 36 in noncarious cervical cavities and five in anterior approximal cavities ) , and assessed after three years . The retention rate was 97 % for the cervical restorations ; however , 16 restorations showed some degree of marginal discoloration , sometimes severe . Color match and surface integrity were highly satisfactory throughout the trial . Dyract has now been superseded by Dyract AP , and the manufacturers should consider recommending m and atory enamel etching"
] |
4116b5f0-06ff-11f0-808a-c43d1ab1c353
|
Objective To evaluate evidence from published r and omised controlled trials ( RCTs ) for the use of task-shifting strategies for cardiovascular disease ( CVD ) risk reduction in low-income and middle-income countries ( LMICs ) . Design Systematic review of RCTs that utilised a task-shifting strategy in the management of CVD in LMICs . Data Sources We search ed the following data bases for relevant RCTs : PubMed from the 1940s , EMBASE from 1974 , Global Health from 1910 , Ovid Health Star from 1966 , Web of Knowledge from 1900 , Scopus from 1823 , CINAHL from 1937 and RCTs from Clinical Trials.gov . Eligibility criteria for selecting studies We focused on RCTs published in English , but without publication year . We included RCTs in which the intervention used task shifting ( non-physician healthcare workers involved in prescribing of medications , treatment and /or medical testing ) and non-physician healthcare providers in the management of CV risk factors and diseases ( hypertension , diabetes , hyperlipidaemia , stroke , coronary artery disease or heart failure ) , as well as RCTs that were conducted in LMICs . We excluded studies that are not RCTs . Results Of the 2771 articles identified , only three met the predefined criteria . All three trials were conducted in practice -based setting s among patients with hypertension ( 2 studies ) and diabetes ( 1 study ) , with one study also incorporating home visits . The duration of the studies ranged from 3 to 12 months , and the task-shifting strategies included provision of medication prescriptions by nurses , community health workers and pharmacists and telephone follow-up posthospital discharge . Both hypertension studies reported a significant mean blood pressure reduction ( 2/1 mm Hg and 30/15 mm Hg ) , and the diabetes trial reported a reduction in the glycated haemoglobin levels of 1.87 % . Conclusions There is a dearth of evidence on the implementation of task-shifting strategies to reduce the burden of CVD in LMICs . Effective task-shifting interventions targeted at reducing the global CVD epidemic in LMICs are urgently needed
|
[
"Abstract Background : Disease management programmes ( DMPs ) improve quality of care for patients with heart failure ( HF ) . However , only a limited number of trials have studied the efficacy of such programmes for patients with heart failure with preserved ejection fraction ( HFPEF ) . Objective : To estimate the impact of a structured , nurse-led patient education programme and care plan in general practice on outcome parameters and events in patients with HFPEF . Methods : Single blinded r and omized clinical trial with an intervention over six months and a follow-up during 12 additional months . In the control group , the patients ( n = 41 ) were managed according to Russian national guidelines . Patients in the intervention group ( n = 44 ) received education on individual lifestyle changes and modifications of cardiovascular disease ( CVD ) risk factors , home-based exercise training and weekly nurse consultations in addition to usual care . Results : Six months after their inclusion , patients in the intervention group significantly improved body mass index , waist circumference , six-min walk test distance , total cholesterol , low-density lipoprotein , left ventricular end-diastolic volume index , quality of life and level of anxiety . After 18 months , there were 11 deaths ( 25 % ) or hospitalizations in the intervention group and 12 ( 29 % ) in the control group ( P = 0.134 ) . Cardiovascular mortality and readmission rate were not reduced significantly after six months of follow-up : the hazard ratio was 0.47 ( 95 % CI : 0.17–1.28 ; P = 0.197 ) . After 18 months , this was 0.85 ( 0.42–1.73 ; P = 0.658 ) . Conclusion : This primary care based DMP for patients with HFPEF improved the patients ’ emotional status and quality of life , positively influenced body weight , functional capacity and lipid profile , and attenuated heart remodelling",
"OBJECTIVE To evaluate a simple cardiovascular risk management package for assessing and managing cardiovascular risk using hypertension as an entry point in primary care facilities in low-re source setting s. METHODS Two geographically distant regions in two countries ( China and Nigeria ) were selected and 10 pairs of primary care facilities in each region were r and omly selected and matched . Regions were then r and omly assigned to a control group , which received usual care , or to an intervention group , which applied the cardiovascular risk management package . Each facility enrolled 60 consecutive patients with hypertension . Intervention sites educated patients about risk factors at baseline and initiated treatment with hydrochlorothiazide at 4 months in patients at medium risk of a cardiovascular event , according to a st and ardized treatment algorithm . Systolic blood pressure change from baseline to 12 months was the primary outcome measure . FINDINGS The study included 2397 patients with baseline hypertension : 1191 in 20 intervention facilities and 1206 in 20 control facilities . Systolic and diastolic blood pressure decreased more in intervention patients than in controls . However , at 12 months more than half of patients still had uncontrolled hypertension ( systolic blood pressure > 140 mmHg and /or diastolic blood pressure > 90 mmHg ) . Behavioural risk factors had improved among intervention patients in Nigeria but not in China . Only about 2 % of hypertensive patients required referral to the next level of care . CONCLUSION Even in low-re source setting s , hypertensive patients can be effectively assessed and managed in primary care facilities",
"Objective To assess the effectiveness of a community based lifestyle intervention on blood pressure in children and young adults in a developing country setting . Design Cluster r and omised controlled trial . Setting 12 r and omly selected geographical census based clusters in Karachi , Pakistan . Participants 4023 people aged 5 - 39 years . Intervention Three monthly family based home health education delivered by lay health workers . Main outcome measure Change in blood pressure from r and omisation to end of follow-up at 2 years . Results Analysed using the intention to treat principle , the change in systolic blood pressure ( adjusted for age , sex , and baseline blood pressure ) was significant ; it increased by 1.5 ( 95 % confidence interval 1.1 to 1.9 ) mm Hg in the control group and by 0.1 ( −0.3 to 0.5 ) mm Hg in the home health education group ( P for difference between groups=0.02 ) . Findings for diastolic blood pressure were similar ; the change was 1.5 mm Hg greater in the control group than in the intervention group ( P=0.002 ) . Conclusions Simple , family based home health education delivered by trained lay health workers significantly ameliorated the usual increase in blood pressure with age in children and young adults in the general population of Pakistan , a low income developing country . This strategy is potentially feasible for up-scaling within the existing healthcare systems of Indo-Asia . Trial registration Clinical trials NCT00327574",
"Background : Research in industrialized countries has demonstrated that a key factor limiting the control of hypertension is poor patient adherence and that the most successful interventions for long-term adherence employ multiple strategies . Very little data exist on this question in low-income countries , wherein medication-taking behavior may be less well developed . Method : We conducted a treatment adherence trial of 544 patients [ mean age ∼63 years , mean blood pressure ( BP ) ∼168/92 mmHg ] with previously untreated hypertension in urban and rural Nigeria . Eligible participants were r and omized to one of two arms : clinic management only , or clinic management and home visits . Both interventions included three elements : a community based , nurse-led treatment program with physician backup ; facilitation of clinic visits and health education ; and the use of diuretics and a & bgr ; blocker as needed . After initial diagnosis , the management protocol was implemented by a nurse with physician backup . Participants were evaluated monthly for 6 months . Results : Medication adherence was assessed with pill count and urine testing . Drop-out rates , by treatment group , ranged from 12 to 28 % . Among participants who completed the 6-month trial , overall adherence was high ( ∼77 % of participants took > 98 % of prescribed pills ) . Adherence did not differ by treatment arm , but was better at the rural than the urban site and among those with higher baseline BP . Hypertension control ( BP that medication adherence can be high in developing world setting s in clinic attenders",
"We conducted a r and omized controlled trial for 12 weeks in patients with type 2 diabetes living in a rural part of Korea . The intervention group ( n = 35 ) was managed by a diabetes centre which provided specialized management mediated by a primary health-care nurse who used a PDA-type blood glucometer with a bar code detector to measure the capillary glucose levels . The control group ( n = 36 ) received usual care . Compared with baseline , HbA1c was significantly reduced at three-month follow-up in the intervention group ( 8.0 % vs. 7.5 % ; P group . Total cholesterol was significantly reduced in the intervention group ( 10.7 mmol/L vs. 10.4 mmol/L ; P = 0.043 ) . Fasting plasma glucose and triglyceride levels were lower at follow-up in both groups , but the difference was not significant . The new system could be implemented widely and would contribute to improving the quality of diabetes care , even in isolated rural areas",
"Background To evaluate the efficacy of Counselling and Advisory Care for Health ( COACH ) programme in managing dyslipidaemia among primary care practice s in Malaysia . This open-label , parallel , r and omised controlled trial compared the COACH programme delivered by primary care physicians alone ( PCP arm ) and primary care physicians assisted by nurse educators ( PCP-NE arm ) . Methods This was a multi-centre , open label , r and omised trial of a disease management programme ( COACH ) among dyslipidaemic patients in 21 Malaysia primary care practice s. The participating centres enrolled 297 treatment naïve subjects who had the primary diagnosis of dyslipidaemia ; 149 were r and omised to the COACH programme delivered by primary care physicians assisted by nurse educators ( PCP-NE ) and 148 to care provided by primary care physicians ( PCP ) alone . The primary efficacy endpoint was the mean percentage change from baseline LDL-C at week 24 between the 2 study arms . Secondary endpoints included mean percentage change from baseline of lipid profile ( TC , LDL-C , HDL-C , TG , TC : HDL ratio ) , Framingham Cardiovascular Health Risk Score and absolute risk change from baseline in blood pressure parameters at week 24 . The study also assessed the sustainability of programme efficacy at week 36 . Results Both study arms demonstrated improvement in LDL-C from baseline . The least squares ( LS ) mean change from baseline LDL-C were −30.09 % and −27.54 % for PCP-NE and PCP respectively . The difference in mean change between groups was 2.55 % ( p=0.288 ) , with a greater change seen in the PCP-NE arm . Similar observations were made between the study groups in relation to total cholesterol change at week 24 . Significant difference in percentage change from baseline of HDL-C were observed between the PCP-NE and PCP groups , 3.01 % , 95 % CI 0.12 - 5.90 , p=0.041 , at week 24 . There was no significant difference in lipid outcomes between 2 study groups at week 36 ( 12 weeks after the programme had ended ) . Conclusion Patients who received coaching and advice from primary care physicians ( with or without the assistance by nurse educators ) showed improvement in LDL-cholesterol . Disease management services delivered by PCP-NE demonstrated a trend towards add-on improvements in cholesterol control compared to care delivered by physicians alone ; however , the improvements were not maintained when the services were withdrawn . Trial registration National Medical Research Registration ( NMRR ) Number : NMRR-08 - 287 - 1442Trial Registration Number ( Clinical Trials.gov Identifier ) :",
"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",
"OBJECTIVE To compare the effects of low-level facility-based interventions on patient retention rates for cardiovascular ( CV ) disease in an environment of task shifting and nurse-led care in rural health districts in Central Cameroon . METHODS This study is an open-label , three-arm , cluster-r and omised trial in nurse-led facilities . All three groups implemented a treatment contract . The control group ( group 1 ) had no additional intervention , group 2 received the incentive of 1 month of free treatment every forth month of regularly respected visits , and group 3 received reminder letters in case of a missed follow-up visit . The primary outcome was patient retention at 1 year . Secondary outcomes were adherence to follow-up visit schemes and changes in blood pressure ( BP ) and blood glucose levels . Patients ' monthly spending for drugs and transport was calculated retrospectively . RESULTS A total of 33 centres and 221 patients were included . After 1 year , 109 patients ( 49.3 % ) remained in the programme . Retention rates in groups 2 and 3 were 60 % and 65 % , respectively , against 29 % in the control group . The differences between the intervention groups and the control group were significant ( P differences in BP or fasting plasma glucose trends between retained patients in the study groups . Average monthly cost to patients for antihypertensive medication was € 1.1 ± 0.9 and for diabetics € 1.2 ± 1.1 . Transport costs to the centres were on average € 1.1 ± 1.0 for hypertensive patients and € 1.1 ± 1.6 for patients with diabetes . CONCLUSIONS Low-cost interventions suited to an environment of task shifting and nurse-led care and needing minimal additional re sources can significantly improve retention rates in CV disease management in rural Africa . The combination of a treatment contract and reminder letters in case of missed appointments was an effective measure to retain patients in care",
"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",
"AIM The aim of this study was to examine the effect of a cardiac rehabilitation programme on health behaviours and physiological risk parameters in patients with coronary heart disease in Chengdu , China . BACKGROUND Epidemiological studies indicate a dose- , level- and duration -dependent relationship exists between cardiac behavioural and physiological risks and coronary heart disease incidence as well as subsequent cardiac morbidity and mortality . Cardiac risk factor modification has become the very primary goal of modern cardiac rehabilitation programmes . DESIGN METHODS A r and omized controlled trial was conducted . Coronary heart disease patients ( n = 167 ) who met the sampling criteria in two tertiary medical centres in Chengdu , south-west China , were r and omly assigned to either an intervention group ( the cardiac rehabilitation programme ) or control group ( the routine care ) . The change of health behaviours ( walking performance , step II diet adherence , medication adherence , smoking cessation ) and physiological risk parameters ( serum lipids , blood pressure , body weight ) were assessed to evaluate the programme effect . RESULTS Patients in the intervention group demonstrated a significantly better performance in walking , step II diet adherence , medication adherence ; a significantly greater reduction in serum lipids including triglyceride , total cholesterol , low-density lipoprotein ; and significantly better control of systolic and diastolic blood pressure at three months . The majority of these positive impacts were maintained at six months . The effect of the programme on smoking cessation , body weight , serum high-density lipoprotein , was not confirmed . CONCLUSIONS A cardiac rehabilitation programme led by a nurse can significantly improve the health behaviours and cardiac physiological risk parameters in coronary heart disease patients . Nurses can fill significant treatment gaps in the risk factor management of patients with coronary heart disease . RELEVANCE TO CLINICAL PRACTICE This study raises attention regarding the important roles nurses can play in cardiac rehabilitation and the unique way for nurses to meet the rehabilitative care needs of coronary heart disease patients . Furthermore , the hospital-home bridging nature of the programme also created a model for interfacing the acute care and community rehabilitative care",
"BACKGROUND Patients with end stage renal failure require dialysis and strict adherence to treatment plans to sustain life . However , non-adherence is a common and serious problem among patients with chronic kidney disease . There is a scarcity of studies in examining the effects of disease management programmes on patients with chronic kidney disease . OBJECTIVES This paper examines whether the study group receiving the disease management programme have better improvement than the control group , comparing outcomes at baseline ( O1 ) , at 7 weeks at the completion of the programme ( O2 ) and at 13 weeks ( O3 ) . METHODS This is a r and omized controlled trial . The outcome measures were non-adherence in diet , fluid , dialysis and medication , quality of life , satisfaction , symptom control , complication control and health service utilisation . RESULTS There was no significant difference between the control and study group for the baseline measures , except for sleep . Significant differences ( p diet degree non-adherence , sleep , symptom , staff encouragement , overall health and satisfaction . Sustained effects at O3 were noted in the outcome measures of continuous ambulatory peritoneal dialysis ( CAPD ) non-adherence degree , sleep , symptom , and effect of kidney disease . CONCLUSIONS Many studies exploring chronic disease management have neglected the group with end stage renal failure and this study fills this gap . This study has employed an innovative model of skill mix using specialist and general nurses and demonstrated patient improvement in diet non-adherence , CAPD non-adherence , aspects of quality of life and satisfaction with care . Re design ing chronic disease management programmes helps to optimize the use of different levels of skills and re sources to bring about positive outcomes",
"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",
"BACKGROUND Type 2 diabetes mellitus is increasing in incidence and research has shown that normalization of blood glucose levels can moderate the risk of microvascular and neurological complications . AIM The purpose of this study was to investigate the effect of nurse telephone calls on glycosylated haemoglobin ( HbA1c ) levels and adherence to diabetes control recommendations . METHODS A r and omized design with control and experimental groups being assessed pre- and post intervention was used to assess the effectiveness of nurse telephone calls . Twenty patients were r and omly assigned to an intervention group and 16 to a control group . The goal of the intervention was to keep blood glucose concentrations close to the normal range ( HbA1c continued education and reinforcement of diet , exercise , medication adjustment recommendations , as well as frequent self-monitoring of blood glucose levels . Telephone intervention was performed twice per week for the first month and then weekly for the second and third month . Participants were requested to write self-management logs including blood glucose levels , diet and an exercise diary . A dietitian analysed the diet diaries and participants were informed about their results by telephone or mail . All medication adjustments were communicated to participants ' doctors . The HbA1c and diabetes adherence were measured before and after the intervention . RESULTS Patients in the intervention group had a mean decrease of 1.2 % in HbA1c levels and those in the control group had a mean increase of 0.6 % in HbA1c levels . The intervention group had greater diet and blood glucose testing adherence than the control group . CONCLUSION These findings indicate that a nurse telephone intervention can improve HbA1c , and diet and blood glucose testing adherence",
"AIM To test the effects of a postdischarge transitional care programme among patients with coronary heart disease . BACKGROUND . Coronary heart disease is a leading cause of death worldwide . Effective postdischarge care can help patients maintain a healthy lifestyle and thereby control the risk factors . Transitional care is under-developed in mainl and China . DESIGN A r and omised controlled trial . METHOD The control group ( n = 100 ) received routine care and the study group ( n = 100 ) received the postdischarge transitional care programme , which consisted of predischarge assessment , structured home visits and telephone follow-ups within four weeks after discharge . Subjects were recruited in 2002 - 2003 , with data collected at baseline before discharge , two days and four and 12 weeks after discharge . RESULTS Participants in the study group had significantly better underst and ing in diet , medications and health-related lifestyle behaviour at day 2 and in weeks 4 and 12 and better underst and ing in exercise at weeks 4 and 12 . There were significant differences between the control and study groups in diet and health-related lifestyle at day 2 and weeks 4 and 12 , in medication at weeks 4 and 12 and exercise at week 12 . There was no difference in hospital readmission between the two groups . The study group was very satisfied with the care . There was no difference in willingness to pay for nurse follow-up services between groups . CONCLUSION This study is an original effort to establish and test a nurse-led transitional care model in China . Results demonstrate that transitional care is effective in mainl and China , concurring with studies done elsewhere . RELEVANCE TO CLINICAL PRACTICE This study has constructed a transitional care model for patients with coronary heart disease in the context of the Chinese population which is effective in enhancing healthy lifestyle among these patients",
"AIM The aim of this study was to determine the effect of anti-hypertensive patient-oriented education and in-home monitoring for medication adherence and management of hypertension in a primary care setting , by providing education on healthy lifestyle behaviours and medication adherence . BACKGROUND Hypertension is the third most common cause of death worldwide . Prevalence of hypertension in Turkey is approximately 30 % in the general population and 45 - 50 % in population over 50 . DESIGN R and omised controlled study . METHODS This study conducted in Turkey used a study group comprised of 120 subjects ( 40 Group A , 40 Group B , 40 controls ) , all previously diagnosed with hypertension and who started medication therapy at least one year prior to start of study . The study was conducted between February-November 2006 at public primary health care facilities and homes of the study participants . Participants in Group A and B received a total of six monthly education sessions , four times during clinic visits and two home visits . Medication adherence education for Groups A and B and education about healthy lifestyle behaviours for Group B were administered in a structured and individualised format . The control group was routinely monitored in health care facilities . RESULTS Healthy lifestyle behaviours and perception of self-efficacy regarding medication adherence showed improvement after education sessions in Groups A and B. Systolic and diastolic blood pressures of subjects in Group A and B showed a significant decrease compared with those of the control group ; the blood pressure decrease in Group B was greater than in Group A. CONCLUSION Nurses play an important role in uncontrolled hypertension detection and can improve medication adherence and healthy lifestyle behaviours . RELEVANCE TO CLINICAL PRACTICE Patient education medication adherence alone and in combination with healthy lifestyle behaviour teaching is an effective tool for blood pressure reduction in the hypertensive population in primary health care setting"
] |
4116b62c-06ff-11f0-808a-c43d1ab1c353
|
Controversy exists among trials assessing whether prolonged antioxidant vitamin supplementation improves endothelial function in type 2 diabetes mellitus ( T2DM ) subjects . The aim of this study was to systematic ally review and quantify the effect of antioxidant vitamin supplementation on endothelial function in T2DM subjects . MEDLINE , Cochrane , Scopus and Web of Science were search ed up to February 2013 for r and omized controlled trials assessing the effect of antioxidant vitamin E and /or C supplementation on endothelial function in T2DM subjects . Ten r and omized controlled trials comparing antioxidant vitamin-supplemented and control groups ( overall n = 296 ) met the inclusion criteria . Post-intervention st and ardized mean difference ( SMD ) in endothelial function did not reach statistical significance between groups ( 0.35 ; 95 % confidence interval = -0.17 , 0.88 ; P = 0.18 ) . In subgroup analysis , post-intervention endothelial function was significantly improved by antioxidant vitamin supplementation in T2DM subgroups with body mass index ( BMI ) ≤ 29.45 kg m(-2 ) ( SMD = 1.02 ; P T2DM subgroups with BMI > 29.45 kg m(-2 ) ( SMD = -0.07 ; P = 0.70 ) . In meta-regression , an inverse association was found between BMI and post-intervention SMD in endothelial function ( B = -0.024 , P = 0.02 ) . Prolonged antioxidant vitamin E and /or C supplementation could be effective to improve endothelial function in non-obese T2DM subjects
|
[
"Vascular disease accounts for the majority of the clinical complications in diabetes mellitus . As an exaggerated oxidative stress degree has been postulated as the link between diabetes mellitus and endothelial function , a possible positive effect of plasma vitamin E ( Vit . E ) administration on brachial reactivity could be postulated . Our study aims at investigating the possible effect of chronic Vit . E administration on brachial reactivity , oxidative stress indexes , and intracellular magnesium and calcium content in type II diabetic patients free of diabetic complications . Forty adult , type II diabetic patients were enrolled in the study , which was deigned as a double blind , r and omized vs. placebo trial . At baseline all patients underwent the following tests : 1 ) anthropometric and metabolic examinations , 2 ) evaluation of oxidative stress indexes , 3 ) intracellular magnesium and calcium measurements , and 4 ) determination of arterial compliance and distensibility . Then , all patients were r and omly assigned to Vit . E treatment at a dose of 600 mg/day ( Evion Forte ; n = 20 ) or placebo ( n = 20 ) over 8 weeks . At the end of this treatment period , a complete reevaluation of the patients was made . Vit . E treatment was associated with a significant improvement in the percent change in brachial artery diameter ( P oxidative stress indexes ( P Vit . E group , the percent change in brachial artery diameter correlated positively with the percent change in oxidative stress indexes ( oxidized/reduced glutathione , Trolox-equivalent antioxidant capacity , thiobarbituric acid reaction products , lipid peroxides ) and intracellular cation content ( magnesium and calcium ) . After adjustment for age , sex , body mass index , and wait/hip ratio , all of these correlations remained significant ( P brachial artery diameter was still correlated with the percent change in oxidative stress indexes ( P percent change in brachial artery diameter and oxidative stress indexes was no longer significant after adjustment for intracellular Mg and Ca2 + . In conclusion , our study demonstrates that chronic administration of Vit . E improves brachial artery reactivity in patients with type II diabetes mellitus . Such an effect seems mediated by a reduction in oxidative stress and a regulation of intracellular calcium and magnesium contents",
"Manifestations of vascular disease , including microvascular changes , constitute the major part of the morbidity and mortality in diabetic patients . Oxidative stress has been suggested to play an important role in the vascular dysfunction of diabetic patients . Furthermore , epidemiological observations indicate a beneficial effect of an increased dietary intake of antioxidants . The present study tested the hypothesis that the antioxidant ascorbic acid influences microcirculatory function in patients with Type II diabetes . Patients with Type II diabetes were treated with 1 g of ascorbic acid three times a day for 2 weeks in a r and omized placebo-controlled double-blind cross-over design . Microvascular reactivity was assessed by vital capillaroscopy and PRH ( post-occlusive reactive hyperaemia ) . hs-CRP ( high-sensitivity C-reactive protein ) , IL-6 ( interleukin-6 ) , IL-1ra ( interleukin-1 receptor antagonist ) and ox-LDL ( oxidized low-density lipoprotein ) were analysed . The results showed no significant change in microvascular reactivity assessed after 2 weeks of ascorbic acid treatment . TtP ( time to peak ) was 12.0+/-3.3 s before and 11.2+/-3.5 s after ascorbic acid ( n=17 ) . In comparison , TtP was 11.5+/-2.9 s before and 10.6+/-2.8 s after placebo ( not significant ) . IL-1ra , IL-6 , hs-CRP and ox-LDL did not change significantly after ascorbic acid , neither as absolute or relative values . In conclusion , in contrast with some studies reported previously , we could not demonstrate an effect of continuous oral treatment with ascorbic acid on microvascular reactivity assessed at the level of individual capillaries . Furthermore , we found no indication of an effect on inflammatory cytokines or ox-LDL",
"Endothelial dysfunction is a hallmark of Type 2 diabetes related to hyperglycemia and oxidative stress . Nitric oxide-dependent vasodilator actions of insulin may augment glucose disposal . Thus endothelial dysfunction may worsen insulin resistance . Intra-arterial administration of vitamin C improves endothelial dysfunction in diabetes . In the present study , we investigated effects of high-dose oral vitamin C to alter endothelial dysfunction and insulin resistance in Type 2 diabetes . Plasma vitamin C levels in 109 diabetic subjects were lower than healthy ( 36 + /- 2 microM ) levels . Thirty-two diabetic subjects with low plasma vitamin C ( were subsequently enrolled in a r and omized , double-blind , placebo-controlled study of vitamin C ( 800 mg/day for 4 wk ) . Insulin sensitivity ( determined by glucose clamp ) and forearm blood flow in response to ACh , sodium nitroprusside ( SNP ) , or insulin ( determined by plethysmography ) were assessed before and after 4 wk of treatment . In the placebo group ( n = 17 subjects ) , plasma vitamin C ( 22 + /- 3 microM ) , fasting glucose ( 159 + /- 12 mg/dl ) , insulin ( 19 + /- 7 microU/ml ) , and SI(Clamp ) [ 2.06 + /- 0.29 x 10(-4 ) dl x kg(-1 ) x min(-1)/(microU/ml ) ] did not change significantly after placebo treatment . In the vitamin C group ( n = 15 subjects ) , basal plasma vitamin C ( 23 + /- 2 microM ) increased to 48 + /- 6 microM ( P 80 microM ) . No significant changes in fasting glucose ( 156 + /- 11 mg/dl ) , insulin ( 14 + /- 2 microU/ml ) , SI(Clamp ) [ 2.71 + /- 0.46 x 10(-4 ) dl x kg(-1 ) x min(-1)/(microU/ml ) ] , or forearm blood flow in response to ACh , SNP , or insulin were observed after vitamin C treatment . We conclude that high-dose oral vitamin C therapy , result ing in incomplete replenishment of vitamin C levels , is ineffective at improving endothelial dysfunction and insulin resistance in Type 2 diabetes",
"OBJECTIVE To examine the effect of vitamin C on forearm vasodilatory response to reactive hyperemia and on plasma level of plasminogen activator inhibitor 1 ( PAI-1 ) , von Willebr and factor ( vWF ) , tissue plasminogen activator ( tPA ) , antithrombin III ( ATIII ) , proteins C and S , and factors V ( fV ) and VII ( fVII ) in patients with both type 2 diabetes and CAD . RESEARCH DESIGN AND METHODS A total of 39 patients with type 2 diabetes and CAD were divided into two groups and received vitamin C ( 2 g/day ) or no antioxidant for 4 weeks . Forearm blood flow was determined using venous occlusion gauge-strain plethysmography at baseline and after treatment . Forearm vasodilatory response to reactive hyperemia ( RH% ) or nitrate ( NTG% ) was defined as the percent change of flow from baseline to the maximum flow during reactive hyperemia or after administration of nitrate , respectively . Biochemical markers were determined by enzyme-linked immunosorbent assay ( ELISA ) or other st and ard methods . RESULTS RH% was significantly increased after treatment with vitamin C ( from 62.4 + /- 7.2 to 83.1 + /- 9.3 % , P = 0.024 ) but remained unaffected in the control group . Vitamin C decreased plasma levels of fV ( from 143 + /- 5.4 to 123 + /- 6.03 % , P = 0.038 ) , vWF ( from 133.5 + /- 14.5 to 109.5 + /- 11.4 % , P = 0.016 ) , and tPA ( from 12.3 + /- 0.99 to 8.40 + /- 0.60 ng/ml , P = 0.001 ) , whereas these levels remained unaffected in the control group . The changes in RH% , vWF , and tPA were significantly greater ( P = 0.028 , 0.036 , and 0.007 , respectively ) in the vitamin C-treated group than in the control group . Levels of ATIII , proteins S and C , fVII , and PAI-1 remained unchanged in all groups . CONCLUSIONS Short-term treatment with high doses of vitamin C improved RH% and decreased plasma levels of tPA and vWF in patients with type 2 diabetes and CAD",
"We examined the effects of high-dosage vitamin E treatment over a 12-month period on the vascular reactivity of micro- and macrocirculation and left ventricular function in diabetic patients . Subjects ( n = 89 ) were r and omized to vitamin E ( 1,800 IU daily ) or placebo and were followed for 12 months . High-resolution ultrasound images were used to measure the flow-mediated dilation ( FMD ; endothelium dependent ) and nitroglycerin-induced dilation ( NID ; endothelium independent ) of the brachial artery . Laser Doppler perfusion imaging was used to measure vascular reactivity in the forearm skin . Left ventricular function was evaluated using transthoracic echocardiogram . At the end of the 6-month period , a worsening in endothelium-dependent skin vasodilation ( P = 0.02 ) and rise in endothelin levels ( P = 0.01 ) were found in the vitamin E compared with the placebo group . At the end of the 12-month period , a worsening was observed in NID ( P = 0.02 ) and a marginal worsening was seen in systolic blood pressure ( P = 0.04 ) and FMD ( P = 0.04 ) in the vitamin E compared with the placebo group . In addition C-reactive protein levels decreased marginally in the vitamin E compared with the placebo group ( P = 0.05 ) . No changes were observed in left ventricular function . We concluded that long-term treatment with 1,800 IU of vitamin E has no beneficial effects on endothelial or left ventricular function in diabetic patients . Because vitamin E-treated patients had a worsening in some vascular reactivity measurements when compared with control subjects , the use of high dosages of vitamin E can not be recommended",
"The aims of the study were to evaluate the short-term effects of a new thermosensitive , vitamin E ( V-E ) mousse on local free radicals ( FR ) and skin flux in diabetic microangiopathy . A group of 40 patients with diabetic microangiopathy was included . The variation in measure ments of skin FR was evaluated by the D-Rom test . Subjects were between 45 and 65 years with type II diabetes and good metabolic control . E-mousse ® , a thermoactive preparation of acetate vitamin E ( 20 % ) , was applied twice daily on the whole surface of the leg ( below knee ) and foot for 3 weeks . The contralateral leg was untreated acting as control . Subjects with age between 45 and 65 years with type II diabetes ( diagnosed at least 5 years before ) and good metabolic control ( blood sugar informed consent . Patients with uncontrolled diabetes , peripheral vascular disease , and severe lower limbs infec tions were excluded . Local free radicals ( FR ) and laser Doppler flux including the venoarteriolar response ( VAR ) were evaluated . The tolerability was evaluated by a semiquantitative score . Of the 40 included patients 34 completed the study . The 2 groups were comparable . At 3 weeks there was no decrease in FR in controls ; the decrease in the treatment group was 45.3 % ( p group RF decreased ( p No significant variations were observed in the control group . The variation in symptomatic score was from a total value of 8 to 5 in the control group and from 8 to 1 in the treatment group ( p 0.02 ) . Their tolerability was good . In conclusion local treatment with E-mousse for 3 weeks in diabetic microangiopathy improves skin microcirculation and the metabolic condition as shown by the decrease in FR",
"BACKGROUND Insulin therapy may influence cardiovascular disease ( CVD ) and lipid metabolism in type 2 diabetes ( T2D ) . Exaggerated postpr and ial lipaemia ( PPL ) is a feature of diabetic dyslipidaemia affecting CVD via enhanced oxidative stress ( OS ) and endothelial dysfunction . We assessed endothelial function and OS during PPL following insulin and vitamin C. Twenty ( 17 M ) T2D patients were studied ( mean Hba1c 8.4 % ) at baseline , following 6 weeks of insulin lispro ( 0.2 Iu kg-1 ) and vitamin C 1-g daily . Eight-h lipid and glucose profiles were measured following a fatty meal . Endothelial function ( flow-mediated vasodilatation : FMD ) and OS were measured at fasting , 4 h and 8 h. MATERIAL S AND METHODS Glucose , body mass index , and total and LDL cholesterol remained unchanged . FMD improved . Placebo group : fasting , 1.1 + /- 1.2 to 4.2 + /- 1.1 % ( P Vitamin C group : fasting , 0.9 + /- 1.1 to 6.1 + /- 1.3 % ( P Post-pr and ial lipaemia was attenuated : TG area-under-curve ( mmol L-1 8 h-1 ) , 52.6 + /- 11 to 39.1 + /- 12.5 ( placebo group ) , P Oxidative stress was reduced , with greater changes in the vitamin C group . CONCLUSION Insulin may thus exert vascular benefits in T2D , by modifying fasting and postpr and ial lipid metabolism result ing in reduced OS and improved EF . Vitamin C therapy may augment the vascular benefits of insulin in T2D through additional effects on OS and EF",
"AIMS Vascular endothelial dysfunction , an early marker of atherosclerosis , has been demonstrated in Type 2 diabetes mellitus ( DM ) . Vitamin E preserves endothelial function in animal models of diabetes and reduces cardiovascular risk . We examined endothelial function and the effect of vitamin E supplements in uncomplicated Type 2 DM . METHODS Forty-eight subjects with Type 2 DM and 21 controls had endothelial function assessed using forearm venous occlusion plethysmography with endothelium-independent ( sodium nitroprusside ) and dependent ( acetylcholine , bradykinin ) vasodilators . Those with diabetes received 1600 i.u . daily oral alpha-tocopherol or placebo , double-blind for 8 weeks , and had endothelial function reassessed . RESULTS The diabetic group had higher HbA1c ( 6.9+/-1.4 vs 4.8+/-0.6 % ; P systolic ( 145+/-15 vs. 130+/-16 mm Hg ; P diastolic blood pressure ( 79+/-8 vs. 76+/-9 mm Hg ; P = 0.15 ) . There was blunted vasodilation to acetylcholine ( 15 microg/min ; P Vasodilation to sodium nitroprusside and bradykinin was similar ( all P>0.1 ) . Alpha-tocopherol did not affect vasodilation to nitroprusside ( P>0.1 ) , acetylcholine ( P>0.1 ) or bradykinin ( P>0.1 ) . CONCLUSIONS There may be receptor-specific endothelial dysfunction in subjects with uncomplicated Type 2 DM . This is not improved by treatment with alpha-tocopherol",
"Type II diabetes is characterized by increased oxidative stress , endothelial dysfunction and hypertension . We investigated whether short-term treatment with oral vitamin C reduces oxidative stress and improves endothelial function and blood pressure in subjects with Type II diabetes . Subjects ( n = 35 ) received vitamin C ( 1.5 g daily in three doses ) or matching placebo for 3 weeks in a r and omized , double-blind , parallel-group design . Plasma concentrations of 8-epi-prostagl and in F(2alpha ) ( 8-epi-PGF(2alpha ) ) , a non-enzymically derived oxidation product of arachidonic acid , were used as a marker of oxidative stress . Endothelial function was assessed by measuring forearm blood flow responses to brachial artery infusion of the endothelium-dependent vasodilator acetylcholine ( with nitroprusside as an endothelium-independent control ) and by the pulse wave responses to systemic albuterol ( endothelium-dependent vasodilator ) and glyceryl trinitrate ( endothelium-independent vasodilator ) . Plasma concentrations of vitamin C increased from 58+/-6 to 122+/-10 micromol/l after vitamin C , but 8-epi-PGF(2alpha ) levels ( baseline , 95+/-4 pg/l ; after treatment , 99+/-5 pg/l ) , blood pressure ( baseline , 141+/-5/80+/-2 mmHg ; after treatment , 141+/-5/81+/-3 mmHg ) and endothelial function , as assessed by the systemic vasodilator response to albuterol and by the forearm blood flow response to acetylcholine , were not significantly different from baseline or placebo . Thus treatment with vitamin C ( 1.5 g daily ) for 3 weeks does not significantly improve oxidative stress , blood pressure or endothelial function in patients with Type II diabetes",
"Oxidative stress decreases the bioavailability of endothelium-derived nitric oxide in diabetic patients . We investigated whether impaired endothelium-dependent vasodilation ( EDV ) in diabetes can be improved by long-term administration of oral antioxidants . Forty-nine diabetic subjects [ 26 Type 1 ( T1 ) and 23 Type 2 ( T2 ) ] and 45 matched healthy control subjects were r and omized to receive oral vitamin C ( 1,000 mg ) and vitamin E ( 800 IU ) daily or matching placebo for 6 mo . Vascular ultrasonography was used to determine brachial artery EDV and endothelium-independent vasodilation ( EIV ) . EDV was decreased in both T1 ( 4.9 + /- 0.9 % , P = 0.015 ) and T2 ( 4.1 + /- 1.0 % , P EIV was decreased in T2 ( 15.0 + /- 1.2 % , P antioxidant vitamins increased EDV in T1 ( by 3.4 + /- 1.4 % , P = 0.023 ) but not T2 subjects ( by 0.5 . + /- 0.4 % , P = 0.3 ) . Antioxidant therapy had no significant affect on EIV . Oral antioxidant therapy improves EDV in T1 but not T2 diabetes . These results are consistent with the lack of clinical benefit in studies that have included primarily T2 diabetic patients",
"Objective Oxidative stress has been suggested to play a role in the development of diabetes , hypertension and vascular dysfunction . Vitamin E , a major lipid-soluble dietary antioxidant , has two major dietary forms , α-tocopherol and γ-tocopherol . The potential importance of γ-tocopherol has largely been overlooked . Our aim was to investigate the effect of α-tocopherol and γ-tocopherol supplementation on 24-h ambulatory blood pressure ( BP ) and heart rate , vascular function and oxidative stress in individuals with type 2 diabetes . Method Fifty-eight individuals with type 2 diabetes were r and omized in a double-blind , placebo-controlled trial . Participants were r and omized to a daily dose of 500 mg/day RRR-α-tocopherol , 500 mg/day mixed tocopherols ( 60 % γ-tocopherol ) or placebo for 6 weeks . Primary endpoints were 24-h ambulatory BP and heart rate , endothelium-dependent and independent vasodilation and plasma and urinary F2-isoprostanes . Results Treatment with α-tocopherol significantly increased systolic BP [ 7.0 ( 5.2 , 8.8 ) mmHg , P [ 5.3 ( 4.0 , 6.5 ) mmHg , P 0.0001 ] , pulse pressure [ 1.8 ( 0.6 , 3.0 ) mmHg , P Treatment with mixed tocopherols significantly increased systolic BP [ 6.8 ( 4.9 , 8.6 ) mmHg , P BP [ 3.6 ( 2.3 , 4.9 ) mmHg , P [ 3.2 ( 2.0 , 4.4 ) mmHg , P 0.0001 ] and heart rate [ 1.8 ( 0.5 , 3.2 ) bpm , P Treatment with α-tocopherol or mixed tocopherols significantly reduced plasma F2-isoprostanes versus placebo , but had no effect on urinary F2-isoprostanes . Endothelium-dependent and independent vasodilation was not affected by either treatment . Conclusion In contrast to our initial hypothesis , treatment with either α- or mixed tocopherols significantly increased BP , pulse pressure and heart rate in individuals with type 2 diabetes",
"Endothelium-dependent vasodilation is impaired in humans with diabetes mellitus . Inactivation of endothelium-derived nitric oxide by oxygen-derived free radicals contributes to abnormal vascular reactivity in experimental models of diabetes . To determine whether this observation is relevant to humans , we tested the hypothesis that the antioxidant , vitamin C , could improve endothelium-dependent vasodilation in forearm resistance vessels of patients with non-insulin-dependent diabetes mellitus . We studied 10 diabetic subjects and 10 age-matched , nondiabetic control subjects . Forearm blood flow was determined by venous occlusion plethysmography . Endothelium-dependent vasodilation was assessed by intraarterial infusion of methacholine ( 0.3 - 10 micrograms/min ) . Endothelium-independent vasodilation was measured by intraarterial infusion of nitroprusside ( 0.3 - 10 micrograms/min ) and verapamil ( 10 - 300 micrograms/min ) . Forearm blood flow dose-response curves were determined for each drug before and during concomitant intraarterial administration of vitamin C ( 24 mg/min ) . In diabetic subjects , endothelium-dependent vasodilation to methacholine was augmented by simultaneous infusion of vitamin C ( P = 0.002 ) ; in contrast , endothelium-independent vasodilation to nitroprusside and to verapamil were not affected by concomitant infusion of vitamin C ( P = 0.9 and P = 0.4 , respectively ) . In nondiabetic subjects , vitamin C administration did not alter endothelium-dependent vasodilation ( P = 0.8 ) . We conclude that endothelial dysfunction in forearm resistance vessels of patients with non-insulin-dependent diabetes mellitus can be improved by administration of the antioxidant , vitamin C. These findings support the hypothesis that nitric oxide inactivation by oxygen-derived free radicals contributes to abnormal vascular reactivity in diabetes"
] |
4116b6f4-06ff-11f0-808a-c43d1ab1c353
|
Modafinil is an FDA -approved eugeroic that directly increases cortical catecholamine levels , indirectly upregulates cerebral serotonin , glutamate , orexin , and histamine levels , and indirectly decreases cerebral gamma-amino-butrytic acid levels . In addition to its approved use treating excessive somnolence , modafinil is thought to be used widely off-prescription for cognitive enhancement . However , despite this popularity , there has been little consensus on the extent and nature of the cognitive effects of modafinil in healthy , non-sleep-deprived humans . This problem is compounded by method ological discrepancies within the literature , and reliance on psychometric tests design ed to detect cognitive effects in ill rather than healthy population s. In order to provide an up-to- date systematic evaluation that addresses these concerns , we search ed MEDLINE with the terms " modafinil " and " cognitive " , and review ed all result ant primary studies in English from January 1990 until December 2014 investigating the cognitive actions of modafinil in healthy non-sleep-deprived humans . We found that whilst most studies employing basic testing paradigms show that modafinil intake enhances executive function , only half show improvements in attention and learning and memory , and a few even report impairments in divergent creative thinking . In contrast , when more complex assessment s are used , modafinil appears to consistently engender enhancement of attention , executive functions , and learning . Importantly , we did not observe any preponderances for side effects or mood changes . Finally , in light of the method ological discrepancies encountered within this literature , we conclude with a series of recommendations on how to optimally detect valid , robust , and consistent effects in healthy population s that should aid future assessment of neuroenhancement
|
[
"Abstract : In a double-blind , parallel groups study , 60 healthy student volunteers ( 29 men and 31 women , aged 19 - 22 years ) were r and omly allocated to receive placebo , 100 or 200 mg modafinil . Two hours later , in the early evening , they completed an extensive cognitive battery . The 3 groups did not differ in self-ratings of sleepiness or tiredness before the testing session , and there were no treatment-associated changes in these or in mood ratings during the tests . Modafinil was without effect in several tests of reaction time and attention , but the 200-mg group was faster at simple color naming of dots and performed better than placebo in the Rapid Visual Information Processing test of sustained attention . Modafinil was without effect on spatial working memory , but the 100-mg group performed better in the backward part of the digit span test . Modafinil was without effect on verbal short-term memory ( story recall ) , but 100 mg improved digit span forward , and both doses improved pattern recognition , although this was accompanied by a slowing of response latency in the 200-mg group . There were no significant effects of modafinil compared with placebo in tests of long-term memory , executive function , visuospatial and constructional ability , or category fluency . These results suggest that the benefits of modafinil are not clearly dose-related , and those from 100 mg are limited to the span of immediate verbal recall and short-term visual recognition memory , which is insufficient for it to be considered as a cognitive enhancer in non-sleep-deprived individuals",
"Abstract Rationale . Modafinil , a novel wake-promoting agent , has been shown to have a similar clinical profile to that of conventional stimulants such as methylpheni date . We were therefore interested in assessing whether modafinil , with its unique pharmacological mode of action , might offer similar potential as a cognitive enhancer , without the side effects commonly experienced with amphetamine-like drugs . Objectives . The main aim of this study was to evaluate the cognitive enhancing potential of this novel agent using a comprehensive battery of neuropsychological tests . Methods . Sixty healthy young adult male volunteers received either a single oral dose of placebo , or 100 mg or 200 mg modafinil prior to performing a variety of tasks design ed to test memory and attention . A r and omised double-blind , between-subjects design was used . Results . Modafinil significantly enhanced performance on tests of digit span , visual pattern recognition memory , spatial planning and stop-signal reaction time . These performance improvements were complemented by a slowing in latency on three tests : delayed matching to sample , a decision-making task and the spatial planning task . Subjects reported feeling more alert , attentive and energetic on drug . The effects were not clearly dose dependent , except for those seen with the stop-signal paradigm . In contrast to previous findings with methylpheni date , there were no significant effects of drug on spatial memory span , spatial working memory , rapid visual information processing or attentional set-shifting . Additionally , no effects on paired associates learning were identified . Conclusions . These data indicate that modafinil selectively improves neuropsychological task performance . This improvement may be attributable to an enhanced ability to inhibit pre-potent responses . This effect appears to reduce impulsive responding , suggesting that modafinil may be of benefit in the treatment of attention deficit hyperactivity disorder",
"Functional magnetic resonance imaging ( fMRI ) can be used to detect regional brain responses to changes in sensory stimuli . We have used fMRI to determine the amount of visual and auditory cortical activation in 12 normal subjects and 12 subjects with the narcoleptic syndrome , using a multiplexed visual and auditory stimulation paradigm . In both normal and narcoleptic subjects , mean cortical activation levels during the presentation of periodic visual and auditory stimulation showed no appreciable differences with either age or sex . Normal subjects showed higher levels of visual activation at 10:00 hours than 15:00 hours , with a reverse pattern in narcoleptic subjects ( P = 0.007 ) . The group differences in spatial extent of cortical activation between control and narcoleptic subjects were small and statistically insignificant . The alerting action , and imaging response , to a single oral dose of the sleep-preventing drug modafinil 400 mg were then determined and compared with placebo in both the 12 normal ( 8 given modafinil , 4 placebo ) and 12 narcoleptic subjects ( 8 modafinil , 4 placebo ) . Modafinil caused an increase in self-reported levels of alertness in 7 of 8 narcoleptic subjects , but there was no significant difference between mean pretreatment and post-treatment activation levels as determined by fMRI for either normal or narcoleptic syndrome subjects given modafinil . However , in the modafinil-treated group of 8 normal and 8 narcoleptic subjects , there was a clock time independent correlation between the initial level of activation as determined by the pretreatment scan and the post-treatment change in activation ( visual , P = 0.002 ; and auditory , P = 0.001 ) . No correlation was observed in placebo-treated subjects ( P = 0.99 and 0.77 , respectively ) . Although limited by the small number of subjects , and the lack of an objective measure of alertness , the findings of this study suggest that low cortical activation levels in both normal and narcoleptic subjects are increased following the administration of modafinil . Functional magnetic resonance imaging may be a valuable addition to established studies of attention",
"Methamphetamine (MA)-dependent individuals exhibit deficits in cognition and prefrontal cortical function . Therefore , medications that improve cognition in these subjects may improve the success of therapy for their addiction , especially when cognitive behavioral therapies are used . Modafinil has been shown to improve cognitive performance in neuropsychiatric patients and healthy volunteers . We therefore conducted a r and omized , double-blind , placebo-controlled , cross-over study , using functional magnetic resonance imaging , to examine the effects of modafinil on learning and neural activity related to cognitive function in abstinent , MA-dependent , and healthy control participants . Modafinil ( 200 mg ) and placebo were administered orally ( one single dose each ) , in counterbalanced fashion , 2 h before each of two testing sessions . Under placebo conditions , MA-dependent participants showed worse learning performance than control participants . Modafinil boosted learning in MA-dependent participants , bringing them to the same performance level as control subjects ; the control group did not show changes in performance with modafinil . After controlling for performance differences , MA-dependent participants showed a greater effect of modafinil on brain activation in bilateral insula/ventrolateral prefrontal cortex and anterior cingulate cortices than control participants . The findings suggest that modafinil improves learning in MA-dependent participants , possibly by enhancing neural function in regions important for learning and cognitive control . These results suggest that modafinil may be a suitable pharmacological adjunct for enhancing the efficiency of cognitive-based therapies for MA dependence",
"Improving cognition in people with neuropsychiatric disorders remains a major clinical target . By themselves pharmacological and non-pharmacological approaches have shown only modest effects in improving cognition . In the present study we tested a recently-proposed methodology to combine CT with a ' cognitive-enhancing ' drug to improve cognitive test scores and exp and ed on previous approaches by delivering combination drug and CT , over a long intervention of repeated sessions , and used multiple tasks to reveal the cognitive processes being enhanced . We also aim ed to determine whether gains from this combination approach generalised to untrained tests . In this proof of principle r and omised-controlled trial thirty-three healthy volunteers were r and omised to receive either modafinil or placebo combined with daily cognitive training over two weeks . Volunteers were trained on tasks of new- language learning , working memory and verbal learning following 200 mg modafinil or placebo for ten days . Improvements in trained and untrained tasks were measured . Rate of new- language learning was significantly enhanced with modafinil , and effects were greatest over the first five sessions . Modafinil improved within-day learning rather than between-day retention . No enhancement of gains with modafinil was observed in working memory nor rate of verbal learning . Gains in all tasks were retained post drug-administration , but transfer effects to broad cognitive abilities were not seen . This study shows that combining CT with modafinil specifically elevates learning over early training sessions compared to CT with placebo and provides a proof of principle experimental paradigm for pharmacological enhancement of cognitive remediation",
"Background Surgeons are usually exposed to high workloads leading to fatigue and stress . This not only increases the likelihood of mistakes during surgery but also puts pressure on surgeons to use drugs to counteract fatigue , distress , concentration deficits , burnout or symptoms of depression . The prevalence of surgeons taking pharmacological cognitive enhancement ( CE ) or mood enhancement ( ME ) drugs has not been systematic ally assessed so far . Methods Surgeons who attended five international conferences in 2011 were surveyed with an anonymous self-report question naire ( AQ ) regarding the use of prescription or illicit drugs for CE and ME and factors associated with their use . The R and omized Response Technique ( RRT ) was used in addition . The RRT guarantees a high degree of anonymity and confidentiality when a person is asked about stigmatizing issues , such as drug abuse . Results A total of 3,306 question naires were distributed and 1,145 entered statistical analysis ( response rate : 36.4 % ) . According to the AQ , 8.9 % of all surveyed surgeons confessed to having used a prescription or illicit drug exclusively for CE at least once during lifetime . As one would expect , the prevalence rate assessed by RRT was approximately 2.5-fold higher than that of the AQ ( 19.9 % ; 95 % confidence interval ( CI ) , 15.9 % to 23.9 % , N = 1,105 ) . An even larger discrepancy between the RRT and AQ was observed for the use of antidepressants with a 6-fold higher prevalence ( 15.1 % ; 95 % CI , 11.3 % to 19.0 % , N = 1,099 ) as compared to 2.4 % with the AQ . Finally , logistic regression analysis revealed that pressure to perform at work ( odds ratio ( OR ) : 1.290 ; 95 % CI , 1.000 to 1.666 ; P = 0.05 ) or in private life ( OR : 1.266 ; 95 % CI , 1.038 to 1.543 ; P = 0.02 ) , and gross income ( OR : 1.337 ; 95 % CI , 1.091 to 1.640 ; P = 0.005 ) , were positively associated with the use of drugs for CE or ME . Conclusions The use of illicit and prescription drugs for CE or ME is an underestimated phenomenon among surgeons which is generally attributable to high workload , perceived workload , and private stress . Such intake of drugs is associated with attempts to counteract fatigue and loss of concentration . However , drug use for CE may lead to addiction and to overestimation of one ’s own capabilities , which can put patients at risk . Coping strategies should be taught during medical education",
"Modafinil differs from other arousal-enhancing agents in chemical structure , neurochemical profile , and behavioral effects . Most functional neuroimaging studies to date examined the effect of modafinil only on information processing underlying executive cognition , but cognitive enhancers in general have been shown to have pronounced effects on emotional behavior , too . We examined the effect of modafinil on neural circuits underlying affective processing and cognitive functions . Healthy volunteers were enrolled in this double-blinded placebo-controlled trial ( 100 mg/day for 7 days ) . They underwent BOLD fMRI while performing an emotion information-processing task that activates the amygdala and two prefrontally dependent cognitive tasks — a working memory ( WM ) task and a variable attentional control ( VAC ) task . A clinical assessment that included measurement of blood pressure , heart rate , the Hamilton anxiety scale , and the profile of mood state ( POMS ) question naire was also performed on each test day . BOLD fMRI revealed significantly decreased amygdala reactivity to fearful stimuli on modafinil compared with the placebo condition . During executive cognition tasks , a WM task and a VAC task , modafinil reduced BOLD signal in the prefrontal cortex and anterior cingulate . Although not statistically significant , there were trends for reduced anxiety , for decreased fatigue-inertia and increased vigor-activity , as well as decreased anger-hostility on modafinil . Modafinil in low doses has a unique physiologic profile compared with stimulant drugs : it enhances the efficiency of prefrontal cortical cognitive information processing , while dampening reactivity to threatening stimuli in the amygdala , a brain region implicated in anxiety",
"Rationale Modafinil is a well-tolerated psychostimulant drug with low addictive potential that is used to treat patients with narcolepsy or attention deficit disorders and to enhance vigilance in sleep-deprived military personal . So far , underst and ing of the cognitive enhancing effects of modafinil and the relevant neurobiological mechanisms are incomplete . Objectives The aim of this study was to investigate the effects of modafinil on working memory processes in humans and how they are related to noradrenergic stimulation of the prefrontal cortex . Methods Sixteen healthy volunteers ( aged 20–29 years ) received either modafinil 200 mg or placebo using a double blind crossover design . Two computerized working memory tasks were administered , a numeric manipulation task that requires short-term maintenance of digit-sequences and different degrees of manipulation as well as delayed matching task that assesses maintenance of visuo-spatial information over varying delay lengths . The battery was supplemented by st and ardized paper pencil tasks of attentional functions . Results Modafinil significantly reduced error rates in the long delay condition of the visuo-spatial task and in the manipulation conditions , but not in the maintenance condition of the numeric task . Analyses of reaction times showed no speed-accuracy trade-off . Attentional control tasks ( letter cancellation , trail-making , catch trials ) were not affected by modafinil . Conclusions In healthy volunteers without sleep deprivation modafinil has subtle stimulating effects on maintenance and manipulation processes in relatively difficult and monotonous working memory tasks , especially in lower performing subjects . Overlapping attentional and working memory processes have to be considered when study ing the noradrenergic modulation of the prefrontal cortex",
"There is intense interest in the development of effective cognitive enhancing drugs which would have therapeutic application across a number of neurological and psychological disorders including dementia , schizophrenia and depression . However , development in this area has been limited by the absence of sensitive biomarkers which can be used to detect and refine therapeutic-like action in phase 1 clinical studies . The aim of the present study was therefore to develop a measure of cognition relevant to the action of c and i date cognitive enhancers which might be sensitive to pharmacological manipulation in healthy volunteers . Healthy volunteers ( n = 34 ) were r and omised to receive a single dose of modafinil ( 100 mg ) or placebo . Five hours post dose , attentional flexibility in learning was assessed using a novel implicit learning task . Volunteers also completed an auditory digit span task and visual analogue scales ( VAS ) . Modafinil increased alertness as measured by the VAS . In the implicit learning task , modafinil enhanced learning rates in terms of both accuracy and reaction time , suggesting an increase in implicit rule learning . These results suggest that the novel learning task should be explored as a biomarker of early cognitive improvement which could be more sensitive than conventional measures",
"Background Modafinil is employed for the treatment of narcolepsy and has also been , off-label , used to treat cognitive dysfunction in neuropsychiatric disorders . In a previous study , we have reported that single dose administration of modafinil in healthy young subjects enhances fluid reasoning and affects resting state activity in the Fronto Parietal Control ( FPC ) and Dorsal Attention ( DAN ) networks . No changes were found in the Salience Network ( SN ) , a surprising result as the network is involved in the modulation of emotional and fluid reasoning . The insula is crucial hub of the SN and functionally divided in anterior and posterior subregions . Methodology Using a seed-based approach , we have now analyzed effects of modafinil on the functional connectivity ( FC ) of insular subregions . Principal Findings Analysis of FC with resting state fMRI ( rs-FMRI ) revealed increased FC between the right posterior insula and the putamen , the superior frontal gyrus and the anterior cingulate cortex in the modafinil-treated group . Conclusions Modafinil is considered a putative cognitive enhancer . The rs-fMRI modifications that we have found are consistent with the drug cognitive enhancing properties and indicate subregional targets of action . Trial Registration Clinical Trials.gov",
"Modafinil is a selective wakefulness-promoting agent that has been shown to enhance cognitive performance under conditions of sleep deprivation but which has equivocal effects in normal young volunteers . In a double-blind parallel group design study , 45 non-sleep-deprived middle-aged volunteers ( 20 men and 25 women , aged 50 - 67 years ) were r and omly allocated to receive two capsules containing placebo , 100 or 200 mg modafinil , and 3 h later they completed 100 mm visual analogue scales of mood and bodily symptoms , before and after an extensive battery of cognitive tests [ pen and paper and the Cambridge Neuropsychological Test Automated Battery ( CANTAB ) ] . There were no significant treatment-associated changes in ratings of mood or bodily symptoms and no significant effects on most of the cognitive tests used in this study . The group treated with modafinil ( 200 mg ) was significantly faster in a simple colour naming of dots and also significantly better in a test of constructional ability ( Clock Drawing Test ) compared with the placebo group . However , subjects in the 200-mg group also made significantly more total errors in the Intra/Extradimensional Set Shift ( ID/ED ) task than both the other groups . Thus , this study found limited evidence of cognitive-enhancing properties of modafinil in healthy middle-aged volunteers",
"Rationale The majority of studies investigating the cognitive effects of modafinil , a wake-promoting compound , demonstrate some improvements in attention . The potential of the drug to selectively benefit distinct components of attention has yet to be fully explored in healthy adults . Objective The present study was conducted to investigate modafinil ’s effect on specific cognitive tasks that tax components of attention switching . One required the rapid switching of attention between stimuli , and another contained an embedded working memory component on top of the attentional shift requirements . Additionally , prospect i ve memory was examined , which requires the interruption of an ongoing activity to retrieve and act upon a previously formed intention . Material s and methods Healthy non-smoking volunteers , matched on age , intelligence , and baseline cognitive ability , received either a capsule that contained 200 mg modafinil or placebo . Subjective measures of mood and physiological response were taken throughout the experimental session , and the tasks were completed between 2 and 3 h post-dosing . Results Two hundred milligrams modafinil improved accuracy without a reaction time trade-off , in both conditions of the attention-shifting task , but only when re sources were most challenged . In contrast , the drug afforded no improvement in prospect i ve remembering or in the ongoing task that was interrupted . Conclusion Modafinil appears to promote rapid switching of attention in conditions that are most dem and ing , whilst it offers no benefits in a task that requires unpredictable and infrequent disengagement of attention from an ongoing task in order to act upon an alternative task",
"Background Modafinil is a medication licensed for the treatment of narcolepsy . However , it has been reported that healthy individuals without wakefulness disorders are using modafinil off-label to enhance cognitive functioning . Although some studies have reported that modafinil improves cognitive task performance in healthy volunteers , numerous other studies have failed to detect cognitive enhancing effects of modafinil on several well-established neuropsychological tasks . Interestingly , several clinical and pre clinical studies have found that improved cognitive task performance by modafinil is accompanied by slower response times . This observation raises the question as to whether this slowing of response time in healthy volunteers is a necessary and sufficient condition for cognitive enhancement with modafinil . The aim of the current experiment was to explore this question by investigating the effects of modafinil on the Hayling Sentence Completion Test ( HSCT ) . Methodology Sixty-four healthy volunteers received either a single dose ( 200 mg ) of modafinil ( n = 32 ) or placebo ( n = 32 ) in a r and omized , double-blind , placebo-controlled , parallel group study in which the principal outcome measures were response latencies on the response initiation and response inhibition sections of the HSCT . Principal Findings Participants dosed with modafinil had significantly longer mean response latencies on the HSCT for both the response initiation and response inhibition compared to participants dosed with placebo . However , participants in both groups made a similar number of errors on each of these measures , indicating that modafinil did not enhance the accuracy of performance of the task relative to placebo . Conclusions This study demonstrated that administration of single 200 mg doses of modafinil to healthy individuals increased the latency of responses in the performance of the HSCT , a task that is highly sensitive to prefrontal executive function , without enhancing accuracy of performance . This finding may provide important clues to defining the limitations of modafinil as a putative cognitive enhancer . Trial Registration Clinical Trials.gov",
"Modafinil is a selective wakefulness-promoting agent with beneficial effects in narcolepsy and conditions of sleep deprivation . In a double-blind study we examined its effects in 30 healthy , non sleep-deprived students ( 19 men and 11 women , aged 19 - 23 years ) , who were r and omly allocated to placebo , 100 or 200 mg modafinil and 3 h later completed 100 mm visual analogue scales relating to mood and bodily symptoms , before and after an extensive battery of cognitive tests ( pen and paper and CANTAB ) . There were no significant differences between the three treatment groups on any of the cognitive tests used in this study . There was a significant post-treatment change in the factor measuring ' somatic anxiety ' and in individual ratings of ' shaking ' , ' palpitations ' , ' dizziness ' , ' restlessness ' , ' muscular tension ' , ' physical tiredness ' and ' irritability ' , which was mainly due to significantly higher ratings of somatic anxiety in the 100 mg group compared with the other two groups . Further changes in mood were revealed after the stress of cognitive testing , with the 100 mg group showing greater increases in the ' psychological anxiety ' and the ' aggressive mood ' factors ( as measured from the Bond and Lader scales )",
"Summary .Modafinil is a novel vigilance-enhancing agent . We were interested if modafinil would also enhance motor excitability and improve motor performance and attention in healthy subjects . Ten volunteers received either a single oral dose of placebo or 200 mg modafinil . A r and omized double-blind crossover design was used . Transcranial magnetic stimulation was employed to test intracortical inhibition , intracortical facilitation , the cortical silent period and to obtain stimulus-response curves . In addition , M responses and F waves were recorded . Reaction time tasks , the nine-hole-peg test and the d2 attention test were also applied . These studies were performed prior to and 3 and 24 hours after drug ingestion . Modafinil did not change excitatory or inhibitory properties in the motor cortex . It did not alter corticospinal excitability and alpha motoneuronal excitability . In the modafinil group and in the placebo group , performance of the nine-hole-peg test and the d2 test improved to a similar extend over time . Thus , this study does not demonstrate significant differences between a single dose of modafinil and placebo in healthy subjects",
"In a double-blind , placebo-controlled study , postmenopausal women ( 53 - 65 years old ) were r and omly assigned to 7-day treatment with Ginkgo ( 120 mg/day , n=15 ) or matched placebo ( n=16 ) . They were given a battery of cognitive tests and measurements of mood and menopausal symptoms at baseline ( before treatment began ) and at the end of 7 days . The group treated with Ginkgo was significantly better than the placebo group in a matching-to- sample test of nonverbal memory , but the groups did not differ in immediate or delayed paragraph recall or in delayed recall of pictures . In a test of frontal lobe function ( rule shifting ) and in the Paced Auditory Serial Addition Test ( PASAT ) ( which measures sustained attention but also involves frontal lobe function ) , the group treated with Ginkgo performed significantly better than the placebo group . However , the groups did not differ in a test of planning . The treatments did not differ in their effects on the volunteers ' ratings of menopausal symptoms , sleepiness , bodily symptoms or aggression . The benefits of Ginkgo on memory and frontal lobe function found in this study are modest but are unlikely to be secondary to major mood changes",
"OBJECTIVE Since high frequency oscillations ( HFOs ) evoked by upper limb stimulation are susceptible to arousal fluctuation , we verified whether administration of modafinil , a vigilance promoting drug , modifies such responses at different levels of the somatosensory system . METHODS HFOs were obtained in 6 healthy volunteers by 500 - 700 Hz filtering of right median nerve somatosensory evoked potentials , before and 2 hours after the administration of 100 mg modafinil . Raw data were further su bmi tted to brain electrical source analysis . RESULTS Modafinil significantly increased subcortical HFOs , as well as the strength of a dipolar source at the base of the skull . CONCLUSIONS Our data suggest that modafinil exerts its action also at the level of the brain-stem , where it interferes with the processing of somatosensory ascending inputs",
"Background Although antihistamines are known for their sedative adverse effects , fexofenadine was previously shown to have stimulating effects . These stimulant effects were rather mild in magnitude and were only demonstrated in tasks with a high workload . Aim The present study was set up to compare the magnitude of the stimulant effect of fexofenadine with those of 2 psychostimulants , modafinil and methylpheni date . Method Sixteen healthy volunteers ( 5 males and 11 females ; mean age , 21.8 years ) participated in a 4-way , placebo-controlled , crossover study . The effects of fexofenadine ( 360 mg ) , modafinil ( 200 mg ) , methylpheni date ( 20 mg ) , and placebo were compared in a critical tracking , divided attention , motor impulsivity , and vigilance task . Results In this study , no significant stimulant effects of fexofenadine were found in any of the tasks . Modafinil only improved reaction time in the vigilance task , whereas methylpheni date improved performance in the divided attention and vigilance tasks . In addition , performance after methylpheni date treatment was also better than after fexofenadine in the divided attention and vigilance tasks . Conclusion From the results , it can be concluded that the stimulating effects of methylpheni date are confirmed , whereas the stimulating effects of fexofenadine were not demonstrated in this study . It is evident that the stimulating effects of fexofenadine , which were apparent in previous studies , are not of the same magnitude as the effects of known psychostimulants such as methylpheni date",
"A double‐blind , intra‐individual cross‐over comparison of the mental performance of 18 aging , non‐deteriorated individuals during two 4‐week periods of piracetam ( 1‐acetamide‐2‐pyrrolidone ) and placebo administration was performed using conventional and computerized perceptual‐motor tasks . In a majority of these tasks the subjects did significantly better when on piracetam than on placebo , a finding consistent with ratings completed by two independent observers . The findings indicate new avenues for the treatment of individuals with reduced mental performance possibly related to disturbed alertness — a neglected group of psychiatric conditions",
"Modafinil is indicated for the management of excessive daytime sleepiness ; however , recent studies have examined a broad range of potential uses . Given that clinical uses of modafinil may be exp and ing , this study compared modafinil and d-amphetamine effects on subjective and performance measures . Across 11 sessions , 11 healthy adults were tested after oral doses of placebo ( 5 sessions ) , modafinil ( 1.75 mg/kg , 3.50 mg/kg , or 7.00 mg/kg ) , and d-amphetamine ( 0.035 mg/kg , 0.070 mg/kg , 0.140 mg/kg ) under double-blind , r and omized conditions . Assessment s of cognitive performance and subjective effects were completed before drug administration , 30 min after drug administration , and at hourly intervals after drug administration for 5 hr . Modafinil increased ratings on the Amphetamine and Morphine Benzedrine Group scales of the Addiction Research Center Inventory ( ARCI ) and increased ratings on the Vigor and Total Positive scales of the Profile of Mood States . d-Amphetamine increased visual analog ratings of feeling stimulated and liking the drug and increased ratings on the Morphine Benzedrine Group scale of the ARCI . Both medications significantly reduced visual analog scale ratings of feeling sleepy , and modafinil decreased ratings on the ARCI Pentobarbital-Chlorpromazine-Alcohol Group scale . Both medications sustained performance that deteriorated across time on the Sternberg Number Recognition Test . Modafinil also enhanced performance rate on the Digit-Symbol Substitution Task above baseline levels and increased response rate on the Repeated Acquisition of Response Sequences Task . These results suggest that modafinil engenders alerting effects and increases performance in healthy non-sleep-deprived individuals comparable with that of d-amphetamine",
"Effects of a combination of caffeine and glucose were assessed in two double-blind , placebo-controlled , cross-over studies during extended performance of cognitively dem and ing tasks . In the first study , 30 participants received two drinks containing carbohydrate and caffeine ( 68 g/38 mg ; 68 g/46 mg , respectively ) and a placebo drink , in counter-balanced order , on separate days . In the second study 26 participants received a drink containing 60 g of carbohydrate and 33 mg of caffeine and a placebo drink . In both studies , participants completed a 10-min battery of tasks comprising 2-min versions of Serial 3s and Serial 7s subtraction tasks and a 5-min version of the Rapid Visual Information Processing task ( RVIP ) , plus a rating of ' mental fatigue ' , once before the drink and six times in succession commencing 10 min after its consumption . In comparison to placebo , all three active drinks improved the accuracy of RVIP performance and both the drink with the higher level of caffeine in first study and the active drink in the second study result ed in lower ratings of mental fatigue . These results indicate that a combination of caffeine and glucose can ameliorate deficits in cognitive performance and subjective fatigue during extended periods of cognitive dem and",
"Nootropyl ( Piracetam ) a drug reported to facilitate learning in animals was tested for its effect on man by administering it to normal volunteers . The subjects were given 3 × 4 capsules at 400 mg per day , in a double blind study . Each subject learned series of words presented as stimuli upon a memory drum . No effects were observed after 7 days but after 14 days verbal learning had significantly increased"
] |
4116b744-06ff-11f0-808a-c43d1ab1c353
|
Purpose Several factors may influence the risk of recurrence after an episode of acute colonic diverticulitis . Until now , a comprehensive systematic overview and evaluation of relevant risk factors have not been presented . This review aim ed at assembling and evaluating current evidence on risk factors for recurrence after conservatively treated acute colonic diverticulitis . Methods PubMed , Embase , and Cochrane data bases were search ed for studies evaluating risk factors for recurrence after acute diverticulitis treated non-surgically defined as antibiotic treatment , percutaneous abscess drainage , or by observation . R and omized clinical trials and observational studies were included . Analyzed outcome variables were extracted and grouped . No meta- analysis was performed due to low inter- study comparability . Variables were rated according to their likelihood of causing recurrence ( no/low , medium , high ) . Results Of 1153 screened records , 35 studies were included , enrolling 396,676 patients with acute diverticulitis . A total of 50,555 patients experienced recurrences . Primary diverticulitis with abscess formation and young age increased the risk of recurrence . Readmission risk was higher within the first year after remission . In addition , the risk of subsequent diverticulitis more than doubled after two earlier episodes of diverticulitis and the risk increased further for every episode . Conclusions The best treatment strategy for recurrent diverticulitis is undetermined . However , the risk of a new recurrence seemed to increase after each recurrence making elective resection a viable option at some point after multiple recurrences depending on patient risk factors and preferences
|
[
"Purpose This study included all patients treated at the University Hospital of Geneva for a first episode of uncomplicated diverticulitis . Risks of recurrence and treatment failure were evaluated by comparing the results between short-course and long-course intravenous ( IV ) antibiotic therapy groups . Methods The records of all patients hospitalized at our facility from January 2007 to February 2012 for a first episode of uncomplicated diverticulitis ( Hinchey Ia ) , as confirmed by computed tomography , were prospect ively collected . We published an auxiliary analysis from this registered study at Clinical trials.gov ( identifier number : NCT01015378 ) . Two groups of patients were considered : one received a short-course IV antibiotic arm ( ceftriaxone and metronidazole ) for up to 5 days ( followed by 5 days of oral antibiotics ) ; the other received a long-course IV arm between days 5 and 10 . The primary outcome was the recurrence-free survival time . Results Follow-up was completed for 256 patients -50 % men and 50 % women , with a median age of 56 years ( range , 24 - 85 years ) . The average follow-up was 50 months ( range , 19 - 89 months ) . Of the 256 patients included in the study , 46 patients received a short-course IV antibiotic treatment and 210 received a long-course treatment . The recurrence-free survivals were very similar between the two groups , which was supported by a log rank test ( P = 0.772 ) . Four treatment failures , all in the long-course IV antibiotic treatment group , occurred . Conclusion Treatment of diverticulitis with a short IV antibiotic treatment is possible and does not modify the recurrence rate in patients with uncomplicated diverticulitis",
"BACKGROUND & AIMS No therapy has been proven to prevent the recurrence of diverticulitis . Mesalamine has shown efficacy in preventing relapse in inflammatory bowel disease , and there is preliminary evidence that it might be effective for diverticular disease . We investigated the efficacy of mesalamine in preventing recurrence of diverticulitis in 2 identical but separate phase 3 , r and omized , double-blind , placebo-controlled , multicenter trials ( identical confirmatory trials were conducted for regulatory reasons ) . METHODS We evaluated the efficacy and safety of multimatrix mesalamine vs placebo in the prevention of recurrent diverticulitis in 590 ( PREVENT1 ) and 592 ( PREVENT2 ) adult patients with ≥1 episodes of acute diverticulitis in the previous 24 months that resolved without surgery . Patients received mesalamine ( 1.2 g , 2.4 g , or 4.8 g ) or placebo once daily for 104 weeks . The primary end point was the proportion of recurrence-free patients at week 104 . Diverticulitis recurrence was defined as surgical intervention at any time for diverticular disease or presence of computed tomography scan results demonstrating bowel wall thickening ( > 5 mm ) and /or fat str and ing consistent with diverticulitis . For a portion of the study , recurrence also required the presence of abdominal pain and an increase in white blood cells . RESULTS Mesalamine did not reduce the rate of diverticulitis recurrence at week 104 . Among patients in PREVENT1 , 53%-63 % did not have disease recurrence , compared with 65 % of those given placebo . Among patients in PREVENT2 , 59%-69 % of patients did not have disease recurrence , compared with 68 % of those given placebo . Mesalamine did not reduce time to recurrence , and the proportions of patients requiring surgery were comparable among treatment groups . No new adverse events were identified with mesalamine administration . CONCLUSIONS Mesalamine was not superior to placebo in preventing recurrent diverticulitis . Mesalamine is not recommended for this indication . Clinical Trials.gov ID : NCT00545740 and NCT00545103",
"Background and aim Recurrence of diverticulitis is frequent within 5 years from the uncomplicated first attack , and its prophylaxis is still unclear . We have undertaken a multicentre , r and omised , double-blind , placebo-controlled pilot study in order to evaluate the role of mesalazine in preventing diverticulitis recurrence as well as its effects on symptoms associated to diverticular disease . Methods Ninety-six patients with the recent first episode of uncomplicated diverticulitis were r and omised to receive mesalazine 800 mg twice daily for 10 days every month or placebo for 24 months . The primary efficacy end point was the diverticulitis recurrence at intention to treat analysis . Clinical evaluations were performed using the Therapy Impact Question naire ( TIQ ) for physical condition and quality of life at admission and at 3-month intervals . Treatment tolerability and routine biochemistry parameters as well as the use of additional drugs were also evaluated . Results Ninety-two patients ( mean age , 61.5 ) completed the study , 45 of whom received mesalazine , and 47 , placebo . Diverticulitis relapse incidence in mesalazine-treated group was 5/45 ( 11 % ) at the 12th month and 6/45 ( 13 % ) at the 24th month ; in the placebo-treated group , the correspondent rates were 13 % ( 6/47 ) and 28 % ( 13/47 ) , respectively . Mean values of TIQ at 24 months were significantly better in mesalazine-treated group than in placebo-treated group ( p = 0.02 ) ; in addition , average additional drug consumption was significantly lower ( −20.4 % , p in mesalazine than in placebo . Conclusions Diverticulitis recurrence occurred in as many as 28 % of patients under placebo within 24 months from the initial episode . Intermittent prophylaxis with mesalazine did not significantly reduce the risk of relapse but induced a significant improvement of patients ' physical conditions and significantly lowered the additional consumption of other gastrointestinal drugs",
"Background The evidence is sparse concerning the natural history of acute diverticulitis after successful conservative management . This observational study aim ed to evaluate the rate , severity , and need of surgery for recurrence after a first episode of acute diverticulitis successfully managed conservatively . Methods All patients admitted for acute diverticulitis between 1994 and 2011 were considered for inclusion in the study . Severity of the first episode , demographic data , comorbidities , management , recurrence , and elective or emergency surgery during the follow-up period were prospect ively recorded . Results The study included 560 patients . The mean follow-up period was of 67.2 ± 44.4 months . Severe diverticulitis was diagnosed in 22.3 % of the cases . Recurrence was observed in 14.8 % of the patients , and the rate of severe recurrence was 3.4 % . Most of the recurrences occurred during the first year of follow-up evaluation . Chronic corticoid therapy ( P = 0.043 ) and the presence of more than one abscess ( P to recurrence . In the event of a mild recurrence , the first episode was either mild or severe ( P = 0.172 ) . In the case of severe recurrence , most patients presented with a previous severe diverticulitis ( P elective operation , and 1.4 % of them underwent emergency surgery . Conclusion The rate of severe recurrence after successful nonoperative management of acute diverticulitis was low , and emergency surgery was rare . Prophylactic surgery , even in cases of recovered severe diverticulitis , should be considered on a case-by-case basis . Strict follow-up assessment during the first year is advised",
"BACKGROUND Colonic diverticulitis shows a high recurrence rate . AIMS To assess the efficacy of three different therapeutic strategies in preventing diverticulitis recurrence . MATERIAL S AND METHODS One hundred thirty patients suffering from Acute Uncomplicated Diverticulitis ( AUD ) ( 81 males , 49 females , mean age 64.71 years , range 40 - 85 ) were prospect ively assessed . After obtaining remission , considered present when both endoscopic and histological damage were absent , the patients were treated with mesalazine 1.6 g/day ( 59 patients , group A ) , or rifaximin 800 mg/day for 7 days every month ( 52 patients , group B ) . Clinical , endoscopic and histological follow-up was performed after 6 , 12 and thereafter every 12 months after diagnosis of AUD . RESULTS Seven patients were excluded from final evaluation because they were lost to follow-up . Fifty-five group A patients and 49 group B patients patients were available for the final assessment at the end of a 24-month follow-up . Sustained remission was significantly higher in group A with respect to group B. CONCLUSIONS Patients taking mesalazine have lower risk of diverticulitis recurrence than patients taking rifaximin because of the lower prevalence of persisting endoscopic and histological inflammation",
"Purpose While the incidence of right colonic diverticulitis ( RCD ) is rare in Western countries , the right colon is the most common site of diverticulitis in Asian countries . However , its recurrent pattern and management were rarely studied . This study was design ed to eluci date the pattern of recurrence in RCD . Methods Of the 154 patients admitted as right colonic diverticulitis between February 2004 and March 2012 , 104 patients were enrolled , prospect ively . The recurrence rate , size , multiplicity , location , diagnostic criteria score , and predisposing factors were evaluated based on Hinchey ’s classification of diverticulitis . Results There were 104 patients with right colonic diverticulitis in this study , and 20 patients ( 19.2 % ) recurred after medical treatment . When the diverticula were not located in the right colon , the recurrence rate was significantly higher than the diverticula located only in the right colon ( p = 0.004 ) . The recurrence rate of diverticulitis for a single diverticulum was significantly lower than that for multiple diverticula ( p = 0.02 ) . Of the 20 patients with recurrence , 1 ( 5 % ) patient underwent laparoscopic diverticulectomy due to a misdiagnosis of diverticulitis as appendicitis . The remaining 19 patients ( 95 % ) received nonoperative management and recovered without any sequelae . Conclusions The recurrence rate was 19.2 % , and the predisposing factors were the location of diverticula and the multiplicity of primary diverticula . The re-recurrence rate of recurred patients was 26.3 % . The recurred lesions were controlled simply by nonoperative management . Elective surgery was also a treatment option",
"PURPOSE : The purpose of our study was to determine the clinical and CT predictors of recurrent disease after a first episode of diverticulitis that was successfully managed nonoperatively . METHODS : We retrospectively analyzed 954 consecutive patients who presented to our institution with diverticulitis from 2002 to 2008 . Patients were identified with International Classification of Diseases , 9th Revision/Current Procedural Terminology codes . Patients were excluded if they had subsequent colectomy based on the first attack ( n = 81 ) , or if the attack they had between 2002 and 2008 was not their first attack ( n = 201 ) . We evaluated CT variables chosen by a panel of expert gastrointestinal radiologists . These radiologists review ed the available published literature for CT imaging characteristics thought to predict diverticulitis severity . CT variables ( n = 20 ) were determined by prospect i ve reevaluation of scans by blinded study radiologists . Clinical variables ( n = 43 ) were coded based on a retrospective chart review . Univariate analysis of variables in relation to recurrent disease was performed by a log-rank test of Kaplan-Meier estimates . Multivariate analysis was performed using Cox proportional hazards modeling . Variables with P study population included 672 patients ; mean age , 61 ± 15 years ; mean follow-up , 42.8 ± 24 months . The index presentation of diverticulitis was most commonly located in the sigmoid colon ( 72 % ) , followed by descending colon ( 33 % ) , right colon ( 5 % ) , and transverse colon ( 3 % ) . Overall recurrence at 5 years was 36 % by ( 95 % CI 31.4%–40.6 % ) Kaplan-Meier estimate . Complicated recurrence ( fistula , abscess , free perforation ) occurred in 3.9 % ( 95 % CI 2.2%–5.6 % ) of patients at 5 years by Kaplan-Meier estimate . Family history of diverticulitis ( HR 2.2 , 95 % CI 1.4–3.2 ) , length of involved colon > 5 cm ( HR 1.7 , 95 % CI 1.3–2.3 ) , and retroperitoneal abscess ( HR 4.5 , 95 % CI 1.1–18.4 ) were associated with diverticulitis recurrence . Right colon disease ( HR 0.27 , 95 % CI 0.09–0.86 ) was associated with freedom from recurrence . CONCLUSION : Although diverticulitis recurrence is common following an initial attack that has been managed medically , complicated recurrence is uncommon . Patients who present with a family history of diverticulitis , long segment of involved colon , and /or retroperitoneal abscess are at higher risk for recurrent disease . Patients who present with right-sided diverticulitis are at low risk for recurrent disease . These findings should be taken into consideration when counseling patients regarding the potential benefits of prophylactic colectomy",
"The natural history of sigmoid diverticulitis has been inferred from population ‐based or retrospective studies . This study assessed the risk of a recurrent attack following the first episode of uncomplicated diverticulitis",
"BACKGROUND : Initial nonoperative management of diverticular abscess has become the st and ard of care ; however , the need for elective resection after this index episode is unclear . OBJECTIVE : The purpose of this study was to assess the long-term outcomes of expectant management after initial nonoperative treatment of diverticular abscess . DESIGN : This was a retrospective chart review with prospect i ve telephone follow-up of patients . SETTING S : The study was conducted at a large tertiary academic colorectal surgery practice in Canada . PATIENTS : Adult patients with CT-documented acute sigmoid diverticulitis complicated by abscess managed nonoperatively from 2000 to 2013 were included . INTERVENTIONS : Long-term definitive nonoperative management of diverticular abscess . MAIN OUTCOME MEASURES : The primary outcome was emergency sigmoidectomy or death from recurrent diverticulitis . Secondary outcomes were recurrent diverticulitis and elective sigmoidectomy for diverticulitis . RESULTS : Of 135 patients with acute diverticulitis complicated by abscess , a total of 73 patients were managed with nonoperative intent and long-term expectant management . The median follow-up was 62 ( Q1 to Q3 : 28–98 ) months . After resolution of the index episode , 22 patients [ 30.1 % ( 95 % CI , 19.6%–40.6 % ) ] experienced a recurrent episode of diverticulitis at a median of 23 ( range , 9–40 ) months . Two patients [ 2.7 % ( 95 % CI , –1.0 % to 6.4 % ) ] had a recurrent episode with peritonitis that required sigmoidectomy with stoma at 6 and 64 months . Both patients underwent reversal after 4 and 8 months . Seven [ 9.6 % ( 95 % CI , 2.8%–16.4 % ) ] patients experienced a complicated recurrence and underwent an elective sigmoidectomy [ median time to colectomy , 33 ( range , 16–56 ) months ] . Thirteen patients [ 17.8 % ( 95 % CI , 9.0%–26.6 % ) ] experienced an uncomplicated recurrence , all of whom were managed with continued nonoperative intent [ median follow-up , 81 ( range , 34–115 ) months ] . No mortality occurred . On multivariate logistic regression , female gender ( p = 0.048 ) and a previous episode of uncomplicated diverticulitis before the index diverticular abscess ( p = 0.020 ) were associated with a recurrent episode . LIMITATIONS : This study was limited by its retrospective design and modest sample size . CONCLUSIONS : After initial successful nonoperative management of diverticulitis with abscess , expectant management with nonoperative intent is a safe long-term option with low rates of surgery , especially in the emergency setting . See Video , Supplemental Digital Content 1 , on the nonoperative management of diverticular abscess at http://links.lww.com/DCR/A234"
] |
4116b78a-06ff-11f0-808a-c43d1ab1c353
|
Bode , R.K. , Heinemann , A.W. , Semik , P. , & Mallinson T. ( 2004 ) . Relative importance of rehabilitation therapy characteristics on functional outcomes for persons with stroke . Stroke , 35 , 2537 - 2542 . Data synthesis : Systematic review s and meta-analyses Gage , H. , & Storey L. ( 2004 ) . Rehabilitation for Parkinson 's disease : A systematic review of available evidence . Clinical Rehabilitation , 18 , 463 - 482
|
[
"Advances in medical treatment combined with changes in the demographics of persons who are becoming infected with autoimmune deficiency syndrome ( AIDS ) have transformed this illness from a rapidly progressing to a chronically disabling condition in a short period of time . This paper describes the development , implementation , and outcomes of a program of vocational services for persons with AIDS . This program was studied using a single group design , in which participatory action research strategies were used to investigate and improve the program as it unfolded . In addition to examining the overall outcomes of services , the study aim ed to discover which components were most helpful to participants and which participants were most likely to benefit from the program . Of 129 participants of who initially enrolled , 39 dropped out before finishing the program . Sixty of the 90 participants who completed the program achieved employment , returned to school , or began a volunteer position or internship . Consequently , the overall success rate was 46.5 % and the success rate for program completers was 66.7 % . The occupational narrative , which participants told in their initial assessment interview , was closely associated with both program completion and successful outcomes . This association adds support to the importance of narrative for underst and ing participants and predicting future behavior , as well as for the therapy process",
"Abstract Objective To evaluate an occupational therapy intervention to improve outdoor mobility after stroke . Design R and omised controlled trial . Setting General practice registers , social services departments , a primary care rehabilitation service , and a geriatric day hospital . Participants 168 community dwelling people with a clinical diagnosis of stroke in previous 36 months : 86 were allocated to the intervention group and 82 to the control group . Interventions Leaflets describing local transport services for disabled people ( control group ) and leaflets with assessment and up to seven intervention sessions by an occupational therapist ( intervention group ) . Main outcome measures Responses to postal question naires at four and 10 months : primary outcome measure was response to whether participant got out of the house as much as he or she would like , and secondary outcome measures were response to how many journeys outdoors had been made in the past month and scores on the Nottingham extended activities of daily living scale , Nottingham leisure question naire , and general health question naire . Results Participants in the treatment group were more likely to get out of the house as often as they wanted at both four months ( relative risk 1.72 , 95 % confidence interval 1.25 to 2.37 ) and 10 months ( 1.74 , 1.24 to 2.44 ) . The treatment group reported more journeys outdoors in the month before assessment at both four months ( median 37 in intervention group , 14 in control group : P mobility scores on the Nottingham extended activities of daily living scale were significantly higher in the intervention group , but there were no significant differences in the other secondary outcomes . No significant differences were observed in these measures at 10 months . Conclusion A targeted occupational therapy intervention at home increases outdoor mobility in people after stroke",
"Objective : To evaluate the long-term effects of joint protection on health status of people with early rheumatoid arthritis ( RA ) . Design : A four-year follow-up of a r and omized , controlled , assessor-blinded trial was conducted . Setting : Two rheumatology outpatient departments . Participants : People with rheumatoid arthritis less than five years since diagnosis . Interventions : Two 8-hour interventions were originally compared : a st and ard arthritis education programme , including 21/2 hours of joint protection based on typical UK occupational therapy practice ( plus 51/2 hours on RA , exercise , pain management , diet and foot care ) ; and a joint protection programme , using educational-behavioural training . Main measures : Adherence to joint protection , pain , h and pain on activity , Arthritis Impact Measurement Scales 2 and Arthritis Self-efficacy were recorded at 0 and 4 years . Results : Sixty-five people attended the joint protection and 62 the st and ard programmes . Groups at entry were similar in age ( 51 years ; 49 years ) , disease duration ( 21 months : 17.5 months ) and use of nonsteroidal anti-inflammatory and disease-modifying drugs . At four years , the joint protection group continued to have significantly better : joint protection adherence ( p=0.001 ) ; early morning stiffness ( p=0.01 ) ; AIMS 2 activities of daily living ( ADL ) scores ( p=0.04 ) compared with the st and ard group . The joint protection group also had significantly fewer h and deformities : metacarpophalangeal ( MCP ) ( p=0.02 ) and wrist joints ( p=0.04 ) . Conclusion : Attending an educational = behavioural joint protection programme significantly improves joint protection adherence and maintains functional ability long term . This approach is more effective than st and ard methods of training and should be more widely adopted",
"Study Design . R and omized parallel-group comparative trial with a 6-month follow-up period . Objective . To compare , in chronic low back pain patients , the effectiveness of a functional restoration program , including intensive physical training , occupational therapy , and psychological support to an active individual therapy consisting of 3 hours physical therapy per week during 5 weeks . Summary of Background Data . Controlled studies conducted in the United States showed a benefit of functional restoration in patients with low back pain , especially on return to work . R and omized Canadian and European trials had less favorable results . In France , there has been up to now no r and omized study . Controlled studies suggested a positive effect of functional restoration programs . Methods . Eighty-six patients with low back pain were r and omized to either the functional restoration ( 44 patients ) or the active individual therapy ( 42 patients ) program . One person in each group never started the program . Two patients did not complete the functional restoration program , and one was lost to follow-up at 6 months . The mean number of sick-leave days in the 2 previous years was 6 months . Results . After adjustment on the variable ≪ workplace enrolled in an ergonomic program ≫ , the mean number of sick-leave days was significantly lower in the functional restoration group . Physical criteria and treatment appreciation were also better . There was no significant difference in the intensity of pain , the quality of life and functional indexes , the psychological characteristics , the number of contacts with the medical system , and the drug intake . Conclusions . This study demonstrates the effectiveness of a functional restoration program on important outcome measures , such as sick leave , in a country that has a social system that protects people facing difficultiesat work",
"OBJECTIVES To compare costs and outcome of occupational therapy-led assessment with social worker-led assessment of older people , in terms of their independence and quality of life . DESIGN Cost-effectiveness analysis alongside a r and omised controlled trial . The analysis took viewpoints of health services and patients . The primary outcome measure for cost-effectiveness was dependency using the Community Dependency Index ( CDI ) . Secondary outcomes included utility scores based on the EuroQoL ( EQ-5D ) . Re source use was measured for each patient , from clinical records and from patient carer interviews at 8 months . Unit costs of health and social care re sources were derived from local sources and national data sets . Cost-effectiveness was analysed using cost-effectiveness acceptability curves . RESULTS There were no differences between the two arms of the trial in terms of cost-effectiveness . There is an apparent increase in mean cost per case for the occupational therapy arm but this is not statistically significant ( mean difference in cost per case 542 pounds , 95 % CI 434 - 1,519 pounds ) . Mean total costs of care per participant were 4,379 pounds and 3,837 pounds for the occupational therapy and social work arms , respectively . At best the intervention would improve outcomes at a cost of 14,000 pounds per quality -adjusted life year ( QALY ) . The probability of such an outcome was social work or an occupational therapy service is successful in making care assessment s that enable an older person to remain in their own home",
"BACKGROUND Occupational therapy ( OT ) aims at improving performance of daily living tasks , facilitating successful adjustments in lifestyle , and preventing losses of function . OBJECTIVE To evaluate the effects of a pragmatic , comprehensive OT programme on self management and health status of people with early rheumatoid arthritis ( RA ) ( METHODS A r and omised , controlled \" assessor blinded \" trial was conducted with assessment s made at entry , 6 , 12 , and 24 months . Main outcomes were AIMS 2 : physical function ( PF ) , pain visual analogue scale ( VAS ) , and Arthritis Self-Efficacy Scale ( ASES ) . RESULTS Groups had similar disease duration ( 9 months OT ( n = 162 ) v 10 months control ( n = 164 ) ) . The OT group received 7.57 ( SD 3.04 ) hours of therapy . Self management significantly increased in the OT group . Otherwise , there were no significant differences in any outcome measures , or between groups , by ACR functional class : AIMS 2 : PF ( F = 0.04 ; p = 0.96 ) ; pain VAS ( F = 0.29 ; p = 0.74 ) ; total ASES score ( F = 0.93 ; p = 0.39 ) . CONCLUSIONS OT improved self management but not health status in early RA . Functional ability remains reasonably good for many in the first five years , so preventive benefits of self management may not yet be apparent and longer follow up is needed . Although many considered the education and therapy useful , insufficient numbers in the OT group used self management sufficiently to make a difference . Behavioural approaches can improve adherence and , potentially , the long term benefits . Future research should evaluate OT as a complex intervention and develop programmes from a theoretical and evidence base",
"OBJECTIVE The Canadian Occupational Performance Measure ( COPM ) is a client-centered measure , design ed to detect changes in occupational performance over time . The main aim of our study was to examine the test-retest reliability of the Norwegian version of the COPM in patients with ankylosing spondylitis ( AS ) in 3 different retest modes of data collection . METHODS A total of 119 patients with AS completed the baseline COPM interview before r and omization into one of 3 modes of retest data collection performed 2 weeks later : by personal interview , telephone interview , or mailed question naire . Scores were computed for Performance and Satisfaction , and the 2 sets of scores were examined for reliability by intraclass correlations ( ICC ) , and by the Bl and -Altman procedure for calculation of smallest detectable difference ( SDD ) . RESULTS The ICC coefficients for Performance and Satisfaction were as follows : 0.92 and 0.93 ( rescoring by personal interview ) , 0.73 and 0.73 ( rescoring by telephone interview ) , and 0.90 and 0.90 ( rescoring by mail ) . SDD for the Performance and Satisfaction scores were 1.47 and 1.80 , respectively , for rescoring by personal interview ; 3.14 and 4.00 for rescoring by telephone interview ; and 2.20 and 2.41 for rescoring by mailed survey . CONCLUSION The results confirm that the COPM is a reliable instrument for use in clinical practice in patients with AS , and may serve as an instrument to promote a patient-centered approach in the planning and evaluation of rehabilitation programs . Mailed question naires may replace personal interview in followup examinations , while rescoring by telephone interview is less reliable",
"OBJECTIVES To test whether Stepping On , a multifaceted community-based program using a small-group learning environment , is effective in reducing falls in at-risk people living at home . DESIGN A r and omized trial with subjects followed for 14 months . SETTING The interventions were conducted in community venues , with a follow-up home visit . PARTICIPANTS Three hundred ten community residents aged 70 and older who had had a fall in the previous 12 months or were concerned about falling . INTERVENTION The Stepping On program aims to improve fall self-efficacy , encourage behavioral change , and reduce falls . Key aspects of the program are improving lower-limb balance and strength , improving home and community environmental and behavioral safety , encouraging regular visual screening , making adaptations to low vision , and encouraging medication review . Two-hour sessions were conducted weekly for 7 weeks , with a follow-up occupational therapy home visit . MEASUREMENTS The primary outcome measure was falls , ascertained using a monthly calendar mailed by each participant . RESULTS The intervention group experienced a 31 % reduction in falls ( relative risk (RR)=0.69 , 95 % confidence interval (CI)=0.50 - 0.96 ; P=.025 ) . This was a clinical ly meaningful result demonstrating that the Stepping On program was effective for community-residing elderly people . Secondary analysis of subgroups showed that it was particularly effective for men ( n=80 ; RR=0.32 , 95 % CI=0.17 - 0.59 ) . CONCLUSION The results of this study renew attention to the idea that cognitive-behavioral learning in a small-group environment can reduce falls . Stepping On offers a successful fall-prevention option",
"BACKGROUND Few studies evaluate whether short-term intervention effects are maintained over time for families caring for persons with dementia . This article examines whether treatment effects found at 6 months following active treatment were sustained at 12 months for 127 family caregivers who participated in an occupational therapy intervention tested as part of the National Institutes of Health Re sources for Enhancing Alzheimer 's Caregiver Health ( REACH ) initiative . METHODS A r and omized two-group design was implemented with three assessment points : baseline , 6 months , and 12 months . Caregivers were r and omly assigned to a usual care control group or intervention that consisted of six occupational therapy sessions to help families modify the environment to support daily function of the person with dementia and reduce caregiver burden . Following 6-month active treatment , a maintenance phase consisted of one home and three brief telephone sessions to reinforce strategy use and obtain closure . Non-inferiority statistical analysis was used to evaluate whether intervention caregivers maintained treatment benefits from 6 to 12 months in comparison to controls . RESULTS For the sample of 127 at 6 months , caregivers in intervention reported improved skills ( p = .028 ) , less need for help providing assistance ( p = .043 ) , and fewer behavioral occurrences ( p = .019 ) compared to caregivers in control . At 12 months , caregiver affect improved ( p = .033 ) , and there was a trend for maintenance of skills and reduced behavioral occurrences , but not for other outcome measures . CONCLUSION An in-home skills training program helps sustain caregiver affect for those enrolled for more than 1 year . More frequent professional contact and ongoing skills training may be necessary to maintain other clinical ly important outcomes such as reduced upset with behaviors",
"Objective : ( 1 ) To assess whether a rehabilitation day hospital programme is associated with a reduced h and icap level of stroke patients . ( 2 ) To estimate the relationship between the London H and icap Scale ( LHS ) and other outcome measures . ( 3 ) To examine the effect of demographic parameters ( age , gender , family status , education ) on LHS scores . Design : A prospect i ve longitudinal survey . Setting : An urban geriatric rehabilitation day hospital . Subjects : Two hundred and seven elderly stroke patients admitted between December 1999 and February 2001 . Main outcome measures : London H and icap Scale ( LHS ) , Functional Independent Measure ( FIM ) , Nottingham Extended ADL Index , timed get up and go test . Results : LHS scores at discharge changed significantly ( p mobility , physical independence and occupation . The overall change in LHS score was 2.3 points ( 20 % ) ; effect size 0.43 . A significant relationship was found between discharge score of LHS and admission score of FIM , Nottingham Index , timed get up and go and age . Multiple linear regressions did not identify a good predictor for the discharge score of LHS . Higher education was associated with higher LHS scores on admission ( p= 0.016 ) but with less success in correcting h and icap ( p= 0.046 ) . Conclusions : A day hospital programme is associated with reduced level of h and icap in stroke patients . The LHS is a useful and simple scale for measuring change in these patients . LHS in stroke patients correlates with other outcome measures , yet they can not be used interchangeably . A significant relationship between education and level of h and icap exists",
"OBJECTIVES The aims of this study were to evaluate changes in occupational performance among chronic pain patients after a pain management program and to explore relationships between these changes and demographic and clinical factors , psychosocial functioning and psychological well-being . SUBJECTS 188 consecutive patients were included . METHODS Changes were registered by using Canadian Occupational Performance Measure , Multidimensional Pain Inventory and Psychological General Well-Being Index . RESULTS There were statistically significant positive changes in occupational performance . Patients with sickness compensation had significantly higher changes in occupational performance than those without sickness compensation . The patients with a profile group as interpersonally distressed had statistically significant higher change scores on occupational performance than the adaptive coper group . Furthermore , increases in changes on general activity level , general health , and vitality and decreases in pain severity were associated with positive changes on perceived occupational performance and performance satisfaction . CONCLUSION Changes in occupational performance , psychological well-being and psychosocial functioning seem all to be of relevance in the evaluation of pain management programs . Psychosocial profiles and sickness compensation has relevance for directions on changes in occupational performance , whereas other demographic and clinical factors do not",
"Background : Occupational therapy ( OT ) has been defined as a task of rehabilitation for disabled patients , giving them maximal function and independence to sustain specific activities of daily living . Objectives : To evaluate the effectiveness of OT as an adjunctive measuring during pulmonary rehabilitation ( PR ) of hospitalized COPD patients . Methods : A prospect i ve clinical trial with parallel groups was undertaken in severely disabled COPD patients ( n = 71 , age 73 ± 5 years ) . They were assigned to either OT+PR ( n = 47 , FEV1 46 ± 21%pred . ) or PR ( n = 24 , FEV1 44 ± 12%pred . ) . PR consisted of eighteen 3-hour daily sessions , whilst OT ( domestic activities ) was added 3 times a week up to nine 1-hour sessions . Six-min walk ( 6MWD ) with evaluation of BORG dyspnea ( D ) and leg fatigue ( F ) scores at end of effort , breathlessness sensation ( B ) by means of the MRC scale as well as the number of functions lost in the Basic Activity of Daily Living ( BADL ) categories were assessed as outcomes before ( T₀ ) and after ( T1 ) rehabilitation . Results : 6MWD ( from 165 ± 63 to 233 ± 66 and from 187 ± 52 to 234 ± 65 m in the OT+PR and PR groups , respectively ) , D ( from 4.9 ± 2.1 to 3.2 ± 1.6 and from 5.3 ± 2.1 to 3.4 ± 2.1 ) , F ( from 6.1 ± 0.5 to 4.5 ± 1.7 and from 5.9 ± 0.8 to 4.3 ± 0.8 ) and B ( from 4.3 ± 0.9 to 3.0 ± 0.9 and from 4.2 ± 1.0 to 3.2 ± 0.8 ) had similarly improved ( p The percentage distribution of patients across the BADL categories significantly changed ( p = 0.004 ) in OT+PR ( from 17 to 61 % , from 70 to 34 % and from 23 to 5 % in categories A , B and C , respectively ) but not in the PR group . Conclusions : The addition of OT to comprehensive PR is able to specifically improve the outcome of severely disabled COPD in patients",
"Background It is not clear whether occupational therapy is of value for hip fracture patients . Patients and methods In a r and omized trial we studied the effects of an early , individualized , postoperative occupational training ( OT ) program on the ability of hip fracture patients to perform ADL and IADL . Secondary endpoints were self-reported fear of pain and pain when performing ADL and IADL . The need for technical aids and /or home adaptations was also investigated . 100 eligible patients ( aged ≥65 years , with independent residence ) were r and omized 50:50 to an OT or control group ( conventional care ) . During their hospital stay , members of the OT group received individual daily training which included the use of technical aids . Before discharge , the occupational therapist paid a home visit together with the patient . All patients were assessed 2–4 days after surgery , at discharge and after 2 months , using the Klein-Bell ADL scale and a modified version of the Disability Rating Index . Results At discharge , the OT group had better ability to dress , to take care of personal hygiene and bathing activities independently , and to make toilet visits . Age , sex , type of fracture or length of stay at the hospital made no significant contribution to explaining the better ADL ability on discharge . After 2 months , all patients had regained their ADL and IADL abilities . Half of the patients required technical aids and adaptations in their homes . Interpretation Individualized OT-training speed up the ability of patients to perform ADL , thus enhancing the likelihood of patients returning to independent living and reducing the need for postoperative care at home"
] |
4116b7d0-06ff-11f0-808a-c43d1ab1c353
|
Published studies have reported widely divergent estimates of the prevalence of chronic pain among individuals with ( traumatic ) spinal cord injury ( SCI ) . To develop an estimate based on a synthesis of the research , we used search es of MEDLINE , CINAHL , PsycINFO , and other bibliographic data bases and an ancestor search to identify articles published since 1966 in any language that reported a pain prevalence rate for at least 30 subjects with certain or likely traumatic SCI . Data on sample makeup , study quality indicators , and pain prevalence were abstract ed independently by two research ers . A total of 42 studies reported pain prevalence rates that ranged from 26 % to 96 % , with a fairly even spread between these extremes . The reported rate did not appear to be related to study quality . Pain prevalence in the combined sample s did not appreciably differ between males and females , those with complete versus incomplete SCI , and those with paraplegia versus tetraplegia . We conclude that too much heterogeneity was present in the reports to calculate a post-SCI pain prevalence rate using meta-analytic methods . Further research is needed to determine whether rates are related to sample makeup ( e.g. , average subject age ) , research methods used ( e.g. , telephone interview vs self-report instruments ) , or even the definition of " chronic " pain
|
[
"Developing an evidence base for making public health decisions will require using data from evaluation studies with r and omized and nonr and omized design s. Assessing individual studies and using studies in quantitative research syntheses require transparent reporting of the study , with sufficient detail and clarity to readily see differences and similarities among studies in the same area . The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement provides guidelines for transparent reporting of r and omized clinical trials . We present the initial version of the Transparent Reporting of Evaluations with Nonr and omized Design s ( TREND ) statement . These guidelines emphasize the reporting of theories used and descriptions of intervention and comparison conditions , research design , and methods of adjusting for possible biases in evaluation studies that use nonr and omized design",
"Some patients with spinal cord injury ( SCI ) complain of severe pain . The purpose of this study was to investigate the prevalence and classification of SCI-related pain , in terms of severity , location , aggravating and alleviating factors . 47 SCI individuals were studied between 15 and 67 years of age . Sixty-one percent of subjects experienced pain of moderate to severe intensity . 32 subjects complained of pain in the lower limbs , five patients had pain in the visceral region , eight in the pelvic and perineal areas . The pain duration was for a median of 5 weeks . The patients with pain were older ( median 41 years ) than those without pain ( median 23 years ) . Pain was reported to be more intense in the evening and at night . The incidence of pain was higher in patients with thoracolumbar and incomplete spinal cord lesions . Inactivity , stress , weather change , overactivity were identified as aggravating factors . Sleep and rest were demonstrated as alleviating factors",
"& NA ; Reliable and valid measures of pain are essential for conducting clinical trials of pain treatments . Perhaps the most important aspect of a pain measure 's validity is its sensitivity , or ability to detect changes in pain over time and due to treatment . Several factors may affect a measure 's sensitivity , including the complexity of the rating task for the measure , the number of pain intensity levels assessed by the measure , the dimension of pain assessed ( e.g. pain intensity vs. pain relief ) , and the number of individual ratings ( e.g. single rating vs. composite score ) used to create the measure . The purpose of this study was to compare the relative sensitivity of three measures of outcome and a composite made up of all three measures for detecting analgesic effects in two sample s of persons participating in a r and omized controlled trial . One hundred and twenty‐three patients who had undergone knee surgery and 124 women who had undergone a laparotomy were given one of three medications in the day after their surgery : morphine , ketorolac , or placebo . Two measures of pain intensity ( a visual analog scale ( VAS ) and a 4‐point verbal rating scale ( VRS ) ) were administered at baseline , and these measures plus a 5‐point VRS of pain relief were administered at 16 additional time points up to 24 h following surgery . As predicted , we found variability in the sensitivity of the outcome measures used in these studies , with the 4‐point VRS showing less sensitivity than the VAS or relief ratings . However , contrary to our prediction , a composite measure of outcome made up of all three measures was not consistently superior to the individual measures for detecting treatment effects . Finally , we found that pain relief ratings were related to , but also distinct from , change in pain intensity as measured by changes in pain intensity ratings from baseline to each postmedication assessment point . These findings have important implication s for the assessment of pain in clinical trials",
"A prospect i ve longitudinal study employing repeated measures was used to isolate factors which might predispose a person to depression two years after sustaining spinal cord injury ( SCI ) . Thirty-one subjects who suffered acute spinal injuries result ing in permanent loss of movement , and who had no head injuries or any pre-existing psychopathology , were at least 17 years of age , and who were able to speak English , participated in the study . Using the Beck Depression Inventory ( BDI ) as a measure of depression , a regression analysis demonstrated that the experience of pain two years post-injury and feeling out of control of one 's life prior to hospital discharge were predictive of depression two years post-injury . No demographic variables or injury characteristics such as level of lesion or completeness of lesion were related to long-term depression . Pain management and rehabilitation techniques that enhance the individual 's belief of control over their lives are therefore recommended as interventions that could act to reduce depression in the long term in persons with spinal cord injury",
"Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics . Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain . The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4‐point categorical scale",
"OBJECTIVES Non-painful sensory phenomena or “ phantom ” sensations are common after spinal cord injury . However , the physiological mechanisms responsible for these sensations are poorly understood . The aim of this study , therefore , was to document in a prospect i ve fashion the time course , prevalence , and features of non-painful sensory phenomena after spinal cord injury , and to determine whether there was a relation between the presence of these sensations and completeness , level of injury , and type of spinal cord injury . METHODS Patients admitted to an acute spinal injuries unit were interviewed after admission and at several time points over a 2 year period to determine the presence and characteristics of non-painful sensations . Sensations were divided into simple and complex , with complex referring to sensations that incorporated a sensation of volume , length , posture , or movement . RESULTS The present study showed that the large majority ( 90 % ) of patients experience either type of sensation and most complex sensations ( 60 % ) are first experienced within 24 hours after the injury . Complex sensations were more common in those patients who had complete spinal cord injuries . The presence of either type of sensation did not seem to be related to the level of injury or the type of injury ( cord syndrome ) . A relatively small proportion ( 22 % ) of patients reported that the postural sensations were related to their position at the time of injury and sensations were more commonly related to a familiar , comfortable , or often used position before the spinal cord injury . CONCLUSION Complex sensations such as postural illusions seem to be due to functional changes in the CNS that may occur almost immediately after spinal cord injury . These sensations may be related to a strong sensory memory “ imprint ” that has been established before injury"
] |
4116b816-06ff-11f0-808a-c43d1ab1c353
|
Aim of the study Probiotic administration to preterm infants has the potential to prevent necrotising enterocolitis ( NEC ) . Data from r and omised controlled trials ( RCT ) are conflicting but meta-analyses seem to support this intervention . To date , these analyses have not focused on surgical NEC . We aim ed to determine the effect of probiotic administration to preterm infants on prevention of surgical NEC . Methods A systematic review of RCTs of probiotic administration to preterm infants was performed . Studies were included if RCT outcomes included any of ( 1 ) Bell ’s stage 3 NEC ; ( 2 ) surgery for NEC ; and ( 3 ) deaths attributable to NEC . Article selection and data extraction were performed independently by two authors ; conflicts were adjudicated by a third author . Data were meta-analysed using Review Manager V.5.3 . A r and om effects model was decided on a priori because of the heterogeneity of study design ; data are risk ratio ( RR ) with 95 % CI . Main results Thirty-five RCTs reported NEC as an outcome . Seventeen reported surgical NEC ; all RCTs were included . A variety of probiotic products was administered across studies . Description of surgical NEC in most studies was poor . Only 6/16 specifically reported incidence of surgery for NEC , 12/17 Bell ’s stage 3 and 13/17 NEC-associated mortality . Although there was a trend towards probiotic administration reducing stage 3 NEC , this was not significant ( RR 0.74 ( 0.52–1.05 ) , p=0.09 ) . There was no effect of probiotics on the RR of surgery for NEC ( RR 0.84 ( 0.56–1.25 ) , p=0.38 ) . Probiotics did , however , reduce the risk of NEC-associated mortality ( RR 0.56 ( 0.34–0.93 ) , p=0.03 ) . Conclusion Despite 35 RCTs on probiotic prevention of NEC , evidence for prevention of surgical NEC is not strong , partly due to poor reporting . In studies included in this meta- analysis , probiotic administration was associated with a reduction in NEC-related mortality
|
[
"OBJECTIVE The use of probiotics is increasingly popular in preterm neonates , as they may prevent necrotizing enterocolitis sepsis and improve growth and feeding tolerance . There is only limited literature on Saccharomyces boulardii CNCM I-745 ( S. boulardii ) in preterm infants . METHOD A prospect i ve , r and omized , case-controlled trial with the probiotic S. boulardii ( 50mg/kg twice daily ) was conducted in newborns with a gestational age of 30 - 37 weeks and a birth weight between 1500 and 2500 g . RESULTS 125 neonates were enrolled ; 63 in the treatment and 62 in the control group . Weight gain ( 16.14±1.96 vs. 10.73±1.77g/kg/day , p and formula intake at maximal enteral feeding ( 128.4±6.7 vs. 112.3±7.2mL/kg/day , p the time needed to reach full enteral feeding was significantly shorter in the probiotic group ( 0.4±0.1 vs. 1.7±0.5 days , p no significant difference in sepsis . Necrotizing enterocolitis did not occur . No adverse effects related to S. boulardii were observed . CONCLUSION Prophylactic supplementation of S. boulardii at a dose of 50mg/kg twice a day improved weight gain , improved feeding tolerance , and had no adverse effects in preterm infants > 30 weeks old",
"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",
"Background : The increase in invasive fungal infections ( IFIs ) in neonatal intensive care unit ( NICU ) is jeopardizing the survival of preterm neonates . Probiotics modulating the intestinal microflora of preterm neonates may minimize enteral fungal colonization . Aims : This study was to examine whether probiotic supplementation in neonates reduced fungal septicemia . Material s and Methods : This prospect i ve , r and omized , double blind trial investigating the supplementation of preterm infants with a probiotic was done from May 2012 to April 2013 , with 112 subjects r and omized into two groups . Primary outcome : Decreased fungal colonization in gastrointestinal tract . Others : Incidence of late onset septicemia ; duration of the primary hospital admission ; number of days until full enteral feeds established . Results : Full feed establishment was earlier in probiotics group compared to placebo group ( P = 0.016 ) . The duration of hospitalization was less in the probiotic group ( P = 0.002 ) . Stool fungal colonization , an important outcome parameter was 3.03 ± 2.33 × 105 colony formation units ( CFU ) in the probiotics group compared to 3 ± 1.5 × 105 CFU in the placebo group ( P = 0.03 ) . Fungal infection is less in the study group ( P = 0.001 ) . Conclusion : The key features of our study were reduced enteral fungal colonization , reduce invasive fungal sepsis , earlier establishment of full enteral feeds , and reduced duration of hospital stay in the probiotics group",
"BACKGROUND Probiotics are used for the prevention of necrotizing enterocolitis ( NEC ) because of their positive effects on intestinal motor function , modulation of inflammatory response , and mucosal barrier function . OBJECTIVE The objective was to assess whether the combined use of Lactobacillus casei and Bifidobacterium breve may prevent the occurrence of NEC stage ≥ 2 by the criteria of Bell in very-low-birth-weight preterm infants . DESIGN A double-blind , r and omized , controlled clinical trial was conducted in 231 preterm infants weighing from 750 to 1499 g at birth . The intervention group was composed of 119 infants who received human milk with probiotic supplementation ( B. breve and L. casei ) and a control group of 112 infants who received human milk containing no probiotics . The primary outcome was the occurrence of NEC stage ≥ 2 as defined by Bell 's modified criteria . RESULTS Four confirmed cases of NEC stage ≥ 2 by Bell 's criteria occurred only in the control group . CONCLUSIONS Oral supplementation of B. breve and L. casei reduced the occurrence of NEC ( Bell 's stage ≥ 2 ) . It was considered that an improvement in intestinal motility might have contributed to this result . This trial was registered at www.is rct in.org as number 67165178 ( International St and ard R and omized Controlled Trial )",
"BACKGROUND & AIMS Recent studies have suggested that the gut microflora has metabolic effects . We aim ed to evaluate postnatal growth in preterm infants who received different probiotic supplements , and to assess the safety of probiotic administration . METHODS This prospect i ve , r and omized , double-blind , controlled trial was performed at three tertiary care neonatal units . Preterm infants were r and omly assigned to receive daily supplementation over 4 - 6 weeks with placebo ( group C ) or probiotics ( group P ) . Group P comprised three subgroups : P1 received Bifidobacterium lactis , P2 received Bifidobacterium longum , and P3 received B. lactis and B. longum . We assessed postnatal growth during the supplementation period and up to a corrected gestational age ( GA ) of 41 weeks when body composition was assessed using whole-body dual-energy X-ray absorptiometry . Aerobic and anaerobic blood cultures were performed on suspicion of late-onset sepsis . RESULTS The study comprised 199 preterm infants with a mean GA of 29.1 ± 1.4 weeks and a mean birth weight of 1173 ± 210 g , who received a placebo ( group C , n = 52 ) or probiotics ( group P , n = 147 ) from the first week of life . At the end of the supplementation period , no statistically significant differences were seen between the groups in relation to the mean body weight ( group C = 1906 ± 23 g , group P = 1875 ± 14 g , p = 0.25 ) , length , or head circumference . The incidence rates of necrotizing enterocolitis and late-onset sepsis were similar in the two groups . At the corrected GA of 41 weeks , there were no differences between the groups with respect to anthropometric measurements or body composition analysis . CONCLUSIONS Preterm infants receiving Bifidobacterium supplements did not exhibit better postnatal growth compared with those who received placebo treatment . No adverse effects were associated with probiotic administration . Registered under Clinical Trials.gov Identifier no. NCT01379417",
"BACKGROUND Probiotics have strain specific effects and the effects of fungi in preventing diseases in preterm infants have been investigated poorly . Saccharomyces boulardii is a yeast which acts both as a probiotic and a polyamine producer . AIM The objective of this study was to investigate the efficacy of S. boulardii in preventing necrotizing enterocolitis ( NEC ) or sepsis in very low birth weight infants . STUDY DESIGN AND SUBJECTS A prospect i ve , double blind , placebo controlled trial was conducted in preterm infants ( ≤ 32 GWs , ≤ 1500 g birth weight ) . They were r and omized either to receive feeding supplementation with S. boulardii 50 mg/kg every 12 h or placebo , starting with the first feed until discharged . OUTCOME MEASURES Necrotizing enterocolitis ( NEC ) or sepsis and NEC or death . RESULTS Birth weight and gestational age of the study ( n = 104 ) and the control ( n = 104 ) groups were 1126 ± 232 vs 1162 ± 216 g and 28.8 ± 2.2 vs 28.7 ± 2.1 weeks , respectively . Neither the incidence of stage ≥ 2 NEC or death nor stage ≥ 2 NEC or late onset culture proven sepsis was significantly lower in the study group when compared with the control group ( 9.6 % vs 7.7 % , p = 0.62 ; 28.8 % vs 23 % , p = 0.34 ) . Time to reach 100 mL/kg/day of enteral feeding ( 11.9 ± 7 vs 12.6 ± 7 days , p = 0.37 ) was not different between the groups . CONCLUSIONS Saccharomyces boulardii did not decrease the incidence of NEC or sepsis",
"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",
"Objective : To evaluate the efficacy of probiotics in the prevention of gastrointestinal colonization by C and ida species , of late-onset sepsis and neurological outcome in preterm newborns . Study Design : A prospect i ve study was conducted in 249 preterms who were subdivided into three groups : one group ( n=83 ) was supplemented with Lactobacillus ( L. ) reuteri , one group with L. rhamnosus ( n=83 ) and the other with no supplementation ( n=83 ) . The fungal colonization in the gastrointestinal tract , the late onset of sepsis and clinical parameters were recorded . A neurological structured assessment was further performed at 1 year of age . Result : C and ida stool colonization was significantly higher ( P L. reuteri group presented a significantly higher reduction in gastrointestinal symptoms than did the L. rhamnosus and control groups . Infants treated with probiotics showed a statistically significant lower incidence of abnormal neurological outcome than did the control group . Conclusion : The use of both probiotics seems to be effective in the prevention of gastrointestinal colonization by C and ida , in the protection from late-onset sepis and in reducing abnormal neurological outcomes in preterms",
"BACKGROUND AND OBJECTIVE : It has been suggested that probiotics may decrease infant mortality and nosocomial infections because of their ability to suppress colonization and translocation of bacterial pathogens in the gastrointestinal tract . We design ed a large double-blinded placebo-controlled trial using Lactobacillus reuteri to test this hypothesis in preterm infants . METHODS : Eligible infants were r and omly assigned during the first 48 hours of life to either daily probiotic administration or placebo . Infants in the intervention group were administered enterally 5 drops of a probiotic preparation containing 108 colony-forming units of L reuteri DSM 17938 until death or discharge from the NICU . RESULTS : A total of 750 infants ≤2000 g were enrolled . The frequency of the primary outcome , death , or nosocomial infection , was similar in the probiotic and placebo groups ( relative risk 0.87 ; 95 % confidence interval : 0.63–1.19 ; P = .376 ) . There was a trend toward a lower rate of nosocomial pneumonia in the probiotic group ( 2.4 % vs 5.0 % ; P = .06 ) and a nonsignificant 40 % decrease in necrotizing enterocolitis ( 2.4 % vs 4.0 % ; P = .23 ) . Episodes of feeding intolerance and duration of hospitalization were lower in infants ≤ 1500 g ( 9.6 % vs 16.8 % [ P = .04 ] ; 32.5 days vs 37 days [ P = .03 ] ) . CONCLUSIONS : Although L reuteri did not appear to decrease the rate of the composite outcome , the trends suggest a protective role consistent with what has been observed in the literature . Feeding intolerance and duration of hospitalization were decreased in premature infants ≤1500",
"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 Probiotics may reduce necrotising enterocolitis and late-onset sepsis after preterm birth . However , there has been concern about the rigour and generalisability of some trials and there is no agreement about whether or not they should be used routinely . We aim ed to test the effectiveness of the probiotic Bifidobacterium breve BBG-001 to reduce necrotising enterocolitis , late-onset sepsis , and death in preterm infants . METHODS In this multicentre , r and omised controlled phase 3 study ( the PiPS trial ) , we recruited infants born between 23 and 30 weeks ' gestational age within 48 h of birth from 24 hospitals in southeast Engl and . Infants were r and omly assigned ( 1:1 ) to probiotic or placebo via a minimisation algorithm r and omisation programme . The probiotic intervention was B breve BBG-001 suspended in dilute elemental infant formula given enterally in a daily dose of 8·2 to 9·2 log10 CFU ; the placebo was dilute infant formula alone . Clinicians and families were masked to allocation . The primary outcomes were necrotising enterocolitis ( Bell stage 2 or 3 ) , blood culture positive sepsis more than 72 h after birth ; and death before discharge from hospital . All primary analyses were by intention to treat . This trial is registered with IS RCT N , number 05511098 and EudraCT , number 2006 - 003445 - 17 . FINDINGS Between July 1 , 2010 , and July 31 , 2013 , 1315 infants were recruited ; of whom 654 were allocated to probiotic and 661 to placebo . Five infants had consent withdrawn after r and omisation , thus 650 were analysed in the probiotic group and 660 in the placebo group . Rates of the primary outcomes did not differ significantly between the probiotic and placebo groups . 61 infants ( 9 % ) in the probiotic group had necrotising enterocolitis compared with 66 ( 10 % ) in the placebo group ( adjusted risk ratio 0·93 ( 95 % CI 0·68 - 1·27 ) ; 73 ( 11 % ) infants in the probiotics group had sepsis compared with 77 ( 12 % ) in the placebo group ( 0·97 ( 0·73 - 1·29 ) ; and 54 ( 8 % ) deaths occurred before discharge home in the probiotic group compared with 56 ( 9 % ) in the placebo group ( 0·93 [ 0·67 - 1·30 ] ) . No probiotic-associated adverse events were reported . INTERPRETATION There is no evidence of benefit for this intervention in this population ; this result does not support the routine use of B breve BBG-001 for prevention of necrotising enterocolitis and late-onset sepis in very preterm infants . FUNDING UK National Institute for Health Research Health Technology Assessment programme",
"BACKGROUND AND OBJECTIVE : Late-onset sepsis frequently complicates prematurity , contributing to morbidity and mortality . Probiotics may reduce mortality and necrotizing enterocolitis ( NEC ) in preterm infants , with unclear effect on late-onset sepsis . This study aim ed to determine the effect of administering a specific combination of probiotics to very preterm infants on culture-proven late-onset sepsis . METHODS : A prospect i ve multicenter , double-blinded , placebo-controlled , r and omized trial compared daily administration of a probiotic combination ( Bifidobacterium infantis , Streptococcus thermophilus , and Bifidobacterium lactis , containing 1 × 109 total organisms ) with placebo ( maltodextrin ) in infants born before 32 completed weeks ’ gestation weighing The primary outcome was at least 1 episode of definite late-onset sepsis . RESULTS : Between October 2007 and November 2011 , 1099 very preterm infants from Australia and New Zeal and were r and omized . Rates of definite late-onset sepsis ( 16.2 % ) , NEC of Bell stage 2 or more ( 4.4 % ) , and mortality ( 5.1 % ) were low in controls , with high breast milk feeding rates ( 96.9 % ) . No significant difference in definite late-onset sepsis or all-cause mortality was found , but this probiotic combination reduced NEC of Bell stage 2 or more ( 2.0 % versus 4.4 % ; relative risk 0.46 , 95 % confidence interval 0.23 to 0.93 , P = .03 ; number needed to treat 43 , 95 % confidence interval 23 to 333 ) . CONCLUSIONS : The probiotics B infantis , S thermophilus , and B lactis significantly reduced NEC of Bell stage 2 or more in very preterm infants , but not definite late-onset sepsis or mortality . Treatment with this combination of probiotics appears to be safe",
"Background A r and omised , double-blind clinical trial was undertaken in order to assess the effectiveness of probiotics in the prevention of necrotising enterocolitis ( NEC ) in newborns weighing Methods We studied a group of 150 patients who were r and omised in two groups after parental consent was obtained , to receive either a daily feeding supplementation with a multispecies probiotic ( Lactobacillus acidophilus , Lactobacillus rhamnosus , Lactobacillus casei , Lactobacillus plantarum , Bifidobacteruim infantis , Streptococcus thermophillus ) 1 g per day plus their regular feedings or to receive their regular feedings with nothing added ( control group ) , over the period of January 2007 through June 2010 . Clinicians in care of the infants were blinded to the group assignment . Results The primary outcome was the development of NEC . Both groups were comparable , with no differences during hospitalisation , including the type of nutrition received . Blood cultures obtained from cases that developed sepsis did not reveal lactobacillus or Bifidobacteria growth . No differences were detected in terms of NEC risk reduction ( RR : 0.54 , 95 % CI 0.21 to 1.39 ) although we did observe a clear trend in the reduction of NEC frequency in the studied cases : 6 ( 8 % ) versus 12 ( 16 % ) in the control group . When the combined risk of NEC or death was calculated as a post hoc analysis , we found a significantly lower risk ( RR : 0.39 , 95 % CI 0.17 to 0.87 ) for the study group . Conclusions Probiotics may offer potential benefits for premature infants and are a promising strategy in the reduction of the risk of NEC in preterm newborns",
"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",
"Objective To evaluate the effect of oral Lactobacillus reuteri ( L reuteri ) first on the incidence and severity of Necrotising enterocolitis ( NEC ) and second on sepsis . Design Prospect i ve r and omised controlled study . Setting Tertiary neonatal intensive care unit . Patients and interventions Preterm infants with a gestational age of ≤32 weeks and a birth weight of ≤1500 g were included ( n=400 ) . Infants in the first group were given 100 million CFU/day ( 5 drops ) of lyophilised L reuteri ( DSM 17938 ) mixed in breast milk or formula , starting from first feeding until discharge . Participants in the control group were given a placebo . Main outcome measures To determine and compare the frequency of NEC and /or death after 7 days , frequency of proven sepsis , rates of feeding intolerance and duration of hospital stay . Results There was no statistically significant difference between groups in terms of frequency of NEC stage ≥2 ( 4 % vs 5 % ; p=0.63 ) or overall NEC or mortality rates ( 10 % vs 13.5 % ; p=0.27 ) . Frequency of proven sepsis was significantly lower in the probiotic group compared to the control group ( 6.5 % vs 12.5 % ; p=0.041 ) . A significant difference was also observed with regard to rates of feeding intolerance ( 28 % vs 39.5 % ; p=0.015 ) and duration of hospital stay ( 38 ( 10–131 ) vs 46 ( 10–180 ) days ; p=0.022 ) . Conclusions Our results show that oral L reuteri does not seem to affect the overall rates of NEC and /or death in preterm infants followed up in the neonatal intensive care unit , and significant reductions were observed in the frequency of proven sepsis , rates of feeding intolerance and duration of hospital stay . Trial registration number NCT01531179",
"CONTEXT Sepsis is a common and severe complication in premature neonates , particularly those with very low birth weight ( VLBW ) ( Whether lactoferrin , a mammalian milk glycoprotein involved in innate immune host defenses , can reduce the incidence of sepsis is unknown . In animal models , the probiotic Lactobacillus rhamnosus GG ( LGG ) enhances the activity of lactoferrin but has not been studied in human infants . OBJECTIVE To establish whether bovine lactoferrin ( BLF ) , alone or in combination with LGG , reduces the incidence of late-onset sepsis in VLBW neonates . DESIGN , SETTING , AND PATIENTS Prospect i ve , multicenter , double-blind , placebo-controlled , r and omized trial conducted in 11 Italian tertiary neonatal intensive care units . Patients were 472 VLBW infants enrolled from October 1 , 2007 , through July 31 , 2008 , and assessed until discharge for development of sepsis . INTERVENTION Infants were r and omly assigned to receive orally administered BLF ( 100 mg/d ) alone ( n = 153 ) , BLF plus LGG ( 6 x 10(9 ) colony-forming units/d ) ( n = 151 ) , or placebo ( n = 168 ) from birth until day 30 of life ( day 45 for neonates First episode of late-onset sepsis , ie , sepsis occurring more than 72 hours after birth with isolation of any pathogen from blood or from peritoneal or cerebrospinal fluid . RESULTS Demographic , clinical , and management characteristics of the 3 groups were similar , including type of feeding and intake of maternal milk . Incidence of late-onset sepsis was significantly lower in the BLF and BLF plus LGG groups ( 9/153 [ 5.9 % ] and 7/151 [ 4.6 % ] , respectively ) than in the control group receiving placebo ( 29/168 [ 17.3 % ] ) ( risk ratio , 0.34 ; 95 % confidence interval , 0.17 - 0.70 ; P = .002 for BLF vs control and risk ratio , 0.27 ; 95 % confidence interval , 0.12 - 0.60 ; P bacterial and fungal sepsis . No adverse effects or intolerances to treatment occurred . CONCLUSION Compared with placebo , BLF supplementation alone or in combination with LGG reduced the incidence of a first episode of late-onset sepsis in VLBW neonates . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N53107700",
"Abstract Objective : To study the effect of synbiotics in reducing incidence and severity of necrotizing enterocolitis ( NEC ) among preterm neonates . Methods : This r and omized controlled trial conducted in a tertiary care teaching hospital , south India , included 220 enterally fed preterm neonates who were r and omized to receive either synbiotics or no intervention . The synbiotic contained Lactobacillus , Bifidobacterium and fructo-oligosaccharide . The demographic parameters , risk factors for NEC and outcome including incidence of NEC , its severity , sepsis and mortality were evaluated . Results : Multiple pregnancies , preeclampsia and prolonged rupture of membranes were important maternal characteristics . The average birth weight and gestational age of the preterm neonates was 1.4 kg and 31 weeks , respectively . There was a 50 % reduction in the incidence of NEC of all stages in preterm infants who received synbiotics compared to the non-intervention group ( 7.4 % versus 14.5 % ) . Administration of synbiotics did not reduce the severity of NEC , sepsis or mortality . Conclusion : Enteral supplementation of synbiotics along with breastmilk results in a tendancy to decrease the incidence of NEC among preterm neonates",
"Background Probiotic supplementation significantly reduces the risk of necrotising enterocolitis ( NEC ) and all cause mortality in preterm neonates . Independent quality assessment is important before introducing routine probiotic supplementation in this cohort . Aim To assess product quality , and confirm that Bifidobacterium breve ( B. breve ) M-16V supplementation will increase fecal B. breve counts without adverse effects . Methods and Participants Strain identity ( 16S rRNA gene sequencing ) , viability over 2 year shelf-life were confirmed , and microbial contamination of the product was ruled out . In a controlled trial preterm neonates ( Gestation were r and omly allocated to either B. breve M-16V ( 3 × 109 cfu/day ) or placebo ( dextrin ) supplementation until the corrected age 37 weeks . Stool sample s were collected before ( S1 ) and after 3 weeks of supplementation ( S2 ) for study ing fecal B. breve levels using quantitative PCR ( Primary outcome ) . Secondary outcomes included total fecal bifidobacteria and NEC≥Stage II . Categorical and continuous outcomes were analysed using Chi-square and Mann-Whitney tests , and McNemar and Wilcoxon signed-rank tests for paired comparisons . Results A total of 159 neonates ( Probiotic : 79 , Placebo : 80 ) were enrolled . Maternal and neonatal demographic characteristics were comparable between the groups . The proportion of neonates with detectable B. breve increased significantly post intervention : Placebo : [ S1:2/66 ( 3 % ) , S2 : 25/66 ( 38 % ) , p : [ S1 : 29/74 ( 40 % ) , S2 : 67/74 ( 91 % ) , p in both groups were below detection ( There were no adverse effects including probiotic sepsis and no deaths . NEC≥Stage II occurred in only 1 neonate ( placebo group ) . Conclusion B. breve M-16V is a suitable probiotic strain for routine use in preterm neonates . Trial Registration Australia New Zeal and Clinical Trial Registry ACTRN",
"OBJECTIVE . The goal was to investigate the efficacy of orally administered probiotics in preventing necrotizing enterocolitis for very low birth weight preterm infants . METHODS . A prospect i ve , blinded , r and omized , multicenter controlled trial was conducted at 7 NICUs in Taiwan , to evaluate the beneficial effects of probiotics in necrotizing enterocolitis among very low birth weight infants ( birth weight : and were assigned r and omly to 2 groups after parental informed consent was obtained . Infants in the study group were given Bifidobacterium bifidum and Lactobacillus acidophilus , added to breast milk or mixed feeding ( breast milk and formula ) , twice daily for 6 weeks . Infants in the control group were fed with breast milk or mixed feeding . The clinicians caring for the infants were blinded to the group assignment . The primary outcome measurement was death or necrotizing enterocolitis ( Bell 's stage ≥2 ) . RESULTS . Four hundred thirty-four infants were enrolled , 217 in the study group and 217 in the control group . The incidence of death or necrotizing enterocolitis ( stage ≥2 ) was significantly lower in the study group ( 4 of 217 infants vs 20 of 217 infants ) . The incidence of necrotizing enterocolitis ( stage ≥2 ) was lower in the study group , compared with the control group ( 4 of 217 infants vs 14 of 217 infants ) . No adverse effect , such as sepsis , flatulence , or diarrhea , was noted . CONCLUSION . Probiotics , in the form of Bifidobacterium and Lactobacillus , fed enterally to very low birth weight preterm infants for 6 weeks reduced the incidence of death or necrotizing enterocolitis",
"Background This study evaluated the benefit of Bifidobacterium bifidum OLB6378 ( B. bifidum ) in very low-birthweight ( VLBW ) infants ( birthweight for the acceleration of enteral feeding . Methods A cluster-r and omized , double-blind , placebo-controlled trial was conducted in 19 hospitals , divided into two groups : the B group ( n = 10 hospitals ; B. bifidum given to infants within 48 h of birth ) and the P group ( n = 9 hospitals ; infants received a placebo ) . The primary outcome was establishment of enteral feeding after birth , defined as the postnatal day at which enteral feeding exceeded 100 mL/(kg/day ) . Secondary outcomes were defined as incidence of morbidity and somatic growth before discharge . Results Overall , 283 VLBW infants were enrolled in the study : B group , n = 153 ; and P group , n = 130 . Enteral feeding was established within 21 days after birth in 233 infants , of whom 119 received B. bifidum and 114 received placebo until their bodyweight reached 2000 g. Enteral feeding was established significantly earlier in the B group , at 11.0 ± 3.6 days versus 12.1 ± 3.8days in P group ( P unit was not different between groups , but the incidence of late-onset sepsis among all enrolled infants was significantly lower in the B group ( 3.9 % , 6/153 ) than in the P group ( 10.0 % , 13/130 ; P in the incidence of other adverse outcomes including mortality . Conclusions B. bifidum in VLBW infants accelerated the establishment of enteral feeding after birth without increasing the incidence of adverse effects ",
"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 OF THE STUDY Preterm infants are managed with antibiotics for sepsis , including suspected or probable sepsis . This leads to a delayed and abnormal colonization of the gut with potentially pathogenic organisms and a microbiome , which lacks biodiversity and increases the risk for late-onset sepsis ( LOS ) . Probiotics have been proven to reduce the risk for necrotizing enterocolitis , but evidence for prevention of LOS is inconclusive . Probiotic effect depends also on the strain used , dose and indication for use . This study evaluated Bacillus clausii probiotic administered prophylactically to preterm neonates for prevention of LOS . OBJECTIVES To study B.clausii given prophylactically to preterm neonates for prevention of LOS . DESIGN Double-blinded , placebo-controlled , r and omized trial . SETTING S Tertiary care neonatal unit in India . PARTICIPANTS Consecutive preterm neonates INTERVENTION R and omized to receive either probiotic or placebo for 6 weeks , discharge from hospital , death or occurrence of sepsis , whichever was earlier . PRIMARY OUTCOME Incidence of definite and probable LOS in probiotic group compared with placebo . RESULTS Of 326 eligible preterm infants , 244 were enrolled and 82 were excluded . Of these , 120 were stratified as extreme preterm and r and omized to receive placebo ( n = 59 ) and probiotic ( n = 61 ) . Of 124 babies stratified as very preterm , an equal number was r and omized to receive placebo ( n = 62 ) and probiotic ( n = 62 ) . There was no significant difference in the incidence of LOS between the two arms in the extreme preterm group [ 29 % vs. 23 % ; relative risk ( RR ) 1.27 ; 95 % confidence interval ( CI ) 0.88 - 1.66 ; p = 0.36 ] and the very preterm group ( 13 % vs. 10 % ; RR 1.33 ; 95 % CI 0.96 - 1.70 ; p = 0.32 ) . Full feeds were achieved significantly faster in the probiotic group in both the extreme preterm ( RR 0.82 ; 95 % CI 0.74 - 0.88 ) and the very preterm ( RR 0.67 ; 95 % 0.32 - 0.77 ) . CONCLUSIONS Prophylactic administration of B.clausii to preterm neonates did not result in a significant difference in the incidence of LOS as compared with placebo ",
"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",
"Summary Background Late-onset infections are an important cause of morbidity and mortality in preterm infants . The purpose of our prospect i ve r and omised study was to establish whether a combination of probiotics ( Lactobacillus acidophilus , Enterococcus faecium and Bifidobacterium infantum ) affects the incidence of late-onset sepsis and other infections in very low birthweight infants ( birthweight under 1500 g , gestational age under 33 weeks ) . Methods From 80 included infants , one half received probiotics ( L. acidophilus , E. faecium and B. infantum ) in the ratio 1.5:1:1.5 , at a dose of 0.6 × 107 colony-forming units twice daily , given with the first portions of milk until discharge , whereas the other half did not . Results In the group receiving probiotics , 16 children had late-onset sepsis compared with 29 in the group without probiotics ; p = 0.006 . The number of late-onset septic events was lower ( 30 ) in the group receiving probiotics than in the group that did not receive probiotics ( 69 ) ; p = 0.003 . Furthermore , fewer children had at least one late-onset infection ( 20 infants in the group receiving probiotics compared with 32 in the group without them ; p = 0.009 ) . There were less episodes of late-onset infections in the group receiving probiotics ( 35 ) than in the group without probiotics ( 79 ) ; p = 0.002 . Conclusions A combination of probiotics at a low dose ( 1.2 × 107 colony-forming units ) decreased the frequency of late-onset sepsis and other infections , as described in previous studies . In addition , children were discharged at a lower postmenstrual age . There were no side effects of probiotics reported",
"OBJECTIVE To evaluate the efficacy of orally administered probiotics in preventing necrotizing enterocolitis ( NEC ) in preterm very low birth weight ( VLBW ) infants . STUDY DESIGN Ar and omized double blind controlled trial . PLACE AND DURATION OF STUDY The Paediatrics Department of Sylhet M.A.G. Osmani Medical College Hospital , Sylhet Bangladesh , from July 2012 to June 2015 . METHODOLOGY Preterm ( 28 - 33 weeks gestation ) VLBW ( birth weight 1000 - 1499 g ) neonates were enrolled . The study group was fed with probiotics once daily with breast milk from first feeding , and the control group with only breast milk without the addition of probiotics . Both the groups received other st and ard care . The primary outcome was the development of NEC ( stage II and III ) , categorized by modified Bell 's classification . RESULTS In 108 neonates , development of NEC was significantly lower in the study group than that of control group [ 1 ( 1.9 % ) vs. 6 ( 11.5 % ) ; p=0.044 ] . Age of achievement of full oral feeding was significantly earlier in the study group than that in the control group ( 14.88 ±3.15 and 18.80 ±4.32 days ; p Duration of hospital stay was significantly short in the study group compared to the control group ( 15.82 ±2.94 days vs. 19.57 ±4.26 days ; p CONCLUSION Probiotic supplementation reduces the frequency of necrotising enterocolitis in preterm neonates with very low birth weight . It is also associated with faster achievement of full oral feeding and short duration of hospital stay ",
"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",
"Objective : The objective of this trial was to test whether probiotic-supplemented feeding to extremely low-birth-weight ( ELBW ) infants will improve growth as determined by decreasing the percentage of infants with weight below the 10th percentile at 34 weeks postmenstrual age ( PMA ) . Other important outcome measures , such as improving feeding tolerance determined by tolerating larger volume of feeding per day and reducing antimicrobial treatment days during the first 28 days from the initiation of feeding supplementation were also evaluated . Study Design : We conducted a multicenter r and omized controlled double-blinded clinical study . The probiotics-supplementation ( PS ) group received Lactobacillus rhamnosus GG and Bifidobacterium infantis added to the first enteral feeding and continued once daily with feedings thereafter until discharge or until 34 weeks ( PMA ) . The control ( C ) group received unsupplemented feedings . Infant weight and feeding volumes were recorded daily during the first 28 days of study period . Weights were also recorded at 34 weeks PMA . Result : A total of 101 infants were enrolled ( PS 50 versus C 51 ) . There was no difference between the two groups in the percentage of infants with weight below the 10th percentile at 34 weeks PMA ( PS group 58 % versus C group 60 % , ( P value 0.83 ) ) or in the average volume of feeding during 28 days after study entry ( PS group 59 ml kg−1 versus C group 71 ml kg−1 , ( P value 0.11 ) ) . Calculated growth velocity was higher in the PS group compared with the C group ( 14.9 versus 12.6 g per day , ( P value 0.05 ) ) . Incidences of necrotizing enterocolitis ( NEC ) , as well as mortality were similar between the two groups . Conclusion : Although probiotic-supplemented feedings improve growth velocity in ELBW infants , there was no improvement in the percentage of infants with growth delay at 34 weeks PMA . There were no probiotic-related adverse events reported",
"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 ",
"OBJECTIVE To test the efficacy of probiotic and prebiotic , alone or combined ( synbiotic ) , on the prevention of necrotizing enterocolitis ( NEC ) in very low birth weight ( VLBW ) infants . STUDY DESIGN A prospect i ve , r and omized , controlled trial was conducted at 5 neonatal intensive care units in Turkey . VLBW infants ( n = 400 ) were assigned to a control group and 3 study groups that were given probiotic ( Bifidobacterium lactis ) , prebiotic ( inulin ) , or synbiotic ( Bifidobacterium lactis plus inulin ) added to breastmilk or formula for a maximum of 8 weeks before discharge or death . The primary outcome was NEC ( Bell stage ≥2 ) . RESULTS The rate of NEC was lower in probiotic ( 2.0 % ) and synbiotic ( 4.0 % ) groups compared with prebiotic ( 12.0 % ) and placebo ( 18.0 % ) groups ( P The times to reach full enteral feeding were faster ( P the rates of clinical nosocomial sepsis were lower ( P = .004 ) , stays in the neonatal intensive care unit were shorter , ( P = .002 ) , and mortality rates were lower ( P = .003 ) for infants receiving probiotics , prebiotics , or synbiotic than controls . The use of antenatal steroid ( OR 0.5 , 95 % CI 0.3 - 0.9 ) and postnatal probiotic ( alone or in synbiotic ) ( OR 0.5 , 95 % CI 0.2 - 0.8 ) decreased the risk of NEC , and maternal antibiotic exposure increased this risk ( OR 1.9 , 95 % CI 1.1 - 3.6 ) . CONCLUSIONS In VLBW infants , probiotic ( Bifidobacterium lactis ) and synbiotic ( Bifidobacterium lactis plus inulin ) but not prebiotic ( inulin ) alone decrease NEC",
"OBJECTIVE To test the hypothesis that normalizing the intestinal flora by administration of prophylactic probiotics would provide a natural defense , thereby reducing both the incidence and severity of necrotizing enterocolitis ( NEC ) in preterm neonates . STUDY DESIGN Neonates were r and omized to either receive a daily feeding supplementation with a probiotic mixture ( Bifidobacteria infantis , Streptococcus thermophilus , and Bifidobacteria bifidus ; Solgar , Israel ) of 10(9 ) colony forming units (CFU)/day or to not receive feed supplements . NEC was grade d according to Bell 's criteria . RESULTS For 72 study and 73 control infants , respectively , birth weight ( 1152 + /- 262 g vs 1111 + /- 278 g ) , gestational age ( 30 + /- 3 weeks vs 29 + /- 4 weeks ) , and time to reach full feeds ( 14.6 + /- 8.7 days vs 17.5 + /- 13.6 days ) were not different . The incidence of NEC was reduced in the study group ( 4 % vs 16.4 % ; P=.03 ) . NEC was less severe in the probiotic-supplemented infants ( Bell 's criteria 2.3 + /- 0.5 vs 1.3 + /- 0.5 ; P=.005 ) . Three of 15 babies who developed NEC died , and all NEC-related deaths occurred in control infants . CONCLUSION Probiotic supplementation reduced both the incidence and severity of NEC in our premature neonatal population",
"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",
"BACKGROUND Necrotizing enterocolitis ( NEC ) is the most serious gastrointestinal problem in very low birth weight preterm infants . Multiple risk factors activate the inflammatory cascade leading to high expressions of pro-inflammatory mediators causing bowel injury in NEC . The anti-inflammatory effect of probiotics is due to the inhibition and reduction of inflammatory signal in intestinal epithelium . OBJECTIVE To evaluate the efficacy of probiotics supplementation in the prevention of NEC among very low birth weight preterm infants . STUDY DESIGN A prospect i ve r and omized controlled trial . MATERIAL AND METHOD All preterm infants with gestational age less than or equal to 34 weeks and birth weight less than or equal to 1,500 grams admitted in neonatal care unit , Queen Sirikit National Institute of Child Health during June 1st , 2012 and January 31th , 2013 were enrolled in this study . They were r and omized into two groups , study and control group . Infants in the study group were fed Infloran ( Lactobacillus acidophilus 1 x 10(9 ) and Bifidobacterium bifidum 1 x 10(9 ) organisms ) dose 125 mg/kg/dose twice a day with breast milk or premature formula from the start of feeding until 6 weeks or discharge . Infants in the control group were fed with either breast milk or premature formula alone . The primary outcome was NEC stage ≥ 2 . RESULTS Sixty infants completed the study , 31 infants in the study group and 29 infants in the control group . The baseline characteristic data of infants were similar except for more males in the present study group . Incidence of NEC stage ≥ 2 were similar in both the groups , 3.2 vs. 3.4 % ( p = 0.74 ) . There were no deaths during the study period . Days to reach full feeding , 150 ml/kg/day , were no differences between the two groups , 12.03 ± 5.49 days vs. 13.76 ± 8.25 days ( p = 0.31 ) . No adverse effects such as sepsis , flatulence or diarrhea were noted . CONCLUSION In this study , there was no difference in incidence of NEC stage ≥ 2 between the two groups . No adverse effects of probiotics supplementation were observed",
"OBJECTIVE To assess the effect of probiotics on the incidence of necrotizing enterocolitis ( NEC ) in premature infants born to human immunodeficiency virus (HIV)-positive and HIV-negative women . PATIENTS AND METHODS HIV-exposed and HIV-unexposed premature infants were r and omized to either the probiotic or the placebo group . The probiotic consisted of 1 × 10(9 ) colony-forming units , Lactobacillus rhamnosus GG and Bifidobacterium infantis per day . RESULTS In total , 74 HIV-exposed and 110 HIV-unexposed infants were enrolled and r and omized . The incidence of death [ 4 ( 5.4 % ) vs. 7 ( 6 % ) ; p = 0.79 ] and NEC [ 4 ( 5 % ) vs. 5 ( 5 % ) ; p = 0.76 ] did not differ significantly between the HIV-exposed and HIV-unexposed groups . A significant difference was found for total NEC incidence between the study and control groups [ 3 ( 3 % ) vs. 6 ( 6 % ) ; p = 0.029 ] . The incidence of NEC in the HIV-exposed group differed significantly [ Bells I 2 ( 5 % ) vs. Bells III 2 ( 5 % ) ; p = 0.045 ) . CONCLUSION Probiotic supplementation reduced the incidence of NEC in the premature very low birth weight infants ; however , results failed to show a lower incidence of NEC in HIV-exposed premature infants . A reduction in the severity of disease was found in the HIV-exposed study group",
"BACKGROUND Gut bacteria might predispose to or protect from necrotising enterocolitis , a severe illness linked to prematurity . In this observational prospect i ve study we aim ed to assess whether one or more bacterial taxa in the gut differ between infants who subsequently develop necrotising enterocolitis ( cases ) and those who do not ( controls ) . METHODS We enrolled very low birthweight ( 1500 g and lower ) infants in the primary cohort ( St Louis Children 's Hospital ) between July 7 , 2009 , and Sept 16 , 2013 , and in the secondary cohorts ( Kosair Children 's Hospital and Children 's Hospital at Oklahoma University ) between Sept 12 , 2011 and May 25 , 2013 . We prospect ively collected and then froze stool sample s for all infants . Cases were defined as infants whose clinical courses were consistent with necrotising enterocolitis and whose radiographs fulfilled criteria for Bell 's stage 2 or 3 necrotising enterocolitis . Control infants ( one to four per case ; not fixed ratios ) with similar gestational ages , birthweight , and birth date s were selected from the population after cases were identified . Using primers specific for bacterial 16S rRNA genes , we amplified and then pyrosequenced faecal DNA from stool sample s. With use of Dirichlet multinomial analysis and mixed models to account for repeated measures , we identified host factors , including development of necrotising enterocolitis , associated with gut bacterial population s. FINDINGS We studied 2492 stool sample s from 122 infants in the primary cohort , of whom 28 developed necrotising enterocolitis ; 94 infants were used as controls . The microbial community structure in case stools differed significantly from those in control stools . These differences emerged only after the first month of age . In mixed models , the time-by-necrotising-enterocolitis interaction was positively associated with Gammaproteobacteria ( p=0·0010 ) and negatively associated with strictly anaerobic bacteria , especially Negativicutes ( p=0·0019 ) . We studied 1094 stool sample s from 44 infants in the secondary cohorts . 18 infants developed necrotising enterocolitis ( cases ) and 26 were controls . After combining data from all cohorts ( 166 infants , 3586 stools , 46 cases of necrotising enterocolitis ) , there were increased proportions of Gammaproteobacteria ( p=0·0011 ) and lower proportions of both Negativicutes ( p=0·0013 ) and the combined Clostridia-Negativicutes class ( p=0·0051 ) in infants who went on to develop necrotising enterocolitis compared with controls . These associations were strongest in both the primary cohort and the overall cohort for infants born at less than 27 weeks ' gestation . INTERPRETATION A relative abundance of Gammaproteobacteria ( ie , Gram-negative facultative bacilli ) and relative paucity of strict anaerobic bacteria ( especially Negativicutes ) precede necrotising enterocolitis in very low birthweight infants . These data offer c and i date targets for interventions to prevent necrotising enterocolitis , at least among infants born at less than 27 weeks ' gestation . FUNDING National Institutes of Health ( NIH ) , Foundation for the NIH , the Children 's Discovery Institute",
"OBJECTIVE To compare stool colonization among premature infants receiving high-dose probiotics versus st and ard dose . STUDY DESIGN This blinded , r and omized , placebo-controlled trial was conducted in a Level III neonatal unit . Eligibility criteria were gestational age 27 - 33 weeks , age malformations and necrotizing enterocolitis/sepsis were exclusions . A total of 149 subjects were r and omly allocated to groups A through D ( received 12-hourly probiotic supplements of 10(10 ) cells for 21 days , 10(10 ) cells for 14 days , 10(9 ) cells for 21 days and placebo , respectively ) . Key outcome was stool colonization by a probiotic organism at 28 days . RESULTS Colonization with Lactobacillus and Bifidobacterium was significantly higher in groups A , B , and C versus placebo respectively , but groups A through C did not differ from each other . There were trends toward more colony forming unit ( cfu ) of Lactobacillus and Bifidobacterium per milliliter of stool in group A versus B and B versus C. Groups A and B and spontaneous preterm labor ( SPL ) independently predicted high Lactobacillus counts on day 28 ; groups A , B , and C and SPL predicted high Bifidobacterium counts . CONCLUSION Proportion of infants colonized with probiotic species was similar with high-dose and st and ard dose regimes"
] |
4116b85c-06ff-11f0-808a-c43d1ab1c353
|
Workplace stressors have been indicated to play a role in the development of neck and upper extremity pain possibly through an increase of sustained ( low-level ) muscle activity . The aim of this review was to study the effects of workplace stressors on muscle activity in the neck-shoulder and forearm muscles . An additional aim was to find out whether the muscles of the neck-shoulder and the forearm are affected differently by different types of workplace stressors . A systematic literature search was conducted on studies investigating the relation between simulated or realistic workplace stressors and neck-shoulder and forearm muscle activity . For studies meeting the inclusion criteria , a risk of bias assessment was performed and data were extracted for synthesis . Results were pooled when possible and otherwise described . Twenty-eight articles met the inclusion criteria , reporting data of 25 different studies . Except for one field study , all included studies were laboratory studies . Data of 19 articles could be included in the meta- analysis and revealed a statistically significant , medium increase in neck-shoulder and forearm muscle activity as a result of workplace stressors . In subgroup analyses , we found an equal effect of different stressor types ( i.e. cognitive/emotional stress , work pace , and precision ) on muscle activity in both body regions . In conclusion , simulated workplace stressors result in an increase in neck-shoulder and forearm muscle activity . No indications were found that different types of stressors affect these body regions differently . These conclusions are fully based on laboratory studies , since field studies on this topic are currently lacking
|
[
"A laboratory study was conducted to determine the effects of work pace on typing force , electromyographic ( EMG ) activity , and subjective discomfort . We found that as participants typed faster , their typing force and finger flexor and extensor EMG activity increased linearly . There was also an increase in subjective discomfort , with a sharp threshold between participants ' self-selected pace and their maximum typing speed . The results suggest that participants self-select a typing pace that maximizes typing speed and minimizes discomfort . The fastest typists did not produce significantly more finger flexor EMG activity but did produce proportionately less finger extensor EMG activity compared with the slower typists . We hypothesize that fast typists may use different muscle recruitment patterns that allow them to be more efficient than slower typists at striking the keys . In addition , faster typists do not experience more discomfort than slow typists . These findings show that the relative pace of typing is more important than actual typing speed with regard to discomfort and muscle activity . These results suggest that typists may benefit from skill training to increase maximum typing speed . Potential applications of this research includes skill training for typists",
"OBJECTIVE Assessment of the age effect in relation to computer work . BACKGROUND Increasingly , more older people are using computers , while hardware and software are not design ed with special consideration of their needs . METHODS Eight young and nine older females performed different computer mouse tasks . Shoulder muscle activity was recorded from the right deltoid muscle , right and left upper trapezius muscle , and the neck extensor muscles . RESULTS Mean trapezius muscle activity was significantly higher in the older people ( 2.8%/3.7 % EMG(max ) for R/L ) compared to the young ( 1.1%/1.2 % EMG(max ) ) . There was a tendency to a higher activity in the older people for the deltoid muscle and the neck extensor muscles . There were small differences in shoulder muscle activation levels between mouse actions , target directions , and between precision dem and s. CONCLUSIONS Shoulder muscle activity during computer work is affected by age , but only to a minor extent by the type of computer mouse task . The deltoid and the trapezius muscle activities are low during computer mouse use when there is efficient forearm support by the table . Relevance An increasing number of people use computers for hours every day . Intensive use of computers increases the risk of development of work-related musculoskeletal symptoms in the shoulder region",
"The present study evaluated the specific effects of motor dem and and visual dem and s on the ability to control motor output in terms of performance and muscle activation . Young and elderly subjects performed multidirectional pointing tasks with the computer mouse . Three levels of mouse gain and three levels of target size were used . All subjects demonstrated a reduced working speed and hit rate at the highest mouse gain ( 1:8 ) when the target size was small . The young group had an optimum at mouse gain 1:4 . The elderly group was most sensitive to the combination of high mouse gain and small targets and thus , this age group should avoid this combination . Decreasing target sizes ( i.e. increasing visual dem and ) reduced performance in both groups despite that motor dem and was maintained constant . Therefore , it is recommended to avoid small screen objects and letters . Forearm muscle activity was only to a minor degree influenced by mouse gain ( and target sizes ) indicating that stability of the forearm/h and is of significance during computer mouse control . The study has implication s for ergonomists , pointing device manufacturers and software developers",
"The aim was to investigate whether quantitative job dem and s influence muscle activity among women , and whether there are gender differences in duration of computer , mouse , and keyboard use and muscle activity of shoulder and forearm muscles during work . The study was carried out in an occupational setting , and 24 women and 11 men from a municipal administration participated . The duration of computer , mouse , and keyboard use was measured by a commercial software package . Quantitative job dem and s were registered by question naire . Electromyography ( EMG ) was measured bilaterally from the upper trapezius and the extensor digitorum communis muscles . No association was found between self-reported quantitative job dem and s and muscle activity among the women ( n=24 ) . The women used the keyboard more frequently ( p=0.020 ) and tended to perform fewer mouse clicks compared to men ( p=0.057 ) , but no difference was seen in EMG activity between men ( n=11 ) and women ( n=11 ) from the same department . However , office assistants ( six women ) showed significantly higher static EMG activity levels ( p=0.042 ) and almost significantly shorter EMG gap times ( p=0.060 ) than the rest of the subjects ( 5 women and 11 men ) . This indicated that shorter muscular resting periods among female office assistants as compared to the other subjects were due to differences in job content rather than gender differences",
"Abstract . The overall aim of this study was to investigate whether time pressure and verbal provocation has any effect on physiological and psychological reactions during work with a computer mouse . It was hypothesised that physiological reactions other than muscle activity ( i.e. wrist movements , forces applied to the computer mouse ) would not be affected when working under stressful conditions . Fifteen subjects ( 8 men and 7 women ) participated , performing a st and ardised text-editing task under stress and control conditions . Blood pressure , heart rate , heart rate variability , electromyography , a force-sensing computer mouse and electrogoniometry were used to assess the physiological reactions of the subjects . Mood ratings and ratings of perceived exertion were used to assess their psychological reactions . The time pressure and verbal provocation ( stress situation ) result ed in increased physiological and psychological reactions compared with the two control situations . Heart rate , blood pressure and muscle activity in the first dorsal interosseus , right extensor digitorum and right trapezius muscles were greater in the stress situation . The peak forces applied to the button of the computer mouse and wrist movements were also affected by condition . Whether the increases in the physiological reactions were due to stress or increased speed/productivity during the stress situation is discussed . In conclusion , work with a computer mouse under time pressure and verbal provocation ( stress conditions ) led to increased physiological and psychological reactions compared to control conditions",
"Work-related upper extremity disorders ( WRUEDs ) that result from keyboarding tasks are prevalent and costly . Although the precise mechanisms causing the disorder are not yet fully understood , several risk factors have been proposed . These include the repetitive nature of the motor task and the associated sustained static working postures , but also more psychological factors such as mental load . Epidemiological surveys have shown that WRUEDs are more prone to develop in the postural muscles of the neck/shoulder area than in the executive muscles controlling the h and . The present study investigated whether the activation patterns of these two muscle types are differentially affected by an additional mental load during the performance of a repetitive tapping task . Participants tapped various keying patterns with their dominant index finger at two prescribed tempi . Mental load was manipulated by means of an auditory short-term memory task . We recorded the EMG activity of two neck/shoulder muscles ( trapezius and deltoid ) , two upper arm muscles ( biceps and triceps ) , and four forearm muscles ( flexor digitorum superficialis , extensor digitorum , extensor carpi radialis longus and extensor carpi ulnaris ) and analyzed the kinematics and impact forces of the index finger . The results confirmed that the upper limb has two functions . Specifically , activity of the executive distal musculature was increased during tapping at the higher pace , while the activity of the postural upper limb musculature was elevated due to the memory task . We argue that continuously increased muscular activity can lead to fatigue and thus eventually cause musculoskeletal complaints . The results are discussed with respect to biomechanical adaptation strategies that deal with the consequences of increased noise in the neuromotor system due to enhanced mental processing",
"The overall aim was to investigate the effect of psychosocial loads on trapezius muscle activity during computer keying work and during short and long breaks . In 12 female subjects , surface electromyography ( EMG ) was recorded bilaterally from the upper trapezius muscle during a st and ardized one h and keying task — interspaced with short ( 30 s ) and long ( 4 min ) breaks — in sessions with and without a combination of cognitive and emotional stressors . Adding psychosocial loads to the same physical work did not increase the activity of the trapezius muscle on either the keying or the control side , both of which remained at median and static EMG activity levels of around 5 % and 2.5 % of the maximal voluntary electrical activity ( EMGmax ) , respectively . The difference between the keying and the control side was significant ; and further the control side activity was significantly increased above resting level . During both short and long breaks , exposure to psychosocial loads also did not increase the activity of the trapezius muscle either on the side of the keying or the control h and . Of note is that during long breaks the muscle activity of the keying side as well as that of the control side remained at the same level as during the short breaks , which was increased above resting level . This was to be seen from the static and the median EMG activity levels as well as gap times , the overall mean values being : 0.4%EMGmax , 1.1%EMGmax , and 50 % in gap time , respectively . In conclusion : psychosocial loads are not solely responsible for increased non-postural muscle activity ; and increasing the duration of breaks does not per se cause muscle relaxation",
"The influence of stress-induced muscle effort during computer utilization was tested in patients with repetitive strain injury ( RSI ) . Twenty academic research ers with a formal medical diagnosis of RSI and 20 matched controls , r and omly selected from a sample of 71 colleagues with and without RSI , typed after stress ( induced via an intelligence/skill task under social pressure ) and after relaxation . Results indicated that both groups had more electromyography ( EMG ) activity in the shoulder muscles during typing after stress than after relaxation , but that patients started with higher baseline muscle activity . Furthermore , EMG activity of different muscle groups during typing after stress correlated among controls , but not among patients . Finally , analysis of intake forms showed that patients scored higher than controls on neuroticism and alexithymia , but not on extraversion , openness , agreeableness and conscientiousness . It was concluded that deviations in muscle activity during computer utilization , as well as neuroticism and alexithymia , may be risk factors for RSI",
"Computer-mouse work is characterized by repetitive movements combined with mental dem and s. The present purpose was to study how the body responded to simulated Computer Aided Design ( CAD ) work without memory dem and and when a high short-term memory dem and was introduced . Nine female subjects repetitively performed a task which involved 15 s of elevation of the right index and middle fingers followed by 6 s of rest . Every second time the fingers rested , the left index finger was required to type a six-figure number , either ‘ 123456 ’ ( without memory dem and ) or a r and om number shown half a minute before ( with memory dem and ) . After 7 min of performing the task without memory dem and , the memory dem and was introduced and continued for 1 h. Introduction of memory dem and result ed in increased heart rate ( 77 ← 84 beats/min ) , blood pressure ( systolic 129 ← 140 mmHg ; diastolic 72 ← 79 mmHg ) and forearm extensor muscle activity ( wrist , 2.7 ← 4.5 % EMGmax ; finger , 5.6 ← 7.5 % EMGmax ) and finger flexor muscle activity ( 0.7 1.2 % EMGmax ) indicating increased co-contraction . Hereafter , muscle activity and cardiovascular response tended to decrease . Self-reported stress and rating of perceived exertion ( RPE ) for the right shoulder increased throughout the period . Two additional sub- studies were inlcuded , which focused on adaptation to the physical load , showing a decrease in muscle activity and arousal , and re introduction of the memory load , showing a lower response as compared to the initial response . The practical consequences of the findings suggest that job content should have variable mental dem and",
"The present study examined the effects of physical and mental workload during computer tasks on muscle activity and physiological measures . Activity in cervical postural muscles and distal forearm muscles , heart rate and blood pressure were compared among three tasks and rest periods of 15 min each in an experimental study design . Fourteen healthy pain-free adults participated ( 7 males , mean age = 23.2 ± 3.0 years ) and the tasks were : ( 1 ) copy-typing ( “ typing ” ) , ( 2 ) typing at progressively faster speed ( “ pacing ” ) , ( 3 ) mental arithmetic plus fast typing ( “ subtraction ” ) . Typing task was performed first , followed by the other two tasks in a r and om order . Median muscle activity ( 50th percentile ) was examined in 5-min intervals during each task and each rest period , and statistically significant differences in the “ time ” factor ( within task ) and time × task factors was found in bilateral cervical erector spinae and upper trapezius muscles . In contrast , distal forearm muscle activity did not show any significant differences among three tasks . All muscles showed reduced activity to about the baseline level within first 5 min of the rest periods . Heart rate and blood pressure showed significant differences during tasks compared to baseline , and diastolic pressure was significantly higher in the subtraction than pacing task . The results suggest that cervical postural muscles had higher reactivity than forearm muscles to high mental workload tasks , and cervical muscles were also more reactive to tasks with high physical dem and compared to high mental workload . Heart rate and blood pressure seemed to respond similarly to high physical and mental workloads"
] |
4116b8a2-06ff-11f0-808a-c43d1ab1c353
|
According to rapid development of chemotherapy in advanced non-small cell lung cancer ( NSCLC ) , the Japan Lung Cancer Society has been up date d its own guideline annually since 2010 . In this latest version , all of the procedure was carried out in accordance with grading of recommendations assessment , development and evaluation ( GRADE ) system . It includes comprehensive literature search , systematic review , and determination of the recommendation by multidisciplinary expert panel which consisted of medical doctors , pharmacists , nurses , statisticians , and patients from patient advocacy group . Recently , we have had various types of chemotherapeutic drugs like kinase inhibitors or immune-checkpoint inhibitors . Thus , the guideline proposes to categorize patients into three entities : ( 1 ) driver oncogene-positive , ( 2 ) PD-L1 ≥ 50 % , and ( 3 ) others . Based on this subgroup , 31 clinical questions were described . We believe that this attempt enables clinicians to choose appropriate treatment easier . Here , we report an English version of the Japan Lung Cancer Society Guidelines 2018 for NSCLC , stages IV
|
[
"BACKGROUND Several studies have shown the efficacy , tolerability , and ease of administration of pemetrexed-an antifolate antineoplastic agent-in patients with advanced non-small-cell lung cancer . We assessed pemetrexed as maintenance therapy in patients with this disease . METHODS This r and omised double-blind study was undertaken in 83 centres in 20 countries . 663 patients with stage IIIB or IV disease who had not progressed on four cycles of platinum-based chemotherapy were r and omly assigned ( 2:1 ratio ) to receive pemetrexed ( 500 mg/m(2 ) , day 1 ) plus best supportive care ( n=441 ) or placebo plus best supportive care ( n=222 ) in 21-day cycles until disease progression . Treatment was r and omised with the Simon and Pocock minimisation method . Patients and investigators were masked to treatment . All patients received vitamin B(12 ) , folic acid , and dexamethasone . The primary endpoint of progression-free survival and the secondary endpoint of overall survival were analysed by intention to treat . This study is registered with Clinical Trials.gov , number NCT00102804 . FINDINGS All r and omly assigned participants were analysed . Pemetrexed significantly improved progression-free survival ( 4.3 months [ 95 % CI 4.1 - 4.7 ] vs 2.6 months [ 1.7 - 2.8 ] ; hazard ratio [ HR ] 0.50 , 95 % CI 0.42 - 0.61 , p overall survival ( 13.4 months [ 11.9 - 15.9 ] vs 10.6 months [ 8.7 - 12.0 ] ; HR 0.79 , 0.65 - 0.95 , p=0.012 ) compared with placebo . Treatment discontinuations due to drug-related toxic effects were higher in the pemetrexed group than in the placebo group ( 21 [ 5 % ] vs three [ 1 % ] ) . Drug-related grade three or higher toxic effects were higher with pemetrexed than with placebo ( 70 [ 16 % ] vs nine [ 4 % ] ; p fatigue ( 22 [ 5 % ] vs one [ 1 % ] , p=0.001 ) and neutropenia ( 13 [ 3 % ] vs 0 , p=0.006 ) . No pemetrexed-related deaths occurred . Relatively fewer patients in the pemetrexed group than in the placebo group received systemic post-discontinuation therapy ( 227 [ 51 % ] vs 149 [ 67 % ] ; p=0.0001 ) . INTERPRETATION Maintenance therapy with pemetrexed is well tolerated and offers improved progression-free and overall survival compared with placebo in patients with advanced non-small-cell lung cancer . FUNDING Eli Lilly",
"Background : Patient-level data from 2 phase III studies in patients with previously untreated , advanced-stage , nonsquamous non – small cell lung cancer ( NSCLC ) were pooled to examine outcomes with bevacizumab and chemotherapy based on age . Methods : Data from patients r and omized to paclitaxel – carboplatin (PC)+bevacizumab in the Eastern Cooperative Oncology Group 4599 ( E4599 ) and PointBreak studies were pooled and compared with E4599 patients r and omized to PC alone . Patients were grouped by age : below 65 , 65 to 74 , 70 to 74 , below 75 , and 75 years or above . A multivariable model was used to calculate hazard ratios ( HRs ) and corresponding 95 % confidence intervals ( CIs ) using time-to-event outcomes . Adverse events ( AEs ) were assessed by age group in each study . Results : The PC+bevacizumab and PC arms comprised 901 and 444 patients , respectively . PC+bevacizumab was associated with significant increases in overall survival relative to PC in patients below 65 years ( hazards ratio [ HR ] , 0.75 ; 95 % confidence interval [ CI ] , 0.62 - 0.89 ) , 65 to 74 years ( HR , 0.80 ; 95 % CI , 0.64 - 1.00 ) , 70 to 74 years ( HR , 0.68 ; 95 % CI , 0.48 - 0.96 ) , and below 75 years ( HR , 0.78 ; 95 % CI , 0.68 - 0.89 ) but not in those aged 75 years or above ( HR , 1.05 ; 95 % CI , 0.70 - 1.57 ) . Increased incidence of grade ≥3 AEs was reported with PC+bevacizumab versus PC in patients below 75 years ( 63 % vs. 48 % ; P survival benefits associated with PC+bevacizumab extend to patient subgroups below 75 years with advanced-stage NSCLC ; no benefit , however , was observed for bevacizumab-eligible patients who were 75 years or above",
"BACKGROUND We conducted a r and omized , placebo-controlled , double-blind trial to determine whether the epidermal growth factor receptor inhibitor erlotinib prolongs survival in non-small-cell lung cancer after the failure of first-line or second-line chemotherapy . METHODS Patients with stage IIIB or IV non-small-cell lung cancer , with performance status from 0 to 3 , were eligible if they had received one or two prior chemotherapy regimens . The patients were stratified according to center , performance status , response to prior chemotherapy , number of prior regimens , and prior platinum-based therapy and were r and omly assigned in a 2:1 ratio to receive oral erlotinib , at a dose of 150 mg daily , or placebo . RESULTS The median age of the 731 patients who underwent r and omization was 61.4 years ; 49 percent had received two prior chemotherapy regimens , and 93 percent had received platinum-based chemotherapy . The response rate was 8.9 percent in the erlotinib group and less than 1 percent in the placebo group ( P median duration of the response was 7.9 months and 3.7 months , respectively . Progression-free survival was 2.2 months and 1.8 months , respectively ( hazard ratio , 0.61 , adjusted for stratification categories ; P Overall survival was 6.7 months and 4.7 months , respectively ( hazard ratio , 0.70 ; P erlotinib . Five percent of patients discontinued erlotinib because of toxic effects . CONCLUSIONS Erlotinib can prolong survival in patients with non-small-cell lung cancer after first-line or second-line chemotherapy",
"This r and omised multicentre trial was conducted to establish the optimal duration of palliative chemotherapy in advanced non-small-cell lung cancer ( NSCLC ) . We compared a policy of three vs six courses of new-generation platinum-based combination chemotherapy with regard to effects on quality of life ( QoL ) and survival . Patients with stage IIIB or IV NSCLC and WHO performance status ( PS ) 0–2 were r and omised to receive three ( C3 ) or six ( C6 ) courses of carboplatin ( area under the curve ( AUC ) 4 , Chatelut 's formula , equivalent to Calvert 's AUC 5 ) on day 1 and vinorelbine 25 mg m−2 on days 1 and 8 of a 3-week cycle . Key end points were QoL at 18 weeks , measured with EORTC Quality of Life Question naire (QLQ)-C30 and QLQ-LC13 , and overall survival . Secondary end points were progression-free survival and need of palliative radiotherapy . Two hundred and ninety-seven patients were r and omised ( C3 150 , C6 147 ) . Their median age was 65 years , 30 % had PS 2 and 76 % stage IV disease . Seventy-eight and 54 % of C3 and C6 patients , respectively , completed all scheduled chemotherapy courses . Compliance with QoL question naires was 88 % . There were no significant group differences in global QoL , pain or fatigue up to 26 weeks . The dyspnoea palliation rate was lower in the C3 arm at 18 and 26 weeks ( P analysis . Median survival in the C3 group was 28 vs 32 weeks in the C6 group ( P=0.75 , HR 1.04 , 95 % CI 0.82–1.31 ) . One- and 2-year survival rates were 25 and 9 % vs 25 and 5 % in the C3 and C6 arm , respectively . Median progression-free survival was 16 and 21 weeks in the C3 and C6 groups , respectively ( P=0.21 , HR 0.86 , 95 % CI 0.68–1.08 ) . In conclusion , palliative chemotherapy with carboplatin and vinorelbine beyond three courses conveys no survival or consistent QoL benefits in advanced NSCLC",
"BACKGROUND The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib are approved for first-line treatment of EGFR mutation-positive non-small-cell lung cancer ( NSCLC ) . We aim ed to compare the efficacy and safety of afatinib and gefitinib in this setting . METHODS This multicentre , international , open-label , exploratory , r and omised controlled phase 2B trial ( LUX-Lung 7 ) was done at 64 centres in 13 countries . Treatment-naive patients with stage IIIB or IV NSCLC and a common EGFR mutation ( exon 19 deletion or Leu858Arg ) were r and omly assigned ( 1:1 ) to receive afatinib ( 40 mg per day ) or gefitinib ( 250 mg per day ) until disease progression , or beyond if deemed beneficial by the investigator . R and omisation , stratified by EGFR mutation type and status of brain metastases , was done central ly using a vali date d number generating system implemented via an interactive voice or web-based response system with a block size of four . Clinicians and patients were not masked to treatment allocation ; independent review of tumour response was done in a blinded manner . Co primary endpoints were progression-free survival by independent central review , time-to-treatment failure , and overall survival . Efficacy analyses were done in the intention-to-treat population and safety analyses were done in patients who received at least one dose of study drug . This ongoing study is registered with Clinical Trials.gov , number NCT01466660 . FINDINGS Between Dec 13 , 2011 , and Aug 8 , 2013 , 319 patients were r and omly assigned ( 160 to afatinib and 159 to gefitinib ) . Median follow-up was 27·3 months ( IQR 15·3 - 33·9 ) . Progression-free survival ( median 11·0 months [ 95 % CI 10·6 - 12·9 ] with afatinib vs 10·9 months [ 9·1 - 11·5 ] with gefitinib ; hazard ratio [ HR ] 0·73 [ 95 % CI 0·57 - 0·95 ] , p=0·017 ) and time-to-treatment failure ( median 13·7 months [ 95 % CI 11·9 - 15·0 ] with afatinib vs 11·5 months [ 10·1 - 13·1 ] with gefitinib ; HR 0·73 [ 95 % CI 0·58 - 0·92 ] , p=0·0073 ) were significantly longer with afatinib than with gefitinib . Overall survival data are not mature . The most common treatment-related grade 3 or 4 adverse events were diarrhoea ( 20 [ 13 % ] of 160 patients given afatinib vs two [ 1 % ] of 159 given gefitinib ) and rash or acne ( 15 [ 9 % ] patients given afatinib vs five [ 3 % ] of those given gefitinib ) and liver enzyme elevations ( no patients given afatinib vs 14 [ 9 % ] of those given gefitinib ) . Serious treatment-related adverse events occurred in 17 ( 11 % ) patients in the afatinib group and seven ( 4 % ) in the gefitinib group . Ten ( 6 % ) patients in each group discontinued treatment due to drug-related adverse events . 15 ( 9 % ) fatal adverse events occurred in the afatinib group and ten ( 6 % ) in the gefitinib group . All but one of these deaths were considered unrelated to treatment ; one patient in the gefitinib group died from drug-related hepatic and renal failure . INTERPRETATION Afatinib significantly improved outcomes in treatment-naive patients with EGFR-mutated NSCLC compared with gefitinib , with a manageable tolerability profile . These data are potentially important for clinical decision making in this patient population . FUNDING Boehringer Ingelheim",
"Background : A phase III trial was conducted to compare the safety and efficacy of erlotinib with that of gefitinib in advanced non-small cell lung cancer harbouring epidermal growth factor receptor mutations in exon 19 or 21 . Methods : Eligible patients were r and omised to receive erlotinib ( 150 mg per day ) or gefitinib ( 250 mg per day ) orally until disease progression or unacceptable toxicity . We aim ed to determine whether erlotinib is superior to gefitinib in efficacy . The primary end point was progression-free survival . Results : A total of 256 patients were r and omised to receive erlotinib ( N=128 ) or gefitinib ( N=128 ) . Median progression-free survival was not better with erlotinib than with gefitinib ( 13.0 vs 10.4 months , 95 % confidence interval ( CI ) 0.62–1.05 , P=0.108 ) . The corresponding response rates and median overall survival were 56.3 % vs 52.3 % ( P=0.530 ) and 22.9 vs 20.1 months ( 95 % CI 0.63–1.13 , P=0.250 ) , respectively . There were no significant differences in grade 3/4 toxicities between the two arms ( P=0.172 ) . Conclusions : The primary end point was not met . Erlotinib was not significantly superior to gefitinib in terms of efficacy in advanced non-small cell lung cancer with epidermal growth factor receptor mutations in exon 19 or 21 , and the two treatments had similar toxicities",
"Abstract Background Chemotherapy remains a viable option for the management of advanced non-small-cell lung cancer ( NSCLC ) despite recent advances in molecular targeted therapy and immunotherapy . We evaluated the efficacy of oral 5-fluorouracil-based S-1 as second- or third-line therapy compared with st and ard docetaxel therapy in patients with advanced NSCLC . Patients and methods Patients with advanced NSCLC previously treated with ≥1 platinum-based therapy were r and omized 1 : 1 to docetaxel ( 60 mg/m2 in Japan , 75 mg/m2 at all other study sites ; day 1 in a 3-week cycle ) or S-1 ( 80–120 mg/day , depending on body surface area ; days 1–28 in a 6-week cycle ) . The primary endpoint was overall survival . The non-inferiority margin was a hazard ratio ( HR ) of 1.2 . Results A total of 1154 patients ( 577 in each arm ) were enrolled , with balanced patient characteristics between the two arms . Median overall survival was 12.75 and 12.52 months in the S-1 and docetaxel arms , respectively [ HR 0.945 ; 95 % confidence interval ( CI ) 0.833–1.073 ; P = 0.3818 ] . The upper limit of 95 % CI of HR fell below 1.2 , confirming non-inferiority of S-1 to docetaxel . Difference in progression-free survival between treatments was not significant ( HR 1.033 ; 95 % CI 0.913–1.168 ; P = 0.6080 ) . Response rate was 8.3 % and 9.9 % in the S-1 and docetaxel arms , respectively . Significant improvement was observed in the EORTC QLQ-C30 global health status over time points in the S-1 arm . The most common adverse drug reactions were decreased appetite ( 50.4 % ) , nausea ( 36.4 % ) , and diarrhea ( 35.9 % ) in the S-1 arm , and neutropenia ( 54.8 % ) , leukocytopenia ( 43.9 % ) , and alopecia ( 46.6 % ) in the docetaxel arm . Conclusion S-1 is equally as efficacious as docetaxel and offers a treatment option for patients with previously treated advanced NSCLC . Clinical trial number Japan Pharmaceutical Information Center , JapicCTI-101155",
"Introduction : Alectinib has shown marked efficacy and safety in patients with anaplastic lymphoma receptor tyrosine kinase gene ( ALK ) rearrangement – positive NSCLC and a good performance status ( PS ) . It has remained unclear whether alectinib might also be beneficial for such patients with a poor PS . Methods : Eligible patients with advanced ALK rearrangement – positive NSCLC and a PS of 2 to 4 received alectinib orally at 300 mg twice daily . The primary end point of the study was objective response rate ( ORR ) , and the most informative secondary end point was rate of PS improvement . Results : Between September 2014 and December 2015 , 18 patients were enrolled in this phase II study . Of those patients , 12 , five , and one had a PS of 2 , 3 , or 4 , respectively , whereas four patients had received prior crizotinib treatment . The ORR was 72.2 % ( 90 % confidence interval : 52.9–85.8 % ) . The ORR did not differ significantly between patients with a PS of 2 and those with a PS of 3 or higher ( 58.3 % and 100 % , respectively [ p = 0.114 ] ) . The PS improvement rate was 83.3 % ( 90 % confidence interval : 64.8–93.1 % , p The median progression‐free survival was 10.1 months . Toxicity was mild , with the frequency of adverse events of grade 3 or higher being low . Neither dose reduction nor withdrawal of alectinib because of toxicity was necessary . Conclusions : Alectinib is a treatment option for patients with ALK rearrangement – positive NSCLC and a poor PS",
"BACKGROUND Atezolizumab is a humanised antiprogrammed death-lig and 1 ( PD-L1 ) monoclonal antibody that inhibits PD-L1 and programmed death-1 ( PD-1 ) and PD-L1 and B7 - 1 interactions , reinvigorating anticancer immunity . We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer . METHODS We did a r and omised , open-label , phase 3 trial ( OAK ) in 194 academic or community oncology centres in 31 countries . We enrolled patients who had squamous or non-squamous non-small-cell lung cancer , were 18 years or older , had measurable disease per Response Evaluation Criteria in Solid Tumors , and had an Eastern Cooperative Oncology Group performance status of 0 or 1 . Patients had received one to two previous cytotoxic chemotherapy regimens ( one or more platinum based combination therapies ) for stage IIIB or IV non-small-cell lung cancer . Patients with a history of autoimmune disease and those who had received previous treatments with docetaxel , CD137 agonists , anti-CTLA4 , or therapies targeting the PD-L1 and PD-1 pathway were excluded . Patients were r and omly assigned ( 1:1 ) to intravenously receive either atezolizumab 1200 mg or docetaxel 75 mg/m2 every 3 weeks by permuted block r and omisation ( block size of eight ) via an interactive voice or web response system . Co primary endpoints were overall survival in the intention-to-treat ( ITT ) and PD-L1-expression population TC1/2/3 or IC1/2/3 ( ≥1 % PD-L1 on tumour cells or tumour-infiltrating immune cells ) . The primary efficacy analysis was done in the first 850 of 1225 enrolled patients . This study is registered with Clinical Trials.gov , number NCT02008227 . FINDINGS Between March 11 , 2014 , and April 29 , 2015 , 1225 patients were recruited . In the primary population , 425 patients were r and omly assigned to receive atezolizumab and 425 patients were assigned to receive docetaxel . Overall survival was significantly longer with atezolizumab in the ITT and PD-L1-expression population s. In the ITT population , overall survival was improved with atezolizumab compared with docetaxel ( median overall survival was 13·8 months [ 95 % CI 11·8 - 15·7 ] vs 9·6 months [ 8·6 - 11·2 ] ; hazard ratio [ HR ] 0·73 [ 95 % CI 0·62 - 0·87 ] , p=0·0003 ) . Overall survival in the TC1/2/3 or IC1/2/3 population was improved with atezolizumab ( n=241 ) compared with docetaxel ( n=222 ; median overall survival was 15·7 months [ 95 % CI 12·6 - 18·0 ] with atezolizumab vs 10·3 months [ 8·8 - 12·0 ] with docetaxel ; HR 0·74 [ 95 % CI 0·58 - 0·93 ] ; p=0·0102 ) . Patients in the PD-L1 low or undetectable subgroup ( TC0 and IC0 ) also had improved survival with atezolizumab ( median overall survival 12·6 months vs 8·9 months ; HR 0·75 [ 95 % CI 0·59 - 0·96 ] ) . Overall survival improvement was similar in patients with squamous ( HR 0·73 [ 95 % CI 0·54 - 0·98 ] ; n=112 in the atezolizumab group and n=110 in the docetaxel group ) or non-squamous ( 0·73 [ 0·60 - 0·89 ] ; n=313 and n=315 ) histology . Fewer patients had treatment-related grade 3 or 4 adverse events with atezolizumab ( 90 [ 15 % ] of 609 patients ) versus docetaxel ( 247 [ 43 % ] of 578 patients ) . One treatment-related death from a respiratory tract infection was reported in the docetaxel group . INTERPRETATION To our knowledge , OAK is the first r and omised phase 3 study to report results of a PD-L1-targeted therapy , with atezolizumab treatment result ing in a clinical ly relevant improvement of overall survival versus docetaxel in previously treated non-small-cell lung cancer , regardless of PD-L1 expression or histology , with a favourable safety profile . FUNDING F. Hoffmann-La Roche Ltd , Genentech ,",
"BACKGROUND The efficacy of ceritinib in patients with untreated anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer ( NSCLC ) is not known . We assessed the efficacy and safety of ceritinib versus platinum-based chemotherapy in these patients . METHODS This r and omised , open-label , phase 3 study in untreated patients with stage IIIB/IV ALK-rearranged non-squamous NSCLC was done in 134 centres across 28 countries . Eligible patients were assigned via interactive response technology to oral ceritinib 750 mg/day or platinum-based chemotherapy ( [ cisplatin 75 mg/m2 or carboplatin AUC 5 - 6 plus pemetrexed 500 mg/m2 ] every 3 weeks for four cycles followed by maintenance pemetrexed ) ; r and omisation was stratified by World Health Organization performance status ( 0 vs 1 - 2 ) , previous neoadjuvant or adjuvant chemotherapy , and presence of brain metastases as per investigator 's assessment at screening . Investigators and patients were not masked to treatment assignment . The primary endpoint was blinded independent review committee assessed progression-free survival , based on all r and omly assigned patients ( the full analysis set ) . Efficacy analyses were done based on the full analysis set . All safety analyses were done based on the safety set , which included all patients who received at least one dose of study drug . This trial is registered with Clinical Trials.gov , number NCT01828099 . FINDINGS Between Aug 19 , 2013 , and May 11 , 2015 , 376 patients were r and omly assigned to ceritinib ( n=189 ) or chemotherapy ( n=187 ) . Median progression-free survival ( as assessed by blinded independent review committee ) was 16·6 months ( 95 % CI 12·6 - 27·2 ) in the ceritinib group and 8·1 months ( 5·8 - 11·1 ) in the chemotherapy group ( hazard ratio 0·55 [ 95 % CI 0·42 - 0·73 ] ; p were diarrhoea ( in 160 [ 85 % ] of 189 patients ) , nausea ( 130 [ 69 % ] ) , vomiting ( 125 [ 66 % ] ) , and an increase in alanine aminotransferase ( 114 [ 60 % ] ) in the ceritinib group and nausea ( in 97 [ 55 % ] of 175 patients ) , vomiting ( 63 [ 36 % ] ) , and anaemia ( 62 [ 35 % ] ) in the chemotherapy group . INTERPRETATION First-line ceritinib showed a statistically significant and clinical ly meaningful improvement in progression-free survival versus chemotherapy in patients with advanced ALK-rearranged NSCLC . FUNDING Novartis Pharmaceuticals Corporation",
"BACKGROUND Nivolumab , a fully human IgG4 programmed death 1 ( PD-1 ) immune-checkpoint-inhibitor antibody , disrupts PD-1-mediated signaling and may restore antitumor immunity . METHODS In this r and omized , open-label , international phase 3 study , we assigned patients with nonsquamous non-small-cell lung cancer ( NSCLC ) that had progressed during or after platinum-based doublet chemotherapy to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of 75 mg per square meter of body-surface area every 3 weeks . The primary end point was overall survival . RESULTS Overall survival was longer with nivolumab than with docetaxel . The median overall survival was 12.2 months ( 95 % confidence interval [ CI ] , 9.7 to 15.0 ) among 292 patients in the nivolumab group and 9.4 months ( 95 % CI , 8.1 to 10.7 ) among 290 patients in the docetaxel group ( hazard ratio for death , 0.73 ; 96 % CI , 0.59 to 0.89 ; P=0.002 ) . At 1 year , the overall survival rate was 51 % ( 95 % CI , 45 to 56 ) with nivolumab versus 39 % ( 95 % CI , 33 to 45 ) with docetaxel . With additional follow-up , the overall survival rate at 18 months was 39 % ( 95 % CI , 34 to 45 ) with nivolumab versus 23 % ( 95 % CI , 19 to 28 ) with docetaxel . The response rate was 19 % with nivolumab versus 12 % with docetaxel ( P=0.02 ) . Although progression-free survival did not favor nivolumab over docetaxel ( median , 2.3 months and 4.2 months , respectively ) , the rate of progression-free survival at 1 year was higher with nivolumab than with docetaxel ( 19 % and 8 % , respectively ) . Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression ( ≥1 % , ≥5 % , and ≥10 % ) of the PD-1 lig and . Treatment-related adverse events of grade 3 or 4 were reported in 10 % of the patients in the nivolumab group , as compared with 54 % of those in the docetaxel group . CONCLUSIONS Among patients with advanced nonsquamous NSCLC that had progressed during or after platinum-based chemotherapy , overall survival was longer with nivolumab than with docetaxel . ( Funded by Bristol-Myers Squibb ; CheckMate 057 Clinical Trials.gov number , NCT01673867 . )",
"BACKGROUND Ramucirumab is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGFR-2 . We aim ed to assess efficacy and safety of treatment with docetaxel plus ramucirumab or placebo as second-line treatment for patients with stage IV non-small-cell-lung cancer ( NSCLC ) after platinum-based therapy . METHODS In this multicentre , double-blind , r and omised phase 3 trial ( REVEL ) , we enrolled patients with squamous or non-squamous NSCLC who had progressed during or after a first-line platinum-based chemotherapy regimen . Patients were r and omly allocated ( 1:1 ) with a central ised , interactive voice-response system ( stratified by sex , region , performance status , and previous maintenance therapy [ yes vs no ] ) to receive docetaxel 75 mg/m(2 ) and either ramucirumab ( 10 mg/kg ) or placebo on day 1 of a 21 day cycle until disease progression , unacceptable toxicity , withdrawal , or death . The primary endpoint was overall survival in all patients allocated to treatment . We assessed adverse events according to treatment received . This study is registered with Clinical Trials.gov , number NCT01168973 . FINDINGS Between Dec 3 , 2010 , and Jan 24 , 2013 , we screened 1825 patients , of whom 1253 patients were r and omly allocated to treatment . Median overall survival was 10·5 months ( IQR 5·1 - 21·2 ) for 628 patients allocated ramucirumab plus docetaxel and 9·1 months ( 4·2 - 18·0 ) for 625 patients who received placebo plus docetaxel ( hazard ratio 0·86 , 95 % CI 0·75 - 0·98 ; p=0·023 ) . Median progression-free survival was 4·5 months ( IQR 2·3 - 8·3 ) for the ramucirumab group compared with 3·0 months ( 1·4 - 6·9 ) for the control group ( 0·76 , 0·68 - 0·86 ; p treatment-emergent adverse events in 613 ( 98 % ) of 627 patients in the ramucirumab safety population and 594 ( 95 % ) of 618 patients in the control safety population . The most common grade 3 or worse adverse events were neutropenia ( 306 patients [ 49 % ] in the ramucirumab group vs 246 [ 40 % ] in the control group ) , febrile neutropenia ( 100 [ 16 % ] vs 62 [ 10 % ] ) , fatigue ( 88 [ 14 % ] vs 65 [ 10 % ] ) , leucopenia ( 86 [ 14 % ] vs 77 [ 12 % ] ) , and hypertension ( 35 [ 6 % ] vs 13 [ 2 % ] ) . The numbers of deaths from adverse events ( 31 [ 5 % ] vs 35 [ 6 % ] ) and grade 3 or worse pulmonary haemorrhage ( eight [ 1 % ] vs eight [ 1 % ] ) did not differ between groups . Toxicities were manageable with appropriate dose reductions and supportive care . INTERPRETATION Ramucirumab plus docetaxel improves survival as second-line treatment of patients with stage IV NSCLC . FUNDING Eli Lilly",
"BACKGROUND Patients with advanced squamous-cell non-small-cell lung cancer ( NSCLC ) who have disease progression during or after first-line chemotherapy have limited treatment options . This r and omized , open-label , international , phase 3 study evaluated the efficacy and safety of nivolumab , a fully human IgG4 programmed death 1 ( PD-1 ) immune-checkpoint-inhibitor antibody , as compared with docetaxel in this patient population . METHODS We r and omly assigned 272 patients to receive nivolumab , at a dose of 3 mg per kilogram of body weight every 2 weeks , or docetaxel , at a dose of 75 mg per square meter of body-surface area every 3 weeks . The primary end point was overall survival . RESULTS The median overall survival was 9.2 months ( 95 % confidence interval [ CI ] , 7.3 to 13.3 ) with nivolumab versus 6.0 months ( 95 % CI , 5.1 to 7.3 ) with docetaxel . The risk of death was 41 % lower with nivolumab than with docetaxel ( hazard ratio , 0.59 ; 95 % CI , 0.44 to 0.79 ; P overall survival rate was 42 % ( 95 % CI , 34 to 50 ) with nivolumab versus 24 % ( 95 % CI , 17 to 31 ) with docetaxel . The response rate was 20 % with nivolumab versus 9 % with docetaxel ( P=0.008 ) . The median progression-free survival was 3.5 months with nivolumab versus 2.8 months with docetaxel ( hazard ratio for death or disease progression , 0.62 ; 95 % CI , 0.47 to 0.81 ; P expression of the PD-1 lig and ( PD-L1 ) was neither prognostic nor predictive of benefit . Treatment-related adverse events of grade 3 or 4 were reported in 7 % of the patients in the nivolumab group as compared with 55 % of those in the docetaxel group . CONCLUSIONS Among patients with advanced , previously treated squamous-cell NSCLC , overall survival , response rate , and progression-free survival were significantly better with nivolumab than with docetaxel , regardless of PD-L1 expression level . ( Funded by Bristol-Myers Squibb ; CheckMate 017 Clinical Trials.gov number , NCT01642004 . )",
"Introduction : This study compared survival without toxicity in patients with advanced , nonsquamous non-small cell lung cancer who were treated with first-line pemetrexed/carboplatin or docetaxel/carboplatin . Methods : This multicenter , open-label , parallel-group , phase 3 trial comprised patients r and omized ( 1:1 ) to pemetrexed/carboplatin ( n = 128 ) or docetaxel/carboplatin ( n = 132 ) . Patients received treatment on day 1 of each 21-day cycle ( maximum of six cycles ) . Treatment included carboplatin ( area under the curve = 5 mg/ml × min ) and pemetrexed ( 500 mg/m2 ) or docetaxel ( 75 mg/m2 ) . The primary outcome measure , survival without treatment-emergent grade 3/4 toxicity , was defined as the time from r and omization to the first treatment-emergent grade 3/4 adverse event or death and was analyzed using a log-rank test . The analysis population included 106 patients in the pemetrexed/carboplatin ( Pem/Carb ) group and 105 patients in the docetaxel/carboplatin ( Doc/Carb ) group . Results : Survival without treatment-emergent grade 3/4 toxicity was significantly longer in the Pem/Carb versus the Doc/Carb group ( log-rank p 0.001 ; median survival without treatment-emergent grade 3/4 toxicity : 3.2 versus 0.7 months ; adjusted hazard ratio = 0.45 [ 95 % confidence interval : 0.34–0.61 ] ) . Overall survival was similar in the Pem/Carb versus the Doc/Carb group ( log-rank p = 0.934 ; median survival : 14.9 versus 14.7 months ; adjusted hazard ratio = 0.93 [ 95 % confidence interval : 0.66–1.32 ] ) . Compared with the Doc/Carb group , fewer patients in the Pem/Carb group experienced grade 3/4 drug-related , treatment-emergent neutropenia , leukopenia , or febrile neutropenia , and more patients experienced anemia and thrombocytopenia . There were three study drug-related deaths during treatment in each group . Conclusions : The favorable benefit-to-risk profile of pemetrexed/carboplatin suggests that pemetrexed/carboplatin is an appropriate first-line treatment option for chemonaïve patients with advanced , nonsquamous non-small cell lung cancer",
"BACKGROUND Outcomes are poor for patients with previously treated , advanced or metastatic non-small-cell lung cancer ( NSCLC ) . The anti-programmed death lig and 1 ( PD-L1 ) antibody atezolizumab is clinical ly active against cancer , including NSCLC , especially cancers expressing PD-L1 on tumour cells , tumour-infiltrating immune cells , or both . We assessed efficacy and safety of atezolizumab versus docetaxel in previously treated NSCLC , analysed by PD-L1 expression levels on tumour cells and tumour-infiltrating immune cells and in the intention-to-treat population . METHODS In this open-label , phase 2 r and omised controlled trial , patients with NSCLC who progressed on post-platinum chemotherapy were recruited in 61 academic medical centres and community oncology practice s across 13 countries in Europe and North America . Key inclusion criteria were Eastern Cooperative Oncology Group performance status 0 or 1 , measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 ( RECIST v1.1 ) , and adequate haematological and end-organ function . Patients were stratified by PD-L1 tumour-infiltrating immune cell status , histology , and previous lines of therapy , and r and omly assigned ( 1:1 ) by permuted block r and omisation ( with a block size of four ) using an interactive voice or web system to receive intravenous atezolizumab 1200 mg or docetaxel 75 mg/m(2 ) once every 3 weeks . Baseline PD-L1 expression was scored by immunohistochemistry in tumour cells ( as percentage of PD-L1-expressing tumour cells TC3≥50 % , TC2≥5 % and overall survival in the intention-to-treat population and PD-L1 subgroups at 173 deaths . Biomarkers were assessed in an exploratory analysis . We assessed safety in all patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT01903993 . FINDINGS Patients were enrolled between Aug 5 , 2013 , and March 31 , 2014 . 144 patients were r and omly allocated to the atezolizumab group , and 143 to the docetaxel group . 142 patients received at least one dose of atezolizumab and 135 received docetaxel . Overall survival in the intention-to-treat population was 12·6 months ( 95 % CI 9·7 - 16·4 ) for atezolizumab versus 9·7 months ( 8·6 - 12·0 ) for docetaxel ( hazard ratio [ HR ] 0·73 [ 95 % CI 0·53 - 0·99 ] ; p=0·04 ) . Increasing improvement in overall survival was associated with increasing PD-L1 expression ( TC3 or IC3 HR 0·49 [ 0·22 - 1·07 ; p=0·068 ] , TC2/3 or IC2/3 HR 0·54 [ 0·33 - 0·89 ; p=0·014 ] , TC1/2/3 or IC1/2/3 HR 0·59 [ 0·40 - 0·85 ; p=0·005 ] , TC0 and IC0 HR 1·04 [ 0·62 - 1·75 ; p=0·871 ] ) . In our exploratory analysis , patients with pre-existing immunity , defined by high T-effector-interferon-γ-associated gene expression , had improved overall survival with atezolizumab . 11 ( 8 % ) patients in the atezolizumab group discontinued because of adverse events versus 30 ( 22 % ) patients in the docetaxel group . 16 ( 11 % ) patients in the atezolizumab group versus 52 ( 39 % ) patients in the docetaxel group had treatment-related grade 3 - 4 adverse events , and one ( the atezolizumab group versus three ( 2 % ) patients in the docetaxel group died from a treatment-related adverse event . INTERPRETATION Atezolizumab significantly improved survival compared with docetaxel in patients with previously treated NSCLC . Improvement correlated with PD-L1 immunohistochemistry expression on tumour cells and tumour-infiltrating immune cells , suggesting that PD-L1 expression is predictive for atezolizumab benefit . Atezolizumab was well tolerated , with a safety profile distinct from chemotherapy . FUNDING F Hoffmann-La Roche/Genentech",
"PURPOSE Crizotinib confers improved progression-free survival compared with chemotherapy in anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer ( NSCLC ) , but progression invariably occurs . We investigated the efficacy and safety of alectinib , a potent and selective ALK inhibitor with excellent CNS penetration , in patients with crizotinib-refractory ALK-positive NSCLC . PATIENTS AND METHODS Alectinib 600 mg was administered orally twice daily . The primary end point was objective response rate ( ORR ) by central independent review committee ( IRC ) . RESULTS Of the 138 patients treated , 84 patients ( 61 % ) had CNS metastases at baseline , and 122 were response evaluable ( RE ) by IRC . ORR by IRC was 50 % ( 95 % CI , 41 % to 59 % ) , and the median duration of response ( DOR ) was 11.2 months ( 95 % CI , 9.6 months to not reached ) . In 96 patients ( 79 % ) previously treated with chemotherapy , the ORR was 45 % ( 95 % CI , 35 % to 55 % ) . Median IRC-assessed progression-free survival for all 138 patients was 8.9 months ( 95 % CI , 5.6 to 11.3 months ) . CNS disease control rate was 83 % ( 95 % CI , 74 % to 91 % ) , and the median CNS DOR was 10.3 months ( 95 % CI , 7.6 to 11.2 months ) . CNS ORR in 35 patients with baseline measurable CNS lesions was 57 % ( 95 % CI , 39 % to 74 % ) . Of the 23 patients with baseline CNS metastases ( measurable or nonmeasurable ) and no prior radiation , 10 ( 43 % ) had a complete CNS response . At 12 months , the cumulative CNS progression rate ( 24.8 % ) was lower than the cumulative non-CNS progression rate ( 33.2 % ) for all patients . Common adverse events were constipation ( 33 % ) , fatigue ( 26 % ) , and peripheral edema ( 25 % ) ; most were grade 1 to 2 . CONCLUSION Alectinib is highly active and well tolerated in patients with advanced , crizotinib-refractory ALK-positive NSCLC , including those with CNS metastases",
"PURPOSE Despite recent improvements in supportive care , treatment-related death ( TRD ) remains a serious problem for lung cancer patients undergoing systemic chemotherapy . However , few studies have formally assessed possible changes in the TRD rate over the past two decades . PATIENTS AND METHODS We search ed phase III trials to address the role of systemic treatment of advanced non-small-cell lung cancer ( NSCLC ) . Time trend was assessed using linear regression analysis . RESULTS The overall incidence of TRD was calculated from 119 trials including 263 chemotherapy arms ( 46 477 patients ) , with information about the causes of deaths available for 197 arms ( 75 % , 30 147 patients ) . Cisplatin-based regimens were the most frequently investigated . The crude TRD rate in the overall cohort of 119 trials was 1.26 % and has been notably consistent over the investigated time ( P = 0.762 ) . The most common cause of death was febrile neutropenia , with no significant change in its incidence over the years ( P = 0.139 ) . In contrast , deaths due to renal toxicity decreased significantly ( P = 0.042 ) , whereas deaths due to pulmonary disorder increased significantly ( P = 0.007 ) . Among the pharmacological agents investigated , docetaxel ( Taxotere ) and epidermal growth factor receptor-tyrosine kinase inhibitors ( EGFR-TKIs ) were associated with relatively high rates of deaths from pulmonary disorders , but EGFR-TKIs were not associated with death from any other cause . CONCLUSIONS Despite of potential confounders in our results , the overall TRD rate has remained low , but not negligible , in phase III trials for advanced NSCLC , over the past two decades . Notably , the incidence and pattern of TRD stratified by cause have changed considerably",
"OBJECTIVE The phase III IUNO trial assessed the benefit of maintenance erlotinib versus erlotinib at progression in advanced/metastatic non-small-cell lung cancer ( NSCLC ) that had not progressed following four cycles of platinum-based chemotherapy . MATERIAL S AND METHODS Patients had stage IIIB/IV NSCLC , no known epidermal growth factor receptor (EGFR)-activating mutation , and objective response or disease stabilization after platinum-based induction chemotherapy . Central EGFR-mutation testing was undertaken on tumors from patients with unknown or wild-type EGFR status following local testing . Patients were r and omized to receive blinded maintenance erlotinib 150mg/day ( ' early erlotinib ' ) or placebo . Those who progressed on placebo received open-label erlotinib ( ' late erlotinib ' ) ; patients who progressed on erlotinib received approved second-line chemotherapy or best supportive care . Primary endpoint : overall survival ( OS ) . RESULTS 643 patients were r and omized to receive maintenance erlotinib ( n=322 ) or placebo ( n=321 ) . As of March 23 , 2015 , 242 ( 75.2 % ) OS events had occurred with ' early erlotinib ' versus 235 ( 73.2 % ) with ' late erlotinib ' . Median OS was 9.7 and 9.5 months with ' early erlotinib ' and ' late erlotinib ' , respectively ( HR , 1.02 , 95 % CI : 0.85 - 1.22 ; log-rank p=0.82 ) . No progression-free survival , objective response rate , or disease control rate benefit was observed with maintenance erlotinib . 410 patients entered the second-line phase of the study : 160 patients ( 50 % ) from the maintenance erlotinib arm and 250 patients ( 78 % ) from the maintenance placebo arm . The pattern of adverse events ( AEs ) was consistent with previous trials ; 11 patients who received blinded erlotinib and 3 who received placebo died during the blinded maintenance phase due to nontreatment-related AEs . CONCLUSIONS OS with maintenance erlotinib was not superior to second-line treatment in patients whose tumor did not harbor an EGFR-activating mutation . Safety results were consistent with the established safety profile of erlotinib . Thus , maintenance treatment with erlotinib in patients with advanced/metastatic NSCLC without EGFR-activating mutations is considered unfavorable",
"PURPOSE To confirm the promising phase II results of docetaxel monotherapy , this phase III trial was conducted of chemotherapy for patients with advanced non-small-cell lung cancer ( NSCLC ) who had previously failed platinum-containing chemotherapy . PATIENTS AND METHODS A total of 373 patients were r and omized to receive either docetaxel 100 mg/m(2 ) ( D100 ) or 75 mg/m(2 ) ( D75 ) versus a control regimen of vinorelbine or ifosfamide ( V/I ) . The three treatment groups were well-balanced for key patient characteristics . RESULTS Overall response rates were 10.8 % with D100 and 6.7 % with D75 , each significantly higher than the 0.8 % response with V/I ( P = .001 and P = .036 , respectively ) . Patients who received docetaxel had a longer time to progression ( P = .046 , by log-rank test ) and a greater progression-free survival at 26 weeks ( P = .005 , by chi(2 ) test ) . Although overall survival was not significantly different between the three groups , the 1-year survival was significantly greater with D75 than with the control treatment ( 32 % v 19 % ; P = .025 , by chi(2 ) test ) . Prior exposure to paclitaxel did not decrease the likelihood of response to docetaxel , nor did it impact survival . There was a trend toward greater efficacy in patients whose disease was platinum-resistant rather than platinum-refractory and in patients with performance status of 0 or 1 versus 2 . Toxicity was greatest with D100 , but the D75 arm was well-tolerated . CONCLUSION This first r and omized trial in this setting demonstrates that D75 every 3 weeks can offer clinical ly meaningful benefit to patients with advanced NSCLC whose disease has relapsed or progressed after platinum-based chemotherapy",
"BACKGROUND For non-small cell lung cancer ( NSCLC ) patients with epidermal growth factor receptor ( EGFR ) mutations , first-line gefitinib produced a longer progression-free survival interval than first-line carboplatin plus paclitaxel but did not show any survival advantage in the North East Japan 002 study . This report describes the quality of life ( QoL ) analysis of that study . METHODS Chemotherapy-naïve patients with sensitive EGFR-mutated , advanced NSCLC were r and omized to receive gefitinib or chemotherapy ( carboplatin and paclitaxel ) . Patient QoL was assessed weekly using the Care Notebook , and the primary endpoint of the QoL analysis was time to deterioration from baseline on each of the physical , mental , and life well-being QoL scales . Kaplan-Meier probability curves and log-rank tests were employed to clarify differences . RESULTS QoL data from 148 patients ( 72 in the gefitinib arm and 76 in the carboplatin plus paclitaxel arm ) were analyzed . Time to defined deterioration in physical and life well-being significantly favored gefitinib over chemotherapy ( hazard ratio [ HR ] of time to deterioration , 0.34 ; 95 % confidence interval [ CI ] , 0.23 - 0.50 ; p QoL was maintained much longer in patients treated with gefitinib than in patients treated with st and ard chemotherapy , indicating that gefitinib should be considered as the st and ard first-line therapy for advanced EGFR-mutated NSCLC in spite of no survival advantage",
"BACKGROUND Low-dose erlotinib may be as effective as gefitinib or erlotinib at full dose in non-small cell lung cancer ( NSCLC ) patients with activating mutations of the epidermal growth factor receptor ( EGFR ) gene . METHODS Patients with chemotherapy pretreated NSCLC harbouring EGFR mutations received erlotinib at 50 mg/d until disease progression or unacceptable toxicities . The dose was escalated to 150 mg/d in patients showing no response ( i.e. without major tumour shrinkage according to Response Evaluation Criteria in Solid Tumours ( RECIST ) ) to the initial dose during the first 4 weeks . The primary end-point was the objective response rate at the dose of 50 mg/d . RESULTS Thirty-four patients from seven institutes were enrolled . The study was closed early when no response was confirmed in 15 patients , excluding the possibility that the primary end-point would be met . The objective response and disease control rates at the dose of 50 mg/d as determined by an independent review committee were 54.5 % and 84.8 % , respectively . Four additional patients achieved partial response with increased 150 mg/d dose . Progression-free survival and median survival times during the entire period of the study were 9.5 and 28.5 months , respectively . Treatment-related toxicities were generally mild , the most common being skin disorders and diarrhoea . Only one case experienced grade 3 toxicity , which was transient increase of hepatic enzymes . CONCLUSION The primary end-point was not met ; low-dose erlotinib is not recommended for fit patients with NSCLC harbouring EGFR mutations . However , it may merit further evaluation for elderly or frail patients",
"PURPOSE The phase III BEYOND trial was undertaken to confirm in a Chinese patient population the efficacy seen with first-line bevacizumab plus platinum doublet chemotherapy in globally conducted studies . PATIENTS AND METHODS Patients age ≥ 18 years with locally advanced , metastatic , or recurrent advanced nonsquamous non-small-cell lung cancer ( NSCLC ) were r and omly assigned to receive carboplatin ( area under the curve , 6 ) intravenously and paclitaxel ( 175 mg/m(2 ) ) intravenously ( CP ) on day 1 of each 3-week cycle , for ≤ six cycles , plus placebo ( Pl+CP ) or bevacizumab ( B+CP ) 15 mg/kg intravenously , on day 1 of each cycle , until progression , unacceptable toxicity , or death . The primary end point was progression-free survival ( PFS ) ; secondary end points were objective response rate , overall survival , exploratory biomarkers , safety . RESULTS A total of 276 patients were r and omly assigned , 138 to each arm . PFS was prolonged with B+CP versus Pl+CP ( median , 9.2 v 6.5 months , respectively ; hazard ratio [ HR ] , 0.40 ; 95 % CI , 0.29 to 0.54 ; P rate was improved with B+CP compared with Pl+CP ( 54 % v 26 % , respectively ) . Overall survival was also prolonged with B+CP compared with Pl+CP ( median , 24.3 v 17.7 months , respectively ; HR , 0.68 ; 95 % CI , 0.50 to 0.93 ; P = .0154 ) . Median PFS was 12.4 months with B+CP and 7.9 months with Pl+CP ( HR , 0.27 ; 95 % CI , 0.12 to 0.63 ) in EGFR mutation-positive tumors and 8.3 and 5.6 months , respectively ( HR , 0.33 ; 95 % CI , 0.21 to 0.53 ) , in wild-type tumors . Safety was similar to previous studies of B+CP in NSCLC ; no new safety signals were observed . CONCLUSION The addition to bevacizumab to carboplatin/paclitaxel was well tolerated and result ed in a clinical ly meaningful treatment benefit in Chinese patients with advanced nonsquamous NSCLC",
"PURPOSE PointBreak ( A Study of Pemetrexed , Carboplatin and Bevacizumab in Patients With Nonsquamous Non-Small Cell Lung Cancer ) compared the efficacy and safety of pemetrexed ( Pem ) plus carboplatin ( C ) plus bevacizumab ( Bev ) followed by pemetrexed plus bevacizumab ( PemCBev ) with paclitaxel ( Pac ) plus carboplatin ( C ) plus bevacizumab ( Bev ) followed by bevacizumab ( PacCBev ) in patients with advanced nonsquamous non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Patients with previously untreated stage IIIB or IV nonsquamous NSCLC and Eastern Cooperative Oncology Group performance status of 0 to 1 were r and omly assigned to receive pemetrexed 500 mg/m(2 ) or paclitaxel 200 mg/m(2 ) combined with carboplatin area under the curve 6 and bevacizumab 15 mg/kg every 3 weeks for up to four cycles . Eligible patients received maintenance until disease progression : pemetrexed plus bevacizumab ( for the PemCBev group ) or bevacizumab ( for the PacCBev group ) . The primary end point of this superiority study was overall survival ( OS ) . RESULTS Patients were r and omly assigned to PemCBev ( n = 472 ) or PacCBev ( n = 467 ) . For PemCBev versus PacCBev , OS hazard ratio ( HR ) was 1.00 ( median OS , 12.6 v 13.4 months ; P = .949 ) ; progression-free survival ( PFS ) HR was 0.83 ( median PFS , 6.0 v 5.6 months ; P = .012 ) ; overall response rate was 34.1 % versus 33.0 % ; and disease control rate was 65.9 % versus 69.8 % . Significantly more study drug-related grade 3 or 4 anemia ( 14.5 % v 2.7 % ) , thrombocytopenia ( 23.3 % v 5.6 % ) , and fatigue ( 10.9 % v 5.0 % ) occurred with PemCBev ; significantly more grade 3 or 4 neutropenia ( 40.6 % v 25.8 % ) , febrile neutropenia ( 4.1 % v 1.4 % ) , sensory neuropathy ( 4.1 % v 0 % ) , and alopecia ( grade 1 or 2 ; 36.8 % v 6.6 % ) occurred with PacCBev . CONCLUSION OS did not improve with the PemCBev regimen compared with the PacCBev regimen , although PFS was significantly improved with PemCBev . Toxicity profiles differed ; both regimens demonstrated tolerability",
"Oral S-1 plus cisplatin is noninferior to docetaxel plus cisplatin in terms of overall survival with favorable QoL data . S-1 plus cisplatin is an option for the first-line treatment of patients with advanced NSCLC",
"BACKGROUND With use of EGFR tyrosine-kinase inhibitor monotherapy for patients with activating EGFR mutation-positive non-small-cell lung cancer ( NSCLC ) , median progression-free survival has been extended to about 12 months . Nevertheless , new strategies are needed to further extend progression-free survival and overall survival with acceptable toxicity and tolerability for this population . We aim ed to compare the efficacy and safety of the combination of erlotinib and bevacizumab compared with erlotinib alone in patients with non-squamous NSCLC with activating EGFR mutation-positive disease . METHODS In this open-label , r and omised , multicentre , phase 2 study , patients from 30 centres across Japan with stage IIIB/IV or recurrent non-squamous NSCLC with activating EGFR mutations , Eastern Cooperative Oncology Group performance status 0 or 1 , and no previous chemotherapy for advanced disease received erlotinib 150 mg/day plus bevacizumab 15 mg/kg every 3 weeks or erlotinib 150 mg/day monotherapy as a first-line therapy until disease progression or unacceptable toxicity . The primary endpoint was progression-free survival , as determined by an independent review committee . R and omisation was done with a dynamic allocation method , and the analysis used a modified intention-to-treat approach , including all patients who received at least one dose of study treatment and had tumour assessment at least once after r and omisation . This study is registered with the Japan Pharmaceutical Information Center , number JapicCTI-111390 . FINDINGS Between Feb 21 , 2011 , and March 5 , 2012 , 154 patients were enrolled . 77 were r and omly assigned to receive erlotinib and bevacizumab and 77 to erlotinib alone , of whom 75 patients in the erlotinib plus bevacizumab group and 77 in the erlotinib alone group were included in the efficacy analyses . Median progression-free survival was 16·0 months ( 95 % CI 13·9 - 18·1 ) with erlotinib plus bevacizumab and 9·7 months ( 5·7 - 11·1 ) with erlotinib alone ( hazard ratio 0·54 , 95 % CI 0·36 - 0·79 ; log-rank test p=0·0015 ) . The most common grade 3 or worse adverse events were rash ( 19 [ 25 % ] patients in the erlotinib plus bevacizumab group vs 15 [ 19 % ] patients in the erlotinib alone group ) , hypertension ( 45 [ 60 % ] vs eight [ 10 % ] ) , and proteinuria ( six [ 8 % ] vs none ) . Serious adverse events occurred at a similar frequency in both groups ( 18 [ 24 % ] patients in the erlotinib plus bevacizumab group and 19 [ 25 % ] patients in the erlotinib alone group ) . INTERPRETATION Erlotinib plus bevacizumab combination could be a new first-line regimen in EGFR mutation-positive NSCLC . Further investigation of the regimen is warranted . FUNDING Chugai Pharmaceutical Co",
"PURPOSE To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non-small-cell lung cancer who had previously been treated with platinum-based chemotherapy . Secondary end points included assessment of response ( docetaxel arm only ) , toxicity , and quality of life . PATIENTS AND METHODS Patients with performance statuses of 0 to 2 and stage IIIB/IV non-small-cell lung cancer with either measurable or evaluable lesions were eligible for entry onto the study if they had undergone one or more platinum-based chemotherapy regimens and if they had adequate hematology and biochemistry parameters . They were excluded if they had symptomatic brain metastases or if they had previously been treated with paclitaxel . Patients were stratified by performance status and best response to cisplatin chemotherapy and were then r and omized to treatment with docetaxel 100 mg/m(2 ) ( 49 patients ) or 75 mg/m(2 ) ( 55 patients ) or best supportive care . Patients in both arms were assessed every 3 weeks . RESULTS One hundred four patients ( 103 of whom were eligible for entry onto the study ) were well balanced for prognostic factors . Of 84 patients with measurable lesions , six ( 7 . 1 % ) achieved partial responses ( three patients at each dose level ) . Time to progression was longer for docetaxel patients than for best supportive care patients ( 10.6 v 6.7 weeks , respectively ; P median survival ( 7.0 v 4.6 months ; log-rank test , P = .047 ) . The difference was more significant for docetaxel 75 mg/m(2 ) patients , compared with corresponding best supportive care patients ( 7.5 v 4.6 months ; log-rank test , P = .010 ; 1-year survival , 37 % v 11 % ; chi(2 ) test , P = .003 ) . Febrile neutropenia occurred in 11 patients treated with docetaxel 100 mg/m(2 ) , three of whom died , and in one patient treated with docetaxel 75 mg/m(2 ) . Grade 3 or 4 nonhematologic toxicity , with the exception of diarrhea , occurred at a similar rate in both the docetaxel and best supportive care groups . CONCLUSION Treatment with docetaxel is associated with significant prolongation of survival , and at a dose of 75 mg/m(2 ) , the benefits of docetaxel therapy outweigh the risks",
"BACKGROUND Pembrolizumab is a humanized monoclonal antibody against programmed death 1 ( PD-1 ) that has antitumor activity in advanced non-small-cell lung cancer ( NSCLC ) , with increased activity in tumors that express programmed death lig and 1 ( PD-L1 ) . METHODS In this open-label , phase 3 trial , we r and omly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50 % of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab ( at a fixed dose of 200 mg every 3 weeks ) or the investigator 's choice of platinum-based chemotherapy . Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression . The primary end point , progression-free survival , was assessed by means of blinded , independent , central radiologic review . Secondary end points were overall survival , objective response rate , and safety . RESULTS Median progression-free survival was 10.3 months ( 95 % confidence interval [ CI ] , 6.7 to not reached ) in the pembrolizumab group versus 6.0 months ( 95 % CI , 4.2 to 6.2 ) in the chemotherapy group ( hazard ratio for disease progression or death , 0.50 ; 95 % CI , 0.37 to 0.68 ; P estimated rate of overall survival at 6 months was 80.2 % in the pembrolizumab group versus 72.4 % in the chemotherapy group ( hazard ratio for death , 0.60 ; 95 % CI , 0.41 to 0.89 ; P=0.005 ) . The response rate was higher in the pembrolizumab group than in the chemotherapy group ( 44.8 % vs. 27.8 % ) , the median duration of response was longer ( not reached [ range , 1.9 + to 14.5 + months ] vs. 6.3 months [ range , 2.1 + to 12.6 + ] ) , and treatment-related adverse events of any grade were less frequent ( occurring in 73.4 % vs. 90.0 % of patients ) , as were grade 3 , 4 , or 5 treatment-related adverse events ( 26.6 % vs. 53.3 % ) . CONCLUSIONS In patients with advanced NSCLC and PD-L1 expression on at least 50 % of tumor cells , pembrolizumab was associated with significantly longer progression-free and overall survival and with fewer adverse events than was platinum-based chemotherapy . ( Funded by Merck ; KEYNOTE-024 Clinical Trials.gov number , NCT02142738 . )",
"BACKGROUND NEJ002 study , comparing gefitinib with carboplatin ( CBDCA ) and paclitaxel ( PTX ; Taxol ) as the first-line treatment for advanced non-small cell lung cancer ( NSCLC ) harboring an epidermal growth factor receptor ( EGFR ) mutation , previously reported superiority of gefitinib over CBDCA/PTX on progression-free survival ( PFS ) . Subsequent analysis was carried out mainly regarding overall survival ( OS ) . MATERIAL S AND METHODS For all 228 patients in NEJ002 , survival data were up date d in December , 2010 . Detailed information regarding subsequent chemotherapy after the protocol treatment was also assessed retrospectively and the impact of some key drugs on OS was evaluated . RESULTS The median survival time ( MST ) was 27.7 months for the gefitinib group , and was 26.6 months for the CBDCA/PTX group ( HR , 0.887 ; P=0.483 ) . The OS of patients who received platinum throughout their treatment ( n=186 ) was not statistically different from that of patients who never received platinum ( n=40 ) . The MST of patients treated with gefitinib , platinum , and pemetrexed ( PEM ) or docetaxel ( DOC , Taxotere ; n=76 ) was around 3 years . CONCLUSIONS No significant difference in OS was observed between gefitinib and CBDCA/PTX in the NEJ002 study , probably due to a high crossover use of gefitinib in the CBDCA/PTX group . Considering the many benefits and the risk of missing an opportunity to use the most effective agent for EGFR-mutated NSCLC , the first-line gefitinib is strongly recommended",
"BACKGROUND Platinum-based doublet chemotherapy is recommended to treat advanced non-small-cell lung cancer ( NSCLC ) in fit , non-elderly adults , but monotherapy is recommended for patients older than 70 years . We compared a carboplatin and paclitaxel doublet chemotherapy regimen with monotherapy in elderly patients with advanced NSCLC . METHODS In this multicentre , open-label , phase 3 , r and omised trial we recruited patients aged 70 - 89 years with locally advanced or metastatic NSCLC and WHO performance status scores of 0 - 2 . Patients received either four cycles ( 3 weeks on treatment , 1 week off treatment ) of carboplatin ( on day 1 ) plus paclitaxel ( on days 1 , 8 , and 15 ) or five cycles ( 2 weeks on treatment , 1 week off treatment ) of vinorelbine or gemcitabine monotherapy . R and omisation was done central ly with the minimisation method . The primary endpoint was overall survival , and analysis was done by intention to treat . This trial is registered , number NCT00298415 . FINDINGS 451 patients were enrolled . 226 were r and omly assigned monotherapy and 225 doublet chemotherapy . Median age was 77 years and median follow-up was 30.3 months ( range 8.6 - 45.2 ) . Median overall survival was 10.3 months for doublet chemotherapy and 6.2 months for monotherapy ( hazard ratio 0.64 , 95 % CI 0.52 - 0.78 ; p 1-year survival was 44.5 % ( 95 % CI 37.9 - 50.9 ) and 25.4 % ( 19.9 - 31.3 ) , respectively . Toxic effects were more frequent in the doublet chemotherapy group than in the monotherapy group ( most frequent , decreased neutrophil count ( 108 [ 48.4 % ] vs 28 [ 12.4 % ] ; asthenia 23 [ 10.3 % ] vs 13 [ 5.8 % ] ) . INTERPRETATION Despite increased toxic effects , platinum-based doublet chemotherapy was associated with survival benefits compared with vinorelbine or gemcitabine monotherapy in elderly patients with NSCLC . We feel that the current treatment paradigm for these patients should be reconsidered . FUNDING Intergroupe Francophone de Cancérologie Thoracique , Institut National du Cancer",
"BACKGROUND The efficacy of the ALK inhibitor crizotinib as compared with st and ard chemotherapy as first-line treatment for advanced ALK-positive non-small-cell lung cancer ( NSCLC ) is unknown . METHODS We conducted an open-label , phase 3 trial comparing crizotinib with chemotherapy in 343 patients with advanced ALK-positive nonsquamous NSCLC who had received no previous systemic treatment for advanced disease . Patients were r and omly assigned to receive oral crizotinib at a dose of 250 mg twice daily or to receive intravenous chemotherapy ( pemetrexed , 500 mg per square meter of body-surface area , plus either cisplatin , 75 mg per square meter , or carboplatin , target area under the curve of 5 to 6 mg per milliliter per minute ) every 3 weeks for up to six cycles . Crossover to crizotinib treatment after disease progression was permitted for patients receiving chemotherapy . The primary end point was progression-free survival as assessed by independent radiologic review . RESULTS Progression-free survival was significantly longer with crizotinib than with chemotherapy ( median , 10.9 months vs. 7.0 months ; hazard ratio for progression or death with crizotinib , 0.45 ; 95 % confidence interval [ CI ] , 0.35 to 0.60 ; P Objective response rates were 74 % and 45 % , respectively ( P Median overall survival was not reached in either group ( hazard ratio for death with crizotinib , 0.82 ; 95 % CI , 0.54 to 1.26 ; P=0.36 ) ; the probability of 1-year survival was 84 % with crizotinib and 79 % with chemotherapy . The most common adverse events with crizotinib were vision disorders , diarrhea , nausea , and edema , and the most common events with chemotherapy were nausea , fatigue , vomiting , and decreased appetite . As compared with chemotherapy , crizotinib was associated with greater reduction in lung cancer symptoms and greater improvement in quality of life . CONCLUSIONS Crizotinib was superior to st and ard first-line pemetrexed-plus-platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC . ( Funded by Pfizer ; PROFILE 1014 Clinical Trials.gov number , NCT01154140 . )",
"BACKGROUND Activating mutations in EGFR are important markers of response to tyrosine kinase inhibitor ( TKI ) therapy in non-small-cell lung cancer ( NSCLC ) . The OPTIMAL study compared efficacy and tolerability of the TKI erlotinib versus st and ard chemotherapy in the first-line treatment of patients with advanced EGFR mutation-positive NSCLC . METHODS We undertook an open-label , r and omised , phase 3 trial at 22 centres in China . Patients older than 18 years with histologically confirmed stage IIIB or IV NSCLC and a confirmed activating mutation of EGFR ( exon 19 deletion or exon 21 L858R point mutation ) received either oral erlotinib ( 150 mg/day ) until disease progression or unacceptable toxic effects , or up to four cycles of gemcitabine plus carboplatin . Patients were r and omly assigned ( 1:1 ) with a minimisation procedure and were stratified according to EGFR mutation type , histological subtype ( adenocarcinoma vs non-adenocarcinoma ) , and smoking status . The primary outcome was progression-free survival , analysed in patients with confirmed disease who received at least one dose of study treatment . The trial is registered at Clinical Trials.gov , number NCT00874419 , and has completed enrolment ; patients are still in follow-up . FINDINGS 83 patients were r and omly assigned to receive erlotinib and 82 to receive gemcitabine plus carboplatin ; 82 in the erlotinib group and 72 in the chemotherapy group were included in analysis of the primary endpoint . Median progression-free survival was significantly longer in erlotinib-treated patients than in those on chemotherapy ( 13.1 [ 95 % CI 10.58 - 16.53 ] vs 4.6 [ 4.21 - 5.42 ] months ; hazard ratio 0.16 , 95 % CI 0.10 - 0.26 ; p grade 3 or 4 toxic effects than was erlotinib ( including neutropenia in 30 [ 42 % ] of 72 patients and thrombocytopenia in 29 [ 40 % ] patients on chemotherapy vs no patients with either event on erlotinib ) ; the most common grade 3 or 4 toxic effects with erlotinib were increased alanine aminotransferase concentrations ( three [ 4 % ] of 83 patients ) and skin rash ( two [ 2 % ] patients ) . Chemotherapy was also associated with increased treatment-related serious adverse events ( ten [ 14 % ] of 72 patients [ decreased platelet count , n=8 ; decreased neutrophil count , n=1 ; hepatic dysfunction , n=1 ] vs two [ 2 % ] of 83 patients [ both hepatic dysfunction ] ) . INTERPRETATION Compared with st and ard chemotherapy , erlotinib conferred a significant progression-free survival benefit in patients with advanced EGFR mutation-positive NSCLC and was associated with more favourable tolerability . These findings suggest that erlotinib is important for first-line treatment of patients with advanced EGFR mutation-positive NSCLC . FUNDING F Hoffmann-La Roche Ltd ( China ) ; Science and Technology Commission of Shanghai Municipality",
"Background Alectinib , a highly selective inhibitor of anaplastic lymphoma kinase ( ALK ) , has shown systemic and central nervous system ( CNS ) efficacy in the treatment of ALK‐positive non – small‐cell lung cancer ( NSCLC ) . We investigated alectinib as compared with crizotinib in patients with previously untreated , advanced ALK‐positive NSCLC , including those with asymptomatic CNS disease . Methods In a r and omized , open‐label , phase 3 trial , we r and omly assigned 303 patients with previously untreated , advanced ALK‐positive NSCLC to receive either alectinib ( 600 mg twice daily ) or crizotinib ( 250 mg twice daily ) . The primary end point was investigator‐assessed progression‐free survival . Secondary end points were independent review committee – assessed progression‐free survival , time to CNS progression , objective response rate , and overall survival . Results During a median follow‐up of 17.6 months ( crizotinib ) and 18.6 months ( alectinib ) , an event of disease progression or death occurred in 62 of 152 patients ( 41 % ) in the alectinib group and 102 of 151 patients ( 68 % ) in the crizotinib group . The rate of investigator‐assessed progression‐free survival was significantly higher with alectinib than with crizotinib ( 12‐month event‐free survival rate , 68.4 % [ 95 % confidence interval ( CI ) , 61.0 to 75.9 ] with alectinib vs. 48.7 % [ 95 % CI , 40.4 to 56.9 ] with crizotinib ; hazard ratio for disease progression or death , 0.47 [ 95 % CI , 0.34 to 0.65 ] ; P ) ; the median progression‐free survival with alectinib was not reached . The results for independent review committee – assessed progression‐free survival were consistent with those for the primary end point . A total of 18 patients ( 12 % ) in the alectinib group had an event of CNS progression , as compared with 68 patients ( 45 % ) in the crizotinib group ( cause‐specific hazard ratio , 0.16 ; 95 % CI , 0.10 to 0.28 ; P the alectinib group ( response rate , 82.9 % ; 95 % CI , 76.0 to 88.5 ) and in 114 patients in the crizotinib group ( response rate , 75.5 % ; 95 % CI , 67.8 to 82.1 ) ( P=0.09 ) . Grade 3 to 5 adverse events were less frequent with alectinib ( 41 % vs. 50 % with crizotinib ) . Conclusions As compared with crizotinib , alectinib showed superior efficacy and lower toxicity in primary treatment of ALK‐positive NSCLC . ( Funded by F. Hoffmann – La Roche ; ALEX Clinical Trials.gov number , NCT02075840 .",
"Three hundred patients with symptomatic , locally advanced or metastatic NSCLC not requiring immediate radiotherapy were enrolled into this r and omized multicentre trial comparing gemcitabine + BSC vs BSC alone . Patients allocated gemcitabine received 1000 mg/m2on days 1 , 8 and 15 of a 28-day cycle , for a maximum of six cycles . The main aim of this trial was to compare patient assessment of a predefined subset of commonly reported symptoms ( SS14 ) from the EORTC QLQ-C30 and LC13 scales . The primary end-points were defined as ( 1 ) the percentage change in mean SS14 score between baseline and 2 months and ( 2 ) the proportion of patients with a marked ( ≥ 25 % ) improvement in SS14 score between baseline and 2 months sustained for ≥4 weeks . The secondary objectives were to compare treatments with respect to overall survival , and multidimensional QL parameters . The treatment groups were balanced with regard to age , gender , Karnofsky performance status ( KPS ) and disease stage ( 40 % had metastatic disease ) . The percentage change in mean SS14 score from baseline to 2 months was a 10 % decrease ( i.e. improvement ) for gemcitabine plus BSC and a 1 % increase ( i.e. deterioration ) for BSC alone ( P = 0.113 , two- sample t -test ) . A sustained ( ≥ 4 weeks ) improvement ( ≥25 % ) on SS14 was recorded in a significantly higher proportion of gemcitabine + BSC patients ( 22 % ) than in BSC alone patients ( 9 % ) ( P = 0.0014 , Pearson 's chi-squared test ) . The QLQ-C30 and L13 subscales showed greater improvement in the gemcitabine plus BSC arm ( in 11 domains ) than in the BSC arm ( one symptom item ) . There was greater deterioration in the BSC alone arm ( six domains/items ) than in the gemcitabine + BSC arm ( three QL domains ) . Tumour response occurred in 19 % ( 95 % CI 13–27 ) of gemcitabine patients . There was no difference in overall survival : median 5.7 months ( 95 % CI 4.6–7.6 ) for gemcitabine + BSC patients and 5.9 months ( 95 % CI 5.0–7.9 ) ( log-rank , P = 0.84 ) for BSC patients , and 1-year survival was 25 % for gemcitabine + BSC and 22 % for BSC . Overall , 74 ( 49 % ) gemcitabine + BSC patients and 119 ( 79 % ) BSC patients received palliative radiotherapy . The median time to radiotherapy was 29 weeks for gemcitabine + BSC patients and 3.8 weeks for BSC . Patients treated with gemcitabine + BSC reported better QL and reduced disease-related symptoms compared with those receiving BSC alone . These improvements in patient-assessed QL were significant in magnitude and were sustained . © 2000 Cancer Research",
"Introduction : PRONOUNCE compared the efficacy and safety of pemetrexed+carboplatin followed by pemetrexed ( Pem+Cb ) with paclitaxel+carboplatin+bevacizumab followed by bevacizumab ( Pac+Cb+Bev ) in patients with advanced nonsquamous non – small-cell lung cancer ( NSCLC ) . Methods : Patients ≥18 years of age with stage IV nonsquamous NSCLC ( American Joint Committee on Cancer v7.0 ) , and Eastern Cooperative Oncology Group performance status 0/1 were r and omized ( 1:1 ) to four cycles of induction Pem+Cb ( pemetrexed , 500 mg/m2 , carboplatin , area under the curve = 6 ) followed by Pem maintenance or Pac+Cb+Bev ( paclitaxel , 200 mg/m2 , carboplatin , area under the curve = 6 , and bevacizumab , 15 mg/kg ) followed by Bev maintenance in the absence of progressive disease or discontinuation . The primary objective was progression-free survival ( PFS ) without grade 4 toxicity ( G4PFS ) . Secondary end points were PFS , overall survival ( OS ) , overall response rate ( ORR ) , disease control rate ( DCR ) , and safety . Re source utilization was also assessed . Results : Baseline characteristics of the patients r and omized to Pem+Cb ( N = 182 ) and Pac+Cb+Bev ( N = 179 ) were well balanced between the arms . Median ( months ) G4PFS was 3.91 for Pem+Cb and 2.86 for Pac+Cb+Bev ( hazard ratio = 0.85 , 90 % confidence interval , 0.7–1.04 ; p = 0.176 ) ; PFS , OS , ORR , or DCR did not differ significantly between the arms . Significantly more drug-related grade 3/4 anemia ( 18.7 % versus 5.4 % ) and thrombocytopenia ( 24.0 % versus 9.6 % ) were reported for Pem+Cb . Significantly more grade 3/4 neutropenia ( 48.8 % versus 24.6 % ) , grade 1/2 alopecia ( 28.3 % versus 8.2 % ) , and grade 1/2 sensory neuropathy were reported for Pac+Cb+Bev . Number of hospitalizations and overall length of stay did not differ significantly between the arms . Conclusions : Pem+Cb did not produce significantly better G4PFS compared with Pac+Cb+Bev . Pem+Cb was not superior in PFS , OS , ORR , or DCR compared with Pac+Cb+Bev . Both regimens were well tolerated , although , toxicity profiles differed",
"BACKGROUND To compare the efficacy and toxicity of three platinum-based combination regimens against cisplatin plus irinotecan ( IP ) in patients with untreated advanced non-small-cell lung cancer ( NSCLC ) by a non-inferiority design . PATIENTS AND METHODS A total of 602 patients were r and omly assigned to one of four regimens : cisplatin 80 mg/m(2 ) on day 1 plus irinotecan 60 mg/m(2 ) on days 1 , 8 , 15 every 4 weeks ( IP ) carboplatin AUC 6.0 min x mg/mL ( area under the concentration-time curve ) on day 1 plus paclitaxel 200 mg/m(2 ) on day 1 every 3 weeks ( TC ) ; cisplatin 80 mg/m(2 ) on day 1 plus gemcitabine 1000 mg/m(2 ) on days 1 , 8 every 3 weeks ( GP ) ; and cisplatin 80 mg/m(2 ) on day 1 plus vinorelbine 25 mg/m(2 ) on days 1 , 8 every 3 weeks ( NP ) . RESULTS The response rate , median survival time , and 1-year survival rate were 31.0 % , 13.9 months , 59.2 % , respectively , in IP ; 32.4 % , 12.3 months , 51.0 % in TC ; 30.1 % , 14.0 months , 59.6 % in GP ; and 33.1 % , 11.4 months , 48.3 % in NP . No statistically significant differences were found in response rate or overall survival , but the non-inferiority of none of the experimental regimens could be confirmed . All the four regimens were well tolerated . CONCLUSION The four regimens have similar efficacy and different toxicity profiles , and they can be used to treat advanced NSCLC patients",
"Introduction : Anaplastic lymphoma kinase (ALK)-rearranged non – small-cell lung cancer ( NSCLC ) is sensitive to ALK inhibitors , but resistance develops . This study assessed the maximum-tolerated dose , safety , pharmacokinetics ( PK ) , and antitumor activity of ceritinib , a novel ALK inhibitor ( ALKi ) , in Japanese patients with ALK-rearranged malignancies . Methods : This phase I , multicenter , open-label study ( NCT01634763 ) enrolled adult patients with ALK-rearranged ( by fluorescence in situ hybridization and /or immunohistochemistry ) locally advanced/metastatic malignancy that had progressed despite st and ard therapy . The study comprised two parts : dose escalation and dose expansion . Ceritinib ( single-dose ) was administered orally in the 3-day PK run-in period , then once daily , in 21-day cycles . Adaptive dose escalations were guided by a Bayesian model . Results : Twenty patients ( 80 % with ALKi treatment history [ ALKi-pretreated ] ; 19 NSCLC ; one inflammatory myofibroblastic tumor ) received ceritinib 300 to 750 mg ( 19 during dose escalation , one in dose expansion ) . Two dose-limiting toxicities occurred : grade 3 lipase increase ( 600 mg ) ; grade 3 drug-induced liver injury ( 750 mg ) . The most common adverse events were gastrointestinal ( nausea : 95 % ; diarrhea , vomiting : 75 % ) . Ceritinib PK profile was dose proportional across 300 to 750 mg dosages ; steady state was reached by day 15 . Overall response rate was 55 % ( 11 of 20 patients ) . Among patients with NSCLC , partial response was observed in two of four ALKi-naive patients , five of nine crizotinib-pretreated patients , two of four alectinib-pretreated patients , and one of two crizotinib and alectinib/ASP3026 pretreated patients . The ASP3026-pretreated inflammatory myofibroblastic tumor patient achieved partial response . Conclusions : Ceritinib maximum-tolerated dose was 750 mg once daily in Japanese patients . Antitumor activity was observed irrespective of prior ALKi treatment history . Dose expansion , examining the activity of ceritinib in alectinib-resistant patients , is ongoing",
"Background : Bevacizumab , the anti-vascular endothelial growth factor agent , provides clinical benefit when combined with platinum-based chemotherapy in first-line advanced non-small-cell lung cancer . We report the final overall survival ( OS ) analysis from the phase III AVAiL trial . Patients and methods : Patients ( n = 1043 ) received cisplatin 80 mg/m2 and gemcitabine 1250 mg/m2 for up to six cycles plus bevacizumab 7.5 mg/kg ( n = 345 ) , bevacizumab 15 mg/kg ( n = 351 ) or placebo ( n = 347 ) every 3 weeks until progression . Primary end point was progression-free survival ( PFS ) ; OS was a secondary end point . Results : Significant PFS prolongation with bevacizumab compared with placebo was maintained with longer follow-up { hazard ratio ( HR ) [ 95 % confidence interval ( CI ) ] 0.75 ( 0.64–0.87 ) , P = 0.0003 and 0.85 ( 0.73–1.00 ) , P = 0.0456 } for the 7.5 and 15 mg/kg groups , respectively . Median OS was > 13 months in all treatment groups ; nevertheless , OS was not significantly increased with bevacizumab [ HR ( 95 % CI ) 0.93 ( 0.78–1.11 ) , P = 0.420 and 1.03 ( 0.86–1.23 ) , P = 0.761 ] for the 7.5 and 15 mg/kg groups , respectively , versus placebo . Most patients ( ∼62 % ) received multiple lines of post study treatment . Up date d safety results are consistent with those previously reported . Conclusions : Final analysis of AVAiL confirms the efficacy of bevacizumab when combined with cisplatin – gemcitabine . The PFS benefit did not translate into a significant OS benefit , possibly due to high use of efficacious second-line therapies",
"BACKGROUND Bevacizumab , a monoclonal antibody against vascular endothelial growth factor , has been shown to benefit patients with a variety of cancers . METHODS Between July 2001 and April 2004 , the Eastern Cooperative Oncology Group ( ECOG ) conducted a r and omized study in which 878 patients with recurrent or advanced non-small-cell lung cancer ( stage IIIB or IV ) were assigned to chemotherapy with paclitaxel and carboplatin alone ( 444 ) or paclitaxel and carboplatin plus bevacizumab ( 434 ) . Chemotherapy was administered every 3 weeks for six cycles , and bevacizumab was administered every 3 weeks until disease progression was evident or toxic effects were intolerable . Patients with squamous-cell tumors , brain metastases , clinical ly significant hemoptysis , or inadequate organ function or performance status ( ECOG performance status , > 1 ) were excluded . The primary end point was overall survival . RESULTS The median survival was 12.3 months in the group assigned to chemotherapy plus bevacizumab , as compared with 10.3 months in the chemotherapy-alone group ( hazard ratio for death , 0.79 ; P=0.003 ) . The median progression-free survival in the two groups was 6.2 and 4.5 months , respectively ( hazard ratio for disease progression , 0.66 ; P Rates of clinical ly significant bleeding were 4.4 % and 0.7 % , respectively ( P deaths in the chemotherapy-plus-bevacizumab group , including 5 from pulmonary hemorrhage . CONCLUSIONS The addition of bevacizumab to paclitaxel plus carboplatin in the treatment of selected patients with non-small-cell lung cancer has a significant survival benefit with the risk of increased treatment-related deaths . ( Clinical Trials.gov number , NCT00021060 .",
"BACKGROUND Vinorelbine prolongs survival and improves quality of life in elderly patients with advanced non-small-cell lung cancer ( NSCLC ) . Some studies have also suggested that gemcitabine is well tolerated and effective in such patients . We compared the effectiveness and toxicity of the combination of vinorelbine plus gemcitabine with those of each drug given alone in an open-label , r and omized phase III trial in elderly patients with advanced NSCLC . METHODS Patients aged 70 years and older , enrolled between December 1997 and November 2000 , were r and omly assigned to receive intravenous vinorelbine ( 30 mg/m(2 ) of body surface area ) , gemcitabine ( 1200 mg/m(2 ) ) , or vinorelbine ( 25 mg/m(2 ) ) plus gemcitabine ( 1000 mg/m(2 ) ) . All treatments were delivered on days 1 and 8 every 3 weeks for a maximum of six cycles . The primary endpoint was survival . Survival curves were drawn using the Kaplan-Meier method and analyzed by the Mantel-Haenszel test . Secondary endpoints were quality of life and toxicity . RESULTS Of 698 patients available for intention-to-treat analysis , 233 were assigned to receive vinorelbine , 233 to gemcitabine , and 232 to vinorelbine plus gemcitabine . Compared with each single drug , the combination treatment did not improve survival . The hazard ratio of death for patients receiving the combination treatment was 1.17 ( 95 % confidence interval [ CI ] = 0.95 to 1.44 ) that of patients receiving vinorelbine and 1.06 ( 95 % CI = 0.86 to 1.29 ) that of patients receiving gemcitabine . Although quality of life was similar across the three treatment arms , the combination treatment was more toxic than the two drugs given singly . CONCLUSION The combination of vinorelbine plus gemcitabine is not more effective than single-agent vinorelbine or gemcitabine in the treatment of elderly patients with advanced NSCLC",
"BACKGROUND Non-small-cell lung cancer with sensitive mutations of the epidermal growth factor receptor ( EGFR ) is highly responsive to EGFR tyrosine kinase inhibitors such as gefitinib , but little is known about how its efficacy and safety profile compares with that of st and ard chemotherapy . METHODS We r and omly assigned 230 patients with metastatic , non-small-cell lung cancer and EGFR mutations who had not previously received chemotherapy to receive gefitinib or carboplatin-paclitaxel . The primary end point was progression-free survival ; secondary end points included overall survival , response rate , and toxic effects . RESULTS In the planned interim analysis of data for the first 200 patients , progression-free survival was significantly longer in the gefitinib group than in the st and ard-chemotherapy group ( hazard ratio for death or disease progression with gefitinib , 0.36 ; P gefitinib group had a significantly longer median progression-free survival ( 10.8 months , vs. 5.4 months in the chemotherapy group ; hazard ratio , 0.30 ; 95 % confidence interval , 0.22 to 0.41 ; P response rate ( 73.7 % vs. 30.7 % , P median overall survival was 30.5 months in the gefitinib group and 23.6 months in the chemotherapy group ( P=0.31 ) . The most common adverse events in the gefitinib group were rash ( 71.1 % ) and elevated aminotransferase levels ( 55.3 % ) , and in the chemotherapy group , neutropenia ( 77.0 % ) , anemia ( 64.6 % ) , appetite loss ( 56.6 % ) , and sensory neuropathy ( 54.9 % ) . One patient receiving gefitinib died from interstitial lung disease . CONCLUSIONS First-line gefitinib for patients with advanced non-small-cell lung cancer who were selected on the basis of EGFR mutations improved progression-free survival , with acceptable toxicity , as compared with st and ard chemotherapy . ( UMIN-CTR number , C000000376 .",
"PURPOSE Phase I data ( ASCEND-1 ) showed ceritinib efficacy in patients with ALK-rearranged non-small-cell lung cancer ( NSCLC ) , regardless of brain metastases status and with or without prior therapy with an inhibitor of the ALK protein . Data are presented from a phase II trial ( ASCEND-2 ) in which ceritinib efficacy and safety were evaluated in patients who had ALK-rearranged NSCLC previously treated with at least one platinum-based chemotherapy and who had experienced progression during crizotinib treatment as their last prior therapy . PATIENTS AND METHODS Patients with advanced ALK-rearranged NSCLC , including those with asymptomatic or neurologically stable baseline brain metastases , received oral ceritinib 750 mg/d . Whole-body and intracranial responses were investigator assessed ( according to RECIST version 1.1 ) . Patient-reported outcomes were evaluated with the Lung Cancer Symptom Scale and European Organisation for Research and Treatment of Cancer surveys ( the core-30 and the 13-item lung cancer-specific quality -of-life question naires ) . RESULTS All 140 patients enrolled had received two or more previous treatment regimens , and all patients had received crizotinib . The median duration of exposure and the follow-up time with ceritinib were 8.8 months ( range , 0.1 to 19.4 months ) and 11.3 months ( range , 0.1 to 18.9 months ) , respectively . Investigator-assessed overall response rate was 38.6 % ( 95 % CI , 30.5 % to 47.2 % ) . Secondary end points , all investigator assessed , included disease control rate ( 77.1 % ; 95 % CI , 69.3 % to 83.8 % ) , time to response ( median , 1.8 months ; range , 1.6 to 5.6 months ) , duration of response ( median , 9.7 months ; 95 % CI , 7.1 to 11.1 months ) , and progression-free survival ( median , 5.7 months ; 95 % CI , 5.4 to 7.6 months ) . Of 100 patients with baseline brain metastases , 20 had active target lesions at baseline ; investigator-assessed intracranial overall response rate was 45.0 % ( 95 % CI , 23.1 % to 68.5 % ) . The most common adverse events ( majority , grade 1 or 2 ) for all treated patients were nausea ( 81.4 % ) , diarrhea ( 80.0 % ) , and vomiting ( 62.9 % ) . Patient-reported outcomes showed a trend toward improved symptom burden . The global quality -of-life score was maintained during treatment . CONCLUSION Consistent with its activity in ASCEND-1 , ceritinib treatment provided clinical ly meaningful and durable responses with manageable tolerability in chemotherapy- and crizotinib-pretreated patients , including those with brain metastases",
"BACKGROUND The r and omized , phase III AVAPERL trial evaluated the safety and efficacy of bevacizumab maintenance with or without pemetrexed in nonsquamous nonsmall-cell lung cancer ( nsNSCLC ) . Progression-free survival ( PFS ) was significantly prolonged with bevacizumab-pemetrexed , but overall survival ( OS ) data were immature . In this article , we report an independent , up date d analysis of survival outcomes in AVAPERL . PATIENTS AND METHODS Patients with advanced nsNSCLC received first-line bevacizumab ( 7.5 mg/kg ) , cisplatin ( 75 mg/m(2 ) ) , and pemetrexed ( 500 mg/m(2 ) ) every 3 weeks ( q3w ) for four cycles . Nonprogressing patients were r and omized to maintenance bevacizumab ( 7.5 mg/kg ) or bevacizumab-pemetrexed ( 500 mg/m(2 ) ) q3w until progression or consent withdrawal . The primary end point of the trial was PFS ; in this independent OS analysis , participating study centers were contacted to collect survival data on patients still alive at the time of the first analysis . RESULTS A total of 376 patients received induction treatment . Disease control was confirmed in 71.9 % of patients ; 253 patients were r and omized to maintenance treatment with bevacizumab ( n = 125 ) or bevacizumab-pemetrexed ( n = 128 ) . At a median follow-up of 14.8 months , patients allocated to bevacizumab-pemetrexed had significantly improved PFS versus those on bevacizumab when measured from r and omization [ 7.4 versus 3.7 months , hazard ratio ( HR ) , 0.57 , 95 % confidence interval ( CI ) 0.44 - 0.75 ) ; P OS events occurred in 58 % of all patients . OS was numerically longer with bevacizumab-pemetrexed versus bevacizumab when measured from r and omization [ 17.1 versus 13.2 months , HR 0.87 ( 0.63 - 1.21 ) ; P = 0.29 ] . Second-line therapy was administered in 77 % and 70 % of patients in the bevacizumab and bevacizumab-pemetrexed arms , respectively . No new adverse events were reported during this up date d analysis . CONCLUSION In an unselected population of nsNSCLC patients achieving disease control on platinum-based induction therapy , maintenance with bevacizumab-pemetrexed was associated with a nonsignificant increase in OS over bevacizumab alone",
"BACKGROUND Recent studies of pemetrexed have identified a predictive role for non-small cell lung cancer ( NSCLC ) histology . We further review ed the differential efficacy of pemetrexed according to histology in two large , phase III NSCLC trials . METHODS One study tested pemetrexed versus docetaxel in previously treated patients ( n = 571 ) and the other tested cisplatin plus pemetrexed versus cisplatin plus gemcitabine in chemotherapy-naive patients ( n = 1,725 ) with advanced NSCLC . Cox proportional hazard models were used to test for covariate-adjusted treatment-by-histology interactions ( THIs ) for overall survival ( OS ) and progression-free survival ( PFS ) . For each histologic subgroup , the Kaplan-Meier method was used to estimate unadjusted within-arm medians , and Cox models were used to estimate covariate-adjusted between-arm hazard ratios ( HRs ) . RESULTS In both studies , treatment arms were well balanced for histology . THIs were statistically significant ( p OS and PFS . Nonsquamous patients treated with pemetrexed-based therapy experienced longer survival than the comparators ( HR , 0.78 and 0.84 , respectively ) , whereas squamous patients had shorter survival ( HR , 1.56 and 1.23 , respectively ) . Whereas the efficacy of pemetrexed regimens differed according to histology , it did not differ for docetaxel or for cisplatin plus gemcitabine . Pemetrexed was well tolerated across histologic groups . CONCLUSIONS The consistency of these results across studies confirms the predictive effect of histology for pemetrexed and the survival advantage for pemetrexed in patients with nonsquamous histology . These analyses suggest pemetrexed should not be recommended for the treatment of squamous cell carcinoma , but , because of efficacy and safety advantages , pemetrexed may be preferable to other agents for treatment of patients with nonsquamous NSCLC",
"PURPOSE We compared the efficacy of combination chemotherapy versus single-agent therapy in patients with advanced non-small-cell lung cancer . PATIENTS AND METHODS A total of 561 eligible patients were r and omly assigned to receive paclitaxel alone or in combination with carboplatin . RESULTS The response rate was 17 % in the paclitaxel arm and 30 % in the carboplatin-paclitaxel arm ( P Median failure-free survival was 2.5 months in the paclitaxel arm and 4.6 months in the carboplatin-paclitaxel arm ( P = .0002 ) . Median survival times were 6.7 months ( 95 % CI , 5.8 to 7.8 ) and 8.8 months ( 95 % CI , 8.0 to 9.9 ) , and 1-year survival rates were 32 % ( 95 % CI , 27 % to 38 % ) , and 37 % ( 95 % CI , 32 % to 43 % ) , respectively . The overall survival distributions were not statistically different : hazard ratio = 0.91 ( 95 % CI , 0.77 to 1.17 ; P = .25 ) . Hematological toxicity and nausea were more frequent in the combination arm , but febrile neutropenia and toxic deaths were equally low in both arms . There was no significant survival difference in elderly patients . Performance status 2 patients treated with combination chemotherapy had a better survival rate than those treated with single-agent therapy ( P = .019 ) . CONCLUSION Combination chemotherapy improves response rate and failure-free survival compared with single-agent therapy , but there was no statistically significant difference in the primary end point of overall survival . The results in elderly patients were similar to younger patients . Performance status 2 patients had a superior outcome when treated with combination chemotherapy",
"BACKGROUND Erlotinib has been shown to improve progression-free survival compared with chemotherapy when given as first-line treatment for Asian patients with non-small-cell lung cancer ( NSCLC ) with activating EGFR mutations . We aim ed to assess the safety and efficacy of erlotinib compared with st and ard chemotherapy for first-line treatment of European patients with advanced EGFR-mutation positive NSCLC . METHODS We undertook the open-label , r and omised phase 3 EURTAC trial at 42 hospitals in France , Italy , and Spain . Eligible participants were adults ( > 18 years ) with NSCLC and EGFR mutations ( exon 19 deletion or L858R mutation in exon 21 ) with no history of chemotherapy for metastatic disease ( neoadjuvant or adjuvant chemotherapy ending ≥ 6 months before study entry was allowed ) . We r and omly allocated participants ( 1:1 ) according to a computer-generated allocation schedule to receive oral erlotinib 150 mg per day or 3 week cycles of st and ard intravenous chemotherapy of cisplatin 75 mg/m(2 ) on day 1 plus docetaxel ( 75 mg/m(2 ) on day 1 ) or gemcitabine ( 1250 mg/m(2 ) on days 1 and 8) . Carboplatin ( AUC 6 with docetaxel 75 mg/m(2 ) or AUC 5 with gemcitabine 1000 mg/m(2 ) ) was allowed in patients unable to have cisplatin . Patients were stratified by EGFR mutation type and Eastern Cooperative Oncology Group performance status ( 0 vs 1 vs 2 ) . The primary endpoint was progression-free survival ( PFS ) in the intention-to-treat population . We assessed safety in all patients who received study drug ( ≥ 1 dose ) . This study is registered with Clinical Trials.gov , number NCT00446225 . FINDINGS Between Feb 15 , 2007 , and Jan 4 , 2011 , 174 patients with EGFR mutations were enrolled . One patient received treatment before r and omisation and was thus withdrawn from the study ; of the remaining patients , 86 were r and omly assigned to receive erlotinib and 87 to receive st and ard chemotherapy . The preplanned interim analysis showed that the study met its primary endpoint ; enrolment was halted , and full evaluation of the results was recommended . At data cutoff ( Jan 26 , 2011 ) , median PFS was 9·7 months ( 95 % CI 8·4 - 12·3 ) in the erlotinib group , compared with 5·2 months ( 4·5 - 5·8 ) in the st and ard chemotherapy group ( hazard ratio 0·37 , 95 % CI 0·25 - 0·54 ; p . Main grade 3 or 4 toxicities were rash ( 11 [ 13 % ] of 84 patients given erlotinib vs none of 82 patients in the chemotherapy group ) , neutropenia ( none vs 18 [ 22 % ] ) , anaemia ( one [ 1 % ] vs three [ 4 % ] ) , and increased amino-transferase concentrations ( two [ 2 % ] vs 0 ) . Five ( 6 % ) patients on erlotinib had treatment-related severe adverse events compared with 16 patients ( 20 % ) on chemotherapy . One patient in the erlotinib group and two in the st and ard chemotherapy group died from treatment-related causes . INTERPRETATION Our findings strengthen the rationale for routine baseline tissue-based assessment of EGFR mutations in patients with NSCLC and for treatment of mutation-positive patients with EGFR tyrosine-kinase inhibitors . FUNDING Spanish Lung Cancer Group , Roche Farma , Hoffmann-La Roche , and Red Temática de Investigacion Cooperativa en Cancer",
"OBJECTIVE Erlotinib has been reported to be useful for treatment of non-small-cell lung cancer harboring mutation of the epidermal growth factor receptor gene EGFR-mt . However , no prospect i ve trial has yet assessed the utility of erlotinib in Japanese patients . METHODS Patients with EGFR-mt ( exon 19/21 ) non-small-cell lung cancer who had previously received one to two chemotherapy regimens were enrolled in this trial . Erlotinib was initially administered at a dose of 150 mg/day orally until disease progression or unacceptable toxicities occurred . The primary endpoint was the objective response rate . RESULTS Twenty-six patients were enrolled between February 2009 and January 2011 . Objective response was observed in 14 patients ( 53.8 % , 95 % confidence interval : 33.4 - 73.4 % ) , and the disease control rate reached 80.8 % ( 95 % confidence interval : 60.7 - 93.5 % ) . After a median follow-up time of 17.3 months ( range : 5.8 - 29.5 months ) , the median progression-free survival was 9.3 months ( 95 % confidence interval : 7.6 - 11.6 months ) . The median survival time is yet to be determined . Major toxicities were skin disorder and liver dysfunction ; most episodes were grade 2 or less , and all were tolerable . Only one patient with grade 3 skin rash discontinued the study . No patients developed interstitial lung disease , and there were no treatment-related deaths . CONCLUSIONS This prospect i ve study is the first to have investigated the usefulness of erlotinib in Japanese patients with previously treated EGFR-mt non-small-cell lung cancer . Although this trial could not meet the primary endpoint , erlotinib was well tolerated and showed clinical benefit such as promising disease control rate or progression-free survival in this population , similar to gefitinib",
"BACKGROUND We aim ed to assess the effect of afatinib on overall survival of patients with EGFR mutation-positive lung adenocarcinoma through an analysis of data from two open-label , r and omised , phase 3 trials . METHODS Previously untreated patients with EGFR mutation-positive stage IIIB or IV lung adenocarcinoma were enrolled in LUX-Lung 3 ( n=345 ) and LUX-Lung 6 ( n=364 ) . These patients were r and omly assigned in a 2:1 ratio to receive afatinib or chemotherapy ( pemetrexed-cisplatin [ LUX-Lung 3 ] or gemcitabine-cisplatin [ LUX-Lung 6 ] ) , stratified by EGFR mutation ( exon 19 deletion [ del19 ] , Leu858Arg , or other ) and ethnic origin ( LUX-Lung 3 only ) . We planned analyses of mature overall survival data in the intention-to-treat population after 209 ( LUX-Lung 3 ) and 237 ( LUX-Lung 6 ) deaths . These ongoing studies are registered with Clinical Trials.gov , numbers NCT00949650 and NCT01121393 . FINDINGS Median follow-up in LUX-Lung 3 was 41 months ( IQR 35 - 44 ) ; 213 ( 62 % ) of 345 patients had died . Median follow-up in LUX-Lung 6 was 33 months ( IQR 31 - 37 ) ; 246 ( 68 % ) of 364 patients had died . In LUX-Lung 3 , median overall survival was 28.2 months ( 95 % CI 24.6 - 33.6 ) in the afatinib group and 28.2 months ( 20.7 - 33.2 ) in the pemetrexed-cisplatin group ( HR 0.88 , 95 % CI 0.66 - 1.17 , p=0.39 ) . In LUX-Lung 6 , median overall survival was 23.1 months ( 95 % CI 20.4 - 27.3 ) in the afatinib group and 23.5 months ( 18.0 - 25.6 ) in the gemcitabine-cisplatin group ( HR 0.93 , 95 % CI 0.72 - 1.22 , p=0.61 ) . However , in preplanned analyses , overall survival was significantly longer for patients with del19-positive tumours in the afatinib group than in the chemotherapy group in both trials : in LUX-Lung 3 , median overall survival was 33.3 months ( 95 % CI 26.8 - 41.5 ) in the afatinib group versus 21.1 months ( 16.3 - 30.7 ) in the chemotherapy group ( HR 0.54 , 95 % CI 0.36 - 0.79 , p=0.0015 ) ; in LUX-Lung 6 , it was 31.4 months ( 95 % CI 24.2 - 35.3 ) versus 18.4 months ( 14.6 - 25.6 ) , respectively ( HR 0.64 , 95 % CI 0.44 - 0.94 , p=0.023 ) . By contrast , there were no significant differences by treatment group for patients with EGFR Leu858Arg-positive tumours in either trial : in LUX-Lung 3 , median overall survival was 27.6 months ( 19.8 - 41.7 ) in the afatinib group versus 40.3 months ( 24.3-not estimable ) in the chemotherapy group ( HR 1.30 , 95 % CI 0.80 - 2.11 , p=0.29 ) ; in LUX-Lung 6 , it was 19.6 months ( 95 % CI 17.0 - 22.1 ) versus 24.3 months ( 19.0 - 27.0 ) , respectively ( HR 1.22 , 95 % CI 0.81 - 1.83 , p=0.34 ) . In both trials , the most common afatinib-related grade 3 - 4 adverse events were rash or acne ( 37 [ 16 % ] of 229 patients in LUX-Lung 3 and 35 [ 15 % ] of 239 patients in LUX-Lung 6 ) , diarrhoea ( 33 [ 14 % ] and 13 [ 5 % ] ) , paronychia ( 26 [ 11 % ] in LUX-Lung 3 only ) , and stomatitis or mucositis ( 13 [ 5 % ] in LUX-Lung 6 only ) . In LUX-Lung 3 , neutropenia ( 20 [ 18 % ] of 111 patients ) , fatigue ( 14 [ 13 % ] ) and leucopenia ( nine [ 8 % ] ) were the most common chemotherapy-related grade 3 - 4 adverse events , while in LUX-Lung 6 , the most common chemotherapy-related grade 3 - 4 adverse events were neutropenia ( 30 [ 27 % ] of 113 patients ) , vomiting ( 22 [ 19 % ] ) , and leucopenia ( 17 [ 15 % ] ) . INTERPRETATION Although afatinib did not improve overall survival in the whole population of either trial , overall survival was improved with the drug for patients with del19 EGFR mutations . The absence of an effect in patients with Leu858Arg EGFR mutations suggests that EGFR del19-positive disease might be distinct from Leu858Arg-positive disease and that these subgroups should be analysed separately in future trials . FUNDING Boehringer Ingelheim",
"PURPOSE To investigate the efficacy of erlotinib versus docetaxel in previously treated patients with advanced non-small-cell lung cancer ( NSCLC ) in an epidermal growth factor receptor ( EGFR ) -unselected patient population . PATIENTS AND METHODS The primary end point was progression-free survival ( PFS ) . Secondary end points included overall survival ( OS ) , response rate , safety , and analyses on EGFR wild-type tumors . Patients with stage IIIB or IV NSCLC , previous treatment with one or two chemotherapy regimens , evaluable or measurable disease , and performance status of 0 to 2 were eligible . RESULTS From August 2009 to July 2012 , 150 and 151 patients were r and omly assigned to erlotinib ( 150 mg daily ) and docetaxel ( 60 mg/m(2 ) every 3 weeks ) , respectively . EGFR wild-type NSCLC was present in 109 and 90 patients in the erlotinib and docetaxel groups , respectively . Median PFS for erlotinib versus docetaxel was 2.0 v 3.2 months ( hazard ratio [ HR ] , 1.22 ; 95 % CI , 0.97 to 1.55 ; P = .09 ) , and median OS was 14.8 v 12.2 months ( HR , 0.91 ; 95 % CI , 0.68 to 1.22 ; P = .53 ) , respectively . In a subset analysis of EGFR wild-type tumors , PFS for erlotinib versus docetaxel was 1.3 v 2.9 months ( HR , 1.45 ; 95 % CI , 1.09 to 1.94 ; P = .01 ) , and OS was 9.0 v 10.1 months ( HR , 0.98 ; 95 % CI , 0.69 to 1.39 ; P = .91 ) , respectively . CONCLUSION Erlotinib failed to show an improvement in PFS or OS compared with docetaxel in an EGFR-unselected patient population",
"PURPOSE This phase III trial aim ed to confirm the superiority of weekly docetaxel and cisplatin over docetaxel monotherapy in elderly patients with advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Chemotherapy-naïve patients with stage III , stage IV , or recurrent NSCLC age ≥ 70 years with a performance status of 0 or 1 who were considered unsuitable for bolus cisplatin administration were r and omly assigned to receive docetaxel 60 mg/m(2 ) on day 1 , every 3 weeks , or docetaxel 20 mg/m(2 ) plus cisplatin 25 mg/m(2 ) on days 1 , 8 , and 15 , every 4 weeks . The primary end point was overall survival ( OS ) . RESULTS In the first interim analysis , OS of the doublet arm was inferior to that of the monotherapy arm ( hazard ratio [ HR ] , 1.56 ; 95 % CI , 0.98 to 2.49 ) , and the predictive probability that the doublet arm would be statistically superior to the monotherapy arm on final analysis was 0.996 % , which led to early study termination . In total , 276 patients with a median age of 76 years ( range , 70 to 87 years ) were enrolled . At the up date d analysis , the median survival time was 14.8 months for the monotherapy arm and 13.3 months for the doublet arm ( HR , 1.18 ; 95 % CI , 0.83 to 1.69 ) . The rates of grade ≥ 3 neutropenia and febrile neutropenia were higher in the monotherapy arm , and those of anorexia and hyponatremia were higher in the doublet arm . CONCLUSION This study failed to demonstrate any survival advantage of weekly docetaxel plus cisplatin over docetaxel monotherapy as first-line chemotherapy for advanced NSCLC in elderly patients",
"BACKGROUND Despite recent advances in the treatment of advanced non-small-cell lung cancer , there remains a need for effective treatments for progressive disease . We assessed the efficacy of pembrolizumab for patients with previously treated , PD-L1-positive , advanced non-small-cell lung cancer . METHODS We did this r and omised , open-label , phase 2/3 study at 202 academic medical centres in 24 countries . Patients with previously treated non-small-cell lung cancer with PD-L1 expression on at least 1 % of tumour cells were r and omly assigned ( 1:1:1 ) in blocks of six per stratum with an interactive voice-response system to receive pembrolizumab 2 mg/kg , pembrolizumab 10 mg/kg , or docetaxel 75 mg/m(2 ) every 3 weeks . The primary endpoints were overall survival and progression-free survival both in the total population and in patients with PD-L1 expression on at least 50 % of tumour cells . We used a threshold for significance of p overall survival and a threshold of p progression-free survival . This trial is registered at Clinical Trials.gov , number NCT01905657 . FINDINGS Between Aug 28 , 2013 , and Feb 27 , 2015 , we enrolled 1034 patients : 345 allocated to pembrolizumab 2 mg/kg , 346 allocated to pembrolizumab 10 mg/kg , and 343 allocated to docetaxel . By Sept 30 , 2015 , 521 patients had died . In the total population , median overall survival was 10.4 months with pembrolizumab 2 mg/kg , 12.7 months with pembrolizumab 10 mg/kg , and 8.5 months with docetaxel . Overall survival was significantly longer for pembrolizumab 2 mg/kg versus docetaxel ( hazard ratio [ HR ] 0.71 , 95 % CI 0.58 - 0.88 ; p=0.0008 ) and for pembrolizumab 10 mg/kg versus docetaxel ( 0.61 , 0.49 - 0.75 ; p Median progression-free survival was 3.9 months with pembrolizumab 2 mg/kg , 4.0 months with pembrolizumab 10 mg/kg , and 4.0 months with docetaxel , with no significant difference for pembrolizumab 2 mg/kg versus docetaxel ( 0.88 , 0.74 - 1.05 ; p=0.07 ) or for pembrolizumab 10 mg/kg versus docetaxel ( HR 0.79 , 95 % CI 0.66 - 0.94 ; p=0.004 ) . Among patients with at least 50 % of tumour cells expressing PD-L1 , overall survival was significantly longer with pembrolizumab 2 mg/kg than with docetaxel ( median 14.9 months vs 8.2 months ; HR 0.54 , 95 % CI 0.38 - 0.77 ; p=0.0002 ) and with pembrolizumab 10 mg/kg than with docetaxel ( 17.3 months vs 8.2 months ; 0.50 , 0.36 - 0.70 ; p progression-free survival was significantly longer with pembrolizumab 2 mg/kg than with docetaxel ( median 5.0 months vs 4.1 months ; HR 0.59 , 95 % CI 0.44 - 0.78 ; p=0.0001 ) and with pembrolizumab 10 mg/kg than with docetaxel ( 5.2 months vs 4.1 months ; 0.59 , 0.45 - 0.78 ; p Grade 3 - 5 treatment-related adverse events were less common with pembrolizumab than with docetaxel ( 43 [ 13 % ] of 339 patients given 2 mg/kg , 55 [ 16 % ] of 343 given 10 mg/kg , and 109 [ 35 % ] of 309 given docetaxel ) . INTERPRETATION Pembrolizumab prolongs overall survival and has a favourable benefit-to-risk profile in patients with previously treated , PD-L1-positive , advanced non-small-cell lung cancer . These data establish pembrolizumab as a new treatment option for this population and vali date the use of PD-L1 selection . FUNDING Merck &",
"Background : The purpose of this study was to evaluate gemcitabine – carboplatin ( GCb ) versus single-agent gemcitabine ( G ) in patients with advanced non-small cell lung cancer ( NSCLC ) and a performance status ( PS ) of 2 . The primary endpoint was clinical benefit . Patients and Methods : Patients were r and omly assigned to either 1250 mg/m2 of G ( arm A ) or 1250 mg/m2 of G plus carboplatin area under the curve of 3 ( arm B ) . Both treatments were given on days 1 and 14 and were repeated every 28 days for up to four cycles . Results : Among the 90 eligible patients ( 47 in arm A and 43 in arm B ) , in arm A , two ( 4 % ) had partial responses ( 95 % CI , 0.52%–14.5 % ) and 10 ( 21 % ) had stable disease ( 95 % CI , 10.7%–35.7 % ) . In arm B , six ( 14 % ) had partial responses ( 95 % CI , 5.3%–27.9 % ) and nine ( 21 % ) had stable disease ( 95 % CI , 10%–36 % ) ( p = 0.14 ) . No significant difference was found in terms of clinical benefit between the two treatment groups after two cycles of treatment or at the end of chemotherapy . Furthermore , no association was found between clinical benefit and response to treatment ( p > 0.05 ) . Median survival was 4.8 months ( 95 % CI , 2.45–7.25 ) for arm A and 6.7 months ( 95 % CI , 2.47–10.8 ) for arm B ( p = 0.49 ) . Neutropenia ( p = 0.007 ) and thrombocytopenia ( p terms of severe toxicities ( p > 0.05 in all cases ) . Conclusion : No significant difference was found in terms of clinical benefit in patients with NSCLC and PS 2 who received single-agent G or GCb . Nevertheless , GCb caused more toxicity , particularly neutropenia and thrombocytopenia",
"INTRODUCTION The epidermal growth factor receptor ( EGFR ) tyrosine-kinase inhibitor erlotinib is associated with survival benefits in patients with EGFR mutation-positive non-small-cell lung cancer ( NSCLC ) . This phase II , single-arm study examined the efficacy and safety of first-line erlotinib in Japanese patients with EGFR mutation-positive NSCLC . METHODS Eligible patients received erlotinib 150 mg/day until disease progression or unacceptable toxicity . The primary endpoints were progression-free survival ( PFS ) and safety . RESULTS A high degree of concordance was observed between different mutation testing method ologies , suggesting feasibility of early , rapid detection of EGFR mutations . Median PFS was 11.8 months ( 95 % confidence interval [ CI ] : 9.7 - 15.3 ) at data cut-off ( 1 June 2012 ) ( n = 102 ) . Exon 19 deletions seemed to be associated with longer PFS compared with L858R mutations ; T790 M mutations were tentatively linked with shorter PFS . The safety profile was as expected : rash ( any grade ; 83 % ) and diarrhea ( any grade ; 81 % ) were most common . Six interstitial lung disease (ILD)-like cases were reported , and 5 were confirmed as ILD-like events by the extramural committee . Two patients died of treatment-related pneumonitis ( JAPIC Clinical Trials Information number : Japic CTI-101085 ) . CONCLUSION Erlotinib should be considered for first-line treatment in this subset of Japanese patients , with close monitoring for ILD-like events",
"RATIONALE Interstitial lung disease ( ILD ) occurs in Japanese patients with non-small cell lung cancer ( NSCLC ) receiving gefitinib . OBJECTIVES To eluci date risk factors for ILD in Japanese patients with NSCLC during treatment with gefitinib or chemotherapy . METHODS In a prospect i ve epidemiologic cohort , 3,166 Japanese patients with advanced/recurrent NSCLC were followed for 12 weeks on 250 mg gefitinib ( n = 1,872 treatment periods ) or chemotherapy ( n = 2,551 ) . Patients who developed acute ILD ( n = 122 ) and r and omly selected control subjects ( n = 574 ) entered a case-control study . Adjusted incidence rate ratios were estimated from case-control data by odds ratios ( ORs ) with 95 % confidence intervals ( CIs ) using logistic regression . Crude ( observed ) incidence rates and risks were calculated from cohort data . MEASUREMENTS AND MAIN RESULTS The observed ( unadjusted ) incidence rate over 12 weeks was 2.8 ( 95 % CI , 2.3 - 3.3 ) per 1,000 person-weeks , 4.5 ( 3.5 - 5.4 ) for gefitinib versus 1.7 ( 1.2 - 2.2 ) for chemotherapy ; the corresponding observed naive cumulative incidence rates at the end of 12-week follow-up were 4.0 % ( 3.0 - 5.1 % ) and 2.1 % ( 1.5 - 2.9 % ) , respectively . Adjusted for imbalances in risk factors between treatments , the overall OR for gefitinib versus chemotherapy was 3.2 ( 1.9 - 5.4 ) , elevated chiefly during the first 4 weeks ( 3.8 [ 1.9 - 7.7 ] ) . Other ILD risk factors in both groups included the following : older age , poor World Health Organization performance status , smoking , recent NSCLC diagnosis , reduced normal lung on computed tomography scan , preexisting chronic ILD , concurrent cardiac disease . ILD-related deaths in patients with ILD were 31.6 % ( gefitinib ) versus 27.9 % ( chemotherapy ) ; adjusted OR , 1.05 ( 95 % CI , 0.3 - 3.2 ) . CONCLUSIONS ILD was relatively common in these Japanese patients with NSCLC during therapy with gefitinib or chemotherapy , being higher in the older , smoking patient with preexisting ILD or poor performance status . The risk of developing ILD was higher with gefitinib than chemotherapy , mainly in the first 4 weeks",
"Introduction : Recent studies have demonstrated that first-line treatment with gefitinib , an epidermal growth factor receptor (EFGR)–targeted tyrosine kinase inhibitor , is significantly superior to st and ard chemotherapy for advanced non – small-cell lung cancer ( NSCLC ) harboring EGFR sensitive mutations . Meanwhile , the efficacy of gefitinib therapy among elderly population s diagnosed with EGFR-mutated NSCLC has not yet been eluci date d. The purpose of this study was to investigate the efficacy and feasibility of gefitinib for chemotherapy-naive patients aged 75 or older with NSCLC harboring EGFR mutations ; generally , these patients have no indication for treatment with platinum doublets . Methods : Chemotherapy-naive patients aged 75 years or older with performance status 0 to 1 and advanced NSCLC harboring EGFR mutations , as determined by the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method , were enrolled . The enrolled patients received 250 mg/day of gefitinib orally . Results : Between January 2008 and May 2009 , 31 patients were enrolled , all of whom were eligible . The median age was 80 ( range , 75–87 ) years . Twenty-five patients ( 81 % ) were women , and 30 patients ( 97 % ) had adenocarcinoma . The overall response rate was 74 % ( 95 % confidence interval , 58%–91 % ) , and the disease control rate was 90 % . The median progression-free survival was 12.3 months . The common adverse events were rash , diarrhea , and liver dysfunction . One treatment-related death because of interstitial lung disease occurred . Conclusions : This is the first study that verified safety and efficacy of first-line treatment with gefitinib in elderly patients having advanced NSCLC with EGFR mutation . Considering its strong antitumor activity and mild toxicity , first-line gefitinib may be preferable to st and ard chemotherapy for this population",
"PURPOSE To compare pemetrexed/carboplatin with a st and ard regimen as first-line therapy in advanced non-small-cell lung cancer NSCLC . PATIENTS AND METHODS Patients with stage IIIB or IV NSCLC and performance status of 0 to 2 were r and omly assigned to receive pemetrexed 500 mg/m(2 ) plus carboplatin area under the curve ( AUC ) = 5 ( Calvert 's formula ) on day 1 or gemcitabine 1,000 mg/m(2 ) on days 1 and 8 plus carboplatin AUC = 5 on day 1 every 3 weeks for up to four cycles . The primary end point was health-related quality of life ( HRQoL ) defined as global quality of life , nausea/vomiting , dyspnea , and fatigue reported on the European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 and the lung cancer-specific module LC13 during the first 20 weeks . Secondary end points were overall survival and toxicity . Results Four hundred thirty-six eligible patients were enrolled from April 2005 to July 2006 . Patients who completed the baseline question naire were analyzed for HRQoL ( n = 427 ) , and those who received > or = one cycle of chemotherapy were analyzed for toxicity ( n = 423 ) . Compliance of HRQoL question naires was 87 % . There were no significant differences for the primary HRQoL end points or in overall survival between the two treatment arms ( pemetrexed/carboplatin , 7.3 months ; gemcitabine/carboplatin , 7.0 months ; P = .63 ) . The patients who received gemcitabine/carboplatin had more grade 3 to 4 hematologic toxicity than patients who received pemetrexed/carboplatin , including leukopenia ( 46 % v 23 % , respectively ; P neutropenia ( 51 % v 40 % , respectively ; P = .024 ) , and thrombocytopenia ( 56 % v 24 % , respectively ; P gemcitabine/carboplatin arm received transfusions of RBCs and platelets , whereas the frequencies of neutropenic infections and thrombocytopenic bleedings were similar on both arms . CONCLUSION Pemetrexed/carboplatin provides similar HRQoL and survival when compared with gemcitabine/carboplatin with less hematologic toxicity and less need for supportive care",
"BACKGROUND Patients with non-small-cell lung cancer harbouring mutations in the epidermal growth factor receptor ( EGFR ) gene respond well to the EGFR-specific tyrosine kinase inhibitor gefitinib . However , whether gefitinib is better than st and ard platinum doublet chemotherapy in patients selected by EGFR mutation is uncertain . METHODS We did an open label , phase 3 study ( WJTOG3405 ) with recruitment between March 31 , 2006 , and June 22 , 2009 , at 36 centres in Japan . 177 chemotherapy-naive patients aged 75 years or younger and diagnosed with stage IIIB/IV non-small-cell lung cancer or postoperative recurrence harbouring EGFR mutations ( either the exon 19 deletion or L858R point mutation ) were r and omly assigned , using a minimisation technique , to receive either gefitinib ( 250 mg/day orally ; n=88 ) or cisplatin ( 80 mg/m(2 ) , intravenously ) plus docetaxel ( 60 mg/m(2 ) , intravenously ; n=89 ) , administered every 21 days for three to six cycles . The primary endpoint was progression-free survival . Survival analysis was done with the modified intention-to-treat population . This study is registered with UMIN ( University Hospital Medical Information Network in Japan ) , number 000000539 . FINDINGS Five patients were excluded ( two patients were found to have thyroid and colon cancer after r and omisation , one patient had an exon 18 mutation , one patient had insufficient consent , and one patient showed acute allergic reaction to docetaxel ) . Thus , 172 patients ( 86 in each group ) were included in the survival analyses . The gefitinib group had significantly longer progression-free survival compared with the cisplatin plus docetaxel goup , with a median progression-free survival time of 9.2 months ( 95 % CI 8.0 - 13.9 ) versus 6.3 months ( 5.8 - 7.8 ; HR 0.489 , 95 % CI 0.336 - 0.710 , log-rank p Myelosuppression , alopecia , and fatigue were more frequent in the cisplatin plus docetaxel group , but skin toxicity , liver dysfunction , and diarrhoea were more frequent in the gefitinib group . Two patients in the gefitinib group developed interstitial lung disease ( incidence 2.3 % ) , one of whom died . INTERPRETATION Patients with lung cancer who are selected by EGFR mutations have longer progression-free survival if they are treated with gefitinib than if they are treated with cisplatin plus docetaxel . FUNDING West Japan Oncology Group ( WJOG ) : a non-profit organisation supported by unrestricted donations from several pharmaceutical companies",
"BACKGROUND Alectinib , a potent , highly selective , CNS-active inhibitor of anaplastic lymphoma kinase ( ALK ) , showed promising efficacy and tolerability in the single-arm phase 1/2 AF-001JP trial in Japanese patients with ALK-positive non-small-cell lung cancer . Given those promising results , we did a phase 3 trial to directly compare the efficacy and safety of alectinib and crizotinib . METHODS J-ALEX was a r and omised , open-label , phase 3 trial that recruited ALK inhibitor-naive Japanese patients with ALK-positive non-small-cell lung cancer , who were chemotherapy-naive or had received one previous chemotherapy regimen , from 41 study sites in Japan . Patients were r and omly assigned ( 1:1 ) via an interactive web response system using a permuted-block method stratified by Eastern Cooperative Oncology Group performance status , treatment line , and disease stage to receive oral alectinib 300 mg twice daily or crizotinib 250 mg twice daily until progressive disease , unacceptable toxicity , death , or withdrawal . The primary endpoint was progression-free survival assessed by an independent review facility . The efficacy analysis was done in the intention-to-treat population , and safety analyses were done in all patients who received at least one dose of the study drug . The study is ongoing and patient recruitment is closed . This study is registered with the Japan Pharmaceutical Information Center ( number JapicCTI-132316 ) . FINDINGS Between Nov 18 , 2013 , and Aug 4 , 2015 , 207 patients were recruited and assigned to the alectinib ( n=103 ) or crizotinib ( n=104 ) groups . At data cutoff for the second interim analysis , 24 patients in the alectinib group had discontinued treatment compared with 61 in the crizotinib group , mostly due to lack of efficacy or adverse events . At the second interim analysis ( data cutoff date Dec 3 , 2015 ) , an independent data monitoring committee determined that the primary endpoint of the study had been met ( hazard ratio 0·34 [ 99·7 % CI 0·17 - 0·71 ] , stratified log-rank p data . Median progression-free survival had not yet been reached with alectinib ( 95 % CI 20·3-not estimated ) and was 10·2 months ( 8·2 - 12·0 ) with crizotinib . Grade 3 or 4 adverse events occurred at a greater frequency with crizotinib ( 54 [ 52 % ] of 104 ) than alectinib ( 27 [ 26 % ] of 103 ) . Dose interruptions due to adverse events were also more prevalent with crizotinib ( 77 [ 74 % ] of 104 ) than with alectinib ( 30 [ 29 % ] of 103 ) , and more patients receiving crizotinib ( 21 [ 20 % ] ) than alectinib ( nine [ 9 % ] ) discontinued the study drug because of an adverse event . No adverse events with a fatal outcome occurred in either treatment group . INTERPRETATION These results provide the first head-to-head comparison of alectinib and crizotinib and have the potential to change the st and ard of care for the first-line treatment of ALK-positive non-small-cell lung cancer . The dose of alectinib ( 300 mg twice daily ) used in this study is lower than the approved dose in countries other than Japan ; however , this limitation is being addressed in the ongoing ALEX study . FUNDING Chugai Pharmaceutical Co ,",
"PURPOSE This multicenter phase II study was undertaken to investigate the efficacy and feasibility of gefitinib for patients with advanced non-small-cell lung cancer ( NSCLC ) harboring epidermal growth factor receptor ( EGFR ) mutations without indication for chemotherapy as a result of poor performance status ( PS ) . PATIENTS AND METHODS Chemotherapy-naïve patients with poor PS ( patients 20 to 74 years of age with Eastern Cooperative Oncology Group PS 3 to 4 , 75 to 79 years of age with PS 2 to 4 , and > or= 80 years of age with PS 1 to 4 ) who had EGFR mutations examined by the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method were enrolled and received gefitinib ( 250 mg/d ) alone . RESULTS Between February 2006 and May 2007 , 30 patients with NSCLC and poor PS , including 22 patients with PS 3 to 4 , were enrolled . The overall response rate was 66 % ( 90 % CI , 51 % to 80 % ) , and the disease control rate was 90 % . PS improvement rate was 79 % ( P or= PS 3 at baseline to median progression-free survival , median survival time , and 1-year survival rate were 6.5 months , 17.8 months , and 63 % , respectively . No treatment-related deaths were observed . CONCLUSION This is the first report indicating that EGFR mutation-positive patients with extremely poor PS benefit from first-line gefitinib . Because there previously has been no st and ard treatment for these patients with short life expectancy other than best supportive care , examination of EGFR mutations as a biomarker is recommended in this patient population",
"BACKGROUND Dacomitinib is a second-generation , irreversible EGFR tyrosine kinase inhibitor . We compared its efficacy and safety with that of the reversible EGFR tyrosine kinase inhibitor gefitinib in the first-line treatment of patients with advanced EGFR-mutation-positive non-small-cell lung cancer ( NSCLC ) . METHODS In this international , multicentre , r and omised , open-label , phase 3 study ( ARCHER 1050 ) , we enrolled adults ( aged ≥18 years or ≥20 years in Japan and South Korea ) with newly diagnosed advanced NSCLC and one EGFR mutation ( exon 19 deletion or Leu858Arg ) at 71 academic medical centres and university hospitals in seven countries or special administrative regions . We r and omly assigned participants ( 1:1 ) to receive oral dacomitinib 45 mg/day ( in 28-day cycles ) or oral gefitinib 250 mg/day ( in 28-day cycles ) until disease progression or another discontinuation criterion was met . R and omisation , stratified by race and EGFR mutation type , was done with a computer-generated r and om code assigned by a central interactive web response system . The primary endpoint was progression-free survival assessed by masked independent review in the intention-to-treat population . Safety was assessed in all patients who received at least one dose of study treatment . This study is registered with Clinical Trials.gov , number NCT01774721 , and is ongoing but no longer recruiting patients . FINDINGS Between May 9 , 2013 , and March 20 , 2015 , 452 eligible patients were r and omly assigned to receive dacomitinib ( n=227 ) or gefitinib ( n=225 ) . Median duration of follow-up for progression-free survival was 22·1 months ( 95 % CI 20·3 - 23·9 ) . Median progression-free survival according to masked independent review was 14·7 months ( 95 % CI 11·1 - 16·6 ) in the dacomitinib group and 9·2 months ( 9·1 - 11·0 ) in the gefitinib group ( hazard ratio 0·59 , 95 % CI 0·47 - 0·74 ; p 3 - 4 adverse events were dermatitis acneiform ( 31 [ 14 % ] of 227 patients given dacomitinib vs none of 224 patients given gefitinib ) , diarrhoea ( 19 [ 8 % ] vs two [ 1 % ] ) , and raised alanine aminotransferase levels ( two [ 1 % ] vs 19 [ 8 % ] ) . Treatment-related serious adverse events were reported in 21 ( 9 % ) patients given dacomitinib and in ten ( 4 % ) patients given gefitinib . Two treatment-related deaths occurred in the dacomitinib group ( one related to untreated diarrhoea and one to untreated cholelithases/liver disease ) and one in the gefitinib group ( related to sigmoid colon diverticulitis/rupture complicated by pneumonia ) . INTERPRETATION Dacomitinib significantly improved progression-free survival over gefitinib in first-line treatment of patients with EGFR-mutation-positive NSCLC and should be considered as a new treatment option for this population . FUNDING SFJ Pharmaceuticals Group and Pfizer",
"BACKGROUND Ceritinib is a next-generation anaplastic lymphoma kinase ( ALK ) inhibitor , which has shown robust anti-tumour efficacy , along with intracranial activity , in patients with ALK-rearranged non-small-cell lung cancer . In phase 1 and 2 studies , ceritinib has been shown to be highly active in both ALK inhibitor-naive and ALK inhibitor-pretreated patients who had progressed after chemotherapy ( mostly multiple lines ) . In this study , we compared the efficacy and safety of ceritinib versus single-agent chemotherapy in patients with advanced ALK-rearranged non-small-cell lung cancer who had previously progressed following crizotinib and platinum-based doublet chemotherapy . METHODS In this r and omised , controlled , open-label , phase 3 trial , we recruited patients aged at least 18 years with ALK-rearranged stage IIIB or IV non-small-cell lung cancer ( with at least one measurable lesion ) who had received previous chemotherapy ( one or two lines , including a platinum doublet ) and crizotinib and had subsequent disease progression , from 99 centres across 20 countries . Other inclusion criteria were a WHO performance status of 0 - 2 , adequate organ function and laboratory test results , a life expectancy of at least 12 weeks , and having recovered from previous anticancer treatment-related toxicities . We r and omly allocated patients ( 1:1 ; with blocking [ block size of four ] ; stratified by WHO performance status [ 0 vs 1 - 2 ] and presence or absence of brain metastases ) to oral ceritinib 750 mg per day fasted ( in 21 day treatment cycles ) or chemotherapy ( intravenous pemetrexed 500 mg/m2 or docetaxel 75 mg/m2 [ investigator choice ] , every 21 days ) . Patients who discontinued chemotherapy because of progressive disease could cross over to the ceritinib group . The primary endpoint was progression-free survival , assessed by a masked independent review committee using Response Evaluation Criteria in Solid Tumors 1.1 in the intention-to-treat population , assessed every 6 weeks until month 18 and every 9 weeks thereafter . This trial is registered with Clinical Trials.gov , number NCT01828112 , and is ongoing but no longer recruiting patients . FINDINGS Between June 28 , 2013 , and Nov 2 , 2015 , we r and omly allocated 231 patients ; 115 ( 50 % ) to ceritinib and 116 ( 50 % ) to chemotherapy ( 40 [ 34 % ] to pemetrexed , 73 [ 63 % ] to docetaxel , and three [ 3 % ] discontinued before receiving treatment ) . Median follow-up was 16·5 months ( IQR 11·5 - 21·4 ) . Ceritinib showed a significant improvement in median progression-free survival compared with chemotherapy ( 5·4 months [ 95 % CI 4·1 - 6·9 ] for ceritinib vs 1·6 months [ 1·4 - 2·8 ] for chemotherapy ; hazard ratio 0·49 [ 0·36 - 0·67 ] ; p events were reported in 49 ( 43 % ) of 115 patients in the ceritinib group and 36 ( 32 % ) of 113 in the chemotherapy group . Treatment-related serious adverse events were similar between groups ( 13 [ 11 % ] in the ceritinib group vs 12 [ 11 % ] in the chemotherapy group ) . The most frequent grade 3 - 4 adverse events in the ceritinib group were increased alanine aminotransferase concentration ( 24 [ 21 % ] of 115 vs two [ 2 % ] of 113 in the chemotherapy group ) , increased γ glutamyltransferase concentration ( 24 [ 21 % ] vs one [ 1 % ] ) , and increased aspartate aminotransferase concentration ( 16 [ 14 % ] vs one [ 1 % ] in the chemotherapy group ) . Six ( 5 % ) of 115 patients in the ceritinib group discontinued because of adverse events compared with eight ( 7 % ) of 116 in the chemotherapy group . 15 ( 13 % ) of 115 patients in the ceritinib group and five ( 4 % ) of 113 in the chemotherapy group died during the treatment period ( from the day of the first dose of study treatment to 30 days after the final dose ) . 13 ( 87 % ) of the 15 patients who died in the ceritinib group died because of disease progression and two ( 13 % ) died because of an adverse event ( one [ 7 % ] cerebrovascular accident and one [ 7 % ] respiratory failure ) ; neither of these deaths were considered by the investigator to be treatment related . The five ( 4 % ) deaths in the chemotherapy group were all due to disease progression . INTERPRETATION These findings show that patients derive significant clinical benefit from a more potent ALK inhibitor after failure of crizotinib , and establish ceritinib as a more efficacious treatment option compared with chemotherapy in this patient population . FUNDING Novartis Pharmaceuticals Corporation",
"Summary Background Many patients with advanced non-small-cell lung cancer ( NSCLC ) receive only active supportive care because of poor performance status or presence of several comorbidities . We investigated whether erlotinib improves clinical outcome in these patients . Methods TOPICAL was a double-blind , r and omised , placebo-controlled , phase 3 trial , done at 78 centres in the UK . Eligibility criteria were newly diagnosed , pathologically confirmed NSCLC ; stage IIIb or IV ; chemotherapy naive ; no symptomatic brain metastases ; deemed unsuitable for chemotherapy because of poor ( ≥2 ) Eastern Cooperative Oncology Group performance status or presence of several comorbidities , or both ; and estimated life expectancy of at least 8 weeks . Patients were r and omly assigned ( by phone call , in a 1:1 ratio , stratified by disease stage , performance status , smoking history , and centre , block size 10 ) to receive oral placebo or erlotinib ( 150 mg per day ) until disease progression or unacceptable toxicity . Investigators , clinicians , and patients were masked to assignment . The primary endpoint was overall survival . Analyses were by intention to treat , and prespecified subgroup analyses included development of a rash due to erlotinib within 28 days of starting treatment . This study is registered , number IS RCT N 77383050 . Findings Between April 14 , 2005 , and April 1 , 2009 , we r and omly assigned 350 patients to receive erlotinib and 320 to receive placebo . We followed up patients until March 31 , 2011 . 657 patients died ; median overall survival did not differ between groups ( erlotinib , 3·7 months , 95 % CI 3·2–4·2 , vs placebo , 3·6 months , 3·2–3·9 ; unadjusted hazard ratio [ HR ] 0·94 , 95 % CI 0·81–1·10 , p=0·46 ) . 59 % ( 178 of 302 ) of patients assigned erlotinib and who were assessable at 1 month developed first-cycle rash , which was the only independent factor associated with overall survival . Patients with first-cycle rash had better overall survival ( HR 0·76 , 95 % CI 0·63–0·92 , p=0·0058 ) , compared with placebo . Compared with placebo , overall survival seemed to be worse in the group that did not develop first-cycle rash ( 1·30 , 1·05–1·61 , p=0·017 ) . Grade 3 or 4 diarrhoea was more common with erlotinib than placebo ( 8 % [ 28 of 334 ] vs 1 % [ four of 313 ] , p=0·0001 ) , as was high- grade rash ( 23 % [ 79 of 334 ] vs 2 % [ five of 313 ] , p adverse events were much the same between groups . Interpretation Patients with NSCLC who are deemed unsuitable for chemotherapy could be given erlotinib . Patients who develop a first-cycle rash should continue to receive erlotinib , whereas those who do not have a rash after 28 days should discontinue erlotinib , because of the possibility of decreased survival . Funding Cancer Research UK , Roche",
"OBJECTIVES Ramucirumab plus docetaxel prolongs survival in patients with non-small cell lung cancer ( NSCLC ) with disease progression after platinum-based therapy . This phase II , double-blind , r and omized , placebo-controlled study assessed efficacy and safety of second-line ramucirumab-docetaxel in Japanese patients with NSCLC . MATERIAL S AND METHODS Patients with NSCLC with progression after platinum-based therapy ( 28 Japanese sites ; 19 December , 2012 to 22 May , 2015 ) were r and omized ( computer-generated sequence ) to ramucirumab 10mg/kg or placebo , followed by docetaxel 60mg/m(2 ) ( Day 1 , 21-day cycle ) . Prior epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor ( TKI ) monotherapy was prohibited in the primary population , but EGFR mutation-positive NSCLC patients who were treated with EGFR-TKI were enrolled as a separate exploratory population . Primary endpoint was progression-free survival ( PFS ) ; secondary outcomes included overall survival , tumor response rates , and safety . Investigator tumor assessment s were used for the efficacy endpoints . RESULTS In the primary population ( N=160 r and omized , n=157 treated ) , median ( 95 % CI ) PFS was longer with ramucirumab-docetaxel ( 5.22 [ 3.52 - 6.97 ] months ; n=76 ) than with placebo-docetaxel ( 4.21 [ 2.83 - 5.62 ] months ; n=81 ) ; hazard ratio 0.83 ( 95 % CI 0.59 - 1.16 ) . Median ( 95 % CI ) overall survival was 15.15 ( 12.45 - 26.55 ) months with ramucirumab-docetaxel and 14.65 ( 11.93 - 24.44 ) months with placebo-docetaxel ( hazard ratio [ 95 % CI ] 0.86 [ 0.56 - 1.32 ] ) . Objective response rate ( 28.9 % vs 18.5 % ) and disease control rate ( 78.9 % vs 70.4 % ) were numerically greater with ramucirumab-docetaxel than with placebo-docetaxel . Incidence and severity of most adverse events were similar , but febrile neutropenia was more common with ramucirumab-docetaxel ( 34.2 % ) than with placebo-docetaxel ( 19.8 % ) . CONCLUSION Second-line ramucirumab-docetaxel improved PFS similar to that seen in the REVEL trial with a manageable safety profile in Japanese patients with NSCLC",
"Introduction : Safety of Avastin in Lung ( MO19390 ) was an international , open-label , single-arm study , which assessed the safety and efficacy of first-line bevacizumab ( Avastin ® ) in combination with st and ard chemotherapy in patients ( n = 2212 ) with advanced or recurrent non-small cell lung cancer ( NSCLC ) . A preplanned subgroup analysis was performed to examine these outcomes in elderly patients older than 65 years . Methods : Eligible patients with nonsquamous NSCLC received up to six cycles of bevacizumab ( 7.5 or 15 mg/kg ) plus any st and ard of care chemotherapy . Patients who did not experience disease progression after induction therapy continued bevacizumab therapy until disease progression or unacceptable toxicity . The primary end point was safety ; secondary end points included time to disease progression ( TTP ) and overall survival ( OS ) . Results : Data were evaluated for 623 patients older than 65 years ( mean age 70.6 ) . The majority were Whites ( 86.2 % ) with stage IV disease ( 79.7 % ) and had adenocarcinoma ( 83.5 % ) . The incidence of adverse events ( AEs ) of special interest was similar for elderly and younger patients ( any grade bleeding 38.2 % versus 38.3 % ; any grade hypertension 33.1 % versus 30.6 % ; any grade proteinuria 33.4 % versus 29.3 % ) . Most AEs were grade less than or equal to 2 . Serious AEs were reported in 45.3 and 34.7 % of elderly and younger patients , respectively . Median OS was similar in elderly and younger patients ( 14.6 months in both age groups ) , as were TTP ( 8.2 versus 7.6 months ) , response rate ( 49.3 % versus 52.4 % ) , and disease control rate ( 89.3 % versus 88.4 % ) . Similar results were seen in a post hoc comparison of the older than 70 years and 70 years or younger subgroups : TTP was 8.6 months versus 7.7 months , respectively ; OS was 14.6 months in both subgroups ; response rate was 49 % and 52 % , respectively ; incidence of AEs of special interest was comparable . Conclusion : Patients older than 65 years with nonsquamous NSCLC derive a similar clinical benefit from first-line bevacizumab-based therapy as their younger counterparts and do not experience increased toxicity",
"BACKGROUND Afatinib-an oral irreversible ErbB family blocker-improves progression-free survival compared with pemetrexed and cisplatin for first-line treatment of patients with EGFR mutation-positive advanced non-small-cell lung cancer ( NSCLC ) . We compared afatinib with gemcitabine and cisplatin-a chemotherapy regimen widely used in Asia-for first-line treatment of Asian patients with EGFR mutation-positive advanced NSCLC . METHODS This open-label , r and omised phase 3 trial was done at 36 centres in China , Thail and , and South Korea . After central testing for EGFR mutations , treatment-naive patients ( stage IIIB or IV cancer [ American Joint Committee on Cancer version 6 ] , performance status 0 - 1 ) were r and omly assigned ( 2:1 ) to receive either oral afatinib ( 40 mg per day ) or intravenous gemcitabine 1000 mg/m(2 ) on day 1 and day 8 plus cisplatin 75 mg/m(2 ) on day 1 of a 3-week schedule for up to six cycles . R and omisation was done central ly with a r and om number-generating system and an interactive internet and voice-response system . R and omisation was stratified by EGFR mutation ( Leu858Arg , exon 19 deletions , or other ; block size three ) . Clinicians and patients were not masked to treatment assignment , but the independent central imaging review group were . Treatment continued until disease progression , intolerable toxic effects , or withdrawal of consent . The primary endpoint was progression-free survival assessed by independent central review ( intention-to-treat population ) . This study is registered with Clinical Trials.gov , NCT01121393 . FINDINGS 910 patients were screened and 364 were r and omly assigned ( 242 to afatinib , 122 to gemcitabine and cisplatin ) . Median progression-free survival was significantly longer in the afatinib group ( 11·0 months , 95 % CI 9·7 - 13·7 ) than in the gemcitabine and cisplatin group ( 5·6 months , 5·1 - 6·7 ; hazard ratio 0·28 , 95 % CI 0·20 - 0·39 ; p grade 3 or 4 adverse events in the afatinib group were rash or acne ( 35 [ 14·6 % ] of 239 patients ) , diarrhoea ( 13 [ 5·4 % ] ) , and stomatitis or mucositis ( 13 [ 5·4 % ] ) , compared with neutropenia ( 30 [ 26·5 % ] of 113 patients ) , vomiting ( 22 [ 19·5 % ] ) , and leucopenia ( 17 [ 15·0 % ] ) in the gemcitabine and cisplatin group . Treatment-related serious adverse events occurred in 15 ( 6·3 % ) patients in the afatinib group and nine ( 8·0 % ) patients in the gemcitabine and cisplatin group . INTERPRETATION First-line afatinib significantly improves progression-free survival with a tolerable and manageable safety profile in Asian patients with EGFR mutation-positive advanced lung NSCLC . Afatinib should be considered as a first-line treatment option for this patient population . FUNDING Boehringer Ingelheim",
"PURPOSE This phase III trial compared the efficacy and safety of albumin-bound paclitaxel ( nab-paclitaxel ) plus carboplatin with solvent-based paclitaxel ( sb-paclitaxel ) plus carboplatin in advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS In all , 1,052 untreated patients with stage IIIB to IV NSCLC were r and omly assigned 1:1 to receive 100 mg/m(2 ) nab-paclitaxel weekly and carboplatin at area under the concentration-time curve ( AUC ) 6 once every 3 weeks ( nab-PC ) or 200 mg/m(2 ) sb-paclitaxel plus carboplatin AUC 6 once every 3 weeks ( sb-PC ) . The primary end point was objective overall response rate ( ORR ) . RESULTS On the basis of independent assessment , nab-PC demonstrated a significantly higher ORR than sb-PC ( 33 % v 25 % ; response rate ratio , 1.313 ; 95 % CI , 1.082 to 1.593 ; P = .005 ) and in patients with squamous histology ( 41 % v 24 % ; response rate ratio , 1.680 ; 95 % CI , 1.271 to 2.221 ; P effective as sb-PC in patients with nonsquamous histology ( ORR , 26 % v 25 % ; P = .808 ) . There was an approximately 10 % improvement in progression-free survival ( median , 6.3 v 5.8 months ; hazard ratio [ HR ] , 0.902 ; 95 % CI , 0.767 to 1.060 ; P = .214 ) and overall survival ( OS ; median , 12.1 v 11.2 months ; HR , 0.922 ; 95 % CI , 0.797 to 1.066 ; P = .271 ) in the nab-PC arm versus the sb-PC arm , respectively . Patients ≥ 70 years old and those enrolled in North America showed a significantly increased OS with nab-PC versus sb-PC . Significantly less grade ≥ 3 neuropathy , neutropenia , arthralgia , and myalgia occurred in the nab-PC arm , and less thrombocytopenia and anemia occurred in the sb-PC arm . CONCLUSION The administration of nab-PC as first-line therapy in patients with advanced NSCLC was efficacious and result ed in a significantly improved ORR versus sb-PC , achieving the primary end point . nab-PC produced less neuropathy than sb-PC",
"PURPOSE To study the prognostic value for overall survival of baseline assessment of functional status , comorbidity , and quality of life ( QoL ) in elderly patients with advanced non-small-cell lung cancer treated with chemotherapy . PATIENTS AND METHODS Data from 566 patients enrolled onto the phase III r and omized Multicenter Italian Lung Cancer in the Elderly Study ( MILES ) study were analyzed . Functional status was measured as activities of daily living ( ADL ) and instrumental ADL ( IADL ) . The presence of comorbidity was assessed with a checklist of 33 items ; items 29 and 30 of the European Organisation for Research and Treatment of Cancer ( EORTC ) core question naire QLQ-C30 ( EORTC QLQ-C30 ) were used to estimate QoL. ADL was dichotomized as none versus one or more dependency . For IADL and QoL , three categories were defined using first and third quartiles as cut points . Comorbidity was summarized using the Charlson scale . Analysis was performed by Cox model , and stratified by treatment arm . RESULTS Better values of baseline QoL ( P = .0003 ) and IADL ( P = .04 ) were significantly associated with better prognosis , whereas ADL ( P = .44 ) and Charlson score ( P = .66 ) had no prognostic value . Performance status 2 ( P = .006 ) and a higher number of metastatic sites ( P = .02 ) also predicted shorter overall survival . CONCLUSIONS Pretreatment global QoL and IADL scores , but not ADL and comorbidity , have significant prognostic value for survival of elderly patients with advanced non-small-cell lung cancer who were treated with chemotherapy . Using these scores in clinical practice might improve prognostic prediction for treatment planning",
"BACKGROUND The combination of nedaplatin , a cisplatin derivative , and docetaxel showed promising activity for advanced squamous cell lung carcinoma in a previous phase 1 - 2 study . We compared nedaplatin plus docetaxel with cisplatin plus docetaxel in patients with previously untreated advanced or relapsed squamous cell lung carcinoma to determine effects on overall survival . METHODS We did a r and omised , open-label , phase 3 study at 53 institutions in Japan . Eligibility criteria included pathologically proven squamous cell lung cancer with stage IIIB/IV or postoperative recurrence , age 20 - 74 years , Eastern Cooperative Oncology Group performance status of 0 - 1 , no previous chemotherapy or recurrence more than a year after previous adjuvant chemotherapy , and adequate organ function . Patients were r and omly assigned ( 1:1 ) to 100 mg/m(2 ) nedaplatin and 60 mg/m(2 ) docetaxel intravenously , or 80 mg/m(2 ) cisplatin and 60 mg/m(2 ) docetaxel , every 3 weeks for four to six cycles ( at the treating oncologist 's discretion ) . R and omisation was done central ly at the West Japan Oncology Group data centre via a computer-generated allocation sequence with dynamic minimisation that balanced stage ( IIIB/IV or postoperative recurrent ) , sex , and institution . The primary endpoint was overall survival in the modified intention-to-treat population ( ie , all patients who were r and omly assigned and met the inclusion criteria ) . Safety analyses were done in all r and omly assigned patients who received at least one dose of the study regimen . This trial is registered with the UMIN Clinical Trials Registry , number UMIN000002015 , and is closed to new participants . FINDINGS Between July 6 , 2009 , and July 26 , 2012 , 355 patients were r and omly assigned . 349 patients were included in the modified intention-to-treat analysis ( 177 in the nedaplatin group and 172 in the cisplatin group ) . Overall survival was significantly longer in the nedaplatin group ( median 13·6 months , 95 % CI 11·6 - 15·6 ) than in the cisplatin group ( 11·4 months,10·2 - 12·2 ; hazard ratio 0·81 , 95 % CI 0·65 - 1·02 ; p=0·037 , one-sided stratified log-rank test ) . Grade 3 or worse nausea ( seven of 177 patients in the nedaplatin group and 25 of 175 in the cisplatin group ) , fatigue ( six vs 20 ) , hyponatraemia ( 24 vs 53 ) , and hypokalaemia ( four vs 15 ) were more frequent in the cisplatin group than in the nedaplatin group , whereas grade 3 or worse leucopenia ( 98 vs 77 ) , neutropenia ( 146 vs 123 ) , and thrombocytopenia ( 16 vs none ) were more frequent in the nedaplatin group than in the cisplatin group . Treatment-related deaths occurred in four and three patients in nedaplatin and cisplatin groups , respectively . INTERPRETATION Overall survival was significantly longer with nedaplatin plus docetaxel than with cisplatin plus docetaxel , and the regimens had different safety profiles . Nedaplatin plus docetaxel could be a new treatment option for advanced or relapsed squamous cell lung cancer . FUNDING West Japan Oncology Group and Sanofi",
"PURPOSE Appropriate therapy for Eastern Cooperative Oncology Group ( ECOG ) performance status ( PS ) -2 patients with advanced non-small-cell lung cancer ( NSCLC ) remains challenging . PS-2 patients on ECOG 1594 had a median survival ( MS ) of only 4.1 months and 1-year overall survival ( OS ) of 19 % . Three percent had grade 5 toxicity . PATIENTS AND METHODS ECOG 1599 , the first PS 2-specific , US cooperative group trial for treatment-naïve advanced NSCLC , r and omly assigned patients to dose-attenuated carboplatin/paclitaxel ( the least toxic regimen in ECOG 1594 ) or gemcitabine/cisplatin ( which yielded an MS of 7.9 months in PS-2 patients ) . Patients received either carboplatin ( area under the concentration-time curve , 6 ) and paclitaxel 200 mg/m2 every 3 weeks ( CbP ) or gemcitabine 1 g/m2 days 1 and 8 and cisplatin 60 mg/m2 day 1 every 3 weeks ( CG ) . RESULTS One hundred three patients were enrolled ; 100 proved eligible . Median age was 66 years ; 46 % had at least 5 % weight loss ; 88 % had stage IV or recurrent disease . Median number of cycles administered was three per arm . CbP featured more grade 3 neutropathy ( 10 % v 0 % ) and more grade > or = 3 neutropenia ( 59 % v 33 % ) , whereas CG yielded more grade 3 thrombocytopenia ( 33 % v 14 % ) , more grade 3 fatigue ( 22 % v 14 % ) , and more grade > or = 1 creatinine elevations ( 43 % v 6 % ) . One grade 5 toxicity , confined to the CbP arm , occurred . Response rate , time to progression , MS , and 1-year OS rates for CG and CbP , were 23 % , 4.8 months , 6.9 months , and 25 % , and 14 % , 4.2 months , 6.2 months , and 19 % , respectively . CONCLUSION Platinum-based combination chemotherapy for PS-2 patients with NSCLC is feasible with acceptable toxicity , but survival in these patients remains inferior to that of PS-0 to -1 patients",
"PURPOSE To compare the efficacy and toxicity of pemetrexed versus docetaxel in patients with advanced non-small-cell lung cancer ( NSCLC ) previously treated with chemotherapy . PATIENTS AND METHODS Eligible patients had a performance status 0 to 2 , previous treatment with one prior chemotherapy regimen for advanced NSCLC , and adequate organ function . Patients received pemetrexed 500 mg/m(2 ) intravenously ( i.v . ) day 1 with vitamin B(12 ) , folic acid , and dexamethasone or docetaxel 75 mg/m(2 ) i.v . day 1 with dexamethasone every 21 days . The primary end point was overall survival . RESULTS Five hundred seventy-one patients were r and omly assigned . Overall response rates were 9.1 % and 8.8 % ( analysis of variance P = .105 ) for pemetrexed and docetaxel , respectively . Median progression-free survival was 2.9 months for each arm , and median survival time was 8.3 versus 7.9 months ( P = not significant ) for pemetrexed and docetaxel , respectively . The 1-year survival rate for each arm was 29.7 % . Patients receiving docetaxel were more likely to have grade 3 or 4 neutropenia ( 40.2 % v 5.3 % ; P febrile neutropenia ( 12.7 % v 1.9 % ; P neutropenia with infections ( 3.3 % v 0.0 % ; P = .004 ) , hospitalizations for neutropenic fever ( 13.4 % v 1.5 % ; P hospitalizations due to other drug related adverse events ( 10.5 % v 6.4 % ; P = .092 ) , use of granulocyte colony-stimulating factor support ( 19.2 % v 2.6 % , P all grade alopecia ( 37.7 % v 6.4 % ; P pemetrexed . CONCLUSION Treatment with pemetrexed result ed in clinical ly equivalent efficacy outcomes , but with significantly fewer side effects compared with docetaxel in the second-line treatment of patients with advanced NSCLC and should be considered a st and ard treatment option for second-line NSCLC when available",
"PURPOSE To compare single-agent pemetrexed ( P ) versus the combination of carboplatin and pemetrexed ( CP ) in first-line therapy for patients with advanced non-small-cell lung cancer ( NSCLC ) with an Eastern Cooperative Oncology Group ( ECOG ) performance status ( PS ) of 2 . PATIENTS AND METHODS In a multicenter phase III r and omized trial , patients with advanced NSCLC , ECOG PS of 2 , any histology at first and later amended to nonsquamous only , no prior chemotherapy , and adequate organ function were r and omly assigned to P alone ( 500 mg/m(2 ) ) or CP ( area under the curve of 5 and 500 mg/m(2 ) , respectively ) administered every 3 weeks for a total of four cycles . The primary end point was overall survival ( OS ) . RESULTS A total of 205 eligible patients were enrolled from eight centers in Brazil and one in the United States from April 2008 to July 2011 . The response rates were 10.3 % for P and 23.8 % for CP ( P = .032 ) . In the intent-to-treat population , the median PFS was 2.8 months for P and 5.8 months for CP ( hazard ratio [ HR ] , 0.46 ; 95 % CI , 0.35 to 0.63 ; P median OS was 5.3 months for P and 9.3 months for CP ( HR , 0.62 ; 95 % CI , 0.46 to 0.83 ; P = .001 ) . One-year survival rates were 21.9 % and 40.1 % , respectively . Similar results were seen when patients with squamous disease were excluded from the analysis . Anemia ( grade 3 , 3.9 % ; grade 4 , 11.7 % ) and neutropenia ( grade 3 , 1 % ; grade 4 , 6.8 % ) were more frequent with CP . There were four treatment-related deaths in the CP arm . CONCLUSION Combination chemotherapy with CP significantly improves survival in patients with advanced NSCLC and ECOG PS of 2",
"PURPOSE Docetaxel has shown activity in elderly patients with advanced non-small-cell lung cancer ( NSCLC ) . This r and omized phase III trial evaluated the efficacy and safety of docetaxel versus vinorelbine ( the current st and ard treatment ) in elderly patients . PATIENTS AND METHODS Chemotherapy-naïve patients age 70 years or older with stage IIIB/IV NSCLC and performance status 2 or lower were eligible . Patients r and omly received docetaxel 60 mg/m2 ( day 1 ) or vinorelbine 25 mg/m2 ( days 1 and 8) every 21 days for four cycles . The primary end point was overall survival . Overall disease-related symptom improvement was assessed using an eight-item question naire . RESULTS In total , 182 patients were enrolled . Median age was 76 years ( range , 70 years to 86 years ) . There was no statistical difference in median overall survival with docetaxel versus vinorelbine ( 14.3 months v 9.9 months ; hazard ratio , 0.780 ; 95 % CI , 0.561 to 1.085 ; P = .138 ) . There was a significant difference in median progression-free survival ( 5.5 months v 3.1 months ; P Response rates were also significantly improved with docetaxel versus vinorelbine ( 22.7 % v 9.9 % ; P = .019 ) . The most common grade 3 to 4 toxicities were neutropenia ( 82.9 % for docetaxel ; 69.2 % for vinorelbine ; P = .031 ) and leukopenia ( 58.0 % for docetaxel ; 51.7 % for vinorelbine ) . Other toxicities were mild and generally well tolerated . Docetaxel improved overall disease-related symptoms over vinorelbine ( odds ratio , 1.86 ; 95 % CI , 1.09 to 3.20 ) . CONCLUSION Docetaxel improved progression-free survival , response rate , and disease-related symptoms versus vinorelbine . Overall survival was not statistically significantly improved at this time . Docetaxel monotherapy may be considered as an option in the st and ard treatment of elderly patients with advanced NSCLC",
"BACKGROUND Vinorelbine , a semisynthetic vinca alkaloid , represents a well-tolerated treatment for elderly patients with advanced non-small-cell lung cancer ( NSCLC ) . We explored the quality of life ( QoL ) of such patients in a multicenter r and omized trial that compared vinorelbine treatment with supportive care alone . METHODS Eligible patients were 70 years of age or older , had stage IV or IIIB NSCLC that was ineligible for radiotherapy , and had a performance status of 0 - 2 ( a status of fully active to a status of capable of all self-care but unable to work ) . Vinorelbine was given intravenously on days 1 and 8 of a 21-day treatment cycle , for a total of six cycles . QoL was evaluated with European Organization for Research and Treatment of Cancer question naires QLQ-C30 and QLQ-LC13 , and the QoL data were analyzed by fitting a linear mixed model for each QoL scale . Survival curves were plotted and were compared with the Mantel-Haenszel test . Relative hazards of death and 95 % confidence intervals ( CIs ) were estimated by the Cox model . RESULTS Investigators , blinded to the results , stopped the trial early because of a low enrollment rate . ( From April 1996 to November 1997 , 191 of the 350 targeted patients were r and omly assigned . ) Data from 161 patients have been analyzed . Vinorelbine-treated patients scored better than control patients on QoL functioning scales , and they reported fewer lung cancer-related symptoms but reported worse toxicity-related symptoms . There was a statistically significant ( two-sided P = .03 ) survival advantage for patients receiving vinorelbine ; median survival increased from 21 to 28 weeks in the vinorelbine-treated group . The relative hazard of death for vinorelbine-treated patients was 0.65 ( 95 % CI = 0.45 - 0.93 ) . CONCLUSION Vinorelbine improves survival of elderly patients with advanced NSCLC and possibly improves overall",
"PURPOSE Severe ( grade > or= 3 ) pulmonary hemorrhage ( PH ) in advanced non-small-cell lung cancer was observed in two prospect i ve , r and omized , phase II ( N = 99 ) and phase III ( N = 878 ) trials of bevacizumab plus carboplatin and paclitaxel . Retrospective case-control and cohort analyses were conducted to identify associated radiographic and clinical risk factors for PH . PATIENTS AND METHODS Six patients with PH from the phase II trial , 15 potential PH patients with hemorrhage at any site from the phase III trial , and their matched controls were evaluated with review of baseline and on-treatment radiographs by an independent radiology facility , blinded to patient/control status . Patients with severe ( grade > or= 3 ) PH from each trial were matched with up to three controls based on sex , age group , histology ( phase II ) , or sex and age group ( phase III ) . RESULTS Seven PH patients in the phase III trial were identified as severe PH . Six of the patients were early onset ( occurred bevacizumab ) and one was late onset . Baseline tumor cavitation , not tumor location , was identified as the only potential risk factor for patients with early onset . Combined analysis of severe PH patients from the phase II and phase III trials ( n = 13 ) , compared with their pooled matched controls ( n = 42 ) , did not identify any additional baseline radiographic or clinical variables associated with PH . CONCLUSION PH was an uncommon event . Based on these analyses , baseline tumor cavitation may be a potential risk factor for PH . No other baseline clinical variables were predictive for PH although the number of events was small",
"PURPOSE Fit elderly patients with advanced non-small-cell lung cancer ( NSCLC ) benefit from platinum-based , two-drug chemotherapy . Bevacizumab ( B ) in combination with carboplatin ( C ) and paclitaxel ( P ) improves survival for advanced , nonsquamous NSCLC , as evidence d in Eastern Cooperative Oncology Group ( ECOG ) 4599 . We conducted a subset analysis of ECOG 4599 to determine the outcome for elderly patients . PATIENTS AND METHODS ECOG 4599 r and omly assigned patients with advanced nonsquamous NSCLC to PC or to PCB . We analyzed outcome in patients who were at least 70 years of age at the time of study entry . Patient characteristics , efficacy , and toxicity data were compared between PC and PCB for the elderly . Outcomes for elderly and younger patients ( treated with PCB were also compared . RESULTS Among elderly patients ( n = 224 ; 26 % ) , there was a trend towards higher response rate ( 29 % v 17 % ; P = .067 ) and progression-free survival ( 5.9 v 4.9 months ; P = .063 ) with PCB compared with PC , although overall survival ( PCB = 11.3 months ; PC = 12.1 months ; P = .4 ) was similar . Grade 3 to 5 toxicities occurred in 87 % of elderly patients with PCB versus 61 % with PC ( P deaths in the PCB arm compared with two with PC . Elderly patients had higher incidence of grade 3 to 5 neutropenia , bleeding , and proteinuria with PCB compared with younger patients . CONCLUSION In elderly NSCLC patients , PCB was associated with a higher degree of toxicity , but no obvious improvement in survival compared with PC . Data from this unplanned , retrospective analysis justify prospect i ve evaluation of the therapeutic index of PCB regimen in elderly patients",
"Purpose ARCHER 1050 , a r and omized , open-label , phase III study of dacomitinib versus gefitinib in treatment-naïve patients with advanced non-small-cell lung cancer ( NSCLC ) and activating mutations in EGFR , reported significant improvement in progression-free survival with dacomitinib . The mature overall survival ( OS ) analysis for the intention-to-treat population is presented here . Patients and Methods In this multinational , multicenter study , patients age 18 years or older ( ≥ 20 years in Japan and Korea ) who had an Eastern Cooperative Oncology Group performance status of 0 or 1 and newly diagnosed NSCLC with activating mutations in EGFR ( exon 19 deletion or exon 21 L858R ) were enrolled and r and omly assigned in a 1:1 manner to dacomitinib ( n = 227 ) or gefitinib ( n = 225 ) . R and om assignment was stratified by race ( Japanese , Chinese , other East Asian , or non-Asian ) and EGFR mutation type . The final OS analysis was conducted with a data cutoff date of February 17 , 2017 ; at that time 220 deaths ( 48.7 % ) were observed . Results During a median follow-up time of 31.3 months , 103 ( 45.4 % ) and 117 ( 52.0 % ) deaths occurred in the dacomitinib and gefitinib arms , respectively . The estimated hazard ratio for OS was 0.760 ( 95 % CI , 0.582 to 0.993 ; two-sided P = .044 ) . The median OS was 34.1 months with dacomitinib versus 26.8 months with gefitinib . The OS probabilities at 30 months were 56.2 % and 46.3 % with dacomitinib and gefitinib , respectively . Preliminary subgroup analyses for OS that are based on baseline characteristics were consistent with the primary OS analysis . Conclusion In patients with advanced NSCLC and EGFR activating mutations , dacomitinib is the first second-generation epidermal growth factor receptor tyrosine kinase inhibitor ( TKI ) to show significant improvement in OS in a phase III r and omized study compared with a st and ard-of-care TKI . Dacomitinib should be considered one of the st and ard treatment options for these patients",
"BACKGROUND Alectinib -- a highly selective , CNS-active , ALK inhibitor-showed promising clinical activity in crizotinib-naive and crizotinib-resistant patients with ALK-rearranged ( ALK-positive ) non-small-cell lung cancer ( NSCLC ) . We aim ed to assess the safety and efficacy of alectinib in patients with ALK-positive NSCLC who progressed on previous crizotinib . METHODS We did a phase 2 study at 27 centres in the USA and Canada . We enrolled patients aged 18 years or older with stage IIIB-IV , ALK-positive NSCLC who had progressed after crizotinib . Patients were treated with oral alectinib 600 mg twice daily until progression , death , or withdrawal . The primary endpoint was the proportion of patients achieving an objective response by an independent review committee using Response Evaluation Criteria in Solid Tumors , version 1.1 . Response endpoints were assessed in the response-evaluable population ( ie , patients with measurable disease at baseline who received at least one dose of study drug ) , and efficacy and safety analyses were done in the intention-to-treat population ( all enrolled patients ) . This study is registered with Clinical Trials.gov , number NCT01871805 . The study is ongoing and patients are still receiving treatment . FINDINGS Between Sept 4 , 2013 , and Aug 4 , 2014 , 87 patients were enrolled into the study ( intention-to-treat population ) . At the time of the primary analysis ( median follow-up 4·8 months [ IQR 3·3 - 7·1 ] ) , 33 of 69 patients with measurable disease at baseline had a confirmed partial response ; thus , the proportion of patients achieving an objective response by the independent review committee was 48 % ( 95 % CI 36 - 60 ) . Adverse events were predominantly grade 1 or 2 , most commonly constipation ( 31 [ 36 % ] ) , fatigue ( 29 [ 33 % ] ) , myalgia 21 [ 24 % ] ) , and peripheral oedema 20 [ 23 % ] ) . The most common grade 3 and 4 adverse events were changes in laboratory values , including increased blood creatine phosphokinase ( seven [ 8 % ] ) , increased alanine aminotransferase ( five [ 6 % ] ) , and increased aspartate aminotransferase ( four [ 5 % ] ) . Two patients died : one had a haemorrhage ( judged related to study treatment ) , and one had disease progression and a history of stroke ( judged unrelated to treatment ) . INTERPRETATION Alectinib showed clinical activity and was well tolerated in patients with ALK-positive NSCLC who had progressed on crizotinib . Therefore , alectinib could be a suitable treatment for patients with ALK-positive disease who have progressed on crizotinib . FUNDING F Hoffmann-La Roche",
"IMPORTANCE Targeting oncogenic drivers ( genomic alterations critical to cancer development and maintenance ) has transformed the care of patients with lung adenocarcinomas . The Lung Cancer Mutation Consortium was formed to perform multiplexed assays testing adenocarcinomas of the lung for drivers in 10 genes to enable clinicians to select targeted treatments and enroll patients into clinical trials . OBJECTIVES To determine the frequency of oncogenic drivers in patients with lung adenocarcinomas and to use the data to select treatments targeting the identified driver(s ) and measure survival . DESIGN , SETTING , AND PARTICIPANTS From 2009 through 2012 , 14 sites in the United States enrolled patients with metastatic lung adenocarcinomas and a performance status of 0 through 2 and tested their tumors for 10 drivers . Information was collected on patients , therapies , and survival . INTERVENTIONS Tumors were tested for 10 oncogenic drivers , and results were used to select matched targeted therapies . MAIN OUTCOMES AND MEASURES Determination of the frequency of oncogenic drivers , the proportion of patients treated with genotype-directed therapy , and survival . RESULTS From 2009 through 2012 , tumors from 1007 patients were tested for at least 1 gene and 733 for 10 genes ( patients with full genotyping ) . An oncogenic driver was found in 466 of 733 patients ( 64 % ) . Among these 733 tumors , 182 tumors ( 25 % ) had the KRAS driver ; sensitizing EGFR , 122 ( 17 % ) ; ALK rearrangements , 57 ( 8 % ) ; other EGFR , 29 ( 4 % ) ; 2 or more genes , 24 ( 3 % ) ; ERBB2 ( formerly HER2 ) , 19 ( 3 % ) ; BRAF , 16 ( 2 % ) ; PIK3CA , 6 ( median survival was 3.5 years ( interquartile range [ IQR ] , 1.96 - 7.70 ) for the 260 patients with an oncogenic driver and genotype-directed therapy compared with 2.4 years ( IQR , 0.88 - 6.20 ) for the 318 patients with any oncogenic driver(s ) who did not receive genotype-directed therapy ( propensity score-adjusted hazard ratio , 0.69 [ 95 % CI , 0.53 - 0.9 ] , P = .006 ) . CONCLUSIONS AND RELEVANCE Actionable drivers were detected in 64 % of lung adenocarcinomas . Multiplexed testing aided physicians in selecting therapies . Although individuals with drivers receiving a matched targeted agent lived longer , r and omized trials are required to determine if targeting therapy based on oncogenic drivers improves survival . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01014286",
"Background Osimertinib is an oral , third‐generation , irreversible epidermal growth factor receptor tyrosine kinase inhibitor ( EGFR‐TKI ) that selectively inhibits both EGFR‐TKI – sensitizing and EGFR T790 M resistance mutations . We compared osimertinib with st and ard EGFR‐TKIs in patients with previously untreated , EGFR mutation – positive advanced non – small‐cell lung cancer ( NSCLC ) . Methods In this double‐blind , phase 3 trial , we r and omly assigned 556 patients with previously untreated , EGFR mutation – positive ( exon 19 deletion or L858R ) advanced NSCLC in a 1:1 ratio to receive either osimertinib ( at a dose of 80 mg once daily ) or a st and ard EGFR‐TKI ( gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily ) . The primary end point was investigator‐assessed progression‐free survival . Results The median progression‐free survival was significantly longer with osimertinib than with st and ard EGFR‐TKIs ( 18.9 months vs. 10.2 months ; hazard ratio for disease progression or death , 0.46 ; 95 % confidence interval [ CI ] , 0.37 to 0.57 ; P The objective response rate was similar in the two groups : 80 % with osimertinib and 76 % with st and ard EGFR‐TKIs ( odds ratio , 1.27 ; 95 % CI , 0.85 to 1.90 ; P=0.24 ) . The median duration of response was 17.2 months ( 95 % CI , 13.8 to 22.0 ) with osimertinib versus 8.5 months ( 95 % CI , 7.3 to 9.8 ) with st and ard EGFR‐TKIs . Data on overall survival were immature at the interim analysis ( 25 % maturity ) . The survival rate at 18 months was 83 % ( 95 % CI , 78 to 87 ) with osimertinib and 71 % ( 95 % CI , 65 to 76 ) with st and ard EGFR‐TKIs ( hazard ratio for death , 0.63 ; 95 % CI , 0.45 to 0.88 ; P=0.007 [ nonsignificant in the interim analysis ] ) . Adverse events of grade 3 or higher were less frequent with osimertinib than with st and ard EGFR‐TKIs ( 34 % vs. 45 % ) . Conclusions Osimertinib showed efficacy superior to that of st and ard EGFR‐TKIs in the first‐line treatment of EGFR mutation – positive advanced NSCLC , with a similar safety profile and lower rates of serious adverse events . ( Funded by AstraZeneca ; FLAURA Clinical Trials.gov number , NCT02296125 .",
"BACKGROUND First-line chemotherapy for advanced non-small-cell lung cancer ( NSCLC ) is usually limited to four to six cycles . Maintenance therapy can delay progression and prolong survival . The oral epidermal growth factor receptor ( EGFR ) tyrosine-kinase inhibitor erlotinib has proven efficacy and tolerability in second-line NSCLC . We design ed the phase 3 , placebo-controlled Sequential Tarceva in Unresectable NSCLC ( SATURN ; BO18192 ) study to assess use of erlotinib as maintenance therapy in patients with non-progressive disease following first-line platinum-doublet chemotherapy . METHODS Between December , 2005 , and May , 2008 , 1949 patients were included in the run-in phase ( four cycles of platinum-based chemotherapy ) . At the end of the run-in phase , 889 patients who did not have progressive disease were entered into the main study , and were r and omly allocated using a 1:1 adaptive r and omisation method through a third-party interactive voice response system to receive erlotinib ( 150 mg/day ; n=438 ) or placebo ( n=451 ) until progression or unacceptable toxicity . Patients were stratified by EGFR immunohistochemistry status , stage , Eastern Cooperative Oncology Group performance status , chemotherapy regimen , smoking history , and region . Co- primary endpoints were progression-free survival ( PFS ) in all analysable patients irrespective of EGFR status , and PFS in patients whose tumours had EGFR protein overexpression , as determined by immunohistochemistry . This study is registered with www . Clinical Trials.gov , number NCT00556712 . FINDINGS 884 patients were analysable for PFS ; 437 in the erlotinib group and 447 in the placebo group . After a median follow-up of 11.4 months for the erlotinib group and 11.5 months for the placebo group , median PFS was significantly longer with erlotinib than with placebo : 12.3 weeks for patients in the erlotinib group versus 11.1 weeks for those in the placebo group ( HR 0.71 , 95 % CI 0.62 - 0.82 ; p ) . PFS was also significantly longer in patients with EGFR-positive immunohistochemistry who were treated with erlotinib ( n=307 ) compared with EGFR-positive patients given placebo ( n=311 ; median PFS 12.3 weeks in the erlotinib group vs 11.1 weeks in the placebo group ; HR 0.69 , 0.58 - 0.82 ; p grade 3 or higher adverse events were rash ( 37 [ 9 % ] of 443 patients in the erlotinib group vs none of 445 in the placebo group ) and diarrhoea ( seven [ 2 % ] of 443 patients vs none of 445 ) . Serious adverse events were reported in 47 patients ( 11 % ) on erlotinib compared with 34 patients ( 8 % ) on placebo . The most common serious adverse event was pneumonia ( seven cases [ 2 % ] with erlotinib and four [ < 1 % ] with placebo ) . INTERPRETATION Maintenance therapy with erlotinib for patients with NSCLC is well tolerated and significantly prolongs PFS compared with placebo . First-line maintenance with erlotinib could be considered in patients who do not progress after four cycles of chemotherapy . FUNDING F Hoffmann-La Roche",
"BACKGROUND Erlotinib is registered for treatment of all patients with advanced non-small-cell lung cancer ( NSCLC ) . However , its efficacy for treatment of patients whose tumours are EGFR wild-type-which includes most patients -is still contentious . We assessed the efficacy of erlotinib compared with a st and ard second-line chemotherapy in such patients . METHODS We did this r and omised controlled trial in 52 Italian hospitals . We enrolled patients who had metastatic NSCLC , had had platinum-based chemotherapy , and had wild-type EGFR as assessed by direct sequencing . Patients were r and omly assigned central ly ( 1:1 ) to receive either erlotinib orally 150 mg/day or docetaxel intravenously 75 mg/m(2 ) every 21 days or 35 mg/m(2 ) on days 1 , 8 , and 15 , every 28 days . R and omisation was stratified by centre , stage , type of first-line chemotherapy , and performance status . Patients and investigators who gave treatments or assessed outcomes were not masked to treatment allocation , investigators who analysed results were . The primary endpoint was overall survival in the intention-to-treat population . The study is registered at Clinical Trials.gov , number NCT00637910 . FINDINGS We screened 702 patients , of whom we genotyped 540 . 222 patients were enrolled ( 110 assigned to docetaxel vs 112 assigned to erlotinib ) . Median overall survival was 8·2 months ( 95 % CI 5·8 - 10·9 ) with docetaxel versus 5·4 months ( 4·5 - 6·8 ) with erlotinib ( adjusted hazard ratio [ HR ] 0·73 , 95 % CI 0·53 - 1·00 ; p=0·05 ) . Progression-free survival was significantly better with docetaxel than with erlotinib : median progression-free survival was 2·9 months ( 95 % CI 2·4 - 3·8 ) with docetaxel versus 2·4 months ( 2·1 - 2·6 ) with erlotinib ( adjusted HR 0·71 , 95 % CI 0·53 - 0·95 ; p=0·02 ) . The most common grade 3 - 4 toxic effects were : low absolute neutrophil count ( 21 [ 20 % ] of 104 in the docetaxel group vs none of 107 in the erlotinib group ) , skin toxic effects ( none vs 15 [ 14 % ] ) , and asthenia ( ten [ 10 % ] vs six [ 6 % ] ) . INTERPRETATION Our results show that chemotherapy is more effective than erlotinib for second-line treatment for previously treated patients with NSCLC who have wild-type EGFR tumours",
"BACKGROUND Most patients with non-small-cell lung cancer tumours that have EGFR mutations have deletion mutations in exon 19 or the Leu858Arg point mutation in exon 21 , or both ( ie , common mutations ) . However , a subset of patients ( 10 % ) with mutations in EGFR have tumours that harbour uncommon mutations . There is a paucity of data regarding the sensitivity of these tumours to EGFR inhibitors . Here we present data for the activity of afatinib in patients with advanced non-small-cell lung cancer that have tumours harbouring uncommon EGFR mutations . METHODS In this post-hoc analysis , we used prospect ively collected data from tyrosine kinase inhibitor-naive patients with EGFR mutation-positive advanced ( stage IIIb-IV ) lung adenocarcinomas who were given afatinib in a single group phase 2 trial ( LUX-Lung 2 ) , and r and omised phase 3 trials ( LUX-Lung 3 and LUX-Lung 6 ) . Analyses were done in the intention-to-treat population , including all r and omly assigned patients with uncommon EGFR mutations . The type of EGFR mutation ( exon 19 deletion [ del19 ] , Leu858Arg point mutation in exon 21 , or other ) and ethnic origin ( LUX-Lung 3 only ; Asian vs non-Asian ) were pre-specified stratification factors in the r and omised trials . We categorised all uncommon mutations as : point mutations or duplications in exons 18 - 21 ( group 1 ) ; de-novo Thr790Met mutations in exon 20 alone or in combination with other mutations ( group 2 ) ; or exon 20 insertions ( group 3 ) . We also assessed outcomes in patients with the most frequent uncommon mutations , Gly719Xaa , Leu861Gln , and Ser768Ile , alone or in combination with other mutations . Response was established by independent radiological review . These trials are registered with Clinical Trials.gov , numbers NCT00525148 , NCT00949650 , and NCT01121393 . FINDINGS Of 600 patients given afatinib across the three trials , 75 ( 12 % ) patients had uncommon EGFR mutations ( 38 in group 1 , 14 in group 2 , 23 in group 3 ) . 27 ( 71·1 % , 95 % CI 54·1 - 84·6 ) patients in group 1 had objective responses , as did two ( 14·3 % , 1·8 - 42·8 ) in group 2 and two ( 8·7 % , 1·1 - 28·0 ) in group 3 . Median progression-free survival was 10·7 months ( 95 % CI 5·6 - 14·7 ) in group 1 , 2·9 months ( 1·2 - 8·3 ) in group 2 ; and 2·7 months ( 1·8 - 4·2 ) in group 3 . Median overall survival was 19·4 months ( 95 % CI 16·4 - 26·9 ) in group 1 , 14·9 months ( 8·1 - 24·9 ) in group 2 , and 9·2 months ( 4·1 - 14·2 ) in group 3 . For the most frequent uncommon mutations , 14 ( 77·8 % , 95 % CI 52·4 - 93·6 ) patients with Gly719Xaa had an objective response , as did nine ( 56·3 % , 29·9 - 80·2 ) with Leu861Gln , and eight ( 100·0 % , 63·1 - 100·0 ) with Ser768Ile . INTERPRETATION Afatinib was active in non-small-cell lung cancer tumours that harboured certain types of uncommon EGFR mutations , especially Gly719Xaa , Leu861Gln , and Ser768Ile , but less active in other mutations types . Clinical benefit was lower in patients with de-novo Thr790Met and exon 20 insertion mutations . These data could help inform clinical decisions for patients with non-small-cell lung cancer harbouring uncommon EGFR mutations . FUNDING Boehringer Ingelheim",
"AIMS Retrospective analyses from first-line clinical studies in advanced non-small cell lung cancer ( NSCLC ) have reported conflicting results on progression-free survival ( PFS ) and overall survival benefits with the addition of bevacizumab to chemotherapy in elderly patients . Here we report effectiveness and safety outcomes by age subgroup for patients with NSCLC in the ARIES observational cohort study . MATERIAL S AND METHODS ARIES enrolled patients with advanced non-squamous NSCLC who received first-line bevacizumab-containing treatment per physician 's choice . Kaplan-Meier estimates were used to calculate medians and 95 % confidence intervals for PFS and overall survival for patients aged RESULTS In total , 1967 patients receiving first-line treatment with bevacizumab and chemotherapy were enrolled . The median PFS and overall survival values were 6.4 ( 95 % confidence interval = 6.0 - 6.8 ) and 14.2 ( 95 % confidence interval = 12.7 - 15.2 ) months for patients aged the median PFS and overall survival values were 6.6 ( 95 % confidence interval = 6.3 - 6.9 ) and 13.5 ( 95 % confidence interval = 12.6 - 14.5 ) months , respectively , and 6.6 ( 95 % confidence interval = 5.9 - 7.1 ) and 11.6 ( 95 % confidence interval = 10.0 - 12.5 ) months , respectively , for patients ≥75 years . Incidence proportions of bevacizumab-associated adverse events were generally similar across all age groups . CONCLUSIONS Data from the ARIES study suggest that treatment with bevacizumab in combination with chemotherapy is a viable first-line treatment option for elderly bevacizumab-eligible patients with advanced non-squamous NSCLC",
"PURPOSE In the phase III PARAMOUNT trial , pemetrexed continuation maintenance therapy reduced the risk of disease progression versus placebo ( hazard ratio [ HR ] , 0.62 ; 95 % CI , 0.49 to 0.79 ; P overall survival ( OS ) and up date d safety data . PATIENTS AND METHODS In all , 939 patients with advanced nonsquamous non-small-cell lung cancer ( NSCLC ) received four cycles of pemetrexed-cisplatin induction therapy ; then , 539 patients with no disease progression and Eastern Cooperative Oncology Group performance status 0 or 1 were r and omly assigned ( 2:1 ) to maintenance pemetrexed ( 500 mg/m(2 ) on day 1 of 21-day cycles ; n = 359 ) or placebo ( n = 180 ) . Log-rank test compared OS between arms as measured from r and om assignment ( α = .0498 ) . RESULTS The mean number of maintenance cycles was 7.9 ( range , one to 44 ) for pemetrexed and 5.0 ( range , one to 38 ) for placebo . After 397 deaths ( pemetrexed , 71 % ; placebo , 78 % ) and a median follow-up of 24.3 months for alive patients ( 95 % CI , 23.2 to 25.1 months ) , pemetrexed therapy result ed in a statistically significant 22 % reduction in the risk of death ( HR , 0.78 ; 95 % CI , 0.64 to 0.96 ; P = .0195 ; median OS : pemetrexed , 13.9 months ; placebo , 11.0 months ) . Survival on pemetrexed was consistently improved for all patient subgroups , including induction response : complete/partial responders ( n = 234 ) OS HR , 0.81 ; 95 % CI , 0.59 to 1.11 and stable disease ( n = 285 ) OS HR , 0.76 ; 95 % CI , 0.57 to 1.01 ) . Postdiscontinuation therapy use was similar : pemetrexed , 64 % ; placebo , 72 % . No new safety findings emerged . Drug-related grade 3 to 4 anemia , fatigue , and neutropenia were significantly higher in pemetrexed-treated patients . CONCLUSION Pemetrexed continuation maintenance therapy is well-tolerated and offers superior OS compared with placebo , further demonstrating that it is an efficacious treatment strategy for patients with advanced nonsquamous NSCLC and good performance status who did not progress during pemetrexed-cisplatin induction therapy "
] |
4116b8e8-06ff-11f0-808a-c43d1ab1c353
|
CONTEXT Multiple risk behaviors are common and associated with developing chronic conditions such as heart disease , cancer , or Type 2 diabetes . A systematic review , meta- analysis , and meta-regression of the effectiveness of multiple risk behavior interventions was conducted . EVIDENCE ACQUISITION Six electronic data bases including MEDLINE , EMBASE , and PsycINFO were search ed to August 2016 . RCTs of non-pharmacologic interventions in general adult population s were selected . Studies targeting specific at-risk groups ( such as people screened for cardiovascular risk factors or obesity ) were excluded . Studies were screened independently . Study characteristics and outcomes were extracted and risk of bias assessed by one research er and checked by another . The Behaviour Change Wheel and Oxford Implementation Index were used to code intervention content and context . EVIDENCE SYNTHESIS R and om-effects meta-analyses were conducted . Sixty-nine trials involving 73,873 individuals were included . Interventions mainly comprised education and skills training and were associated with modest improvements in most risk behaviors : increased fruit and vegetable intake ( 0.31 portions , 95 % CI=0.17 , 0.45 ) and physical activity ( st and ardized mean difference , 0.25 ; 95 % CI=0.13 , 0.38 ) , and reduced fat intake ( st and ardized mean difference , -0.24 ; 95 % CI=-0.36 , -0.12 ) . Although reductions in smoking were found ( OR=0.78 , 95 % CI=0.68 , 0.90 ) , they appeared to be negatively associated with improvement in other behaviors ( such as diet and physical activity ) . Preliminary evidence suggests that sequentially changing smoking alongside other risk behaviors was more effective than simultaneous change . But most studies assessed simultaneous rather than sequential change in risk behaviors ; therefore , comparisons are sparse . Follow-up period and intervention characteristics impacted effectiveness for some outcomes . CONCLUSIONS Interventions comprising education ( e.g. , providing information about behaviors associated with health risks ) and skills training ( e.g. , teaching skills that equip participants to engage in less risky behavior ) and targeting multiple risk behaviors concurrently are associated with small changes in diet and physical activity . Although on average smoking was reduced , it appeared changes in smoking were negatively associated with changes in other behaviors , suggesting it may not be optimal to target smoking simultaneously with other risk behaviors
|
[
"Purpose . Examine the effects of three iterative tailored feedback letters addressing smoking ; physical activity ; and fruit , vegetable , and fat intake , and test the additional effects of providing feedback on action plans . Design . A tailored , print-based intervention was developed and tested in a r and omized control trial with a posttest after 9 months . Setting . A total of 2827 respondents agreed to participate . They were recruited from a r and om sample of 35,000 addresses obtained through the Dutch national telephone company . Subjects . The mean age was 49 years , and 55 % were female . Intervention . The experimental group received three printed tailored letters , and the control group received three printed generic letters . Respondents from the experimental group r and omly received either a third letter with tailored information or tailored information and action-planning feedback . Measures . The question naire assessed physical activity ; smoking ; consumption of fruit , vegetables and fat ; motivational determinants ; action plans ; and demographics . Results . Tailored information result ed in more improvement over time than generic information for the intake of fruit , vegetables , and fat and for physical activity . No differences between the conditions were found for smoking because of high cessation rates in all conditions . Action-planning feedback did not increase the effects . Conclusions . Tailored lifestyle information can be effective for adults in changing nutrition behavior and physical activity",
"Background This paper explores smoking cessation participants ’ perceptions of attempting weight management alongside smoking cessation within the context of a health improvement intervention implemented in Glasgow , Scotl and . Methods One hundred and thirty-eight participants were recruited from smoking cessation classes in areas of multiple deprivation in Glasgow and r and omised to intervention , receiving dietary advice , or to control groups . The primary outcome of the study was to determine the % change in body weight . Semi-structured interviews were conducted with a purposive sample of 15 intervention and 15 control participants at weeks 6 ( during the intervention ) and 24 ( at the end of the intervention ) . The current paper , though predominantly qualitative , links perceptions of behaviour modification to % weight change and cessation rates at week 24 thereby enabling a better underst and ing of the mediators influencing multiple behaviour change . Results Our findings suggest that participants who perceive separate behaviour changes as part of a broader approach to a healthier lifestyle , and hence attempt behaviour changes concurrently , may be at comparative advantage in positively achieving dual outcomes . Conclusions These findings highlight the need to assess participants ’ preference for attempting multiple behaviour changes sequentially or simultaneously in addition to assessing their readiness to change . Further testing of this hypothesis is warranted . Trial Registration IS RCT",
"Objective To quantify the potential combined impact of four health behaviours on incidence of stroke in men and women living in the general community . Design Population based prospect i ve study ( EPIC-Norfolk ) . Setting Norfolk , United Kingdom . Participants 20 040 men and women aged 40 - 79 with no known stroke or myocardial infa rct ion at baseline survey in 1993 - 7 , living in the general community , and followed up to 2007 . Main outcome measure Participants scored one point for each health behaviour : current non-smoking , physically not inactive , moderate alcohol intake ( 1 - 14 units a week ) , and plasma concentration of vitamin C ≥50 µmol/l , indicating fruit and vegetable intake of at least five servings a day , for a total score ranging from 0 to 4 . Results There were 599 incident strokes over 229 993 person years of follow-up ; the average follow-up was 11.5 years . After adjustment for age , sex , body mass index ( BMI ) , systolic blood pressure , cholesterol concentration , history of diabetes and aspirin use , and social class , compared with people with the four health behaviours the relative risks for stroke for men and women were 1.15 ( 95 % confidence interval 0.89 to 1.49 ) for three health behaviours , 1.58 ( 1.22 to 2.05 ) for two , 2.18 ( 1.63 to 2.92 ) for one , and 2.31 ( 1.33 to 4.02 ) for none ( P predict more than a twofold difference in incidence of stroke in men and women",
"Background We report the main results , among adults , of a cluster-r and omised-trial of Well London , a community-engagement programme promoting healthy eating , physical activity and mental well-being in deprived neighbourhoods . The hypothesis was that benefits would be neighbourhood-wide , and not restricted to intervention participants . The trial was part of a multicomponent process/ outcome evaluation which included non-experimental components ( self-reported behaviour change amongst participants , case studies and evaluations of individual projects ) which suggested health , well-being and social benefits to participants . Methods Twenty matched pairs of neighbourhoods in London were r and omised to intervention/control condition . Primary outcomes ( five portions fruit/vegetables/day ; 5 × 30 m of moderate intensity physical activity/week , abnormal General Health Question naire (GHQ)-12 score and Warwick – Edinburgh Mental Well-being Scale ( WEMWBS ) score ) were measured by postintervention question naire survey , among 3986 adults in a r and om sample of households across neighbourhoods . Results There was no evidence of impact on primary outcomes : healthy eating ( relative risk [ RR ] 1.04 , 95 % CI 0.93 to 1.17 ) ; physical activity ( RR:1.01 , 95 % CI 0.88 to 1.16 ) ; abnormal GHQ12 ( RR:1.15 , 95 % CI 0.84 to 1.61 ) ; WEMWBS ( mean difference [ MD ] : −1.52 , 95 % CI −3.93 to 0.88 ) . There was evidence of impact on some secondary outcomes : reducing unhealthy eating-score ( MD : −0.14 , 95 % CI −0.02 to 0.27 ) and increased perception that people in the neighbourhood pulled together ( RR : 1.92 , 95 % CI 1.12 to 3.29 ) . Conclusions The trial findings do not provide evidence supporting the conclusion of non-experimental components of the evaluation that intervention improved health behaviours , well-being and social outcomes . Low participation rates and population churn likely compromised any impact of the intervention . Imprecise estimation of outcomes and sampling bias may also have influenced findings . There is a need for greater investment in refining such programmes before implementation ; new methods to underst and , longitudinally different pathways residents take through such interventions and their outcomes , and new theories of change that apply to each pathway",
"PURPOSE To investigate the long-term ( 6- and 12-month ) effects of the Strong Healthy Women intervention on health-related behaviors , weight and body mass index ( BMI ) , and weight gain during pregnancy . Strong Healthy Women is a small-group behavioral intervention for pre- and interconceptional women design ed to modify key risk factors for adverse pregnancy outcomes ; pretest-posttest findings from a r and omized , controlled trial have been previously reported . The following questions are addressed : 1 ) were significant pretest-posttest changes in health-related behaviors ( previously reported ) maintained over the 12-month follow-up period ; 2 ) did the intervention impact weight and BMI over the 12-month follow-up period ; and 3 ) did the intervention impact pregnancy weight gain for those who gave birth during the follow-up period ? METHODS Data are from 6- and 12-month follow-up telephone interviews of women in the original trial of the Strong Healthy Women intervention ( n = 362 ) and from birth records for singleton births ( n = 45 ) during the 12-month follow-up period . Repeated measures regression was used to evaluate intervention effects . MAIN FINDINGS At the 12-month follow-up , participants in the Strong Healthy Women intervention were significantly more likely than controls to use a daily multivitamin with folic acid and to have lower weight and BMI . The intervention 's effect on reading food labels for nutritional values dropped off between the 6- and 12-month follow-up . Among those who gave birth to singletons during the follow-up period , women who participated in the intervention had lower average pregnancy weight gain compared with controls . Although the intervention effect was no longer significant when controlling for pre-pregnancy obesity , the adjusted means show a trend toward lower weight gain in the intervention group . CONCLUSION These findings provide important evidence that the Strong Healthy Women behavior change intervention is effective in modifying important risk factors for adverse pregnancy outcomes and may improve an important pregnancy outcome , weight gain during pregnancy . Because the intervention seems to help women manage their weight in the months after the intervention and during pregnancy , it may be an effective obesity prevention strategy for women before , during , and after the transition to motherhood",
"Background Computer tailoring and motivational interviewing show promise in promoting lifestyle change , despite few head-to-head comparative studies . Purpose Vitalum is a r and omized controlled trial in which the efficacy of these methods was compared in changing physical activity and fruit and vegetable consumption in middle-aged Dutch adults . Methods Participants ( n = 1,629 ) were recruited via 23 general practice s and r and omly received either four tailored print letters , four motivational telephone calls , two of each type of intervention , or no information . The primary outcomes were absolute change in self-reported physical activity and fruit and vegetable consumption . Results All three intervention groups ( i.e. , the tailored letters , the motivational calls , and the combined version ) were equally and significantly more effective than the control group in increasing physical activity ( hours/day ) , intake of fruit ( servings/day ) , and consumption of vegetables ( grams/day ) from baseline to the intermediate measurement ( week 25 ) , follow-up 1 ( week 47 ) and 2 ( week 73 ) . Effect sizes ( Cohen ’s d ) ranged from 0.15 to 0.18 . Participants rated the interventions positively ; interviews were more positively evaluated than letters . Conclusions Tailored print communication and telephone motivational interviewing or their combination are equally successful in changing multiple behaviors",
"Background Few studies have evaluated how to combine dietary and physical activity ( PA ) interventions to enhance adherence . Purpose We tested how sequential versus simultaneous diet plus PA interventions affected behavior changes . Methods Two hundred participants over age 44 years not meeting national PA and dietary recommendations ( daily fruit and vegetable servings and percent of calories from saturated fat ) were r and omized to one of four 12-month telephone interventions : sequential ( exercise first or diet first ) , simultaneous , or attention control . At 4 months , the other health behavior was added in the sequential arms . Results Ninety-three percent of participants were retained through 12 months . At 4 months , only exercise first improved PA , and only the simultaneous and diet-first interventions improved dietary variables . At 12 months , mean levels of all behaviors in the simultaneous arm met recommendations , though not in the exercise- and diet-first arms . Conclusions We observed a possible behavioral suppression effect of early dietary intervention on PA that merits investigation",
"Background This intervention aim ed to ascertain whether a low-cost , accessible , physical activity and nutrition program could improve physical activity and nutrition behaviours of insufficiently active 60–70 year olds residing in Perth , Australia . Methods A 6-month home-based r and omised controlled trial was conducted on 478 older adults ( intervention , n = 248 ; control , n = 230 ) of low to medium socioeconomic status . Both intervention and control groups completed postal question naires at baseline and post-program , but only the intervention participants received project material s. A modified fat and fibre question naire measured nutritional behaviours , whereas physical activity was measured using the International Physical Activity Question naire . Generalised estimating equation models were used to assess the repeated outcomes over both time points . Results The final sample consisted of 176 intervention participants and 199 controls ( response rate 78.5 % ) with complete data . After controlling for demographic and other confounding factors , the intervention group demonstrated increased participation in strength exercise ( p walking ( p = 0.029 ) and vigorous activity ( p = 0.015 ) , together with significant reduction in mean sitting time ( p nutritional behaviours for the intervention group were also evident in terms of fat avoidance ( p fat intake ( p = 0.021 ) and prevalence of frequent fruit intake ( p = 0.008 ) . Conclusions A minimal contact , low-cost and home-based physical activity program can positively influence seniors ’ physical activity and nutrition behaviours . Trial registration anzctr.org.au Identifier :",
"Background Web-based computer-tailored interventions for multiple health behaviors can have a significant public health impact . Yet , few r and omized controlled trials have tested this assumption . Objective The objective of this paper was to test the effects of a sequential and simultaneous Web-based tailored intervention on multiple lifestyle behaviors . Methods A r and omized controlled trial was conducted with 3 tailoring conditions ( ie , sequential , simultaneous , and control conditions ) in the Netherl and s in 2009 - 2012 . Follow-up measurements took place after 12 and 24 months . The intervention content was based on the I-Change model . In a health risk appraisal , all respondents ( N=5055 ) received feedback on their lifestyle behaviors that indicated whether they complied with the Dutch guidelines for physical activity , vegetable consumption , fruit consumption , alcohol intake , and smoking . Participants in the sequential ( n=1736 ) and simultaneous ( n=1638 ) conditions received tailored motivational feedback to change unhealthy behaviors one at a time ( sequential ) or all at the same time ( simultaneous ) . Mixed model analyses were performed as primary analyses ; regression analyses were done as sensitivity analyses . An overall risk score was used as outcome measure , then effects on the 5 individual lifestyle behaviors were assessed and a process evaluation was performed regarding exposure to and appreciation of the intervention . Results Both tailoring strategies were associated with small self-reported behavioral changes . The sequential condition had the most significant effects compared to the control condition after 12 months ( T1 , effect size=0.28 ) . After 24 months ( T2 ) , the simultaneous condition was most effective ( effect size=0.18 ) . All 5 individual lifestyle behaviors changed over time , but few effects differed significantly between the conditions . At both follow-ups , the sequential condition had significant changes in smoking abstinence compared to the simultaneous condition ( T1 effect size=0.31 ; T2 effect size=0.41 ) . The sequential condition was more effective in decreasing alcohol consumption than the control condition at 24 months ( effect size=0.27 ) . Change was predicted by the amount of exposure to the intervention ( total visiting time : beta=–.06 ; P=.01 ; total number of visits : beta=–.11 ; P appreciated well by respondents without significant differences between conditions . Conclusions Although evidence was found for the effectiveness of both programs , no simple conclusive finding could be drawn about which intervention mode was more effective . The best kind of intervention may depend on the behavior that is targeted or on personal preferences and motivation . Further research is needed to identify moderators of intervention effectiveness . The results need to be interpreted in view of the high and selective dropout rates , multiple comparisons , and modest effect sizes . However , a large number of people were reached at low cost and behavioral change was achieved after 2 years . Trial Registration Nederl and s Trial Register : NTR 2168 ; http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=2168 ( Archived by WebCite at http://www.webcitation.org/6MbUqttYB )",
"AIM To examine whether exercise counselling increases smoking abstinence and reduces tobacco withdrawal and gains in weight and body fat . DESIGN A r and omized controlled trial . SETTING A community-based stop smoking clinic . PARTICIPANTS Two hundred and ninety-nine male and female smokers . INTERVENTION Participants were assigned r and omly to a 7-week smoking cessation programme , including nicotine replacement therapy plus either ( i ) exercise counselling , or ( ii ) health education advice with equal contact time as for the exercise counselling condition . MEASUREMENTS Six weeks of smoking abstinence was confirmed by expired carbon monoxide . FINDINGS There was no significant difference in smoking abstinence between the exercise group ( n = 154 ) and the controls ( n = 145 ) at 6 weeks ( 39.6 % versus 38.6 % ) , nor was there any difference in gains in weight or body fat , although those in the exercise group increased their exercise levels . Exercise participants reported less tension , anxiety and stress than the controls during the first week of smoking abstinence ( P = 0.03 , 0.01 and 0.04 , respectively ) , less irritability throughout 2 weeks of abstinence ( P = 0.03 ) , and less restlessness throughout 3 weeks of abstinence ( P = 0.04 ) . CONCLUSIONS Adding brief exercise counselling to a smoking cessation programme did not increase smoking abstinence or reduce gains in weight or body fat significantly , although exercise levels were raised and there were some beneficial effects on psychological symptoms",
"OBJECTIVE To determine if an interactive , computerized Video Doctor counseling tool improves self-reported diet and exercise in pregnant women . METHODS A r and omized trial comparing a Video Doctor intervention to usual care in ethnically diverse , low-income , English-speaking pregnant women was conducted . Brief messages about diet , exercise , and weight gain were delivered by an actor-portrayed Video Doctor twice during pregnancy . RESULTS In the Video Doctor group ( n=158 ) , there were statistically significant increases from baseline in exercise ( + 28 min ) , intake of fruits and vegetables , whole grains , fish , avocado and nuts , and significant decreases in intake of sugary foods , refined grains , high fat meats , fried foods , solid fats , and fast food . In contrast , there were no changes from baseline for any of these outcomes in the usual care group ( n=163 ) . Nutrition knowledge improved significantly over time in both groups but more so in the Video Doctor group . Clinician-patient discussion s about these topics occurred significantly more frequently in the Video Doctor group . There was no difference in weight gain between groups . CONCLUSION A brief Video Doctor intervention can improve exercise and dietary behaviors in pregnant women . PRACTICE IMPLICATION S The Video Doctor can be integrated into prenatal care to assist clinicians with effective diet and exercise counseling",
"Study objective : There is little guidance on how to select the best available evidence of health effects of social interventions . The aim of this paper was to assess the implication s of setting particular inclusion criteria for evidence synthesis . Design : Analysis of all relevant studies for one systematic review , followed by sensitivity analysis of the effects of selecting studies based on a two dimensional hierarchy of study design and study population . Setting : Case study of a systematic review of the effectiveness of interventions in promoting a population shift from using cars towards walking and cycling . Main results : The distribution of available evidence was skewed . Population level interventions were less likely than individual level interventions to have been studied using the most rigorous study design s ; nearly all of the population level evidence would have been missed if only r and omised controlled trials had been included . Examining the studies that were excluded did not change the overall conclusions about effectiveness , but did identify additional categories of intervention such as health walks and parking charges that merit further research , and provided evidence to challenge assumptions about the actual effects of progressive urban transport policies . Conclusions : Unthinking adherence to a hierarchy of study design as a means of selecting studies may reduce the value of evidence synthesis and reinforce an “ inverse evidence law ” whereby the least is known about the effects of interventions most likely to influence whole population s. Producing generalisable estimates of effect sizes is only one possible objective of evidence synthesis . Mapping the available evidence and uncertainty about effects may also be important",
"BACKGROUND The prevention of initiation of tobacco , alcohol and drug use is a major societal challenge , for which the existing research literature is generally disappointing . This study aim ed to test the effectiveness of adaptation of Motivational Interviewing ( MI ) for universal prevention purpose s , i.e. to prevent initiation of new substance use among non-users , and to reduce risks among existing users . METHODS Cluster r and omised trial with 416 students aged 16 - 19 years old recruited in 12 London Further Education colleges without regard to substance use status . Individualised MI was compared with st and ard practice classroom-delivered Drug Awareness intervention , both delivered over the course of one lesson . Prevalence , initiation and cessation rates for the 3 target behaviours of cigarette smoking , alcohol consumption and cannabis use , along with reductions in use and harm indicators after both 3 and 12 months were assessed . RESULTS This adaptation of MI was not demonstrated to be effective in either intention-to-treat or sub-group analyses for any outcome . Unexpected lower levels of cannabis initiation and prevalence were found in the Drug Awareness control condition . CONCLUSIONS This particular adaptation of MI is ineffective as a universal drug prevention intervention and does not merit further study",
"Objective . To evaluate the effectiveness of a 12-week home-based postal and telephone physical activity and nutrition pilot program for seniors . Methods . The program was delivered by mailed material and telephone calls . The main intervention consisted of a booklet tailored for seniors containing information on dietary guidelines , recommended physical activity levels , and goal setting . Dietary and walking activity outcomes were collected via a self-administered postal question naire pre- and postintervention and analysed using linear mixed regressions . Of the 270 seniors recruited , half were r and omly selected for the program while others served as the control group . Results . The program elicited favourable responses . Postintervention walking for exercise/recreation showed an average gain of 27 minutes per week for the participants in contrast to an average drop of 5 minutes for the controls ( P err and walking for both groups . The intervention group ( n = 114 ) demonstrated a significant increase in fibre intake ( P reduction in fat intake ( P > .05 ) compared to controls ( n = 134 ) . Conclusions . The participants became more aware of their health and wellbeing after the pilot program , which was successful in increasing time spent walking for recreation and improving fibre intake",
"Background Fear of weight gain is a barrier to smoking cessation and significant cause of relapse for many people . The provision of nutritional advice as part of a smoking cessation programme may assist some in smoking cessation and perhaps limit weight gain . The aim of this study was to determine the effect of a structured programme of dietary advice on weight change and food choice , in adults attempting smoking cessation . Methods Cluster r and omised controlled design . Classes r and omised to intervention commenced a 24-week intervention , focussed on improving food choice and minimising weight gain . Classes r and omised to control received “ usual care ” . Results Twenty-seven classes in Greater Glasgow were r and omised between January and August 2008 . Analysis , including those who continued to smoke , showed that actual weight gain and percentage weight gain was similar in both groups . Examination of data for those successful at giving up smoking showed greater mean weight gain in intervention subjects ( 3.9 ( SD 3.1 ) vs. 2.7 ( SD 3.7 ) kg ) . Between group differences were not significant ( p = 0.23 , 95 % CI −0.9 to 3.5 ) . In comparison to baseline improved consumption of fruit and vegetables and breakfast cereal were reported in the intervention group . A higher percentage of control participants continued smoking ( 74 % vs. 66 % ) . Conclusions The intervention was not successful at minimising weight gain in comparison to control but was successful in facilitating some sustained improvements in the dietary habits of intervention participants . Improved quit rates in the intervention group suggest that continued contact with advisors may have reduced anxieties regarding weight gain and encouraged cessation despite weight gain . Research should continue in this area as evidence suggests that the negative effects of obesity could outweigh the health benefits achieved through reductions in smoking prevalence . Trial registration Current Controlled Trials IS RCT",
"PURPOSE This study examined the effects of brief image-based interventions , including a multiple behavior health contract , a one-on-one tailored consultation , and a combined consultation plus contract intervention , for impacting multiple health behaviors of students in a university health clinic . METHODS A total of 155 college students attending a major southern university were recruited to participate in a study evaluating a health promotion program titled Project Fitness during the fall 2005 and spring 2006 . Participants were r and omly assigned to one of three treatments as they presented at the clinic : 1 ) a multiple behavior health contract , 2 ) a one-on-one tailored consultation , or 3 ) a combined consultation plus contract intervention . Baseline and 1-month post-intervention data were collected using computer-assisted question naires in a quiet office within the student health clinic . RESULTS Omnibus repeated- measures analyses of variance were significant for drinking driving behaviors , F(2,136 ) = 4.43 , p = .01 , exercise behaviors , F(5,140 ) = 6.12 , p = .00 , nutrition habits , F(3,143 ) = 5.37 , p = .00 , sleep habits , F(2,144 ) = 5.03 , p = .01 , and health quality of life , F(5,140 ) = 3.09 , p = .01 , with improvements on each behavior across time . Analysis of group-by-time interaction effects showed an increase in the use of techniques to manage stress , F(2,144 ) = 5.48 , p = .01 , and the number of health behavior goals set in the last 30 days , F(2,143 ) = 5.35 , p = .01 , but only among adolescents receiving the consultation , or consultation plus contract . Effect sizes were consistently larger across health behaviors , and medium in size , when both consult and contract were used together . CONCLUSIONS Brief interventions using a positive goal image of fitness , and addressing a number of health habits using a contract and consultation strategy alone , or in combination , have the potential to influence positive changes in multiple health behaviors of college students attending a university primary health care clinic",
"Objective . The authors tested the impact on cardiovascular risk profiles of African American women ages 40 years and older after one year of participation in one of three church-based nutrition and physical activity strategies : a st and ard behavioral group intervention , the st and ard intervention supplemented with spiritual strategies , or self-help strategies . Methods . Women were screened at baseline and after one year of participation . The authors analyzed intention-to-treat within group and between groups using a generalized estimating equations adjustment for intra-church clustering . Because spiritual strategies were added to the st and ard intervention by participants themselves , the results from both active groups were similar and , thus , combined for comparisons with the self-help group . Results . A total of 529 women from 16 churches enrolled . Intervention participants exhibited significant improvements in body weight ( −1.1 lbs ) , waist circumference ( −0.66 inches ) , systolic blood pressure ( −1.6 mmHg ) , dietary energy ( −117 kcal ) , dietary total fat ( −8 g ) , and sodium intake ( −145 mg ) . The self-help group did not . In the active intervention group , women in the top decile for weight loss at one year had even larger , clinical ly meaningful changes in risk outcomes ( −19.8 lbs ) . Conclusions . Intervention participants achieved clinical ly important improvements in cardiovascular disease risk profiles one year after program initiation , which did not occur in the self-help group . Church-based interventions can significantly benefit the cardiovascular health of African American women",
"OBJECTIVE An automated health counselor agent was design ed to promote both physical activity and fruit and vegetable consumption through a series of simulated conversations with users on their home computers . METHODS The agent was evaluated in a 4-arm r and omized trial of a two-month daily contact intervention comparing : ( a ) physical activity ; ( b ) fruit and vegetable consumption ; ( c ) both interventions ; and ( d ) a non-intervention control . Physical activity was assessed using daily pedometer steps . Daily servings of fruit and vegetables were assessed using the NIH/NCI self-report Fruit and Vegetable Scan . RESULTS Participants in the physical activity intervention increased their walking on average compared to the control group , while those in the fruit and vegetable intervention and combined intervention decreased walking . Participants in the fruit and vegetable intervention group consumed significantly more servings per day compared to those in the control group , and those in the combined intervention reported consuming more compared to those in the control group . CONCLUSION Automated health intervention software design ed for efficient re-use is effective at changing health behavior . PRACTICE IMPLICATION S Automated health behavior change interventions can be design ed to facilitate translation and adaptation across multiple behaviors",
"College students are engaging in high rates of behavior related to risk of infection from Human Immunodeficiency Virus ( HIV ) and other sexually transmitted diseases ( STDs ) . A cognitive-behavioral skills training program for heterosexual college females focused on sexual assertiveness skills and the reduction of risk-related behaviors was design ed and evaluated compared with an education-only program . Participants completed pre-intervention , post-intervention , and one-month follow-up assessment s of : ( a ) HIV/STD-related knowledge and beliefs ; ( b ) sexual , alcohol , and drug-related behaviors ; and ( c ) sexual assertiveness role-plays . Skills training participants compared to education-only participants scored higher on sexual assertiveness skills , specific knowledge of HIV infection , and self-efficacy to perform lower risk sexual behaviors and reported a reduction in risk-related behaviors at post-intervention and follow-up assessment s. The effectiveness of behavioral skills in HIV risk-reduction programs for college students is discussed",
"Healthy Body Healthy Spirit was a multicomponent intervention to increase fruit and vegetable ( F & V ) consumption and physical activity ( PA ) delivered through Black churches . Sixteen churches were r and omly assigned to 3 intervention conditions . At baseline , 1,056 individuals were recruited across the 16 churches , of which 906 ( 86 % ) were assessed at 1-year follow-up . Group 1 received st and ard educational material s , Group 2 received culturally targeted self-help nutrition and PA material s , and Group 3 received the same intervention as did Group 2 as well as 4 telephone counseling calls based on motivational interviewing ( MI ) delivered over the course of 1 year . At 1-year follow-up , Groups 2 and 3 showed significant changes in both F & V intake and PA . Changes were somewhat larger for F & V. For F & V , but not PA , there was a clear additive effect for the MI intervention",
"OBJECTIVE To assess the effectiveness of a brief face-to-face health promotion intervention which included a ' pledge ' using brief negotiation techniques , compared with st and ard advice-giving techniques , delivered in a community setting . DESIGN A parallel group pre-post design using r and omised matched groups . Lifestyle helpers delivered the intervention ( one consultation per participant ) . Diet , physical activity and anthropometric measurements were collected at baseline , 6 months and 12 months . Qualitative data were also collected . SETTING Middlesbrough ( UK ) . SUBJECTS Adults living in low socio-economic areas . RESULTS Recruitment and engagement of lifestyle helpers was difficult , and initial expectations that local health authority staff working in the community and community champions would act as lifestyle helpers were not realised . As a consequence , recruitment of participants was lower than anticipated . One hundred and twenty-eight adults were recruited and the retention rate was 48 % at 12 months . Barriers to participation included poor health and competing commitments . No significant differences in change in diet or physical activity behaviours , or BMI , between the intervention and control groups were observed . The control group had a significantly greater decrease in waist circumference at 12 months compared with the intervention group . CONCLUSIONS This exploratory trial provides important insights in terms of recruiting lifestyle helpers for community-based health promotion interventions , specifically ( i ) the priorities and limitations in terms of time ( regardless of their general enthusiasm ) for staff employed by the local health authority , and ( ii ) the willingness of potential community champions to serve their local community in areas where community identity and ' spirit ' are seen as lacking",
"BACKGROUND Major questions remain unanswered about how best to accomplish multiple behavior change . The purpose of this study was to evaluate whether there are differences in successfully changing multiple behaviors in computer-tailored sequential and simultaneous interventions for physical activity ( PA ) promotion and fat intake ( FI ) reduction . METHODS Participants ( N=567 ) were r and omly assigned to receive an intervention for PA and FI simultaneously ; PA at baseline and FI at 3 months ; or FI at baseline and PA at 3 months . Successful behavior change at 6 months was defined as : > 60 min PA increase and /or 5 % FI reduction . Using multinomial logistic regression the odds ratios of successful behaviors change ( none , PA only , FI only , or both ) were determined for intervention mode , gender , age , BMI and education . RESULTS Overall drop-out was 26 % . There was no behavior change for 20.2 % of participants ; 30.5 % successfully decreased FI ; 15.8 % successfully increased PA ; 33.5 % successfully changed both behaviors . Intervention mode , gender and age were not associated with successful behavior change . Compared to those that did not change any behaviors : participants that successfully changed FI were more likely to be overweight/obese ( OR=1.85 ) ; and participants that successfully changed both behaviors were more likely to be overweight/obese ( OR=2.13 ) and have lower education ( OR=2.46 ) . CONCLUSIONS Success in changing multiple behaviors was not associated with intervention mode ; both simultaneous and sequential interventions can be applied . Being overweight might be an extra motivator to change health behaviors",
"Culturally-specific HIV risk reduction interventions for Hispanic women are needed . SEPA ( Salud/Health , Educación/Education , Promoción/Promotion , y/ and Autocuidado/Self-care ) is a culturally-specific and theoretically-based group intervention for Hispanic women . The SEPA intervention consists of five sessions covering STI and HIV prevention ; communication , condom negotiation and condom use ; and violence prevention . A r and omized trial tested the efficacy of SEPA with 548 adult U.S. Hispanic women ( SEPA n = 274 ; delayed intervention control n = 274 ) who completed structured interviews at baseline and 3 , 6 , and 12 months post-baseline . Intent-to-treat analyses indicated that SEPA decreased positive urine sample s for Chlamydia ; improved condom use , decreased substance abuse and IPV ; improved communication with partner , improved HIV-related knowledge , improved intentions to use condoms , decreased barriers to condom use , and increased community prevention attitudes . Culturally-specific interventions have promise for preventing HIV for Hispanic women in the U.S. The effectiveness of SEPA should be tested in a translational community trial . ResumenIntervenciones culturalmente específicas son necesarias para la reducción de riesgo de contraer VIH en las mujeres hispanas . SEPA ( Salud/Health , Educación/Education , Promoción/Promotion , y Autocuidado/Self-care ) es una intervención grupal culturalmente específica con bases teóricas diseñada para mujeres Hispanas . La intervención SEPA consiste en cinco sesiones que cubren temas relacionados con la prevención de ITS - VIH , comunicación , negociación y uso del condón ; y prevención de la violencia . Utiliz and o un estudio r and omizado se probó la eficacia de SEPA con una muestra de 548 mujeres hispanas que viven en los Estados Unidos de Norteamérica ( SEPA n = 274 ; grupo control n = 274 ) . Las participantes respondieron una entrevistas estructuradas al inicio del estudio y a los 3 , 6 , y 12 meses posteriores a la intervención . Los result ados del análisis señalan que las mujeres que participaron en SEPA disminuyeron las muestras positivas de Chlamydia en orina , aumentaron el uso del condón , disminuyeron el abuso de sustancias y los episodios de violencia de pareja , mejoraron la comunicación de pareja , aumentaron el conocimiento sobre VIH , mejoraron la intención de utilizar condón , percibieron menores barreras para uso del condón , y mejoraron las actividades de prevención en la comunidad . Las intervenciones culturalmente específicas son promisorias para la prevención del VIH en las mujeres hispanas que viven en los Estados Unidos de Norteamérica . La efectividad de SEPA debe ser probada en la comunidad",
"The WATCH ( Wellness for African Americans Through Churches ) Project was a r and omized trial comparing the effectiveness of 2 strategies to promote colorectal cancer preventive behaviors among 587 African American members of 12 rural North Carolina churches . Using a 2 X 2 factorial research design , the authors compared a tailored print and video ( TPV ) intervention , consisting of 4 individually tailored newsletters and targeted videotapes , with a lay health advisor ( LHA ) intervention . Results showed that the TPV intervention significantly improved ( p .05 ) fruit and vegetable consumption ( 0.6 servings ) and recreational physical activity ( 2.5 metabolic task equivalents per hour ) and , among those 50 and older ( n = 287 ) , achieved a 15 % increase in fecal occult blood testing screening ( p = .08 ) . The LHA intervention did not prove effective , possibly because of suboptimal reach and diffusion",
"OBJECTIVE To determine if a clinic-based behavioral intervention program for low-income mid-life women that emphasizes use of community re sources will increase moderate intensity physical activity ( PA ) and improve dietary intake . METHODS R and omized trial conducted from May 2003 to December 2004 at one community health center in Wilmington , NC . A total of 236 women , ages 40 - 64 , were r and omized to receive an Enhanced Intervention ( EI ) or Minimal Intervention ( MI ) . The EI consisted of an intensive phase ( 6 months ) including 2 individual counseling sessions , 3 group sessions , and 3 phone calls from a peer counselor followed by a maintenance phase ( 6 months ) including 1 individual counseling session and 7 monthly peer counselor calls . Both phases included efforts to increase participants ' use of community re sources that promote positive lifestyle change . The MI consisted of a one-time mailing of pamphlets on diet and PA . Outcomes , measured at 6 and 12 months , included the comparison of moderate intensity PA between study groups as assessed by accelerometer ( primary outcome ) and question naire , and dietary intake assessed by question naire and serum carotenoids ( 6 months only ) . RESULTS For accelerometer outcomes , follow-up was 75 % at 6 months and 73 % at 12 months . Though moderate intensity PA increased in the EI and decreased in the MI , the difference between groups was not statistically significant ( p=0.45 ; multivariate model , p=0.08 ) ; however , moderate intensity PA assessed by question naire ( 92 % follow-up at 6 months and 75 % at 12 months ) was greater in the EI ( p=0.01 ; multivariate model , p=0.001 ) . For dietary outcomes , follow-up was 90 % for question naire and 92 % for serum carotenoids at 6 months and 74 % for question naire at 12 months . Dietary intake improved more in the EI compared to the MI ( question naire at 6 and 12 months , p EI did not improve objective ly measured PA , but was associated with improved self-reported and objective measures of dietary intake",
"BACKGROUND The Arizona Well-Integrated Screening and Evaluation for Women Across the Nation ( WISEWOMAN ) project used provider counseling , health education , and community health workers ( CHWs ) to target chronic disease risk factors in uninsured , primarily Hispanic women over age 50 . METHODS Participants were recruited from two Tucson clinics participating in the National Breast and Cervical Cancer Early Detection Program ( NBCCEDP ) . Women were r and omly assigned into one of three intervention groups : ( 1 ) provider counseling , ( 2 ) provider counseling and health education , or ( 3 ) provider counseling , health education , and CHW support . At baseline and 12 months ( 1998 - 2000 ) , participants were measured for height , weight , waist and hip circumference , and blood pressure . Blood tests were conducted to check blood glucose , cholesterol , and triglyceride levels . At each time point , participants also completed 24-hour dietary recalls and question naires focusing on their physical activity levels . RESULTS A total of 217 women participated in baseline and 12-month follow-up . Three fourths were Hispanic . All three intervention groups showed an increase in self-reported weekly minutes of moderate-to-vigorous physical activity , with no significant differences between the groups . Significantly more women who received the comprehensive intervention of provider counseling , health education , and CHW support progressed to eating five fruits and vegetables per day , compared with participants who received only provider counseling or provider counseling plus health education . CONCLUSIONS All three interventions increased moderate-to-vigorous physical activity but not fruit and vegetable consumption . The intervention group with provider counseling , health education , and CHW support significantly increased the number of women meeting national recommendations for fruit and vegetable consumption",
"BACKGROUND Faith-based interventions hold promise for promoting health in ethnic minority population s. To date , however , few of these interventions have used a community-based participatory research ( CBPR ) approach , have targeted both physical activity and healthy eating , and have focused on structural changes in the church . PURPOSE To report the results of a group r and omized CBPR intervention targeting physical activity and healthy eating in African-American churches . DESIGN Group RCT . Data were collected from 2007 to 2011 . Statistical analyses were conducted in 2012 . SETTING / PARTICIPANTS Seventy-four African Method ist Episcopal ( AME ) churches in South Carolina and 1257 members within them participated in the study . INTERVENTION Churches were r and omized to an immediate ( intervention ) or delayed ( control ) 15-month intervention that targeted organizational and environmental changes consistent with the structural ecologic model . A CBPR approach guided intervention development . Intervention churches attended a full-day committee training and a full-day cook training . They also received a stipend and 15 months of mailings and technical assistance calls to support intervention implementation . MAIN OUTCOME MEASURES Primary outcomes were self-reported moderate- to vigorous-intensity physical activity ( MVPA ) , self-reported fruit and vegetable consumption , and measured blood pressure . Secondary outcomes were self-reported fat- and fiber-related behaviors . Measurements were taken at baseline and 15 months . Intent-to-treat repeated measures ANOVA tested group X time interactions , controlling for church clustering , wave , and size , and participant age , gender , and education . Post hoc ANCOVAs were conducted with measurement completers . RESULTS There was a significant effect favoring the intervention group in self-reported leisure-time MVPA ( d=0.18 , p=0.02 ) , but no effect for other outcomes . ANCOVA analyses showed an intervention effect for self-reported leisure-time MVPA ( d=0.17 , p=0.03 ) and self-reported fruit and vegetable consumption ( d=0.17 , p=0.03 ) . Trainings were evaluated very positively ( training evaluation item means of 4.2 - 4.8 on a 5-point scale ) . CONCLUSIONS This faith-based structural intervention using a CBPR framework showed small but significant increases in self-reported leisure-time MVPA . This program has potential for broad-based dissemination and reach . TRIAL REGISTRATION This study is registered at www . clinical trials.gov NCT00379925",
"OBJECTIVE This study examined whether 3-month outcomes of a brief image-based multiple behavior intervention on health habits and health-related quality of life of college students were sustained at 12-month follow-up without further intervention . METHODS A r and omized control trial was conducted with 303 undergraduates attending a public university in southeastern US . Participants were r and omized to receive either a brief intervention or usual care control , with baseline , 3-month , and 12-month data collected during fall of 2007 . RESULTS A significant omnibus MANOVA interaction effect was found for health-related quality of life , p=0.01 , with univariate interaction effects showing fewer days of poor spiritual health , social health , and restricted recent activity , p's driving after drinking , p=0.04 , and moderate exercise , p=0.04 , in favor of the brief intervention . Effect sizes typically increased over time and were small except for moderate size effects for social health-related quality of life . CONCLUSION This study found that 3-month outcomes from a brief image-based multiple behavior intervention for college students were partially sustained at 12-month follow-up"
] |
4116b924-06ff-11f0-808a-c43d1ab1c353
|
The term neuroenhancement refers to improvement in the cognitive , emotional and motivational functions of healthy individuals through , inter alia , the use of drugs . Of known interventions , psychopharmacology provides readily available options , such as methylpheni date and modafinil . Both drugs are presumed to be in widespread use as cognitive enhancers for non-medical reasons . Based on a systematic review and meta- analysis we show that expectations regarding the effectiveness of these drugs exceed their actual effects , as has been demonstrated in single- or double-blind r and omised controlled trials . Only studies with sufficient extractable data were included in the statistical analyses . For methylpheni date an improvement of memory was found , but no consistent evidence for other enhancing effects was uncovered . Modafinil on the other h and , was found to improve attention for well-rested individuals , while maintaining wakefulness , memory and executive functions to a significantly higher degree in sleep deprived individuals than did a placebo . However , repeated doses of modafinil were unable to prevent deterioration of cognitive performance over a longer period of sleep deprivation though maintaining wakefulness and possibly even inducing overconfidence in a person 's own cognitive performance
|
[
"AIMS To examine the prevalence rates and correlates of non-medical use of prescription stimulants ( Ritalin , Dexedrine or Adderall ) among US college students in terms of student and college characteristics . DESIGN A self-administered mail survey . SETTING One hundred and nineteen nationally representative 4-year colleges in the United States . PARTICIPANTS A representative sample of 10 904 r and omly selected college students in 2001 . MEASUREMENTS Self-reports of non-medical use of prescription stimulants and other substance use behaviors . FINDINGS The life-time prevalence of non-medical prescription stimulant use was 6.9 % , past year prevalence was 4.1 % and past month prevalence was 2.1 % . Past year rates of non-medical use ranged from zero to 25 % at individual colleges . Multivariate regression analyses indicated non-medical use was higher among college students who were male , white , members of fraternities and sororities and earned lower grade point averages . Rates were higher at colleges located in the north-eastern region of the US and colleges with more competitive admission st and ards . Non-medical prescription stimulant users were more likely to report use of alcohol , cigarettes , marijuana , ecstasy , cocaine and other risky behaviors . CONCLUSIONS The findings of the present study provide evidence that non-medical use of prescription stimulants is more prevalent among particular subgroups of US college students and types of colleges . The non-medical use of prescription stimulants represents a high-risk behavior that should be monitored further and intervention efforts are needed to curb this form of drug use",
"OBJECTIVES Modafinil has recently been approved for the treatment of shift work sleep disorder , making it potentially available for shift-working emergency physicians . The authors ' objectives were to determine whether modafinil improved cognitive performance of emergency physicians following overnight shifts and to record symptoms and subjective evaluations of the effect of modafinil on the participants . METHODS This was a r and omized , double-blind , placebo-controlled crossover study that followed CONSORT guidelines . Participants were assigned to one of two study groups , with study sessions occurring at least seven weeks apart , and received either modafinil or placebo depending on their r and om allocation . Testing after night shifts included a coding task and an AX version of the Continuous Performance Task , both of which test cognitive function . Participants also completed visual analog scales for three subjective outcomes , and symptoms were elicited . RESULTS Modafinil facilitated performance on long interstimulus-interval AX trials ( F [ 1 , 23 ] = 6.65 , p = 0.1 ) and marginally reduced errors on AY trials in the Continuous Performance Task ( F [ 1 , 23 ] = 3.59 , p = 0.07 ) , suggesting facilitation of sustained attention , cognitive control , and working memory . Additionally , modafinil , compared with placebo , facilitated performance on the coding task at the first session . Subjective data from visual analog scales confirmed that modafinil increased perceived alertness during the simulated patient care sessions but worsened sleep onset when opportunities for sleep arose . CONCLUSIONS Modafinil increased certain aspects of cognitive function and subjectively improved participants ' ability to attend post-night-shift didactic sessions but made it more difficult for participants to fall asleep when opportunities for sleep arose",
"Aims /hypothesisOur hypothesis is that reducing release of the inhibitory neurotransmitter gamma-aminobutyric acid ( GABA ) with modafinil will enhance symptomatic and hormonal responses to hypoglycaemia . Methods Nine healthy men received , in r and om order , two 100-mg doses of modafinil or placebo , followed by an insulin clamp in which plasma glucose was either reduced stepwise to 2.4 mmol/l or was sustained at euglycaemia ( four studies ) . Catecholamines , symptom scores and cognitive function were measured . Results Modafinil had no effect on the measured parameters during euglycaemia . During hypoglycaemia , autonomic symptom scores were significantly higher with modafinil ( increase at lowest plasma glucose concentration 271.3±118.9 vs 211.2±80.4/40 min , p=0.019 ) , and the heart rate response was increased ( 12,928±184 vs 6773±148 bpm/140 min , p=0.016 ) . Deterioration in performance of two cognitive tasks was reduced : Stroop colour – word test ( 613±204 vs 2375±161/65 min , p=0.009 ) and accuracy of a simple reaction task ( 11.3±1.8 vs 9.4±3.7 , p=0.039 ) . Conclusions /interpretationWe conclude that modafinil improves adrenergic sensitivity and some aspects of cognitive function at hypoglycaemia , possibly by reducing neuronal central GABA concentrations",
"Common complaints among shift workers are sleep disruptions and increased sleepiness while working , which may contribute to shift workers being more susceptible to diminished performance and work-related accidents . The purpose of this double-blind , within-participant study was to examine the effects of the alerting agent modafinil on cognitive/psychomotor performance , mood , and measures of sleep during simulated shift work . In all , 11 participants completed this 23-day residential laboratory study . They received a single oral modafinil dose ( 0 , 200 , 400 mg ) 1 h after waking for three consecutive days under two shift conditions : day shift and night shift . Shifts alternated three times during the study , and shift conditions were separated by an ‘ off ’ day . When participants received placebo , cognitive performance and subjective ratings of mood were disrupted during the night shift , relative to the day shift . Objective and subjective measures of sleep were also disrupted , but to a lesser extent . Modafinil reversed disruptions in cognitive performance and mood during the night shift . While modafinil produced few effects on sleep measures during the night shift , the largest dose produced several sleep alterations during the day shift . These data demonstrate that abrupt shift changes produced cognitive performance impairments and mood disruptions during night shift work . Therapeutic doses of modafinil attenuated night-shift-associated disruptions , but the larger dose produced some sleep impairments when administered during day-shift work",
"The rate of onset of a drug 's effect is an important determinant of its abuse potential . This experiment examined the acute behavioral effects of orally administered sustained-release methylpheni date ( SR ; 20 - 40 mg ) , immediate-release methylpheni date ( IR ; 20 - 40 mg ) , and placebo in 10 healthy volunteers . Drug effects were assessed before drug administration and periodically afterwards for 6 hr using drug-effect question naires and performance measures that are sensitive to the acute effects of stimulants . The IR formulation produced stimulant-like drug effects ( e.g. , increased ratings of \" good effects \" ) that generally varied as a function of dose and time . The SR formulation produced only transient effects on these measures . These findings are consistent with previous research on the influence of rate of onset using other drugs and suggest that the abuse potential of IR methylpheni date may be greater than that of SR methylpheni date",
"So that reinforcing and subjective effects of methylpheni date as a function of dose and level of sleepiness could be evaluated , 21 volunteers received methylpheni date ( 5 , 10 , or 20 mg ) or placebo on 2 sampling days . After 4 and 8 hr time in bed ( TIB ) , they chose their preferred capsule on 5 days . Methylpheni date was chosen more frequently after 4 hr TIB ( 60 % ) than it was after 8 hr TIB ( 33 % ) . The strongest preference ( 68 % ) was seen in the 10-mg group . At 10 and 20 mg , stimulant-like subjective effects were reported . The 10-mg group was more adversely affected by the restricted bedtime and showed more pronounced drug effects with methylpheni date . These results indicate that sleepiness modulates the reinforcing and subjective effects of methylpheni date",
"The indirect catecholamine agonist methylpheni date ( Ritalin ) is the drug treatment of choice in attention deficit/hyperactivity disorder ( AD/HD ) , one of the most common behavioral disorders of childhood ( DSM-IV ) , although symptoms may persist into adulthood . Methylpheni date can enhance cognitive performance in adults and children diagnosed with AD/HD ( Kempton et al. , 1999 ; Riordan et al. , 1999 ) and also in normal human volunteers on tasks sensitive to frontal lobe damage , including aspects of spatial working memory ( SWM ) performance ( Elliott et al. , 1997 ) . The present study investigated changes in regional cerebral blood flow ( rCBF ) induced by methylpheni date during performance of a self-ordered SWM task to define the neuroanatomical loci of the beneficial effect of the drug . The results show that the methylpheni date -induced improvements in working memory performance occur with task-related reductions in rCBF in the dorsolateral prefrontal cortex and posterior parietal cortex . The beneficial effects of methylpheni date on working memory were greatest in the subjects with lower baseline working memory capacity . This is to our knowledge the first demonstration of a localization of a drug-induced improvement in SWM performance in humans and has relevance for underst and ing the treatment of AD/HD",
"Rationale Methylpheni date , a dopaminergic and noradrenergic reuptake inhibitor , has been shown in young , healthy adult volunteers to produce pronounced effects on working memory and sustained attention . We were interested in assessing whether similar improvements could be conferred upon elderly volunteers in order to gain a more complete underst and ing of the effects of age on monoaminergic manipulations of working memory and attention , as well as to explore the potential for pharmacological intervention in attention and executive dysfunction disorders in this age group . Objectives The main aim of the study was to characterise the dose-related effects of methylpheni date on a range of neuropsychological functions in elderly healthy volunteers . Methods Sixty healthy elderly adult male volunteers received either a single oral dose of placebo , 20 mg or 40 mg methylpheni date prior to performing a variety of tasks design ed to assess memory , attention and executive function . A r and omised double-blind , between-subjects design was used . Results Methylpheni date had significant cardiovascular and subjective effects . However , unlike in younger volunteers , no significant effects of drug on working memory ( spatial span and spatial working memory ) , response inhibition ( stop-signal ) or sustained attention ( rapid visual information processing ) were seen . Subtle effects on latency similar to those in younger volunteers were identified : both doses of methylpheni date result ed in a slowing in response time during set-shifting and decision-making . Conclusions The results of this study demonstrate that , in elderly subjects , the cognitive effects of methylpheni date are grossly attenuated and distinct from the profile previously described in younger volunteers . It is suggested that methylpheni date may not be appropriate as a pharmacological intervention in elderly patient groups , such as those reporting age-related cognitive decline",
"Abstract Previous studies of the effects of the psychomotor stimulant , methylpheni date , have concentrated on vigilance and reaction time tasks . In this study , the effects of methylpheni date on more complex aspects of cognition were studied using tasks from the CANTAB battery and related tests which have been shown to be sensitive to frontal lobe dysfunction . Twenty-eight young healthy men participated in a counterbalanced , double-blind , placebo-controlled study of the effects of methylpheni date . Cognitive assessment included tests of spatial working memory , planning , verbal fluency , attentional set-shifting and sustained attention . Methylpheni date had significant effects on performance of the tests of spatial working memory and planning but not on the attentional and fluency tests . When the drug was taken on the first test session , performance on the spatial tests was enhanced by the drug compared to placebo . However , when the drug was taken second , performance accuracy was impaired whereas response latencies were decreased . These results are consistent with a hypothesis that methylpheni date influences performance in two conflicting ways ; enhancing executive aspects of spatial function on novel tasks but impairing previously established performance . This pattern of effects is discussed within the framework of dual , interacting arousal mechanisms",
"ABSTRACT Objective : To assess the pharmacodynamics of armodafinil compared with modafinil and placebo on measures of alertness in healthy volunteers undergoing sleep loss . Research design and methods : In a double-blind , active- and placebo-controlled , parallel-group study , 107 healthy male volunteers ( aged 18–40 years ) were r and omized to receive a single oral dose of armodafinil ( 100 , 150 , 200 , or 300 mg ) , modafinil ( 200 mg ) , or placebo administered at 19:25 h. Main outcome measures : The primary outcome was the Maintenance of Wakefulness Test ( MWT ) , administered every 2 hours from 22:00–08:00 h. Secondary outcomes included the Psychomotor Vigilance Task ( PVT ) and the Karolinska Sleepiness Scale . Blood sample s for pharmacokinetic analysis were collected hourly . Adverse events were evaluated throughout the 2‐day laboratory stay and by telephone on day 9 . Results : All four doses of armodafinil , and the dose of 200 mg modafinil , improved wakefulness as measured by increased MWT latencies ( treatment effect , p reduced PVT lapses of attention ( treatment effect , p Armodafinil at 200 mg result ed in comparable Cmax , a later tmax , and higher plasma concentrations 6–14 hours post-drug administration than with 200 mg modafinil . Following armodafinil , longer MWT latencies and fewer PVT lapses 6 to ≈ 14 hours post-drug administration were observed compared with modafinil . Armodafinil doses were well tolerated , with the most common adverse events including abdominal pain , nausea , and headache . There were reports of tachycardia/palpitations . Decreased mean sleep efficiency and increased mean blood pressure were also observed . Conclusion : Armodafinil improved alertness at all doses studied . Relative to modafinil 200 mg , armodafinil 200 mg showed a comparable peak plasma concentration with higher concentrations 6–14 hours post-drug , and improved wakefulness and sustained attention for a longer time post-dose . Both drugs were well tolerated ; however , further research on the efficacy , safety , and tolerability of armodafinil in patients with disorders of excessive sleepiness ( ES ) is required",
"Self-monitoring refers to the ability to assess accurately one 's own performance in a specific environment . The present study investigated the effects of the stimulating drugs modafinil ( 300 mg ) and d-amphetamine ( 20 mg ) on the ability to self-monitor cognitive performance during 64 h of sleep deprivation ( SD ) and sustained mental work . Two cognitive tasks were investigated : a visual ( perceptual ) judgement task and a complex mental addition task . Subjects in the placebo condition displayed marked circadian and SD effects on cognitive task performance but their self-monitoring was substantively undisturbed by SD . Subjects performing under the influence of d-amphetamine likewise displayed highly proficient self-monitoring throughout the SD period . In contrast , modafinil had a disruptive effect on self-monitoring , inducing a reliable ' overconfidence ' effect ( i.e. an overestimation of actual cognitive performance ) , which was particularly marked 2 - 4 h post-dose . Although modafinil has proven to be a safe and effective countermeasure to the effects of extensive SD on cognitive task performance , we encourage a more comprehensive underst and ing of the relation between its subjective and performance enhancing effects before the drug is recommended as a viable fatigue countermeasure",
"Bupropion is a weak inhibitor of noradrenaline ( NE ) and dopamine ( DA ) reuptake and has no direct action on serotonin ( 5-HT ) neuronal elements . In the rat brain , bupropion suppresses NE neuron firing activity via the activation of α2-adrenoceptors and increases that of 5-HT neurons through an indirect action on NE neurons . Twenty-five healthy young male volunteers , with no previous history of psychiatric disorders , were r and omized to one of four 7-day regimens : placebo , bupropion ( 150 mg ) once daily , bupropion ( 150 mg ) twice a day , and methylpheni date SR ( 20 mg daily ) . To assess the activity of the NE reuptake process , the blood pressure response to intravenous tyramine was determined . A decrease in the systolic pressure response to tyramine was considered evidence of NE reuptake inhibition . Effects on 5-HT reuptake were assessed by measuring whole blood 5-HT concentration , with a decrease serving as an index of 5-HT reuptake blockade . The Profile of Mood States ( POMS ) scale was used to assess behavioral and psychological changes . Neither bupropion nor methylpheni date altered the tyramine pressor response , in contrast to previous data that demonstrated decreases were obtained with NE reuptake inhibitors . Neither drug modified 5-HT concentrations . However , POMS scores revealed that bupropion at a dosage of 150 mg/day increased composedness , agreeability , and energy , whereas 300 mg/day improved only attention . In contrast , methylpheni date improved only energy . These data provide no evidence that bupropion acts as an inhibitor of NE or 5-HT reuptake in healthy humans . Presumably it enhances synaptic availability of NE by increasing release . Yet , because its behavioral profile is different from that of methylpheni date , it may not share all the biochemical properties of psychostimulants",
"On 4 days , 6 volunteers received 10 mg methylpheni date or placebo at 0900 after 4 or 8 hr time in bed ( TIB ) and then on 4 days after 4 or 8 hr TIB chose their preferred capsule . On sampling days , 4 hr TIB increased multiple sleep latency test ( MSLT ) scores and Fatigue scale scores on the Profile of Mood States ( POMS ) . In both TIBs , the drug increased the MSLT and POMS Vigor and Tension scale scores . It reduced POMS Fatigue scores and improved divided attention performance to a greater extent after 4 versus 8 hr . Drug was chosen on 88 % of days after 4 hr , but only 29 % of days after 8 hr . Preference for the drug depends on sleepiness and is mediated by performance-enhancing and fatigue-altering effects",
"This study investigated the effects of methylpheni date in a memory scanning task with two levels of high cognitive load ( memory set sizes 2 and 4 presented in displays of size 4 ) and two response requirements ( simple mapping or rotation ) . Twenty young adults were tested under placebo and methylpheni date ( 0.3 mg/Kg ) in a double-blind protocol . As expected , memory load increased misses , false alarms , confusions , and failures to respond by the deadline . In turn , the rotation requirement increased confusions and nonresponses . Reaction time ( RT ) was slowed by both factors . P3b latency also was increased by memory load and , to some extent , by the rotation requirement . These results are consistent with the proposition that P3b latency reflects largely evaluation , rather than response processes . Misses and reaction time were decreased in response to targets presented in the center vs. the periphery of the display . Confusions , however , showed the opposite trend . The display position did not affect P3b latency . These results can be explained by assuming that the subject was focusing on the center of the display and that accuracy diminished when stimuli were presented toward the periphery of the display . The stimulant challenge speeded up reaction times overall and specifically reduced the slowing effect of rotation . However , P3b latency was not affected by methylpheni date , so that the speeding of reaction time by the stimulant can be attributed to post-evaluation processes",
"Background Abuse of methylpheni date , a treatment of attentiondeficit/hyperactivity disorder , is reported to be increasing among students for the purpose of improving cognition . Methods A single capsule , containing methylpheni date ( 20 mg ) or placebo , was administered to healthy young adults orally following 24 hours of sleep deprivation . Measurements included percent change in score from sleep-deprived baseline on four st and ardized tests of cognitive function : Hopkins Verbal Learning , Digit Span , Modified Stroop , and Trail Making tests . Measurements also included percent changes in blood pressure and heart rate from sleepdeprived baseline and plasma methylpheni date concentration . Results Differences in cognitive test performance were not observed between intervention groups . In subjects receiving methylpheni date , mean percent changes from baseline for systolic blood pressure and heart rate were increased relative to placebo between 90 and 210 minutes following capsule administration ( maximum increases of 9.45 % and 11.03 % , respectively ) . The timing of peak differences in physiologic measures did not correlate with peak serum methylpheni date concentrations . Exit question naire ratings of “ capsule effect ” and perceived performance on the postcapsule administration of the most challenging cognitive test were both higher ( p = .044 and p = .009 , respectively ) for the methylpheni date group than for the placebo group . Conclusions Cognitive improvement among sleep-deprived young adults was not observed following methylpheni date administration . Benefits perceived by abusers may relate to increased confidence and sense of well-being , as well as to sympathetic nervous system stimulation . Moreover , methylpheni date administration results in physiologic effects that could be harmful to certain individuals",
"Methylpheni date ( 0.65 mg/kg ) , clonidine ( 200 μg ) or placebo were administered to normal adult males undertaking a dichotic monitoring task in which they were required to detect nominated target words and discriminate them from phonemic distractors . Following placebo , performance was better when attention was focused than when divided . Following clonidine , subjects were poorer and slower at discriminating targets during both divided and focused attention and subjectively were withdrawn and reported difficulties with concentration . Methylpheni date had no effect on target discrimination or response time but raised the rate of response and had marked effects on spontaneous behaviour in which an increased attention capacity was generally reported . The effects on attention of the pharmacological agents employed in this study are attributed to their effects on central monoamines . The disparity noted between objective and subjective assessment s of attention is discussed in terms of the voluntary allocation of effort",
"Modafinil , a medication for the excessive sleepiness associated with narcolepsy , has been hypothesized to improve not just alertness but mood as well . The purpose of this study was to determine how treatment with modafinil affects mood in healthy volunteers . Normal healthy volunteers ( n = 12 , 10 men and 2 women ; 30 - 44 years ) underwent a 3-day , counterbalanced , r and omized , crossover , inpatient trial of modafinil ( 400 mg daily ) versus placebo with 4-day washout period between 2 treatments . Mood was assessed daily using both the Positive and Negative Affect Schedule and a general mood scale , which consisted of 10 bipolar adjective ratings based on a severity scale ranging from 1 to 10 . Modafinil increased general mood and Negative Affect scales relative to placebo and had a significant effect on Positive Affect scales . These results suggest that modafinil may have general mood-elevating effects accompanied by increased negative affect ( anxiety ) . The findings may have implication s for clinical practice , in particular for the adjunctive use of modafinil in treatment-resistant depression",
"The purpose of this study was to determine the effects of magnesium pemoline ( Cylert ) and methylpheni date ( Ritalin ) on the memory and mood of normal aging persons . Seventy-eight subjects , aged 60 and over , were r and omly assigned in double blind fashion to one of the two drug conditions or to a placebo . Subjects were administered the WAIS vocabulary subtest , the Guild Memory Test , and a mood scale at the beginning of the study and the mood scale and alternate forms of the memory test in the middle and at the end of the experiment . Laboratory examinations were conducted at the beginning and end of the six week period and physical examinations were given weekly . Results showed no differential drug effects between the three groups on any of the six memory functions measured or between sub-groups of differing intellectual levels . There were , however , tentative indications that Cylert increased depression and worrisomeness and that Ritalin reduced fatigue . No physical side effects or significant changes in laboratory examinations were found on all but two subjects . These two individuals , apparently hypersensitive to Cylert , showed hepatic toxicity , but the result ant elevations on some tests quickly subsided when the drug was withdrawn",
"Summary — Modafinil , a new psychostimulant , was evaluated in eight healthy volunteers subjected to 60 hours of sleep deprivation . During continued wakefulness , vigilance was evaluated by self‐ assessment question naires , analogue visual scales , multiple sleep latency tests ( MSLT ) , sleep logs , and continuous ambulatory electroencephalographic recordings ( EEG ) . Modafinil ( 200 mg ) or a placebo was given every 8 hours for three days ; the sessions were separated by a 15 day wash out period . Results indicated a satisfactory level of vigilance , both subjective and objective , after the administration of modafinil , characterised by the quasi total absence of microsleep episodes which gradually occurred under placebo conditions . The confirmed wakening potency of modafinil makes this substance suitable for therapeutic use in patients with sleep disorders such as Gelineau 's syndrome and hypersomnia",
"The effects of methylpheni date ( 0.3 mg/kg ) on young adults paired-associate learning ( PAL ) of consonant-vowel-consonant ( CVC ) pairs and concomitant event-related potentials were assessed . The stimulant elevated mood and heart rate but did not affect PAL performance . For the first CVC , there were amplitude increases with learning for P3b at Pz , P2 at midline sites , and for a negative slow wave at Cz . For the second CVC , P3b and positive slow wave amplitude declined with learning . Increases in P3b amplitude to the first CVC were attributed to increments in stimulus meaningfulness . Decreases in P3b amplitude to the second CVC were interpreted as result ing from fewer disconfirmed expectations of feedback . The negative slow wave following the first CVC was viewed as a contingent negative variation . Methylpheni date increased parietal P3b amplitude for CVC 2 , averaged over learning phases"
] |
4116b96a-06ff-11f0-808a-c43d1ab1c353
|
Background Medial stabilized total knee joint replacement ( TKJR ) construct is design ed to closely replicate the kinematics of the knee . Little is known regarding comparison of clinical functional outcomes of patients utilising vali date d patient reported outcome measures ( PROM ) after medial stabilized TKJR and other construct design s. Purpose To perform a systematic review of the available literature related to the assessment of clinical functional outcomes following a TKJR employing a medial stabilized construct design . Methods The review was performed with a Preferred Reporting Items for Systematic Review and Meta-Analyses ( PRISMA ) algorithm . The literature search was performed using variouscombinations of keywords . The statistical analysis was completed using Review Manager ( RevMan ) , Version 5.3 . Results In the nineteen unique studies identified , there were 2,448 medial stabilized TKJRs implanted in 2,195 participants , there were 1,777 TKJRs with non-medial stabilized design constructs implanted in 1,734 subjects . The final mean Knee Society Score ( KSS ) value in the medial stabilized group was 89.92 compared to 90.76 in the non-medial stabilized group , with the final KSS mean value difference between the two groups was statistically significant and favored the non-medial stabilized group ( SMD 0.21 ; 95 % CI : 0.01 to 0.41 ; p = 004 ) . The mean difference in the final WOMAC values between the two groups was also statistically significant and favored the medial stabilized group ( SMD : -0.27 ; 95 % CI : -0.47 to -0.07 ; p = 0.009 ) . Moderate to high values ( I2 ) of heterogeneity were observed during the statistical comparison of these functional outcomes . Conclusion Based on the small number of studies with appropriate statistical analysis , we are unable to reach a clear conclusion in the clinical performance of medial stabilized knee replacement construct . Level of Evidence Level II
|
[
"PURPOSE To report clinical results and demonstrate posterior femoral translation ( PFT ) in medial pivot total knee arthroplasty ( TKA ) of posterior cruciate ligament ( PCL ) retaining type . MATERIAL S AND METHODS A prospect i ve study was performed upon thirty consecutive subjects who were operated on with medial pivot TKA of PCL retaining type between March 2009 and March 2010 and had been followed up for at least 2 years . Clinical ly , the knee society knee score and function score were used . In full extension and active flexion lateral radiograph , anteroposterior ( AP ) condylar position and magnitude of PFT was determined . RESULTS At last follow-up , the mean knee society knee score and function score improved significantly compared to preoperative scores . The AP condylar positions were consistently posterior to midline throughout the entire range of flexion . The PFTs averaged 0.31 ( ±0.12 ) of half length of tibial base plate and were greater in higher flexion cases ( r = 0.56 , p = 0.0012 ) . There were no cases having either component migration or radiolucent line wider than 2 mm except for one case showing instability related to trauma . CONCLUSIONS In medial pivot TKA of PCL retaining type , clinical outcomes were satisfactory and posterior femoral translations were consistently observed during progressive flexions of knees at two- to three-year follow-up",
"OBJECTIVES To study responsiveness and establish the minimal clinical ly important differences ( MCIDs ) and minimal detectable change ( MDC ) in patients undergoing total knee replacement ( TKR ) using the Short Form 36 ( SF-36 ) and Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . METHODS Prospect i ve observational study in three public hospitals of all consecutive patients on waiting lists to undergo TKR intervention with diagnosis of knee osteoarthritis ( OA ) . Patients were asked to complete before the intervention and at 6 months and 2 years afterward the SF-36 and the WOMAC health-related quality of life question naires ( HRQoL ) , and additional transition questions which measured the changes in their joint at 6 months . In both question naires the possible range of values is from 0 to 100 points . RESULTS In WOMAC improvement at 6 months after a TKR was between 27 ( stiffness ) and 31 points ( pain ) . The SF-36 showed improvements between the 28.3 points of role physical and 2.79 of general health . From 6 months to 2 years , WOMAC improvements were between 2 and 6 points . The MCID ranged from 14.52 ( stiffness ) to 22.87 ( pain ) on the WOMAC and in the physical domains of SF-36 from 11.56 ( physical function ) to 16.86 ( bodily pain ) . On the WOMAC , the MDC ranged from 13.11 ( function ) to 29.12 ( stiffness ) , and on SF-36 from 19.50 ( physical function ) to 41.23 ( social functioning ) . CONCLUSIONS The MCID for TKR is around 15 on WOMAC , while with the SF-36 of at least 10 points . These values should not be considered as absolute thresholds",
"Abstract Purpose To compare the clinical midterm results in ADVANCE total knee arthroplasty ( TKA ) with double-high ( DH ) insert , with same type implant with medial-pivot ( MP ) insert . Method Forty ADVANCE TKAs were r and omly divided into two groups , and two different design insert , DH insert , and MP insert were used in each group . At midterm , 4–5 years after surgery , Knee Society Scores ( KSS ) , Knee Society Functional Scores ( KSFS ) , range of motion ( ROM ) , and UCLA activity score were assessed and reported in this study . Results Midterm clinical results , including ROM and KSS , were comparable with both groups . KSFS and UCLA activity score were equally good between the two groups . Conclusion The results in this study revealed equally good clinical results with these types of implants at midterm follow-up , although the significant better ROM has not achieved by using DH insert . We concluded that the selection of inserts only could not achieve the better clinical results , including ROM and activity level in this study .Level of evidence Therapeutic studies —investigating the results of treatment , Level II",
"Abstract Purpose The main objective of this study was to compare the functional results and the impact on quality of life after a single-radius or a multiradius TKA implantation . The secondary objectives were to compare range of motion , satisfaction and the ability to perform daily life activities with both types of implant . It was hypothesized that the single-radius TKA would lead to better functional results and better quality of life than the multiradius TKA . Methods This is a prospect i ve non-r and omized study that included 250 cases of a single-radius TKA and 224 of a multiradius posterior-stabilized TKA implanted with the same surgical and rehabilitation protocol . Results In the 1- and 5-year follow-up , we found similar knee KSS scores ( 89.7 ± 12.1 in the multiradius group and 90.3 ± 11.7 in the single-radius group ) and functional KSS scores ( 78.6 ± 21.4 in the multiradius group and 75.8 ± 20.9 in the single-radius group ) . The pain and the Physical SF-36 scores were also similar . Range of motion ( 112 ° ± 12 ° in the multiradius group and 112 ± 12 ° in the single-radius group ) , patients ’ satisfaction and the ability to perform daily life activities were also similar in both groups . Conclusion The use of a single-radius or a multiradius posterior-stabilized knee prosthesis can improve the function of the knee and the patients ’ quality of life in a similar way at the short-term and midterm follow-up . Moreover , range of motion , patient satisfaction and the ability to perform daily life activities are similar with both types of prosthesis . As both types of prosthesis can improve the function and quality of life of the patients in a similar way , the sagittal radius of the femoral component should not be considered the main factor when choosing the model of TKA.Level of evidence Therapeutic study : Prospect i ve comparative study , Level",
" A total of 344 patients underwent bilateral total knee replacement ( TKR ) using a different prosthesis on each side . Four knee prostheses were used : anterior and posterior cruciate-retaining ( ACL-PCL ) , posterior cruciate-retaining ( PCL ) , medial or lateral pivot ( MLP ) , and posterior cruciate-substituting ( PS ) . All patients had good or excellent results . The range of movement , relief from pain , alignment , and stability did not vary among any of the prostheses . Forty-one of 46 patients ( 89 % ) preferred the ACL-PCL to the PS knee and 27 of 35 patients ( 77 % ) the MLP knee to the PS knee . Of the patients with an ACL-PCL knee on one side and a MLP on the other , an equal number preferred each type . The MLP knee was preferred to the PCL by 34 ( 79 % ) patients . PS and PCL knees were preferred equally . Patients with bilateral TKRs preferred retention of both their cruciate ligaments or substitution with a medial or lateral pivot prosthesis",
"BACKGROUND There is limited information comparing the results of fixed-bearing total knee replacement and mobile-bearing total knee replacement in patients with osteoarthritis who are younger than fifty-one years and who have a fixed-bearing implant in one knee and a mobile-bearing implant in the other . The purpose of this study was to compare our long-term clinical and radiographic results of fixed-bearing total knee replacement and mobile-bearing total knee replacement in a group of patients from this population . METHODS We prospect ively compared the results of 108 patients with osteoarthritis who were younger than fifty-one years ( mean age , forty-five years ) who had received a fixed-bearing prosthesis in one knee and a rotating platform mobile-bearing prosthesis in the other . The mean follow-up was 16.8 years ( range , fifteen to eighteen years ) . The patients were assessed clinical ly and radiographically . Knee motion and function were assessed as a primary outcome . Patients were assessed with question naires , and each knee was assessed separately . RESULTS Although there was significant improvement in both groups of knees , there was no significant difference between the groups ( i.e. , fixed-bearing and mobile-bearing knees ) with regard to the mean postoperative knee motion ( 126 ° and 128 ° , respectively ; p = 0.79 ) , the mean Knee Society knee clinical score ( 95 and 94 points , respectively ; p = 0.79 ) , or the Knee Society knee functional score ( 84 and 85 points , respectively ; p = 0.19 ) at the latest follow-up . In the fixed-bearing group , one knee was revised because of infection , two for aseptic loosening of the tibial component , and two because of wear of the tibial polyethylene insert . In the rotating platform mobile-bearing group , two knees were revised because of instability and one because of infection . The Kaplan-Meier survivorship for revision at 16.8 years of follow-up was 95 % ( 95 % confidence interval , 91 to 100 ) for the fixed-bearing prosthesis and 97 % ( 95 % confidence interval , 93 to 100 ) for the rotating platform mobile-bearing prosthesis . CONCLUSIONS Long-term results of both fixed and mobile-bearing total knee arthroplasties were encouraging in patients who were younger than fifty-one years of age with osteoarthritis . However , we found no superiority of the mobile-bearing total knee prosthesis over the fixed-bearing total knee prosthesis",
"Within the context of a double blind r and omized controlled parallel trial of 2 nonsteroidal antiinflammatory drugs , we vali date d WOMAC , a new multidimensional , self-administered health status instrument for patients with osteoarthritis of the hip or knee . The pain , stiffness and physical function subscales fulfil conventional criteria for face , content and construct validity , reliability , responsiveness and relative efficiency . WOMAC is a disease-specific purpose built high performance instrument for evaluative research in osteoarthritis clinical trials",
"The purpose of this r and omized , single-blind clinical trial was to compare a rotating platform ( RP ) total knee arthroplasty to a fixed-bearing ( FB ) total knee arthroplasty . Ninety-five knees in 69 patients were implanted by 2 surgeons . There were no significant differences in the preoperative demographics . At a minimum of 2-year follow-up , clinical outcomes and complication rates were similar , with the exception that the RP group had significantly better stair-climbing scores ( P = .04 ) . Postoperative range of motion was equally good in both groups ( FB knees , 1 ° -125 ° ; RP knees , 1 - 126 ° ) . There were no bearing dislocations in the RP group . In conclusion , this RP design performs at least as well as the FB version , and the RP patients reported better stair-climbing ability . Enthusiasm for this finding should be tempered by the relatively small sample size",
"Background A knee design with a ball- and -socket articulation of the medial compartment has a femoral rollback profile similar to the native knee . Compared to a conventional , posterior-stabilized knee design , it provides AP stability throughout the entire ROM . However , it is unclear whether this design difference translates to clinical and functional improvement . Questions / purpose sWe asked whether the medially conforming ball- and -socket design differences would be associated with ( 1 ) improved ROM ; and ( 2 ) improved American Knee Society , WOMAC , Oxford Knee , SF-36 , and Total Knee Function Question naire scores compared to a conventional , fixed-bearing posterior-stabilized TKA . Patients and Methods We enrolled 82 patients in a single-center , single-blinded , r and omized , controlled trial comparing the medially conforming ball- and -socket design knee prosthesis to a posterior-stabilized total knee prosthesis . Our primary end point was ROM . Our secondary end points were American Knee Society , WOMAC , Oxford Knee , SF-36 , and Total Knee Function Question naire scores . All patients were followed at 1 and 2 years . Results The mean ROM was 100.1 ° and 114.9 ° in the posterior-stabilized and medially conforming ball- and -socket groups , respectively . The physical component scores of SF-36 and Total Knee Function Question naire were better in the medially conforming ball- and -socket group . We found no difference in American Knee Society , WOMAC , and Oxford Knee scores . Conclusions Both implant design s similarly relieved pain and improved function . The medially conforming ball- and -socket articulation provided better high-end function as reflected by the Total Knee Function Question naire . Level of Evidence Level I , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence",
"The Advance Medial Pivot Total Knee Arthroplasty ( Wright Medical Technology , Arlington , Tennessee , USA ) has been design ed to reproduce modern ideas of knee kinematics . We report a prospect i ve clinical outcome study of 284 arthroplasties in 225 consecutive patients with a mean follow-up of 6.7 years ( range 4 to 9 years ) . For evaluation , both objective and subjective clinical rating systems and serial radiographs were used . At final follow-up , 10 ( 4.4 % ) patients ( 10 knees ) only were lost from follow-up and four ( 1.8 % ) patients ( five knees ) had died for reasons unrelated to the surgery with their knees performing well . There was an 82 % compliance in the intervals of follow-up evaluation . All patients showed a statistically significant improvement ( p=0.01 ) in the Knee Society clinical rating system , WOMAC question naire , SF-12 question naire , and Oxford knee score . The majority of patients ( 92 % ) were able to perform age-appropriate activities with a mean knee flexion of 117 degrees ( range 85 degrees to 135 degrees ) at final follow-up . Survival analysis showed a cumulative success rate of 99.1 % at 5 years . Two ( 0.7 % ) arthoplasties , in which patient selection and surgical errors were identified , were revised due to aseptic loosening , one due to infection and one due to a traumatic dislocation . This study demonstrates satisfactory mid-term clinical results for this knee design"
] |
4116b9b0-06ff-11f0-808a-c43d1ab1c353
|
Background . High HDL-cholesterol ( HDL-C ) values are negatively correlated with cardiovascular diseases . This review analyses the effect of the supplementation with various Mediterranean diet products ( artichoke , bergamot , and olive oil ) and Asian diet products ( red yeast rice ) on the HDL-C value in dyslipidemic subjects . Methods . A systematic review has been done involving all the English written studies published from the 1st of January 1958 to the 31st of March 2016 . Results . The results of this systematic review indicate that the dietary supplementation with red yeast rice , bergamot , artichoke , and virgin olive oil has promising effects on the increase of HDL-C serum levels . The artichoke leaf extract and virgin olive oil appear to be particularly interesting , while bergamot extract needs further research and the effect of red yeast rice seems to be limited to patients with previous myocardial infa rct ion . Conclusions . Various MediterrAsian diet products or natural extracts may represent a potential intervention treatment to raise HDL-C in dyslipidemic subjects
|
[
"Cardiovascular diseases are the chief causes of death in the UK , and are associated with high circulating levels of total cholesterol in the plasma . Artichoke leaf extracts ( ALEs ) have been reported to reduce plasma lipids levels , including total cholesterol , although high quality data is lacking . The objective of this trial was to assess the effect of ALE on plasma lipid levels and general well-being in otherwise healthy adults with mild to moderate hypercholesterolemia . 131 adults were screened for total plasma cholesterol in the range 6.0 - 8.0 mmol/l , with 75 suitable volunteers r and omised onto the trial . Volunteers consumed 1280 mg of a st and ardised ALE , or matched placebo , daily for 12 weeks . Plasma total cholesterol decreased in the treatment group by an average of 4.2 % ( from 7.16 ( SD 0.62 ) mmol/l to 6.86 ( SD 0.68 ) mmol/l ) and increased in the control group by an average of 1.9 % ( 6.90 ( SD 0.49 ) mmol/l to 7.03 ( 0.61 ) mmol/l ) , the difference between groups being statistically significant ( p=0.025 ) . No significant differences between groups were observed for LDL cholesterol , HDL cholesterol or triglyceride levels . General well-being improved significantly in both the treatment ( 11 % ) and control groups ( 9 % ) with no significant differences between groups . In conclusion , ALE consumption result ed in a modest but favourable statistically significant difference in total cholesterol after 12 weeks . In comparison with a previous trial , it is suggested that the apparent positive health status of the study population may have contributed to the modesty of the observed response",
"The British Regional Heart Study ( BRHS ) reported in 1986 that much of the inverse relation of high-density lipoprotein cholesterol ( HDLC ) and incidence of coronary heart disease was eliminated by covariance adjustment . Using the proportional hazards model and adjusting for age , blood pressure , smoking , body mass index , and low-density lipoprotein cholesterol , we analyzed this relation separately in the Framingham Heart Study ( FHS ) , Lipid Research Clinics Prevalence Mortality Follow-up Study ( LRCF ) and Coronary Primary Prevention Trial ( CPPT ) , and Multiple Risk Factor Intervention Trial ( MRFIT ) . In CPPT and MRFIT ( both r and omized trials in middle-age high-risk men ) , only the control groups were analyzed . A 1-mg/dl ( 0.026 mM ) increment in HDLC was associated with a significant coronary heart disease risk decrement of 2 % in men ( FHS , CPPT , and MRFIT ) and 3 % in women ( FHS ) . In LRCF , where only fatal outcomes were documented , a 1-mg/dl increment in HDLC was associated with significant 3.7 % ( men ) and 4.7 % ( women ) decrements in cardiovascular disease mortality rates . The 95 % confidence intervals for these decrements in coronary heart and cardiovascular disease risk in the four studies overlapped considerably , and all contained the range 1.9 - 2.9 % . HDLC levels were essentially unrelated to non-cardiovascular disease mortality . When differences in analytic methodology were eliminated , a consistent inverse relation of HDLC levels and coronary heart disease event rates was apparent in BRHS as well as in the four American studies",
"Aim : To evaluate whether the consumption of virgin argan oil ( VAO ) is associated with a change in serum lipids and reduces the risk of cardiovascular disease in healthy Moroccans . Methods : Sixty volunteers consumed butter ( 25 g/day ) during 2 weeks ( stabilization period ) and were r and omly divided into two groups : the treatment group received 25 g/day of VAO during 3 weeks ( intervention period ) , and the control group received 25 g/day of extra virgin olive oil ( EVO ) . Throughout the study , weight , blood pressure , and daily food intake were measured . Serum total cholesterol and low- and high-density lipoprotein cholesterol , triglycerides , and apolipoproteins A-I and B were measured at the end of each diet period . Results : Analysis of food intake showed that the daily diet is isocaloric for the butter regimen ( 2,537 ± 244 kcal/day ) as well as for the VAO and EVO regimens ( 2,561± 246 and 2,560 ± 253 kcal/day , respectively ) . Analysis of the lipid intake showed a reduction in saturated fatty acids with VAO and EVO regimens ( 27 ± 1.4 and 26.4 ± 3.4 % , respectively ) as compared with the stabilization period ( 41.6 ± 2.4 % ) . The analysis of serum lipids showed a significant increase in high-density lipoprotein cholesterol and apolipoprotein A-I in both VAO group ( 8.4 % , p = 0.012 , and 5.2 % , p = 0.027 , respectively ) and EVO group ( 17.3 % , p = 0.001 , and 5.9 % , p = 0.036 , respectively ) . However , low-density lipoprotein cholesterol and apolipoprotein B ( 13.8 % , p = 0.037 , and 7.8 % , p = 0.039 , respectively ) decreased significantly only in EVO group as compared with the stabilization period , while triglycerides decreased significantly by 17.5 % ( p = 0.039 ) only in VAO group . Conclusion : These results confirm the cholesterol-lowering effect of EVO and show for the first time the triglyceride-lowering effect of VAO in men",
"The aim of this study was to determine whether eicosapentaenoic acid ( EPA ) or docosahexaenoic acid ( DHA ) , or both , were responsible for the triglyceride (TG)-lowering effects of fish oil . EPA ( 91 % pure ) and DHA ( 83 % pure ) , a fish oil concentrate ( FOC ; 41 % EPA and 23 % DHA ) and an olive oil ( OO ) placebo ( all ethyl esters ) were tested . A total of 49 normolipidemic subjects participated . Each subject was given placebo for 2–3 wk and one of the n-3 supplements for 3 wk in r and omized , blinded trials . The target n-3 fatty acid ( FA ) intake was 3 g/day in all studies . Blood sample s were drawn twice at the end of each supplementation phase and analyzed for lipids , lipoproteins , and phospholipid FA composition . In all groups , the phospholipid FA composition changed to reflect the n-3 FA given . On DHA supplementation , EPA levels increased to a small but significant extent , suggesting that some retroconversion may have occurred . EPA supplementation did not raise DHA levels , however , FOC and EPA produced significant decreases in both TG and very low density lipoprotein ( VLDL ) cholesterol ( C ) levels ( P low density lipoprotein ( LDL ) cholesterol levels ( P cholesterol , triglyceride , VLDL , LDL , or high density lipoprotein ( HDL ) levels , but it did cause a significant increase in the HDL2/HDL3 cholesterol ratio . We conclude that EPA appears to be primarily responsible for TG-lowering ( and LDL-C raising ) effects of fish oil",
"An open-labeled r and omized trial with parallel groups was carried out to study the effects of Dif1stat ® ( Monascus purpureus – Linear aliphatic alcohols – Niacin ) in the treatment of primary moderate hypercholesterolemia . The trial lasted 8 months . The patients , males and females , were assigned to two groups : A ( # 130 ) , treated with diet , and B ( # 110 ) su bmi tted to diet + Dif1stat ® . After 4 months , group A did not show significant changes in Total cholesterol ( TC ) , LDL-cholesterol ( LDLC ) , HDL-cholesterol ( HDLC ) or non-HDL-cholesterol ( non-HDLC ) . The same group , showed a reduction in TC ( –22 % ) , LDLC ( –30 % ) and non-HDLC ( –27 % ) after 8 months ( P ≤ 0.001 ) . After 4 months , TC ( –21.3 % ) , LDLC ( –29 % ) , and non-HDLC ( –26 % ) were significantly lowered in group B ( P ≤ 0.001 ) . In group B , TC , LDLC and non-HDLC showed a further reduction after 8 months : –29.4 , –38 and –37 % , respectively ( P ≤ 0.001 ) . Even triglycerides ( TG ) decreased significantly ( –33 % ) ( P ≤ 0.001 ) . After 8 months , group B showed a significant reduction of TG ( –33 % ) ( P ≤ 0.001 ) , when compared to group A. Some safety parameters were significantly reduced in both groups : AST and γ-GT in group A after 4 and 8 months , as well as ALT , AST and γ-GT in group B after 8 months ( P ≤ 0.001 ) . Dif1stat ® , given with a suitable diet , was well tolerated in the long-term and induced an anti-atherogenic plasma lipid and lipoprotein profile , in patients with moderate hypercholesterolemia",
"BACKGROUND The mechanisms involved in the increased mortality from coronary artery disease in British Indo-Asians are not well understood . OBJECTIVES This study aim ed to investigate whether British Indo-Asian Sikhs have higher plasma triacylglycerol concentrations , lower platelet phospholipid levels , and lower dietary intakes of long-chain n-3 polyunsaturated fatty acids ( PUFAs ) than do age- and weight-matched Europeans and whether moderate dietary fish-oil intake can reverse these differences . DESIGN A r and omized , double-blind , placebo-controlled , parallel , fish-oil intervention study was performed . After a 2-wk run-in period , 44 Europeans and 40 Indo-Asian Sikhs were r and omly assigned to receive either 4.0 g fish oil [ 1.5 g eicosapentaenoic acid ( EPA ) and 1.0 g docosahexaenoic acid ( DHA ) ] or 4.0 g olive oil ( control ) daily for 12 wk . RESULTS At baseline , the Indo-Asians had significantly higher plasma triacylglycerol , small dense LDL , apolipoprotein B , and dietary and platelet phospholipid n-6 PUFA values and significantly lower long-chain n-3 PUFAs ( EPA and DHA ) than did the Europeans . A significant decrease in plasma triacylglycerol , plasma apolipoprotein B-48 , and platelet phospholipid arachidonic acid concentrations and a significant increase in plasma HDL concentrations and platelet phospholipid EPA and DHA levels were observed after fish-oil supplementation . No significant effect of ethnicity on the responses to fish-oil supplementation was observed . CONCLUSIONS Moderate fish-oil supplementation contributes to a reversal of lipid abnormalities and low n-3 PUFA levels in Indo-Asians and should be considered as an important , yet simple , dietary manipulation to reduce CAD risk in Indo-Asians with an atherogenic lipoprotein phenotype",
"The aim of the present study was to evaluate whether olive oils high in phenolic compounds influence the oxidative/antioxidative status in humans . Healthy men ( n = 12 ) participated in a double-blind , r and omized , crossover study in which 3 olive oils with low ( LPC ) , moderate ( MPC ) , and high ( HPC ) phenolic content were given as raw doses ( 25 mL/d ) for 4 consecutive days preceded by 10-d washout periods . Volunteers followed a strict very low-antioxidant diet the 3 d before and during the intervention periods . Short-term consumption of olive oils decreased plasma oxidized LDL ( oxLDL ) , 8-oxo-dG in mitochondrial DNA and urine , malondialdehyde in urine ( P increased HDL cholesterol and glutathione peroxidase activity ( P olive oil administered . At d 4 , oxLDL after MPC and HPC , and 8-oxo-dG after HPC administration ( 25 mL , respectively ) , were reduced when the men were in the postpr and ial state ( P Phenolic compounds in plasma increased dose dependently during this stage with the phenolic content of the olive oils at 1 , 2 , 4 , and 6 h , respectively ( P concentrations increased in plasma and urine sample s in a dose-dependent manner after short-term consumption of the olive oils ( P oxidative/antioxidative status of healthy men who consumed a very low-antioxidant diet",
"BACKGROUND We examined the cholesterol-lowering effects of a proprietary Chinese red-yeast-rice supplement in an American population consuming a diet similar to the American Heart Association Step I diet using a double-blind , placebo-controlled , prospect ively r and omized 12-wk controlled trial at a university research center . OBJECTIVE We evaluated the lipid-lowering effects of this red-yeast-rice dietary supplement in US adults separate from effects of diet alone . DESIGN Eighty-three healthy subjects ( 46 men and 37 women aged 34 - 78 y ) with hyperlipidemia [ total cholesterol , 5.28 - 8.74 mmol/L ( 204 - 338 mg/dL ) ; LDL cholesterol , 3.31 - 7.16 mmol/L ( 128 - 277 mg/dL ) ; triacylglycerol , 0.62 - 2.78 mmol/L ( 55 - 246 mg/dL ) ; and HDL cholesterol 0.78 - 2.46 mmol/L ( 30 - 95 mg/dL ) ] who were not being treated with lipid-lowering drugs participated . Subjects were treated with red yeast rice ( 2.4 g/d ) or placebo and instructed to consume a diet providing 30 % of energy from fat , total cholesterol , total triacylglycerol , and HDL and LDL cholesterol measured at weeks 8 , 9 , 11 , and 12 . RESULTS Total cholesterol concentrations decreased significantly between baseline and 8 wk in the red-yeast-rice-treated group compared with the placebo-treated group [ ( x+/-SD ) 6.57+/-0.93 mmol/L ( 254+/-36 mg/dL ) to 5.38+/-0.80 mmol/L ( 208+/-31 mg/dL ) ; P LDL cholesterol and total triacylglycerol were also reduced with the supplement . HDL cholesterol did not change significantly . CONCLUSIONS Red yeast rice significantly reduces total cholesterol , LDL cholesterol , and total triacylglycerol concentrations compared with placebo and provides a new , novel , food-based approach to lowering cholesterol in the general population",
"BACKGROUND Short-term trials showed that conjugated linoleic acid ( CLA ) may reduce body fat mass ( BFM ) and increase lean body mass ( LBM ) , but the long-term effect of CLA was not examined . OBJECTIVE The objective of the study was to ascertain the 1-y effect of CLA on body composition and safety in healthy overweight adults consuming an ad libitum diet . DESIGN Male and female volunteers ( n = 180 ) with body mass indexes ( in kg/m(2 ) ) of 25 - 30 were included in a double-blind , placebo-controlled study . Subjects were r and omly assigned to 3 groups : CLA-free fatty acid ( FFA ) , CLA-triacylglycerol , or placebo ( olive oil ) . Change in BFM , as measured by dual-energy X-ray absorptiometry , was the primary outcome . Secondary outcomes included the effects of CLA on LBM , adverse events , and safety variables . RESULTS Mean ( + /- SD ) BFM in the CLA-triacylglycerol and CLA-FFA groups was 8.7 + /- 9.1 % and 6.9 + /- 9.1 % , respectively , lower than that in the placebo group ( P LBM than did subjects receiving placebo ( P = 0.002 ) . These changes were not associated with diet or exercise . LDL increased in the CLA-FFA group ( P = 0.008 ) , HDL decreased in the CLA-triacylglycerol group ( P = 0.003 ) , and lipoprotein(a ) increased in both CLA groups ( P Fasting blood glucose concentrations remained unchanged in all 3 groups . Glycated hemoglobin rose in all groups from month 0 concentrations , but there was no significant difference between groups . Adverse events did not differ significantly between groups . CONCLUSION Long-term supplementation with CLA-FFA or CLA-triacylglycerol reduces BFM in healthy overweight adults",
"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",
"Drug therapy for hypercholesterolaemia has remained controversial mainly because of insufficient clinical trial evidence for improved survival . The present trial was design ed to evaluate the effect of cholesterol lowering with simvastatin on mortality and morbidity in patients with coronary heart disease ( CHD ) . 4444 patients with angina pectoris or previous myocardial infa rct ion and serum cholesterol 5.5 - 8.0 mmol/L on a lipid-lowering diet were r and omised to double-blind treatment with simvastatin or placebo . Over the 5.4 years median follow-up period , simvastatin produced mean changes in total cholesterol , low-density-lipoprotein cholesterol , and high-density-lipoprotein cholesterol of -25 % , -35 % , and + 8 % , respectively , with few adverse effects . 256 patients ( 12 % ) in the placebo group died , compared with 182 ( 8 % ) in the simvastatin group . The relative risk of death in the simvastatin group was 0.70 ( 95 % CI 0.58 - 0.85 , p = 0.0003 ) . The 6-year probabilities of survival in the placebo and simvastatin groups were 87.6 % and 91.3 % , respectively . There were 189 coronary deaths in the placebo group and 111 in the simvastatin group ( relative risk 0.58 , 95 % CI 0.46 - 0.73 ) , while noncardiovascular causes accounted for 49 and 46 deaths , respectively . 622 patients ( 28 % ) in the placebo group and 431 ( 19 % ) in the simvastatin group had one or more major coronary events . The relative risk was 0.66 ( 95 % CI 0.59 - 0.75 , p escaping such events were 70.5 % and 79.6 % . This risk was also significantly reduced in subgroups consisting of women and patients of both sexes aged 60 or more . Other benefits of treatment included a 37 % reduction ( p risk of undergoing myocardial revascularisation procedures . This study shows that long-term treatment with simvastatin is safe and improves survival in CHD patients",
"BACKGROUND The inverse association between moderate drinking and coronary heart disease mortality is well established . This study was performed to investigate the kinetics of the alcohol-induced increases in apo A-1 , HDL cholesterol , and paraoxonase ( PON ) activity , as well as to study whether the alcohol-induced increases in PON activity differ within different PON polymorphisms , and to investigate whether moderate alcohol consumption has similar effects on the outcome measures in postmenopausal women as in middle-aged men . METHODS In a r and omized , diet-controlled , crossover study , 10 middle-aged men and 9 postmenopausal women , all apparently healthy , nonsmoking , and moderate alcohol drinkers , consumed beer or no-alcohol beer ( control ) with evening dinner during two successive periods of 3 weeks . During the beer period , alcohol intake equaled 40 and 30 g/day for men and women , respectively . The total diet was supplied to the subjects and had essentially the same composition during these 6 weeks . Before each treatment was a 1-week washout period , in which the subjects were not allowed to drink alcoholic beverages . RESULTS Moderate alcohol consumption significantly increased serum apo A-I level after 5 days ( 3.7 % , p serum HDL cholesterol level was increased ( 6.8 % , p serum PON activity was increased ( 3.7 % , p Serum apo A-I , HDL cholesterol , and PON activity were significantly increased during 3 weeks of moderate alcohol consumption as compared with no alcohol consumption . Moreover , the results suggest that there is a sequence in induction of these parameters . After an increase in apo A-I , HDL cholesterol is increased followed by an increase in PON activity . Increased serum HDL cholesterol level and PON activity may be a mechanism of action not only in healthy middle-aged men but also in postmenopausal women , underlying the reduced coronary heart disease risk in moderate drinkers",
"Objective : We studied whether consumption of phenol-rich extra virgin olive oil affects the susceptibility of low density lipoproteins ( LDL ) to oxidation and other markers of oxidation in humans . Design : R and omized cross-over intervention trial , stratified according to sex , age and energy intake . Setting : Division of Human Nutrition and Epidemiology , Wageningen University , The Netherl and s . Subjects : Forty-six healthy men and women completed the study .Intervention : Subjects consumed two diets supplying 69 g per day of extra virgin olive oil either rich or poor in phenols for 3 weeks each . The mean difference in phenol intake between the treatments was 18 mg per day . Vitamin E intake was low during the whole study . Fasting blood sample s were taken twice at the end of each period . Results : Resistance of LDL and high density lipoprotein ( HDL ) to oxidation was not affected by treatment . The mean lag time of copper-induced formation of conjugated dienes was 1.6 min shorter in LDL and 0.4 min longer in HDL after the high phenol diet . Other markers of antioxidant capacity in plasma were also not affected : mean lipid hydroperoxides were 0.07 µmol/l higher , mean malondialdehydes were 0.001 µmol/l higher , mean protein carbonyls were 0.001 nmol/mg protein lower , and the mean ferric reducing ability of plasma ( FRAP ) was 0.006 mmol/l higher after the high phenol diet . All 95 % confidence intervals enclosed zero . Serum cholesterol concentrations were not affected by the treatment . Conclusion : Consumption of 18 mg per day of phenols from extra virgin olive oil for 3 weeks did not affect LDL or HDL oxidation or other markers of antioxidant capacity in fasting plasma sample s . Sponsorship : Supported by the International Olive Oil Council and the Foundation for Nutrition and Health Research .European Journal of Clinical Nutrition ( 2001 ) 55 ,",
"Results of well-controlled prospect i ve clinical trials showed the efficacy of lipid-lowering therapies in the reduction of cardiovascular ( CV ) events in western population s , but they were not reported with a Chinese population . This multicenter study was conducted to determine the effects of Xuezhikang ( XZK ) , a partially purified extract of red yeast rice , on lipoprotein and CV end points in Chinese patients who experienced a previous myocardial infa rct ion . Nearly 5,000 of these patients with average low-density lipoprotein cholesterol levels at baseline were r and omly assigned either to placebo or to XZK daily for an average of 4.5 years . The primary end point was a major coronary event that included nonfatal myocardial infa rct ion and death from coronary heart disease . Frequencies of the primary end point were 10.4 % in the placebo group and 5.7 % in the XZK-treated group , with absolute and relative decreases of 4.7 % and 45 % , respectively . Treatment with XZK also significantly decreased CV and total mortality by 30 % and 33 % , the need for coronary revascularization by 1/3 , and lowered total and low-density lipoprotein cholesterol and triglycerides , but raised high-density lipoprotein cholesterol levels . In conclusion , long-term therapy with XZK significantly decreased the recurrence of coronary events and the occurrence of new CV events and deaths , improved lipoprotein regulation , and was safe and well tolerated",
"Objective : To assess fasting lipid responses to a docosahexaenoic acid ( DHA ) supplement in men and women with below-average levels of high-density lipoprotein ( HDL ) cholesterol . Methods : This r and omized , double-blind , controlled clinical trial included 57 subjects , 21–80 years of age , with fasting HDL cholesterol concentrations ≤44 mg/dL ( men ) and ≤54 mg/dL ( women ) , but ≥35 mg/dL. Subjects were r and omly assigned to receive either 1.52 g/day DHA from capsules containing DHA-rich algal triglycerides or olive oil ( control ) for six weeks . Results : There were no significant differences between groups in baseline lipid values . The DHA supplemented group showed significant changes [ −43 ( DHA ) vs. −14 ( controls ) mg/dL , p = 0.015 ] and percent changes [ −21 % ( DHA ) vs. −7 % ( controls ) , p = 0.009 ] in triglycerides , total ( 12 vs. 3 mg/dL ; p = 0.021 and 6 % vs. 2 % ; p = 0.018 ) and low-density lipoprotein ( 17 vs. 3 mg/dL ; p = 0.001 and 12 % vs. 3 % ; p = 0.001 ) cholesterol concentrations , and in the triglyceride to HDL cholesterol ratio ( −1.33 vs. −0.50 , p = 0.010 ) , compared with controls . In addition , there was a significant reduction in the percentage of LDL cholesterol carried by small , dense particles in the DHA supplemented group ( changes = −10 % vs. −3 % , p = 0.025 ) . Conclusions : Supplementation with 1.52 g/d of DHA in men and women with below-average HDL cholesterol concentrations raised the LDL cholesterol level , but had favorable effects on triglycerides , the triglyceride/HDL cholesterol ratio and the fraction of LDL cholesterol carried by small , dense particles . Further research is warranted to evaluate the net impact of these alterations on cardiovascular risk ",
"BACKGROUND Xuezhikang ( XZK ) is an extract of fermented red yeast rice that has lipid-lowering properties . OBJECTIVE To evaluate the effects of XZK on lipids in subjects with dyslipidemia but no coronary heart disease . METHODS A total of 116 adults with baseline non-high-density lipoprotein cholesterol ( non-HDL-C ) levels of approximately 208 mg/dL and low-density lipoprotein cholesterol ( LDL-C ) levels of approximately 175 mg/dL were r and omized to either placebo or XZK 1200 or 2400 mg daily and treated for 12 weeks . RESULTS A majority of the patients were white ( 53.4 % ) or Asian ( 37.1 % ) . Daily XZK 1200 mg and 2400 mg for 4 to 12 weeks result ed in statistically significant ( P in non-HDL-C ( ∼24 % reduction ) and LDL-C ( ∼27 % reduction ) compared with placebo . XZK treatment at either dose enabled approximately 50 % of subjects to reduce their LDL-C levels by ≥ 30 % . Doubling the XZK daily dose from 1200 to 2400 mg at treatment week 8 caused an additional 4.6 % reduction in LDL-C. Significant benefits were also observed across secondary efficacy variables , including total cholesterol ( TC ) , apolipoprotein B ( Apo B ) , triglycerides , HDL-C , the TC/HDL-C ratio , and the Apo B/Apo A-I ratio , at treatment week 8 or 12 . XZK was safe and well tolerated . Safety and tolerability profiles were similar across treatment groups . Most adverse events were gastrointestinal . No subject experienced myopathy or markedly elevated liver transaminases or creatine kinase . CONCLUSION Xuezhikang significantly reduced non-HDL-C and LDL-C , and was well tolerated . Further , longer-term studies in more diverse patient population s are needed to corroborate these findings",
"BACKGROUND Statins are the most commonly prescribed drugs to reduce cardiometabolic risk . Besides the well-known efficacy of such compounds in both preventing and treating cardiometabolic disorders , some patients experience statin-induced side effects . We hypothesize that the use of natural bergamot-derived polyphenols may allow patients undergoing statin treatment to reduce effective doses while achieving target lipid values . The aim of the present study is to investigate the occurrence of an enhanced effect of bergamot-derived polyphenolic fraction ( BPF ) on rosuvastatin-induced hypolipidemic and vasoprotective response in patients with mixed hyperlipidemia . METHODS A prospect i ve , open-label , parallel group , placebo-controlled study on 77 patients with elevated serum LDL-C and triglycerides was design ed . Patients were r and omly assigned to a control group receiving placebo ( n=15 ) , two groups receiving orally administered rosuvastatin ( 10 and 20mg/daily for 30 days ; n=16 for each group ) , a group receiving BPF alone orally ( 1000 mg/daily for 30 days ; n=15 ) and a group receiving BPF ( 1000 mg/daily given orally ) plus rosuvastatin ( 10mg/daily for 30 days ; n=15 ) . RESULTS Both doses of rosuvastatin and BPF reduced total cholesterol , LDL-C , the LDL-C/HDL-C ratio and urinary mevalonate in hyperlipidemic patients , compared to control group . The cholesterol lowering effect was accompanied by reductions of malondialdehyde , oxyLDL receptor LOX-1 and phosphoPKB , which are all biomarkers of oxidative vascular damage , in peripheral polymorphonuclear cells . CONCLUSIONS Addition of BPF to rosuvastatin significantly enhanced rosuvastatin-induced effect on serum lipemic profile compared to rosuvastatin alone . This lipid-lowering effect was associated with significant reductions of biomarkers used for detecting oxidative vascular damage , suggesting a multi-action enhanced potential for BPF in patients on statin therapy",
"Background : This study aim ed to investigate the possible relationships between adiponectin and leptin , blood lipids such as total cholesterol , high-density lipoprotein cholesterol ( HDL-C ) , low-density lipoprotein cholesterol ( LDL-C ) , and triglycerides ( TG ) as well as other clinical biomarkers in hyperlipidemia patients treated with red yeast rice . Methods : 30 patients with primary hyperlipidemia were recruited , treated with red rice yeast capsules 600 mg twice a day for 8 weeks , and followed up for 4 weeks . The primary endpoint was the mean difference in LDL-C from baseline to week 8 , while the secondary endpoints were the mean percentage changes from baseline of total cholesterol , TG , HDL-C , adiponectin , and leptin . Results : At week 8 , the decrease in LDL-C and total cholesterol was -38.11 ± 30.90 mg/dl ( p in adiponectin was 35.83 ± 67.85 μg/ml ( p = 0.017 ) as compared to baseline . Adiponectin also correlated positively with HDL-C ( r2 = 0.39 ; p = 0.001 ) . Serum leptin correlated negatively with TG ( r2 = 0.19 ; p = 0.035 ) , and there was a trend of correlation between leptin and HDL-C , but this was not statistically significant ( r2 = 0.16 ; p = 0.052 ) . Conclusion : Red yeast rice can significantly increase adiponectin and can significantly lower LDL-C and total cholesterol levels . Adiponectin correlates positively with HDL-C while serum leptin correlates negatively with TG . Red yeast rice has a potentially protective effect in obesity-related and cardiovascular diseases",
"Efficacy and tolerability of artichoke dry extract ( drug/extract ratio 25 - 35:1 , aquous extract , CY450 ) as coated tablets containing 450 mg extract ( tradename : Valverde Artischocke bei Verdauungsbeschwerden ) was investigated in the treatment of hyperlipoproteinemia and compared with placebo . 143 adult patients with initial total cholesterol of > 7.3 mmol/l ( > 280 mg/dl ) were included in a double blind , r and omized , placebo controlled , multi-center clinical trial . Patients received 1,800 mg artichoke dry extract per day or placebo over 6 weeks . Changes of total cholesterol and LDL-cholesterol from baseline to the end of treatment showed a statistically significant superiority ( p = 0.0001 ) of artichoke dry extract over placebo . The decrease of total cholesterol in the CY450 group was 18.5 % compared to 8.6 % in the placebo group . LDL-cholesterol decrease in the CY450 group was 22.9 % and 6.3 % for placebo . LDL/HDL ratio showed a decrease of 20.2 % in the CY450 group and 7.2 % in the placebo group . There were no drug related adverse events during this study indicating an excellent tolerability of artichoke dry extract . This prospect i ve study could contribute clear evidence to recommend artichoke dry extract CY450 for treating hyperlipoproteinemia and , thus , prevention of atherosclerosis and coronary heart disease",
"BACKGROUND In patients with high cholesterol levels , lowering the cholesterol level reduces the risk of coronary events , but the effect of lowering cholesterol levels in the majority of patients with coronary disease , who have average levels , is less clear . METHODS In a double-blind trial lasting five years we administered either 40 mg of pravastatin per day or placebo to 4159 patients ( 3583 men and 576 women ) with myocardial infa rct ion who had plasma total cholesterol levels below 240 mg per deciliter ( mean , 209 ) and low-density lipoprotein ( LDL ) cholesterol levels of 115 to 174 mg per deciliter ( mean , 139 ) . The primary end point was a fatal coronary event or a nonfatal myocardial infa rct ion . RESULTS The frequency of the primary end point was 10.2 percent in the pravastatin group and 13.2 percent in the placebo group , an absolute difference of 3 percentage points and a 24 percent reduction in risk ( 95 percent confidence interval , 9 to 36 percent ; P = 0.003 ) . Coronary bypass surgery was needed in 7.5 percent of the patients in the pravastatin group and 10 percent of those in the placebo group , a 26 percent reduction ( P=0.005 ) , and coronary angioplasty was needed in 8.3 percent of the pravastatin group and 10.5 percent of the placebo group , a 23 percent reduction ( P=0.01 ) . The frequency of stroke was reduced by 31 percent ( P=0.03 ) . There were no significant differences in overall mortality or mortality from noncardiovascular causes . Pravastatin lowered the rate of coronary events more among women than among men . The reduction in coronary events was also greater in patients with higher pretreatment levels of LDL cholesterol . CONCLUSIONS These results demonstrate that the benefit of cholesterol-lowering therapy extends to the majority of patients with coronary disease who have average cholesterol levels",
"Currently , no consensus has been reached regarding the management of hyperlipidemia in patients who develop statin-associated myalgia ( SAM ) . Many statin-intolerant patients use alternative lipid-lowering therapies , including red yeast rice . The present trial evaluated the tolerability of red yeast rice versus pravastatin in patients unable to tolerate other statins because of myalgia . The study was conducted in a community-based setting in Philadelphia , Pennsylvania . A total of 43 adults with dyslipidemia and a history of statin discontinuation because of myalgia were r and omly assigned to red yeast rice 2,400 mg twice daily or pravastatin 20 mg twice daily for 12 weeks . All subjects were concomitantly enrolled in a 12-week therapeutic lifestyle change program . The primary outcomes included the incidence of treatment discontinuation because of myalgia and a daily pain severity score . The secondary outcomes were muscle strength and plasma lipids . The incidence of withdrawal from medication owing to myalgia was 5 % ( 1 of 21 ) in the red yeast rice group and 9 % ( 2 of 22 ) in the pravastatin group ( p = 0.99 ) . The mean pain severity did not differ significantly between the 2 groups . No difference was found in muscle strength between the 2 groups at week 4 ( p = 0.61 ) , week 8 ( p = 0.81 ) , or week 12 ( p = 0.82 ) . The low-density lipoprotein cholesterol level decreased 30 % in the red yeast rice group and 27 % in the pravastatin group . In conclusion , red yeast rice was tolerated as well as pravastatin and achieved a comparable reduction of low-density lipoprotein cholesterol in a population previously intolerant to statins ",
"This cost-consequences analysis of the Air Force/Texas Coronary Atherosclerosis Prevention Study compares the costs of lovastatin treatment with the costs of cardiovascular hospitalizations and procedures . The cost of lovastatin treatment was defined as the average retail price and the cost of drug safety monitoring and adverse experiences . Costs were determined by actual rates of hospitalizations and procedures . Within a trial , lovastatin treatment cost approximately $ 4,654/patient . Lovastatin treatment significantly reduced the cumulative rate of cardiovascular hospitalizations and procedures ( p = 0.002 ) . Over the duration of the study , the cumulative number of cardiovascular hospitalizations and related therapeutic procedures was significantly reduced by 29 % . The time to first cardiovascular-related hospitalization or procedure was significantly extended by lovastatin ( p = 0.002 ) . Lovastatin reduced the frequency of cardiovascular hospitalization ( 28 % ) , and cardiovascular therapeutic ( 32 % ) and diagnostic procedures ( 23 % ) . Among therapeutic procedures , treatment reduced coronary artery bypass graft surgery by 19 % and percutaneous transluminal coronary angioplasty by 37 % . Total cardiovascular-related hospital days were reduced by 26 % ( p = 0.025 ) . The between-group offset in direct medical costs was $ 524 , which result ed in a 11 % cost offset of lovastatin therapy over the mean study duration of 5.2 years . Lovastatin provides meaningful reductions in cardiovascular-related re source utilization and reductions in direct cardiovascular-related costs associated with the onset of coronary disease",
"Moderate alcohol consumption is associated with a reduced risk of coronary heart disease . Part of this inverse association may be explained by its effects on HDL . Paraoxonase , an HDL-associated enzyme , has been suggested to protect against LDL oxidation . We examined the effects of moderate consumption of red wine , beer and spirits in comparison with mineral water on paraoxonase activity in serum . In this diet-controlled , r and omised , cross-over study 11 healthy middle-aged men consumed each of the beverages with evening dinner for 3 weeks . At the end of each 3 week period , blood sample s were collected pre- and postpr and ially and after an overnight fast . Fasting paraoxonase activity was higher after intake of wine ( P paraoxonase activity were strongly correlated with coincident increases in concentrations of HDL-C and apo A-I ( r=0.60 , P serum paraoxonase may be one of the biological mechanisms underlying the reduced coronary heart disease risk in moderate alcohol",
"Summary . Background : Evidence from in vitro studies suggests that antioxidant olive oil phenolic compounds can prevent LDL oxidation . However , in vivo evidence in support of this hypothesis is sparse . Aim of the study : to establish the antioxidant effect of olive oils with differences in their phenolic compounds content in humans Methods : A controlled , double blind , cross-over , r and omized , clinical trial using three similar olive oils with increasing phenolic concentration ( from 0 to 150 mg/Kg ) was conducted in 30 healthy volunteers . Olive oils were administered over three periods of 3 weeks preceded by two-week washout periods . Results : Urinary tyrosol and hydroxytyrosol increased ( p in vivo plasma oxidized LDL decreased ( p = 0.006 ) , and ex vivo resistance of LDL to oxidation increased ( p = 0.012 ) with the phenolic content of the olive oil administered . After virgin olive oil administration , an increase ( p = 0.029 ) was observed in HDL cholesterol levels . Conclusions : Sustained consumption of virgin olive oil with the high phenolic content was more effective in protecting LDL from oxidation and in rising HDL cholesterol levels than that of other type of olive oils . Dose-dependent changes in oxidative stress markers , and phenolic compounds in urine , were observed with the phenolic content of the olive oil administered . Our results support the hypothesis that virgin olive oil consumption could provide benefits in the prevention of oxidative processes",
"The aim of this study was to evaluate the effects of artichoke leaf extract ( ALE ) supplementation ( 250 mg , 2 b.i.d . ) on the lipid pattern . A r and omized , double-blind , placebo-controlled clinical trial was performed on 92 overweight subjects with primary mild hypercholesterolaemia for 8 weeks . Forty-six subjects were r and omized to supplementation ( age : 54.2 ± 6.6 years , body mass index ( BMI ): 25.8 ± 3.9 kg/m2 , male/female : 20/26 ) and 46 subjects to placebo ( age : 53.8 ± 9.0 years , BMI : 24.8 ± 1.6 kg/m2 , male/female : 21/25 ) . Verum supplementation was associated with a significant increase in mean high-density lipoprotein (HDL)-cholesterol ( p mean change in HDL-cholesterol ( HDL-C ) ( p = 0.004 ) . A significantly decreased difference was also found for the mean change in total cholesterol ( p = 0.033 ) , low-density lipoprotein (LDL)-cholesterol ( p ) , total cholesterol/HDL ratio ( p and LDL/HDL ratio ( p and placebo treatment were compared . These results indicate that ALE could play a relevant role in the management of mild hypercholesterolaemia , favouring in particular the increase in HDL-C , besides decreasing total cholesterol and LDL-cholesterol ",
"Objective — Olive oil polyphenols have shown beneficial properties against cardiovascular risk factors . Their consumption has been associated with higher cholesterol content in high-density lipoproteins ( HDL ) . However , data on polyphenol effects on HDL quality are scarce . We , therefore , assessed whether polyphenol-rich olive oil consumption could enhance the HDL main function , its cholesterol efflux capacity , and some of its quality -related properties , such HDL polyphenol content , size , and composition . Approach and Results — A r and omized , crossover , controlled trial with 47 healthy European male volunteers was performed . Participants ingested 25 mL/d of polyphenol-poor ( 2.7 mg/kg ) or polyphenol-rich ( 366 mg/kg ) raw olive oil in 3-week intervention periods , preceded by 2-week washout periods . HDL cholesterol efflux capacity significantly improved after polyphenol-rich intervention versus the polyphenol-poor one ( + 3.05 % and −2.34 % , respectively ; P=0.042 ) . Incorporation of olive oil polyphenol biological metabolites to HDL , as well as large HDL ( HDL2 ) levels , was higher after the polyphenol-rich olive oil intervention , compared with the polyphenol-poor one . Small HDL ( HDL3 ) levels decreased , the HDL core became triglyceride-poor , and HDL fluidity increased after the polyphenol-rich intervention . Conclusions — Olive oil polyphenols promote the main HDL antiatherogenic function , its cholesterol efflux capacity . These polyphenols increased HDL size , promoted a greater HDL stability reflected as a triglyceride-poor core , and enhanced the HDL oxidative status , through an increase in the olive oil polyphenol metabolites content in the lipoprotein . Our results provide for the first time a first-level evidence of an enhancement in HDL function by polyphenol-rich olive oil"
] |
4116b9f6-06ff-11f0-808a-c43d1ab1c353
|
Background The majority of patients with overweight and type 2 diabetes show insufficient levels of daily physical activity ( PA ) and usually are among the least likely to engage in or adhere to any form of generic PA . Active video games ( exergames ) may be a solution to motivate these individuals to overcome their sedentary lifestyle . Objectives This systematic review was conducted to review the current evidence for the effectiveness of exergaming in overweight and type 2 diabetes mellitus and thus to evaluate the suitability of these games to be used as tools for exercise promotion that meet current PA guidelines . Methods We search ed electronic bibliographic data bases ( PubMed , Embase , Web of Science , OpenGrey , and the Cochrane Central Register of Controlled Trials ) up to March 2015 . R and omized controlled trials ( RCT ) and cross-sectional studies published in English in a peer- review ed journal and analyzing the effects of exergames on objective ly measured intensity parameters of PA in overweight ( body mass index [ BMI ] ≥25 kg/m2 ) adults ( mean age ≥18 years ) with and without type 2 diabetes were included . Study selection , data extraction , and quality assessment were performed independently by two review authors . Primary outcomes included changes in oxygen uptake ( VO2 ) , energy expenditure ( EE ) , heart rate ( HR ) , or activity counts . Secondary outcomes were enjoyment of treatment , exercise adherence , ratings of perceived exertion ( RPE ) , changes in body composition , and changes in blood parameters ( serum glucose , long-term blood glucose , blood cholesterol , triglycerides , or serum lactate ) . Results Of 2845 records , 14 publications ( 11 studies ) met the inclusion criteria . All included studies ( ten experimental , cross-sectional laboratory studies and one RCT ) were able to show increases in either VO2 , EE , HR , or activity counts . However , effects of exergaming in terms of changes in these intensity parameters varied significantly between game modes and consoles as well as because of the vastly differing duration s of exergame activity between studies . One of the included studies had a low risk of bias , and three had a high risk of bias ; seven studies had an unclear risk of bias as the study description was insufficient . No studies were found investigating the changes in objective ly measured PA intensity parameters in patients with type 2 diabetes . Conclusion This review suggests that exergames are able to increase PA among overweight individuals . However , the inconsistent results and the overall poor or moderate method ological quality do not permit judgment on whether exergames are suitable to meet PA guidelines in this target group . The lack of research regarding the effects of exergames in type 2 diabetes indicates a great need for future research
|
[
"Aims /hypothesis . The aim of the Diabetes Prevention Study is to assess the efficacy of an intensive diet-exercise programme in preventing or delaying Type II ( non-insulin-dependent ) diabetes mellitus in subjects with impaired glucose tolerance , to evaluate the effects of the intervention programme on cardiovascular risk factors and to assess the determinants for the progression to diabetes in persons with impaired glucose tolerance . Methods . A total of 523 overweight subjects with impaired glucose tolerance ascertained by two oral glucose tolerance tests were r and omised to either a control or intervention group . The control subjects received general information at the start of the trial about the lifestyle changes necessary to prevent diabetes and about annual follow-up visits . The intervention subjects had seven sessions with a nutritionist during the first year and a visit every 3 months thereafter aim ed at reducing weight , the intake of saturated fat and increasing the intake of dietary fibre . Intervention subjects were also guided individually to increase their physical activity . Results . During the first year , weight loss in the first 212 study subjects was 4.7 ± 5.5 vs 0.9 ± 4.1 kg in the intervention and control group , respectively ( p The plasma glucose concentrations ( fasting : 5.9 ± 0.7 vs 6.4 ± 0.8 mmol/l , p in blood pressure , serum lipids and anthropometric indices in the intervention group . Conclusion /interpretation . The interim results show the efficacy and feasibility of the lifestyle intervention programme . [ Diabetologia ( 1999 ) 42 : 793–801",
"Sports- and fitness-themed video games using motion controllers have been found to produce physical activity . It is possible that motion controllers may also enhance energy expenditure when applied to more sedentary games such as action games . Young adults ( N = 100 ) were r and omized to play three games using either motion-based or traditional controllers . No main effect was found for controller or game pair ( P > .12 ) . An interaction was found such that in one pair , motion control ( mean [ SD ] 0.96 [ 0.20 ] kcal · kg−1 · hr−1 ) produced 0.10 kcal · kg−1 · hr−1 ( 95 % confidence interval 0.03 to 0.17 ) greater energy expenditure than traditional control ( 0.86 [ 0.17 ] kcal · kg−1 · hr−1 , P = .048 ) . All games were sedentary . As currently implemented , motion control is unlikely to produce moderate intensity physical activity in action games . However , some games produce small but significant increases in energy expenditure , which may benefit health by decreasing sedentary behavior ",
"Abstract Douris , PC , McDonald , B , Vespi , F , Kelley , NC , and Herman , L. Comparison between Nintendo Wii Fit aerobics and traditional aerobic exercise in sedentary young adults . J Strength Cond Res 26(4 ) : 1052–1057 , 2012—Exergaming is becoming a popular recreational activity for young adults . The purpose was to compare the physiologic and psychological responses of college students playing Nintendo Wii Fit , an active video game console , vs. an equal duration of moderate-intensity brisk walking . Twenty-one healthy sedentary college-age students ( mean age 23.2 ± 1.8 years ) participated in a r and omized , double cross-over study , which compared physiologic and psychological responses to 30 minutes of brisk walking exercise on a treadmill vs. 30 minutes playing Nintendo Wii Fit “ Free Run ” program . Physiologic parameters measured included heart rate , rate pressure product , respiratory rate , and rating of perceived exertion . Participants ' positive well-being , psychological distress , and level of fatigue associated with each exercise modality were quantified using the Subjective Exercise Experience Scale . The mean maximum heart rate ( HRmax ) achieved when exercising with Wii Fit ( 142.4 ± 20.5 b·min−1 ) was significantly greater ( p = 0.001 ) compared with exercising on the treadmill ( 123.2 ± 13.7 b·min−1 ) . Rate pressure product was also significantly greater ( p = 0.001 ) during exercise on the Wii Fit . Participants ' rating of perceived exertion when playing Wii Fit ( 12.7 ± 3.0 ) was significantly greater ( p = 0.014 ) when compared with brisk walking on the treadmill ( 10.1 ± 3.3 ) . However , psychologically when playing Wii Fit , participants ' positive well-being decreased significantly ( p = 0.018 ) from preexercise to postexercise when compared with exercising on the treadmill . College students have the potential to surpass exercise intensities achieved when performing a conventional st and ard for moderate-intensity exercise when playing Nintendo Wii Fit “ Free Run ” with a self-selected intensity . We concluded that Nintendo Wii Fit “ Free Run ” may act as an alternative to traditional moderate-intensity aerobic exercise in fulfilling the American College of Sports Medicine requirements for physical activity",
"OBJECTIVES To compare the prevalence and correlates of meeting current recommendations for physical activity in older adults with and without diabetes mellitus ( DM ) in the United States . DESIGN A cross-sectional , population -based sample . SETTING The 2007 Behavioral Risk Factor Surveillance Survey , which employs r and om-digit dialing to interview noninstitutionalized U.S. adults . PARTICIPANTS Ninety-nine thous and one hundred seventy-two adults ( 18,370 with DM ) aged 65 and older . MEASUREMENTS The age-adjusted prevalence and the odds ratios for physical activity patterns ( defined on the basis of the physical activity guidelines from the American Diabetes Association ( ADA 2007 ) and the Department of Health and Human Services ( DHHS 2008 ) ) were obtained using multiple logistic regression analyses . The correlates of meeting physical activity recommendations were assessed using log-binomial regression analyses . RESULTS Overall , 25 % and 42 % of older adults with diabetes mellitus met recommendations for total physical activity based on the ADA 2007 and the DHHS 2008 guidelines , respectively . Adults with DM were 31 % to 34 % ( P engage in physical activity at recommended levels and 13 % to 19 % ( P physically active at insufficient levels than those without DM . Analyses limited to participants who reported no disability yielded similar results . In adults with DM , older age ( ≥ 75 ) ; being female ; being non-Hispanic black ; and having obesity , coronary heart disease , and disability were associated with less likelihood , whereas advanced educational status was associated with greater likelihood of meeting physical activity recommendations . CONCLUSION In the United States , efforts to boost physical activity participation in older adults with DM are needed",
"Clinical trials have demonstrated that lifestyle changes can prevent type 2 diabetes , but the importance of leisure-time physical activity ( LTPA ) is still unclear . We carried out post hoc analyses on the role of LTPA in preventing type 2 diabetes in 487 men and women with impaired glucose tolerance who had completed 12-month LTPA question naires . The subjects were participants in the Finnish Diabetes Prevention Study , a r and omized controlled trial of lifestyle changes including diet , weight loss , and LTPA . There were 107 new cases of diabetes during the 4.1-year follow-up period . Individuals who increased moderate-to-vigorous LTPA or strenuous , structured LTPA the most were 63 - 65 % less likely to develop diabetes . Adjustment for changes in diet and body weight during the study attenuated the association somewhat ( upper versus lower third : moderate-to-vigorous LTPA , relative risk 0.51 , 95 % CI 0.26 - 0.97 ; strenuous , structured LTPA , 0.63 , 0.35 - 1.13 ) . Low-intensity and lifestyle LTPA and walking also conferred benefits , consistent with the finding that the change in total LTPA ( upper versus lower third : 0.34 , 0.19 - 0.62 ) was the most strongly associated with incident diabetes . Thus increasing physical activity may substantially reduce the incidence of type 2 diabetes in high-risk individuals",
"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",
"BACKGROUND Interactive stationary bikes provide positive affective experiences and physiological benefits ; however , research is limited . METHODS This study compared usage of GameBikes to traditional stationary bikes among families in the home following a 6-week r and omized , controlled trial design . Parents completed question naires featuring constructs of the theory of planned behavior ( TPB ) . Usage was tracked by all family members and belief elicitation with GameBike families followed the trial . RESULTS Usage across the trial was significantly different for children in favor of the GameBike group ( t36 = 2.61 , P = .01 , d = .85 ) . No differences were identified for parents . Significant time effects for parents ' ( F5,48 = 5.07 , P children 's ( F5,32 = 8.24 , P usage were found with declines across 6 weeks . Affective attitude was the only significant TPB variable between groups at both time one ( t57 = 2.53 , P = .01 ; d = .65 ) and follow-up ( t52 = 2.70 , P = .01 ; d = .74 ) in favor of the GameBike group . Elicited beliefs were primarily affective- and control-based . CONCLUSIONS The results provide support for use of interactive video games to augment current PA initiatives . Larger-scale trials with longer duration s are warranted",
"The purpose of this study was to evaluate the effectiveness of interactive video games ( combined with stationary cycling ) on health-related physical fitness and exercise adherence in comparison with traditional aerobic training ( stationary cycling alone ) . College-aged males were stratified ( aerobic fitness and body mass ) and then assigned r and omly to experimental ( n = 7 ) or control ( n = 7 ) conditions . Program attendance , health-related physical fitness ( including maximal aerobic power ( VO2 max ) , body composition , muscular strength , muscular power , and flexibility ) , and resting blood pressure were measured before and after training ( 60%-75 % heart rate reserve , 3 d/week for 30 min/d for 6 weeks ) . There was a significant difference in the attendance of the interactive video game and traditional training groups ( 78 % + /- 18 % vs. 48 % + /- 29 % , respectively ) . VO2 max was significantly increased after interactive video game ( 11 % + /- 5 % ) but not traditional ( 3 % + /- 6 % ) training . There was a significantly greater reduction in resting systolic blood pressure after interactive video game ( 132 + /- 6 vs. 123 + /- 6 mmHg ) than traditional ( 131 + /- 7 vs. 128 + /- 8 mmHg ) training . There were no significant changes in body composition after either training program . Attendance mediated the relationships between condition and changes in health outcomes ( including VO2 max , vertical jump , and systolic blood pressure ) . The present investigation indicates that a training program that links interactive video games to cycle exercise results in greater improvements in health-related physical fitness than that seen after traditional cycle exercise training . It appears that greater attendance , and thus a higher volume of physical activity , is the mechanism for the differences in health-related physical fitness",
"OBJECTIVES To examine the energy expenditure and heart rate response while playing active video games , and the effect of gaming experience on energy expenditure . DESIGN Cross-sectional study . PARTICIPANTS AND INTERVENTIONS Twenty-eight healthy participants ( 18 male , age 19 to 27 years ) played either Wii Sports Boxing , Tennis and Baseball , or Wii Sports Boxing and Wii Fit Free Jogging . MAIN OUTCOME MEASURES Percentage maximal heart rate ( % HRmax ) and metabolic equivalents ( METs ) were measured during 15 minutes of rest and during each game . RESULTS Mean % HRmax and METs while playing each of the four games were as follows : Wii Fit Free Jogging 71 % [ st and ard deviation ( SD ) 13 % ] , 5.9 ( SD 1.8 ) ; Wii Sports Boxing 58 % ( SD 13 % ) , 3.2 ( SD 1.1 ) ; Wii Sports Baseball 42 % ( SD 6 % ) , 2.0 ( SD 0.5 ) ; and Wii Sports Tennis 42 % ( SD 7 % ) , 2.0 ( SD 0.4 ) . Subjects with gaming experience achieved a lower heart rate playing Wii Sports Tennis compared with subjects without gaming experience . CONCLUSIONS Wii Sports Boxing , Tennis and Baseball are light-intensity activities , and Wii Fit Free Jogging is a moderate-intensity activity . Experience of gaming may affect the exercise intensity of games requiring controller skill",
"UNLABELLED Tayl OBJECTIVES To quantify energy expenditure in older adults playing interactive video games while st and ing and seated , and secondarily to determine whether participants ' balance status influenced the energy cost associated with active video game play . DESIGN Cross-sectional study . SETTING University research center . PARTICIPANTS Community-dwelling adults ( N=19 ) aged 70.7±6.4 years . INTERVENTION Participants played 9 active video games , each for 5 minutes , in r and om order . Two games ( boxing and bowling ) were played in both seated and st and ing positions . MAIN OUTCOME MEASURES Energy expenditure was assessed using indirect calorimetry while at rest and during game play . Energy expenditure was expressed in kilojoules per minute and metabolic equivalents ( METs ) . Balance was assessed using the mini-BESTest , the Activities-specific Balance Confidence Scale , and the Timed Up and Go ( TUG ) . RESULTS Mean ± SD energy expenditure was significantly greater for all game conditions compared with rest ( all P≤.01 ) and ranged from 1.46±.41 METs to 2.97±1.16 METs . There was no significant difference in energy expenditure , activity counts , or perceived exertion between equivalent games played while st and ing and seated . No significant correlations were observed between energy expenditure or activity counts and balance status . CONCLUSIONS Active video games provide light-intensity exercise in community-dwelling older people , whether played while seated or st and ing . People who are unable to st and may derive equivalent benefits from active video games played while seated . Further research is required to determine whether sustained use of active video games alters physical activity levels in community setting s for this population",
"Background Physical activity promotes health in older adults but participation rates are low . Interactive video dance games can increase activity in young persons but have not been design ed for use with older adults . The purpose of this research was to evaluate healthy older adults ’ interest and participation in a dance game adapted for an older user . Methods Healthy older adults were recruited from 3 senior living setting s and offered three months of training and supervision using a video dance game design ed for older people . Before and after the program , data was collected on vital signs , physical function and self reported quality of life . Feedback was obtained during and after training . Results Of 36 persons who entered ( mean age 80.1 + 5.4 years , 83 % female ) , 25 completed the study . Completers were healthier than noncompleters . Completers showed gains in narrow walk time , self-reported balance confidence and mental health . While there were no serious adverse events , 4 of 11 noncompleters withdrew due to musculoskeletal complaints . Conclusions Adapted Interactive video dance is feasible for some healthy older adults and may help achieve physical activity goals",
"BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin",
"Kraft , JA , Russell , WD , Bowman , TA , Selsor III , CW , and Foster , GD . Heart rate and perceived exertion during self-selected intensities for exergaming compared to traditional exercise in college-age participants . J Strength Cond Res 25(6 ) : 1736 - 1742 , 2011—Exergames may be useful for promoting physical activity in younger population s. Heart rate ( HRs ) responses and rating of perceived exertion ( RPE ) at self-selected intensities were compared in college-age participants during 2 modes of exergame activity vs. traditional exercise . Thirty-seven participants ( men : 20 , women : 17 ) completed 3 30-minute self-selected intensity trials : ( a ) video game interactive bicycle ergometer ( GB ) ( CatEye GB300 ) , ( b ) interactive video dance game ( Dance Dance Revolution [ DDR ] ) , and ( c ) traditional cycle ergometer ( CE ) while watching television . Mean HR , peak HR ( PkHR ) , and minutes above target HR ( THR ) were significantly higher for GB ( 144 ± 22 b·min−1 [ 57 % HR reserve ( HRR ) ] , 161 ± 23 b·min−1 , and 22.5 ± 11.1 minutes ) than for DDR ( 119 ± 16 b·min−1 [ 37 % HRR ] , 138 ± 20 b·min−1 , and 11.2 ± 11.9 minutes ) or for CE ( 126 ± 20 b·min−1 [ 42 % HRR ] , 144 ± 24 b·min−1 , and 14.2 ± 12.6 minutes ) . The RPE was significantly higher for GB ( 4.2 ± 1.5 ) and CE ( 3.8 ± 1.2 ) than for DDR ( 2.7 ± 1.3 ) . Recovery HR ( RecHR ) ( 15 minutes postexercise ) was significantly higher for GB ( 91 ± 14 b·min−1 ) than for DDR ( 80 ± 11 b·min−1 ) and neared significance vs. CE ( 84 ± 14 b·min−1 , p = 0.059 ) . No difference in PkHR , RecHR , or minutes above THR was observed between DDR and CE . Session RPE was significantly higher for GB ( 4.6 ± 1.7 ) and CE ( 4.1 ± 1.6 ) than for DDR ( 2.8 ± 1.5 ) . All modes elicited extended proportions of time above THR ; GB : 75 % , DDR : 37 % , and CE : 47 % . Results support that exergames are capable of eliciting physiological responses necessary for fitness improvements . Practitioners might consider exergames as periodic activity options for clients needing motivation to be regularly active",
"OBJECTIVES It has been reported that a higher galvanic skin response is seen when playing video games against another human player than when playing alone , which suggests increased effort . The objectives of this study were to compare energy expenditure when playing two popular active video game consoles , and to compare energy expenditure when playing in single and multiplayer modes . DESIGN Crossover trial with r and omised playing order . PARTICIPANTS Fourteen healthy adults with a mean age of 21 [ st and ard deviation ( SD ) 3 ] years . METHODS AND INTERVENTIONS Energy expenditure was measured using an indirect calorimeter at rest , during 10 minutes of play on Xbox Kinect ™ Reflex Ridge in both single and multiplayer modes , and during 10 minutes of play on Wii ™ Sports Boxing in both single and multiplayer modes . MAIN OUTCOME MEASURES Metabolic equivalents ( METs ) , heart rate , oxygen consumption and kilocalories expended . RESULTS The energy expenditure during all gaming conditions was of a light intensity . Playing on the Xbox Kinect elicited greater energy expenditure than playing on the Wii [ mean difference=0.9 METs , 95 % confidence interval ( CI ) 0.2 to 1.5 ] . Playing games in multiplayer mode led to greater energy expenditure ( mean difference=0.5 METs , 95 % CI 0.1 to 0.9 ) and heart rate ( mean difference=7.9 beats/minute , 95 % CI 2.0 to 13.8 ) than playing in single player mode . CONCLUSIONS No gaming condition required moderate-intensity activity in this group of young healthy adults . Potential explanations for the difference in energy expenditure seen between consoles and modes are discussed",
"Bonetti , AJ , Drury , DG , Danoff , JV , and Miller , TA . Comparison of acute exercise responses between conventional video gaming and isometric resistance exergaming . J Strength Cond Res 24(7 ) : 1799 - 1803 , 2010-Exergaming is a relatively new type of entertainment that couples physical activity and video gaming . To date , research that has focused on the physiologic responses to exergaming has been focused exclusively on aerobic-type activities . The purpose of this project was to describe the acute exercise responses ( i.e. , oxygen uptake [ & OV0312;O2 ] , heart rate , and rate of perceived exertion [ RPE ] ) to exergaming using full-body isometric muscle resistance and to determine whether these responses are different during single- versus opponent-based play . Male subjects ( n = 32 ) were r and omly and equally divided into either an experimental ( EXP ) or control ( CON ) group . Acute exercise responses ( & OV0312;O2 , heart rate , and RPE ) were measured in all subjects during both solo- and opponent-based video game play . Subjects in the EXP group played using a controller that relied on full-body isometric muscle resistance to manipulate the on-screen character , whereas CON subjects used a conventional h and held controller . During solo play , the EXP group exhibited significantly higher values for & OV0312;O2 ( 9.60 ±0.50 mL/kg/min ) and energy expenditure ( 3.50 ± 0.14 kcal/min ) than the CON group ( & OV0312;O2 5.05 ± 0.16 mL/kg/min ; energy expenditure 1.92 ± 0.07 kcal/min ) . These changes occurred with no significant differences in RPE or heart rate between the groups . These results suggest that whole-body isometric exergaming results in greater energy expenditure than conventional video gaming , with no increase in perceived exertion during play . This could have important implication s regarding long-term energy expenditure in gamers"
] |
4116ba3c-06ff-11f0-808a-c43d1ab1c353
|
There is evidence that vitamin D status is associated with type 2 diabetes . Many observational studies have been performed investigating the relationship of vitamin D status and circulating biomarkers of glycemic regulation . To find out whether this association holds , we conducted a systematic review and meta- analysis of cross sectional and longitudinal studies . We search ed Pubmed , Medline and Embase , all through June 2017 . The studies were selected to determine the effect of vitamin D on the parameters of glucose metabolism in diabetic and non-diabetic subjects . Correlation coefficients from all studies were pooled in a r and om effects meta- analysis . The risk of bias was assessed using Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) system . We found significant inverse relationship of vitamin D status with glycemic level in both diabetic ( r = −0.223 , 95 % CI = −0.184 to −0.261 , p = 0.000 ) and non-diabetic ( r = −0.073 , 95 % CI = −0.052 to −0.093 , p = 0.000 ) subjects . This meta- analysis concludes that hypovitaminosis D is associated with increased risk of hyperglycemia both in diabetic and non-diabetic subjects . A future strategy for the prevention of impaired glycemic regulation could be individualized supplementation of vitamin
|
[
"Summary Of the 305 premenopausal females in a cross-sectional study in r and omly selected communities of Karachi , Pakistan , 90.1 % showed to be vitamin D deficient . Age , town of residence , and housing structure were significant predictors of vitamin D levels . Measures to address D deficiency and its associated long latency effects are urgently needed . Aims This study aims to find out the prevalence and risk factors of vitamin D deficiency in community-dwelling premenopausal females in Karachi . Methods A cross-sectional study was conducted in r and omly selected communities downtown ( Saddar ) and suburbs ( Gulshan and Malir Town ) in Karachi , Pakistan . Information related to sociodemographics ( age , education , employment , and household income ) , housing structure , sunlight exposure , and skin pigmentation as well as dietary intake ( using a food frequency question naire ) was collected . Serum vitamins D3 levels were also measured . Mean and SD was computed for continuous variables and frequency and proportions were computed for categorical variables . Data were further analyzed by Chi-square test and ANOVA . Multiple linear regression analysis was done to find out determinants of vitamin D ( VD ) levels . Results Total of 305 premenopausal females were recruited . Mean age , BMI , and waist circumference of the study participants was 31.97 ± 8 years , 25.06 ± 5.6 kg/m2 , and 88.42 ± 13.3 cm , respectively . Majority of the females were vitamin D deficient ( 91.50 % ) with mean vitamin D levels of 21.77 ± 21.66 nm/L. Mean vitamin D levels were significantly different among females residing in downtown and suburbs . High frequency of vitamin D deficiency was observed in females dwelling in downtown ( Saddar ) . According to the results of multiple linear regression analysis , determinants of VD levels were age , town of residence , and housing structure . Conclusion High prevalence of vitamin D deficiency is seen in females in the community of Karachi , Pakistan . Age , town of residence , and housing structure were the significant predictors of vitamin D levels . Measures to combat the issue of D deficiency and its associated long latency effects are urgently needed",
"Data on the association between vitamin D status and actual change in glycemic measures are limited . We examined the prospect i ve association between a predicted 25-hydroxyvitamin D ( 25(OH)D ) score and change in fasting plasma glucose concentration over a mean follow-up of 7 years , in 2571 men and women ( mean age 54 years ) without diabetes in the Framingham Offspring Study cohort . After adjustment for age , sex , body mass index and fasting plasma glucose at baseline , higher predicted 25(OH)D score at baseline was associated with a smaller 7-year increase in fasting plasma glucose concentrations ( 0.23 mmol/l versus 0.35 mmol/l for highest versus lowest tertile of 25(OH)D score , respectively , P-trend=0.002 ) . Vitamin D status may be an important determinant for change in fasting plasma glucose concentration among middle-aged and older adults without diabetes",
"OBJECTIVE This study aim ed to examine vitamin D status as a determinant for development of type 2 diabetes and deterioration of glucose homeostasis . RESEARCH DESIGN AND METHODS A r and om sample of the general population of Copenhagen , Denmark , was taken as part of the Inter99 study . Included were 6,405 men and women aged 30–65 years at baseline ( 1999–2001 ) , with 4,296 participating in the follow-up examination 5 years later ( 2004–2006 ) . Vitamin D was determined at baseline as serum 25-hydroxyvitamin D [ 25(OH)D ] . Diabetes was defined based on an oral glucose tolerance test and a glycosylated hemoglobin ( HbA1c ) test . Secondary outcomes included continuous markers of glucose homeostasis . RESULTS The risk of incident diabetes associated with a 10 nmol/L increase in 25(OH)D was odds ratio ( OR ) 0.91 ( 95 % CI 0.84–0.97 ) in crude analyses . The association became statistically nonsignificant after adjustment for confounders , with an OR per 10 nmol/L of 0.94 ( 0.86–1.03 ) . Low 25(OH)D status was significantly associated with unfavorable longitudinal changes in continuous markers of glucose homeostasis after adjustment for confounders . Fasting and 2-h glucose and insulin as well as the degree of insulin resistance increased significantly more during follow-up among those with low 25(OH)D levels compared with those with higher levels . CONCLUSIONS Low 25(OH)D status was not significantly associated with incident diabetes after adjustment for confounders . However , it was significantly associated with unfavorable longitudinal changes in continuous markers of glucose homeostasis , indicating that low vitamin D status could be related to deterioration of glucose homeostasis",
"Summary Vitamin D status was assessed in 142 elderly Dutchmen participating in a prospect i ve population -based study of environmental factors in the aetiology of non-insulin-dependent diabetes mellitus . Of the men aged 70–88 years examined between March and May 1990 , 39 % were vitamin D depleted . After adjustment for confounding by age , BMI , physical activity , month of sampling , cigarette smoking and alcohol intake the 1-h glucose and area under the glucose curve during a st and ard 75-g oral glucose tolerance test ( OGTT ) were inversely associated with the serum concentration of 25-OH vitamin D ( r = −0.23 , p patients total insulin concentrations during OGTT were also inversely associated with the concentration of 25-OH vitamin D ( r = −0.18 to −0.23 , p ) . Hypovitaminosis D may be a significant risk factor for glucose intolerance . [ Diabetologia ( 1997 ) 40 : 344–347",
"OBJECTIVE To study the association between vitamin D status and the risk of incident impaired fasting glucose ( IFG ) and diabetes in a population -based cohort of diabetes-free subjects . RESEARCH DESIGN AND METHODS In a historical prospect i ve cohort study of subjects from the Clalit Health Services data base , which includes information on nearly 4 million people , diabetes-free subjects aged 40–70 years with serum 25-hydroxycholecalciferol ( 25-OHD ) measurements available were followed for 2 years to assess the development of IFG and diabetes in five 25-OHD subgroups : ≥25 , 25.1–37.5 , 37.6–50 , 50.1–75 , and > 75 nmol/L. RESULTS The baseline cohort included 117,960 adults : 83,526 normoglycemic subjects and 34,434 subjects with IFG . During follow-up , 8,629 subjects ( 10.3 % of the normoglycemic group ) developed IFG , and 2,162 subjects ( 1.8 % of the total cohort ) progressed to diabetes . A multivariable model adjusted for age , sex , population group , immigrant status , BMI , season of vitamin D measurement , LDL and HDL cholesterol , triglycerides , estimated glomerular filtration rate , history of hypertension or cardiovascular disease , Charlson comorbidity index , smoking , and socioeconomic status revealed an inverse association between 25-OHD and the risk of progression to IFG and diabetes . The odds of transitioning from normoglycemia to IFG , from normoglycemia to diabetes , and from IFG to diabetes in subjects with a 25-OHD level ≤25 nmol/L were greater than those of subjects with a 25-OHD level > 75 nmol/L [ odds ratio 1.13 ( 95 % CI 1.03–1.24 ) , 1.77 ( 1.11–2.83 ) , and 1.43 ( 1.16–1.76 ) , respectively ] . CONCLUSIONS Vitamin D deficiency appears to be an independent risk factor for the development of IFG and diabetes ",
"Background & objectives : Patients with diabetes and vitamin-D insufficiency have increased insulin resistance . Similar observations among individuals with prediabetes are not well documented . The aim of this study was to find the occurrence of vitamin-D insufficiency/deficiency among individuals with prediabetes and to evaluate the relationship between vitamin-D status and insulin resistance . Methods : One hundred fifty seven individuals with prediabetes who fulfilled all the inclusion and exclusion criteria underwent clinical examination , anthropometric measurements ( waist circumference , waist-hip ratio , waist-height ratio ) and blood sampling after overnight fast for estimation of fasting blood glucose , fasting insulin , 25(OH)vitamin-D , intact parathyroid hormone ( iPTH ) and lipid profile . One hour post 75 g glucose ( 1hPG ) blood glucose during oral glucose tolerance test was measured . Results : Vitamin-D deficiency/insufficiency was found in 115 ( 73.25 % ) individuals with prediabetes . Severe vitamin-D deficiency ( vitamin-D levels ( highest insulin resistance ( HOMA2-IR : 2.04 ± 0.67 ) . Serum 25(OH)D had a statistically significant inverse correlation with insulin resistance ( HOMA2-IR ; r=-0.33 ; P=0.008 ) , and positive correlation with insulin sensitivity ( QUICKI ; r=0.39 ; P=0.002 ) , after adjusting for BMI and HbA1c . There was no correlation between vitamin-D status and estimated beta cell mass ( HOMA-β ) . The mean waist-height ratio among individuals with prediabetes was 0.57 ( normal155 mg/dl had significantly higher BMI and worse insulin resistance , and 1hPG correlated well with 2 hour post glucose blood glucose ( r=0.57 ; P Vitamin-D deficiency/insufficiency may have some role in the development/worsening of insulin resistance in individuals with prediabetes in our country who have a high cardiovascular risk . Prospect i ve studies on a large group of individuals need to be done to confirm the findings",
"Objective Epidemiological studies have provided evidence of an association between vitamin D insufficiency and type 2 diabetes . Vitamin D levels have decreased among Inuit in Greenl and , and type 2 diabetes is increasing . We hypothesized that the decline in vitamin D could have contributed to the increase in type 2 diabetes , and therefore investigated associations between serum 25(OH)D3 as a measure of vitamin D status and glucose homeostasis and glucose intolerance in an adult Inuit population . Methods 2877 Inuit ( ≥18 years ) r and omly selected for participation in the Inuit Health in Transition study were included . Fasting- and 2hour plasma glucose and insulin , C-peptide and HbA1c were measured , and associations with serum 25(OH)D3 were analysed using linear and logistic regression . A sub sample of 330 individuals who also donated a blood sample in 1987 , were furthermore included . Results After adjustment , increasing serum 25(OH)D3 ( per 10 nmol/L ) was associated with higher fasting plasma glucose ( 0.02 mmol/L , p = 0.004 ) , 2hour plasma glucose ( 0.05 nmol/L , p = 0.002 ) and HbA1c ( 0.39 % , p beta-cell function ( -1.00 mmol/L , p ) . Serum 25(OH)D3 was positively associated with impaired fasting glycaemia ( OR : 1.08 , p = 0.001 ) , but not with IGT or type 2 diabetes . Conclusions Our results did not support an association between low vitamin D levels and risk of type 2 diabetes . Instead , we found weak positive associations between vitamin D levels and fasting- and 2hour plasma glucose levels , HbA1c and impaired fasting glycaemia , and a negative association with beta-cell function , underlining the need for determination of the causal relationship",
"OBJECTIVE Vitamin D deficiency is associated with an unfavorable metabolic profile in observational studies . The intention was to compare insulin sensitivity ( the primary end point ) and secretion and lipids in subjects with low and high serum 25(OH)D ( 25-hydroxyvitamin D ) levels and to assess the effect of vitamin D supplementation on the same outcomes among the participants with low serum 25(OH)D levels . RESEARCH DESIGN AND METHODS Participants were recruited from a population -based study ( the Tromsø Study ) based on their serum 25(OH)D measurements . A 3-h hyperglycemic clamp was performed , and the participants with low serum 25(OH)D levels were thereafter r and omized to receive capsules of 20,000 IU vitamin D3 or identical-looking placebo twice weekly for 6 months . A final hyperglycemic clamp was then performed . RESULTS The 52 participants with high serum 25(OH)D levels ( 85.6 ± 13.5 nmol/L [ mean ± SD ] ) had significantly higher insulin sensitivity index ( ISI ) and lower HbA1c and triglycerides ( TGs ) than the 108 participants with low serum 25(OH)D ( 40.3 ± 12.8 nmol/L ) , but the differences in ISI and TGs were not significant after adjustments . After supplementation , serum 25(OH)D was 142.7 ± 25.7 and 42.9 ± 17.3 nmol/L in 49 of 51 completing participants r and omized to vitamin D and 45 of 53 r and omized to placebo , respectively . At the end of the study , there were no statistically significant differences in the outcome variables between the two groups . CONCLUSIONS Vitamin D supplementation to apparently healthy subjects with insufficient serum 25(OH)D levels does not improve insulin sensitivity or secretion or serum lipid profile ",
"OBJECTIVE To examine cross-sectional relationships between plasma vitamin D and cardiometabolic risk factors in young adults . DESIGN Data were collected from interviews , physical examinations and biomarker measurements . Total plasma 25-hydroxyvitamin D ( 25(OH)D ) was measured using LC-t and em MS . Associations between 25(OH)D and cardiometabolic risk factors were modelled using weighted linear regression with robust estimates of st and ard errors . SETTING Individuals born in Jerusalem during 1974 - 1976 . SUBJECTS Participants of the Jerusalem Perinatal Study ( n 1204 ) interviewed and examined at age 32 years . Participants were over sample d for low and high birth weight and for maternal pre-pregnancy obesity . RESULTS Mean total 25(OH)D concentration among participants was 21·7 ( sd 8·9 ) ng/ml . Among males , 25(OH)D was associated with homeostatic model assessment of insulin resistance ( natural log-transformed , β=-0·011 , P=0·004 ) after adjustment for BMI . However , these associations were not present among females ( P for sex interaction=0·005 ) . CONCLUSIONS We found evidence for inverse associations of 25(OH)D with markers of insulin resistance among males , but not females , in a healthy , young adult Caucasian population . Prospect i ve studies and studies conducted on other population s investigating sex-specific effects of vitamin D on cardiometabolic risk factors are warranted",
"It is unclear whether vitamin D lowers risk of type 2 diabetes ( T2D ) . In an observational study , we assessed the prospect i ve association between plasma 25-hydroxyvitamin D ( 25(OH)D ) and incident T2D , and evaluated whether it holds up for genetically determined elevated 25(OH)D. We used a case-cohort study nested within the German arm of the European Prospect i ve Investigation into Cancer . From a total cohort of 53,088 participants with a mean follow-up of 6.6 years , we identified a r and om subcohort of 2,121 participants ( 57 % women ) and 1,572 incident cases of T2D . 25(OH)D was measured in baseline plasma sample s retrieved from frozen storage . Mean plasma 25(OH)D in the subcohort was 47.1 ( 5th–95th percentile 19.6–80.7 ) nmol/L. After controlling for age , sex , center , season of blood draw , education , and lifestyle , the hazard of T2D decreased across increasing plasma concentrations of 25(OH)D ( P linear trend non-linear after adjustment for BMI and waist circumference ( P non-linearity concentrations below ~45 nmol/L ( hazard ratio per 5 nmol/L higher 25(OH)D 0.91 , 95 % CI 0.84–0.98 ) . A score predicting genetically determined plasma 25(OH)D by weighting four independent single-nucleotide polymorphisms by their effect on 25(OH)D , explained 3.7 % of the variance in 25(OH)D. The hazard ratio ( 95 % CI ) per 5 nmol/L higher genetically predicted 25(OH)D was 0.98 ( 0.89–1.08 ) in the entire study sample and 1.06 ( 0.93–1.21 ) in the sub- sample with 25(OH)D 25(OH)D with T2D , but further research in large-scale consortia is needed",
"Abstract Objective Patients with chronic kidney disease have a very high prevalence of deficiency of 25-hydroxyvitamin D [ 25(OH)D ] . We evaluate the association between 25(OH)D and diabetic nephropathy ( DN ) in a Chinese sample with type 2 diabetes mellitus . Method The subjects were patients with diabetes mellitus who were hospitalized at our hospital during the period from June 2012 to July 2014 . Serum levels of 25(OH)D were tested at admission . DN was defined as a urinary albumin-to-creatinine ratio ≥30 mg/g in a r and om spot urine sample . Multivariate analyses were performed using logistic regression models . Results We found that serum 25(OH)D levels were significantly lower in diabetes with DN as compared to without DN [ 8.5 ( IQR 6.8–11.3 ) vs. 13.9 ( IQR 11.2–18.2 ) ng/ml , P of serum 25(OH)D levels as an indicator for diagnosis of DN was projected to be 10.5 ng/ml , which yielded a sensitivity of 82.6 % and a specificity of 72.7 % , with the area under the curve at 0.807 [ 95 % confidence interval ( CI ) 0.764–0.849 ] . Multivariate logistic regression analysis adjusted for common risk factors showed that with serum 25(OH)D level ≤10.5 ng/ml was an independent indicator of DN [ odds ratio ( OR ) = 6.559 ; 95 % CI 2.864–11.368 ] . Conclusions Our findings suggested that diabetes with DN had lower serum 25(OH)D levels and that determination of 25(OH)D statuses might be used to identify patients at increased risk of developing nephropathy complications",
"AIMS In recent years , there has been an effort to underst and possible roles of 25(OH)D , including its role in the immune system particularly on T cell medicated immunity , pancreatic insulin secretion and insulin action . 25(OH)D stimulates the cell differentiation and reduces cell proliferation , which is essential for cell growth and wound healing . However , data on the association between low level of plasma 25(OH)D and diabetic foot syndrome are scarce . MATERIAL S AND METHODS Circulating plasma levels of 25(OH)D were measured in diabetic patients with ulcer ( n=162 ) and without ulcer ( n=162 ) in a prospect i ve cohort hospital based study . RESULTS Of these patients , 85.1 % had type 2 diabetes . Subjects with diabetic foot ulcer showed lower median plasma level of 25(OH)D [ 6.3(4.2 - 11.1 ) vs 28.0(21.4 - 37.0 ) ] ng/ml after adjusting the age and BMI . Regardless of the low levels of 25(OH)D in cases and controls , it was associated with neuropathy , sex ( female ) , duration of ulcer healing , and smoking status and independent of confounding factors , including BMI ( kg/m² ) , A1c ( % ) , hypertension , nephropathy , foot ulcer , retinopathy , CAD , PAD , HDL-C ( mg/dl ) and LDL-C ( mg/dl ) . The factors which predict the risk of developing ulcer independent of 25(OH)D status were A1c ( > 6.9 % ) [ OR 4.37 ; RR 1.77 ] , HDL-C ( LDL-C ( > 100mg/dl ) [ OR 1.07 ; RR 1.03 ] , triglycerides ( > 200mg/dl ) [ OR 1.40 ; RR 1.19 ] , neuropathy [ OR 6.88 ; RR 3.12 ] , retinopathy [ OR 3.34 ; RR 1.91 ] , hypertension [ OR 1.64 ; RR 1.28 ] , nephropathy [ OR 3.12 ; RR 1.87 ] and smoking [ OR 4.53 ; RR 2.99 ] using odds and risk ratios . CONCLUSION It is not clear whether the suppression of delayed wound healing seen during 25(OH)D deficiency is due to the secondary effect or is a direct action of vitamin D on certain components of the immune system . Long-term r and omized trials are needed to see the impact of vitamin D supplementation on the outcome of diabetic foot patients",
"OBJECTIVES To examine whether ( 1 ) serum 25-hydroxyvitamin D level ( 25[OH]D ) is a risk factor for hyperglycemia , as assessed by glycated hemoglobin ( HbA1c ) , in African American men ( AAM ) and ( 2 ) 25(OH)D is a predictor of HbA1c in AAM and Caucasian American men ( CAM ) . METHODS We prospect ively assessed 25(OH)D and HbA1c in 1,074 men , out patients with and without diabetes , at an urban Veteran Administration Medical Center ( 66.8 % AAM , 26.4 % CAM , 6 % Hispanic , 0.4 % Asian , and 0.4 % Native American men ) . Multivariate regression analyzed the determinants of HbA1c after accounting for potential confounders . RESULTS We found high prevalence of low ( 30 ng/mL ) 25(OH)D ( 81 % ) and elevated ( ≥5.7 % ) HbA1c ( 53.5 % ) . The 25(OH)D was inversely associated with HbA1c in all men ( r = -0.12 , P included body mass index ( BMI ) , age , 25(OH)D levels , systolic blood pressure ( BP ) , triglycerides , high-density lipoprotein ( HDL ) , and current alcohol use ( P while glomerular filtration rate ( GFR ) and marital status showed borderline significance ( P = .08 and .09 , respectively ) . In AAM these determinants included BMI , 25(OH)D levels , systolic BP , and current alcohol use ( P included BMI , age , and triglycerides ( P = .01 , .03 , and .004 , respectively ) but not 25(OH)D levels ( P = .50 ) . CONCLUSION Circulating low 25(OH)D is a risk factor for hyperglycemia , as assessed by HbA1c , in AAM . The 25(OH)D level is an independent determinant of HbA1c in AAM , but not in CAM , including men with and without diabetes",
"OBJECTIVES To test the hypothesis that changes in DNA methylation are involved in vitamin D deficiency-related immune cell regulation using an unbiased genome-wide approach combined with a genomic and epigenomic integrative approach . STUDY DESIGN We performed a genome-wide methylation scan using the Illumina HumanMethylation 27 BeadChip on leukocyte DNA of 11 cases of vitamin D deficiency ( serum 25-hydroxyvitamin D [ 25(OH)D ] ≤ 25 nmol/L ) and 11 age-matched controls ( [ 25(OH)D ] > 75 nmol/L ) ; the subjects were African American normal-weight ( body mass index The Limma package was used to analyze each CpG site for differential methylation between cases and controls . To correct for multiple testing , the set of raw P values were converted to false discovery rates ( FDRs ) . We also compared our findings with the recent data from Genome-Wide Association Studies of circulating 25(OH)D levels and then performed a permutation test to examine whether the \" double hit \" genes were r and omly enriched . RESULTS A total of 79 CpG sites achieved raw P significant at the methylation level ( DHCR7 : cg07487535 , P = .015 and cg10763288 , P = .017 ; CYP2R1 : cg25454890 , P = .040 ; CYP24A1 : cg18956481 , P = .022 ) , reflecting significant enrichment ( P = .0098 ) . CONCLUSION Severe vitamin D deficiency is associated with methylation changes in leukocyte DNA . The genomic and epigenomic approach reinforce the crucial roles played by the DHCR7 , CYP2R1 , and CYP24A1 genes in vitamin D metabolism",
"BACKGROUND & AIMS To investigate the relationship between levels of 25-hydroxyvitamin D and the incidence of type 2 diabetes in a Spanish population . METHODS We undertook a population -based prospect i ve study in a population from southern Spain . The first phase of the study ( 1996 - 1998 ) included 1226 individuals . Of this original cohort , 988 persons were reassessed in 2002 - 2004 and 961 in 2005 - 2007 . Measurements were made of 25-hydroxyvitamin D and intact parathyroid hormone in 2002 - 2004 and an oral glucose tolerance test was done in three time points . RESULTS The incidence of diabetes in subjects with 25-hydroxyvitamin D levels ≤ 18.5 ng/mL ( percentile 25 ) was 12.4 % vs 4.7 % in subjects with levels > 18.5 ng/mL. The likelihood of having diabetes during the four years of follow-up was significantly lower in the subjects with higher levels of 25-hydroxyvitamin D [ OR = 0.17 ( 0.05 - 0.61 ) ] . None of the subjects with levels higher than 30 ng/mL developed diabetes . CONCLUSION In this prospect i ve study , we found a significant inverse association between serum 25-hydroxyvitamin D levels and the risk for type 2 diabetes in a population from the south of Spain",
"Purpose This paper visualizes the available data on vitamin D status on a global map , examines the existing heterogeneities in vitamin D status and identifies research gaps . Methods A graphical illustration of global vitamin D status was developed based on a systematic review of the worldwide literature published between 1990 and 2011 . Studies were eligible if they included sample s of r and omly selected males and females from the general population and assessed circulating 25-hydroxyvitamin D [ 25(OH)D ] levels . Two different age categories were selected : children and adolescents ( 1–18 years ) and adults ( > 18 years ) . Studies were chosen to represent a country based on a hierarchical set of criteria . Results In total , 200 studies from 46 countries met the inclusion criteria , most coming from Europe . Forty-two of these studies ( 21 % ) were classified as representative . In children , gaps in data were identified in large parts of Africa , Central and South America , Europe , and most of the Asia/Pacific region . In adults , there was lack of information in Central America , much of South America and Africa . Large regions were identified for which the mean 25(OH)D levels were below 50 nmol/L. Conclusions This study provides an overview of 25(OH)D levels around the globe . It reveals large gaps in information in children and adolescents and smaller but important gaps in adults . In view of the importance of vitamin D to musculoskeletal growth , development , and preservation , and of its potential importance in other tissues , we strongly encourage new research to clearly define 25(OH)D status around the world"
] |
4116ba82-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND Mild vitamin B-12 deficiency is common among older adults , but evidence for setting dietary recommendations is limited because most studies have administered vitamin B-12 via nonoral routes or at doses several hundred times higher than current recommendations . Furthermore , different biomarkers of vitamin B-12 status have not been systematic ally review ed . OBJECTIVE The aim was to assess the effectiveness of biomarkers of vitamin B-12 status through a systematic review of published r and omized controlled trials of oral vitamin B-12 supplementation . DESIGN Methods included a structured search strategy on Ovid MEDLINE , EMBASE ( Ovid ) , and Cochrane data bases ; formal inclusion and exclusion criteria ; data extraction ; validity assessment ; and meta- analysis . RESULTS Eight r and omized controlled trials were included , and all studies measured serum and plasma total vitamin B-12 , 3 studies measured methylmalonic acid , and 6 studies measured total homocysteine response . All 3 biomarkers were found to be effective measures of altered vitamin B-12 intake in population s with low and borderline baseline vitamin B-12 status ( P effectiveness of plasma holotranscobalamin , which was measured in only one r and omized controlled trial . CONCLUSIONS The available evidence suggests that plasma and serum concentrations of total vitamin B-12 , methylmalonic acid , and total homocysteine are all effective biomarkers of a change in vitamin B-12 intake ; however , because the available data were limited , it was not possible to examine fully the factors that could explain the substantial heterogeneity in total vitamin B-12 . Future trials should include low-dose vitamin B-12 in adults across the entire age spectrum and measure the holotranscobalamin response to supplementation
|
[
"Animal source foods ( ASF ) can provide micronutrients in greater amounts and more bioavailable forms compared to plant source foods , but their intake is low in many poor population s. However , the impact of ASF on micronutrient status of undernourished population s has not been assessed . Supplemental meat ( 60 - 85 g/d ) , milk ( 200 - 250 mL/d ) or energy ( isocaloric with the meat and milk , 240 - 300 kcal/d ) were r and omly assigned to 555 undernourished school children aged 5 - 14 y in a rural malaria-endemic area of Kenya , at one school meal daily for one school year . Blood and stool sample s were collected at baseline and after 1 y to assess stool parasites , malaria , hemoglobin , serum or plasma C-reactive protein , ferritin , iron , zinc , copper , vitamin B-12 , folate and retinol , and erythrocyte riboflavin . At baseline , there was a high prevalence of micronutrient deficiencies ( iron , zinc , vitamins A and B-12 and riboflavin ) , yet plasma ferritin was low in few children , and none had low serum copper . At the end of the year of supplementation , plasma vitamin B-12 concentrations were significantly increased in children fed the Meat or Milk meal ; prevalence of severe plus moderate deficiency fell from 80.7 % at baseline to 64.1 % in the Meat group and from 71.6 to 45.1 % in the Milk group , respectively . No significant improvement was observed in the status of other micronutrients compared to the Energy and Control groups , although malaria and other infections may have obscured effects . Supplementation with small amounts of meat or milk reduced the high prevalence of vitamin B-12 deficiency in these children",
"BACKGROUND Vitamin B-12 deficiency is associated with cognitive impairment in older people . However , evidence from r and omized trials of the effects of vitamin B-12 supplementation on cognitive function is limited and inconclusive . OBJECTIVE The objective was to investigate whether daily supplementation with high doses of oral vitamin B-12 alone or in combination with folic acid has any beneficial effects on cognitive function in persons aged > /=70 y with mild vitamin B-12 deficiency . DESIGN In a double-blind , placebo-controlled trial , 195 subjects were r and omly assigned to receive 1000 microg vitamin B-12 , 1000 microg vitamin B-12 + 400 microg folic acid , or placebo for 24 wk . Vitamin B-12 status was assessed on the basis of methylmalonic acid , total homocysteine ( tHcy ) , and holotranscobalamin ( holoTC ) concentrations before and after 12 and 24 wk of treatment . Cognitive function was assessed before and after 24 wk of treatment with the use of an extensive neuropsychologic test battery that included the domains of attention , construction , sensomotor speed , memory , and executive function . RESULTS Vitamin B-12 status did not change significantly after treatment in the placebo group ; however , oral vitamin B-12 supplementation corrected mild vitamin B-12 deficiency . Vitamin B-12 + folic acid supplementation increased red blood cell folate concentrations and decreased tHcy concentrations by 36 % . Improvement in memory function was greater in the placebo group than in the group who received vitamin B-12 alone ( P = 0.0036 ) . Neither supplementation with vitamin B-12 alone nor that in combination with folic acid was accompanied by any improvement in other cognitive domains . CONCLUSION Oral supplementation with vitamin B-12 alone or in combination with folic acid for 24 wk does not improve cognitive function",
"We have previously shown that a modest vitamin supplement containing folic acid , vitamin B-12 and vitamin B-6 is effective in reducing elevated plasma homocysteine concentrations . The effect of supplementation of the individual vitamins on moderate hyperhomocysteinemia has now been investigated in a placebo-controlled study . One hundred men with hyperhomocysteinemia were r and omly assigned to five groups and treated with a daily dose of placebo , folic acid ( 0.65 mg ) , vitamin B-12 ( 0.4 mg ) , vitamin B-6 ( 10 mg ) or a combination of the three vitamins for 6 wk . Folic acid supplementation reduced plasma homocysteine concentrations by 41.7 % ( P vitamin B-12 supplement lowered homocysteine concentrations by 14.8 % ( P plasma homocysteine concentrations . The combination of the three vitamins reduced circulating homocysteine concentrations by 49.8 % , which was not significantly different ( P = 0.48 ) from the reduction achieved by folate supplementation alone . Our results indicate that folate deficiency may be an important cause of hyperhomocysteinemia in the general population",
"The BOSSANOVA study , a r and omized double-blind trial , was design ed to test the ability of very low oral doses of vitamin B-12 to increase the serum vitamin B-12 concentration in elderly subjects with food-bound vitamin B-12 malabsorption , and to determine whether there was a dose response . We also aim ed to quantitatively assess the most efficient dose to be added to flour in addition to folic acid ( flour cofortification with vitamin B-12 and folic acid ) . Sixty-seven patients were r and omly assigned to 1 of 6 groups receiving various daily oral doses of vitamin B-12 ( i.e. , 2.5 , 5 , 10 , 20 , 40 , or 80 microg/d ) for 30 d. The dose-response was tested for different biological variables using a mixed model , taking into account the variable 's initial value ( between-subject effect ) , a linear log-dose effect , and a linear log ( dosextime ) interaction , where time was d 15 or d 30 . We planned to determine the amount of oral vitamin B-12 that would increase the serum vitamin B-12 concentration by 37 pmol/L ( 50 ng/L ) . Significant between-subject effects were found for serum vitamin B-12 , plasma homocysteine , and methylmalonic acid concentrations , but a log-dose effect was found only for vitamin B-12 ( P slope of the line tended to be higher ( P=0.07 ) at d 30 than at d 15 . For a mean serum vitamin B-12 increase of 37 pmol/L , a dose of 5.9 ( 95 % CI , 0.9 - 12.1 ) microg/d was needed . We concluded that very low oral doses of vitamin B-12 increased serum vitamin B-12 concentrations in elderly subjects with sub clinical vitamin B-12 deficiency , following a log-dose pattern . Our results could be beneficial in the design of a public health program for safe flour cofortification with folic acid",
"BACKGROUND A high prevalence of cobalamin deficiency occurs in the elderly population , which may be treated orally or with injections . Little is known about the relative bioavailability of crystalline cobalamin added to food products . OBJECTIVE The objective was to assess the effect of supplementation with 1000 microg crystalline cobalamin , carried either by a milk product or a capsule , on cobalamin status in mildly cobalamin-deficient elderly Dutch persons . DESIGN Two double-blind r and omized controlled intervention studies , each covering a 12-wk supplementation period , were carried out in parallel . Mildly cobalamin-deficient elderly persons ( n = 112 ) were separately recruited for the milk and capsule trials . Mild cobalamin deficiency was defined as a cobalamin concentration between 100 and 300 pmol/L and a plasma methylmalonic acid ( MMA ) concentration > or = 0.30 micromol/L. Allocation to the placebo or cobalamin carrier was carried out independently in both trials . RESULTS In the fortified-milk group , the mean ( + /-SD ) increase in serum cobalamin was 250 + /- 96 pmol/L , the median ( 5th and 95th percentiles ) decrease in plasma MMA was 0.19 ( -0.76 , -0.04 ) micromol/L , and the median decrease in plasma homocysteine was 4.0 ( -7.3 , 3.0 ) micromol/L. All changes were significantly different from those in the placebo milk group ( P serum cobalamin was 281 + /- 136 pmol/L , the median decrease in plasma MMA was 0.18 ( -2.95 , 0.14 ) micromol/L , and the median decrease in plasma homocysteine was 1.8 ( -10.6 , 2.4 ) micromol/L ; all changes were significantly different from those in the placebo capsule group ( P 0.40 ) . CONCLUSION Crystalline cobalamin added to milk is an effective alternative to cobalamin capsules for improving cobalamin status",
"UNLABELLED Hyperhomocysteinemia may contribute to the development of osteoporosis . The relationship of Hcy and vitamin B12 with bone turnover markers , BUA , and fracture incidence was studied in 1267 subjects of the Longitudinal Aging Study Amsterdam . High Hcy and low vitamin B12 concentrations were significantly associated with low BUA , high markers of bone turnover , and increased fracture risk . INTRODUCTION Hyperhomocysteinemia may contribute to the development of osteoporosis . Vitamin B12 is closely correlated to homocysteine ( Hcy ) . The main objective of our study was to examine the association of Hcy and vitamin B12 status and the combined effect of these two with broadb and ultrasound attenuation ( BUA ) , bone turnover markers , and fracture . MATERIAL S AND METHODS Subjects were 615 men and 652 women with a mean age of 76 + /- 6.6 ( SD ) years of the Longitudinal Aging Study Amsterdam ( LASA ) . At baseline ( 1995/1996 ) , blood sample s were taken after an overnight fast for dairy products . Plasma Hcy was measured with IMx , serum vitamin B12 with competitive immunoassay ( IA ) luminescence , serum osteocalcin ( OC ) with immunoradiometric assay ( IRMA ) , and urinary excretion of deoxypyridinoline ( DPD ) with competitive IA and corrected for creatinine ( Cr ) concentration . CVs were 4 % , 5 % , 8 % , and 5 % , respectively . BUA was assessed in the heel bone twice in both the right and left calcaneus . Mean BUA value was calculated from these four measurements . CV was 3.4 % . After baseline measurements in 1995 , a 3-year prospect i ve follow-up of fractures was carried out until 1998/1999 . Subjects were grouped by using two different approaches on the basis of their vitamin B12 concentration , normal versus low ( 15 microM ) or highest quartile ( Q4 ) versus normal quartiles ( Q1-Q3 ) . Analysis of covariance was performed to calculate mean values of BUA , OC , and DPD/Cr(urine ) based on the specified categories of Hcy and vitamin B12 and adjusted for several confounders ( potential confounders were age , sex , body weight , body height , current smoking [ yes/no ] , mobility , cognition ) . The relative risk ( RR ) of any fracture was assessed with Cox regression analysis . Quartiles were used when Hcy and vitamin B12 were separately studied in their relationship with fracture incidence . RESULTS Fourteen percent of the men and 9 % of the women had high Hcy ( > 15 microM ) and low vitamin B12 ( vitamin B12 levels 15 microM had lower BUA , higher DPD/Cr , and higher OC concentrations than their counterparts . In men , no differences were found between the different Hcy and vitamin B12 categories in adjusted means of BUA , OC , or DPD/Cr(urine ) . Twenty-eight men and 43 women sustained a fracture during the 3-year follow-up period . The adjusted RR for fractures ( 95 % CI ) for men with high Hcy and /or low vitamin B12 concentrations was 3.8 ( 1.2 - 11.6 ) compared with men with normal Hcy and vitamin B12 concentrations . Women with high Hcy and /or low vitamin B12 concentrations had an adjusted RR for fractures of 2.8 ( 1.3 - 5.7 ) . CONCLUSIONS High Hcy and low vitamin B12 concentrations were significantly associated with low BUA , high markers of bone turnover , and increased fracture risk",
"Background and Purpose — The Vitamin Intervention for Stroke Prevention trial ( VISP ) intention-to-treat analysis did not show efficacy of combined vitamin therapy for recurrent vascular events in patients with nondisabling stroke . Reasons for lack of efficacy may have included folate fortification of grain products , inclusion of the recommended daily intake for B12 in the low-dose arm , treatment with parenteral B12 in patients with low B12 levels in both study arms , a dose of B12 too low for patients with malabsorption , supplementation with non study vitamins , and failure of patients with significant renal impairment to respond to vitamin therapy . We conducted an efficacy analysis limited to patients most likely to benefit from the treatment , based on hypotheses arising from evidence developed since VISP was initiated . The criteria for this subgroup were defined before any data analysis . Methods — For this analysis , we excluded patients with low and very high B12 levels at baseline ( 637 pmol/L , representing the 25th and 95th percentiles ) , to exclude those likely to have B12 malabsorption or to be taking B12 supplements outside the study and patients with significant renal impairment ( glomerular filtration rate Results — This subgroup represents 2155 patients ( 37 % female ) , with a mean age of 66±10.7 years . For the combined end point of ischemic stroke , coronary disease , or death , there was a 21 % reduction in the risk of events in the high-dose group compared with the low-dose group ( unadjusted P=0.049 ; adjusted for age , sex , blood pressure , smoking , and B12 level P=0.056 ) . In Kaplan – Meier survival analysis comparing 4 groups , patients with a baseline B12 level at the median or higher r and omized to high-dose vitamin had the best overall outcome , and those with B12 less than the median assigned to low-dose vitamin had the worst ( P=0.02 for combined stroke , death , and coronary events ; P=0.03 for stroke and coronary events ) . Conclusions — In the era of folate fortification , B12 plays a key role in vitamin therapy for total homocysteine . Higher doses of B12 , and other treatments to lower total homocysteine may be needed for some patients",
"Objective : To determine if poor dietary intake can explain the cobalamin-related abnormalities often seen in the elderly . Design : Prospect i ve laboratory survey with a follow-up dietary assessment . Setting : Social centers for the elderly and an outpatient clinic . Subjects : Ninety-five free-living subjects > 60 y old with abnormal or suspicious findings in cobalamin-related tests and 78 subjects > 60 y old with normal results . Interventions : Serum cobalamin , methylmalonic acid and homocysteine determinations to assess cobalamin status and a one year food-frequency question naire to assess cobalamin intake . Results : Only three of the 173 subjects ( 1.7 % ) , one of whom had normal cobalamin status , ingested Sixty-nine subjects ( 39.9 % ) ingested abnormal serum cobalamin or metabolite values than those ingesting > 6 μg . Ordering all subjects by quintiles according to cobalamin intake revealed no significant trends or differences in any of the serum values either . Moreover , arranging subjects by results of tests of cobalamin status showed that the subjects with abnormal cobalamin status did not differ in cobalamin intake from those with normal cobalamin status , although they did differ in use of supplements . Finally , cobalamin intake , with or without supplements , did not correlate with serum cobalamin or metabolite levels . The absence of any association between cobalamin status and intake contrasts sharply with the significant correlation between folate intake and folate status ( P=0.0001 ) . Conclusions : The high frequency of mildly abnormal cobalamin status in the elderly can not be attributed to poor intake of cobalamin . Nondietary explanations , such as malabsorption and other phenomena , must always be sought to explain mild cobalamin deficiency in the elderly . Sponsorship : This study was supported by grants DK 32640 and HL 52234 from the National Institutes of Health and by the NIH National Center for Research Re sources of the GCRC grant MO1 RR-43 . Computational assistance was provided by the NIH NCRR GCRC MO1 RR-43 CDMAS project",
"BACKGROUND We examined the effect of oral vitamin B(12 ) treatment on fluctuations in plasma total cobalamin and its binding proteins transcobalamin ( TC ) and haptocorrin ( HC ) . METHODS Patients ( n = 88 ; age range , 38 - 80 years ) undergoing coronary angiography ( part of the homocysteine-lowering Western Norway B-Vitamin Intervention Trial ) were allocated to daily oral treatment with ( a ) vitamin B(12 ) ( 0.4 mg ) , folic acid ( 0.8 mg ) , and vitamin B(6 ) ( 40 mg ) ; ( b ) vitamin B(12 ) and folic acid ; ( c ) vitamin B(6 ) ; or ( d ) placebo . EDTA blood was obtained before treatment and 3 , 14 , 28 , and 84 days thereafter . RESULTS The intraindividual variation for patients not treated with B(12 ) was approximately 10 % for plasma total cobalamin , total TC , apo-TC , and apo-HC , and holo-TC and TC saturation . In B(12)-treated patients , the maximum change in concentrations was observed already after 3 days for total TC ( -16 % ) , holo-TC ( + 54 % ) , and TC saturation ( + 82 % ) . At this time holo-HC ( + 20 % ) and plasma total cobalamin ( + 28 % ) showed an initial burst , but had increased further at 84 days . All changes were highly significant compared with the control group ( P Oral vitamin B(12 ) treatment produces maximal effects on total TC , holo-TC , and TC saturation within 3 days , whereas maximal increases in holo-HC and plasma total cobalamin occur later . The results support the view that holo-TC is an early marker of changes in cobalamin homeostasis",
"The purpose of this study was to test whether low serum vitamin B-12 levels are associated with more rapid bone loss in elderly women . We archived sera and measured calcaneal bone mineral density ( BMD ) in community-dwelling white women , aged 65 yr and over , who participated in the Study of Osteoporotic Fractures . BMD of the hip and subregions was measured 2 yr later . Repeat measurements of calcaneal and hip BMD were obtained after 5.9 and 3.5 yr of follow-up , respectively . Serum vitamin B-12 assays were performed in 83 r and omly selected participants with initial and repeat measurements of BMD who were not taking estrogen replacement therapy at baseline . After adjusting for age , weight , and clinic site , women with vitamin B-12 levels at or below 280 pg/ml ( 207.2 pmol/liter ; lowest quintile ) experienced an annual change of -1.6 % ( 95 % confidence interval , -2.4 % to -0.8 % ) in total hip BMD , compared with -0.2 % ( -0.5 % to 0.2 % ) in women with levels above 280 pg/ml ( P = 0.003 ) . Results were similar when subregions of the hip were analyzed separately . Serum vitamin B-12 levels were not significantly associated with calcaneal bone loss . We conclude that low serum vitamin B-12 levels are associated with increased rates of hip , but not calcaneal , bone loss in older women",
"OBJECTIVES Because the effects of lower-dose oral cobalamin ( Cbl ) supplements on older people with cobalamin deficiency are not known , we determined whether oral Cbl supplements at three different dose levels would normalize elevated serum methylmalonic acid ( MMA ) and total homocysteine ( tHcy ) concentrations . DESIGN Sequential nonr and omized intervention study of three dose levels . SETTING S Two university-based senior care clinics . PARTICIPANTS Twenty-three older adults ( aged > /=65 ) with serum Cbl levels of 221 pmol/L ( 300 pg/mL ) or lower and serum MMA greater than 271 nmol/L who had been enrolled in a previous screening study for Cbl deficiency ( mean age 79 + /- 9 ; 17 male , 6 female ; 17 white , 6 other ) . INTERVENTION Sequential daily treatment with 25 microg oral cobalamin , followed by 100 microg and 1,000 microg cobalamin each for a 6-week period . MEASUREMENTS Serum MMA , tHcy , and other metabolites at baseline and after each 6-week dosing interval . RESULTS Treatment with 25 microg and 100 microg lowered but did not normalize MMA levels in most subjects . A dose of 1,000 microg/day proved to be the most effective in lowering MMA levels to within normal limits . Serum tHcy was normalized in six of 11 subjects who had elevated tHcy pretreatment with oral Cbl alone and in one subject in combination with a multivitamin . CONCLUSIONS Most Cbl-deficient older people require more than 100 microg of oral Cbl to normalize serum MMA , which is a larger dose than is available in most st and ard multivitamins and Cbl supplements",
"OBJECTIVES To determine the effect of small doses of oral cyanocobalamin supplements in older patients with low or borderline serum vitamin B12 concentrations but no other evidence of pernicious anemia ( PA ) . DESIGN R and omized , double-blind , placebo-controlled study assessing the efficacy of oral cyanocobalamin 10 microg and 50 microg daily for 1 month . SETTING Two geriatric hospitals in the North Western Health Care Network , Melbourne , Australia . PARTICIPANTS Thirty-one in patients with serum vitamin B12 levels between 100 and 150 pmol/L , without PA , other malabsorption disorders , or progressive neurological or terminal illness . The mean age was 81.4 years . INTERVENTION After informed consent , a medical and drug history was taken and the Mini-Mental State Examination ( MMSE ) completed . A dietitian made assessment of oral cobalamin intake . Blood was taken for serum vitamin B12 , serum and red cell folate assay , full blood examination , fasting serum gastrin , parietal and intrinsic factor antibodies , fasting serum homocysteine , and creatinine . Patients were then r and omized to receive 10 microg oral cyanocobalamin , 50 microg oral cyanocobalamin , or placebo treatment for 1 month , after which the investigations and clinical examinations were repeated . MEASUREMENTS Percentage change in the level of vitamin B12 , homocysteine , folate , and red cell parameters and absolute changes in MMSE were calculated and compared between groups . The groups were compared on the number of responders who improved their level of B12 by 20 % . Chi-square calculations on changes in serum vitamin B12 concentration were also performed . RESULTS Mean serum vitamin B12 + /- st and ard deviation improved by 51.7 + /- 47.1 % in the 50-microg group , 40.2 + /- 34.4 % in the 10-microg group , and 11.7 + /- 24.5 % in the placebo group . The change in the 50-microg cyanocobalamin group was significantly greater than that in the placebo group ( P=.044 ) . The change in the 10-microg cyanocobalamin group was not significantly different from that in the placebo group ( P=.186 ) . Eight of 10 subjects in each treatment group were classified as responders , compared with two of 11 in the placebo group ( P=.004 ) . Homocysteine levels fell in patients receiving cyanocobalamin , but this fall failed to reach statistical significance . There were no significant changes in the other parameters measured . CONCLUSION Cyanocobalamin supplementation of 50 microg but not 10 microg daily produced a significant increase in serum vitamin B12 . This result has implication s for the management of patients with subnormal or borderline serum vitamin B12 concentrations and for food fortification with vitamin B12",
"People in India have a high prevalence of low vitamin B12 status and high plasma total homocysteine ( tHcy ) concentrations . In a proof of principle trial , we studied the effect of oral vitamin B12 ( 500 microg ) and /or 100 g cooked green leafy vegetables ( GLV ) every alternate day in a 2x2 factorial design over a 6-week period . Forty-two non-pregnant vegetarian women ( age 20 - 50 years ) were r and omly allocated to four study groups . Clinical measurements were made at the beginning and at the end of the study , and blood sample s were collected before , and 2 and 6 weeks after commencement of intervention . Forty women completed the trial . Twenty-six women had low vitamin B12 status ( 15 micromol/L ) . GLV supplementation did not alter plasma folate or tHcy . Vitamin B12 supplementation increased plasma vitamin B12 concentration ( 125 to 215 pmol/L , p tHcy concentration ( 18.0 to 13.0 micromol/L , p Plasma vitamin B12 and tHcy concentrations did not change in those who did not receive vitamin B12 , and there was no change in plasma folate concentration in any of the groups . Blood haemoglobin concentration increased marginally within first two weeks in those women who received vitamin B12 ( by 3 g/L , p macrocytosis decreased from 2 to zero . There was no change in vibration sensory threshold during the period of the study . High-dose per oral vitamin B12 supplementation significantly reduced plasma tHcy within 2 weeks but did not achieve normal plasma tHcy concentration even after 6 weeks . People in India have a high prevalence of low vitamin B12 status and high plasma total homocysteine ( tHcy ) concentrations",
"BACKGROUND Supplementation with high doses of oral cobalamin is as effective as cobalamin administered by intramuscular injection to correct plasma markers of vitamin B(12 ) deficiency , but the effects of lower oral doses of cobalamin on such markers are uncertain . METHODS We conducted a r and omized , parallel-group , double-blind , dose-finding trial to determine the lowest oral dose of cyanocobalamin required to normalize biochemical markers of vitamin B(12 ) deficiency in older people with mild vitamin B(12 ) deficiency , defined as a serum vitamin B(12 ) level of 100 to 300 pmol/L ( 135 - 406 pg/mL ) and a methylmalonic acid level of 0.26 mumol/L or greater . We assessed the effects of daily oral doses of 2.5 , 100 , 250 , 500 , and 1000 mug of cyanocobalamin administered for 16 weeks on biochemical markers of vitamin B(12 ) deficiency in 120 people . The main outcome measure was the dose of oral cyanocobalamin that produced 80 % to 90 % of the estimated maximal reduction in the plasma methylmalonic acid concentration . RESULTS Supplementation with cyanocobalamin in daily oral doses of 2.5 , 100 , 250 , 500 , and 1000 mug was associated with mean reductions in plasma methylmalonic acid concentrations of 16 % , 16 % , 23 % , 33 % , and 33 % , respectively . Daily doses of 647 to 1032 mug of cyanocobalamin were associated with 80 % to 90 % of the estimated maximum reduction in the plasma methylmalonic acid concentration . CONCLUSION The lowest dose of oral cyanocobalamin required to normalize mild vitamin B(12 ) deficiency is more than 200 times greater than the recommended dietary allowance , which is approximately 3 mug daily",
"OBJECTIVES The performance of holotranscobalamin ( holoTC ) was compared with the other markers of vitamin B12 deficiency , and the influence of age , renal function , and thyroid status was examined . DESIGN AND INTERVENTIONS We examined 937 individuals not treated with vitamin B12 but in whom vitamin B12 deficiency was suspected because of a plasma methylmalonic acid ( MMA ) above 0.28 micromol L(-1 ) within the past 4 years . Besides laboratory tests , a structured interview and a neurological examination were performed amongst 534 individuals . Amongst these , 140 individuals qualified for a r and omized trial ( MMA 0.40 - 2.00 micromol L(-1 ) ) . They were r and omized to injections with vitamin B12 or placebo and re-examined after 3 months . SETTING One university hospital in Aarhus , Denmark . RESULTS The ROC curves indicate that holoTC ( AUC : 0.90 ) compared favourable with plasma vitamin B12 ( AUC : 0.85 ) for identifying individuals likely to have vitamin B12 deficiency ( MMA > or = 0.75 micromol L(-1 ) and plasma total homocysteine ( tHcy ) > or = 15 micromol L(-1 ) ) , and further that holoTC ( AUC : 0.91 ) might replace combined testing with plasma vitamin B12 and the metabolites . No association was observed between the biochemical markers and symptoms and signs possibly related to vitamin B12 deficiency . HoloTC , TC saturation , plasma vitamin B12 , MMA , and tHcy were significantly associated with plasma creatinine ( all with P tHcy was significantly associated with thyroid stimulating hormone ( P=0.02 ) . CONCLUSIONS HoloTC shows promise as first-line tests for diagnosing early vitamin B12 deficiency",
"Homocysteine , a non-protein-forming sulfur amino acid , has attracted attention because elevated concentrations of circulating total homocysteine are associated with an increased risk for vascular disease ( 1 , 2 ) . Homocysteine is also a sensitive functional marker of inadequate cellular folate and vitamin B12 concentrations ( 3 ) . Inadequate status of these vitamins has important health consequences that may be independent of their role in homocysteine metabolism . Low folate concentrations increase a woman 's risk for having a baby with a neural tube defect ( 4 , 5 ) , and an inadequate vitamin B12 concentration is known to produce various neurologic and cognitive effects ( 6 , 7 ) . Persons with low circulating folate or vitamin B12 concentrations have higher fasting total homocysteine concentrations ( 8 - 10 ) , and elevated fasting total homocysteine concentrations are usually normalized by treatment with folic acid and vitamin B12 ( 6 , 11 - 14 ) . However , less is known about the importance of these vitamins as risk factors for high homocysteine concentration in the general population . Only three studies have examined the relation between homocysteine concentration and its vitamin determinants in sample s that were design ed to be representative of U.S. national ( 8) or regional ( 9 , 10 ) population s. One of these studies ( 9 ) reported that approximately two thirds of all cases of moderately elevated total homocysteine concentrations were potentially attributable to low vitamin concentrations , but estimation of the proportion of cases with high homocysteine concentrations that can be attributed to inadequate vitamin status is complicated by the lack of a st and ard definition of a high total homocysteine concentration . In the absence of a definition based on increased risk for an adverse health outcome , such as vascular disease , upper reference limits from sample s of healthy persons without established risk factors for high homocysteine concentrations have been used to define a high total homocysteine concentration ( 10 , 15 - 17 ) . We previously described the distribution of total serum homocysteine concentrations in participants 12 years of age or older from the third National Health and Nutrition Examination Survey ( NHANES III ) , a population -based sample of U.S. residents ( 18 ) . These data present a unique opportunity to develop population reference ranges for serum total homocysteine concentration and to determine the extent to which elevated homocysteine concentrations are associated with low circulating vitamin concentrations in a representative sample of U.S. residents . Methods Participants The NHANES III was developed to obtain nationally representative information on the health and nutritional status of the civilian , noninstitutionalized U.S. population ( 19 , 20 ) . Homocysteine concentrations were measured as part of an NHANES III surplus sera project on serum sample s from participants 12 years of age or older who were seen during phase II of this survey ( 19911994 ) . This project is described in greater detail elsewhere ( 18 ) . Homocysteine concentrations were measured at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University by using the high-performance liquid chromatography method of Araki and Sako ( 21 ) . The interassay coefficient of variation for this assay was 6 % . Folate and vitamin B12 were determined for phase 2 specimens at the Centers for Disease Control and Prevention central laboratory by using a Quanta Phase II radioassay kit ( Bio-Rad Laboratories , Hercules , California ) , and analyses are described in detail in the NHANES III Laboratory Procedures Manual ( 22 ) . The coefficients of variation for folate and vitamin B12 were 6 % and 7 % , respectively . Informed consent was obtained from all respondents . The NHANES III protocol was approved by the National Center for Health Statistics NHANES Institutional Review Board , and measurement of serum homocysteine was approved by the Human Investigations Review Committee at the New Engl and Medical Center . We used the following search strategy , combining Medical Subject Headings ( MeSH terms ) and text words , to identify all population -based studies relating vitamin status to circulating homocysteine concentrations : ( [ homocysteine ( MeSH ] OR homocysteine [ Text Word ] ) AND ( vitamins [ MeSH ] OR vitamin [ Text Word ] ] ) AND ( epidemiologic studies [ MeSH ] OR data collection [ MeSH ] OR survey [ Text Word ] ] . This search identified 137 citations , of which 16 were review s. We selected original studies that 1 ) were design ed to be representative of national , regional , or local population s and 2 ) described the relation between circulating homocysteine concentrations and either intake or circulating concentrations of folate or vitamin B12 . As of 1 March 1999 , 3 articles met our criteria ( 8 - 10 ) . Statistical Analysis We used sample weights in analyses to account for unequal probability of selection and nonresponse and to produce estimates of means and percentiles that were representative of the noninstitutionalized , civilian U.S. population . We used SUDAAN statistical software ( 23 ) to account for the complex survey design in the variance estimates . Because total homocysteine , folate , and vitamin B12 values were skewed , logarithmic transformations were applied . To show the relations between total homocysteine concentrations and vitamin concentrations , we classified participants into age- and sex-specific vitamin decile categories and estimated the geometric mean of the serum total homocysteine concentration within each decile . Analyses were adjusted for ethnicity and serum creatinine concentration . In addition , the relation between total homocysteine and folate concentrations was adjusted for vitamin B12 concentrations , and the relation between total homocysteine and vitamin B12 was adjusted for folate concentrations . We tested the associations between homocysteine and vitamins for interactions with age , sex , and ethnicity . We tested for trend of total homocysteine concentration across vitamin concentrations by using linear regression with the logarithm of the continuous vitamin concentration as the independent variable , adjusting as described above . We showed the trend by using the SYSTAT LOWESS procedure to fit smoothed curves ( 24 ) to the geometric mean total homocysteine concentrations in the vitamin decile categories ( 25 ) . It has been suggested that population reference ranges for the total homocysteine concentration be established in sample s of persons without established risk factors for a high homocysteine concentration ( 10 , 15 - 17 ) . For our reference sample , we included persons whom we assumed to be folate- and vitamin B12-replete ( that is , their serum concentrations of both vitamins were above the 50th percentile ) and had normal serum creatinine concentrations ( were excluded . We used the 5th and the 95th percentiles from the reference sample to estimate population reference ranges . To identify the potential impact of low vitamin concentrations on high total homocysteine concentration , we needed to establish values for high total homocysteine and low vitamin concentrations . We used the sex-specific 95th percentiles in the participants 20 to 39 years of age ( the reference sample ) to define high total homocysteine concentrations for all age groups . We used this reference sample because homocysteine concentrations changed little with age in this group , unlike in the other age groups ( 18 ) . We defined low vitamin concentrations as a folate concentration less than 11 nmol/L ( 26 , 27 ) and a vitamin B12 concentration less than 185 pmol/L ( 28 , 29 ) . We calculated the prevalence of high total homocysteine concentration ; the prevalence ratio for high total homocysteine concentration ; the attributable risk percentage ; and the population attributable risk percentage for persons with low concentrations of folate , vitamin B12 , or both compared with persons who had adequate concentrations of both of these vitamins . The attributable risk percentage estimates the excess cases of high homocysteine concentrations among persons with low vitamin concentrations , whereas the population attributable risk percentage takes into account the prevalence of low vitamin concentrations in the population and estimates the excess of high homocysteine concentrations associated with low vitamin concentrations in the entire population . We used the design effect for total homocysteine concentration , which is the ratio of the complex sampling design variance derived by using SUDAAN software ( 23 ) to the simple r and om sample variance calculated by using SAS software ( 30 ) , to determine the recommended minimum sample size needed to achieve stable estimates of means , proportions , and percentiles according to the National Center for Health Statistics analytic guidelines ( 19 ) . On the basis of an average design effect of approximately 1.4 for our sample , means and medians derived from fewer than 42 participants , 10th and 90th percentiles derived from fewer than 112 participants , and 5th and 95th percentiles derived from fewer than 224 participants were deemed unstable . Sample size for stable estimates of the proportions varied by the magnitude of the proportion , ranging from 42 for proportions of 0.5 to 224 for proportions of 0.05 or 0.95 . We indicate in the text and tables statistics that did not meet the appropriate sample size . We categorized participants into three ethnic groups : non-Hispanic white , non-Hispanic black , and Mexican American . We excluded persons from other ethnic groups ( n=436 ) because their inclusion produced unstable estimates of mean total homocysteine concentration after adjustment for ethnicity . Our analyses are based on 8086 participants with complete data on serum total homocysteine , folate , vitamin B12 , and creatinine concentrations . Results Table 1 shows selected characteristics of the sample by sex and ethnic group . On average , non-Hispanic white"
] |
4116bac8-06ff-11f0-808a-c43d1ab1c353
|
Background Gross motor skills are fundamental to childhood development . The effectiveness of current physical therapy options for children with mild to moderate gross motor disorders is unknown . The aim of this study was to systematic ally review the literature to investigate the effectiveness of conservative interventions to improve gross motor performance in children with a range of neurodevelopmental disorders . Methods A systematic review with meta- analysis was conducted . MEDLINE , EMBASE , AMED , CINAHL , PsycINFO , PEDro , Cochrane Collaboration , Google Scholar data bases and clinical trial registries were search ed . Published r and omised controlled trials including children 3 to ≤18 years with ( i ) Developmental Coordination Disorder ( DCD ) or Cerebral Palsy ( CP ) ( Gross Motor Function Classification System Level 1 ) or Developmental Delay or Minimal Acquired Brain Injury or Prematurity ( receiving non-pharmacological or non-surgical interventions from a health professional and ( iii ) gross motor outcomes obtained using a st and ardised assessment tool . Meta- analysis was performed to determine the pooled effect of intervention on gross motor function . Method ological quality and strength of meta- analysis recommendations were evaluated using PEDro and the GRADE approach respectively . Results Of 2513 papers , 9 met inclusion criteria including children with CP ( n = 2 ) or DCD ( n = 7 ) receiving 11 different interventions . Only two of 9 trials showed an effect for treatment . Using the least conservative trial outcomes a large beneficial effect of intervention was shown ( SMD:-0.8 ; 95 % CI:-1.1 to −0.5 ) with “ very low quality ” GRADE ratings . Using the most conservative trial outcomes there is no treatment effect ( SMD:-0.1 ; 95 % CI:-0.3 to 0.2 ) with “ low quality ” GRADE ratings . Study limitations included the small number and poor quality of the available trials . Conclusion Although we found that some interventions with a task-orientated framework can improve gross motor outcomes in children with DCD or CP , these findings are limited by the very low quality of the available evidence . High quality intervention trials are urgently needed
|
[
"Evidence -based practice involves the use of evidence from systematic review s and r and omised controlled trials , but the extent of this evidence in physiotherapy has not previously been surveyed . The aim of this survey is to describe the quantity and quality of r and omised controlled trials and the quantity of systematic review s relevant to physiotherapy . The Physiotherapy Evidence Data base ( PEDro ) was search ed . The quality of trials was assessed with the PEDro scale . The search identified a total of 2,376 r and omised controlled trials and 332 systematic review s. The first trial was published in 1955 and the first review was published in 1982 . Since that time , the number of trials and review s has grown exponentially . The mean PEDro quality score has increased from 2.8 in trials published between 1955 and 1959 to 5.0 for trials published between 1995 and 1999 . There is a substantial body of evidence about the effects of physiotherapy . However , there remains scope for improvements in the quality of the conduct and reporting of clinical trials",
"Twenty days of complex motor skill training in adult rats was previously demonstrated to rehabilitate motor performance deficits induced by binge alcohol exposure in neonatal rats . This follow-up study evaluated morphological plasticity in the paramedian lobule of the cerebellum ( PML ) using the same treatment and training regimens . On postnatal days ( PD ) 4 - 9 , female Long-Evans rats were given either alcohol ( Alcohol Exposure - AE , 4.5 g/kg/day via artificial rearing ) , exposure to gastrostomy control ( GC ) artificial rearing procedures , or reared normally as suckle controls ( SC ) . After weaning , all rats were housed two to three per cage . At 180 days old , rats were r and omly assigned either to a rehabilitation condition ( RC : given 20 days of complex motor skill training ) , or to an inactive condition ( IC : remained in their home cage ) . The AE rats were delayed in acquiring the training , but there were no group differences in performance over the last 2 weeks of training . Unbiased stereological techniques were used to evaluate PML volume , Purkinje cell and parallel fiber synapse density . Although total volume of PML was significantly reduced in the AE rats , complex motor skill training result ed in a significant increase in the PML molecular layer in all three postnatal treatment groups . The RC animals from the SC and AE groups had more parallel fiber synapses per Purkinje cell than corresponding IC animals . These data support the hypothesis that ' rehabilitative ' motor training stimulates synaptogenesis in the PML , and that Purkinje neurons that survive the early postnatal alcohol insult are capable of substantial experience-induced plasticity",
"Children with developmental coordination disorder ( DCD ) have been demonstrated to show a deficit of inhibitory control in volitional shifts of attention . The aim of this study was to use ecological intervention to investigate the efficacy of table-tennis training on treating both problems with attentional networks and motor disorder in children with DCD . Forty-three children aged 9 - 10 years old were screened using the Movement Assessment Battery for Children and divided into DCD ( n=27 ) and typically developing ( TD , n=16 ) groups . Children with DCD were then quasi-r and omly assigned to either a DCD-training group who underwent a ten-week table-tennis training program with a frequency of 3 times a week or a DCD non-training group . Before and after training , the capacity of inhibitory control was examined with the endogenous Posner paradigm task for DCD and TD groups . Table-tennis training result ed in significant improvement of cognitive and motor functions for the children with DCD . The study demonstrated that exercise intervention employed within the school setting can benefit the inhibitory control and motor performance in children with DCD . However , future research efforts should continue to clarify whether the performance gains could be maintained over time",
"Objective The aim of this study was to evaluate the effect of a treadmill program on gross motor function , walking speed , and spasticity of ambulatory adolescents with spastic cerebral palsy ( diplegia and tetraplegia ) . Design In this r and omized controlled trial , 22 adolescents ( 13–19 yrs old ) from a special school for children with physical disabilities were r and omly allocated to the experimental and control training groups . The experimental training group underwent a treadmill program without body weight support at a comfortable speed . The control group received treatment with conventional physiotherapy , which consisted of three sets of exercises with mat activities , balance , gait training , and functional gross motor activities . The program lasted 12 wks with a frequency of three times per week for both groups . Pretest and posttest measurements of self-selected walking speed , gross motor function , and spasticity were conducted . Results The analysis of covariance findings examining posttest differences between groups were significant with respect to self-selected walking speed ( F = 8.545 , P = 0.000 ) and gross motor function ( F = 9.088 , P = 0.007 ) , whereas no significance was found for spasticity . Conclusions Treadmill training may improve the walking speed and gross motor function of adolescents with spastic cerebral palsy , without adverse effects on spasticity",
"Background The average age for the diagnosis of cerebral palsy ( CP ) is 19 months . Recent neuroplasticity literature suggests that intensive , task-specific intervention ought to commence as early as possible and in an enriched environment , during the critical period of neural development . Active motor interventions are effective in some population s , however the effects of active motor interventions on the motor outcomes of infants with CP have not been research ed thoroughly , but pilot work is promising . The aim of this study was to determine the short- term effects of “ GAME ” ; a new and novel goal -oriented activity-based , environmental enrichment therapy programme on the motor development of infants at high risk of CP and test study procedures for a r and omized controlled trial ( RCT ) . Methods Pragmatic 2-group pilot RCT to assess motor outcomes , goal attainment , parent well-being and home environment quality , after 12-weeks of GAME intervention versus st and ard care . GAME included : creation of movement environments to elicit motor behaviours ; parent training in motor learning and task analysis ; frequent practice of motor tasks using a programme that was individualised to the child , was varied and focused on self-initiated movement . Data were analyzed using multiple regression . Results Thirteen infants were consented , r and omised , treated and completed the study . At study conclusion , the GAME group ( n = 6 ) demonstrated an advantage in Total Motor Quotient of 8.05 points on the Peabody Developmental Motor Scale-2 ( PDMS-2 ) compared to the st and ard care group ( n = 7 ) ( p < .001 ) . No significant differences existed between groups on any other measure . Conclusions GAME appears to offer a promising and feasible new motor intervention for CP , with favourable short-term motor outcomes . A pressing need exists for an adequately powered RCT with long-term end points , to determine if GAME may advance these children ’s motor trajectory",
"The aim of the present study was to examine the effects of balance training with visual feedback on stance and gait in school-age children with hemiplegic cerebral palsy . Ten participants between 5 and 11 years of age were assigned to either the training or the control group according to an aged-stratified r and omization . The training corresponded to three sessions per week during six weeks . Stance and gait parameters- based on force plate data , were assessed three times in both groups : ( a ) at the beginning of the study ( before training ) ; ( b ) after six weeks ; ( c ) after ten weeks . Spatial and temporal parameters were calculated . The results for stance showed that the training improved the performances on the tasks that were trained . More interesting , the results for gait showed that the walking pattern became more symmetrical after the training",
"This r and omized controlled trial aim ed to investigate the effect of short-term intensive TKD training on the isokinetic knee muscle strength and reactive and static balance control of children with developmental coordination disorder ( DCD ) . Among the 44 children with DCD ( mean age : 7.6 ± 1.3 years ) recruited , 21 were r and omly assigned to undergo daily TKD training for 1h over three consecutive months , with the remaining 23 children being assigned to the DCD control group . Eighteen typically developing children ( mean age : 7.2 ± 1.0 years ) received no training as normal controls . Knee extensor and flexor muscle strength and reactive and static balance control were assessed using an isokinetic machine ( with low , moderate and high movement velocities ) , a motor control test ( MCT ) and a unilateral stance test ( UST ) , respectively . A repeated measures MANCOVA revealed a significant group through time interaction effect in isokinetic outcomes at 180 ° /s and in the UST outcome . Post hoc analysis demonstrated that DCD-TKD children 's isokinetic knee muscle strength , specifically at 180 ° /s , was as high as that of the normal control children ( p>0.0083 ) after TKD training . Moreover , UST body sway velocity was slower in the DCD-TKD group than in the DCD control group ( p0.05 ) after TKD training . However , no such improvement in balance was observed in the MCT ( p>0.025 ) . The results show that children with DCD who undergo a 3-month program of intensive TKD training experience improvements in isokinetic knee muscle strength at 180 ° /s and static single-leg st and ing balance control , but do not benefit from improved reactive balance control ",
"The process-oriented treatment ( POR chi ) approach is a time-limited programme aim ed at increasing the kinaesthetic performance of children with mild motor problems in order to improve their motor performance . The approach was compared with a traditional or general motor approach and with no treatment in a r and omized clinical trial of 75 children with developmental co-ordination disorder . The children were assessed before and after treatment and after a six-week follow-up period . The results were mixed . The study provides evidence of the severity of so-called ' mild ' motor problems of children referred to occupational therapy . The data suggest that these children do not improve spontaneously , and that their motor problems are very resistant to treatment . The data also suggest that an appropriate treatment strategy might be one that involves direct , repetitive training of a specific skill",
"Children with developmental coordination disorder ( DCD ) have poorer postural control and are more susceptible to falls and injuries than their healthy counterparts . Sports training may improve sensory organization and balance ability in this population . This study aim ed to evaluate the effects of three months of Taekwondo ( TKD ) training on the sensory organization and st and ing balance of children with DCD . It is a r and omized controlled trial . Forty-four children with DCD ( mean age : 7.6±1.3 years ) and 18 typically developing children ( mean age : 7.2±1.0 years ) participated in the study . Twenty-one children with DCD were r and omly selected to undergo daily TKD training for three months ( 1 h per day ) . Twenty-three children with DCD and 18 typically developing children received no training as controls . Sensory organization and st and ing balance were evaluated using a sensory organization test ( SOT ) and unilateral stance test ( UST ) , respectively . Repeated measures MANCOVA showed a significant group by time interaction effect . Post hoc analysis demonstrated that improvements in the vestibular ratio ( p=0.003 ) and UST sway velocity ( p=0.007 ) were significantly greater in the DCD-TKD group than in the DCD-control group . There was no significant difference in the average vestibular ratio or UST sway velocity between the DCD-TKD and normal-control group after three months of TKD training ( p>0.05 ) . No change was found in the somatosensory ratio after TKD training ( p>0.05 ) . Significant improvements in visual ratios , vestibular ratios , SOT composite scores and UST sway velocities were also observed in the DCD-TKD group after training ( p≤0.01 ) . Three months of daily TKD training can improve sensory organization and st and ing balance for children with DCD . Clinicians can suggest TKD as a therapeutic leisure activity for this population",
"BACKGROUND Binge-like alcohol exposure in neonatal rats during the brain growth spurt causes deficits in adult neurogenesis in the hippocampal dentate gyrus ( DG ) . Previous data from our laboratory demonstrated that 12 days of voluntary wheel running ( WR ) beginning on postnatal day ( PD ) 30 significantly increased the number of newly generated cells evident in the DG on PD42 in both alcohol-exposed ( AE ) and control rats , but 30 days later a sustained beneficial effect of WR was evident only in control rats . This study tested the hypothesis that housing rats in environmental complexity ( EC ) following WR would promote the survival of the newly generated cells stimulated by WR , particularly in AE rats . METHODS On PD4 to 9 , pups were intubated with alcohol in a binge-like manner ( 5.25 g/kg/d ) , sham-intubated ( SI ) , or reared normally . In Experiment 1 , animals were either assigned to WR during PD30 to 42 or socially housed ( SH ) . On PD42 , animals were injected with bromodeoxyuridine ( BrdU ; 200 mg/kg ) and perfused 2 hours later to confirm the WR-induced stimulation of proliferation . In Experiment 2 , all animals received WR on PD30 to 42 and were injected with BrdU on the last full day of WR . On PD42 , animals were r and omly assigned either to EC ( WR/EC ) or to SH ( WR/SH ) for 30 days and subsequently perfused and brains were processed for immunohistochemical staining to identify BrdU+- , Ki67 + - , and BrdU+/NeuN+-labeled cells in DG . RESULTS In Experiment 1 , WR exposure significantly increased the number of proliferating cells in all 3 postnatal conditions . In Experiment 2 , the AE rats given WR/SH had significantly fewer BrdU+ cells compared with control rats given WR/SH . However , WR/EC experience significantly increased the number of surviving BrdU+ cells in both the AE and SI groups compared with WR/SH rats of the same neonatal treatment . Approximately 80 % of the surviving BrdU+ cells in the DG across the conditions were colabeled with NeuN. CONCLUSIONS WR followed by EC could provide a behavioral model for developing interventions in humans to ameliorate hippocampal-dependent impairments associated with fetal alcohol spectrum disorders",
"This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . \" Quality \" as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence",
"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 this study was to evaluate neuromotor task training ( NTT ) , a recently developed child-centred and task-oriented treatment programme for children with developmental coordination disorder ( DCD ) . A treatment and a non-treatment control group of children with DCD were included . Children were selected if they scored below the 15th centile on the Movement Assessment Battery for Children ( MABC ) . The children in the treatment group were recently referred for physiotherapy ( n=26 ; 20 males , 6 females ; mean age 7y 2mo [ SD 1y 3mo ] ) . The parents of the non-treated children were concerned about their children 's motor performance and responded to advertisements for free testing ( n=13 ; 10 males , 3 females ; mean age 7y 2mo [ SD 2y 1mo ] ) . Before and after nine weekly 30-minute sessions of NTT or at least 9 weeks of no intervention , the MABC and the Test of Gross Motor Development - 2 ( TGMD-2 ) were administered . Therapists reported per session on treatment goals and tasks trained . The results indicate that motor performance does not improve spontaneously and that NTT is effective . During the intervention period , only the treated group improved on the MABC and the TGMD-2 . Children improved most on tasks similar to those trained . In older children with poorer motor patterns , NTT 's treatment success was higher . The Child Behavior Checklist subscales withdrawn , thought problems , anxious/depressed , and delinquency were determinants of effects on motor patterns",
"BACKGROUND Children with Developmental Co-ordination Disorder ( DCD ) experience poor motor and psychosocial outcomes . Interventions are often limited within the healthcare system , and little is known about how technology might be used within schools or homes to promote the motor skills and /or psychosocial development of these children . This study aim ed to evaluate whether short , regular school-based sessions of movement experience using a commercially available home video game console ( Nintendo 's Wii Fit ) would lead to benefits in both motor and psychosocial domains in children with DCD . METHODS A r and omized crossover controlled trial of children with movement difficulties/DCD was conducted . Children were r and omly assigned to an intervention ( n = 10 ) or comparison ( n = 8) group . The intervention group spent 10 min thrice weekly for 1 month using Wii Fit during the lunch break , while the comparison group took part in their regular Jump Ahead programme . Pre- and post-intervention assessment s considered motor proficiency , self-perceived ability and satisfaction and parental assessment of emotional and behavioural problems . RESULTS Significant gains were seen in motor proficiency , the child 's perception of his/her motor ability and reported emotional well-being for many , but not all children . CONCLUSIONS This study provides preliminary evidence to support the use of the Wii Fit within therapeutic programmes for children with movement difficulties . This simple , popular intervention represents a plausible method to support children 's motor and psychosocial development . It is not possible from our data to say which children are most likely to benefit from such a programme and particularly what the dose and duration should be . Further research is required to inform across these and other questions regarding the implementation of virtual reality technologies in therapeutic services for children with movement difficulties",
"The aim of the current study was to test the hypothesis that children with probable Developmental Coordination Disorder have an increased risk of reduced moderate to vigorous physical activity ( MVPA ) , using data from a large population based study . Prospect ively collected data from 4331 children ( boys=2065 , girls=2266 ) who had completed motor coordination testing at 7 years and accelerometry at 12 years were analysed from the Avon Longitudinal Study of Parents and Children ( ALSPAC ) . Probable DCD ( p-DCD ) was defined , using criteria based on the DSM IV classification , as those children below the 15th centile of the ALSPAC Coordination Test at seven years who had a functional impairment in activities of daily living or h and writing , excluding children with a known neurological diagnosis or IQ Secondary exposure variables consisted of subtests from the ALSPAC Coordination test ( manual dexterity , ball skills and balance ) . Objective measurement of the average daily minutes of MVPA was recorded as ≥3600 counts per minute ( cpm ) using actigraph accelerometry . Boys with p-DCD were less physically active than boys without DCD ( mean difference in MVPA 4.36 cpm , t=2.69 ; p=0.007 ) . For boys , targeting skill ( bean bag toss ) was related to increased MVPA , after adjustment for confounding factors including neonatal , family and environmental factors as well as Body Mass Index at age seven and 12 years ( β=0.76 , t=3.37 , p in level of MVPA in girls with and without p-DCD ( mean difference 1.35 min , t=0.97 , p=0.31 ) , which may reflect the low levels of MVPA of girls in this cohort . Our findings suggest that the presence of movement difficulties , particularly poor targeting ( bean bag toss/ball skills ) , at a young age is a potential risk factor for reduced MVPA in boys",
"ABSTRACT Aquatic therapy is an intervention for children with Developmental Coordination Disorder ( DCD ) that has not been investigated formally . This was a pilot r and omized controlled trial to investigate the feasibility and preliminary effectiveness of an aquatic therapy program to improve motor skills of children with DCD . Thirteen children ( mean age 7 years 1 month ; 10 males ) with DCD were r and omly allocated to receive either six sessions of aquatic therapy ( once weekly session of 30 min for 6–8 weeks ) or to a wait-list ( control group ) . The intervention and measures were demonstrated to be feasible , but barriers , such as limited appointment times and accessibility , were encountered . Analysis of covariance indicated that at posttest , mean scores on the Movement Assessment Battery were higher for children who received aquatic therapy compared to those on the wait-list ( p = .057 ) . Similar trends were noted on the physical competence portion of the Pictorial Scale of Perceived Competence and Social Acceptance ( p = .058 ) . Participation levels , as measured by a parent question naire , showed improvement for both groups . Potential facilitators and barriers to implementation of an aquatic therapy for children with DCD are discussed",
"BACKGROUND The self-concept of children is influenced by developmental co-ordination disorder ( DCD ) . The aim was to determine the most effective method in enhancing motor proficiency and self-concept of 7- to 9-year-old children with DCD . METHODS Teachers at nine different schools identified 201 possible DCD c and i date s. The Movement Assessment Battery for Children identified 58 with DCD ( 36 boys and 22 girls ) . Self-concept and anxiety were determined by the Tennessee Self-Concept Scale ( Child Form ) and Child Anxiety Scale respectively . The children were r and omly grouped into four experimental groups [ motor intervention ( MI ) , self-concept ( SC ) enhancing intervention , psycho-motor intervention ( P-MI ) and a control group ( CG ) ] . A two-way analysis of variance ( anova ) with a group factor and a repeated measures over time followed by a Bonferroni post hoc analysis and separate one-way anovas followed by a Tukey post hoc analysis were conducted to determine between-group and within-group differences at the pre- , post- and re-tests . Effect sizes ( d ) were calculated to determine the practical significance of statistical differences ( P motor proficiency was found in the SC group , while the MI , P-MI and CG groups improved significantly ( P 0.05 ) motor proficiency . A tendency of lower anxiety ( P > 0.05 ) was found in the SC , while the total self-concept of the P-MI showed the biggest improvement ( P Motor proficiency and self-concept of children with DCD benefit from intervention , but both should be addressed for optimal benefits"
] |
4116bb04-06ff-11f0-808a-c43d1ab1c353
|
According to a systematic review on the use of selective serotonin reuptake inhibitors ( SSRIs ) in adult depression that was recently published in BMC Psychiatry , the results of which have been widely disseminated in lay media , these drugs increase the risk for serious adverse events ( SAEs ) while exerting poor antidepressant efficacy . A cursory analysis , however , suggests the analysis of SAEs conducted by the authors to be marred by both method ological inaccuracies and blatant errors . After having corrected for these apparent mistakes , we conducted a sensitivity analysis in which we also accounted for a possible moderating effect of age ; while this suggests SSRIs to be safe drugs in the non-elderly , they do confirm what is already known , that is , that they may enhance the risk for SAEs in the old . Given the loose definition of SAE , including also innocuous phenomena , the possible clinical significance of the latter observation , however , remains unclear until the nature and actual impact of the SAEs in question have been clarified . Moreover , with respect to efficacy , we find the paper in BMC Psychiatry misleading : first , the authors seem unaware of the well-established shortcomings associated with the conventional efficacy parameter on which their analysis is based , second , they have included suboptimal SSRI doses and third , they have missed some pivotal trials . Unless there are explanations for the many peculiarities in this paper that have escaped us , and which may be satisfactorily clarified by the authors , it seems important that the conclusions presented in this paper be publicly rectified
|
[
"Background : Major depressive disorder occurs commonly in association with alcohol dependence , both in clinical sample s and in the community . Efforts to treat major depressive disorder in alcoholics with antidepressants have yielded mixed results . This multicenter , double-blind , placebo-controlled trial of sertraline was design ed to address many of the potential method ological shortcomings of studies of co-occurring disorders . Method : Following a 1-week , single-blind , placebo lead-in period , 328 patients with co-occurring major depressive disorder and alcohol dependence were r and omly assigned to receive 10 weeks of treatment with sertraline ( at a maximum dose of 200 mg/d ) or matching placebo . R and omization was stratified , based on whether initially elevated scores on the 17-item Hamilton Depression Rating Scale declined with cessation of heavy drinking , result ing in a sample of 189 patients with Hamilton Depression Rating Scale scores ≥17 ( group A ) and 139 patients with Hamilton Depression Rating Scale scores ≤16 ( group B ) . Results : Both depressive symptoms and alcohol consumption decreased substantially over time in both groups . There were no reliable medication group differences on depressive symptoms or drinking behavior in either group A or B patients . Conclusion : Despite careful attention to method ological considerations , this study does not provide consistent support for the use of sertraline to treat co-occurring major depressive disorder and alcohol dependence . The high rate of response among placebo-treated patients may help to explain these findings . Further research is needed to identify efficacious treatments for patients with these commonly co-occurring disorders",
"Vilazodone is a selective serotonin reuptake inhibitor and 5-HT1A partial agonist approved for major depressive disorder ( MDD ) treatment in adults . This was a 10-week , multicenter , double-blind , placebo-controlled and active-controlled , fixed-dose trial ( NCT01473381 ) . Adult patients with MDD ( Diagnostic and Statistical Manual of Mental Disorders , 4th ed . , text revision criteria ) were r and omized 1 : 1 : 1 : 1 to vilazodone 20 or 40 mg/day , citalopram 40 mg/day , or placebo . Primary efficacy : Montgomery – Åsberg Depression Rating Scale ( MADRS ) ; secondary efficacy : Clinical Global Impressions-Severity and sustained response ( MADRS total score⩽12 for at least the last two consecutive double-blind visits ) . The intent-to-treat population comprised 1133 patients , ( placebo=281 ; vilazodone 20 mg/day=288 ; vilazodone 40 mg/day=284 ; citalopram=280 ) . MADRS and Clinical Global Impressions-Severity score change from baseline to week 10 was significantly greater for vilazodone 20 mg/day , vilazodone 40 mg/day , and citalopram versus placebo . Sustained response rates were numerically higher , but not significantly different , in all active treatment groups versus placebo . The most common adverse events ( ≥5 % of vilazodone patients , twice the rate of placebo ) were diarrhea , nausea , vomiting ( vilazodone 40 mg/day only ) , and insomnia . Improved sexual function ( Changes in Sexual Functioning Question naire scores ) was seen in all groups ; between-group differences were not significant . Vilazodone 20 and 40 mg/day demonstrated efficacy and tolerability in the treatment of MDD",
"This multicenter study compared the efficacy and safety of citalopram and placebo in a population of moderately to severely depressed patients with melancholia . This r and omized , double-blind , parallel-group study compared citalopram ( flexible dose ; 20 - 80 mg/day ) with placebo in 180 psychiatric out patients with a DSM-III diagnosis of major depression or bipolar disorder , depressed , who also met DSM-III criteria for melancholia . Following a 1-week placebo washout period , patients meeting study entry criteria were r and omized to 4 weeks of double-blind treatment with either citalopram or placebo . Efficacy measures included the Hamilton Rating Scale for Depression ( HAM-D ) , the Clinical Global Impressions ( CGI ) Scale , and the Zung Self-Rating Depression Scale . Patients treated with citalopram showed significantly greater improvement at endpoint than placebo patients on the HAM-D , CGI , and Zung scales . On the HAM-D , citalopram patients exhibited significantly greater improvement than placebo patients after 1 week of double-blind treatment and at all subsequent study visits . Endpoint analyses of the HAM-D subscales demonstrated that citalopram produced significant improvement of the psychomotor retardation , cognitive disturbance , sleep disturbance , and melancholia symptom clusters . Nausea , dry mouth , somnolence , dizziness , and increased sweating were reported at higher rates by citalopram-treated patients than by placebo-treated patients , but there were no significant citalopram-placebo differences in the incidence of activation ( e.g. , anxiety , nervousness , insomnia ) or sexual dysfunction . Analysis of electrocardiograms , vital signs , and laboratory tests did not reveal any clinical ly significant effects of citalopram treatment . The results of this study indicate that citalopram is safe and effective in the treatment of depressed patients with melancholia , and is associated with a favorable side effect profile and a potentially rapid onset of action",
"BACKGROUND Citalopram , the most selective serotonin reuptake inhibitor ( SSRI ) , is a bicyclic phthalane derivative with a chemical structure that is unrelated to that of other SSRIs and available antidepressants . The drug is approved for use in 69 countries . This 6-week , fixed-dose , placebo-controlled , parallel-arm , multicenter trial was performed to confirm its efficacy and safety in treatment of out patients with major depression in the United States . METHOD Six hundred and fifty adult out patients with moderate-to-severe major depression ( DSM-III-R ) were r and omly assigned to receive citalopram at doses of 10 mg ( N = 131 ) , 20 mg ( N = 130 ) , 40 mg ( N = 131 ) , or 60 mg ( N = 129 ) or placebo ( N = 129 ) once daily . Outcome assessment s were the 21-item Hamilton Rating Scale for Depression ( HAM-D ) , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and the Clinical Global Impressions scale . RESULTS Between-group comparisons of the change from baseline to endpoint revealed significantly greater improvement in the citalopram patients relative to the placebo patients on all 3 efficacy measures . Patients r and omly assigned to 40 mg/day and 60 mg/day of citalopram showed significantly greater improvement than placebo on all efficacy measures , as well as on the HAM-D symptom clusters measuring depressed mood , melancholia , cognitive disturbance , and psychomotor retardation . Patients who received 10 mg/day and 20 mg/day of citalopram also showed consistent improvement relative to placebo on all efficacy ratings , with statistical significance demonstrated in the MADRS response rate , the HAM-D depressed mood item , and the HAM-D melancholia subscale . Citalopram was well tolerated , with only 15 % of patients discontinuing for adverse events . The side effects most commonly associated with citalopram treatment were nausea , dry mouth , somnolence , insomnia , and increased sweating . CONCLUSION Citalopram was significantly more effective than placebo in the treatment of moderate-to-severe major depression , especially symptoms of depressed mood and melancholia , with particularly robust effects shown at doses of 40 and 60 mg/day . Citalopram was well tolerated in spite of forced upward titration to fixed-dose levels , with a low incidence of anxiety , agitation , and nervousness",
"OBJECTIVE Empirical evidence has only weakly supported antidepressant treatment for patients with co-occurring depression and alcohol dependence . While some studies have demonstrated that antidepressants reduce depressive symptoms in individuals with depression and alcohol dependence , most studies have not found antidepressant treatment helpful in reducing excessive drinking in these patients . The authors provide results from a double-blind , placebo-controlled trial that evaluated the efficacy of combining approved medications for depression ( sertraline ) and alcohol dependence ( naltrexone ) in treating patients with both disorders . METHOD A total of 170 depressed alcohol-dependent patients were r and omly assigned to receive 14 weeks of treatment with sertraline ( 200 mg/day [ N=40 ] ) , naltrexone ( 100 mg/day [ N=49 ] ) , the combination of sertraline plus naltrexone ( N=42 ) , or double placebo ( N=39 ) while receiving weekly cognitive-behavioral therapy . RESULTS The sertraline plus naltrexone combination produced a higher alcohol abstinence rate ( 53.7 % ) and demonstrated a longer delay before relapse to heavy drinking ( median delay=98 days ) than the naltrexone ( abstinence rate : 21.3 % ; delay=29 days ) , sertraline ( abstinence rate : 27.5 % ; delay=23 days ) , and placebo ( abstinence rate : 23.1 % ; delay=26 days ) groups . The number of patients in the medication combination group not depressed by the end of treatment ( 83.3 % ) approached significance when compared with patients in the other treatment groups . The serious adverse event rate was 25.9 % , with fewer reported with the medication combination ( 11.9 % ) than the other treatments . CONCLUSIONS More depressed alcohol-dependent patients receiving the sertraline plus naltrexone combination achieved abstinence from alcohol , had delayed relapse to heavy drinking , reported fewer serious adverse events , and tended to not be depressed by the end of treatment",
"OBJECTIVE There have been few placebo-controlled trials of selective serotonin reuptake inhibitors for depressed elderly patients . This placebo-controlled study of sertraline was design ed to confirm the results of non-placebo-controlled trials . METHOD The subjects were out patients age 60 years or older who had a DSM-IV diagnosis of major depressive disorder and a total score on the 17-item Hamilton Depression Rating Scale of 18 or higher . The patients were r and omly assigned to 8 weeks of double-blind treatment with placebo or a flexible daily dose of 50 or 100 mg of sertraline . The primary outcome variables were the Hamilton scale and Clinical Global Impression ( CGI ) scales for severity and improvement . RESULTS A total of 371 patients assigned to sertraline and 376 assigned to placebo took at least one dose . At endpoint , the patients receiving sertraline evidence d significantly greater improvements than those receiving placebo on the Hamilton depression scale and CGI severity and improvement scales . The mean changes from baseline to endpoint in Hamilton score were -7.4 points ( SD=6.3 ) for sertraline and -6.6 points ( SD=6.4 ) for placebo . The rate of CGI-defined response at endpoint was significantly higher for sertraline ( 45 % ) than for placebo ( 35 % ) , and the time to sustained response was significantly shorter for sertraline ( median , 57 versus 61 days ) . There were few discontinuations due to treatment-related adverse events , 8 % for sertraline and 2 % for placebo . CONCLUSIONS Sertraline was effective and well tolerated by older adults with major depression , although the drug-placebo difference was not large in this 8-week trial",
"Agomelatine ( S 20098 ) has a unique and new pharmacological profile . It is a melatoninergic agonist and selective antagonist of 5-HT2C receptors , and has been shown to be active in several animal models of depression . The aim of this study was to determine the active dose of agomelatine in the treatment of major depressive disorder ( DSM-IV criteria ) . The methodology used was a conventional double-blind design comparing three different doses of agomelatine ( 1 , 5 and 25 mg once a day ) with placebo over an 8-week treatment period . Paroxetine was used as the study validator . Seven hundred and eleven patients with a baseline mean score of 27.4 on the 17-item Hamilton Rating Scale for Depression ( HAM-D ) were included . On the pivotal analysis , the mean final HAM-D total score ( Full Analysis Set LOCF ) demonstrated agomelatine 25 mg to be statistically more effective than placebo . This was confirmed by other analyses and criteria ( responders , remission , sub population of severely depressed patients , Montgomery – Åsberg Depression Rating Scale , Clinical Global Impression-Severity of Illness ) . Agomelatine 25 mg alleviated the anxiety associated with depression , as measured on Hamilton Anxiety Scale . Paroxetine was found to be effective on pivotal analysis and most of the secondary criteria used to vali date the study methodology and population . Agomelatine , whatever the dose , showed good acceptability with a side-effects profile close to that of placebo . In conclusion , this study demonstrates that agomelatine is efficient in the treatment of major depressive disorder and that 25 mg is the target dose",
"OBJECTIVE Management of depression in elderly patients presents a significant medical challenge , and there is a need for further clinical trials . The authors examined the efficacy and tolerability of escitalopram and fluoxetine versus placebo in the treatment of elderly patients with major depressive disorder ( MDD ) . METHODS This was an 8-week , r and omized , double-blind comparison of the efficacy and tolerability of escitalopram ( 10 mg/day ) and fluoxetine ( 20 mg/day ) , to placebo in elderly patients with MDD . The prospect ively defined primary efficacy parameter was the change from baseline in mean Montgomery-Asberg Depression Rating Scale ( MADRS ) total score at endpoint , using last observation carried forward . RESULTS The intent-to-treat set comprised 517 patients ; the escitalopram group included 173 patients ; fluoxetine , 164 patients ; and placebo , 180 patients . Mean age was 75 years , with a range of 65 to 93 . Formally , this was a \" failed study \" ( i.e. , neither active treatment was superior to placebo ) , and the efficacy results should , therefore , be interpreted with caution . On the basis of the primary efficacy parameter , fluoxetine showed significantly lower efficacy than both escitalopram and placebo , which were not significantly different from each other . Rates of withdrawal because of adverse events/lack of efficacy were : placebo ( 2.8%/4.4 % , respectively ) , escitalopram ( 9.8%/1.7 % , respectively ) , and fluoxetine ( 12.2%/1.8 % , respectively ) . No single adverse event occurred at an incidence > or = 10 % in escitalopram-treated patients . CONCLUSIONS Both escitalopram and fluoxetine were well tolerated by elderly patients with MDD . Neither demonstrated superior efficacy on primary endpoint versus placebo",
"Paroxetine is a novel antidepressant that selectively inhibits neuronal reuptake of serotonin . Results are reported from a 6-week , double-blind trial of paroxetine , imipramine , and placebo in 120 out patients with DSM-III major depression . Paroxetine was significantly superior to placebo on almost all measures . This included the main outcome variable , the Hamilton Rating Scale for Depression ( HAM-D ) , and its factor scores , anxiety-somatization , cognitive disturbance , psychomotor retardation , and sleep disturbance . There were no significant differences between paroxetine and imipramine on the same scales . Imipramine-treated patients were significantly more likely than those taking placebo to report one or more adverse effects , which were predominantly anticholinergic in nature . There was no significant difference in the number of paroxetine and placebo patients who reported one or more adverse effects . The results of this and similar studies indicate that paroxetine is an effective treatment in major depression and has a favorable side effect profile",
" A total of 149 patients in 7 centers in Denmark , Norway and Sweden entered a 6‐week double‐blind trial intended to assess the antidepressant effect and safety of citalopram vs placebo in depressed elderly patients ( 65 years of age or older ) who might also suffer from somatic disorders and /or senile dementia . Results of ratings on the Hamilton Rating Scale for Depression , the Montgomery‐Åsberg Depression Rating Scale and the Clinical Global Impression Scale provided consistent evidence that the citalopram‐treated patients improved more than the placebo‐treated patients . Results of ratings on the Gottfries‐Bråne‐Steen dementia rating scale indicated that both cognitive and emotional functioning improved significantly more in the citalopram‐treated subgroup of patients with dementia than in the placebo‐treated subgroup",
" Aprepitant is a neurokinin 1 receptor antagonist approved for prevention of chemotherapy‐induced and post‐operative nausea and vomiting . Early studies demonstrated promising antidepressant activity as monotherapy , although this was unsupported by subsequent phase 3 trials . This phase 2 study evaluated whether aprepitant potentiated the antidepressant effects of paroxetine"
] |
4116bb4a-06ff-11f0-808a-c43d1ab1c353
|
Background The overarching goal of health policies is to maximize health and societal benefits . Economic evaluations can play a vital role in assessing whether or not such benefits occur . This paper review s the application of modelling techniques in economic evaluations of drug and alcohol interventions with regard to ( i ) modelling paradigms themselves ; ( ii ) perspectives of costs and benefits and ( iii ) time frame . Methods Papers that use modelling approaches for economic evaluations of drug and alcohol interventions were identified by carrying out search es of major data bases . Results Thirty eight papers met the inclusion criteria . Overall , the cohort Markov models remain the most popular approach , followed by decision trees , Individual based model and System dynamics model ( SD ) . Most of the papers adopted a long term time frame to reflect the long term costs and benefits of health interventions . However , it was fairly common among the review ed papers to adopt a narrow perspective that only takes into account costs and benefits borne by the health care sector . Conclusions This review paper informs policy makers about the availability of modelling techniques that can be used to enhance the quality of economic evaluations for drug and alcohol treatment interventions
|
[
"HIV remains a major cause of preventable morbidity and mortality with 100000 new infections and an estimated 62000 deaths in 2011 . At the same time unhealthy alcohol consumption is an important risk factor for HIV acquisition and progression . Kenya has one of the highest rates of unhealthy alcohol use worldwide and as many as 13 % of new HIV infections in Kenya may be attributable to unhealthy alcohol use . R and omized controlled trials ( RCTs ) of cognitive behavioral therapy (CBT)-based interventions addressing unhealthy alcohol consumption in Kenya show promising results increasing abstinence by 45 % and decreasing risky sex . However alcohol remains conspicuously absent from programming in HIV and substance abuse . In low-re source setting s the benefits of scaling up an effective intervention must be balanced against the opportunity costs of using those re sources to scale up alternative interventions with potential benefit ( for example increasingly eligibility for first-line antiretroviral therapy ) . Accordingly the research ers used a published vali date d computer simulation of the HIV epidemic in Kenya incorporating HIV transmission and disease progression to evaluate the cost-effectiveness of the alcohol intervention reported by Papas et al. Given the uncertainty surrounding costs of scale-up they varied costing assumption over a wide range to identify the threshold at which its incremental cost-effectiveness ratio ( ICER ) descended below those of alternative re source uses ( e.g. when an alcohol intervention brought more “ health ” than alternative re source uses ) . [ excerpt",
"AIMS To evaluate the cost-effectiveness of rapid hepatitis C virus ( HCV ) and simultaneous HCV/HIV antibody testing in substance abuse treatment programs . DESIGN We used a decision analytic model to compare the cost-effectiveness of no HCV testing referral or offer , off-site HCV testing referral , on-site rapid HCV testing offer and on-site rapid HCV and HIV testing offer . Base case inputs included 11 % undetected chronic HCV , 0.4 % undetected HIV , 35 % HCV co-infection among HIV-infected , 53 % linked to HCV care after testing antibody-positive and 67 % linked to HIV care . Disease outcomes were estimated from established computer simulation models of HCV [ Hepatitis C Cost-Effectiveness ( HEP-CE ) ] and HIV [ Cost-Effectiveness of Preventing AIDS Complications ( CEPAC ) ] . SETTING AND PARTICIPANTS Data on test acceptance and costs were from a national r and omized trial of HIV testing strategies conducted at 12 substance abuse treatment programs in the United States . MEASUREMENTS Lifetime costs ( 2011 US$ ) and quality -adjusted life years ( QALYs ) discounted at 3 % annually ; incremental cost-effectiveness ratios ( ICERs ) . FINDINGS On-site rapid HCV testing had an ICER of $ 18,300/QALY compared with no testing , and was more efficient than ( dominated ) off-site HCV testing referral . On-site rapid HCV and HIV testing had an ICER of $ 64,500/QALY compared with on-site rapid HCV testing alone . In one- and two-way sensitivity analyses , the ICER of on-site rapid HCV and HIV testing remained ICER remained cost-effective at a < $ 100,000/ quality -adjusted life year threshold",
"Background Screening and brief intervention ( SBI ) is a comprehensive , integrated public health approach to identify and deliver a spectrum of early detection and intervention services for substance use in general medical care setting s. Although the SBI approach has shown promise for alcohol use , relatively little is known about its effectiveness for illicit drug use . We are evaluating the SBI approach for drug use using a rigorous r and omized controlled trial . The purpose of the report is to describe the overall trial and its programmatic and method ological strengths with a focus on health educator ( HE ) selection and training . In addition , the baseline characteristics of the recently enrolled multiethnic cohort are described . Methods / design A r and omized two-group repeated measures design is being used in which drug-related outcomes of an intervention group will be compared with those of an attention-placebo control group . Selection of bicultural paraprofessional HEs — their training in research concepts , comorbid mental health issues , special treatment of marijuana use , and nonscripted enhanced motivational interviewing as well as their ongoing monitoring and evaluation — are among the features described . The HEs enrolled , consented , and conducted an intervention among 700 illicit drug users in two large hospital emergency departments/trauma units . To be eligible , a participant needed to be an adult ( age ≥18 years ) , an English or Spanish speaker , awake and able to give consent , and reachable by telephone to schedule a six-month follow-up interview . Discussion A comprehensive HE training protocol combined with rigorous , ongoing process measurement result ed in skill mastery in many areas and a successful participant recruitment period . Strengths and limitations of the study protocol are discussed as well as the characteristics of those recruited . This trial will be among the first to provide information about the effectiveness of SBI for illicit drug use . Outcome analysis has not yet been completed , but demonstrated programming and design successes have implication s for future research and service delivery . Trial registration",
"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",
"Objectives To determine whether nalmefene combined with psychosocial support is cost-effective compared with psychosocial support alone for reducing alcohol consumption in alcohol-dependent patients with high/very high drinking risk levels ( DRLs ) as defined by the WHO , and to evaluate the public health benefit of reducing harmful alcohol-attributable diseases , injuries and deaths . Design Decision modelling using Markov chains compared costs and effects over 5 years . Setting The analysis was from the perspective of the National Health Service ( NHS ) in Engl and and Wales . Participants The model considered the licensed population for nalmefene , specifically adults with both alcohol dependence and high/very high DRLs , who do not require immediate detoxification and who continue to have high/very high DRLs after initial assessment . Data sources We modelled treatment effect using data from three clinical trials for nalmefene ( ESENSE 1 ( NCT00811720 ) , ESENSE 2 ( NCT00812461 ) and SENSE ( NCT00811941 ) ) . Baseline characteristics of the model population , treatment re source utilisation and utilities were from these trials . We estimated the number of alcohol-attributable events occurring at different levels of alcohol consumption based on published epidemiological risk-relation studies . Health-related costs were from UK sources . Main outcome measures We measured incremental cost per quality -adjusted life year ( QALY ) gained and number of alcohol-attributable harmful events avoided . Results Nalmefene in combination with psychosocial support had an incremental cost-effectiveness ratio ( ICER ) of £ 5204 per QALY gained , and was therefore cost-effective at the £ 20 000 per QALY gained decision threshold . Sensitivity analyses showed that the conclusion was robust . Nalmefene plus psychosocial support led to the avoidance of 7179 alcohol-attributable diseases/injuries and 309 deaths per 100 000 patients compared to psychosocial support alone over the course of 5 years . Conclusions Nalmefene can be seen as a cost-effective treatment for alcohol dependence , with substantial public health benefits . Trial registration numbers This cost-effectiveness analysis was developed based on data from three r and omised clinical trials : ESENSE 1 ( NCT00811720 ) , ESENSE 2 ( NCT00812461 ) and SENSE ( NCT00811941 )",
"BACKGROUND Economic evaluations in health care involve the identification , measurement , valuation , and then comparison of the costs ( inputs ) and outcomes of treatments or preventive activities . The aim was to analyze the cost-utility of six-month methadone maintenance treatment program in a Lithuanian primary health care setting . METHODS A prospect i ve study design was used . All the information was obtained through the vali date d question naires at the baseline and 3- and 6-month follow-ups . WHOQOL-BREF was used to assess the quality of life ; the costs were assessed using the DATCAP methodology from the perspective of a patient and outpatient clinic during follow-up period . RESULTS A total of 102 opioid-dependent patients were recruited in the study ; 512 follow-up patient-months were obtained . The methadone maintenance treatment has significantly improved physical , psychological , and environmental components of quality of life during follow-up . Total program costs were 61 288.87 EUR . Cost paid by a patient comprised about 31 % of total program costs . Cost per quality -adjusted life-month ( QALM ) for physical domain was 2227.55 EUR ; for psychological domain , 1879.50 EUR ; for social domain , 5467.64 EUR ; and for environmental domain , 4626.47 EUR . Costs per QALM and quality -adjusted life-year ( QALY ) for total quality of life in the maintenance program were 2864.00 EUR and 34 368.00 EUR , respectively . CONCLUSIONS Our results showed that 6-month methadone maintenance program was effective in the terms of quality -of-life improvement . Methadone maintenance treatment program was less effective in terms of cost per QALY",
"Models for the economic evaluation of health technologies provide valuable information to decision makers . The choice of model structure is rarely discussed in published studies and can affect the results produced . Many papers describe good modelling practice , but few describe how to choose from the many types of available models . This paper develops a new taxonomy of model structures . The horizontal axis of the taxonomy describes assumptions about the role of expected values , r and omness , the heterogeneity of entities , and the degree of non-Markovian structure . Commonly used aggregate models , including decision trees and Markov models require large population numbers , homogeneous sub-groups and linear interactions . Individual models are more flexible , but may require replications with different r and om numbers to estimate expected values . The vertical axis of the taxonomy describes potential interactions between the individual actors , as well as how the interactions occur through time . Models using interactions , such as system dynamics , some Markov models , and discrete event simulation are fairly uncommon in the health economics but are necessary for modelling infectious diseases and systems with constrained re sources . The paper provides guidance for choosing a model , based on key requirements , including output requirements , the population size , and system complexity",
"Abstract Background and aim : Buprenorphine offers an alternative to methadone in the treatment of heroin dependence , and has the advantage of allowing alternate-day dosing . This study is the first to examine the cost effectiveness of buprenorphine as maintenance treatment for heroin dependence in a primary care setting using economic and clinical data collected within a r and omised trial . Study design and methods : The study was a r and omised , open-label , 12-month trial of 139 heroin-dependent patients in a community setting receiving individualised treatment regimens of buprenorphine or methadone . Those who were currently on a methadone program ( n = 57 ; continuing therapy subgroup ) were analysed separately from new treatment recipients ( n = 82 ; initial therapy subgroup ) . The study took a broad societal perspective and included health , crime and personal costs . Data on re source use and outcomes were a combination of clinical records and self report at interview . The main outcomes were incremental cost per additional day free of heroin use and per QALY . An analysis of uncertainty calculated the likelihood of net benefits for a range of acceptable money values of outcomes . All costs were in 1999 Australian dollars ( $ A ) . Results : The estimated mean number of heroin-free days did not differ significantly between those r and omised to methadone ( 225 [ 95 % CI 91 , 266 ] ) , or buprenorphine ( 222 [ 95 % CI 194 , 250 ] ) over the year of the trial . Buprenorphine was associated with an average 0.03 greater QALYs over 52 weeks ( not significant ) . The total cost was $ A17 736 ( 95 % CI −$A2981 , $ A38 364 ) with methadone and $ A11 916 ( 95 % CI $ A7697 , $ A16 135 ) with buprenorphine ; costs excluding crime were $ A4513 ( 95 % CI $ A3495 , $ A5531 ) and $ A5651 ( 95 % CI $ A4202 , $ A7100 ) . With additional heroin-free days as the outcome , and crime costs included buprenorphine has a lower cost but less heroin-free days . If crime costs are excluded buprenorphine has a higher cost and worse outcome than methadone . With additional QALYs as the outcome , the cost effectiveness of buprenorphine is $ A39 404 if crime is excluded , but buprenorphine is dominant if crime is included . Conclusions : The trial found no significant differences in costs or outcomes between methadone and buprenorphine maintenance in this particular setting . Although some of the results suggest that methadone may have a cost advantage , it is difficult to infer from the trial data that offering buprenorphine as an alternative would have a significant effect on total costs or outcomes . The point estimates of costs and outcomes suggest that buprenorphine may have an advantage in those initiating therapy . The confidence intervals were wide , however , and the likelihood of net benefits from substituting one treatment for another was close to 50 %",
"IMPORTANCE The United States has invested substantially in screening and brief intervention for illicit drug use and prescription drug misuse , based in part on evidence of efficacy for unhealthy alcohol use . However , it is not a recommended universal preventive service in primary care because of lack of evidence of efficacy . OBJECTIVE To test the efficacy of 2 brief counseling interventions for unhealthy drug use ( any illicit drug use or prescription drug misuse)-a brief negotiated interview ( BNI ) and an adaptation of motivational interviewing (MOTIV)-compared with no brief intervention . DESIGN , SETTING , AND PARTICIPANTS This 3-group r and omized trial took place at an urban hospital-based primary care internal medicine practice ; 528 adult primary care patients with drug use ( Alcohol , Smoking , and Substance Involvement Screening Test [ ASSIST ] substance-specific scores of ≥4 ) were identified by screening between June 2009 and January 2012 in Boston , Massachusetts . INTERVENTIONS Two interventions were tested : the BNI is a 10- to 15-minute structured interview conducted by health educators ; the MOTIV is a 30- to 45-minute intervention based on motivational interviewing with a 20- to 30-minute booster conducted by master's-level counselors . All study participants received a written list of substance use disorder treatment and mutual help re sources . MAIN OUTCOMES AND MEASURES Primary outcome was number of days of use in the past 30 days of the self-identified main drug as determined by a vali date d calendar method at 6 months . Secondary outcomes included other self-reported measures of drug use , drug use according to hair testing , ASSIST scores ( severity ) , drug use consequences , unsafe sex , mutual help meeting attendance , and health care utilization . RESULTS At baseline , 63 % of participants reported their main drug was marijuana , 19 % cocaine , and 17 % opioids . At 6 months , 98 % completed follow-up . Mean adjusted number of days using the main drug at 6 months was 12 for no brief intervention vs 11 for the BNI group ( incidence rate ratio [ IRR ] , 0.97 ; 95 % CI , 0.77 - 1.22 ) and 12 for the MOTIV group ( IRR , 1.05 ; 95 % CI , 0.84 - 1.32 ; P = .81 for both comparisons vs no brief intervention ) . There were also no significant effects of BNI or MOTIV on any other outcome or in analyses stratified by main drug or drug use severity . CONCLUSIONS AND RELEVANCE Brief intervention did not have efficacy for decreasing unhealthy drug use in primary care patients identified by screening . These results do not support widespread implementation of illicit drug use and prescription drug misuse screening and brief intervention . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00876941"
] |
4116bb9a-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND & AIMS Dietary approaches to stop hypertension ( DASH ) diet is associated with improved blood pressure and risk of cardiovascular diseases . It is proposed that DASH might also improve systemic inflammatory markers like highly sensitive C-reactive protein ( hs-CRP ) ; however , interventional studies have led to conflicting results . The aim of current systematic review was to summarize results of r and omized clinical trials examining the effect of DASH on inflammatory biomarkers . METHODS R and omized trials which assessed the effect of adherence to DASH diet on the circulating inflammatory biomarkers in adults were identified through search ing PubMed , EMBASE , Scopus and Google Scholar up to December 2016 . Difference in Mean change and its corresponding st and ard deviation in inflammatory markers between intervention and control groups were calculated to be used as effect size . R and om effects model was used to calculate the summary effects . RESULTS Seven trials were eligible and six studies with 451 participants were included in the meta- analysis which measured hs-CRP as the biomarker of systemic inflammation . The DASH diet significantly decreased serum hs-CRP levels [ mean difference ( MD ) = -1.01 , 95 % confidence interval ( CI ) : -1.64 , -0.38 ; I-squared ( I2 ) = 67.7 % ] compared to usual diets ; however , the effect was not significant when it was compared with healthy diets ( MD = 0.10 mg/L ; 95%CI : -0.16 , 0.37 ; I2 = 94.0 % ) . The reduction in serum hs-CRP levels was greater in trials lasted eight weeks or more . CONCLUSION Adherence to DASH diet is effective in improving circulating serum inflammatory biomarkers in adults , compared with usual diet ; therefore , it could be a valuable strategy to suppress inflammation process
|
[
"Background — The role of C-reactive protein ( CRP ) in predicting vascular events and response to statin therapy remains uncertain . Additional large prospect i ve studies are required . Methods and Results — Baseline CRP was related to risk over 3.2 years for primary a combined end point ( definite or suspected death from coronary heart disease , nonfatal myocardial infa rct ion , and fatal or nonfatal stroke ; n=865 events ) and secondary ( coronary heart disease events or stroke alone ) and tertiary ( stroke plus transient ischemic attack ) end points in the Prospect i ve Study of Pravastatin in the Elderly at Risk ( n=5804 men and women ; age , 70 to 82 years ) . CRP levels were higher in subjects who had a subsequent primary end-point event compared with those who did not ( geometric mean ; 3.64 mg/L [ SD , 3.08 mg/L ] versus 3.01 mg/L [ SD , 3.05 mg/L ] ; P CRP correlated positively with body mass index and smoking status and negatively with high-density lipoprotein cholesterol . The unadjusted hazard ratio for the primary end point was 1.48 ( 95 % CI , 1.26 to 1.74 ) in a comparison of top and bottom thirds for CRP , falling to 1.36 ( 95 % CI , 1.15 to 1.61 ) with adjustment for established predictors and body mass index . Similar results were obtained for other end points or when results were examined separately by history of vascular disease . However , baseline CRP added minimally to risk prediction beyond conventional predictors and did not relate to the magnitude of pravastatin benefit . Conclusions — Elevated CRP minimally enhances cardiovascular disease prediction beyond established vascular risk factors and does not predict response to statin therapy in elderly subjects at risk . These data suggest that CRP has limited clinical value in cardiovascular disease risk stratification or predicting response to statin therapy in elderly people",
"Background —Inflammatory mediators regulate key aspects of lipid metabolism . We hypothesized that inflammation could diminish the cholesterol-lowering effect of a reduced-fat/low-cholesterol diet . Methods and Results —After a 2-week run-in period on a control diet ( 37 % total fat , 16 % saturated fat ) , 100 participants were r and omized to the control or DASH diet ( 27 % total fat , 6 % saturated fat ) for 12 weeks . Median C-reactive protein ( CRP ) at baseline was 2.37 mg/L ( interquartile range , 1.20 , 3.79 ) . The DASH diet , net of control , had no effect on CRP . Overall , there were significant net reductions in total ( −0.34 mmol/L ) , LDL ( −0.29 mmol/L ) , and HDL ( −0.12 mmol/L ) cholesterol from the DASH diet ( each , P change in triglycerides ( + 0.05 mmol/L , P = 0.21 ) . Baseline CRP was strongly associated with lipid responsiveness to the DASH diet . Total and LDL cholesterol were reduced to a greater degree in those with a “ low ” ( below median ) compared with a “ high ” ( above median ) baseline CRP ( total , −9.8 % versus −3 % ; P for interaction=0.006 ; LDL cholesterol , −11.8 % versus −3 % ; P for interaction=0.009 ) . Reductions in HDL cholesterol ( −8.8 % ) were similar in persons with low versus high CRP . Triglycerides were increased in those with a high CRP but not in those with a low CRP ( 19.8 % versus + 0 % ; P for interaction=0.019 ) . Conclusions —In this study , the presence of increased CRP was associated with less total and LDL cholesterol reduction and a greater increase in triglycerides from a reduced-fat/low-cholesterol diet . These findings document an additional mechanism by which inflammation might increase cardiovascular disease risk",
"Background : A Step I diet with lean beef compared with lean white meat both decrease LDL cholesterol . To our knowledge , no studies have evaluated a low – saturated fatty acid ( SFA ) ( lean beef . Objective : We studied the effect on LDL cholesterol of cholesterol-lowering diets with varying amounts of lean beef [ ie , Dietary Approaches to Stop Hypertension ( DASH ) : 28 g beef/d ; Beef in an Optimal Lean Diet ( BOLD ) : 113 g beef/d ; and Beef in an Optimal Lean Diet plus additional protein ( BOLD+ ) : 153 g beef/d ] compared with that of a healthy American diet ( HAD ) . Design : Thirty-six hypercholesterolemic participants ( with LDL-cholesterol concentrations > 2.8 mmol/L ) were r and omly assigned to consume each of the 4 diets ( HAD : 33 % total fat , 12 % SFA , 17 % protein , and 20 g beef/d ) , DASH ( 27 % total fat , 6 % SFA , 18 % protein , and 28 g beef/d ) , BOLD ( 28 % total fat , 6 % SFA , 19 % protein , and 113 g beef/d ) , and BOLD+ ( 28 % total fat , 6 % SFA , 27 % protein , and 153 g beef/d ) for 5 wk . Results : There was a decrease in total cholesterol ( TC ) and LDL-cholesterol concentrations ( P respectively ) . Apolipoprotein A-I , C-III , and C-III bound to apolipoprotein A1 particles decreased after BOLD and BOLD+ diets compared with after the HAD , and there was a greater decrease in apolipoprotein B after consumption of the BOLD+ diet than after consumption of the HAD ( P 0.05 for both ) . LDL cholesterol and TC decreased after consumption of the DASH , BOLD , and BOLD+ diets when the baseline C-reactive protein ( CRP ) concentration was ; LDL cholesterol and TC decreased when baseline CRP concentration was > 1 mg/L with the BOLD and BOLD+ diets . Conclusions : Low-SFA , heart-healthy dietary patterns that contain lean beef elicit favorable effects on cardiovascular disease ( CVD ) lipid and lipoprotein risk factors that are comparable to those elicited by a DASH dietary pattern . These results , in conjunction with the beneficial effects on apolipoprotein CVD risk factors after consumption of the BOLD and BOLD+ diets , which were greater with the BOLD+ diet , provide support for including lean beef in a heart-healthy dietary pattern . This trial was registered at clinical trials.gov as NCT00937898",
"Background : Population s eating mainly vegetarian diets have lower blood pressure levels than those eating omnivorous diets . Epidemiologic findings suggest that eating fruits and vegetables lowers blood pressure",
"We tested whether lowering of blood pressure ( BP ) on the dietary approaches to stop hypertension ( DASH ) diet was associated with changes in peripheral vascular function : endothelial function , assessed by flow-mediated vasodilatation ( FMD ) of the brachial artery , and subcutaneous adipose tissue blood flow ( ATBF ) . We also assessed effects on heart rate variability ( HRV ) as a measure of autonomic control of the heart . We allocated 27 men and women to DASH diet and control groups . We measured FMD , ATBF and HRV on fasting and after ingestion of 75 g glucose , before and after 30 days on dietary intervention , aim ing for weight maintenance . The control group did not change their diet . The DASH-diet group complied with the diet as shown by significant reductions in systolic ( P and diastolic ( P=0.005 ) BP , and in plasma C-reactive protein ( P LDL-cholesterol ( P apolipoprotein B ( P=0.001 ) , a novel finding . Body weight changed by FMD , or in ATBF , in the DASH-diet group , although heart rate fell ( P Glucose and insulin concentrations did not change . In this small-scale study , the DASH diet lowered BP independently of peripheral mechanisms",
"BACKGROUND Diets high in fiber are associated with lower levels of inflammatory markers . This study examined the reduction in inflammation from a diet supplemented with fiber compared with a diet naturally high in fiber . METHODS R and omized crossover intervention trial of 2 diets , a high-fiber ( 30-g/d ) Dietary Approaches to Stop Hypertension ( DASH ) diet or fiber-supplemented diet ( 30 g/d ) , after a baseline ( regular ) diet period of 3 weeks . There were 35 participants ( 18 lean normotensive and 17 obese hypertensive individuals ) aged 18 to 49 years . RESULTS The study included 28 women and 7 men ; 16 ( 46 % ) were black , the remainder white . The mean ( SD ) fiber intake on baseline diets was 11.9 ( 0.3 ) g/d ; on the high-fiber DASH diet , 27.7 ( 0.6 ) g/d ; and on the supplemented diet , 26.3 ( 0.4 ) g/d . Overall , the mean C-reactive protein ( CRP ) level changed from 4.4 to 3.8 mg/L ( -13.7 % ; P = .046 ) in the high-fiber DASH diet group and to 3.6 mg/L ( -18.1 % ) in the fiber-supplemented diet group ( P = .03 ) . However , CRP levels decreased in the 18 lean normotensive participants in either intervention diet group ( 2.0 mg/L [ baseline ] vs 1.4 mg/L [ high-fiber DASH ] vs 1.2 mg/L [ supplemented ] ) ; P.05 ) in obese hypertensive participants . Neither age nor race influenced the response of CRP levels to the diets . No evidence of a crossover effect was detected . CONCLUSIONS The results demonstrate that fiber intake of about 30 g/d ) from a diet naturally rich in fiber or from a supplement can reduce levels of CRP . Further research is needed to more clearly eluci date the differential effect seen in lean vs obese individuals and whether modification of dietary fiber may be helpful in modulating inflammation and its consequent cardiovascular consequences",
"BACKGROUND AND AIM Compared to a DASH-type diet , an intensively applied dietary portfolio reduced diastolic blood pressure at 24 weeks as a secondary outcome in a previous study . Due to the importance of strategies to reduce blood pressure , we performed an exploratory analysis pooling data from intensively and routinely applied portfolio treatments from the same study to assess the effect over time on systolic , diastolic and mean arterial pressure ( MAP ) , and the relation to sodium ( Na(+ ) ) , potassium ( K(+ ) ) , and portfolio components . METHODS AND RESULTS 241 participants with hyperlipidemia , from four academic centers across Canada were r and omized and completed either a DASH-type diet ( control n = 82 ) or a dietary portfolio that included , soy protein , viscous fibers and nuts ( n = 159 ) for 24 weeks . Fasting measures and 7-day food records were obtained at weeks 0 , 12 and 24 , with 24-h urines at weeks 0 and 24 . The dietary portfolio reduced systolic , diastolic and mean arterial blood pressure compared to the control by 2.1 mm Hg ( 95 % CI , 4.2 to -0.1 mm Hg ) ( p = 0.056 ) , 1.8 mm Hg ( CI , 3.2 to 0.4 mm Hg ) ( p = 0.013 ) and 1.9 mm Hg ( CI , 3.4 to 0.4 mm Hg ) ( p = 0.015 ) , respectively . Blood pressure reductions were small at 12 weeks and only reached significance at 24 weeks . Nuts , soy and viscous fiber all related negatively to change in mean arterial pressure ( ρ = -0.15 to -0.17 , p ≤ 0.016 ) as did urinary potassium ( ρ = -0.25 , p = 0.001 ) , while the Na(+)/K(+ ) ratio was positively associated ( ρ = 0.20 , p = 0.010 ) . CONCLUSIONS Consumption of a cholesterol-lowering dietary portfolio also decreased blood pressure by comparison with a healthy DASH-type diet . CLINICAL TRIAL REG . NO . : NCT00438425 , clinical trials.gov",
"BACKGROUND AND AIMS C-reactive protein ( CRP ) is a marker of inflammation which has been shown in multiple prospect i ve epidemiological studies to predict the risk of cardiovascular disease and metabolic syndrome . Dietary patterns may influence the risk of diseases through the effects of CRP on inflammation . The aim of this study was to examine the relationship of dietary patterns with CRP in blood , taking into consideration gender and blood pressure . METHODS AND RESULTS The present cross-sectional analysis included 7574 participants from a large , population -based study of middle-aged Koreans . Four dietary patterns , including ' fruit ' , ' vegetable ' , ' meat ' and ' coffee ' , were derived using factor analysis . Multiple linear regressions were used to evaluate the association between dietary patterns and CRP after adjusting for age , sex , education , waist circumference , smoke status and alcohol consumption . We found that the ' vegetable ' pattern was inversely associated with CRP ( Ptrend = 0.01 ) . The adjusted mean CRP was 0.04 mg/dl lower ( 95 % CI -0.07 , -0.01 ) for subjects in the highest quartile of the ' vegetable ' pattern compared with those in the lowest quartile . This inverse association was more pronounced in men with hypertensive blood ; CRP concentrations across increasing quartile categories of the ' vegetable ' pattern score were 0.1 , 0.14 , and 0.15 mg/dl reduction compared to the 1st quartile ( the lowest quartile ) ( Ptrend = 0.04 , Plinearity = 0.02 ) . CONCLUSIONS The inverse association of the ' vegetable ' pattern with CRP was assessed , and the association appeared to be more predominant in men with hypertensive blood pressure",
"Few studies exist regarding the effects of the Dietary Approaches to Stop Hypertension ( DASH ) diet on novel cardiovascular risk factors among type 2 diabetic patients . We evaluated the effects of the DASH eating pattern on C-reactive protein ( CRP ) level , coagulation abnormalities , and hepatic function tests in type 2 diabetic patients . In this r and omized , crossover clinical trial , 31 type 2 diabetic patients consumed a control diet or the DASH diet for 8 wk . The DASH diet was rich in fruits , vegetables , whole grains , and low-fat dairy products and low in saturated fat , total fat , cholesterol , refined grains , and sweets , with a total of 2400 mg/d sodium . The control diet was a st and ard diet for diabetic patients . There was a 4-wk washout between the 2 trial phases . The main outcome measures were CRP level , coagulation indices , and hepatic function tests . The mean percent change for plasma CRP level was -26.9 ± 3.5 % after the DASH diet period and -5.1 ± 3.8 % after the control diet period ( P = 0.02 ) . Decreases in both alanine aminotransferase and aspartate aminotransferase levels were greater after consuming the DASH diet compared with the control diet ( -14.8 ± 3.0 % vs -6.6 ± 3.4 % ; P = 0.001 ; -29.4 ± 3.7 % vs -5.9 ± 1.4 % ; P = 0.001 , respectively ) . The decrease in the plasma fibrinogen level during the DASH diet period ( -11.4 ± 3.6 % ) was greater than that during the control diet ( 0.5 ± 3.4 % ) ( P = 0.03 ) . Among diabetic patients , the DASH diet can play an important role in reducing inflammation , plasma levels of fibrinogen , and liver aminotransferases . Future longer term studies are recommended"
] |
4116bbea-06ff-11f0-808a-c43d1ab1c353
|
Although higher dietary intakes of magnesium ( Mg ) seem to correspond to lower diabetes incidence , research concerning Mg supplementation in people with or at risk of diabetes is limited . Thus , we aim ed to investigate the effect of oral Mg supplementation on glucose and insulin-sensitivity parameters in participants with diabetes or at high risk of diabetes compared with placebo . A literature search in PubMed , EMBASE , SCOPUS , Cochrane Central Register of Controlled Trials and Clinical trials.gov without language restriction , was undertaken . Eligible studies were r and omized controlled trials ( RCTs ) investigating the effect of oral Mg supplementation vs placebo in patients with diabetes or at high risk of diabetes . St and ardized mean differences ( SMD ) and 95 % confidence intervals ( CIs ) were used for summarizing outcomes with at least two studies ; other outcomes were summarized descriptively . Eighteen RCTs ( 12 in people with diabetes and 6 in people at high risk of diabetes ) were included . Compared with placebo ( n=334 ) , Mg treatment ( n=336 ) reduced fasting plasma glucose ( studies = 9 ; SMD=−0.40 ; 95 % CI : −0.80 to −0.00 ; I2=77 % ) in people with diabetes . In conditions in people at high risk of diabetes ( Mg : 226 ; placebo=227 participants ) , Mg supplementation significantly improved plasma glucose levels after a 2 h oral glucose tolerance test ( three studies ; SMD=−0.35 ; 95 % CI : −0.62 to −0.07 ; I2=0 % ) and demonstrated trend level reductions in HOMA-IR ( homeostatic model assessment -insulin resistance ; five studies ; SMD=−0.57 ; 95 % CI : −1.17 to 0.03 ; I2=88 % ) . Mg supplementation appears to have a beneficial role and improves glucose parameters in people with diabetes and also improves insulin-sensitivity parameters in those at high risk of diabetes
|
[
"OBJECTIVE Hypomagnesemia occurs in 25–38 % of patients with type 2 diabetes . Several studies have suggested an association between magnesium ( Mg ) depletion and insulin resistance and /or reduction of insulin secretion in these cases . Our purpose was to evaluate if Mg supplementation ( as magnesium oxide [ MgO ] ) would improve metabolic control in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS We studied 128 patients with type 2 diabetes ( 32 men , 96 women , aged 30–69 years ) , treated by diet or diet plus oral antidiabetic drugs , in the Bahia Federal University Hospital , Brazil . Patients at risk for hypomagnesemia or with reduced renal function were excluded . This study was a clinical r and omized double-blind placebo-controlled trial . Patients received either placebo , 20.7 mmol MgO , or 41.4 mmol MgO daily(elementary Mg ) for 30 days . Mg concentrations were measured in plasma , in mononuclear cells , and in 24-h urine sample s. Fasting blood glucose , HbA1 , and fructosamine were used as parameters of metabolic control . RESULTS Of the patients , 47.7 % had low plasma Mg , and 31.1 % had low intramononuclear Mg levels . Intracellular Mg in patients with diabetes was significantly lower than in the normal population ( 62 blood donors ; 1.4 ± 0.6 vs. 1.7 ± 0.6 μg/mg of total proteins ) . No correlation was found between plasma and intracellular Mg concentrations ( r = −0.179 ; P = 0.15 ) or between Mg concentrations and glycemic control ( r = −0.165 ; P = 0.12 ) . Intracellular Mg levels were lower in patients with peripheral neuropathy than in those without ( 1.2 ± 0.5 vs. 1.5 ± 0.6 μg/mg ) . Similar findings were observed in patients with coronary disease ( 1.0 ± 0.5 vs. 1.5 ± 0.6 μg/mg ) . In the placebo and in the 20.7 mmol Mg groups , neither a change in plasma and intracellular levels nor an improvement in glycemic control were observed . Replacement with 41.4 mmol Mg tended to increase plasma , cellular , and urine Mg and caused a significant fall ( 4.1 ± 0.8 to 3.8 ± 0.7 mmol/1 ) in fructosamine ( normal , 1.87–2.87 mmol/1 ) . CONCLUSIONS Mg depletion is common in poorly controlled patients with type 2 diabetes , especially in those with neuropathy or coronary disease . More prolonged use of Mg in doses that are higher than usual is needed toestablish its routine or selective administration in patients with type 2 diabetes to improve control or prevent chronic complications",
"Oral magnesium ( Mg ) supplementation can improve insulin sensitivity and secretion in patients with Type 2 diabetes mellitus ( DM ) . We studied the effect of Mg supplementation on glycaemic control , blood pressure , and plasma lipids in insulin-requiring patients with Type 2 DM . Fifty moderately controlled patients were r and omized to 15 mmol Mg or placebo daily for 3 months . Plasma Mg , glucose , HbA1c , lipids , erythrocyte Mg , Mg and glucose concentrations in 24-h urine , and systolic and diastolic pressure were measured before and after 3 months treatment . Plasma Mg concentration was higher after supplementation than after placebo ( 0.82 + /- 0.07 vs 0.78 + /- 0.08 mmol l(-1 ) , p Mg excretion ( 5.5 + /- 1.9 vs 3.7 + /- 1.4 mmol 24 h(-1 ) , p = 0.004 ) but erythrocyte Mg concentrations were similar . No significant differences were found in glycaemic control ( glucose : 10.7 + /- 3.8 vs 11.6 + /- 6.2 mmol l(-1 ) , p = 0.8 ; HbA1c : 8.9 + /- 1.6 vs 9.1 + /- 1.2 % , p = 0.8 ) , lipids or blood pressure . On-treatment analysis ( 34 patients : 18 on Mg , 16 on placebo ) yielded similar results . An increase in plasma Mg concentration irrespective of medication was associated with a tendency to a decrease in diastolic pressure ( increased plasma Mg vs no increase : -4.0 + /- 10.1 vs + 2.5 + /- 12.0 mmHg , p = 0.059 ) . Three months ' oral Mg supplementation of insulin-requiring patients with Type 2 DM increased plasma Mg concentration and urinary Mg excretion but had no effect on glycaemic control or plasma lipid concentrations",
"BACKGROUND AND AIMS It has been suggested that magnesium deficiency is associated with the triggering of acute phase response , which may contribute to type 2 diabetes and cardiovascular disease risk . We undertook this study to determine whether oral magnesium supplementation modifies serum levels of high-sensitivity C-reactive protein ( hsCRP ) in apparently healthy subjects with prediabetes and hypomagnesemia . METHODS A total of 62 men and non-pregnant women aged 18 - 65 year , with new diagnosis of prediabetes ( glucose 5.6 were enrolled in a clinical double-blind placebo-controlled trial and r and omly allocated to receive either magnesium chloride ( 30 mL of MgCl2 5 % solution ) or NaHCO3 0.1 % solution , once daily for 3 months . RESULTS At basal conditions , anthropometric and biochemical variables were similarly distributed in both groups . At the end of follow-up , participants who received magnesium chloride showed higher serum magnesium levels ( 0.86 ± 0.08 vs. 0.69 ± 0.16 mmol/L , p = 0.002 ) and lower hsCRP levels ( 4.8 ± 15.2 vs. 17.1 ± 21.0 nmol/L , p = 0.01 ) compared with participants in the control group . CONCLUSIONS Oral magnesium supplementation decreases hsCRP levels in apparently healthy subjects with prediabetes and hypomagnesemia",
"AIM This study evaluated the efficacy of oral magnesium supplementation in the reduction of plasma glucose levels in adults with prediabetes and hypomagnesaemia . METHODS A total of 116 men and non-pregnant women , aged 30 to 65 years with hypomagnesaemia and newly diagnosed with prediabetes , were enrolled into a r and omized double-blind placebo-controlled trial to receive either 30 mL of MgCl2 5 % solution ( equivalent to 382 mg of magnesium ) or an inert placebo solution once daily for four months . The primary trial endpoint was the efficacy of magnesium supplementation in reducing plasma glucose levels . RESULTS At baseline , there were no significant statistical differences in terms of anthropometric and biochemical variables between individuals in the supplement and placebo groups . At the end of follow-up , fasting ( 86.9 ± 7.9 and 98.3 ± 4.6 mg/dL , respectively ; P = 0.004 ) and post-load glucose ( 124.7 ± 33.4 and 136.7 ± 23.9 mg/dL , respectively ; P = 0.03 ) levels , HOMA-IR indices ( 2.85 ± 1.0 and 4.1 ± 2.7 , respectively ; P = 0.04 ) and triglycerides ( 166.4 ± 90.6 and 227.0 ± 89.7 , respectively ; P = 0.009 ) were significantly decreased , whereas HDL cholesterol ( 45.6 ± 10.9 and 46.8 ± 9.2 mg/dL , respectively ; P = 0.04 ) and serum magnesium ( 1.96 ± 0.27 and 1.60 ± 0.26 mg/dL , respectively ; P = 0.005 ) levels were significantly increased in those taking MgCl2 compared with the controls . A total of 34 ( 29.4 % ) people improved their glucose status ( 50.8 % and 7.0 % in the magnesium and placebo groups , respectively ; P that magnesium supplementation reduces plasma glucose levels , and improves the glycaemic status of adults with prediabetes and hypomagnesaemia",
"OBJECTIVE To evaluate the impact of oral magnesium supplementation on risk factors for end-organ disease in patients with non-insulin-dependent diabetes mellitus ( NIDDM ) . DESIGN A 16-week r and omized , double-blind , placebo-controlled crossover trial . SETTING Outpatient center of an academic family medicine residency program . PATIENTS Twenty-eight patients ( age range , 28 to 84 years ; 57.1 % black ; 85.7 % women ) with NIDDM controlled by diet and /or an oral hypoglycemic , with a serum cholesterol levels over 5.20 mmol/L ( 200 mg/dL ) . INTERVENTION Following a 2-week placebo run-in period , each patient was r and omized to receive either sustained-release magnesium chloride ( Slo-Mag ) , 384 mg/d , or an identical-appearing placebo for 6 weeks . After a 2-week interim washout period , each patient was then treated with the alternative regimen for an additional 6-week period . MAIN OUTCOME MEASURES The systolic and diastolic blood pressure and levels of serum glucose , low-density and high-density lipoprotein and total cholesterol , triglycerides , and serum and total erythrocyte magnesium were measured at the beginning , midpoint , and end of each 6-week treatment phase . RESULTS Systolic blood pressure fell an average of 7.4 mm Hg ( P diastolic blood pressure or levels of serum glucose , low-density and high-density lipoprotein and total cholesterol , triglycerides , or serum and erythrocyte magnesium . CONCLUSIONS Oral magnesium supplementation in the doses and duration studied is modestly effective in reducing systolic blood pressure in patients with NIDDM but has little impact on other important biochemical parameters related to diabetes-associated end-organ disease",
"We evaluated the effects of oral magnesium supplementation on plasma lipid concentrations in patients with non-insulin-dependent diabetes mellitus . Twenty-six persons with non-insulin-dependent diabetes mellitus received 4.5 g magnesium pidolate/d for one month , and 17 persons received placebo . Before and at the end of the treatment period cholesterol concentration , triglycerides , LDL cholesterol , HDL cholesterol , and plasma and erythrocyte magnesium were evaluated . Chronic magnesium supplementation produced a significant reduction of plasma cholesterol and LDL cholesterol , and an increase of HDL cholesterol . These results suggest that oral supplementation of magnesium may be useful in the treatment of hyperlipidaemia in patients with non-insulin-dependent diabetes mellitus",
"In eight aged non-insulin-dependent diabetes mellitus ( NIDDM ) subjects , insulin response and action were studied before and after chronic magnesium supplementation ( 2 g/day ) to diet . Chronic magnesium supplementation to diet versus placebo produced 7 ) a significant increase in plasma ( 0.83 ± 0.05 vs. 0.78 ± 0.06 mM , P erythrocyte ( 2.03 ± 0.06 vs. 1.88 ± 0.09 mM , P levels , 2 ) an increase in acute insulin response ( AIR ) ( 4.0 ± 0.6 vs. - 1 .6 ± 0.6 mU/L , P .05 ) to glucose pulse , and 3 ) an increase in glucose infusion rate ( GIR ) ( 3.6 ± 0.6 vs. 2.9 ± 0.5 mg kg∼1 min−1 P min ) glucose clamp . Net increase in AIR , glucose disappearance rate after glucose pulse , and GIR were significantly and positively correlated to the net increase in erythrocyte magnesium content calculated after chronic magnesium supplementation to diet . In conclusion , our data suggest that NIDDM subjects may benefit from therapeutic chronic administration of magnesium salts",
"The aim of the present study was to investigate the effects of magnesium supplementation on glucose uptake and substrate oxidation in noninsulin-dependent ( type II ) diabetic patients . Nine elderly non-obese noninsulin-dependent ( type II ) diabetic patients , treated by diet only , participated in the study , which was design ed as r and omized , double blind , and cross-over . Each patient was followed up for a pre study period of 3 weeks before inviting him/her to receive placebo or magnesium supplementation ( 15.8 mmol/day ) for 4 weeks . At the end of each treatment period , a euglycemic hyperinsulinemic glucose clamp with simultaneous D-[3 - 3H]glucose infusion and indirect calorimetry was performed . Magnesium supplementation result ed in significantly increased plasma and erythrocyte magnesium levels , whereas body weight and fasting plasma glucose did not change . In the last 60 min of the glucose clamp , insulin-mediated glucose disappearance , total body glucose disposal ( 24.5 + /- 0.4 vs. 28.2 + /- 0.7 mumol/kg.min ; P glucose oxidation ( 13.0 + /- 0.4 vs. 16.3 + /- 0.8 mumol/kg.min ; P Endogenous glucose production , nonoxidative glucose disposal , lipid and protein oxidation , and insulin MCR were not affected . In conclusion , a 4-week magnesium supplementation improves insulin sensitivity and glucose oxidation in the course of a euglycemic-hyperinsulinemic glucose clamp in noninsulin-dependent diabetic patients . Long term studies are needed to determine whether magnesium supplementation is useful in the management of type II diabetes",
"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 Magnesium deficiency is associated with poor physical performance , but no trials are available on how magnesium supplementation affects elderly people 's physical performance . OBJECTIVE The aim of our study was to investigate whether 12 wk of oral magnesium supplementation can improve physical performance in healthy elderly women . DESIGN In a parallel-group , r and omized controlled trial , 139 healthy women ( mean ± SD age : 71.5 ± 5.2 y ) attending a mild fitness program were r and omly allocated to a treatment group ( 300 mg Mg/d ; n = 62 ) or a control group ( no placebo or intervention ; n = 77 ) by using a computer-generated r and omization sequence , and research ers were blinded to their grouping . After assessment at baseline and again after 12 wk , the primary outcome was a change in the Short Physical Performance Battery ( SPPB ) ; secondary outcomes were changes in peak torque isometric and isokinetic strength of the lower limbs and h and grip strength . RESULTS A total of 124 participants allocated to the treatment ( n = 53 ) or control ( n = 71 ) group were considered in the final analysis . At baseline , the SPPB scores did not differ between the 2 groups . After 12 wk , the treated group had a significantly better total SPPB score ( Δ = 0.41 ± 0.24 points ; P = 0.03 ) , chair st and times ( Δ = -1.31 ± 0.33 s ; P and 4-m walking speeds ( Δ = 0.14 ± 0.03 m/s ; P = 0.006 ) than did the control group . These findings were more evident in participants with a magnesium dietary intake lower than the Recommended Dietary Allowance . No significant differences emerged for the secondary outcomes investigated , and no serious adverse effects were reported . CONCLUSIONS Daily magnesium oxide supplementation for 12 wk seems to improve physical performance in healthy elderly women . These findings suggest a role for magnesium supplementation in preventing or delaying the age-related decline in physical performance",
"Background : Magnesium is the second most abundant intracellular cation . It plays an important role in insulin homeostasis and glucose metabolism through multiple enzymatic reactions . With increasing data on magnesium deficiency in diabetic patients and epidemiological studies demonstrating magnesium deficiency as a risk factor for diabetes , it is logical to search for its possible beneficial effects on diabetes control and prevention . We aim ed to determine whether oral magnesium supplementation improves metabolic control , lipid profile and blood pressure in patients with type II diabetes . Methods : Fifty four patients with type II diabetes were included in a r and omized double blind placebocontrolled clinical trial . Patients received either placebo or 300 mg elemental magnesium ( as magnesium sulfate -MgSo4- ) daily , for 3 months . Metabolic control , lipid profile , blood pressure , magnesium status , hepatic enzymes , hemoglobin concentration , and anthropometric indices were determined in the beginning and at the end of the study . Results : Daily administration of 300 mg elemental magnesium for 3 months , significantly improved fasting blood glucose ( 183.9±15.43 to 125.8±6.52 vs. 196.5±28.12 to 136.5±7.94 , p ( 239.1±74.75 to 189.1±60mg/dl vs. 246.4±97.37 to 247.8±86.74mg/dl , p . Conclusion : Oral magnesium supplementation with proper dosage has beneficial effects on blood glucose , lipid profile , and blood pressure in patients with type II diabetes",
"To test the hypothesis that magnesium depletion might be of importance for the development of vascular complications in diabetes mellitus we performed a r and omized , double-blind , placebo-controlled study during 12 months with 20 - 30 mmol/day of oral magnesium hydroxide in 28 type 1 diabetic patients . Urinary albumin excretion , Cr-EDTA-clearance and certain blood cardiovascular risk factors were measured . At the end of the study there were no significant differences of these parameters between the two groups , except that serum triglyceride values increased in three magnesium treated patients who either showed an increase in blood glycosylated hemoglobin values or body weight during the study",
"BACKGROUND AND AIM Little is known about the effect of magnesium on insulin sensitivity and BP in healthy individuals . Therefore , we investigated whether magnesium could improve insulin sensitivity and blood pressure ( BP ) in normo-magnesemic nondiabetic overweight adults . METHODS AND RESULTS In a double-blinded , placebo-controlled , r and omized trial , a total of 155 participants ( BMI > or = 23 kg/m(2 ) ) received either 12.3 mmol ( 300 mg ) of elemental magnesium in the form of magnesium oxide ( n=75 ) or placebo ( n=80 ) each day for 12 weeks , constituting the intent-to-treat population . A repeated- measures ANOVA was used to evaluate the between-group changes in variables during the study . The baseline characteristics between the intervention and control groups were similar . There were no significant differences between the groups in the pattern of change of the homeostasis model assessment insulin resistance index , BP over time during the 12-week study . In subgroup analysis , magnesium supplementation ( n=8 , 27 , and 24 , respectively ) lowered BP much more than placebo ( n=16 , 29 , and 25 , respectively ) in those subjects whose systolic BP > or = 140 mmHg , diastolic BP 80 - 90 mmHg , and diastolic BP > or = 90 mmHg at the start of the study ( P=0.016 , 0.043 , and 0.023 , respectively ) ; in comparison , those subjects whose initial BP reading was low at baseline did not show a change in BP . No significant adverse events related to magnesium supplementation were recorded . CONCLUSIONS These results suggested that magnesium supplementation does not reduce BP and enhance insulin sensitivity in normo-magnesemic nondiabetic overweight people . However , it appears that magnesium supplementation may lower BP in healthy adults with higher BP",
"OBJECTIVE To investigate the effects of long-term high-dose oral magnesium ( Mg ) therapy ( 30 mmol/day ) in patients with type II diabetes . Low plasma magnesium levels have been reported in type II diabetes and are associated with insulin resistance and diabetic late complications . RESEARCH DESIGN AND METHODS Forty patients with type II diabetes and hypomagnesemia were observed in a r and omized double-blind placebo-controlled trial for 3 months ( body mass index : 28 ± 4 kg/m2 ; HbA1c : 7.4 ± 0.8 % ) . Plasma and urine magnesium and metabolic control parameters were determined , and side effects were considered , especially with regard to patients ' compliance . RESULTS A significant increase in plasma magnesium levels was observed after 3 months of treatment ( Mg : 0.73 ± 0.8 vs. 0.81 ±0.1 mmol/1 ) , reaching magnesium levels of the control group ( 0.88 ± 0.8 mmol/1 ; NS ) ; metabolic control , however , was not altered ( HbA1c : 7.2 ± 0.7 vs. 7.4 ± 0.9 % ) . Six months after the end of the trial , plasma magnesium declined to pretreatment levels ( Mg : 0.73 ± 0.07 mmol/1 ) . The prevalence of side effects was high at the beginning and was reduced significantly during treatment . CONCLUSIONS We conclude that oral magnesium replacement therapy corrects hypomagnesemia after a minimum treatment period of 3 months . These observations might be important for the prevention of diabetic late complications",
"The effect of magnesium ( Mg ) and ascorbic acid ( AA ) supplementation on metabolic control was assessed in 56 outpatient diabetics . A 90-day run-in period was followed by two 90-day treatment periods , during which Mg ( 600 mg/day ) and AA ( 2 g/day ) were administered in a r and omized double-blind cross-over fashion . A decrease in systolic and diastolic blood pressure ( 132 + /- 3 vs. 138 + /- 4 and 77 + /- 2 vs. 82 + /- 2 mm Hg ; p insulin-dependent diabetes mellitus subjects during Mg supplementation . No beneficial effect of Mg supplementation was observed on glycemic control , lipids or blood pressure in non-insulin-dependent diabetes mellitus ( NIDDM ) subjects . AA supplementation improved glycemic control among NIDDM subjects and both fasting blood glucose ( 9.1 + /- 0.5 vs. 10.1 + /- 0.6 mmol/l ; p HbA1c ( 8.5 + /- 0.3 vs. 9.3 + /- 0.3 % ; p AA supplementation on cholesterol ( 5.9 + /- 0.2 vs. 6.2 + /- 0.2 mmol/l ; p triglycerides ( 2.2 + /- 0.2 vs. 2.5 + /- 0.2 ; p AA supplementation may have a beneficial effect in NIDDM subjects on both glycemic control and blood lipids"
] |
4116bc30-06ff-11f0-808a-c43d1ab1c353
|
Despite the overwhelming evidence supporting the effectiveness of antihypertensive medication , hypertension remains poorly controlled in low and middle-income countries ( LMICs ) . Lifestyle intervention studies reporting effects on blood pressure published from January 1977 to September 2012 were search ed on various data bases . From the 6211 references identified , 52 were included in the systematic review ( 12 , 024 participants ) and 43 were included in the meta- analysis ( in total 6779 participants ) . We calculated and pooled effect sizes in mmHg with r and om-effects models . We grouped interventions into behavioral counseling ( 1831 participants ) , dietary modification ( 1831 participants ) , physical activity ( 1014 participants ) and multiple interventions ( 2103 participants ) . Subgroup analysis and meta-regression were used to evaluate origins of heterogeneity . Lifestyle interventions significantly lowered blood pressure levels in LMIC population s , including in total 6779 participants . The changes achieved in SBP ( 95 % confidence interval ) were : behavioral counseling -5.4 ( -10.7 , -0.0 ) mmHg , for dietary modification -3.5 ( -5.4 , -1.5 ) mmHg , for physical activity -11.4 ( -16.0 , -6.7 ) mmHg and for multiple interventions -6.0 ( -8.9 , -3.3 ) mmHg . The heterogeneity was high across studies and the quality was generally low . Subgroup analyses showed smaller sample s reporting larger effect sizes ; intervention lasting less than 6 months showed larger effect sizes and intention-to-treat analysis showed smaller effect sizes Lifestyle interventions may be of value in preventing and reducing blood pressure in LMICs . Nevertheless , the overall quality and sample size of the studies included were low . Improvements in the size and quality of studies evaluating lifestyle interventions are required
|
[
"Background Cardiovascular disease remains the leading killer of women in most developed areas of the world . Rates of physical inactivity and poor nutrition , which are two of the most important modifiable risk factors for cardiovascular disease in women , are substantial . This study sought to examine the effectiveness of a community-based lifestyle-modification program on increasing women 's physical activity in a r and omized trial guided by community-based participatory research ( CBPR ) methods . Methods A total of 335 healthy , 25–64 years old women who had been selected by a multiple-stage stratified cluster r and om sampling method in Bushehr Port/I.R. Iran , were r and omized into control and intervention groups . The intervention group completed an 8-week lifestyle modification program for increasing their physical activity , based on a revised form of Choose to Move program ; an American Heart Association Physical Activity Program for Women . Audio-taped activity instructions with music and practical usage of the educational package were given to the intervention group in weekly home-visits by 53 volunteers from local non-governmental and community-based organizations . Results Among the participants , the percentage who reported being active ( at lease 30 minutes of moderate intensity physical activity for at least 5 days a week , or at least 20 minutes of vigorous physical activity for at least three days a week ) increased from 3 % and 2.7 % at baseline to 13.4 % and 3 % ( p minutes of physical activity per week ( mean = 139.81 , SE = 23.35 ) than women in the control group ( mean = 40.14 , SE = 12.65 ) at week 8 ( p decrease in systolic blood pressure ( -10.0 mmHg ) than the control group women ( + 2.0 . mmHg ) . The mean ranks for posttest healthy heart knowledge in the intervention and control groups were 198.91 and 135.77 , respectively ( P CBPR methods can be effective for the short-term adoption of physical activity behavior among women . The development of participatory process to support the adequate delivery of lifestyle-modification programs is feasible and an effective healthcare delivery strategy for cardiovascular community health promotion . Trial Registration",
"Reduced-sodium , increased-potassium salt substitutes lower blood pressure but may also have direct effects on vascular structure and arterial function . This study aim ed to test the effects of long-term salt substitution on indices of these outcomes . The China Salt Substitute Study was a r and omized , controlled trial design ed to establish the effects of salt substitute ( 65 % sodium chloride , 25 % potassium chloride , 10 % magnesium sulfate ) compared with regular salt ( 100 % sodium chloride ) on blood pressure among 600 high-risk individuals living in six rural areas in northern China over a 12-month intervention period . Data on central aortic blood pressure , aortic pressure augmentation ( AUG ) , augmentation index ( AIx ) , the differences of the peak of first and baseline waves ( P1–P0 ) and pulse wave reflection time ( RT ) were collected at r and omization and at the completion of follow-up in 187 participants using the Sphygmocor pulse wave analysis system . Mean baseline blood pressure was 150.1/91.4 mm Hg , mean age was 58.4 years , 41 % were male and three quarters had a history of vascular disease . After 12 months of intervention , there were significant net reductions in peripheral ( 7.4 mm Hg , P=0.009 ) and central ( 6.9 mm Hg , P=0.011 ) systolic blood pressure levels and central pulse pressure ( 4.5 mm Hg , P=0.012 ) and correspondingly there was a significant net reduction in P1–P0 ( 3.0 mm Hg , P=0.007 ) , borderline significant net reduction in AUG ( 1.5 mm Hg , P=0.074 ) and significant net increase in RT ( 2.59 ms , P=0.001 ) . There were no detectable reductions in peripheral ( 2.8 mm Hg , P=0.14 ) or central ( 2.4 mm Hg , P=0.13 ) diastolic blood pressure levels or AIx ( 0.06 % , P=0.96 ) . In conclusion , over the 12-month study period the salt substitute significantly reduced not only peripheral and central systolic blood pressure but also reduced arterial stiffness",
"OBJECTIVE The prevalence of type 2 diabetes , especially in developing countries , has grown over the past decades . We performed a controlled clinical study to determine whether a community-based , group-centered public health intervention addressing nutrition and exercise can ameliorate glycemic control and associated cardiovascular risk factors in type 2 diabetic patients in rural Costa Rica . RESEARCH DESIGN AND METHODS A total of 75 adults with type 2 diabetes , mean age 59 years , were r and omly assigned to the intervention group or the control group . All participants received basic diabetes education . The subjects in the intervention group participated in 11 weekly nutrition classes ( 90 min each session ) . Subjects for whom exercise was deemed safe also participated in triweekly walking groups ( 60 min each session ) . Glycosylated hemoglobin , fasting plasma glucose , total cholesterol , triglycerides , HDL and LDL cholesterol , height , weight , BMI , and blood pressure were measured at baseline and the end of the study ( after 12 weeks ) . RESULTS The intervention group lost 1.0 + /- 2.2 kg compared with a weight gain in the control group of 0.4 + /- 2.3 kg ( P = 0.028 ) . Fasting plasma glucose decreased 19 + /- 55 mg/dl in the intervention group and increased 16 + /- 78 mg/dl in the control group ( P = 0.048 ) . Glycosylated hemoglobin decreased 1.8 + /- 2.3 % in the intervention group and 0.4 + /- 2.3 % in the control group ( P = 0.028 ) . CONCLUSIONS Glycemic control of type 2 diabetic patients can be improved through community-based , group-centered public health interventions addressing nutrition and exercise . This pilot study provides an economically feasible model for programs that aim to improve the health status of people with type 2 diabetes",
"In a r and omized , single-blind , controlled trial , 621 patients were assigned either intervention diet A ( group A , 310 patients ) or control diet B ( group B , 311 patients ) for a period of 24 weeks . After 24 weeks as revealed by dietary question naires , group A patients received : ( 1 ) a diet with a higher percentage of calories from fruits and vegetables and complex carbohydrates ; ( 2 ) a higher polyunsaturated/saturated fat ratio diet ; and ( 3 ) a larger amount of soluble dietary fiber , antioxidant vitamins and minerals and low saturated fat and cholesterol than group B. Group A patients also did more physical and yogic exercises than group B. Adherence to diet and exercise was obtained through question naires and information obtained was quantified into a formula . After 24 weeks , the overall score of diet and exercises was significantly higher in group A than in group B. There was a significant decrease in serum total cholesterol ( 13.3 % ) , low-density lipoprotein cholesterol ( 16.9 % ) , triglycerides ( 19.2 % ) , fasting blood glucose ( 19.5 % ) and blood pressures ( 11.5/6.2 mm Hg ) in the intervention group compared with initial levels and changes in group B. The effect of exercise on the decrease in risk factors was additive . Within group A , overall score for diet and exercise was greater in 1 subset of 116 patients in the intervention group which had maximal lifestyle changes . A separate analysis of data in this subgroup revealed a greater decrease in risk factors compared with risk factor changes in the remaining 194 patients with less higher overall score ; this indicated that the relation of lifestyle changes with reduction in risk factors may be of causal nature . ( ABSTRACT TRUNCATED AT 250 WORDS",
" A total of 3,318 men and women from a region in rural China were r and omized to receive daily either a multiple vitamin/mineral supplement or a placebo . Deaths that occurred in the participants were ascertained and classified according to cause over the 6-year period from 1985 to 1991 . At the end of supplementation , blood pressure readings were taken , and the prevalence of hypertension was determined . There was a slight reduction in overall mortality in the supplement group ( relative risk ( RR ) = 0.93 , 95 percent confidence interval ( CI ) 0.75 - 1.16 ) , with the decreased relative risk most pronounced for cerebrovascular disease deaths ( RR = 0.63 , 95 percent CI 0.37 - 1.07 ) . This benefit was greater for men ( RR = 0.42 , 95 percent CI 0.19 - 0.93 ) than for women ( RR = 0.93 , 95 percent CI 0.44 - 1.98 ) . Among the survivors , the presence of elevations in both systolic and diastolic blood pressures was less common in those who received the supplement ( RR for men = 0.43 , 95 % CI 0.28 - 0.65 ; RR for women = 0.92 , 95 percent CI 0.68 - 1.24 ) . This study indicates that supplementation with a multivitamin/mineral combination may have reduced mortality from cerebrovascular disease and the prevalence of hypertension in this rural population with a micronutrient-poor diet",
"Resistance training increases muscle strength in older adults , decreasing the effort necessary for executing physical tasks , and reducing cardiovascular load during exercise . This hypothesis has been confirmed during strength-based activities , but not during aerobic-based activities . This study determined whether different resistance training regimens , strength training ( ST , constant movement velocity ) or power training ( PT , concentric phase performed as fast as possible ) can blunt the increase in cardiovascular load during an aerobic stimulus . Older adults ( 63.9 ± 0.7 years ) were r and omly allocated to : control ( N = 11 ) , ST ( N = 13 , twice a week , 70 - 90 % 1-RM ) and PT ( N = 15 , twice a week , 30 - 50 % 1-RM ) groups . Before and after 16 weeks , oxygen uptake ( VO(2 ) ) , systolic blood pressure ( SBP ) , heart rate ( HR ) , and rate pressure product ( RPP ) were measured during a maximal treadmill test . Resting SBP and RPP were similarly reduced in all groups ( combined data = -5.7 ± 1.2 and -5.0 ± 1.7 % , respectively , P 0.05 ) . Maximal SBP , HR and RPP did not change . The increase in measured VO(2 ) , HR and RPP for the increment in estimated VO(2 ) ( absolute load ) decreased similarly in all groups ( combined data = -9.1 ± 2.6 , -14.1 ± 3.9 , -14.2 ± 3.0 % , respectively , P the increments in the cardiovascular variables for the increase in measured VO(2 ) did not change . In elderly subjects , ST and PT did not blunt submaximal or maximal HR , SBP and RPP increases during the maximal exercise test , showing that they did not reduce cardiovascular stress during aerobic tasks",
"This study was conducted in three stages in a semi-rural region of Eskisehir , Turkey . In the first stage , individuals selected by r and om sampling were evaluated for cardiovascular disease risk factors . In the second stage , Group I and Group II training material s were r and omly distributed . In the third stage , the subjects were screened one year later to assess and determine if there had been any changes in their attitudes towards the dangers of cardiovascular diseases . The number of active smokers significantly decreased after the training in the both groups . The percentage of people with regulated blood pressure exhibited an increase in Group II more than Group",
"Objective Dietary sodium and potassium consumption is associated with blood pressure levels . The objective of this study was to define a practical and low-cost method for the control of blood pressure by modification of these dietary cations in rural Chinese . Methods This study was a double-blind , r and omized , controlled trial design ed to establish the long-term effects of a reduced-sodium , high-potassium salt substitute ( 65 % sodium chloride , 25 % potassium chloride , 10 % magnesium sulphate ) compared to normal salt ( 100 % sodium chloride ) on blood pressure among high-risk individuals . Following a 4-week run-in period on salt substitute , participants were r and omly assigned to replace their household salt with either the study salt substitute or normal salt for a 12-month period . Results The mean age of the 608 r and omized participants was 60 years and 56 % of them were female . Sixty-four percent had a history of vascular disease and 61 % were taking one or more blood pressure-lowering drugs at entry . Mean baseline blood pressure was 159/93 mmHg ( SD 26/14 ) . The mean overall difference in systolic blood pressure between r and omized groups was 3.7 mmHg ( 95 % confidence interval 1.6–5.9 , P diastolic blood pressure . Conclusion Salt substitution produced a substantial and sustained systolic blood pressure reduction in this population , and should be actively promoted as a low-cost alternate or adjunct to drug therapy for people consuming significant quantities of salt",
"BACKGROUND Hypertension ( H ) is associated with a large number of co-morbidities , including obesity . The correlation between two variables has been investigated . OBJECTIVE To analyze the correlation between the loss of body mass and blood pressure reduction in hypertensive patients undergoing exercising programs ( EP ) . METHODS One hundred eleven hypertensive patients with overweight or obesity were r and omly divided into an experimental group ( EG ) . Out of these , 57 ( 58 + /- 8.9 years old ) participated in a three-month EP conducted three times a week in aerobic exercise sessions from 50 % to 70 % of VO2 peak for 30 to 60 minutes and resistance exercises ; and a control group ( CG ) with 54 ( 60 + /- 7.7 years old ) who did not participate in the EP . In the EG , blood pressure ( BP ) was measured before each session and the measurement of anthropometric variables ( AV ) at the beginning of the program and after three months . In the CG the BP and the VA were evaluated in the doctor 's office at the beginning and at the end of the study . Data were expressed as mean + /- st and ard deviation ( SD ) . Pearson correlation and t test were used . A value of p AV and BP at the beginning and at the end of the study . In the EG , there was no significant alteration in the AV , however , there was blood pressure reduction of 12 % in systolic BP ( -17.5 mmHg , p = 0.001 ) and 9 % in Diastolic BP ( -8.1 mmHg , p = 0 . 01 ) at the end of the study . There was no correlation between the AV and decrease in BP ( r = 0.1 ) . CONCLUSION The blood pressure reduction was not correlated with reduction of anthropometric measures after the exercising period",
"OBJECTIVE To research on the relationship of the patient and his/her family as a non-pharmacological factor for blood hypertension . To determine whether a hyposodic , hypocaloric , hypofat , and hypocholesterolemic diet decreases the blood tension . To determine whether physical exercises in the patient and his/her family help to reduce the hypertension . To observe whether the psychological therapy of muscles relaxation helps to reduce the hypertension . To evaluate in the sample of families , the experience of each member , as well as their suggestions and complaints about the programme . To design the strategic model to control the blood tension by ambulatory means . DESIGN Controlled intervention study , descriptive , non-r and omized , prospect i ve . PLACEMENT : Primary care . PATIENTS AND OTHER PARTICIPANTS Study group of 10 patients , 10 wives , and 12 children , and control group of 10 patients excluding family members . INTERVENTIONS With both groups ( study and control ) there were meetings every 15 days for 6 months according to an established schedule . In the meetings there were given talks , pamphlets , physical exercises , muscles relaxation therapy , all about blood hypertension . There were question naires before and after each activity . MEASURING AND MAIN RESULTS : In both groups ( study and control ) there was a statistically significant ( t the weight . The blood systolic tension decreased in both positions , seated and st and ing , in the study group ( difference statistically significant ) but not so in the control group , although there was a non-significant difference ( decrease of 1.5 mmHg ) in the seated position . The diastolic tension decreased significantly in the study group both in seated and st and ing positions , not so in the control group . CONCLUSIONS The study sample showed that systolic tension seated and st and ing had a statistically significant reduction in the study group but not so in the control group . The weight had statistically significant reduction in both study and control groups . Total cholesterol had statistically significant decrease in the study group but not in the control group . HDL-C had statistically significant reduction in the study group ; in the control group there was a decrease but not statistically significant . The triglycerides did not decrease statistically significant in any of the groups ( study and control )",
"OBJECTIVE This paper evaluates the effectiveness of a Public Health program for the elderly based on health promotion and pathologies prevention , in order to avoid complications associated with illnesses and improves the quality of life ( QOL ) in elderly adults ( EA ) . METHODS A 12 month intervention studies used 700 EA r and omized in 2 groups : intervention and control . Each group was su bmi tted to pre-post intervention measurements that included weight , height , blood pressure ( BP ) , cholesterol , lipids , glycaemia , cardiovascular ( infa rct , stroke ) and bone fractures events , hospitalization , and a QOL survey . Intervention consisted of periodic physical activity to fortify muscular groups , as well as recreational activities , nutritional and food manipulation training visits . A medical student was assigned to each participant from the intervention group to assure periodical contact and to share activities . The control group continued with their normal activities during observational period . RESULTS The intervention group showed a significant reduction in the BP , lipids and cholesterol values compared to control group . Reduction on cardiovascular events ( -31 % ) , hip fractures ( -18.2 % ) and number of hospital admittance ( -21.1 % ) were obtained for group A in relation to B. The QOL survey showed 28.7 % improvement for group A compared with 33.4 % improvement compared with control group . CONCLUSION The health program with exhaustive follow-up administration , significantly reduced risk factors and complications associated with aging",
"BACKGROUND Even though the effectiveness of mediation and relaxation skills is controversial in blood pressure control , extensive field studies are limited . A national study targeting 50 communities r and omly selected from northern Taiwan was conducted to test and compare the effectiveness of hypertension control incorporating three strategies . METHODS Five hundred ninety hypertensives identified from 3,128 adults at a screening survey among the 50 communities were invited to participate in the study and were r and omly assigned to three treatment modalities , ( a ) relaxation techniques training at home , ( b ) routine blood pressure measurement by a health professional , and ( c ) reading self-learning packages , or to a control group . RESULTS After a 2-month intervention period , the three treatment groups showed a significant reduction in systolic blood pressure levels compared with the control group ( 11.0 mm Hg for group 1 , 9.2 mm Hg for group 2 , and 5.1 mm Hg for group 3 ) . The relaxation group had the most significant reduction in systolic blood pressure levels , followed by the routine blood pressure monitoring group and the self-learning group . However , the effect of relaxation training at home was not significantly greater than routine blood pressure measurement by a health professional",
"Lamina , S. Comparative effect of interval and continuous training programs on serum uric acid in management of hypertension : a r and omized controlled trial . J Strength Cond Res 25(3 ) : 719 - 726 , 2011-The purpose of the study was to investigate the effect of interval and continuous training program on blood pressure and serum uric acid ( SUA ) levels in subjects with hypertension . Three hundred and fifty-seven male patients with mild to moderate systolic blood pressure ( SBP ) between 140 and 179 and diastolic blood pressure ( DBP ) between 90 and 109 mm Hg essential hypertension were age-matched and grouped into interval , continuous , and control groups . The interval ( work : rest ratio of 1:1 ) and continuous groups were involved in an 8-week interval and continuous training program of 45 - 60 minutes , at intensities of 60 - 79 % of heart rate maximum , whereas the control group remained sedentary during this period . SBP , DBP , maximum oxygen uptake ( & OV0312;o2max ) and SUA concentration were assessed . One-way analysis of variance and Scheffe and Pearson correlation tests were used in data analysis . Findings of the study revealed significant effect of exercise training program on & OV0312;o2max , SBP , DBP , and SUA . However , there was no significant difference between the interval and continuous groups . Changes in & OV0312;o2max negatively correlated with changes in SUA ( r = −0.220 ) at p moderate-intensity interval and continuous training programs are effective and neither seems superior to the other in the nonpharmacological management of hypertension and may prevent cardiovascular events through the downregulation of SUA in hypertension . Findings of the study support the recommendations of moderate-intensity interval and continuous training programs as adjuncts for nonpharmacological management of essential hypertension",
"OBJECTIVES To evaluate the effects on blood pressure , lipid profile , and anxiety status on subjects received a 12-week Tai Chi Chuan exercise program . DESIGN R and omized controlled study of a Tai Chi Chuan group and a group of sedentary life controls . SETTING Taipei Medical University Hospitals and University campus in the Taipei , Taiwan , area . SUBJECTS Two ( 2 ) selected groups of 76 healthy subjects with blood pressure at high-normal or stage I hypertension . INTERVENTION A 12-week Tai Chi Chuan exercise training program was practice d regularly with a frequency of 3 times per week . Each session included 10-minute warm-up , 30-minute Tai Chi exercise , 10-minute cool-down . Exercise intensity was estimated to be approximately 64 % of maximal heart rate . OUTCOME MEASURES Blood pressure , lipid profile and anxiety status ( State-Trait Anxiety Inventory ; STAI ) were evaluated . RESULTS After 12-weeks of Tai Chi training , the treatment group showed significant decrease in systolic blood pressure of 15.6 mm Hg and diastolic blood pressure 8.8 mm Hg . The serum total cholesterol level decreased 15.2 mg/dL and high-density lipoprotein cholesterol increased 4.7 mg/dL. By using STAI evaluation , both trait anxiety and state anxiety were decreased . CONCLUSIONS This study shows that under well- design ed conditions , Tai Chi exercise training could decrease blood pressure and results in favorable lipid profile changes and improve subjects ' anxiety status . Therefore , Tai Chi could be used as an alternative modality in treating patients with mild hypertension , with a promising economic effect",
"OBJECTIVE To evaluate the effect on decrease in blood pressure of modifying risk factors for stroke , such as blood lipid profiles , diet habits and indices of body weight , through a family-based nutrition health education programme among hypertensive patients and pre-hypertensive subjects without taking any antihypertensive drugs . DESIGN AND SETTING This was a community-based prospect i ve study . The study population was r and omly selected from communities in Taipei ; potential subjects were invited by telephone to participate . SUBJECTS After excluding subjects whose blood pressure was normal and those using antihypertensive drugs , there were 390 participants included in the study . Subjects in the intervention group ( n 293 ) received nutrition health education on blood pressure control and stroke-related risk factor modification at each visit . Non-intervention subjects ( n 97 ) only acquired a general education sheet available in clinics . The blood pressure of study subjects was measured at baseline and 6-month follow-up to evaluate the intervention 's effect on decrease in blood pressure . RESULTS Significant decreases of 2.0 mmHg and 5.9 mmHg in systolic blood pressure were observed both in pre-hypertensive and hypertensive subjects in the intervention group . Additionally , intervention subjects with improvement of total cholesterol and LDL cholesterol , decrease in indices of body weight and increase in consumption of fruit and vegetables also had significant lowering of blood pressure . CONCLUSIONS The present study provided evidence that the blood pressure of pre-hypertensive and hypertensive subjects could decrease significantly , without taking antihypertensive drugs , after modifying blood lipid profiles and waist by dietary habits changed through a family-based nutrition heath education programme , result ing in a significant effect on stroke risk reduction",
"BACKGROUND The aging process is associated with the development of several diseases , which can be attenuated by the practice of physical activities . Aerobic training is an effective method to maintain and improve cardiovascular function . Additionally , it has a crucial role in the prevention and treatment of several chronic-degenerative diseases , especially diabetes mellitus . } OBJECTIVE To verify the effect of a 13-week aerobic training program on blood pressure ( BP ) , body mass index ( BMI ) and glycemia levels in elderly women with type-2 diabetes mellitus ( DM2 ) . METHODS Eleven sedentary elderly women with DM2 , aged 61.0 ± 9.1 years , were su bmi tted a 13-week aerobic training program , constituting group G2 . Eleven controlled elderly women ( aged 60.2 ± 6.8 years ) were not su bmi tted to the aerobic training , constituting the control group ( G1 ) . G1 attended educational lectures once a week , whereas G2 walked three times a week . RESULTS Both groups presented a significant decrease in glycemia and diastolic blood pressure levels . No significant decreases in BMI were observed after the aerobic training in either group . CONCLUSION The 13-week aerobic training program was enough to promote significant decrease in the diastolic blood pressure and glycemia levels ; therefore , this type of exercise training decreases the risk factors for cardiovascular and metabolic diseases ",
"AIM To assess the effects of health training course aim ed at educating middle-aged women of low socio-economic status in Turkey how to better control high blood pressure . METHODS The intervention study included 400 r and omly selected women aged ( mean+/-st and ard deviation ) 34.1+/-8.6 years . After their body size and blood pressure were measured , the women were r and omly divided into two groups . The intervention group underwent public health training on high blood pressure control and obesity reduction , whereas control group had no training at all . After six months , blood pressure and body size of women in both groups were measured again . RESULTS Overall , the initial high blood pressure and obesity ratio in the intervention and control group were 20.0 % and 31.7 % , respectively . After 6 months of the intervention program , the number of women within the optimal weight range significantly increased in the intervention group compared with control group ( p=0.009 ) . After the intervention program , the number of women with normal weight and normal blood pressure in the intervention group significantly increased ( weight : 130 women before vs 150 after , p=0.001 ; blood pressure : 160 women before vs 173 after , p percentage of meals consisting of fried food in the intervention group was lower by 31.9 % , and by 5.0 % in the control group . After the intervention the percentage of boiled food increased by 15.7 % in the intervention group , compared with no change in the control group . The consumption of food high in salt decreased by 5.5 % in the control and by 72.2 % in the intervention group . Similarly , the percentage of women who exercised almost doubled in the intervention group , whereas there was no change in the control group . CONCLUSION The changes in the lifestyle significantly reduced hypertension and obesity ratio among women . The public health center can provide initial health training support as a part of the broader public health management program , aim ed at helping people tackle health problems",
"OBJECTIVE To assess the impact of a food-based intervention on blood pressure ( BP ) in free-living South African men and women aged 50 - 75 years , with drug-treated mild-to-moderate hypertension . METHODS A double-blind controlled trial was undertaken in eighty drug-treated mild-to-moderate hypertensive subjects r and omised to an intervention ( n 40 ) or control ( n 40 ) arm . The intervention was 8-week provision of six food items with a modified cation content ( salt replacement ( SOLO ) , bread , margarine , stock cubes , soup mix and a flavour enhancer ) and 500 ml of maas ( fermented milk)/d . The control diet provided the same quantities of the targeted foods but of st and ard commercial composition and 500 ml/d of artificially sweetened cooldrink . FINDINGS The intervention effect estimated as the contrast of the within-diet group changes in BP from baseline to post-intervention was a significant reduction of 6.2 mmHg ( 95 % CI 0.9 , 11.4 ) for systolic BP . The largest intervention effect in 24 h BP was for wake systolic BP with a reduction of 5.1 mmHg ( 95 % CI 0.4 , 9.9 ) . For wake diastolic BP the reduction was 2.7 mmHg ( 95 % CI -0.2 , 5.6 ) . CONCLUSIONS Modification of the cation content of a limited number of commonly consumed foods lowers BP by a clinical ly significant magnitude in treated South African hypertensive patients of low socio-economic status . The magnitude of BP reduction provides motivation for a public health strategy that could be adopted through lobbying of the food industry by consumer and health agencies",
"Background Exercise-based cardiac rehabilitation improves exercise capacity and reduces cardiac risk factors . The purpose of this pilot study was to examine the effects of a home-based cardiac exercise program ( HBCEP ) on exercise tolerance , serum lipids , and self-efficacy in coronary heart disease patients in Turkey . Self-efficacy theory provided the framework for this study 's intervention . Design The study design was a pre-test and post-test experimental , r and omized assignment . Method The study included 30 participants in a home-based cardiac exercise program ( HBCEP ; mean age = 54.7 ± 7.8 ) and 30 in control ( C ; mean age = 52.7 ± 6.5 ) . The Phase II cardiac exercise program included three 45 - 60-min sessions per week for 12 weeks , and the enhancement of self-efficacy through educational sessions and the use of goal setting , modelling , and physiological feedback strategies . Both groups were comparable in their medical regimen , exercise capacity , and other measured variables pre-intervention . At baseline and after 12 weeks , exercise capacity was evaluated by exercise testing using the Bruce Protocol , self-efficacy was measured with the Cardiac Exercise Self Efficacy Index , and serum lipid values were measured . Results At the completion of the 12-week exercise program , the exercise capacity ( P ) , total cholesterol ( P = 0.004 ) , triglycerides ( P = 0.048 ) , high-density lipoprotein-cholesterol ( P = 0.001 ) , low-density lipoprotein-cholesterol ( P = 0.039 ) , and self-efficacy ( P Turkey can be successful in having patients adhere to a prescribed exercise program and reduce risk factors . Enhanced self-efficacy may have mediated the improved behavioural outcomes",
"AIM The aim of this study was to examine the effect of a cardiac rehabilitation programme on health behaviours and physiological risk parameters in patients with coronary heart disease in Chengdu , China . BACKGROUND Epidemiological studies indicate a dose- , level- and duration -dependent relationship exists between cardiac behavioural and physiological risks and coronary heart disease incidence as well as subsequent cardiac morbidity and mortality . Cardiac risk factor modification has become the very primary goal of modern cardiac rehabilitation programmes . DESIGN METHODS A r and omized controlled trial was conducted . Coronary heart disease patients ( n = 167 ) who met the sampling criteria in two tertiary medical centres in Chengdu , south-west China , were r and omly assigned to either an intervention group ( the cardiac rehabilitation programme ) or control group ( the routine care ) . The change of health behaviours ( walking performance , step II diet adherence , medication adherence , smoking cessation ) and physiological risk parameters ( serum lipids , blood pressure , body weight ) were assessed to evaluate the programme effect . RESULTS Patients in the intervention group demonstrated a significantly better performance in walking , step II diet adherence , medication adherence ; a significantly greater reduction in serum lipids including triglyceride , total cholesterol , low-density lipoprotein ; and significantly better control of systolic and diastolic blood pressure at three months . The majority of these positive impacts were maintained at six months . The effect of the programme on smoking cessation , body weight , serum high-density lipoprotein , was not confirmed . CONCLUSIONS A cardiac rehabilitation programme led by a nurse can significantly improve the health behaviours and cardiac physiological risk parameters in coronary heart disease patients . Nurses can fill significant treatment gaps in the risk factor management of patients with coronary heart disease . RELEVANCE TO CLINICAL PRACTICE This study raises attention regarding the important roles nurses can play in cardiac rehabilitation and the unique way for nurses to meet the rehabilitative care needs of coronary heart disease patients . Furthermore , the hospital-home bridging nature of the programme also created a model for interfacing the acute care and community rehabilitative care",
"BACKGROUND Due to the existing controversies in literature about the potential benefits of resistance exercise training ( RT ) on arterial blood pressure ( BP ) at rest , and the lack of studies conducted with elderly hypertensive individuals , RT is seldom recommended as a non-pharmacological treatment for arterial hypertension . OBJECTIVE To verify the effect of progressive RT on BP , HR , and RPP in elderly women with controlled hypertension . METHODS 20 elderly women ( 66.8 + /- 5.6 years of age ) , with a sedentary lifestyle , monitored with anti-hypertensive medication , participated in a 12-week RT program ( resistance training group - RTG ) . Twenty-six elderly women ( 65.3 + /- 3.4 years of age ) with controlled hypertension did not engage in physical exercise during the study period , and composed the control group . RESULTS After RT , there was a significant reduction in SBP , MBP , and DP values at rest . No significant drops in DBP and HR values at rest were observed after RT in both groups . The reduction in the RTG was 10.5 mmHg , 6.2 mmHg , and 2218.6 mmHg x bpm for SBP , MBP , and RPP , respectively . CONCLUSION Progressive RT reduced SBP , MBP , and RPP values at rest of hypertensive elderly women who were on anti-hypertensive 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",
"Background Cardiovascular disease is a major cause of morbidity/mortality in non-developed countries . Reports of the effects of non-pharmacological interventions on global cardiovascular risk in Latin American adults , however , are scarce . Objective To compare the change in global cardiovascular risk induced by a tailored , Adult Treatment Panel-III compliant nutrition program versus the same program with addition of supervised , regular physical activity in Colombian adults . Design The study was a r and omized , controlled trial . Methods Seventy-five Colombian patients aged 40–70 years and with Framingham-estimated global cardiovascular risk of 1 % or higher were r and omly assigned to a nutritional intervention program or a combined nutritional intervention-physical exercise program for 16 weeks . Patients underwent medical and anthropometric evaluation , bioelectrical impedance , lipid profile and Framingham global cardiovascular risk determination at baseline and at the end of follow-up . Results The groups were comparable at baseline ; 21 persons in the nutritional intervention program group and 27 in the nutritional intervention-physical exercise program group completed the follow-up . Global cardiovascular risk modification ( mean ± SE ) was −2.04 ± 1.1 absolute percentage points ( relative reduction 19.6 % ) in the nutritional intervention-physical exercise program group , compared with 0.23 ± 0.9 ( relative increase 2.8 % ) in the nutritional intervention program group . Mean difference in global cardiovascular risk modification between groups reached borderline statistical significance in ANCOVA ( P = 0.054 ) . Reductions in systolic and diastolic blood pressure , waist circumference and low-density lipoprotein cholesterol were similar , but the nutritional intervention-physical exercise program group achieved significantly greater improvements in body weight , body mass index , percentage body fat and high-density lipoprotein cholesterol . Conclusions Our data suggest that a structured nutritional intervention-physical exercise program is more efficacious than a nutritional intervention program in the reduction of global cardiovascular risk and cardiovascular risk factors , in only 16 weeks",
"OBJECTIVE Assess the influence of physical activity on the blood pressure of hypertensive elderly patients on non-pharmacological treatment ( NPT ) . METHODS The authors studied men and women , over 60 years , with stage I hypertension who were not using antihypertensive medication . These patients had been r and omly allocated to one of two groups : Control Group ( CG ) - oriented to NPT ; and Study Group ( SG ) - NPT and a program that included supervised physical activity consisting of 1-hour sessions , 3 times a week . Duration of the study was 6 months . Screening and follow-up tests every 3 months , at Visits 1 , 2 and 3 included a clinical evaluation , ECG , a treadmill stress test , Ambulatory Blood Pressure Measurement ( ABPM ) and an Echocardiogram . The authors used the Friedman test for the evolutionary analysis of the intra-groups means and Student 's t test to compare independent data between groups . RESULTS Twenty-four patients were r and omized in the SG ( 5 men ) and 21 in the CG ( 4 men ) . The 6-month follow-up period was completed by 22 patients in the SG and 13 in the CG . Blood pressures found by the ABPM in V1 , V2 and V3 were 134.2 + /-14.5 , 136.1 + /-9 and 143.7+/-13.9 mmHg for Systolic Blood Pressure in the CG ; and 135.6 + /-11.4 , 138.7 + /-12.2 and 133.9 + /-8.5 mmHg in the SG . For Diastolic Blood Pressure , values in the CG were 78.7+/-5.8 , 82.3+/-6.2 and 83.3 + /-9.2 mmHg ; and in the SG , 80.1 + /-6.8 , 81+/-6.6 and 80.8 + /-7.3 mmHg . CONCLUSION Programmed and supervised physical activity was more efficient for maintaining adequate blood pressure control in these elderly with stage I hypertension in the study group , when compared to the control group",
"This study evaluated a structured and integrated intervention program on diabetes management in individuals with type 2 diabetes in Shanghai , China . Men and women with type 2 diabetes and body mass index > 23 kg/m2 were r and omized into a 24-week , prospect i ve , r and omized clinical trial . The Reference Group ( n=50 ) received diabetes education including diet and physical activity instruction only ; the Intervention Group ( n=100 ) received more intensive intervention , including diabetes education with frequent blood glucose monitoring , nutritional counseling , meal plans with diabetes-specific nutritional meal replacement , and weekly progress up date s with study staff . Major study assessment s were obtained at baseline , and after 12 and /or 24 weeks of intervention . The Intervention Group improved fasting blood glucose , insulin , systolic and diastolic blood pressures compared to Reference Group ( p HbA1c was lower ( p Weight loss was modest , but significant differences were observed between groups ( p Weight change from baseline after 12 and 24 weeks was -2.8 + /- 0.2 % and -3.7 + /- 0.3 % , respectively , in the Intervention Group vs -1.8 + /- 0.4 % and -2.5 + /- 0.4 % in the Reference Group . Additionally , waist and hip circumferences and waist : hip ratio decreased in the Intervention compared to the Reference Group ( p that Chinese men and women with type 2 diabetes following an integrated intervention program including diabetes education , frequent blood glucose monitoring and daily use of a diabetes-specific meal replacement , can achieve significant improvements in glycemic control and markers of cardiovascular health",
"Objective To describe the secular changes in the prevalence , awareness , treatment and control of hypertension . Design Two independent cross-sectional population surveys using st and ardized methods conducted between the early 1980s and mid-1990s . Setting Twenty-four geographically defined population s of the WHO MONICA Project . Participants R and omly selected men and women aged 35–64 years . The total number of participants was 69 907 . Main outcome measures Two definitions of hypertension were used : 160/95 mmHg or above and 140/90 mmHg or above for systolic or diastolic blood pressure . Subjects on antihypertensive drug treatment were considered to be hypertensive regardless of their blood pressure . Treated subjects whose measured blood pressure level was less than 160/95 or 140/90 mmHg according to the two definitions , respectively , were considered to be adequately treated . Results The age-adjusted prevalence of hypertension decreased in most and increased in only a few population s. For both definitions of hypertension , the proportion of hypertensive subjects who were aware of their condition increased in three-quarters of the male population s and in two-thirds of the female population s. Furthermore , the proportion of hypertensive individuals on antihypertensive drug treatment increased in three-quarters of the population s. In the final survey , hypertension tended to be better treated and controlled in women than in men . Nevertheless , a large proportion of patients receiving antihypertensive drug therapy still had inadequately controlled blood pressure levels . Conclusion Although awareness and treatment of hypertension according to the data obtained during the late 1980s to the mid-1990s increased in several population s , the effectiveness of antihypertensive treatment showed the continuing need for improvements",
"To determine the effectiveness of a yoga program on blood pressure and stress , a group of hypertensive patients in Thail and were studied , with the experimental group showing significantly decreased mean stress scores and blood pressure , heart rate , and body mass index levels compared with the control group . Further studies are suggested to determine the effects of yoga on hypertension in Thail and",
"Context Observational studies suggest that higher intake of vegetable protein is associated with lower blood pressures . Contribution This double-blind trial from China r and omly assigned 302 adults with high-normal or mildly elevated blood pressures ( diastolic blood pressure of 80 to 99 mm Hg , systolic blood pressure of 130 to 159 mm Hg , or both ) to daily cookies containing 40 g of either soybean protein or complex carbohydrates . At 12 weeks , soybean cookies reduced diastolic and systolic blood pressure values by about 3 to 4 mm Hg more than did the carbohydrate cookies . Caution s The follow-up duration was short . Implication s Soybean protein supplementation might help lower blood pressure in some people . The Editors Hypertension has become a global public health challenge , affecting approximately 50 million individuals in the United States and 1 billion individuals worldwide ( 1 , 2 ) . The prevalence of hypertension has increased dramatically in developing countries during the past several decades ( 1 , 3 ) and has increased slightly in the United States according to a recent national survey ( 4 ) . Hypertension is not only very common but is also an important major modifiable risk factor for cardiovascular disease , stroke , and chronic kidney disease ( 5 - 7 ) . Lifestyle modification , including nutritional intervention , provides an important approach for preventing and treating hypertension ( 2 , 8) . Clinical trials have documented that weight loss , exercise , alcohol restriction , sodium reduction , and potassium supplementation reduce blood pressure in both hypertensive and prehypertensive persons ( 2 , 8) . The effect of dietary macronutrients on blood pressure has not been well studied , although clinical trials indicate that diets rich in fruits , vegetables , and low-fat dairy products and with reduced saturated and total fat ( Dietary Approaches to Stop Hypertension [ DASH ] diet ) lower blood pressure ( 9 ) . Several epidemiologic studies have observed an inverse relationship between dietary protein intake and blood pressure ( 10 - 14 ) . The few clinical trials that examined the effect of an increased intake of dietary protein on blood pressure produced conflicting results ( 10 , 15 , 16 ) . In most of these trials , change in blood pressure was not the primary outcome of interest , the sample size was small , and only a single blood pressure measurement was obtained at the baseline and termination visits ( 10 ) . We conducted a r and omized , double-blind , controlled multicenter trial to test the effect of soybean protein supplementation on systolic and diastolic blood pressure among individuals with prehypertension or stage 1 hypertension in 3 sample s of community residents in the People 's Republic of China . Methods Our study was a r and omized , double-blind , complex carbohydratecontrolled multicenter clinical trial design ed to test the efficacy of 40 g of isolated soybean protein supplementation per day in lowering systolic and diastolic blood pressure among individuals with prehypertension or stage 1 hypertension . Three clinical centers in the People 's Republic of China , located in Beijing , Xiulo ( Hebei province ) , and Wuhan ( Hubei province ) , participated in the trial . Demographic characteristics and lifestyle , including dietary habits , were similar in the 3 communities . In Beijing , the clinical center used a 2 2 factorial design to assign the study participants to soybean protein and potassium ( 60 mmol/d ) interventions ( 17 ) . The other 2 centers used a 2-group parallel design to assign the study participants to soybean protein supplements or a complex carbohydrate control . Investigators obtained informed consent before the initial screening visit and before r and omization . The institutional review boards at the Tulane University Health Sciences Center and the Cardiovascular Institute of the Chinese Academy of Medical Sciences approved the protocol . Study Participants Trial participants were men and women 35 to 65 years of age who had an average systolic blood pressure of 130 to 159 mm Hg , diastolic blood pressure of 80 to 99 mm Hg , or both based on an average of 9 readings ( 3 observations at each of 3 screening visits ) . The criteria for exclusion were self-reported use of antihypertensive medications in the previous 2 months ; a history of cardiovascular disease , diabetes mellitus , cancer , chronic obstructive pulmonary disease , psychiatric disease , or any other serious life-threatening illness that required regular medical treatment ; serum creatinine level of 150.3 mol/L or greater ( 1.7 mg/dL ) at the screening examination ; or alcohol intake of 21 drinks or more per week or at least 40 g/d . We also excluded women who were pregnant or who intended to become pregnant during the study . The study sites conducted community-based blood pressure prescreening to recruit the trial participants . We invited 862 persons who met blood pressure and other criteria at prescreening and who were willing to participate in the trial to the study clinics for screening visits . Of them , 302 persons met all eligibility criteria and were r and omly assigned ( Figure 1 ) . Of the 302 trial participants , 150 were recruited from Beijing , 84 were recruited from Hebei province , and 68 were recruited from Hubei province . Figure 1 . Study participant flow chart . Intervention We r and omly allocated 150 study participants to soybean protein supplementation and 152 study participants to the control group by using a computer-generated scheme . We stratified the r and omization by clinical site and used a block size of 4 . We also stratified the r and omization by potassium supplementation allocation at the Beijing clinical site , result ing in an equal proportion of study participants receiving potassium intervention in the soybean protein supplement group ( 37 of 74 participants ) and the control group ( 38 of 76 participants ) . An effect of an interaction between soybean protein and potassium supplementation on blood pressure was not evident . The r and omization assignment schedule was concealed in an ordered set of sealed envelopes , which were opened only after the study coordinator had confirmed a participant 's eligibility . Apart from the study coordinator , all research personnel , including the blood pressure technicians , and the study participants were unaware of treatment assignment . Study participants who were assigned to the intervention group received 40 g of isolated soybean protein supplement per day in cookies for 12 weeks , while those in the control group received 40 g of complex carbohydrate from wheat in cookies during the same period . The Sanjiang Food Company ( Heilongjiang province , People 's Republic of China ) provided the isolated soybean protein supplements . The soybean protein and control cookies were prepared central ly in Beijing and had the same appearance and taste . The daily nutritional content of the cookies was similar for those in the soybean protein supplement group and the control group , except for dietary protein and carbohydrate content : total energy ( 594.0 kcal vs. 577.1 kcal ) , protein ( 49.0 g vs. 12.9 g ) , carbohydrate ( 64.8 g vs. 95.3 g ) , fat ( 15.4 g vs. 16.1 g ) , saturated fat ( 2.4 g vs. 2.6 g ) , monounsaturated fat ( 6.2 g vs. 6.3 g ) , polyunsaturated fat ( 7.0 g vs. 7.2 g ) , and sodium ( 145.3 mg vs. 145.8 mg ) . The Food Science and Human Nutrition Laboratory of Iowa State University , Ames , Iowa , and Ralston Analytical Laboratories , St. Louis , Missouri , measured isoflavones in duplicate . The measurements were almost the same between the 2 laboratories , and we report the average . The daily portion of the soybean protein cookies contained 76.4 mg of total isoflavone , 44.9 mg of genistein , 26.5 mg of daidzein , and 4.9 mg of glycitein . During the intervention , a study dietitian instructed study participants to reduce other food intake so that the total energy intake would be constant during the course of the trial . Most study participants consumed study cookies in place of their usual breakfast , and a few study participants consumed study cookies in place of their usual lunch . Participants were also instructed to maintain their usual level of physical activity , alcohol intake , and dietary sodium intake . We monitored each participant 's body weight biweekly during the study and provided dietary consultation when we observed more than a 2-kg weight gain . The study participants returned unconsumed cookies at their 6- and 12-week follow-up visits after r and omization . The study coordinator counted the number of cookies returned , and we used this to assess the participants ' adherence to their assigned intervention . Measurements We collected information on demographic characteristics , medical history , medication use , alcohol consumption , and physical activity at baseline . Study staff members who were trained and certified in the use of Hawksley r and om-zero sphygmomanometers measured blood pressure . Blood pressure readings were taken from the right arm with appropriately sized cuffs after the participant had been seated quietly for 5 minutes . We obtained 3 blood pressure measurements at each of the 3 screening visits before intervention and at the follow-up visits at 6 and 12 weeks after r and omization . We measured weight , height , and waist circumference by using a st and ard protocol and calculated body mass index as kg/m2 . Experienced and trained research staff conducted a 24-hour dietary recall at the screening visit , the 6-week visit , and the 12-week visit . We calculated dietary nutrient intake on the basis of the China Food Composition Tables ( 18 ) . We obtained a 24-hour urinary specimen at the screening visit , the 6-week visit , and the 12-week visit to measure urinary excretion of sodium and potassium . Study staff assessed the presence of side effects ( 15 items ) by using a st and ard question naire at the 12-week follow-up visit . Statistical Analysis We design ed our trial to provide more than 80 % statistical power to detect a 3.0 mm Hg reduction in systolic blood pressure and a 2.0 mm Hg",
"AIM The aim of this study was to determine the effect of anti-hypertensive patient-oriented education and in-home monitoring for medication adherence and management of hypertension in a primary care setting , by providing education on healthy lifestyle behaviours and medication adherence . BACKGROUND Hypertension is the third most common cause of death worldwide . Prevalence of hypertension in Turkey is approximately 30 % in the general population and 45 - 50 % in population over 50 . DESIGN R and omised controlled study . METHODS This study conducted in Turkey used a study group comprised of 120 subjects ( 40 Group A , 40 Group B , 40 controls ) , all previously diagnosed with hypertension and who started medication therapy at least one year prior to start of study . The study was conducted between February-November 2006 at public primary health care facilities and homes of the study participants . Participants in Group A and B received a total of six monthly education sessions , four times during clinic visits and two home visits . Medication adherence education for Groups A and B and education about healthy lifestyle behaviours for Group B were administered in a structured and individualised format . The control group was routinely monitored in health care facilities . RESULTS Healthy lifestyle behaviours and perception of self-efficacy regarding medication adherence showed improvement after education sessions in Groups A and B. Systolic and diastolic blood pressures of subjects in Group A and B showed a significant decrease compared with those of the control group ; the blood pressure decrease in Group B was greater than in Group A. CONCLUSION Nurses play an important role in uncontrolled hypertension detection and can improve medication adherence and healthy lifestyle behaviours . RELEVANCE TO CLINICAL PRACTICE Patient education medication adherence alone and in combination with healthy lifestyle behaviour teaching is an effective tool for blood pressure reduction in the hypertensive population in primary health care setting"
] |
4116bc76-06ff-11f0-808a-c43d1ab1c353
|
OBJECTIVE To evaluate the quality of evidence and the strength of recommendation for yoga as an ancillary intervention in rheumatic diseases . METHODS Medline / PubMed , Scopus , the Cochrane Library and IndMED were search ed through February 2013 . R and omized controlled trials ( RCTs ) comparing yoga with control interventions in patients with rheumatic diseases were included . Two authors independently assessed the risk of bias using the Cochrane Back Review Group risk of bias tool . The quality of evidence and the strength of the recommendation for or against yoga were grade d according to the GRADE recommendations . RESULTS Eight RCTs with a total of 559 subjects were included ; two RCTs had a low risk of bias . In two RCTs on FM syndrome , there was very low evidence for effects on pain and low evidence for effects on disability . In three RCTs on OA , there was very low evidence for effects on pain and disability . Based on two RCTs , very low evidence was found for effects on pain in RA . No evidence for effects on pain was found in one RCT on CTS . No RCT explicitly reported safety data . CONCLUSION Based on the results of this review , only weak recommendations can be made for the ancillary use of yoga in the management of FM syndrome , OA and RA at this point
|
[
"The aim of this study was to measure the effects of a bi-weekly Raj yoga program on rheumatoid arthritis ( RA ) disease activity . Subjects were recruited from among RA patients in Dubai , United Arab Emirates by email invitations of the RA data base . Demographic data , disease activity indices , health assessment question naire ( HAQ ) , and quality of life ( QOL ) by SF-36 were documented at enrollment and after completion of 12 sessions of Raj yoga . A total of 47 patients were enrolled : 26 yoga and 21 controls . Baseline demographics were similar in both groups . Patients who underwent yoga had statistically significant improvements in DAS28 and HAQ , but not QOL . Our pilot study of 12 sessions of yoga for RA was able to demonstrate statistically significant improvements in RA disease parameters . We believe that a longer duration of treatment could result in more significant improvements",
"Objectives : Published preliminary findings from a r and omized-controlled trial suggest that an 8-week Yoga of Awareness intervention may be effective for improving symptoms , functional deficits , and coping abilities in fibromyalgia . The primary aims of this study were to evaluate the same intervention ’s posttreatment effects in a wait-list group and to test the intervention ’s effects at 3-month follow-up in the immediate treatment group . Methods : Unpaired t tests were used to compare data from a per protocol sample of 21 women in the immediate treatment group who had completed treatment and 18 women in the wait-list group who had completed treatment . Within-group paired t tests were performed to compare posttreatment data with 3-month follow-up data in the immediate treatment group . The primary outcome measure was the Fibromyalgia Impact Question naire Revised ( FIQR ) . Multilevel r and om-effects models were also used to examine associations between yoga practice rates and outcomes . Results : Posttreatment results in the wait-list group largely mirrored results seen at posttreatment in the immediate treatment group , with the FIQR Total Score improving by 31.9 % across the 2 groups . Follow-up results showed that patients sustained most of their posttreatment gains , with the FIQR Total Score remaining 21.9 % improved at 3 months . Yoga practice rates were good , and more practice was associated with more benefit for a variety of outcomes . Discussion : These findings indicate that the benefits of Yoga of Awareness in fibromyalgia are replicable and can be maintained",
"OBJECTIVES The study objectives were to evaluate the efficacy of integrating hatha yoga therapy with therapeutic exercises for osteoarthritis ( OA ) of the knee joints . DESIGN This was a prospect i ve , r and omized , active controlled trial . Two hundred and fifty ( 250 ) participants who had OA knees and who were between 35 and 80 years ( yoga 59.56±9.54 ) and ( control 59.42±10.66 ) from the outpatient department of Ebnezar Orthopedic Center , Bengaluru , were r and omly assigned to receive hatha yoga therapy or therapeutic exercises after transcutaneous electrical stimulation and ultrasound treatment ( 20 minutes per day ) . Both of the groups practice d supervised interventions ( 40 minutes per day ) for 3 months . One hundred and eighteen ( 118 ) ( yoga ) and 117 ( control ) subjects were available for the final analysis . RESULTS There were significant differences within ( Wilcoxon 's , p . Walking pain in the yoga ( 37.3 % , 64.9 % ) and control ( 24.9 % , 42 % ) , knee disability in the yoga ( 59.7 % , 83 % ) and control ( 32.7 % , 53.6 % ) , range of knee flexion in yoga ( 12.7 % , 26.5 % right , 13.5 % , 28 % left ) and control ( 6.9 % , 13.3 % right , 5.6 % , 11.5 % left ) , joint tenderness in yoga ( 52.3 % , 86.1 % ) and control ( 28 % , 57.1 % ) , swelling in yoga ( 55.4 % , 85.9 % ) and control ( 32.1 % , 60 % ) , crepitus in yoga ( 44.0 % , 79.9 % ) and control ( 27.0 % , 47.8 % ) and walking time in yoga ( 26.6 % , 52.8 % ) and control ( 9.3 % , 21.6 % ) , all improved more in the yoga than the control groups on the 15th and 90th day , respectively . CONCLUSIONS An integrated approach of hatha yoga therapy is better than therapeutic exercises as an adjunct to transcutaneous electrical stimulation and ultrasound treatment in improving walking pain , range of knee flexion , walking time , tenderness , swelling , crepitus , and knee disability in patients with OA knees",
"This study aim ed at study ing the effect of yogic package ( YP ) with some selected pranayama , cleansing practice s and meditation on pain intensity , inflammation , stiffness , pulse rate ( PR ) , blood pressure ( BP ) , lymphocyte count ( LC ) , C-reactive protein ( CRP ) and serum uric acid ( UA ) level among subjects of rheumatoid arthritis ( RA ) . R and omized control group design was employed to generate pre and post data on participants and controls . Repealed Measure ANOVAs with Bonferroni adjustment were applied to check significant overall difference among pre and post means of participants and controls by using PASW ( SPSS Inc. 18th Version ) . Observed result favored statistically significant positive effect of YP on selected RA parameters and symptoms under study at P improvement in RA severity after 40-day practice of YP . It concluded that YP is a significant means to reduce intensity of RA",
"& 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",
"OBJECTIVES This study aim ed to verify whether techniques of yoga with and without the addition of Tui Na might improve pain and the negative impact of fibromyalgia ( FMS ) on patients ' daily life . DESIGN Forty ( 40 ) FMS women were r and omized into two groups , Relaxing Yoga ( RY ) and Relaxing Yoga plus Touch ( RYT ) , for eight weekly sessions of stretching , breathing , and relaxing yogic techniques . RYT patients were further su bmi tted to manipulative techniques of Tui Na . OUTCOME MEASURE Outcome measures comprised the Fibromyalgia Impact Question naire ( FIQ ) , pain threshold at the 18 FMS tender points , and a verbal graduation of pain assessed before treatment and on the followup . The visual analog scale ( VAS ) for pain was assessed before and after each session and on the follow-up . RESULTS Seventeen ( 17 ) RYT and 16 RY patients completed the study . Both RY and RYT groups showed improvement in the FIQ and VAS scores , which decreased on all sessions . The RYT group showed lower VAS and verbal scores for pain on the eighth session , but this difference was not maintained on the follow-up . Conversely , RY VAS and verbal scores were significantly lower just on the follow-up . CONCLUSIONS These study results showed that yogic techniques are valid therapeutic methods for FMS . Touch addition yielded greater improvement during the treatment . Over time , however , RY patients reported less pain than RYT . These results suggest that a passive therapy may possibly decrease control over FMS symptoms",
"Aim : This study was design ed to evaluate the efficacy of addition of integrated yoga therapy to therapeutic exercises in osteoarthritis ( OA ) of knee joints . Material s and Methods : This was a prospect i ve r and omized active control trial . A total of t participants with OA of knee joints between 35 and 80 years ( yoga , 59.56 ± 9.54 and control , 59.42 ± 10.66 ) from the outpatient department of Dr. John 's Orthopedic Center , Bengaluru , were r and omly assigned to receive yoga or physiotherapy exercises after transcutaneous electrical stimulation and ultrasound treatment of the affected knee joints . Both groups practice d supervised intervention ( 40 min per day ) for 2 weeks ( 6 days per week ) with followup for 3 months . The module of integrated yoga consisted of shithilikaranavyayama ( loosening and strengthening ) , asanas , relaxation techniques , pranayama , meditation and didactic lectures on yama , niyama , jnana yoga , bhakti yoga , and karma yoga for a healthy lifestyle change . The control group also had supervised physiotherapy exercises . A total of 118 ( yoga ) and 117 ( control ) were available for final analysis . Results : Significant differences were observed within ( P all domains of the Short Form-36 ( P approach of yoga therapy is better than therapeutic exercises as an adjunct to transcutaneous electrical stimulation and ultrasound treatment in improving knee disability and quality of life in patients with OA knees",
"Aim : To study the effect of integrated yoga on pain , morning stiffness and anxiety in osteoarthritis of knees . Material s and Methods : Two hundred and fifty participants with OA knees ( 35–80 years ) were r and omly assigned to yoga or control group . Both groups had transcutaneous electrical stimulation and ultrasound treatment followed by intervention ( 40 min ) for two weeks with follow up for three months . The integrated yoga consisted of yogic loosening and strengthening practice s , asanas , relaxation , pranayama and meditation . The control group had physiotherapy exercises . Assessment s were done on 15th ( post 1 ) and 90th day ( post 2 ) . Results : Resting pain ( numerical rating scale ) reduced better ( P yoga group ( post 1=33.6 % and post 2=71.8 % ) than control group ( post 1=13.4 % and post 2=37.5 % ) . Morning stiffness decreased more ( P in yoga ( post 1=68.6 % and post 2=98.1 % ) than control group ( post 1=38.6 % and post 2=71.6 % ) . State anxiety ( STAI-1 ) reduced ( P control group ; trait anxiety ( STAI 2 ) reduced ( P % ) . Systolic blood pressure reduced ( P in yoga group ( post 1=−7.93 % and post 2=−15.7 % ) than the control group ( post 1=−1.8 % and post 2=−3.8 % ) . Diastolic blood pressure reduced ( P in yoga group ( post 1=−7.6 % and post 2=−16.4 % ) than the control group ( post 1=−2.1 % and post 2=−5.0 % ) . Pulse rate reduced ( P Integrated approach of yoga therapy is better than physiotherapy exercises as an adjunct to transcutaneous electrical stimulation and ultrasound treatment in reducing pain , morning stiffness , state and trait anxiety , blood pressure and pulse rate in patients with OA knees",
"OBJECTIVE Yoga and relaxation techniques have traditionally been used by nonmedical practitioners to help alleviate musculoskeletal symptoms . The objective of this study was to collect controlled observations of the effect of yoga on the h and s of patients with osteoarthritis ( OA ) . METHODS Patients with OA of the h and s were r and omly assigned to receive either the yoga program or no therapy . Yoga techniques were supervised by one instructor once/week for 8 weeks . Variables assessed were pain , strength , motion , joint circumference , tenderness , and h and function using the Stanford H and Assessment question naire . RESULTS The yoga treated group improved significantly more than the control group in pain during activity , tenderness and finger range of motion . Other trends also favored the yoga program . CONCLUSION This yoga derived program was effective in providing relief in h and OA . Further studies are needed to compare this with other treatments and to examine longterm effects",
"CONTEXT Carpal tunnel syndrome is a common complication of repetitive activities and causes significant morbidity . OBJECTIVE To determine the effectiveness of a yoga-based regimen for relieving symptoms of carpal tunnel syndrome . DESIGN R and omized , single-blind , controlled trial . SETTING A geriatric center and an industrial site in 1994 - 1995 . PATIENTS Forty-two employed or retired individuals with carpal tunnel syndrome ( median age , 52 years ; range , 24 - 77 years ) . INTERVENTION Subjects assigned to the yoga group received a yoga-based intervention consisting of 11 yoga postures design ed for strengthening , stretching , and balancing each joint in the upper body along with relaxation given twice weekly for 8 weeks . Patients in the control group were offered a wrist splint to supplement their current treatment . MAIN OUTCOME MEASURES Changes from baseline to 8 weeks in grip strength , pain intensity , sleep disturbance , Phalen sign , and Tinel sign , and in median nerve motor and sensory conduction time . RESULTS Subjects in the yoga groups had significant improvement in grip strength ( increased from 162 to 187 mm Hg ; P = .009 ) and pain reduction ( decreased from 5.0 to 2.9 mm ; P = .02 ) , but changes in grip strength and pain were not significant for control subjects . The yoga group had significantly more improvement in Phalen sign ( 12 improved vs 2 in control group ; P = .008 ) , but no significant differences were found in sleep disturbance , Tinel sign , and median nerve motor and sensory conduction time . CONCLUSION In this preliminary study , a yoga-based regimen was more effective than wrist splinting or no treatment in relieving some symptoms and signs of carpal tunnel syndrome"
] |
4116bcbc-06ff-11f0-808a-c43d1ab1c353
|
Background / Aims : In 2008 , the American Diabetes Association recommended low-carbohydrate or low-fat diets for weight management in patients with established type 2 diabetes ( T2D ) , while the amount of monounsaturated fatty acids ( MUFA ) was not specified . This systematic review focused on the effects of diets high in MUFA versus diets low in MUFA on important risk factors of T2D ( i.e. plasma glucose , insulin , homeostasis model assessment of insulin resistance and glycosylated haemoglobin , HbA1c ) . Methods : Nine r and omized controlled intervention trials with a total of 1,547 participants and a running time of at least 6 months , comparing diets high versus low in MUFA among adults with abnormal glucose metabolism ( T2D , impaired glucose tolerance and insulin resistant ) , being overweight or obese , have been included in the meta- analysis . We performed a r and om effects meta- analysis to determine the weighted mean differences with 95 % confidence intervals using the software package Review Manager 5.0.25 of the Cochrane Collaboration . Results : Significant differences in HbA1c were found ( weighted mean difference –0.21 % , 95 % CI –0.40 to –0.02 ; p = 0.03 ) , favouring the high MUFA groups . In contrast , fasting plasma glucose , fasting plasma insulin as well as the homeostasis model assessment of insulin resistance were not affected by the amounts of MUFA in the dietary protocol s. Conclusions : In summary , this systematic review found that high MUFA diets appear to be effective in reducing HbA1c , and therefore , should be recommended in the dietary regimes of T2D
|
[
"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",
"OBJECTIVE To test the effects of two Mediterranean diet ( MedDiet ) interventions versus a low-fat diet on incidence of diabetes . RESEARCH DESIGN AND METHODS This was a three-arm r and omized trial in 418 nondiabetic subjects aged 55–80 years recruited in one center ( PREDIMED-Reus , northeastern Spain ) of the Prevención con Dieta Mediterránea [ PREDIMED ] study , a large nutrition intervention trial for primary cardiovascular prevention in individuals at high cardiovascular risk . Participants were r and omly assigned to education on a low-fat diet ( control group ) or to one of two MedDiets , supplemented with either free virgin olive oil ( 1 liter/week ) or nuts ( 30 g/day ) . Diets were ad libitum , and no advice on physical activity was given . The main outcome was diabetes incidence diagnosed by the 2009 American Diabetes Association criteria . RESULTS After a median follow-up of 4.0 years , diabetes incidence was 10.1 % ( 95 % CI 5.1–15.1 ) , 11.0 % ( 5.9–16.1 ) , and 17.9 % ( 11.4–24.4 ) in the MedDiet with olive oil group , the MedDiet with nuts group , and the control group , respectively . Multivariable adjusted hazard ratios of diabetes were 0.49 ( 0.25–0.97 ) and 0.48 ( 0.24–0.96 ) in the MedDiet supplemented with olive oil and nuts groups , respectively , compared with the control group . When the two MedDiet groups were pooled and compared with the control group , diabetes incidence was reduced by 52 % ( 27–86 ) . In all study arms , increased adherence to the MedDiet was inversely associated with diabetes incidence . Diabetes risk reduction occurred in the absence of significant changes in body weight or physical activity . CONCLUSIONS MedDiets without calorie restriction seem to be effective in the prevention of diabetes in subjects at high cardiovascular risk",
"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",
"Saturated fatty acids ( SFA ) and monounsaturated fatty acids ( MUFA ) show different effects on the development of insulin resistance . In this study , we compared the effect of dietary SFA and MUFA on the insulin signaling pathway in the skeletal muscle of a type 2 diabetic animal model . Twenty-nine-week-old male Otsuka Long-Evans Tokushima fatty ( OLETF ) rats were r and omly divided into three groups and fed one of the following diets for 3 weeks ; a normal chow diet , an SFA ( lard oil ) enriched or a MUFA ( olive oil ) enriched high-fat diet . The vastus lateralis muscle was used for analyses . Insulin tolerance test showed improved insulin sensitivity in rats fed the MUFA diet , as compared to those fed the SFA diet ( p reduced IRS-1 expression and phosphorylated PI3 K levels in skeletal muscle , as compared with a chow diet ( p muscle IRS-2 expression and phosphorylated ERK1/2 was significantly increased in rats fed the SFA diet ( p Membrane translocation of glucose transporter type 4 decreased in the skeletal muscle of rats fed the SFA diet , as compared to those fed a chow diet ( p insulin signaling pathway in skeletal muscle were not observed in rats fed the MUFA diet . In conclusion , the beneficial effect of dietary MUFA on insulin sensitivity is associated with a conserved IRS-1/PI3 K insulin signaling pathway which was altered by dietary SFA",
"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",
"OBJECTIVE —The purpose of this study was to examine the relationship of glycemic control and exogenous and endogenous insulin levels with all-cause and cause-specific mortality ( ischemic heart disease and stroke ) in an older-onset diabetic population . RESEARCH DESIGN AND METHODS —The Wisconsin Epidemiologic Study of Diabetic Retinopathy ( WESDR ) is an ongoing , prospect i ve , population -based cohort study of individuals with diabetes first examined in 1980–1982 . A stratified sample of all individuals with diabetes diagnosed at 30 years of age or older was labeled “ older-onset ” ( n = 1,370 ) . Those participating in the 1984–1986 examination phase ( n = 1,007 ) were included in the analysis . Endogenous insulin was determined by measurements of plasma C-peptide ( in nanomoles per liter ) , and exogenous insulin was calculated in units per kilogram per day . Glycemic control was determined by levels of glycosylated hemoglobin ( HbA1 ) . RESULTS —After 16 years of follow-up , 824 individuals died ( all-cause mortality ) ; 358 deaths involved ischemic heart disease and 137 involved stroke . C-peptide and HbA1 were significantly associated with all-cause and ischemic heart disease mortality in our study . The hazard ratio ( 95 % CI ) values for all-cause mortality were 1.12 ( 1.07–1.17 ) per 1 % increase in HbA1 , 1.20 ( 0.85–1.69 ) per 1 unit · kg−1 · day−1 increase in exogenous insulin , and 1.15 ( 1.04–1.29 ) per 1 nmol/l increase in C-peptide and for ischemic heart disease mortality were 1.14 ( 1.06–1.22 ) , 1.50 ( 0.92–2.46 ) , and 1.19 ( 1.02–1.39 ) for HbA1 , exogenous insulin , and C-peptide , respectively , after adjusting for relevant confounders . C-peptide was associated with stroke mortality only among men ( 1.65 [ 1.07–2.53 ] ) . CONCLUSIONS —Our results show that individuals with higher endogenous insulin levels are at higher risk of all-cause , ischemic heart disease , and stroke mortality",
"BACKGROUND Insulin sensitivity ( Si ) is improved by weight loss and exercise , but the effects of the replacement of saturated fatty acids ( SFAs ) with monounsaturated fatty acids ( MUFAs ) or carbohydrates of high glycemic index ( HGI ) or low glycemic index ( LGI ) are uncertain . OBJECTIVE We conducted a dietary intervention trial to study these effects in participants at risk of developing metabolic syndrome . DESIGN We conducted a 5-center , parallel design , r and omized controlled trial [ RISCK ( Reading , Imperial , Surrey , Cambridge , and Kings ) ] . The primary and secondary outcomes were changes in Si ( measured by using an intravenous glucose tolerance test ) and cardiovascular risk factors . Measurements were made after 4 wk of a high-SFA and HGI ( HS/HGI ) diet and after a 24-wk intervention with HS/HGI ( reference ) , high-MUFA and HGI ( HM/HGI ) , HM and LGI ( HM/LGI ) , low-fat and HGI ( LF/HGI ) , and LF and LGI ( LF/LGI ) diets . RESULTS We analyzed data for 548 of 720 participants who were r and omly assigned to treatment . The median Si was 2.7 × 10(-4 ) mL · μU(-1 ) · min(-1 ) ( interquartile range : 2.0 , 4.2 × 10(-4 ) mL · μU(-1 ) · min(-1 ) ) , and unadjusted mean percentage changes ( 95 % CIs ) after 24 wk treatment ( P = 0.13 ) were as follows : for the HS/HGI group , -4 % ( -12.7 % , 5.3 % ) ; for the HM/HGI group , 2.1 % ( -5.8 % , 10.7 % ) ; for the HM/LGI group , -3.5 % ( -10.6 % , 4.3 % ) ; for the LF/HGI group , -8.6 % ( -15.4 % , -1.1 % ) ; and for the LF/LGI group , 9.9 % ( 2.4 % , 18.0 % ) . Total cholesterol ( TC ) , LDL cholesterol , and apolipoprotein B concentrations decreased with SFA reduction . Decreases in TC and LDL-cholesterol concentrations were greater with LGI . Fat reduction lowered HDL cholesterol and apolipoprotein A1 and B concentrations . CONCLUSIONS This study did not support the hypothesis that isoenergetic replacement of SFAs with MUFAs or carbohydrates has a favorable effect on Si . Lowering GI enhanced reductions in TC and LDL-cholesterol concentrations in subjects , with tentative evidence of improvements in Si in the LF-treatment group . This trial was registered at clinical trials.gov as IS RCT N29111298",
"BACKGROUND Lifestyle interventions can prevent the deterioration of impaired glucose tolerance to manifest type 2 diabetes , at least as long as the intervention continues . In the extended follow-up of the Finnish Diabetes Prevention Study , we assessed the extent to which the originally-achieved lifestyle changes and risk reduction remain after discontinuation of active counselling . METHODS Overweight , middle-aged men ( n=172 ) and women ( n=350 ) with impaired glucose tolerance were r and omly assigned to intensive lifestyle intervention or control group . After a median of 4 years of active intervention period , participants who were still free of diabetes were further followed up for a median of 3 years , with median total follow-up of 7 years . Diabetes incidence , bodyweight , physical activity , and dietary intakes of fat , saturated fat , and fibre were measured . FINDINGS During the total follow-up , the incidence of type 2 diabetes was 4.3 and 7.4 per 100 person-years in the intervention and control group , respectively ( log-rank test p=0.0001 ) , indicating 43 % reduction in relative risk . The risk reduction was related to the success in achieving the intervention goals of weight loss , reduced intake of total and saturated fat and increased intake of dietary fibre , and increased physical activity . Beneficial lifestyle changes achieved by participants in the intervention group were maintained after the discontinuation of the intervention , and the corresponding incidence rates during the post-intervention follow-up were 4.6 and 7.2 ( p=0.0401 ) , indicating 36 % reduction in relative risk . INTERPRETATION Lifestyle intervention in people at high risk for type 2 diabetes result ed in sustained lifestyle changes and a reduction in diabetes incidence , which remained after the individual lifestyle counselling was stopped",
"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",
"BACKGROUND The nature of dietary fats and fasting concentrations of triglycerides affect postpr and ial hypertriglyceridemia and glucose homeostasis . OBJECTIVES The objectives were to examine the effects of meals enriched in monounsaturated fatty acids ( MUFAs ) or saturated fatty acids ( SFAs ) on postpr and ial lipid , glucose , and insulin concentrations and to examine the extent of β cell function and insulin sensitivity in subjects with high fasting triglyceride concentrations . DESIGN Fourteen men with fasting hypertriglyceridemia and normal glucose tolerance were given meals ( ≈10 kcal/kg body weight ) containing MUFAs , SFAs , or no fat . Blood sample s were collected at baseline and hourly over 8 h for analysis . RESULTS The high-fat meals significantly increased postpr and ial concentrations of triglycerides , nonesterified fatty acids , and insulin and postpr and ial indexes of β cell function . However , postpr and ial indexes of insulin sensitivity decreased significantly . These effects were significantly attenuated with MUFAs relative to SFAs . CONCLUSIONS MUFAs postpr and ially buffered β cell hyperactivity and insulin intolerance relative to SFAs in subjects with high fasting triglyceride concentrations . These data suggest that , in contrast with SFAs , MUFA-based strategies may provide cardiovascular benefits to persons at risk by limiting lipid and insulin excursions and may contribute to optimal glycemic control after meal challenges",
"Context Several studies suggest that blood glucose levels are associated with cardiovascular disease , even at blood glucose values that do not meet diagnostic criteria for diabetes . Contribution Among adult residents of Norfolk , United Kingdom , there was a continuous relationship between hemoglobin A1c levels and cardiovascular disease and total mortality . This relationship was apparent even among persons without diabetes . Implication s These observations justify the need for studies that address whether improvements in glycemic control might improve health outcomes in persons who do not have diabetes . The Editors Diabetes mellitus is of major and increasing global public health importance ( 1 ) . Persons with diabetes are at increased risk for premature disability and death associated with vascular , renal , retinal , and neuropathic complications . Raised fasting and postchallenge blood glucose levels in an oral glucose tolerance test are used to diagnose diabetes . The diagnostic threshold is based on the shape of the risk curve between glucose levels and specific microvascular complications of diabetes ( 2 - 6 ) . Diabetes also increases the risk for macrovascular diseases , such as coronary heart disease and stroke ( 7 ) . In contrast to microvascular disease , increasing evidence suggests that the relationship between blood glucose level and macrovascular disease is continuous and does not have an obvious threshold ( 2 , 8 , 9 ) . Hemoglobin A1c concentration is an indicator of average blood glucose concentrations over the preceding 3 months ; it is useful for characterizing dysglycemia in population studies because it is simpler to perform than the oral glucose tolerance test ( 10 ) . In a 3-year follow-up of men in a prospect i ve study , we previously reported that hemoglobin A1c concentrations were related to cardiovascular disease and all-cause mortality ( 11 ) . However , we had insufficient power to examine risk relationships at concentrations close to the diagnostic threshold of 7 % or to examine the relationship in women . We report the relation between hemoglobin A1c concentrations and fatal and nonfatal coronary heart disease , cardiovascular disease events , and all-cause mortality in men and women after an average of 6 years of follow-up . Methods The European Prospect i ve Investigation into Cancer in Norfolk ( EPICNorfolk ) is a prospect i ve population study of 25 623 men and women who were between 40 and 79 years of age and who resided in Norfolk , United Kingdom . Participants were recruited from general practice registers . Information on the recruitment process is available elsewhere ( 12 ) . Between 1993 and 1997 , participants completed a health and lifestyle question naire . Participants were asked whether a doctor had ever told them that they have any of the conditions contained in a list that included diabetes , heart attack , and stroke . People with known diabetes were defined as those who responded yes to the diabetes option of this question . Smoking history was derived from responses ( yes or no ) to the questions : Have you ever smoked as much as 1 cigarette a day for as long as a year ? and Do you smoke cigarettes now ? At a clinic , trained nurses performed a health examination for each participant . Body mass index was estimated as weight (kg)/height ( m2 ) , and waist-to-hip ratio was determined by measurements of the circumference of the waist and hips . Blood pressure was measured by using an Accutorr ( Data scope , Mahwah , New Jersey ) noninvasive blood pressure monitor after the participant had been seated for 5 minutes . The mean of 2 readings was used for analysis . Nonfasting blood sample s were taken ; sample s for assay were stored in a refrigerator at 4 C until transport within 1 week of sampling to the Department of Clinical Biochemistry , University of Cambridge . Starting in 1995 , hemoglobin A1c was measured on fresh EDTA blood sample s by using high-performance liquid chromatography ( BioRad Diamat Automated Glycosylated Haemoglobin Analyser , Hemel Hempstead , United Kingdom ) . We report results for follow-up to January 2003 , an average of about 6 years . All participants were flagged for death certification at the Office of National Statistics ; vital status was obtained for the entire cohort . Trained nosologists coded death certificates according to the International Classification of Diseases , Ninth or Tenth Revisions ( ICD-9 or ICD-10 ) . Cardiovascular death ( stroke , coronary heart disease , and other vascular causes ) was defined as those whose underlying cause of death was coded as ICD-9 400448 or ICD-10 I10I79 . Death from coronary heart disease was defined as those whose cause of death was coded as ICD-9 410414 or ICD-10 I22I25 . Participants admitted to a hospital were identified by their National Health Service number . Hospitals were linked to the East Norfolk Health Authority data base , which identifies all hospital contacts throughout Engl and and Wales for Norfolk residents . We used the same ICD diagnostic codes described in the preceding paragraphs to ascertain hospital episodes of cardiovascular disease and coronary heart disease in our cohort . Participants were identified as having a coronary heart disease event during follow-up if they had a hospital admission or died with coronary heart disease as the cause of death . Of the coronary heart disease events identified , 21 % ( 112 of 529 ) were fatal ; of the cardiovascular disease events , 23 % ( 197 of 806 ) were fatal . In men , 24 % ( 76 of 321 ) of deaths were attributed to heart disease and 29 % ( 117 of 321 ) were attributed to cardiovascular disease . In women , 18 % ( 36 of 200 ) of deaths were attributed to heart disease and 35 % ( 70 of 200 ) were attributed to cardiovascular causes . The Norwich Ethics Committee approved the study , and participants gave signed informed consent . Statistical Analysis These analyses , undertaken by using SPSS software , version 10.0 ( SPSS , Inc. , Chicago , Illinois ) , included 10 232 men and women age 45 to 79 years who completed the health and lifestyle question naire and had available hemoglobin A1c measurements . We divided the cohort into 7 categories on the basis of baseline data : known diabetes , high likelihood of previously undiagnosed diabetes ( no personal history of diabetes but a hemoglobin A1c concentration 7 % ) , and hemoglobin A1c concentrations in 0.5percentage point intervals ( risk factor distributions and then coronary heart disease , cardiovascular disease , and all-cause mortality rates by hemoglobin A1c and diabetes category . Age-adjusted odds ratios were calculated by using logistic regression models . We used a Cox proportional hazards model to determine the independent contribution of hemoglobin A1c to total mortality and cardiovascular and coronary heart disease after adjustment for age , body mass index , waist-to-hip ratio , systolic blood pressure , blood cholesterol concentrations , cigarette smoking , and history of heart attack or stroke . Participants with missing baseline data for 1 or more risk factors ( 130 men and 186 women ) were excluded from the multivariate analyses . Role of the Funding Sources The funding sources had no role in the design , conduct , and reporting of the study or in the decision to su bmi t the manuscript for publication . Results Table 1 presents characteristics of the participants according to hemoglobin A1c concentration and self-reported diabetes . Those with known diabetes had higher mean ( SD ) hemoglobin A1c concentrations ( 8.0 % 1.9 % ) than the rest of the study sample ( 5.3 % 0.7 % ) . They were older and had a higher body mass index , waist-to-hip ratio , and systolic blood pressure ; they were also more likely to report having had a previous heart attack or stroke . Participants with probable but previously undiagnosed diabetes ( hemoglobin A1c 7 % ) shared these characteristics . Mean risk factor levels rose with increasing concentration of hemoglobin A1c less than 7 % . Table 1 . Distribution of Variables by Hemoglobin A1c Concentration and Known Diabetes in 4662 Men and 5570 Women Age 45 to 79 Years ( European Prospect i ve Investigation into Cancer in Norfolk , 1995 to 1997 ) Table 2 shows adjusted odds ratios for hemoglobin A1c concentrations , diabetes status , and outcomes . Persons with known or undiagnosed diabetes had a greater risk for all-cause mortality and cardiovascular or coronary heart disease than those without diabetes . Risk for coronary heart or cardiovascular disease and total mortality increased throughout the whole range of hemoglobin A1c concentrations ; those with hemoglobin A1c concentrations less than 5 % had the lowest rates . For men , a gradient of increasing rates through the distribution was apparent for all end points . For women , odds ratios for cardiovascular or coronary heart disease did not increase significantly until the hemoglobin A1c concentration reached 6 % ; odds ratios were very high in women with concentrations greater than 7 % . Table 2 . Rates and Age-Adjusted Relative Risks for Total Coronary Heart Disease Events , Cardiovascular Disease Events , and All-cause Mortality by Category of Hemoglobin A1c Concentration and Known Diabetes in 4462 Men and 5570 Women Age 45 to 79 Years ( European Prospect i ve Investigation into Cancer in Norfolk , 1995 to 2003 ) Table 3 shows outcomes after adjustment for age alone and then after adjustment for age and other risk factors . In men , known diabetes predicted coronary heart and cardiovascular disease events and total mortality with approximate 2-fold relative risks . These relative risks were only slightly attenuated after adjustment for known risk factors . In women , known diabetes status predicted an approximate 5-fold increase in risk for coronary heart and 3-fold increase in risk for cardiovascular disease events ; these increases were attenuated after adjustment for known risk factors to 3-fold and 2-fold risk , respectively . In men and women , hemoglobin A1c concentrations predicted an increased risk for"
] |
4116bd02-06ff-11f0-808a-c43d1ab1c353
|
AIMS High blood pressure is known to be associated with future risk of atrial fibrillation . Whether such risks can be reduced with antihypertensive therapy is less clear . We conducted a systematic review and meta- analysis of large-scale r and omized trials that have reported the effect of antihypertensive agents on atrial fibrillation . METHODS AND RESULTS MEDLINE was search ed for r and omized trials published between 1966 and February 2014 . R and omized , controlled trials were eligible for inclusion if they tested an antihypertensive agent and reported atrial fibrillation as an outcome . Atrial fibrillation , reported as trial outcome or adverse event , and study characteristics were extracted by investigators . In 27 trials with 214 763 r and omized participants and 9929 events of atrial fibrillation , pooled using inverse-variance weighted fixed effects meta- analysis , antihypertensive therapy reduced the risk of atrial fibrillation by 10 % [ risk ratio ( RR ) 0.90 ; 95 % confidence interval ( CI ) 0.86 , 0.94 ] . However , the proportional effects differed significantly between trials ( P patients with no prior heart disease , or patients with coronary artery disease but no heart failure , no significant effects were found ( RR 1.02 ; CI 0.88 , 1.18 and RR 0.95 ; CI 0.89 , 1.01 , respectively ) . Conversely , proportional effects were larger in trials that predominantly included patients with heart failure ( RR 0.81 ; CI 0.74 , 0.87 ) . When classes of medication were compared against each other , no significant differences in effects on atrial fibrillation were observed . CONCLUSIONS Antihypertensive therapy reduces the risk of atrial fibrillation modestly but benefits appear to be larger in patients with heart failure , with no clear evidence of benefit in patients without heart failure . Previous suggestions of class-specific effects could not be confirmed in this more comprehensive analysis
|
[
"BACKGROUND The beneficial effects of beta-blockers on long-term outcome after acute myocardial infa rct ion were shown before the introduction of thrombolysis and angiotensin-converting-enzyme ( ACE ) inhibitors . Generally , the patients recruited to these trials were at low risk : few had heart failure , and none had measurements of left-ventricular function taken . We investigated the long-term efficacy of carvedilol on morbidity and mortality in patients with left-ventricular dysfunction after acute myocardial infa rct ion treated according to current evidence -based practice . METHODS In a multicentre , r and omised , placebo-controlled trial , 1959 patients with a proven acute myocardial infa rct ion and a left-ventricular ejection fraction of were r and omly assigned 6.25 mg carvedilol ( n=975 ) or placebo ( n=984 ) . Study medication was progressively increased to a maximum of 25 mg twice daily during the next 4 - 6 weeks , and patients were followed up until the requisite number of primary endpoints had occurred . The primary endpoint was all-cause mortality or hospital admission for cardiovascular problems . Analysis was by intention to treat . FINDINGS Although there was no difference between the carvedilol and placebo groups in the number of patients with the primary endpoint ( 340 [ 35 % ] vs 367 [ 37 % ] , hazard ratio 0.92 [ 95 % CI 0.80 - 1.07 ] ) , all-cause mortality alone was lower in the carvedilol group than in the placebo group ( 116 [ 12 % ] vs 151 [ 15 % ] , 0.77 [ 0.60 - 0.98 ] , p=0.03 ) . Cardiovascular mortality , non-fatal myocardial infa rct ions , and all-cause mortality or non-fatal myocardial infa rct ion were also lower on carvedilol than on placebo . INTERPRETATION In patients treated long-term after an acute myocardial infa rct ion complicated by left-ventricular systolic dysfunction , carvedilol reduced the frequency of all-cause and cardiovascular mortality , and recurrent , non-fatal myocardial infa rct ions . These beneficial effects are additional to those of evidence -based treatments for acute myocardial infa rct ion including ACE inhibitors",
"BACKGROUND Atrial fibrillation is the most common supraventricular arrhythmia in patients with acute myocardial infa rct ion . Recent advances in pharmacological treatment of myocardial infa rct ion may have changed the impact of this arrhythmia . OBJECTIVE To assess the incidence and prognosis of atrial fibrillation complicating myocardial infa rct ion in a large population of patients receiving optimal treatment , including angiotensin converting enzyme ( ACE ) inhibitors . METHODS Data were derived from the GISSI-3 trial , which included 17 944 patients within the first 24 hours after acute myocardial infa rct ion . Atrial fibrillation was recorded during the hospital stay , and follow up visits were planned at six weeks and six months . Survival of the patients at four years was assessed through census offices . RESULTS The incidence of in-hospital atrial fibrillation or flutter was 7.8 % . Atrial fibrillation was associated with indicators of a worse prognosis ( age > 70 years , female sex , higher Killip class , previous myocardial infa rct ion , treated hypertension , high systolic blood pressure at entry , insulin dependent diabetes , signs or symptoms of heart failure ) and with some adverse clinical events ( reinfa rct ion , sustained ventricular tachycardia , ventricular fibrillation ) . After adjustment for other prognostic factors , atrial fibrillation remained an independent predictor of increased in-hospital mortality : 12.6%v 5 % , adjusted relative risk ( RR ) 1.98 , 95 % confidence interval ( CI ) 1.67 to 2.34 . Data on long term mortality ( four years after acute myocardial infa rct ion ) confirmed the persistent negative influence of atrial fibrillation ( RR 1.78 , 95 % CI 1.60 to 1.99 ) . CONCLUSIONS Atrial fibrillation is an indicator of worse prognosis after acute myocardial infa rct ion , both in the short term and in the long term , even in an unselected population",
"BACKGROUND Treatment with angiotensin-converting-enzyme ( ACE ) inhibitors reduces mortality among survivors of acute myocardial infa rct ion , but whether to use ACE inhibitors in all patients or only in selected patients is uncertain . METHODS We screened 6676 consecutive patients with 7001 myocardial infa rct ions confirmed by enzyme studies . A total of 2606 patients had echocardiographic evidence of left ventricular systolic dysfunction ( ejection fraction , On days 3 to 7 after infa rct ion , 1749 patients were r and omly assigned to receive oral tr and olapril ( 876 patients ) or placebo ( 873 patients ) . The duration of follow-up was 24 to 50 months . RESULTS During the study period , 304 patients ( 34.7 percent ) in the tr and olapril group died , as compared with 369 ( 42.3 percent ) in the placebo group ( P = 0.001 ) . The relative risk of death in the tr and olapril group , as compared with the placebo group , was 0.78 ( 95 percent confidence interval , 0.67 to 0.91 ) . Tr and olapril also reduced the risk of death from cardiovascular causes ( relative risk , 0.75 ; 95 percent confidence interval , 0.63 to 0.89 ; P = 0.001 ) and sudden death ( relative risk , 0.76 ; 95 percent confidence interval , 0.59 to 0.98 ; P = 0.03 ) . Progression to severe heart failure was less frequent in the tr and olapril group ( relative risk , 0.71 ; 95 percent confidence interval , 0.56 to 0.89 ; P = 0.003 ) . In contrast , the risk of recurrent myocardial infa rct ion ( fatal or nonfatal ) was not significantly reduced ( relative risk , 0.86 ; 95 percent confidence interval , 0.66 to 1.13 ; P = 0.29 ) . CONCLUSIONS Long-term treatment with tr and olapril in patients with reduced left ventricular function soon after myocardial infa rct ion significantly reduced the risk of overall mortality , mortality from cardiovascular causes , sudden death , and the development of severe heart failure . That mortality was reduced in a r and omized study enrolling 25 percent of consecutive patients screened should encourage the selective use of ACE inhibition after myocardial infa rct ion",
"OBJECTIVES This study was design ed to test the hypothesis of whether amlodipine reduces the risk for death in patients with heart failure due to a nonischemic cardiomyopathy . BACKGROUND A pre-specified subgroup analysis in an earlier , large-scale , placebo-controlled study suggested that amlodipine might reduce the risk for death in patients with heart failure due to a nonischemic cardiomyopathy . METHODS To evaluate this hypothesis , 1654 patients with severe heart failure due to a nonischemic cardiomyopathy ( ejection fraction were r and omly assigned to amlodipine ( target dose : 10 mg/d ) or placebo added to conventional therapy for heart failure for a median of 33 months . RESULTS There were 278 deaths in the amlodipine group and 262 deaths in the placebo group ( hazard ratio : 1.09 ; 95 % confidence interval [ CI ] : 0.92 to 1.29 ; p = 0.33 ) . The differences between the 2 groups in the risks for cardiovascular death and hospitalization were also not significant . When the results from patients with a nonischemic cardiomyopathy in both the earlier trial and in the current study were combined , there was no evidence of a favorable or unfavorable effect of amlodipine on mortality ( hazard ratio : 0.97 ; 95 % CI : 0.83 to 1.13 ; p = 0.66 ) . Both trials , however , observed higher frequencies of peripheral edema and pulmonary edema and lower frequencies of uncontrolled hypertension and chest pain in patients treated with amlodipine . CONCLUSIONS These results of the current trial , viewed together with the results from the earlier study , indicate that amlodipine does not exert favorable effects on the clinical course of patients with heart failure , regardless of the presence or absence of underlying coronary artery disease . These findings indicate the need for great caution when striking benefits are observed in subgroups of patients or in trials not primarily design ed to assess such effects",
"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 . )",
"BACKGROUND In patients who have vascular disease or high-risk diabetes without heart failure , angiotensin-converting-enzyme ( ACE ) inhibitors reduce mortality and morbidity from cardiovascular causes , but the role of angiotensin-receptor blockers ( ARBs ) in such patients is unknown . We compared the ACE inhibitor ramipril , the ARB telmisartan , and the combination of the two drugs in patients with vascular disease or high-risk diabetes . METHODS After a 3-week , single-blind run-in period , patients underwent double-blind r and omization , with 8576 assigned to receive 10 mg of ramipril per day , 8542 assigned to receive 80 mg of telmisartan per day , and 8502 assigned to receive both drugs ( combination therapy ) . The primary composite outcome was death from cardiovascular causes , myocardial infa rct ion , stroke , or hospitalization for heart failure . RESULTS Mean blood pressure was lower in both the telmisartan group ( a 0.9/0.6 mm Hg greater reduction ) and the combination-therapy group ( a 2.4/1.4 mm Hg greater reduction ) than in the ramipril group . At a median follow-up of 56 months , the primary outcome had occurred in 1412 patients in the ramipril group ( 16.5 % ) , as compared with 1423 patients in the telmisartan group ( 16.7 % ; relative risk , 1.01 ; 95 % confidence interval [ CI ] , 0.94 to 1.09 ) . As compared with the ramipril group , the telmisartan group had lower rates of cough ( 1.1 % vs. 4.2 % , P angioedema ( 0.1 % vs. 0.3 % , P=0.01 ) and a higher rate of hypotensive symptoms ( 2.6 % vs. 1.7 % , P rate of syncope was the same in the two groups ( 0.2 % ) . In the combination-therapy group , the primary outcome occurred in 1386 patients ( 16.3 % ; relative risk , 0.99 ; 95 % CI , 0.92 to 1.07 ) ; as compared with the ramipril group , there was an increased risk of hypotensive symptoms ( 4.8 % vs. 1.7 % , P syncope ( 0.3 % vs. 0.2 % , P=0.03 ) , and renal dysfunction ( 13.5 % vs. 10.2 % , P CONCLUSIONS Telmisartan was equivalent to ramipril in patients with vascular disease or high-risk diabetes and was associated with less angioedema . The combination of the two drugs was associated with more adverse events without an increase in benefit . ( Clinical Trials.gov number , NCT00153101 [ Clinical Trials.gov ] . )",
"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 Atrial fibrillation ( AF ) is frequently encountered in patients with heart failure ( HF ) and is also a predictor of morbidity and mortality in this population . Recent experimental studies have shown electrical and structural atrial remodeling with increased fibrosis in animals with HF and have suggested a preventive effect of ACE inhibitors ( ACEi ) on the development of AF . To verify the hypothesis that ACEi prevent the development of AF in patients with HF , we conducted a retrospective analysis of the patients from the Montreal Heart Institute ( MHI ) included in the Studies Of Left Ventricular Dysfunction ( SOLVD ) . Methods and Results Clinical charts were review ed and serial ECGs interpreted by a single cardiologist blinded to drug allocation . Patients with AF or flutter on the baseline ECG were excluded . Baseline characteristics were obtained from the SOLVD data bases . The mean follow‐up was 2.9±1.0 years . Of the 391 patients r and omly assigned at MHI , 374 were in sinus rhythm at the time of r and om assignment , with 186 taking enalapril and 188 taking placebo . Baseline characteristics were similar in the two groups except for a higher incidence of previous myocardial infa rct ion in the enalapril group . Fifty‐five patients had AF during the follow‐up : 10 ( 5.4 % ) in the enalapril group and 45 ( 24 % ) in the placebo group ( P enalapril was the most powerful predictor for risk reduction of AF ( hazard ratio , 0.22 ; 95 % CI , 0.11 to 0.44 ; P enalapril markedly reduces the risk of development of atrial fibrillation in patients with left ventricular dysfunction . ( Circulation . 2003;107:2926‐2931 .",
"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 Angiotensin-converting-enzyme ( ACE ) inhibitors have been used for more than a decade to treat high blood pressure , despite the lack of data from r and omised intervention trials to show that such treatment affects cardiovascular morbidity and mortality . The Captopril Prevention Project ( CAPPP ) is a r and omised intervention trial to compare the effects of ACE inhibition and conventional therapy on cardiovascular morbidity and mortality in patients with hypertension . METHODS CAPPP was a prospect i ve , r and omised , open trial with blinded endpoint evaluation . 10,985 patients were enrolled at 536 health centres in Sweden and Finl and . Patients aged 25 - 66 years with a measured diastolic blood pressure of 100 mm Hg or more on two occasions were r and omly assigned captopril or conventional antihypertensive treatment ( diuretics , beta-blockers ) . Analysis was by intention-to-treat . The primary endpoint was a composite of fatal and non-fatal myocardial infa rct ion , stroke , and other cardiovascular deaths . FINDINGS Of 5492 patients assigned captopril and 5493 assigned conventional therapy , 14 and 13 , respectively , were lost to follow-up . Primary endpoint events occurred in 363 patients in the captopril group ( 11.1 per 1000 patient-years ) and 335 in the conventional-treatment group ( 10.2 per 1000 patient-years ; relative risk 1.05 [ 95 % CI 0.90 - 1.22 ] , p=0 - 52 ) . Cardiovascular mortality was lower with captopril than with conventional treatment ( 76 vs 95 events ; relative risk 0.77 [ 0.57 - 1 - 04 ] , p=0.092 ) , the rate of fatal and non-fatal myocardial infa rct ion was similar ( 162 vs 161 ) , but fatal and non-fatal stroke was more common with captopril ( 189 vs 148 ; 1.25 [ 1 - 01 - 1 - 55 ] . p=0.044 ) . INTERPRETATION Captopril and conventional treatment did not differ in efficacy in preventing cardiovascular morbidity and mortality . The difference in stroke risk is probably due to the lower levels of blood pressure obtained initially in previously treated patients r and omised to conventional therapy",
"We performed a post hoc analysis of the Systolic Hypertension in the Elderly Program data base to assess the incidence of atrial fibrillation in the elderly hypertensive population , its influence on cardiovascular events , and whether antihypertensive treatment can prevent its onset . The Systolic Hypertension in the Elderly Program was a double-blind placebo-controlled trial in 4736 subjects with isolated systolic hypertension aged ≥60 years . Atrial fibrillation was an exclusion criterion from the trial . Participants were r and omly assigned to stepped care treatment with chlorthalidone and atenolol ( n=2365 ) or placebo ( n=2371 ) . The occurrence of atrial fibrillation and cardiovascular events over 4.7 years as well as the determination of cause of death at 4.7 and 14.3 years were followed . Ninety-eight subjects ( 2.06 % ) developed atrial fibrillation over 4.7 years mean follow-up , without significant difference between treated and placebo groups . Atrial fibrillation increased the risk for : total cardiovascular events ( RR 1.69 ; 95 % CI 1.21 to 2.36 ) , rapid death ( RR 3.29 ; 95 % CI 1.08 to 10.00 ) , total ( RR 5.10 ; 95 % CI 3.12 to 8.37 ) and nonfatal left ventricular failure ( RR 5.31 ; 95 % CI 3.09 to 9.13 ) . All-cause and total cardiovascular death were significantly increased in the atrial fibrillation group at 4.7 years ( HR 3.44 ; 95 % CI 2.18 to 5.42 ; HR 2.39 ; 95 % CI 1.05 to 5.43 ) and 14.3 years follow-up ( HR 2.33 ; 95 % CI 1.83 to 2.98 ; HR 2.21 ; 95 % CI 1.54 to 3.17 ) . Atrial fibrillation increased the risk for total cardiovascular events , rapid death , and left ventricular failure . All-cause mortality and total cardiovascular mortality were significantly increased in hypertensives with atrial fibrillation at 4.7 and 14.3 years follow-up",
"AIMS Large r and omized trials have shown that beta-blockers reduce mortality and hospital admissions in patients with heart failure . The effects of beta-blockers in elderly patients with a broad range of left ventricular ejection fraction are uncertain . The SENIORS study was performed to assess effects of the beta-blocker , nebivolol , in patients > /=70 years , regardless of ejection fraction . METHODS AND RESULTS We r and omly assigned 2128 patients aged > /=70 years with a history of heart failure ( hospital admission for heart failure within the previous year or known ejection fraction nebivolol ( titrated from 1.25 mg once daily to 10 mg once daily ) , and 1061 to placebo . The primary outcome was a composite of all cause mortality or cardiovascular hospital admission ( time to first event ) . Analysis was by intention to treat . Mean duration of follow-up was 21 months . Mean age was 76 years ( SD 4.7 ) , 37 % were female , mean ejection fraction was 36 % ( with 35 % having ejection fraction > 35 % ) , and 68 % had a prior history of coronary heart disease . The mean maintenance dose of nebivolol was 7.7 mg and of placebo 8.5 mg . The primary outcome occurred in 332 patients ( 31.1 % ) on nebivolol compared with 375 ( 35.3 % ) on placebo [ hazard ratio ( HR ) 0.86 , 95 % CI 0.74 - 0.99 ; P=0.039 ] . There was no significant influence of age , gender , or ejection fraction on the effect of nebivolol on the primary outcome . Death ( all causes ) occurred in 169 ( 15.8 % ) on nebivolol and 192 ( 18.1 % ) on placebo ( HR 0.88 , 95 % CI 0.71 - 1.08 ; P=0.21 ) . CONCLUSION Nebivolol , a beta-blocker with vasodilating properties , is an effective and well-tolerated treatment for heart failure in the elderly",
"BACKGROUND The efficacy of new antihypertensive drugs has been question ed . We compared the effects of conventional and newer antihypertensive drugs on cardiovascular mortality and morbidity in elderly patients . METHODS We did a prospect i ve , r and omised trial in 6614 patients aged 70 - 84 years with hypertension ( blood pressure > or = 180 mm Hg systolic , > or = 105 mm Hg diastolic , or both ) . Patients were r and omly assigned conventional antihypertensive drugs ( atenolol 50 mg , metoprolol 100 mg , pindolol 5 mg , or hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily ) or newer drugs ( enalapril 10 mg or lisinopril 10 mg , or felodipine 2.5 mg or isradipine 2 - 5 mg daily ) . We assessed fatal stroke , fatal myocardial infa rct ion , and other fatal cardiovascular disease . Analysis was by intention to treat . FINDINGS Blood pressure was decreased similarly in all treatment groups . The primary combined endpoint of fatal stroke , fatal myocardial infa rct ion , and other fatal cardiovascular disease occurred in 221 of 2213 patients in the conventional drugs group ( 19.8 events per 1000 patient-years ) and in 438 of 4401 in the newer drugs group ( 19.8 per 1000 ; relative risk 0.99 [ 95 % CI 0.84 - 1.16 ] , p=0.89 ) . The combined endpoint of fatal and non-fatal stroke , fatal and non-fatal myocardial infa rct ion , and other cardiovascular mortality occurred in 460 patients taking conventional drugs and in 887 taking newer drugs ( 0.96 [ 0.86 - 1.08 ] , p=0.49 ) . INTERPRETATION Old and new antihypertensive drugs were similar in prevention of cardiovascular mortality or major events . Decrease in blood pressure was of major importance for the prevention of cardiovascular events",
"Background Atrial fibrillation ( AF ) is the most common arrhythmia and increases cardiovascular risk in hypertensive patients . Therefore , in the Valsartan Antihypertensive Long-term Use Evaluation ( VALUE ) a prespecified objective was to compare the effects of valsartan and amlodipine on new-onset AF . Methods A total of 15 245 hypertensive patients at high cardiovascular risk received valsartan 80–160 mg/day or amlodipine 5–10 mg/day combined with additional antihypertensive agents . Electrocardiograms were obtained every year and analyzed central ly for evidence of left ventricular hypertrophy and new-onset AF . Results At baseline , AF was diagnosed in 2.6 % of 7649 valsartan recipients and 2.6 % of 7596 amlodipine recipients . During antihypertensive treatment the incidence of at least one documented occurrence of new-onset AF was 3.67 % with valsartan and 4.34 % with amlodipine { unadjusted hazard ratio 0.843 , [ 95 % confidence interval ( CI ) : 0.713 , 0.997 ] , P = 0.0455}. The incidence of persistent AF was 1.35 % with valsartan and 1.97 % with amlodipine [ unadjusted hazard ratio 0.683 ( 95 % CI : 0.525 , 0.889 ) , P = 0.0046 ] . Conclusions Valsartan-based treatment reduced the development of new-onset AF , particularly sustained AF in hypertensive patients , compared with amlodipine-based therapy . These findings suggest that angiotensin II receptor blockers may result in greater benefits than calcium antagonists in hypertensive patients at risk of new-onset AF",
"In 1972 - -1973 , 785 symptom-free men , aged 40 to 49 years , without target organ damage , with systolic blood pressures between 150 and 179 mm Hg and diastolic blood pressure below 110 mm Hg , were assigned at r and om to one of two groups : ( 406 to a drug treatment group and 379 to a control group ) for a five-year controlled drug treatment trial to evaluate the effect of therapy on cardiovascular complications . Drug treatment started with hydrochlorothiazide . If systolic blood pressure remained above 140 mm Hg and /or diastolic blood pressure above 90 mm Hg , alphamethyldopa was added . If there were side effects , methyldopa was replaced with propranolol . The control group was not given a placebo . The mean observation time was 66 months ( range 60 to 78 months ) . A difference in blood pressure between groups of about 17 mm Hg systolic and 10 mm Hg diastolic was maintained throughout the study . The study protocol had a rather low \" ethical \" blood pressure roof , 180 mm Hg systolic and /or 110 mm Hg diastolic . Seventeen percent of the control group had an increase in blood pressure above this level during the trial , and drug treatment was started . There was no effect on major cardiovascular morbidity comparing groups as established by r and omization , with 18 events in the treatment group and 20 events in the control group . There was no difference between the groups in total mortality and mortality from cardiovascular events . However , in the subgroups with diastolic blood pressure greater than or equal to 100 mm Hg before r and omization , there was a probable reduction in total morbidity from cardiovascular events in favor or the group receiving drug therapy , 7.6 and 16.4 percent events in the treated and control groups , respectively . Cerebrovascular events occurred only in the control group , 7 versus 0 . Two cases of fatal aortic aneurysms also occurred in the control group . Other \" pressure \" complications , such as marked left ventricular hypertrophy in the electrocardiogram and left ventricular failure , occurred only in the control group . However , regarding coronary heart disease , including sudden death , the incidence tended to be higher in the treated group , although it was not statistically significant . Only 13 men ( 1.7 percent ) failed to meet for regular examinations . At the end of the study these men were also followed up with regard to possible cardiovascular events",
"OBJECTIVES Whether beta-blockers reduce atrial arrhythmias and , when added to an angiotensin-converting enzyme ( ACE ) inhibitor , ventricular arrhythmia is unknown . BACKGROUND Ventricular and atrial arrhythmias are common after acute myocardial infa rct ion ( AMI ) and are associated with a poor prognosis . Angiotensin-converting enzyme inhibitors reduce the incidence of both types of arrhythmia . METHODS The antiarrhythmic effect of carvedilol was examined in a placebo-controlled multicenter trial , the Carvedilol Post-Infa rct Survival Control in Left Ventricular Dysfunction ( CAPRICORN ) study , which enrolled 1,959 patients with reduced left ventricular systolic function after AMI , 98 % of whom were treated with an ACE inhibitor . RESULTS The incidence of atrial fibrillation/flutter was 53 to 984 ( 5.4 % ) in the placebo group and 22 to 975 ( 2.3 % ) in the carvedilol group , giving a carvedilol/placebo hazard ratio ( HR ) of 0.41 ( 95 % confidence interval [ CI ] 0.25 to 0.68 ; p = 0.0003 ) . The corresponding rates of ventricular tachycardia/flutter/fibrillation were 38 to 984 ( 3.9 % ) and 9 to 975 ( 0.9 % ) ( HR 0.24 , 95 % CI 0.11 to 0.49 ; p Carvedilol has a powerful antiarrhythmic effect after AMI , even in patients already treated with an ACE inhibitor . Carvedilol suppresses atrial as well as ventricular arrhythmias in these patients",
"BACKGROUND Atrial fibrillation ( AF ) in heart failure ( HF ) is generally considered a negative prognostic factor . Recent studies indicate that the incidence of AF might be decreased by renin angiotensin aldosterone system inhibitors . The identification of a treatment to prevent its occurrence is likely to improve patients outcome . The aims of these subanalyses of Val-HeFT were to assess ( a ) the effects of valsartan in the prevention of AF , ( b ) the independent predictors of this event , and ( c ) the prognostic role of AF occurrence . METHODS AND RESULTS The occurrence of AF was evaluated based on adverse event reports in the patients with HF enrolled in Val-HeFT . Patients were r and omized to valsartan or placebo on top of their prescribed treatments for HF . During the mean 23 months of follow-up , AF was reported in 287/4395 patients ( 6.53 % ) in sinus rhythm at baseline , of whom 113/2205 ( 5.12 % ) were allocated to valsartan and 174/2190 ( 7.95 % ) to placebo ( P = .0002 ) . Multivariable analysis showed that brain natriuretic peptide ( BNP ) levels at baseline above the median value ( HR 2.28 , 95 % CI 1.75 - 2.98 ) , age over 70 years ( HR 1.51 , 95 % CI 1.17 - 1.95 ) , male sex ( HR 1.53 , 95 % CI 1.07 - 2.18 ) , and the valsartan treatment ( HR 0.63 , 95 % CI 0.49 - 0.81 ) were independently associated with AF occurrence . Cox multivariable regression analysis showed that occurrence of AF was independently associated with a worse prognosis , with the adjusted hazard risks for all-cause mortality and combined mortality/morbidity of 1.40 ( 95 % CI 1.16 - 1.58 ) and 1.38 ( 95 % CI 1.12 - 1.70 ) , respectively . CONCLUSIONS The results of the present study demonstrate that ( a ) adding valsartan to prescribed therapy for HF significantly reduces the incidence of AF by 37 % ; ( b ) BNP level and advanced age were the strongest independent predictors for AF occurrence ; and ( c ) AF occurrence further worsens the outcome in patients with HF",
"BACKGROUND The level to which systolic blood pressure should be controlled in hypertensive patients without diabetes remains unknown . We tested the hypothesis that tight control compared with usual control of systolic blood pressure would be beneficial in such patients . METHODS In this r and omised open-label trial undertaken in 44 centres in Italy , 1111 non-diabetic patients with systolic blood pressure 150 mm Hg or greater were r and omly assigned to a target systolic blood pressure of less than 140 mm Hg ( usual control ; n=553 ) or less than 130 mm Hg ( tight control ; n=558 ) . After stratification by centre , we used a computerised r and om function to allocate patients to either group . Observers who were unaware of r and omisation read electrocardiograms and adjudicated events . Open-label agents were used to reach the r and omised targets . The primary endpoint was the rate of electrocardiographic left ventricular hypertrophy 2 years after r and omisation . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00421863 . RESULTS Over a median follow-up of 2.0 years ( IQR 1.93 - 2.03 ) , systolic and diastolic blood pressure were reduced by a mean of 23.5/8.9 mm Hg ( SD 10.6/7.0 ) in the usual-control group and by 27.3/10.4 mm Hg ( 11.0/7.5 ) in the tight-control group ( between-group difference 3.8 mm Hg systolic [ 95 % CI 2.4 - 5.2 ] , p usual-control group and in 55 of 484 patients ( 11.4 % ) of the tight-control group ( odds ratio 0.63 ; 95 % CI 0.43 - 0.91 ; p=0.013 ) . A composite cardiovascular endpoint occurred in 52 ( 9.4 % ) patients in the usual-control group and in 27 ( 4.8 % ) in the tight-control group ( hazard ratio 0.50 , 95 % CI 0.31 - 0.79 ; p=0.003 ) . Side-effects were rare and did not differ significantly between the two groups . INTERPRETATION Our findings lend support to a lower blood pressure goal than is recommended at present in non-diabetic patients with hypertension . FUNDING Boehringer-Ingelheim , Sanofi-Aventis , Pfizer",
"Background Event adjudication in r and omized controlled trials is thought to be a necessary step to remove noise and potential bias from the results [ 1,2 ] . However , this hypothesis has not been widely evaluated . We conducted a meta- analysis of a series of cardiovascular outcomes trials and estimated the effect of adjudication on treatment estimates and on the number of outcomes included the trials . Methods Data were retrieved from all cardiovascular outcomes trials conducted at the Population Health Research Institute ( PHRI ) between 1993 and 2006 . These data included 10 trials with over 9000 events from 95 038 individuals . Differences in the log odds ratios between adjudicated and reported outcomes were analyzed and summarized using a ratio of odds ratios . Both masked and unmasked trials were included in this analysis . Results There were no effects of event adjudication on the estimates of treatment effect for the primary outcomes , myocardial infa rct ion ( MI ) , stroke , or cardiovascular/vascular death . For the trial primary outcomes , the effect of adjudication vs. reported events was OR ratio = 1.00 [ 95 % confidence interval ( CI ) : 0.97—1.02 ] . There were also no significant differences in the number of outcomes included in the trials . Results were the same for masked and unmasked trials . Limitations The number of unmasked trials were small , and this analysis was restricted to cardiovascular endpoints reported from trials managed by a single coordinating center , with similar sets of procedures . Individual patient data were not used for the analysis . Conclusions This systematic meta- analysis failed to detect any effect of event adjudication on study conclusions and the numbers of events included in the final analyses were minimally changed . Given the considerable effort required to perform adjudication , there is a need to demonstrate that this process does indeed increase the sensitivity of trials . There is a need to conduct more systematic analyses of the effect of event adjudication in other trials to determine if this process is truly worthwhile",
"BACKGROUND Atrial fibrillation ( AF ) is frequent in patients with chronic heart failure ( CHF ) . Experimental and small patient studies have demonstrated that blocking the renin-angiotensin-aldosterone system may prevent AF . In the CHARM program , the effects of the angiotensin receptor blocker c and esartan on cardiovascular mortality and morbidity were evaluated in a broad spectrum of patients with symptomatic CHF . CHARM provided the opportunity to prospect ively determine the effect of c and esartan on the incidence of new AF in this CHF population . METHODS 7601 patients with symptomatic CHF and reduced or preserved left ventricular systolic function were r and omized to c and esartan ( target dose 32 mg once daily , mean dose 24 mg ) or placebo in the 3 component trials of CHARM . The major outcomes were cardiovascular death or CHF hospitalization and all-cause mortality . The incidence of new AF was a prespecified secondary outcome . Median follow-up was 37.7 months . A conditional logistic regression model for stratified data was used . RESULTS 6379 patients ( 83.9 % ) did not have AF on their baseline electrocardiogram . Of these , 392 ( 6.15 % ) developed AF during follow-up , 177 ( 5.55 % ) in the c and esartan group and 215 ( 6.74 % ) in the placebo group ( odds ratio 0.812 , 95 % CI 0.662 - 0.998 , P = .048 ) . After adjustment for baseline covariates , the odds ratio was 0.802 ( 95 % CI 0.650 - 0.990 , P = .039 ) . There was no heterogeneity of the effects of c and esartan in preventing AF between the 3 component trials ( P = .57 ) . CONCLUSIONS Treatment with the angiotensin receptor blocker c and esartan reduced the incidence of AF in a large , broadly-based , population of patients with symptomatic CHF",
"AIMS The aim of this study was to investigate serious clinical outcomes associated with atrial fibrillation ( AF ) and the effects of routine blood pressure lowering on such outcomes in the presence or absence of AF , among individuals with type 2 diabetes . METHODS AND RESULTS About 11 140 patients with type 2 diabetes ( 7.6 % of whom had AF at baseline ) were r and omized to a fixed combination of perindopril and indapamide or placebo in the Action in Diabetes and Vascular Disease : preterAx and diamicroN-MR Controlled Evaluation ( ADVANCE ) study . We compared total mortality and cardiovascular disease outcomes and effects of r and omized treatment for 4.3 years on such outcomes between patients with and without AF at baseline . After multiple adjustments , AF was associated with a 61 % ( 95 % confidence interval 31 - 96 , P of all-cause mortality and comparable higher risks of cardiovascular death , stroke , and heart failure ( all P perindopril and indapamide produced similar relative , but greater absolute , risk reductions for all-cause and cardiovascular mortalities in patients with AF , compared with those without AF . The number of patients needed to be treated with perindopril-indapamide for 5 years to prevent one cardiovascular death was 42 for patients with AF and 120 for patients without AF at baseline . CONCLUSION Atrial fibrillation is relatively common in type 2 diabetes and is associated with substantially increased risks of death and cardiovascular events in patients with type 2 diabetes . This arrhythmia identifies individuals who are likely to obtain greater absolute benefits from blood pressure-lowering treatment . Atrial fibrillation in diabetic patients should be regarded as a marker of particularly adverse outcome and prompt aggressive management of all risk factors",
"BACKGROUND Atrial fibrillation is the most common cardiac arrhythmia , and no current therapy is ideal for control of this condition . Experimental studies suggest that angiotensin II-receptor blockers ( ARBs ) can influence atrial remodeling , and some clinical studies suggest that they may prevent atrial fibrillation . METHODS We conducted a large , r and omized , prospect i ve , placebo-controlled , multicenter trial to test whether the ARB valsartan could reduce the recurrence of atrial fibrillation . We enrolled patients who were in sinus rhythm but had had either two or more documented episodes of atrial fibrillation in the previous 6 months or successful cardioversion for atrial fibrillation in the previous 2 weeks . To be eligible , patients also had to have underlying cardiovascular disease , diabetes , or left atrial enlargement . Patients were r and omly assigned to receive valsartan or placebo . The two primary end points were the time to a first recurrence of atrial fibrillation and the proportion of patients who had more than one recurrence of atrial fibrillation over the course of 1 year . RESULTS A total of 1442 patients were enrolled in the study . Atrial fibrillation recurred in 371 of the 722 patients ( 51.4 % ) in the valsartan group , as compared with 375 of 720 ( 52.1 % ) in the placebo group ( adjusted hazard ratio , 0.97 ; 96 % confidence interval [ CI ] , 0.83 to 1.14 ; P=0.73 ) . More than one episode of atrial fibrillation occurred in 194 of 722 patients ( 26.9 % ) in the valsartan group and in 201 of 720 ( 27.9 % ) in the placebo group ( adjusted odds ratio , 0.89 ; 99 % CI , 0.64 to 1.23 ; P=0.34 ) . The results were similar in all predefined subgroups of patients , including those who were not receiving angiotensin-converting-enzyme inhibitors . CONCLUSIONS Treatment with valsartan was not associated with a reduction in the incidence of recurrent atrial fibrillation . ( Clinical Trials.gov number , NCT00376272 ."
] |
4116bd48-06ff-11f0-808a-c43d1ab1c353
|
OBJECTIVE Little is known about the extent to which physical activity ( PA ) levels change following total knee or hip joint replacement relative to pain , physical function , and quality of life . Our objective was to conduct a systematic review and meta- analysis on changes in PA relative to pain , quality of life , and physical function after total knee or hip joint replacement . METHODS We search ed the PubMed ( Medline ) , Embase , and CINAHL data bases for peer- review ed , English- language cohort studies measuring PA with an accelerometer from presurgery to postsurgery . R and om-effects models were used to produce st and ardized mean differences ( SMDs ) for PA , quality of life , pain , and physical function outcomes . Heterogeneity was assessed using I2 . RESULTS Seven studies ( 336 participants ) met the eligibility criteria . No significant increase in PA was found at 6 months ( SMD 0.14 [ 95 % confidence interval ( 95 % CI ) -0.05 , 0.34 ] ; I2 = 0 % ) and a small to moderately significant effect was found for increasing PA at 12 months ( SMD 0.43 [ 95 % CI 0.22 , 0.64 ] ; I2 = 0 % ) . Large improvements were found at 6 months in physical function ( SMD 0.97 [ 95 % CI 0.12 , 1.82 ] ; I2 = 92.3 % ) , pain ( SMD -1.47 [ 95 % CI -2.28 , -0.65 ] ; I2 = 91.6 % ) , and quality of life ( SMD 1.02 [ 95 % CI 0.30 , 1.74 ] ; I2 = 83.2 % ) . CONCLUSION Physical activity did not change at 6 months , and a small to moderate improvement was found at 12 months postsurgery , despite large improvements in quality of life , pain , and physical function . Reasons for the lack of increased PA are unknown but may be behavioral in nature , as a sedentary lifestyle is difficult to change . Changing sedentary behavior should be a future focus of research in this subgroup
|
[
"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",
"Background Intensive diet and physical activity interventions have been found to reduce cardiovascular disease ( CVD ) risk , but are re source intensive . The American Heart Association recently recommended motivational interviewing ( MI ) as an effective approach for low-intensity interventions to promote health-related outcomes such as weight loss . However , there is limited research evaluating the long-term effectiveness of MI-based interventions on health-related outcomes associated with CVD risk . The current research evaluated the effectiveness of a six-month low-intensity MI intervention in a UK primary -care setting in maintaining reductions in CVD risk factors at12 months post-intervention . Methods Primary -care patients were r and omised to an intervention group that received st and ard exercise and nutrition information plus up to five face-to-face MI sessions , delivered by a physical activity specialist and registered dietician over a 6-month period , or to a minimal intervention comparison group that received the st and ard information only . Follow-up measures of behavioural ( vigorous and moderate physical activity , walking , physical activity stage-of-change , fruit and vegetable intake , and dietary fat intake ) and biomedical ( weight , body mass index [ BMI ] , blood pressure , cholesterol ) outcomes were taken immediately post-intervention and at a 12-month follow-up occasion . Results Intent-to-treat analyses revealed significant differences between groups for walking and cholesterol . Obese and hypercholesterolemic patients at baseline exhibited significant improvements in BMI and cholesterol respectively among those allocated to the intervention group compared to the comparison group . Post-intervention improvements in other health-related outcomes including blood pressure , weight , and BMI were not maintained . Conclusions The present study suggests that a low-intensity MI counselling intervention is effective in bringing about long-term changes in some , but not all , health-related outcomes ( walking , cholesterol levels ) associated with CVD risk . The intervention was particularly effective for patients with elevated levels of CVD risk factors at baseline . Based on these findings future interventions should be conducted in a primary care setting and target patients with high risk of CVD . Future research should investigate how the long-term gains in health-related outcomes brought about by the MI-counselling intervention in the current study could be extended to a wider range of health outcomes",
"Background After total knee arthroplasty ( TKA ) only 75 - 89 % of patients are satisfied . Because patient satisfaction is a prime goal of all orthopaedic procedures , optimization of patient satisfaction is of major importance . Factors related to patient satisfaction after TKA have been explored , but no studies have included two potentially relevant factors , i.e. the functional capacity of daily activities and actual daily activity . This present prospect i ve study examines whether functional capacity and actual daily activity ( in addition to an extensive set of potential factors ) contribute to patient satisfaction six months after TKA . Methods A total of 44 patients were extensively examined preoperatively and six months post surgery . Functional capacity was measured with three capacity tests , focusing on walking , stair climbing , and chair rising . Actual daily activity was measured in the patient 's home situation by means of a 48-hour measurement with an Activity Monitor . To establish which factors were related to patient satisfaction six months post surgery , logistic regression analyses were used to calculate odds ratios . Results Preoperative and postoperative functional capacity and actual daily activity had no relation with patient satisfaction . Preoperatively , only self-reported mental functioning was positively related to patient satisfaction . Postoperatively , based on multivariate analysis , only fulfilled expectations regarding pain and experienced pain six months post surgery were related to patient satisfaction . Conclusions Functional capacity and actual daily activity do not contribute to patient satisfaction after TKA . Patients with a better preoperative self-reported mental functioning , and patients who experienced less pain and had fulfilled expectations regarding pain postoperatively , were more often satisfied ",
"Abstract Limitation in daily physical activity is one of the reasons for total hip arthroplasty ( THA ) or total knee arthroplasty ( TKA ) . However , studies of the effects of THA or TKA generally do not determine actual daily activity as part of physical functioning . We determined the effect of THA or TKA on patients ’ actual physical activity and body function ( pain , stiffness ) , capacity to perform tasks , and self-reported physical functioning . We also assessed whether there are differences in the effect of the surgery between patients undergoing THA or TKA and whether the improvements vary between these different outcome measures . We recruited patients with long-st and ing end-stage osteoarthritis of the hip or knee awaiting THA or TKA . Measurements were performed before surgery and 3 and 6 months after surgery . Actual physical activity improved by 0.7 % . Patients ’ body function , capacity , and self-reported physical functioning also improved . The effects of the surgery on these aspects of physical functioning were similar for THA and TKA . The effect on actual physical activity ( 8 % ) was smaller than on body function ( 80%–167 % ) , capacity ( 19%–36 % ) , and self-reported physical functioning ( 87%–112 % ) . Therefore , in contrast to the large effect on pain and stiffness , patients ’ capacity , and their self-reported physical functioning , the improvement in actual physical activity of our patients was less than expected 6 months after surgery . Level of Evidence : Level I , prospect i ve study . See the Guidelines for Authors for a complete description of levels of evidence",
"The primary objective of this study was to use step activity monitoring to quantify activity changes after total hip arthroplasty in patients 50 years or less . Secondly , we investigated whether step activity measurements correlated with the Harris hip and UCLA scores . We prospect ively analyzed 37 patients ( age ≤ 50 ) treated with primary THA . Patient activity was recorded with a step activity monitor . Harris hip and UCLA scores were analyzed . Total daily stride counts increased by an average of 30.0 % . Increases were noted in the percent of daily time spent at high , moderate and low activity . Increases in daily time spent at high activity moderately correlated with the UCLA activity score but did not correlate with the HHS . Both the UCLA score and the HHS did not correlate with mean daily strides . Following THA , patients ≤ 50 years of age increase their activity by taking more daily strides and improve their activity profile by spending more time at higher activity . Improvements in step activity moderately correlate with improvements in UCLA scores",
"We have evaluated the quality of life and functional outcome after unilateral primary total hip replacement ( THR ) . Between 5 January 1998 and 31 July 2000 , we recruited a consecutive series of 627 patients undergoing this procedure and investigated them prospect ively . Each was assessed before operation and review ed after six months , 18 months , three years and five years . The Short Form-36 Health Survey ( SF-36 ) and Harris Hip scores were evaluated at each appointment . All dimensions of the SF-36 except for mental health and general health perception , improved significantly after operation and this was maintained throughout the follow-up . The greatest improvement was seen at the six-month assessment . On average , women reported lower SF-36 scores pre-operatively , but the gender difference did not continue post-operatively . The Harris Hip scores improved significantly after operation , reaching a plateau after 18 months . The improved quality of life was sustained five years after THR",
"The present single-centre prospect i ve follow-up study assessed the objective changes in physical activity undertaken before and after total hip arthroplasty ( THA ) using accelerometry . We enrolled 12 female patients who underwent home-based accelerometry assessment one month before and six months after the THA procedure . We assessed the daily amount of physical activity and energy expenditure related to physical activities . We also recorded the intensity of the physical activity , and pre- and post-operative clinical evaluation with the Harris Hip Score ( HHS ) . At 6 months after surgery , we found a statistically significant increase of the total energy cost of physical activity ( DA ) ( P=0.02 ) , without significant increase of activity time ( P>0.05 ) . The energy cost of moderate/vigorous activity was statistically significant increased after surgery ( P=0.008 ) . Finally , HHS improved form 53.9±15.3 pre-operatively to 78.1±12.2 post-operatively ( P=0.03 ) . In our patients , the improvement was significant only for the total energy cost of daily activity . Thus , although patients did not exhibit a more active lifestyle , as shown by the slight increase of the activity time , they significantly increased the amount of moderate or vigorous activities performed after surgery",
"OBJECTIVE To quantify the magnitude of change seen with pain , function , and quality of life outcomes 6 months after total hip and knee arthroplasties ( THA , TKA ) within a community based cohort of a regional health district . METHODS An inception cohort of 504 patients who received primary THA ( 228 ) or TKA ( 276 ) was prospect ively followed . All patients resided in the community and were assessed within one month prior to surgery and 6 months postoperatively . Health related quality of life measures were evaluated with the Western Ontario and McMaster Universities ( WOMAC ) Osteoarthritis Index and the Medical Outcome Survey Short Form SF-36 . Perioperative factors were extracted from medical charts . Health services utilization data were collected from regional health data bases . RESULTS Over 75 % of patients reported improvement in joint-specific pain and function , regardless of the type of joint replaced . Other health dimensions such as social function , bodily pain , physical function , vitality , and general health showed significant improvement after surgery . Those psychosocial dimensions with modest changes had baseline values comparable to age and sex adjusted normal values ; whereas , bodily pain and physical function , which had large changes , had values lower than the normal values . Ninety-one percent of patients receiving THA were satisfied with their surgery , whereas 77 % were satisfied with their TKA . The average length of stay was 7 days and the in-hospital complication rate was 0.34 per patient . CONCLUSION Large improvements were reported for pain and function after joint arthroplasties , while small to moderate changes were seen in other areas related to quality of life . Patients with hip arthroplasties showed greater improvement in pain and function and were more satisfied with their outcomes than patients with knee arthroplasties . Although pain and function show large improvements , bodily pain and physical function were less than the values reported in the general population",
"ABSTRACT The primary objective of the present study was to examine the role of pain‐related psychological factors in predicting pain and disability following Total Knee Arthroplasty ( TKA ) . The study sample consisted of 75 ( 46 women , 29 men ) individuals with osteoarthritis of the knee who were scheduled for TKA . Measures of pain severity , pain catastrophizing , depression , and pain‐related fears of movement were completed prior to surgery . Participants completed measures of pain severity and self‐reported disability 6 weeks following surgery . Consistent with previous research , cross‐sectional analyses revealed significant correlations among measures of pre‐surgical pain severity , pain catastrophizing , depression and pain‐related fears of movement . Prospect i ve analyses revealed that pre‐surgical pain severity and pain catastrophizing were unique predictors of post‐surgical pain severity ( 6‐week follow‐up ) . Pain‐related fears of movement were predictors of post‐surgical functional difficulties in univariate analyses , but not when controlling for pre‐surgical co‐morbidities ( e.g. back pain ) . The results of this study add to a growing literature highlighting the prognostic value of psychological variables in the prediction of post‐surgical health outcomes . The results support the view that the psychological determinants of post‐surgical pain severity differ from the psychological determinants of post‐surgical disability . The results suggest that interventions design ed to specifically target pain‐related psychological risk factors might improve post‐surgical outcomes"
] |
4116bd8e-06ff-11f0-808a-c43d1ab1c353
|
PURPOSE Although many total hip bearing implants are widely used all over the world , simultaneous comparisons across the numerous available bearing surfaces are rare . The purpose of this study was to compare the survivorship of total hip arthroplasty ( THA ) with six available bearing implants . METHODS We conducted a systematic review of r and omized controlled trials ( RCTs ) reporting survivorship or revision of ceramic-on-ceramic ( CoC ) , ceramic-on-conventional polyethylene ( CoPc ) , ceramic-on-highly-crosslinked polyethylene ( CoPxl ) , metal-on-conventional polyethylene ( MoPc ) , metal-on-highly-crosslinked polyethylene ( MoPxl ) , or metal-on-metal ( MoM ) bearing implants . The synthesis of present evidence was performed by both the traditional direct-comparison meta- analysis and network meta- analysis . RESULTS In total , 40 RCTs involving a total of 5321 THAs were identified . The pooled data of network meta- analysis showed no difference in relative risk ( RR ) of revision across CoC , CoPc , CoPxl and MoPxl bearings . However , the MoM bearing was demonstrated with a significant higher risk of revision compared with CoC ( RR 5.10 ; 95 % CI=1.62 to 16.81 ) , CoPc ( RR 4.80 ; 95 % CI=1.29 to 17.09 ) , or MoPxl ( RR 3.85 ; 95 % CI=1.16 to 14.29 ) , and the MoPc bearing was indicated with a higher risk of revision compared with CoC ( RR 2.83 ; 95 % CI=1.20 to 6.63 ) . The ranking probabilities of the effective interventions also revealed the inferiority of the MoM and MoPc implants in survivorship ( both 0 % , 95 % CI=0 % to 0 % ) compared with CoC ( 39 % , 95 % CI=0 % to 100 % ) , CoPc ( 33 % , 95 % CI=0 % to 100 % ) , CoPxl ( 7 % , 95 % CI=0 % to 100 % ) or MoPxl ( 21 % , 95 % CI=0 % to 100 % ) . CONCLUSIONS The present evidence indicated the similar performance in survivorship among CoC , CoPc , CoPxl and MoPxl bearing implants , and that all likely have superiority compared with the MoM and MoPc bearing implants in THA procedures . Long-term RCT data are required to confirm these conclusions and better inform clinical decisions
|
[
" Highly cross-linked polyethylene was developed to reduce articular bearing wear in total hip arthroplasty . In vitro studies have shown reduced wear in comparison with conventional polyethylene . A double-blind , prospect i ve , r and omized trial was performed comparing highly cross-linked and conventional polyethylene in 119 patients . The primary outcome variables were linear , 3-dimensional , and volumetric wear as determined by analysis of digitized radiographs using vali date d wear measurement software . Linear , 3-dimensional , and volumetric wear rates were significantly less in the highly cross-linked polyethylene group between 6 months and 4 years postoperatively ( P highly cross-linked polyethylene reduces short-term polyethylene wear . The intermediate and long-term clinical results of highly cross-linked polyethylene remain unknown pending further follow-up",
"This prospect i ve r and omized study aims to compare the outcome between an alumina ceramic-on-ceramic ( CC ) articulation with a ceramic on ultra-high-molecular-weight polyethylene articulation ( CP ) . Fifty-six hips in 55 patients with mean age 42.2 ( range , 19 - 56 ) each received uncemented components , a 28-mm alumina head with r and omization of acetabular liner . Mean St Michael 's outcome score for each group with up to 10 years follow-up ( median , 8 years ; range , 1 - 10 ) was 22.8 and 22.9 , respectively ( P = .819 ) . Wear was identified in all but 1 CP replacement , but only 12 of the 23 CC . Mean wear in the CP group was 0.11 mm/y and 0.02 mm/yr in the CC group ( P wear in the polyethylene group , there was no significant difference in midterm outcome between the 2 groups",
"Wear and osteolysis continue to be major reasons for revision surgery in THA . Ceramic-on-ceramic bearings eliminate polyethylene wear debris . The newest generation of these bearings incorporate nanosized , yttria-stabilized tetragonal zirconia particles producing an alumina matrix composite . We asked whether this new material would perform as well as a conventional bearing in terms of functional hip scores , radiographic migration and osteolysis , complications and survival . As part of a US FDA investigational device exemption study ( G000075 ) , we conducted an initial prospect i ve safety study of 21 alumina matrix composite femoral heads articulating on alumina liners followed by a prospect i ve , r and omized study with 44 more of these articulations and 45 zirconia femoral heads on polyethylene liners . The minimum followup for all patients was 26 months ( mean , 73 months ; range , 26–108 months ) . Harris hip scores and radiographic findings were similar in the two groups as was survivorship ( trial 95 % versus control 93 % ) . There were three reoperations in the trial group and three in the control group . A fractured head retrieval showed a 33 % monoclinic transformation with an increase in surface roughness from 3 to 5 nm at the main wear zone . While our numbers were insufficient to compare device-related complications , the trial device performed as well as the control device in terms of reoperation , and clinical and radiographic outcome . The alumina matrix composite femoral head on an alumina liner provided high survivorship . Level of Evidence : Level II , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence",
"Background Although hip arthroplasty reliably relieves pain and improves function , problems have arisen with wear and osteolysis . Highly crosslinked polyethylene has been developed to address this problem although at present there is limited clinical evidence it does so longer term . Questions / purpose sWe compared the in vivo wear of st and ard versus highly crosslinked polyethylene ( HXLP ) in primary total hip arthroplasty at a minimum of 5-year followup . Methods We enrolled 122 patients in a prospect i ve , double-blinded , r and omized trial and followed them annually to assess their progress . Annual radiographs were analyzed using previously vali date d edge detection software to assess for two-dimensional , three-dimensional , and volumetric wear . The mean follow up was 5.5 years ( range , 4.1 to 7 years ) . Results The two-dimensional wear measurements for HXLP showed lower wear compared to the conventional group ( 0.05 mm/year versus 0.26 mm/year , respectively ) . Three-dimensional and volumetric wear were similarly lower in the HXLP group . Conclusions Highly crosslinked polyethylene undergoes substantially less wear than conventional polyethylene at medium term . The effect of hip arthroplasty longevity will need to be assessed with longer-term studies , but this may lead to a decreased need for revision as a result of less wear and osteolysis . Level of Evidence Level I , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence",
"Abstract Wear particle-induced osteolysis is a major cause of aseptic loosening in THA . Increasing wear resistance of polyethylene ( PE ) occurs by increasing the cross-link density and early reports document low wear rates with such implants . To confirm longer-term reductions in wear we compared cross-linked polyethylene ( irradiation in nitrogen , annealing ) with historical polyethylene ( irradiation in air ) in a prospect i ve , r and omized clinical study involving 48 patients who underwent THAs with a minimum followup of 7 years ( mean , 8 years ; range , 7–9 years ) . The insert material was the only variable . The Harris hip score , radiographic signs of osteolysis , and polyethylene wear were recorded annually . Twenty-three historical and 17 moderately cross-linked polyethylene inserts were analyzed ( five patients died , three were lost to followup ) . At 8 years , the wear rate was lower for cross-linked polyethylene ( 0.088 ± 0.03 mm/year ) than for the historical polyethylene ( 0.142 ± 0.07 mm/year ) . This reduction ( 38 % ) did not diminish with time ( 33 % at 5 years ) . Acetabular cyst formation was less frequent ( 39 % versus 12 % ) , affected fewer DeLee and Charnley zones ( 17 % versus 4 % ) , and was less severe for the cross-linked polyethylene . The only revision was for an aseptically loose cup in the historical polyethylene group . Moderately cross-linked polyethylene maintained its wear advantage with time and produced less osteolysis , showing no signs of aging at mid-term followup . Level of Evidence : Level I , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence",
"We carried out a prospect i ve r and omised study design ed to compare the penetration rate of acetabular polyethylene inserts of identical design but different levels of cross-linking at a minimum of four years follow-up . A total of 102 patients ( 102 hips ) were r and omised to receive either highly cross-linked Durasul , or contemporary Sulene polyethylene inserts at total hip replacement . A single blinded observer used the Martell system to assess penetration of the femoral head . At a mean follow-up of 4.9 years ( 4.2 to 6.1 ) the mean femoral head penetration rate was 0.025 mm/year ( SD 0.128 ) in the Durasul group compared with 0.106 mm/year ( SD 0.109 ) in the Sulene group ( Mann-Whitney test , p = 0.0027 ) . The mean volumetric penetration rate was 29.24 mm(3)/year ( SD 44.08 ) in the Durasul group compared with 53.32 mm(3)/year ( SD 48.68 ) in the Sulene group . The yearly volumetric penetration rate was 55 % lower in the Durasul group ( Mann-Whitney test , p = 0.0058 ) . Longer term results are needed to investigate whether less osteolysis will occur",
"BACKGROUND The use of highly cross-linked polyethylene is now commonplace in total hip arthroplasty . Hip simulator studies and short-term in vivo measurements have suggested that the wear rate of highly cross-linked polyethylene is significantly less than that of conventional ultra-high molecular weight polyethylene . However , long-term data to support its use are limited . The aim of this study was to compare the intermediate-term steady-state wear of highly cross-linked polyethylene compared with that of conventional ultra-high molecular weight polyethylene acetabular liners in a prospect i ve , double-blind , r and omized controlled trial with use of radiostereometric analysis . METHODS Fifty-four patients were r and omized to receive hip replacements with either conventional ultra-high molecular weight polyethylene acetabular liners ( Zimmer ) or highly cross-linked polyethylene liners ( Longevity ; Zimmer ) . All patients received a cemented , collarless , polished , tapered femoral component ( CPT ; Zimmer ) and an uncemented acetabular component ( Trilogy ; Zimmer ) . Clinical outcomes were assessed and the three-dimensional penetration of the head into the socket was determined for a minimum of seven years . Linear regression was used to calculate the steady-state wear rate following the creep-dominated penetration seen during the first year . RESULTS At a minimum of seven years postoperatively , the mean total femoral head penetration was significantly lower in the highly cross-linked polyethylene group ( 0.33 mm ; 95 % confidence interval [ CI ] , ±0.10 mm ) than it was in the ultra-high molecular weight polyethylene group ( 0.55 mm ; 95 % CI , ±0.10 mm ) ( p = 0.005 ) . The mean steady-state wear rate of highly cross-linked polyethylene was 0.005 mm/yr ( 95 % CI , ±0.015 mm/yr ) , compared with 0.037 mm/yr ( 95 % CI , ±0.019 mm/yr ) for conventional ultra-high molecular weight polyethylene ( p = 0.007 ) . No patient in the highly cross-linked polyethylene group had a wear rate above the osteolysis threshold of 0.1 mm/yr , compared with 9 % of patients in the ultra-high molecular weight polyethylene group . CONCLUSIONS This study demonstrates that highly cross-linked polyethylene has a significantly lower steady-state wear rate compared with that of conventional ultra-high molecular weight polyethylene . Longer-term follow-up is required to determine if this will translate into improved clinical performance and longevity of these implants",
"The results of a prospect i ve multicenter trial comparing 357 hips r and omized to total hip arthroplasty with either ceramic-ceramic or ceramic-polyethylene couplings are presented . No statistically significant difference in clinical outcomes scores between the ceramic-ceramic and ceramic-polyethylene groups was observed at any time interval . The mean linear rate was statistically lower ( P ceramic-ceramic group ( 30.5 μm/year ) when compared with the ceramic-polyethylene group ( 218.2 μm/year ) . The rates of ceramic implant fracture ( 2.6 % ) and audible component-related noise ( 3.1 % ) were statistically higher in the ceramic-ceramic group when compared with the ceramic-polyethylene group ( P in the dislocation or revision rate between the groups at the time of last clinical follow-up",
"Purpose Very few studies have compared alumina-on-alumina ceramic and alumina-on-highly cross-linked polyethylene bearings in the same patient . The purpose of this prospect i ve r and omised study was to compare the clinical and radiographic results and the prevalence of osteolysis in cementless total hip arthroplasty using an alumina-on-alumina and alumina-on-highly cross-linked polyethylene bearings in young active patients . Methods We prospect ively compared the results of 100 patients ( 200 hips ) who had undergone a cementless total hip arthroplasty with an alumina-on-alumina ceramic bearing in one hip and an alumina-on-highly cross-linked polyethylene in the other . There were 66 men and 34 women with a mean age of 45.3 years ( range , 21–49 years ) at the time of surgery . The mean follow-up was 12.4 years ( range , 11–13 years ) . The patients were assessed clinical ly and radiographically at three months , one year , and annually thereafter . Results Harris hip , Western Ontario and McMaster Universities Osteoarthritis Index , and University of California , Los Angeles activity scores did not show statistically significant differences between the two groups of bearings preoperatively or at the time of final follow-up . Radiographic findings of the component were not significantly different between the two groups . The mean polyethylene linear penetration was 0.031 ± 0.004 mm per year . No hips in either group displayed osteolysis . The Kaplan-Meier survivorship with revision as the end point at 12.4 years was 100 % ( 95 % confidence interval [ CI ] , 94–100 % ) for the femoral component in both groups and 99 % ( 95 % CI , 93–100 % ) for the acetabular component . Conclusion The clinical and radiographic results of using an alumina-on-alumina ceramic and alumina-on-highly cross-linked polyethylene bearings were similar",
"BACKGROUND The results of total hip arthroplasty in patients with osteonecrosis of the femoral head are not always optimal . The use of alumina-on-alumina interfaces in young and active patients may decrease wear and lower the rate of aseptic loosening of the implant and appears to be an attractive alternative to the use of conventional cobalt-chromium-on-polyethylene bearings . The purpose of this study was to evaluate the safety and efficacy of the alumina-on-alumina bearing in patients with osteonecrosis and to compare this group of patients to a group of similarly treated patients with osteoarthritis and a group of patients who received conventional cobalt-chromium-on-polyethylene bearings . METHODS Patients were selected from a United States Investigational Device Exemption multicenter prospect i ve r and omized clinical study that was initiated in 1996 . Seventy patients with osteonecrosis of the femoral head ( seventy-nine hips ) received a cementless alumina-on-alumina bearing system and were directly matched to seventy-six patients with osteoarthritis of the hip ( seventy-nine hips ) who were managed with the same implant . Both groups were compared with twenty-five patients ( twenty-six hips ) with osteonecrosis and twenty-five patients ( twenty-six hips ) with osteoarthritis who were managed with a cementless cobalt-chromium-on-polyethylene bearing system . All patients received a cementless hydroxyapatite-coated femoral stem and were followed both clinical ly and radiographically . RESULTS The clinical outcomes for alumina-on-alumina bearings were similar for both osteonecrotic and osteoarthritic hips . The seven-year survival probability was 95.5 % for the osteonecrotic hips and 89.4 % for the osteoarthritic hips in the alumina-on-alumina bearing group and 92.3 % for the osteonecrotic hips and 92.9 % for the osteoarthritic hips in the cobalt-chromium-on-polyethylene bearing group . At the time of the most recent follow-up , the mean Harris hip score was 96 points for both the osteonecrotic and the osteoarthritic hips in the alumina-on-alumina group and 96 points for the osteonecrotic hips and 97 points for the osteoarthritic hips in the cobalt-chromium-on-polyethylene bearing group . CONCLUSIONS The results of the use of alumina-on-alumina and cobalt-chromium-on-polyethylene bearings in cementless st and ard total hip implants in patients with osteonecrosis and osteoarthritis were comparable . The low revision rate for the alumina-on-alumina bearing is encouraging and offers a promising option for younger , more active patients who have this challenging disease . LEVEL OF EVIDENCE Therapeutic Level III . See Instructions to Authors on jbjs.org for a complete description of levels of evidence",
"The creep and wear behaviour of highly cross-linked polyethylene and st and ard polyethylene liners were examined in a prospect i ve , double-blind r and omised , controlled trial using radiostereometric analysis . We r and omised 54 patients to receive hip replacements with either highly cross-linked polyethylene or st and ard liners and determined the three-dimensional penetration of the liners over three years . After three years the mean total penetration was 0.35 mm ( SD 0.14 ) for the highly cross-linked polyethylene group and 0.45 mm ( SD 0.19 ) for the st and ard group . The difference was statistically significant ( p = 0.0184 ) . From the pattern of penetration it was possible to discriminate creep from wear . Most ( 95 % ) of the creep occurred within six months of implantation and nearly all within the first year . There was no difference in the mean degree of creep between the two types of polyethylene ( highly cross-linked polyethylene 0.26 mm , SD 0.17 ; st and ard 0.27 mm , SD 0.2 ; p = 0.83 ) . There was , however , a significant difference ( p = 0.012 ) in the mean wear rate ( highly cross-linked polyethylene 0.03 mm/yr , SD 0.06 ; st and ard 0.07 mm/yr , SD 0.05 ) . Creep and wear occurred in significantly different directions ( p = 0.01 ) ; creep was predominantly proximal whereas wear was anterior , proximal and medial . We conclude that penetration in the first six months is creep-dominated , but after one year virtually all penetration is due to wear . Highly cross-linked polyethylene has a 60 % lower rate of wear than st and ard polyethylene and therefore will probably perform better in the long term",
"Ceramic-on-ceramic coupling is thought to be a durable alternative to metal- or alumina-on-polyethylene pairing . No evidence exists suggesting superior clinical and radiological results for hydroxyapatite-coated stems versus uncoated stems . The aim of this study is to report the performance of an alumina-on-alumina bearing cementless total hip arthroplasty and to compare stems with a tapered design with and without hydroxyapatite coating . We prospect ively analysed the results of cementless tapered femoral stems ( 40 hydroxyapatite-coated versus 22 uncoated stems ) , a metal-backed fibre mesh hydroxyapatite-coated socket and alumina-on-alumina pairing . Of 75 hips studied , 62 were available for follow-up ( mean of 10.5 years after surgery ) . The average Harris hip score was 90 . Only one hydroxyapatite-coated stem was revised for aseptic loosening . One instance of non-progressive osteolysis was detected around a screw of a cup . All other components showed radiographic signs of stable ingrowth . Hydroxyapatite coating of the stem had no significant impact on the clinical or radiological results . Total hip arthroplasty with the presented implant and pairing provides a durable st and ard for all patients requiring hip joint replacement against which all newer generations of cementless implants should be judged",
"AIM In this prospect i ve r and omised study , the influence of different bearing material s on migration and wear was measured and their effect on the function of the artificial joint and the patient outcome was investigated . Mid-term results were recorded so that recommendations can be made on the use of certain bearings , which minimise wear and thus the danger of subsequent aseptic loosening . METHOD Sixty-six patients met the inclusion criteria and were willing to take part in the study . These patients were r and omised to 2 groups . All of them had total hip arthroplasty with implantation of a cementless Bicontact stem and Plasmacup using a cementless press-fit technique . Thirty-five of these patients were given a ceramic-ceramic bearing and 31 patients a ceramic-polyethylene bearing ( gamma sterilised/nitrogen environment ) . At the most recent follow-up , they underwent detailed clinical and radiological examination and evaluation by means of the Harris Hip Score , Hannover function question naire and single-film X-ray analysis ( EBRA ) . RESULTS The overall follow-up rate was 65.2 % ( 43 of 66 ) and the mean follow-up period was 8.1 ( 7.1 - 9.2 ) years . The median Harris Hip Score at the time of follow-up was 90.1 ( 58.7 - 99.9 ) points . The average Hannover function score was 87.14 % ( 63.9 - 100 ) . In 4 of 66 cases ( 6.1 % ) there was a tendency for the Plasmacup to subsidence in the first postoperative months that was slight but detectable by EBRA ; however , this stopped subsequently . This primary subsidence was independent of the chosen bearing material . No significant difference in the clinical and radiological parameters was found between the two groups . CONCLUSION The very good results with regard to the rate of loosening confirm the press-fit cup fixation concept . The study shows a similar medium-term result for the ceramic-ceramic and ceramic-polyethylene bearing so that use of both bearings can continue to be recommended . Only long-term studies with sufficiently large numbers of patients will be able to show whether significant differences can be detected between the two slide bearings with regard to wear and migration behaviour and so that a recommendation can be given to the surgeon",
"The higher failure rate of total hip arthroplasty ( THA ) in young , active patients remains a challenge for surgeons . Recently , larger-diameter femoral heads combined with an alumina matrix composite ceramic ( BIOLOX Delta ; CeramTec AG , Plochingen , Germany ) articulation was developed to improve implant longevity and meet patients ' activity dem and s while reducing the risk of component-related complications . The purpose of this study was to determine whether this new device may provide advantages for young , active patients . A prospect i ve , r and omized , controlled trial was conducted on 93 patients ( 113 THAs ) with more than 3 years of follow-up . Patients were r and omly divided into a study group ( 51 THAs ) with a 36-mm Delta ceramic-on-ceramic ( COC ) articulation and a control group ( 62 THAs ) with a common-sized alumina ceramic head on polyethylene liner ( COP ) articulation . Clinical and radiographic results were collected to compare the outcomes and complications , including implant-related failures , osteolysis , and noises . The large-diameter Delta COC articulation provided greater range of motion improvement ( 6.1 ° more ) , similar Harris Hip Scores , and similar complication rates compared with the alumina COP articulation . This study suggests that in the short term , the large-diameter Delta COC articulation results in better range of motion with no higher complication rates ; however , mid-term ( 8 - 10 years ) or longer follow-up is necessary to determine its superiority in young , active patients",
"Polyethylene wear and associated osteolysis are major limitations to the long-term success of total hip arthroplasty . In vitro laboratory studies suggest polyethylene wear in THA may be substantially reduced with ceramic femoral heads . We evaluated the potential value of zirconia ceramic on conventional polyethylene as an “ alternative bearing ” for total hip arthroplasty in a prospect i ve , r and omized clinical trial in comparison with femoral heads made of Co-Cr-Mo . Patients were evaluated with st and ardized clinical outcome instruments , and measurement of head penetration was performed with computerized wear measurement software . Study enrollment was halted because of a recall of the zirconia heads . At that time , 30 total hip arthroplasties with Co-Cr-Mo heads and 30 total hip arthroplasties with zirconia heads had been performed . Mean followup was similar for both groups ( Co-Cr-Mo = 51.7 months ; zirconia = 51.2 months ) . The mean annual head penetration rate was low and similar for both groups ( Co-Cr-Mo = 0.060 mm/year ; and zirconia = 0.055 mm/year ) . In view of the recently reported potential for zirconia ceramics to undergo monoclinic phase transformation in vivo , with result ant increased fracture risk and degradation of wear properties , we do not recommend use of zirconia femoral heads as an “ alternative bearing ” for total hip arthroplasty . Level of Evidence : Level II , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence",
"The purpose of the investigation was to assess the clinical and radiographic outcomes in four bearing surfaces . Eighty patients ( 91 hips ) undergoing total hip arthroplasty between 2004 and 2007 were r and omized to one of four bearing surfaces : ( 1 ) cobalt-chrome ( CoCr ) and ultra-high molecular weight polyethylene ( UHMWPE ) ; ( 2 ) CoCr and XLPE ; ( 3 ) Oxinium and UHMWPE ; and ( 4 ) Oxinium and XLPE . The mean follow-up for this study was 6.8 years . There were no significant differences in clinical outcomes . The linear wear rates for the four groups were 0.241 mm/year , 0.076 mm/year , 0.238 mm/year and 0.061 mm/year respectively . HXLPE results in significantly less wear than UHMWPE . However , we found no significant reduction in wear rate by using Oxinium in place of CoCr femoral heads at early follow-up",
"This study determined how ceramic-on-ceramic bearing THA affected joint-specific pain , function and stiffness in the first five postoperative years compared with ceramic-on-highly-crosslinked-polyethylene bearing THA . Subjects less than 61 years of age were r and omized to ceramic-on-ceramic ( CERAMIC ) [ n = 48 ] or ceramic-on-highly-crosslinked-polyethylene ( POLYETHYLENE ) [ n = 44 ] bearing THA . Subjects were assessed using the Western Ontario McMaster Osteoarthritis Index ( WOMAC ) and the R AND 12-Item Health Survey ( R AND -12 ) preoperatively , and at one and five years postoperatively . 92 subjects(50 ( 54 % ) males ; average age = 52 ( SD 6.6 ) years ) were enrolled . 78 ( 85 % ) subjects returned five years postoperatively . All subjects reported improvements at one and five years in all measured indices with no group differences detected . Seven ( 8 % ) subjects experienced postoperative THA complications , none related to bearing surfaces ; two subjects ( POLYETHYLENE ) required revision for instability . Both bearing surfaces provided excellent short-term results in younger subjects",
"The ideal bearing surface for young patients undergoing total hip replacement ( THR ) remains controversial . We report the five-year results of a r and omised controlled trial comparing the clinical and radiological outcomes of 102 THRs in 91 patients who were These patients were r and omised to receive a cobalt-chrome on ultra-high-molecular-weight polyethylene , cobalt-chrome on highly cross-linked polyethylene , or a ceramic-on-ceramic bearing . In all , 97 hip replacements in 87 patients were available for review at five years . Two hips had been revised , one for infection and one for peri-prosthetic fracture . At the final follow-up there were no significant differences between the groups for the mean Western Ontario and McMaster Universities osteoarthritis index ( pain , p = 0.543 ; function , p = 0.10 ; stiffness , p = 0.99 ) , Short Form-12 ( physical component , p = 0.878 ; mental component , p = 0.818 ) or Harris hip scores ( p = 0.22 ) . Radiological outcomes revealed no significant wear in the ceramic group . Comparison of st and ard and highly cross-linked polyethylene , however , revealed an almost threefold difference in the mean annual linear wear rates ( 0.151 mm/year versus 0.059 mm/year , respectively ) ( p < 0.001 )",
"Background Polyethylene ( PE ) wear particles are believed to cause aseptic loosening and thereby impair function in hip arthroplasty . Highly crosslinked polyethylene ( XLPE ) has low short- and medium-term wear rates . However , the long-term wear characteristics are unknown and it is unclear whether reduced wear particle burden improves function and survival of cemented hip arthroplasty . Questions / purpose sWe asked whether XLPE wear rates remain low up to 10 years and whether this leads to improved implant fixation , periprosthetic bone quality , and clinical function compared to conventional PE . Methods We r and omized 60 patients ( 61 hips ) to receive either PE or XLPE cemented cups combined with a cemented stem . At 10 years postoperatively , 51 patients ( 52 hips ) were evaluated for polyethylene wear and component migration estimation by radiostereometry , for radiolucent lines , bone densitometry , and Harris hip and pain scores . Revisions were recorded . Results XLPE cups had a lower mean three-dimensional wear rate between 2 and 10 years compared to conventional PE hips : 0.005 mm/year versus 0.056 mm/year . We found no differences in cup migration , bone mineral density , radiolucencies , functional scores , and revision rate . There was a trend toward improved stem fixation in the XLPE group . The overall stem failure rate was comparably high , without influencing wear rate in XLPE hips . Conclusions XLPE displayed a low wear rate up to 10 years when used in cemented THA , but we found no clear benefits in any other parameters . Further research is needed to determine whether cemented THA design s with XLPE are less prone to stem loosening . Level of Evidence Level I , therapeutic study . See the Instructions for Authors for a complete description of levels of evidence",
" Between 1999 and 2001 , 90 patients underwent total hip replacement using the same uncemented acetabular and femoral components with a 28 mm metallic femoral head but with prospect i ve r and omisation of the acetabular liner to either Durasul highly cross-linked polyethylene or nitrogen-sterilised Sulene polyethylene . We assessed 83 patients at a minimum follow-up of ten years . Linear penetration of the femoral head was estimated at six weeks , six and 12 months and annually thereafter , using the Dorr method , given the non-spherical shape of the acetabular component . There was no loosening of any component ; only one hip in the Sulene group showed proximal femoral osteolysis . The mean penetration of the femoral head at six weeks was 0.08 mm ( 0.02 to 0.15 ) for the Durasul group and 0.16 mm ( 0.05 to 0.28 ) for the Sulene group ( p = 0.001 ) . The mean yearly linear penetration was 64.8 % lower for the Durasul group at 0.05 mm/year ( sd 0.035 ) for the Sulene group and 0.02 mm/year ( sd 0.016 ) for the Durasul ( p Mean linear femoral head penetration at ten years was 61 % less in the Durasul than Sulene group . Highly cross-linked polyethylene gives excellent results at ten years",
"Although the published studies on the outcomes of total hip arthroplasty ( THA ) performed with currently available ceramic components show high survivorship and low bearing wear at midterm followup , concern over ceramic fracture and squeaking persist . For these reasons , the use of ceramic is limited . Recently , a new alumina matrix composite material ( Delta ceramic ) with improved material properties was developed to address these concerns . We report the early outcomes and complications of a prospect i ve , r and omized , multicenter trial of 263 patients ( 264 hips ) at eight centers , comparing a Delta ceramic-on-ceramic ( COC ) articulation with a Delta ceramic head-crosslinked polyethylene bearing combination ( COP ) . There were 177 COC hips and 87 COP hips . Complications were reported for all patients , whereas clinical and radiographic results were provided for the 233 patients with minimum 2-year followup ( average , 31.2 months ; range , 21–49 months ) . The Harris hip scores and clinical , radiographic , and survivorship outcomes were similar in both groups . There were four ( 2 % ) revisions in the COC group and two ( 2 % ) in the COP group . We encountered three intraoperative ceramic liner-related events . In addition , one patient receiving the COC underwent revision for chipping of the ceramic liner , and a second had ceramic fragmentation on followup radiographs but has not undergone revision . These liner related complications remain a concern . No patient reported squeaking in either group ; this leaves us hopeful the new material will lessen the frequency of squeaking . In the short term , the Delta COC articulation provided similar functional scores and survivorship and complication rates with the ceramic head mated with crosslinked polyethylene . Level of Evidence : Level I , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence",
"We investigated the efficacy of combining highly cross-linked polyethylene with ceramic heads on further reduction in polyethylene wear compared with the combination with cobalt-chromium heads via PolyWare computer-assisted method . A prospect i ve cohort study was performed on 102 cementless total hip arthroplasties using Longevity ( Zimmer , Warsaw , Ind ) highly cross-linked polyethylene liners . Either 26-mm zirconia heads or 26-mm cobalt-chromium heads were r and omly used in 51 hips each . At a mean follow-up of 6.7 years , no significant differences were identified between the groups for total penetration rate and steady-state wear rate . Osteolysis was not observed in any hips in either group . In conclusion , no advantage was seen for the 26-mm zirconia head compared with the 26-mm cobalt-chromium head in this period",
"Abstract Ceramic-on-ceramic bearings in THA are a popular alternative to overcome wear concerns in traditional metal-polyethylene bearings . However , squeaking is a potentially worrisome phenomenon in ceramic-on-ceramic THAs which we observed in some of our patients . We review ed all 42 patients who underwent 43 ceramic-on-ceramic noncemented THAs during the time of the study . Squeaking , defined as a reproducible sound of squeaking , clicking , or grating , occurred in nine of 43 implants ( 20.9 % ) . St and ard radiographs were normal . We used CT imaging to determine cup anteversion and inclination angles , comparing the squeaking hips with those of a r and omly selected control group , but found no differences . We then hypothesized specific design features ( stem size , cup size , head size , and neck length of the head ) would be risk factors for squeaking . We found a difference in neck length between squeaking and nonsqueaking implants . A neck length of −4 mm or shorter result ed in a relative risk of 5.56 ( 95 % confidence interval , 1.14–27.01 ) for squeaking . We found a high incidence of squeaking in our population , and we believe this phenomenon is an underreported side effect of these types of bearings . A short neck length of the femoral implant was a risk factor for squeaking in ceramic-on-ceramic THA . Level of Evidence : Level III , therapeutic study",
"The purpose of this study was to compare highly cross-linked polyethylene wear between the zirconia head and the cobalt-chromium head in Japanese patients . A prospect i ve , r and omized study was performed to evaluate the outcomes in 32 hips that had zirconia heads and in 30 hips that had cobalt-chromium heads . The mean follow-up periods of both groups were same ( 5 years ) . There were no significant differences between the zirconia head and the cobalt-chromium head in the mean polyethylene linear wear per year and the mean volumetric polyethylene wear per year in the steady phase . This study indicates that zirconia head offers no benefits over metal head in terms of wear reduction at 5 years in Japanese patients who have lightweight and thin polyethylene liners",
"BACKGROUND A ceramic femoral head is an alternative to a metal femoral head for the bearing surface of total hip arthroplasty . The purpose of this study was to compare polyethylene wear in patients who had undergone bilateral total hip arthroplasty with implants that differed only with regard to the material used for the femoral head : a zirconia head was used on one side , and a cobalt-chromium head was inserted on the contralateral side . METHODS A prospect i ve , r and omized study was performed to evaluate the outcomes in fifty-two patients who had undergone sequential bilateral primary total hip replacement . A zirconia head was used in one hip , and a cobalt-chromium head was used in the other . There were forty-eight men and four women ; the mean age at the time of surgery was 44.2 years . The mean duration of follow-up was 7.1 years . Clinical and radiographic evaluations were performed preoperatively and at six weeks ; three , six , and twelve months ; and yearly postoperatively . Linear wear of the polyethylene liner was measured radiographically . Two femoral components with a zirconia head had aseptic loosening and were revised . The explanted heads were evaluated with use of interferometry , environmental scanning electron microscopy , and x-ray diffraction studies . RESULTS The mean polyethylene wear rate was 0.08 mm/yr in association with the zirconia heads and 0.17 mm/yr in association with the cobalt-chromium heads ( p = 0.004 ) . The mean amount of volumetric polyethylene wear was 350.8 mm3 in association with the zirconia heads and 744.7 mm3 in association with the cobalt-chromium heads ( p = 0.004 ) . With regard to surface roughness , the Ra values of the two explanted zirconia heads were 15.87 and 17.35 nm and the Rpm values were 153.86 and 156.18 nm . Two identical zirconia heads that had not been implanted had Ra values of 5.31 and 5.48 nm and Rpm values of 65.27 and 66.35 nm . Four unimplanted cobalt-chromium heads that were identical to the ones implanted in this study had Ra values ranging between 25 and 50 nm and Rpm values ranging between 262.6 and 525.2 nm . Little phase transformation was noted in the two revised zirconia heads . CONCLUSIONS The mean amount and rate of polyethylene wear were significantly lower in the hips with a zirconia head than they were in the hips with a cobalt-chromium head , presumably because the zirconia heads had a smoother articulating surface",
"We conducted a prospect i ve single-blinded r and omised controlled trial to compare the functional and quality of life outcomes in two groups of patients between 60 and 80 years of age undergoing THR ; the first receiving a small head ( 28–32 mm ) metal on polyethylene ( MoP ) articulation , and the second receiving a large head ( 44–54 mm ) metal on metal ( MoM ) articulation . We recruited 49 patients and r and omised them into one of the two groups ( 22 MoP and 27 MoM ) . The results demonstrated no statistical difference in any of the assessed functional outcomes at any follow-up point ( p>0.05 ) . There were no dislocations or revisions in either group . Although it has been suggested that large head MoM articulations in THA offer superior stability and function , our results suggest that small head MoP articulations can achieve comparable ROM , function and quality of life at short-term follow-up"
] |
4116bdd4-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND Iron deficiency and iron deficiency anaemia ( IDA ) are common in young children . It has been suggested that the lack of iron may have deleterious effects on children 's psychomotor development and cognitive function . To evaluate the benefits of iron therapy on psychomotor development and cognitive function in children with IDA , a Cochrane review was carried out in 2001 . This is an up date of that review . OBJECTIVES To determine the effects of iron therapy on psychomotor development and cognitive function in iron deficient anaemic children less than three years of age . SEARCH METHODS We search ed the following data bases in April 2013 : Cochrane Central Register of Controlled Trials ( CENTRAL ) , MEDLINE , EMBASE , CINAHL , PsycINFO , LILACS , Clinical Trials.gov and World Health Organization International Clinical Trials Registry Platform ( ICTRP ) . We also search ed the reference lists of review articles and reports , and ran citation search es in the Science Citation Index for relevant studies identified by the primary search . We also contacted key authors . SELECTION CRITERIA Studies were included if children less than three years of age with evidence of IDA were r and omly allocated to iron or iron plus vitamin C versus a placebo or vitamin C alone , and assessment of developmental status or cognitive function was carried out using st and ardised tests by observers blind to treatment allocation . DATA COLLECTION AND ANALYSIS Two review authors independently screened titles and abstract s retrieved from the search es and assessed full-text copies of all potentially relevant studies against the inclusion criteria . The same review authors independently extracted data and assessed the risk of bias of the eligible studies . Data were analysed separately depending on whether assessment s were performed within one month of beginning iron therapy or after one month . MAIN RESULTS We identified one eligible study in the up date search that had not been included in the original review . In total , we included eight trials . Six trials , including 225 children with IDA , examined the effects of iron therapy on measures of psychomotor development and cognitive function within 30 days of commencement of therapy . We could pool data from five trials . The pooled difference in pre- to post-treatment change in Bayley Scale Psychomotor Development Index ( PDI ) between iron and placebo groups was -1.25 ( 95 % confidence interval ( CI ) -4.56 to 2.06 , P value = 0.65 ; I(2 ) = 33 % for heterogeneity , r and om-effects meta- analysis ; low quality evidence ) and in Bayley Scale Mental Development Index ( MDI ) was 1.04 ( 95 % CI -1.30 to 3.39 , P value = 0.79 ; I(2 ) = 31 % for heterogeneity , r and om-effects meta- analysis ; low quality evidence ) .Two studies , including 160 r and omised children with IDA , examined the effects of iron therapy on measures of psychomotor development and cognitive function more than 30 days after commencement of therapy . One of the studies reported the mean number of skills gained after two months of iron therapy using the Denver Developmental Screening Test . The intervention group gained 0.8 ( 95 % CI -0.18 to 1.78 , P value = 0.11 , moderate quality of evidence ) more skills on average than the control group . The other study reported that the difference in pre- to post-treatment change in Bayley Scale PDI between iron-treated and placebo groups after four months was 18.40 ( 95 % CI 10.16 to 26.64 , P value Bayley Scale MDI was 18.80 ( 95 % CI 10.17 to 27.43 , P value iron treatment of young children with IDA has an effect on psychomotor development or cognitive function within 30 days after commencement of therapy . The effect of longer-term treatment remains unclear . There is an urgent need for further large r and omised controlled trials with long-term follow-up
|
[
"OBJECTIVE To determine whether extended oral iron therapy corrects lower developmental test scores in infants with iron-deficiency anemia . STUDY DESIGN Double-blind , controlled trial in Costa Rica involving 32 12- to 23-month-old infants with iron-deficiency anemia and 54 nonanemic control subjects . Anemic infants were treated with orally administered iron for 6 months ; half the nonanemic children were treated with iron and half with placebo . Developmental test scores and hematologic status were evaluated before treatment , after 3 months , and after 6 months . RESULTS Iron-deficient anemic infants received lower mental test scores than nonanemic infants at all three time points ( p motor test scores . More of the anemic infants were rated as unusually tearful and unhappy . Anemic infants came from families with lower maternal education and less support for child development and were less likely to be breast fed , were weaned earlier , and consumed more cow milk . CONCLUSIONS Lower mental test scores persisted in infants with iron-deficiency anemia despite extended oral iron therapy and an excellent hematologic response . Iron-deficiency anemia may serve as a marker for a variety of nutritional and family disadvantages that may adversely affect infant development",
"To assess the effects of iron therapy on developmental test scores in infants with iron deficiency anemia , 68 Guatemalan babies 6 to 24 months of age , with and without mild iron deficiency anemia , were tested with the Bayley Scales of Infant Development before and after one week of oral iron treatment . The two major findings of the study were developmental deficits in the anemic group prior to treatment , and lack of rapid improvement with short-term oral iron therapy . The mean pretreatment Mental Development Index of the anemic group was significantly lower than that of nonanemic infants . The anemic group 's pretreatment Psychomotor Development Index was also lower than that of the nonanemic control group . In a double-blind r and omized study , six to eight days of oral iron therapy did not reverse these deficits . Consequently , the deficits of the anemic group can not be unequivocably attributed to iron lack . However , no significant differences were found between anemic and nonanemic groups in birth histories , socioeconomic level , or general nutritional status which might otherwise explain the lower developmental test scores of the anemic babies ",
"Iron deficiency anemia has long been thought to have effects on the central nervous system ( CNS ) . Finding direct evidence of this in human infants , however , has been challenging . Auditory brainstem responses ( ABRs ) provide a noninvasive means of examining an aspect of the CNS that is rapidly maturing during the age period when iron deficiency is most common . ABRs represent the progressive activation of the auditory pathway from the acoustic nerve ( wave I ) to the lateral lemniscus ( wave V ) . The central conduction time ( CCT , or wave I-V interpeak latency ) is considered an index of CNS development because myelination of nerve fibers and maturation of synaptic relays lead to an exponential reduction in the CCT from birth to 24 mo . In 55 otherwise healthy , 6-mo-old Chilean infants ( 29 with iron deficiency anemia and 26 nonanemic control infants ) , the CCT was longer in those who had been anemic at 6 mo , with differences becoming more pronounced at 12- and 18-mo follow-ups despite effective iron therapy . The pattern of results --differences in latencies but not amplitudes , more effects on the late ABR components ( waves III and V ) , and longer CCTs ( as an overall measure of nerve conduction velocity)--suggested altered myelination as a promising explanation , consistent with recent laboratory work documenting iron 's essential role in myelin formation and maintenance . This study shows that iron deficiency anemia in 6-mo-old infants is associated with adverse effects on at least one aspect of CNS development and suggests the fruitfulness of study ing other processes that are rapidly myelinating during the first 2 y of life",
"The behavioral effects of iron deficiency and its treatment were evaluated in a double-blind r and omized controlled community-based study of 191 Costa Rican infants , 12 to 23 months of age , with various degrees of iron deficiency . The Bayley Scales of Infant Development were administered before and both 1 week and 3 months after IM or oral administration of iron . Appropriate placebo-treated control infants were also tested . Infants with iron deficiency anemia showed significantly lower mental and motor test scores , even after considering factors relating to birth , nutrition , family background , parental IQ , and the home environment . After 1 week , neither IM nor oral iron treatments differed from placebo treatment in effects on scores . After 3 months , lower mental and motor test scores were no longer observed among iron-deficient anemic infants whose anemia and iron deficiency were both corrected ( 36 % ) . However , significantly lower mental and motor test scores persisted among the majority of initially anemic infants ( 64 % ) who had more severe or chronic iron deficiency . Although no longer anemic , they still showed biochemical evidence of iron deficiency after 3 months of treatment . These persistent lower scores suggest either that iron therapy adequate for correcting anemia is insufficient to reverse behavioral and developmental disturbances in many infants or that certain ill effects are long-lasting , depending on the timing , severity , or chronicity of iron deficiency anemia in infancy",
"Abstract Objective : To measure the effects of iron supplementation and anthelmintic treatment on iron status , anaemia , growth , morbidity , and development of children aged 6–59 months . Design : Double blind , placebo controlled r and omised factorial trial of iron supplementation and anthelmintic treatment . Setting : Community in Pemba Isl and , Zanzibar . Participants : 614 preschool children aged 6–59 months . Main outcome measures : Development of language and motor skills assessed by parental interview before and after treatment in age appropriate subgroups . Results : Before intervention , anaemia was prevalent and severe , and geohelminth infections were prevalent and light — Plasmodium falciparum infection was nearly universal . Iron supplementation significantly improved iron status , but not haemoglobin status . Iron supplementation improved language development by 0.8 ( 95 % confidence interval 0.2 to 1.4 ) points on the 20 point scale . Iron supplementation also improved motor development , but this effect was modified by baseline haemoglobin concentrations ( P=0.015 for interaction term ) and was apparent only in children with baseline haemoglobin concentrations iron treatment increased scores by 1.1 ( 0.1 to 2.1 ) points on the 18 point motor scale . Mebendazole significantly reduced the number and severity of infections caused by Ascaris lumbricoides and Trichuris trichiura , but not by hookworms . Mebendazole increased development scores by 0.4 ( −0.3 to 1.1 ) points on the motor scale and 0.3 ( −0.3 to 0.9 ) points on the language scale . Conclusions : Iron supplementation improved motor and language development of preschool children in rural Africa . The effects of iron on motor development were limited to children with more severe anaemia ( baseline haemoglobin concentration . Mebendazole had a positive effect on motor and language development , but this was not statistically significant . What is already known on this topic Iron is needed for development and functioning of the human brain Anaemic children show developmental delays , but it is not yet clear whether iron deficiency causes these deficits or whether iron supplementation can reverse them Helminth infections in schoolchildren are associated with cognitive deficits , but few studies have been made of helminth infection and early child development What this study adds Low doses of oral iron supplementation given daily improved language development in children aged 1–4 years in Zanzibar Iron supplementation improved motor development , but only in children with initial haemoglobin concentrations below 90 g/l The effects of routine anthelmintic treatment on motor and language milestones were positive , but non-significant , with our sample",
"In a double-blind , placebo-control prospect i ve cohort study of 196 infants from birth to 15 months of age , assessment was made at 12 months of age of the relationship between iron status and psychomotor development , the effect of a short-term ( 10-day ) trial of oral iron vs placebo , and the effect of long-term ( 3 months ) oral iron therapy . Development was assessed with the mental and psychomotor indices and the infant behavior record of the Bayley Scales of Infant Development in 39 anemic , 30 control , and 127 nonanemic iron-deficient children . Anemic infants had significantly lower Mental and Psychomotor Developmental Index scores than control infants or nonanemic iron-deficient infants ( one-way analysis of variance , P less than .0001 ) . Control infants and nonanemic iron-deficient infants performed comparably . No difference was noted between the effect of oral administration of iron or placebo after 10 days or after 3 months of iron therapy . Among anemic infants a hemoglobin concentration less than 10.5 g/dL and duration of anemia of greater than 3 months were correlated with significantly lower motor and mental scores ( P less than .05 ) . Anemic infants failed specifically in language capabilities and body balance-coordination skills when compared with controls . These results , in a design in which intervening variables were closely controlled , suggest that when iron deficiency progresses to anemia , but not before , adverse influences in the performance of developmental tests appear and persist for at least 3 months despite correction of anemia with iron therapy . If these impairments prove to be long st and ing , prevention of iron deficiency anemia in early infancy becomes the only way to avoid them",
"Iron-deficient anaemic infants perform worse in tests of mental and motor development than do iron-sufficient infants of a comparable age . A r and omised , double-blind trial was done to monitor the effects of iron supplementation on performance in the Bayley scales of mental and motor development among 12 - 18-month-old infants in Indonesia . Iron-deficient anaemic infants ( n = 50 ) were assigned r and omly to receive dietary ferrous sulphate or placebo for 4 month . Similar treatment r and omisation was done among nonanaemic iron-deficient ( n = 29 ) and iron-sufficient ( n = 47 ) infants . Before intervention , the mean mental and motor scores of the iron-deficient anaemic infants were significantly ( p developmental delays were reversed among iron-deficient anaemic infants who had received iron but they remained the same among placebo-treated iron-deficient anaemic infants . Neither ferrous sulphate nor placebo had significant effects on the scores of the other two iron-status classes . The poor performance of 12 - 18-month-old iron-deficient anaemic infants in the Bayley scales of mental and motor development can be improved to the level of performance of iron-sufficient infants by treatment with ferrous sulphate",
"Eighteen- to 60-month-old iron-deficient anemic children given iron therapy ( n = 25 ) and a control group matched for mother 's educational level showed no significant difference in mean mental development score at baseline . The control group 's mean score was increased significantly over baseline score at 3 and 6 months and was significantly higher than the experimental group 's mean score at 3 months . Although the experimental group demonstrated hematologic correction over 6 months , mean mental development score showed no significant improvement . Scores for an iron deficient not anemic group given iron ( n = 22 ) , despite complete hematologic correction over the six months of observation , and for its control group , did not change significantly . Baseline scores for an iron-deficient not anemic placebo group ( n = 23 ) and for its control group were not significantly different . At 3 months the control group score had increased significantly , whereas that for the experimental group had not . When experimental and control subjects were matched on baseline mental development score , the control subjects experienced increases in scores over time , further confirming an impaired ability to improve scores with repeated testing in the experimental groups . Behavioral rating data ( responsiveness to examiner , responsiveness to environment , and emotional tone ) revealed significant differences between the iron-deficient anemic group and its control group at 3 and 6 months , with the control group rated more responsive , suggesting that iron deficiency , alone or in association with anemia , may have some lasting effect on behavior and development . Group differences were also found between the mean number of occurrences of multiple stressful events . Failure to show improvement in scores in the iron-deficient anemic group may reflect the fact that those children were less testable than were children in the control group , despite repeated testings , a theory supported by the infant behavior rating data . This may be related to some irreversible behavioral deficit or to an adverse environmental milieu ( e.g. , stress )",
"Previous work at this hospital and elsewhere has shown that anaemia in toddlers is common and is associated with psychomotor delay . It seemed unclear , however , whether this association was cause and effect or merely due to the same underprivileged environment . A double blind r and omised intervention study was , therefore , performed . After an initial assessment 97 children with anaemia ( haemoglobin 8 - 11 g/dl ) aged 17 - 19 months received either iron and vitamin C or vitamin C only ( control group ) for two months and were then reassessed . The children who received the iron had an increased rate of weight gain and more of them achieved the expected rate of development . While iron deficiency anaemia is unlikely to be the only factor in the slower development of children living in underprivileged circumstances , it can at least be easily identified and treated . Routine child health surveillance in such areas should include a haemoglobin determination",
"OBJECTIVE To determine the efficacy of iron-fortified infant formula in preventing developmental delays and abnormal behavior . DESIGN Double-blind , r and omized , controlled trial . SETTING Urban hospital clinic . PARTICIPANTS A total of 283 healthy , bottle-fed infants from very low income families . Children with prematurity , low birth weight , and major anomalies and those who had received more than 2 weeks of evaporated-milk feedings were excluded . The groups were similar for sociodemographic background variables . Fifty-eight infants ( 20.5 % ) dropped out before any outcome data were gathered ; 225 , 204 , 186 , and 154 remained at 6- , 9- , 12- , and 15-month assessment s , respectively . INTERVENTION Iron-fortified formula ( 12.8 mg iron per liter ) versus regular formula ( 1.1 mg iron per liter ) . MAIN OUTCOME MEASURES Iron status was measured on venous blood by determination of hemoglobin , serum iron and iron-binding capacity , serum ferritin , and free erythrocyte protoporphyrin values . The Bayley Scales of Infant Development ( mental and psychomotor indexes ) and two factors of the Infant Behavior Record ( test affect and task orientation ) were the outcomes of interest . RESULTS All measures of iron status were significantly different between groups ( p Psychomotor development patterns differed between groups ( F3,520 , 3.4 ; p = 0.02 ) with time . Mean values were similar at 6 months but differed at 9 and 12 months of age ( p Mental development and behavior were not affected . CONCLUSIONS Iron-fortified formula significantly reduced iron deficiency in a high-risk group of infants and prevented a decline in psychomotor development quotients . This effect may be transient , and its long-term significance needs further study",
"In a prospect i ve cohort study of 196 infants from birth to age 15 mo , the relationship of iron status to psychomotor development , the effect of a short-term trial of oral iron or placebo , and the effect of longer-term oral iron therapy was assessed . Development was assessed with the Bayley Scale of Infant Development in anemic , nonanemic , iron-deficient , and control children . Anemic infants had significantly lower indices than did control or nonanemic , iron-deficient infants . Control infants and nonanemic , iron-deficient infants performed comparably . No difference between the effect of oral administration of iron or placebo was noted after 10 d or 3 mo of iron therapy . A hemoglobin concentration of less than 105 g/L and anemia duration greater than 3 mo were correlated with significantly lower motor and mental scores , suggesting that when iron deficiency progresses to anemia , adverse influences in the performance of developmental tests appear and persist , despite iron therapy"
] |
4116be1a-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND Median parapatellar approach is the most used for total knee arthroplasty ( TKA ) . With the advent of enhanced recovery and shorter length of hospital stay , there is an increasing pressure on surgeons to perform surgery through smaller incisions . Minimally invasive ( MIS ) TKA allows earlier functional recovery ; it is not clear if this is associated with more complications . It is also unclear if computer-assisted minimally invasive ( MIS CA ) TKA has any affect on improving patient outcomes . We performed a systematic review and meta- analysis comparing MIS CA vs MIS TKA . METHODS We performed an extensive literature search including both r and omized controlled studies and prospect i ve cohort studies . All data reported on component alignment , surgical time , complications , knee flexion , and postoperative functional knee scores were included for analysis . RESULTS Ten studies were suitable for inclusion result ing in 490 patients with MIS CA and 503 MIS patients . There was no significant difference in the outliers on complications , knee flexion , and postoperative functional scores . Coronal plane tibial component showed statistically significant number of outliers in the MIS group demonstrating superior component positioning in the MIS CA group . Operative time was significantly longer in the MIS CA group with a mean increase of 32 minutes . CONCLUSIONS Computer-assisted minimally invasive TKA is superior than the st and ard MIS TKA in terms of component positioning ; however , it is unclear if this will have any long-term clinical implication s. The increased operative time , although clinical ly relevant , does not appear to be associated with an increase in complications
|
[
"Abstract Introduction Up to now , no prospect i ve , r and omized comparisons between minimal invasive and computer-assisted total knee arthroplasty ( MICA-TKA ) , and minimal invasive technique ( MI-TKA ) has been documented to evaluate not only clinical , but also radiologic results of the MICA-TKA . This prospect i ve , r and omized study was performed to compare the short-term results of MICA-TKA with minimal invasive technique MI-TKA for 6-month follow-up . Patients and methods We reported the clinical and radiological results of 80 subjects who had cruciate-substituting , TKA-implanted primary total knee arthroplasties using either minimal invasive and computer-assisted technique ( 40 patients Group I ) or minimal invasive technique ( 40 patients , Group II ) . Tourniquet time , length of skin incision , and total blood loss were compared . Knee society scores ( KSSs ) , knee society functional scores ( KSFSs ) , range of motion ( ROM ) , and radiographic results were assessed and reported preoperatively and at 6-month follow-up . Results The accuracy of the implantations in relation to the coronal mechanical axis in Group I was superior to that of Group II ( P femoral rotational profile revealed the prosthesis in Group I that was implanted with significantly less internal rotation than in Group II . The average blood loss in patients of Group I was significantly reduced as compared to patients of Group II . No significant difference was detected in terms of tourniquet time or length of skin incision . Clinical results , with regard to ROMs and KSSs , as well as KSFSs were equally good in both the groups . Conclusions Better alignment and similarity of good clinical results at short-term follow-up may provide subjects who receive MICA-TKA with long-term endurance of their implants . Further studies on longer-term outcomes and functional improvements are required to vali date these possibilities",
"Several choices of instrument systems are available for minimally invasive surgical approaches . There are reports that one alternative , the quadriceps sparing , side-cutting instrumentation , results in diminished implantation accuracy . A total of 108 patients were r and omized to undergo TKA either using side-cutting implant instrumentation ( Group A ) or anterior – posterior mini-incision instrumentation ( Group B ) . All TKAs were operated on with a minimal invasive , mini-midvastus surgical approach . 50 % of the TKAs were performed with computer-assistance in each cohort . The radiographic parameters , clinical outcomes and knee scores were evaluated preoperatively and 3 months postoperative . In Group B , we found significantly higher accuracy for the mechanical axis of the limb ( range ±3 ° : Group A 54 % versus Group B 89 % , p = 0.001 ) , medial proximal tibial angle ( range ±3 ° : Group A 85 % versus Group B 98 % , p = 0.027 ) and tibial slope ( range ±3 ° : Group A 59 % versus Group B 85 % , p = 3 ° ) in Group B. Clinical outcomes and knee scores were similar in both groups and were not influenced by computer-assistance . Using the anterior – posterior , mini-incision instruments for minimally invasive TKA will lead to higher implantation accuracy when compared to the quadriceps sparing side-cutting instrumentation . The navigation technique could not compensate for shortcomings of the side-cutting instrumentation . The clinical relevance of this study is that the quadriceps sparing side-cutting instrumentation should not be used for TKA because of unacceptable reduced implantation accuracy ",
"Background A combination of two emerging technologies , computer-assisted navigation and minimally invasive surgery , in total knee arthroplasty has gained increasing interests from orthopedic surgeons around the world . To date , there has never been any midterm study for clinical and radiographic outcomes from using an electromagnetic computer-assisted navigation system . In this study , we aim ed to systematic ally compare clinical and radiographic outcomes of minimally invasive surgery in total knee arthroplasty ( MIS-TKA ) performed with and without electromagnetic computer-assisted navigation at immediate and midterm follow-ups . Methods A total of 151 patients ( 160 knees ) who underwent MIS-TKA were r and omized to be operated with electromagnetic computer-assisted navigation ( group I : 75 patients , 80 knees ) or without the navigation ( group II : 76 patients , 80 knees ) . The clinical and radiographic outcomes of immediate , 6-week postoperative follow-up and average 6.1-year follow-up were compared . Results On immediate , 6-week postoperative follow-up , clinical and radiographic outcomes did not reveal any difference between the two groups except for the fact that the operative time was longer in the navigation group . On 6.1-year follow-up , a total of 58 patients ( 63 knees ) from group I and 58 patients ( 61 knees ) from group II were reevaluated . There were no significant differences in clinical and radiographic loosening and in complications between the two groups . Conclusion In this study , no significant differences of clinical and radiographic outcomes were found for immediate and midterm follow-ups of MIS-TKA performed with and without electromagnetic computer-assisted navigation except for the additional operating time in the navigation group",
"BACKGROUND Both Minimally Invasive surgery ( MIS ) and Computer-Assisted Surgery ( CAS ) are useful in Total Knee Arthroplasty ( TKA ) . Minimally invasive total knee arthroplasty was associated with decreased blood loss , shorter hospital stays , and increased range of motion . Computer-assisted surgery in total knee arthroplasty was developed to improve the positioning of implants during surgery . OBJECTIVE To evaluate radiographic results relative to component position and limb alignment when using a navigation system compared with conventional technique in MIS-TKA . MATERIAL AND METHOD A prospect i ve control study was performed in 180 patients who underwent total knee arthroplasty by one surgeon . All patients were r and omly divided into two groups , Conventional and Navigation TKA . Intra- , post-operative data , and postoperative limb alignment were recorded for comparison in both groups . RESULTS The postoperative mechanical axis was within 3 degrees of neutral mechanical alignment in 94 % of the navigation group and 87 % in conventional group ( p = 0.13 ) . Registration time of navigation group is 13.58 minutes . No statistical significant difference was found in tourniquet time and postoperative blood loss in both groups . CONCLUSION The use of navigation in total knee arthroplasty increases accuracy in limb and implants alignment , and does not increase complications and surgical times",
"The aim of this trial was to compare the radiological results of 74 patients undergoing a mini-invasive total knee replacement ( TKR ) using either a traditional alignment guide ( MIS group ) or a computer assisted alignment system ( MICA group ) . All the patients were prospect ively r and omised to either group and the same implant was used for both groups . At 8 months post-operatively , the frontal femoral component angle ( FFC ) , the frontal tibial component angle ( FTC ) , the hip-knee-ankle angle ( HKA ) and the sagittal orientation of components ( slopes ) were evaluated respectively . The slopes of the femoral component and the FTC angle were statistically better aligned in the MICA group ( p MICA group showed both a significant fewer number of outliners and a significant higher number of implants with all five radiological parameters ideally aligned . The operative time was statistically longer in the computer assisted group",
"A prospect i ve cohort study of 100 patients undergoing primary minimally invasive total knee arthroplasty was carried out to determine blood loss after this procedure and to examine the efficacy of navigation on blood saving . The patients were divided into two groups according to the surgical technique , and underwent either computer-assisted navigation or manual procedures . All operations were performed by a single surgeon using an identical approach . To minimize blood loss , an intraoperative tourniquet was used , but no postoperative drainage was applied . Although the mean surgical time was longer in the navigated group than in the manual group ( 119.2 vs. 90.9 min ; p reductions in hemoglobin level ( 1.40 vs. 1.38 g/dL ; p = 0.642 ) and calculated blood loss ( 470.77 vs. 482.73 mL ; p = 0.796 ) were similar in both groups . Four patients in both groups required blood transfusion . With minimally invasive techniques and drainage avoidance , our study suggests that the blood loss after minimally invasive total knee arthroplasty was not significantly affected by the use of imageless navigation",
"BACKGROUND There is little information on the feasibility of computer navigation when using a minimally invasive approach for total knee arthroplasty , during which the anatomic l and marks for registration may be obscured . The purpose of the present study was to determine the radiographic accuracy of this technique and to compare the rate of functional recovery between patients who underwent computer-assisted minimally invasive arthroplasty and those who underwent conventional total knee arthroplasty . METHODS One hundred and eight consecutive patients were r and omized to undergo computer-assisted minimally invasive total knee arthroplasty or conventional total knee arthroplasty . Perioperative pain management was st and ardized . The clinical parameters , long-leg radiographs , and functional assessment scores were evaluated for six months postoperatively . RESULTS Patients who underwent computer-assisted minimally invasive total knee arthroplasty had a significantly longer operative time ( by a mean of twenty-four minutes ) and a significantly shorter inpatient stay ( 3.3 compared with 4.5 days ) in comparison with those who underwent conventional arthroplasty ( p computer-assisted minimally invasive total knee arthroplasty group were able to walk independently for more than thirty minutes at one month ( p = 0.04 ) . The percentage of patients with a coronal tibiofemoral angle within + /-3 degrees of the ideal was 92 % for the computer-assisted minimally invasive total knee arthroplasty group , compared with 68 % for the conventional total knee arthroplasty group ( p = 0.003 ) . CONCLUSIONS Although specific clinical parameters reflect an early increased rate of functional recovery in association with computer-assisted minimally invasive total knee arthroplasty within the first postoperative month , the main advantage of this technique over conventional total knee arthroplasty is improved postoperative radiographic alignment without increased short-term complications"
] |
4116be60-06ff-11f0-808a-c43d1ab1c353
|
The aims of this systematic review are ( 1 ) to compare the prevalence of xerostomia and hyposalivation between patients taking antihypertensive drugs with a control group ( CG ) , ( 2 ) to compare salivary flow rate between patients treated with a CG , and ( 3 ) to identify which antihypertensives produce xerostomia . This systematic review was carried out according to the preferred reporting items for systematic review s and meta-analyses ( PRISMA ) guidelines . To evaluate method ological quality of the eligible studies Cochrane Collaboration tool for assessing the risk of bias for clinical trials and the modified Newcastle-Ottawa scale case-control studies were used . The data bases were search ed for studies up to November 19th 2019 . The search strategy yielded 6201 results and 13 publications were finally included ( five clinical trials and eight case-control studies ) . The results of the included studies did not provide evidence to state that patients taking antihypertensives suffer more xerostomia or hyposalivation than patients not taking them . With regard to salivary flow , only two clinical studies showed a significant decrease in salivary flow and even one showed a significant increase after treatment . The case-control studies showed great variability in salivary flow , but in this case most studies showed how salivary flow is lower in patients medicated with antihypertensive drugs . The great variability of antihypertensive drugs included , the types of studies and the outcomes collected made it impossible to study which antihypertensive drug produces more salivary alterations . The quality assessment showed how each of the studies was of low method ological quality . Therefore , future studies about this topic are necessary to confirm whether antihypertensive drugs produce salivary alterations
|
[
"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",
"Salivary flow and the influence of drugs on this were studied in subjects with borderline hypertension and in normotensive subjects . Saliva production at rest was lower in borderline hypertensive subjects than in normotensive subjects . Plasma catecholamine levels were similar in both groups of subjects studied . Intravenous injections of propranolol and phentolamine did not enhance saliva secretion in the borderline hypertensive group , whereas atropine caused the secretion to decrease in both groups . Intravenous infusions of neostigmine led to a dose-dependent increase of salivary flow . The dose-response curve for the stimulating effect of neostigmine on saliva production was shifted to the right in borderline hypertensive as compared with normotensive subjects . The results of the study support the assumption that in subjects with borderline hypertension parasympathetic influence on the salivary gl and s is reduced",
"Aim of this study was to evaluate the effect on saliva flow rate and composition and on perceived xerostomia . The study used a Latin square design , all subjects being once daily ( at 7.00 a.m. ) taking the bendroflumethiazide ( 2.5 mg ) , furosemide ( 40 mg ) , or placebo , in a r and omised order . Each treatment period of 7 days was separated by wash-out periods of 14 days . Unstimulated and paraffin chewing stimulated whole saliva , and 3 % citric acid stimulated parotid and subm and ibular-sublingual secretion were collected twice daily , at 7.30 a.m. , with the patients in a fasting condition ( morning values ) , and at 10.30 a.m. , about 2 h after intake of a st and ard breakfast ( lunchtime values ) , on day 0 ( baseline ) , day 1 ( acute treatment ) , and day 7 ( chronic treatment ) . Saliva flow rates were measured and all four secretions were analysed for the concentration of sodium , potassium , chloride , and total protein . Xerostomia was assessed by means of a Visual Analogue Scale . Statistical analysis used the Wilcoxon signed rank test . For flow rate , only that of subm and ibular-sublingual secretion was affected , significantly so in the morning during chronic treatment with both drugs . In resting whole saliva the output of both sodium and chloride tended to decrease especially during treatment with bendroflumethiazide , while in subm and ibular-sublingual secretion the output of all the electrolytes was decreased , especially for potassium and chloride and during treatment with furosemide . Further , xerostomia tended to increase during treatment with furosemide , statistically significant at lunchtime during chronic treatment . In conclusion , this study has demonstrated a modest effect on salivary flow rate and a more pronounced effect on saliva composition , especially in subm and ibular-sublingual secretion during treatment of healthy volunteers with therapeutic doses of two different diuretics , encouraging clinical studies in hypertensive patients and basic research as to the presence of a thiazide sensitive Na-Cl cotransporter in human salivary gl and"
] |
4116bea6-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND Fibromyalgia is a chronic disorder characterized by widespread muscular tenderness , pain , fatigue , and cognitive difficulties . Nonpharmacological treatment options , such as physical activity , are important for people with fibromyalgia . There are strong recommendations to support engagement in physical activity for symptom management among adults with fibromyalgia . Dance is a mode of physical activity that may allow individuals with fibromyalgia to improve their physical function , health , and well-being . Dance has the potential to promote improved pain processing while simultaneously providing the health and social benefits of engaging in physical activity that contributes to symptom management and overall function rehabilitation . However , we are unaware of current evidence on dance as a nonpharmacological/physical activity intervention for adults with fibromyalgia . OBJECTIVE The aims of this study were to underst and how dance is used therapeutically by individuals with fibromyalgia ; to examine the extent , range and nature of research activity in the area ; and to determine the value of undertaking a systematic review of interventions . METHODS We used and adapted the Arksey and O'Malley scoping framework . The search strategy involved a comprehensive search of main health and electronic social data bases , trial registries and grey literature without language limits . Pairs of review ers independently screened and extracted data and evaluated the method ological quality of r and omized control trials . RESULTS Twenty-one unique records for 13 studies met inclusion criteria ; the studies included mostly middle-aged women . Types of dance included were aerobic dance , belly dance , dance movement therapy , biodanza and Zumba . Intervention parameters were different among studies . Frequency varied between one to three times a week ; all were done in small group setting s. Studies evaluated a variety of outcomes in the symptoms , wellness , psychosocial , physical functioning , balance and fitness categories ; no studies evaluated the safety or adverse events systematic ally which is a major weakness of the literature . CONCLUSIONS There are few studies in the field of dance and fibromyalgia , suggesting research is in its infancy but slowly growing . They are of European and South American origin , focusing on female participants and a limited number of dance modes . Because the body of literature is small , of low quality and highly heterogeneous , we concluded that a systematic review of interventions on dance is not warranted at this time
|
[
"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 Exergames are a new form of rehabilitation that combine the characteristics of physical exercise and the benefits of non-immersive virtual reality ( VR ) . Effects of this novel therapy in women fibromyalgia are still unknown . The objective was to evaluate the effects of exergame-based intervention on mobility skills , balance and fear of falling in women with fibromyalgia . Methods This study was a r and omized controlled trial with concealed allocation . Seventy-six women with fibromyalgia were divided into two groups : the exercise group received an eight week intervention based on exergames , while the control group continued their usual activities . Mobility skills were evaluated using the timed up and go test , while balance was assessed using the functional reach test , and the CTSIB protocol . Fear of falling was evaluated on a scale of 0–100 ( 0 , no fear ; 100 , extreme fear ) . Measurements were performed before and after the intervention . A repeated- measures linear mixed model was used to compare the effects of the intervention between the two groups . Results The exercise group was significantly quicker than the control group in the timed up and go test ( MD , −0.71 ; 95 % CI [ −1.09–0.32 ] ; p improvements in functional reach and a reduced fear of falling ( MD , 4.34 ; 95 % CI [ 1.39–7.30 ] ; p = 0.005 and MD , −9.85 ; 95 % CI [ −0.19–−0.08 ] ; p = 0.048 , respectively ) . Discussion The improved TUG observed herein was better than the smallest real difference . Based on the results on mobility skills , balance and fear of falling , exergames may be an effective tool as a therapy for women with fibromyalgia",
"OBJECTIVE To evaluate the effects of an exergame-based intervention on a population sample of women with fibromyalgia . DESIGN Single-blinded , r and omized controlled trial with 8-week intervention . SETTING Fibromyalgia center . PARTICIPANTS Participants ( all women ) ( N=83 ) were divided into 2 groups : an exercise group ( n=42 ; mean age ± SD , 52.52±9.73y ) and a nonexercise group ( n=41 ; mean age ± SD , 52.47±8.75y ) . INTERVENTIONS Women in the exercise group completed an 8-week exergame-based training program , which was focused on postural control and coordination of the upper and lower limbs , aerobic conditioning , strength , and mobility . Women ( groups of 3 ) were encouraged to exercise for 120 minutes ( over 2 sessions ) per week . MAIN OUTCOME MEASURES Main outcome measures included pain and disease effect , which were assessed with the Fibromyalgia Impact Question naire ( FIQ ) , a specific measure for fibromyalgia . Secondary outcome measure included quality of life , which was assessed with the EuroQoL-5 Dimensions-5 Levels ( EQ-5D-5L ) generic instrument . RESULTS The results showed that 97.62 % of participants in the exercise group completed the 8-week intervention . The exercise group showed a significant improvement ( P the EQ-5D-5L utility index , and in 3 of 5 dimensions . For the FIQ , significant improvements were observed in the dimensions of pain , stiffness , anxiety , and feel good . The FIQ score was also reduced . The mean between-group improvement was 8.25 ( 95 % confidence interval , 2.85 - 13.65 ) . CONCLUSIONS The results and levels of compliance/adherence suggest this exergame-based training program is an effective intervention for reducing pain and increasing health-related quality of life in women with fibromyalgia",
"OBJECTIVE To determine the level of improvement , as regards pain , impact on fibromyalgia and depression , achieved by patients with fibromyalgia by comparing aquatic biodanza and stretching exercises . DESIGN R and omised controlled trial with two intervention groups . LOCATION Five health centres ( Almeria ) . PATIENTS A total of 82 fibromyalgia patients between 18 and 65 years old , diagnosed by American College of Rheumatology criteria , were included , with 12 patients declining to take part in the study . The 70 remaining patients were r and omly assigned to two groups of 35 patients each : aquatic biodanza and stretching exercises . Those who did not attend in at least 14 sessions or changed their treatment during the studio were excluded . The final sample consisted of 19 patients in aquatic biodanza group and 20 in stretching group . The limitations of the study included , the open evaluation design and a sample size reduced by defaults . MAIN MEASURES The outcome measures were sociodemographic data , quality of life ( Fibromyalgia Impact Question naire ) , pain ( McGill-Melzack question naire ; and Visual Analogue Scale ) , pressure algometry ( Wagner FPI10 algometer ) and depression ( Beck Inventory ) . These were carried out before and after a 12-week therapy . RESULTS The mean age of the sample was 55.41 years . The mean period from diagnosis was 13.44 years . The sample consisted mainly of housewives . There were significant differences ( P pain ( P fibromyalgia impact ( P depression ( P biodanza aquatic exercises improve pain and quality of life in fibromyalgia patients",
"OBJECTIVES The aim of the present study was to assess the effectiveness of belly dance as a treatment option for patients with fibromyalgia . METHODS Eighty female patients with fibromyalgia between 18 to 65 years were r and omly allocated to a dance group ( n=40 ) and control group ( n=40 ) . Patients in the dance group underwent 16 weeks of belly dance twice a week , while the patients in the control group remained on a waiting list . The patients were evaluated with regard to pain ( VAS ) , function ( 6MWT ) , quality of life ( FIQ and SF-36 ) , depression ( Beck Inventory ) , anxiety ( STAI ) and self-image ( BDDE ) . Evaluations were carried out at baseline , 16 weeks and 32 weeks by a blinded assessor . RESULTS The dance group achieved significant improvements in VAS for pain ( p as well as the pain ( p ) , emotional aspects ( p ) and mental health ( p Belly dance can be used in the treatment of fibromyalgia to reduce pain and improve functional capacity , quality of life and self-image",
"Objective : To compare the effects of traditional dancing with formal exercise training in terms of functional and cardiovascular benefits and motivation in patients with chronic heart failure . Design : R and omized controlled trial . Setting : Sports Medicine Laboratory . Subjects : Fifty-one Greek male patients aged 67.1±5.5 years with chronic heart failure of New York Heart Association ( NYHA ) class II – III , participated in an eight-month study . Interventions : They were r and omly assigned to either training with Greek traditional dances ( group A , n=18 ) , formal exercise training ( group B , n=16 ) or a sedentary control group ( group C , n=17 ) . Main measures : At entry and the end of the study all patients underwent cardiopulmonary exercise testing , functional ability assessment and quality of life evaluations . The Intrinsic Motivation Inventory was also used to assess participants ’ subjective experience . Results : After training group A showed increased peak oxygen consumption by 33.8 % ( 19.5 vs. 26.1 ml/kg/min , p ) , maximal treadmill tolerance by 48.5 % ( p a decreased Slope of expired minute ventilation for carbon dioxide output ( VE/VCO2 ) slope by 18 % ( p improvement in the quality of life indices . Intrinsic Motivation Inventory was increased only in group A by 26.2 % ( 3.08 vs. 3.87 , p Conclusions : Exercise training in chronic heart failure patients with Greek traditional dances led to functional and cardiovascular benefits similar to formal exercise training and to a higher level of motivation",
"OBJECTIVE The objective of this study was to determine the effects of a 3-month Biodanza intervention in women with fibromyalgia ( FM ) . DESIGN This was a controlled trial . SETTING /LOCATION The study was conducted at a university research laboratory and social center . SUBJECTS The study comprised 59 women with FM recruited from a local association of patients with FM . Participants were allocated to the Biodanza intervention group ( n = 27 ) or usual-care group ( n = 32 ) . INTERVENTION The Biodanza intervention was carried out once a week for 3 months . OUTCOME MEASURES The outcome measures included the following : Pain threshold , body composition ( body-mass index and estimated body fat percentage ) , physical fitness ( 30-second chair st and , h and grip strength , chair sit and reach , back scratch , blind flamingo , 8 feet up and go , and 6-minute walk test ) and psychologic outcomes ( Fibromyalgia Impact Question naire [ FIQ ] , Short-Form Health Survey 36 , V and erbilt Pain Management Inventory , Hospital Anxiety and Depression Scale , General Self-Efficacy Scale , and Rosenberg Self-Esteem Scale ) . RESULTS We observed a significant interaction effect ( group*time ) for pain threshold of several tender points ( left [ L ] and right [ R ] side of the anterior cervical and supraspinatus , trapezius L and lateral epicondyle R , algometer score , tender points count ) , body fat percentage , and FIQ total score . In the intervention group , post hoc analysis revealed a significant improvement in pain threshold of the anterior cervical R and L and supraspinatus R and L tender points ( all p algometer score ( p = 0.008 ) , tender point count ( p = 0.002 ) , body fat percentage ( p = 0.001 ) , and FIQ total score ( p = 0.003 ) . CONCLUSIONS A 3-month ( one session per week ) Biodanza intervention shows improvements on pain , body composition , and FM impact in female patients",
"INTRODUCTION The importance of physical exercise for patients with fibromyalgia ( FM ) is very clear in the literature . Dancing is a type of aerobic exercise that has great acceptance . In addition to the beneficial effects of aerobic exercise , Zumba works on motor coordination and also has socializing as a part that should be included in patients with fibromyalgia . OBJECTIVES To evaluate the effectiveness of Zumba dancing in improving pain , functional capacity , quality of sleep and quality of life of women with fibromyalgia . DESIGN A pre-post treatment design . METHODS We evaluated 19 women with fibromyalgia , selected by convenience . Data were collected in the second half of 2016 . Zumba dancing was performed twice a week for 12 weeks . Patients were evaluated at week 0 ( T0 ) and at week 12 ( T12 ) , by the following instruments : VAS ( Visual Analogic Scale ) , Likert Scale , TUG ( Timed Up an Go Test ) , 6MWT ( Six-minute Walk Test ) , FIQ ( Fibromyalgia Impact Question naire ) , PSQI ( Pittsburgh Sleep Quality Index ) , ESS ( Epworth Sleepiness Scale ) and SF-36 quality of life . RESULTS We found differences in pain ( VAST0 = 6.21 and VAST12 = 4.53 ) with p = 0.001 and in the domain physical functioning of SF36 ( T0 = 42.37 and T12 = 52.11 ) with p = 0.04 . No differences were found for the other variables between the times . CONCLUSION Zumba dancing as a form of treatment for three months for patients with fibromyalgia was effective in improving pain and physical functioning . Future controlled and r and omized clinical trials should be performed to improve the evidence of Zumba dancing in women with fibromyalgia"
] |
4116bee2-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND Seasonal affective disorder ( SAD ) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring . The prevalence of SAD in the United States ranges from 1.5 % to 9 % , depending on latitude . The predictable seasonal aspect of SAD provides a promising opportunity for prevention . This is one of four review s on the efficacy and safety of interventions to prevent SAD ; we focus on agomelatine and melatonin as preventive interventions . OBJECTIVES To assess the efficacy and safety of agomelatine and melatonin ( in comparison with each other , placebo , second-generation antidepressants , light therapy , psychological therapy or lifestyle interventions ) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD . SEARCH METHODS We conducted a search of the Specialised Register of the Cochrane Depression , Anxiety and Neurosis Review Group ( CCDANCTR ) to 11 August 2015 . The CCDANCTR contains reports of relevant r and omised controlled trials from EMBASE ( 1974 to date ) , MEDLINE ( 1950 to date ) , PsycINFO ( 1967 to date ) and the Cochrane Central Register of Controlled Trials ( CENTRAL ) . Furthermore , we search ed the Cumulative Index to Nursing and Allied Health Literature ( CINAHL ) , Web of Knowledge , The Cochrane Library and the Allied and Complementary Medicine Data base ( AMED ) ( to 26 May 2014 ) . We conducted a grey literature search ( e.g. in clinical trial registries ) and h and search ed the reference lists of all included studies and pertinent review articles . SELECTION CRITERIA To examine efficacy , we planned to include r and omised controlled trials ( RCTs ) on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study . To examine adverse events , we intended to include non-r and omised studies . We planned to include studies that compared agomelatine versus melatonin , or agomelatine or melatonin versus placebo , any second-generation antidepressant ( SGA ) , light therapy , psychological therapies or lifestyle changes . We also intended to compare melatonin or agomelatine in combination with any of the comparator interventions listed above versus the same comparator intervention as monotherapy . DATA COLLECTION AND ANALYSIS Two review authors screened abstract s and full-text publications against the inclusion criteria . Two review authors planned to independently extract data and assess risk of bias of included studies . We planned to pool data for meta- analysis when participant groups were similar and when studies assessed the same treatments by using the same comparator and presented similar definitions of outcome measures over a similar duration of treatment ; however , we identified no studies for inclusion . MAIN RESULTS We identified 2986 citations through electronic search es and review s of reference lists after de-duplication of search results . We excluded 2895 records during title and abstract review and assessed 91 articles at full-text level for eligibility . We identified no controlled studies on use of melatonin and agomelatine to prevent SAD and to improve patient-centred outcomes among adults with a history of SAD . AUTHORS ' CONCLUSIONS No available method ologically sound evidence indicates that melatonin or agomelatine is or is not an effective intervention for prevention of SAD and improvement of patient-centred outcomes among adults with a history of SAD . Lack of evidence clearly shows the need for well-conducted , controlled studies on this topic . A well-conducted RCT of melatonin or agomelatine for prevention of SAD would assess the comparative benefits and risks of these interventions against others currently used to treat the disorder
|
[
"OBJECTIVE This study evaluates the efficacy of agomelatine , the first antidepressant that is an agonist at MT(1)/MT(2 ) receptors and an antagonist at 5-HT(2C ) receptor , in the prevention of relapse of depression following successful response . METHOD Patients with DSM-IV-TR major depressive disorder who responded to an 8- or 10-week course of agomelatine 25- or 50-mg daily treatment were r and omly assigned to receive continuation treatment with agomelatine ( n=165 ) or placebo ( n=174 ) during a 24-week , r and omized , double-blind treatment period . The main outcome measure was time to relapse during the double-blind treatment period . The cumulative probability of relapse was calculated using the Kaplan-Meier method of survival analysis . The study was conducted from February 2005 to February 2007 . RESULTS During the 6-month evaluation period , the incidence of relapse was significantly lower in patients who continued treatment than in those switched to placebo ( P=.0001 ) . The cumulative relapse rate at 6 months for agomelatine-treated patients was 21.7 % ; that for placebo-treated patients was 46.6 % . Agomelatine was also superior to placebo in preventing relapse in the subset of patients with baseline 17-item Hamilton Depression Rating Scale total score > or = 25 . Measures of tolerability and safety of both doses of agomelatine were similar to placebo . No pattern of early relapse or adverse events suggestive of withdrawal symptoms was obtained after abrupt cessation of agomelatine . CONCLUSIONS The findings are important in 2 respects . First , agomelatine is an effective and safe antidepressant continuation therapy , which confirms efficacy seen in short-term studies . Second , few early relapses were observed in the patient group switched to placebo : the survival curve for placebo separated gradually from that of patients taking agomelatine . We suggest this reflects solely the underlying properties of the illness , which is only possible due to the lack of discontinuation syndrome after agomelatine withdrawal . It underlines the novel clinical profile of agomelatine , which quite likely reflects its innovative pharmacology . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N53193024",
"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 ",
"Rationale The novel antidepressant agomelatine acts as a melatonergic ( MT1 and MT2 ) receptor agonist and as a serotonin-2C receptor antagonist . Previous studies showed that agomelatine is able to restore disrupted circadian rhythms , which were implicated in the pathophysiology of seasonal affective disorder ( SAD ) . Objectives The aim of this study was to investigate the efficacy and tolerability of agomelatine in the treatment of SAD . Material s and methods Thirty-seven acutely depressed SAD patients were included in an open study with agomelatine ( 25 mg/day in the evening ) over 14 weeks . Efficacy assessment s included the Structured Interview Guide for the Hamilton Depression Rating Scale ( SAD version ; SIGH-SAD ) , the Clinical Global Impression of Severity ( CGI-S ) and Improvement ( CGI-I ) , the Circscreen , a self-rating scale for the assessment of sleep and circadian rhythm disorders , and the Hypomania Scale . Results Agomelatine led to a progressive and statistically significant decrease of SIGH-SAD , CGI-S , and CGI-I scores from week 2 onward ( p on the Circscreen improved significantly during the study ( p agomelatine over 14 weeks yielded a response rate of 75.7 % ( SIGH-SAD remission rate ( SIGH-SAD Scores on the Hypomania Scale were consistently low during the study . Agomelatine showed good overall tolerability : throughout the study only one adverse event ( mild fatigue ) was related to the study drug . Conclusions The results of this study suggest that seasonal depression may be effectively and safely treated with agomelatine",
"OBJECTIVE This study evaluates the efficacy of agomelatine , the first antidepressant to be an agonist at MT(1)/MT(2 ) receptors and an antagonist at 5-HT(2C ) receptors , versus sertraline with regard to the amplitude of the circadian rest-activity cycle and depressive and anxiety symptoms in patients with major depressive disorder ( MDD ) . METHOD Out patients with DSM-IV-TR-defined MDD received either agomelatine 25 to 50 mg ( n = 154 ) or sertraline 50 to 100 mg ( n = 159 ) during a 6-week , r and omized , double-blind treatment period . The study was conducted from 2005 to 2006 . The main outcome measure was the relative amplitude of the individual rest-activity cycles , expressed as change from baseline to week 6 and collected from continuous records using wrist actigraphy and sleep logs . Secondary outcome measures were sleep efficiency and sleep latency , both derived from actigraphy , and efficacy on depression symptoms ( 17-Item Hamilton Depression Rating Scale total score and Clinical Global Impressions scale scores ) and anxiety symptoms ( Hamilton Anxiety Rating Scale total score and subscores ) . RESULTS A significant difference in favor of agomelatine compared to sertraline on the relative amplitude of the circadian rest-activity cycle was observed at the end of the first week ( P = .01 ) . In parallel , a significant improvement of sleep latency ( P sleep efficiency ( P sertraline . Over the 6-week treatment period , depressive symptoms improved significantly more with agomelatine than with sertraline ( P anxiety symptoms ( P the circadian rest-activity/sleep-wake cycle in depressed patients at week 1 reflects early improvement in sleep and daytime functioning . Higher efficacy results were observed with agomelatine as compared to sertraline on both depressive and anxiety symptoms over the 6-week treatment period , together with a good tolerability profile . These findings indicate that agomelatine offers promising benefits for MDD patients . TRIAL REGISTRATION www.is rct n.org : IS RCT N49376288",
"BACKGROUND The suppression of melatonin by light at 00.30 hours has been shown to be greater in winter than in summer on patients with seasonal affective disorder ( SAD ) but not in matched normal controls . METHOD In this study 12 patients with SAD and 12 matched normal controls were exposed to morning light therapy in the winter . Melatonin profiles and sensitivity to light were measured before and after treatment . RESULTS The SAD but not the normal group showed a phase advance of melatonin rhythms in response to phototherapy . There was an association between phase position and phase shift in the SAD but not in the normal group . CONCLUSIONS There may be instability of circadian rhythms in SAD mediated by a high-amplitude phase response curve , rather than a fixed phase abnormality as had been previously suggested . This instability may be secondary to impaired serotoninergic function in the afferent pathways to the suprachiasmatic nuclei",
"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",
"Melatonin , at the same doses used to treat circadian-rhythm related sleep disturbances , had no effect on the depressive symptoms in seasonal affective disorder ( SAD ) patients , whether given early ( 7 a.m. ) or late ( 11 p.m. ) for a week . Slight improvements in sleep were seen with nighttime administration . The circadian rhythmicity of urinary 6-sulphatoxymelatonin was not modified in any way . Melatonin at this dosage ( 5 mg/day ) or at these two times is therefore not a potential alternative treatment for SAD ; light remains the therapy of choice",
"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",
"BACKGROUND Thirty-eight patients with SAD participated in a light visor study addressing two questions . 1 . Can the development of a depressive episode be prevented by daily exposure to bright light started before symptom onset in early fall and continued throughout the winter ? 2 . Does the light have to be visible in order to have beneficial effects ? METHODS Three groups participated in the study : I ( n = 14 ) received bright white light ( 2500 lux ) ; II , ( n = 15 ) received infrared light ( 0.18 lux ) ; III ( n = 9 , control group ) did not receive any light treatment at all . RESULTS Infrared light is just as effective as bright white light . Both are more effective than the control condition . CONCLUSIONS Light visors can be effectively used to prevent the development of SAD . The fact that exposure to infrared light was as effective as exposure to bright white light questions the specific role of visible light in the treatment of SAD",
"The Seasonal Pattern Assessment Question naire ( SPAQ ) was mailed to a sample population balanced for sex and r and omly selected from local telephone directories in four areas : Nashua , NH , New York , NY , Montgomery County , MD , and Sarasota , FL . On the basis of responses to this question naire , prevalence rates of winter seasonal affective disorder ( winter SAD ) , summer seasonal affective disorder ( summer SAD ) , and subsyndromal winter SAD were estimated for the four areas . Rates of winter SAD and subsyndromal SAD were found to be significantly higher at the more northern latitudes , while no correlation was found between latitude and summer SAD . The positive correlation between latitude and prevalence of winter SAD applied predominantly to the age groups over 35",
"BACKGROUND The best available treatment for seasonal affective disorder ( SAD ) is light therapy . Yet , this treatment does not prevent recurrence of depression in subsequent seasons . The aim of the study is to gain preliminary insight in the efficacy of Mindfulness Based Cognitive Therapy ( MBCT ) in the prevention of SAD recurrence . METHODS This is a r and omized controlled pilot study , in which SAD patients in remission were r and omly allocated to an individual format of MBCT or a control condition ( i.e. treatment as usual ) . MBCT was given between May and June 2011 , when there was no presence of depressive symptoms . The Inventory for Depressive Symptomatology Self-Report ( IDS-SR ) , which patients received on a weekly basis from September 2011 to April 2012 , was used to assess moment of recurrence ( ≥20 ) and severity at moment of recurrence . RESULTS 23 SAD patients were r and omized to MBCT and 23 to the control condition . Kaplan-Meier survival curve showed that the groups did not differ in moment of recurrence ( χ²(1).41 , p=.52 ) . T-tests showed no group difference in mean IDS-SR scores at moment of recurrence ( t(31)=-.52 , p=.61 ) . LIMITATIONS The results are limited by small sample size ( n=46 ) and missing data of weekly IDS-SR assessment s. CONCLUSION The findings of this pilot RCT suggest that individual MBCT is not effective in preventing a SAD recurrence when offered in a symptom free period ( i.e. spring )",
"This study aim ed to explore the effects of melatonin on sleep , waking up and well being in subjects with varying degrees of seasonal or weather-associated changes in mood and behaviour . Fifty-eight healthy adults exhibiting subsyndromal seasonal affective disorder ( s-SAD ) and /or the negative or positive type of weather-associated syndrome ( WAS ) were r and omised to either 2 mg of sustained-release melatonin or placebo tablets 1 - 2 h before a desired bedtime for 3 weeks . Outcome measures were changes from baseline in sleep quality , sleepiness after waking , atypical depressive symptoms and health-related quality of life by week three . Early morning salivary melatonin concentrations were measured at baseline and treatment cessation in all subjects . Melatonin administration significantly improved the quality of sleep ( P=0.03 ) and vitality ( P=0.02 ) in the subjects with s-SAD , but attenuated the improvement of atypical symptoms and physical parameters of quality of life compared to placebo in the subjects with WAS , positive type"
] |
4116bf28-06ff-11f0-808a-c43d1ab1c353
|
OBJECTIVE Attention-deficit/hyperactivity disorder ( ADHD ) is a psychiatric disorder affecting 5 % of children . Methylpheni date ( MPH ) is a common medication for ADHD . Studies examining MPH 's effect on pediatric ADHD patients ' brain function using functional magnetic resonance imaging ( fMRI ) have not been compiled . The goals of this systematic review were to determine ( 1 ) which areas of the brain in pediatric ADHD patients are modulated by a single dose of MPH , ( 2 ) whether areas modulated by MPH differ by task type performed during fMRI data acquisition , and ( 3 ) whether changes in brain activation due to MPH relate to clinical improvements in ADHD-related symptoms . METHODS We search ed the electronic data bases PubMed and PsycINFO ( 1967 - 2011 ) using the following terms : ADHD AND ( methylpheni date OR MPH OR ritalin ) AND ( neuroimaging OR MRI OR fMRI OR BOLD OR event related ) , and identified 200 abstract s , 9 of which were review ed based on predefined criteria . RESULTS In ADHD patients the middle and inferior frontal gyri , basal ganglia , and cerebellum were most often affected by MPH . The middle and inferior frontal gyri were frequently affected by MPH during inhibitory control tasks . Correlation between brain regions and clinical improvement was not possible due to the lack of symptom improvement measures within the included studies . CONCLUSIONS Throughout nine task-based fMRI studies investigating MPH 's effect on the brains of pediatric patients with ADHD , MPH result ed in increased activation within frontal lobes , basal ganglia , and cerebellum . In most cases , this increase " normalized " activation of at least some brain areas to that seen in typically developing children
|
[
"Methylpheni date ( Ritalin ) is the most commonly prescribed psychoactive drug in children for the treatment of attention deficit hyperactivity disorder ( ADHD ) , yet the mechanisms responsible for its therapeutic effects are poorly understood . Whereas methylpheni date blocks the dopamine transporter ( main mechanism for removal of extracellular dopamine ) , it is unclear whether at doses used therapeutically it significantly changes extracellular dopamine ( DA ) concentration . Here we used positron emission tomography and [(11)C]raclopride ( D2 receptor radiolig and that competes with endogenous DA for binding to the receptor ) to evaluate whether oral methylpheni date changes extracellular DA in the human brain in 11 healthy controls . We showed that oral methylpheni date ( average dose 0.8 + /- 0.11 mg/kg ) significantly increased extracellular DA in brain , as evidence d by a significant reduction in B(max)/K(d ) ( measure of D2 receptor availability ) in striatum ( 20 + /- 12 % ; p methylpheni date at doses within the therapeutic range significantly increases extracellular DA in human brain . This result coupled with recent findings of increased dopamine transporters in ADHD patients ( which is expected to result in reductions in extracellular DA ) provides a mechanistic framework for the therapeutic efficacy of methylpheni date . The increase in DA caused by the blockade of dopamine transporters by methylpheni date predominantly reflects an amplification of spontaneously released DA , which in turn is responsive to environmental stimulation . Because DA decreases background firing rates and increases signal-to-noise in target neurons , we postulate that the amplification of weak DA signals in subjects with ADHD by methylpheni date would enhance task-specific signaling , improving attention and decreasing distractibility . Alternatively methylpheni date -induced increases in DA , a neurotransmitter involved with motivation and reward , could enhance the salience of the task facilitating the \" interest that it elicits \" and thus improving performance",
"BACKGROUND Attention-deficit/hyperactivity disorder is a psychiatric disorder that starts in childhood . The mechanism of action of methylpheni date , the most common treatment for attention deficit hyperactivity disorder , is unclear . In vitro , the affinity of methylpheni date for the norepinephrine transporter ( NET ) is higher than that for the dopamine transporter ( DAT ) . The goal of this study was to use positron emission tomography to measure the occupancy of brain norepinephrine transporter by methylpheni date in vivo in humans . METHODS We used (S , S)-[¹¹C ] methylreboxetine ( [¹¹C]MRB ) to determine the effective dose 50 ( ED₅₀ ) of methylpheni date for NET . In a within-subject design , healthy subjects ( n = 11 ) received oral , single-blind placebo and 2.5 , 10 , and 40 mg of methylpheni date 75 min before [¹¹C]MRB injection . Dynamic positron emission tomography imaging was performed for 2 hours with the High Resolution Research Tomograph . The multilinear reference tissue model with occipital cortex as the reference region was used to estimate binding potential non-displaceable ( BP(ND ) ) in the thalamus and other NET-rich regions . RESULTS BP(ND ) was reduced by methylpheni date in a dose-dependent manner in thalamus and other NET-rich regions . The global ED₅₀ was estimated to be .14 mg/kg ; therefore , the average clinical maintenance dose of methylpheni date ( .35-.55 mg/kg ) produces 70 % to 80 % occupancy of NET . CONCLUSIONS For the first time in humans , we demonstrate that oral methylpheni date significantly occupies NET at clinical ly relevant doses . The ED₅₀ is lower than that for DAT ( .25 mg/kg ) , suggesting the potential relevance of NET inhibition in the therapeutic effects of methylpheni date in attention-deficit/hyperactivity disorder",
"CONTEXT Previous studies have reported hypofunction , structural abnormalities , and biochemical abnormalities of the dorsal anterior midcingulate cortex ( daMCC ) in attention-deficit/hyperactivity disorder ( ADHD ) . Stimulant medications are effective treatments for ADHD , but their neural effects have not been fully characterized . OBJECTIVE To determine whether the methylpheni date hydrochloride osmotic-release oral system ( OROS ) would increase functional magnetic resonance imaging ( fMRI ) activation , compared with placebo , in the daMCC and other frontoparietal regions subserving attention during the Multi- Source Interference Task ( MSIT ) . DESIGN R and omized , placebo-controlled , 6-week , before-after fMRI study . SETTING Academic medical center ambulatory clinic . PATIENTS Twenty-one adults with ADHD r and omized to 6 weeks of treatment with methylpheni date OROS ( n = 11 ) or placebo ( n = 10 ) . INTERVENTIONS Patients underwent fMRI twice while performing the MSIT ( scan 1 at baseline and scan 2 at 6 weeks ) . MAIN OUTCOME MEASURES Group-averaged , r and om-effects , repeated- measures , general linear model analyses were used to compare daMCC ( and whole-brain ) fMRI activation during the MSIT . Individual-based daMCC volume-of-interest confirmatory analyses and behavioral data are also presented . RESULTS Performance and baseline fMRI measures in the daMCC and other a priori brain regions did not differ between groups . Group comparisons showed a group x scan interaction and t test confirmation of higher activation in the daMCC at 6 weeks in the methylpheni date OROS group than in the placebo group ( P Individual daMCC volume-of-interest analyses confirmed group-averaged findings and suggested that daMCC activity might be related to clinical response . Methylpheni date OROS also produced higher activation in the dorsolateral prefrontal cortex and the parietal cortex at 6 weeks . CONCLUSION Methylpheni date OROS increased daMCC activation during the MSIT and may act , in part , by normalizing daMCC hypofunction in ADHD",
"Background Children with attention-deficit/hyperactivity disorder ( ADHD ) have deficits in performance monitoring often improved with the indirect catecholamine agonist methylpheni date ( MPH ) . We used functional magnetic resonance imaging to investigate the effects of single-dose MPH on activation of error processing brain areas in medication-naive boys with ADHD during a stop task that elicits 50 % error rates . Methods Twelve medication-naive boys with ADHD were scanned twice , under either a single clinical dose of MPH or placebo , in a r and omized , double-blind design while they performed an individually adjusted tracking stop task , design ed to elicit 50 % failures . Brain activation was compared within patients under either drug condition . To test for potential normalization effects of MPH , brain activation in ADHD patients under either drug condition was compared with that of 13 healthy age-matched boys . Results During failed inhibition , boys with ADHD under placebo relative to control subjects showed reduced brain activation in performance monitoring areas of dorsomedial and left ventrolateral prefrontal cortices , thalamus , cingulate , and parietal regions . MPH , relative to placebo , upregulated activation in these brain regions within patients and normalized all activation differences between patients and control subjects . During successful inhibition , MPH normalized reduced activation observed in patients under placebo compared with control subjects in parietotemporal and cerebellar regions . Conclusions MPH normalized brain dysfunction in medication-naive ADHD boys relative to control subjects in typical brain areas of performance monitoring , comprising left ventrolateral and dorsomedial frontal and parietal cortices . This could underlie the amelioration of MPH of attention and academic performance in ADHD",
"BACKGROUND Previous studies have demonstrated the short-term efficacy of pharmacotherapy and behavior therapy for attention-deficit/hyperactivity disorder ( ADHD ) , but no longer-term ( i.e. , > 4 months ) investigations have compared these 2 treatments or their combination . METHODS A group of 579 children with ADHD Combined Type , aged 7 to 9.9 years , were assigned to 14 months of medication management ( titration followed by monthly visits ) ; intensive behavioral treatment ( parent , school , and child components , with therapist involvement gradually reduced over time ) ; the two combined ; or st and ard community care ( treatments by community providers ) . Outcomes were assessed in multiple domains before and during treatment and at treatment end point ( with the combined treatment and medication management groups continuing medication at all assessment points ) . Data were analyzed through intent-to-treat r and om-effects regression procedures . RESULTS All 4 groups showed sizable reductions in symptoms over time , with significant differences among them in degrees of change . For most ADHD symptoms , children in the combined treatment and medication management groups showed significantly greater improvement than those given intensive behavioral treatment and community care . Combined and medication management treatments did not differ significantly on any direct comparisons , but in several instances ( oppositional/aggressive symptoms , internalizing symptoms , teacher-rated social skills , parent-child relations , and reading achievement ) combined treatment proved superior to intensive behavioral treatment and /or community care while medication management did not . Study medication strategies were superior to community care treatments , despite the fact that two thirds of community-treated subjects received medication during the study period . CONCLUSIONS For ADHD symptoms , our carefully crafted medication management was superior to behavioral treatment and to routine community care that included medication . Our combined treatment did not yield significantly greater benefits than medication management for core ADHD symptoms , but may have provided modest advantages for non-ADHD symptom and positive functioning outcomes",
"We argue that impulsiveness is characterized by compromised timing functions such as premature motor timing , decreased tolerance to delays , poor temporal foresight and steeper temporal discounting . A model illustration for the association between impulsiveness and timing deficits is the impulsiveness disorder of attention-deficit hyperactivity disorder ( ADHD ) . Children with ADHD have deficits in timing processes of several temporal domains and the neural substrates of these compromised timing functions are strikingly similar to the neuropathology of ADHD . We review our published and present novel functional magnetic resonance imaging data to demonstrate that ADHD children show dysfunctions in key timing regions of prefrontal , cingulate , striatal and cerebellar location during temporal processes of several time domains including time discrimination of milliseconds , motor timing to seconds and temporal discounting of longer time intervals . Given that impulsiveness , timing abnormalities and more specifically ADHD have been related to dopamine dysregulation , we tested for and demonstrated a normalization effect of all brain dysfunctions in ADHD children during time discrimination with the dopamine agonist and treatment of choice , methylpheni date . This review together with the new empirical findings demonstrates that neurocognitive dysfunctions in temporal processes are crucial to the impulsiveness disorder of ADHD and provides first evidence for normalization with a dopamine reuptake inhibitor",
"Youth with attention deficit hyperactivity disorder ( ADHD ) have deficits in interference inhibition , which can be improved with the indirect catecholamine agonist methylpheni date ( MPH ) . Functional magnetic resonance imaging was used to investigate the effects of a single dose of MPH on brain activation during interference inhibition in medication-naïve ADHD boys . Medication-naïve boys with ADHD were scanned twice , in a r and omized , double-blind design , under either a single clinical dose of MPH or placebo , while performing a Simon task that measures interference inhibition and controls for the oddball effect of low-frequency appearance of incongruent trials . Brain activation was compared within patients under either drug condition . To test for potential normalization effects of MPH , brain activation in ADHD patients under either drug condition was compared with that of healthy age-matched comparison boys . During incongruent trials compared with congruent – oddball trials , boys with ADHD under placebo relative to controls showed reduced brain activation in typical areas of interference inhibition , including right inferior prefrontal cortex , left striatum and thalamus , mid-cingulate/supplementary motor area , and left superior temporal lobe . MPH relative to placebo upregulated brain activation in right inferior prefrontal and premotor cortices . Under the MPH condition , patients relative to controls no longer showed the reduced activation in right inferior prefrontal and striato-thalamic regions . Effect size comparison , furthermore , showed that these normalization effects were significant . MPH significantly normalized the fronto-striatal underfunctioning in ADHD patients relative to controls during interference inhibition , but did not affect medial frontal or temporal dysfunction . MPH therefore appears to have a region-specific upregulation effect on fronto-striatal activation",
"BACKGROUND Our objective was to estimate the lifetime prevalence of psychopathology in a sample of youth with and without attention deficit hyperactivity disorder ( ADHD ) through young adulthood using contemporaneous diagnostic and analytic techniques . METHOD We conducted a case-control , 10-year prospect i ve study of ADHD youth . At baseline , we assessed consecutively referred male , Caucasian children with ( n=140 ) and without ( n=120 ) DSM-III-R ADHD , aged 6 - 18 years , ascertained from psychiatric and pediatric sources to allow for generalizability of results . At the 10-year follow-up , 112 ( 80 % ) and 105 ( 88 % ) of the ADHD and control children , respectively , were reassessed ( mean age 22 years ) . We created the following categories of psychiatric disorders : Major Psychopathology ( mood disorders and psychosis ) , Anxiety Disorders , Antisocial Disorders ( conduct , oppositional-defiant , and antisocial personality disorder ) , Developmental Disorders ( elimination , language , and tics disorder ) , and Substance Dependence Disorders ( alcohol , drug , and nicotine dependence ) , as measured by blinded structured diagnostic interview . RESULTS The lifetime prevalence for all categories of psychopathology were significantly greater in ADHD young adults compared to controls , with hazard ratios and 95 % confidence intervals of 6.1 ( 3.5 - 10.7 ) , 2.2 ( 1.5 - 3.2 ) , 5.9 ( 3.9 - 8.8 ) , 2.5 ( 1.7 - 3.6 ) , and 2.0 ( 1.3 - 3.0 ) , respectively , for the categories described above . CONCLUSIONS By their young adult years , ADHD youth were at high risk for a wide range of adverse psychiatric outcomes including markedly elevated rates of antisocial , addictive , mood and anxiety disorders . These prospect i ve findings provide further evidence for the high morbidity associated with ADHD across the life-cycle and stress the importance of early recognition of this disorder for prevention and intervention strategies",
"OBJECTIVES To evaluate the pharmacodynamic effects of an experimental ( EXP ) delivery of methylpheni date ( MPH ) in children with attention-deficit/hyperactivity disorder and to investigate the situational nature of effects in laboratory classroom and playground setting s. METHOD A \" sipping \" study methodology was used to deliver a bolus followed by small but increasing MPH doses as the EXP regimen . A r and omized , double-blind crossover design was used to compare the EXP regimen to a thrice-daily ( TID ) regimen and a placebo ( PLA ) regimen . Measures of efficacy were obtained from a Motionlogger actigraph to quantify activity and from the Swanson , Kotkin , Agler , M-Flynn , and Pelham ( SKAMP ) rating scale to quantify two domains of behavior ( attention and deportment ) . RESULTS Compared with PLA , both EXP and TID delivery of MPH produced large , significant reductions in activity and inappropriate behavior in the classroom , but the two MPH regimens did not differ in onset or duration of effects across the day . The MPH effects were situationally dependent and were smaller for the playground than for the classroom setting s. CONCLUSIONS The findings of this \" proof of concept \" study support the efficacy of a continuous , ascending delivery of MPH . The situational effects of MPH provide support for the theory of selective effects of stimulants , dependent on the dem and s of the environment",
"OBJECTIVE Recent studies have suggested that attention deficit hyperactivity disorder ( ADHD ) is associated with abnormalities in basal ganglia and prefrontal cortical functioning . However , these studies have primarily relied upon cognitive tasks that reflect impulse control rather than attentional mechanisms . METHOD The authors used functional magnetic resonance imaging to investigate the neural correlates of selective and divided attention in a r and omized , double-blind , placebo-controlled pharmacological challenge with methylpheni date in 15 adolescents with ADHD ( ages 14 - 17 ) , eight adolescents with reading disorder ( ages 12 - 17 ) , and four adolescents with both reading disorder and ADHD ( ages 14 - 18 ) who were scanned during both a methylpheni date and a placebo session . Fourteen healthy comparison subjects ( ages 12 - 20 ) who were not given methylpheni date served as the primary comparison group . RESULTS During the divided attention task , unmedicated subjects with ADHD or reading disorder recruited the left ventral basal ganglia significantly less than the healthy comparison subjects . Methylpheni date led to an increase in activation in this region but had no effect on task performance . Subjects with ADHD also recruited the middle temporal gyrus significantly less than the comparison subjects , but methylpheni date did not have a direct effect on activation in this region . CONCLUSIONS These results suggest that ADHD is associated with abnormal processing in attentional networks , with specific dysfunction in striatal circuitry . Methylpheni date may act to normalize activity within this network",
"BACKGROUND AND AIMS Children with attention deficit/hyperactivity disorder ( ADHD ) often show deficits in working memory performance . Methylpheni date ( MPH ) is an effective medication to improve these cognitive difficulties . This study aim ed to clarify which effect MPH induces on the underlying functional networks of working memory . METHODS Fourteen boys diagnosed with ADHD and 12 healthy controls were investigated using functional magnetic resonance imaging ( fMRI ) . Each patient was tested twice , once with medication and once without . The fMRI experiments consisted of three verbal N-back tasks with increasing difficulty . Functional images were acquired on a 3 Tesla head scanner . RESULTS On the behavioral level , medicated patients performed similar to healthy controls and significantly better than without medication . On the functional level , patients showed the expected frontal and parietal activations , which were more pronounced in the 2- and 3-back tasks . Healthy controls showed significantly more activation in these regions and additional activation in the cerebellum . Interestingly , patients showed an additional effect of laterality . Left-sided frontal and parietal activation in patients was significantly less pronounced than in controls . CONCLUSION Functional data indicate different activation patterns in verbal working memory tasks between healthy controls and patients with ADHD irrespective of medication condition . Intake of MPH led to a clear improvement on a behavioral level . However , this effect was not reflected by changes in functional brain organization . MPH-induced changes leading to better performance in verbal working memory tasks might be very subtle and therefore not detectable by fMRI",
"Debate still surrounds the nature of the role of the dorsolateral prefrontal gyrus ( DLPFC ) in time perception . This region is frequently associated with working memory and is thus implicated as a so-called \" accumulator \" within a hypothesized internal clock model . However , we hypothesized that this region may have a more primary role in time perception . To test this hypothesis we used functional magnetic resonance imaging ( fMRI ) to examine the neural correlates of relatively pure time perception with a temporal discrimination task where intervals of 1 s had to be discriminated from those of 1.3 , 1.4 , and 1.5 s. Time perception in this particular time domain within the \" perceived present \" has not previously been investigated using fMRI . By using relatively short time periods to be discriminated and also contrasting activation with an order judgment task , we aim ed to minimize the confounding aspects of sustained attention and working memory . In a group of 20 healthy right-h and ed adult males , neural activation associated with time discrimination was found in a predominantly right hemispheric network of right dorsolateral and inferior prefrontal cortices , right supplementary motor area , and left cerebellum . We conclude that right DLPFC , rather than having a purely working memory function , might be more central ly involved in time perception than previously thought",
"BACKGROUND Although abnormalities in the regional cerebral blood flow ( rCBF ) responses to methylpheni date ( MPH ) treatment have been reported in children with attention deficit hyperactivity disorder ( ADHD ) , there are few prospect i ve longitudinal studies assessing the long-term effects of MPH and discontinuation effects after chronic treatment . METHODS The authors studied ten drug-naive children ( 2 girls , 8 boys , mean age+/-S.D.=9.60+/-1.96 ) diagnosed with ADHD by the Diagnostic and Statistical Manual of Mental Disorders ( DSM-IV ) diagnostic criteria , using (99m)Tc-HMPAO-single photon emission computed tomography ( SPECT ) . Patients were studied at baseline ( visit 1 ) , after 2 months of MPH treatment ( visit 2 ) and after a drug-free period of 2 months following 12 months of MPH treatment ( visit 3 ) at doses of 1 mg/kg/day . We evaluated SPECT data visually and semi-quantitatively . RESULTS Two months of chronic MPH treatment result ed in visually detectable improvement in hypoperfusion in the right frontal cortex and all areas of temporal cortex with the exception of left lateral temporal cortex . This improvement was still detectable on visual evaluations of SPECT data after 2 months of treatment discontinuation . The treatment effects that were detected visually were not statistically significant in semi-quantitative analyses . CONCLUSIONS Treatment effects of chronic MPH treatment may persist long after the discontinuation of the treatment",
"BACKGROUND Children with Attention Deficit Hyperactivity Disorder ( ADHD ) have deficits in motivation and attention that can be ameliorated with the indirect dopamine agonist Methylpheni date ( MPH ) . We used functional magnetic resonance imaging ( fMRI ) to investigate the effects of MPH in medication-naïve children with ADHD on the activation and functional connectivity of \" cool \" attentional as well as \" hot \" motivation networks . METHODS 13 medication-naïve children with ADHD were scanned twice , under either an acute clinical dose of MPH or Placebo , in a r and omised , double-blind design , while they performed a rewarded continuous performance task that measured vigilant selective attention and the effects of reward . Brain activation and functional connectivity was compared to that of 13 healthy age-matched controls to test for normalisation effects of MPH . RESULTS MPH normalised performance deficits that were observed in children with ADHD compared to controls . Under placebo , children with ADHD showed reduced activation and functional inter-connectivity in bilateral fronto-striato-parieto-cerebellar networks during the attention condition , but enhanced activation in the orbitofrontal and superior temporal cortices for reward . MPH within children with ADHD enhanced the activation of fronto-striato-cerebellar and parieto-temporal regions . Compared to controls , MPH normalised differences during vigilant attention in parieto-temporal activation and fronto-striatal and fronto-cerebellar connectivity ; MPH also normalised the enhanced orbitofrontal activation in children with ADHD in response to reward . CONCLUSIONS MPH normalised attention differences between children with ADHD and controls by both up-regulation of dysfunctional fronto-striato-thalamo-cerebellar and parieto-temporal attention networks and down-regulation of hyper-sensitive orbitofrontal activation for reward processing . MPH thus shows context -dependent dissociative modulation of both motivational and attentional neuro-functional networks in children with ADHD"
] |
4116bf6e-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND Balneotherapy ( or spa therapy , mineral baths ) for patients with arthritis is one of the oldest forms of therapy . One of the aims of balneotherapy is to soothe the pain and as a consequence to relieve patients ' suffering and make them feel well . In this up date we included one extra study . OBJECTIVES To assess the effectiveness of balneotherapy for patients with osteoarthritis ( OA ) . SEARCH STRATEGY We search ed the following data bases up to October 2006 : EMBASE , PubMed , the Cochrane ' Rehabilitation and Related Therapies ' Field data base , PEDro , CENTRAL ( Issue 3 , 2006 ) and performed reference checking and communicated with authors to retrieve eligible studies . SELECTION CRITERIA R and omised controlled trials ( RCT ) comparing balneotherapy with any intervention or no intervention . At least 90 % of the patient population had to be diagnosed with OA . DATA COLLECTION AND ANALYSIS Two authors independently assessed quality and extracted data . Disagreements were solved by consensus . In the event of clinical heterogeneity or lack of data we refrained from statistical pooling . MAIN RESULTS Seven trials ( 498 patients ) were included in this review . Two studies compared spa-treatment with no treatment . One study evaluated baths as an add-on treatment to home exercises and another compared thermal water from Cserkeszölö with tap water ( placebo ) . Three studies evaluated sulphur or Dead Sea baths with no treatment or mineral baths with tap water baths or no treatment . Only one of the trials performed an intention-to-treat analysis and two studies provided data to perform an intention-to-treat analysis ourselves . A ' quality of life ' outcome was reported by one trial . We found : silver level evidence concerning the beneficial effects on pain , quality of life and analgesic intake of mineral baths compared to no treatment ( SMD between 1.82 and 0.34 ) . a statistically significant difference in pain and function of Dead Sea + sulphur versus no treatment , only at end of treatment ( WMD 5.7 , 95%CI 3.3 to 8.1 ) , but not at 3 month follow-up ( WMD 2.6 , 95%CI -1.1 to 6.3 ) . no statistically significant differences in pain or function at one or three months of Dead Sea baths versus no treatment ( WMD 0.5 , 95%CI -0.6 to 1.6 ) or at one or three months of sulphur baths versus no treatment ( WMD 0.4 , 95%CI -0.9 to 1.7 ) . Adverse events were not measured in the included trials . AUTHORS ' CONCLUSIONS We found silver level evidence ( www.cochranemsk.org ) concerning the beneficial effects of mineral baths compared to no treatment . Of all other balneological treatments no clear effects were found . However , the scientific evidence is weak because of the poor method ological quality and the absence of an adequate statistical analysis and data presentation . Therefore , the noted " positive findings " should be viewed with caution
|
[
"OBJECTIVE To conduct a preliminary investigation of the effects on floatation spa therapy on quality of life in patients with osteoarthritis to see if controlled trials are warranted . DESIGN Uncontrolled clinical trial . SETTING Private floatation spa therapy centre . PATIENTS Fourteen patients with chronic osteoarthritis of the weight-bearing joints , of whom four dropped out . INTERVENTION Six weekly sessions of floatation spa therapy . OUTCOME MEASURES SF36 , AIMS 2 and MYMOP quality -of-life question naires . MAIN RESULTS All patients improved . Differences between baseline and discharge scores showed statistically significant improvement for MYMOP , but not AIMS 2 or SF-36 . CONCLUSIONS Controlled trials of floatation spa therapy for patients with osteoarthritis are warranted",
"Forty patients with classical or definite rheumatoid arthritis in a stage of active disease were treated for two weeks at a spa hotel . The patients were divided into four groups of 10 . Group I was treated with daily mud packs , group II with daily hot sulphur baths , group III with a combination of mud packs and hot sulphur baths , and group IV served as a control group . The patients were assessed by a rheumatologist who was blinded to the treatment modalities . Statistically significant improvement for a period of up to three months was observed in the three treatment groups in most of the clinical indices . Improvement in the control group was minor in comparison and not statistically significant . No significant improvement was observed in any of the laboratory variables measured . Except for three mild cases of thermal reaction there were no side effects",
"Thirty patients with classical or definite rheumatoid arthritis were r and omly divided into two groups of fifteen patients each of similar age , sex , duration and severity of disease , and medical treatment . All patients were treated once a day with bath salts heated to 35 degrees C for twenty minutes . Group I received Dead Sea bath salts and Group II , the control group , received sodium chloride ( NaCl ) . The study was double-blind and of two weeks ' duration . All patients were evaluated by one rheumatologist both before treatment , and two weeks later at the end of the treatment period . Follow-up evaluations were made one and three months after conclusion of the treatments . The clinical parameters evaluated included duration of morning stiffness , fifteen meter walk time , h and -grip strength , activities of daily living , circumference of proximal interphalangeal joints , number of active joints , Ritchie index and the patient 's own assessment of disease activity . The laboratory parameters evaluated included erythrocyte sedimentation rate and serum levels of amyloid A , rheumatoid factor , sodium , potassium , calcium and magnesium . A statistically significant improvement ( p less than 0.01 or p less than 0.05 ) was observed in Group I only , in most of the clinical parameters assessed . Maximal therapeutic effect was obtained at the end of the treatment and lasted up to one month",
"Abstract The purpose of this study was to evaluate the immediate and delayed effects of balneotherapy at the Dead Sea on patients with psoriatic arthritis ( PsA ) . A total of 42 patients with PsA were treated at the Dead Sea for 4 weeks . Patients were r and omly allocated into two groups : group 1 ( 23 patients ) and group 2 ( 19 patients ) . Both groups received daily exposure to sun ultraviolet rays and regular bathing at the Dead Sea . Group 1 was also treated with mud packs and sulfur baths . Patients were assessed by a dermatologist and a rheumatologist 3 days before arrival , at the end of treatment , and at weeks 8 , 16 , and 28 from the start of treatment . The clinical indices assessed were morning stiffness , right and left h and grip , number of tender joints , number of swollen joints , Schober test , distance from finger to floor when bending forward , patient 's self- assessment of disease severity , inflammatory neck and back pain and psoriasis area and severity index ( PASI ) score . Comparison between groups disclosed a similar statistically significant improvement for variables such as PASI , morning stiffness , patient self- assessment , right and left grip , Schober test and distance from finger to floor when bending forward . For variables such as tender and swollen joints , and inflammatory neck and back pain , improvement over time was statistically significant in group 1 . Addition of mud packs and sulfur baths to sun ultraviolet exposure and Dead Sea baths seems to prolong beneficial effects and improves inflammatory back pain",
"BACKGROUND A beneficial effect was observed in patients with psoriasis vulgaris following balneotherapy with Dead Sea bath salt . OBJECTIVES To evaluate the possible role of trace elements in the effectiveness of balneotherapy . METHODS Serum levels of 11 trace elements were analyzed in 23 patients with psoriasis vulgaris who participated in a double-blind controlled study of balneotherapy with either Dead Sea bath salt ( 12 patients ) or common salt ( 11 patients ) . Thirteen healthy volunteers served as controls . RESULTS The mean pre-treatment serum levels of boron , cadmium , lithium and rubidium were significantly lower in patients compared to controls , whereas the mean pre-treatment serum level of manganese was significantly higher in patients compared to controls . Balneotherapy with Dead Sea bath salt result ed in a significant decrease ( P = 0.0051 ) in the mean serum level of manganese from 0.10 + /- 0.05 mol/L to 0.05 + /- 0.02 mumol/L. The mean reduction in the serum level of manganese differed significantly ( P = 0.002 ) between responders ( % Psoriasis Area and Severity Index score reduction > or = 25 ) and non-responders ( % PASI score reduction balneotherapy with Dead Sea bath salt the mean serum level of lithium decreased in responders by 0.01 + /- 0.02 mumol/L , whereas its level in non-responders increased by 0.03 + /- 0.03 mumol/L. ( P = 0.015 ) . CONCLUSIONS Manganese and lithium may play a role in the effectiveness of balneotherapy with Dead Sea bath salt for psoriasis",
"OBJECTIVE To determine the efficacy of combined spa-exercise therapy in addition to st and ard treatment with drugs and weekly group physical therapy in patients with ankylosing spondylitis ( AS ) . METHODS A total of 120 Dutch out patients with AS were r and omly allocated into 3 groups of 40 patients each . Group 1 ( mean age 48 + /- 10 years ; male : female ratio 25:15 ) was treated in a spa resort in Bad Hofgastein , Austria ; group 2 ( mean age 49 + /- 9 years ; male : female ratio 28:12 ) in a spa resort in Arcen , The Netherl and s. The control group ( mean age 48 + /- 10 years ; male : female ratio 34:6 ) stayed at home and continued their usual drug treatment and weekly group physical therapy during the intervention weeks . St and ardized spa-exercise therapy of 3 weeks duration consisted of group physical exercises , walking , correction therapy ( lying supine on a bed ) , hydrotherapy , sports , and visits to either the Gasteiner Heilstollen ( Austria ) or sauna ( Netherl and s ) . After spa-exercise therapy all patients followed weekly group physical therapy for another 37 weeks . Primary outcomes were functional ability , patient 's global well-being , pain , and duration of morning stiffness , aggregated in a pooled index of change ( PIC ) . RESULTS Analysis of variance showed a statistically significant time-effect ( P spa-exercise therapy , the mean difference in PIC between group 1 and controls was 0.49 ( 95 % confidence interval [ CI ] 0.16 - 0.82 , P = 0.004 ) and between group 2 and controls was 0.46 ( 95 % CI 0.15 - 0.78 , P = 0.005 ) . At 16 weeks , the difference between group 1 and controls was 0.63 ( 95 % CI 0.23 - 1.02 , P = 0.002 ) and between group 2 and controls was 0.34 ( 95 % CI--0.05 - 0.73 ; P = 0.086 ) . At 28 and 40 weeks , more improvement was found for group 1 compared with controls ( P = 0.012 and P = 0.062 , respectively ) but not for group 2 compared with controls . CONCLUSION In patients with AS , a 3-week course of combined spa-exercise therapy , in addition to drug treatment and weekly group physical therapy alone , provides beneficial effects . These beneficial effects may last for at least 40 weeks",
"The objective of this study was to evaluate the effect of spa therapy on clinical parameters of patients with gonarthrosis . Patients with gonarthrosis ( n=33 ) underwent a 2-week spa therapy using three treatment regimes and a 20-week follow-up as follows : group I ( n=11 ) had mineral water baths and hot native mineral mud packs , group II ( n=12 ) had mineral water baths and rinsed mineral-free mud packs and group III ( n=10 ) had tap water baths and mineral-free mud packs . The patients and the assessing rheumatologist were blinded to the difference in the treatment protocol s. A significant improvement in the index of severity of the knee ( ISK ) , as well as night pain scores , was achieved in group I. Improvement in physical findings and a reduction in pain ratings on a visual analogue scale ( VAS ) did not reach statistical significance . Analgesic consumption was significantly decreased in both groups I and III for up to 12 weeks . Global improvement assessed by patients and physician was observed in all three groups up to 16 weeks but persisted to the end of the follow-up period in group I only . Patients with gonarthrosis seemed to benefit from spa therapy under all three regimes . However , for two parameters ( night pain and ISK ) the combination of mineral water baths and mud packs ( group I ) appeared to be superior",
"The effect of \" Kangal Hot Spring with Fish \" in the treatment of psoriasis is investigated . The study was carried out on 87 patients with psoriasis vulgaris and the patients were evaluated by a dermatologist for 21 days . The evaluation of the disease was performed using PASI ( Psoriasis Area and Severity Index ) scores . Recurrences were investigated in the patient population , who had been previously treated in the same hot spring . The first examination scores were significantly higher than the scores of the 3 , 6 , 9 , 12 , 15 and 21 days after treatment ( p Longer remission periods , when compared to the topical corticosteroid treatment , expressed by the 35 patients previously treated in hot spring ( p < 0.01 ) . Spa therapy under observation of a dermatologist may be effective and useful for psoriasis vulgaris patients",
"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",
"Objective : The present exploratory study sought to examine the changes of well-being associated with 3 weeks of resort based spa therapy . This is a traditional form of health enhancement incorporating balneotherapy , physical therapies , and health education in an inpatient setting . Patients and Method : Subjects were spa patients ( n = 153 , mean age 58 years ) with chronic pain and other age related complaints of moderately higher than normal prevalence . The well-being variables were vegetative complaints , pain , fatigue , positive and negative mood , and health satisfaction assessed at the beginning and end of spa treatment as well as 5 weeks and 12 months thereafter . Results : Well-being improved significantly in all variables during spa therapy , the improvement continuing with a slight deterioration at 5 weeks after the stay . After 12 months , vegetative complaints and fatigue had again reached pre-spa levels , whereas pain , positive and negative mood as well as health satisfaction remained improved . Both patients with high and low levels of pain increase their well-being , although pain patients showed greater improvements in some of the measures . Subjects not responding to spa therapy were older and showed less health satisfaction . Conclusions : The results suggest that spa therapy may be a powerful tool in enhancing well-being in progressed middle aged adults with common health impairments",
"Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists",
"Abstract : Fibromyalgia ( FS ) is an idiopathic chronic pain syndrome defined by widespread non-articular musculoskeletal pain and generalised tender points . As there is no effective treatment , patients with this condition have impaired quality of life ( QoL ) . The aim of this study was to assess the possible effect of balneotherapy at the Dead Sea area on the QoL of patients with FS . Forty-eight subjects participated in the study ; half of them received balneotherapy , and half did not . Their QoL ( using SF-36 ) , psychological well-being and FS-related symptoms were assessed prior to arrival at the spa hotel in the Dead Sea area , at the end of the 10-day stay , and 1 and 3 months later . A significant improvement was reported on most subscales of the SF-36 and on most symptoms . The improvement in physical aspects of QoL lasted usually 3 months , but on psychological measures the improvement was shorter . Subjects in the balneotherapy group reported higher and longer-lasting improvement than subjects in the control group . In conclusion , staying at the Dead Sea spa , in addition to balneotherapy , can transiently improve the QoL of patients with FS . Other studies with longer follow-up are needed to support our findings",
"OBJECTIVE To quantify the efficacy of a series of baths containing natural radon and carbon dioxide ( 1.3 kBq/l , 1.6 g carbon dioxide/l on average ) versus artificial carbon dioxide baths alone in patients with rheumatoid arthritis . SUBJECTS Sixty patients participating in an in-patient rehabilitation programme including a series of 15 baths were r and omly assigned to two groups . DESIGN Pain intensity ( 100 mm visual analogue scale ) and functional restrictions [ Keitel functional test , Arthritis Impact Measurement Scales ( AIMS question naire ) ] were measured at baseline , after completion of treatment and 3 and 6 months thereafter . To investigate whether the overall value of the outcomes was the same in both groups , the overall mean was analysed by Student 's t-test for independent sample s. RESULTS The two groups showed a similar baseline situation . After completion of treatment , relevant clinical improvements were observed in both groups , with no notable group differences . However , the follow-up revealed sustained effects in the radon arm , and a return to baseline levels in the sham arm . After 6 months , marked between-group differences were found for both end-points ( pain intensity : -16.9 % , 95 % confidence interval -27.6 to -6.2 % ; AIMS score : 0.57 , 95 % confidence interval 0.16 to 0.98 ) . The between-group differences were statistically significant for both overall means ( pain intensity , P : = 0.04 ; AIMS , P : = 0.01 ) . CONCLUSION Marked short-term improvements in both groups at the end of treatment may have masked potential specific therapeutic effects of radon baths . However , after 6 months of follow-up the effects were lasting only in patients of the radon arm . This suggests that this component of the rehabilitative intervention can induce beneficial long-term effects",
"OBJECTIVE The aim of this study was to evaluate the therapeutic effects of hydrotherapy which combines elements of warm water immersion and exercise . It was predicted that hydrotherapy would result in a greater therapeutic benefit than either of these components separately . METHODS One hundred thirty-nine patients with chronic rheumatoid arthritis were r and omly assigned to hydrotherapy , seated immersion , l and exercise , or progressive relaxation . Patients attended 30-minute sessions twice weekly for 4 weeks . Physical and psychological measures were completed before and after intervention , and at a 3-month followup . RESULTS All patients improved physically and emotionally , as assessed by the Arthritis Impact Measurement Scales 2 question naire . Belief that pain was controlled by chance happenings decreased , signifying improvement . In addition , hydrotherapy patients showed significantly greater improvement in joint tenderness and in knee range of movement ( women only ) . At followup , hydrotherapy patients maintained the improvement in emotional and psychological state . CONCLUSIONS Although all patients experienced some benefit , hydrotherapy produced the greatest improvements . This study , therefore , provides some justification for the continued use of hydrotherapy",
"Background : Due to possible antiinflammatory effects , sulfur baths are widely used for the treatment of rheumatic diseases . Previously it was demonstrated that drinking cures with sulfur can improve the antioxidative defense system and lower the peroxide levels of patients with chronic degenerative osteoarthritis . Objective : This study therefore sought to investigate the effect of 3-week therapy with sulfur baths on antioxidative defense systems , peroxide concentrations , and lipid levels in patients with degenerative osteoarthritis . Patients and Methods : After r and omization one group of patients ( n = 19 ) received sulfur baths during their stay at a health resort ( sulfur group ) , whereas the other age-matched patient group served as controls ( n = 19 , control group ) , only receiving spa therapy . Total cholesterol levels , HDL , LDL , triglycerides and the antioxidative status , glutathione peroxidase , and superoxide dismutase ( SOD ) activities , and peroxide concentration , as an oxidative stress parameter , were evaluated at the begin and end of therapy . Results : A 17.2 % decline in peroxide concentrations ( p = 0.10 , n.s . ) and significant lower SOD activities ( p therapy total cholesterol levels changed differentially ( p = 0.007 ) in the sulfur group ( from 229.11 ± 34.47 mg/dl to 217.46 ± 40.45 mg/dl ) and in the control group ( from 197.63 ± 34.66 mg/dl to 207.95 ± 33.02 mg/dl ) . A similar significant group difference was found for LDL ( p = 0.017 ) , with a 5.9 % reduction in the sulfur group and a 6.1 % increase in the control group . Triglyceride concentrations were nonsignificantly reduced in both groups after 3 weeks at the health resort ( sulfur group 11.2 % , control group 20.2 % ) . HDL values only minimally changed in both groups . Conclusions : The results presented here suggest that a sulfur bath therapy could cause a reduction in oxidative stress , alterations of SOD activities , and a tendency towards improvement of lipid levels ",
"Spa therapy is frequently used in daily rheumatological practice , but its benefit remains to be evaluated . A prospect i ve r and omized controlled study was conducted in 1993 in patients with osteoarthritis of the hip , knee or lumbar spine . Treatment was either spa therapy at Vichy ( France ) of 3 weeks duration ( spa group ) or usual therapy ( control group ) . Assessment criteria were pain ( visual analogue scale ) , functional impairment ( Lequesne 's index for hip or knee disease , Main and Waddell 's for lumbar spinal diseases ) , quality of life index [ revised Arthritis Impact Measurement Scale ( AIMS 2 ) ] , and analgesic and /or non-steroidal anti-inflammatory drug ( NSAID ) consumption . Patients were included by r and omization into one of the two arms ( spa or control ) and assessment criteria were collected before spa therapy or the control period , and 3 and 24 weeks thereafter . A total of 188 patients ( lumbar spine 95 , knee 64 , hip 29 ) were included in the study ( spa group 91 , control group 97 ) . Changes in the assessment criteria after a 6 month follow-up period showed improvement in terms of pain , functional impairment and quality of life , with a reduced intake of symptomatic drugs ( NSAID and analgesic drugs ) in the spa group . This study suggests that spa therapy of 3 weeks duration has a prolonged , beneficial , symptomatic effect in osteoarthritis",
"OBJECTIVE To determine whether hydrotherapy in a thermomineral institution is superior to the same hydrotherapy in an ordinary hospital exercise-bath . DESIGN Controlled therapeutic trial . SETTING The thermomineral institution at Arcen and the exercise bath at the Maasl and Hospital in Sittard , the Netherl and s. PATIENTS AND METHODS 46 patients with rheumatoid arthritis were treated in a by a skilled physiotherapist , according to a st and ardized exercise-scheme : 27 were treated in the thermomineral institution and 19 ( control-group ) in the hospital exercise-bath . Each patient received 12 treatments in 12 weeks . ENDPOINTS PARAMETERS : Morning stiffness , erythrocyte sedimentation rate , Ritchie index , amount of pain , answers to 11 questions concerning the activities of daily life , and psychosocial aspects of the disease . The various subjective and objective parameters were scored by the same physician . RESULTS Statistically significant improvement was observed in both groups concerning morning stiffness . Other subjective parameters improved , but did not reach significance . Objective parameters did not change significantly . Between-group differences were not found . CONCLUSION Hydrotherapy has a positive effect on some subjective but not on objective parameters in patients with rheumatoid arthritis , whether it is applied in a thermomineral institution or an ordinary hospital exercise bath",
"A quantitative systematic review , or meta- analysis , uses statistical methods to combine the results of multiple studies . Meta-analyses have been done for systematic review s of therapeutic trials , diagnostic test evaluations , and epidemiologic studies . Although the statistical methods involved may at first appear to be mathematically complex , their purpose is simple : They are trying to answer four basic questions . Are the results of the different studies similar ? To the extent that they are similar , what is the best overall estimate ? How precise and robust is this estimate ? Finally , can dissimilarities be explained ? This article provides some guidance in underst and ing the key technical aspects of the quantitative approach to these questions . We have avoided using equations and statistical notations ; interested readers will find implementations of the described methods in the listed references . We focus here on the quantitative synthesis of reports of r and omized , controlled , therapeutic trials because far more meta-analyses on therapeutic studies than on other types of studies have been published . For practical reasons , we present a stepwise description of the tasks that are performed when statistical methods are used to combine data . These tasks are 1 ) deciding whether to combine data and defining what to combine , 2 ) evaluating the statistical heterogeneity of the data , 3 ) estimating a common effect , 4 ) exploring and explaining heterogeneity , 5 ) assessing the potential for bias , and 6 ) presenting the results . Deciding Whether To Combine Data and Defining What To Combine By the time one performs a quantitative synthesis , certain decisions should already have been made about the formulation of the question and the selection of included studies . These topics were discussed in two previous articles in this series [ 1 , 2 ] . Statistical tests can not compensate for lack of common sense , clinical acumen , and biological plausibility in the design of the protocol of a meta- analysis . Thus , a reader of a systematic review should always address these issues before evaluating the statistical methods that have been used and the results that have been generated . Combining poor- quality data , overly biased data , or data that do not make sense can easily produce unreliable results . The data to be combined in a meta- analysis are usually either binary or continuous . Binary data involve a yes/no categorization ( for example , death or survival ) . Continuous data take a range of values ( for example , change in diastolic blood pressure after antihypertensive treatment , measured in mm Hg ) . When one is comparing groups of patients , binary data can be summarized by using several measures of treatment effect that were discussed earlier in this series [ 3 ] . These measures include the risk ratio ; the odds ratio ; the risk difference ; and , when study duration is important , the incidence rate . Another useful clinical measure , the number needed to treat ( NNT ) , is derived from the inverse of the risk difference [ 3 ] . Treatment effect measures , such as the risk ratio and the odds ratio , provide an estimate of the relative efficacy of an intervention , whereas the risk difference describes the intervention 's absolute benefit . The various measures of treatment effect offer complementary information , and all should be examined [ 4 ] . Continuous data can be summarized by the raw mean difference between the treatment and control groups when the treatment effect is measured on the same scale ( for example , diastolic blood pressure in mm Hg ) , by the st and ardized mean difference when different scales are used to measure the same treatment effect ( for example , different pain scales being combined ) , or by the correlation coefficients between two continuous variables [ 5 ] . The st and ardized mean difference , also called the effect size , is obtained by dividing the difference between the mean in the treatment group and the mean in the control group by the SD in the control group . Evaluating the Statistical Heterogeneity of the Data This step is intended to answer the question , Are the results of the different studies similar ( homogeneous ) ? It is important to answer this question before combining any data . To do this , one must calculate the magnitude of the statistical diversity ( heterogeneity ) of the treatment effect that exists among the different sets of data . Statistical diversity can be thought of as attributable to one or both of two causes . First , study results can differ because of r and om sampling error . Even if the true effect is the same in each study , the results of different studies would be expected to vary r and omly around the true common fixed effect . This diversity is called the within- study variance . Second , each study may have been drawn from a different population , depending on the particular patients chosen and the interventions and conditions unique to the study . Therefore , even if each study enrolled a large patient sample , the treatment effect would be expected to differ . These differences , called r and om effects , describe the between- study variation with regard to an overall mean of the effects of all of the studies that could be undertaken . The test most commonly used to assess the statistical significance of between- study heterogeneity is based on the chi-square distribution [ 6 ] . It provides a measure of the sum of the squared differences between the results observed and the results expected in each study , under the assumption that each study estimates the same common treatment effect . A large total deviation indicates that a single common treatment effect is unlikely . Any pooled estimate calculated must account for the between- study heterogeneity . In practice , this test has low sensitivity for detecting heterogeneity , and it has been suggested that a liberal significance level , such as 0.1 , should be used [ 6 ] . Estimating a Common Effect The questions that this step tries to answers are , 1 ) To the extent that data are similar , what is their best common point estimate of a therapeutic effect , and 2 ) how precise is this estimate ? The mathematical process involved in this step generally involves combining ( pooling ) the results of different studies into an overall estimate . Compared with the results of individual studies , pooled results can increase statistical power and lead to more precise estimates of treatment effect . Each study is given a weight according to the precision of its results . The rationale is that studies with narrow CIs should be weighted more heavily than studies with greater uncertainty . The precision is generally expressed by the inverse of the variance of the estimate of each study . The variance has two components : the variance of the individual study and the variance between different studies . When the between- study variance is found to be or assumed to be zero , each study is simply weighted by the inverse of its own variance , which is a function of the study size and the number of events in the study . This approach characterizes a fixed-effects model , as exemplified by the Mantel-Haenszel method [ 7 , 8 ] or the Peto method [ 9 ] for dichotomous data . The Peto method has been particularly popular in the past . It has the advantage of simple calculation ; however , although it is appropriate in most cases , it may introduce large biases if the data are unbalanced [ 10 , 11 ] . On the other h and , r and om-effects models also add the between- study variance to the within- study variance of each individual study when the pooled mean of the r and om effects is calculated . The r and om-effects model most commonly used for dichotomous data is the DerSimonian and Laird estimate of the between- study variance [ 12 ] . Fixed- and r and om-effects models for continuous data have also been described [ 13 ] . Pooled results are generally reported as a point estimate and CI , typically a 95 % CI . Other quantitative techniques for combining data , such as the Confidence Profile Method [ 14 ] , use Bayesian methods to calculate posterior probability distributions for effects of interest . Bayesian statistics are based on the principle that each observation or set of observations should be viewed in conjunction with a prior probability describing the prior knowledge about the phenomenon of interest [ 15 ] . The new observations alter this prior probability to generate a posterior probability . Traditional meta- analysis assumes that nothing is known about the magnitude of the treatment effect before r and omized trials are performed . In Bayesian terms , the prior probability distribution is noninformative . Bayesian approaches may also allow the incorporation of indirect evidence in generating prior distributions [ 14 ] and may be particularly helpful in situations in which few data from r and omized studies exist [ 16 ] . Bayesian analyses may also be used to account for the uncertainty introduced by estimating the between- study variance in the r and om-effects model , leading to more appropriate estimates and predictions of treatment efficacy [ 17 ] . Exploring and Explaining Heterogeneity The next important issue is whether the common estimate obtained in the previous step is robust . Sensitivity analyses determine whether the common estimate is influenced by changes in the assumptions and in the protocol for combining the data . A comparison of the results of fixed- and r and om-effects models is one such sensitivity analysis [ 18 ] . Generally , the r and om-effects model produces wider CIs than does the fixed-effects model , and the level of statistical significance may therefore be different depending on the model used . The pooled point estimate per se is less likely to be affected , although exceptions are possible [ 19 ] . Other sensitivity analyses may include the examination of the residuals and the chi-square components [ 13 ] and assessment of the effect of deleting each study in turn . Statistically significant results that depend on a single study may require further exploration . Cumulative Meta- Analysis",
"Abstract . The effects of thermal water from Cserkeszölö in Hungary were appraised in a r and omised , double blind study conducted on 58 patients with osteoarthritis of the knee . Balneotherapy was delivered as a 15-day course of 30-min daily sessions performed with thermal water ( active treatment ) or tap water of similar colour and odour ( placebo treatment ) . The musculoskeletal status of participants was evaluated at baseline , at the end of the balneotherapy course , and 3 months later . Study endpoints ( initial pain , range of motion , tenderness on palpation , stair climbing , physicians ' opinion and subjective rating by patients , and ambulation ) were assessed using visual analogue scales and symptom scores . Both groups improved ; however , the magnitude of improvement was significantly greater in patients treated with thermal water from Cserkeszölö",
"BACKGROUND Balneotherapy at the Dead Sea area has been applied in various inflammatory rheumatic diseases such as rheumatoid arthritis and psoriatic arthritis . The efficacy of balneotherapy at the Dead Sea area for the treatment of degenerative rheumatic diseases has not yet been formally evaluated . OBJECTIVE To evaluate the efficacy of balneotherapy at the Dead Sea area in patients suffering from osteoarthritis of the knees . METHODS Forty patients were r and omly allocated into four groups of 10 patients . Group I was treated by bathing in a sulphur pool , group 2 by bathing in the Dead Sea , group 3 by a combination of sulphur pool and bathing in the Dead Sea , and group 4 served as the control group receiving no balneotherapy . The duration of balneotherapy was 2 weeks . RESULTS Significant improvement as measured by the Lequesne index of severity of osteoarthritis was observed in all three treatment groups , but not in the control group . This improvement lasted up to 3 months of follow-up in patients in all three treatment groups . CONCLUSION Balneotherapy at the Dead Sea area has a beneficial effect on patients with osteoarthritis of the knees , an effect that lastas at least 3 months",
" 26 patients with osteoarthritis of the knees were r and omly divided into 2 groups of 13 each with patients of similar ages , sex distribution and duration and severity of disease . All were treated with daily baths at 34 - 35 degrees C for 20 min . containing Dead Sea bath salts ( Group I ) or sodium chloride ( Group II ) . The study was double-blind and of 2 weeks duration . Patients were evaluated by a rheumatologist before , at the end of treatment and 1 month later . Clinical parameters evaluated included index of severity of osteoarthritis , patient 's assessment of disease severity , range of movement of knees , soft tissue swelling , effusion and crepitus . There was significant improvement in the index of severity of osteoarthritis at the end of the treatment in both groups ( p improvement in either group in the other parameters assessed",
"OBJECTIVES Several studies suggest a beneficial overall effect of spa therapy in chronic musculoskeletal diseases . The present open controlled study investigated the effects of spa therapy at Bourbonne-Les-Bains , France , in patients with hip or knee osteoarthritis or low back pain . PATIENTS AND METHODS In 1998 , 102 men and women older than 50 years were included in the study . All had low back pain or lower limb osteoarthritis , and none had contraindications to spa therapy . Quality of life was assessed three times at intervals of 4 weeks , twice before and once immediately after 3 weeks of spa therapy , using the Duke Health Profile ( five dimensions and five dysfunctions ) . RESULTS Mean age was 66.4 years , and 67 % of the patients were women . Quality of life was markedly decreased as compared to the population at large ( 1996 , CFES ) . The two pretreatment evaluations produced similar quality -of-life scores . Spa therapy was associated with significant improvements in overall quality of life ( P=0.004 ) , self-esteem ( P=0.009 ) , and pain ( P=0.01 ) . CONCLUSION These findings support those of other studies conducted in France and in other European countries . They indicate that patients report meaningful improvements in their quality of life after spa therapy",
" Thirty-six patients with active rheumatoid arthritis were treated for 12 days at the Ein Gedi Spa . The patients were allocated r and omly to four study groups . Group 1 ( n = 9 ) was treated with daily baths in the Dead Sea , group 2 ( n = 9 ) was treated with daily sulphur baths , group 3 ( n = 10 ) was treated with a combination of daily Dead Sea bathing and sulphur baths , and group 4 ( n = 8) served as a control group . All patients were assessed by a rheumatologist who was blinded to the treatment modalities and group allocation . Clinical parameters assessed included : duration of morning stiffness , 15 m walk time , grip strength , activities of daily living , patient 's assessment of disease severity , number of active joints , and the Ritchie articular index . Statistically significant improvement lasting up to 3 months was observed only in the three treatment groups",
"Hydrotherapy for OA of the hip has rarely been evaluated in controlled studies . Forty-seven patients with OA of the hip were followed for 18 weeks . Patients were r and omly allocated either to a regimen of home exercises or to twice weekly hydrotherapy for 6 weeks in addition to home exercises . There was an improvement seen in both subjective and objective measures in both groups with treatment . There was no significant difference between the two groups . Response to treatment appeared independent of age , sex and radiological severity . We conclude that for most patients , a carefully grade d and supervised regimen of home exercises is beneficial and there is little benefit in adding hydrotherapy to this regimen",
"To treat cases of psoriasis , various modifications of the original Ingram method were tested for increased effectiveness and minimized side reactions . Our modified method consists of 0.1 - 0.5 % anthralin ointment application and selective UVB phototherapy with adjunctive warm water bath and the application of emollients . The object of this study was to evaluate the effectiveness and duration of remission in response to our modified Ingram method and compare the data with the severity of psoriasis . The clearing rate was higher and the failure rate was lower in the moderate group . The number of occasions on which therapy was used and the duration of this therapy were greater in the severe group , but there were no significant differences except for the number of occasions of therapy to the trunk . Fifty-eight percent of the moderate group did not relapse in more than one year , but 63 % of the severe group relapsed within six months . The results of this study showed that the modified Ingram regimen is an effective therapeutic modality in psoriasis , especially in the moderate group",
"BACKGROUND / PURPOSE Apart from climatotherapy and spa therapy , combined treatment with salt water baths and artificial UV radiation ( balneophototherapy ) has been advocated for the treatment of psoriasis . As there is a lack of controlled studies on balneophototherapy ( BPT ) , we conducted a r and omized , one-blind , right/left comparison with salt water versus tap water in order to investigate the significance of the salt concentration in the efficacy of BPT . METHODS Ten psoriasis patients with chronic plaques on the elbows were included in the study . One elbow was soaked in 24 % NaCl solution and the other in tap water . Subsequently , broadb and UVB irradiation was administered . BPT was performed 4 times weekly with a total of 30 treatments . RESULTS A highly significant ( P clinical baseline score was observed after 30 treatments ; however , there was no significant ( P>0.5 ) difference in clearance of the psoriatic lesions between the sites soaked in salt water and tap water . CONCLUSION Our results suggest that any additional benefit of soaking in salt water and tap water in BPT are unlikely to be due to the salinity of the liquids",
"BACKGROUND Balneotherapy has been successfully used to treat various rheumatic diseases , but has only recently been evaluated for the treatment of fibromyalgia . Since no effective treatment exists for this common rheumatic disease , complementary methods of treatment have been attempted . OBJECTIVES To assess the effectiveness of balneotherapy at the Dead Sea area in the treatment of patients suffering from both fibromyalgia and psoriatic arthritis . METHODS Twenty-eight patients with psoriatic arthritis and fibromyalgia were treated with various modalities of balneotherapy at the Dead Sea area . Clinical indices assessed were duration of morning stiffness , number of active joints , a point count of 18 fibrositic tender points , and determination of the threshold of tenderness in nine fibrositic and in four control points using a dolorimeter . RESULTS The number of active joints was reduced from 18.4 + /- 10.9 to 9 + /- 8.2 ( P number of tender points was reduced from 12.6 + /- 2 to 7.1 + /- 5 in men ( P dolorimetric threshold readings after the treatment period in women ( P number of active joints and the reduction in the number of tender points in the same patients ( r = 0.2 ) . CONCLUSIONS Balneotherapy at the Dead Sea area appears to produce a statistically significant substantial improvement in the number of active joints and tender points in both male and female patients with fibromyalgia and psoriatic arthritis . Further research is needed to eluci date the distinction between the benefits of staying at the Dead Sea area without balneotherapy and the effects of balneotherapy in the study population",
"THE AUTHORS examined the effectiveness of the thermal water of Puspokladany on 62 patients suffering from osteoarthritis of the knee in a double-blind , placebo controlled study . Thermal water decreased pain in movement and tenderness of the knee significantly compared to that of the control group . Bath-reaction ( increase of ESR , leukocyte number and spontaneous pain ) was observed only in the group treated with thermal water . The results indi cate , that the thermal water of Puspokladany is suitable for treating patients suffering from degenerative arthopathies . In a previous announcement , Varga and his colleagues had established that a 20-days bath treat ment in the thermal water of Puspokladany signifi cantly reduced the pain of spondylosis patients when the treatment was applied in the undiluted thermal water . Bath reaction was shown on the patients who were treated in the undiluted thermal water , which was proved by the significant increase of the leucocyte number . The present paper deals with the study and tests we conducted to establish the effect of Puspokla dany 's thermal water on patients with osteoarthritis of the knee"
] |
4116bfb4-06ff-11f0-808a-c43d1ab1c353
|
Concerns have been raised about the adverse effect of fructose on blood pressure . International dietary guidelines , however , have not addressed fructose intake directly . A systematic review and meta- analysis was conducted to assess the effect of fructose in isocaloric exchange for other carbohydrates on systolic , diastolic , and mean arterial blood pressures . Studies were identified using Medline , Embase , and Cochrane data bases ( through January 9 , 2012 ) . Human clinical trials of isocaloric oral fructose exchange for other carbohydrate sources for ≥7 days were included in the analysis . Data were pooled by the generic inverse variance method using r and om-effects models and expressed as mean differences with 95 % CI . Heterogeneity was assessed by the Q-statistic and quantified by I(2 ) . Study quality was assessed using the Heyl and Method ological Quality Score . Thirteen isocaloric ( n=352 ) and 2 hypercaloric ( n=24 ) trials met the eligibility criteria . Overall , fructose intake in isocaloric exchange for other carbohydrates significantly decreased diastolic ( mean difference : -1.54 [ 95 % CI : -2.77 to -0.32 ] ) and mean arterial pressure ( mean difference : -1.16 [ 95 % CI : -2.15 to -0.18 ] ) . There was no significant effect of fructose on systolic blood pressure ( mean difference : -1.10 [ 95 % CI : -2.46 to 0.44 ] ) . The hypercaloric fructose feeding trials found no significant overall mean arterial blood pressure effect of fructose in comparison with other carbohydrates . To confirm these results , longer and larger trials are needed . Contrary to previous concerns , we found that isocaloric substitution of fructose for other carbohydrates did not adversely affect blood pressure in humans
|
[
" Twelve carbohydrate-sensitive men selected due to their abnormally high insulin responses to a sucrose load and 12 men with normal insulin responses were fed diets containing 0 , 7.5 , and 15 % fructose for 5 wk each in a cross-over design . The diets contained 43 % total carbohydrate , 42 % fat , and 15 % protein . Initial fasting total cholesterol and low-density lipoprotein cholesterol were higher in the hyperinsulinemic men than in the controls . Diastolic blood pressure was not affected by diet , but systolic blood pressure was slightly higher after the men consumed the 0 % fructose diet . Free fatty acids were not different . Total plasma cholesterol and low-density lipoprotein cholesterol were higher after the men consumed 7.5 and 15 % fructose than when they consumed the 0 % fructose diet . Plasma triglyceride increased significantly as fructose in the diets of the hyperinsulinemics increased , but was not affected in the controls . These changes in blood lipids are associated with heart disease",
"The effect of dietary fructose ( 20 % of carbohydrate calories , 45 - 65 g day-1 for 4 weeks ) on glycaemic control , serum lipid , lipoprotein and apoprotein A-I and A-II concentrations and on insulin sensitivity was studied in 10 type 2 diabetic patients . The study was done in a r and omized , double-blind fashion with crystalline fructose or placebo administered evenly during 4 meals or snacks per day . The patients were hospitalized throughout the study periods . The fasting plasma glucose concentration decreased during the fructose ( from 10.7 + /- 1.4 mmol l-1 to 8.0 + /- 0.8 mmol l-1 , P control diet ( from 10.1 + /- 0.9 mmol l-1 to 8.0 + /- 0.7 mmol l-1 , P mean diurnal blood glucose concentration also fell both during the fructose ( from 10.8 + /- 0.5 mmol l-1 to 8.4 + /- 0.3 mmol l-1 , P HbA1 concentration improved ( P Insulin sensitivity increased by 34 % ( P Serum insulin , triglyceride , apoprotein A-I and A-II concentrations , body weight , blood pressure and blood lactate remained unchanged during both diets . In conclusion , substitution of moderate amounts of fructose for complex carbohydrates can improve glycaemic control and insulin sensitivity in patients with type 2 diabetes",
"Overconsumption of fructose , particularly in the form of soft drinks , is increasingly recognized as a public health concern . The acute cardiovascular responses to ingesting fructose have not , however , been well-studied in humans . In this r and omized crossover study , we compared cardiovascular autonomic regulation after ingesting water and drinks containing either glucose or fructose in 15 healthy volunteers ( aged 21 - 33 yr ) . The total volume of each drink was 500 ml , and the sugar content 60 g. For 30 min before and 2 h after each drink , we recorded beat-to-beat heart rate , arterial blood pressure , and cardiac output . Energy expenditure was determined on a minute-by-minute basis . Ingesting the fructose drink significantly increased blood pressure , heart rate , and cardiac output but not total peripheral resistance . Glucose ingestion result ed in a significantly greater increase in cardiac output than fructose but no change in blood pressure and a concomitant decrease in total peripheral resistance . Ingesting glucose and fructose , but not water , significantly increased blood pressure variability and decreased cardiovagal baroreflex sensitivity . Energy expenditure increased by a similar amount after glucose and fructose ingestion , but fructose elicited a significantly greater increase in respiratory quotient . These results show that ingestion of glucose and fructose drinks is characterized by specific hemodynamic responses . In particular , fructose ingestion elicits an increase in blood pressure that is probably mediated by an increase in cardiac output without compensatory peripheral vasodilatation",
"The objective of the research was to determine the blood pressure ( BP ) lowering effects in older people of 50 g carbohydrate drinks with varying carbohydrate content using a r and omised , cross-over study with ten ( six females ) healthy older subjects ( mean age 72.20 ( sem 1.50 ) years ) . BP , heart rate and glucometer-derived blood glucose levels were determined at baseline and following the ingestion of equal volumes ( 300 ml ) of water and carbohydrate drinks with varying nutrient content ( glucose , sucrose and fructose ) . A significant decline in BP over the first 60 min was seen following glucose ( systolic BP ( SBP ) P diastolic BP ( DBP ) P mean arterial BP ( MAP ) P=0.03 ) and sucrose ( SBP P glucose than sucrose ingestion ( SBP 7.33 ( sem 2.19 ) v. 21.00 ( sem 4.30 ) min ( P=0.03 ) and MAP 11.22 ( sem 3.10 ) v. 17.00 ( sem 3.78 ) min ( P=0.03 ) ) . BP increased after water ingestion ( SBP P=0.04 , DBP P=0.18 , MAP P=0.02 ) but did not change after fructose ingestion ( SBP P=0.36 , DBP P=0.81 , MAP P=0.34 ) . Post hoc analyses revealed that the BP ( SBP , DBP and MAP ) decrease following glucose and sucrose ingestion were similar but significantly greater than following fructose or water ingestion . Sucrose , which is used widely ( table sugar ) , reduces BP as much as glucose . In contrast to this , fructose ingestion causes no change in BP . Further studies are required to determine if the substitution of glucose or sucrose with fructose may be beneficial in the medical management of older people with severe symptomatic postpr and ial hypotension",
"An increasing amount of fructose in the diet is suggested to play a causal role in the pathogenesis of the metabolic syndrome , type 2 diabetes and fatty liver . Our aim was to investigate and compare the effects of very high fructose and very high glucose in hyperenergetic diets on glucose and lipid metabolism and on fat depots in healthy humans . We conducted an exploratory , prospect i ve , r and omised , single-blinded , intervention trial . Participants in addition to a balanced weight-maintaining diet received 150 g of fructose or glucose/d for 4 weeks . Insulin sensitivity was estimated from oral glucose tolerance tests . Visceral and subcutaneous abdominal fat was determined with MRI . Liver fat and intramyocellular lipids of the tibialis anterior muscle were measured with (1)H magnetic resonance spectroscopy . A total of twenty healthy subjects ( fructose group n 10 and glucose group n 10 ; twelve males and eight females ) completed the study . They had a mean age of 30·5 ( SEM 2·0 ) years and a mean BMI of 25·9 ( SEM 0·5 ) kg/m(2 ) . Insulin sensitivity appeared to decrease both in the fructose and glucose groups . TAG markedly increased in the fructose group . No strong alterations or treatment effects were found for liver fat , visceral fat , subcutaneous abdominal fat and intramyocellular lipids of the tibialis anterior muscle . In conclusion , the effects of very high fructose and very high glucose in hyperenergetic diets on glucose metabolism and body fat composition were not different in the healthy participants of the present study . However , elevation of plasma TAG seemed to be fructose-specific",
"Higher uric acid levels are associated with an increased risk for developing hypertension . Higher intake of fructose increases plasma uric acid levels and higher intake of vitamin C reduces uric acid levels , but whether these nutrients are independently associated with the risk for developing hypertension is unknown . We studied this question by analyzing data from participants of three large and independent prospect i ve cohorts : Nurses ' Health Study 1 ( n = 88,540 ) , Nurses ' Health Study 2 ( n = 97,315 ) , and the Health Professionals Follow-up Study ( n = 37,375 ) . Relative risks and 95 % confidence intervals for incident hypertension were computed according to quintiles of fructose intake and categories of vitamin C intake using multivariable Cox proportional hazards regression . Fructose intake was not associated with the risk for developing hypertension ; the multivariable relative risks ( 95 % confidence intervals ) for the highest compared with the lowest quintile of fructose intake were 1.02 ( 0.99 to 1.06 ) in Nurses ' Health Study 1 , 1.03 ( 0.98 to 1.08 ) in Nurses ' Health Study 2 , and 0.99 ( 0.93 to 1.05 ) in Heath Professionals Follow-up Study . Regarding vitamin C , the relative risks for individuals who consumed > or = 1500 mg/d compared with those who consumed fructose and vitamin C intake do not substantially influence the risk for developing hypertension"
] |
4116bffa-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND Clostridium difficile infection ( CDI ) can lead to complications , recurrence , and death . Numerous studies have assessed risk factors for these unfavourable outcomes , but systematic review s or meta-analyses published so far were limited in scope or in quality . METHODS A systematic review was completed according to PRISMA guidelines . An electronic search in five data bases was performed . Studies published until October 2013 were included if risk factors for at least one CDI outcome were assessed with multivariate analyses . RESULTS 68 studies were included : 24 assessed risk factors for recurrence , 18 for complicated CDI , 8 for treatment failure , and 30 for mortality . Most studies accounted for mortality in the definition of complicated CDI . Important variables were inconsistently reported , such as previous episodes and use of antibiotics . Substantial heterogeneity and method ological limitations were noted , mainly in the sample size , the definition of the outcomes and periods of follow-up , precluding a meta- analysis . Older age , use of antibiotics after diagnosis , use of proton pump inhibitors , and strain type were the most frequent risk factors for recurrence . Older age , leucocytosis , renal failure and co-morbidities were frequent risk factors for complicated CDI . When considered alone , mortality was associated with age , co-morbidities , hypo-albuminemia , leucocytosis , acute renal failure , and infection with ribotype 027 . CONCLUSION Laboratory parameters currently used in European and American guidelines to define patients at risk of a complicated CDI are adequate . Strategies for the management of CDI should be tailored according to the age of the patient , biological markers of severity , and underlying co-morbidities
|
[
"Many laboratories use enzyme immunoassays ( EIAs ) for the diagnosis of Clostridium difficile infection ( CDI ) . More recently , polymerase chain reaction (PCR)-based diagnosis has been described as a sensitive test . Real-time PCR for the detection of C. difficile toxin A and B genes was evaluated . A prospect i ve evaluation was performed on stool sample s from 150 hospitalized adult patients and 141 healthy volunteers . PCR was compared to toxigenic culture ( TC ) , direct cytotoxicity test ( CTT ) , ImmunoCard ® Toxin A and B ( Meridian Bioscience ) , and enzyme-linked immunosorbent assay ( ELISA ) ( Vidas ) . The results were correlated with clinical data using a st and ardized question naire . The diagnostic yield of the PCR was further evaluated after implementation . Using toxigenic culture as the gold st and ard , the sensitivity and specificity of PCR were 100 and 99.2 % , respectively . Patients were categorized as follows : TC/PCR-positive ( n = 17 ) and negative TC ( n = 133 ) . The differences in these groups were more frequent use of antibiotics and leukocytosis ( p diagnostic yield of PCR was evaluated during a period of 6 months and showed an increase of positive patients by 50 % . PCR for the detection of toxigenic C. difficile has a high sensitivity and can rule out CDI , but can not differentiate CDI from asymptomatic carriage . Clinicians should be aware of this in order to prevent inappropriate treatment and delay of other diagnostics",
"BACKGROUND The incidence and severity of Clostridium difficile infections are increasing , and there is a need to optimize the prevention of complicated disease . OBJECTIVE To identify modifiable processes of care associated with an altered risk of C difficile complications . METHODS A retrospective cohort study ( with prospect i ve case ascertainment ) of all C difficile infections during 2007⁄2008 at a tertiary care hospital was conducted . RESULTS Severe complications were frequent ( occurring in 97 of 365 [ 27 % ] C difficile episodes ) , with rapid onset ( median three days postdiagnosis ) . On multivariable analysis , nonmodifiable predictors of complications included repeat infection ( OR 2.67 ) , confusion ( OR 2.01 ) , hypotension ( OR 0.97 per increased mmHg ) and elevated white blood cell count ( OR 1.04 per 109 cells⁄L ) . Protection from complications was associated with initial use of vancomycin ( OR 0.24 ) ; harm was associated with ongoing use of exacerbating antibiotics ( OR 3.02 ) . CONCLUSION C difficile infections often occur early in the disease course and are associated with high complication rates . Clinical factors that predicted a higher risk of complications included confusion , hypotension and leukocytosis . The most effective ways to improve outcomes for patients with C difficile colitis are consideration of vancomycin as first-line treatment for moderate to severe cases , and the avoidance of unnecessary antibiotics",
"We performed a Monte Carlo study to evaluate the effect of the number of events per variable ( EPV ) analyzed in logistic regression analysis . The simulations were based on data from a cardiac trial of 673 patients in which 252 deaths occurred and seven variables were cogent predictors of mortality ; the number of events per predictive variable was ( 252/7 =) 36 for the full sample . For the simulations , at values of EPV = 2 , 5 , 10 , 15 , 20 , and 25 , we r and omly generated 500 sample s of the 673 patients , chosen with replacement , according to a logistic model derived from the full sample . Simulation results for the regression coefficients for each variable in each group of 500 sample s were compared for bias , precision , and significance testing against the results of the model fitted to the original sample . For EPV values of 10 or greater , no major problems occurred . For EPV values less than 10 , however , the regression coefficients were biased in both positive and negative directions ; the large sample variance estimates from the logistic model both overestimated and underestimated the sample variance of the regression coefficients ; the 90 % confidence limits about the estimated values did not have proper coverage ; the Wald statistic was conservative under the None hypothesis ; and paradoxical associations ( significance in the wrong direction ) were increased . Although other factors ( such as the total number of events , or sample size ) may influence the validity of the logistic model , our findings indicate that low EPV can lead to major problems",
"BACKGROUND New therapies are needed to manage the increasing incidence , severity , and high rate of recurrence of Clostridium difficile infection . METHODS We performed a r and omized , double-blind , placebo-controlled study of two neutralizing , fully human monoclonal antibodies against C. difficile toxins A ( CDA1 ) and B ( CDB1 ) . The antibodies were administered together as a single infusion , each at a dose of 10 mg per kilogram of body weight , in patients with symptomatic C. difficile infection who were receiving either metronidazole or vancomycin . The primary outcome was laboratory-documented recurrence of infection during the 84 days after the administration of monoclonal antibodies or placebo . RESULTS Among the 200 patients who were enrolled ( 101 in the antibody group and 99 in the placebo group ) , the rate of recurrence of C. difficile infection was lower among patients treated with monoclonal antibodies ( 7 % vs. 25 % ; 95 % confidence interval , 7 to 29 ; P recurrence rates among patients with the epidemic BI/NAP1/027 strain were 8 % for the antibody group and 32 % for the placebo group ( P=0.06 ) ; among patients with more than one previous episode of C. difficile infection , recurrence rates were 7 % and 38 % , respectively ( P=0.006 ) . The mean duration of the initial hospitalization for in patients did not differ significantly between the antibody and placebo groups ( 9.5 and 9.4 days , respectively ) . At least one serious adverse event was reported by 18 patients in the antibody group and by 28 patients in the placebo group ( P=0.09 ) . CONCLUSIONS The addition of monoclonal antibodies against C. difficile toxins to antibiotic agents significantly reduced the recurrence of C. difficile infection . ( Clinical Trials.gov number , NCT00350298 .",
"OBJECTIVE toxigenic Clostridium difficile is responsible for a spectrum of disease severity ranging from mild diarrhoea to fulminant colitis . This study attempts to determine the proportion of patients in each category of severity and evaluate the risk factors for a more prolonged and complicated course . DESIGN prospect i ve cohort study . SETTING university teaching hospital . SUBJECTS all patients with symptomatic C. difficile infection during 4 months of an outbreak ( January-April 1995 ) ; n=73 ; median age 74 years ( range 17 - 91 ) . MEASUREMENTS incidence of C. difficile-associated disease ( CDAD ) ; severity of disease ; percentage of patients in each category of severity ; risk factors for severe disease/prolonged symptoms ( univariate and multivariable analyses ) . RESULTS the incidence of CDAD was 0.93 % . Of the cases identified , 18 ( 24.7 % ) had mild , self-limiting disease ; 26 ( 35.6 % ) had moderately severe disease ; 23 ( 31.5 % ) had prolonged symptoms and six ( 8.2 % ) had a complicated course . Although CDAD was more common in older patients ( P CDAD included low Barthel and abbreviated mental test scores ( P recent endoscopy ( P=0.03 ) . Logistic regression analysis revealed the following independent predictors of severe CDAD : endoscopy [ odds ratios ( OR ) 4.0 , P=0.03 ] and cognitive impairment ( OR 11.0 , P infection included dehydration , malnutrition and faecal incontinence ( which was statistically significantly associated with more severe disease ; P CDAD include functional disability , cognitive impairment , and recent endoscopy . Anticipation of severe CDAD may limit morbidity and mortality",
"BACKGROUND Clostridium difficile infection is a serious diarrheal illness associated with substantial morbidity and mortality . Patients generally have a response to oral vancomycin or metronidazole ; however , the rate of recurrence is high . This phase 3 clinical trial compared the efficacy and safety of fidaxomicin with those of vancomycin in treating C. difficile infection . METHODS Adults with acute symptoms of C. difficile infection and a positive result on a stool toxin test were eligible for study entry . We r and omly assigned patients to receive fidaxomicin ( 200 mg twice daily ) or vancomycin ( 125 mg four times daily ) orally for 10 days . The primary end point was clinical cure ( resolution of symptoms and no need for further therapy for C. difficile infection as of the second day after the end of the course of therapy ) . The secondary end points were recurrence of C. difficile infection ( diarrhea and a positive result on a stool toxin test within 4 weeks after treatment ) and global cure ( i.e. , cure with no recurrence ) . RESULTS A total of 629 patients were enrolled , of whom 548 ( 87.1 % ) could be evaluated for the per- protocol analysis . The rates of clinical cure with fidaxomicin were noninferior to those with vancomycin in both the modified intention-to-treat analysis ( 88.2 % with fidaxomicin and 85.8 % with vancomycin ) and the per- protocol analysis ( 92.1 % and 89.8 % , respectively ) . Significantly fewer patients in the fidaxomicin group than in the vancomycin group had a recurrence of the infection , in both the modified intention-to-treat analysis ( 15.4 % vs. 25.3 % , P=0.005 ) and the per- protocol analysis ( 13.3 % vs. 24.0 % , P=0.004 ) . The lower rate of recurrence was seen in patients with non – North American Pulsed Field type 1 strains . The adverse-event profile was similar for the two therapies . CONCLUSIONS The rates of clinical cure after treatment with fidaxomicin were noninferior to those after treatment with vancomycin . Fidaxomicin was associated with a significantly lower rate of recurrence of C. difficile infection associated with non – North American Pulsed Field type 1 strains . ( Funded by Optimer Pharmaceuticals ; Clinical Trials.gov number , NCT00314951 .",
"BACKGROUND Neutrophil recruitment coordinated by intestinal interleukin (IL)-8 secretion is a key component in the pathogenesis of Clostridium difficile infection ( CDI ) . We hypothesized that a common single-nucleotide polymorphism ( SNP ) in the -251 region of the IL-8 gene promoter may be predictive of recurrent CDI . METHODS This was a prospect i ve cohort study of hospitalized adult patients with CDI who were admitted to a large , university-affiliated medical center from 2007 through 2008 . Patients were monitored for 3 months after diagnosis of CDI and assessed for recurrent CDI ( defined as a return of diarrhea that required treatment after initial symptom resolution ) . DNA was isolated from blood sample s , and genetic sequencing was performed using polymerase chain reaction and pyrosequencing . The association between IL-8 genotype and recurrent CDI was assessed using univariate and multivariate statistics . RESULTS Ninety-six patients with a mean ( ± st and ard deviation ) age of 61 ± 16 years ( 54 % of whom were female and 63 % of whom were white ) were identified . The overall incidence of recurrent CDI was 24 % . IL-8 allele frequency was similar to previously reported findings ( for A/A , 27 % ; for A/T , 53 % ; and for T/T , 20 % ) . The incidence of recurrent CDI was 38 % in patients with the A/A allele and 19 % in all other patients ( relative risk , 2.1 ; 95 % confidence interval , 1.04 - 4.13 ) ( P = .043 ) . CONCLUSIONS This study indicates that a common SNP in the IL-8 gene promoter is an independent predictor of recurrent CDI . Our results could offer risk stratification for patients at high risk for recurrent CDI",
"BACKGROUND Most Clostridium difficile infection ( CDI ) surveillance programs neither specify the diagnostic method to be used nor stratify rates accordingly . We assessed the difference in healthcare-associated CDI ( HA-CDI ) incidence and complication rates obtained by 2 vali date d diagnostic methods . METHODS This was a prospect i ve cohort study of patients for whom a C. difficile test was ordered between 1 August 2010 and 31 July 2011 . All specimens were tested in parallel by a commercial polymerase chain reaction ( PCR ) assay targeting toxin B gene tcdB , and a 3-step algorithm detecting glutamate dehydrogenase and toxins A and B by enzyme immunoassay and cell culture cytotoxicity assay ( EIA/CCA ) . CDI incidence rate ratios were calculated using univariate Poisson regression . RESULTS A total of 1321 stool sample s were tested during a period totaling 95 750 patient-days . Eighty-five HA-CDI cases were detected by PCR and 56 cases by EIA/CCA ( P = .01 ) . The overall incidence rate was 8.9 per 10 000 patient-days ( 95 % confidence interval [ CI ] , 7.1 - 10.9 ) by PCR and 5.8 per 10 000 patient-days ( 95 % CI , 4.4 - 7.4 ) by EIA/CCA ( P = .01 ) . The incidence rate ratio comparing PCR and EIA/CCA was 1.52 ( 95 % CI , 1.08 - 2.13 ; P = .015 ) . Overall complication rate was 27 % ( 23/85 ) when CDI was diagnosed by PCR and 39 % ( 22/56 ) by EIA/CCA ( P = .16 ) . Cases detected by PCR only were less likely to develop a complication of CDI compared with cases detected by both PCR and EIA/CCA ( 3 % vs 39 % , respectively ; P 50 % increase in the CDI incidence rate . St and ardization of diagnostic methods may be indicated to improve interhospital comparison",
"Risk factors of severity ( need for surgical intervention , intensive care or fatal outcome ) were analysed in hospital-acquired Clostridium difficile infection ( CDI ) in a 777-bed community hospital . In a prospect i ve analytical cross-sectional study , age ( ≥65 years ) , sex , CDI characteristics , underlying diseases , severity of comorbidity and PCR ribotypes were tested for associations with severe CDI . In total , 133 cases of hospital-acquired CDI ( mean age 74.4 years ) were identified , result ing in an incidence rate of 5.7/10,000 hospital-days . A recurrent episode of diarrhoea occurred in 25 cases ( 18.8 % ) and complications including toxic megacolon , dehydration and septicaemia in 69 cases ( 51.9 % ) . Four cases ( 3.0 % ) required ICU admission , one case ( 0.8 % ) surgical intervention and 22 cases ( 16.5 % ) died within the 30-day follow-up period . Variables identified to be independently associated with severe CDI were severe diarrhoea ( odds ratio [ OR ] 3.64 , 95 % confidence interval [ CI ] 1.19–11.11 , p = 0.02 ) , chronic pulmonary disease ( OR 3.0 , 95 % CI 1.08–8.40 , p = 0.04 ) , chronic renal disease ( OR 2.9 , 95 % CI 1.07–7.81 , p = 0.04 ) and diabetes mellitus ( OR 4.30 , 95 % CI 1.57–11.76 , p = 0.004 ) . The case fatality of 16.5 % underlines the importance of increased efforts in CDI prevention , in particular for patients with underlying diseases",
"Host anti-toxin immune responses play important roles in Clostridium difficile disease and outcome . The relationship between host immune and inflammatory responses during severe C. difficile infection ( CDI ) and the risk of mortality has yet to be defined . We aim ed to investigate the host systemic IgG anti-toxin immune responses , the in vitro cytotoxicity of the infecting C. difficile ribotyped strain , and the host inflammatory markers and their relationship to CDI disease severity and risk of mortality . Inflammatory markers , co-morbidities and CDI outcomes were recorded in a prospect i ve cohort of 150 CDI cases . Serum anti-cytotoxin A ( TcdA ) and anti-TcdB IgG titres were measured by ELISA and the infecting C. difficile isolate was ribotyped and the in vitro cytotoxin titre assessed . A low median anti-TcdA IgG titre was significantly associated with 30-day all-cause mortality ( P High cytotoxin titres correlated with increased inflammatory markers but also higher anti-TcdA and -TcdB ( P responses result ing in a lower risk of mortality . On multivariate analysis , predictors of mortality were peak white cell count > 20 × 10(9 ) l(-1 ) [ odds ratio ( OR ) 11.53 ; 95 % confidence interval ( CI ) 2.38 - 55.92 ] , creatinine concentration > 133 µmol l(-1 ) ( OR 6.54 ; 95 % CI 1.47 - 29.07 ) , Horn 's index > 3 ( OR 4.09 ; 95 % CI 0.76 - 22.18 ) and low anti-TcdA IgG ( OR 0.97 ; 95 % CI 0.95 - 0.99 ) , but not ribotype , cytotoxin titre or anti-TcdB IgG. Thus , host pro-inflammatory and humoral responses correlate with the cytotoxin titre of the infecting strain and effective anti-toxin immune responses reduce the risk of mortality",
"BACKGROUND & AIMS Recent studies of Clostridium difficile infection ( CDI ) have indicated a dramatic increase in metronidazole failure . The aims of this study were to compare current and historical rates of metronidazole failure and to identify risk factors for metronidazole failure . METHODS Eighty-nine patients with CDI in 2004 to 2006 were followed for 60 days and were compared with a historical cohort of 63 CDI patients studied prospect ively in 1998 . Metronidazole failure was defined as persistent diarrhea after 10 days of therapy or a change of therapy to vancomycin . Stool sample s were analyzed for the presence of the North American pulsed-field gel electrophoresis type-1 ( NAP-1 ) strain . RESULTS Metronidazole failure rates were 35 % in both cohorts . There was no difference in the median time to resolution of diarrhea ( 8 vs 5 d ; P = .52 ) or the proportion with > 10 days of diarrhea ( 35 % vs 29 % ; P = .51 ) . Risk factors for metronidazole failure included recent cephalosporin use ( odds ratio [ OR ] , 32 ; 95 % confidence interval [ CI ] , 5 - 219 ) , CDI on admission ( OR , 23 ; 95 % CI , 3 - 156 ) , and transfer from another hospital ( OR , 11 ; 95 % CI , 2 - 72 ) . The frequency of NAP-1 infection in patients with and without metronidazole failure was similar ( 26 % vs 21 % ; P = .67 ) . CONCLUSIONS We found no difference in metronidazole failure rates in 1998 and 2004 to 2006 . Patients with recent cephalosporin use , CDI on admission , and transfer from another hospital were more likely to metronidazole failure . Infection with the epidemic NAP-1 strain was not associated with metronidazole failure in endemic CDI",
"OBJECTIVES To determine the effect of advancing age on the clinical outcomes of Clostridium difficile ( CDI ) treatment . DESIGN Regression modeling of results from two double-blind r and omized multicenter studies on the treatment of primary and first recurrent cases of CDI to examine for effects of age and study drug on outcomes of cure ( resolution of diarrhea ) , recurrence within 4 weeks of completing successful therapy , and cure without recurrence . SETTING Participants were r and omized into studies in the United States , Canada , and Europe . PARTICIPANTS Nine hundred ninety-nine individuals with toxin-positive CDI were r and omized to receive vancomycin ( 125 mg 4 times daily ) or fidaxomicin ( 200 mg twice daily ) for 10 days . MEASUREMENTS The effect of advancing age in those aged 18 to 40 years and in 10-year increments thereafter was examined . RESULTS The model predicts a 17 % lower clinical cure , 17 % greater recurrence , and 13 % lower sustained clinical response by advancing decade than in those younger than 40 ( P Clinical cure was similar in the fidaxomicin and vancomycin treatment groups , although fidaxomicin was associated with a more than 50 % lower relative risk for recurrence than vancomycin ( P infection with the BI strain type , inpatient status , renal insufficiency , leukocytosis , hypoalbuminemia , and concomitant medication exposure . CONCLUSION Measurable and progressive deterioration in CDI treatment outcomes occurred with advancing age in those aged 40 and older , highlighting the need for prevention and treatment strategies . Fidaxomicin treatment was associated with a 60 % lower risk of recurrence than vancomycin after adjusting for age , concomitant antibiotics , and C. difficile strain",
"Background and Aim : Clostridium difficile has been increasingly diagnosed in hospitalized patients . An association between proton pump inhibitors ( PPIs ) use and Clostridium difficile-associated disease ( CDAD ) and between recurrent CDAD has been suggested . The aim of this study is to investigate whether PPI use is associated with the development of recurrent CDAD . Methods : This was a retrospective case-control study of patients with CDAD at Yeungnam University Medical Center , seen from January 2004 to December 2008 . C. difficile infection was diagnosed by the presence of C. difficile toxin in the stool . Those with recurrent disease were matched with nonrecurrent controls using multivariate matched sampling methods that incorporated the propensity score . Results : Recurrent CDAD developed in 28 ( 14.1 % ) of the 198 patients with diarrhea and positive C. difficile stool toxin assays . Multivariate analysis of the total population of recurrent versus nonrecurrent CDAD revealed that additional use of non-C. difficile antimicrobial therapy ( concomitant with the treatment or after or both ) , poor response to therapy with metronidazole or vancomycin , and recent gastrointestinal surgery were risk factors for recurrent CDAD . We were able to match 21 recurrent CDAD subjects with 21 without recurrent CDAD . Among the matched patients only PPI use was associated with recurrent CDAD ( ie , 47.6 % vs. 4.8 % , P=0.004 for recurrent vs. nonrecurrent CDAD , respectively ) . Conclusions : Among the matched patient groups , only PPI therapy was associated with recurrent CDAD . Prospect i ve studies are needed to clarify whether avoidance of PPIs or specific cotherapies will reduce the incidence of recurrent C. difficile-associated diarrhea",
"Recurrent Clostridium difficile diarrhea ( RCDD ) occurs in 20 % of patients after they have received st and ard antibiotic treatment with vancomycin or metronidazole , but the reasons for the recurrences are largely unknown . Patients receiving vancomycin or metronidazole for active C. difficile diarrhea ( CDD ) were referred to our study centers for treatment and a 2-month follow-up as part of a r and omized placebo-controlled trial . Sixty patients had RCDD ( median number of episodes , 3.0 ; range , 2 - 9 episodes ) and 64 were having their first episode of CDD . Patients with RCDD had more-severe abdominal pain and were more likely to have fever but initially responded well to antibiotic therapy . Data on sequential episodes showed no progression in disease severity . Five factors were associated with a higher risk of RCDD : the number of previous CDD episodes , onset of the initial disease in the spring , exposure to additional antibiotics for treatment of other infections , infection with immunoblot type 1 or 2 strains of C. difficile , and female gender . These factors may help to identify patients who are more likely to develop RCDD and require careful medical supervision",
"OBJECTIVES Clostridium difficile infection ( CDI ) represents a cause of substantial morbidity , particularly for older adults . Although older age is a risk factor for CDI , few studies have specifically focused on clinical outcomes in older adults , particularly the \" oldest \" old . DESIGN Retrospective review . SETTING University of Michigan Health System . PARTICIPANTS All patients aged 80 and older with a positive cytotoxin assay for C. difficile and a clinical course consistent with CDI during 2006 . MEASUREMENTS Clinical data were recorded , including comorbid conditions and treatment regimens , as well as outcomes , including treatment failure , infection relapse , and 90-day mortality . RESULTS Seventy patients aged 80 and older ( mean 84.0+/-4.1 ) with CDI were identified . Metronidazole was given as initial therapy in 65 ( 92.8 % ) ; 18 of these 65 ( 27.7 % ) experienced treatment failure , requiring subsequent use of oral vancomycin . Serious adverse events included three episodes of toxic megacolon , two requiring colectomy . One death was directly attributable to CDI . All-cause mortality was 8.6 % at 30 days and 17.1 % at 90 days . Higher white blood cell ( WBC ) counts were independently associated with treatment failure ( P=.02 ) and coronary artery disease with 90-day mortality ( P=.02 ) . CONCLUSION In older adults with CDI , treatment failure on metronidazole occurred frequently and was associated with higher WBC count . Larger prospect i ve studies are needed to determine risk factors for treatment failure and relapse in order to develop better paradigms for CDI treatment in older adults . Initial therapy with vancomycin may be appropriate for elderly patients , especially those with elevated WBC counts ",
"Abstract Background : Concerns regarding the poor response of severe Clostridium difficile infection ( CDI ) treated with metronidazole have arisen over the last 5 y. Methods : We conducted a prospect i ve , non-interventional study of CDI cases at our institution to evaluate the role of drug resistance , co-morbidities , and the emergence of hypervirulent strains on patient outcomes . A total of 118 adult in patients with diarrhea and a positive stool for C. difficile toxin immunoassay had positive stool cultures and were included in the study . All 118 isolates had vancomycin and metronidazole susceptibility testing via the E-test method ; rep-PCR was performed on 47 isolates . Of the 118 study patients , 107 were treated with either metronidazole or vancomycin . Results : Initial therapy was metronidazole in 98.1 % ( n = 105 ) and vancomycin in 1.9 % ( n = 2 ) patients . Evaluable clinical response within 5 days of treatment was noted in 52.5 % ( 52/99 ) of cases . The mean duration of treatment was 11.7 ± 7.2 days . The 30-day all-cause mortality rate was 24.6 % ( 29/118 ) . Recurrence occurred in 23.6 % ( 21/89 ) . A recent stay in the intensive care unit was associated with increased 30-day mortality ( odds ratio 3.58 , p = 0.012 ) . There were no isolates resistant to metronidazole or vancomycin . Only 1 isolate was possibly related to the NAP1/BI/027 reference strain . No strain-related differences in deaths or recurrence were noted . Conclusions : Deaths related to CDI in our study appear to be related to multiple factors and did not appear to be independently related to antibiotic susceptibility , strain type , or treatment duration",
"OBJECTIVE To describe the epidemiology , diagnosis , risk factors , patient impact , and treatment strategies for recurrent Clostridium difficile-associated disease ( CDAD ) . DESIGN Data were collected as part of a blinded , placebo-controlled clinical trial testing a new combination treatment for recurrent CDAD . Retrospective data regarding prior CDAD episodes were collected from interviews and medical-chart review . Prospect i ve data on the current CDAD episode , risk factors , and recurrence rates were collected during a 2-month follow-up . SETTING S National referral study . PARTICIPANTS Patients with recurrent CDAD . INTERVENTIONS Treatment with a 10-day course of low-dose ( 500 mg/d ) or high-dose ( 2 g/d ) vancomycin or metronidazole ( 1 g/d ) . RESULTS Recurrent CDAD was found to have a lengthy course involving multiple episodes of diarrhea , abdominal cramping , nausea , and fever . CDAD may recur over several years despite frequent treatment with antibiotics . Recurrence rates were similar regardless of the choice or dose of antibiotic . Recurrent CDAD is not a trivial disease : patients may have multiple episodes ( as many as 14 ) , may require hospitalization , and the mean lifetime cost of direct medical care was $ 10,970 per patient . Fortunately , the disease does not become progressively more severe as the number of episodes increase . Two risk factors predictive for recurrent CDAD were found : increasing age and a decreased quality -of-life score at enrollment . CONCLUSIONS Recurrent CDAD is a persistent disease that may result in prolonged hospital stays , additional medical costs , and rare serious complications",
"BACKGROUND Clostridium difficile is the most common cause of nosocomial diarrhea , affecting up to 10 % of hospitalized patients . Preliminary studies suggest an association between vitamin D status and C difficile infections ( CDIs ) . Our goal was to investigate whether serum 25-hydroxyvitamin D ( 25(OH)D ) levels are associated with CDI severity . METHODS We prospect ively enrolled patients diagnosed with CDI and divided them into 2 severity groups : group A ( positive toxin A/B enzyme immunoassay only ) and group B ( positive toxin A/B enzyme immunoassay with abdominal computed tomography scan findings consistent with colitis ) . Serum 25(OH)D levels ( 25(OH)D3 , 25(OH)D2 , and total 25(OH)D ) were measured on all patients after diagnosis of CDI . We performed multivariable logistic regression analyses to investigate the association between 25(OH)D levels and CDI severity , while adjusting for age , Deyo-Charlson Comorbidity Index , recent hospitalization , and vitamin D supplementation . RESULTS One hundred patients were enrolled between July 2011 and February 2013 . The mean ( st and ard deviation ) cohort age and Deyo-Charlson Comorbidity Index were 62 ( 19 ) years and 4 ( 3 ) , respectively ; 54 % of patients were male . Mean serum total 25(OH)D level was 22 ( 10 ) ng/mL. Mean 25(OH)D3 level was significantly higher in group A ( n = 71 ) than in group B ( n = 29 ) : 21 ( 1 ) vs 15 ( 2 ) ng/mL , respectively ( P = .005 ) . There was no observed difference in mean 25(OH)D2 levels and total 25(OH)D levels between the 2 groups . Multivariable logistic regression analysis demonstrated an association between 25(OH)D3 levels and CDI severity ( adjusted odds ratio , 0.92 ; 95 % confidence interval , 0.87 - 0.98 ) . CONCLUSIONS We found a significant inverse association between 25(OH)D3 levels and CDI severity . Further studies are needed to determine whether vitamin D supplementation can improve outcomes in patients with CDI",
"BACKGROUND Treatment of Clostridium difficile infection ( CDI ) is often limited by recurrence in 25 % of cases . The objective of this study was to determine risk factors of CDI recurrence during a provincial endemic . METHODS Data was prospect ively collected for 1 year in a Montréal hospital . Inclusion criteria were : age ≥ 18 years ; admission for ≥ 72 h ; CDI diagnosis during current admission ; no CDI diagnosis in the previous 3 months . RESULTS A total of 121 patients were included , of which 42 % were female . Mean age was 77 years , with a median Charlson comorbidity index of 5 . Forty patients ( 33 % ) had recurrent disease within 2 months of initial CDI treatment . There were 20 deaths ( 17 % ) within the 2-month follow-up period . Higher risk of CDI recurrence was independently associated with older age ( HR=2.26 for each decade ) , female gender ( HR=1.56 ) , and lymphopenia at completion of CDI treatment ( HR=2.18 ) , while a positive C. difficile antitoxin serology was protective ( HR=0.17 ) . CDI recurrence was not associated with either lymphopenia at time of diagnosis , underlying comorbidities , severity or treatment of the initial CDI episode , or re-exposure to antibiotics during the follow-up period . CONCLUSION Lymphopenia at the end of CDI treatment appears to be a strong marker for CDI recurrence . This available and inexpensive test may identify patients who are at higher risk of CDI recurrence",
"Previous studies have shown conflicting results concerning mortality related to Clostridium difficile infection . The objective of this study was to determine the impact of C. difficile infection on short- and long-term mortality in hospitalised patients with antibiotic-associated diarrhoea . We therefore undertook a prospect i ve case-control study of 217 hospitalised patients who received antibiotics , developed diarrhoea and underwent stool enzyme immunoassay for C. difficile TOX A/B. The Kaplan-Meier and the log-rank test were used to determine univariate survival analysis and a Cox regression model for multivariate analysis of 28 day and long-term mortality . Fifty-two ( 24 % ) of the 217 patients who met the study criteria were positive for C. difficile TOX A/B. The crude 28 day and long-term mortality rates of the entire cohort were 12.4 % and 56 % , respectively . On Cox regression analysis , hypoalbuminaemia , impaired functional capacity and elevated serum urea levels were found to be the only independent and statistically significant variables associated with long-term mortality . C. difficile toxin positivity per se was not associated with increased short- or long-term mortality rates . In conclusion , hypoalbuminaemia , renal failure , and impaired function capacity predict mortality due to antibiotic-associated diarrhoea , but C. difficile involvement by itself does not further increase the risk of death in these patients",
"BACKGROUND We have reported that symptom-free carriers of Clostridium difficile have a systemic anamnestic immune response to toxin A. The aim of this study was to determine whether an acquired immune response to toxin A , during an episode of C. difficile diarrhoea , influences risk of recurrence . METHODS We prospect ively studied 63 patients with nosocomial C. difficile diarrhoea . Serial serum IgA , IgG , and IgM concentrations against C. difficile toxin A , toxin B , or non-toxin antigens were measured by ELISA . Individuals were followed for 60 days . FINDINGS 19 patients died ( 30 % ) . Of the 44 who survived , 22 had recurrent C. difficile diarrhoea . Patients with a single episode of C. difficile diarrhoea ( n=22 ) had higher concentrations of serum IgM against toxin A on day 3 of their first episode of diarrhoea than those with recurrent diarrhoea ( n=22 , p=0.004 ) . On day 12 , serum IgG values against toxin A were higher in patients who had a single episode of diarrhoea ( n=7 ) than in those who subsequently had recurrent diarrhoea ( n=9 , p=0.009 ) . The odds ratio for recurrence associated with a low concentration of serum IgG against toxin A , measured 12 days after onset of C. difficile diarrhoea , was 48.0 ( 95 % CI 3.5 - 663 ) . INTERPRETATION A serum antibody response to toxin A , during an initial episode of C. difficile diarrhoea , is associated with protection against recurrence"
] |
4116c040-06ff-11f0-808a-c43d1ab1c353
|
To evaluate the effects of therapeutic exercise on pain , stiffness , quality of life , physical function , disease activity , health-related fitness and cardiovascular risk factors in adults with spondyloarthritis ( SpA ) . Electronic data bases ( Cochrane Central Register of Controlled Trials , EMBASE , MEDLINE / PubMed , PEDro , AMED , CINAHL ) were systematic ally search ed from inception to October 2013 using medical subject headings and keywords . This was supplemented by search ing conference abstract s and a h and search of reference lists of included studies . R and omised and quasi-r and omised studies of adults with SpA in which at least one of the comparison groups received an exercise intervention were included . Outcomes of interest were pain , stiffness , quality of life , physical function and disease activity . Secondary outcomes were health-related fitness and cardiovascular risk factors . Two review ers independently screened studies for inclusion . Method ological quality was assessed by two review ers using the Cochrane risk of bias tool and the PEDro scale . Twenty-four studies , involving 1,498 participants , were included . Meta-analyses were not undertaken due to clinical heterogeneity , and this review focuses on qualitative synthesis . Moderate evidence supports exercise interventions in improving physical function , disease activity and chest expansion compared to controls ; there is low-level evidence of improved pain , stiffness , spinal mobility and cardiorespiratory function . Supervised group exercise yields better outcomes than unsupervised home exercise . The addition of aerobic components to flexibility programmes improves cardiorespiratory outcomes , but not cardiovascular risk factors . The most effective exercise protocol remains unclear . Current evidence suggests that therapeutic exercises are beneficial for adults with ankylosing spondylitis ; effects on other SpA subtypes are unknown
|
[
"Fernández-de-las-Peñas C , Alonso-Blanco C , Morales-Cabezas M , Miangolarra-Page JC : Two exercise interventions for the management of patients with ankylosing spondylitis : A r and omized controlled trial . Am J Phys Med Rehabil 2005;84:407–419 . Objective : The purpose of this clinical trial was to evaluate the impact of a 4-month comprehensive protocol of strengthening and flexibility exercises developed by our research group versus conventional exercises for patients with Ankylosing Spondylitis ( AS ) on functional and mobility outcomes . Design : R and omized controlled trial . Forty-five patients diagnosed with AS according to the modified criteria of New York were allocated to control or experimental groups using a r and om numbers table . The control group was treated with a conventional protocol of physical therapy in AS , whereas the experimental group was treated with the protocol suggested by our research group . The conventional intervention consisted of 20 exercises : motion and flexibility exercises of the cervical , thoracic , and lumbar spine ; stretching of the shortened muscles ; and chest expansion exercises . The experimental protocol is based on the postural affectation of the AS and the treatment of the shortened muscle chains in these patients according to the Global Posture Reeducation ( GPR ) method . This intervention employs specific strengthening and flexibility exercises in which the shortened muscle chains are stretched and strengthened . The study lasted 4 mos . During this period , patients received a weekly group session managed by an experienced physiotherapist . Each session lasted an hour , and there were 15 total sessions . Changes in activity , mobility , and functional capacity were evaluated by an assessor blinded to the intervention , using the following previously vali date d scores from the Bath group : BASMI ( tragus to wall distance , modified Schöber test , cervical rotation , lumbar side flexion , and intermalleolar distance ) , BASDAI ( The Bath Ankylosing Spondylitis Disease Activity Index ) , and BASFI ( The Bath Ankylosing Spondylitis Functional Index ) . Results : Both groups showed an improvement ( prepost scores ) in all the outcome measures , mobility measures of the BASMI index , as well as in BASFI and BASDAI indexes . In the control group , the improvement in tragus to wall distance ( P = 0.009 ) and in lumbar side flexion ( P = 0.02 ) was statistically significant . Although the rest of the outcomes also improved , they did not reach a significant level ( P > 0.05 ) . In the experimental group , the improvement in all the clinical measures of the BASMI index ( P the BASFI index ( P = 0.003 ) was statistically significant . The intergroup comparison between the improvement ( prepost scores ) in both groups showed that the experimental group obtained a greater improvement than the control group in all the clinical measures of the BASMI index , except in tragus to wall distance , as well as in the BASFI index . Conclusions : The experimental protocol developed by our research group , based on the GPR method and specific strengthening and flexibility exercises of the muscle chains , offers promising results in the management of patients suffering from AS . Further trials on this topic are required",
"We investigated the effects of home-based daily exercise on joint mobility , functional capacity , pain , and depression in patients with ankylosing spondylitis ( AS ) . The patients were r and omly assigned to a wait-list control group or to an exercise-therapy group . The exercise-therapy group performed a 20-min exercise program once per day for 8 consecutive weeks . After 8 weeks , compared with the control group , the exercise group showed improvements in joint mobility ( cervical flexion , extension , shoulder flexion , abduction , hip abduction , and knee flexion ) , finger – floor distance , and functional capacity . Pain and depression scores were significantly lower after the exercise program in the exercise group than in the control group . These findings indicate that exercise therapy increases joint mobility and functional capacity , and decreases pain and depression in patients with AS . Home-based exercise , which is easily accessible to patients , might be an effective intervention for AS",
"AIM The aim of the study was to compare the effects of conventional exercise ( CE ) , swimming and walking on the pulmonary functions , aerobic capacity , quality of life , Bath indexes and psychological symptoms in patients with ankylosing spondylitis ( AS ) . METHODS Forty-five patients were r and omised into either swimming ( group 1 ) , walking ( group 2 ) , CE group ( group 3 ) . Patients in Group 1 performed CE and swimming , patients in Group 2 performed CE and walking and patients in Group 3 performed CE only . Exercise sessions were performed three times a week for a period of six weeks . Patients were assessed before and after the rehabilitation program , with respect to , pulmonary function test ( forced vital capacity [ FVC , mL ] , forced expiration volume in one second [ FEV1 , mL ] , FEV1/FVC ( % ) and vital capacity [ VC , mL ] ) , maximal oxygen uptake ( pV.O2 ) , 6-minute walking test ( 6MWT ) , Bath Ankylosing Spondylitis Functional Index , Bath Ankylosing Spondylitis Disease Activity Index , Bath Ankylosing Spondylitis Metrology Index , Nottingham Health Profile and Beck Depression Inventory . RESULTS There were significant increases in pVO2 and 6MWT after treatment in Groups 1 and 2 ( P FeV1 , FVC and VC improved significantly with treatment in all three groups ( P energy , emotional reaction and physical mobility sub-scores of NHP in three exercise groups after completion of the exercise program ( P , walking and CE had beneficial effects on the quality of life and pulmonary functions . Aerobic exercises such as swimming and walking in addition to CE increased functional capacities of patients",
"The optimal management of ankylosis spondylitis ( AS ) involves a combination of nonpharmacologic and pharmacologic treatment aim ing to maximize health-related quality of life . The primary objective of our study was to demonstrate the benefits of an original multimodal exercise program combining Pilates , McKenzie and Heckscher techniques on pulmonary function in patients with AS , while secondary objectives were to demonstrate the benefits of the same program on function and disease activity . This is a r and omized controlled study on ninety-six consecutive patients with AS ( axial disease subset ) , assigned on a 1:1 rationale into two groups based on their participation in the Pilates , McKenzie and Heckscher ( group I ) or in the classical kinetic program ( group II ) . The exercise program consisted of 50-min sessions performed 3 times weekly for 48 weeks . St and ard assessment s were done at week 0 and 48 and included pain , modified Schober test ( mST ) and finger – floor distance ( FFD ) , chest expansion ( CE ) and vital capacity ( VC ) , as well as disease activity Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) , functional Bath Ankylosing Spondylitis Functional Index ( BASFI ) and metrology index Bath Ankylosing Spondylitis Metrology Index ( BASMI ) . Groups were comparable at baseline ; we demonstrated significant improvement between baseline and after 48 weeks of regular kinetic training for all AS-related parameters in both groups . However , significant improvement was found in pain , lumbar spine motility ( mST , FFD ) , BASFI , BASDAI and BASMI in AS performing the specific multimodal exercise program at the end of study ( p = 0.001 ) . Although there were significant improvements in CE in both groups as compared to baseline ( group I , p = 0.001 ; group II , p = 0.002 ) , this parameter increased significantly only in group I ( p = 0.001 ) . VC measurements were not significantly changed at the end of the study ( group I , p = 0.127 ; group II , p = 0.997 ) , but we found significant differences within groups ( p = 0.011 ) . A multimodal training combining Pilates , McKenzie and Heckscher exercises performed regularly should be included in the routine management of patients with AS for better control of function , disease activity and pulmonary function ",
"Objective : To vali date and refine two sets of c and i date criteria for the classification/diagnosis of axial spondyloarthritis ( SpA ) . Methods : All Assessment of SpondyloArthritis international Society ( ASAS ) members were invited to include consecutively new patients with chronic ( ⩾3 months ) back pain of unknown origin that began before 45 years of age . The c and i date criteria were first tested in the entire cohort of 649 patients from 25 centres , and then refined in a r and om selection of 40 % of cases and thereafter vali date d in the remaining 60 % . Results : Upon diagnostic work-up , axial SpA was diagnosed in 60.2 % of the cohort . Of these , 70 % did not fulfil modified New York criteria and , therefore , were classified as having “ non-radiographic ” axial SpA. Refinement of the c and i date criteria result ed in new ASAS classification criteria that are defined as : the presence of sacroiliitis by radiography or by magnetic resonance imaging ( MRI ) plus at least one SpA feature ( “ imaging arm ” ) or the presence of HLA-B27 plus at least two SpA features ( “ clinical arm ” ) . The sensitivity and specificity of the entire set of the new criteria were 82.9 % and 84.4 % , and for the imaging arm alone 66.2 % and 97.3 % , respectively . The specificity of the new criteria was much better than that of the European Spondylarthropathy Study Group criteria modified for MRI ( sensitivity 85.1 % , specificity 65.1 % ) and slightly better than that of the modified Amor criteria ( sensitivity 82.9 , specificity 77.5 % ) . Conclusion : The new ASAS classification criteria for axial SpA can reliably classify patients for clinical studies and may help rheumatologists in clinical practice in diagnosing axial SpA in those with chronic back pain . Trial registration number : NCT00328068",
"Objective . To evaluate the effect of combining incentive spirometer exercise ( ISE ) with a conventional exercise ( CE ) on patients with ankylosing spondylitis ( AS ) stabilized by tumor necrosis factor ( TNF ) inhibitor therapy by comparing a combination group with a CE-alone group . Methods . Forty-six patients ( 44 men , 2 women ) were r and omized to the combination group ( ISE plus CE ; n = 23 ) or the CE group ( n = 23 ) . The CE regimen of both groups consisted of 20 exercises performed for 30 min once a day . The ISE was performed once a day for 30 min . The trial duration was 16 weeks . Patients were assessed before and at the end of treatment by measuring the Bath Ankylosing Spondylitis Disease Activity Index , Bath Ankylosing Spondylitis Functional Index ( BASFI ) , chest expansion , finger to floor distance , pulmonary function measures , and 6-min walk distance . Results . Both groups improved significantly in terms of chest expansion ( p finger to floor distance ( p BASFI ( p forced vital capacity ( p total lung capacity ( p vital capacity ( p functional disability and pulmonary function measures . Conclusion . Combining ISE with a CE can provide positive results in patients whose AS has been clinical ly stabilized by TNF inhibitor therapy",
"The objective of this study is to assess the effects of Global Postural Reeducation ( GPR ) in patients with ankylosing spondylitis and compare GPR with group conventional segmental self-stretching and breathing exercises . This is a controlled interventional study of 38 patients divided into 2 groups : a GPR group ( n = 22 ) and a control group ( n = 16 ) . Both groups were treated for more than 4 months . With the GPR group patients , positions that stretched the shortened muscle chains were used . With the control group patients , conventional segmental self-stretching and breathing exercises were performed . The variables analyzed were pain intensity , morning stiffness , spine mobility , chest expansion , functional capacity ( Health Assessment Question naire – Spondyloarthropathies – HAQ-S ) , quality of life ( Medical Outcome Study Short Form 36 Healthy Survey – SF-36 ) , and disease activity ( Bath Ankylosing Spondylitis Disease Activity Index – BASDAI ) . Statistical analysis was used with a significance level of P in morning stiffness ( P = 0.013 ) , spine mobility parameters , except finger-floor distance ( P = 0.118 ) , in chest expansion ( P = 0.028 ) , and in the physical aspect component of the SF-36 ( P = 0.001 ) . The results of this study showed that individual treatment with GPR ( overall stretching ) seems to have better clinical outcomes than group treatment with conventional segmental self-stretching and breathing exercises for patients with ankylosing spondylitis",
"The objective of this study was to investigate the effects of Pilates on pain , functional status , and quality of life in patients with ankylosing spondylitis . The study was performed as a r and omized , prospect i ve , controlled , and single-blind trial . Fifty-five participants ( 30 men , 25 women ) who were under a regular follow-up protocol in our Rheumatology Clinic with the diagnosis of AS according to the modified New York criteria were included in the study . The participants were r and omly assigned into two groups : in group I , Pilates exercise program of 1 h was given by a certified trainer to 30 participants 3 times a week for 12 weeks , and in group II , design ed as the control group , 25 participants continued previous st and ard treatment programs . In groups , pre-(week 0 ) and post treatment ( week 12 and week 24 ) evaluation was performed by one of the authors who was blind to the group allocation . Primary outcome measure was functional capacity . Evaluation was done using the Bath Ankylosing Spondylitis Functional Index ( BASFI ) . Exploratory outcome measures were Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) , Bath Ankylosing Spondylitis Metrology Index ( BASMI ) , Chest expansion , and ankylosing spondylitis quality of life ( ASQOL ) question naire . In group I , BASFI showed significant improvement at week 12 ( P = 0.031 ) and week 24 ( P = 0.007 ) . In group II , this parameter was not found to have significantly changed at week 12 and week 24 . Comparison of the groups showed significantly superior results for group I at week 24 ( P = 0.023 ) . We suggest Pilates exercises as an effective and safe method to improve physical capacity in AS patients . Our study is the first clinical study design ed to investigate the role of Pilates method in AS treatment . We believe that further research with more participants and longer follow-up periods could help assess the therapeutic value of this popular physical exercise method in AS",
"Objective . To assess the 2- ( T1 ) and 6-month ( T2 ) followup effects on pain , spine mobility , physical function , and disability outcome of a rehabilitation intervention in patients with ankylosing spondylitis ( AS ) stabilized with tumor necrosis factor ( TNF ) inhibitor therapy . Methods . Sixty-two out patients ( 49 men , 13 women , mean age 47.5 ± 10.6 yrs ) were r and omized to rehabilitation plus an educational-behavioral ( n = 20 ) program , to an educational-behavioral program only ( n = 20 ) , or to a control group ( n = 22 ) . The educational-behavioral program included 2 educational meetings and 12 rehabilitation exercise sessions ( stretching , strengthening , chest and spine/hip joint flexibility exercises ) , which patients then performed at home . Outcome assessment at the end of rehabilitation training ( T1 ) and at T2 was based on spinal pain intensity in the previous 4 weeks by self-report visual analog scale ( VAS ; 100 mm : 0 = no pain , 100 = maximum pain ) , BASMI , BASFI , BASDAI , and on chest expansion and the active range of motion of the cervical and lumbar spine measured by a pocket goniometer . Results . The 3 groups were comparable at baseline . On intragroup comparison at T1 , the rehabilitation group showed significant improvement in the BASMI and BASDAI , in chest expansion , and in most spinal active range of motion measurements . BASFI and cervical and lumbar VAS scores improved in both the rehabilitation and educational-behavioral groups . The positive results achieved in the rehabilitation group were maintained at the 6-month followup . Conclusion . Combining intensive group exercise with an educational-behavioral program can provide promising results in the management of patients with clinical ly stabilized AS on TNF inhibitor treatment",
"Objective : To compare the effect of balneotherapy on physical activity and quality of life as well as the symptoms of pain and stiffness with exercise alone in ankylosing spondylitis ( AS ) patients . Methods : A total of 60 patients who had a diagnosis of AS according to the modified New York criteria were included in the study . The patients were r and omly assigned to two groups . In Group I ( n = 30 ) the patients received balneotherapy in a therapeutic pool for 30 min once a day for 3 weeks . All patients received instructions on the exercise programme , which they were requested to repeat once a day for 30 min during the study . The patients in this group continued the same exercise programme after the end of the balneotherapy protocol to complete a course of 6 months . In Group II the patients were given the same exercise protocol but did not receive balneotherapy . Patients were evaluated before the start of the study and at 3 weeks and 24 weeks . Evaluation parameters were daily and night pain , morning stiffness , the patient 's global evaluation and the physician 's global evaluation ( according to a scoring system of 1 to 5 ) , the Bath Ankylosing Spondilitis Disease Activity Index ( BASDAI ) , Bath Ankylosing Spondylitis Functional Index ( BASFI ) , Dougados Functional Index ( DFI ) , tragus – wall distance , chest expansion , modified Shober test ( MST ) , fingertip – fibula head distance , and Nottingham Health Profile ( NHP ) . Results : Evaluations were completed in 54 patients in the two groups . Comparison of the groups showed significantly superior results for Group I for parameters of BASDAI , NHP total , pain , physical activity , tiredness and sleep score , patient 's global evaluation and the physician 's global evaluation at 3 weeks , but only for the parameters of patient 's global evaluation and MST at 24 weeks . Conclusion : Balneotherapy has a supplementary effect on improvement in disease activity and functional parameters in AS patients immediately after the treatment period . However , in the light of our medium‐term evaluation results , we suggest that further research is needed to assess the role of balneotherapy applied for longer duration s in AS patients",
"The objective of this non-r and omised controlled trial was to evaluate the impact of group-based exercise programme and a home-based exercise programme on Bath Ankylosing Spondylitis Indices , depression and quality of life in patients with ankylosing spondylitis ( AS ) . Approximately 41 patients in a rehabilitation unit were divided into two groups , either group- or home-based exercise programme . Exercise sessions were performed three times a week for a period of 6 weeks . The patients were compared before and after the rehabilitation programme , with respect to Bath Ankylosing Spondylitis Functional Index ( BASFI ) , Bath Ankylosing Spondylitis Disease Assessment Index ( BASDAI ) , Bath Ankylosing Spondylitis Metrology Index ( BASMI ) , Beck Depression Inventory ( BDI ) and The Nottingham Health Profile ( NHP ) . A statistically significant improvement was observed on BASDAI , BASMI and energy , pain , reaction of emotional and sleep subscores of NHP in both exercise groups after the exercise programme ( p BASFI , BDI and social and mobility subscores of NHP in both exercise groups ( p > 0.05 ) . No statistically significant differences were found between the two exercise programmes ( p > 0.05 ) . Group and home-based exercise programmes are efficient in improving symptoms and mobility and had an important effect on quality of life in patients with AS . Home-based exercise programme , as it is cheaper , more easily performed and efficient , may be preferable for the management programme in AS",
"This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . \" Quality \" as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence",
"BACKGROUND AND PURPOSE Few r and omized controlled studies have examined the effects of exercise in patients with ankylosing spondylitis ( AS ) . This study investigated the effects of a 12-week , multimodal exercise program in patients with AS . SUBJECTS A convenience sample of 30 patients with AS ( 18 male , 12 female ) , with a mean age of 34.9 years ( SD=6.28 ) , participated in the study . Twenty-six subjects were classified as having stage I AS and 4 subjects were classified as having stage II AS according to the modified New York Criteria . METHODS This study was a r and omized controlled trial . Subjects were assigned to either a group that received an exercise program or to a control group . The exercise program consisted of 50 minutes of multimodal exercise , including aerobic , stretching , and pulmonary exercises , 3 times a week for 3 months . Subjects in both groups received medical treatment for AS , but the exercise group received the exercise program in addition to the medical treatment . All subjects received a physical examination at baseline and at 12 weeks . The examinations were conducted under the supervision of a physician who specialized in physical medicine and rehabilitation and included the assessment of spinal mobility using 2 methods : clinical measurements ( chin-to-chest distance , Modified Schober Flexion Test , occiput-to-wall distance , finger-to-floor distance , and chest expansion ) and inclinometer measurements ( gross hip flexion , gross lumbar flexion , and gross thoracic flexion ) . In addition , vital capacity was measured by a physiologist , and physical work capacity was evaluated by a doctorally prepared exercise instructor . RESULTS The measurements of the exercise group for chest expansion , chin-to-chest distance , Modified Schober Flexion Test , and occiput-to-wall distance were significantly better than those of the control group after the 3-month exercise period . The spinal movements of the exercise group improved significantly at the end of exercise program , but those of the control group showed no significant change . In addition , the results showed that the posttraining value of gross thoracic flexion of the exercise group was significantly higher than that of the control group . Physical work capacity and vital capacity values improved in the exercise group but decreased in the control group . DISCUSSION AND CONCLUSION In this study , a multimodal exercise program including aerobic , stretching , and pulmonary exercises provided in conjunction with routine medical management yielded greater improvements in spinal mobility , work capacity , and chest expansion",
"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 .",
"OBJECTIVE The aim of this study was to evaluate the impact of two different home-based daily exercise programs on pulmonary functions in the patients with ankylosing spondylitis ( AS ) . METHODS Fifty-one patients with AS were distributed into three groups . Group 1 ( n=19 ) was given a conventional exercise regimen . Group 2 ( n=19 ) received exercises based on the Global Posture Reeducation ( GPR ) method . Group 3 ( n=13 ) was accepted as the control group . Patients were assessed according to pain , functional capacity ( The Bath Ankylosing Spondylitis Functional Index - BASFI ) , disease activity ( The Bath Ankylosing Spondylitis Disease Activity Index - BASDAI ) , chest expansion , pulmonary function parameters , and 6-min walk distance ( 6MWD ) test . RESULTS Although there were significant improvements for BASDAI and BASFI scores in all groups , significant improvements in the VAS pain , chest expansion , pulmonary function parameters and 6MWD test were observed in the exercise groups . The improvements in pain , functional capacity , disease activity , chest expansion , pulmonary function parameters and 6MWD test were better in the exercise groups than in the control group . The GPR method result ed in greater improvements than the conventional exercise program in specific pulmonary function parameters like forced vital capacity , forced expiratory volume in 1s , and peak expiratory flow parameters . CONCLUSION Both exercises are efficient in improving pulmonary functions . Since the improvements in pulmonary function tests were greater in the patients who performed the exercise according to GPR method , motivated patients should be encouraged to perform this exercise program",
"OBJECTIVE Home based self-care is essential for successful management of ankylosing spondylitis ( AS ) . We design ed an intervention package aim ed at promoting self-care and regular longterm exercise and evaluated its effect on outcome . METHOD Members of our data base ( n = 4569 ) were r and omly selected and r and omized to an intervention group ( IG ) or a followup control group ( CG ) . The intervention consisted of an exercise/information video , exercise progress chart , patient education booklet , and AS exercise reminder stickers . The outcome measures were function ( BASFI ) , disease activity ( BASDAI ) , global well being ( BAS-G ) , exercise self-efficacy ( ESE ) , arthritis self-efficacy ( SES ) , and quantity of AS mobility/aerobic exercise assessed at baseline and 6 months . RESULTS Of the 200 subjects , 155 completed the study ( 75 IG and 80 CG ) . Baseline analysis showed no differences between the CG and the IG . At 6 months , analysis revealed no statistically significant between-group differences for the BASFI , BASDAI , and BAS-G. although the p value of 0.08 for function approached significance . Self-efficacy for exercise showed a significant improvement in the IG ( p = 0.045 ) . There were no between-group differences for the SES pain and other symptoms subscales . Finally , there was a significant increase in self-reported AS mobility ( p aerobic exercise ( p An exercise intervention package design ed to promote self-management in AS ( 1 ) significantly improves self-efficacy for exercise ; ( 2 ) significantly improves self-reported levels of exercise ; ( 3 ) reveals a trend for improvement in function ( BASFI )",
"PURPOSE To study the effects of adding supervised group physical therapy to unsupervised individualized therapy in ankylosing spondylitis . METHODS One hundred forty-four patients were r and omized to exercises at home , or the same plus weekly group physical therapy for 9 months . Endpoints were spinal mobility , fitness ( maximum work capacity by ergometry ) , functioning ( Sickness Impact Profile , Health Assessment Question naire for the Spondylarthropathies , and Functional Index ) , and patient 's global assessment of change on a 10-cm visual analogue scale . RESULTS Thoracolumbar flexion and extension increased by an average of 0.5 cm ( 9 % ) after home exercises , and by 0.9 cm ( 16 % ) after group therapy . Maximum load in ergometry decreased by 2 W ( 1 % ) after home exercises , but increased by 7 W ( 4 % ) after group therapy . Global assessment improved by 0.3 ( 6 % ) after home exercises , and by 1.7 ( 34 % ) after group therapy . These three differences were statistically significant . There were no significant differences in chest expansion , cervical rotation , or the self- assessment s of functioning . CONCLUSIONS Group physical therapy proved superior to individualized therapy in improving thoracolumbar mobility and fitness , and had an important effect on global health reported by the patients",
"Objective : To compare , in patients with ankylosing spondylitis ( AS ) , the effectiveness on pain , functional and psychological status of an intensive group exercise programme under the supervision of a physiotherapist and a home physiotherapy programme . Design : Fifty-one patients with AS were r and omly allocated into study and control groups . The study was design ed as a prospect i ve , double-blind study . Setting : Outpatient department , Istanbul Medical Faculty . Subjects : Patients who consulted with complaints of pain , morning stiffness and restricted range of movement with a confirmed diagnosis of ankylosing spondylitis . Interventions : Before exercise , both groups were given an education programme about AS . For group I patients an intensive exercise programme was organized under the supervision of a physiotherapist for six weeks . Group II patients had to practise exercises individually at home . Main outcome measures : Both groups were evaluated and compared for pain , functional and psychological status before treatment , at the end of treatment and three months after treatment using a visual analogue scale ( VAS ) for pain , Beck Depression Scale and Bath Ankylosing Spondylitis Functional Index ( BASFI ) . Results : Six patients withdrew , four from group I. Results from the remaining 45 showed more positive changes in the patients undertaking group exercise at six weeks and three months after treatment . Values showed a statistical significant difference in favour of group I. Conclusion : Group exercise in hospital may be more effective than home-based exercises at reducing impairment associated with ankylosing spondylitis"
] |
4116c086-06ff-11f0-808a-c43d1ab1c353
|
Background Yoga , a popular mind-body practice , may produce changes in cardiovascular disease ( CVD ) and metabolic syndrome risk factors . Design This was a systematic review and r and om-effects meta- analysis of r and omized controlled trials ( RCTs ) . Methods Electronic search es of MEDLINE , EMBASE , CINAHL , PsycINFO , and The Cochrane Central Register of Controlled Trials were performed for systematic review s and RCTs through December 2013 . Studies were included if they were English , peer- review ed , focused on asana-based yoga in adults , and reported relevant outcomes . Two review ers independently selected articles and assessed quality using Cochrane ’s Risk of Bias tool . Results Out of 1404 records , 37 RCTs were included in the systematic review and 32 in the meta- analysis . Compared to non-exercise controls , yoga showed significant improvement for body mass index ( −0.77 kg/m2 ( 95 % confidence interval −1.09 to −0.44 ) ) , systolic blood pressure ( −5.21 mmHg ( −8.01 to −2.42 ) ) , low-density lipoprotein cholesterol ( −12.14 mg/dl ( −21.80 to −2.48 ) ) , and high-density lipoprotein cholesterol ( 3.20 mg/dl ( 1.86 to 4.54 ) ) . Significant changes were seen in body weight ( −2.32 kg ( −4.33 to −0.37 ) ) , diastolic blood pressure ( −4.98 mmHg ( −7.17 to −2.80 ) ) , total cholesterol ( −18.48 mg/dl ( −29.16 to −7.80 ) ) , triglycerides ( −25.89 mg/dl ( −36.19 to −15.60 ) , and heart rate ( −5.27 beats/min ( −9.55 to −1.00 ) ) , but not fasting blood glucose ( −5.91 mg/dl ( −16.32 to 4.50 ) ) nor glycosylated hemoglobin ( −0.06 % Hb ( −0.24 to 0.11 ) ) . No significant difference was found between yoga and exercise . One study found an impact on smoking abstinence . Conclusions There is promising evidence of yoga on improving cardio-metabolic health . Findings are limited by small trial sample sizes , heterogeneity , and moderate quality of RCTs
|
[
"Although the onset and progression of coronary heart disease ( CHD ) involve multiple risk factors , few intervention studies have attempted to modify these factors simultaneously . This pilot study tested the effect of a multimodality intervention involving dietary , exercise , herbal food supplement , and stress reduction approaches from a traditional system of natural medicine , Maharishi Vedic Medicine ( MVM ) . The primary outcome measure was carotid intima-media thickness ( IMT ) , a noninvasive measure of peripheral atherosclerosis and surrogate measure of coronary atherosclerosis . Comparison groups included modern medicine ( conventional dietary , exercise , and multivitamin approaches ) and usual care ( no added intervention ) . Of 57 healthy seniors ( mean age 74 years ) r and omized to the 3 treatment groups , 46 completed IMT post-testing . Carotid IMT was determined by B-mode ultrasound before and after 1 year of treatment . IMT decreased in a larger fraction of MVM subjects ( 16 of 20 ) than in the modern ( 5 of 9 ) and usual care ( 7 of 14 ) groups combined ( i.e. , 12 of 23 ; odds ratio 3.7 , p = 0.05 ) . For subjects with multiple CHD risk factors ( \" high-risk \" subjects , n = 15 ) , IMT decreased more in the MVM ( -0.32 + /- 0.23 mm , mean + /- SD ) than in the usual care ( + 0.022 + /- 0.085 ; p = 0.009 ) or modern ( -0.082 + /- 0.095 , p = 0.10 ) groups . Within-group reductions in IMT were significant for all MVM subjects ( -0.15 + /- 0.21 , n = 20 , p = 0.004 ) and for high-risk MVM subjects ( n = 6 , p = 0.01 ) . These results show that this multimodality traditional approach can attenuate atherosclerosis in older subjects , particularly those with marked CHD risk ",
"Background : Hypertension is the most prevalent non-communicable disease causing significant morbidity/mortality through cardiovascular , cerebrovascular , and renal complications . Objectives : This community-based study tested the efficacy of non-pharmacological interventions in preventing/controlling hypertension . Material s and Methods : This is a cross-over r and omized controlled trial ( RCT ) of the earlier RCT ( 2007 ) of non-pharmacological interventions in hypertension , conducted in the urban service area of our Institute . The subjects , prehypertensive and hypertensive young adults ( 98 subjects : 25 , 23 , 25 , 25 in four groups ) were r and omly allotted into a group that he/she had not belonged to in the earlier RCT : Control ( New Group I ) , Physical Exercise ( NG II)-brisk walking for 50 to 60 minutes , three to four days/week , Salt Intake Reduction ( NG III ) to at least half of their previous intake , Yoga ( NG IV ) for 30 to 45 minutes/day , five days/week . Blood pressure was measured before and after eight weeks of intervention . Analysis was by ANOVA with a Games-Howell post hoc test . Results : Ninety-four participants ( 25 , 23 , 21 , 25 ) completed the study . All three intervention groups showed significant reduction in BP ( SBP/DBP mmHg : 5.3/6.0 in NG II , 2.5/2.0 in NG III , and 2.3/2.4 in NG IV , respectively ) , while the Control Group showed no significant difference . Persistence of significant reduction in BP in the three intervention groups after cross-over confirmed the biological plausibility of these non-pharmacological interventions . This study reconfirmed that physical exercise was more effective than Salt Reduction or Yoga . Salt Reduction , and Yoga were equally effective . Conclusion : Physical exercise , salt intake reduction , and yoga are effective non-pharmacological methods for reducing blood pressure in young pre-hypertensive and hypertensive adults",
"Highly stressed employees are subject to greater health risks , increased cost , and productivity losses than those with normal stress levels . To address this issue in an evidence -based manner , worksite stress management programs must be able to engage individuals as well as capture data on stress , health indices , work productivity , and health care costs . In this r and omized controlled pilot , our primary objective was to evaluate the viability and proof of concept for two mind-body workplace stress reduction programs ( one therapeutic yoga-based and the other mindfulness-based ) , in order to set the stage for larger cost-effectiveness trials . A second objective was to evaluate 2 delivery venues of the mindfulness-based intervention ( online vs. in-person ) . Intention-to-treat principles and 2 ( pre and post ) × 3 ( group ) repeated- measures analysis of covariance procedures examined group differences over time on perceived stress and secondary measures to clarify which variables to include in future studies : sleep quality , mood , pain levels , work productivity , mindfulness , blood pressure , breathing rate , and heart rate variability ( a measure of autonomic balance ) . Two hundred and thirty-nine employee volunteers were r and omized into a therapeutic yoga worksite stress reduction program , 1 of 2 mindfulness-based programs , or a control group that participated only in assessment . Compared with the control group , the mind-body interventions showed significantly greater improvements on perceived stress , sleep quality , and the heart rhythm coherence ratio of heart rate variability . The two delivery venues for the mindfulness program produced basically equivalent results . Both the mindfulness-based and therapeutic yoga programs may provide viable and effective interventions to target high stress levels , sleep quality , and autonomic balance in employees",
"There is growing evidence that yoga may offer a safe and cost-effective intervention for Type 2 Diabetes mellitus ( DM 2 ) . However , systematic review s are lacking . This article critically review s the published literature regarding the effects of yoga-based programs on physiologic and anthropometric risk profiles and related clinical outcomes in adults with DM 2 . We performed a comprehensive literature search using four computerized English and Indian scientific data bases . The search was restricted to original studies ( 1970–2006 ) that evaluated the metabolic and clinical effects of yoga in adults with DM 2 . Studies targeting clinical population s with cardiovascular disorders that included adults with comorbid DM were also evaluated . Data were extracted regarding study design , setting , target population , intervention , comparison group or condition , outcome assessment , data analysis and presentation , follow-up , and key results , and the quality of each study was evaluated according to specific predetermined criteria . We identified 25 eligible studies , including 15 uncontrolled trials , 6 non-r and omized controlled trials and 4 r and omized controlled trials ( RCTs ) . Overall , these studies suggest beneficial changes in several risk indices , including glucose tolerance and insulin sensitivity , lipid profiles , anthropometric characteristics , blood pressure , oxidative stress , coagulation profiles , sympathetic activation and pulmonary function , as well as improvement in specific clinical outcomes . Yoga may improve risk profiles in adults with DM 2 , and may have promise for the prevention and management of cardiovascular complications in this population . However , the limitations characterizing most studies preclude drawing firm conclusions . Additional high- quality RCTs are needed to confirm and further eluci date the effects of st and ardized yoga programs in population s with DM 2",
"The effect of practicing yoga for the management of type II Diabetes was assessed in this systematic review through search ing related electronic data bases and the grey literature to the end of May 2007 using Ovid . All r and omized controlled clinical trials ( RCTs ) comparing yoga practice with other type of intervention or with regular practice or both , were included regardless of language or type of publication . Each study was assessed for quality by two independent review ers . Mean difference was used for summarizing the effect of each study outcomes with 95 % confidence intervals . Pooling of the studies did not take place due to the wide clinical variation between the studies . Publication bias was assessed by statistical methods . Five trials with 363 participants met the inclusion criteria with medium to high risk of bias and different intervention characteristics . The studies ’ results show improvement in outcomes among patients with diabetes type II . These improvements were mainly among short term or immediate diabetes outcomes and not all were statistically significant . The results were inconclusive and not significant for the long-term outcomes . No adverse effects were reported in any of the included studies . Short-term benefits for patients with diabetes may be achieved from practicing yoga . Further research is needed in this area . Factors like quality of the trials and other method ological issues should be improved by large r and omized control trials with allocation concealment to assess the effectiveness of yoga on diabetes type II . A definitive recommendation for physicians to encourage their patients to practice yoga can not be reached at present",
"OBJECTIVES To observe the effect of regular yogic practice s and self-discipline in reducing body fat and elevated lipids in CAD patients . METHOD In this study one hundred seventy ( 170 ) subjects , of both sexes having coronary artery disease were r and omly selected form Department of Cardiology . Subjects were divided in to two groups r and omly in yoga group and in non-yoga group , eighty five ( 85 ) in each group . Out of these ( 170 subjects ) , one hundred fifty four ( 154 ) completed the study protocol . TIME LINE : The yogic intervention consisted of 35 - 40 min/day , five days in a week till six months in the Department of Physiology CSMMU UP Lucknow . Body fat testing and estimation of lipid profile were done of the both groups at zero time and after six months of yogic intervention in yoga group and without yogic intervention in non yoga group . RESULTS In present study , BMI ( p fat % ( p fat free mass ( p SBP ( p DBP ( p heart rate ( p total cholesterol ( p triglycerides ( p HDL ( p low density lipoprotein ( p SBP , DBP , heart rate , body fat% , total cholesterol , triglycerides and LDL after regular yogic practice s is beneficial for cardiac and hypertensive patients . Therefore yogic practice s included in this study are helpful for the patients of coronary artery disease",
"Background Yoga is a popular therapy for diabetes but its efficacy is contested . The aim of this study was to explore the feasibility of research ing community based yoga classes in Type 2 diabetes with a view to informing the design of a definitive , multi-centre trial Methods The study design was an exploratory r and omised controlled trial with in-depth process evaluation . The setting was two multi-ethnic boroughs in London , UK ; one with average and one with low mean socio-economic deprivation score . Classes were held at a sports centre or GP surgery . Participants were 59 people with Type 2 diabetes not taking insulin , recruited from general practice lists or opportunistically by general practice staff . The intervention group were offered 12 weeks of a twice-weekly 90-minute yoga class ; the control group was a waiting list for the yoga classes . Both groups received advice and leaflets on healthy lifestyle and were encouraged to exercise . Primary outcome measure was HbA1c . Secondary outcome measures included attendance , weight , waist circumference , lipid levels , blood pressure , UKPDS cardiovascular risk score , diabetes-related quality of life ( ADDQoL ) , and self-efficacy . Process measures were attendance at yoga sessions , self-reported frequency of practice between taught sessions , and qualitative data ( interviews with patients and therapists , ethnographic observation of the yoga classes , and analysis of documents including minutes of meetings , correspondence , and exercise plans ) . Results Despite broad inclusion criteria , around two-thirds of the patients on GP diabetic registers proved ineligible , and 90 % of the remainder declined to participate . Mean age of participants was 60 + /- 10 years . Attendance at yoga classes was around 50 % . Nobody did the exercises regularly at home . Yoga teachers felt that most participants were unsuitable for ' st and ard ' yoga exercises because of limited flexibility , lack of basic fitness , co-morbidity , and lack of confidence . There was a small fall in HbA1c in the yoga group which was not statistically significant and which was not sustained six months later , and no significant change in other outcome measures . Conclusion The benefits of yoga in type 2 diabetes suggested in some previous studies were not confirmed . Possible explanations ( apart from lack of efficacy ) include recruitment challenges ; practical and motivational barriers to class attendance ; physical and motivational barriers to engaging in the exercises ; inadequate intensity and /or duration of yoga intervention ; and insufficient personalisation of exercises to individual needs . All these factors should be considered when design ing future trials . Trial registration National Research Register ( 1410 ) and Current Controlled Trials ( IS RCT N63637211 )",
"OBJECTIVES To study the effectiveness of yoga intervention on oxidative stress , glycemic status , blood pressure and anthropometry in prediabetes . DESIGN R and omized-controlled trial . PARTICIPANTS Twenty nine prediabetes subjects aged 30 - 75 years . SETTING Yoga was conducted at 4 different community diabetes clinics in Mangalore , India . INTERVENTIONS Participants were r and omized to either 3-month yoga or wait-list control groups . MAIN OUTCOME MEASURES Malondialdehyde , glutathione , vitamin C , vitamin E , superoxide dismutase , plasma glucose , glycated haemoglobin , BMI , waist circumference , waist-to-hip ratio and blood pressure . RESULTS Yoga intervention result ed in a significant decline in malondialdehyde ( p BMI , waist circumference , systolic blood pressure and fasting glucose levels at follow-up . No significant improvement in glycated haemoglobin , waist-to-hip ratio or any of the antioxidants was observed . CONCLUSIONS Yoga intervention may be helpful in control of oxidative stress in prediabetes subjects . Yoga can also be beneficial in reduction in BMI , waist circumference , systolic blood pressure and fasting glucose . Effect of yoga on antioxidant parameters was not evident in this study . The findings of this study need to be confirmed in larger trials involving active control groups",
"A study was undertaken to observe any beneficial effect of yogic practice s during training period on the young trainees . 54 trainees of 20 - 25 years age group were divided r and omly in two groups i.e. yoga and control group . Yoga group ( 23 males and 5 females ) was administered yogic practice s for the first five months of the course while control group ( 21 males and 5 females ) did not perform yogic exercises during this period . From the 6th to 10th month of training both the groups performed the yogic practice s. Physiological parameters like heart rate , blood pressure , oral temperature , skin temperature in resting condition , responses to maximal and submaximal exercise , body flexibility were recorded . Psychological parameters like personality , learning , arithmetic and psychomotor ability , mental well being were also recorded . Various parameters were taken before and during the 5th and 10th month of training period . Initially there was relatively higher sympathetic activity in both the groups due to the new work/training environment but gradually it subsided . Later on at the 5th and 10th month , yoga group had relatively lower sympathetic activity than the control group . There was improvement in performance at submaximal level of exercise and in anaerobic threshold in the yoga group . Shoulder , hip , trunk and neck flexibility improved in the yoga group . There was improvement in various psychological parameters like reduction in anxiety and depression and a better mental function after yogic practice",
"Background Yoga has been shown to be a simple and economical therapeutic modality that may be considered as a beneficial adjuvant for type 2 diabetes mellitus . This study investigated the impact of Hatha yoga and conventional physical training ( PT ) exercise regimens on biochemical , oxidative stress indicators and oxidant status in patients with type 2 diabetes . Methods This prospect i ve r and omized study consisted of 77 type 2 diabetic patients in the Hatha yoga exercise group that were matched with a similar number of type 2 diabetic patients in the conventional PT exercise and control groups . Biochemical parameters such as fasting blood glucose ( FBG ) , serum total cholesterol ( TC ) , triglycerides , low-density lipoprotein ( LDL ) , very low-density lipoproteins ( VLDL ) and high-density lipoprotein ( HDL ) were determined at baseline and at two consecutive three monthly intervals . The oxidative stress indicators ( malondialdehyde – MDA , protein oxidation – POX , phospholipase A2 – PLA2 activity ) and oxidative status [ superoxide dismutase ( SOD ) and catalase activities ] were measured . Results The concentrations of FBG in the Hatha yoga and conventional PT exercise groups after six months decreased by 29.48 % and 27.43 % respectively ( P serum TC in both groups ( P concentrations of VLDL in the managed groups after six months differed significantly from baseline values ( P = 0.036 ) . Lipid peroxidation as indicated by MDA significantly decreased by 19.9 % and 18.1 % in the Hatha yoga and conventional PT exercise groups respectively ( P activity of SOD significantly increased by 24.08 % and 20.18 % respectively ( P = 0.031 ) . There was no significant difference in the baseline and 6 months activities of PLA2 and catalase after six months although the latter increased by 13.68 % and 13.19 % in the Hatha yoga and conventional PT exercise groups respectively ( P = 0.144 ) . Conclusion The study demonstrate the efficacy of Hatha yoga exercise on fasting blood glucose , lipid profile , oxidative stress markers and antioxidant status in patients with type 2 diabetes and suggest that Hatha yoga exercise and conventional PT exercise may have therapeutic preventative and protective effects on diabetes mellitus by decreasing oxidative stress and improving antioxidant status . Trial Registration Australian New Zeal and Clinical Trials Registry ( ANZCTR ) :",
"In this study 258 patients from the Department of Cardiology in Chhatrapati Shahuji Maharaj Medical University , Lucknow were selected to participate . All had been diagnosed with coronary artery disease . They were r and omly divided into 2 groups , the yoga group and the non-yoga group , 129 in each group ; 208 completed the study protocol . The yogic intervention consisted of 35 - 40 min/day , 5 days a week over a period of 18 months in the Department of Physiology . Autonomic function testing was done in both the groups at zero time and after 18 months . We observed a statistically significant reduction in body mass index , waist circumference , systolic and diastolic blood pressure , and heart rate ( P < 0.05 ) , i.e. , a significant positive effect was observed when yoga therapy was used as an adjunct in patients with coronary artery disease",
"Physical activity energy expenditure ( PAEE ) is a determinant of prognosis and fitness in older patients with coronary heart disease ( CHD ) . PAEE and total energy expenditure ( TEE ) are closely related to fatness , physical function , and metabolic risk in older individuals . The goal of this study was to assess effects of resistance training on PAEE , TEE , and fitness in older women with chronic CHD and physical activity limitations ( N = 51 , mean age : 72 + 5 yr ) . The study intervention consisted of a progressive , 6-mo program of resistance training vs. a control group condition of low-intensity yoga and deep breathing . The study interventions were completed by 42 of the 51 participants . The intervention group manifested a 177 + /- 213 kcal/day ( + 9 % ) increase in TEE , pre- to posttraining , measured by the doubly labeled water technique during a nonexercise 10-day period ( P resting metabolic rate measured by indirect calorimetry ( P PAEE ( P upper and lower body strength , but no change in fat-free mass , measured by dual X-ray absorptiometry , or left ventricular function , measured by echocardiography and Doppler . Women in the control group showed no alterations in TEE or its determinants . There were no changes between groups in body composition , aerobic capacity , or measures of mental depression . These results demonstrate that resistance training of 6-mo duration leads to an increase in TEE and PAEE in older women with chronic CHD",
"Various modes of physical activity , combined with dieting , have been widely recommended to prevent or delay type 2 diabetes . Among these , yoga holds promise for reducing risk factors for type 2 diabetes by promoting weight loss , improving glucose levels and reducing blood pressure and lipid levels . This pilot study aim ed to assess the feasibility of implementing a 12-week yoga program among adults at high risk for type 2 diabetes . Twenty-three adults ( 19 Whites and 4 non-Whites ) were r and omly assigned to the yoga intervention group or the educational group . The yoga group participated in a 3-month yoga intervention with sessions twice per week and the educational group received general health educational material s every 2 weeks . All participants completed question naires and had blood tests at baseline and at the end of 3 months . Effect sizes were reported to summarize the efficacy of the intervention . All participants assigned to the yoga intervention completed the yoga program without complication and expressed high satisfaction with the program ( 99.2 % ) . Their yoga session attendance ranged from 58.3 to 100 % . Compared with the education group , the yoga group experienced improvements in weight , blood pressure , insulin , triglycerides and exercise self-efficacy indicated by small to large effect sizes . This preliminary study indicates that a yoga program would be a possible risk reduction option for adults at high risk for type 2 diabetes . In addition , yoga holds promise as an approach to reducing cardiometabolic risk factors and increasing exercise self-efficacy for this group",
"The prevalence of prehypertension and Stage 1 hypertension continues to increase despite being amenable to non-pharmacologic interventions . Iyengar yoga ( IY ) has been purported to reduce blood pressure ( BP ) though evidence from r and omized trials is lacking . We conducted a r and omized controlled trial to assess the effects of 12 weeks of IY versus enhanced usual care ( EUC ) ( based on individual dietary adjustment ) on 24-h ambulatory BP in yoga-naïve adults with untreated prehypertension or Stage 1 hypertension . In total , 26 and 31 subjects in the IY and EUC arms , respectively , completed the study . There were no differences in BP between the groups at 6 and 12 weeks . In the EUC group , 24-h systolic BP ( SBP ) , diastolic BP ( DBP ) and mean arterial pressure ( MAP ) significantly decreased by 5 , 3 and 3 mmHg , respectively , from baseline at 6 weeks ( P 24 h SBP was reduced by 6 mmHg at 12 weeks compared to baseline ( P = .05 ) . 24 h DBP ( P MAP ( P cortisol metabolism to explain the decrease in BP in the IY group at 12 weeks . Twelve weeks of IY produces clinical ly meaningful improvements in 24 h SBP and DBP . Larger studies are needed to establish the long term efficacy , acceptability , utility and potential mechanisms of IY to control BP",
"BACKGROUND Tobacco smoking remains the leading preventable cause of death among American women . Aerobic exercise has shown promise as an aid to smoking cessation because it improves affect and reduces nicotine withdrawal symptoms . Studies outside the realm of smoking cessation have shown that yoga practice also reduces perceived stress and negative affect . METHODS This pilot study examines the feasibility and initial efficacy of yoga as a complementary therapy for smoking cessation . Fifty-five women were given 8-week group-based cognitive behavioral therapy for smoking cessation and were r and omized to a twice-weekly program of Vinyasa yoga or a general health and wellness program ( contact control ) . The primary outcome measure was 7-day point prevalence abstinence at the end of treatment vali date d by saliva cotinine testing . Longitudinal analyses were also conducted to examine the effect of intervention on smoking cessation at 3- and 6-month follow-up . We examined the effects of the intervention on potential mediating variables ( e.g. , confidence in quitting smoking , self-efficacy ) , as well as measures of depressive symptoms , anxiety , and perceived health ( SF-36 ) . RESULTS At end of treatment , women in the yoga group had a greater 7-day point-prevalence abstinence rate than controls ( odds ratio [ OR ] , 4.56 ; 95 % CI , 1.1 - 18.6 ) . Abstinence remained higher among yoga participants through the six month assessment ( OR , 1.54 ; 95 % CI , 0.34 - 6.92 ) , although differences were no longer statistically significant . Women participating in the yoga program also showed reduced anxiety and improvements in perceived health and well-being when compared with controls . CONCLUSIONS Yoga may be an efficacious complementary therapy for smoking cessation among women",
"AIMS AND OBJECTIVES Promoting physical fitness of young-older adults is essential in reducing healthcare expenditures which would occur in the future for those with chronic health problems . The silver yoga exercise programme was developed to accommo date the reduced body flexibility experienced by many older adults and was critically review ed by experts and pilot-tested with community-dwelling older adults . This study aim ed to test older adults ' physical fitness after a 24-week silver yoga exercise programme and to examine whether the programme could be further shortened to fit senior activity centres ' programme design s. DESIGN A quasi-experimental , pre-post tests design was used : baseline , at 12-week and at 24-week periods . METHODS Convenience sample s of 204 subjects were recruited from eight senior activity centres and 176 subjects completed the study . Subjects were r and omly assigned into three groups based on the centres : ( 1 ) Experiment I : complete silver yoga with stretching and meditation , ( 2 ) Experiment II : shortened silver yoga without the guided-imagery meditation and ( 3 ) Wait-list control . The interventions were conducted three times per week for 24 weeks . Physical fitness indicators included body compositions , cardiovascular-respiratory functions , physical functions and the range of motion . RESULTS At the end of the 24-week period , the physical fitness of subjects in Experiments I and II had significantly improved whether or not guided-imagery meditation was used and all had better physical fitness than subjects in the control group ( all p physical fitness of older adults in both the 70-minute complete silver yoga group and the 55-minute shortened silver yoga group had significantly improved after the interventions . It was recommended that the silver yoga programme be shortened by eliminating the guided-imagery meditation . RELEVANCE TO CLINICAL PRACTICE The shortened silver yoga exercise programme is recommended to be incorporated as an activity programme in community- setting s to promote the physical fitness of older adults ",
"The purpose of this study was to compare the short-term effects of an intensive lifestyle modification ( ILM ) program on lipid peroxidation and antioxidant systems in patients with coronary artery disease ( CAD ) . Twenty-two patients in the control group continued to receive their conventional treatment with lipid-lowering drugs , whereas 22 patients in the experimental group were assigned to intensive lifestyle modification ( ILM ) without taking any lipid-lowering agent . The ILM program comprised dietary advice on low-fat diets , high antioxidants and high fiber intakes , yoga exercise , stress management and smoking cessation . After 4 months of intervention , patients in the experimental group revealed a statistically significant increase in plasma total antioxidants , plasma vitamin E and erythrocyte glutathione ( GSH ) compared to patients in the control group . There was no significant change in plasma malondialdehyde ( MDA ) , a circulating product of lipid peroxidation , in either group . We concluded that the ILM program increased circulating antioxidants and reduced oxidative stress in patients with CAD",
"Context : Hypertension is a major chronic lifestyle disease . Several non-pharmacological interventions are effective in bringing down the blood pressure ( BP ) . This study focuses on the effectiveness of such interventions among young adults . Aims : To measure the efficacy of physical exercise , reduction in salt intake , and yoga , in lowering BP among young ( 20 - 25 ) pre-hypertensives and hypertensives , and to compare their relative efficacies . Setting s and Design : The study was done in the urban service area of JIPMER . Pre-hypertensives and hypertensives , identified from previous studies , constituted the universe . The participants were r and omized into one control and three interventional groups . Material s and Methods : A total of 113 subjects : 30 , 28 , 28 and 27 in four groups respectively participated for eight weeks : control ( I ) , physical exercise ( II ) - brisk walking for 50 - 60 minutes , four days/week , salt intake reduction ( III ) - to at least half of their previous intake , and practice of yoga ( IV ) - for 30 - 45 minutes/day on at least five days/week . Statistical Analysis Used : Efficacy was assessed using paired t test and ANOVA with Games Howell post hoc test . An intention to treat analysis was also performed . Results : A total of 102 participants ( 29 , 27 , 25 and 21 in groups I , II , III and IV ) completed the study . All three intervention groups showed a significant reduction in BP ( SBP/DBP : 5.3/6.0 in group II , 2.6/3.7 in III , and 2.0/2.6 mm Hg in IV respectively ) . There was no significant change ( SBP/DBP : 0.2/0.5 mmHg ) of BP in control group ( I ) . Physical exercise was most effective ( considered individually ) ; salt intake reduction and yoga were also effective . Conclusions : Physical exercise , salt intake reduction , and yoga are effective non-pharmacological interventions in significantly reducing BP among young hypertensives and pre-hypertensives . These can therefore be positively recommended for hypertensives . There is also a case to deploy these interventions in the general population",
"UNLABELLED In younger people the increase in aerobic capacity following training is related , in part , to blood volume ( BV ) expansion and the consequent improvements in maximal cardiac output . This training-induced hypervolemia is associated with a decrease in cardiopulmonary baroreflex ( CPBR ) control of peripheral vascular tone . PURPOSE To test the hypothesis that improvement in peak oxygen consumption ( VO2peak ) during training in older women is associated with specific central adaptations , such as BV expansion and a reduction in CPBR control of vascular tone . METHODS Seventeen healthy older women were r and omized into training ( N = 9 , 71 + /- 2 yr ) and control ( N = 8 , 73 + /- 3 yr ) groups . The training group exercised three to four times per wk for 30 min at 60 % peak heart rate for 12 wk and then 40 - 50 min at 75 % peak heart rate for 12 wk . The control group participated in yoga exercises over the same time period . We measured resting BV ( Evans blue dye ) , VO2peak , and the forearm vascular resistance response to unloading low pressure mechanoreceptors during low levels of lower body negative pressure ( through -20 mm Hg ) before and after aerobic training . The slope of the increase in forearm vascular resistance ( response ) per unit decrease in central venous pressure ( stimulus ) was used to assess CPBR responsiveness . RESULTS Aerobic training increased VO2peak 14.2 % from 24.2 mL x kg(-1 ) x min(-1 ) to 27.7 mL x kg(-1 ) x min(-1 ) ( P younger subjects . Blood volume ( 59.9 + /- 1.9 and 60.9 + /- 1.9 mL x kg[-1 ] ) and CPBR function ( -3.98 + /- 0.92 and -3.46 + /- 0.94 units x mm(-1 ) Hg ) were similar before and after training . CONCLUSIONS These data indicate that the inability to induce adaptations in CPBR function may limit BV expansion during training in older women . In addition , the absence of these specific adaptations may contribute to the relatively poor improvements in VO2peak in older women during short ( 10 - 12 wk ) periods of training",
"It is unclear whether the age-associated reduction in baroreflex sensitivity is modifiable by exercise training . The effects of aerobic exercise training and yoga , a non-aerobic control intervention , on the baroreflex of elderly persons was determined . Baroreflex sensitivity was quantified by the alpha-index , at high frequency ( HF ; 0.15 - 0.35 Hz , reflecting parasympathetic activity ) and mid-frequency ( MF ; 0.05 - 0.15 Hz , reflecting sympathetic activity as well ) , derived from spectral and cross-spectral analysis of spontaneous fluctuations in heart rate and blood pressure . Twenty-six ( 10 women ) sedentary , healthy , normotensive elderly ( mean 68 years , range 62 - 81 years ) subjects were studied . Fourteen ( 4 women ) of the sedentary elderly subjects completed 6 weeks of aerobic training , while the other 12 ( 6 women ) subjects completed 6 weeks of yoga . Heart rate decreased following yoga ( 69 + /- 8 vs. 61 + /- 7 min-1 , P aerobic training ( 66 + /- 8 vs. 63 + /- 9 min-1 , P = 0.29 ) . VO2 max increased by 11 % following yoga ( P aerobic training ( P alpha MF ( 6.5 + /- 3.5 vs. 6.2 + /- 3.0 ms mmHg-1 , P = 0.69 ) or alpha HF ( 8.5 + /- 4.7 vs. 8.9 + /- 3.5 ms mmHg-1 , P = 0.65 ) occurred after aerobic training . Following yoga , alpha HF ( 8.0 + /- 3.6 vs. 11.5 + /- 5.2 ms mmHg-1 , P alpha MF ( 6.5 + /- 3.0 vs. 7.6 + /- 2.8 ms mmHg-1 , P = 0.29 ) increased . Short- duration aerobic training does not modify the alpha-index at alpha MF or alpha HF in healthy normotensive elderly subjects . alpha HF but not alpha MF increased following yoga , suggesting that these parameters are measuring distinct aspects of the baroreflex that are separately modifiable",
"Abstract Tracy , BL and Hart , CEF . Bikram yoga training and physical fitness in healthy young adults . J Strength Cond Res 27(3 ) : 822–830 , 2013—There has been relatively little longitudinal controlled investigation of the effects of yoga on general physical fitness , despite the widespread participation in this form of exercise . The purpose of this exploratory study was to examine the effect of short-term Bikram yoga training on general physical fitness . Young healthy adults were r and omized to yoga training ( N = 10 , 29 ± 6 years , 24 sessions in 8 weeks ) or a control group ( N = 11 , 26 ± 7 years ) . Each yoga training session consisted of 90-minute st and ardized supervised postures performed in a heated and humidified studio . Isometric deadlift strength , h and grip strength , lower back/hamstring and shoulder flexibility , resting heart rate and blood pressure , maximal oxygen consumption ( treadmill ) , and lean and fat mass ( dual-energy x-ray absorptiometry ) were measured before and after training . Yoga subjects exhibited increased deadlift strength , substantially increased lower back/hamstring flexibility , increased shoulder flexibility , and modestly decreased body fat compared with control group . There were no changes in h and grip strength , cardiovascular measures , or maximal aerobic fitness . In summary , this short-term yoga training protocol produced beneficial changes in musculoskeletal fitness that were specific to the training stimulus",
"The effect of yogic lifestyle on the lipid status was studied in angina patients and normal subjects with risk factors of coronary artery disease . The parameters included the body weight , estimation of serum cholesterol , triglycerides , HDL , LDL and the cholesterol - HDL ratio . A baseline evaluation was done and then the angina patients and risk factors subjects were r and omly assigned as control ( n = 41 ) and intervention ( yoga ) group ( n = 52 ) . Lifestyle advice was given to both the groups . An integrated course of yoga training was given for four days followed by practice at home . Serial evaluation of both the groups was done at four , 10 and 14 weeks . Dyslipidemia was a constant feature in all cases . An inconsistent pattern of change was observed in the control group of angina ( n = 18 ) and risk factor subjects ( n = 23 ) . The subjects practising yoga showed a regular decrease in all lipid parameters except HDL . The effect started from four weeks and lasted for 14 weeks . Thus , the effect of yogic lifestyle on some of the modifiable risk factors could probably explain the preventive and therapeutic beneficial effect observed in coronary artery disease",
"CONTEXT Premenstrual stress affects 75 % of women of childbearing age and yoga has been found to be beneficial in many psycho-somatic disorders . AIMS To investigate the effect of integrated yoga on autonomic parameters and psychological well-being during both pre and post phases of menstrual cycle in healthy young female subjects . SETTING S AND DESIGN Present study is a r and omized control trial and was conducted in the Department of Physiology , Lady Hardinge Medical College , New Delhi , India . MATERIAL AND METHODS Fifty apparently healthy females in the age group of 18 - 20 years were r and omized into two groups : Group I ( n=25 ) consisted of subjects who practice d yoga 35 - 40 minutes per day , six times per week for the duration of three menstrual cycles . Training was given by qualified yoga instructor . Group II ( n=25 ) subjects acted as controls . Following parameters were recorded at the beginning and after completion of three menstrual cycles in all the subjects : Height , weight ( BW ) , Resting Heart Rate ( HR ) , Resting Systolic ( SBP ) and Diastolic Blood Pressure ( DBP ) , parasympathetic reactivity tests including Expiration-Inspiration Ratio ( E : I ratio ) and 30:15 ratio , sympathetic reactivity tests including BP changes due to Isometric H and Grip ( IHG ) exercise , and Cold Pressor Test ( CPT ) . Assessment of psychological status was done by administering DIPAS ( Defense Institute of Physiology and Allied Sciences ) inventories of Anger self report scale , Trait Anxiety , Sense of well-being and Depression scale . STATISTICAL ANALYSIS Intra-group comparison of physiological parameters was done by using paired ' t ' test , whereas intra-group comparison of non-parameteric data such as scores of anxiety , depression , anger and sense of well-being was done by Wilcoxon signed-rank test . Inter-group comparison of parameters was done by Students ' t ' test for parametric tests and Mann-Whitney ' U ' test for non-parameteric tests . RESULTS There was significantly higher BW , resting SBP , DBP , sympathetic activity and blunting of parasympathetic reactivity and also , significantly higher scores of anger , depression , anxiety and decreased score of well-being in premenstrual phase as compared to postmenstrual phase in both the groups in initial cycle . There was significantly higher percentage decrease in BW , HR , SBP & DBP in yoga group as compared to control group in both the phases from initial to second and onwards between second and third menstrual cycle . Also , decrease in anger , depression and anxiety and increase in well-being score was significant in yoga group as compared to control group from initial to second and third cycle in premenstrual phase while the change was significant only in depression score in postmenstrual phase . CONCLUSION Our study shows that there was significant alteration of autonomic functions and psychological status in premenstrual phase when compared with postmenstrual phase in young healthy females . Also , regular practice of yoga has beneficial effects on both phases of menstrual cycle by bringing parasympathodominance and psychological well-being probably by balancing neuro-endocrinal axis",
"BACKGROUND Yoga has potential for benefit for patients with coronary artery disease though objective , angiographic studies are lacking . MATERIAL AND METHODS We evaluated possible role of lifestyle modification incorporating yoga , on retardation of coronary atherosclerotic disease . In this prospect i ve , r and omized , controlled trial , 42 men with angiographically proven coronary artery disease ( CAD ) were r and omized to control ( n = 21 ) and yoga intervention group ( n = 21 ) and were followed for one year . The active group was treated with a user-friendly program consisting of yoga , control of risk factors , diet control and moderate aerobic exercise . The control group was managed by conventional methods i.e. risk factor control and American Heart Association step I diet . RESULTS At one year , the yoga groups showed significant reduction in number of anginal episodes per week , improved exercise capacity and decrease in body weight . Serum total cholesterol , LDL cholesterol and triglyceride levels also showed greater reductions as compared with control group . Revascularisation procedures ( coronary angioplasty or bypass surgery ) were less frequently required in the yoga group ( one versus eight patients ; relative risk = 5.45 ; P = 0.01 ) . Coronary angiography repeated at one year showed that significantly more lesions regressed ( 20 % versus 2 % ) and less lesions progressed ( 5 % versus 37 % ) in the yoga group ( chi-square = 24.9 ; P compliance to the total program was excellent and no side effects were observed . CONCLUSION Yoga lifestyle intervention retards progression and increases regression of coronary atherosclerosis in patients with severe coronary artery disease . It also improves symptomatic status , functional class and risk factor profile",
"The cardiovascular and behavioral adaptations associated with a 4-month program of aerobic exercise training were examined in 101 older men and women ( mean age = 67 years ) . Subjects were r and omly assigned to an Aerobic Exercise group , a Yoga and Flexibility control group , or a Waiting List control group . Prior to and following the 4-month program , subjects underwent comprehensive physiological and psychological evaluations . Physiological measures included measurement of blood pressure , lipids , bone density , and cardiorespiratory fitness including direct measurements of peak oxygen consumption ( VO2 ) and anaerobic threshold . Psychological measures included measures of mood , psychiatric symptoms , and neuropsychological functioning . This study demonstrated that 4 months of aerobic exercise training produced an overall 11.6 % improvement in peak VO2 and a 13 % increase in anaerobic threshold . In contrast , the Yoga and Waiting List control groups experienced no change in cardiorespiratory fitness . Other favorable physiological changes observed among aerobic exercise participants included lower cholesterol levels , diastolic blood pressure levels , and for subjects at risk for bone fracture , a trend toward an increase in bone mineral content . Although few significant psychological changes could be attributed to aerobic exercise training , participants in the two active treatment groups perceived themselves as improving on a number of psychological and behavioral dimensions",
"On the basis of medical officers diagnosis , thirty three ( N = 33 ) hypertensives , aged 35 - 65 years , from Govt . General Hospital , Pondicherry , were examined with four variables viz , systolic and diastolic blood pressure , pulse rate and body weight . The subjects were r and omly assigned into three groups . The exp . group-I underwent selected yoga practice s , exp . group-II received medical treatment by the physician of the said hospital and the control group did not participate in any of the treatment stimuli . Yoga imparted in the morning and in the evening with 1 hr/session . day-1 for a total period of 11-weeks . Medical treatment comprised drug intake every day for the whole experimental period . The result of pre-post test with ANCOVA revealed that both the treatment stimuli ( i.e. , yoga and drug ) were effective in controlling the variables of hypertension",
"OBJECTIVES To evaluate effects of Hatha yoga and Omkar meditation on cardiorespiratory performance , psychologic profile , and melatonin secretion . SUBJECTS AND METHODS Thirty healthy men in the age group of 25 - 35 years volunteered for the study . They were r and omly divided in two groups of 15 each . Group 1 subjects served as controls and performed body flexibility exercises for 40 minutes and slow running for 20 minutes during morning hours and played games for 60 minutes during evening hours daily for 3 months . Group 2 subjects practice d selected yogic asanas ( postures ) for 45 minutes and pranayama for 15 minutes during the morning , whereas during the evening hours these subjects performed preparatory yogic postures for 15 minutes , pranayama for 15 minutes , and meditation for 30 minutes daily , for 3 months . Orthostatic tolerance , heart rate , blood pressure , respiratory rate , dynamic lung function ( such as forced vital capacity , forced expiratory volume in 1 second , forced expiratory volume percentage , peak expiratory flow rate , and maximum voluntary ventilation ) , and psychologic profile were measured before and after 3 months of yogic practice s. Serial blood sample s were drawn at various time intervals to study effects of these yogic practice s and Omkar meditation on melatonin levels . RESULTS Yogic practice s for 3 months result ed in an improvement in cardiorespiratory performance and psychologic profile . The plasma melatonin also showed an increase after three months of yogic practice s. The systolic blood pressure , diastolic blood pressure , mean arterial pressure , and orthostatic tolerance did not show any significant correlation with plasma melatonin . However , the maximum night time melatonin levels in yoga group showed a significant correlation ( r = 0.71 , p yogic practice s can be used as psychophysiologic stimuli to increase endogenous secretion of melatonin , which , in turn , might be responsible for improved sense of well-being",
"Previous studies have indicated that Yoga exercise has a positive effect on reducing blood pressure and heart rate . However , no r and omized controlled studies to date have investigated its effects on arterial compliance . The purpose of this study was to investigate the effects of an 8-month Yoga intervention on arterial compliance and muscle strength in normal premenopausal women 35 - 50 years of age . Thirty-four women were r and omly assigned either to a Yoga exercise group ( YE , n = 16 ) or a control group ( CON , n = 18 ) . Participants in YE group performed 60 minutes of an Ashtanga Yoga series 2 times/week with one day between sessions for 8 months . Each Yoga session consisted of 15 minutes of warm-up exercises , 35 minutes of Ashtanga Yoga postures and 10 minutes of cool-down with relaxation ; and the session intensity was progressively increased during the 8 months . Participants in CON were encouraged to maintain their normal daily lifestyles monitored by the bone-specific physical activity question naire at 2 month intervals for 8 months . Arterial compliance ( pulse contour analysis ) and muscle strength ( 1 Repetition Maximum ) were assessed at baseline and after the intervention . Arterial compliance of the large and small arteries was not affected by the 8 month Yoga training ( p > 0.05 ) . Also , there were no significant ( p > 0.05 ) group , time , or group × time interaction effects for cardiovascular variables . YE group significantly ( p improved leg press muscle strength compared to CON ( 11.4 % vs. -6.5 % ) . Eight months of Ashtanga Yoga training was beneficial for improving leg press strength , but not arterial compliance in premenopausal women . Key pointsThe 8 month Yoga training did not affect arterial compliance of the large and small arteries . None of the cardiovascular variables were changed by the Yoga intervention . Isotonic muscle strength was not altered by the Yoga intervention , with the exception of leg press",
"To determine the effectiveness of a yoga program on blood pressure and stress , a group of hypertensive patients in Thail and were studied , with the experimental group showing significantly decreased mean stress scores and blood pressure , heart rate , and body mass index levels compared with the control group . Further studies are suggested to determine the effects of yoga on hypertension in Thail and",
"OBJECTIVE --To determine the long term effects of relaxation therapy on 24 hour ambulatory intra-arterial blood pressure in patients with mild untreated and uncomplicated hypertension . DESIGN --Four week screening period followed by r and omisation to receive either relaxation therapy or non-specific counselling for one year . Ambulatory intra-arterial blood pressure was measured before and after treatment . SETTING --Outpatient clinic in Amsterdam 's university hospital . SUBJECTS--35 Subjects aged 20 - 60 who were being treated by general practitioners for hypertension but were referred to take part in the study . At three consecutive screening visits all subjects had a diastolic blood pressure without treatment of 95 - 110 mm Hg . Subjects were excluded if they had damaged target organs , secondary hypertension , diabetes mellitus , a cholesterol concentration greater than 8 mmol/l , or a history of malignant hypertension . INTERVENTIONS --The group allocated to relaxation therapy was trained for eight weeks ( one hour a week ) in muscle relaxation , yoga exercises , and stress management and continued exercising twice daily for one year with monthly visits to the clinic . The control group had the same attendance schedule but had no training and were requested just to sit and relax twice a day . All subjects were asked not to change their diet or physical activity . MAIN OUTCOME MEASURE -- Changes in ambulatory intra-arterial blood pressure after one year of relaxation therapy or non-specific counselling . RESULTS --Mean urinary sodium excretion , serum concentration of cholesterol , and body weight did not change in either group . Diastolic pressures measured by sphygmomanometry were 2 and 3 mm Hg lower in subjects in the relaxation group and control group respectively at the one year follow up compared with initial readings . The mean diastolic ambulatory intra-arterial pressure during the daytime had not changed after one year in either group , but small treatment effects could not be excluded : the mean change for the relaxation group was -1 mm Hg ( 95 % confidence interval -6 to 3.9 mm Hg ) and for the control group -0.4 mm Hg ( -5.3 to 4.6 mm Hg ) . Mean ambulatory pressure in the evening also had not changed over the year , and in both groups nighttime pressure was 5 mm Hg higher . The variability in blood pressure was the same at both measurements . CONCLUSIONS --Relaxation therapy was an ineffective method of lowering 24 hour blood pressure , being no more beneficial than non-specific advice , support , and reassurance -- themselves ineffective as a treatment for hypertension",
"OBJECTIVE The present study was conducted to assess the effectiveness of yoga in the management of dyslipidemia in patients of type 2 diabetes mellitus . METHODS This r and omized parallel study was carried out in Medical College Triv and rum , Kerala , India . Hundred type 2 diabetics with dyslipidemia were r and omized into control and yoga groups . The control group was prescribed oral hypoglycemic drugs . The yoga group practice d yoga daily for 1 h duration along with oral hypoglycemic drugs for 3 months . The lipid profiles of both the groups were compared at the start and at the end of 3 months . RESULTS After intervention with yoga for a period of 3 months the study group showed a decrease in total cholesterol , triglycerides and LDL , with an improvement in HDL . CONCLUSION Yoga , being a lifestyle incorporating exercise and stress management training , targets the elevated lipid levels in patients with diabetes through integrated approaches",
"This report summarizes the current evidence on the effects of yoga interventions on various components of mental and physical health , by focussing on the evidence described in review articles . Collectively , these review s suggest a number of areas where yoga may well be beneficial , but more research is required for virtually all of them to firmly establish such benefits . The heterogeneity among interventions and conditions studied has hampered the use of meta- analysis as an appropriate tool for summarizing the current literature . Nevertheless , there are some meta-analyses which indicate beneficial effects of yoga interventions , and there are several r and omized clinical trials ( RCT 's ) of relatively high quality indicating beneficial effects of yoga for pain-associated disability and mental health . Yoga may well be effective as a supportive adjunct to mitigate some medical conditions , but not yet a proven st and -alone , curative treatment . Larger-scale and more rigorous research with higher method ological quality and adequate control interventions is highly encouraged because yoga may have potential to be implemented as a beneficial supportive/adjunct treatment that is relatively cost-effective , may be practice d at least in part as a self-care behavioral treatment , provides a life-long behavioural skill , enhances self-efficacy and self-confidence and is often associated with additional positive side effects"
] |
4116c0c2-06ff-11f0-808a-c43d1ab1c353
|
Objective : To synthesize evidence on older adults ’ sedentary behavior and physical activity during rehabilitation and recovery for hip fracture ( 1 ) across the care continuum and ( 2 ) from clinical interventions . Design : We conducted a systematic review of peer- review ed publications using CINAHL , Embase , Ovid MEDLINE , PsycINFO , and SportD iscus ( last search : 17 October 2017 ) . Study selection : We included studies that measured sedentary behavior and physical activity of older adults with hip fracture using activity monitors ( e.g. accelerometers ) . We identified literature at Level 1 ( title and abstract ) and Level 2 ( full text ) , and conducted forward and backward search es . We assessed observational studies ’ adherence to reporting guidelines and intervention studies ’ risk of bias . Results : We included 14 studies ( 882 participants ) . Four studies reported sedentary behavior data , while all studies reported information on physical activity . Setting s included hospital , rehabilitation centers , and the community . Nine studies were observational ; five were experimental design . Older adults had excessive sedentary time ( > 10 hours/day ) and low physical activity . Participants ’ average upright time differed across setting s. During hospital stay , it ranged 16–52 minutes/day , while in the community , it ranged 51–261 minutes/day . Data from five interventions reported on physical activity change : two studies increased between 14 and 27 minutes/day . Another study reported participants accumulated 6994 steps/day at the end of the intervention , but for two other interventions , activity was below 5000 steps/day . Conclusion : Based on available evidence , older adults with hip fracture engage in prolonged sedentary behavior and have low levels of physical activity during rehabilitation and recovery
|
[
"Objective : To investigate if motivational interviewing improved physical activity , self-efficacy , quality of life , mobility and mental health in people living in the community after hip fracture . Design : Single-blind r and omized controlled trial . Setting : Community . Participants : A total of 30 adults after hip fracture who had been discharged from rehabilitation to independent living in the community and allocated to a control group ( n = 14 ) or an intervention group ( n = 16 ) . Intervention : All participants received usual care . The intervention group also received eight weekly sessions of motivational interviewing as additional input , with the control group having no additional matching input . Main outcomes : The primary outcome was physical activity levels as measured by an accelerometer ( steps taken per day , time spent walking per day , and time spent sitting or lying each day ) . Secondary outcomes included self-efficacy ( confidence about walking and not falling ) , health-related quality of life , mobility and mental health . Results : Relative to usual care , the motivational interviewing group took significantly more steps per day ( mean = 1237 steps , 95 % confidence interval ( CI ) 12 to 2463 ) , walked for longer per day ( mean = 14.4 minutes , 95 % CI 0.6 to 28.8 ) , had improved self-efficacy evidence d by being more confident about walking ( mean = 1.6 units out of 10 , 95 % CI 0.3 to 2.9 ) and not falling ( mean = 1.1 units out of 10 , 95 % CI 0.3 to 1.9 ) and improved health-related quality of life and mental health . Conclusion : This study provides preliminary evidence that motivational interviewing can result in clinical ly meaningful improvements in physical activity and psychosocial outcomes for people recovering from hip fracture",
"Background : Exercise is an important strategy with potential to improve recovery in older adults following a hip fracture . Purpose : The purpose of this study was to test the impact of a self-efficacy based intervention , the Exercise Plus Program , and the different components of the intervention , on self-efficacy , outcome expectations , and exercise behavior among older women post-hip fracture . Methods : Participants were r and omized to one of four groups : exercise plus , exercise only , plus only ( i.e. , motivation ) , or routine care . Data collection was done at baseline ( within 22 days of fracture ) , 2 , 6 , and 12 months post-hip fracture . Results : A total of 209 women were recruited with an average age of 81.0 years ( SD=6.9 ) . The majority was White ( 97.1 % ) , was widowed ( 57.2 % ) , and had a high school education ( 66.7 % ) . Generalized Estimating Equations were used to perform repeated measures analyses . No differences in trajectories of recovery were observed for self-efficacy or outcome expectations . A statistically significant difference in the overall trajectory of time in exercise was seen ( p home-based exercise program and that the plus only , exercise only , and the exercise plus groups all increased exercise",
"Background This study is part of the Trondheim Hip Fracture Trial , where we compared free-living physical behavior in daily life 4 and 12 months following hip surgery for patients managed with comprehensive geriatric care ( CGC ) in a geriatric ward with those managed with orthopedic care ( OC ) in an orthopedic ward . Methods This is a single centre , prospect i ve , r and omized controlled trial . 397 hip fracture patients were r and omized to CGC ( n = 199 ) or OC ( n = 198 ) in the Emergency Department with follow-up assessment s performed four and 12 months post-surgery . Outcomes were mean upright time , number and length of upright events recorded continuously for four days at four and 12 months post-surgery by an accelerometer-based activity monitor . Missing data were h and led by multiple imputation and group differences assessed by linear regression with adjustments for gender , age and fracture type . Results There were no group differences in participants ’ pre-fracture characteristics . Estimated group difference in favor of CGC in upright time at 4 months was 34.6 min ( 17.4 % , CI 9.6 to 59.6 , p = .007 ) and at 12 months , 27.7 min ( 13.9 % , CI 3.5 to 51.8 , p = .025 ) . Average and maximum length of upright events was longer in the CGC ( p ’s number of upright events ( p ’s > .452 ) . Conclusion Participants treated with CGC during the hospital stay improved free-living physical behavior more than those treated with OC both 4 and 12 months after surgery , with more time and longer periods spent in upright . Results support findings from the same study for functional outcomes , and demonstrate that CGC impacts daily life as long as one year after surgery . Trials registration Clinical Trials.gov , NCT00667914 , April 18 ,",
"INTRODUCTION Consumer-based physical activity monitors ( PAMs ) are becoming increasingly popular , with multiple global organisations recommending physical activity levels that equate to 10,000 steps per day for optimal health . We therefore aim ed to compare the step count of five PAMs to a visual step count to identify the most accurate monitors at varying gait speeds , along with the optimal anatomical placement site . METHODS Participants completed 3min on a treadmill for five speeds ( 5.0 km/h , 6.5 km/h , 8.0 km/h , 10 km/h , 12 km/h ) . An Actigraph wGT3XBT-BT was placed on the waist and wrist , a FitBit One on the waist , and a Fitbit Flex , Fitbit Charge HR and Jawbone UP24 on both wrists . A video of participant 's lower limbs was recorded for visual count . Analyses of variance ( ANOVAs ) were conducted to examine the effects of gait speed and device placement site on step count accuracy . RESULTS Thirty-one participants ( mean age 24.3±5.2yrs ) took part . Step count error ranged from 41.3±13.8 % for the wrist-worn Actigraph to only 0.04±4.3 % and -0.3±4.0 % for the waist-worn Fitbit One and Actigraph , respectively . Across all gait speeds , waist-worn devices achieved better accuracy than those on the wrist ( p accurate wrist-worn consumer-based device at slower speeds ( p=0.026 ) , with the Fitbit Flex , and Fitbit Charge HR increasing in accuracy to match the Jawbone at higher speeds . CONCLUSION The accuracy and reliability of consumer-based PAMs and the Actigraph is affected by anatomical placement site and walking speed . The Fitbit One and Actigraph on the waist were the strongest performers across all speeds",
"BACKGROUND This report describes changes in eight areas of functioning after a hip fracture , identifies the point at which maximal levels of recovery are reached in each area , and evaluates the sequence of recuperation across multiple functional domains . METHODS . Community-residing hip fracture patients ( n = 674 ) admitted to eight hospitals in Baltimore , Maryl and , 1990 - 1991 were followed prospect ively for 2 years from the time of hospitalization . Eight areas of function ( i.e. , upper and lower extremity physical and instrumental activities of daily living ; gait and balance ; social , cognitive , and affective function ) were measured by personal interview and direct observation during hospitalization at 2 , 6 , 12 , 18 , and 24 months . Levels of recovery are described in each area , and time to reach maximal recovery was estimated using Generalized Estimating Equations and longitudinal data . RESULTS Most areas of functioning showed progressive lessening of dependence over the first postfracture year , with different levels of recovery and time to maximum levels observed for each area . New dependency in physical and instrumental tasks for those not requiring equipment or human assistance prefracture ranged from as low as 20.3 % for putting on pants to as high as 89.9 % for climbing five stairs . Recuperation times were specific to area of function , ranging from approximately 4 months for depressive symptoms ( 3.9 months ) , upper extremity function ( 4.3 months ) , and cognition ( 4.4 months ) to almost a year for lower extremity function ( 11.2 months ) . CONCLUSIONS Functional disability following hip fracture is significant , patterns of recovery differ by area of function , and there appears to be an orderly sequence by which areas of function reach their maximal levels",
"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 There is little consensus on how many hours of accelerometer wear time is needed to reflect a usual day . This study identifies the bias in daily physical activity ( PA ) estimates caused by accelerometer wear time . METHODS 124 adults ( age = 41 ± 11 years ; BMI = 27 ± 7 kg·m⁻² ) contributed approximately 1,200 days accelerometer wear time . Five 40 day sample s were r and omly selected with 10 , 11 , 12 , 13 , and 14 h·d⁻¹ of wear time . Four semisimulation data sets ( 10 , 11 , 12 , 13 h·d⁻¹ ) were created from the reference 14 h·d⁻¹ data set to assess Absolute Percent Error ( APE ) . Repeated- measures ANOVAs compared min·d⁻¹ between 10 , 11 , 12 , 13 h·d⁻¹ and the reference 14 h·d⁻¹ for inactivity ( light ( 100 - 1951 cts·min⁻¹ ) , moderate ( 1952 - 5724 cts·min⁻¹ ) , and vigorous ( ≥5725 cts·min⁻¹ ) PA . RESULTS APE ranged from 5.6%-41.6 % ( 10 h·d⁻¹ = 28.2%-41.6 % ; 11 h·d⁻¹ = 20.3%-36.0 % ; 12 h·d⁻¹ = 13.5%-14.3 % ; 13 h·d⁻¹ = 5.6%-7.8 % ) . Min·d⁻¹ differences were observed for inactivity , light , and moderate PA between 10 , 11 , 12 , and 13 h·d⁻¹ and the reference ( P minimum accelerometer wear time of 13 h·d⁻¹ is needed to provide a valid measure of daily PA when 14 h·d⁻¹ is used as a reference",
"Hip fractures in older persons are associated with both low levels of daily physical activity and loss of outdoor mobility . The aim was to investigate if accelerometer-based measures of physical behaviour can be used to determine if people undertake outdoor walking and to provide reference values for physical behaviour outcomes related to outdoor mobility . Older persons ( n = 245 ) , ≥70 years , one year after hip fracture , participated . Six objective measures of physical behaviour collected by an activity monitor were compared with self-reported outdoor mobility assessed with the Nottingham Extended ADL scale . All measures of time and length in upright periods were significantly lower in participants who reported not walking outdoors ( p Maximum length of upright events discriminated best between groups , with 31 minutes as a threshold to determine if a person is more likely to report that they walk outdoors ( sensitivity : 0.805 , specificity : 0.704 , and AUC : 0.871 ) or 41 minutes or more to determine if a person is more likely to report outdoor walking on their own ( AUC : 0.891 ) . Physical behaviour variables from activity monitoring can provide information about patterns of physical behaviour related to outdoor activity performance",
"BACKGROUND This study is a part of the r and omized controlled trial , the Trondheim Hip Fracture Trial , and it compared physical behavior and function during the first postoperative days for hip fracture patients managed with comprehensive geriatric care ( CGC ) with those managed with orthopedic care ( OC ) . METHODS Treatment comprised CGC with particular focus on mobilization , or OC . A total of 397 hip fracture patients , age 70 years or older , home dwelling , and able to walk 10 m before the fracture , were included . Primary outcome was measurement of upright time ( st and ing and walking ) recorded for 24 hours the fourth day postsurgery by a body-worn accelerometer-based activity monitor . Secondary outcomes were number of upright events on Day 4 , need for assistance in ambulation measured by the Cumulated Ambulation score on Days 1 - 3 , and lower limb function measured by the Short Physical Performance Battery on Day 5 postsurgery . RESULTS A total of 317 ( CGC n = 175 , OC n = 142 ) participants wore the activity monitor for a 24-hour period . CGC participants had significantly more upright time ( mean 57.6 vs 45.1 min , p = .016 ) , higher number of upright events ( p = .005 ) and better Short Physical Performance Battery scores ( p = .002 ) , than the OC participants . Cumulated Ambulation score did not differ between groups ( p = .234 ) . CONCLUSIONS When treated with CGC , compared with OC , older persons suffering a hip fracture spent more time in upright , had more upright events , and had better lower limb function early after surgery despite no difference in their need for assistance during ambulation",
"Sedentary behavior is associated with deleterious health outcomes . This study evaluated the association between sedentary time and physical function among postmenopausal women in the Women 's Health Initiative Observational Study . Data for this prospect i ve cohort study were collected between 1993–1998 ( enrollment ) and 2009 , with an average of 12.3 follow-up years . Analyses included 61,609 women ( aged 50–79 years at baseline ) . Sedentary time was estimated by question naire ; physical function was measured using the R AND SF-36 physical function scale . Mixed-model analysis of repeated measures was used to estimate the relationship of sedentary time exposures and changes in physical function adjusting for relevant covariates . Compared to women reporting sedentary time of ≤6 hours/day , those with greater amounts of sedentary time ( > 6–8 hours/day , > 8–11 hours/day , > 11 hours/day ) reported lower physical function between baseline and follow up ( coefficient = −0.78 , CI = −0.98 , −0.57 , −1.48 , CI = −1.71 , −1.25 , −3.13 , and CI = −3.36 , −2.89 , respectively P 0.001 ) . Sedentary time was strongly associated with diminished physical function and most pronounced among older women and those reporting the greatest sedentary time . Maintaining physical function with age may be improved by pairing messages to limit sedentary activities with those promoting recommended levels of physical activity",
"Background . Comprehensive stroke unit care , incorporating acute care and rehabilitation , may promote early physical activity after stroke . However , previous information regarding physical activity specific to the acute phase of stroke and the comprehensive stroke unit setting is limited to one stroke unit . This study describes the physical activity undertaken by patients within 14 days after stroke admitted to a comprehensive stroke unit . Methods . This study was a prospect i ve observational study . Behavioural mapping was used to determine the proportion of the day spent in different activities . Therapist reports were used to determine the amount of formal therapy received on the day of observation . The timing of commencement of activity out of bed was obtained from the medical records . Results . On average , patients spent 45 % ( SD 25 ) of the day in some form of physical activity and received 58 ( SD 34 ) minutes per day of physiotherapy and occupational therapy combined . Mean time to first mobilisation out of bed was 46 ( SD 32 ) hours post-stroke . Conclusions . This study suggests that commencement of physical activity occurs earlier and physical activity is at a higher level early after stroke in this comprehensive stroke unit , when compared to studies of other acute stroke models of care",
"Background Following publication of the PRISMA statement , the UK Centre for Review s and Dissemination ( CRD ) at the University of York in Engl and began to develop an international prospect i ve register of systematic review s with health-related outcomes . The objectives were to reduce unplanned duplication of review s and provide transparency in the review process , with the aim of minimizing reporting bias . Methods An international advisory group was formed and a consultation undertaken to establish the key items necessary for inclusion in the register and to gather views on various aspects of functionality . This article describes the development of the register , now called PROSPERO , and the process of registration . Results PROSPERO offers free registration and free public access to a unique prospect i ve register of systematic review s across all areas of health from all around the world . The dedicated web-based interface is electronically search able and available to all prospect i ve registrants . At the moment , inclusion in PROSPERO is restricted to systematic review s of the effects of interventions and strategies to prevent , diagnose , treat , and monitor health conditions , for which there is a health-related outcome .Ideally , registration should take place before the research ers have started formal screening against inclusion criteria but review s are eligible as long as they have not progressed beyond the point of completing data extraction .The required data set captures the key attributes of review design as well as the administrative details necessary for registration .Su bmi tted registration forms are checked against the scope for inclusion in PROSPERO and for clarity of content before being made publicly available on the register , rejected , or returned to the applicant for clarification . The public records include an audit trail of major changes to planned methods , details of when the review has been completed , and links to result ing publications when provided by the authors . Conclusions There has been international support and an enthusiastic response to the principle of prospect i ve registration of protocol s for systematic review s and to the development of PROSPERO .In October 2011 , PROSPERO contained 200 records of systematic review s being undertaken in 26 countries around the world on a diverse range of interventions",
"OBJECTIVES To investigate the effects of intensive acute hospital physiotherapy for patients with isolated hip fractures . DESIGN , SETTING Single-institution , prospect i ve , r and omised trial at a level 1 trauma centre in Melbourne , March 2014 - January 2015 . PARTICIPANTS 92 patients aged 65 years or more with isolated hip fractures . Patients were excluded if the fracture was subtrochanteric or pathological , or if post-operative orders required the patient to be non-weight-bearing on the operated leg . INTERVENTIONS R and omisation to usual care physiotherapy ( daily ; control group ) or intensive physiotherapy ( three times daily ; intervention group ) . MAIN OUTCOME MEASURES Outcomes were assessed at post-operative Day 5 , at discharge , and at 6 months . The primary outcome was the modified Iowa Level of Assistance ( mILOA ) score , with other outcome measures including Timed Up and Go test performance and hospital length of stay ( LOS ) . RESULTS After controlling for sex , anaesthetic type and home setting , the between-group difference in Day 5 mILOA score favoured the intervention group ( mean difference v control group , -2.7 points ; P = 0.04 ) . Hospital LOS was also shorter for the intervention group ( median , 24.4 days v 35.0 days ; P = 0.01 ) . A Cox proportional hazard model that controlled for potential confounders indicated that the probability of discharge was greater for intervention group patients at all time points following surgery ( P Re-admission and complication rates and 6-month outcomes for the two groups were not significantly different . CONCLUSIONS Intensive acute hospital physiotherapy is safe and reduces hospital LOS after an isolated hip fracture . This has the potential to improve bed flow , given the large numbers of inpatient beds occupied by this patient population . TRIAL REGISTRATION Clinical Trials Registry # NCT02088437",
"Abstract Purpose : To find out how much physical activity in the form of walking can be tolerated by adults admitted for inpatient rehabilitation after hip fracture . Method : Using a phase I dose – response design , in addition to usual scheduled rehabilitation care participants without cognitive impairment were supervised to walk for a prescribed length of time on 5 consecutive days . Doses started at 3 min and were escalated when three participants successfully completed a dose . Secondary outcomes included physical activity and the Ambulatory Self-Confidence Question naire ( ASCQ ) . Results : The maximum tolerated dose of walking for the 13 participants ( 4 men and 9 women ; mean age 81 years , SD 10 ) was 6 min . At 10 min only 1 of 5 participants was able to complete the dose . The main reason for not tolerating the prescribed dose was fatigue . Participants had relatively low levels of daily physical activity ( mean 507 steps/day ) , and lacked confidence in their walking ( ASCQ mean 4.6 ) . Conclusion : Physical activity guidelines for older people are not appropriate for patients in active inpatient rehabilitation recovering from hip fracture where other factors such as fatigue may limit physical activity levels . These results can be taken into account when design ing rehabilitation programmes after hip fracture . Implication s for Rehabilitation Hip fracture is a common and serious fracture with ongoing disability for which people require inpatient rehabilitation to prepare for return to independent living in the community . The maximum tolerated dose of walking of 6 minutes suggests physical activity guidelines for older people are not applicable for those receiving active inpatient rehabilitation after hip fracture . The maximum tolerated dose of walking of 6 minutes during inpatient rehabilitation suggests rehabilitation programmes be structured to allow adequate time for recovery",
"QUESTION Are ambulant patients who are admitted for inpatient rehabilitation for a lower limb orthopaedic condition active enough to meet current physical activity guidelines ? DESIGN Prospect i ve observational study . PARTICIPANTS Adults admitted for inpatient rehabilitation for a lower limb orthopaedic condition who were cognitively alert and able to walk independently or with assistance . OUTCOME MEASURES Participants wore an activity monitor for three full days . Daily time spent in moderate intensity physical activity was used to determine whether the levels of physical activity recommended in clinical guidelines were achieved . RESULTS Fifty-four participants with a mean age of 74 years ( SD 11 ) took a median of 398 ( IQR 140 to 993 ) steps per day and spent a median of 8 ( IQR 3 to 16 ) minutes walking per day . No participant completed a 10-minute bout of moderate intensity physical activity during the monitoring period . One participant accumulated 30 minutes of moderate intensity physical activity and nine participants accumulated 15 minutes of moderate intensity physical activity in a day . Physical activity was associated with shorter length of stay ( r=-0.43 ) and higher functional status on discharge ( r=0.39 ) . CONCLUSIONS Adults with lower limb orthopaedic conditions in inpatient rehabilitation are relatively inactive and do not meet current physical activity guidelines for older adults . Results of this study indicate that strategies to increase physical activity are required"
] |
4116c108-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND Studies have also shown that non-ulcer dyspepsia ( NUD ) patients have higher scores of anxiety , depression , neurotism , chronic tension , hostility , hypochondriasis and tendency to be more pessimistic when compared with the community controls . However , the role of psychological interventions in NUD remains uncertain . OBJECTIVES This review aims to determine the effectiveness of psychological interventions including psychotherapy , psychodrama , cognitive behavioural therapy , relaxation therapy and hypnosis in the improvement of either individual or global dyspepsia symptom scores and quality of life scores in patients with NUD . SEARCH STRATEGY Trials were identified by search ing the Cochrane Controlled Trials Register ( Issue 3 - 1999 ) , MEDLINE ( 1966 - 99 ) , EMBASE ( 1988 - 99 ) , PsycLIT ( 1987 - 1999 ) and CINAHL ( 1982 - 99 ) . Bibliographies of retrieved articles were also search ed and experts in the field were contacted . Search es were up date d on 10 December 2002 and 21 January 2004 . The search es were re-run on 24 January 2005 and no new trials were found SELECTION CRITERIA All r and omised controlled trials ( RCTs ) or quasi-r and omised studies assessing the effectiveness of psychological interventions ( including psychotherapy , psychodrama , cognitive behavioural therapy , relaxation therapy and hypnosis ) for non-ulcer dyspepsia ( NUD ) were identified . DATA COLLECTION AND ANALYSIS Data collected included both individual and global dyspepsia symptom scores and quality of life ( QoL ) scores . MAIN RESULTS We identified only four trials each using different psychological interventions ; three presented results in a manner that did not allow synthesis of the data to form a meta- analysis . All trials suggested that psychological interventions benefit dyspepsia symptoms and this effect persists for one year . However , all trials used statistical techniques that adjusted for baseline differences between groups . This should not be necessary for a r and omised trial that is adequately powered suggesting that the sample size was too small . Unadjusted data was not statistically significant . The other problems of psychological intervention included low recruitment and high drop out rate , which has been shown to be greater in patients receiving group therapy . AUTHORS ' CONCLUSIONS There is insufficient evidence from this review to confirm the efficacy of psychological intervention in NUD
|
[
"Abstract Objective : To examine the additional effect of cognitive behavioural therapy for patients with medically unexplained physical symptoms in comparison with optimised medical care . Design : R and omised controlled trial with follow up assessment s six and 12 months after the baseline evaluation . Setting : General medical outpatient clinic in a university hospital . Subjects : An intervention group of 39 patients and a control group of 40 patients . Interventions : The intervention group received between six and 16 sessions of cognitive behavioural therapy . Therapeutic techniques used included identification and modification of dysfunctional automatic thoughts and behavioural experiments aim ed at breaking the vicious cycles of the symptoms and their consequences . The control group received optimised medical care . Main outcome measures : The degree of change , frequency and intensity of the presenting symptoms , psychological distress , functional impairment , hypochondriacal beliefs and attitudes , and ( at 12 months of follow up ) number of visits to the general practitioner . Results : At six months of follow up the intervention group reported a higher recovery rate ( odds ratio 0.40 ; 95 % confidence interval 0.16 to 1.00 ) , a lower mean intensity of the physical symptoms ( difference −1.2 ; −2.0 to −0.3 ) , and less impairment of sleep ( odds ratio 0.38 ; 0.15 to 0.94 ) than the controls . After adjustment for coincidental baseline differences the intervention and control groups also differed with regard to frequency of the symptoms ( 0.32 ; 0.13 to 0.77 ) , limitations in social ( 0.35 ; 0.14 to 0.85 ) and leisure ( 0.36 ; 0.14 to 0.93 ) activities , and illness behaviour ( difference −2.5 ; −4.6 to −0.5 ) . At 12 months of follow up the differences between the groups were largely maintained . Conclusion : Cognitive behavioural therapy seems to be a feasible and effective treatment in general medical patients with unexplained physical symptoms",
" A total of 117 depressed clients , stratified for severity , completed 8 or 16 sessions of manualized treatment , either cognitive-behavioral psychotherapy ( CB ) or psychodynamic-interpersonal psychotherapy ( PI ) . Each of 5 clinician-investigators treated clients in all 4 treatment conditions . On most measures , CB and PI were equally effective , irrespective of the severity of depression or the duration of treatment . However , there was evidence of some advantage to CB on the Beck Depression Inventory ( Beck , Ward , Mendelson , Mock , & Erbaugh , 1961 ) . There was no evidence that CB 's effects were more rapid than those of PI , nor did the effects of each treatment method vary according to the severity of depression . There was no overall advantage to 16-session treatment over 8-session treatment . However , those presenting with relatively severe depression improved substantially more after 16 than after 8 sessions",
"BACKGROUND Patients with functional dyspepsia ( FD ) have more complaints than just the dyspepsia . METHOD One hundred FD patients were assessed with regard to psychologic , medical , and social factors , before r and omization , in a study of cognitive therapy . They were asked to list their main problem areas or ' target complaints ' . RESULTS Dyspepsia was the third most frequent target complaint ( 26 patients ) , and anxiety was the most frequent one ( 65 patients ) . Patients identifying dyspepsia as a target complaint differed from the other FD patients in several aspects . They had significantly more dyspeptic symptoms ( p multiple somatic complaints ( p = 0.001 ) , depression ( p = 0.025 ) , general psychopathology ( p = 0.043 ) , the global assessment scale ( p = 0.001 ) , and the General Health Question naire ( p = 0.040 ) . However , they did not have more somatic predisposing factors like consumption of alcohol and coffee or infection with Helicobacter pylori than the patients with other target complaints . CONCLUSIONS Anxiety and not dyspepsia was the most frequent target complaint , and patients who identified dyspepsia as a target complaint did not have more somatic predisposing factors",
"30 patients with severe refractory irritable-bowel syndrome were r and omly allocated to treatment with either hypnotherapy or psychotherapy and placebo . The psychotherapy patients showed a small but significant improvement in abdominal pain , abdominal distension , and general well-being but not in bowel habit . The hypnotherapy patients showed a dramatic improvement in all features , the difference between the two groups being highly significant . In the hypnotherapy group no relapses were recorded during the 3-month follow-up period , and no substitution symptoms were observed",
"Economic models have suggested that population Helicobacter pylori screening and treatment may be a cost‐effective method of reducing mortality from gastric cancer . These models are conservative as they do not consider that the programme may reduce health service peptic ulcer and other dyspepsia costs . We have evaluated the economic impact of population H. pylori screening and treatment over 2 years in a r and omized controlled trial and have incorporated the results into an economic model exploring the impact of H. pylori eradication on peptic ulcer disease and gastric cancer",
"Gastrointestinal ( GI ) complaints are among the most common symptoms in primary care yet are frequently unexplained and often lead to costly diagnostic testing . We sought to determine the prevalence of psychiatric disorders in patients with unexplained GI complaints undergoing upper endoscopy , and the likelihood of endoscopic abnormalities in patients with and without psychiatric diagnoses . We prospect ively evaluated 116 adult patients who were undergoing upper endoscopy to evaluate GI complaints . All subjects received a structured psychiatric interview prior to endoscopy using PRIME-MD , and endoscopists were blinded to the PRIME-MD results . Psychiatric disorders were detected in 70 ( 60 % ) patients . Overall , there were 113 diagnoses ( some patients had multiple disorders ) with the most common being somatoform ( 44 % ) , depressive ( 29 % ) , and anxiety ( 19 % ) disorders . Only 29 patients had major endoscopic abnormalities , including esophageal disease ( 14 ) , peptic ulcer ( 9 ) , severe gastritis ( 4 ) , gastric cancer ( 1 ) , and esophageal cancer ( 1 ) . There was a much higher prevalence of psychiatric disorders in patients without major endoscopic abnormalities ( 74 % vs. 21 % , p Psychiatric disease was strongly predictive of endoscopic findings ( OR for major abnormality = 0.11 in women , and 0.40 in men ) , especially if somatoform disorder was present ( OR = 0.15 ) . We conclude that , with a simple question naire , psychiatric disorders can be diagnosed in a large proportion of patients with unexplained GI complaints who are referred for upper endoscopy . The presence of a psychiatric disorder , particularly if somatoform , makes it unlikely that endoscopy will reveal significant GI disease",
"One hundred two patients with irritable bowel syndrome were studied in a controlled trial of psychological treatment involving psychotherapy , relaxation , and st and ard medical treatment compared with st and ard medical treatment alone . Patients were only selected if their symptoms had not improved with st and ard medical treatment over the previous 6 months . At 3 months , the treatment group showed significantly greater improvement than the controls on both gastroenterologists ' and patients ' ratings of diarrhea and abdominal pain , but constipation changed little . Good prognostic factors included overt psychiatric symptoms and intermittent pain exacerbated by stress , whereas those with constant abdominal pain were helped little by this treatment . This study has demonstrated that psychological treatment is feasible and effective in two thirds of those patients with irritable bowel syndrome who do not respond to st and ard medical treatment",
"BACKGROUND & AIMS This study aim ed to determine whether brief psychodynamic-interpersonal ( PI ) psychotherapy is more efficacious than a psychological control for patients with chronic , intractable functional dyspepsia ( FD ) , and whether patients with abnormal gastric function respond differently than those with normal gastric function . METHODS Ninety-five consecutive patients with chronic symptoms of FD who had failed to respond to conventional pharmacologic treatments were approached . Thirty-seven received PI psychotherapy , and 36 the control condition ( supportive therapy ) . Patients completed self-report question naires before and after treatment and 12 months later . The patients ' gastroenterologists , who were blind to the study groups , conducted independent ratings before and after treatment . Forty-nine patients also underwent a radioisotope gastric emptying study . An intention-to-treat analysis was used with baseline scores as covariates . RESULTS At the end of treatment , there were significant advantages for PI psychotherapy compared with controls for the gastroenterologists ' ( P = 0.002 ) and patients ' total symptom score ( P = 0.015 ) . One year after treatment , the symptomatic scores were similar . However , a sub analysis showed that PI therapy was superior to the control condition at 1 year , when patients with severe heartburn were excluded . There was no difference in outcome between patients with normal and abnormal gastric emptying . CONCLUSIONS PI therapy may have both short- and long-term effects in patients with dyspepsia , but further evaluation is required . Its cost-effectiveness needs to be determined",
"BACKGROUND & AIMS We have shown hypnotherapy ( HT ) to be effective in irritable bowel syndrome , with long-term improvements in symptomatology and quality of life ( QOL ) . This study aim ed to assess the efficacy of HT in functional dyspepsia ( FD ) . METHODS A total of 126 FD patients were r and omized to HT , supportive therapy plus placebo medication , or medical treatment for 16 weeks . Percentage change in symptomatology from baseline was assessed after the 16-week treatment phase ( short-term ) and after 56 weeks ( long-term ) with 26 HT , 24 supportive therapy , and 29 medical treatment patients completing all phases of the study . QOL was measured as a secondary outcome . RESULTS Short-term symptom scores improved more in the HT group ( median , 59 % ) than in the supportive ( 41 % ; P = 0.01 ) or medical treatment ( 33 % ; P = 0.057 ) groups . HT also benefited QOL ( 42 % ) compared with either supportive therapy ( 10 % [ P HT significantly improved symptoms ( 73 % ) compared with supportive therapy ( 34 % [ P QOL improved significantly more with HT ( 44 % ) than with medical treatment ( 20 % [ P QOL did improve in the supportive therapy ( 43 % ) group , but 5 of these patients commenced taking antidepressants during follow-up . A total of 90 % of the patients in the medical treatment group and 82 % of the patients in the supportive therapy group commenced medication during follow-up , whereas none in the HT group did so ( P visited their general practitioner or gastroenterologist significantly less ( median , 1 ) than did those in the supportive therapy ( median , 4 ) and medical treatment ( median , 4 ) groups during follow-up ( P HT is highly effective in the long-term management of FD . Furthermore , the dramatic reduction in medication use and consultation rate provide major economic advantages",
"BACKGROUND A contribution of Helicobacter pylori gastritis to the pathogenesis of non-ulcer dyspepsia ( NUD ) remains uncertain . METHODS Administration of an appropriate clinical question naire followed by endoscopy allowed us to select , among 139 out patients with dyspepsia , 87 non-ulcer dyspepsia patients with more severe and group-distinctive symptoms , 35 of whom were classified as having ulcer-like ( ULD ) . 38 as dysmotility-like ( DLD ) , and 14 as reflux-like dyspepsia ( RLD ) . Biopsy specimens were evaluated for H. pylori gastritis in accordance with the Sydney system . The 70 H. pylori-positive cases were treated with omeprazole , 20 mg twice daily , and amoxycillin , 1 g three times daily for 2 weeks . RESULTS Higher rates of H. pylori colonization were found histologically in the gastric mucosa of ULD ( 91 % ) and RLD ( 86 % ) than in that of DLD ( 68 % ) or asymptomatic ( 42 % ) patients . ULD differed from RLD patients in their higher score of antritis activity . Three and 6 months after H. pylori eradication ULD ( but not DLD ) showed significant regression of dypspetic symptoms scores . CONCLUSIONS It seems likely that H. pylori gastritis , with special reference to active antritis , is among causative factors of ULD . Its role in the pathogenesis of RLD and DLD needs further investigation",
"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",
"Non-ulcer dyspepsia , also termed \" nervous dyspepsia , \" is a heterogeneous syndrome : ulcerlike symptoms can occur with the irritable bowel syndrome , gastroesophageal reflux , and other disorders . In addition , there is a significant subgroup of non-ulcer dyspepsia sufferers who have no disorder associated with , and no known cause for , their dyspepsia , and the dyspepsia in this subgroup is given the provisional name of \" essential dyspepsia . \" The aim of this study was to assess if psychological factors are associated with patients who present with essential dyspepsia . Psychometric testing was carried out on 76 essential dyspepsia patients ( including 18 patients with gastroduodenitis ) , 76 r and omly selected dyspepsia-free community controls ( matched for age , sex , and social class ) , and 66 duodenal ulcer controls . Essential dyspepsia patients were retested a mean of 3.6 mo later . Using stepwise regression analysis , the initial scores of essential dyspepsia and duodenal ulcer subjects showed them to be more neurotic , anxious , and depressed than community controls ; these abnormalities persisted in essential dyspepsia patients on retesting and were not affected by the symptom status . It is concluded that essential dyspepsia patients who present for investigation with symptoms are more likely to be persistently neurotic , anxious , and depressed than dyspepsia-free controls , and this is unrelated to the presence of symptoms , but the association may not be of major clinical significance , as the numerical differences observed between groups were small and the correlation coefficients were low",
"BACKGROUND & AIMS Psychotherapy and antidepressants are effective in patients with severe irritable bowel syndrome ( IBS ) , but the cost-effectiveness of either treatment in routine practice has not been established . METHODS Patients with severe IBS were r and omly allocated to receive 8 sessions of individual psychotherapy , 20 mg daily of the specific serotonin reuptake inhibitor ( SSRI ) antidepressant , paroxetine , or routine care by a gastroenterologist and general practitioner . Primary outcome measures of abdominal pain , health-related quality of life , and health care costs were determined after 3 months of treatment and 1 year later . RESULTS A total of 257 subjects ( 81 % response rate ) from 7 hospitals were recruited ; 59 of 85 patients ( 69 % ) r and omized to psychotherapy and 43 of 86 ( 50 % ) of the paroxetine group completed the full course of treatment . Both psychotherapy and paroxetine were superior to treatment as usual in improving the physical aspects of health-related quality of life ( SF-36 physical component score improvement , 5.2 [ SEM , 1.26 ] , 5.8 [ SEM , 1.0 ] , and -0.3 [ SEM , 1.17 ] ; P health care costs compared with treatment as usual ( psychotherapy , $ 976 [ SD , $ 984 ] ; paroxetine , $ 1252 [ SD , $ 1616 ] ; and treatment as usual , $ 1663 [ SD , $ 3177 ] ) . CONCLUSIONS For patients with severe IBS , both psychotherapy and paroxetine improve health-related quality of life at no additional cost",
"Patients with functional dyspepsia were assigned at r and om to cognitive psychotherapy ( 10 sessions of 50 min duration , n = 50 ) or to a control group ( no treatment , n = 50 ) . Before treatment all patients were assessed on psychological , somatic and lifestyle factors . If allocated to the therapy group all patients were also asked to define the main problems they wanted to discuss in therapy ( ' target complaints ' ) . The patients were evaluated at the end of therapy ( after 4 months ) and at 1 yr follow-up . Outcome measures were dyspeptic symptoms , scores on ' target complaints ' and psychological parameters . Both groups showed improvement in dyspeptic and psychological parameters after 1 yr . The improvement in the control group was attributed to a non- specific effect of increased interest and attention . The therapy group showed greater reduction than the control group on dyspeptic symptoms [ days of epigastric pain ( p = 0.050 ) , nausea ( p = 0.024 ) , heartburn ( p = 0.021 ) , diarrhoea ( p = 0.002 ) and constipation ( p = 0.047 ) ] ; and on scores on ' target complaints ' ( p = 0.001 )",
"There is currently no vali date d question naire that assesses both the presence and severity of dyspepsia "
] |
4116c14e-06ff-11f0-808a-c43d1ab1c353
|
Objectives : This systematic review aim ed to identify and evaluate prognostic factors for long-term ( ≥6 mo ) physical functioning in patients with chronic musculoskeletal pain following multidisciplinary rehabilitation ( MDR ) . Material s and Methods : Electronic search es conducted in MEDLINE , PsycINFO , EMBASE , CINAHL , Web of Science , and Cochrane CENTRAL revealed 25 original research reports , published 1983 - 2016 , ( n=9436 ) . Potential prognostic factors relating to initial pain and physical and psychological functioning were synthesized qualitatively and quantitatively in r and om effects meta-analyses . The level of evidence ( LoE ) was evaluated with Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) . Results : Pain-related factors ( intensity and chronicity ) were not associated with function/disability at long-term follow-up , odds ratio (OR)=0.84 ; 95 % confidence interval ( CI ) , 0.65 - 1.07 and OR=0.97 ; 95 % CI , 0.93 - 1.00 , respectively ( moderate LoE ) . A better function at follow-up was predicted by Physical factors ; higher levels of initial self-reported functioning , OR=1.07 ; 95 % CI , 1.02 - 1.13 ( low LoE ) , and Psychological factors ; low initial levels of emotional distress , OR=0.77 ; 95 % CI , 0.65 - 0.92 , low levels of cognitive and behavioral risk factors , OR=0.85 ; 95 % CI , 0.77 - 0.93 and high levels of protective cognitive and behavioral factors , OR=1.49 ; 95 % CI , 1.17 - 1.90 ( moderate LoE ) . Discussion : While pain intensity and long-term chronicity did not predict physical functioning in chronic pain patients after MDR , poor pretreatment physical and psychological functioning influenced the prognosis negatively . Thus , treatment should further target and optimize these modifiable factors and an increased focus on positive , psychological protective factors may perhaps provide an opening for yet untapped clinical gains
|
[
"Objectives : To assess the effectiveness of multidisciplinary rehabilitation in the treatment of fibromyalgia in comparison to st and ard medical care . Methods : Seventy-nine men and women were r and omly assigned to one of two groups . The intervention group consisted of a rheumatologist and physical therapist intake and discharge , 18 group supervised exercise therapy sessions , 2 group pain and stress management lectures , 1 group education lecture , 1 group dietary lecture , and 2 massage therapy sessions . The control group consisted of st and ard medical care with the patients ' family physician . Outcome measures included self-perceived health status , pain-related disability , average pain intensity , depressed mood , days in pain , hours in pain , prescription and nonprescription medication usage , and work status . Outcomes were measured at the end of the 6-week intervention and at 15-month follow-up . Results : Thirty-five out of 43 patients from the intervention group and 36 out of 36 patients from the control group completed the study . There were no statistically significant differences between the 2 groups prior to intervention . Intention-to-treat analysis revealed that the intervention group , in comparison to the control group , experienced statistically significant changes at intervention completion in self-perceived health status , average pain intensity , pain related disability , depressed mood , days in pain , and hours in pain , but no significant differences in nonprescription drug use , prescription drug use , or work status . At 15 months , all health outcomes retained their significance except health status . Nonprescription and prescription drug use demonstrated significant reductions at 15 months . Binary logistic regression indicated that long-term changes in Pain Disability Index were influenced by long-term exercise adherence and income status . Conclusions : Positive health-related outcomes in this mostly unresponsive condition can be obtained with a low-cost , group multidisciplinary intervention in a community-based , non clinical setting",
"Study Design . A prospect i ve clinical trial was conducted that involved six groups of patients with chronic low back pain selected from a large cohort ( N = 816 ) . Objectives . To correlate pretreatment baseline variables with outcome parameters after treatment in a functional restoration program or in control programs , to identify possible factors predictive of the need for functional restoration . Summary of Background Data . Since the functional restoration program was first described , research has focused on identifying patients who will or will not benefit from such a program . The value of previous studies is limited , however , because predictive factors from a control group were not \" subtracted . \" Methods . Eight hundred sixteen patients with chronic low back disability were included . All had a structured medical examination , including various physical tests before participation in either a functional restoration program ( n = 621 ) or shorter \" control \" outpatient programs ( n = 144 ) . A smaller group of the cohort ( n = 51 ) had no treatment and served as a pure control group . Six groups were selected from the cohort : Three underwent an identical functional restoration program and three underwent different outpatient control programs . Several baseline demographic , physical , and socioeconomic variables were correlated to 1‐year outcome parameters . Results . Age , days of sick leave , connection to the work force , and back pain intensity , were significantly correlated to success 1 year after entry into the study in all groups , no matter what kind of treatment was administered . Back muscle endurance , sports activity , activity of daily living scores , and vibrations were of importance in some outcome parameters for success after functional restoration . Smoking was positively correlated to disability pension . Days of sick leave and , in functional restoration , ability to work were the only factors that were correlative with statistics for people who withdrew . Conclusions . Different factors can be identified as predictive of outcome in a functional restoration program , but most of these factors were also shown to predict success for shorter control outpatient programs or of no treatment",
"Background Few data are available on the course of and predictors for disability in patients with chronic nonspecific low back pain ( CNSLBP ) . Objective The purpose of this study was to describe the course of disability and identify clinical ly important prognostic factors of low-back-pain – specific disability in patients with CNSLBP receiving multidisciplinary therapy . Design A prospect i ve cohort study was conducted . Methods A total of 1,760 patients with CNSLBP who received multidisciplinary therapy were evaluated for their course of disability and prognostic factors at baseline and at 2- , 5- , and 12-month follow-ups . Recovery was defined as 30 % reduction in low back pain – specific disability at follow-up compared with baseline and as absolute recovery if the score on the Quebec Back Pain Disability Scale ( QBPDS ) was ≤20 points at follow-up . Potential prognostic factors were identified using multivariable logistic regression analysis . Results Mean patient-reported disability scores on the QBPDS ranged from 51.7 ( SD=15.6 ) at baseline to 31.7 ( SD=15.2 ) , 31.1 ( SD=18.2 ) , and 29.1 ( SD=20.0 ) at 2 , 5 , and 12 months , respectively . The prognostic factors identified for recovery at 5 and 12 months were younger age and high scores on disability and on the 36-Item Short-Form Health Survey ( SF-36 ) ( Physical and Mental Component Summaries ) at baseline . In addition , at 5-month follow-up , a shorter duration of complaints was a positive predictor , and having no comorbidity and less pain at baseline were additional predictors at 12-month follow-up . Limitations Missing values at 5- and 12-month follow-ups were 11.1 % and 45.2 % , respectively . Conclusion After multidisciplinary treatment , the course of disability in patients with CNSLBP continued to decline over a 12-month period . At 5- and 12-month follow-ups , prognostic factors were identified for a clinical ly relevant decrease in disability scores on the QBPDS",
"Considering the enormous costs of intensive multidisciplinary treatment , predictive tests for therapy outcome are needed to evaluate patients ’ performance potential and increase cost effectiveness . Somatic parameters are commonly used to evaluate health status and serve as an additional means of forecasting the prognosis , yet little is known of their validity . In this study , we investigated the prognostic value of somatic parameters regarding the outcome of multidisciplinary treatment in patients with subacute low back pain . The study was design ed as a prospect i ve cohort study of 162 patients . Somatic parameters were assessed with three physical performance tests ( Villiger test , Oesch test , Biering – Sørensen test ) before treatment ( T0 ) , after 3 weeks ’ inpatient therapy ( T1 ) and at 6-month follow-up ( T2 ) . Psychometric characteristics of subjective pain perception ( VAS ) , a pain disability index ( PDI ) and a physical capability index ( FFbH-R ) were recorded . Correlation coefficients between the physical performance test scores and psychometric characteristics were calculated . To predict therapy outcome , discriminant analyses were performed . A control group ( n = 30 ) was evaluated at similar time points without receiving any therapy . Our results demonstrate good discrimination between patients and controls by means of the investigated performance tests and exhibit a significant negative correlation with the psychometric data . Lower outcome values at study entry correlated with higher pain intensity and disability after multidisciplinary treatment . However , the statistical magnitude of correlation was relatively low and further discriminant analysis did not reveal any predictive value . Consequently the physical performance tests do not have a prognostic value regarding therapy outcome",
"Background Whiplash associated disorders ( WAD ) have dramatic consequences for individual and public health . Risk factors for better and worse outcomes are important to optimize management . This study aim ed to determine short- and mid-term associative co-factors of neck pain relief , improved physical functioning , and improved working capacity ( dependent variables ) in patients suffering from whiplash associated disorder who participated in a st and ardized , inpatient pain management program . Methods Naturalistic , observational , prospect i ve cohort study . Outcome was measured by st and ardized assessment instruments . Co-factors covered sociodemographics , comorbidities , social participation , affective health , and coping abilities . Stepwise , multivariate linear regression analysis was performed at discharge and at the 6-month follow-up . Results All regression models explained high proportions of variance ( 53.3 % – 72.1 % ) . The corresponding baseline level was significantly associated with a change in every dependent variable ( explained variances : 11.4%-56.7 % ) . Pain relief significantly depended on improved function and vice-versa ( 3.4%-14.8 % ) . Improved ability to decrease pain was associated with pain relief at discharge ( 9.6 % ) . Functional improvement was associated with decreased catastrophizing ( 19.4 % ) at discharge and decreased depression ( 20.5 % ) at the 6 month follow-up . Conclusions Pain relief , improved physical function and working capacity were associated with each other . Improved coping ( catastrophizing and ability to decrease pain ) and reduced depression may act as important predictors for pain relief and improved function . These findings offer toe-holds for optimized therapy of chronic WAD",
"Background The prevalence of chronic musculoskeletal pain is high , with widespread negative economic , psychological , and social consequences for the individual . It is therefore important to find ways to predict the outcome of rehabilitation programmes in terms of function in daily life . The aims of this study were to investigate the improvements over time from multidisciplinary rehabilitation in terms of pain and function , and analyse the relative impact of individual and psychosocial factors as predictors of function in daily life in individuals with chronic musculoskeletal pain . Methods A prospect i ve study was conducted among one hundred and forty three ( N = 143 ) musculoskeletal pain patients . Measures of pain , function , and functional health status were obtained at baseline , after 5 weeks of intensive training , at the end of the 57-week rehabilitation programme , and at a 1 year follow-up , using vali date d self-administrated measures . Linear regression analysis was applied to investigate the relative impact of musculoskeletal pain , individual- , and psychosocial factors in function . Results The participants studied showed a significant increase in function during the 57 weeks rehabilitation period . There was also a significant increase in function from the end of the rehabilitation period ( 57th week ) to the one year follow-up measures . Pain intensity associated significantly with pain experience over all measurement periods . High levels of pain intensity ( β = .42 * * ) and pain experience ( β = .37 * ) , and poor psychological capacity ( β = -.68 * ) at baseline , as well as poor physiological capacity ( β = -.44 * * ) and high levels of anxiety ( β = .48 * * ) and depression ( β = .58 * * * ) at the end of the rehabilitation program were the most important prognostic factors of variance in functioning over the 4 measurement periods . Conclusion The data suggest that physical capacity , emotional distress and coping skills should be priority areas in rehabilitation programmes to improve functioning in daily life",
"Background The effectiveness of multidisciplinary treatment in chronic widespread pain ( CWP ) is limited . The considerable heterogeneity among patients is a likely explanation . Knowledge on predictors of the outcome of multidisciplinary treatment can help to optimize treatment effectiveness . The purpose of this study was to identify predictors of multidisciplinary treatment outcome in patients with CWP . Methods Data were used from baseline and 6 months follow-up measurements of a prospect i ve cohort study of 120 CWP . Regression models were used to assess whether baseline variables predicted treatment outcome . Outcome domains included : pain , pain interference , depression , and global perceived effect ( GPE ) . Potential predictors included : psychological distress , illness and self-efficacy beliefs , fear-avoidance beliefs and behaviour , symptoms , disability , and socio-demographic factors . Results Greater improvement in pain was predicted by more pain at baseline and male gender . Greater improvement in interference of pain in daily life was predicted by more interference of pain in daily life at baseline , lower levels of anxiety , a stronger belief in personal control , less belief in consequences , male gender , and a higher level of education . Greater improvement in depression was predicted by higher baseline values of depression , stronger beliefs in personal control , and a higher level of education . Better outcome on GPE was predicted by less pain , less fatigue , and a higher level of education . Conclusion Less anxiety , stronger beliefs in personal control , less belief in consequences , less pain , less fatigue , higher level of education , and male gender are predictors of better outcome of multidisciplinary treatment in CWP . Tailoring treatment to these specific patient characteristics or selecting eligible patients for multidisciplinary treatment may further improve treatment outcome",
"Purpose The aim of this longitudinal study is to determine the factors which predict a successful 1-year outcome from an intensive combined physical and psychological ( CPP ) programme in chronic low back pain ( CLBP ) patients . Methods A prospect i ve cohort of 524 selected consecutive CLBP patients was followed . Potential predictive factors included demographic characteristics , disability , pain and cognitive behavioural factors as measured at pre-treatment assessment . The primary outcome measure was the oswestry disability index ( ODI ) . A successful 1-year follow-up outcome was defined as a functional status equivalent to ‘ normal ’ and healthy population s ( ODI ≤22 ) . The 2-week residential programme fulfills the recommendations in international guidelines . For statistical analysis we divided the data base into two equal sample s. A r and om sample was used to develop a prediction model with multivariate logistic regression . The remaining cases were used to vali date this model . Results The final predictive model suggested being ‘ in employment ’ at pre-treatment [ OR 3.61 ( 95 % CI 1.80–7.26 ) ] and an initial ‘ disability score ’ [ OR 0.94 ( 95 % CI 0.92–0.97 ) ] as significant predictive factors for a successful 1-year outcome ( R2 = 22 % ; 67 % correctly classified ) . There was no predictive value from measures of psychological distress . Conclusion CLBP patients who are in work and mild to moderately disabled at the start of a CPP programme are most likely to benefit from it and to have a successful treatment outcome . In these patients , the disability score falls to values seen in healthy population s. This small set of factors is easily identified , allowing selection for programme entry and triage to alternative treatment regimes",
"& NA ; A better knowledge of differential treatment outcomes for subgroups of chronic spinal pain patients may , for instance , help clinicians in treatment planning or pain research ers in treatment outcome research . The purpose of this prospect i ve study was to evaluate the predictive validity of a subgroup classification based on the Swedish version of the ( West Haven Yale ) Multidimensional Pain Inventory , the MPI‐S. Patients referred to a vocational rehabilitation program were classified into one of three groups , labeled ‘ adaptive copers ’ , ‘ dysfunctional ’ patients , and ‘ interpersonally distressed ’ patients , and followed over an 18‐month follow‐up period . The outcome variables were absence from work ( defined as sick listing plus early retirement ) , general health status , and utilization of health care re sources . To our knowledge , the predictive validity of the MPI subgroups has not been evaluated regarding sick listing and early retirement after rehabilitation . As hypothesized , the results showed that the ‘ dysfunctional ’ patient group had significantly more registered absences from work and reported higher utilization of health care , over the follow‐up period compared to the ‘ adaptive copers ’ . Furthermore , as hypothesized , the ‘ interpersonally distressed ’ and ‘ dysfunctional ’ patient groups report a poorer general health status than the ‘ adaptive copers ’ over the whole follow‐up period . However , contrary to our hypothesis , the proportion of improved patients did not differ significantly between the subgroups . Altogether , the predictive validity of the MPI‐S subgroup classification was mainly confirmed . The clinical implication s of this study suggest that the matching of treatment to patient needs may enhance treatment outcome , reduce pain and suffering among chronic spinal pain patients and facilitate a better health economic allocation of treatment re sources",
"Purpose : To explore the change in kinesiophobia in relation to activity limitation after a multidisciplinary rehabilitation programme in patients with chronic back pain . Method : A prospect i ve cohort study was made including 265 patients . Data were collected at baseline , after rehabilitation , and at 6-months follow-up . Outcome measures were the Tampa Scale for kinesiophobia ( TSK ) and the disability rating index ( DRI ) . The smallest detectable change ( SDC ) in TSK was set to 8 scores . Relationships between kinesiophobia and activity limitation/physical ability were explored with regard to subgroups with high , medium and low baseline TSK scores , and for those patients who did or did not reach the SDC in TSK . Results : Improvements in TSK showed high effect sizes in the groups with high and medium baseline TSK scores . Improvements in DRI showed medium effect sizes in all three TSK subgroups . One third of the patients reached the SDC in TSK , and this group also improved significantly more in DRI . The correlation between change in TSK and change in DRI was low . Half of the patients with high TSK score at baseline remained having high DRI at follow-up . Conclusions : Improvement in physical ability was not related to the initial degree of kinesiophobia but to the SDC in TSK . To prevent patients with high kinesiophobia from preserving high activity limitations , it might be useful to include targeted treatment of kinesiophobia . Implication s for Rehabilitation Intensive multidisciplinary rehabilitation decreases kinesiophobia and activity limitation in patients with chronic back pain . Patients improving > 8 scores on the Tampa Scale for kinesiophobia are likely to increase their physical ability . Patients with an initially high degree of kinesiophobia as well as a high level of activity limitation need targeted treatment of kinesiophobia to increase their physical ability"
] |
4116c194-06ff-11f0-808a-c43d1ab1c353
|
Background : Coronary heart disease ( CHD ) is a major cause of death worldwide . Cardiac rehabilitation , an evidence -based CHD secondary prevention programme , remains underutilized . Telehealth may offer an innovative solution to overcome barriers to cardiac rehabilitation attendance . We aim ed to determine whether contemporary telehealth interventions can provide effective secondary prevention as an alternative or adjunct care compared with cardiac rehabilitation and /or usual care for patients with CHD . Methods : Relevant r and omized controlled trials evaluating telehealth interventions in CHD patients with at least three months ’ follow-up compared with cardiac rehabilitation and /or usual care were identified by search ing electronic data bases . We checked reference lists , relevant conference lists , grey literature and keyword search ing of the Internet . Main outcomes included all-cause mortality , rehospitalization/cardiac events and modifiable risk factors . ( PROSPERO registration number 77507 . ) Results : In total , 32 papers reporting 30 unique trials were identified . Telehealth was not significant associated with a lower all-cause mortality than cardiac rehabilitation and /or usual care ( risk ratio (RR)=0.60 , 95 % confidence interval (CI)=0.86 to 1.24 , p=0.42 ) . Telehealth was significantly associated with lower rehospitalization or cardiac events ( RR=0.56 , 95 % CI=0.39 to 0.81 , p lower weighted mean difference ( WMD ) at medium to long-term follow-up than comparison groups for total cholesterol ( WMD= −0.26 mmol/l , 95 % CI= −0.4 to −0.11 , p low-density lipoprotein ( WMD= −0.28 , 95 % CI = −0.50 to −0.05 , p=0.02 ) and smoking status ( RR=0.77 , 95 % CI = 0.59 to 0.99 , p=0.04 ] . Conclusions : Telehealth interventions with a range of delivery modes could be offered to patients who can not attend cardiac rehabilitation , or as an adjunct to cardiac rehabilitation for effective secondary prevention
|
[
"Background Cardiovascular disease ( CVD ) is the leading cause of death worldwide . Secondary prevention is essential , but participation rates for cardiac rehabilitation are low . Furthermore , current programmes do not accomplish that patients with CVD change their lifestyle in a way that their individual risk factors for recurrent events decrease , therefore more effective interventions are needed . In this study , the effectiveness of the Hartcoach-programme , a telephonic secondary prevention program focussing on self management , is studied . Methods / design A multicenter , r and omised parallel-group study is being conducted . Participants are 400 patients with acute myocardial infa rct ion ( STEMI , NSTEMI , ) and patients with chronic or unstable angina pectoris ( IAP ) . Patients are recruited through the participating hospitals and r and omly assigned to the experimental group ( Hartcoach-programme plus usual care ) or the control group ( usual care).The Hartcoach-programme consists of a period of six months during which the coach contacts the patient every four to six weeks by telephone . Coaches train patients to take responsibility for the achievement and maintenance of the defined target levels for their particular individual modifiable risk factors . Target levels and treatment goals are agreed by the nurse and patient together . Data collection is blinded and occurs at baseline and after 26 weeks ( post-intervention ) . Primary outcome is change in cardiovascular risk factors ( cholesterol , body mass index , waist circumference , blood pressure , physical activity and diet ) . Secondary outcomes include chances in glucose , HbA1c , medication adherence , self-management and quality of life . Discussion This study evaluates the effects of the Hartcoach-programme on the reduction of individual risk factors of patients with CVDs . Patients who are not invited to follow a hospital based rehabilitation programme or patients who are unable to adhere to such a programme , may be reached by this home based Hartcoach-programme . If positive results are found , the implementation of the Hartcoach-programme will be extended , having implication s for the management of many people with CVD.Trial registration",
"Aim To determine the effectiveness and cost-effectiveness of a mobile phone intervention to improve exercise capacity and physical activity behaviour in people with ischaemic heart disease ( IHD ) . Methods and results In this single-blind , parallel , two-arm , r and omized controlled trial adults ( n = 171 ) with IHD were r and omized to receive a mobile phone delivered intervention ( HEART ; n = 85 ) plus usual care , or usual care alone ( n = 86 ) . Adult participants aged 18 years or more , with a diagnosis of IHD , were clinical ly stable as out patients , able to perform exercise , able to underst and and write English , and had access to the Internet . The HEART ( Heart Exercise And Remote Technologies ) intervention involved a personalized , automated package of text messages and a secure website with video messages aim ed at increasing exercise behaviour , delivered over 24 weeks . All participants were able to access usual community-based cardiac rehabilitation , which involves encouragement of physical activity and an offer to join a local cardiac support club . All outcomes were assessed at baseline and 24 weeks and included peak oxygen uptake ( PVO2 ; primary outcome ) , self-reported physical activity , health-related quality of life , self-efficacy and motivation ( secondary outcomes ) . Results showed no differences in PVO2 between the two groups ( difference −0.21 ml kg−1 min−1 , 95 % CI : −1.1 , 0.7 ; p = 0.65 ) at 24 weeks . However significant treatment effects were observed for selected secondary outcomes , including leisure time physical activity ( difference 110.2 min/week , 95 % CI : −0.8 , 221.3 ; p = 0.05 ) and walking ( difference 151.4 min/week , 95 % CI : 27.6 , 275.2 ; p = 0.02 ) . There were also significant improvements in self-efficacy to be active ( difference 6.2 % , 95 % CI : 0.2 , 12.2 ; p = 0.04 ) and the general health domain of the SF36 ( difference 2.1 , 95 % CI : 0.1 , 4.1 ; p = 0.03 ) at 24 weeks . The HEART programme was considered likely to be cost-effective for leisure time activity and walking . Conclusions A mobile phone intervention was not effective at increasing exercise capacity over and above usual care . The intervention was effective and probably cost-effective for increasing physical activity and may have the potential to augment existing cardiac rehabilitation services",
"Background There is a strong will and need to find alternative models of health care delivery driven by the ever-increasing burden of chronic diseases . Objective The purpose of this 1-year trial was to study whether a structured mobile phone-based health coaching program , which was supported by a remote monitoring system , could be used to improve the health-related quality of life ( HRQL ) and /or the clinical measures of type 2 diabetes and heart disease patients . Methods A r and omized controlled trial was conducted among type 2 diabetes patients and heart disease patients of the South Karelia Social and Health Care District . Patients were recruited by sending invitations to r and omly selected patients using the electronic health records system . Health coaches called patients every 4 to 6 weeks and patients were encouraged to self-monitor their weight , blood pressure , blood glucose ( diabetics ) , and steps ( heart disease patients ) once per week . The primary outcome was HRQL measured by the Short Form ( 36 ) Health Survey ( SF-36 ) and glycosylated hemoglobin ( HbA1c ) among diabetic patients . The clinical measures assessed were blood pressure , weight , waist circumference , and lipid levels . Results A total of 267 heart patients and 250 diabetes patients started in the trial , of which 246 and 225 patients concluded the end-point assessment s , respectively . Withdrawal from the study was associated with the patients ’ unfamiliarity with mobile phones — of the 41 dropouts , 85 % ( 11/13 ) of the heart disease patients and 88 % ( 14/16 ) of the diabetes patients were familiar with mobile phones , whereas the corresponding percentages were 97.1 % ( 231/238 ) and 98.6 % ( 208/211 ) , respectively , among the rest of the patients ( P=.02 and P=.004 ) . Withdrawal was also associated with heart disease patients ’ comorbidities—40 % ( 8/20 ) of the dropouts had at least one comorbidity , whereas the corresponding percentage was 18.9 % ( 47/249 ) among the rest of the patients ( P=.02 ) . The intervention showed no statistically significant benefits over the current practice with regard to health-related quality of life — heart disease patients : beta=0.730 ( P=.36 ) for the physical component score and beta=-0.608 ( P=.62 ) for the mental component score ; diabetes patients : beta=0.875 ( P=.85 ) for the physical component score and beta=-0.770 ( P=.52 ) for the mental component score . There was a significant difference in waist circumference in the type 2 diabetes group ( beta=-1.711 , P=.01 ) . There were no differences in any other outcome variables . Conclusions A health coaching program supported with telemonitoring did not improve heart disease patients ' or diabetes patients ' quality of life or their clinical condition . There were indications that the intervention had a differential effect on heart patients and diabetes patients . Diabetes patients may be more prone to benefit from this kind of intervention . This should not be neglected when developing new ways for self-management of chronic diseases . Trial Registration Clinical Trials.gov NCT01310491 ; http:// clinical trials.gov/ct2/show/NCT01310491 ( Archived by WebCite at http://www.webcitation.org/6Z8l5FwAM )",
"Background Angina affects more than 50 million people worldwide . Secondary prevention interventions such as cardiac rehabilitation are not widely available for this population . An Internet-based version could offer a feasible alternative . Objective Our aim was to examine the effectiveness of a Web-based cardiac rehabilitation program for those with angina . Methods We conducted a r and omized controlled trial , recruiting those diagnosed with angina from general practitioners ( GPs ) in primary care to an intervention or control group . Intervention group participants were offered a 6-week Web-based rehabilitation program ( “ ActivateYourHeart ” ) . The program was introduced during a face-to-face appointment and then delivered via the Internet ( no further face-to-face contact ) . The program contained information about the secondary prevention of coronary heart disease ( CHD ) and set each user goals around physical activity , diet , managing emotions , and smoking . Performance against goals was review ed throughout the program and goals were then reset/modified . Participants completed an online exercise diary and communicated with rehabilitation specialists through an email link/synchronized chat room . Participants in the control group continued with GP treatment as usual , which consisted of being placed on a CHD register and attending an annual review . Outcomes were measured at 6-week and 6-month follow-ups during face-to-face assessment s. The primary outcome measure was change in daily steps at 6 weeks , measured using an accelerometer . Secondary outcome measures were energy expenditure ( EE ) , duration of sedentary activity ( DSA ) , duration of moderate activity ( DMA ) , weight , diastolic/systolic blood pressure , and body fat percentage . Self-assessed question naire outcomes included fat/fiber intake , anxiety/depression , self-efficacy , and quality of life ( QOL ) . Results A total of 94 participants were recruited and r and omized to the intervention ( n=48 ) or the usual care ( n=46 ) group ; 84 and 73 participants completed the 6-week and 6-month follow-ups , respectively . The mean number of log-ins to the program was 18.68 ( SD 13.13 , range 1 - 51 ) , an average of 3 log-ins per week per participant . Change in daily steps walked at the 6-week follow-up was + 497 ( SD 2171 ) in the intervention group and –861 ( SD 2534 ) in the control group ( 95 % CI 263 - 2451 , P=.02 ) . Significant intervention effects were observed at the 6-week follow-up in EE ( + 43.94 kcal , 95 % CI 43.93 - 309.98 , P=.01 ) , DSA ( –7.79 minutes , 95 % CI –55.01 to –7.01 , P=.01 ) , DMA ( + 6.31 minutes , 95 % CI 6.01 - 51.20 , P=.01 ) , weight ( –0.56 kg , 95 % CI –1.78 to –0.15 , P=.02 ) , self-efficacy ( 95 % CI 0.30 - 4.79 , P=.03 ) , emotional QOL score ( 95 % CI 0.01 - 0.54 , P=.04 ) , and angina frequency ( 95 % CI 8.57 - 35.05 , P=.002 ) . Significant benefits in angina frequency ( 95 % CI 1.89 - 29.41 , P=.02 ) and social QOL score ( 95 % CI 0.05 - 0.54 , P=.02 ) were also observed at the 6-month follow-up . Conclusions An Internet-based secondary prevention intervention could be offered to those with angina . A larger pragmatic trial is required to provide definitive evidence of effectiveness and cost-effectiveness . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 90110503 ; http://www.controlled-trials.com/IS RCT N90110503/IS RCT N90110503 ( Archived by WebCite at http://www.webcitation.org/6RYVOQFKM )",
"Background Adherence to evidence -based therapies such as medications and exercise remains poor among patients after a myocardial infa rct ion ( MI ) . Text message reminders have been shown to improve rates of adherence to medication and exercise , but the existing studies have been of short duration . Objective Two single-center r and omized controlled pilot trials were conducted to evaluate the impact of text message reminders over 12 months on adherence to cardiac medications and exercise among patients receiving cardiac rehabilitation after hospitalization for MI . Methods In the medication adherence trial , 34 patients were r and omized to receive usual care alone or usual care plus daily text message reminders delivered at the time of day at which medications were to be taken . In the exercise adherence trial , 50 patients were r and omized to receive usual care alone or usual care plus 4 daily text messages reminding them to exercise as directed . Results The text message reminders led to a mean 14.2 percentage point improvement in self-reported medication adherence over usual care ( P exercise per month over usual care and a nonsignificant increase of 1.2 metabolic equivalents ( METS ; P=.06 ) in exercise capacity as assessed by a BRUCE protocol at 12 months . Conclusions Text message reminders significantly increased adherence to medication and exercise among post-MI patients receiving care in a structured cardiac rehabilitation program . This technology represents a simple and scalable method to ensure consistent use of evidence -based cardiovascular therapies . Trial Registration Clinical trials.gov NCT02783287 ; https:// clinical trials.gov/ct2/show/NCT02783287 ( Archived by WebCite at http://www.webcitation.org/6sBnvNb05",
"Objective Cardiac rehabilitation ( CR ) is pivotal in preventing recurring events of myocardial infa rct ion ( MI ) . This study aims to investigate the effect of a smartphone-based home service delivery ( Care Assessment Platform ) of CR ( CAP-CR ) on CR use and health outcomes compared with a traditional , centre-based programme ( TCR ) in post-MI patients . Methods In this unblinded r and omised controlled trial , post-MI patients were r and omised to TCR ( n=60 ; 55.7±10.4 years ) and CAP-CR ( n=60 ; 55.5±9.6 years ) for a 6-week CR and 6-month self-maintenance period . CAP-CR , delivered in participants ’ homes , included health and exercise monitoring , motivational and educational material delivery , and weekly mentoring consultations . CAP-CR uptake , adherence and completion rates were compared with TCR using intention-to-treat analyses . Changes in clinical outcomes ( modifiable lifestyle factors , biomedical risk factors and health-related quality of life ) across baseline , 6 weeks and 6 months were compared within , and between , groups using linear mixed model regression . Results CAP-CR had significantly higher uptake ( 80 % vs 62 % ) , adherence ( 94 % vs 68 % ) and completion ( 80 % vs 47 % ) rates than TCR ( p improvements in 6-minute walk test from baseline to 6 weeks ( TCR : 537±86–584±99 m ; CAP-CR : 510±77–570±80 m ) , which was maintained at 6 months . CAP-CR showed slight weight reduction ( 89±20–88±21 kg ) and also demonstrated significant improvements in emotional state ( K10 : median ( IQR ) 14.6 ( 13.4–16.0 ) to 12.6 ( 11.5–13.8 ) ) , and quality of life ( EQ5D-Index : median ( IQR ) 0.84 ( 0.8–0.9 ) to 0.92 ( 0.9–1.0 ) ) at 6 weeks . Conclusions This smartphone-based home care CR programme improved post-MI CR uptake , adherence and completion . The home-based CR programme was as effective in improving physiological and psychological health outcomes as traditional CR . CAP-CR is a viable option towards optimising use of CR services . Trial registration number ANZCTR12609000251224",
"Objective : To determine if the improved risk factor profile at 1 year attributed to the Choice of Health Options In prevention of Cardiovascular Events ( CHOICE ) program was maintained at 4 years . Design : Single-blind r and omized controlled trial with post-hoc 47 ± 6 months follow-up ( 76 % complete ) . Setting : Australian tertiary referral hospital . Patients : Two hundred and eight acute coronary syndrome survivors . Interventions : Acute coronary syndrome survivors not accessing cardiac rehabilitation ( CR ) were r and omized to control ( n = 72 ) or CHOICE ( n = 72 ) comprising the tailored risk factor reduction packaged as a clinic visit and 3 months phone support . A contemporary CR reference group were also recruited ( n = 64 ) . Blinded risk assessment occurred at baseline , 1 and 4 years . Main outcome measures : Total cholesterol , systolic blood pressure , smoking status , physical activity . Results : One year improvements in all the modifiable risk factors achieved in CHOICE were maintained at 4 years . CHOICE and control were well-matched at baseline . At 4 years , there was a trend towards lower total cholesterol in CHOICE compared with controls ( mean 4.0 ± 0.1 vs. 4.2 ± 0.1 mmol/l , P = 0.05 ) , significantly better systolic blood pressure ( mean 132.2 ± 2.1 vs. 136.8 ± 2.0 mmHg , P = 0.01 ) , physical activity scores ( 1200 ± 209 vs. 968 ± 196 metabolic equivalent min/week , P = 0.02 ) and proportion with three or more risk factors above national targets ( 20 vs. 42 % , P = 0.02 ) . Participants in CHOICE were at higher baseline risk than CR but at 4 years they had similar risk factor profiles . Conclusion : Participants in CHOICE maintained favorable changes in coronary risk profile at 4 years compared with control , indicating that CHOICE is an effective long-term intervention among those not accessing facility-based CR",
"BACKGROUND Globally , attendance at cardiac rehabilitation ( CR ) is between 15 and 30 % . Alternative models of individualised care are recommended to promote participation in CR , however there has been no prospect i ve testing of different duration s of such models . We aim ed to replicate the previously proven Choice of Health Options In prevention of Cardiovascular Events ( CHOICE ) intervention , and to determine if an extended version ( CHOICEplus ) would confer additional benefits . METHODS Acute coronary syndrome ( ACS ) survivors not accessing centre-based CR ( n=203 ) were r and omised to CHOICE for 3 months ( n=100 ) or CHOICEplus for 24 months ( n=103 ) at four urban hospitals . The program comprised telephone-based tailored risk-factor reduction . RESULTS CHOICE and CHOICEplus were equivalent demographically and in risk profile at baseline . At 24 months , lipid profiles improved significantly and fewer patients had ≥3 risk factors above target compared to baseline in both groups . There were no significant differences between groups . CONCLUSIONS The 24-month CHOICEplus program did not confer additional benefit above the brief 3-month CHOICE intervention . However , participation in either CHOICE and CHOICEplus significantly improved cardiovascular risk profile in ACS survivors . Importantly , the study was feasible , and the intervention translated readily across four hospitals . Overall , this study adds to the existing evidence for brief individualised approaches to CR",
"BACKGROUND Previous reports indicate risk factors and lifestyle behaviors may deteriorate early after completion of a cardiac rehabilitation program ( CRP ) . We hypothesized that a modest risk factor and lifestyle management intervention after a CRP would significantly reduce overall cardiovascular risk using the Framingham risk score compared with usual care after 4 years . METHODS Patients with ischemic heart disease ( n = 302 ) were r and omized after a CRP to either usual care or intervention ( exercise sessions , telephone follow-ups , counseling sessions , and reports to the participants ' family physicians ) . The Framingham risk score , risk factors , and lifestyle behaviors were compared after 4 years . RESULTS Data were available for 130 intervention and 119 usual care participants . The intervention result ed in 15.5 hours of direct participant contact . Framingham score , total cholesterol , low-density lipoprotein cholesterol , and systolic blood pressure were significantly improved in the intervention group after adjusting for baseline factors . There were no significant differences with respect to lifestyle factors between the groups . CONCLUSIONS A modest risk factor and lifestyle management intervention result ed in a significant reduction to global risk compared with usual care and should be considered after CRP",
"OBJECTIVES To determine the proportion of patients with established coronary heart disease ( CHD ) in two Australian studies ( VIC-I in 1996 - 1998 , and VIC-II in 1999 - 2000 ) who achieved their risk-factor targets as recommended by the National Heart Foundation of Australia , and to compare this proportion with those in studies from the United Kingdom ( ASPIRE ) , Europe ( EUROASPIRE I and II ) and the United States ( L-TAP ) . DESIGN AND SETTING Prospect i ve cohort study with VIC-I set in a single Melbourne university teaching hospital and VIC-II set in six university teaching hospitals in Melbourne , Victoria . PARTICIPANTS 460 patients ( 112 in VIC-I , 348 in VIC-II ) who completed follow-up in the control groups of two r and omised controlled trials of a coaching intervention in patients with established CHD . MAIN OUTCOME MEASURES The treatment gap ( 100 % , minus the percentage of patients achieving the target level for a particular modifiable risk factor ) at six months after hospitalisation . RESULTS The treatment gap declined from 96.4 % ( 95 % CI , 91%-99 % ) to 74.1 % ( 95 % CI , 69%-79 % ) for total cholesterol concentration ( TC ) treatment gap between VIC-I and VIC-II appears to be entirely explained by an increase in the number of patients prescribed lipid-lowering drugs . The treatment gaps in the UK and two European studies were substantially greater . The treatment gap for blood pressure ( systolic > or = 140 mmHg and /or diastolic > or = 90 mmHg ) in VIC-II was 39.5 % , again less than corresponding European data . There were 8.1 % of patients who had unrecognised diabetes in VIC-II ( fasting glucose level > or = 7 mmol/L ) , making a total of 25.6 % of VIC-II patients with diabetes , self-reported or unrecognised . The proportion of patients in VIC-II who were obese ( body mass index > or = 30 kg/m2 ) was similar to the overseas studies , while fewer patients in VIC-II smoked compared with those in the UK and European studies . CONCLUSIONS A substantial treatment gap exists in Victorian patients with established CHD . The treatment gap compares well with international surveys and , at least in the lipid area , is diminishing",
"Background Mobile technology has the potential to deliver behavior change interventions ( mHealth ) to reduce coronary heart disease ( CHD ) at modest cost . Previous studies have focused on single behaviors ; however , cardiac rehabilitation ( CR ) , a component of CHD self-management , needs to address multiple risk factors . Objective The aim was to investigate the effectiveness of a mHealth-delivered comprehensive CR program ( Text4Heart ) to improve adherence to recommended lifestyle behaviors ( smoking cessation , physical activity , healthy diet , and nonharmful alcohol use ) in addition to usual care ( traditional CR ) . Methods A 2-arm , parallel , r and omized controlled trial was conducted in New Zeal and adults diagnosed with CHD . Participants were recruited in-hospital and were encouraged to attend center-based CR ( usual care control ) . In addition , the intervention group received a personalized 24-week mHealth program , framed in social cognitive theory , sent by fully automated daily short message service ( SMS ) text messages and a supporting website . The primary outcome was adherence to healthy lifestyle behaviors measured using a self-reported composite health behavior score ( ≥3 ) at 3 and 6 months . Secondary outcomes included clinical outcomes , medication adherence score , self-efficacy , illness perceptions , and anxiety and /or depression at 6 months . Baseline and 6-month follow-up assessment s ( unblinded ) were conducted in person . Results Eligible patients ( N=123 ) recruited from 2 large metropolitan hospitals were r and omized to the intervention ( n=61 ) or the control ( n=62 ) group . Participants were predominantly male ( 100/123 , 81.3 % ) , New Zeal and European ( 73/123 , 59.3 % ) , with a mean age of 59.5 ( SD 11.1 ) years . A significant treatment effect in favor of the intervention was observed for the primary outcome at 3 months ( AOR 2.55 , 95 % CI 1.12 - 5.84 ; P=.03 ) , but not at 6 months ( AOR 1.93 , 95 % CI 0.83 - 4.53 ; P=.13 ) . The intervention group reported significantly greater medication adherence score ( mean difference : 0.58 , 95 % CI 0.19 - 0.97 ; P=.004 ) . The majority of intervention participants reported reading all their text messages ( 52/61 , 85 % ) . The number of visits to the website per person ranged from zero to 100 ( median 3 ) over the 6-month intervention period . Conclusions A mHealth CR intervention plus usual care showed a positive effect on adherence to multiple lifestyle behavior changes at 3 months in New Zeal and adults with CHD compared to usual care alone . The effect was not sustained to the end of the 6-month intervention . A larger study is needed to determine the size of the effect in the longer term and whether the change in behavior reduces adverse cardiovascular events . Trial Registration ACTRN 12613000901707 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?id=364758&is Review = true ( Archived by WebCite at http://www.webcitation.org/6c4qhcHKt",
"IMPORTANCE Cardiovascular disease prevention , including lifestyle modification , is important but underutilized . Mobile health strategies could address this gap but lack evidence of therapeutic benefit . OBJECTIVE To examine the effect of a lifestyle-focused semipersonalized support program delivered by mobile phone text message on cardiovascular risk factors . DESIGN AND SETTING The Tobacco , Exercise and Diet Messages ( TEXT ME ) trial was a parallel-group , single-blind , r and omized clinical trial that recruited 710 patients ( mean age , 58 [ SD , 9.2 ] years ; 82 % men ; 53 % current smokers ) with proven coronary heart disease ( prior myocardial infa rct ion or proven angiographically ) between September 2011 and November 2013 from a large tertiary hospital in Sydney , Australia . INTERVENTIONS Patients in the intervention group ( n = 352 ) received 4 text messages per week for 6 months in addition to usual care . Text messages provided advice , motivational reminders , and support to change lifestyle behaviors . Patients in the control group ( n=358 ) received usual care . Messages for each participant were selected from a bank of messages according to baseline characteristics ( eg , smoking ) and delivered via an automated computerized message management system . The program was not interactive . MAIN OUTCOMES AND MEASURES The primary end point was low-density lipoprotein cholesterol ( LDL-C ) level at 6 months . Secondary end points included systolic blood pressure , body mass index ( BMI ) , physical activity , and smoking status . RESULTS At 6 months , levels of LDL-C were significantly lower in intervention participants , with concurrent reductions in systolic blood pressure and BMI , significant increases in physical activity , and a significant reduction in smoking . The majority reported the text messages to be useful ( 91 % ) , easy to underst and ( 97 % ) , and appropriate in frequency ( 86 % ) . [ table : see text ] . CONCLUSIONS AND RELEVANCE Among patients with coronary heart disease , the use of a lifestyle-focused text messaging service compared with usual care result ed in a modest improvement in LDL-C level and greater improvement in other cardiovascular disease risk factors . The duration of these effects and hence whether they result in improved clinical outcomes remain to be determined . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12611000161921",
"Background Providing information is an important part of st and ard care and treatment for acute myocardial infa rct ion in patients . Evidence exists indicating that acute myocardial infa rct ion patients experience an information gap in the period immediately after discharge from the hospital . The aim of this study was to assess the short-term effects of a nurse-led telephone follow-up intervention to provide information and support to patients with acute myocardial infa rct ion after their discharge from hospital . Design and method A prospect i ve r and omized , controlled trial with a 6-month follow-up was conducted . A total of 288 patients were allocated to either an intervention group ( n = 156 ) or a control group ( n = 132 ) . The latter received routine post-discharge care . The primary endpoint measured at 3 and 6 months after discharge was the health-related quality of life using the 36-item Short Form Health Survey . Secondary endpoints included smoking and exercise habits . Results In both groups , health-related quality of life improved significantly over time on most subscales . A statistically significant difference in favour of the intervention group was found on the 36-item Short Form Health Survey Physical Health Component Summary Scale ( P=0.034 ) after 6 months . No difference was found between the groups on the Mental Health Component Summary Scale . We found a significant difference with respect to frequency of physical activity in favour of the intervention group after 6 months ( P=0.004 ) . More participants in the intervention group than the control group had ceased smoking at the 6-month follow-up ( P=0.055 ) . Conclusion A nurse-led systematic telephone follow-up intervention significantly improved the physical dimension of health-related quality of life in patients in the intervention group compared with usual care patients . Participation in this intervention also seemed to promote health behaviour change in patients after acute myocardial infa rct ion",
"Background : In this study , we tested the efficacy of a low-intensity lifestyle intervention aim ed at reducing the risk of cardiovascular disease among mid-life individuals . Methods : We conducted a r and omized controlled trial in which participants were r and omly assigned either to receive a health report card with counselling ( from a Telehealth nurse ) on smoking , exercise , nutrition and stress or to receive usual care . The patients were divided into 2 groups on the basis of risk : the primary prevention group , with a Framingham risk score of 10 % or higher ( intervention , n = 157 ; control , n = 158 ) , and the secondary prevention group , who had a diagnosis of coronary artery disease ( intervention , n = 153 ; control , n = 143 ) . The primary outcome was a change in the Framingham global risk score between baseline and 1-year follow-up . Data were analyzed separately for the 2 prevention groups using an intention-to-treat analysis controlling for covariates . Results : Within the primary prevention group , there were statistically significant changes for the treatment group relative to the controls , from baseline to year 1 , in Framingham score ( intervention , –3.10 [ 95 % confidence interval ( CI ) –3.98 to –2.22 ] ; control , –1.30 [ 95 % CI –2.18 to –0.42 ] ; p 0.01 ) and scores for total cholesterol ( intervention , –0.41 [ 95 % CI –0.59 to –0.23 ] ; control , –0.14 [ 95 % CI –0.32 to 0.04 ] ; p ( intervention , –7.49 [ 95 % CI –9.97 to –5.01 ] ; control , –3.58 [ 95 % CI –6.08 to –1.08 ] ; p level ( intervention , 0.30 [ 95 % CI 0.13 to 0.47 ] ; control , –0.05 [ 95 % CI –0.22 to 0.12 ] ; p confidence ( intervention , 0.20 [ 95 % CI 0.09 to 0.31 ] ; control , 0.04 [ 95 % CI –0.07 to 0.15 ] ; p intervention addressing multiple risk factors for primary prevention at 1 year using Framingham risk score report cards and telephone counselling . ( Requirement for clinical trial registration waived [ enrolment completed before requirement became applicable ] .",
"BACKGROUND Patients with myocardial infa rct ion ( MI ) seldom reach recommended targets for secondary prevention . This study evaluated a smartphone application ( \" app \" ) aim ed at improving treatment adherence and cardiovascular lifestyle in MI patients . DESIGN Multicenter , r and omized trial . METHODS A total of 174 ticagrelor-treated MI patients were r and omized to either an interactive patient support tool ( active group ) or a simplified tool ( control group ) in addition to usual post-MI care . Primary end point was a composite nonadherence score measuring patient-registered ticagrelor adherence , defined as a combination of adherence failure events ( 2 missed doses registered in 7-day cycles ) and treatment gaps ( 4 consecutive missed doses ) . Secondary end points included change in cardiovascular risk factors , quality of life ( European Quality of Life-5 Dimensions ) , and patient device satisfaction ( System Usability Scale ) . RESULTS Patient mean age was 58 years , 81 % were men , and 21 % were current smokers . At 6 months , greater patient-registered drug adherence was achieved in the active vs the control group ( nonadherence score : 16.6 vs 22.8 [ P = .025 ] ) . Numerically , the active group was associated with higher degree of smoking cessation , increased physical activity , and change in quality of life ; however , this did not reach statistical significance . Patient satisfaction was significantly higher in the active vs the control group ( system usability score : 87.3 vs 78.1 [ P = .001 ] ) . CONCLUSIONS In MI patients , use of an interactive patient support tool improved patient self-reported drug adherence and may be associated with a trend toward improved cardiovascular lifestyle changes and quality of life . Use of a disease-specific interactive patient support tool may be an appreciated , simple , and promising complement to st and ard secondary prevention",
"Objective : To evaluate cost , adherence and effects on cardiovascular function and quality of life of a home-based cardiac rehabilitation programme for patients with coronary disease . Design : A r and omized , prospect i ve controlled trial . Setting : Department of Rehabilitation , University Hospital , Brazil . Subjects : Thirty-nine low-risk patients were assigned to a home exercise training group ( n = 19 ) or a control group ( n = 20 ) . Interventions : The home group performed home-based training for three months with biweekly telephone monitoring . Main outcome measures : The aerobic capacity and the quality of life ( Medical Outcomes Study 36-Item Short Form Survey ( SF-36 ) ) of all patients were evaluated before and after the three-month period . Adherence was evaluated weekly . Programme cost was estimated using the Brazilian Classification of Medical Procedures . Results : After training , the home group had higher peak Vo2 from 28.8 ( 6.4 ) to 31.7 ( 8.1 ) mL/kg per minute , peak heart rate from 135 ( 22 ) to 143 ( 20 ) bpm , work rate from 4780 ( 2021 ) to 7103 ( 3057 ) kpm/min and exercise time from 11.5 ( 1.9 ) to 13.6 ( 2.3 ) minutes ( P ≤ 0.05 ) . The control group showed reduction in peak Vo2 from 28.6 ( 6.6 ) to 26.8 ( 7.2 ) mL/kg per minute , peak Vo2 pulse from 15.5 ( 3.9 ) to 14.3 ( 3.8 ) mL/bpm and exercise time from 11.5 ( 2.3 ) to 11.4 ( 2.7 ) minutes ( P ≤ 0.05 ) . The home group reported improvements in all domains of SF-36 . The control group showed improvement in only three domains of SF-36 . In the home group the average cost per patient was US$ 502.71 and the adherence achieved 100 % . Conclusion : The programme seems to provide an efficient low-cost approach to cardiac rehabilitation in low-risk patients",
"Background Telephone counseling in chronic disease self-management is increasing , but has not been tested in studies that control for quality of medical care . Objective To test the effectiveness of a six-session outpatient telephone-based counseling intervention to improve secondary prevention ( behaviors , medication ) in patients with acute coronary syndrome ( ACS ) following discharge from hospital , and impact on physical functioning and quality of life at 8 months post-discharge . Design Patient-level r and omized trial of hospital quality improvement ( QI-only ) versus quality improvement plus brief telephone coaching in three months post-hospitalization ( QI-plus ) . Data : medical record , state vital records , patient surveys ( baseline , three and eight months post-hospitalization ) . Analysis : pooled-time series generalized estimating equations to analyze repeated measures ; intention-to-treat analysis . Participants Seven hundred and nineteen patients admitted to one of five hospitals in two contiguous mid-Michigan communities enrolled ; 525 completed baseline surveys . Measurements We measured secondary prevention behaviors , physical functioning , and quality of life . Results QI-plus patients showed higher self-reported physical activity ( OR = 1.53 ; p = .01 ) during the first three months , with decline after active intervention was withdrawn . Smoking cessation and medication use were not different at 3 or 8 months ; functional status and quality of life were not different at 8 months . Conclusions Telephone coaching post-hospitalization for ACS was modestly effective in accomplishing short-term , but not long-term life-style behavior change . Previous positive results shown in primary care did not transfer to free-st and ing telephone counseling as an adjunct to care following hospitalization",
"Community studies have demonstrated suboptimal achievement of lipid targets in the management of patients with coronary heart disease ( CHD ) . An effective strategy is required for the application of evidence -based prevention therapy for CHD . The objective of this study was to test coaching as a technique to assist patients in achieving the target cholesterol level of coronary intervention ) to receive either the coaching intervention ( n = 121 ) or usual medical care ( n = 124 ) . The primary outcome measure was fasting serum total cholesterol ( TC ) , serum triglyceride ( TG ) , high-density lipoprotein cholesterol ( HDL-C ) , and calculated low-density lipoprotein cholesterol ( LDL-C ) level , measured at 6 months post-r and omization . At 6 months , the serum TC and LDL-C levels were significantly lower in the coaching intervention group ( n = 107 ) than the usual care group ( n = 112 ) : mean TC ( 95%CI ) 5.00 ( 4.82 - 5.17 ) mmol/L versus 5.54 ( 5.36 - 5.72 ) mmol/L ( P LDL-C ( 95%CI ) 3.11 ( 2.94 - 3.29 ) mmol/L versus 3.57 ( 3.39 - 3.75 ) mmol/L ( P Coaching had no impact on TG or on HDL-C levels . Multivariate analysis showed that being coached ( P coaching intervention is best explained by both adherence to drug therapy and to dietary advice given . Coaching may be an appropriate method to reduce the treatment gap in applying evidence -based medicine to the \" real world .",
"Less than 25 % of eligible patients attend cardiac rehabilitation programs ( CRP ) , with geographical proximity being a predominant barrier . Therefore , we undertook a pilot study to assess the feasibility and safety of using the Internet as a medium for delivery of an interactive \" virtual \" CRP ( vCRP ) to patients at a distance . Fifteen patients on the waiting list for a local hospital-based CRP were r and omized to either an Internet-based vCRP or observational control . The vCRP consisted of on-line intake forms , one-on-one chat sessions with a nurse , dietitian , and exercise specialist , downloadable exercise heart rate monitoring , education and data monitoring of blood pressure , weight , and glucose . Participants were assessed for exercise capacity , risk factors , and lifestyle behaviors at baseline and at 12 weeks . Those in the vCRP logged onto the Internet-based CRP an average of 4.2 times per week . There were no adverse events in the vCRP participants . The vCRP group significantly improved their HDL-C , triglycerides , total cholesterol : HDL-C ratio , exercise capacity as assessed in metabolic equivalents , weekly physical activity , and exercise specific self-efficacy ( p vCRP group were similar to historical controls in a st and ard CRP . Feedback from exit interviews of the vCRP participants was unanimously positive . This Internet-based CRP result ed in clinical ly significant improvements in risk factors and exercise capacity similar to that of a st and ard CRP . The high user acceptance indicated that this program may have the potential to effectively manage patients who do not have access to traditional hospital-based CRP",
"Background Digital health interventions ( DHI ) have been shown to improve intermediates of cardiovascular health , but their impact on cardiovascular ( CV ) outcomes has not been fully explored . The aim of this study was to determine whether DHI administered during cardiac rehabilitation ( CR ) would reduce CV‐related emergency department ( ED ) visits and rehospitalizations in patients after percutaneous coronary intervention ( PCI ) for acute coronary syndrome ( ACS ) . Methods We r and omized patients undergoing CR following ACS and PCI to st and ard CR ( n = 40 ) or CR + DHI ( n = 40 ) for 3 months with 3 patients withdrawing from CR prior to initiation in the treatment arm and 6 in the control group . The DHI incorporated an online and smartphone‐based CR platform asking the patients to report of dietary and exercise habits throughout CR as well as educational information toward patients ' healthy lifestyles . We obtained data regarding ED visits and rehospitalizations at 180 days , as well as other metrics of secondary CV prevention at baseline and 90 days . Results Baseline demographics were similar between the groups . The DHI + CR group had improved weight loss compared to the control group ( −5.1 ± 6.5 kg vs. −0.8 ± 3.8 kg , respectively , P = .02 ) . Those in the DHI + CR group also showed a non‐significant reduction in CV‐related rehospitalizations plus ED visits compared to the control group at 180 days ( 8.1 % vs 26.6 % ; RR 0.30 , 95 % CI 0.08‐1.10 , P = .054 ) . Conclusions The current study demonstrated that complementary DHI significantly improves weight loss , and might offer a method to reduce CV‐related ED visits plus rehospitalizations in patients after ACS undergoing CR . The study suggests a role for DHI as an adjunct to CR to improve secondary prevention of CV disease . Trial registration This trial is registered at clinical trials.gov ( NCT01883050 )",
"Background Participation in coronary heart disease secondary prevention programs is low . Innovative programs to meet this treatment gap are required . Purpose To aim of this study is to describe the effectiveness of a telephone-delivered secondary prevention program for myocardial infa rct ion patients . Methods Four hundred and thirty adult myocardial infa rct ion patients in Brisbane , Australia were r and omised to a 6-month secondary prevention program or usual care . Primary outcomes were health-related quality of life ( Short Form-36 ) and physical activity ( Active Australia Survey ) . Results Significant intervention effects were observed for health-related quality of life on the mental component summary score ( p = 0.02 ) , and the social functioning ( p = 0.04 ) and role-emotional ( p = 0.03 ) subscales , compared with usual care . Intervention participants were also more likely to meet recommended levels of physical activity ( p = 0.02 ) , body mass index ( p = 0.05 ) , vegetable intake ( p = 0.04 ) and alcohol consumption ( p = 0.05 ) . Conclusions Telephone-delivered secondary prevention programs can significantly improve health outcomes and could meet the treatment gap for myocardial infa rct ion patients",
"PURPOSE Despite demonstrated benefits of cardiac rehabilitation and risk factor reduction , only 11 % to 38 % of eligible patients with cardiovascular disease ( CVD ) participate in cardiac rehabilitation programs . Women and older adults are particularly less likely to participate in cardiac rehabilitation . In an effort to broaden access to cardiac rehabilitation , the authors developed an alternative Internet-based program that allows nurse case managers to provide risk factor management training , risk factor education , and monitoring services to patients with CVD . METHODS The evaluation consisted of a r and omized , clinical trial involving 104 patients with CVD , 53 of whom used the program as a special intervention ( SI ) for 6 months and 51 of whom received usual care ( UC ) . RESULTS The results indicate that fewer cardiovascular events occurred among the SI subjects ( 15.7 % ) than among the UC subjects ( 4.1 % ) ( P = .053 ) , result ing in a gross cost savings of $ 1418 US dollars per patient . With a projected program cost of $ 453 USD per patient , the return on investment is estimated at 213 % . More weight loss occurred in the SI group ( -3.68 pounds ) than in the UC group ( + .47 pounds ) ( P = .003 ) . The differences between the two groups in terms of blood pressure , lipid levels , depression scores , minutes of exercise , and dietary habits were not statistically significant . CONCLUSION An Internet-based case management system could be used as a cost-effective intervention for patients with CVD , either independently or in conjunction with traditional cardiac rehabilitation",
"This r and omized , controlled trial evaluated the impact of personalized follow-up on compliance rates in high-risk patients receiving combination lipid-lowering therapy over 2 years . A r and om sample of 30 patients 7 - 30 days after cardiac surgery had baseline fasting low-density lipoprotein levels higher than 130 mg/dl . All patients received lovastatin 20 mg/day and colestipol 5 g twice/day . Weekly telephone contact was made with each patient for 12 weeks . Short- and long-term compliance was assessed by pill and packet counts and refill records . Compliance and lipid profile results were significantly better in the intervention group ( p parameters except high-density lipoprotein . However , this effect was not apparent during the first 12 weeks of therapy . Short-term telephone follow-up favorably affected compliance and lipid profile results up to 2 years after start of therapy",
"BACKGROUND Although the potential to reduce hospitalisation and mortality in chronic heart failure ( CHF ) is well reported , the feasibility of receiving healthcare by structured telephone support or telemonitoring is not . AIMS To determine ; adherence , adaptation and acceptability to a national nurse-coordinated telephone-monitoring CHF management strategy . The Chronic Heart Failure Assistance by Telephone Study ( CHAT ) . METHODS Triangulation of descriptive statistics , feedback surveys and qualitative analysis of clinical notes . Cohort comprised of st and ard care plus intervention ( SC+I ) participants who completed the first year of the study . RESULTS 30 GPs ( 70 % rural ) r and omised to SC+I recruited 79 eligible participants , of whom 60 ( 76 % ) completed the full 12 month follow-up period . During this time 3619 calls were made into the CHAT system ( mean 45.81 SD+/-79.26 , range 0 - 369 ) , Overall there was an adherence to the study protocol of 65.8 % ( 95 % CI 0.54 - 0.75 ; p=0.001 ) however , of the 60 participants who completed the 12 month follow-up period the adherence was significantly higher at 92.3 % ( 95 % CI 0.82 - 0.97 , p learn or competently use the technology . Participants rated CHAT with a total acceptability rate of 76.45 % . CONCLUSION This study shows that elderly CHF patients can adapt quickly , find telephone-monitoring an acceptable part of their healthcare routine , and are able to maintain good adherence for a least 12 months",
"The effects of a nurse-managed secondary prevention program for patients after acute cardiac events were examined . Special interest was given to gender-specific results . The design was a prospect i ve , r and omized , controlled trial involving 343 patients following 3 weeks of inpatient cardiac rehabilitation , r and omly assigned to either of two study groups . Patients in the treatment group were contacted monthly by phone over 1 year . The main goals of the intervention were the reduction of behavioural coronary risk factors and enhancing quality of life . The program was conducted by specially trained nurses . The control group received written information only . Primary outcome was the Framingham risk score . Follow-up examination after 12 months was completed by 297 patients . Patients in the intervention group showed lower Framingham risk scores as compared to controls . Separate analyses by sex revealed that this was mostly due to the men in the sample . Women , on the other h and , showed a significant rise of clinical ly relevant anxiety/depressiveness in the control but not in the intervention group ; in males there were no differences between study conditions . In conclusion , telephone counselling by specially trained nurses seems a cost-effective way to achieve a lasting reduction in cardiac risk factors and to maintain the effects of cardiac rehabilitation . Effekte eines von Pflegepersonal durchgefuehrten Nachsorgeprogramms fuer Koronarpatienten wurden untersucht . Besondere Aufmerksamkeit galt moeglichen Gendereffekten . Es h and elt sich um eine prospektive , r and omisierte , kontrollierte Studie . 343 Patienten wurden nach stationaerer kardiologischer Rehabilitation auf eine von zwei Studiengruppen r and omisiert . Patienten in der Interventions gruppe wurden über ein Jahr ca . einmal i m Monat telephonisch kontaktiert . Hauptziele der Intervention waren die effektive und nachhaltige Reduktion verhaltensgebundener Risikofaktoren sowie die Verbesserung der Lebensqualitaet . Das Programm wurde von speziell dafuer fortgebildetem Pflegepersonal durchgefuehrt . Die Kontrollgruppe erhielt nur schriftliches Informations material . Primaerer Endpunkt war das globale koronare Risiko ( Framingham Score ) . Von 297 Patienten wurden komplette Date n bei der Abschlussuntersuchung nach 12 Monaten erhalten . Patienten in der Interventions gruppe zeigten niedrigere Framingham-Scores als Kontrollpatienten . Getrennte Analysen nach Geschlecht ergaben , dass dieser Effekt hauptsaechlich auf die Maenner zurueckzufuehren ist ; bei den Frauen zeigten sich keine Unterschiede zwischen den Studiengruppen . Auf der and eren Seite zeigte sich bei den Frauen in der Kontrollgruppe eine deutliche Zunahme an Angst bzw . Depressivitaet ; ein entsprechender Effekt f and sich bei den Maennern nicht . Telefonische Nachsorge durch speziell fortgebildetes Pflegepersonal scheint ein kostenguenstiger Weg zu sein , koronare Risikofaktoren zu reduzieren und die Effekte von kardiologischer Rehabilitation aufrechtzuerhalten . Se evaluaron los result ados de un programa secundario de prevención dirigido por el personal de enfermería para pacientes que han sufrido un trastorno cardiovascular agudo . Se dio una especial importancia a los result ados específicos para cada sexo . Se trata de un estudio prospect ivo , aleatorizado , comparativo , en el que participaron 343 pacientes tras 3 semanas de haber recibido rehabilitación cardiovascular , a quienes se dividieron en dos grupos , de manera aleatoria . Los pacientes del grupo que recibió tratamiento fueron contactados por teléfono una vez al mes durante 1 año . Los principales objetivos de la intervención fueron reducir los factores de riesgo de las cardiopatías arterioscleróticas relacionados con el actuar de los pacientes , y mejorar la calidad de vida de éstos . La realización del programa estuvo a cargo de un grupo de enfermeras y enfermeros especialmente entrenados para ello . El grupo de referencia recibió información sólo por escrito . Los result ados iniciales se obtuvieron aplic and o la escala de riesgo de Framingham . En las valoraciones de seguimiento , realizadas tras 12 meses , participaron 292 pacientes . Los valores en la escala de riesgo de Framingham fueron más bajos en los pacientes del grupo que recibió la intervención que en el grupo de referencia . Los análisis según el sexo revelaron que el aporte mayor a este result ado provino de los varones de la muestra . Por su parte , las mujeres del grupo de referencia presentaron un aumento importante de la ansiedad/depresión relacionada con el proceso de enfermedad , lo cual no se apreció en el grupo que recibió tratamiento . Entre los varones no se apreciaron diferencias relacionadas con las condiciones del estudio . En conclusión , el apoyo emocional por vía telefónica brindado por el personal de enfermería especialmente entrenado para ello parece ser una manera rentable de disminuir de forma perdurable los factores de riesgo para las cardiopatías arterioscleróticas , así como de perpetuar los result ados de la rehabilitación cardiovascular . Cette étude examine les effets d'un programme de prévention secondaire sous surveillance du personnel infirmier pour les patients ayant souffert d'incidents cardiaques aigus . Une attention toute particulière a été donnée aux résultats selon le sexe . L'essai était de type prospect if , r and omisé et contrôlé , avec la participation de 343 patients après 3 semaines de rééducation cardiaque dans des conditions d'hospitalisation , affectés de manière aléatoire à l'un ou l'autre des deux groupes d'étude . Les patients appartenant au groupe de traitement ont été contactés tous les mois par téléphone sur une période de 1 an . Les principaux objectifs de l'intervention étaient la réduction des facteurs comportementaux de risque coronaire et l'amélioration de la qualité de vie . Le programme était administré par des infirmiers spécialement formés . Le groupe témoin recevait simplement des informations écrites . Le principal résultat était le score de risque de Framingham . 297 patients ont subi des examens de suivi après 12 mois . Les patients appartenant au groupe d'intervention ont affiché des scores de risque de Framingham inférieurs à ceux du groupe témoin . Les analyses séparées par sexe révèlent que la différence porte principalement sur les hommes . Les femmes , par contre , affichent une augmentation significative des tendances dépressives/à l'anxiété , cliniquement pertinente dans le groupe témoin , contrairement au groupe d'intervention ; chez les hommes , on ne note aucune différence entre les conditions d'étude . En conclusion , le conseil téléphonique administré par des infirmiers spécialement formés semble constituer un mode économique et efficace pour parvenir à une réduction durable des facteurs de risques cardiaques et préserver les effets de la rééducation cardiaque",
"AIM Previous studies have reported lifestyle and risk factor deterioration following completion of a cardiac rehabilitation program ( CRP ) . We report the results of a one-year Extensive Lifestyle Management Intervention ( ELMI ) aim ed at preventing these adverse changes . METHODS AND RESULTS A total of 302 men and women with ischaemic heart disease were recruited following completion of a CRP and r and omized to either the ELMI ( consisting of exercise sessions , telephone follow-ups and risk factor and lifestyle counselling ) or usual care . The primary outcome was global cardiovascular risk using the Framingham and Procam risk scores . Secondary outcomes included risk factors and lifestyle behaviours . Baseline characteristics were similar between the two groups . Adherence to the ELMI was high . There was a non-significant trend in favour of the ELMI between for both the Framingham ( 6.6+/-3.1 to 6.2+/-2.9 vs 6.6+/-3.2 to 6.7+/-3.2 , P=0.138 ) and Procam ( 20.0+/-20.0 to 20.6+/-19.5 vs 19.1+/-18.7 to 21.8+/-19.1 , P=0.089 ) scores . There were no differences in secondary outcomes . CONCLUSIONS A one-year multi-factorial post-CRP intervention results in modest , non-significant benefits to global risk compared to usual care . The absence of deterioration in the usual care group may be due to improved practice s in usual care",
"BACKGROUND Previous research indicates that patients exiting a 12-week cardiac rehabilitation program ( CRP ) have difficulty maintaining an adequate exercise program . Thus , the authors ' purpose was to determine if a home-based exercise program would enable patients to maintain/improve their blood lipids , body composition , and functional capacity after exiting the CRP . METHODS Thirty-one patients exiting an initial 12-week CRP were assigned r and omly to the home-based ( HB ) intervention or the st and ard care ( SC ) condition . After one home visit , the HB participants ( n = 16 ) were contacted by telephone every other week by CRP staff and completed and returned weekly exercise logs . The SC participants ( n = 15 ) had no contact with the CRP other than to schedule follow-up tests . A third group ( n = 17 ) , r and omly selected from patients that elected to remain in the center-based CRP ( CB ) for the same duration , also were examined . All groups underwent exercise testing , fasting blood lipid analysis , and body composition assessment before starting CRP ( 0 M ) , after 3 months ( 3 M ) in a st and ard CRP , and after 9 months ( 12 M ) in either HB , SC , or CB condition ( 12 months after starting CRP ) . RESULTS Analysis of variance indicated that there were significant increases in metabolic equivalents and high-density lipoprotein , in all three groups , over time . However , analysis of covariance revealed no significant differences between the HB , SC , and CB groups at 12 M for any variable . CONCLUSIONS These data indicate that the HB program was as effective as the CB program at improving/maintaining functional capacity , blood lipids , and body weight/composition . The similar success of the SC group is likely due to their prior experience in CRP and knowledge of follow-up testing . Home-based maintenance program could be offered as a low-cost alternative to CB programs",
"Background Finding innovative and cost-efficient care strategies that induce long-term health benefits in cardiac patients constitutes a big challenge today . The aim of this Telerehab III follow-up study was to assess whether a 6-month additional cardiac telerehabilitation programme could induce long-term health benefits and remain cost-efficient after the tele-intervention ended . Methods and results A total of 126 cardiac patients first completed the multicentre , r and omised controlled telerehabilitation trial ( Telerehab III , time points t0 to t1 ) . They consequently entered the follow-up study ( t1 ) with evaluations 2 years later ( t2 ) . A quantitative analysis of peak aerobic capacity ( VO2 peak , primary endpoint ) , international physical activity question naire self-reported physical activity and HeartQoL quality of life ( secondary endpoints ) was performed . The incremental cost-effectiveness ratio was calculated . Even though a decline in VO2 peak ( 24 ± 8 ml/[min*kg ] at t1 and 22 ± 6 ml/[min*kg ] at t2 ; P ≤ 0.001 ) was observed within the tele-intervention group patients ; overall they did better than the no tele-intervention group ( P = 0.032 ) . Dividing the incremental cost ( −€878/patient ) by the differential incremental quality -adjusted life years ( QALYs ) ( 0.22 QALYs ) yielded an incremental cost-effectiveness ratio of –€3993/QALY . Conclusions A combined telerehabilitation and centre-based programme , followed by transitional telerehabilitation induced persistent health benefits and remained cost-efficient up to 2 years after the end of the intervention . A partial decline of the benefits originally achieved did occur once the tele-intervention ended . Healthcare professionals should reflect on how innovative cost-efficient care models could be implemented in st and ard care . Future research should focus on key behaviour change techniques in technology-based interventions that enable full persistence of long-term behaviour change and health benefits . This study is registered in the IS RCT N registry ( IS RCT N29243064 )",
"BACKGROUND Lifestyle modification is an integral component of cardiac secondary prevention , while it has been confirmed that myocardial infa rct ion ( MI ) patients ' health-related behaviors are heavily influenced by their illness perception . OBJECTIVES To evaluate the effect of a telephone follow-up intervention for improving MI patients ' illness perception and lifestyle . DESIGN A r and omized controlled trial , longitudinal research design was employed . SETTING S Cardiac care units in four major general hospitals in Guangzhou , China . PARTICIPANTS Inclusion criteria were being diagnosed with an initial acute MI , being able to communicate orally in M and arin or Cantonese and read in Chinese , and living in Guangzhou . Exclusion criteria were with continuing uncontrolled arrhythmias or heart failure , being illiteracy , or with a history of major psychiatric illness , exercise-induced asthma , uncontrolled diabetes , or evidence of dementia . METHOD 124 patients admitted with the first acute MI were r and omized to receive either routine care or routine care plus a telephone follow-up intervention , which consist of a pre-discharge education and three telephone follow-up instructions . Data were collected before discharge , at the 6th and the 12th week after discharge from hospital , respectively . RESULTS At the 6th and the 12th week after discharge , patients in the intervention group had significantly positive perceptions about symptoms of MI ( mean difference 3.27 , 95 % confidence interval 2.48 - 4.07 , p how long their illness would last ( mean difference -0.69 , 95 % confidence interval -0.91 to -0.47 , p positive beliefs about the controllability ( F=4.23 , p=.04 ) and more improved beliefs about the causes of MI than the control group . Moreover , the intervention improved the patients ' nutrition ( F=5.16 , p=.03 ) and physical activity at the 12-week follow-up ( mean difference 0.37 , 95 % confidence interval 0.17 - 0.58 , p telephone follow-up intervention can result in improved illness perception and lifestyle after MI . It could be incorporated into current hospital treatment regimens for MI to improve patients ' quality of life ",
"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",
"PURPOSE : Efficient ways are needed to implement the secondary prevention ( SP ) of coronary heart disease . Because few studies have investigated Web-based SP programs , our aim was to determine the usefulness of a new Web-based telemonitoring system , connecting patients provided with self-measurement devices and care managers via mobile phone text messages , as a tool for SP . METHODS : A single-blind , r and omized controlled , clinical trial of 203 acute coronary syndrome ( ACS ) survivors , was conducted at a hospital in Madrid , Spain . All patients received lifestyle counseling and usual-care treatment . Patients in the telemonitoring group ( TMG ) sent , through mobile phones , weight , heart rate , and blood pressure ( BP ) weekly , and capillary plasma lipid profile and glucose monthly . A cardiologist accessed these data through a Web interface and sent recommendations via short message service . Main outcome measures were BP , body mass index ( BMI ) , smoking status , low-density lipoprotein-cholesterol ( LDL-c ) , and glycated hemoglobin A1c ( HbA1c ) . RESULTS : At 12-month followup , TMG patients were more likely ( RR = 1.4 ; 95 % CI = 1.1−1.7 ) to experience improvement in cardiovascular risk factors profile than control patients ( 69.6 % vs 50.5 % , P = .010 ) . More TMG patients achieved treatment goals for BP ( 62.1 % vs 42.9 % , P = .012 ) and HbA1c ( 86.4 % vs 54.2 % , P = .018 ) , with no differences in smoking cessation or LDL-c . Body mass index was significantly lower in TMG ( −0.77 kg/m2 vs + 0.29 kg/m2 , P = .005 ) . CONCLUSIONS : A telemonitoring program , via mobile phone messages , appears to be useful for improving the risk profile in ACS survivors and can be an effective tool for secondary prevention , especially for overweight patients",
"Objective : To determine the effect of a new CHOICE ( Choice of Health Options In prevention of Cardiovascular Events ) programme on cardiovascular risk factors in acute coronary syndrome ( ACS ) survivors . Design : Single-blind r and omised controlled trial . Setting : Tertiary referral hospital in Sydney Australia . Patients : 144 ACS survivors who were not accessing st and ard cardiac rehabilitation . Data were also collected on a further 64 ACS survivors attending st and ard cardiac rehabilitation . Intervention : The CHOICE group ( n = 72 ) participated in a brief , patient-centred , modular programme comprising a clinic visit plus telephone support , encompassing m and atory cholesterol lowering and tailored preferential risk modification . The control group ( n = 72 ) participated in continuing conventional care but no central ly coordinated secondary prevention . Main outcome measures : Values for total cholesterol , systolic blood pressure , smoking status and physical activity . Results : CHOICE and control groups were well matched at baseline . At 12 months , the CHOICE group ( n = 67 ) had significantly better risk factor levels than controls ( n = 69 ) for total cholesterol ( TC ) ( mean ( SEM ) 4.0 ( 0.1 ) vs 4.7 ( 0.1 ) mmol/l , p systolic blood pressure ( 131.6 ( 1.8 ) vs 143.9 ( 2.3 ) mm Hg , p body mass index ( 28.9 ( 0.7 ) vs 31.2 ( 0.7 ) kg/m2 , p = 0.025 ) and physical activity ( 1369.1 ( 167.2 ) vs 715.1 ( 103.5 ) METS/kg/min , p = 0.001 ) as well as a better knowledge of risk factor targets . Also at 1 year , fewer CHOICE participants ( 21 % ) had three or more risk factors above widely recommended levels then controls ( 72 % ) ( p CHOICE programme significantly improved the modifiable risk profiles and risk factor knowledge of ACS survivors over 12 months . CHOICE is an effective alternative for dealing with the widespread underuse of existing secondary prevention programmes . Trial registration number : IS RCT"
] |
4116c1da-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND Bipolar disorder is a common condition associated with high morbidity ; developing efficacious , safe treatments is therefore essential . Lithium is an effective maintenance treatment for bipolar disorder . It acts as mood stabiliser and reduces the risk of suicide . However , evidence assessing the efficacy of lithium in the treatment of acute mania is less robust . Current evidence -based guidelines cite multiple anti-dopaminergic and mood-stabilising agents as initial treatments : more definite evidence is needed to decide if lithium should be the first-line therapy . OBJECTIVES 1 . To assess the effects of lithium in comparison with placebo or other active treatment in alleviating the acute symptoms of a manic or mixed episode in people with bipolar disorder.2 . To review the acceptability and tolerability of treatment with lithium in comparison with placebo or other active treatments in alleviating the acute symptoms of a manic or mixed episode in people with bipolar disorder . SEARCH METHODS We search ed the Cochrane Common Mental Disorders Controlled Trials Register , CENTRAL , MEDLINE , Embase , and PsycINFO . We also search ed the World Health Organization trials portal ( ICTRP ) and Clinical Trials.gov . We checked the reference lists of all included studies and relevant systematic review s. We have incorporated studies from search es to 18 May 2018 into the current analyses . SELECTION CRITERIA Prospect i ve r and omised controlled studies comparing lithium with placebo or alternative drug treatment in treatment of acute mania . We included anyone with bipolar disorder , male and female , of any age . DATA COLLECTION AND ANALYSIS At least two review authors independently extracted data and assessed method ological quality . We used odds ratios ( ORs ) to analyse binary efficacy outcomes , and mean differences ( MDs ) or st and ardised mean differences ( SMDs ) for continuously distributed outcomes . We used a fixed-effect model unless heterogeneity was moderate or substantial , in which case we used a r and om-effects model . We used Review Manager 5 to analyse data . We assessed the certainty of evidence for individual outcomes using the GRADE approach . MAIN RESULTS We found 36 r and omised controlled studies comparing lithium with placebo , one of 12 drugs , or electroconvulsive therapy for treatment of acute mania . Studies included male and female participants ( n = 4220 ) , of all ages , who all fitted criteria for a manic episode within the context of a diagnosis of bipolar disorder . Risk of bias was variable ; 12 studies had a high risk of bias in one domain and 27 gave inadequate information on r and omisation leading to an ' unclear ' rating for selection bias . Lithium versus placeboHigh-certainty evidence found that lithium was an effective treatment for acute mania and was more effective than placebo at inducing a response ( OR 2.13 , 95 % confidence interval ( CI ) 1.73 to 2.63 ; participants = 1707 ; studies = 6 ; I2 = 16 % ; high-certainty evidence ) , or remission ( OR 2.16 , 95 % CI 1.73 to 2.69 ; participants = 1597 ; studies = 5 ; I2 = 21 % ; high-certainty evidence ) .Lithium was more likely than placebo to cause tremor ( OR 3.25 , 95 % CI 2.10 to 5.04 ; participants = 1241 ; studies = 6 ; I2 = 0 % ; high-certainty evidence ) , and somnolence ( OR 2.28 , 95 % CI 1.46 to 3.58 ; participants = 1351 ; studies = 7 ; I2 = 0 % ; high-certainty evidence ) .There was insufficient evidence to determine the effect of lithium for all-cause dropouts ( OR 0.76 ; 95 % CI 0.46 to 1.25 ; participants = 1353 ; studies = 7 ; I2 = 75 % ; moderate-certainty evidence ) , and weight gain ( OR 1.48 , 95 % CI 0.56 to 3.92 ; participants = 735 , studies = 3 ; I2= 51 % ; moderate-certainty evidence ) .Lithium versus antipsychotics or mood stabilisersFor the outcome of inducing a response , there was only very low-certainty evidence regarding lithium compared to haloperidol ( MD -2.40 , 95 % CI -6.31 to 1.50 ; participants = 80 ; studies = 3 ; I2 = 95 % ) , quetiapine ( OR 0.66 , 95 % CI 0.28 to 1.55 ; participants = 335 ; studies = 2 ; I2 = 71 % ) , and carbamazepine ( SMD 0.21 , 95 % CI -0.18 to 0.60 ; participants = 102 ; studies = 3 ; I2 = 0%).Lithium was probably less likely to induce a response than olanzapine ( OR 0.44 , 95 % CI 0.20 to 0.94 ; participants = 180 ; studies = 2 ; I2 = 0 % ; moderate-certainty evidence ) .Lithium may be less likely to induce a response than risperidone ( MD 7.28 , 95 % CI 5.22 to 9.34 ; participants = 241 ; studies = 3 ; I2 = 49 % ; low-certainty evidence ) .There was no evidence of a difference between lithium and valproate ( OR 1.22 , 95 % CI 0.87 to 1.70 ; participants = 607 ; studies = 5 ; I2 = 22 % ; moderate-certainty evidence ) .There was moderate-certainty evidence that lithium was more effective than topiramate at treating acute mania ( OR 2.28 , 95 % CI 1.63 to 3.20 ; participants = 660 ; studies = 1 ) . Data on adverse events for these comparisons contained too few studies to provide high-certainty evidence . AUTHORS ' CONCLUSIONS This systematic review indicates that lithium is more effective than placebo as a treatment for acute mania but increases the risk for somnolence and tremor . Limited evidence suggests little or no difference between lithium and other mood stabilisers ( valproate , carbamazepine ) or antipsychotics ( risperidone , quetiapine , haloperidol ) . Olanzapine may be an exception , as it is probably slightly more effective than lithium . There is uncertain evidence that risperidone may also be more effective than lithium . Lithium is probably more effective at treating acute mania than topiramate . When compared to placebo , lithium was more likely to cause adverse events . However , when compared to other drugs , too few studies provided data on adverse effects to provide high-certainty evidence . More , rigorously design ed , large-scale studies are needed to definitively conclude if lithium is superior to other interventions in treating acute mania
|
[
"The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder . The third version is based explicitly on the available evidence and presented , like previous Clinical Practice Guidelines , as recommendations to aid clinical decision making for practitioners : it may also serve as a source of information for patients and carers , and assist audit . The recommendations are presented together with a more detailed review of the corresponding evidence . A consensus meeting , involving experts in bipolar disorder and its treatment , review ed key areas and considered the strength of evidence and clinical implication s. The guidelines were drawn up after extensive feedback from these participants . The best evidence from r and omized controlled trials and , where available , observational studies employing quasi-experimental design s was used to evaluate treatment options . The strength of recommendations has been described using the GRADE approach . The guidelines cover the diagnosis of bipolar disorder , clinical management , and strategies for the use of medicines in short-term treatment of episodes , relapse prevention and stopping treatment . The use of medication is integrated with a coherent approach to psychoeducation and behaviour change",
"OBJECTIVE This study was carried out to compare the efficacy of lithium carbonate with that of valproate in acute mania and to determine whether pretreatment clinical characteristics , such as the presence of a mixed affective state , might predict a differential response to the two drugs . METHOD Twenty-seven patients meeting DSM-III-R criteria for acute manic episodes underwent a 3-week , r and omized , double-blind , parallel-groups trial of treatment with lithium carbonate or valproate . Symptom severity was measured by using the Schedule for Affective Disorders and Schizophrenia , change version ( SADS-C ) , the Global Assessment Scale ( GAS ) , and the Brief Psychiatric Rating Scale ( BPRS ) . Drug effects were compared by using repeated measures analysis of variance ( ANOVA ) . RESULTS At the end of the study , nine of 14 patients treated with valproate and 12 of 13 patients treated with lithium had responded favorably , as measured by changes in the SADS-C mania , BPRS , and GAS scores . Elevated pretreatment SADS-C depression scores were associated with good response to valproate . ANOVA revealed a significant interaction between drug and mixed affective state with respect to treatment response . CONCLUSIONS Lithium and valproate were both effective in improving manic symptoms , and lithium was slightly more efficacious overall . Unlike the case with lithium , favorable response to valproate was associated with high pretreatment depression scores . Therefore , treatment with valproate alone may be particularly effective in manic patients with mixed affective states",
"In an 18-hospital collaborative study , 255 newly admitted manic patients were r and omly assigned to lithium carbonate or chlorpromazine for a three-week period . Patients were classified as highly active or mildly active on the basis of degree of motor activity shown at admission . Treatments were compared in terms of early terminations , symptom change , and toxicity . The following results were obtained : ( 1 ) Chlorpromazine was clearly superior to lithium carbonate in treating the highly active patient . Chlorpromazine acted more quickly , produced significantly fewer dropouts , and had a lower incidence of severe side effects . ( 2 ) The difference between lithium carbonate and chlorpromazine was less pronounced among mildly active patients . Lithium carbonate , however , appeared to be the better treatment . Both drugs effectively reduced manic symptomatology but lithium carbonate left the patient feeling less sluggish and fatigued . Lithium carbonate also produced fewer severe side effects than chlorpromazine",
"Two drug trials in schizoaffective patients are reported . Nineteen \" schizomanic \" patients were treated for one month , on a double blind basis , with chlorpromazine or lithium and 41 \" schizodepressive \" patients with amitriptyline , chlorpromazine or both . In the schizodepressive patients there was a trend to a better response to chlorpromazine , but drug response generally was poor , only 20 per cent of patients recovering within the month . In the schizomanic patients lithium seemed as effective as chlorpromazine , which supports the view that these patients were suffering from a variant of mania",
"The objective of this study was to compare the efficacy and safety of valproate and lithium in bipolar I patients experiencing a manic or a mixed episode . This international , r and omized , open-label , parallel-group , equivalence study included 268 patients with bipolar I disorder . The starting dose of valproate was 20 mg/kg/day and that of lithium was 800 mg/day . Treatment duration was 12 weeks . The primary outcome measure was mean change in Young Mania Rating Scale score between baseline and study end . Secondary outcome measures were response and remission rates , change in Montgomery and Åsberg Depression Rating Scale and Clinical Global Impression Bipolar Disorder instrument score , and occurrence of adverse events . The mean change from baseline in Young Mania Rating Scale score was 15.8±5.3 in the lithium group and 17.3±9.4 in the valproate group . The 90 % confidence interval of the intergroup difference ( −0.69 ; 3.31 ) was within prespecified equivalence limits . Response rates were 72.6 % in the lithium group and 79.5 % in the valproate group . Remission rates were 58.5 and 71.9 % , respectively . No intergroup differences were observed in median time to treatment response ( 21 days ) or change in Clinical Global Impression Bipolar Disorder instrument or Montgomery and Åsberg Depression Rating Scale scores . Adverse events were reported in 42.8 % of patients in the lithium group and 41.5 % in the valproate group . Valproate and lithium showed comparable efficacy and tolerability in the treatment of acute mania over 12 weeks",
"Sulpiride , in this open study of acute manic patients , had a clear antimanic action with all eight patients responding to sulpiride treatment without the need for other antipsychotic drugs . Plasma prolactin concentrations were increased and oestrogen-stimulated neurophysin concentrations decreased by sulpiride but were unchanged by lithium treatment , whereas TSH concentrations showed a rapid increase following the introduction of lithium therapy",
"Previous investigations of the treatment of mania have result ed in uncertainty about the efficacy of lithium versus a neuroleptic . In addition there have been reports of toxicity with a haloperidol -- lithium combination . In order to determine the comparative efficacy of lithium vs haloperidol vs a combination of haloperidol -- lithium , we studied 21 severely ill manic patients who all met rigorous criteria for bipolar illness and who required in hospital treatment . Subjects were r and omly assigned to 3 groups : ( A ) Lithium plus placebo ( B ) Placebo plus haloperidol and ( C ) Lithium plus haloperidol . The study was conducted in double blind fashion for 3 weeks with the dosages of the medications varied according to clinical response or untoward effects . Subjects on haloperidol and placebo or the haloperidol -- lithium combination were significantly improved after 7 days in comparison to the lithium-treated group . Groups B and C did not differ from each other , either in degree of improvement or in side effects . Inspite of the relatively small sample size the results suggest ( 1 ) that haloperidol is superior to lithium for treating severely ill acute mania and ( 2 ) that while a haloperidol -- lithium combination does not result in a significant increase in side effects , it is not superior to haloperidol alone",
"OBJECTIVE To evaluate the efficacy and tolerability of quetiapine monotherapy versus placebo for the treatment of mania associated with bipolar disorder . METHOD In an international , multicenter , double-blind , parallel-group , 12-week study , patients with a DSM-IV diagnosis of bipolar I disorder ( manic episode ) were r and omly assigned to treatment with quetiapine ( flexibly dosed up to 800 mg/day ) , placebo , or lithium . The primary efficacy measure was change from baseline in Young Mania Rating Scale ( YMRS ) score at day 21 . Data were gathered from April 2001 to May 2002 . RESULTS More patients in the quetiapine ( 72/107 ) and lithium ( 67/98 ) groups completed the study compared with the placebo group ( 35/97 ) . Improvement ( reduction ) in YMRS score was significantly greater for quetiapine than placebo at day 7 ( -8.03 vs. -4.89 ; p quetiapine patients compared with placebo patients fulfilled YMRS response criteria at day 21 ( 53.3 % vs. 27.4 % ; p Quetiapine was also superior to placebo in efficacy at day 21 and day 84 by all secondary measures . Lithium-treated patients improved significantly compared with placebo patients and similarly to quetiapine-treated patients on the primary efficacy measure . The most common adverse events for quetiapine were dry mouth , somnolence , and weight gain , while lithium was associated with tremor and insomnia . The quetiapine and placebo groups had similar , low levels of extrapyramidal symptom-related adverse events . CONCLUSIONS Quetiapine demonstrated superior efficacy to placebo in patients with bipolar mania and was well tolerated",
"Lithium carbonate , haloperidol , and chlorpromazine hydrochloride were compared in a double-blind controlled study with severely ill hospitalized manics . Lithium carbonate and haloperidol produced a highly significant improvement of manic symptoms without sedation . Although producing considerable sedation , chlorpromazine did little to alter the underlying mania qualitatively . Qualitative differences between lithium carbonate and haloperidol indicate that , while haloperidol has a more dramatically rapid impact on behavior-motor activity , lithium carbonate acted more evenly on the entire manic picture , with total normalization realized during active treatment . The majority of lithium carbonate-treated patients met discharge criteria at study termination , but not the patients receiving either neuroleptic drug . The rating scales are not sensitive enough to monitor manic psychopathology ; this accounts for the lack of statistically significant differences among drug groups at treatment termination , despite the widely disparate discharge rates",
" On the basis of 3-week studies , lithium and valproate are both recommended for first-line treatment of acute mania . It is , however , also important to demonstrate that antimanic efficacy can be maintained . This study has been design ed to compare the efficacy and tolerability of valproate and lithium over 12 weeks in the treatment of acute mania in patients with type I bipolar disorder . Three hundred patients with bipolar I disorder presenting with acute mania were r and omized to open treatment with lithium ( starting dose : 400 mg/day ) or valproate ( starting dose : 20 mg/kg/day ) for 12 weeks . The primary efficacy criterion was remission ( YMRS score ≤12 at study end and a reduction of ≥2 on the CGI-BP severity scale ) . Remission rates were 65.5 % ( lithium group ) and 72.3 % ( valproate group ) . Noninferiority of valproate with respect to lithium was demonstrated [ between-group difference : 6.78 % ( 95 % confidence intervals : −3.80 to 17.36 % ) ] . Remission rates assessed by the secondary mixed model repeated measures analysis were significantly greater with valproate than with lithium . Adverse events were reported in 44 % of patients in both groups . Valproate and lithium showed comparable efficacy and tolerability in the treatment of acute mania over 12 weeks",
"For the treatment of acute mania , no single drug is sufficiently effective in daily clinical routine for all patients . Drug combinations are often prescribed but poorly investigated . The present study examined whether a treatment with a neuroleptic drug ( zuclopenthixol ) combined with a benzodiazepine ( clonazepam ) was superior to a treatment with lithium and the same benzodiazepine ( lithium citrate and clonazepam ) . Twenty‐eight hospitalized patients with a DSM‐III‐R manic episode were included , r and omized to fixed drug doses and observed up to 28 days . Degree of mania , side effects and patients satisfaction with the treatment were registered . Approximately two thirds of the patients improved fully or partially on both drug combinations . Furthermore no statistically significant differences were found regarding acceptance and tolerance of the two drug combinations . The present drug combination are only two among several which deserve a thorough examination in order to prevent a r and om polypharmacy for treatment of mania",
"ABSTRACT Objective : To assess the efficacy and tolerability of quetiapine in Chinese patients hospitalized with acute bipolar mania . Methods : This was a 4-week , multicenter , r and omized , double-blind , lithium-controlled , parallel-group study . Secondary endpoints in the primary analysis were : response rate ( ≥ 50 % decrease from baseline in YMRS total score ) and remission rate as defined using 3 criteria : YMRS total score ≤ 12 , YMRS total score ≤ 12 + MADRS total score ≤ 8 , and YMRS total score ≤ 8 . Other measures included : change from baseline at Day 28 in YMRS , PANSS , and MADRS total score . Adverse event ( AE ) data were collected throughout the study . Results : 73 ( 94.8 % ) quetiapine and 62 ( 80.5 % ) lithium patients completed the study . Mean ( SD ) quetiapine doses for the ITT population and responders were 648.2 ( 111.84 ) mg/day and 637.5 ( 118.78 ) mg/day , respectively , while mean lithium concentrations for the ITT population and responders were 0.80 ( 0.28 ) mmol/L and 0.80 ( 0.22 ) mmol/L , respectively . Of patients who responded to quetiapine at Day 28 , 88.3 % were receiving 600–800 mg/day . At Day 28 YMRS response rate was significantly greater with quetiapine than lithium ( 77.9 % vs. 59.7 % , p = 0.0132 ) , and remission rates using the 3 criteria were significantly greater with quetiapine than lithium : YMRS total score ≤ 12 ( 70.1 % vs. 48.1 % , p = 0.0071 ) , YMRS ≤ 12 + MADRS ≤ 8 ( 70.1 % vs. 48.1 % ; p = 0.0071 ) , and YMRS ≤ 8 ( 51.9 % vs. 32.5 % ; p = 0.0147 ) . Significant decreases were observed in PANSS , YMRS , and MADRS total scores for both groups . The most common AEs experienced by patients receiving quetiapine were constipation , dizziness , diarrhea , alanine aminotransferase increase , palpitations , aspartate aminotransferase increase , pharyngolaryngeal pain , upper respiratory tract infection and dry mouth . In patients receiving lithium , the most common AEs were nausea ( 16.9 % ) , constipation ( 13.0 % ) , vomiting ( 13.0 % ) , nasopharyngitis ( 11.7 % ) , dizziness ( 6.5 % ) , diarrhea ( 6.5 % ) , and upper respiratory tract infection ( 6.5 % ) . Conclusion : Quetiapine was shown to be clinical ly effective in patients with acute bipolar mania . There were side effects with quetiapine similar to those reported in other studies that included other ethnic population s of patients",
"It is unclear which maintenance treatment for bipolar disorder is superior in clinical practice . R and omized controlled head-to-head trials of available drugs either do not exist or are inconclusive . We aim ed to compare rates of monotherapy treatment failure in individuals prescribed lithium , valproate , olanzapine or quetiapine by a population -based cohort study using electronic health records . 5,089 patients with bipolar disorder were prescribed lithium ( N=1,505 ) , valproate ( N=1,173 ) olanzapine ( N=1,366 ) or quetiapine ( N=1,075 ) as monotherapy . Treatment failure was defined as time to stopping medication or add-on of another mood stabilizer , antipsychotic , antidepressant or benzodiazepine . In unadjusted analyses , the duration of successful monotherapy was longest in individuals treated with lithium . Treatment failure had occurred in 75 % of those prescribed lithium by 2.05 years ( 95 % CI : 1.63 - 2.51 ) , compared to 0.76 years ( 95 % CI : 0.64 - 0.84 ) for those prescribed quetiapine , 0.98 years ( 95 % CI : 0.84 - 1.18 ) for those prescribed valproate , and 1.13 years for those prescribed olanzapine ( 95 % CI : 1.00 - 1.31 ) . Lithium 's superiority remained in a propensity score matched analysis ; when treatment failure was defined as stopping medication or add-on of a mood stabilizer or antipsychotic ; and when treatment failure was restricted to more than three months after commencing the study drug . Lithium appears to be more successful as monotherapy maintenance treatment than valproate , olanzapine or quetiapine . Lithium is often avoided because of its side effect profile , but alternative treatments may reduce the time to being prescribed more than one drug , with potential additive side effects of these treatments",
"OBJECTIVE The authors tested the hypothesis that divalproex would be more effective than lithium in the long-term management of patients with recently stabilized rapid-cycling bipolar disorder . METHOD A 20-month , double-blind , parallel-group comparison was carried out in recently hypomanic/manic patients who had experienced a persistent bimodal response to combined treatment with lithium and divalproex . Sixty patients were r and omly assigned to lithium or divalproex monotherapy in a balanced design after stratification for illness type ( bipolar I versus bipolar II disorder ) . RESULTS Of the 254 patients enrolled in the open-label acute stabilization phase , 76 % discontinued the study prematurely ( poor adherence : 28 % ; nonresponse : 26 % [ of whom 74 % remained depressed and 26 % remained in a hypomanic/manic/mixed episode ] , intolerable side effects : 19 % ) . Of the 60 patients ( 24 % ) r and omly assigned to double-blind maintenance monotherapy , 53 % relapsed ( 59 % into depression and 41 % into a hypomanic/manic/mixed episode ) , 22 % completed the study , 10 % had intolerable side effects , and 10 % were poorly adherent . The rates of relapse into any mood episode for those given lithium versus divalproex were 56 % and 50 % , respectively ; the rates were 34 % and 29 % for a depressive relapse and 19 % and 22 % for a hypomania/mania relapse . There were no significant differences in time to relapse . The proportion discontinuing prematurely because of side effects was 16 % for lithium and 4 % for divalproex . CONCLUSIONS The hypothesis that divalproex is more effective than lithium in the long-term management of rapid-cycling bipolar disorder is not supported by these data . Preliminary data suggest highly recurrent refractory depression may be the hallmark of rapid-cycling bipolar disorder",
" Thirty-four manic patients were r and omly assigned to treatment with carbamazepine or lithium . Clinical response was rated over 4 weeks . Twenty-eight patients , 14 in each group , completed the full protocol . Serum levels for both drugs were within the accepted therapeutic range . The overall response to treatment was not significantly different between the two groups . Comparison of individual Clinical Global Impressions , Brief Psychiatric Rating Scale , and Beigel-Murphy Manic State Rating Scale change scores showed a more consistent level of improvement across patients in the lithium-treated group compared to a minority of good responders in the carbamazepine-treated group . The findings suggest that carbamazepine has antimanic potential in specific bipolar patients whose clinical characteristics remain to be clearly defined",
"BACKGROUND This multicenter , double-blind , r and omized , controlled study conducted in China examined the efficacy and safety of olanzapine versus lithium in the treatment of patients with bipolar manic/mixed episodes . METHODS Patients with bipolar manic or mixed episode ( DSM-IV criteria ) and Young Mania Rating Scale ( YMRS ) score > or = 20 at screening received olanzapine ( 5 - 20 mg/day , n=69 ) or lithium carbonate ( 600 - 1800 mg/day , n=71 ) for 4 weeks . The primary outcome was mean change from baseline in Clinical Global Impressions-Bipolar Version Overall Severity of Illness ( CGI-BP ) score . Secondary efficacy measures included YMRS , Brief Psychiatric Rating Scale ( BPRS ) , and Montgomery-Asberg Depression Rating Scale ( MADRS ) scores . Safety was also assessed . RESULTS A significantly greater mean change was observed in olanzapine versus lithium patients in CGI-BP ( Overall Severity ) ( P=0.009 ) , YMRS ( P=0.013 ) , BPRS ( P=0.032 ) , and CGI-BP ( Severity of Mania ) ( P=0.012 ) scores . More olanzapine than lithium patients experienced at least one adverse event possibly related to study drug ( P=0.038 ) . More olanzapine patients had a clinical ly significant weight increase ( > or = 7 % of baseline weight ) compared to lithium patients ( P=0.009 ) . More olanzapine patients completed the study than lithium patients , although this difference was not statistically significant ( olz , 91.3 % ; lith , 78.9 % ; P=0.057 ) . LIMITATIONS No placebo arm was included ; however both treatments have previously been reported to be more effective than placebo . CONCLUSIONS These results suggest that olanzapine has superior efficacy to lithium in the acute treatment of patients with bipolar mania over a 4-week period . However , adverse events were experienced by a greater number of olanzapine patients than lithium patients",
" BACKGROUND This study followed manic or mixed bipolar I subjects for an additional 40 weeks after initial r and omization to 12 weeks of lithium versus aripiprazole monotherapy . This is the only long-term , double-blind study comparing lithium and aripiprazole . METHODS Patients continued receiving either aripiprazole 15 or 30 mg/day , or lithium 900 , 1200 or 1500 mg/day in a double-blind fashion for 40 weeks after completing a 12-week double-blind study ( 52 weeks total treatment ) . Efficacy endpoints included adjusted mean change from baseline to Week 52 in Young Mania Rating Scale ( YMRS ) total score and Montgomery-Åsberg Depression Rating Scale ( MADRS ) total scores ( observed cases ) . Remission was defined as YMRS total score≤12 . Safety and tolerability were also assessed . RESULTS Of the 66 patients who entered the extension phase , only 20 patients ( 30.3 % ) completed the entire phase ( aripiprazole n=7 ; lithium n=13 ) . The significant improvement that occurred over the first 12 weeks was maintained over the 40 weeks of blinded continuation ( from Week 12 through Week 52 ) . The most common treatment-emergent adverse events in the extension phase for aripiprazole were akathisia , headache , somnolence , anxiety and nasopharyngitis ( all 8 % ) , and for lithium were insomnia ( 15.8 % ) , headache ( 13.2 % ) , diarrhea ( 13.2 % ) and vomiting ( 10.5 % ) . Mean weight change was + 2.71 kg for lithium and + 5.66 kg for aripiprazole ( p=0.46 ) . LIMITATIONS This trial was not powered to statistically compare active treatments , and long-term completion rates were low in both groups . CONCLUSIONS Aripiprazole monotherapy appears to be equivalently useful to lithium for the extended treatment of mixed or manic bipolar disorder patients",
"BACKGROUND : Lithium is a benchmark treatment for bipolar disorder in adults . Definitive studies of lithium in pediatric bipolar I disorder ( BP-I ) are lacking . METHODS : This multicenter , r and omized , double-blind , placebo-controlled study of pediatric participants ( ages 7–17 years ) with BP-I/manic or mixed episodes compared lithium ( n = 53 ) versus placebo ( n = 28 ) for up to 8 weeks . The a priori primary efficacy measure was change from baseline to the end of study ( week 8/ET ) in the Young Mania Rating Scale ( YMRS ) score , based on last-observation-carried-forward analysis . RESULTS : The change in YMRS score was significantly larger in lithium-treated participants ( 5.51 [ 95 % confidence interval : 0.51 to 10.50 ] ) after adjustment for baseline YMRS score , age group , weight group , gender , and study site ( P = .03 ) . Overall Clinical Global Impression – Improvement scores favored lithium ( n = 25 ; 47 % very much/much improved ) compared with placebo ( n = 6 ; 21 % very much/much improved ) at week 8/ET ( P = .03 ) . A statistically significant increase in thyrotropin concentration was seen with lithium ( 3.0 ± 3.1 mIU/L ) compared with placebo ( –0.1 ± 0.9 mIU/L ; P with respect to weight gain . CONCLUSIONS : Lithium was superior to placebo in reducing manic symptoms in pediatric patients treated for BP-I in this clinical trial . Lithium was generally well tolerated in this patient population and was not associated with weight gain , distinguishing it from other agents commonly used to treat youth with bipolar disorder",
"OBJECTIVE To evaluate the efficacy and tolerability of topiramate monotherapy in adults with acute manic or mixed episodes of bipolar I disorder . METHODS In four trials , adults hospitalized with acute mania , a diagnosis of bipolar I disorder , history of > or = 1 previous manic or mixed episodes , and > or = 20 Young Mania Rating Scale ( YMRS ) score were r and omized to double-blind treatment with topiramate ( target doses : 200 , 400 , or 600 mg/day ) or placebo ; two trials included an active comparator ( lithium , 1500 mg/day ) . The core study duration in all trials was 3 weeks ; three trials also had 9-week double-blind extensions . The primary efficacy variable was mean change from baseline in YMRS in the core 3-week study . RESULTS Changes in YMRS score during 3 weeks were not significantly different for topiramate versus placebo ( mean YMRS reductions , -5.1 to -8.4 ) . Mean YMRS reductions in lithium-treated groups were significantly greater ( p placebo and topiramate ) . A similar pattern was observed after 12 weeks of double-blind treatment in studies with double-blind extensions . Paresthesia , appetite decrease , dry mouth , and weight loss were more frequently associated with topiramate than with placebo . CONCLUSIONS These studies do not support the efficacy of topiramate as monotherapy in acute mania or mixed episodes in adults with bipolar I disorder . Topiramate was not associated with mood destabilization measured as mania exacerbation or treatment-emergent depression . Lithium was confirmed as an effective therapy in this population",
"OBJECTIVE This prospect i ve 6-month open trial examined the safety and efficacy of two combination therapies for manic or mixed episodes of pediatric bipolar disorder : ( 1 ) divalproex sodium plus risperidone ( DVPX+Risp ) , or ( 2 ) lithium plus risperidone ( Li+Risp ) . METHODS Thirty-seven ( 37 ) subjects aged 5 and 18 ( age=12.1+/-3.5 years ) with DSM IV current mixed or manic episode and Young Mania Rating Scale ( YMRS ) score > 20 were sequentially assigned to either DVPX+Risp or Li+Risp in a 6-month , prospect i ve open-label trial . Outcome measures included the YMRS , Clinical Global Impression Scale for Bipolar Disorder ( CGI-BP ) , Child Depression Rating Scale-Revised ( CDRS-R ) as well as measures of safety and tolerability . RESULTS Effect sizes ( Cohen 's d ) based on change of YMRS scores from baseline were 4.36 for DVPX+Risp and 2.82 for Li+Risp . Response rates ( > or=50 % change from baseline YMRS score at the end of study ) were 80 % for DVPX+Risp and 82.4 % for Li+Risp . Both combination treatments were well tolerated . Significant improvements ( p efficacy measures , i.e. , YMRS , CGI-BP , and CDRS-R. There were no significant group differences in safety or tolerability , and no serious adverse events during the 6-month trial . CONCLUSION Both DVPX+Risp and Li+Risp show strong effects coupled with safety and tolerability in treating children and adolescents with manic or mixed episodes associated with type I bipolar disorder",
"OBJECTIVE To develop effect sizes for 3 mood stabilizers -- lithium , divalproex sodium , and carbamazepine -- for the acute-phase treatment of bipolar I or II disorder , mixed or manic episode , in children and adolescents aged 8 to 18 years . METHOD Forty-two out patients with a mean age of 11.4 years ( 20 with bipolar I disorder and 22 with bipolar II disorder ) were r and omly assigned to 6 weeks of open treatment with either lithium , divalproex sodium , or carbamazepine . The primary efficacy measures were the weekly Clinical Global Impression Improvement scores and the Young Mania Rating Scale ( Y-MRS ) . RESULTS Using a > or = 50 % change from baseline to exit in the Y-MRS scores to define response , the effect size was 1.63 for divalproex sodium , 1.06 for lithium , and 1.00 for carbamazepine . Using this same response measure with the intent-to-treat sample , the response rates were as follows : sodium divalproex , 53 % ; lithium , 38 % ; and carbamazepine , 38 % ( chi 2(2 ) = 0.85 , p = .60 ) . All 3 mood stabilizers were well tolerated , and no serious adverse effects were seen . CONCLUSIONS Divalproex sodium , lithium , and carbamazepine all showed a large effect size in the open treatment of children and adolescents with bipolar I or II disorder in a mixed or manic episode",
" Thirty-four hospitalized manic patients were r and omized to treatment with either lithium carbonate or an average series of nine bilateral electroconvulsive treatments ( ECTs ) , followed by maintenance with lithium carbonate . Weekly ratings of manic , depressive , and psychotic symptoms were obtained for eight weeks , and patients were followed up monthly for up to two years . Ratings by nonblind and blind observers indicated that the patients who underwent ECT improved more during the first eight weeks than did patients who were treated with lithium carbonate . This was especially true of patients with mixed symptoms of mania and depression and /or extreme manic behavior . Clinical ratings after eight weeks showed no significant differences between the lithium carbonate- and ECT-treated patients . Likewise , the two groups had comparable rates of relapse , recurrence , and rehospitalization during the follow-up period",
"Neuroleptics are of established efficacy in mania . Controlled data on the use of olanzapine in mania is however , absent . In this study , 30 patients meeting DSM-IV criteria for mania were r and omly allocated to receive either olanzapine or lithium in a 4 week double-blind r and omized controlled design . There were no significant outcome differences between the two groups on any of the primary outcome measures , the Brief Psychiatric Rating Scale ( lithium 28.2 ; olanzapine 28.0 ; P = 0.44 ) ; Clinical Global Impression ( CGI ) improvement scale ( lithium 2.75 , olanzapine 2.36 ; P = 0.163 ) or the Mania Scale ( lithium 13.2 , olanzapine 10.2 ; P = 0.315 ) . Olanzapine was however , significantly superior to lithium on the CGI-severity scale at week 4 ( lithium 2.83 , olanzapine 2.29 ; P = 0.025 ) . Olanzapine did not differ from lithium in terms of treatment emergent extrapyramidal side-effects as measured by the Simpson-Angus Scale . Olanzapine appears to be at least as effective as lithium in the treatment of mania",
"A controlled double-blind evaluation of lithium and chlorpromazine in acute manic states is reported . Analysis of the results shows that lithium produced a highly significant improvement in the manic-depressive ( manic phase ) patients but no significant change in the schizoaffective ( excited ) patients . Chlorpromazine produced significant improvement in both diagnostic groups . An analysis of the differences of the two treatments showed that lithium produced the greater change in the manic-depressives , whereas chlorpromazine produced more change than lithium in the schizoaffective group . These differences , however , did not reach statistical significance . The importance of diagnosis for treatment outcome is discussed . Lithium is an effective and specific agent for the control of the manic phase of manic-depressive illness",
" Fifty-four acutely manic patients were allocated to treatment on a double-blind basis with either carbamazepine or lithium carbonate . The short-term effects of treatment were studied over a period of six weeks and the longer term , prophylactic , effects over a period of up to a year . Additional ' rescue ' medication was allowed when clinical ly indicated . There was a high drop-out rate from the trial . Despite this , it appeared that valid comparisons between the two treatments could be made . No statistically significant differences were found , but carbamazepine appeared slightly less effective as a treatment for acute mania and more effective as a prophylactic treatment in this group of patients . Possible predictors of individual responsiveness to each treatment are discussed",
"OBJECTIVE Clinicians treating older patients with bipolar disorder with mood stabilizers need evidence from age-specific r and omized controlled trials . The authors describe findings from a first such study of late-life mania . METHOD The authors compared the tolerability and efficacy of lithium carbonate and divalproex in 224 in patients and out patients age 60 or older with bipolar I disorder who presented with a manic , hypomanic , or mixed episode . Participants were r and omly assigned , under double-blind conditions , to treatment with lithium ( target serum concentration , 0.80 - 0.99 mEq/L ) or divalproex ( target serum valproate concentration , 80 - 99 μg/mL ) for 9 weeks . Participants with an inadequate response after 3 weeks received open adjunctive risperidone . The authors hypothesized that divalproex would be better tolerated and more efficacious than lithium . Tolerability was assessed based on a measure of sedation and on the proportions of participants achieving target concentrations . Efficacy was assessed with the Young Mania Rating Scale ( YMRS ) . RESULTS Attrition rates were similar for lithium and divalproex ( 14 % and 18 % at week 3 and 51 % and 44 % at week 9 , respectively ) . The groups did not differ significantly in sedation . Participants in the lithium group tended to experience more tremor . Similar proportions of participants in the lithium and divalproex groups achieved target concentrations ( 57 % and 56 % , respectively ) . A longitudinal mixed model of improvement ( change from baseline in YMRS score ) favored lithium ( change in score , 3.90 ; 97.5 % CI=1.71 , 6.09 ) . Nine-week response rates did not differ significantly between the lithium and divalproex groups ( 79 % and 73 % , respectively ) . The need for adjunctive risperidone was low and similar between groups ( 17 % and 14 % , respectively ) . CONCLUSIONS Both lithium and divalproex were adequately tolerated and efficacious ; lithium was associated with a greater reduction in mania scores over 9 weeks",
"The single dose pharmacokinetics of 4 lithium preparations ( Camcolit-400 , Priadel , Liskonum , Litarex ) and a new micro-encapsulated formulation were compared in normal volunteers using a balanced cross-over design . The data show an inverse relationship between rate of release and bioavailability . The pharmacokinetic characteristics of Camcolit-400 and Priadel were similar ; both showed earlier and greater peak serum concentrations than the other 3 . The new formulation , which accounted for most of the significant variance , had the slowest rate of release and the lowest bioavailability . Statistical analysis showed significant differences between the 5 preparations for C-max , T-max , 12-h serum levels , AUC and urinary excretion , but not for the 24-h serum levels . No serious untoward side-effects were noted",
"The bioavailability of lithium citrate syrup was compared with that of regular lithium carbonate tablets in 18 healthy male human volunteers . Blood sample s were collected up to 48 h after dosing . Lithium serum concentrations were determined by means of AAS . The absorption rate following oral administration of the syrup was greater ( tmax 0·8 h ) than following administration of regular tablets ( tmax 1·4 h ) . Maximum lithium serum concentrations , however , were only about 10 per cent higher after syrup dosing and serum concentrations result ing from syrup and tablets were almost superimposable from 2 h after dosing . The terminal half‐life of lithium was found to be 22 h after syrup as well as after tablet dosing . No side‐effects were observed during the study . The bioavailability of lithium from syrup relative to tablets was found to be bioequivalent with respect to the maximum lithium serum concentration and the extent of drug absorption ( AUC )",
"Since the original discovery of the antimanic properties of lithium nearly 30 years ago , 1 a large number of studies , as well as extensive clinical experience , have confirmed the efficacy of this drug for the treatment of the manic phase of manic-depressive illness . The recent focus of questions concerning the role of lithium in the treatment of mania has shifted from efficacy per se to comparisons with other drug treatments and the related issue of specificity . This review will , therefore , focus on controlled studies comparing lithium with neuroleptics , following a brief historical review of the earlier studies . The studies comparing lithium with neuroleptics are of special importance not only from a practical point of view but also theoretically , in that they bear on the question of the specificity of lithium against the manic syndrome — a question with implication for the underlying pathophysiology of mania . OPEN SINGLE-BLIND STUDIES Table 1 summarizes",
"A multi-institutional study comparing the antimanic effect of carbamazepine ( CBZ ) and lithium carbonate ( Li ) was performed using a double-blind group comparison design in a series of 105 patients with bipolar disorders . CBZ and Li were given for four weeks using a fixed-flexible method at an equipotent dose ratio of 1:1 , starting from an initial dosage of 400 mg with a maximum dosage of 1200 mg . The final global improvement rate , based on the number of cases showing moderate to marked amelioration of manic symptoms , was 62 % in the CBZ group and 59 % in the Li group , with no significant difference being found between the two groups . Incidence of cutaneous side-effects was significantly higher in the CBZ group . The mean daily dosage and serum level of CBZ in the fourth week were 674 + /- 239 mg and 7.3 + /- 2.4 micrograms/ml respectively ; these were within the therapeutic range . The daily dose and serum level of Li , however , were 710 + /- 239 mg and 0.46 + /- 0.22 mEq/l , and the Li level seemed to be too low to compare its therapeutic effect with that of CBZ . Prior to the present study , approximately 80 % of the patients in both groups had been receiving antipsychotic medication , equivalent to 8.0 mg of haloperidol on average , without favorable response . This medication was maintained unchanged during treatment . While the shortcomings of the present study limit the interpretation of the data , it may be suggested that the usefulness of CBZ as a drug for the treatment of manic states is comparable to that of Li",
" Thirteen manic patients were treated with lithium carbonate and ten manic patients with chlorpromazine in a double-blind , r and omly selected drug trial . Lithium carbonate proved superior to chlorpromazine on all six parameters selected from an objective rating scale . The author discusses the problems militating against a valid research trial utilizing these medications in this type of patient",
"Background : Preliminary data from case reports and small open trials suggest a role for lamotrigine in the treatment of bipolar disorder , although controlled data for the manic phase are lacking . Method : Thirty in patients with a DSM-IV diagnosis of bipolar I disorder , currently manic , were r and omly allocated to receive either lamotrigine ( 25 mg once daily for 1 week , 50 mg once daily for the second week , and 100 mg once daily for the last 2 weeks ) or lithium ( 400 mg twice daily ) in a 4-week r and omized , double-blind , clinical trial . Results : Both treatments improved symptoms of mania , as assessed by the Mania Rating Scale , Brief Psychiatric Rating Scale , Clinical Global Impression severity and improvement scales , and the Global Assessment of Functioning scale . There were no significant differences between groups at any time point , suggesting that the dose escalation required for lamotrigine did not adversely affect its onset of action . Secondary outcome measures , including the use of lorazepam as rescue medication , did not differ between the groups . No significant adverse events were noted in either group . Conclusion : In this pilot study , lamotrigine was as effective as lithium in the treatment of patients with bipolar disorder hospitalised for acute mania",
"Antipsychotic dosing for acute mania has not been well studied . Combined treatment with lithium and an antipsychotic is the most common treatment , but additional antimanic efficacy of a lithium-antipsychotic combination beyond that of an antipsychotic alone has not been well demonstrated . Furthermore , the possibility that lithium could affect antipsychotic dose requirement is believed to have never been studied . In this study , 63 acutely psychotic bipolar manic in patients were r and omly assigned to receive double-blind treatment with 1 of 2 haloperidol doses , 25 mg/day or 5 mg/day , for 21 days . In addition to haloperidol , subjects were r and omly assigned to receive concomitant treatment with placebo , st and ard lithium , or lorazepam 4 mg/day . The high haloperidol dose produced greater improvement and more side effects than did the low dose . Lithium added to the low dose produced a markedly greater clinical response than did the low dose alone . Lorazepam did not improve the outcome for the patients receiving low-dose haloperidol . The clinical response produced by high-dose haloperidol was not enhanced by adding either lithium or lorazepam . All treatment effects emerged by the fourth day of treatment and persisted . Used alone , a haloperidol dose of 5 mg/day is too low for most manic patients , but concomitant lithium produces a dose-dependent enhancement of haloperidol response . Lorazepam 4 mg/day was insufficient to produce an advantage when added to low-dose haloperidol",
"OBJECTIVE Among the available mood stabilizers , it appears that lithium may share an important role for treatment of acute mania . In a study from Sep. 2007 to Apr. 2008 at Razi Psychiatric Hospital we evaluated the efficiency of olanzapine vs. lithium . METHODS Forty ( 40 ) female in patients meeting DSM-IV-TR criteria for acute mania were entered into a 3-week parallel group , double-blind study for r and om assignment to olanzapine or lithium carbonate in a 1:1 ratio . Primary outcome measurements were the changes in Manic State Rating Scale ( MSRS ) at baseline and weekly intervals up to the third week . Similarly , overall illness severity was rated using the Clinical Global Impression-Severity of illness scale ( CGI-S ) at baseline and at the end of the third week . Analysis of the data was accomplished by means of split-plot ( mixed ) and repeated measures analysis of variance ( ANOVA ) and t test . RESULTS While both olanzapine and lithium were found to be significantly helpful in the improvement of manic symptoms ( p lithium was considerably more successful by the end of the third week ( p frequency and intensity of the symptoms ) . CGI-S also showed important improvements with both olanzapine and lithium ( p olanzapine and lithium ) . CONCLUSION Though both olanzapine and lithium were effective in the improvement of manic symptoms , lithium was more beneficial",
"BACKGROUND Lithium carbonate and valproate semisodium are both recommended as monotherapy for prevention of relapse in bipolar disorder , but are not individually fully effective in many patients . If combination therapy with both agents is better than monotherapy , many relapses and consequent disability could be avoided . We aim ed to establish whether lithium plus valproate was better than monotherapy with either drug alone for relapse prevention in bipolar I disorder . METHODS 330 patients aged 16 years and older with bipolar I disorder from 41 sites in the UK , France , USA , and Italy were r and omly allocated to open-label lithium monotherapy ( plasma concentration 0.4 - 1.0 mmol/L , n=110 ) , valproate monotherapy ( 750 - 1250 mg , n=110 ) , or both agents in combination ( n=110 ) , after an active run-in of 4 - 8 weeks on the combination . R and omisation was by computer program , and investigators and participants were informed of treatment allocation . All outcome events were considered by the trial management team , who were masked to treatment assignment . Participants were followed up for up to 24 months . The primary outcome was initiation of new intervention for an emergent mood episode , which was compared between groups by Cox regression . Analysis was by intention to treat . This study is registered , number IS RCT N 55261332 . FINDINGS 59 ( 54 % ) of 110 people in the combination therapy group , 65 ( 59 % ) of 110 in the lithium group , and 76 ( 69 % ) of 110 in the valproate group had a primary outcome event during follow-up . Hazard ratios for the primary outcome were 0.59 ( 95 % CI 0.42 - 0.83 , p=0.0023 ) for combination therapy versus valproate , 0.82 ( 0.58 - 1.17 , p=0.27 ) for combination therapy versus lithium , and 0.71 ( 0.51 - 1.00 , p=0.0472 ) for lithium versus valproate . 16 participants had serious adverse events after r and omisation : seven receiving valproate monotherapy ( three deaths ) ; five lithium monotherapy ( two deaths ) ; and four combination therapy ( one death ) . INTERPRETATION For people with bipolar I disorder , for whom long-term therapy is clinical ly indicated , both combination therapy with lithium plus valproate and lithium monotherapy are more likely to prevent relapse than is valproate monotherapy . This benefit seems to be irrespective of baseline severity of illness and is maintained for up to 2 years . BALANCE could neither reliably confirm nor refute a benefit of combination therapy compared with lithium monotherapy . FUNDING Stanley Medical Research Institute ; Sanofi-Aventis",
"BACKGROUND Achieving therapeutic blood levels of a mood stabilizer as quickly as possible is desirable in patients with acute mania . We examined the feasibility and safety of an accelerated oral loading strategy ( divalproex , 30 mg/kg/day , on days 1 and 2 , followed by 20 mg/kg/day on days 3 - 10 ) design ed to bring serum valproate concentrations to therapeutic levels ( i.e. , above 50 microg/mL ) . METHOD Fifty-nine patients who met DSM-IV diagnostic criteria for current manic episode and who had a Mania Rating Scale score > or = 14 were r and omly assigned on a double-blind basis to receive divalproex oral loading ( N = 20 ) ; divalproex nonloading ( N = 20 ) at a starting dose of 250 mg t.i.d . on days 1 and 2 , followed by st and ard dose titration for days 3 to 10 ; or lithium carbonate ( N = 19 ) at a starting dose of 300 mg t.i.d . , followed by st and ard dose titration for days 3 to 10 . RESULTS Eighty-four percent of the divalproex-loading patients , but only 30 % of the divalproex-nonloading patients , had valproate serum levels above 50 microg/mL at day 3 of the study . None of the lithium-treated patients had serum lithium levels above 0.8 mEq/L at study day 3 . No patient was removed from the study because of an adverse event . There were no significant differences between the groups in the frequencies or types of adverse events . CONCLUSION Accelerated oral loading with divalproex sodium is a feasible and safe method to bring serum valproate concentrations to effective levels rapidly",
" A multi-institutional cooperative study comparing lithium carbonate with chlorpromazine was conducted , using a controlled double-blind design in a series of 80 cases of endogenous manic psychosis , to evaluate the drugs ' clinical utility and efficacy , characteristics of therapeutic effect , and side-effects . Dosages employed were consistently at an equipotent ratio of 4:1 ( lithium carbonate : chlorpromazine ) . Physicians ' overall ratings showed lithium carbonate as significantly superior to chlorpromazine in efficacy for manic psychosis . Improvements of basic mood and of disturbance in speech and voice were prominent with lithium carbonate . Onset of the therapeutic effect of lithium carbonate was within ten days of medication in 65 % of the patients , significantly faster than with chlorpromazine . Side-effects encountered with lithium carbonate therapy at dose levels not higher than 1,800 mg/day were milder and less frequent compared with those seen with chlorpromazine",
"Abstract Background : Bipolar disorder is a chronic illness that may involve multiple relapses and result in substantial psychosocial impairment . However , very few recent studies have investigated the economic burden of the disease . Objective : To assess the frequency of hospitalisation and the inpatient care costs associated with manic episodes in patients with bipolar I disorder in France . Method : A cost-of-illness study was conducted based on available data using a hospital payer perspective . The lifetime prevalence of manic episodes was estimated from published epidemiological data using a r and om-effects meta- analysis . Data were obtained by a computerised literature search using the main scientific and medical data bases . Additional epidemiological references were identified from published studies and textbooks . Data on frequency of hospitalisation and length of stay were collected from a large psychiatric university hospital . Data on unit costs for inpatient care were obtained from the accounting system of the largest hospital group in Paris , France for the year 1999 . Results : Extrapolating from international data on the average prevalence of bipolar I disorder , the proportion of rapid cycling patients and the average cycle duration , we estimated the annual number of manic episodes in patients with bipolar I disorder to be around 265 000 in France . Based on hospital data in Paris , the proportion of manic episodes that require hospitalisation was estimated to be around 63 % . The average length of stay was 32.4 days and the hospitalisation-related costs were estimated to be around 8.8 billion French francs ( € 1.3 billion ) [ 1999 values ] . Conclusion : Our study highlights the lack of medical and economic data on the frequency and hospitalisation-related costs of manic episodes in patients with bipolar I disorder in France . As the lifetime prevalence of bipolar I disorder may be as high as 3 % among adults , further studies are required in order to provide representative national data and to allow economic evaluations of costs related to bipolar I disorder in France",
"OBJECTIVES To evaluate the efficacy and safety of aripiprazole as acute and maintenance of effect monotherapy for acute bipolar mania . METHODS Patients with acute bipolar I mania ( DSM-IV-TR : YMRS > or = 20 ) , manic or mixed ( with or without psychotic features ) were r and omized to double-blind aripiprazole ( 15 - 30 mg/day ; n=155 ) , placebo ( n=165 ) or lithium ( 900 - 1500 mg/day ; n=160 ) ( 1:1:1 ) for 3 weeks . Aripiprazole- and lithium-treated patients remained on blinded treatment for 9 additional weeks . The primary outcome was the mean change from baseline in YMRS Total score ( LOCF ) to Week 3 . Secondary outcomes included the mean change from baseline in YMRS Total score ( LOCF ) at all other timepoints up to Week 12 . RESULTS Aripiprazole demonstrated significantly greater improvement than placebo in mean YMRS Total score from baseline to Day 2 ( -4.3 vs.-2.8 ; p=0.003 ) , and up to Week 3 ( -12.6 vs. -9.0 ; p YMRS Total score was also seen with lithium versus placebo at Week 3 ( -12.0 vs. -9.0 ; p=0.005 ) . Improvements in YMRS Total score were maintained to Week 12 for aripiprazole ( -14.5 ) and lithium ( -12.7 ) . Response rates at Week 3 were significantly higher with aripiprazole ( 46.8 % ) and lithium ( 45.8 % ) than placebo ( 34.4 % ; both p aripiprazole ( 56.5 % ) and lithium ( 49.0 % ) . Most common adverse events with aripiprazole were headache , nausea , akathisia , sedation , and constipation ; with lithium were nausea , headache , constipation , and tremor . CONCLUSIONS Aripiprazole provided statistically significant improvement of acute mania within 2 days , continuing over 3 weeks and sustained over 12 weeks . The magnitude of improvement to Week 12 was similar with aripiprazole and lithium",
"Lithium , at a dosage of 1,800 mg . daily , was found to be effective in the treatment of acute manic states . However , when compared with chlorpromazine by means of a double-blind technique using stringent diagnostic criteria , no significant difference between the two drugs was noted . In regard to the prophylactic effect of lithium , the data presented indicate that this question is still unresolved",
" Fifty-two hospitalized manic patients were r and omized to treatment with either carbamazepine or lithium carbonate after a 2-week drug withdrawal period . All of the prob and s were tertiary referrals with a high proportion of failures of previous lithium and other treatment . Weekly ratings of manic , depressive , and psychotic symptoms were obtained for 8 weeks , and responders were followed up for up to 2 years . One third of patients responded favorably . Double-blind assessment s revealed no statistically reliable differences between the two treatment groups . Patients receiving carbamazepine were somewhat more manageable than patients treated with lithium early in the study , whereas lithium-treated patients remained longer in the follow-up phase . However , numbers of long-term survivors were too small to be conclusive . This study adds to the growing body of evidence that acutely manic patients respond as well to carbamazepine as to lithium . However , monotherapy with either drug is not sufficient for the majority of manic patients who are referred for tertiary care",
"Case reports and studies of other neuroleptics suggest the efficacy of risperidone in the treatment of mania . Forty-five in patients with DSM-IV mania were studied in a 28-day r and omized , controlled , double-blind trial of either 6 mg daily of risperidone , 10 mg daily of haloperidol , or 800 to 1200 mg daily of lithium . The patients in all three groups showed a similar improvement on the total score for all rating scales at day 28 ( Brief Psychiatric rating scale : lithium 9.1 , haloperidol 4.9 , risperidone 6.5 , F = 1.01 , df = 2 , p = 0.37 ; Mania rating scale : lithium 15.7 , haloperidol 10.2 , risperidone 12.4 , F = 1.07 , df = 2 , p = = 0.35 [ analysis of variance ] ) . The Global Assessment of Functioning and Clinical Global Impression data showed a similar pattern of improvement . This study suggests that risperidone is of equivalent efficacy to lithium and haloperidol in the management of acute mania . The extrapyramidal side effects of risperidone and haloperidol were not significantly different",
"CONTEXT There was a paucity of comparative pharmacological research for initial treatment of bipolar I disorder , manic or mixed phase , in children and adolescents . OBJECTIVE To investigate which medication to administer first to antimanic medication-naive subjects . DESIGN , SETTING , AND PARTICIPANTS The Treatment of Early Age Mania ( TEAM ) study recruited 6- to 15-year-old children and adolescents with DSM-IV bipolar I disorder ( manic or mixed phase ) at 5 US sites from 2003 to 2008 into a controlled , r and omized , no-patient-choice , 8-week protocol . Blinded , independent evaluators conducted all baseline and end-point assessment s. INTERVENTIONS Subjects received a titrated schedule of lithium , divalproex sodium , or risperidone . Medications were increased weekly only if there was inadequate response , and no dose-limiting adverse effects , to maximum doses of lithium carbonate ( 1.1 - 1.3 mEq/L ) , divalproex sodium ( 111 - 125 μg/mL ) , and risperidone ( 4 - 6 mg ) . MAIN OUTCOME MEASURES Primary outcome measures were the Clinical Global Impressions for Bipolar Illness Improvement-Mania and the Modified Side Effects Form for Children and Adolescents . RESULTS There were 279 antimanic medication-naive subjects ( mean [ SD ] age , 10.1 [ 2.8 ] years ; 50.2 % female ) who had the following characteristics : 100 % elated mood and /or gr and iosity , 77.1 % psychosis , 97.5 % mixed mania , 99.3 % daily rapid cycling , and mean ( SD ) mania duration of 4.9 ( 2.5 ) years . The mean ( SD ) titrated lithium level was 1.09 ( 0.34 ) mEq/L , and the mean ( SD ) divalproex sodium level was 113.6 ( 23.0 ) μg/mL. The mean ( SD ) titrated risperidone dose was 2.57 ( 1.21 ) mg . Higher response rates occurred with risperidone vs lithium ( 68.5 % vs 35.6 % ; χ(2)(1 ) = 16.9 , P vs divalproex sodium ( 68.5 % vs 24.0 % ; χ(2)(1 ) = 28.3 , P to lithium vs divalproex sodium did not differ . The discontinuation rate was higher for lithium than for risperidone ( χ(2)(1 ) = 6.4 , P = .011 ) . Increased weight gain , body mass index , and prolactin level occurred with risperidone vs lithium ( F(1,212 ) = 45.5 , P vs divalproex sodium ( F(1,212 ) = 34.7 , P .001 , respectively ) . The thyrotropin level increased in subjects taking lithium ( t(62 ) = 11.3 , P CONCLUSIONS Risperidone was more efficacious than lithium or divalproex sodium for the initial treatment of childhood mania but had potentially serious metabolic effects . TRIAL REGISTRATION clinical trials.gov Identifier :",
"Few long‐term studies on bipolar disorder ( BD ) have investigated the incidence and risk factors of suicide attempts ( SAs ) specifically related to illness phases . We examined the incidence of SAs during different phases of BD in a long‐term prospect i ve cohort of bipolar I ( BD‐I ) and bipolar II ( BD‐II ) patients , and risk factors specifically for SAs during major depressive episodes ( MDEs )"
] |
4116c220-06ff-11f0-808a-c43d1ab1c353
|
Patients with permanent pacemakers ( PM ) are at high risk of developing atrial fibrillation ( AF ) . Minimal ventricular pacing modalities have been demonstrated to reduce AF in such patients , although they are not suitable for patients with advanced atrioventricular conduction disease . Recent evidence s suggest that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( i.e. statins ) may represent a new strategy to prevent AF in patients at risk . In this article , we sought to review data regarding the effectiveness of statin therapy in preventing AF patients with a PM . We review ed all available studies that assessed the effect of statin therapy on the occurrence of AF in patients with PM , implanted due to sinus node dysfunction or atrioventricular conduction disease . Moreover , a r and om effect inverse variance-weighted meta- analysis was performed , by entering directly the logarithm of the hazard ratio ( HR ) of AF provided in the multiple Cox regression analyses from each study . Three studies were identified , including 552 patients , of whom 159 received statins . Follow-up ranged from 1 to 2.77 years . Two studies ( one observational and one prospect i ve r and omized ) included predominantly patients with sinus node dysfunction ( 70 % and 91 % of patient population , respectively ) and , consistently , showed a beneficial effect of statins on the occurrence of AF . On the other h and , the study including predominantly patients with atrioventricular block ( 60 % of patient population ) failed to show a beneficial effect of statins on AF occurrence . The HR for AF occurrence for the cumulative data was found to be 0.43 ( 95 % confidence interval : 0.28 - 0.67 , P Statistical heterogeneity between included studies was not detected ( chi(2 ) = 1.68 , P = 0.43 , I(2 ) = 0 % ) , although significant clinical differences were found in terms of study design , patient population s , statins use and dosage and AF-monitoring capabilities . Statins may represent a novel treatment strategy to prevent the occurrence of AF in patients with PM , especially for those who had a PM implanted due to sinus node dysfunction . Basing on our findings , a r and omized clinical trial with a proper design to evaluate the utility of statins in preventing AF in these patients is warranted
|
[
"BACKGROUND In a previous study of 225 patients with sick-sinus syndrome r and omised to either single-chamber atrial pacing ( n=110 ) or single-chamber ventricular pacing ( n=115 ) , we found that after a mean follow-up of 3.3 years , atrial pacing was associated with significantly less atrial fibrillation and thromboembolism whereas there was no significant difference in mortality and heart failure between the two groups . We aim ed to find out whether this beneficial effect of atrial pacing is maintained during extended follow-up of up to 8 years . METHODS Follow-up visits for all patients were at 3 months , 12 months , then once a year at which patients had a physical examination , ECG recording , and pacemaker check-up . Endpoints were mortality , cardiovascular death , atrial fibrillation , thromboembolic events , heart failure , and atrioventricular block . Data was analysed on Dec 31 , 1996 . FINDINGS At long-term follow-up , 39 patients from the atrial group had died versus 57 from the ventricular group ( relative risk 0.66 [ 95 % CI 0.44 - 0.99 ] ; p=0.045 ) . 19 patients from the atrial group and 39 patients from the ventricular group died from a cardiovascular cause ( 0.47 [ 0.27 - 0.82 ] ; p=0.0065 ) . The cumulative incidences of atrial fibrillation and chronic atrial fibrillation were also significantly lower in the atrial group than in the ventricular group ( 0.54 [ 0.33 - 0.89 ] , p=0.012 and 0.35 [ 0.16 - 0.76 ] , p=0.004 , respectively ) . Thromboembolic events occurred in 13 patients in the atrial group and 26 in the ventricular group ( 0.47 [ 0.24 - 0.92 ] , p=0.023 ) . Heart failure was less severe in the atrial group than in the ventricular group ( p freedom from thromboembolic events ( 0.47 [ 0.24 - 0.92 ] , p=0.028 ) and survival from cardiovascular death ( 0.52 [ 0.30 - 0.91 ] , p=0.022 ) , but no longer with overall survival ( 0.71 [ 0.46 - 1.08 ] , p=0.11 ) or chronic atrial fibrillation ( 0.45 [ 0.20 - 1.05 ] , p=0.063 ) . Atrioventricular block occurred in four patients in the atrial group ( 0.6 % annual risk ) . INTERPRETATION The beneficial effect of atrial pacing found in our previous study is enhanced substantially over time . Patients with sick-sinus syndrome should be treated with an atrial rather than ventricular-pacing system because after long-term follow-up , atrial pacing is associated with a significantly higher survival , less atrial fibrillation , fewer thromboembolic complications , less heart failure , and a low-risk of atrioventricular block",
"Background —Some current pacing systems can automatically detect and record atrial tachyarrhythmias that may be asymptomatic . We prospect ively studied a 312-patient ( pt ) subgroup of MOST ( MOde Selection Trial ) , a 2010-patient , 6-year r and omized trial of DDDR versus VVIR pacing in sinus node dysfunction ( SND ) . The purpose of the study was to correlate atrial high rate events ( AHREs ) detected by pacemaker diagnostics with clinical outcomes . Methods and Results —Pacemakers were programmed to log an AHRE when the atrial rate was > 220 bpm for 10 consecutive beats . Analysis was confined to patients with at least 1 AHRE duration exceeding 5 minutes . The 312 patients were median age 74 years , 55 % female , and 60 % had a history of SVT . 160 of 312 ( 51.3 % ) patients enrolled had at least 1 AHRE > 5 minutes duration over median follow-up of 27 months . Cox proportional hazards analysis assessed the relationship of AHREs with clinical events , adjusting for prognostic variables and baseline covariates . The presence of any AHRE was an independent predictor of the following : total mortality ( hazard ratio AHRE versus no AHRE and 95 % confidence intervals=2.48 [ 1.25 , 4.91 ] , P = 0.0092 ) ; death or nonfatal stroke ( 2.79 [ 1.51 , 5.15 ] , P = 0.0011 ) ; and atrial fibrillation ( 5.93 [ 2.88 , 12.2 ] , P = 0.0001 ) . There was no significant effect of pacing mode on the presence or absence of AHREs . Conclusions —AHRE detected by pacemakers in patients with SND identify patients that are more than twice as likely to die or have a stroke , and 6 times as likely to develop atrial fibrillation as similar patients without AHRE",
"Background — Atrial fibrillation ( AF ) after cardiac surgery is associated with increased risk of complications , length of stay , and cost of care . Observational evidence suggests that patients who have undergone previous statin therapy have a lower incidence of postoperative AF . We tested this observation in a r and omized , controlled trial . Methods and Results — Two hundred patients undergoing elective cardiac surgery with cardiopulmonary bypass , without previous statin treatment or history of AF , were enrolled . Patients were r and omized to atorvastatin ( 40 mg/d , n=101 ) or placebo ( n=99 ) starting 7 days before operation . The primary end point was incidence of postoperative AF ; secondary end points were length of stay , 30-day major adverse cardiac and cerebrovascular events , and postoperative C-reactive protein ( CRP ) variations . Atorvastatin significantly reduced the incidence of AF versus placebo ( 35 % versus 57 % , P=0.003 ) . Accordingly , length of stay was longer in the placebo versus atorvastatin arm ( 6.9±1.4 versus 6.3±1.2 days , P=0.001 ) . Peak CRP levels were lower in patients without AF ( P=0.01 ) , irrespective of r and omization assignment . Multivariable analysis showed that atorvastatin treatment conferred a 61 % reduction in risk of AF ( odds ratio 0.39 , 95 % confidence interval 0.18 to 0.85 , P=0.017 ) , whereas high postoperative CRP levels were associated with increased risk ( odds ratio 2.0 , 95 % confidence interval 1.2 to 7.0 , P=0.01 ) . The incidence of major adverse cardiac and cerebrovascular events at 30 days was similar in the 2 arms . Conclusions — Treatment with atorvastatin 40 mg/d , initiated 7 days before surgery , significantly reduces the incidence of postoperative AF after elective cardiac surgery with cardiopulmonary bypass and shortens hospital stay . These results may influence practice patterns with regard to adjuvant pharmacological therapy before cardiac surgery",
"BACKGROUND Increasing evidence suggests that atrial fibrillation ( AF ) is an inflammatory disease . Statins is an anti-inflammatory agent . The present study was conducted to test the efficacy of atorvastatin in preventing paroxysmal AF or atrial high rate episodes ( AHEs ) in patients with bradyarrhythmias and implantation of an atrial-based or dual-chamber pacemaker . METHODS The effect of atorvastatin on time to the first attack of AF or AHE ( > or = 180 per minute and > or = 1 or 10 minutes ) , which was accurately detected by pacemaker interrogation , was evaluated in an open-label prospect i ve r and omized design for 1 year of follow-up . RESULTS Fifty-two patients ( 23 males , 70 + /- 13 years old ) were r and omized to the statin group ( atorvastatin 20 mg/d ) and 54 ( 25 males , 72 + /- 13 years old ) to the nonstatin group . Event-free survivals from AHE > or = 1 minute were not significantly different between the 2 groups ( log-rank P = .410 ) . However , patients in the nonstatin group were more likely to develop AHE > or = 10 minutes than those in the statin group ( log-rank P = .028 ) . Atrial high rate episode > or = 10 minutes occurred in 3 ( 5.8 % ) of 51 patients in the statin group after 1 year of follow-up , and 10 ( 19.2 % ) of 52 patients ( odds ratio 0.26 , P = .041 ) in the nonstatin group . The mean left atrial volume of the statin group was significantly lower than that of the nonstatin group at the end of follow-up ( 39.7 + /- 1.7 vs 43.7 + /- 1.9 mL , P AF ( > or = 10 minutes ) and left atrial enlargement in patients with bradyarrhythmias and implantation of a pacemaker",
"BACKGROUND Dual-chamber ( atrioventricular ) and single-chamber ( ventricular ) pacing are alternative treatment approaches for sinus-node dysfunction that causes clinical ly significant bradycardia . However , it is unknown which type of pacing results in the better outcome . METHODS We r and omly assigned a total of 2010 patients with sinus-node dysfunction to dual-chamber pacing ( 1014 patients ) or ventricular pacing ( 996 patients ) and followed them for a median of 33.1 months . The primary end point was death from any cause or nonfatal stroke . Secondary end points included the composite of death , stroke , or hospitalization for heart failure ; atrial fibrillation ; heart-failure score ; the pacemaker syndrome ; and the quality of life . RESULTS The incidence of the primary end point did not differ significantly between the dual-chamber group ( 21.5 percent ) and the ventricular-paced group ( 23.0 percent , P=0.48 ) . In patients assigned to dual-chamber pacing , the risk of atrial fibrillation was lower ( hazard ratio , 0.79 ; 95 percent confidence interval , 0.66 to 0.94 ; P=0.008 ) , and heart-failure scores were better ( P rates of hospitalization for heart failure and of death , stroke , or hospitalization for heart failure were not significant in unadjusted analyses but became marginally significant in adjusted analyses . Dual-chamber pacing result ed in a small but measurable increase in the quality of life , as compared with ventricular pacing . CONCLUSIONS In sinus-node dysfunction , dual-chamber pacing does not improve stroke-free survival , as compared with ventricular pacing . However , dual-chamber pacing reduces the risk of atrial fibrillation , reduces signs and symptoms of heart failure , and slightly improves the quality of life . Overall , dual-chamber pacing offers significant improvement as compared with ventricular pacing",
"BACKGROUND The epidemiology and clinical implication s of asymptomatic atrial tachyarrhythmias ( AT ) including both atrial fibrillation and flutter in pacemaker recipients with and without arrhythmia history are not well understood . The Atrial High Rate Episodes ( A-HIRATE ) in Pacemaker Patients Trial was design ed to identify and compare the incidence of AT in patients with and without previously diagnosed AT and a st and ard indication for dual chamber pacing , and to provide useful diagnostic information for clinical management . METHODS Four hundred twenty-seven patients were implanted with a pacemaker ( Kappa 7 - 900 , Medtronic , Inc. , Minneapolis , MN , USA ) capable of detecting and storing multiple atrial high rate episodes ( AHRE ) and followed for 2 years . Group I included 331 patients without prior history of AT and Group II included 96 patients with prior AT history . RESULTS Pacemaker diagnostics appropriately detected 93 % of review ed AHRE . The rate of occurrence of first AHRE was significantly higher ( P rate of first AHRE occurrence was 88.6 % for patients in Group II and 53.8 % in Group I at 24 months post-implant . The rate of AHRE occurrence was similar in both groups after the first month post-implant . The majority of stored AHRE were asymptomatic ; symptoms did not correspond to an actual AHRE in most patients . CONCLUSIONS The incidence of AT in pacemaker recipients is high . Most device-detected AHRE are asymptomatic . Prior history of AT is associated with higher arrhythmia burden . AHRE diagnostics have a high positive predictive value for identifying AT events",
"OBJECTIVE It has been recently reported that AF is associated with tissue inflammation . Statins reduce C-reactive protein ( CRP ) levels . However , the effect of statin on atrial fibrillation ( AF ) is unclear . The purpose of the present study was to evaluate the effect of statin on AF in a canine sterile pericarditis model . METHODS Sterile pericarditis was created in 20 dogs r and omly assigned to two groups : a control group ( 10 dogs ) and an atorvastatin treatment group ( 10 dogs ) . Atorvastatin was administered orally ( 2 mg/kg/day ) beginning 1 week before the operation until the end of the study . Before and 2 days after the operation , CRP levels , the duration of induced AF , the atrial effective refractory period ( AERP ) , and intra-atrial conduction time were determined . RESULTS Before the operation , there were no significant differences in any of the parameters between the two groups . On the second postoperative day , the atorvastatin group had a lower CRP level ( 7.6+/-0.5 versus 11.7+/-1.3 mg/dl , P AF duration ( 177+/-57 versus 534+/-189 s , P longer AERP ( 138+/-6 versus 130+/-6 ms , P intra-atrial conduction time ( 46+/-3 versus 51+/-5 ms , P Atorvastatin can prevent maintenance of AF by inhibiting inflammation in the canine sterile pericarditis model . Atorvastatin may thus be a novel therapeutic agent for AF",
"BACKGROUND Conventional dual-chamber pacing maintains atrioventricular synchrony but results in high percentages of ventricular pacing , which causes ventricular desynchronization and has been linked to an increased risk of atrial fibrillation in patients with sinus-node disease . METHODS We r and omly assigned 1065 patients with sinus-node disease , intact atrioventricular conduction , and a normal QRS interval to receive conventional dual-chamber pacing ( 535 patients ) or dual-chamber minimal ventricular pacing with the use of new pacemaker features design ed to promote atrioventricular conduction , preserve ventricular conduction , and prevent ventricular desynchronization ( 530 patients ) . The primary end point was time to persistent atrial fibrillation . RESULTS The mean ( + /-SD ) follow-up period was 1.7+/-1.0 years when the trial was stopped because it had met the primary end point . The median percentage of ventricular beats that were paced was lower in dual-chamber minimal ventricular pacing than in conventional dual-chamber pacing ( 9.1 % vs. 99.0 % , P percentage of atrial beats that were paced was similar in the two groups ( 71.4 % vs. 70.4 % , P=0.96 ) . Persistent atrial fibrillation developed in 110 patients , 68 ( 12.7 % ) in the group assigned to conventional dual-chamber pacing and 42 ( 7.9 % ) in the group assigned to dual-chamber minimal ventricular pacing . The hazard ratio for development of persistent atrial fibrillation in patients with dual-chamber minimal ventricular pacing as compared with those with conventional dual-chamber pacing was 0.60 ( 95 % confidence interval , 0.41 to 0.88 ; P=0.009 ) , indicating a 40 % reduction in relative risk . The absolute reduction in risk was 4.8 % . The mortality rate was similar in the two groups ( 4.9 % in the group receiving dual-chamber minimal ventricular pacing vs. 5.4 % in the group receiving conventional dual-chamber pacing , P=0.54 ) . CONCLUSIONS Dual-chamber minimal ventricular pacing , as compared with conventional dual-chamber pacing , prevents ventricular desynchronization and moderately reduces the risk of persistent atrial fibrillation in patients with sinus-node disease . ( Clinical Trials.gov number , NCT00284830 [ Clinical Trials.gov ] . )",
"OBJECTIVES A r and omized trial was done to compare single-chamber atrial ( AAI ) and dual-chamber ( DDD ) pacing in patients with sick sinus syndrome ( SSS ) . Primary end points were changes in left atrial ( LA ) size and left ventricular ( LV ) size and function as measured by M-mode echocardiography . BACKGROUND In patients with SSS and normal atrioventricular conduction , it is still not clear whether the optimal pacing mode is AAI or DDD pacing . METHODS A total of 177 consecutive patients ( mean age 74 + /- 9 years , 73 men ) were r and omized to treatment with one of three rate-adaptive ( R ) pacemakers : AAIR ( n = 54 ) , DDDR with a short atrioventricular delay ( n = 60 ) ( DDDR-s ) , or DDDR with a fixed long atrioventricular delay ( n = 63 ) ( DDDR-l ) . Before pacemaker implantation and at each follow-up , M-mode echocardiography was done to measure LA and LV diameters . Left ventricular fractional shortening ( LVFS ) was calculated . Analysis was on an intention-to-treat basis . RESULTS Mean follow-up was 2.9 + /- 1.1 years . In the AAIR group , no significant changes were observed in LA or LV diameters or LVFS from baseline to last follow-up . In both DDDR groups , LA diameter increased significantly ( p LVFS decreased significantly ( p Atrial fibrillation was significantly less common in the AAIR group , 7.4 % versus 23.3 % in the DDDR-s group versus 17.5 % in the DDDR-l group ( p = 0.03 , log-rank test ) . Mortality , thromboembolism , and congestive heart failure did not differ between groups . CONCLUSIONS During a mean follow-up of 2.9 + /- 1.1 years , DDDR pacing causes increased LA diameter , and DDDR pacing with a short atrioventricular delay also causes decreased LVFS . No changes occur in LA or LV diameters or LVFS during AAIR pacing . Atrial fibrillation is significantly less common during AAIR pacing",
"OBJECTIVE We hypothesized that a new minimal ventricular pacing mode ( MVP ) that provides AAI/R pacing with ventricular monitoring and back-up DDD/R pacing as needed during AV block ( AVB ) would significantly reduce cumulative percent ventricular pacing compared to DDD/R. BACKGROUND Conventional DDD/R mode often results in high cumulative percent ventricular pacing that may adversely affect ventricular function and increase risk of heart failure and atrial fibrillation . METHODS MVP was made operational in 30 patients with DDD/R implantable cardioverter-defibrillators ( ICDs ) and no history of AVB . Patients were r and omized to one week each in DDD/R and MVP . Holter monitor recordings ( ECG , intracardiac electrograms , and event markers ) and device diagnostics were analyzed for cumulative % atrial paced ( Cum%AP ) , cumulative percent ventricular pacing , and frequency and duration of DDD/R pacing back-up . Diaries were used to report symptoms . RESULTS Age of the study population was 61 years + /- 12 years and 83 % were male . Baseline PR interval was 204 ms + /- 32 ms and programmed AV intervals ( DDD/R ) were 200 ms + /- 50 ms (paced)/167 ms + /- 54 ms ( sensed ) . Cum%AP was similar between MVP and DDD/R ( 47.9 + /- 37 vs 46.3 + /- 36 ) . Cumulative percent ventricular pacing was significantly lower in MVP vs DDD/R ( 3.79 + /- 16.3 vs 80.6 + /- 33.8 , P Back-up DDD/R pacing during MVP operation due to transient AVB occurred in 10 % of patients ( 9.3 + /- 7.4 [ range 1 - 15 ] episodes/patient-day , duration 39.7 minutes + /- 156 minutes ) . Fifteen percent of AV intervals during MVP operation exceeded 300 ms . No significant symptoms were reported during MVP operation . CONCLUSIONS MVP dramatically reduced cumulative percent ventricular pacing compared to DDD/R while maintaining AV synchrony and providing sensor-modulated atrial pacing support . Intermittent oscillations between MVP and DDD/R during transient AV block appeared safe and well tolerated",
"INTRODUCTION Newer implantable pulse generators have data storage capabilities that permit detection of multiple episodes of atrial fibrillation ( AF ) . This study evaluated the clinical predictors and time course of AF development in a general pacemaker population . METHODS AND RESULTS Patients ( n = 231 ) received DDDR pacemakers with features that permit detection and storage of information about the date , time of onset , and duration of multiple , sequential episodes of AF . Patients were followed for 718+/-383 days . Time to first occurrence of AF , interval between first and second episode of AF , and total AF burden were determined at each follow-up visit . AF occurred more often in patients ( 68 % ) with sinus node disease than in patients with AV block ( 37 % ; P Time to first occurrence of AF was 21.2 days ( 95 % confidence interval [ CI ] 14.7 to 30.6 days ) after pacemaker implantation . AF burden initially decreased significantly in patients ( 0.8 hours/day , 95 % CI 0.7 to 0.9 at 8 weeks after implant vs 0.6 hours/day , 95 % CI 0.4 to 0.8 at 12 months after implant ; P = 0.005 ) but then increased significantly during long-term follow-up ( 2.0 hours/day , 95 % CI 1.0 to 3.7 at 48 months after implant ; P = 0.008 ) . The long-term increase in AF burden was seen predominantly in patients with sinus node disease . A prior history of AF and the duration of follow-up were independent predictors of AF occurrence . CONCLUSION AF develops frequently after dual-chamber pacemaker implantation . AF burden increases progressively over the long term",
"BACKGROUND Compared to atrioventricular sequential pacing , ventricular dem and pacing is known to have somewhat more deleterious hemodynamic effects , which probably arise from increased sympathetic tonus and inappropriate baroreceptor activation . Endothelial function is affected by various local and systemic factors including baroreceptor activity . The aim of this study was to explore whether cardiac pacing would have any effect on endothelial functions . METHODS Twelve patients ( six male , mean age : 75 + /- 9 years ) with previously implanted DDD or VDDcardiac pacemakers were included . All patients had stable atrial rhythms during the study . Patients were r and omized to either atrial-based pacing mode ( VDD or DDD ) or ventricular dem and pacing mode ( VVI ) first , and then cross-over was performed with the other pacing mode . Endothelial function was assessed by brachial artery ultrasonography . Basal diameter of the brachial artery , and both flow-mediated dilation ( FMD ) and endothelium-independent vasodilation with nitroglycerin were measured 1 hour after each pacing mode . RESULTS Compared to atrial-based pacing mode , ventricular dem and pacing was associated with a significantly worse FMD both as absolute and percentage values ( 0.17 + /- 0.09 mm vs 0.28 + /- 0.11 mm , P = 0.015 and 4.84 + /- 2.37 % vs 7.00 + /- 2.88 % , P = 0.028 , respectively ) . However , there was no significant difference in nitroglycerin-mediated vasodilation values between the two pacing sessions . CONCLUSIONS Acute ventricular dem and pacing ( VVI pacing ) is clearly associated with attenuation of FMD in patients with atrial-based pacing systems . The attenuation of endothelial vasodilation might have a role in hemodynamic and clinical deterioration in patients with VVI pacemakers",
"Background —It has been suggested that inflammation can have a role in the development of atrial arrhythmias after cardiac surgery and that a genetic predisposition to develop postoperative complications exists . This study was conceived to verify if a potential genetic modulator of the systemic inflammatory reaction to cardiopulmonary bypass ( the −174 G/C polymorphism of the promoter of the Interleukin-6 gene ) has a role in the pathogenesis of postoperative atrial fibrillation ( AF ) . Patients and Results —In 110 primary isolated coronary artery bypass patients the −174G/C Interleukin-6 promoter gene variant was determined . Interleukin-6 , fibrinogen and C-reactive protein plasma levels were determined preoperatively , 24 , 48 , and 72 hours after surgery and at discharge . Heart rate and rhythm were continuously monitored for the first 36 to 48 hours ; daily 12-lead electrocardiograms were performed thereafter until discharge . GG , CT , and CC genotypes were found in 62 , 38 , and 10 patients , respectively . Multivariate analysis ( which included genotype , age , sex , and classical risk factors for AF ) identified the GG genotype as the only independent predictor of postoperative AF . The latter occurred in 33.9 % of GG versus 10.4 % of non-GG patients ( hazard ratio 3.25 , 95%CI 1.23 to 8.62 ) . AF patients had higher blood levels of Interleukin-6 and fibrinogen after surgery ( P the inflammatory response to surgery and to influence the development of postoperative AF . These data suggest an inflammatory component of postoperative atrial arrhythmias and a genetic predisposition to this complication",
"BACKGROUND Atrial fibrillation ( AF ) is not always accompanied by clear-cut symptoms and symptoms suggestive of AF may not correspond to a genuine AF episode . The study prospect ively evaluated the burden of asymptomatic AF episodes in pacemaker patients ( for sick sinus syndrome ) with a history of documented paroxysmal AF . METHODS Consecutive patients were enrolled and implanted with dual-chamber pacemakers equipped with diagnostic features for AF monitoring . Each patient was instructed about typical AF symptoms and was asked to keep a detailed log of symptoms . Stored pacemaker data were analyzed using only AF episodes > 30 s. RESULTS The mean follow-up was 16 + /- 6 months and 102 patients were enrolled ( 73 + /- 7 years , 59 M ) . Thirteen patients ( 13 % ) dropped out with the development of permanent AF and their data were discarded . Twenty-three patients ( 26 % ) without device-stored AF episodes all reported at least one annotated AF episode . There were 1,245 device-stored AF episodes in 66 ( 74 % ) out of 89 patients . Patients reported 1,141 episodes of AF-related symptoms . Only 240 ( 21 % ) corresponded to a genuine device-stored AF event . The sensitivity and positive predictive value of symptoms to detect AF were respectively 19 % and 21 % . Episode duration , rate increase at the onset of the arrhythmia , heart disease , or antiarrhythmic drug therapy showed no statistically significant differences comparing symptomatic and asymptomatic episodes . CONCLUSIONS Many pacemaker patients with paroxysmal AF can develop AF-like symptoms in the absence of device-stored AF . AF-related symptoms have low sensitivity and low positive predictive value in patients with permanent pacemakers",
"OBJECTIVES The present study determined the incidence and time course of atrial fibrillation ( AF ) recurrences in patients with a history of AF and fitted with an implantable monitoring device . BACKGROUND The long-term risk of undetected recurrence of AF in patients receiving stable antiarrhythmic therapy remains uncertain . METHODS In 110 patients with a class I indication for physiologic pacing and a history of AF , a pacemaker with dedicated functions for AF detection and electrogram storage was implanted , and antiarrhythmic drug treatment was optimized . Patients were regularly followed up with evaluation of AF-related symptoms , a resting electrocardiogram ( ECG ) , and interrogation of device memory . The incidence of AF recurrences lasting > 48 h in asymptomatic patients presenting in sinus rhythm ( SR ) at the respective follow-up visit constituted the primary end point of this prospect i ve study . RESULTS During 19 + /- 11 months , 678 follow-up visits were performed . Atrial fibrillation was documented in 51 patients ( 46 % ) by ECG recording and in 97 patients ( 88 % ) by a review of stored electrograms ( p AF recurrences lasting > 48 h in 50 patients , 19 of whom ( 38 % ) were completely asymptomatic and in SR at subsequent follow-up . In 11 ( 16 % ) of 67 patients with device-confirmed freedom from AF for > or =3 months , AF lasting > 48 h recurred subsequently . CONCLUSIONS This prospect i ve study demonstrates a high incidence of recurrent AF despite optimized antiarrhythmic therapy . Of particular note , AF relapses > 48 h remained totally asymptomatic in a significant proportion of patients . Freedom from AF for > or =3 months did not preclude subsequent long-lasting AF recurrence",
"Atrial fibrillation ( AF ) is prevalent in the elderly , in patients with hypertension , and in patients with coronary artery disease ( CAD ) . We hypothesized that statin therapy might be effective in preventing AF in patients with CAD and examined this hypothesis in a sample of patients with chronic stable CAD without AF , followed prospect ively at a large outpatient cardiology practice . The association between statin use and the risk of developing AF was examined univariately and then with adjustment for potential confounding factors . Four hundred forty-nine men and women between the ages of 40 and 87 years were followed for an average of 5 years . Fifty-two patients ( 12 % ) developed AF during follow-up . Statin therapy was used by 59 % of the patients during the study period and was associated with a significantly reduced risk of developing AF ( crude odds ratio , 0.48 , 95 % confidence interval 0.28 to 0.83 ) . This association remained significant after adjustment for potential confounders , including age , hypertension , left ventricular systolic function , occurrence of heart failure or acute ischemic events , and baseline cholesterol and changes in cholesterol levels ( adjusted odds ratio 0.37 , 95 % confidence interval 0.18 to 0.76 ) . Use of statins in patients with chronic stable CAD appears to be protective against AF . The underlying mechanism for this effect is unknown but appears to be independent of the reduction in serum cholesterol levels"
] |
4116c266-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND Adherence to chronic disease management is critical to achieving improved health outcomes , quality of life , and cost-effective health care . As the burden of chronic diseases continues to grow globally , so does the impact of non-adherence . Mobile technologies are increasingly being used in health care and public health practice ( mHealth ) for patient communication , monitoring , and education , and to facilitate adherence to chronic diseases management . OBJECTIVE We conducted a systematic review of the literature to evaluate the effectiveness of mHealth in supporting the adherence of patients to chronic diseases management ( " mAdherence " ) , and the usability , feasibility , and acceptability of mAdherence tools and platforms in chronic disease management among patients and health care providers . METHODS We search ed PubMed , Embase , and EBSCO data bases for studies that assessed the role of mAdherence in chronic disease management of diabetes mellitus , cardiovascular disease , and chronic lung diseases from 1980 through May 2014 . Outcomes of interest included effect of mHealth on patient adherence to chronic diseases management , disease-specific clinical outcomes after intervention , and the usability , feasibility , and acceptability of mAdherence tools and platforms in chronic disease management among target end-users . RESULTS In all , 107 articles met all inclusion criteria . Short message service was the most commonly used mAdherence tool in 40.2 % ( 43/107 ) of studies . Usability , feasibility , and acceptability or patient preferences for mAdherence interventions were assessed in 57.9 % ( 62/107 ) of studies and found to be generally high . A total of 27 studies employed r and omized controlled trial ( RCT ) methods to assess impact on adherence behaviors , and significant improvements were observed in 15 of those studies ( 56 % ) . Of the 41 RCTs that measured effects on disease-specific clinical outcomes , significant improvements between groups were reported in 16 studies ( 39 % ) . CONCLUSIONS There is potential for mHealth tools to better facilitate adherence to chronic disease management , but the evidence supporting its current effectiveness is mixed . Further research should focus on underst and ing and improving how mHealth tools can overcome specific barriers to adherence
|
[
"AIMS To assess Sweet Talk , a text-messaging support system design ed to enhance self-efficacy , facilitate uptake of intensive insulin therapy and improve glycaemic control in paediatric patients with Type 1 diabetes . METHODS One hundred and twenty-six patients fulfilled the eligibility criteria ; Type 1 diabetes for > 1 year , on conventional insulin therapy , aged 8 - 18 years . Ninety-two patients were r and omized to conventional insulin therapy ( n = 28 ) , conventional therapy and Sweet Talk ( n = 33 ) or intensive insulin therapy and Sweet Talk ( n = 31 ) . Goal - setting at clinic visits was reinforced by daily text-messages from the Sweet Talk software system , containing personalized goal -specific prompts and messages tailored to patients ' age , sex and insulin regimen . RESULTS HbA(1c ) did not change in patients on conventional therapy without or with Sweet Talk ( 10.3 + /- 1.7 vs. 10.1 + /- 1.7 % ) , but improved in patients r and omized to intensive therapy and Sweet Talk ( 9.2 + /- 2.2 % , 95 % CI -1.9 , -0.5 , P Sweet Talk was associated with improvement in diabetes self-efficacy ( conventional therapy 56.0 + /- 13.7 , conventional therapy plus Sweet Talk 62.1 + /- 6.6 , 95 % CI + 2.6 , + 7.5 , P = 0.003 ) and self-reported adherence ( conventional therapy 70.4 + /- 20.0 , conventional therapy plus Sweet Talk 77.2 + /- 16.1 , 95 % CI + 0.4 , + 17.4 , P = 0.042 ) . When surveyed , 82 % of patients felt that Sweet Talk had improved their diabetes self-management and 90 % wanted to continue receiving messages . CONCLUSIONS Sweet Talk was associated with improved self-efficacy and adherence ; engaging a classically difficult to reach group of young people . While Sweet Talk alone did not improve glycaemic control , it may have had a role in supporting the introduction of intensive insulin therapy . Scheduled , tailored text messaging offers an innovative means of supporting adolescents with diabetes and could be adapted for other health-care setting s and chronic diseases",
"Lowering blood pressure reduces cardiovascular risk , yet hypertension is poorly controlled in diabetic patients . In a pilot study we demonstrated that a home blood pressure telemonitoring system , which provided self-care messages on the smartphone of hypertensive diabetic patients immediately after each reading , improved blood pressure control . Messages were based on care paths defined by running averages of transmitted readings . The present study tests the system 's effectiveness in a r and omized , controlled trial in diabetic patients with uncontrolled systolic hypertension . Of 244 subjects screened for eligibility , 110 ( 45 % ) were r and omly allocated to the intervention ( n=55 ) or control ( n=55 ) group , and 105 ( 95.5 % ) completed the 1-year outcome visit . In the intention-to-treat analysis , mean daytime ambulatory systolic blood pressure , the primary end point , decreased significantly only in the intervention group by 9.1±15.6 mmHg ( SD ; P not affect anxiety but worsened depression on the Hospital Anxiety and Depression Scale ( baseline , 4.1±3.76 ; exit , 5.2±4.30 ; P=0.014 ) . This study demonstrated that home blood pressure telemonitoring combined with automated self-care support reduced the blood pressure of diabetic patients with uncontrolled systolic hypertension and improved hypertension control . Home blood pressure monitoring alone had no effect on blood pressure . Promoting patient self-care may have negative psychological effects ",
"OBJECTIVE To test whether adding mobile application coaching and patient/provider web portals to community primary care compared with st and ard diabetes management would reduce glycated hemoglobin levels in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS A cluster-r and omized clinical trial , the Mobile Diabetes Intervention Study , r and omly assigned 26 primary care practice s to one of three stepped treatment groups or a control group ( usual care ) . A total of 163 patients were enrolled and included in analysis . The primary outcome was change in glycated hemoglobin levels over a 1-year treatment period . Secondary outcomes were changes in patient-reported diabetes symptoms , diabetes distress , depression , and other clinical ( blood pressure ) and laboratory ( lipid ) values . Maximal treatment was a mobile- and web-based self-management patient coaching system and provider decision support . Patients received automated , real-time educational and behavioral messaging in response to individually analyzed blood glucose values , diabetes medications , and lifestyle behaviors communicated by mobile phone . Providers received quarterly reports summarizing patient ’s glycemic control , diabetes medication management , lifestyle behaviors , and evidence -based treatment options . RESULTS The mean declines in glycated hemoglobin were 1.9 % in the maximal treatment group and 0.7 % in the usual care group , a difference of 1.2 % ( P = 0.001 ) over 12 months . Appreciable differences were not observed between groups for patient-reported diabetes distress , depression , diabetes symptoms , or blood pressure and lipid levels ( all P > 0.05 ) . CONCLUSIONS The combination of behavioral mobile coaching with blood glucose data , lifestyle behaviors , and patient self-management data individually analyzed and presented with evidence -based guidelines to providers substantially reduced glycated hemoglobin levels over 1 year",
"Objective To determine the feasibility and efficacy of a six-month , cell phone-based exercise persistence intervention for patients with chronic obstructive pulmonary disease ( COPD ) following pulmonary rehabilitation . Methods Participants who completed a two-week run-in were r and omly assigned to either MOBILE-Coached ( n = 9 ) or MOBILE-Self-Monitored ( n = 8) . All participants met with a nurse to develop an individualized exercise plan , were issued a pedometer and exercise booklet , and instructed to continue to log their daily exercise and symptoms . MOBILE-Coached also received weekly reinforcement text messages on their cell phones ; reports of worsening symptoms were automatically flagged for follow-up . Usability and satisfaction were assessed . Participants completed incremental cycle and six minute walk ( 6MW ) tests , wore an activity monitor for 14 days , and reported their health-related quality of life ( HRQL ) at baseline , three , and six months . Results The sample had a mean age of 68 ±11 and forced expiratory volume in one second 18 % predicted . Participants reported that logging their exercise and symptoms ( FEV1 ) of 40 ± was easy and that keeping track of their exercise helped them remain active . There were no differences between groups over time in maximal workload , 6MW distance , or HRQL ( p > 0.05 ) ; however , MOBILE-Self-Monitored increased total steps/day whereas MOBILE-Coached logged fewer steps over six months ( p = 0.04 ) . Conclusions We showed that it is feasible to deliver a cell phone-based exercise persistence intervention to patients with COPD post-rehabilitation and that the addition of coaching appeared to be no better than self-monitoring . The latter finding needs to be interpreted with caution since this was a purely exploratory study . Trial registration Clinical Trials.gov ( NCT00373932 )",
"OBJECTIVE To improve quality and efficiency of care for elderly patients with type 2 diabetes , we introduced elderly-friendly strategies to the clinical decision support system (CDSS)-based ubiquitous healthcare ( u-healthcare ) service , which is an individualized health management system using advanced medical information technology . RESEARCH DESIGN AND METHODS We conducted a 6-month r and omized , controlled clinical trial involving 144 patients aged > 60 years . Participants were r and omly assigned to receive routine care ( control , n = 48 ) , to the self-monitored blood glucose ( SMBG , n = 47 ) group , or to the u-healthcare group ( n = 49 ) . The primary end point was the proportion of patients achieving A1C without hypoglycemia at 6 months . U-healthcare system refers to an individualized medical service in which medical instructions are given through the patient ’s mobile phone . Patients receive a glucometer with a public switched telephone network-connected cradle that automatically transfers test results to a hospital-based server . Once the data are transferred to the server , an automated system , the CDSS rule engine , generates and sends patient-specific messages by mobile phone . RESULTS After 6 months of follow-up , the mean A1C level was significantly decreased from 7.8 ± 1.3 % to 7.4 ± 1.0 % ( P proportion of patients with A1C was 30.6 % in the u-healthcare group , 23.4 % in the SMBG group ( 23.4 % ) , and 14.0 % in the control group ( P u-healthcare service achieved better glycemic control with less hypoglycemia than SMBG and routine care and may provide effective and safe diabetes management in the elderly diabetic patients",
"AIM To compare the effectiveness of two methods of follow-up : short message service and telephone follow-up on type 2 diabetes adherence for three months . BACKGROUND Using telemedicine approaches may preserve appropriate blood glucose levels and may improve adherence to diabetes control recommendations in diabetic patients . DESIGN A quasi-experimental , two-group , pretest and post-test design was used in this study to evaluate the effectiveness of nurse 's follow-up via cellular phones and telephones . METHODS The sample consisted of 77 patients with type 2 diabetes that r and omly were assigned to two groups : telephone follow-up ( n = 39 ) and short message service ( n = 38 ) . Telephone interventions were applied by a research er for three months ; twice a week for the first month and every week for the second and third month . For three successive months , the short message service group that received messages about adherence to therapeutic regimen was examined . The data gathering instrument included data sheets - to record glycosylated haemoglobin - and the question naire related to adherence therapeutic regimen . Data gathering was carried out at the beginning of the study and after three and six months . The data were analysed using descriptive and inferential statistic methods with SPSS version 11.5 . RESULTS Results showed that both interventions had significant mean changes in glycosylated haemoglobin . For the telephone group ( p short message service group ( p diet adherence ( p = 0.000 ) , physical exercise ( p = 0.000 ) and medication taking ( p = 0.000 ) adherence in either groups . CONCLUSION Intervention using short message services of cellular phones and nurse-led-telephone follow-up improved HbA1c levels and adherence to diabetes therapeutic regimen for three months in type 2 diabetic patients . RELEVANCE TO CLINICAL PRACTICE Both of follow-up intervention uses in this study can decrease HbA1c levels and escalate adherence to diabetes control recommendations in people with type 2 diabetes for three months",
"Objective To determine whether mobile phone based monitoring improves asthma control compared with st and ard paper based monitoring strategies . Design Multicentre r and omised controlled trial with cost effectiveness analysis . Setting UK primary care . Participants 288 adolescents and adults with poorly controlled asthma ( asthma control question naire ( ACQ ) score ≥1.5 ) from 32 practice s. Intervention Participants were central ly r and omised to twice daily recording and mobile phone based transmission of symptoms , drug use , and peak flow with immediate feedback prompting action according to an agreed plan or paper based monitoring . Main outcome measures Changes in scores on asthma control question naire and self efficacy ( knowledge , attitude , and self efficacy asthma question naire ( KASE-AQ ) ) at six months after r and omisation . Assessment of outcomes was blinded . Analysis was on an intention to treat basis . Results There was no significant difference in the change in asthma control or self efficacy between the two groups ( ACQ : mean change 0.75 in mobile group v 0.73 in paper group , mean difference in change −0.02 ( 95 % confidence interval −0.23 to 0.19 ) ; KASE-AQ score : mean change −4.4 v −2.4 , mean difference 2.0 ( −0.3 to 4.2 ) ) . The numbers of patients who had acute exacerbations , steroid courses , and unscheduled consultations were similar in both groups , with similar healthcare costs . Overall , the mobile phone service was more expensive because of the expenses of telemonitoring . Conclusions Mobile technology does not improve asthma control or increase self efficacy compared with paper based monitoring when both groups received clinical care to guidelines st and ards . The mobile technology was not cost effective . Trial registration Clinical Trials NCT00512837",
"Failing to reach blood pressure ( BP ) goals is one of the main problems in hypertension management . Especially in high-risk patients , intensive monitoring including frequently office visits or new techniques to monitor home BP is required . A total of 60 patients with uncontrolled hypertension were included and r and omized into a group with telemetric BP monitoring ( TBPM ) ( n=30 ) and a control group receiving st and ard care ( n=30 ) . During the 3-month study period , patients received in addition to their antihypertensive pre-treatment up to 2 × 300 mg irbesartan to achieve the required target BP . All patients were instructed to measure their BP once daily in the morning . In the TBPM group automatic alerts were generated by the central data base server using pre-defined algorithms and patients were subsequently contacted by the physician . At baseline mean 24-h ambulant BP monitoring ( ABPM ) was 143.3±11.1/82.6±9.9 mm Hg in the TBPM group and 141.4±12.6/82.1±6.5 mm Hg in the st and ard care group . During treatment mean systolic BP showed a more intensive decrease in the TBPM vs control group ( −17.0±11.1 mm Hg vs −9.8±13.7 mm Hg ; P=0.032 ) . Patients in the TBPM group had a more pronounced night dipping and a higher reduction of mean pulse pressure than controls ( −8.1±5.9 mm Hg vs −2.8±7.4 mm Hg , P=0.004 ) . After 3 months , TBPM-treated patients were given a higher mean daily dose of irbesartan ( 375±187 mg vs 222±147 mg in controls ; P= more effective and faster titration of the antihypertensive agent is possible . The alarm criteria chosen were useful to improve BP control ",
"BACKGROUND Drawing on previous web-based diabetes management programs based on the Chronic Care Model , we exp and ed an intervention to include care management through mobile phones and a game console web browser . METHODS The pilot intervention enrolled eight diabetes patients from the University of Washington in Seattle into a collaborative care program : connecting them to a care provider specializing in diabetes , providing access to their full electronic medical record , allowing wireless glucose uploads and e-mail with providers , and connecting them to the program 's web services through a game system . To evaluate the study , we conducted qualitative thematic analysis of semistructured interviews . RESULTS Participants expressed frustrations with using the cell phones and the game system in their everyday lives , but liked the wireless system for collaborating with a provider on uploaded glucoses and receiving automatic feedback on their blood sugar trends . A majority of participants also expressed that their participation in the trial increased their health awareness . DISCUSSION Mobile communication technologies showed promise within a web-based collaborative care program for type 2 diabetes . Future intervention design should focus on integrating easy-to-use applications within mobile technologies already familiar to patients and ensure the system allows for sufficient collaboration with a care provider",
"Blood glucose ( BG ) monitoring ( BGM ) is an important component of diabetes management . New wireless technologies may facilitate BGM and help to optimize glycemic control . We evaluated an integrated wireless approach with and without a motivational game in youth with diabetes . Forty youth , 8 - 18 years old , each received a h and held device fitted with a wireless modem and diabetes data management software , plus a wireless-enabled BG monitor . Half were r and omized to receive the new technologies along with an integrated motivational game in which the participants would guess a BG level following collection of three earlier readings ( Game Group ) . BG data , insulin doses , and carbohydrate intake were displayed graphically prior to the glucose estimation . The other group received the new technologies alone ( Control Group ) . Both groups were instructed to perform BGM four times daily and transmit their data to a central server via the wireless modem . Feasibility of implementation and outcomes were ascertained after 4 weeks . Ninety-three percent of participants successfully transmitted their data wirelessly to the server . The Game Group transmitted significantly more glucose values than the Control Group ( P less hyperglycemia ( glucose > /=13.9 mmol/L or > /=250 mg/dL ) than the Control Group ( P diabetes knowledge over the 4-week trial ( P hemoglobin A1C values pediatric population with diabetes can successfully implement new technologies to facilitate BGM . Use of a motivational game appears to increase the frequency of monitoring , reduce the frequency of hyperglycemia , and improve diabetes knowledge , and may help to optimize glycemic control",
"OBJECTIVE Low-income and minority adolescents are at high risk for poor asthma outcomes , due in part to adherence . We tested acceptability , feasibility , and effect sizes of an adherence intervention for low socioeconomic status ( SES ) minority youth with moderate- and severe-persistent asthma . Design and Methods Single-site r and omized pilot trial : intervention ( n = 12 ; asthma education , motivational interviewing , problem-solving skills training , 1 month cell-phone with tailored text messaging ) versus control ( n = 14 ; asthma education ; cell-phone without tailored messaging ) . Calculated effect-sizes of relative change from baseline ( 1 and 3 months ) . RESULTS Intervention was judged acceptable and feasible by participants . Participants ( 12 - 18 years , mean = 15.1 , SD = 1.67 ) were 76.9 % African-American , 80.7 % public/no insurance . At 1 and 3 months , asthma symptoms ( Cohen 's d 's = 0.40 , 0.96 ) and HRQOL ( PedsQL ™ ; Cohen 's d 's = 0.23 , 1.25 ) had clinical ly meaningful medium to large effect sizes . CONCLUSIONS This intervention appears promising for at-risk youth with moderate- and severe-persistent asthma",
"OBJECTIVE Widespread use of carbohydrate counting is limited by its complex education . In this study we compared a Diabetes Interactive Diary ( DID ) with st and ard carbohydrate counting in terms of metabolic and weight control , time required for education , quality of life , and treatment satisfaction . RESEARCH DESIGN AND METHODS Adults with type 1 diabetes were r and omly assigned to DID ( group A , n = 67 ) or st and ard education ( group B , n = 63 ) and followed for 6 months . A subgroup also completed the SF-36 Health Survey ( SF-36 ) and World Health Organization-Diabetes Treatment Satisfaction Question naire ( WHO-DTSQ ) at each visit . RESULTS Of 130 patients ( aged 35.7 ± 9.4 years ; diabetes duration 16.5 ± 10.5 years ) , 11 dropped out . Time for education was 6 h ( range 2–15 h ) in group A and 12 h ( 2.5–25 h ) in group B ( P = 0.07 ) . A1C reduction was similar in both groups ( group A from 8.2 ± 0.8 to 7.8 ± 0.8 % and group B from 8.4 ± 0.7 to 7.9 ± 1.1 % ; P = 0.68 ) . Nonsignificant differences in favor of group A were documented for fasting blood glucose and body weight . No severe hypoglycemic episode occurred . WHO-DTSQ scores increased significantly more in group A ( from 26.7 ± 4.4 to 30.3 ± 4.5 ) than in group B ( from 27.5 ± 4.8 to 28.6 ± 5.1 ) ( P = 0.04 ) . Role Physical , General Health , Vitality , and Role Emotional SF-36 scores improved significantly more in group A than in group B. CONCLUSIONS DID is at least as effective as traditional carbohydrate counting education , allowing dietary freedom for a larger proportion of type 1 diabetic patients . DID is safe , requires less time for education , and is associated with lower weight gain . DID significantly improved treatment satisfaction and several quality -of-life dimensions ",
"Aim . To compare the effectiveness of antihypertensive treatment based on telemonitoring of home blood pressure ( BP ) and conventional monitoring of office BP . Methods . Hypertensive patients ( n = 236 ) participated in a r and omized , controlled study . In the intervention group , antihypertensive treatment was based on home BP monitoring . BP readings were registered by a PDA and automatically transmitted to a server , by which the patient and doctor could communicate . In the control group , patients received usual care with office visits to adjust antihypertensive treatment as needed . Primary outcome was difference in systolic daytime ambulatory BP monitoring ( ABPM ) change between baseline and 6 months . Results . In both groups , systolic daytime ABPM decreased significantly from baseline to follow‐up . The decrease in systolic daytime ABPM was −11.9 mmHg in the intervention group and −9.6 mmHg in the control group ( mean difference −2.3 [ 95 % CI −6.1 to −1.5 ] , p = 0.225 ) . The likelihood of daytime ABPM normalization was similar in the two groups [ 32/113 ( 28 % ) vs 46/123 ( 37 % ) , p = 0.139 ] . Conclusion . Antihypertensive treatment based on telemonitoring of home BP was as effective as usual monitoring of office BP with regards to reduction of BP . Trial registration : Clinical Trials.gov identifier : NCT00282334",
"The evaluation in real-life setting s of services for the follow-up and control of hypertensive patients is a complex intervention , which still needs analysis of the roles , tasks , and re sources involved in the basic items : patient , healthcare professional , and the interaction between the two . To evaluate the impact of patient-general practitioner ( GP ) short-messages-based interaction , isolated from other items , on the degree of hypertension control in the follow-up of medium-to-low-risk patients in primary care , a r and omized controlled trial has been performed : 38 GPs enrolled 285 hypertensive patients who recorded the results of self-blood-pressure ( BP ) monitoring , heart rate , and body weight , and completed an optional question naire in an identical manner over a six-month period . The telemedicine group ( TmG ) sent the data to a telemedicine-based system that enabled patient-GP interaction ; the control group ( CG ) recorded the data on paper and could only deliver it to their GP personally in the routine visits . In the TmG , the results were better , but not significantly so , for : 1 ) degree of hypertension control , in terms of the percentage of uncontrolled hypertensives at the final visit ( TmG versus CG : 31.7 % versus 35.6 % ; p = 0.47 ) ; 2 ) reduction in hypertension during follow-up , comparing measurements ( performed by a professional ) at the initial and final visits of systolic BP ( 15.5 versus 11.9 ; p = 0.13 ) and diastolic BP ( 9.6 versus 4.4 ; p = 0.40 ) ; and 3 ) adherence to the protocol within compliance levels of interest in a real-life follow-up service : Gt50 % ( 84.8 % versus 73.3 % ) and Gt25 % ( 92.4.8 % versus 75.4 % ) ( p = 0.053 ) . Other factors such as average values of self-measured systolic BP , diastolic BP and heart rate , acceptability of the protocol , and median number of consultations and hospital admissions were similar in both groups . Outcomes show that , taken alone , the patient-GP short-messages-based interaction has very little impact on the degree of hypertension control in patients with this profile . In complex interventions , to discriminate the impact of each of its components in isolation will enable us to design an efficient follow-up service , little dem and ing in terms of healthcare professional dedication , and optimized in other basic aspects",
"OBJECTIVES To investigate the acceptability and feasibility of using short message services ( SMS ) via cell phones to ensure adherence to management prescriptions by diabetic patients . METHODS Type 2 diabetic patients with 5 or more years of diabetes and having HbA1c between 7.0 % to 10 % were r and omized to the control arm ( n = 105 ) to receive st and ard care and to the intervention arm ( SMS , n = 110 ) . Messages in English on principles of diabetes management were sent once in 3 days , the contents and frequencies varied as per the patients ' preferences . The study duration was 1 year . All participants were advised to report for quarterly clinic visits . A comparative assessment of the clinical , biochemical and anthropometric outcomes was made among the groups at the annual visit . RESULTS Annual review was possible in 71 % of intervention group and 63 % of control group . SMS was acceptable to the patients and the median number requested was 2 per week . HbA1c and plasma lipids improved significantly in the SMS group . CONCLUSIONS The pilot study showed that frequent communication via SMS was acceptable to diabetic patients and it helped to improve the health outcomes",
"Background — This study was design ed to determine whether physician-led remote telemedical management ( RTM ) compared with usual care would result in reduced mortality in ambulatory patients with chronic heart failure ( HF ) . Methods and Results — We enrolled 710 stable chronic HF patients in New York Heart Association functional class II or III with a left ventricular ejection fraction ⩽35 % and a history of HF decompensation within the previous 2 years or with a left ventricular ejection fraction ⩽25 % . Patients were r and omly assigned ( 1:1 ) to RTM or usual care . Remote telemedical management used portable devices for ECG , blood pressure , and body weight measurements connected to a personal digital assistant that sent automated encrypted transmission via cell phones to the telemedical centers . The primary end point was death from any cause . The first secondary end point was a composite of cardiovascular death and hospitalization for HF . Baseline characteristics were similar between the RTM ( n=354 ) and control ( n=356 ) groups . Of the patients assigned to RTM , 287 ( 81 % ) were at least 70 % compliant with daily data transfers and no break for > 30 days ( except during hospitalizations ) . The median follow-up was 26 months ( minimum 12 ) , and was 99.9 % complete . Compared with usual care , RTM had no significant effect on all-cause mortality ( hazard ratio , 0.97 ; 95 % confidence interval , 0.67 to 1.41 ; P=0.87 ) or on cardiovascular death or HF hospitalization ( hazard ratio , 0.89 ; 95 % confidence interval , 0.67 to 1.19 ; P=0.44 ) . Conclusions — In ambulatory patients with chronic HF , RTM compared with usual care was not associated with a reduction in all-cause mortality . Clinical Trial Registration : — URL : http://www . Clinical Trials.gov . Unique identifier : NCT00543881",
"Background Guidelines for optimizing type 1 diabetes in young people advocate intensive insulin therapy coupled with personal support from the health care team . “ Sweet Talk ” is a novel intervention design ed to support patients between clinic visits using text messages sent to a mobile phone . Scheduled messages are tailored to patient profiles and diabetes self-management goals , and generic messages include topical “ newsletters ” and anonymized tips from other participants . The system also allows patients to su bmi t data and questions to the diabetes care team . Objectives The aim was to explore how patients with type 1 diabetes interact with the Sweet Talk system in order to underst and its utility to this user group . Methods Subjects were 64 young people with diabetes who were participating in the intervention arms of a r and omized controlled trial . All text messages su bmi tted to Sweet Talk during a 12-month period were recorded . Messaging patterns and content were analyzed using mixed quantitative and qualitative methods . Results Patients su bmi tted 1180 messages during the observation period ( mean 18.4 , median 6 ) . Messaging frequency ranged widely between participants ( 0 - 240 ) with a subset of 5 high users contributing 52 % of the total . Patients ’ clinical and sociodemographic characteristics were not associated with total messaging frequency , although girls sent significantly more messages unrelated to diabetes than did boys ( P = .002 ) . The content of patients ’ messages fell into 8 main categories : blood glucose readings , diabetes questions , diabetes information , personal health administration , social messages , technical messages , message errors , and message responses . Unprompted su bmi ssion of blood glucose values was the most frequent incoming message type ( 35 % of total ) . Responses to requests for personal experiences and tips generated 40 % of all the incoming messages , while topical news items also generated good responses . Patients also used the service to ask questions , su bmi t information about their self-management , and order supplies . No patients nominated supporters to receive text messages about their self-management goals . Another option that was not used was the birthday reminder service . Conclusions Automated , scheduled text messaging successfully engaged young people with diabetes . While the system was primarily design ed to provide “ push ” support to patients , su bmi ssion of clinical data and queries illustrates that it was seen as a trusted medium for communicating with care providers . Responses to the newsletters and su bmi ssion of personal experiences and tips for circulation to other participants also illustrate the potential value of such interventions for establishing a sense of community . Although participants su bmi tted relatively few messages , positive responses to the system suggest that most derived passive support from reading the messages . The Sweet Talk system could be readily adapted to suit other chronic disease models and age groups , and the results of this study may help to inform the design of future text message support interventions",
"OBJECTIVE Mobile phone short message service ( SMS ) has been suggested as a potentially powerful tool to improve asthma outcomes , and it can overcome external barriers such as time and distance to participate education programs . We wanted to know whether SMS can help to overcome intrinsic barriers such as perceived control of asthma ( PCA ) . SUBJECTS AND METHODS One hundred fifty out patients with asthma were r and omly assigned to the control , traditional , and SMS groups . Patients in all groups received verbal education based on the Global Initiative for Asthma , and patients in the traditional group received additional individualized asthma action plan for self-management with peak expiratory flow monitoring and recording asthma diary , while patients in the SMS group received additional daily SMS reminders on their mobile phone . The six-item PCA Question naire ( PCAQ-6 ) , St and ard Asthma-Specific Quality of Life [ AQLQ(S ) ] , spirometry , blood and induced sputum cell count , follow-up compliance rate , medicine compliance rate , and emergency department ( ED ) visits data were collected at the initial visit and at 12 weeks . RESULTS In total , 71 participants completed the trial for analysis . Patients ' PCAQ-6 score was significantly increased in the SMS and traditional groups ( p of patients ' PCAQ-6 score in the SMS group was higher than in the traditional group ( p=0.018 ) . Patients in the SMS group had the highest AQLQ(S ) score and follow-up rate after 12 weeks . The change in PCAQ-6 score was associated with change in AQLQ(S ) score ( r=0.442 ) . Patients in all groups had better forced expiratory volume in 1 s ( FEV1 % ) and fewer ED visits after 12 weeks , but no significant differences were found among the three groups in the changes of FEV1 % and blood and induced sputum eosinophil counts and neutrophil counts . CONCLUSIONS SMS can improve PCA , and it has a greater advantage in improving follow-up rate and asthma-specific quality of life than traditional programs",
"Background Previous trials of telemonitoring for heart failure management have reported inconsistent results , largely due to diverse intervention and study design s. Mobile phones are becoming ubiquitous and economical , but the feasibility and efficacy of a mobile phone-based telemonitoring system have not been determined . Objective The objective of this trial was to investigate the effects of a mobile phone-based telemonitoring system on heart failure management and outcomes . Methods One hundred patients were recruited from a heart function clinic and r and omized into telemonitoring and control groups . The telemonitoring group ( N = 50 ) took daily weight and blood pressure readings and weekly single-lead ECGs , and answered daily symptom questions on a mobile phone over 6 months . Readings were automatically transmitted wirelessly to the mobile phone and then to data servers . Instructions were sent to the patients ’ mobile phones and alerts to a cardiologist ’s mobile phone as required . Results Baseline question naires were completed and returned by 94 patients , and 84 patients returned post- study question naires . About 70 % of telemonitoring patients completed at least 80 % of their possible daily readings . The change in quality of life from baseline to post- study , as measured with the Minnesota Living with Heart Failure Question naire , was significantly greater for the telemonitoring group compared to the control group ( P = .05 ) . A between-group analysis also found greater post- study self-care maintenance ( measured with the Self-Care of Heart Failure Index ) for the telemonitoring group ( P = .03 ) . Brain natriuretic peptide ( BNP ) levels , self-care management , and left ventricular ejection fraction ( LVEF ) improved significantly for both groups from baseline to post- study , but did not show a between-group difference . However , a subgroup within-group analysis using the data from the 63 patients who had attended the heart function clinic for more than 6 months revealed the telemonitoring group had significant improvements from baseline to post- study in BNP ( decreased by 150 pg/mL , P = .02 ) , LVEF ( increased by 7.4 % , P = .005 ) and self-care maintenance ( increased by 7 points , P = .05 ) and management ( increased by 14 points , P = .03 ) , while the control group did not . No differences were found between the telemonitoring and control groups in terms of hospitalization , mortality , or emergency department visits , but the trial was underpowered to detect differences in these metrics . Conclusions Our findings provide evidence of improved quality of life through improved self-care and clinical management from a mobile phone-based telemonitoring system . The use of the mobile phone-based system had high adherence and was feasible for patients , including the elderly and those with no experience with mobile phones . Trial Registration Clinical Trials.gov",
"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",
"Background Persistently poor glycemic control in adult type 1 diabetes patients is a common , complex , and serious problem initiating significant damage to the cardiovascular , renal , neural , and visual systems . Currently , there is a plethora of low-cost and free diabetes self-management smartphone applications available in online stores . Objective The aim of this study was to examine the effectiveness of a freely available smartphone application combined with text-message feedback from a certified diabetes educator to improve glycemic control and other diabetes-related outcomes in adult patients with type 1 diabetes in a two-group r and omized controlled trial . Methods Patients were recruited through an online type 1 diabetes support group and letters mailed to adults with type 1 diabetes throughout Australia . In a 6-month intervention , followed by a three-month follow-up , patients ( n=72 ) were r and omized to usual care ( control group ) or usual care and the use of a smartphone application ( Glucose Buddy ) with weekly text-message feedback from a Certified Diabetes Educator ( intervention group ) . All outcome measures were collected at baseline and every three months over the study period . Patients ’ glycosylated hemoglobin levels ( HbA1c ) were measured with a blood test and diabetes-related self-efficacy , self-care activities , and quality of life were measured with online question naires . Results The mean age of patients was 35.20 years ( SD 10.43 ) ( 28 male , 44 female ) , 39 % ( 28/72 ) were male , and patients had been diagnosed with type 1 diabetes for a mean of 18.94 years ( SD 9.66 ) . Of the initial 72 patients , 53 completed the study ( 25 intervention , 28 control group ) . The intervention group significantly improved glycemic control ( HbA1c ) from baseline ( mean 9.08 % , SD 1.18 ) to 9-month follow-up ( mean 7.80 % , SD 0.75 ) , compared to the control group ( baseline : mean 8.47 % , SD 0.86 , follow-up : mean 8.58 % , SD 1.16 ) . No significant change over time was found in either group in relation to self-efficacy , self-care activities , and quality of life . Conclusions In adjunct to usual care , the use of a diabetes-related smartphone application combined with weekly text-message support from a health care professional can significantly improve glycemic control in adults with type 1 diabetes . Trial Registration Australian New Zeal and Clinical Trials Registry : ACTRN12612000132842 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?ACTRN=12612000132842 ( Archived by WebCite at http://www.webcitation.org/6Kl4jqn5u )",
"OBJECTIVE Investigate the effectiveness of an educational intervention that used both the cellular phone with a short messaging service ( SMS ) and the Internet on the glycemic control of the patients with type 2 diabetes mellitus . METHODS Twenty-five patients were r and omly assigned to an intervention group and twenty-six to a control group . The intervention was applied for 12 months . The goal of the intervention was to keep blood glucose concentrations close to the normal range ( HbA(1)c access a website by using a cellular phone or to wiring the Internet and input their blood glucose levels weekly . Participants were sent the optimal recommendations by both cellular phone and the Internet weekly . RESULTS Participants in the intervention group had lower HbA(1)c over 12 months when compared with the control group . At 12 months the change from baseline in HbA(1)c was -1.32 in the intervention group versus + 0.81 in the control group . Two hours post-meal glucose ( 2HPMG ) had a significantly greater decline in the intervention group after 12 months when compared with the control group ( -100.0 versus + 18.1mg/dl ) . CONCLUSION This educational intervention using the Internet and a SMS by cellular phone rapidly improved and stably maintained the glycemic control of the patients with type 2 diabetes mellitus",
"Low-income , racial/ethnic minorities are often nonadherent to diabetes medications , have uncontrolled glycemia , and have high rates of diabetes-related morbidity . Cell phones provide a viable modality to support medication adherence , but few cell phone-based interventions have been design ed for low-income persons , a population with more feature phone penetration than smartphone penetration . In an effort to reach the broadest range of patients , we leveraged the voice and text messaging capabilities shared by all cell phones to design the MEssaging for Diabetes intervention . We specifically advanced and adapted an existing tailored text messaging system to include interactive voice response functionality and support the medication adherence barriers of low-income , diverse adults with type 2 diabetes mellitus . We report on the design process and feasibility testing results ( i.e. , technical use patterns and subjective user experiences ) from patients from the target population who used the intervention in one of three user-centered design iterations . The types of challenges encountered in design were related to providing text message content with valued information and support that engages patients . The design process also highlighted the value of obtaining mixed methods data to provide insight into legitimate versus illegitimate missing data , patterns of use , and subjective user experiences . The iterative testing process and results outlined here provide a potential template for other teams seeking to design technology-based self-care support solutions for comparable patient population",
"Background : Medication non-adherence leads to a vast range of negative outcomes in patients with coronary artery disease . An automated web-based system managing short message service ( SMS ) reminders is a telemedicine approach to optimise adherence among patients who frequently forget to take their medications or miss the timing . Aim : This paper sought to investigate the effect of automated SMS-based reminders on medication adherence in patients after hospital discharge following acute coronary syndrome ( ACS ) . Methods : An interventional study was conducted at a tertiary teaching hospital in Malaysia . A total of 62 patients with ACS were equally r and omised to receive either automated SMS reminders before every intake of cardiac medications or only usual care within eight weeks after discharge . The primary outcome was adherence to cardiac medications . Secondary outcomes were the heart functional status , and ACS-related hospital readmission and death rates . Results : There was a higher medication adherence level in the intervention group rather than the usual care group , ( χ2 (2)=18.614 , p of being low adherent among the control group was 4.09 times greater than the intervention group ( relative risk = 4.09 , 95 % confidence interval ( CI ) 1.82–9.18 ) . A meaningful difference was found in heart functional status between the two study groups with better results among patients who received SMS reminders , ( χ2 ( 1 ) = 16.957 , p automated SMS-based reminder system can potentially enhance medication adherence in ACS patients during the early post-discharge period",
" A total of 175 patients with Types 1 and 2 diabetes in primary care and university hospital outpatient departments were r and omized into a study group ( n = 101 ) or usual care ( n = 74 ) . The study group used an e-health application with a diabetes management system and a home care link . Usual care did not involve e-health , i.e. the patients made regular general practitioner visits about every three months . After 12 months HbA1c decreased significantly in both groups of patients . The differences were small , but HbA1c was significantly lower in the study group than the controls . Diastolic blood pressure , fasting plasma glucose , serum total cholesterol , serum LDL-cholesterol and serum triglycerides were significantly lower in the study than in the control group . This was achieved with fewer visits by study patients to doctors and nurses . Use of e-health in diabetes care for 12 months was able to provide equivalent diabetic control to usual care , and improved cardiovascular risk factors",
"BACKGROUND Hypertension is a major risk factor for the long-term complications of diabetes . Mobile , self-measurement of blood pressure is emerging as a method to manage blood pressure in general , but its impact in patients with diabetes is unclear . METHODS We r and omized 137 patients with diabetes and hypertension to either mobile telemonitoring ( n = 72 ) or usual care ( n = 65 ) . Clinic blood pressure was recorded at baseline and after 6 months . Patients in the intervention arm transmitted weekly blood pressure readings wirelessly , using adapted sensors via mobile phones to a central server . Clinicians received the data in real-time and using a web-based application provided management advice to the patient and their physicians . RESULTS Systolic blood pressure fell significantly in the patients in the intervention group ( mean [ 95 % confidence interval ] , -6.5 [ -0.8 to -12.2 ] mm Hg ; P = 0.027 ) and remained unchanged in the control group ( 2.1 [ 9.3 to -5.0 ] mm Hg ; P = 0.57 ) . Patients within the intervention arm of African origin seemed to benefit more from the intervention . In addition , those who achieved a systolic blood pressure of average blood sugars than those with higher readings ( 7.8 [ SD 1.6 ] vs. 8.9 [ SD 2.2 ] mmol/L ; P = 0.02 ) . CONCLUSIONS In patients with diabetes , mobile telemonitoring has potential for delivering intensified care to improve blood pressure control , and its use may be associated with reduced exposure to hyperglycemia",
"A mobile phone with a glucometer integrated into the battery pack ( the ‘ Diabetes Phone ’ ) was launched in Korea in 2003 . We compared its effect on management of type 2 diabetes to the Internet-based glucose monitoring system ( IBGMS ) , which had been studied previously . We conducted a r and omized trial involving 69 patients for three months . Participants were assigned to an Internet group or a phone group . The phone group communicated with medical staff through the mobile phone only . Their glucose-monitoring data were automatically transferred to individual , web-based charts and they received medical recommendations by short message service . The Internet group used the IBGMS . There were no significant differences between the groups at baseline . After three months ' intervention , HbA1c levels of both groups had decreased significantly , from 7.6 % to 6.9 % for the Internet group and from 8.3 % to 7.1 % for the phone group ( P Levels of patient satisfaction and adherence to medical advice were similar . Mobile , bidirectional communication between doctors and patients using the diabetes phone was as effective for glucose control as the previously-studied Internet-based monitoring system and it was good for patient satisfaction and adherence",
"Purpose . This pilot study assessed the feasibility , acceptability , and utility of a text messaging system that allowed teenagers with asthma to generate and control medical reminders sent to their mobile phones . Methods . The 12 teens in the study group were able to create their own reminder text messages , add or change reminders , and determine when and how often the messages were sent to their cell phone . Results . In total , 18 of the 21 unique messages created were reminders to take medication . No teen made changes to their original text messages or delivery schedule on their own . They gave high ratings on the usefulness , acceptability , and ease of use of the text messaging system . Self-reported asthma control at baseline was similar for both the study and comparison groups and did not change significantly . Conclusions . Allowing teens to control the timing and content of reminder text messages may support self-management of chronic disease",
"AIMS The rapidly increasing prevalence of chronic diseases is an important challenge to healthcare systems worldwide . To improve the quality and efficiency of chronic disease care , we investigated the effectiveness and applicability of the Ubiquitous Chronic Disease Care ( UCDC ) system using cellular phones and the internet for overweight patients with both Type 2 diabetes and hypertension . METHODS We conducted a r and omized , controlled clinical trial over 3 months that included 123 patients at a university hospital and a community public health centre . RESULTS After 12 weeks , there were significant improvements in HbA(1c ) in the intervention group ( 7.6 + /- 0.9 % to 7.1 + /- 0.8 % , P systolic and diastolic blood pressure , as well as improvements in total cholesterol , low-density lipoprotein-cholesterol and triglyceride levels in the intervention group . Furthermore , there was a significant increase in adiponectin levels in the intervention group compared with the control group , although high-sensitivity C-reactive protein and interleukin-6 levels did not change in either group . CONCLUSIONS The novel UCDC system presented in this paper improved multiple metabolic parameters simultaneously in overweight patients with both Type 2 diabetes and hypertension",
"Background : Telehealth-supported clinical interventions may improve diabetes self-management . We explored the feasibility of stepwise self-titration of oral glucose-lowering medication guided by a mobile telephone-based telehealth platform for improving glycemic control in type 2 diabetes . Methods : We recruited 14 type 2 diabetes patients to a one-year feasibility study with 1:1 r and omization . Intervention group patients followed a stepwise treatment plan for titration of oral glucose-lowering medication with self-monitoring of glycemia using real-time graphical feedback on a mobile telephone and remote nurse monitoring using a Web-based tool . We carried out an interim analysis at 6 months . Results : We screened 3476 type 2 diabetes patients ; 94 % of the ineligible did not meet the eligibility criteria for hemoglobin A1c ( HbA1c ) or current treatment . Mean ( st and ard deviation ) patient age at baseline was 58 ( 11 ) years , HbA1c was 65 ( 12 ) mmol/mol ( 8.1 % [ 1.1 % ] ) , body mass index was 32.9 ( 6.4 ) kg/m2 , median [ interquartile range ( IQR ) ] diabetes duration was 2.6 ( 0.6 to 4.7 ) years , and 10 ( 71 % ) were men . The median ( IQR ) change in HbA1c from baseline to six months was −10 ( −21 to 3 ) mmol/mol ( −0.9 % [ -1.9 % to 0 % ] ) in the intervention group and −5 ( −13 to 6 ) mmol/mol ( −0.5 % [ -1.2 % to 0.6 % ] ) in the control group . Six out of seven intervention group patients and four out of seven control group patients changed their oral glucose-lowering medication ( p = .24 ) . Conclusions : Self-titration of oral glucose-lowering medication in type 2 diabetes with self-monitoring and remote monitoring of glycemia is feasible , and further studies using adapted recruitment strategies are required to evaluate whether it improves clinical outcomes ",
"BACKGROUND Cell phone text messaging , via the Short Messaging Service ( SMS ) , offers the promise of a highly portable , well-accepted , and inexpensive modality for engaging youth and young adults in the management of their diabetes . This pilot and feasibility study compared two-way SMS cell phone messaging with e-mail reminders that were directed at encouraging blood glucose ( BG ) monitoring . METHODS Forty insulin-treated adolescents and young adults with diabetes were r and omized to receive electronic reminders to check their BG levels via cell phone text messaging or e-mail reminders for a 3-month pilot study . Electronic messages were automatically generated , and participant replies with BG results were processed by the locally developed Computerized Automated Reminder Diabetes System ( CARDS ) . Participants set their schedule for reminders on the secure CARDS website where they could also enter and review BG data . RESULTS Of the 40 participants , 22 were r and omized to receive cell phone text message reminders and 18 to receive e-mail reminders ; 18 in the cell phone group and 11 in the e-mail group used the system . Compared to the e-mail group , users in the cell phone group received more reminders ( 180.4 vs. 106.6 per user ) and responded with BG results significantly more often ( 30.0 vs. 6.9 per user , P = 0.04 ) . During the first month cell phone users su bmi tted twice as many BGs as e-mail users ( 27.2 vs. 13.8 per user ) ; by month 3 , usage waned . CONCLUSIONS Cell phone text messaging to promote BG monitoring is a viable and acceptable option in adolescents and young adults with diabetes . However , maintaining interest levels for prolonged intervals remains a challenge",
"Background : This study examined whether mobile phone-based , one-way video messages about diabetes self-care improve hemoglobin A1c ( A1C ) and self-monitoring of blood glucose ( SMBG ) . Methods : This was a 1-year prospect i ve r and omized trial with two groups . The active intervention lasted 6 months . The study enrolled 65 people with A1C > 8.0 % who were established ( > 6 months ) patients in the endocrinology clinics of the Walter Reed Health Care System . Participants were r and omized to receive “ usual care ” or self-care video messages from their diabetes nurse practitioner . Video messages were sent daily to cell phones of study participants . Hemoglobin A1c and SMBG data were collected at 0 , 3 , 6 , 9 , and 12 months . Results : Participants who received the messages had a larger rate of decline in A1C than people who received usual care ( 0.2 % difference over 12 months , adjusting for covariates ; p = .002 and p = .004 for the interaction between time and group and for the quadratic effect of time by group , respectively ) . Hemoglobin A1c decline was greatest among participants who received video messages and viewed > 10 a month ( 0.6 % difference over 12 months , adjusting for covariates ; p Self-monitoring of blood glucose metrics were not related to the intervention . Conclusions : A one-way intervention using mobile phone-based video messages about diabetes self-care can improve A1C . Engagement with the technology is an important predictor of its success . This intervention is simple to implement and sustain",
"AIM Conventional follow-up of type 1 diabetic patients treated with continuous subcutaneous insulin infusion ( CSII ) was compared with intensive coaching using the Web and the cellular phone network for retrospective data transmission and short message service ( SMS ) . METHODS Thirty poorly controlled patients ( HbA1c 7.5 - 10 % ) were enrolled in a bicenter , open-label , r and omized , 12-month , two-period , crossover study . After a 1-month run-in period , 15 patients were r and omly assigned to receive weekly medical support through SMS based upon weekly review of glucose values , while 15 patients continued to download self-monitored blood glucose ( SMBG ) values on a weekly basis without receiving SMS . After 6 months , patients crossed over to the alternate sequence for 6 additional months . Visits at the clinic were maintained every 3 months . RESULTS Patients with long-st and ing inadequately controlled diabetes ( 24 + /- 13 years ) were included . A non-significant trend to reduction in HbA(1c ) ( -0.25+/-0.94 % , P mean glucose values ( -9.2+/-25 mg/dl , P=0.06 ) during the 6-month SMS sequence was observed as compared with the no-SMS period . No safety issue ( hypoglycemia , glucose variability ) was reported . Adherence to SMBG was not affected by the trial . Quality of life analysis suggests a significant improvement in DQOL global score , as well as the DQOL satisfaction with life subscale , during the SMS sequence . CONCLUSIONS Long-term telemedical follow-up of insulin pump-treated patients using a cellular phone- , SMS- and Web-based platform is feasible , safe , does not alter quality of life and associated with a trend toward improved metabolic control",
"Background : The benefit of mobile health ( mHealth ) on diabetes management among low-income , inner-city patients is largely unknown , particularly for Latino patients . TExT-MED ( Trial to Examine Text Message for Emergency Department Patients with Diabetes ) is a text message-based program design ed to improve disease knowledge , self-efficacy , and glycemic control among low-income , inner-city Latinos . In phase I , 23 patients participated in an acceptability and feasibility study . Contrary to our model , there was no increase in knowledge despite increases in self-efficacy and healthy behaviors . In phase II , we performed a mixed- methods analysis to underst and how TExT-MED achieved these seemingly contradictory findings . Method : We performed a qualitative analysis of focus groups with patients from phase I. We explored patients ' receipt of health information from TExT-MED and other information sources . We used these qualitative findings to perform a mixed- methods analysis of the outcomes from phase I , reanalyzing the quantitative measures of self-efficacy , diabetes knowledge , and healthy behaviors . Results : We conducted two focus groups , one in English and one in Spanish . Through qualitative analysis , we found gender differences in information sources , dietary self-efficacy , and desired educational content . Applying this knowledge , we re-stratified phase I outcomes by gender and found differential changes in diabetes knowledge , self-efficacy , and behaviors . Men had increased self-efficacy while women showed increased knowledge . Conclusions : The efficacy of mHealth on diabetes management was affected by gender . Specifically , men and women differ in their dietary self-efficacy , information sources , and desired topics in future mHealth interventions . To achieve maximal impact , future mHealth interventions should be mindful of this gender difference",
"BACKGROUND Missed scheduled HIV appointments lead to increased mortality , resistance to antiretroviral therapy , and suboptimum virological response . We aim ed to assess whether reminders sent to carers by text message , mobile phone call , or concomitant text message and mobile phone call increase attendance at medical appointments for HIV care in a population of children infected with or exposed to HIV in Cameroon . We also aim ed to ascertain the most cost-effective method of mobile-phone-based reminder . METHODS MORE CARE was a multicentre , single-blind , factorial , r and omised controlled trial in urban , semi-urban , and rural setting s in Cameroon . Carers of children who were infected with or had been exposed to HIV were r and omly assigned electronically in blocks of four and allocated ( 1:1:1:1 ) sequentially to receive a text message and a call , a text message only , a call only , or no reminder ( control ) . Investigators were masked to group assignment . Text messages were sent and calls made 2 or 3 days before a scheduled follow-up appointment . The primary outcomes were efficacy ( the proportion of patients attending a previously scheduled appointment ) and efficiency ( attendance/ [ measures of staff working time × cost of the reminders ] ) , as a measure of cost-effectiveness . The primary analysis was by intention to treat . This study is registered with the Pan African Clinical Trials Register , number PACTR201304000528276 . FINDINGS The study took place between Jan 28 and May 24 , 2013 . We r and omly assigned 242 adult-child ( carer-patient ) pairs into four groups : text message plus call ( n=61 ) , call ( n=60 ) , text message ( n=60 ) , and control ( n=61 ) . 54 participants ( 89 % ) in the text message plus call group , 51 ( 85 % ) in the call group , 45 ( 75 % ) in the text message group , and 31 ( 51 % ) in the control group attended their scheduled appointment . Compared with control , the odds ratios for improvement in the primary efficacy outcome were 7·5 ( 95 % CI 2·9 - 19·0 ; p the primary efficiency outcome , the mean difference for text message versus text message plus call was 1·5 ( 95 % CI 0·7 to 2·4 ; p=0·002 ) , for call versus text message plus call was 1·2 ( 0·7 to 1·6 ; p carers of paediatric patients in low-re source setting s can increase attendance . The most effective method of reminder was text message plus phone call , but text messaging alone was the most efficient ( ie , cost-effective ) method . FUNDING No external funding",
"We have evaluated the feasibility of using the mobile phone short message service ( SMS ) for symptom monitoring in patients with asthma . All consecutive patients admitted to hospital for asthma during an 11-month period were considered for enrolment ( n = 497 ) . Those meeting the inclusion criteria were r and omized into a control ( n = 60 ) and intervention group ( n = 60 ) . Patients in the intervention group received SMS messages according to a structured workflow , while patients in the control group had no SMS support . In the intervention group , the mean response rate to the messages was 82 % . There was an improvement in the Asthma Control Test ( ACT ) scores in 36 subjects in the intervention group compared to 28 subjects in the control group . There were reductions in the number of nebulizations in 54 subjects in the control group compared to 50 subjects in the intervention group , and reductions in emergency department visits in 57 subjects in the control group compared to 51 subjects in the intervention group . However , none of these differences were significant . There was no reduction in admission rates in either group ( P = 0.5 ) . The service was accepted by most patients , but its long-term effectiveness on the management of asthma remains to be determined",
"RATIONALE , AIMS AND OBJECTIVES Utilizing information technology , such as Internet and cellphones , holds great promise in enhancing diabetic care . Yet few studies have examined the impact of cellphone technology on type 2 diabetics ' self-care . The primary aim of the study is to examine the feasibility of utilizing this technology to assist with diabetes self-care in a clinic population as well as its impact on clinical outcomes . METHODS Thirty patients with a diagnosis of type 2 diabetes at two Community Health Centers were r and omized to intervention or control . Intervention patients participated in a brief intervention and received tailored daily messages via cellphone prompting them to enhance their diabetic self-care behaviour . Patients at the control site continued with their st and ard diabetes self-management . RESULTS A mean improvement in HbA1c levels was apparent ( -0.1 , SD = 0.3 % ; P = 0.1534 ) in the intervention group , compared with a mean deterioration in the control ( 0.3 , SD = 1.0 % ; P = 0.3813 ) , yet without statistical significance . Self-efficacy scores improved significantly in the intervention group ( -0.5 , SD = 0.6 ; P = 0.0080 ) compared with no improvement in the control ( 0.0 , SD = 1.0 ; P = 0.9060 ) . Participants encountered numerous technological barriers when attempting to adhere to the intervention protocol . CONCLUSION The results indicate the intervention had a positive impact on some clinical outcome and self-efficacy . Although the technology appears feasible in a clinical setting technology must be made more user-friendly before a larger phase II trial is conducted",
"OBJECTIVE Pharmacologic treatment for secondary prevention of coronary heart disease ( CHD ) is critical to prevent adverse clinical outcomes . In a r and omized controlled trial , we compared antiplatelet and statin adherence among patients with CHD who received : ( 1 ) text messages ( TM ) for medication reminders and education , ( 2 ) educational TM only , or ( 3 ) No TM . METHODS A mobile health intervention delivered customized TM for 30 days . We assessed and analyzed medication adherence with electronic monitoring devices [ Medication Event Monitoring System ( MEMS ) ] by one-way ANOVA and Welch tests , two-way TM response rates by t-tests , and self-reported adherence ( Morisky Medication Adherence Scale ) by Repeated Measures ANOVA . RESULTS Among 90 patients ( 76 % male , mean age 59.2 years ) , MEMS revealed patients who received TM for antiplatelets had a higher percentage of correct doses taken ( p=0.02 ) , percentage number of doses taken ( p=0.01 ) , and percentage of prescribed doses taken on schedule ( p=0.01 ) . TM response rates were higher for antiplatelets than statins ( p=0.005 ) . Self-reported adherence revealed no significant differences among groups . CONCLUSION TM increased adherence to antiplatelet therapy demonstrated by MEMS and TM responses . PRACTICE IMPLICATION S Feasibility and high satisfaction were established . Mobile health interventions show promise in promoting medication adherence",
"BACKGROUND Poor adherence to oral antidiabetics has a negative influence on glycaemic control in type 2 diabetes patients . Real Time Medication Monitoring ( RTMM ) combines real time monitoring of patients ' medication use with SMS reminders sent only if patients forget their medication , aim ing to improve adherence . This study aim ed to investigate the effect of these SMS reminders on adherence to oral antidiabetics in patients using RTMM and investigate patients ' experiences with RTMM . METHODS Data were collected in a RCT involving 104 type 2 diabetes patients with suboptimal adherence to oral antidiabetics . Fifty-six patients were r and omised to receive SMS reminders if they forgot their medication , 48 patients received no reminders . Primary outcome measure was adherence to oral antidiabetics registered with RTMM , measured as : ( 1 ) days without dosing ; ( 2 ) missed doses ; ( 3 ) doses taken within predefined st and ardized time windows . Patients ' experiences were assessed with written question naires . RESULTS Over the six-month study period , patients receiving SMS reminders took significantly more doses within predefined time windows than patients receiving no reminders : 50 % vs. 39 % within a 1-h window ( p=0.003 ) up to 81 % vs. 70 % within a 4-h window ( p=0.007 ) . Reminded patients tended to miss doses less frequently than patients not reminded ( 15 % vs. 19 % , p=0.065 ) . Days without dosing were not significantly different between the groups . The majority of patients reported positive experiences with RTMM and SMS reminders . CONCLUSION RTMM with SMS reminders improves adherence of type 2 diabetes patients , especially the precision with which patients follow their prescribed regimen , and is well accepted by patients . TRIAL REGISTRATION Netherl and s Trial Register NTR1882",
"Background Self-management of asthma may improve asthma outcomes . The Internet has been suggested as a tool for the monitoring and self-management of asthma . However , in a recent study we found that a Web interface had some disadvantages and that users stopped using the application after a short while . Objective The primary objective of this study was to evaluate , from a user perspective , the feasibility of using short message service ( SMS ) for asthma diary data collection through mobile phones . The secondary objective was to investigate patient compliance with an SMS diary , as measured by response rates over time . Methods The study included quantitative response rate data , based on SMS collection , and qualitative data from a traditional focus group setting . In a period of 2 months , the participants received 4 SMS messages each day , including a medication reminder , a request to enter peak flow , data on sleep loss , and medication dosage . Participants were asked to reply to a minimum of 3 of the messages per day . Diary inputs were collected in a data base and the response rate per patient was expressed as the number of diary inputs ( SMS replies ) divided by diary requests ( product of number of days in the study and the number of diary questions per day ) for each participant . After the study period , the participants were invited to a focus group interview addressing the participants ' attitudes to their disease , their experience with the SMS asthma diary , and their future expectations from the SMS asthma diary . Results Twelve patients with asthma ( 6 males , 6 females ) participated in the data collection study . The median age was 38.5 ( range : 13 – 57 ) years . The median response rate per patient was 0.69 ( range : 0.03 – 0.98 ) , ie , half the participants reported more than about two thirds of the requested diary data . Furthermore , response rates were relatively steady during the study period with no signs of decreasing usage over time . From the subsequent focus group interview with 9 users we learned that , in general , the participants were enthusiastic about the SMS diary – it became an integrated part of their everyday life . However , the participants wished for a simpler diary with only one SMS message to respond to and a system with a Web interface for system customization and graphical display of diary data history . Conclusion This study suggests that SMS collection of asthma diary data is feasible , and that SMS may be a tool for supporting the self-management of asthma ( and possibly other chronic diseases ) in motivated and self-efficacious patients because mobile phones are a part of people 's everyday lives and enable active requests for data wherever the patient is . The combination of SMS data collection and a traditional Web page for data display and system customization may be a better and more usable tool for patients than the use of Web-based asthma diaries which suffer from high attrition rates",
"Abstract We investigated the effectiveness of a workplace intervention program that utilized self-monitoring of daily salt excretion by an electronic salt sensor and sent personalized e-mail advice via cellular phone . Forty-one hypertensive male workers were assigned to intervention and control groups , then counseled together . Intervention group members were asked to measure daily salt excretion and received e-mail advice . After 4 weeks , a greater decrease of blood pressure ( BP ) was observed in the intervention group , with significant reductions to daily salt excretion and home BP . The new intervention program is considered useful for BP control among hypertensive workers",
"Home peak expiratory flow ( PEF ) measurement is recommended by asthma guidelines . In a 16-week r and omized controlled study on 16 subjects with asthma ( 24.6 6.5 years old , asthma duration small ze , Cyrillic 6 months ) , we examined Global System for Mobile Communications ( GSM ) mobile telephone short-message service ( SMS ) as a novel means of telemedicine in PEF monitoring . All subjects received asthma education , self-management plan , and st and ard treatment . All measured PEF three times daily and kept a symptom diary . In the study group , therapy was adjusted weekly by an asthma specialist according to PEF values received daily from the patients . There was no significant difference between the groups in absolute PEF , but PEF variability was significantly smaller in the study group ( 16.12 + /- 6.93 % vs. 27.24 + /- 10.01 % , p = 0.049 ) . forced expiratory flow in 1 second ( FEV1 ; % predicted ) in the study group was slightly but significantly increased ( 81.25 + /- 17.31 vs. 77.63 + /- 14.80 , p = 0.014 ) and in the control group , unchanged ( 78.25 + /- 21.09 vs. 78.88 + /- 22.02 , p = 0.497 ) . Mean FEV1 was similar in the two groups both before and after the study . Controls had significantly higher scores for cough ( 1.85 + /- 0.43 vs. 1.42 + /- 0.28 , p night symptoms ( 1.22 + /- 0.23 vs. 0.85 + /- 0.32 , p daily consumption of inhaled medicine , forced vital capacity , or compliance . Per patient , per week , the additional cost of follow-up by SMS was Euros 1.67 ( equivalent to approximately $ 1.30 per 1 Euro ) , and SMS transmission required 11.5 minutes . Although a study group of 40 patients is needed for the follow-up study to achieve the power of 80 % within the 95 % confidence interval , we conclude that SMS is a convenient , reliable , affordable , and secure means of telemedicine that may improve asthma control when added to a written action plan and st and ard follow-up",
"BACKGROUND Aggressive management of blood glucose reduces future diabetes-related complications , but this is difficult to achieve . METHODS This r and omized , controlled study tested the effect of using a wireless two-way pager-based automated messaging system to improve diabetes control through facilitated self-management . The system sent health-related messages to patients , with automatic forwarding of urgent patient responses to the health care team . RESULTS Participants in both the experimental ( pager ) and the control groups experienced an average hemoglobin A1c decrease of 0.1 - 0.3 % . More patients in the pager group were normotensive , and more felt that their health care was better by the end of the study . A total of 79 % of participants enjoyed using the pager , and 68 % wanted to continue using the system . CONCLUSIONS Utilizing a wireless , automated messaging system in clinical practice is a feasible , low-cost , interactive way to facilitate diabetes self-management , which is acceptable to patients . While providing a convenient way for patients and providers to communicate , this system can support automated recording and ready retrieval of these real-time interactions",
"BACKGROUND Less than 63 % of individuals with diabetes meet professional guidelines target of hemoglobin A1c A1c of a cell phone-based diabetes management software system used with web-based data analytics and therapy optimization tools . Secondary aims examined health care provider ( HCP ) adherence to prescribing guidelines and assessed HCPs ' adoption of the technology . METHODS Thirty patients with type 2 diabetes were recruited from three community physician practice s for a 3-month study and evenly r and omized . The intervention group received cell phone-based software design ed by endocrinologists and CDEs ( WellDoc Communications , Inc. , Baltimore , MD ) . The software provided real-time feedback on patients ' blood glucose levels , displayed patients ' medication regimens , incorporated hypo- and hyperglycemia treatment algorithms , and requested additional data needed to evaluate diabetes management . Patient data captured and transferred to secure servers were analyzed by proprietary statistical algorithms . The system sent computer-generated logbooks ( with suggested treatment plans ) to intervention patients ' HCPs . RESULTS The average decrease in A1c for intervention patients was 2.03 % , compared to 0.68 % ( P medications titrated or changed by their HCP compared to controls ( 23 % , P = 0.002 ) . Intervention patients ' HCPs reported the system facilitated treatment decisions , provided organized data , and reduced logbook review time . CONCLUSIONS Adults with type 2 diabetes using WellDoc 's software achieved statistically significant improvements in A1c . HCP and patient satisfaction with the system was clinical ly and statistically significant",
"Background In 2010 , there were approximately 8.8 million incident cases of tuberculosis ( TB ) worldwide . The treatment of TB is at least six months long and may be complicated by a high pill burden . In addition , TB patients often do not take their medication on schedule simply because they forget . Mobile phone text messaging has the potential to help promote TB treatment adherence . We , therefore , propose to conduct a review of current best evidence for the use of mobile phone text messaging to promote patient adherence to TB treatment . Methods This is a systematic review of the literature . We will preferably include r and omized controlled trials ( RCTs ) . However , non-r and omized studies ( NRS ) will be considered if there is an inadequate number of RCTs .We will search PubMed , EMBASE , CINAHL , CENTRAL , Science Citation Index , Africa-Wide Information , and WHOLIS electronic data bases for eligible studies available by 30 November 2012 regardless of language or publication status . We will also check reference lists for additional studies , identify abstract s from conference proceedings and communicate with authors for any relevant material .At least two authors will independently screen search outputs , select studies , extract data and assess the risk of bias ( using separate criteria for RCTs and NRS ) ; resolving discrepancies by discussion and consensus . We will assess clinical heterogeneity by examining the types of participants , interventions and outcomes in each study and pool studies judged to be clinical ly homogenous . We will also assess statistical heterogeneity using the chi-square test of homogeneity and quantify it using the I-square statistic . If study results are found to be statistically homogeneous ( that is heterogeneity P > 0.1 ) , we will pool them using the fixed-effect meta- analysis . Otherwise , we will use r and om-effects meta- analysis . We will calculate risk ratios and their corresponding 95 % confidence intervals for dichotomous outcomes , and mean differences for continuous outcomes . For other outcomes without quantitative data , a descriptive analysis will be used . Discussion Our results can be used by research ers and policy-makers to help inform them of the efficacy of mobile phone text messaging interventions to promote patient adherence to TB treatment",
"BACKGROUND Poor adherence to asthma treatment is a well-recognised challenge and is associated with increased morbidity , mortality and consumption of health care re sources . This study examined the impact of receiving a daily text message reminder on one 's cell phone on adherence to asthma treatment . METHODS A total of 26 subjects aged 18 - 45 years , with a clinical history of asthma and a positive methacholine challenge test ( PD(20) to receive , or to not receive , a daily short message service ( SMS ) reminder on their cell phone to take their anti-asthmatic medication . Inhaled corticosteroids to last for eight weeks and a prescription for four additional weeks were given to the subjects . The primary outcome was adherence to asthma treatment . Secondary outcomes were reimbursement of asthma medication , and change in exhaled nitric oxide levels , lung function , and airway responsiveness . RESULTS The absolute difference in mean adherence rate between the two groups after 12 weeks was 17.8 % , 95 % CI ( 3.2 - 32.3 % ) , p=0.019 . No significant differences were observed between the two r and omisation groups for the secondary outcomes . CONCLUSION Daily text message reminders are already after a short period of observation associated with increased adherence to anti-asthmatic medication",
"STUDY OBJECTIVE Increasingly , low-income inner-city patients with diabetes utilize emergency departments ( EDs ) for acute and chronic care . We seek to determine whether a scalable , low-cost , unidirectional , text message-based mobile health intervention ( TExT-MED ) improves clinical outcomes , increases healthy behaviors , and decreases ED utilization in a safety net population . METHODS We conducted an r and omized controlled trial of 128 adult patients with poorly controlled diabetes ( glycosylated hemoglobin [ Hb A1C ] level ≥8 % ) in an urban , public ED . The TExT-MED group received 2 daily text messages for 6 months in English or Spanish . The primary outcome was change in Hb A1C level . Secondary outcomes included changes in medication adherence , self-efficacy , performance of self-care tasks , quality of life , diabetes-specific knowledge , ED utilization , and patient satisfaction . RESULTS Hb A1C level decreased by 1.05 % in the TExT-MED group compared with 0.60 % in the controls ( Δ0.45 ; 95 % confidence interval [ CI ] -0.27 to 1.17 ) at 6 months . Secondary outcomes favored the TExT-MED group , with the most sizable change observed in self-reported medication adherence ( as measured by the Morisky Medication Adherence Scale , an 8-point vali date d scale with higher scores representing better adherence ) , which improved from 4.5 to 5.4 in the TExT-MED group compared with a net decrease of -0.1 in the controls ( Δ1.1 [ 95 % CI 0.1 to 2.1 ] ) . Effects were larger among Spanish speakers for both medication adherence ( 1.1 versus -0.3 ; Δ1.4 ; 95 % CI 0.2 to 2.7 ) and Hb A1C ( -1.2 % versus -0.4 % ) in the TExT-MED group . The proportion of patients who used emergency services trended lower in the TExT-MED group ( 35.9 % versus 51.6 % ; Δ15.7 % ; 95 % CI 9.4 % to 22 % ) . Overall , 93.6 % of respondents enjoyed TExT-MED and 100 % would recommend it to family/friends . CONCLUSION The TExT-MED program did not result in a statistically significant improvement in Hb A1C . However , trends toward improvement in the primary outcome of Hb A1C and other secondary outcomes , including quality of life , were observed , the most pronounced being improved medication adherence . TExT-MED also decreased ED utilization . These findings were magnified in the Spanish-speaking subgroup . Technologies such as TExT-MED represent highly scalable , low-cost , and widely accessible solutions for safety-net ED population",
"PURPOSE : Efficient ways are needed to implement the secondary prevention ( SP ) of coronary heart disease . Because few studies have investigated Web-based SP programs , our aim was to determine the usefulness of a new Web-based telemonitoring system , connecting patients provided with self-measurement devices and care managers via mobile phone text messages , as a tool for SP . METHODS : A single-blind , r and omized controlled , clinical trial of 203 acute coronary syndrome ( ACS ) survivors , was conducted at a hospital in Madrid , Spain . All patients received lifestyle counseling and usual-care treatment . Patients in the telemonitoring group ( TMG ) sent , through mobile phones , weight , heart rate , and blood pressure ( BP ) weekly , and capillary plasma lipid profile and glucose monthly . A cardiologist accessed these data through a Web interface and sent recommendations via short message service . Main outcome measures were BP , body mass index ( BMI ) , smoking status , low-density lipoprotein-cholesterol ( LDL-c ) , and glycated hemoglobin A1c ( HbA1c ) . RESULTS : At 12-month followup , TMG patients were more likely ( RR = 1.4 ; 95 % CI = 1.1−1.7 ) to experience improvement in cardiovascular risk factors profile than control patients ( 69.6 % vs 50.5 % , P = .010 ) . More TMG patients achieved treatment goals for BP ( 62.1 % vs 42.9 % , P = .012 ) and HbA1c ( 86.4 % vs 54.2 % , P = .018 ) , with no differences in smoking cessation or LDL-c . Body mass index was significantly lower in TMG ( −0.77 kg/m2 vs + 0.29 kg/m2 , P = .005 ) . CONCLUSIONS : A telemonitoring program , via mobile phone messages , appears to be useful for improving the risk profile in ACS survivors and can be an effective tool for secondary prevention , especially for overweight patients",
"Objective : Medication adherence is a complex behavior that is influenced by numerous factors . Applying self-efficacy theory , the primary aim of this r and omized controlled trial was to compare medication self-efficacy among patients with coronary heart disease who received : ( a ) text messages ( TMs ) for medication reminders and education , ( b ) TMs for education , or ( c ) no TMs . The second aim was to identify the personal ( sociodemographic and clinical characteristics ) and psychosocial factors that were associated with and predicted medication adherence . Methods : Customized TMs were delivered over 30 days . Repeated measures analysis of variance was used to analyze medication self-efficacy . A multiple regression analysis was performed at baseline and follow-up to determine variables that were associated with and predicted self-reported medication adherence . Results : Among 90 subjects with mean age 59.2 years ( st and ard deviation ( SD ) 9.4 , range 35–83 ) , total scores for medication self-efficacy improved over 30 days ; however , there was no significant difference in this improvement as a function of the different treatment groups ( p=0.64 ) . Controlling for other variables in the model ( age , education , depression , and social support ) , less depression ( p=0.004 ) and higher social support ( p=0.02 ) positively predicted higher medication adherence in the final model . Conclusions : TM medication reminders and /or health education did not improve medication self-efficacy . Further theory testing of current and future models and interventions are required to underst and variables related to self-efficacy and medication adherence . Addressing psychosocial factors such as depression and social support should be a priority to improve medication adherence among patients with coronary heart disease",
"Self-monitoring of blood glucose is an integral part of diabetes care which may be extended to other biometrics . Cellular and short range communication technologies will be important for the routine usage of these systems . However , the issues of follow-up and patient compliance with these emerging systems have not been yet studied evaluated but could be critical to the adoption of these technologies . We evaluated the impact of mobile telemonitoring on the intensification of care on blood pressure control and exposure to hyperglycaemia in patients with diabetes . We r and omised 137 patients with diabetes to either mobile telemonitoring ( n = 3D72 ) or usual care patients ( n = 3D65 ) for 9 months . In this paper we present some of the clinical results with focus on blood pressure control hypertension and highlight some of the technical and compliance issues that were encountered",
"We conducted a r and omized controlled trial using mobile health technology in an ethnically diverse sample of 137 patients with complicated diabetes . Patients in the intervention group ( n = 72 ) were trained to measure their blood glucose with a sensor which transmitted the readings to a mobile phone via a Bluetooth wireless link . Clinicians were then able to examine and respond to the readings which were viewed with a web-based application . Patients in the control arm of the study ( n = 65 ) did not transmit their readings and received care with their usual doctor in the outpatient and /or primary care setting . The mean follow-up period was 9 months in each group . The default rate was higher in the patients in the intervention arm due to technical problems . In an intention-to-treat analysis there were no differences in HbA1c between the intervention and control groups . In a sub-group analysis of the patients who completed the study , the telemonitoring group had a lower HbA1c than those in the control group : 7.76 % and 8.40 % , respectively ( P = 0.06 )"
] |
4116c2a2-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND Although clinicians sometimes choose amiodarone to convert atrial fibrillation ( AF ) to sinus rhythm , no current and comprehensive systematic review has summarized its effectiveness . OBJECTIVE To review the effectiveness of amiodarone in converting AF to sinus rhythm over a 4-week period . METHODS Two review ers conducted a systematic search for r and omized trials in data bases , complemented by h and search es and contact with experts . Selected trials compared amiodarone with placebo , digoxin , or calcium channel blockers for conversion of AF to sinus rhythm . Review ers evaluated the methodology and extracted data from each primary study . RESULTS Twenty-one studies met eligibility criteria . Duration of AF proved to be a source of heterogeneity , leading to 2 analyses . The relative risk ( RR ) for achieving sinus rhythm was 4.33 ( 95 % confidence interval [ CI ] , 2.76 - 6.77 ) for trials with mean AF duration of greater than 48 hours and 1.40 ( 95 % CI , 1.25 - 1.57 ) for those with AF of 48 hours or less . The risk differences for these 2 groups were 27 % and 26 % , respectively , yielding a number needed to treat of 4 for both groups . The low control event rate among trials with long duration of AF , compared with that of trials with a duration of 48 hours or less , explained the difference in the RR for conversion . We found that the size of the left atrium , presence of cardiovascular disease , and protocol s of amiodarone administration did not influence the magnitude of effect . Serious adverse events were infrequent . CONCLUSIONS Amiodarone is effective for converting AF to sinus rhythm in a wide range of patients . Although use of amiodarone is apparently safe , safety data are too scarce for definitive conclusions
|
[
"Despite the widespread use of amiodarone in non-surgical patients , its role in the management of supraventricular tachyarrhythmias after cardiac surgery is not clear . We set out to compare the relative efficacy of amiodarone and digoxin in the management of atrial fibrillation and flutter in the early postoperative period . This prospect i ve r and omised trial comprised 30 patients , previously in sinus rhythm , who developed sustained atrial fibrillation or flutter following myocardial revascularisation , valve surgery or combined procedures . Amiodarone was administered as an intravenous loading dose followed by a continuous infusion . Digoxin was given as an intravenous loading dose followed by oral maintenance therapy . Electrocardiographic and haemodynamic monitoring was continued for 24 h after the commencement of treatment . There was a marked reduction in heart rate in both groups , mainly in the first 6 h , from 146 to 89 beats per minute in the amiodarone group and from 144 to 95 in the digoxin group . At the end of the 24 h , one of the 15 patients in the amiodarone group and 3 of the 15 patients in the digoxin group remained in atrial fibrillation . No patient in either group developed adverse reactions . We conclude that intravenous amiodarone therapy is safe and at least as effective as digoxin in the initial management of arrhythmias after cardiac surgery",
"OBJECTIVE To assess and compare the safety and efficacy of amiodarone and sotalol in the treatment of patients with recurrent symptomatic atrial fibrillation . DESIGN Prospect i ve , r and omised , single blind , placebo controlled study . SETTING Tertiary cardiac referral centre . PATIENTS 186 consecutive patients ( 97 men , 89 women ; mean ( SD ) age , 63 ( 10 ) years ) with recurrent , symptomatic atrial fibrillation . INTERVENTIONS 65 patients were r and omised to amiodarone , 61 to sotalol , and 60 to placebo . Patients receiving amiodarone were maintained at a dose of 200 mg/day after a 30 day loading phase . The sotalol dose was 160 - 480 mg daily , as tolerated . MAIN OUTCOME MEASURES Recurrence of atrial fibrillation or side effects . RESULTS In the amiodarone group , 31 of the 65 patients developed atrial fibrillation after an average of six months , while 15 ( 11 in sinus rhythm and four in atrial fibrillation ) experienced significant side effects after an average of 16 months . In the sotalol group , relapse to atrial fibrillation occurred in 47 of the 61 patients after an average of eight months ; three experienced side effects during the titration phase . In the placebo group , 53 of the 60 patients developed atrial fibrillation after an average of four months ( p amiodarone and sotalol v placebo ; p amiodarone v sotalol ) . CONCLUSIONS Both amiodarone and sotalol can be used for the maintenance of normal sinus rhythm in patients with symptomatic atrial fibrillation . Amiodarone is more effective but causes more side effects",
"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",
"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",
"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",
"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",
"Abstract Purpose : Atrial fibrillation ( AF ) is a fairly common complication of acute myocardial infa rct ion ( AMI ) . The aim of this study was to examine the safety and efficacy of intravenous amiodarone in converting AF associated with AMI . Methods : Seventy patients with AMI complicated with AF were prospect ively divided into 3 groups : a ) In group D ( n = 26 ) , 0.75 mg digoxin was administered intravenously and thereafter as needed , b ) In group AM ( n = 16 ) , 300 mg of amiodarone was infused over 2 hours followed by 44 mg/hour for up to 60 hours or until sinus rhythm was restored , c ) In group D + AM ( n = 28 ) , 0.75 mg of digoxin was administered ( as in group D ) for the initial 2 hours followed by amiodarone infusion as in group AM . Results : Sinus rhythm was restored : a ) by the end of the 2nd hour in 9/26 patients from group D , 4/16 from group AM , and 10/28 from group D + AM ( p = NS ) , b ) by the end of the 96th hour , in 18/26 patients from group D , and in all patients from group AM and groupd D + AM . The corresponding duration of AF was 51 ± 34 hours , 17 ± 15 hours and 9 ± 13 hours , respectively ( F = 15.4 , p 0.001 ) . AF recurred in 9/26 , 5/16 and 1/28 patients of groups D , AM and D + AM , respectively ( p = 0.026 ) . The required dosage of amiodarone was lower in the D + AM group than in the AM group ( 603 ± 563 mg versus 1058 ± 680 mg , p = 0.037 ) . Conclusions : Intravenous amiodarone was well tolerated in patients with AMI complicated by AF and was effective in decreasing the duration of AF . However , the combination of amiodarone and digoxin was superior to amiodarone alone in restoring sinus rhythm faster , maintaining sinus rhythm longer , and allowing the use of a lower cumulative amount of amiodarone",
"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",
"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",
"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",
"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",
"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",
"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",
"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",
"BACKGROUND Electric conversion of atrial fibrillation is the most widely used and effective treatment for sinus rhythm restoration . However , it has a limited success rate and a high recurrence rate . HYPOTHESIS Pretreatment with calcium channel blocker may improve the efficacy by reversing the so-called \" electric remodeling \" phenomenon , also related to overload in cytosolic calcium . METHODS The efficacy of diltiazem or amiodarone pretreatment ( oral , 1 month before and 1 month after conversion ) on direct-current conversion of persistent atrial fibrillation was assessed in 120 patients , r and omly assigned to 3 matched groups : A ( n = 44 , diltiazem ) ; B ( n = 46 , amiodarone ) , and C ( n = 30 , digoxin ) . RESULTS Before electric conversion , all treatments significantly decreased mean heart rate . Spontaneous conversion to sinus rhythm was achieved in 6 % of patients of group A ( 3 of 46 ) versus 25 % of group B ( 11 of 44 ) and 3 % ( 1 of 30 ) of group C ( A/C vs B , P conversion was more successful in group B ( 91 % ) compared with group A ( 76 % ) and group C ( 67 % ) ( B vs A/C , P electric threshold for effective conversion ( P = not significant ) . At the 24-hour time point , early relapse of atrial fibrillation was similar between groups A and B ( A , 2 % ; B , 3 % ; P = not significant ) and lower than group C ( 12 % ) ( P recurrence rate was lower in group B ( 28 % ) versus groups A ( 56 % ) and C ( 78 % ) ( B vs A/C , P side effects were reported . CONCLUSIONS Although diltiazem seems to be as effective as amiodarone in reducing early atrial fibrillation recurrences , diltiazem is less effective in determining spontaneous or electric conversion , with a higher recurrence rate at 2 months . Diltiazem pretreatment could be considered as only a second choice treatment in those patients in whom amiodarone is contraindicated",
"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"
] |
4116c2de-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND Fibromyalgia ( FM ) is a clinical ly well-defined chronic condition of unknown aetiology characterized by chronic widespread pain that often co-exists with sleep disturbances , cognitive dysfunction and fatigue . Patients often report high disability levels and negative mood . Psychotherapies focus on reducing key symptoms , improving daily functioning , mood and sense of personal control over pain . OBJECTIVES To assess the benefits and harms of cognitive behavioural therapies ( CBTs ) for treating FM at end of treatment and at long-term ( at least six months ) follow-up . SEARCH METHODS We search ed the Cochrane Central Register of Controlled Trials ( CENTRAL ) ( The Cochrane Library 2013 , Issue 8) , MEDLINE ( 1966 to 28 August 2013 ) , PsycINFO ( 1966 to 28 August 2013 ) and SCOPUS ( 1980 to 28 August 2013 ) . We search ed http://www . clinical trials.gov ( web site of the US National Institutes of Health ) and the World Health Organization Clinical Trials Registry Platform ( ICTRP ) ( http://www.who.int/ictrp/en/ ) for ongoing trials ( last search 28 August,2013 ) , and the reference lists of review ed articles . SELECTION CRITERIA We selected r and omised controlled trials of CBTs with children , adolescents and adults diagnosed with FM . DATA COLLECTION AND ANALYSIS The data of all included studies were extracted and the risks of bias of the studies were assessed independently by two review authors . Discrepancies were resolved by discussion . MAIN RESULTS Twenty-three studies with 24 study arms with CBTs were included . A total of 2031 patients were included ; 1073 patients in CBT groups and 958 patients in control groups . Only two studies were without any risk of bias . The GRADE quality of evidence of the studies was low . CBTs were superior to controls in reducing pain at end of treatment by 0.5 points on a scale of 0 to 10 ( st and ardised mean difference ( SMD ) - 0.29 ; 95 % confidence interval ( CI ) -0.49 to -0.17 ) and by 0.6 points at long-term follow-up ( median 6 months ) ( SMD -0.40 ; 95 % CI -0.62 to -0.17 ) ; in reducing negative mood at end of treatment by 0.7 points on a scale of 0 to 10 ( SMD - 0.33 ; 95 % CI -0.49 to -0.17 ) and by 1.3 points at long-term follow-up ( median 6 months ) ( SMD -0.43 ; 95 % CI -0.75 to -0.11 ) ; and in reducing disability at end of treatment by 0.7 points on a scale of 0 to 10 ( SMD - 0.30 ; 95 % CI -0.51 to -0.08 ) and at long-term follow-up ( median 6 months ) by 1.2 points ( SMD -0.52 ; 95 % CI -0.86 to -0.18 ) . There was no statistically significant difference in dropout rates for any reasons between CBTs and controls ( risk ratio ( RR ) 0.94 ; 95 % CI 0.65 to 1.35 ) . AUTHORS ' CONCLUSIONS CBTs provided a small incremental benefit over control interventions in reducing pain , negative mood and disability at the end of treatment and at long-term follow-up . The dropout rates due to any reason did not differ between CBTs and controls
|
[
"OBJECTIVE The rising costs of health care are of great concern , particularly for the chronically ill . Interventions that promote health status and well being while teaching appropriate use of the health care system have led to cost savings among patients with osteoarthritis . We carried out social support and education interventions with patients with fibromyalgia ( FM ) and assessed the effect on health care costs , psychosocial variables , and health status . METHODS Participants were 600 patients with FM who were members of a health maintenance organization . They were r and omly assigned to one of 2 experimental groups ( social support ; social support and education ) or to a no-treatment control group . Assessment s were conducted at baseline and following a one year intervention . Health care cost data were obtained directly from participants ' medical records . RESULTS Results indicated significant reductions in all groups ' costs of prescriptions , laboratory tests , and visits to a nurse , nurse practitioner and /or physicians ' assistant . All groups also showed improvements on variables assessing effect of FM , self-efficacy , depression , and knowledge of FM . The social support and education group was less helpless after one year than the other groups ; differential changes for all other variables were not significant . CONCLUSION The study did not reveal differential changes in health care costs among participants in the experimental and control groups . These findings emphasize the importance of using objective health care utilization data when calculating health care costs , as well as the value of including a no-treatment control group to prevent erroneous conclusions about treatment efficacy",
"This pilot , r and omized controlled trial analyzed the effects of a cognitive behavioral therapy ( CBT , n = 20 ) for insomnia vs a sleep hygiene ( SH , n = 20 ) program on the three attentional networks ( alertness , orienting , and executive function ) and other additional outcome measures ( sleep , pain , depression , anxiety , and daily functioning ) of fibromyalgia patients . The CBT group showed significant improvement in alertness ( F(1 , 28 ) = 11.84 , p = .0018 ) , executive functioning ( F(1 , 28 ) = 15.76 , p = .00059 ) , sleep quality ( F(1 , 38 ) = 6.33 , p = .016 ) , and a trend to improvement in daily functioning ( p > .06 ) , as compared with the SH group . The improvement in executive functioning was significantly related to the changes in sleep ( r = 0.40 , p = .026 ) . A CBT for insomnia represents a useful intervention in fibromyalgia patients not only regarding sleep disturbance but also attentional dysfunction and probably daily functioning",
"The present study focused on the evaluation of the effects of operant behavioural ( OBT ) and cognitive behavioural ( CBT ) treatments for fibromyalgia syndrome ( FMS ) . One hundred and twenty-five patients who fulfilled the American College of Rheumatology criteria for FMS were r and omly assigned to OBT ( n = 43 ) , CBT ( n = 42 ) , or an attention-placebo ( AP ) treatment ( n = 40 ) that consisted of discussion s of FMS-related problems . Assessment s of physical functioning , pain , affective distress , and cognitive and behavioural variables were performed pre-treatment and post-treatment as well as 6 and 12 months post-treatment . Patients receiving the OBT or CBT reported a significant reduction in pain intensity post-treatment ( all Fs > 3.89 , all Ps improvements in cognitive ( all Fs > 7.95 , all P ) and affective variables ( all Fs > 2.99 , all Ps significant improvements in physical functioning and behavioural variables ( all Fs > 5.99 , all Ps deterioration in the outcome variables . The post-treatment effects for the OBT and CBT groups were maintained at both the 6- and 12-month follow-ups . These results suggest that both OBT and CBT are effective in treating patients with FMS with some differences in the outcome measures specifically targeted by the individual treatments compared with an unstructured discussion group . The AP group showed that unstructured discussion of FMS-related problems may be detrimental",
"OBJECTIVE Studies have suggested that the Arthritis Self-Management Program ( ASMP ) course is effective at reducing arthritis pain and health care costs in volunteer participants . There have been no reports of trials of the ASMP in the context of primary care physicians ' practice s , where the potential for spreading the program may be greatest . We conducted a r and omized controlled trial of the ASMP course in a large primary care physician network . METHODS Patients with osteoarthritis , rheumatoid arthritis , or fibromyalgia were recruited for the study . Subjects in the intervention practice s received the 6 week course and those in the control practice s received only the ASMP book , without course . Disability , pain , self-efficacy , mental health , and satisfaction were measured using vali date d instruments at baseline and at 4 months . RESULTS One hundred thirteen patients were recruited for the ASMP course ( intervention ) and completed baseline and 4 month followup question naires . Eighty-four percent completed at least 4 of 6 classes . Seventy-four patients received the ASMP manual ( controls ) and completed both question naires . Patients in the intervention and control groups had similar baseline pain ( p = 0.94 ) , self-efficacy to control pain ( p = 0.90 ) , mental health ( p = 0.10 ) , and vitality scores ( p = 0.21 ) , but those in the intervention arm had slightly less disability ( p = 0.04 ) . At 4 months , there was no significant improvement from baseline in any endpoint and no difference between patients in the intervention and control groups ( all p > 0.2 ) . Patient satisfaction with arthritis care and outcomes was no different for intervention and control patients ( all p > 0.3 ) . All types of health care re source use were similar at baseline and followup for both intervention and control groups ( all p > 0.2 ) . CONCLUSION While the ASMP course has been found to be effective in other patient groups , there were no significant clinical benefits noted at 4 months in patients recruited from primary care practice",
"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",
"A r and omized controlled trial was conducted to assess the efficacy of an individually administered form of cognitive behavioral treatment for fibromyalgia . In an additive design , 76 patients diagnosed with fibromyalgia were r and omly assigned to either the experimental treatment ( affective-cognitive behavioral therapy , 10 individual sessions , one per week ) administered concurrently with treatment-as-usual or to an unaugmented treatment-as-usual condition . Statistical analysis conducted at the end of treatment ( 3 months after the baseline assessment ) and at a followup ( 9 months after the baseline assessment ) indicated that the patients receiving the experimental treatment reported less pain and overall better functioning than control patients , both at posttreatment and at followup . The implication s of these findings for future research are discussed",
"& NA ; Mindfulness‐based stress reduction ( MBSR ) is a structured 8‐week group program teaching mindfulness meditation and mindful yoga exercises . MBSR aims to help participants develop nonjudgmental awareness of moment‐to‐moment experience . Fibromyalgia is a clinical syndrome with chronic pain , fatigue , and insomnia as major symptoms . Efficacy of MBSR for enhanced well‐being of fibromyalgia patients was investigated in a 3‐armed trial , which was a follow‐up to an earlier quasi‐r and omized investigation . A total of 177 female patients were r and omized to one of the following : ( 1 ) MBSR , ( 2 ) an active control procedure controlling for nonspecific effects of MBSR , or ( 3 ) a wait list . The major outcome was health‐related quality of life ( HRQoL ) 2 months post‐treatment . Secondary outcomes were disorder‐specific quality of life , depression , pain , anxiety , somatic complaints , and a proposed index of mindfulness . Of the patients , 82 % completed the study . There were no significant differences between groups on primary outcome , but patients overall improved in HRQoL at short‐term follow‐up ( P = 0.004 ) . Post hoc analyses showed that only MBSR manifested a significant pre‐to‐post‐intervention improvement in HRQoL ( P = 0.02 ) . Furthermore , multivariate analysis of secondary measures indicated modest benefits for MBSR patients . MBSR yielded significant pre‐to‐post‐intervention improvements in 6 of 8 secondary outcome variables , the active control in 3 , and the wait list in 2 . In conclusion , primary outcome analyses did not support the efficacy of MBSR in fibromyalgia , although patients in the MBSR arm appeared to benefit most . Effect sizes were small compared to the earlier , quasi‐r and omized investigation . Several method ological aspects are discussed , e.g. , patient burden , treatment preference and motivation , that may provide explanations for differences . In a 3‐armed r and omized controlled trial in female patients suffering from fibromyalgia , patients benefited modestly from a mindfulness‐based stress reduction intervention",
"OBJECTIVE To study , for the first time , service utilization and costs in fibromyalgia , a prevalent syndrome associated with high levels of pain , functional disability , and emotional distress . METHODS Five hundred thirty-eight fibromyalgia patients from 6 rheumatology centers were enrolled in a 7-year prospect i ve study of fibromyalgia outcome . Patients were assessed every 6 months with vali date d , mailed question naires which included questions regarding fibromyalgia symptoms and severity , utilization of services , and work disability . RESULTS Fibromyalgia patients averaged almost 10 outpatient medical visits per year , and when nontraditional treatments were considered , this number increased to approximately 1 visit per month . Patients were hospitalized at a rate of 1 hospitalization every 3 years . In each 6-month study period , patients used a mean of 2.7 fibromyalgia-related drugs . Costs increased over the course of the study . The mean yearly per-patient cost in 1996 dollars was $ 2,274 . However , results were skewed by high utilizers , and many patients used few services and had limited costs . Total costs and utilization were independently associated with the number of self-reported comorbid or associated conditions , functional disability , and global disease severity . Compared with patients with other rheumatic disorders , those with fibromyalgia were more likely to have lifetime surgical interventions , including back or neck surgery , appendectomy , carpal tunnel surgery , gynecologic surgery , abdominal surgery , and tonsillectomy , and were more likely than other rheumatic disease patients to report comorbid or associated conditions . Almost 50 % of hospitalizations occurring during the study were related to fibromyalgia-associated symptoms . CONCLUSION The average yearly cost for service utilization among fibromyalgia patients is $ 2,274 . Fibromyalgia patients have high lifetime and current rates of utilization of all types of medical services . They report more symptoms and comorbid or associated conditions than patients with other rheumatic conditions , and symptom reporting is linked to service utilization and , to a lesser extent , functional disability and global disease severity ",
"Summary Treatment with Cognitive Behavioral Therapy leads to clinical improvements in fibromyalgia patients , paired with increased activity and connectivity in the brain ’s pain modulatory regions . ABSTRACT Interventions based on Cognitive Behavioral Therapy ( CBT ) are widely used to treat chronic pain , but the brain mechanisms responsible for these treatment effects are poorly understood . The aim of this study was to vali date the relevance of the cortical control theory in response to an exposure‐based form of CBT , Acceptance and Commitment Therapy , in patients with chronic pain . Forty‐three female patients diagnosed with fibromyalgia syndrome were enrolled in a r and omized , 12‐week , waiting‐list controlled clinical trial ( CBT n = 25 ; controls n = 18 ) . CBT was administered in groups of six patients during 12 weekly sessions . Functional magnetic resonance imaging ( fMRI ) during pressure‐evoked pain was assessed before and after treatment or the 12‐week period . Self‐report question naires of depression and anxiety were administered pre‐ and posttreatment as well as 3 months following end of treatment . Patients treated with CBT reported larger improvement of fibromyalgia on the Patient Global Impression of Change measure , and improved depression and anxiety symptoms , compared to the waiting‐list controls . However , there were no effects on clinical pain or pain sensitivity measures . An analysis of fMRI scans revealed that CBT led to increased activations in the ventrolateral prefrontal/lateral orbitofrontal cortex ; regions associated with executive cognitive control . We suggest that CBT changes the brain ’s processing of pain through an altered cerebral loop between pain signals , emotions , and cognitions ; leading to increased access to executive regions for re appraisal of pain . Our data thereby support our hypothesis about the activation of a cortical control mechanism in response to CBT treatment in chronic pain",
"OBJECTIVE Juvenile fibromyalgia syndrome ( FMS ) is a chronic musculoskeletal pain disorder in children and adolescents for which there are no evidence -based treatments . The objective of this multisite , single-blind , r and omized clinical trial was to test whether cognitive-behavioral therapy ( CBT ) was superior to fibromyalgia ( FM ) education in reducing functional disability , pain , and symptoms of depression in juvenile FMS . METHODS Participants were 114 adolescents ( ages 11 - 18 years ) with juvenile FMS . After receiving stable medications for 8 weeks , patients were r and omized to either CBT or FM education and received 8 weekly individual sessions with a therapist and 2 booster sessions . Assessment s were conducted at baseline , immediately following the 8-week treatment phase , and at 6-month followup . RESULTS The majority of patients ( 87.7 % ) completed the trial per protocol . Intent-to-treat analyses showed that patients in both groups had significant reductions in functional disability , pain , and symptoms of depression at the end of the study , and CBT was significantly superior to FM education in reducing the primary outcome of functional disability ( mean baseline to end-of-treatment difference between groups 5.39 [ 95 % confidence interval 1.57 , 9.22 ] ) . Reduction in symptoms of depression was clinical ly significant for both groups , with mean scores in the range of normal/nondepressed by the end of the study . Reduction in pain was not clinical ly significant for either group ( adverse events . CONCLUSION In this controlled trial , CBT was found to be a safe and effective treatment for reducing functional disability and symptoms of depression in adolescents with juvenile FMS",
"In a 2002 systematic review of pediatric clinical trials Eccleston et al. [ 1 ] found that psychological therapies had a significant effect on pain reduction . Although that review sought to include all pain conditions , the available studies at the time focused almost exclusively on treatment of pediatric headache . In recent years , r and omized clinical trials ( RCTs ) have been published on other pediatric pain conditions , including abdominal pain and fibromyalgia . In addition , effects of psychological therapies on clinical outcomes beyond pain reduction , such as functional disability and emotional distress were examined . In this issue of Pain , Palermo et al. [ 4 ] present a timely meta-analytic review paper that reflects on these new developments",
"OBJECTIVE To determine the effectiveness of an intervention Tool Kit of arthritis self-management material s to be sent once through the mail , and to describe the population s reached . METHODS Spanish speakers ( n = 335 ) , non-Hispanic English-speaking African Americans ( n = 156 ) , and other non-Hispanic English speakers ( n = 404 ) were recruited separately and r and omized within each of the 3 ethnic/racial categories to immediately receive the intervention Tool Kit ( n = 458 ) or to a 4-month wait-list control status ( n = 463 ) . At the end of 4 months , controls were sent the Tool Kit . All subjects were followed in a longitudinal study for 9 months . Self-administered measures included health status , health behavior , arthritis self-efficacy , medical care utilization , and demographic variables . Using analyses of covariance and t-tests , analyses were conducted for all participants and for Spanish- and English- language groups . RESULTS At 4 months , comparing all intervention subjects with r and omized wait-list controls , there were significant ( P medical care utilization and self-rated health . The results were maintained at 9 months compared with baseline . On average , the Tool Kit reached persons ages 50 - 56 years with 12 - 15 years of schooling . There were few differences between English- and Spanish- language participants in either the effectiveness or reach variables . CONCLUSION A mailed Arthritis Self-Management Tool Kit proved effective in improving health status , health behavior , and self-efficacy variables for up to 9 months . It also reached younger persons in both English- and Spanish- language groups and Spanish speakers with higher education levels than previous studies of the small-group Arthritis Self-Management Program",
"Abstract Given that studies about the differential efficacy of existing treatments in fibromyalgia syndrome are scarce , the aim of this study was to compare the differential efficacy of a cognitive – behavioral and a pharmacological therapy on fibromyalgia . Using a r and omized controlled clinical trial , 28 fibromyalgic patients were assigned to one of following experimental conditions : ( a ) pharmacological treatment ( i.e. , cyclobenzaprine ) , ( b ) cognitive – behavioral intervention ( i.e. , stress inoculation training ) , ( c ) combined pharmacological and cognitive – behavioral treatment and ( d ) no treatment . The results show the superiority of cognitive – behavioral intervention to reduce the severity of fibromyalgia both at the end of the treatment and at follow-up . We conclude that cognitive – behavioral interventions must be considered a primary treatment of fibromyalgia syndrome",
"& NA ; This paper reports the development of a scale for assessing the quality of reports of r and omised controlled trials for psychological treatments . The Delphi method was used in which a panel of 15–12 experts generated statements relating to treatment and design components of trials . After three rounds , statements with high consensus agreement were review ed by a second expert panel and rewritten as a scale . Evidence to support the reliability and validity of the scale is reported . Three expert and five novice raters assessed sets of 31 and 25 published trials to establish scale reliability ( ICC ranges from 0.91 to 0.41 for experts and novices , respectively ) and item reliability ( Kappa and inter‐rater agreement ) . The total scale score discriminated between trials globally judged as good and poor by experts , and trial quality was shown to be a function of year of publication . Uses for the scale are suggested",
"The logic of the r and omized double-blind placebo control group design is presented , and problems with using the design in psychotherapy are discussed . Placebo effects are estimated by examining clinical trials in medicine and psychotherapy . In medicine , a recent meta- analysis of clinical trials with treatment , placebo , and no treatment arms was conducted ( Hróbjartsson & Gøtzsche , 2001 ) , and it was concluded that placebos have small or no effects . A re- analysis of those studies , presented here , shows that when disorders are amenable to placebos and the design is adequate to detect the effects , the placebo effect is robust and approaches the treatment effect . For psychological disorders , particularly depression , it has been shown that pill placebos are nearly as effective as active medications whereas psychotherapies are more effective than psychological placebos . However , it is shown that when properly design ed , psychological placebos are as effective as accepted psychotherapies",
"OBJECTIVE Sleep problems are common among patients with fibromyalgia ( FM ) . However , it is not known whether poor sleep is a contributing factor in FM or a consequence of the illness . The aim of the current study was to prospect ively investigate the association between self-reported sleep problems and risk of FM among adult women . METHODS We longitudinally studied 12,350 women who did not have FM , musculoskeletal pain , or physical impairments at baseline ( 1984 - 1986 ) . A generalized linear model was used to calculate the adjusted relative risk ( RR ) of FM at followup in 1995 - 1997 . RESULTS Incident FM was reported by 327 women at followup . A dose-dependent association was found between sleep problems and risk of FM ( P for trend sleep problems often or always , compared to women who never experienced sleep problems . Age-stratified analysis showed that women age≥45 years who reported having sleep problems often or always had an adjusted RR of 5.41 ( 95 % CI 2.65 - 11.05 ) , whereas the corresponding RR for women ages 20 - 44 years who reported having sleep problems often or always was 2.98 ( 95 % CI 1.76 - 5.05 ) . CONCLUSION These prospect i ve data indicate a strong dose-dependent association between sleep problems and risk of FM . The association is somewhat , although not significantly , stronger in middle-aged and older women than in younger women",
"& NA ; Both pharmacological and non‐pharmacological interventions have demonstrated efficacy in the management of fibromyalgia ( FM ) . Non‐pharmacological interventions however are far less likely to be used in clinical setting s , in part due to limited access . This manuscript presents the findings of a r and omized controlled trail of an Internet‐based exercise and behavioral self‐management program for FM design ed for use in the context of a routine clinical care . 118 individuals with FM were r and omly assigned to either ( a ) st and ard care or ( b ) st and ard care plus access to a Web‐Enhanced Behavioral Self‐Management program ( WEB‐SM ) grounded in cognitive and behavioral pain management principles . Individuals were assessed at baseline and again at 6 months for primary endpoints : reduction of pain and an improvement in physical functioning . Secondary outcomes included fatigue , sleep , anxiety and depressive symptoms , and a patient global impression of improvement . Individuals assigned to the WEB‐SM condition reported significantly greater improvement in pain , physical functioning , and overall global improvement . Exercise and relaxation techniques were the most commonly used skills throughout the 6 month period . A no‐contact , Internet‐based , self‐management intervention demonstrated efficacy on key outcomes for FM . While not everyone is expected to benefit from this approach , this study demonstrated that non‐pharmacological interventions can be efficiently integrated into routine clinical practice with positive outcomes",
"Introduction No r and omised , controlled trials have been conducted to date on the efficacy of psychological and pharmacological treatments of pain catastrophising ( PC ) in patients with fibromyalgia . Our aim in this study was to assess the effectiveness of cognitive-behaviour therapy ( CBT ) and the recommended pharmacological treatment ( RPT ) compared with treatment as usual ( TAU ) at the primary care level for the treatment of PC in fibromyalgia patients . Methods We conducted a six-month , multicenter , r and omized , blinded , parallel group , controlled trial in which patients were r and omly assigned to one of three study arms : CBT ( n = 57 ) , RPT ( n = 56 ) and TAU at the primary care level ( n = 56 ) . The major outcome of this study was PC in patients with fibromyalgia . The secondary variables were pain acceptance , depression , anxiety , pain , global function and quality of life . Results CBT significantly decreased global PC at the six-month follow-up examination with effect sizes of Cohen 's d = 0.73 and 1.01 compared with RPT and TAU , respectively . CBT was also more effective than RPT and TAU at increasing pain acceptance at the six-month follow-up examination ( effect sizes of Cohen 's d = 0.77 and 0.80 , respectively ) . Compared with RPT and TAU , CBT was more effective at improving global function based on the Fibromyalgia Impact Question naire ( six-month effect sizes Cohen 's d = 0.44 and 0.53 , respectively ) and quality of life based on the European Quality of Life Scale ( six-month effect sizes Cohen 's d = 0.11 and 0.40 , respectively ) . There were no differences among the three treatments with regard to pain and depression . Conclusions CBT shows higher efficacy than RPT and TAU not only in key outcomes in FM , such as function and quality of life , but also in relevant mediators of treatment effects , such as pain catastrophising and pain acceptance . Trial registration IS RCT N : IS RCT",
"Abstract In this pilot study , we compare the efficacy for fibromyalgia of multimodal cognitive behavioral treatments , with and without hypnosis , with that of a purely pharmacological approach , with a multiple baseline N = 1 design . We r and omly assigned six hospital patients to the three experimental conditions . The results suggest that psychological treatment produces greater symptom benefits than the conventional medical treatment only , especially when hypnosis is added . We conclude that hypnosis may be a useful tool to help people with fibromyalgia manage their symptomatology",
"BACKGROUND Self-management has increasingly been recommended as part of st and ard care for fibromyalgia , a common , poorly understood condition with limited treatment options . Data that assess popular self-management recommendations are scarce . We evaluated and compared the effectiveness of 4 common self-management treatments on function , symptoms , and self-efficacy in women with fibromyalgia . METHODS A total of 207 women with confirmed fibromyalgia were recruited from September 16 , 2002 , through November 30 , 2004 , and r and omly assigned to 16 weeks of ( 1 ) aerobic and flexibility exercise ( AE ) ; ( 2 ) strength training , aerobic , and flexibility exercise ( ST ) ; ( 3 ) the Fibromyalgia Self-Help Course ( FSHC ) ; or ( 4 ) a combination of ST and FSHC ( ST-FSHC ) . The primary outcome was change in physical function from baseline to completion of the intervention . Secondary outcomes included social and emotional function , symptoms , and self-efficacy . RESULTS Improvements in the mean Fibromyalgia Impact Question naire score in the 4 groups were -12.7 for the ST-FSHC group , -8.2 for the AE group , -6.6 for the ST group , and -0.3 for the FSHC group . The ST-FSHC group demonstrated greater improvement than the FSHC group ( mean difference , -12.4 ; 95 % confidence interval [ CI ] , -23.1 to -1.7 ) . The ST-FSHC ( mean difference , 13.6 ; 95 % CI , 2.3 to 24.9 ) and AE ( mean difference , 13.1 ; 95 % CI , 1.6 to 25.6 ) groups had similar improvements in physical function scores on the 36-Item Short-Form Health Survey . Bodily pain scores on the 36-Item Short-Form Health Survey improved in the ST-FSHC ( 14.8 ) , AE ( 13.2 ) , and ST ( 5.7 ) groups . Social function , mental health , fatigue , depression , and self-efficacy also improved . The beneficial effect on physical function of exercise alone and in combination with education persisted at 6 months . CONCLUSIONS Progressive walking , simple strength training movements , and stretching activities improve functional status , key symptoms , and self-efficacy in women with fibromyalgia actively being treated with medication . The benefits of exercise are enhanced when combined with targeted self-management education . Our findings suggest that appropriate exercise and patient education be included in the treatment of fibromyalgia",
"Contemporary models of chronic musculoskeletal pain emphasize the critical roles of fear , anxiety , and avoidance as well as biases in attention in the development and maintenance of chronic pain disability . Evidence supports the influence of individual difference variables such as anxiety sensitivity , pain-related anxiety , and catastrophizing on the pain experience and on pain-related attentional biases . Changes in attentional biases have been associated with treatment gains in patients with clinical ly significant anxiety . The Attentional Modification Paradigm ( AMP ) is a modification of the dot-probe paradigm used to facilitate such changes in attentional biases . Given the relationship between chronic musculoskeletal pain and anxiety , AMP may be effective in reducing pain as well . Participants included persons ( n = 17 ) with fibromyalgia and were r and omly assigned to either an AMP condition or a control condition . The participants completed two 15-minute AMP sessions per week for 4 weeks . Those in the AMP condition reported statistically significant and substantial reductions on several individual difference variables relative to those in the control condition , and a greater proportion experienced clinical ly significant reductions in pain . These preliminary results offer a promising new avenue for treating chronic musculoskeletal pain that warrants additional research . Comprehensive results , limitations , and future directions are discussed",
"BACKGROUND Insomnia is common and debilitating to fibromyalgia ( FM ) patients . Cognitive-behavioral therapy ( CBT ) is effective for many types of patients with insomnia , but has yet to be tested with FM patients . This study compared CBT with an alternate behavioral therapy and usual care for improving sleep and other FM symptoms . METHODS This r and omized clinical trial enrolled 47 FM patients with chronic insomnia complaints . The study compared CBT , sleep hygiene ( SH ) instructions , and usual FM care alone . Outcome measures were subjective ( sleep logs ) and objective ( actigraphy ) total sleep time , sleep efficiency , total wake time , sleep latency , wake time after sleep onset , and question naire measures of global insomnia symptoms , pain , mood , and quality of life . RESULTS Forty-two patients completed baseline and continued into treatment . Sleep logs showed CBT-treated patients achieved nearly a 50 % reduction in their nocturnal wake time by study completion , whereas SH therapy- and usual care-treated patients achieved only 20 % and 3.5 % reductions on this measure , respectively . In addition , 8 ( 57 % ) of 14 CBT recipients met strict subjective sleep improvement criteria by the end of treatment compared with 2 ( 17 % ) of 12 SH therapy recipients and 0 % of the usual care group . Comparable findings were noted for similar actigraphic improvement criteria . The SH therapy patients showed favorable outcomes on measures of pain and mental well-being . This finding was most notable in an SH therapy subgroup that self-elected to implement selected CBT strategies . CONCLUSIONS Cognitive-behavioral therapy represents a promising intervention for sleep disturbance in FM patients . Larger clinical trials of this intervention with FM patients seem warranted",
"OBJECTIVE To analyze the long-term efficacy of 2 interventions for female fibromyalgia ( FM ) patients : 1 ) cognitive-behavioral therapy ( CBT ) , and 2 ) a physical exercise (PE)-based strategy . METHODS We conducted a prospect i ve , long-term , r and omized , parallel clinical trial . The outcome variables are physical activity , aerobic capacity , and results of the Fibromyalgia Impact Question naire ( FIQ ) , Short Form 36 , Beck Anxiety and Depression Inventory , Chronic Pain Self-Efficacy Scale , and Chronic Pain Coping Inventory . All were measured at baseline , posttreatment , 6 months , and 1 year . The duration of both treatments was 8 weeks . RESULTS Some items of the FIQ and some strategies to cope with pain improved significantly in both groups after treatment . All variables measuring functional capacity improved significantly in the PE group , whereas only physical activity of the vertebral column improved in the CBT group . There were no differences in anxiety , depression , and self efficacy after treatment in either group . After 1 year of followup , most of the parameters had returned to baseline values in both groups . However , in the PE group , functional capacity remained significantly better . CONCLUSIONS PE and CBT improve clinical manifestations in FM patients only for short periods of time . Improvement in self efficacy and physical fitness are not associated with improvement in clinical manifestations",
"OBJECTIVE There are currently no controlled studies of behavioral interventions for juvenile primary fibromyalgia syndrome ( JPFM ) . In this small- sample r and omized study , we tested the efficacy of a behavioral intervention , i.e. , coping skills training ( CST ) , for the treatment of adolescents with JPFM . Outcomes tested in this study were functional disability , pain intensity , pain-coping efficacy , and depressive symptoms . METHODS Thirty patients with JPFM were r and omly assigned to 8 weeks of either CST or self-monitoring . Adolescents in the CST condition received training in active pain-coping techniques , while those in the self-monitoring condition monitored daily pain intensity and sleep quality with no instructions about behavior change . After posttreatment assessment , subjects were crossed over into the opposite treatment arm for 8 weeks ( so that all adolescents eventually received both CST and self-monitoring ) and were reassessed at Week 16 . RESULTS At Week 8 , adolescents in both conditions showed significant decrease in depressive symptoms and functional disability . Those who received CST showed significantly greater ability to cope with pain than those in the self-monitoring condition and a trend toward decreased pain intensity . At Week 16 , adolescents had significantly lower levels of disability and depressive symptoms compared to baseline , but those who received self-monitoring followed by CST seemed to receive the most benefit . CONCLUSION CST can lead to improved functioning among JPFM patients . Although some of the improvement may be due to increased monitoring and attention , CST provides the specific benefit of improving adolescents ' ability to cope with pain",
"OBJECTIVE To examine the effectiveness of a supervised aerobic exercise program , a self-management education program , and the combination of exercise and education for women with fibromyalgia ( FM ) . METHODS One hundred fifty-two women were r and omized into one of 4 groups : exercise-only , education-only , exercise and education , or control . The duration of the study was 12 weeks . All subjects were analyzed at 3 times : before study , immediately upon completion , and 3 months after completion of the intervention program on measures of disability , self-efficacy , fitness , tender point count , and tender point tenderness . Of the 152 women , complete data were available for 95 and 69 who complied with the protocol . In order to determine the group time interaction , a 2 way analysis of variance with repeated measures was used for each measure . RESULTS The only significant group time interaction was reported with the compliance analysis for the Self-Efficacy Coping with Other Symptoms subscale and the Six Minute Walk . If the program was followed , the combination of a supervised exercise program and group education provided persons with FM with a better sense of control over their symptoms . Fitness improved in the 2 groups undergoing supervised aerobic exercise programs . However , the improvement in fitness was maintained at followup in the exercise-only group and not the combined group . Conclusion . Subjects receiving the combination of exercise and education and who complied with the treatment protocol improved their perceived ability to cope with other symptoms . In addition , a supervised exercise program increased walking distance at post-test , an increase that was maintained at followup in the exercise-only group . Results demonstrate the challenges with conducting exercise and education studies in persons with FM",
"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 evaluate the efficacy of operant pain treatment for fibromyalgia syndrome ( FMS ) in an inpatient setting . METHODS Sixty-one patients who fulfilled the American College of Rheumatology criteria for FMS were r and omly assigned to the operant pain treatment group ( OTG ; n = 40 ) or a st and ardized medical program with an emphasis on physical therapy ( PTG ; n = 21 ) . Pain assessment s were performed before , immediately after , 6 months after , and 15 months after treatment . RESULTS The OTG patients reported a significant and stable reduction in pain intensity , interference , solicitous behavior of the spouse , medication , pain behaviors , number of doctor visits , and days at a hospital as well as an increase in sleeping time . Sixty-five percent of the OTG compared with none of the patients in the PTG showed clinical ly significant improvement . CONCLUSION These results suggest that operant pain treatment provided in an inpatient setting is an effective treatment for FMS , whereas a purely somatically oriented program may lead to a deterioration of the pain problem",
"OBJECTIVE This r and omized controlled clinical trial evaluates the effectiveness of outpatient group cognitive/educational treatment for patients with the fibromyalgia ( FM ) syndrome . We hypothesized that the combination of group education with cognitive treatment aim ed at developing pain coping skills would be more effective than group education alone . METHODS 131 patients with FM were r and omly assigned to 3 conditions : an experimental condition , which was the combined cognitive/educational intervention ( ECO ) ; an attention control condition consisting of group education plus group discussion ( EDI ) ; and a waiting list control ( WLC ) . For the treatment conditions ECO and EDI , assessment s were made 2 weeks before treatment , at start of treatment , at post-treatment , and at 6 and 12 mo followup . WLC patients received only 3 assessment s. RESULTS There were no pretreatment differences between the groups , or between dropouts and patients who remained in the study . At post-treatment , and compared with the WLC , the ECO patients improved in knowledge about FM ( p = 0.007 ) and pain coping ( p pain coping ( p = 0.005 ) and pain control ( p = 0.002 ) . EDI patients reported significantly less fear than ECO patients ( p = 0.005 ) . There were no other differential effects between ECO and EDI at post-treatment or 6 mo or 12 mo followup . Based on the reliability of change index for clinical significance , the relative short term success rates are 6.4 and 18.4 % for ECO and EDI , respectively . CONCLUSION The surplus value of a highly structured , 12 session group cognitive treatment added to group education can not be supported by our study . In EDI , fear reduction might have enhanced pain coping and pain control , while poor compliance , the difficulty of homework assignments , and lack of individual support may have limited the effectiveness of ECO ",
"OBJECTIVE To determine the effectiveness of self-management education and physical training in decreasing fibromyalgia ( FMS ) symptoms and increasing physical and psychological well being . METHODS A pretest-posttest control group design was used . Ninety-nine women with FMS were r and omly assigned to 1 of 3 groups ; 86 completed the study . The education only group received a 6-week self-management course . The education plus physical training group received the course and 6 h of training design ed to assist them to exercise independently . The control group got treatment after 3 months . RESULTS The experimental programs had a significant positive impact on quality of life and self-efficacy . Helplessness , number of days feeling bad , physical dysfunction , and pain in the tender points decreased significantly in one or both of the treated groups when retested 6 weeks after the end of the program . Longterm followup of 67 treated subjects showed significant positive changes on the Fibromyalgia Impact Question naire primarily in the physical training group . Among all subjects , 87 % were exercising at least 3 times/week for 20 min or more ; 46 % said they had increased their exercise level since participating in the program ; 70 % were practicing relaxation strategies as needed ; 46 % were working at least half time as opposed to 37 % at pretest . CONCLUSION Self-efficacy of the treated groups was enhanced significantly by the program . Other changes were smaller and more delayed than had been expected . Recommendations for future trials include a longer education program , more vigorous physical training , and longterm followup",
"Objective : To examine the effects of a wellness intervention , Lifestyle Counts , for women with fibromyalgia syndrome on the level of self-efficacy for health-promoting behaviours , health-promoting activity and perceived quality of life . Design : A r and omized controlled single-blinded trial with treatment and attention-control groups . Setting : Community in the southwestern United States . Subjects : Convenience sample of 187 women ( 98 treatment , 89 attention control ) with fibromyalgia syndrome ( mean age = 53.08 years , SD 9.86 ) . Intervention : The two-phase Lifestyle Counts intervention programme included lifestyle change classes for eight weeks , with goal - setting and telephone follow-up for three months . Participants in the attention-control group were offered an equivalent amount of contact in classes on general disease-related information and health education topics and unstructured follow-up phone calls . Participants were followed for a total of eight months after baseline . Outcome measures : Self-report instruments measuring self-efficacy for health behaviours , health-promotion behaviours and health-related quality of life ( SF-36 and the Fibromyalgia Impact Question naire ) were completed at baseline , two months ( after the classes ) , five months ( after telephone follow-up ) and at eight months . Results : Both groups improved significantly ( P measures of self-efficacy , health behaviours , fibromyalgia impact and quality of life . There were significant group × time interactions for scores on the Health Promoting Lifestyle II subscales of physical activity and stress management . Conclusions : The Lifestyle Counts wellness intervention holds promise for improving health-promoting behaviours and quality of life of women with fibromyalgia syndrome",
"Sleep disturbances play an important role in the exacerbation of pain and other troubling symptoms reported by patients with fibromyalgia ( FM ) . The objective of this trial was to analyze the efficacy of a cognitive-behavioral therapy for insomnia ( CBT-I ) versus a sleep hygiene ( SH ) education program at improving sleep and other clinical manifestations in FM . Sixty-four FM women with insomnia were r and omly assigned to the CBT-I or the SH groups , and 59 completed the treatments ( 30 in the CBT-I group and 29 in the SH group ) . Participants completed several self-report question naires at pre- , post-treatment and follow-ups . The CBT-I group reported significant improvements at post-treatment in several sleep variables , fatigue , daily functioning , pain catastrophizing , anxiety and depression . The SH group only improved significantly in subjective sleep quality . Patients in the CBT-I group showed significantly greater changes than those in the SH group in most outcome measures . The findings underscore the usefulness of CBT-I in the multidisciplinary management of FM",
"OBJECTIVE Sustained improvement in physical functional status was the primary goal of a brief , 6 session cognitive behavioral therapy ( CBT ) protocol for fibromyalgia ( FM ) . METHODS One hundred forty-five patients with FM were r and omly assigned to either ( 1 ) st and ard medical care that included pharmacological management of symptoms and suggestions for aerobic fitness , or ( 2 ) the same st and ard medical treatment plus 6 sessions of CBT aim ed at improving physical functioning . Outcome measures included the Medical Outcome Study Short Form-36 Physical Component Score and McGill ratings of pain . Outcomes were treated dichotomously using a preestablished criterion for clinical ly significant success based upon the reliability of change index from baseline to one year posttreatment . RESULTS Twenty-five percent of the patients receiving CBT were able to achieve clinical ly meaningful levels of longterm improvement in physical functioning , whereas only 12 % of the patients receiving st and ard care achieved the same level of improvement . There were no lasting differences on pain ratings between groups . CONCLUSION Lasting improvements in physical functioning have been among the most difficult outcomes to obtain in studies of FM . These data suggest that the inclusion of CBT to a st and ard medical regimen for FM can favorably influence physical functioning in a subset of patients",
"Abstract Objective : To examine the effects of abruptly withdrawing milnacipran during the 2-week discontinuation phase of a study in which FM patients had received 12 weeks of stable-dose treatment with milnacipran at 100 mg/day . Research design and methods : The effects of withdrawing milnacipran were evaluated prospect ively over a 2-week period ( Weeks 12 to 14 ) using a r and omized , placebo-controlled withdrawal design . Patients who had originally received milnacipran 100 mg/d for 12 weeks were re-r and omized to continue milnacipran ( n = 178 ) or switch directly to placebo ( n = 178 ) ; patients originally receiving placebo continued placebo ( n = 359 ) . Clinical trial registration : Clinical strials.gov ( NCT00314249 ) . Main outcome measures : Loss of efficacy was evaluated by mean changes in pain and functional measures and by percentage of composite responders , defined as patients with simultaneous improvements in pain , global status , and physical functioning . Newly emergent adverse events and changes in vital signs were also recorded . Results : Within 2 weeks , patients switched from milnacipran to placebo had greater mean worsening in pain , functioning , and global status measures when compared with patients continuing treatment . In addition , significantly fewer composite responders were found in patients who discontinued active treatment than in patients who continued receiving milnacipran ( 22.0 % vs 32.3 % , p emergent adverse events were 16.3 % and 18.0 % in patients discontinuing and continuing treatment , respectively . Mean vital sign changes decreased or returned to baseline within 2 weeks of discontinuation . Conclusions : Patients discontinuing milnacipran experienced worsening in multiple efficacy parameters within 2 weeks . Vital sign changes observed with milnacipran during the 12-week stable-dose period decreased or returned to baseline values within 2 weeks after discontinuation of treatment . No new safety concerns were found during this discontinuation period with milnacipran",
"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",
"Objectives : There is evidence that education on pain physiology can have positive effects on pain , disability , and catastrophization in patients with chronic musculoskeletal pain disorders . A double-blind r and omized controlled trial ( RCT ) was performed to examine whether intensive pain physiology education is also effective in fibromyalgia ( FM ) patients , and whether it is able to influence the impaired endogenous pain inhibition of these patients . Methods : Thirty FM patients were r and omly allocated to either the experimental ( receiving pain physiology education ) or the control group ( receiving pacing self-management education ) . The primary outcome was the efficacy of the pain inhibitory mechanisms , which was evaluated by spatially accumulating thermal nociceptive stimuli . Secondary outcome measures included pressure pain threshold measurements and question naires assessing pain cognitions , behavior , and health status . Assessment s were performed at baseline , 2 weeks , and 3 months follow-up . Repeated measures ANOVAS were used to reveal possible therapy effects and effect sizes were calculated . Results : After the intervention the experimental group had improved knowledge of pain neurophysiology ( P their pain in the short term ( P=0.004 ) . Long-term improvements in physical functioning ( P=0.046 ) , vitality ( P=0.047 ) , mental health ( P and general health perceptions ( P lower pain scores and showed improved endogenous pain inhibition ( P=0.041 ) compared with the control group . Discussion : These results suggest that FM patients are able to underst and and remember the complex material about pain physiology . Pain physiology education seems to be a useful component in the treatment of FM patients as it improves health status and endogenous pain inhibition in the long term",
"BACKGROUND The clinical impact of telephone-delivered cognitive behavioral therapy ( TCBT ) , exercise , or a combined intervention in primary care patients with chronic widespread pain ( CWP ) is unclear . METHODS A total of 442 patients with CWP ( meeting the American College of Rheumatology criteria ) were r and omized to receive 6 months of TCBT , grade d exercise , combined intervention , or treatment as usual ( TAU ) . The primary outcome , using a 7-point patient global assessment scale of change in health since trial enrollment ( range : very much worse to very much better ) , was assessed at baseline and 6 months ( intervention end ) and 9 months after r and omization . A positive outcome was defined as \" much better \" or \" very much better . \" Data were analyzed using logistic regression according to the intention-to-treat principle . RESULTS The percentages reporting a positive outcome at 6 and 9 months , respectively , were TAU group , 8 % and 8 % ; TCBT group , 30 % and 33 % ; exercise group , 35 % and 24 % ; and combined intervention group , 37 % and 37 % ( P TAU : TCBT ( 6 months : odds ratio [ OR ] , 5.0 [ 95 % CI , 2.0 - 12.5 ] ; 9 months : OR , 5.4 [ 95 % CI , 2.3 - 12.8 ] ) , exercise ( 6 months : OR , 6.1 [ 95 % CI , 2.5 - 15.1 ] ; 9 months : OR , 3.6 [ 95 % CI , 1.5 - 8.5 ] ) , and combined intervention ( 6 months : OR , 7.1 [ 95 % CI , 2.9 - 17.2 ] ; 9 months : OR , 6.2 [ 95 % CI , 2.7 - 14.4 ] ) . At 6 and 9 months , combined intervention was associated with improvements in the 36-Item Short Form Health Question naire physical component score and a reduction in passive coping strategies . Conclusions on cost-effectiveness were sensitive to missing data . CONCLUSION TCBT was associated with substantial , statistically significant , and sustained improvements in patient global assessment . TRIAL REGISTRATION clinical trials.gov Identifier : IS RCT N67013851",
"UNLABELLED This study compared the efficacy of 2 psychological treatments for fibromyalgia with each other and with st and ard care . Ninety-three patients with fibromyalgia ( FM ) were r and omly assigned to 1 of the 3 experimental conditions : 1 ) multicomponent cognitive-behavioral therapy ( CBT ) ; 2 ) multicomponent CBT with hypnosis ; and 3 ) pharmacological treatment ( st and ard care control group ) . The outcome measures of pain intensity , catastrophizing , psychological distress , functionality , and sleep disturbances were assessed before treatment , immediately after treatment , and at 3- and 6-month follow-up visits . CBT and CBT with hypnosis participants received the st and ard pharmacological management plus 14 weekly , 120-minute-long sessions of psychological treatment . All but 1 session followed a group format ; the remaining session was individual . The analyses indicated that : 1 ) patients with FM who received multicomponent CBT alone or multicomponent CBT with hypnosis showed greater improvements than patients who received only st and ard care ; and 2 ) adding hypnosis enhanced the effectiveness of multicomponent CBT . This study presents new evidence about the efficacy of multicomponent CBT for FM and about the additional effects of hypnosis as a complement to CBT . The relevance and implication s of the obtained results are discussed . PERSPECTIVE This article highlights the beneficial effects of adding hypnosis in a multicomponent cognitive-behavioral group treatment of fibromyalgia patients . Also , this research showed that by adding hypnosis the length of treatment did not increase",
"OBJECTIVE To predict the effects of cognitive-behavioral therapy ( CBT ) and operant-behavioral therapy ( OBT ) in fibromyalgia syndrome ( FMS ) . METHODS A total of 125 patients who fulfilled the American College of Rheumatology FMS criteria were r and omly assigned to CBT ( n = 42 ) , OBT ( n = 43 ) , or attention placebo ( AP ; n = 40 ) . The pretreatment to 12-month followup reliability change index was used to determine clinical ly meaningful changes in pain intensity and physical impairment . Multinominal logistic regression analyses were used to determine the predictors of improvement in pain intensity and physical impairment for the entire sample . Analyses of variance were computed to compare the characteristics of responders and nonresponders in each of the 3 interventions . RESULTS At the 12-month followup , 53.5 % , 45.2 % , and 5 % of patients in the OBT , CBT , and AP groups , respectively , reported clinical ly meaningful improvements in pain intensity . Similarly , 58.1 % , 38.1 % , and 7.5 % of patients treated with OBT , CBT , and AP , respectively , reported clinical ly significant improvements in physical impairment . Prior to treatment , the OBT physical impairment responders displayed significantly more pain behaviors , physical impairment , physician visits , solicitous spouse behaviors , and level of catastrophizing compared with nonresponders . The CBT physical impairment responders , compared with nonresponders , reported higher levels of affective distress , lower coping , less solicitous spouse behavior , and lower pain behaviors . CONCLUSION The results of this study suggest that pretreatment patient characteristics are important predictors of treatment response and may serve as a basis for matching treatments to patient characteristics . Prospect i ve outcome studies are needed to confirm whether the tailoring of treatment actually leads to better outcomes for patients with FMS"
] |
4116c31a-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND Early dietary intakes may influence the development of allergic disease . It is important to determine if dietary polyunsaturated fatty acids ( PUFAs ) given as supplements or added to infant formula prevent the development of allergy . OBJECTIVES To determine the effect of higher PUFA intake during infancy to prevent allergic disease . SEARCH METHODS We used the st and ard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials ( CENTRAL 2015 , Issue 9 ) , MEDLINE ( 1966 to 14 September 2015 ) , EMBASE ( 1980 to 14 September 2015 ) and CINAHL ( 1982 to 14 September 2015 ) . We also search ed clinical trials data bases , conference proceedings , and the reference lists of retrieved articles for r and omised controlled trials and quasi-r and omised trials . SELECTION CRITERIA R and omised and quasi-r and omised controlled trials that compared the use of a PUFA with no PUFA in infants for the prevention of allergy . DATA COLLECTION AND ANALYSIS Two review authors independently selected trials , assessed trial quality and extracted data from the included studies . We used fixed-effect analyses . The treatment effects were expressed as risk ratio ( RR ) with 95 % confidence intervals ( CI ) . We used the GRADE approach to assess the quality of evidence . MAIN RESULTS The search found 17 studies that assessed the effect of higher versus lower intake of PUFAs on allergic outcomes in infants . Only nine studies enrolling 2704 infants reported allergy outcomes that could be used in meta-analyses . Of these , there were method ological concerns for eight . In infants up to two years of age , meta-analyses found no difference in incidence of all allergy ( 1 study , 323 infants ; RR 0.96 , 95 % CI 0.73 to 1.26 ; risk difference ( RD ) -0.02 , 95 % CI -0.12 to 0.09 ; heterogeneity not applicable ) , asthma ( 3 studies , 1162 infants ; RR 1.04 , 95 % CI 0.80 to 1.35 , I2 = 0 % ; RD 0.01 , 95 % CI -0.04 to 0.05 , I2 = 0 % ) , dermatitis/eczema ( 7 studies , 1906 infants ; RR 0.93 , 95 % CI 0.82 to 1.06 , I2 = 0 % ; RD -0.02 , 95 % CI -0.06 to 0.02 , I2 = 0 % ) or food allergy ( 3 studies , 915 infants ; RR 0.81 , 95 % CI 0.56 to 1.19 , I2 = 63 % ; RD -0.02 , 95 % CI -0.06 to 0.02 , I2 = 74 % ) . There was a reduction in allergic rhinitis ( 2 studies , 594 infants ; RR 0.47 , 95 % CI 0.23 to 0.96 , I2 = 6 % ; RD -0.04 , 95 % CI -0.08 to -0.00 , I2 = 54 % ; number needed to treat for an additional beneficial outcome ( NNTB ) 25 , 95 % CI 13 to ∞).In children aged two to five years , meta- analysis found no difference in incidence of all allergic disease ( 2 studies , 154 infants ; RR 0.69 , 95 % CI 0.47 to 1.02 , I2 = 43 % ; RD -0.16 , 95 % CI -0.31 to -0.00 , I2 = 63 % ; NNTB 6 , 95 % CI 3 to ∞ ) , asthma ( 1 study , 89 infants ; RR 0.45 , 95 % CI 0.20 to 1.02 ; RD -0.20 , 95 % CI -0.37 to -0.02 ; heterogeneity not applicable ; NNTB 5 , 95 % CI 3 to 50 ) , dermatitis/eczema ( 2 studies , 154 infants ; RR 0.65 , 95 % CI 0.34 to 1.24 , I2 = 0 % ; RD -0.09 95 % CI -0.22 to 0.04 , I2 = 24 % ) or food allergy ( 1 study , 65 infants ; RR 2.27 , 95 % CI 0.25 to 20.68 ; RD 0.05 , 95 % CI -0.07 to 0.16 ; heterogeneity not applicable).In children aged two to five years , meta- analysis found no difference in prevalence of all allergic disease ( 2 studies , 633 infants ; RR 0.98 , 95 % CI 0.81 to 1.19 , I2 = 36 % ; RD -0.01 , 95 % CI -0.08 to 0.07 , I2 = 0 % ) , asthma ( 2 studies , 635 infants ; RR 1.12 , 95 % CI 0.82 to 1.53 , I2 = 0 % ; RD 0.02 , 95 % CI -0.04 to 0.09 , I2 = 0 % ) , dermatitis/eczema ( 2 studies , 635 infants ; RR 0.81 , 95 % CI 0.59 to 1.09 , I2 = 0 % ; RD -0.04 95 % CI -0.11 to 0.02 , I2 = 0 % ) , allergic rhinitis ( 2 studies , 635 infants ; RR 1.02 , 95 % CI 0.83 to 1.25 , I2 = 0 % ; RD 0.01 , 95 % CI -0.06 to 0.08 , I2 = 0 % ) or food allergy ( 1 study , 119 infants ; RR 0.27 , 95 % CI 0.06 to 1.19 ; RD -0.10 , 95 % CI -0.20 to -0.00 ; heterogeneity not applicable ; NNTB 10 , 95 % CI 5 to ∞ ) . AUTHORS ' CONCLUSIONS There is no evidence that PUFA supplementation in infancy has an effect on infant or childhood allergy , asthma , dermatitis/eczema or food allergy . However , the quality of evidence was very low . There was insufficient evidence to determine an effect on allergic rhinitis
|
[
"BACKGROUND AND OBJECTIVE : Relative deficiency of dietary omega 3 polyunsaturated fatty acids ( n-3 PUFA ) has been implicated in the rising allergy prevalence in Westernized countries . Fish oil supplementation may provide an intervention strategy for primary allergy prevention . The objective of this study was to assess the effect of fish oil n-3 PUFA supplementation from birth to 6 months of age on infant allergic disease . METHODS : In a double-blind r and omized controlled trial , 420 infants at high atopic risk received a daily supplement of fish oil containing 280 mg docosahexaenoic acid and 110 mg eicosapentaenoic acid or a control ( olive oil ) , from birth to age 6 months . PUFA levels were measured in 6-month-old infants ’ erythrocytes and plasma and their mothers ’ breast milk . Eczema , food allergy , asthma and sensitization were assessed in 323 infants for whom clinical follow-up was completed at 12 months of age . RESULTS : At 6 months of age , infant docosahexaenoic acid and eicosapentaenoic acid levels were significantly higher ( both P erythrocyte arachidonic acid levels were lower ( P = .003 ) in the fish oil group . Although n-3 PUFA levels at 6 months were associated with lower risk of eczema ( P = .033 ) and recurrent wheeze ( P = .027 ) , the association with eczema was not significant after multiple comparisons and there was no effect of the intervention per se on the primary study outcomes . Specifically , between-group comparisons revealed no differences in the occurrence of allergic outcomes including sensitization , eczema , asthma , or food allergy . CONCLUSIONS : Postnatal fish oil supplementation improved infant n-3 status but did not prevent childhood allergic disease",
"Long-chain polyunsaturated fatty acids have been associated with aspects of immune regulation including cytokine production . The purpose of this study was to investigate the effect of maternal dietary supplementation with tuna oil , rich in docosahexaenoic acid ( DHA ) , on the concentration of transforming growth factor beta 1 ( TGFβ1 ) and TGFβ2 in breast milk . In this r and omized , dietary intervention trial , mothers of term infants consumed a daily supplement of 2000 mg oil containing either placebo ( n=40 ) , 300 mg DHA ( n=40 ) , or 600 mg DHA ( n=40 ) . The DHA increase in milk and plasma was proportional to dietary DHA . There was no relationship between milk DHA status and TGFβ1 and TGFβ2 levels",
"OBJECTIVES : To evaluate the growth , tolerance , and safety of a new ultraconcentrated liquid human milk fortifier ( LHMF ) design ed to provide optimal nutrients for preterm infants receiving human breast milk in a safe , nonpowder formulation . METHODS : Preterm infants with a body weight ≤1250 g fed expressed and /or donor breast milk were r and omized to receive a control powder human milk fortifier ( HMF ) or a new LHMF for 28 days . When added to breast milk , the LHMF provided ∼20 % more protein than the control HMF . Weight , length , head circumference , and serum prealbumin , albumin , blood urea nitrogen , electrolytes , and blood gases were measured . The occurrence of sepsis , necrotizing enterocolitis , and serious adverse events were monitored . RESULTS : This multicenter , third party – blinded , r and omized controlled , prospect i ve study enrolled 150 infants . Achieved weight and linear growth rate were significantly higher in the LHMF versus control groups ( P = .04 and 0.03 , respectively ) . Among infants who adhered closely to the protocol , the LHMF had a significantly higher achieved weight , length , head circumference , and linear growth rate than the control HMF ( P = .004 , P = .003 , P = .04 , and P = .01 , respectively ) . There were no differences in measures of feeding tolerance or days to achieve full feeding volumes . Prealbumin , albumin , and blood urea nitrogen were higher in the LHMF group versus the control group ( all P difference in the incidence of confirmed sepsis or necrotizing enterocolitis . CONCLUSIONS : Use of a new LHMF in preterm infants instead of powder HMF is safe . Benefits of LHMF include improvements in growth and avoidance of the use of powder products in the NICU",
"Background / Objective : Evidence is accumulating that the long-chain PUFA ( LCPUFA ) are associated with offspring growth and body composition . We investigated the relationship between LCPUFAs in red blood cells ( RBCs ) of pregnant women/breastfeeding mothers and umbilical cord RBCs of their neonates with infant growth and body composition ⩽1 year of age . Subjects/ Methods : In an open-label r and omized , controlled trial , 208 healthy pregnant women received a dietary intervention ( daily supplementation with 1200 mg n-3 LCPUFAs and dietary counseling to reduce arachidonic acid ( AA ) intake ) from the 15th week of gestation until 4 months of lactation or followed their habitual diet . Fatty acids of plasma phospholipids ( PLs ) and RBCs from maternal and cord blood were determined and associated with infant body weight , body mass index ( BMI ) , lean body mass and fat mass assessed by skinfold thickness measurements and ultrasonography . Results : Dietary intervention significantly reduced the n-6/n-3 LCPUFA ratio in maternal and cord-blood plasma PLs and RBCs . Maternal RBCs docosahexaenoic acid ( DHA ) , n-3 LCPUFAs and n-6 LCPUFAs at the 32nd week of gestation were positively related to birth weight . Maternal n-3 LCPUFAs , n-6 LCPUFAs and AA were positively associated with birth length . Maternal RBCs AA and n-6 LCPUFAs were significantly negatively related to BMI and Ponderal Index at 1 year postpartum , but not to fat mass . Conclusion : Maternal DHA , AA , total n-3 LCPUFAs and n-6 LCPUFAs might serve as prenatal growth factors , while n-6 LCPUFAs also seems to regulate postnatal growth . The maternal n-6/n-3 LCPUFA ratio does not appear to have a role in adipose tissue development during early postnatal life",
"Formula supplemented with docosahexaenoic acid ( DHA ) improves retinal function of preterm infants but the optimal dose is unknown . In a r and omized controlled trial we examined the effect of increasing the DHA concentration of human milk and formula on circulating fatty acids of preterm infants . Infants born were fed high-DHA milk ( 1 % total fat as DHA ) or st and ard-DHA milk ( 0.2 - 0.3 % DHA ) until reaching their estimated due date ( EDD ) . Milk arachidonic acid ( AA ) concentration was approximately 0.5 % for both groups . At EDD , erythrocyte membrane phospholipid DHA was elevated in the high-DHA group compared with st and ard-DHA ( mean+/-SD , high-DHA 6.8+/-1.2 , st and ard-DHA 5.2+/-0.7 , p AA was lower ( high-DHA 14.9+/-1.3 , st and ard-DHA 16.0+/-1.2 , p preterm infants human milk and formula with 1 % DHA raises but does not saturate erythrocyte phospholipids with DHA . Milk exceeding 1 % DHA may be required to increase DHA status to levels seen in term infants",
"Background : An appropriate supply of n-3 long-chain polyunsaturated fatty acids ( LC-PUFAs ) during early childhood may enhance cognitive development . Little attention is paid to the fatty acid ( FA ) supply during the complementary feeding period . We examined the polyunsaturated fatty acids ( PUFAs ) and LC-PUFAs pattern in dietary practice of two study groups and evaluated the results against the present Dietary Guidelines in Germany . Methods : The food consumption and FA pattern of dietary practice in subjects from two prospect i ve studies ( n=102 and n=184 , respectively ) at the age of 3 , 6 and 9 months was assessed by weighed diet records , and changes during the first year of life were compared with the food-based dietary guidelines for the first year of life . Results : Dietary practice in the complementary feeding period was clearly dominated by commercial food products . The FA composition in dietary practice was different from the Guideline Diet and the ratio of n-6/n-3 PUFAs was less favorable . Consumption of breast milk or formula was still of major importance for the intake of LC-PUFAs in the complementary feeding period . Conclusion : LC-PUFAs are predominantly provided by breast milk and formula during the first year of life and consequently decrease when milk consumption decreases . For compensation , commercial complementary food might come closer to the Guideline Diet by lowering the n-6/n-3 PUFA ratio through appropriate vegetable oil along with an increase in total fat content up to the legal limit",
"OBJECTIVES Docosahexaenoic acid ( DHA ; 22:6 n-3 ) and arachidonic acid ( AA ; 20:4 n-6 ) are important for development of the central nervous system in mammals . There is a growth spurt in the human brain during the last trimester of pregnancy and the first postnatal months , with a large increase in the cerebral content of AA and DHA . The fetus and the newborn infant depend on maternal supply of DHA and AA . Our hypothesis was that maternal intake of DHA during pregnancy and lactation is marginal and that high intake of this fatty acid would benefit the child . We examined the effect of supplementing pregnant and lactating women with very-long-chain n-3 polyunsaturated fatty acids ( PUFAs ; cod liver oil ) on mental development of the children , compared with maternal supplementation with long-chain n-6 PUFAs ( corn oil ) . METHODS The study was r and omized and double-blinded . Pregnant women were recruited in week 18 of pregnancy to take 10 mL of cod liver oil or corn oil until 3 months after delivery . The cod liver oil contained 1183 mg/10 mL DHA , 803 mg/10 mL eicosapentaenoic acid ( 20:5 n-3 ) , and a total of 2494 mg/10 mL summation operator n-3 PUFAs . The corn oil contained 4747 mg/10 mL linoleic acid ( 18:2 n-6 ) and 92 mg/10 mL alpha-linolenic acid ( 18:3 n-3 ) . The amount of fat-soluble vitamins was identical in the 2 oils ( 117 micro g/mL vitamin A , 1 micro g/mL vitamin D , and 1.4 mg/mL dl-alpha-tocopherol ) . A total of 590 pregnant women were recruited to the study , and 341 mothers took part in the study until giving birth . All infants of these women were scheduled for assessment of cognitive function at 6 and 9 months of age , and 262 complied with the request . As part of the protocol , 135 subjects from this population were invited for intelligence testing with the Kaufman Assessment Battery for Children ( K-ABC ) at 4 years of age . Of the 135 invited children , 90 came for assessment . Six children did not complete the examination . The K-ABC is a measure of intelligence and achievement design ed for children aged 2.5 years through 12.5 years . This multisubtest battery comprises 4 scales : Sequential Processing , Simultaneous Processing , Achievement ( not used in the present study ) , and Nonverbal Abilities . The Sequential Processing and Simultaneous Processing scales are hypothesized to reflect the child 's style of problem solving and information processing . Scores from these 2 scales are combined to form a Mental Processing Composite , which serves as the measure of intelligence in the K-ABC . RESULTS We received dietary information from 76 infants ( 41 in the cod liver oil group and 35 in the corn oil group ) , documenting that all of them were breastfed at 3 months of age . Children who were born to mothers who had taken cod liver oil ( n = 48 ) during pregnancy and lactation scored higher on the Mental Processing Composite of the K-ABC at 4 years of age as compared with children whose mothers had taken corn oil ( n = 36 ; 106.4 [ 7.4 ] vs 102.3 [ 11.3 ] ) . The Mental Processing Composite score correlated significantly with head circumference at birth ( r = 0.23 ) , but no relation was found with birth weight or gestational length . The children 's mental processing scores at 4 years of age correlated significantly with maternal intake of DHA and eicosapentaenoic acid during pregnancy . In a multiple regression model , maternal intake of DHA during pregnancy was the only variable of statistical significance for the children 's mental processing scores at 4 years of age . CONCLUSION Maternal intake of very-long-chain n-3 PUFAs during pregnancy and lactation may be favorable for later mental development of children",
"Background and Objectives : Postdischarge formulas with extra energy and protein improve short-term growth but may also influence long-term body composition in an unwanted manner . Energy- and protein-enriched formulas with an increased protein-to-energy ratio improves gain of lean mass . The objective of the study was to investigate whether feeding a nutrient-enriched formula without extra energy after term , usually 3 to 4 weeks after discharge , would influence growth and body composition in infancy . Methods : In this r and omized controlled trial preterm infants were fed fortified human milk or preterm formula until term . At term , 102 infants were r and omized to a nutrient-enriched formula without extra energy or st and ard formula until 6 months corrected age . Twenty-six infants received unfortified human milk after term . At term and 6 months corrected age , anthropometry and a dual-energy x-ray absorptiometry ( DEXA ) scan were performed . Lean and fat mass ( FM ) were corrected for height . Results : There were no differences in growth or body size between the feeding groups . Infants fed the enriched formula gained less FM and had lower FM corrected for body size at 6 months corrected age than infants fed st and ard formula . Infants fed human milk had lower lean mass and higher FM corrected for body size at 6 months corrected age than formula-fed infants . Conclusions : Feeding nutrient-enriched formula without extra energy after term does not change quantity of growth but does influence type of weight gain and body composition of preterm infants . Infants fed the nutrient-enriched formula had lower FM corrected for body size at 6 months corrected age than infants fed st and ard formula or human milk",
"The purpose of our study was to assess whether a supplement of fish oil ( FO ) and evening primrose oil ( EPO ) for formula-fed infants was capable of avoiding reductions in erythrocyte docosahexaenoic acid ( DHA , 22∶6n−3 ) and arachidonic acid ( AA , 20∶4n−6 ) associated with st and ard formula feeding . Healthy , term infants , whose mothers chose to formula feed , were r and omized to either a placebo or supplemented formula for their first 30 wk of life . A reference group of beast-fed infants also was enrolled . Erythrocyte fatty acids were measured by capillary gas chromatography on day 5 and in weeks 6 , 16 , and 30 . Supplementation of formula with 0.36 % of total fatty acids as DHA result ed in erythrocyte DHA being maintained at or above breast-fed levels for the entire 30-wk study period , and breast feeding ( 0.21 % DHA ) result ed in a modest fall in erythrocyte DHA relative to baseline ( day 5 ) values . The level of erythrocyte DHA in placebo formula-fed infants was halved by week 16 . AA levels decreased in all infants in the first six weeks , but the levels in breast- and placebo formula-fed infants increased with age and returned to approximate baseline ( day 5 ) values by 16 and 30 wk of age , respectively . Erythrocyte AA in FO+EPO-supplemented infants remained low and below breast- and placebo formula-fed levels . Our data suggest that dietary supplementation with DHA at 0.36 % total fatty acids results in erythrocyte DHA levels above those found in breast-fed infants . EPO supplementation was not effective at maintaining erythrocyte AA when given with FO",
"Human milk contains small but nutritionally significant amounts of long-chain polyunsaturated fatty acids ( LCP ) , such as arachidonic ( AA , 20:4n-6 ) and docosahexaenoic ( DHA , 22:6n-3 ) acids , which are not present in most infant formulae . In the present study , the fatty acid composition of plasma and erythrocytes was determined at birth and again at 7 days , 1 and 3 months in 49 healthy full-term infants ( 37 - 42 week 's gestation ) . One group of infants was fed exclusively with human milk ( n=16 ) and the others were r and omly assigned to a st and ard term formula ( F ) ( n=15 ) or the same formula with egg yolk lecithin providing DHA ( 0.15 % ) and AA ( 0.30 % ) ( LCP-F ) ( n=18 ) . Plasma and erythrocyte LCP values of the three dietary groups did not differ at 7 days of age , but the contents of DHA and AA in plasma and erythrocytes at 1 and 3 months were significantly lower ( P plasma or erythrocyte AA or DHA concentrations between the group fed breast milk and the group fed supplemented formula during the period studied",
"OBJECTIVE To test the hypothesis that early enteral supplementing fat and fish oil decreases the duration of parenteral nutrition ( PN ) and increases enteral nutrition ( EN ) before bowel reanastomosis in premature infants with an enterostomy . STUDY DESIGN Premature infants ( r and omized to usual care ( control=18 ) or early supplementing enteral fat supplement and fish oil ( treatment=18 ) . Intravenous lipid was decreased as enteral fat intake was increased . Daily weight , clinical and nutrition data , and weekly length and head circumference were recorded . The primary outcomes were the duration of PN and volume of EN intake , and the secondary outcomes were weight gain ( g/day ) , ostomy output ( mL/kg/d ) , and serum conjugated bilirubin level ( mg/dL ) from initiating feeding to reanastomosis . Data were analyzed by Student t test or Wilcoxon rank sum test . RESULTS There were no differences in the duration of PN , ostomy output , and weight gain between the 2 groups before reanastomosis . However , supplemented infants received less intravenous lipid , had greater EN intake , and lower conjugated bilirubin before reanastomosis , and they also received greater total calorie , had fewer sepsis evaluations and less exposure to antibiotics and central venous catheters before reanastomosis , and had greater weight and length gain after reanastomosis ( all P feeding of a fat supplement and fish oil was associated with decreased exposure to intravenous lipid , increased EN intake , and reduced conjugated bilirubin before reanastomosis and improved weight and length gain after reanastomosis in premature infants with an enterostomy",
"Objective : We investigated how cod liver oil influences the amount of essential fatty acids in mothers ’ breast milk . Design and Intervention : Lactating mothers ( n=22 ) were r and omized into four groups 3–8 weeks after parturition . They were supplemented for 14 days with 0 , 2.5 , 5 and 10 ml cod liver oil ( 7.7 g eicosapentaenoic acid ( EPA , 20:5n-3 ) , 10.2 g docosahexaenoic acid ( DHA , 22:6n-3 ) and 22.9 g n-3 fatty acids in total per 100 ml ) . Results : In maternal plasma phospholipids there was an increase in the content of EPA and DHA in the group supplemented with 10 ml cod liver oil daily ( P≤0.05 ) . DHA concentrations in breast milk pre-supplementation ranged from 0.15 to 1.56 wt% and increased in all supplemented groups ( P≤0.05 ) . The concentration of EPA in breast milk increased in the groups supplemented with 5 or 10 ml cod liver oil ( P≤0.05 ) , whereas the concentration of arachidonic acid ( AA , 20:4n-6 ) did not change in any of the supplemented groups . Total intake of DHA adjusted to body mass index ( BMI ) , correlated to DHA concentrations in plasma ( r=0.49 , P=0.02 ) and breast milk ( r=0.45 , P=0.04 ) . The concentration of tocopherol did not change during the supplementation period , neither in plasma nor in breast milk . Conclusion : Dietary intake of DHA is reflected in the concentration of DHA in breast milk , without affecting the concentration of AA or tocopherol . Sponsorship : Supported by Peter Möller avd . av Orkla",
"Polyunsaturated fatty acids ( PUFAs ) are components of cell membranes and may play an immunomodulating role in the pathogenesis of atopic dermatitis ( AD ) . The goal was to determine the impact of PUFAs on AD by dietary supplementation of infants . Based on the parents ' decision on their babies ' primary feeding , mothers and newborns were r and omized to the supplementation with gamma-linolenic acid ( GLA ) or placebo for up to 6 months . Breastfed infants received GLA by supplementing their mothers . Formula diet was commercial whey hydrolysate unsupplemented with PUFAs . Of 131 eligible infants , 24 developed AD within the first year of life . Of these , nine belonged to the exclusively breastfed group ( n = 58 ) , 14 to the combined-fed group ( n = 53 ) , and one to the never breastfed group ( n = 20 ) . We could not find an influence of GLA on the development of AD . In subjects with AD , at 1 yr of age the serum-immunoglobulin E ( IgE ) was the lowest in the GLA-supplemented group A-subjects . In the GLA-supplemented group , GLA-levels in breast milk were similar in atopic and non-atopic infants . In the non-supplemented group the GLA-content of breast milk was 0.07 % of total fatty acids in atopic infants vs. 0.17 % in non-atopic infants ( p GLA-supplementation could not prevent AD . Interestingly , the number of infants developing AD was the lowest in never breastfed children . In infants suffering from AD , GLA-supplementation seemed to reduce total IgE in the first year of life",
"Conflicting evidence exists on the effect of long-chain polyunsaturated fatty acid ( LCPUFA ) formula supplementation on cardiovascular health in term infants . It is known that LCPUFA supplementation does not affect infant growth , but long term outcome data are not available . The current study investigates whether 2 mo LCPUFA formula supplementation affects cardiovascular and anthropometric development at 9 y. A prospect i ve , double-blind , r and omized trial was performed in healthy term infants : a st and ard formula control group ( CF , n = 169 ) and a LCPUFA-supplemented group [ LF , n = 145 ; 0.45 % ( by wt ) AA and 0.30 % ( by wt ) docosahexaenoic acid ( DHA ) ] . A breastfed group ( BF ; n = 159 ) served as reference . At the age of 9 y , systolic and diastolic blood pressure , heart rate , head circumference , weight , and height were measured . Univariate and multivariate analyses were performed ; 63 to 79 % of children were assessed . None of the cardiovascular or anthropometric measurements differed between the formula groups . Breastfed children had a marginally lower heart rate than formula-fed children , in particular compared with children fed control formula . Blood pressure and parameters of growth including BMI of breast and formula-fed children did not differ . In conclusion , the study suggests that short-term LCPUFA supplementation does not influence cardiovascular and anthropometric development at 9",
"OBJECTIVE Docosahexaenoic acid ( DHA ) and arachidonic acid ( ARA ) are long-chain polyunsaturated fatty acids found in breast milk and recently added to infant formulas . Their importance in infant nutrition was recognized by the rapid accretion of these fatty acids in the brain during the first postnatal year , reports of enhanced intellectual development in breastfed children , and recognition of the physiologic importance of DHA in visual and neural systems from studies in animal models . These considerations led to clinical trials to evaluate whether infant formulas that are supplemented with DHA or both DHA and ARA would enhance visual and cognitive development or whether conversion of linoleic acid and alpha-linolenic acid , the essential fatty acid precursors of ARA and DHA , respectively , at the levels found in infant formulas is sufficient to support adequately visual and cognitive development . Visual and cognitive development were not different with supplementation in some studies , whereas other studies reported benefits of adding DHA or both DHA and ARA to formula . One of the first trials with term infants that were fed formula supplemented with DHA or both DHA and ARA evaluated growth , visual acuity ( Visual Evoked Potential ; Acuity Card Procedure ) , mental and motor development ( Bayley Scales of Infant Development ) , and early language development ( MacArthur Communicative Developmental Inventories ) . Growth , visual acuity , and mental and motor development were not different among the 3 formula groups or between the breastfed and formula-fed infants in the first year of life . At 14 months of age , infants who were fed the formula with DHA but no ARA had lower vocabulary production and comprehension scores than infants who were fed the unsupplemented control formula or who were breastfed , respectively . The present follow-up study evaluated IQ , receptive and expressive vocabulary , visual-motor function , and visual acuity of children from the original trial when they reached 39 months of age . METHODS Infants were r and omized within 1 week after birth and fed a control formula ( n = 65 ) , one containing DHA ( n = 65 ) , or one containing both ARA and DHA ( n = 66 ) to 1 year of age . A comparison group ( n = 80 ) was exclusively breastfed for at least 3 months after which the infants continued to be exclusively breastfed or were supplemented with and /or weaned to infant formula . At 39 months , st and ard tests of IQ ( Stanford Binet IQ ) , receptive vocabulary ( Peabody Picture Vocabulary Test-Revised ) , expressive vocabulary ( mean length of utterance ) , visual-motor function ( Beery Visual-Motor Index ) , and visual acuity ( Acuity Card Procedure ) were administered . Growth , red blood cell fatty acid levels , and morbidity also were evaluated . RESULTS Results were analyzed using analysis of variance or linear regression models . The regression model for IQ , receptive and expressive language , and the visual-motor index controlled for site , birth weight , sex , maternal education , maternal age , and the child 's age at testing . The regression model for visual acuity controlled for site only . A variable selection model also identified which of 22 potentially prognostic variables among different categories ( feeding groups , the child and family demographics , indicators of illness since birth , and environment ) were most influential for IQ and expressive vocabulary . A total of 157 ( 80 % ) of the 197 infants studied at 12 months participated in this follow-up study . Characteristics of the families were representative of US families with children up to 5 years of age , and there were no differences in the demographic or family characteristics among the r and omized formula groups . As expected , the formula and breastfed groups differed in ethnicity , marital status , parental education , and the prevalence of smoking . Sex , ethnicity , gestational age at birth , and birth weight for those who participated at 39 months did not differ from those who did not . The 12-month Bayley mental and motor scores and 14-month vocabulary scores of the children who participated also were were not different from those who did not . At 39 months , IQ , receptive and expressive language , visual-motor function , and visual acuity were not different among the 3 r and omized formula groups or between the breastfed and formula groups . The adjusted means for the control , ARA+DHA , DHA , and breastfed groups were as follows : IQ scores , 104 , 101 , 100 , 106 ; Peabody Picture Vocabulary Test , 99.2 , 97.2 , 95.1 , 97.4 ; mean length of utterance , 3.64 , 3.75 , 3.93 , 4.08 ; the visual-motor index , 2.26 , 2.24 , 2.05 , 2.40 ; and visual acuity ( cycles/degree ) , 30.4 , 27.9 , 27.5 , 28.6 , respectively . IQ was positively associated with female sex and maternal education and negatively associated with the number of siblings and exposure to cigarette smoking in utero and /or postnatally . Expressive language also was positively associated with maternal education and negatively associated with the average hours in child care per week and hospitalizations since birth but only when the breastfed group was included in the analysis . The associations between maternal education and child IQ scores are consistent with previous reports as are the associations between prenatal exposure to cigarette smoke and IQ and early language development . Approximately one third of the variance for IQ was explained by sex , maternal education , the number of siblings , and exposure to cigarette smoke . Growth achievement , red blood cell fatty acid levels , and morbidity did not differ among groups . CONCLUSIONS We reported previously that infants who were fed an unsupplemented formula or one with DHA or with both DHA and ARA through 12 months or were breastfed showed no differences in mental and motor development , but those who were fed DHA without ARA had lower vocabulary scores on a st and ardized , parent-report instrument at 14 months of age when compared with infants who were fed the unsupplemented formula or who were breastfed . When the infants were reassessed at 39 months using age-appropriate tests of receptive and expressive language as well as IQ , visual-motor function and visual acuity , no differences among the formula groups or between the formula and breastfed groups were found . The 14-month observation thus may have been a transient effect of DHA ( without ARA ) supplementation on early vocabulary development or may have occurred by chance . The absence of differences in growth achievement adds to the evidence that DHA with or without ARA supports normal growth in full-term infants . In conclusion , adding both DHA and ARA when supplementing infant formulas with long-chain polyunsaturated fatty acids supports visual and cognitive development through 39 months",
"Background : Intestinal damage and malabsorption caused by chronic environmental enteropathy are associated with growth faltering seen in infants in less-developed countries . Evidence has suggested that supplementary omega-3 ( n−3 ) long-chain PUFAs ( LC-PUFAs ) might ameliorate this damage by reducing gastrointestinal inflammation . LC-PUFA supplementation may also benefit cognitive development . Objective : We tested whether early n−3 LC-PUFA supplementation improves infant intestinal integrity , growth , and cognitive function . Design : A r and omized , double-blind , controlled trial [ 200 mg DHA and 300 mg EPA or 2 mL olive oil/d for 6 mo ] was conducted in a population of 172 rural Gambian infants aged 3–9 mo . The primary endpoints were anthropometric measures and gut integrity [ assessed by using urinary lactulose : mannitol ratios ( LMRs ) ] . Plasma fatty acid status , intestinal mucosal inflammation ( fecal calprotectin ) , daily morbidity , and cognitive development ( 2-step means-end test and an attention assessment ) were secondary endpoints . Results : PUFA supplementation result ed in a significant increase in plasma n−3 LC-PUFA concentrations ( P and midupper arm circumference ( MUAC ) ( effect size : 0.31 z scores ; 95 % CI : 0.06 , 0.56 ; P = 0.017 ) at 9 mo of age . At 12 mo , MUAC remained greater in the intervention group , and we observed significant increases in skinfold thicknesses ( P ≤ 0.022 for all ) . No other significant differences between treatment groups were detected for growth or LMRs at 9 mo or for secondary outcomes . Conclusions : Fish-oil supplementation successfully increased plasma n−3 fatty acid status . However , in young , breastfed Gambian infants , the intervention failed to improve linear growth , intestinal integrity , morbidity , or selected measures of cognitive development . The trial was registered at www.is rct n.org as IS RCT N66645725",
"Background The immune consequences of adding 20:4n-6 and 22:6n-3 fatty acids to preterm infant formula are not known . Methods The effect of feeding preterm infants ( 14–42 days of age ) human milk ( Human Milk group ) , infant formula ( Formula group ) , or formula with added long-chain polyunsaturated fatty acids 20:4n-6 and 22:6n-3 ( Formula + LCP group ) on isolated peripheral blood lymphocytes ( by flow cytometry ) and lipid composition ( by gas – liquid chromatography ) was determined . Lymphocytes were stimulated in vitro with phytohemagglutinin to measure soluble interleukin (sIL)-2R and IL-10 production ( by enzyme-linked immunosorbent assay ) . Results With age , the percentage of CD3+CD4 + T cells and the percentage of CD20 + cells increased in the Human Milk and Formula + LCP groups ( P CD45R0 ( antigen mature ) and less CD45RA ( antigen naive ) at 42 days of age ( P IL-10 production was lower ( P Production of IL-10 by the cells of the Formula + LCP group was not different from that produced by the Human Milk group cells . An age-related decrease ( P sIL-2R production by Formula + LCP lymphocytes was observed , but sIL-2R production at 42 days in the Formula + LCP group did not differ significantly from that in the Human Milk group . Compared with Formula alone , adding LCP to formula result ed in a lower C18:2n-6 and higher C20:4n-6 content in lymphocyte phospholipids ( P Adding LCP to a preterm infant formula result ed in lymphocyte population s , phospholipid composition , cytokine production , and antigen maturity that are more consistent with that in human milk – fed infants . This may affect the ability of the infant to respond to immune challenges",
"Background : Fish consumption during infancy has been regarded as a risk factor for allergic disease but later evidence suggests a protective role . However , method ological limitations in the studies make conclusions uncertain . The aim of this study was to assess the association between fish consumption during the first year of life and development of allergic diseases by age 4",
"Long chain polyunsaturates ( LCP ) status during the early neonatal period is associated with a reduced risk of atopic symptoms and later allergies . In this study , we characterized the immune response of low-risk , term , formula-fed infants r and omized at ≤14 d of age to st and ard term formula ( Formula ) or formula containing LCP ( Formula+LCP ) for 4 wks . Infants exclusively fed human milk were included for comparison . Peripheral blood was collected at 14 and 42 d of age , and lymphocyte phenotype , proliferation , and cytokine production ( IL-2 , IL-4 , IL-6 , IL-10 , IL-12 , IFN-γ , TNF-α , TGFβ ) were assessed after incubation with β-lactoglobulin ( BLG ) and soy protein ( SOY ) . Lymphocyte proliferation did not differ between groups . Compared with human milk-fed infants at 2 wks , formula-fed infants produced more TNF-α and IFN-γ and had more cells expressing ICAM-1 ( CD54 ) after incubation with BLG and SOY ( p fed Formula+LCP produced more TNF-α with SOY ( 3.2-fold ) and IFN-γ ( 3.3-fold ) with BLG compared with infants fed Formula ( p low-risk term infants fed formula before 14 d of age produced more TNF-α and IFN-γ in response to food proteins . Feeding Formula+LCP for 4 wks maintained the higher TNF-α and IFN-γ response to these food proteins",
"Background Human milk is the optimal nutrition for infants . When breastfeeding is not possible , supplementation of infant formula with long chain polyunsaturated fatty acids appears to promote neurodevelopmental outcome and visual function . Plant oils , that are the only source of fat in most of infant formulas , do not contain specific fatty acids that are present in human and cow milk and do not encounter milk fat triglyceride structure . Experimental data suggest that a mix of dairy lipids and plant oils can potentiate endogenous synthesis of n-3 long chain polyunsaturated fatty acids . This trial aims to determine the effect of an infant formula supplemented with a mixture of dairy lipids and plant oils on the erythrocyte membrane omega-3 fatty acid profile in full-term infants ( primary outcome ) . Erythrocyte membrane long chain polyunsaturated fatty acids and fatty acids content , the plasma lipid profile and the insulin-growth factor 1 level , the gastrointestinal tolerance , the changes throughout the study in blood fatty acids content , in growth and body composition are evaluated as secondary outcomes . Methods / Design In a double-blind controlled r and omized trial , 75 healthy full-term infants are r and omly allocated to receive for four months a formula supplemented with a mixture of dairy lipids and plant oils or a formula containing only plant oils or a formula containing plant oils supplemented with arachidonic acid and docosahexaenoic acid . Twenty-five breast-fed infants constitute the reference group . Erythrocyte membrane omega-3 fatty acid profile , long chain polyunsaturated fatty acids and the other fatty acids content , the plasma lipid profile and the insulin-growth factor 1 level are measured after four months of intervention . Gastrointestinal tolerance , the changes in blood fatty acids content , in growth and body composition , assessed by means of an air displacement plethysmography system , are also evaluated throughout the study . Discussion The achievement of an appropriate long chain polyunsaturated fatty acids status represents an important goal in neonatal nutrition . Gaining further insight in the effects of the supplementation of a formula with dairy lipids and plant oils in healthy full-term infants could help to produce a formula whose fat content , composition and structure is more similar to human milk . Trial registration Clinical Trials.gov Identifier",
"We have previously reported a protective effect of maternal omega-3 long-chain polyunsaturated fatty acids ( ω-3 LCPUFA ) supplementation in pregnancy and lactation on IgE-associated eczema and food allergy in the infant during the first year of life . Here we investigate whether the effects of the LCPUFA supplementation on IgE-associated diseases last up to 2 yr of age and assess the relationship between plasma proportions of ω-3 PUFAs and the frequency and severity of infant allergic disease . 145 pregnant women , at risk of having an allergic infant , were r and omized to daily supplementation with 1.6 g eicosapentaenoic acid ( EPA ) and 1.1 g docosahexaenoic acid ( DHA ) or placebo starting in the 25th gestational week and continuing through 3.5 months of breastfeeding . Clinical examinations , skin prick tests and analysis of maternal and infant plasma phospholipid fatty acids and infant specific IgE were performed . No difference in the prevalence of allergic symptoms was found between the intervention groups . The cumulative incidence of IgE-associated disease was lower in the ω-3-supplemented group ( 6/54 , 13 % ) compared with the placebo group ( 19/62 , 30 % , p=0.01 ) . Higher maternal and infant proportions of DHA and EPA were associated with lower prevalence of IgE associated disease ( p=0.01 - 0.05 ) in a dose-dependent manner . Higher maternal and infant proportions of DHA and EPA were found if the infants presented none , when compared with multiple allergic symptoms , ( p ω-3 supplementation offered no obvious preventive effect on the prevalence of clinical symptoms of allergic disease , but the decrease in cumulative incidence of IgE-associated disease seen during the first year still remained until 2 yr of age . Furthermore , high proportions of DHA and EPA in maternal and infant plasma phospholipids were associated with less IgE-associated disease and a reduced severity of the allergic phenotype",
"BACKGROUND Docosahexaenoic acid ( DHA ) and arachidonic acid ( AA ) are long-chain polyunsaturated fatty acids ( LCPs ) that play pivotal roles in growth and neurodevelopment . OBJECTIVE We aim ed to quantify the synthesis of LCPs in preterm infants fed infant formula containing LCPs . DESIGN Twenty-two preterm infants were r and omly assigned to either the no-LCP group ( fed formula without LCPs ; n = 11 ) or the LCP group ( fed formula with LCPs ; n = 11 ) . Dietary LCPs had higher (13)C content than did the endogenously synthesized LCPs , which were derived from linoleic and alpha-linolenic acids . The (13)C content of major selected plasma fatty acids was measured by using gas chromatography-isotope ratio mass spectrometry at birth and at age 1 , 3 , and 7 mo . Absolute LCP synthesis and the percentage of LCP synthesis relative to dietary intake were calculated . RESULTS Percentage AA synthesis was 67.2 + /- 7.8 % , 35.9 + /- 9.8 % , and 29.0 + /- 10.3 % , and that of DHA was 41.7 + /- 14.9 % , 10.5 + /- 8.1 % , and 7.4 + /- 6.2 % at 1 , 3 , and 7 mo old , respectively . Absolute AA synthesis was 26.7 + /- 4.2 , 14.4 + /- 3.9 , and 11.6 + /- 4.1 mg x kg(-1 ) x d(-1 ) and that of DHA was 12.6 + /- 4.5 , 3.2 + /- 2.5 , and 2.3 + /- 1.9 mg x kg(-1 ) . d(-1 ) at 1 , 3 , and 7 mo old , respectively . AA and DHA synthesis decreased significantly ( P AA synthesis was significantly ( P DHA synthesis . CONCLUSIONS By this novel approach , we measured endogenous LCP synthesis in infants receiving dietary LCPs over long periods . By age 7 mo , LCP synthesis was dramatically lower in preterm infants fed LCPs ",
"To determine the effect of feeding formula containing long-chain PUFA ( LCP ) on immune function , healthy term infants were r and omised at age 2 weeks to either a st and ard term formula ( Formula ; n 14 ) or the same formula supplemented with the LCP 20 : 4n-6 and 22 : 6n-3 ( Formula+LCP ; n 16 ) . Peripheral blood was collected at 2 and 6 weeks to measure immune cell response ( the rate of [3H]thymidine uptake and cytokine production after stimulation with phytohaemagglutinin ( PHA ) ) . Compared with cells from infants receiving only human milk ( HM ) , the rate of [3H]thymidine uptake in response to PHA , but not IL-2 production , was lower for Formula+LCP infants ( P TNF-alpha ( unstimulated ) and had a fewer CD3+CD44 + cells before stimulation and fewer CD11c+ cells post-stimulation ( P immune cell distribution ( higher percentage CD3+CD44 + and CD4+CD28 + cells ) and cytokine profile ( lower production of TNF-alpha post-stimulation ) that did not differ from HM infants . Additionally , it was found that feeding infants formula during the first 10 d of life influenced immune function . These infants had a higher percentage of CD3 + , CD4+CD28 + , and lower percentage of CD14 + cells and produced more TNF-alpha and interferon-gamma after PHA stimulation than HM-fed infants ( P presence of specific cell types and function of infant blood immune cells . Since many diseases have a strong immunological component , these immune changes may be of physiological importance to the developing infant",
"BACKGROUND Normal brain and visual development is thought to require exogenous docosahexaenoic acid ( DHA ; 22:6n-3 ) intake , but the amount needed is debatable . Because the supplementation of breastfeeding mothers with DHA increases the DHA content of their infants ' plasma lipids , we hypothesized that it might also improve brain or visual function in the infants . OBJECTIVE The objective was to determine the effect of DHA supplementation of breastfeeding mothers on neurodevelopmental status and visual function in the recipient infant . DESIGN Breastfeeding women received capsules containing either a high-DHA algal oil ( approximately 200 mg DHA/d ) or a vegetable oil ( no DHA ) for 4 mo after delivery . Outcome variables included the fatty acid pattern of maternal plasma phospholipid and milk lipids 4 mo postpartum , the fatty acid pattern of plasma phospholipids and visual function in infants at 4 and 8 mo of age , and neurodevelopmental indexes of the infants at 12 and 30 mo of age . RESULTS Milk lipid and infant plasma phospholipid DHA contents of the supplemented and control groups were approximately 75 % and approximately 35 % higher , respectively , at 4 mo postpartum . However , neither the neurodevelopmental indexes of the infants at 12 mo of age nor the visual function at 4 or 8 mo of age differed significantly between groups . In contrast , the Bayley Psychomotor Development Index , but not the Mental Development Index , of the supplemented group was higher ( P DHA supplementation of breastfeeding mothers results in higher infant plasma phospholipid DHA contents during supplementation and a higher Bayley Psychomotor Development Index at 30 mo of age but results in no other advantages either at or before this age",
"Objectives : The aim of this study was to monitor changes in the fecal microbiota from 9 to 18 months and to investigate the effect of increasing dietary n-3 polyunsaturated fatty acids on the fecal microbiota . Patients and Methods : In a double-blind controlled trial with r and om allocation to daily supplementation with 5 mL of fish oil ( FO ) or sunflower oil ( SO ) from 9 to 18 months of age , stool sample s were collected from 132 healthy Danish infants . Molecular fingerprints of the bacterial DNA were obtained by terminal restriction fragment length polymorphism ( T-RFLP ) . Results : The T-RFLP profiles indicated that a few T-RFs became dominant with age ( bp100 and 102 , both presumed to be Bacteroidetes ) concomitantly with an overall increase in the microbial diversity ( P = 0.04 ) . Breast-feeding influenced both the T-RFLP profiles at 9 months and the changes from 9 to 18 months , and breast-feeding cessation during the trial modified the response to the dietary oils . In the FO group , the increase in bp102 was significantly reduced among children weaned before compared with those weaned during the trial ( P = 0.027 ) , whereas the increase in bp100 was reduced in the preweaned children of the SO group relative to those weaned during the trial ( P = 0.004 ) . This was supported by intervention group differences in the changes in bp102 and bp100 among the earlier weaned children ( P = 0.06 and P = 0.09 , respectively ) . Conclusions : Cessation of breast-feeding played a dominant role relative to developmental changes in the fecal microbiota from 9 to 18 months . FO compared with SO supplementation affected changes in large bacterial groups , but only among children who had stopped breast-feeding before 9 months of age",
"Objective . To determine if dietary long-chain polyunsaturated fatty acids ( LCPUFA ) affect the growth of formula-fed infants relative to breastfed infants . Methods . A r and omized , double-blind trial of three formula-fed groups and a parallel reference group of breastfed infants was conducted . The three treatments were a placebo ( no LCPUFA ) , docosahexaenoic acid ( DHA ) supplemented , and DHA plus arachidonic acid supplemented formulas fed for 12 months . Infant weight , length , head circumference , and fatty acid status were assessed at 6 , 16 , 34 weeks , and 1 year of age . Anthropometrics were repeated at 2 years of age . Results . There were no differences between the r and omized formula groups for weight , length , or head circumference even after adjustment for gender , gestational age , and the actual age at assessment . Post hoc regressions demonstrated a small negative association between DHA status at 16 weeks of age and weight at 1 and 2 years . Conclusions . Dietary LCPUFA do not influence growth of healthy term infants to a clinical ly significant degree",
"Necrotizing enterocolitis ( NEC ) causes approximately 4000 deaths/y and significant morbidity among U.S.-born preterm infants alone . Various combinations of inadequate tissue oxygenation , bacterial overgrowth , and enteral feeding with immaturity may cause the initial damage to intestinal mucosa that culminates in necrosis . Presently , there is not a way to predict the onset of the disease or to prevent its occurrence . As part of risk-benefit assessment , we compared disease in hospitalized preterm infants fed a commercial ( control ) preterm formula or an experimental formula with egg phospholipids for a r and omized , double-masked , clinical study of diet and infant neurodevelopment . Infants fed the experimental formula developed significantly less stage II and III NEC compared with infants fed the control formula ( 2.9 versus 17.6 % , p bronchopulmonary dysplasia ( 23.4 versus 23.5 % ) , septicemia ( 26 versus 31 % ) , and retinopathy of prematurity ( 38 versus 40 % ) . Compared with the control formula , the experimental formula provided 7-fold more esterified choline , arachidonic acid ( AA , 0.4 % of total fatty acids ) , and docosahexaenoic acid ( 0.13 % ) . Phospholipids are constituents of mucosal membranes and intestinal surfactant , and their components , AA and choline , are substrates for intestinal vasodilatory and cytoprotective eicosanoids ( AA ) and the vasodilatory neurotransmitter , acetylcholine ( choline ) , respectively . One or more of these components of egg phospholipids may have enhanced one or more immature intestinal functions to lower the incidence of NEC in this study . Regardless of the potential mechanism , a larger r and omized trial design ed to test the effect of this egg phospholipid-containing formula on NEC seems warranted",
"A double-blind , r and omized , controlled , parallel-group prospect i ve trial was conducted to determine whether a dose-response existed for four different levels of docosahexaenoic acid ( DHA ) supplementation on the cognitive performance of infants . A total of 122 term infants were fed one of four different formulas varying in their DHA composition ( 0.00 , 0.32 , 0.64 , and 0.96 % of total fatty acids as DHA ) from birth to 12 mo . The three DHA-supplemented formulas also contained 0.64 % of total fatty acids as arachidonic acid ( ARA , 20:4n-6 ) . Infants were tested at 4 , 6 , and 9 mo of age on a visual habituation protocol that yielded both behavioral and psychophysiological indices of attention . Infants in all DHA+ARA-supplemented conditions had lower heart rates than those in the unsupplemented condition ; there was no dose-response for this effect . The distribution of time that infants spent in different phases of attention ( a cognitive index derived from the convergence of behavioral and cardiac responses ) varied as a function of dosage . Infants supplemented at the two lower DHA doses spent proportionately more time engaged in active stimulus processing than infants fed the unsupplemented formula , whereas infants fed the highest dose were intermediate and did not differ from any other group",
"Studies on formula-fed infants indicate a beneficial effect of dietary DHA on visual acuity . Cross-sectional studies have shown an association between breast-milk DHA levels and visual acuity in breast-fed infants . The objective in this study was to evaluate the biochemical and functional effects of fish oil ( FO ) supplements in lactating mothers . In this double-blinded r and omized trial , Danish mothers with habitual fish intake below the 50th percentile of the Danish National Birth Cohort were r and omized to microencapsulated FO [ 1.3 g/d long-chain n−3 FA ( n−3 LCPUFA ) ] or olive oil ( OO ) . The intervention started within a week after delivery and lasted 4 mon . Mothers with habitual high fish intake and their infants were included as a reference group . Ninety-seven infants completed the trial ( 44 OO-group , 53 FO-group ) and 47 reference infants were followed up . The primary outcome measures were : DHA content of milk sample s ( 0 , 2 , and 4 mon postnatal ) and of infant red blood cell ( RBC ) membranes ( 4 mon postnatal ) , and infant visual acuity ( measured by swept visual evoked potential at 2 and 4 mon of age ) . FO supplementation gave rise to a threefold increase in the DHA content of the 4-mon milk sample s ( P RBC reflected milk contents ( r=0.564 , P ) . Infant visual acuity was not significantly different in the r and omized groups but was positively associated at 4 mon with infant RBC-DHA ( P=0.004 , multiple regression ) . We concluded that maternal FO supplementation during lactation did not enhance visual acuity of the infants who completed the intervention . However , the results showed that infants with higher RBC levels of n−3 LCPUFA had a better visual acuity at 4 mon of age , suggesting that n−3 LCPUFA may influence visual maturation ",
"Long-chain polyunsaturated fatty acids ( LCPUFA ) are important for normal visual and cortical development . In a previous study of the effects of LCPUFA on cognitive function of term infants at the age of 3 mon , we indicated that infants with evidence of reduced growth parameters at birth and impaired attention control as manifested by a late peak fixation during infant habituation assessment may benefit from LCPUFA supplementation . The aim of this prospect i ve study was to determine whether LCPUFA supplementation and late peak fixation are related to means-end problem-solving ability in these same infants at the age of 9 mon . Term infants ( 58 ) were r and omized to one of two formulas containing either LCPUFA or no LCPUFA and completed 4 mon of feeding with their formula . Cognitive function was assessed at 3 mon of age by measures of infant habituation . Infants ( 20 LCPUFA and 20 no-LCPUFA ) completed the problem-solving assessment at 9 mon . The no-LCPUFA group had lower scores on both measures of intention and number of solutions , but neither of these differences was significant . Analysis of covariance for the effects of group and peak fixation , covaried with gestation and birth weight , showed that the number of solutions was significantly reduced in the late peak-fixation infants receiving no LCPUFA ( P Intention scores tended to be reduced in this group ( P peak-fixation infants who received LCPUFA had solution and intention scores similar to early peak-fixation infants receiving LCPUFA or no LCPUFA . These findings suggest that in term infants who have reduced growth parameters at birth and who show evidence of impaired attention control , information processing and problem-solving ability in infancy may be enhanced by LCPUFA supplementation",
"Long-chain PUFA ( LCP ) deficiency is a frequent complication in cholestatic infants . We investigated the effects of LCP-supplemented formula on EFA status in infants with cholestasis . Twenty-three infants with cholestasis ( biliary atresia after surgery , 8 ; intrahepatic cholestasis , 15 ) aged 1.9 to 4.9 mon ( median 3.1 mon ) were r and omized to receive commercial infant formulas either without LCP or with LCP from egg phospholipids for 1 mon . Liver tests , nutrient intakes , and plasma phospholipid FA ( % w/w ) were determined at baseline and after intervention . At baseline , patients had high serum direct bilirubin levels ( 5.9 ± 3.0 mg/dL ; mean ± SD ) , they were malnourished ( body fat mass : 40 ± 13 % of normal ) and presented with PUFA deficiency [ plasma phospholipid PUFA : 28.43%w/w ( 26.56–30.53 ) in patients vs. 37.02%w/w ( 34.53–39.58 ) in controls ; median ( 1st–3rd quartile ) ] with elevated Mead acid and palmitoleic acid . LCP-supplemented ( n=11 and -nonsupplemented groups ( n=12 ) did not differ in age , indicators of liver function , and EFA status at baseline . After the intervention , LCP-supplemented infants had higher levels of arachidonic acid [ 7.2 ( 5.9–8.8 ) vs. 4.2 ( 3.0–5.3 ) % w/w ; P ] and DHA [ 2.8 ( 2.2–3.2 ) vs. 1.6 ( 1.0–2.1 ) % w/w ; P increased [ BARS concentration : 1.9 ( 1.4–2.2 ) vs. 1.3 ( 1.1–1.6 ) nmol/mL ; P concluded that LCP-supplemented formulae improve LCP status of infants with severe cholestasis but may enhance lipid peroxidation ",
"Abstract n−3 PUFA influence immune functioning and may affect the cytokine phenotype during development . To examine whether maternal fish oil supplementation during lactation could modify later immune responses in children , 122 lactating Danish mothers with a fish intake below the population median were r and omized to groups supplemented for the first 4 mon of lactation with 4.5 g/d of fish oil ( equivalent to 1.5 g/d of n−3 long-chain PUFA ) or olive oil . Fifty-three mothers with a fish intake in the highest quartile of the population were also included . The FA composition of erythrocyte membranes was measured at 4 mon and at 2 1/2 yr . Plasma immunoglobulin E ( IgE ) levels and cytokine production in lipopolysaccharide-stimulated whole-blood cultures were determined at 2 1/2 yr . Erythrocyte n−3 PUFA at 4 mon were higher in infants from the fish oil group compared with the olive oil group ( P The median production of lipopolysaccharide-induced interferon γ(IFN-γ ) in the fish oil group was fourfold higher than that in the olive oil group ( P=0.034 ) , whereas interleukin-10 ( IL-10 ) production was similar . The IFN-γ/IL-10 ratio was twofold higher in the fish oil group ( P=0.019 ) and was positively correlated with 20∶5n−3/20∶4n−6 in erythrocytes at 4 mon ( P=0.050 ) . The percentages of atopic children and plasma IgE were not different in the two groups , but the study was not design ed to look at atopy . Cytokine responses and erythrocyte FA composition in children of mothers with a high fish intake were intermediate in comparison with those in the r and omized groups . Fish oil supplementation during lactation result ed in increased in vitro IFN-γ production in the children 2 yr after the supplementation was given , which may reflect a faster maturation of the immune system",
"This was a r and omized , double-blind trial to determine if a nutrient-enriched ( preterm ) formula supplemented with 0.2 % docosahexaenoic acid ( DHA , 22∶6n−3 ) from a low eicosapentaenoic acid ( 0.06 % ) source of marine oil would enhance visual novelty preference and attention of preterm infants . Both the st and ard and experimental formulas contained 3 % of total fatty acids as linolenic acid ( 18∶3n−3 ) and were fed from approximately three days of age to two months past term . After two months , both diet groups were fed a commercially-available term formula with linolenic acid as the only source of n−3 fatty acid . At 12 mo visual recognition memory ( novelty preference ) and visual attention ( number and duration of discrete looks ) were determined with the Fagan Test of Infant Intelligence . The DHA-supplemented group compared with the control group had more and shorter duration looks in comparisons of familiar and novel stimuli , confirming earlier evidence that DHA can increase information processing speed of preterm infants who otherwise are receiving good intakes of linolenic acid . Because supplementation was stopped at two months and the effects seen at 12 mon , this study demonstrates for the first time that a relatively short period of DHA supplementation can produce significant effects on later visual attention ",
"Several studies have reported that feeding γ-linolenic acid ( GLA ) has result ed in no increase in arachidonic acid ( AA ) in newborns . This result was ascribed to the eicosapentaenoic acid (EPA)-rich fish oil used in these formulas . Docosahexaenoic acid ( DHA ) sources with only minor amounts of EPA are now available , thus the addition of GLA to infant formulas might be considered an alternative to AA supplementation . Sixty-six premature infants were r and omized to feeding one of four formulas [ ST : no GLA , no long-chain polyunsaturated fatty acids ; BO : 0.6 % GLA ( borage oil ) ; BO + FOLOW : 0.6 % GLA , 0.3 % DHA , 0.06 % EPA ; BO + FOHIGH : 0.6 % GLA , 0.3 % DHA , 0.2 % EPA ] or human milk ( HM , nonr and omized ) for 4 wk . Anthropometric measures and blood sample s were obtained at study entry and after 14 and 28 d. There were no significant differences between groups in anthropometric measures , tocopherol , and retinol status at any of the studied time points . The AA content of plasma phospholipids was similar between groups at study start and decreased significantly until day 28 in all formulafed groups , but not in the breast-fed infants [ ST : 6.6±0.2 % , BO : 6.9±0.3 % , BO + FOLOW : 6.9±0.4 % , BO + FOHIGH : 6.7±0.2 % , HM : 8.6±0.5 % , where values are reported as mean ±st and ard error ; all formulas significantly different ( P≤0.05 ) from HM ] . There was no significant influence of GLA or fish oil addition to the diet . GLA had only a very limited effect on AA status which was too small to obtain satisfactory concentrations ( concentrations similar to breast-fed babies ) under the circumstances tested . The effect of GLA on AA is independent of the EPA and DHA content in the diet within the dose ranges studied",
"Early accumulation of n-3 long-chain PUFA ( LCPUFA ) in the brain may contribute to differences in later cognitive abilities . In this study , our objective was to examine whether fish oil ( FO ) supplementation during lactation affects processing speed , working memory , inhibitory control , and socioemotional development at 7 years . Danish mothers ( n = 122 ) were r and omized to FO [ 1.5 g/d n-3 LCPUFA ] or olive oil ( OO ) supplementation during the first 4 months of lactation . The trial also included a high-fish intake ( HFI ) reference group ( n = 53 ) . Ninety-eight children were followed-up with an assessment of processing speed , an age-appropriate Stroop task , and the Strength and Difficulties Question naire at 7 year . A group effect of the intervention ( FO vs. OO ) was found in prosocial behavior scores ; this negative effect was carried by the boys . Exploratory analyses including all participants revealed the speed of processing scores were predicted by maternal n-3 LCPUFA intake during the intervention period ( negative relation ) and maternal education ( positive relation ) . Stroop scores indicative of working memory and inhibitory control were predicted by infant erythrocyte DHA status at 4 months of age ( negative relation ) . Early fish oil supplementation may have a negative effect on later cognitive abilities . Speed of processing and inhibitory control/working memory are differentially affected , with speed of processing showing effects of fish oil intake as a whole , whereas inhibitory control/working memory was related more specifically to DHA status",
"Healthy term infants ( n = 244 ) were r and omized to receive : ( 1 ) control , soy-based formula without supplementation or ( 2 ) docosahexaenoic acid−arachidonic acid ( DHA + ARA ) , soy-based formula supplemented with at least 17 mg DHA/100 kcal ( from algal oil ) and 34 mg ARA/100 kcal ( from fungal oil ) in a double-blind , parallel group trial to evaluate safety , benefits , and growth from 14 to 120 days of age . Anthropometric measurements were taken at 14 , 30 , 60 , 90 , and 120 days of age and 24-h dietary and tolerance recall were recorded at 30 , 60 , 90 , and 120 days of age . Adverse events were recorded throughout the study . Blood sample s were drawn from subsets of 25 infants in each group . Capillary column gas chromatography was used to analyze the percentages of fatty acids in red blood cell ( RBC ) lipids and plasma phospholipids . Compared with the control group , percentages of fatty acids such as DHA and ARA in total RBC and plasma phospholipids were significantly higher in infants in the DHA + ARA group at 120 days of age ( P 0.001 ) . Growth rates did not differ significantly between feeding groups at any assessed time point . Supplementation did not affect the tolerance of formula or the incidence of adverse events . Feeding healthy term infants soy-based formula supplemented with DHA and ARA from single cell oil sources at concentrations similar to human milk significantly increased circulating levels of DHA and ARA when compared with the control group . Both formulas supported normal growth and were well tolerated ",
"BACKGROUND Preterm infants have improved visual outcomes when fed a formula containing 0.2 - 0.4 % docosahexaenoic acid ( DHA ) compared with infants fed no DHA , but the optimal DHA dose is unknown . OBJECTIVE We assessed visual responses of preterm infants fed human milk ( HM ) and formula with a DHA concentration estimated to match the intrauterine accretion rate ( high-DHA group ) compared with infants fed HM and formula containing DHA at current concentrations . DESIGN A double-blind r and omized controlled trial studied preterm infants born at HM or formula containing 1 % DHA ( high-DHA group ) or approximately 0.3 % DHA ( current practice ; control group ) until reaching their estimated due date ( EDD ) . Both groups received the same concentration of arachidonic acid . Sweep visual evoked potential ( VEP ) acuity and latency were assessed at 2 and 4 mo corrected age ( CA ) . Weight , length , and head circumference were assessed at EDD and at 2 and 4 mo CA . RESULTS At 2 mo CA , acuity of the high-DHA group did not differ from the control group [ high-DHA group ( x + /- SD ) : 5.6 + /- 2.4 cycles per degree ( cpd ) , n = 54 ; control group : 5.6 + /- 2.4 cpd , n = 61 ; P = 0.96 ] . By 4 mo CA , the high-DHA group exhibited an acuity that was 1.4 cpd higher than the control group ( high-DHA : 9.6 + /- 3.7 cpd , n = 44 ; control : 8.2 + /- 1.8 cpd ; n = 51 ; P = 0.025 ) . VEP latencies and anthropometric measurements were not different between the high-DHA and control groups . CONCLUSION The DHA requirement of preterm infants may be higher than currently provided by preterm formula or HM of Australian women",
"BACKGROUND Increased consumption of n-3 long-chain polyunsaturated fatty acids ( PUFAs ) has been recommended during pregnancy and lactation . The production of proinflammatory cytokines by human peripheral blood mononuclear cells ( P BMC s ) can be modified by dietary n-3 PUFAs . OBJECTIVE We sought to determine whether dietary supplementation of lactating women with docosahexaenoic acid ( DHA ) can modulate the concentration of cytokines in the aqueous phase of human milk and the production of cytokines by human milk cells ( HMCs ) and P BMC s. DESIGN In this double-blind , prospect i ve , r and omized trial , mothers of healthy full-term infants were asked to consume daily a nutritional supplement of 2000 mg oil containing either placebo ( n = 40 ) , 300 mg DHA + 70 mg eicosapentaenoic acid ( EPA ; n = 40 ) , or 600 mg DHA + 140 mg EPA ( n = 40 ) . The fatty acid composition of plasma , P BMC s , milk , and HMCs from lactating mothers at 4 wk postpartum was measured by gas chromatography . The concentration of interleukin 6 and tumor necrosis factor alpha in milk and the production of interleukin 1beta , tumor necrosis factor alpha , and interleukin 6 by P BMC s and HMCs after stimulation with lipopolysaccharide was measured by enzyme-linked immunosorbent assay . RESULTS At 4 wk postpartum , 82 mothers were still breast-feeding their infants . DHA increases in maternal plasma , P BMC s , milk , and HMCs were proportional to dietary DHA . There was no relation between tissue DHA status and cytokine concentrations . CONCLUSIONS Consumption of DHA and 140 mg EPA/d for 4 wk increased n-3 PUFA concentrations in relevant tissues but did not cause perturbations in cytokine concentrations in human milk",
"( n-3 ) PUFA influence immune function in adults and may also affect immune maturation during development . This r and omized trial is , to our knowledge , the first to investigate whether fish oil supplementation in late infancy modifies immune responses . The study was a 2 x 2 intervention in 64 healthy Danish infants , who received cow 's milk or infant formula alone or with fish oil ( FO ) ( 3.4 + /- 1.1 mL/d ) from 9 to 12 mo of age . Before and after the intervention , fatty acid composition of erythrocyte membranes , plasma IgE , C-reactive protein , and soluble IL-2 receptor concentrations were measured . TNF-alpha , INF-gamma , and IL-10 concentrations in whole-blood cultures , stimulated for 22 h with LPS+phytohemaglutinin ( PHA ) or Lactobacillus paracasei , were also determined . IgA was measured in feces when infants were 10 mo of age . FO supplementation effectively raised erythrocyte ( n-3 ) PUFA ( P L. paracasei-induced INF-gamma ( P = 0.05 ) and tended to reduce LPS+PHA-induced IL-10 ( P = 0.08 ) . The FO intervention did not affect any of the other analyzed immune variables . The erythrocyte content of eicosapentanoic acid was negatively associated with LPS+PHA-induced IL-10 ( r = -0.38 , P = 0.02 ) . Feeding milk rather than formula did not affect cytokine production , but plasma soluble IL-2 receptor concentration was greater in the formula group than in the cow 's milk group ( P = 0.03 ) . Since the capacity to produce INF-gamma has been proposed as a maturation marker for the immune system in early life , this study suggests a faster immune maturation with FO supplementation with no apparent reduction in immune activation . The implication s for later health need further investigation",
"BACKGROUND Factors other than dietary fatty acids could be involved in the variability observed in blood docosahexaenoate ( 22:6n-3 ) and arachidonate ( 20:4n-6 ) status in formula-fed infants . OBJECTIVE We considered the 22:6n-3 and 20:4n-6 status at birth to be one of these factors and studied its influence on postnatal changes in term infants fed 4 different diets . DESIGN The blood phospholipid composition was determined at birth and on day 42 of feeding in 83 term infants fed breast milk , nonsupplemented formula , or 2 different 22:6n-3-supplemented formulas . Relations between 22:6n-3 and 20:4n-6 status at birth and their relative postnatal changes , calculated by the difference between status at the end of the feeding period ( 6 wk of age ) and at birth , were assessed . RESULTS Postnatal changes in the plasma and erythrocyte phospholipids 22:6n-3 and 20:4n-6 were negatively related to their respective concentrations at birth ( P Adjusted mean values for phospholipid 22:6n-3 in nonsupplemented-formula-fed infants and for 20:4n-6 in formula-fed infants decreased significantly more than they did in the other infant groups ( P 22:6n-3 and 20:4n-6 at birth in term infants is one of the major determinants of postnatal changes in these fatty acids . This finding indicates that research is required to characterize environmental , genetic , or both factors , which , in addition to maternal diet , could influence fatty acid status at birth",
"Docosahexaenoic acid ( DHA ; 22:6n-3 ) is important for normal visual development . We hypothesized that preterm infants fed formulas with marine oil as a source of DHA would have better visual acuity than infants fed formulas without marine oil , as measured by the Teller Acuity Card procedure . Marine oil ( P visual acuity , by repeated- measures analysis of variance ( ANOVA ) corrected for the effect of subject . Marine-oil-supplemented infants had better visual acuity than those fed st and ard formulas at 2 and 4 mo of age , by Fishers ' least-squares difference ( LSD ) . Acuity of both dietary groups improved through 6.5 mo of age , then plateaued . Through 4 mo of age , acuity was inversely related to oxygen supplementation ( log10 h ) and positively related to DHA status , by general-linear-models ( GLM ) analysis . After 4 mo of age , birth weight and gestational age were the only variables consistently related to visual acuity by GLM . We conclude that marine-oil-supplemented formula improved visual acuity of preterm infants through 4 mo of age by improving DHA status",
"BACKGROUND Breastfeeding has been reported to benefit visual development in children . A higher concentration of docosahexaneoic acid ( DHA ) in breast milk than in formula has been proposed as one explanation for this association and as a rationale for adding DHA to infant formula , but few long-term data support this possibility . OBJECTIVE The objectives of the study were , first , to test the hypothesis that breastfeeding benefits stereoscopic visual maturation and , second , if that benefit is shown , to ascertain whether it is mediated by the dietary intake of DHA . DESIGN Stereoacuity was measured by using the r and om dot E test ( primary outcome ) , and visual acuity was measured by using the Sonksen-Silver acuity system ( secondary outcome ) in previously breastfed ( n = 78 ) or formula-fed ( n = 184 ) children aged 4 - 6 y who had been followed prospect ively from birth . In the formula-fed group , children were r and omly assigned to receive formula with either DHA or arachidonic acid ( n = 94 ) or a control formula ( n = 90 ) for the first 6 mo . RESULTS Breastfed children had a significantly ( P = 0.001 ) greater likelihood of foveal stereoacuity ( high- grade or Stereoacuity did not differ significantly between children r and omly assigned to DHA-supplemented or control formula . None of the groups differed in Sonksen-Silver visual acuity . CONCLUSIONS These findings support the hypothesis that breastfeeding benefits long-term stereoscopic development . An effect of DHA can not be excluded , but the lack of difference in stereoacuity between infants r and omly assigned to DHA-containing and those assigned to control formula raises the hypothesis that factors in breast milk other than DHA account for the observed benefits",
"Healthy preterm infants fed formula with long-chain n-3 fatty acids ( n-3 LCFAs ) from marine oil have better early visual acuity but lower plasma phosphatidylcholine ( PC ) arachidonic acid ( AA ) and growth than infants fed formula containing linolenic acid ( LLA ) as the sole n-3 fatty acid . This r and omized , double-blind trial was design ed to study the effects of a different source of n-3 LCFAs and a shorter feeding interval on visual acuity ( by Teller Acuity Card ) and growth of preterm infants ( n = 59 ; 747 - 1275 g birth wt ) , some of whom required long periods of supplemental oxygen and developed bronchopulmonary dysplasia ( BPD ) . Infants were studied at 0 , 2 , 4 , 6 , 9 , and 12 mo past term . Plasma PC AA , and normalized weight , length , and head circumference were not influenced by BPD or n-3 LCFAs except that n-3 LCFA-supplemented infants weighed less at 6 ( P head circumferences at 9 mo ( P n-3 LCFAs had lower weight-for-length at 2 , 6 , 9 , and 12 mo ( P n-3 LCFAs improved early ( 2-mo ) but not later acuity among infants without BPD ( P infants with BPD had poorer grating acuity at 2 ( P<0.0002 ) and 4 ( P<0.04 ) mo but not thereafter",
"BACKGROUND The critical period during which the dietary supply of long-chain polyunsaturated fatty acids ( LCPs ) may influence the maturation of cortical function in term infants is unknown . OBJECTIVE The aim of the present study was to determine the relative importance for maturation of the visual cortex of the dietary supply of LCPs during the first 6 wk of life compared with that during weeks 7 - 52 . DESIGN A r and omized controlled clinical trial of LCP supplementation in 65 healthy term infants who were weaned from breast-feeding at 6 wk of age was conducted to determine whether the dietary supply of LCPs after weaning influenced the maturation of visual acuity and stereoacuity . RESULTS Despite a dietary supply of LCPs from breast milk during the first 6 wk of life , infants who were weaned to formula that did not provide LCPs had significantly poorer visual acuity at 17 , 26 , and 52 wk of age and significantly poorer stereoacuity at 17 wk of age than did infants who were weaned to LCP-supplemented formula . Better acuity and stereoacuity at 17 wk was correlated with higher concentrations of docosahexaenoic acid in plasma . Better acuity at 52 wk was correlated with higher concentrations of docosahexaenoic acid in plasma and red blood cells . No significant effects of diet on growth were found . CONCLUSION The results suggest that the critical period during which the dietary supply of LCPs can influence the maturation of cortical function extends beyond 6 wk of age",
"BACKGROUND Egg yolks can be a source of docosahexaenoic acid ( DHA ) and iron but are often associated with adverse consequences on plasma cholesterol . OBJECTIVE Our goal was to investigate the effect of consumption of 4 egg yolks/wk on infant DHA status and hemoglobin , ferritin , and plasma cholesterol concentrations . Secondary outcomes included plasma iron , transferrin , and transferrin saturation . DESIGN This was a r and omized controlled trial comparing no dietary intervention , consumption of 4 regular egg yolks/wk , and consumption of 4 n-3 fatty acid-enriched egg yolks/wk in breast-fed and formula-fed infants from 6 to 12 mo of age . Erythrocyte DHA concentrations , cholesterol , and iron status were assessed at 6 and 12 mo of age . RESULTS Of the 82 breast-fed infants recruited , 23 of 28 ( no intervention ) , 23 of 27 ( regular eggs ) , and 24 of 27 ( n-3 eggs ) completed the trial . Of the 79 formula-fed infants enrolled , 23 of 27 ( no intervention ) , 24 of 26 ( regular eggs ) , and 20 of 26 ( n-3 eggs ) completed the trial . Erythrocyte DHA concentrations were 30 - 40 % higher after the n-3 egg intervention than after treatment with regular eggs or no eggs in both breast-fed and formula-fed infants . Egg treatment had no significant effect on plasma cholesterol , hemoglobin , ferritin , and transferrin but did result in improvements in plasma iron and transferrin saturation compared with no egg treatment . CONCLUSIONS n-3 Fatty acid-enriched eggs may provide a means of increasing dietary DHA during the second 6 mo of life . Egg yolks may also be a useful source of iron during the weaning period and can be safely included in the weaning diet with no perturbations in plasma cholesterol",
"BACKGROUND Whether long-chain polyunsaturated fatty acids ( LCPs ) play a role in the development of the young nervous system in term infants is debated . OBJECTIVE We investigated whether supplementation of formula with LCPs for 2 mo improves the quality of general movements ( GMs ) in healthy term infants at 3 mo of age . DESIGN A prospect i ve , double-blind , r and omized controlled study was conducted with 2 groups of healthy term infants : a control-formula ( CF ) group ( n = 131 ) and an LCP-supplemented-formula ( LF ) group ( n = 119 ) . A breastfed ( BF ) group ( n = 147 ) served as a reference . Information on potential confounders was collected at enrollment . Videotapes were made of the infants ' spontaneous motor behavior at 3 mo of age to assess the quality of their GMs . On the basis of quality , normal GMs were classified as normal-optimal or normal-suboptimal , and abnormal GMs were classified as mildly or definitely abnormal . Attrition at 3 mo of age was 15 % and nonselective . Multivariate regression analyses with adjustment for confounders were carried out to evaluate the effect of the type of feeding . RESULTS None of the infants had definitely abnormal GMs . Infants in the CF group had mildly abnormal GMs significantly more often than did infants in the LF and BF groups ( 31 % compared with 19 % and 20 % , respectively ) . Infants in the BF group had normal-optimal GMs more frequently than did infants in the LF and CF groups ( 34 % compared with 18 % and 21 % , respectively ) . Logistic regression analyses confirmed these findings . CONCLUSION Supplementation of healthy term infants with LCPs during the first 2 mo of life reduces the occurrence of mildly abnormal GMs",
"Maternal ( n-3 ) PUFA deficiency is associated with higher blood pressure ( BP ) later in life in rat offspring , and early intake of ( n-3 ) PUFA in formula-fed infants was shown to modify later BP . BP , heart rate ( HR ) , and heart rate variability ( HRV ) are affected by dietary ( n-3 ) PUFA in adults . In this study , we investigated whether fish oil ( FO ) supplementation of lactating mothers could modify BP , pulse wave velocity ( PWV ) , and HRV in their children after 2 y. Mothers with low fish intake were r and omly assigned to FO or olive oil ( OO ) supplementation for the first 4 mo after delivery . A reference group of mothers with a high habitual fish intake ( HFI ) was also followed . At the follow-up study at 2.5 y of age , BP and PWV were measured , and electrocardiograms were recorded for 0.5 h. FO supplementation significantly increased RBC levels of long-chain ( n-3 ) PUFA of the 4 mo-old children , but at 2.5 y , the FO and OO groups did not differ . BP , PWV , HR , and HRV also did not differ among the groups . However , for all 3 groups , the children 's intake of ( n-3 ) PUFA at 2.5 y was negatively correlated with mean arterial pressure after adjustment for outdoor temperature ( r = -0.245 , P = 0.04 ) . In conclusion , maternal FO supplementation had no overall effect on BP , PWV , or HRV of the children , indicating that ( n-3 ) PUFA intake of Danish mothers may be sufficient in this sense . However , children 's dietary intake of ( n-3 ) PUFA might have a beneficial effect on BP in childhood",
"Animal and epidemiologic studies indicate that early nutrition has lasting effects on metabolism and cardiovascular disease risk . In adults , ( n-3 ) long-chain PUFA ( LCPUFA ) from fish oils improve blood pressure , the lipid profile , and possibly cardiovascular disease mortality . This r and omized trial is the first to investigate the effects of fish oil on blood pressure and the lipid profile in infancy . Healthy term 9-mo old infants ( n = 83 ) were r and omly assigned to 5 mL fish oil daily or no fish oil for 3 mo and to 2 different milk types . Before and after the intervention , blood pressure was measured with an oscillometric device , and blood was sample d for analysis of erythrocyte fatty acid composition and the plasma lipid profile . This paper examines the effects of the fish oil supplement , with adjustment for the effects of the milk intervention when relevant . The fish oil intervention increased erythrocyte ( n-3 ) LCPUFA content ( P systolic blood pressure [ adjusted mean difference ( 95 % CI ) ] 6.3 mm Hg ( 0.9 , 11.7 ) ( P = 0.02 ) , a 0.51 mmol/L ( 0.07 , 0.95 ) higher plasma total cholesterol ( P = 0.02 ) , and a 0.52 mmol/L ( 0.02,1.01 ) higher LDL cholesterol ( P = 0.04 ) than infants not administered fish oil . Plasma triacylglycerol was inversely associated with the erythrocyte content of eicosapentaenoic acid ( r = 0.34 , P < 0.01 ) , a biomarker of fish oil dose . The observed effects of fish oil are in accordance with findings in adults . The long-term health implication s warrant further investigation",
"BACKGROUND Several studies found a benefit of long-chain polyunsaturated fatty acid ( LCP ) supplementation for visual or mental development , but others found no benefit . Likely contributors to differences among studies are the amount of LCP supplementation , functional outcomes , and sample size . OBJECTIVE We evaluated LCP supplementation in amounts typical for human milk ( based on local and worldwide surveys ) in a large cohort of infants by using sweep visual evoked potential ( VEP ) acuity as the functional outcome . DESIGN The study was a double-masked , r and omized , controlled clinical trial in 103 term infants . By age 5 d , infants were r and omly assigned to receive either formula with no docosahexaenoic acid ( DHA ) or arachidonic acid ( ARA ) or formula supplemented with DHA and ARA as 0.36 % and 0.72 % , respectively , of total fatty acids . Sweep VEP acuity was the primary outcome . R and om dot stereoacuity , blood lipid profile , growth , and tolerance were secondary outcomes . RESULTS VEP acuity in the LCP-supplemented group was significantly better than that in the control group at ages 6 , 17 , 26 , and 52 wk . Stereoacuity in the LCP-supplemented group was significantly better than that in the control group at age 17 wk but not at ages 39 and 52 wk . By ages 17 and 39 wk , the red blood cell DHA concentration in the LCP-supplemented group was more than double and more than triple , respectively , that in the control group . Growth of infants fed LCP-supplemented and control formulas did not differ significantly , and both diets were well tolerated . CONCLUSION LCP supplementation of term infant formula during the first year of life yields clear differences in visual function and in total red blood cell lipid composition",
"Between 6 and 12 mo of age , blood levels of the ( n-3 ) long-chain PUFA , docosahexaenoic acid ( DHA ) , in breast-fed infants typically decrease due to diminished maternal DHA stores and the introduction of DHA-poor solid foods displacing human milk as the primary source of nutrition . Thus , we utilized a r and omized , clinical trial format to evaluate the effect of supplemental DHA in solid foods on visual development of breast-fed infants with the primary outcome , sweep visual-evoked potential ( VEP ) acuity , as an index for maturation of the retina and visual cortex . At 6 mo of age , breast-fed infants were r and omly assigned to receive 1 jar ( 113 g)/d of baby food containing egg yolk enriched with DHA ( 115 mg DHA/100 g food ; n = 25 ) or control baby food ( 0 mg DHA ; n = 26 ) . Gravimetric measures were used to estimate the supplemental DHA intake which was 83 mg DHA/d in the supplemented group and 0 mg/d in controls . Although many infants in both groups continued to breast-feed for a mean of 9 mo , RBC DHA levels decreased significantly between 6 and 12 mo ( from 3.8 to 3.0 g/100 g total fatty acids ) in control infants , whereas RBC DHA levels increased by 34 % from 4.1 to 5.5 g/100 g by 12 mo in supplemented infants . VEP acuity at 6 mo was 0.49 logMAR ( minimum angle of resolution ) and improved to 0.29 logMAR by 12 mo in controls . In DHA-supplemented infants , VEP acuity was 0.48 logMAR at 6 mo and matured to 0.14 logMAR at 12 mo ( 1.5 lines on the eye chart better than controls ) . At 12 mo , the difference corresponded to 1.5 lines on the eye chart . RBC DHA levels and VEP acuity at 12 mo were correlated ( r = -0.50 ; P = 0.0002 ) , supporting the need of an adequate dietary supply of DHA throughout 1 y of life for neural development",
"BACKGROUND Studies suggest that low concentrations of n-6 long-chain polyenes in early life are correlated to atopic disease in later life . OBJECTIVE The purpose of the study was to investigate the possible preventive effect of gamma-linolenic acid ( GLA ) supplementation on the development of atopic dermatitis in infants at risk . DESIGN In a double-blind , r and omized , placebo-controlled trial , formula-fed infants ( n = 118 ) with a maternal history of atopic disease received borage oil supplement ( containing 100 mg GLA ) or sunflower oil supplement as a placebo daily for the first 6 mo of life . Main outcome measures were the incidence of atopic dermatitis in the first year of life ( by UK Working Party criteria ) , the severity of atopic dermatitis ( SCORing Atopic Dermatitis ; SCORAD ) , and the total serum immunoglobulin E ( IgE ) concentration at the age of 1 y. RESULTS The intention-to-treat analysis showed a favorable trend for severity of atopic dermatitis associated with GLA supplementation ( x+/- SD SCORAD : 6.32 + /- 5.32 ) in the GLA-supplemented group as compared with 8.28 + /- 6.54 in the placebo group ( P = 0.09 ; P = 0.06 after adjustment for total serum IgE at baseline , age 1 wk ) , but no significant effects on the other atopic outcomes . The increase in GLA concentrations in plasma phospholipids between baseline and 3 mo was negatively associated with the severity of atopic dermatitis at 1 y ( Spearman 's correlation coefficient = -0.233 , P = 0.013 ) . There was no significant effect on total serum IgE concentration . CONCLUSION Early supplementation with GLA in children at high familial risk does not prevent the expression of atopy as reflected by total serum IgE , but it tends to alleviate the severity of atopic dermatitis in later infancy in these children",
"BACKGROUND There are nutritional recommendations that the ratio of linoleic to alpha-linolenic acid ( LA : ALA ) in formula for term infants be between 5:1 and 15:1 . These recommendations were made in the absence of data on functional or clinical outcomes . OBJECTIVE We compared the fatty acid status , visual evoked potential ( VEP ) acuity , and growth of term infants fed formula containing an LA : ALA of 10:1 or 5:1 with those of a breast-fed reference cohort . DESIGN Formula-fed infants were allocated r and omly in a double-blind fashion to receive formula with an LA : ALA of either 10:1 ( 16.9:1.7 ; n = 36 ) or 5:1 ( 16.3:3.3 ; n = 37 ) from near birth to 34 wk of age . Increased ALA was attained by replacing soy oil with low-erucic acid cannola oil . A parallel group of breast-fed infants was also recruited . Infant growth and fatty acid status were assessed at 6 , 16 , and 34 wk of age . VEP acuity was assessed at 16 and 34 wk . RESULTS Infants fed the 5:1 formula had greater docosahexaenoic acid ( DHA ) concentrations in plasma and erythrocyte phospholipids than did infants fed the 10:1 formula , but DHA concentrations of infants fed the 5:1 formula remained less than those in breast-fed infants . The VEP acuity of all formula-fed and breast-fed infants was not significantly different at 16 and 34 wk of age . At birth , infants fed the 5:1 formula were heavier , were longer , and had a greater head circumference than infants assigned to the 10:1 formula group ; this differential was maintained throughout the trial . The rate of gain in weight , length , and head circumference was not significantly different between the 2 formula-fed groups , although breast-fed infants had lower weight and length gains than did formula-fed infants between 16 and 34 wk of age . CONCLUSION Lowering the LA : ALA in formula from 10:1 to 5:1 by using low-erucic acid canola oil result ed in a modest increase in plasma DHA but had no effect on VEP acuity or growth rate",
"OBJECTIVE There have been indications that high intake of n-3 long-chain polyunsaturated fatty acids ( PUFAs ) during pregnancy may increase birth weight and gestational length . In addition , n-3 long-chain PUFAs may be important for the neurobiological development of the infants . High levels of docosahexaenoic acid ( DHA , 22:6 n-3 ) are found in the gray matter of the cerebral cortex and in the retina , and it seems as if the availability of long-chain PUFAs may be limiting cerebral development . The fetus and the newborn are dependent on a high supply from their mothers , either via the placenta or via breast milk . We supplemented pregnant and lactating women with n-3 or n-6 long-chain PUFAs to evaluate the effect on birth weight , gestational length , and infant development . DESIGN We performed a double-blind , r and omized study recruiting 590 pregnant , healthy , Nonei- or primiparous women ( 19 - 35 years old ) in weeks 17 to 19 of pregnancy . The women were provided 10 mL of either cod liver oil or corn oil daily until 3 months after delivery . MAIN OUTCOME MEASURES Primary outcomes were gestational length and birth weight . Electroencephalography ( EEG ) was done on the second day of life and at 3 months of age . Novelty preference ( Fagan test ) was used as an indicator of cognitive function at 6 and 9 months of age . The fatty acid pattern in umbilical plasma phospholipids and in breast milk was measured , and dietary assessment s were performed , both on the mothers during pregnancy and on the infants at 3 months of age . The growth of the infants was followed up to 1 year of age . RESULTS Three hundred forty-one mothers took part in the study until delivery . There were no significant differences in maternal body mass index before pregnancy and at birth , or parity between the 2 groups . Smoking habits and parental education were also similar in the 2 groups . The mean age of the mothers receiving cod liver oil was , by chance , 1 year higher than the age of the mothers receiving corn oil ( 28.6 [ 3.4 ] vs 27.6 [ 3.2 ] years ) . The maternal dietary intake in the 2 groups receiving cod liver oil or corn oil was similar , except for the supplementation . There were no differences in gestational length or birth weight between the cod liver oil group and the corn oil group ( 279.6 [ 9.2 ] vs 279.2 [ 9.3 ] days ; 3609 [ 493 ] vs 3618 [ 527 ] g , respectively ) . Birth length , head circumference , and placental weight were also similar in the 2 groups . The concentrations of the n-3 fatty acids eicosapentaenoic acid ( 20:5 n-3 ) , docosapentaenoic acid ( 22:5 n-3 ) , and DHA in umbilical plasma phospholipids were higher in the cod liver oil group compared with the corn oil group ( 10.8 [ 7.6 ] vs 2.5 [ 1.8 ] microg/mL , 5.0 [ 2.6 ] vs 2.9 [ 1.3 ] microg/mL , 55.8 [ 20.6 ] vs 45.3 [ 12.8 ] microg/mL , respectively ) . Neonates with high concentration of DHA in umbilical plasma phospholipids ( upper quartile ) had longer gestational length than neonates with low concentration ( lower quartile ; 282.5 [ 8.5 ] vs 275.4 [ 9.3 ] days ) . No differences in EEG scores or Fagan scores were found , but neonates with mature EEG ( N = 70 ) had a higher concentration of DHA in umbilical plasma phospholipids than neonates with immature EEG ( N = 51 ) on the second day of life . Dietary information from 251 infants at 3 months of age was collected and 85 % of these infants were exclusively breastfed , in addition to 12 % who were partly breastfed . The breast milk of mothers supplemented with cod liver oil contained more n-3 long-chain PUFAs and less n-6 long-chain PUFAs than breast milk of mothers supplemented with corn oil . There were no significant differences in infant growth during the first year of life between the 2 groups . CONCLUSIONS This study shows neither harmful nor beneficial effects of maternal supplementation of long-chain n-3 PUFAs regarding pregnancy outcome , cognitive development , or growth , as compared with supplementation with n-6 fatty acids . However , it confirms that DHA concentration may be related to gestational length and cerebral maturation of the newborn",
"Fish oil addition to infant formulas has raised concern on whether increased intake of n-3 long-chain polyunsaturated fatty acid ( n-3LCPUFA ) affects infant growth . The objective of this study was to determine whether maternal fish oil supplementation during 0–4 mo of lactation influences growth in infancy and early childhood . In a r and omized , blinded intervention trial , lactating Danish mothers with a fish intake below the population median were r and omized to 4.5 g/d fish oil or olive oil . A reference group of 53 mothers with a fish intake in the highest quartile of the population and their infants were included in the study . Head circumference , weight , length , skinfold thickness , and waist circumference of children were measured at 2 , 4 , and 9 mo and at 2.5 y. One hundred children completed the intervention trial , and 72 were followed up at 2.5 y together with 29 from the reference group . Growth in weight , length , and head circumference did not differ between the r and omized groups up to 9 mo , but at 2.5 y , body composition differed significantly . Children in the fish oil group had larger waist circumference body mass index ( BMI ; 0.6 kg/m2 ; p = 0.022 ) , and head circumference compared with those in the olive oil group . Adjusted for sex , ponderal index at birth and current energy intake , BMI at 2.5 y was associated with docosahexaenoic acid in maternal erythrocytes after the intervention . In conclusion , the n-3LCPUFA intake of lactating mothers may be important for growth of young children . The long-term effect on weight and BMI remains to be investigated",
"BACKGROUND The last trimester of pregnancy is a period of rapid accretion of long-chain polyunsaturated fatty acids , both in the central nervous system and the body as a whole . Human milk contains these fatty acids , whereas some preterm infant formulas do not . Infants fed formulas without these fatty acids have lower plasma and erythrocyte concentrations than infants fed human milk . Pre clinical and clinical studies have demonstrated that single-cell sources ( algal and fungal ) of long-chain polyunsaturated fatty acids are bioavailable . A balanced addition of fatty acids from these oils to preterm formula results in blood fatty acid concentrations in low birth weight infants comparable to those of infants fed human milk . METHODS In the present study the growth , acceptance ( overall incidence of discontinuation , reasons for discontinuation , overall incidence and type of individual adverse events ) , and plasma fatty acid concentrations were compared in three groups of infants fed a long-chain polyunsaturated fatty acid-supplemented preterm infant formula , an unsupplemented control formula , or human milk . The study was prospect i ve , double-blind ( formula groups only ) , and r and omized ( formula groups only ) . Two hundred eighty-eight infants were enrolled ( supplemented formula group , n = 77 ; control formula group , n = 78 ; human milk group , n = 133 ) . RESULTS Anthropometric measurements at enrollment , at first day of full oral feeding , and at both 40 and 48 weeks postconceptional age did not differ between the formula groups , whereas the human milk-fed group initially grew at a lower rate . The incidence of severe adverse events was rare and not significantly different between formula groups . The groups fed either human milk or supplemented formula had long-chain polyunsaturated fatty acid concentrations higher than those in the control formula group . CONCLUSIONS The results of this study demonstrate the safety and efficacy of a preterm formula supplemented with long-chain polyunsaturated fatty acids from single-cell oils",
"Maternal fish oil supplementation during pregnancy has been associated with altered infant immune responses and a reduced risk of infant sensitization and eczema",
"BACKGROUND Preterm infants may be born with deficits of both docosahexaenoic acid ( DHA ) and arachidonic acid ( AA ) , but studies on supplementation of DHA and AA for preterm infants are limited . METHODS Preterm infants with a gestational age between 30 and 37 weeks who met all the inclusion criteria were enrolled in this double blind , r and omized , comparative study . Infants over 2000 g body weight , over 32 weeks of gestation and in full feeding status would enter into the active intervention period of 6 months . Sixteen infants received Neoangelac Plus with AA and DHA supplementation . Eleven infants received Neoangelac without AA and DHA supplementation . The babies had scheduled physical examinations and their cognitive development , visual acuity , and vital signs to be checked . Adverse events were also recorded . RESULTS The mean Mental Development Index ( MDI ) scores for the supplementation and non-supplementation groups were 96.1 + /- 8.6 and 91.7 + /- 10.4 respectively at 6 months and 98.7 + /- 8.0 and 90.5 + /- 6.9 respectively at 1 year . The mean Physical Development Index ( PDI ) scores of these two groups were 102.2 + /- 10.5 and 95.4 + /- 13.2 respectively at 6 months and 98.0 + /- 5.8 and 86.7 + /- 11.1 respectively at 1 year . By repeated measures ANOVA , significant differences existed between groups for MDI and PDI ( p = 0.020 and 0.008 ) . However , there were no differences in visual acuity , physical examination variables or vital signs between these two groups . No obvious adverse effects were observed during the study period . CONCLUSION These results showed possible benefits in the neurodevelopment of larger preterm infants given formula supplemented with DHA and AA",
"Fatty acid compositions of plasma phospholipids ( PL ) , triglycerides ( TG ) and sterol esters ( STE ) were measured by high resolution capillary gas-liquid chromatography in formula fed healthy infants at the ages of 5 days and 1 , 2 , 3 and 4 months . The infants were r and omly assigned to receive either conventional infant formula ( F , n = 10 ) without long-chain polyunsaturates ( LCP ) or the same formula supplemented with LCP ( LCP-F , n = 12 ) in amounts and ratios similar to those characteristic to human milk . From the age of 1 month onwards , percentage contributions of the principal omega-6 LCP , arachidonic acid were significantly higher in plasma lipids of infants fed LCP-F than in those receiving conventional formula without dietary LCP . Values of the principal omega-3 LCP , docosahexaenoic acid were also significantly lower in the infants fed conventional formula than in those receiving LCP-F throughout the study . The data obtained indicate that from the formula supplemented with LCP both arachidonic and docosahexaenoic acids were effectively absorbed and incorporated into infantile plasma lipids . Recent data of the literature suggest that supplementation of infant formula with LCP may beneficially influence visual and psychomotor development also in healthy , term infants",
"OBJECTIVE To investigate the incidence of allergic and respiratory diseases through age 3 years in children fed docosahexaenoic acid (DHA)- and arachidonic acid (ARA)-supplemented formula during infancy . STUDY DESIGN Children who completed r and omized , double-blind studies of DHA/ARA-supplemented ( 0.32%-0.36%/0.64%-0.72 % of total fatty acids , respectively ) versus nonsupplemented ( control ) formulas , fed during the first year of life , were eligible . Blinded study nurses review ed medical charts for upper respiratory infection ( URI ) , wheezing , asthma , bronchiolitis , bronchitis , allergic rhinitis , allergic conjunctivitis , otitis media , sinusitis , atopic dermatitis ( AD ) , and urticaria . RESULTS From the 2 original cohorts , 89/179 children participated ; 38/89 were fed DHA/ARA formula . The DHA/ARA group had significantly lower odds for developing URI ( odds ratio [ OR ] , 0.22 ; 95 % confidence interval [ CI ] , 0.08 - 0.58 ) , wheezing/asthma ( OR , 0.32 ; 95 % CI , 0.11 - 0.97 ) , wheezing/asthma/AD ( OR , 0.25 ; 95 % CI , 0.09 - 0.67 ) , or any allergy ( OR , 0.28 ; 95 % CI , 0.10 - 0.72 ) . The control group had significantly shorter time to first diagnosis of URI ( P = .006 ) , wheezing/asthma ( P = .03 ) , or any allergy ( P = .006 ) . CONCLUSIONS DHA/ARA supplementation was associated with delayed onset and reduced incidence of URIs and common allergic diseases up to 3 years of age",
"Docosahexaenoic acid ( DHA ) accumulates in the brain during the 1st and 2nd years of life . The objective of this study was to see if an increased content of DHA in breast-milk via maternal fish oil (FO)-supplementation affects mental development in term infants . one hundred twenty-two Danish mothers with a habitual fish intake below the population median were r and omized to 4.5 g.d(-1 ) of FO or olive oil ( OO ) for the first four months of lactation . Fifty-three mothers with habitual fish intake in the highest quartile were included as reference group . The effect of the result ing increase in infant DHA-intake and RBC-DHA level was assessed on problem solving ability at nine months and language at one and two years of age . Infants in the three groups performed equally well on the problem test and no association was observed between problem solving and erythrocyte-DHA at four months . Passive vocabulary at one year was lower in the children of the FO- compared with the OO-group ( P Word comprehension at one year was inversely associated with erythrocyte-DHA at four months . The trial indicate a small effect of DHA levels in breast-milk on early language development of breast-fed infants",
"ABSTRACT : Retinal function was assessed by electroretinogram in 32 neonates r and omly assigned to formulas of different ω-3 fatty acid content and in 10 infants fed human milk . All neonates had a birth weight of 1000 - 1500 g and were fed study diets from d 10 to 45 or discharge . Group A received formula containing predominantly 18:2 ω-6 . Group B received a balanced mix of 18:2 ω-6 and 18:3 ω- 3 . Group C was given a formula containing both essential fatty acids and supplemented with marine oil to provide 22:6 ω-3 content similar to that of human milk . The fatty acid composition of plasma and red blood cell ( RBC ) lipids were similar for all groups on entry but marked dietinduced differences were found after feeding the study diets . Group C was comparable to the human milk-fed group , but group A had lower 22:6 ω-3 and ω-3 long-chain polyunsaturated fatty acids ( LCPUFA ) in plasma and RBC membranes . Cone function was not affected by dietary essential fatty acids . Rod electroretinogram thresholds were significantly higher for group A relative to the human milk-fed group and group C and significantly correlated with RBC ω-3 LCPUFA ( r = -0.63 , p content . Rod electroretinogram amplitude was significantly lower for group A relative to the human milkfed group and group C and related to plasma 22:6 ω-3 ( r = 0.55 ) and total ω-3 LCPUFA ( r = 0.58 ) ( both p < 0.0001 ) ; 42 % of the variance was explained by plasma ω-3 LCPUFA , the ratio of ω-6/ω-3 LCPUFA in RBC , and gestational age at birth . Our results support an essential role for ω-3 fatty acids in retinal development",
"BACKGROUND The passage of hard stools is significantly more common in formula fed infants than breast fed infants and this might be the result of differences in fat absorption between breast and formula fed infants . Experimental studies indicate that long chain polyunsaturated fatty acids ( LCPUFAs ) might influence fat hydrolysis and absorption . AIM To investigate the relation of LCPUFA supplementation to stool frequency and consistency during the first 4 months of life . DESIGN Double blind , r and omised , controlled study of 88 healthy infants . RESULTS 1905 stools ( 858 from LCPUFA supplemented infants , 1047 non-supplemented infants ) were examined . The mean ( SEM ) number of stools passed for each three day study period was significantly less in the LCPUFA group ( 5.5 (0.3)v 6.2 ( 0.2 ) ; p number of stools passed with age ( p mean ( SEM ) percentage of hard stools passed by infants in the LCPUFA supplemented group was 7.7 ( 2.1 ) compared with 19.2 ( 2.8 ) for unsupplemented infants ( p = 0.001 ) . CONCLUSION The prevalence of hard stools is significantly reduced in infants fed a formula that is supplemented with LCPUFAs",
"Long‐chain polyunsaturated fatty acids with 20 and 22 carbon atoms ( LCPs ) seem to play an important role during the rapid development of the infant brain in the late fetal and early postnatal period . These LCPs are integral constituents of biological membranes and they are involved in the regulation of functional properties like fluidity , permeability and activity of membrane‐bound enzymes . Human milk contains LCPs in an amount of 0.5–3 wt% of total fatty acids , whereas commercially available infant formulae are almost free of them . Recently , several clinical trials , primarily with preterm infants , have reported that the content of LCPs in the blood and a functional parameter like visual acuity correlate with the content of LCPs in the diet . In this clinical trial we studied the effect of different diets on the fatty acid pattern of plasma and erythrocyte lipids of healthy term infants during the first 3 months of life . Breast‐fed infants were compared with formula‐fed babies who received a commercially available formula without LCPs or a new experimental formula enriched with LCPs that was similar to human milk . The results indicate that the introduction of milk feeding leads to marked differences in the blood lipid composition during the first months of life , independent of the feeding regimen . Secondly , the supplementation of a formula with LCPs seems to result in a blood lipid composition similar to infants fed with human milk . This supports the hypothesis that the newborn term infant has a limited desaturating capacity and depends on an exogenous supply of LCPs during the first months of life",
"Because formula-fed preterm infants may be at risk of omega 3 essential fatty acid deficiency , we tested experimental formulas supplemented with soy oil to provide alpha-linolenic acid or marine oil to provide preformed omega 3 long-chain polyunsaturated fatty acids at a level comparable to that of human milk . This report addresses the effect of feeding formula supplemented with soy oil or with soy and marine oils on growth , clinical tolerance , coagulation test results , changes in erythrocyte membrane fluidity , and plasma concentrations of vitamins A and E in very low birth weight infants from 30 to 57 weeks of postconceptional age . \" Healthy \" preterm infants were maternally selected to receive human milk or selected at r and om to receive commercial ready-to-feed liquid formula , which provided limited omega 3 fatty acid , or experimental formulas supplemented with soy oil or soy and marine oils . Results of this study indicate that formula enriched with soy oil or soy and marine oils containing preformed omega 3 long-chain polyunsaturated fatty acids does not induce abnormalities in growth , clotting function , erythrocyte membrane fluidity , or vitamin A or E levels in healthy very low birth weight preterm infants . Additional studies to evaluate safety in a representative preterm population are required",
"The effect of the dietary n-3 long-chain PUFA , DHA ( 22 : 6n-3 ) , on the growth of pre-term infants is controversial . We tested the effect of higher-dose DHA ( approximately 1 % dietary fatty acids ) on the growth of pre-term infants to 18 months corrected age compared with st and ard feeding practice ( 0·2 - 0·3 % DHA ) in a r and omised controlled trial . Infants born were r and omly allocated to receive breast milk and /or formula with higher DHA or st and ard DHA according to a concealed schedule stratified for sex and birth-weight ( expected date of delivery ( EDD ) . Growth was assessed at EDD , and at 4 , 12 and 18 months corrected age . There was no effect of higher DHA on weight or head circumference at any age , but infants fed higher DHA were 0·7 cm ( 95 % CI 0·1 , 1·4 cm ; P = 0·02 ) longer at 18 months corrected age . There was an interaction effect between treatment and birth weight strata for weight ( P = 0·01 ) and length ( P = 0·04 ) . Higher DHA result ed in increased length in infants born weighing ≥ 1250 g at 4 months corrected age and in both weight and length at 12 and 18 months corrected age . Our data show that DHA up to 1 % total dietary fatty acids does not adversely affect growth ",
"Between May 1993 , and September 1994 , a r and omized , blinded clinical trial was conducted to evaluate measures of growth and body composition in 63 ( 32 males ; 31 females ) healthy , low‐birth‐weight infants ( 940–2250 g ) who were r and omly assigned to an infant formula with docosahexaenoic acid ( 22:6n3 , DHA , 0.2 wt% ) from fish oil or to a control formula . A preterm formula with or without DHA was fed beginning at 7–10 days prior to hospital discharge through 43 weeks postmenstrual age ( PMA ) . Then , from 43‐59 weeks PMA , infants were fed a term infant formula with or without a corresponding amount of DHA . Growth ( weight , length , head circumference ) , regional body fatness ( triceps , subscapular , suprailiac skinfold thicknesses ) , circumferences ( arm , abdominal , chest ) , and estimates of body composition determined by total body electrical conductivity ( TOBEC ) ( fat‐free mass [ FFM ] ) were evaluated . Growth was slower in males fed the DHA formula . They had significantly ( P gains in weight , length , and head circumference between study enrollment to 59 weeks PMA than those fed the control formula . At 51 weeks PMA , males in the DHA group had significantly smaller head circumferences ( P lower FFM ( P weighed less ( P shorter recumbent lengths ( P smaller head circumferences ( P lower FFM ( P formula . Energy intakes from formula ( kcal/d ) , however , were lower at 51 weeks ( P The differences in recumbent length , head circumference , and FFM remained statistically significant after controlling for energy and protein intakes ( P neither FFM nor total body fat ( TBF ) , when expressed as a percentage of total body weight , differed significantly between feeding groups . Among females , there were no significant differences between the feeding groups in measures of growth , body composition , or energy intake . The results indicated that infant formula with fish oil containing DHA and EPA in a 5:1 ratio had a significant , negative effect on growth and body composition in males during the first 6 months of life . It is not clear why the growth deficits were limited to males and not females . The eicosanoids , bioactive metabolites of omega‐3 and omega‐6 fatty acids , may mediate several important growth hormones . The present results do not support the addition of DHA alone in infant formulas . Am . J. Hum . Biol . 11:457–467 , 1999 . © 1999 Wiley‐Liss ,",
"The objective of this study was to evaluate growth and body composition of premature infants who were fed formulas with arachidonic acid ( ARA ; 20:4n6 ) and docosahexaenoic acid ( DHA ; 22:6n3 ) to 1 y of gestation-corrected age ( CA ) . Preterm infants ( 750–1800 g birth weight and were assigned within 72 h of first enteral feeding to one of three formulas : control ( n = 22 ) , DHA+ARA from fish/fungal oil [ DHA+ARA(FF ) ; n = 20 ] , or DHA+ARA from egg/fish oil [ DHA+ARA(EF ) ; n = 18 ] . Human milk feeding was allowed on the basis of the mother 's choice . Infants were fed breast milk and /or preterm formulas with or without 0.26 % DHA and 0.42 % ARA to term CA followed by breast milk or postdischarge preterm formulas with or without 0.16 % DHA and 0.42 % ARA to 12 mo CA . Body composition was measured by dual-energy x-ray absorptiometry . There were no significant differences among the three study groups at any time point in weight , length , or head circumference . Bone mineral content and bone mineral density did not differ among groups . At 12 mo CA , infants who were fed DHA+ARA-supplemented formulas had significantly greater lean body mass ( p less fat mass ( p DHA+ARA-supplemented formulas supported normal growth and bone mineralization in premature infants who were born at . Preterm formulas that had DHA+ARA at the levels and ratios in this study and were fed to 1 y CA led to increased lean body mass and reduced fat mass by 1 y of age",
"Background . It is currently recommended that diet of pregnant mothers contain 200–300 mg DHA/day . Aim . To determine whether DHA supplementation during pregnancy and lactation affects infants ' immune response . Methods . 60 women in ≥3rd pregnancy studied ; 30 r and omly assigned to receive DHA 400 mg/day from 12th week gestation until 4 months postpartum . From breast-fed infants , blood obtained for anti-HBs antibodies , immunoglobulins , lymphocyte subset phenotyping , and intracellular cytokine production . Results . CD4 + lymphocytes did not differ between groups , but CD4CD45RA/CD4 ( naïve cells ) significantly higher in infants in DHA+ group . Proportion of CD4 and CD8 cells producing IFNγ significantly lower in DHA+ group , with no differences in proportion of IL4-producing cells . Immunoglobulins and anti-HBs levels did not differ between groups . Conclusions . In infants of mothers receiving DHA supplementation , a higher percentage of CD4 naïve cells and decreased CD4 and CD8 IFNγ production is compatible with attenuation of a proinflammatory response",
"Aim : To study the influence of dietary‐supplied long‐chain polyunsaturated fatty acids on structural brain maturation in preterm infants and to investigate parameters of functional brain development , relating them to structural maturation . Other studies have suggested that dietary supplementation of long‐chain polyunsaturated fatty acids in preterm infants may enhance their visual development . The influence on structural brain development has never been evaluated . Methods : In a prospect i ve , double‐blind study , 42 formula‐fed premature infants were r and omized to be fed either a st and ard preterm formula without long‐chain polyunsaturated fatty acids or an identical formula supplemented with docosahexaenoic acid ( 0.015 g/100 ml ) and arachidonic acid ( 0.031 g/100ml ) . Infants with significant cerebral damage , retinopathy , chronic disease or feeding problems were excluded . Follow‐up was focused on assessment of cerebral myelination by MRI . Psychomotor , mental and visual development was analysed and flash‐visual evoked potentials were recorded . Results : It was found that progress of myelination , mental and motor development and latencies of visual evoked potentials were not positively influenced by supplementation of long‐chain polyunsaturated fatty acids . At each test age , visual acuity was slightly better in the supplemented infants than in the non‐supplemented infants , but the difference never reached significance",
"Background Incorporation of long chain polyunsaturated fatty acids ( LCP ) into formulas may interfere with mineral metabolism . We investigate mineral balance in preterm infants who were fed a formula with LCP . Methods Infants were r and omized in a double-blind manner , 20 infants in each group , to receive a formula with LCP ( F+LCP ) or without LCP ( F ) for 30 days . Plasma levels ( at the beginning and after 30 days ) and nutritional balance ( after 1 week ) for Ca , P , Mg , Zn , and Cu were obtained for all infants . Results Groups were similar regarding birth weight , gestational age , weight , and corrected age at study start . During the 30-day study period , the groups had comparable milk intake and reached similar and satisfactory weight gains and longitudinal growth . Within each group , there was no change in plasma mineral concentrations over the course of the study , and there were no differences at each time point between groups . All values were within the normal range for age . No differences in mineral balance were detected between the F and F+LCP groups , with both groups demonstrating comparable intake , net retention , and fecal losses of each mineral . Conclusions Adding a content of LCP blend similar to that of human milk to a preterm formula caused no disturbance in Ca , P , Mg , Zn , or Cu nutritional balance",
"Background In a recent meta- analysis , human milk feeding of low birth-weight ( LBW ) infants was associated with a 5.2 point improvement in IQ tests . However , in the studies in this meta- analysis , feeding regimens were used ( unfortified human milk , term formula ) that no longer represent recommended practice . Objective To compare the growth , in-hospital feeding tolerance , morbidity , and development ( cognitive , motor , visual , and language ) of LBW infants fed different amounts of human milk until term chronologic age ( CA ) with those of LBW infants fed nutrient-enriched formulas from first enteral feeding . Methods The data in this study were collected in a previous r and omized controlled trial assessing the benefit of supplementing nutrient-enriched formulas for LBW infants with arachidonic acid and docosahexaenoic acid . Infants ( n = 463 , birth weight , 750–1,800 g ) were enrolled from nurseries located in Chile , the United Kingdom , and the United States . If human milk was fed before hospital discharge , it was fortified ( 3,050–3,300 kJ/L , 22–24 kcal/oz ) . As infants were weaned from human milk , they were fed nutrient-enriched formula with or without arachidonic and docosahexaenoic acids ( 3,300 kJ/L before term , 3,050 kJ/L thereafter ) until 12 months CA . Formula fed infants were given nutrient-enriched formula with or without added arachidonic and docosahexaenoic acids ( 3,300 kJ/L to term , 3,050 kJ/L thereafter ) until 12 months CA . For the purpose s of this evaluation , infants were categorized into four mutually exclusive feeding groups : 1 ) predominantly human milk fed until term CA ( PHM-T , n = 43 ) ; 2 ) ≥ 50 % energy from human milk before hospital discharge ( ≥ 50 % HM , n = 98 ) ; 3 ) from human milk before hospital discharge ( weighed approximately 500 g more at term CA than did PHM-T infants . This absolute difference persisted until 6 months CA . PFF-T infants were also longer ( 1.0–1.5 cm ) and had larger head circumferences ( 0.3–1.1 cm ) than both PHM-T and ≥ 50 % HM infants at term CA . There was a positive association between duration of human milk feeding and the Bayley Mental Index at 12 months CA ( P = 0.032 full and P = 0.073 reduced , statistical models ) after controlling for the confounding variables of home environment and maternal intelligence . Infants with chronic lung disease fed ≥ 50 % HM until term CA ( n = 22 ) had a mean Bayley Motor Index about 11 points higher at 12 months CA compared with infants PFF-T ( n = 24 , P = 0.033 full model ) . Conclusion Our data suggest that , despite a slower early growth rate , human milk fed LBW infants have development at least comparable to that of infants fed nutrient-enriched formula . Exploratory analysis suggests that some subgroups of human milk fed LBW infants may have enhanced development , although this needs to be confirmed in future studies",
"OBJECTIVES To compare the early neurological maturation of premature newborns ( PT ) fed breast milk ( BM ) or a formula containing only 18-carbon polyunsaturated fatty acids ( PUFA ) ( A ) or enriched with long chain ( LC ) PUFA ( B ) . METHODS PT enrolled the 2nd day of enteral feeding ( D0 ) were fed BM ( n = 15 ; 4 dropped out ) or r and omly assigned to A ( n = 11 ; 2 ) or B ( n = 14 ; 1 ) for at least 30 days ( D30 ) . Auditory and visual evoked potentials ( EPs ) and nerve conduction velocity ( NCV ) and plasma and red blood cell ( RBC ) phospholipid composition were determined at D0 and D30 . No difference was found between groups for the D0-D30 changes in EP parameters . The maturation of motor NCV was slower in the B group than in the two other groups . In plasma , the changes were higher in B than in the BM and A groups for linoleic acid ( P higher linoleic acid level than the BM group ( P changes in arachidonic and docosahexaenoic acids . CONCLUSIONS A balanced supply of n-6 and n-3 PUFA without addition of LC-PUFA allowed an adequate early maturation of the central nerve system . The effects of LC-PUFA on the maturation of NCV remain to be confirmed",
"BACKGROUND The composition of long-chain PUFAs ( LCPUFAs ) in the maternal diet may affect obesity risk in the mother 's offspring . OBJECTIVE We hypothesized that a reduction in the n-6 (omega-6):n-3 ( omega-3 ) LCPUFA ratio in the diet of pregnant women and breastfeeding mothers may prevent expansive adipose tissue growth in their infants during the first year of life . DESIGN In a r and omized controlled trial , 208 healthy pregnant women were r and omly assigned to an intervention ( 1200 mg n-3 LCPUFAs as a supplement per day and a concomitant reduction in arachidonic acid intake ) or a control diet from the 15th wk of pregnancy to 4 mo of lactation . The primary outcome was infant fat mass estimated by skinfold thickness ( SFT ) measurements at 4 body sites at 3 - 5 d , 6 wk , and 4 and 12 mo postpartum . Secondary endpoints included sonographic assessment of abdominal subcutaneous and preperitoneal fat , fat distribution , and child growth . RESULTS Infants did not differ in the sum of their 4 SFTs at ≤1 y of life [ intervention : 24.1 ± 4.4 mm ( n = 85 ) ; control : 24.1 ± 4.1 mm ( n = 80 ) ; mean difference : -0.0 mm ( 95 % CI : -1.3 , 1.3 mm ) ] or in growth . Likewise , longitudinal ultrasonography showed no significant differences in abdominal fat mass or fat distribution . CONCLUSIONS We showed no evidence that supplementation with n-3 fatty acids and instructions to reduce arachidonic acid intake during pregnancy and lactation relevantly affects fat mass in offspring during the first year of life . Prospect i ve long-term studies are needed to explore the efficacy of this dietary approach for primary prevention . This trial was registered at clinical trials.gov as NCT00362089",
"BACKGROUND Evidence is accumulating that a dietary supply of long-chain polyunsaturated fatty acids ( LC-PUFAs ) enhances the development of attention and efficient information processing in infants . However , it is uncertain whether LC-PUFAs in infancy influence cognitive development in later childhood . OBJECTIVE The objective was to determine the effects of dietary LC-PUFAs in infancy on measures of cognitive function at age 6 y. DESIGN Infants were r and omly assigned to receive formula containing either docosahexaenoic acid and arachidonic acid or no LCPUFAs for a period of 4 mo . A reference breastfed group was also included . In a follow-up conducted at age 6 y , children received assessment s of intelligence quotient ( IQ ) , attention control ( Day-Night Test ) , and speed of processing on the Matching Familiar Figures Test ( MFFT ) . RESULTS At follow-up there were 71 children in the LC-PUFA group , 76 in the control group , and 88 in the breastfed group . The formula groups did not differ on measures of Full-Scale IQ ( LCPUFA mean = 98.0 ; control mean = 100.9 ) or attention control ( LCPUFA mean = 12.7 ; control mean = 12.8 ) . MFFT error scores were the same for both formula groups , but when making correct responses , the LC-PUFA group was significantly faster ( mean = 6.2 s ) than the control group [ mean = 7.8 s ; F(1 , 131 ) = 6.09 , P = 0.015 ] . CONCLUSIONS IQ scores of children who were fed a formula containing either LC-PUFAs or no LC-PUFAs did not differ at age 6 y. However , children who received LC-PUFAs were faster at processing information compared with children who received unsupplemented formula . Variation in the dietary supply of LC-PUFAs in the first months of life may have long-term consequences for the development of some cognitive functions in later childhood",
"OBJECTIVE To examine whether the timing of introduction of the allergenic foods cow 's milk , hen 's egg , peanuts , tree nuts , soy , and gluten is associated with eczema and wheezing in children 4 years of age or younger . DESIGN Population -based prospect i ve cohort study from fetal life until young adulthood . SETTING Rotterdam , the Netherl and s , from April 2002 through January 2006 . PARTICIPANTS A total of 6905 preschool children participating in the Generation R study . MAIN EXPOSURE Timing of introduction of cow 's milk , hen 's egg , peanuts , tree nuts , soy , and gluten collected by question naires at 6 and 12 months of age . MAIN OUTCOME MEASURES Information on the outcomes eczema and wheezing were obtained by questions from the age-adapted version of the \" International Study of Asthma and Allergies in Childhood \" core question naire and question naire data on parentally reported physician diagnosis for eczema . RESULTS Of 6905 children , wheezing was reported in 31 % at age 2 years and in 14 % at ages 3 and 4 years . Eczema was reported in 38 % , 20 % , and 18 % of children at the ages of 2 , 3 , and 4 years , respectively . The introduction of cow 's milk , hen 's egg , peanuts , tree nuts , soy , and gluten before the age of 6 months was not significantly associated with eczema or wheezing at any age after adjustment for potential confounders ( P > .10 for all comparisons ) . The results did not alter after stratification according to the child 's history of cow 's milk allergy and parental history of atopy . CONCLUSION This study does not support the recommendation for delayed introduction of allergenic foods after age 6 months for the prevention of eczema and wheezing",
"OBJECTIVE To determine the influence of alpha-linolenic acid ( ALA ; 18 : 3omega3 ) intake and , hence , the influence of plasma and /or erythrocyte phospholipid content of docosahexaenoic acid ( DHA ; 22 : 6omega3 ) during early infancy on neurodevelopmental outcome of term infants . METHODS The Bayley Scales of Infant Development ( second edition ) , the Clinical Adaptive Test/ Clinical Linguistic and Auditory Milestone Scale ( CAT/CLAMS ) and the Gross Motor Scale of the Revised Gesell Developmental Inventory were administered at a mean age of 12.26 + /- 0.94 months to 44 normal term infants enrolled in a study evaluating the effects of infant formulas differing only in ALA content ( 0.4 , 1.0 , 1.7 and 3.2 % of total fatty acids ) . RESULTS As reported previously [ Jensen et al. , Lipids 13 ( 1996 ) 107 ; J. Pediatr . 131 ( 1997 ) 200 ] , the group fed the formula with the lowest ALA content had the lowest mean plasma and erythrocyte phospholipid DHA contents at 4 months of age . This group also had the lowest mean score on every neurodevelopmental measure . The difference in mean gross motor developmental quotient of this group versus the group fed the formula with 1.0 % ALA but not of the other groups was statistically significant ( P motor indices correlated positively with each other and with the plasma phospholipid DHA content at 4 months of age ( P=0.02 - 0.03 ) . The CLAMS developmental quotient correlated with the erythrocyte phospholipid content of 20 : 5omega3 ( P < 0.01 ) but not with DHA . CONCLUSIONS These statistically significant correlations suggest that the omega3 fatty acid status during early infancy may be important with respect to neurodevelopmental status at 1 year of age and highlight the need for further studies of this possibility",
"OBJECTIVE To evaluate the effects of dietary intake of the long-chain polyunsaturated fatty acids , arachidonic acid ( AA ) , and docosahexaenoic acid ( DHA ) on multiple indices of infant growth and development . DESIGN A double-masked , r and omized , parallel trial was conducted with term infants fed formulas with or without AA+DHA for 1 year ( N = 239 ) . Reference groups of breastfed infants ( N = 165 ) weaned to formulas with and without AA+DHA were also studied . Infants in the formula groups were r and omized at to a control formula with no AA or DHA ( n = 77 ) or 1 of 2 otherwise identical formulas containing AA+DHA ( AA , 0.46 % and DHA , 0.14 % of total fatty acids ) from either egg-derived triglyceride ( egg-DTG [ n=80 ] ) or fish oil and fungal oil ( fish/fungal [ n = 82 ] ) at levels similar to the average in breast milk sample s as measured in the reference group . All formulas contained 50 % of energy from fat with the essential dietary fatty acids , linoleic acid ( 20 % fatty acids ) and alpha-linolenic acid ( 2 % fatty acids ) . The main study outcomes were AA and DHA levels in plasma and red blood cells , and multiple measures of infant development at multiple ages from birth to 14 months : growth , visual acuity , information processing , general development , language , and temperament . RESULTS AA and DHA levels in plasma and red cells were higher in AA+DHA-supplemented groups than in the control formula group and comparable to those in reference groups . No developmental test results distinguished these groups . Expected differences in family demographics associated with breastfeeding were found , but no advantages to breastfeeding on any of the developmental outcome demonstrated . CONCLUSIONS These findings do not support adding AA+DHA to formulas containing 10 % energy as linoleic acid and 1 % energy as alpha-linolenic acid to enhance growth , visual acuity , information processing , general development , language , or temperament in healthy , term infants during the first 14 months after birth.infant development , breast feeding , infant formula , long-chain polyunsaturated fatty acids , docosahexaenoic acid",
"Objective : To evaluate the growth , feeding and health of babies fed a novel infant formula milk with added long chain polyunsaturated fatty acids ( LCPs ) produced from single-cell sources , at concentrations similar to those found in mature breast milk . Design : R and omized double-blind control trial . Subjects : One-hundred and forty healthy , full-term infants of birth weight 2.5–4.5 kg born at the Maternity Department , East Glamorgan General Hospital , Wales , whose mothers had already decided to bottle feed . Interventions : Subjects were r and omized to two groups ; one ( control group ) to receive a st and ard formula milk and the other to receive the trial milk with added LCPs . Milks were supplied in a double-blind fashion and given for the first 12 weeks of life . Anthropometric measurements were made at recruitment , 3 months , 6 months and 1 y. Feeding diaries were completed at 6 weeks and 3 months , and a parental record was kept of any ill health suffered by the subjects during the first year of life . Results : Of 140 infants recruited , 31 did not complete the protocol . Small but statistically significant differences were found only in the subscapular skinfold thickness at 6 weeks and 3 months , that in the trial group being slightly higher , but unlikely to be of any clinical importance . No differences were found in the feeding patterns of the infants in the two groups . Stool patterns were similar , as were the frequencies of illness and allergy . Conclusions : This study supports the view that LCPs from single-cell sources do not have detrimental effects on the growth , feeding and general health of infants . Sponsorship : The research nurse and equipment used in this study were funded by Cow & Gate Nutricia ( UK ) Ltd . European Journal of Clinical Nutrition ( 2000 ) 54 ,",
"BACKGROUND : Docosahexaenoic acid ( DHA ) has been associated with downregulation of inflammatory responses . OBJECTIVE : To report the effect of DHA supplementation on long-term atopic and respiratory outcomes in preterm infants . METHODS : This study is a multicenter , r and omized controlled trial comparing the outcomes for preterm infants tuna oil ( high-DHA diet ) or soy oil ( st and ard-DHA ) capsules . Data collected included incidence of bronchopulmonary dysplasia ( BPD ) and parental reporting of atopic conditions over the first 18 months of life . RESULTS : Six hundred fifty-seven infants were enrolled ( 322 to high-DHA diet , 335 to st and ard ) , and 93.5 % completed the 18-month follow-up . There was a reduction in BPD in boys ( relative risk [ RR ] : 0.67 [ 95 % confidence interval ( CI ) : 0.47–0.96 ] ; P = .03 ) and in all infants with a birth weight of duration of respiratory support , admission length , or home oxygen requirement . There was a reduction in reported hay fever in all infants in the high-DHA group at either 12 or 18 months ( RR : 0.41 [ 95 % CI : 0.18–0.91 ] ; P = .03 ) and at either 12 or 18 months in boys ( RR : 0.15 [ 0.03–0.64 ] ; P = .01 ) . There was no effect on asthma , eczema , or food allergy . CONCLUSIONS : DHA supplementation for infants of BPD in boys and in all infants with a birth weight of < 1250 g and reduced the incidence of reported hay fever in boys at either 12 or 18 months",
"Objective . To determine whether dietary long-chain polyunsaturated fatty acids ( LCPUFA ) , such as docosahexaenoic acid ( DHA ) and arachidonic acid , affect visual evoked potential ( VEP ) acuity of formula-fed infants , relative to breastfed infants . A secondary objective was to assess the effect of LCPUFA on Bayley 's mental developmental index ( MDI ) and psychomotor developmental index ( PDI ) . Methods . Formula-fed infants were r and omly allocated , in a double-blind manner , to either a placebo ( no LCPUFA;n = 21 ) , DHA supplemented ( n = 23 ) , or DHA+arachidonic acid supplemented formula ( n = 24 ) . Infants were fed their assigned formula from the first week of life until 1 year of age . A parallel reference group of breastfed infants was recruited and followed ( n = 46 ) . Infant VEP acuity was assessed at 16 and 34 weeks , and Bayley 's MDI and PDI were assessed at 1 and 2 years of age . Results . There were no differences among the r and omized formula groups for VEP acuity at either 16 or 34 weeks of age . Breastfed infants had better VEP acuity at 34 weeks of age , but not at 16 weeks , compared with all formula-fed infants . Bayley 's MDI and PDI were similar in the 3 formula-fed groups at 1 and 2 years . Breastfed infants had higher MDI scores than formula-fed infants at 2 years of age even after adjusting for environmental variables . Conclusions . LCPUFA supplementation did not influence VEP acuity development in these well-nourished , formula-fed infants",
"BACKGROUND The optimal method for conducting omega (n-)3 polyunsaturated fatty acid ( PUFA ) supplementation trials in children is unknown . AIM To assess the impact of n-3 and n-6 PUFA intake from the background diet on plasma levels of n-3 and n-6 PUFA in children aged 0 - 3 years , with and without n-3 supplementation . METHODS Subjects were r and omised antenatally to receive either n-3 PUFA supplements and low n-6 PUFA cooking oils and spreads or a control intervention , design ed to maintain usual fatty acid intake . Dietary intake was assessed at 18 months by 3-day weighed food record and at 3 years by food frequency question naire . Plasma phospholipids were measured at both time points . Associations were tested by regression . RESULTS N-3 PUFA intake from background diet did not significantly affect plasma n-3 levels . In contrast , n-6 PUFA intake in background diet was positively related to plasma n-6 levels in both study groups . In addition , n-6 PUFA intake from diet was negatively associated with plasma n-3 levels at 18 months and 3 years ( -0.16%/g n-6 intake , 95%CI -0.29 to -0.03 and -0.05%/g n-6 intake , 95%CI -0.09 to -0.01 , respectively ) in the active group , but not in the control group . CONCLUSION Interventions intending to increase plasma n-3 PUFA in children by n-3 supplementation should also minimise n-6 PUFA intake in the background diet",
"ABSTRACT . : Very low birth weight infants demonstrate significant reductions in red blood cell membrane docosahexaenoic acid ( DHA , 22:6n-3 ) following delivery unless fed human milk . The purpose of the present study was to determine if a dietary source of DHA ( MaxEPA , R. P. Scherer Corporation , Troy , MI ) could prevent the decline in red blood cell phospholipid DHA in very low birth weight infants whose enteral feeding consisted of a preterm formula without DHA . Longitudinal data were obtained on membrane phospholipid DHA in both un supplemented and MaxEPA-supplemented infants by a combination of thin layer and gas chromatography . These infants ( n = 39 ) ranged in age from 10 to 53 days at enrollment ( 0 time ) . At enrollment , phospholipid DHA and arachidonic acid ( 20:4n-6 ) were inversely correlated with age in days . During the study , mean red blood cell phospholipid DHA declined without supplementary DHA as determined by biweekly measurement , but infants supplemented with MaxEPA maintained the same weight percent of phospholipid ( phosphatidylethanolanine , phosphatidylcholine , and phospharidylserine ) DHA as at enrollment . The pattern of red blood cell phospholipid fatty acids in supplemented infants was similar to that reported for preterm infants fed human milk ",
"It is recommended in Europe that low birthweight infants ( LBWI ) who do not receive human milk ( HM ) should be fed formula enriched with long-chain polyunsaturated fatty acids ( LCP ) . The question has been raised whether LCP supplementation to LBWI formula may have adverse effects on antioxidant status in the recipient infant , particularly on the major lipid-soluble antioxidant vitamin E ( alpha-tocopherol , alpha-toc . ) . We studied alpha-toc . status in LBWI fed HM ( n = 15 ) or formula either without ( f , n = 8) or with LCP derived from egg lipids and fish oil ( LCP-F , n = 9 ) on days 4 and 21 of life . Plasma alpha-toc . concentrations increased significantly in infants fed HM [ d. 4 : 4.53 ( 1.31 ) , d. 21 : 6.35 ( 2.18 ) , mg/l , mean ( SD ) , p Plasma alpha-toc./total lipid ratios and erythrocyte membrane alpha-toc . concentrations did not change significantly between days 4 and 21 in either group . In contrast , erythrocyte membrane alpha-toc./total lipid ratios decreased significantly in infants fed LCP-F [ 0.42 ( 0.13 ) vs. 0.31 ( 0.06 ) , p LCP supplementation based on egg lipids and fish oil to formula may induce an early postnatal decrease of alpha-toc./total lipid ratios in erythrocyte membranes of LBWI . Therefore , the effects of different forms of LCP supplementation to infant formula on infantile vitamin E status should be carefully evaluated",
"Probiotics and long-chain PUFA ( LC-PUFA ) may be beneficial supplements for infants who are not breast-fed . The aim of the present study is to evaluate the safety of an infant formula containing the LC-PUFA DHA and arachidonic acid ( AA ) and the probiotic Bifidobacterium lactis by comparing the growth rate of infants fed the supplemented and unsupplemented formulas . One hundred and forty-two healthy , term infants were enrolled in a single-centre , r and omised , double-blind , controlled , parallel-group trial , and allocated to receive either st and ard or probiotic and LC-PUFA-containing experimental formulas . The infants were fed with their assigned formulas for 7 months . The primary outcome ( weight gain ) and the secondary outcomes ( length , head circumference and formula tolerance ) were measured throughout the study . LC-PUFA status was assessed at 4 months of age and immune response to childhood vaccines was measured at 7 months of age . There was no significant difference in growth between the two groups . The 90 % CI for the difference in mean weight gain was - 0.08 , 3.1 g in the intention-to-treat population and 0.1 - 3.8 g in the per protocol population , which lay within the predefined boundaries of equivalence , - 3.9 - 3.9 . There were no significant differences in mean length and head circumference . DHA and AA concentrations were higher in infants in the experimental formula group compared with the control formula group . No influence of the supplements on the response to vaccines was observed . Growth characteristics of term infants fed the starter formula containing a probiotic and LC-PUFA were similar to st and ard formula-fed infants",
"Objectives : A r and omized , double-blind , prospect i ve trial assessed effects of different formula levels of polyunsaturated fatty acids on blood phospholipid docosahexaenoic ( DHA ; 22:6&ohgr;3 ) and arachidonic acids ( ARA ; 20:4&ohgr;6 ) in term infants at 120 days of age . Methods : Healthy , formula-fed term infants ( n = 78 ) were r and omized to 1 ) routine milk-based formula with 8 mg DHA , 21 mg ARA , 110 mg & agr;-linolenic ( ALA ; 18:3&ohgr;3 ) , and 1,000 mg linoleic acids ( LA ; 18:2&ohgr;6 ) per 100 kcal ( Lower-long-chain polyunsaturated fatty acids [ LCPUFA ] ; n = 39 ) or 2 ) routine milk-based formula with 17 mg DHA , 34 mg ARA , 85 mg ALA , and 860 mg LA per 100 kcal ( Higher-LCPUFA ; n = 39 ) . Fatty acid methyl esters from red blood cell ( RBC ) and plasma phospholipid fractions were assessed using capillary column gas chromatography . Results : Compared with infants fed Lower-LCPUFA formula , the Higher-LCPUFA group had significantly greater percentages of fatty acids as DHA in RBC phosphatidylethanolamine ( PE ) , RBC phosphatidylcholine ( PC ) , total RBC , and plasma phospholipids ( P Infants fed Lower-LCPUFA formula had higher percentages of precursor & ohgr;6 fatty acids in the desaturation/elongation pathway but lower percentages of ARA ( RBC PE , RBC PC , and plasma phospholipid , P increase in DHA in blood lipids as preformed dietary DHA . Infants fed DHA at levels similar to human milk had significantly greater percentage of DHAat 120 days of age compared with the Lower-LCPUFA group despite higher precursor levels of ALA",
"A milk formula ( Prematil‐LCP ) containing long‐chain polyunsaturated fatty acids ( LCP ) and with a fatty acid profile closely resembling breast milk has recently been introduced for preterm infants . A double‐blind r and omized controlled trial was performed comparing fatty acid absorption from Prematil‐LCP ( n= 10 ) and st and ard Prematil ( n= 10 ) . Formula‐fed preterm infants underwent 3 d fat balances ( once full enteral feeds were established ) along with a parallel human milk fed group ( n= 11 ) . Plasma sample s were taken on the last day . Median total fat excretion ( absorption , % ) was 2.34 g kg ( 82.0 ) , 2.64 g kg ( 82.9 ) and 1.65 g kg ( 87.8 ) with Prematil , Prematil‐LCP and human milk feeding , respectively . This reflected differences in the excretion and absorption of long‐chain saturated fatty acids . All groups excreted detectable LCP . LCP disappearance was higher in infants fed human milk than in those fed Prematil‐LCP , particularly for n‐6 LCP ( p Nevertheless , excreted LCP equated to feeding . Plasma lipid fatty acid composition reflected differences in dietary LCP intake",
"Early nutrition may program obesity and cardiovascular risk later in life , and one of the potential agents is ( n-3 ) long-chain PUFA ( LCPUFA ) . In this study , our objective was to examine whether fish oil ( FO ) supplementation during lactation affects blood pressure and body composition of children . Danish mothers ( n = 122 ) were r and omized to FO [ 1.5 g/d ( n-3 ) LCPUFA ] or olive oil ( OO ) supplementations during the first 4 mo of lactation . The trial also included a high-fish intake reference group ( n = 53 ) . Ninety-eight children were followed-up with blood pressure and anthropometry measurements at 7 y. Diet and physical activity level ( PAL ) were assessed by 4-d weighed dietary records and ActiReg . The PAL value was 4 % lower ( P = 0.048 ) and energy intake ( EI ) of the boys was 1.1 + /- 0.4 MJ/d higher ( P = 0.014 ) in the FO group than in the OO group . Starch intake was 15 + /- 6 g/d higher ( P = 0.012 ) in the FO group , but there were no other differences in diet . Body composition did not differ between the r and omized groups with or without adjustment for starch intake , EI , and PAL . FO boys had 6 mm Hg higher diastolic and mean arterial blood pressure than OO boys ( P blood pressure was not correlated with maternal RBC ( n-3 ) LCPUFA after the intervention , but PAL values were ( r = -0.277 ; P = 0.038 ) . We previously found higher BMI at 2.5 y in the FO group , but the difference did not persist . The differences in blood pressure , EI , and PAL , particularly among boys , suggest that early ( n-3 ) LCPUFA intake may have adverse effects , which should be investigated in future studies",
"Abstract Recent data indicate that supplementation of infant formula with ω-3 and ω-6 long-chain polyunsaturated fatty acids might offer developmental benefits for full term infants . We investigated biochemical consequences of feeding formula supplemented with egg lipids to provide long-chain polyunsaturated fatty acids and compared triglyceride , cholesterol , lipoprotein cholesterol ( HDL2-cholesterol , HDL3-cholesterol , non-HDL-cholesterol ) and apolipoprotein A-I , A-II and B concentrations in full term infants fed either conventional formula ( n = 10 ) or a formula supplemented with ω-3 and ω-6 long-chain polyunsaturated fatty acids and cholesterol in amounts similar to those found in mature human milk ( n = 12 ) . At the age of 5 days , cholesterol , non-HDL-cholesterol and triglyceride concentrations were significantly higher in infants fed supplemented than in those receiving conventional formula . At the age of 30 days , triglyceride concentrations were significantly higher with supplemented than with conventional formula . Thereafter throughout the study , no significant differences were seen between the two groups . Conclusion Full term infants fed formula supplemented with ω-3 and ω-6 long-chain polyunsaturated fatty acids and cholesterol showed significantly higher plasma cholesterol and triglyceride concentrations than infants receiving conventional formula on day 5 and on days 5 and 30 , respectively . Thereafter no appreciable effect of diet on plasma phospholipid , triglyceride , cholesterol , lipoprotein cholesterol and apolipoprotein concentrations were seen",
"Objective : The aim of the present study was to determine whether an increased supply of energy , protein , essential fatty acids , and vitamin A reduces postnatal growth failure in very-low-birth-weight infants . Methods : Fifty infants with birth weight were r and omized to an intervention ( n = 24 ) or a control ( n = 26 ) feeding protocol within 24 hours after birth . Forty-four infants were included in the final analysis . This study was discontinued because of an increased occurrence of septicemia in the intervention group . Results : The intervention group had a lower mean birth weight ( P = 0.03 ) and a higher proportion of infants small-for-gestational age ( P = 0.04 ) than the control group . Other baseline characteristics were similar . The median ( interquartile range ) energy and protein supplies during the first 4 weeks of life were higher in the intervention group : 139 ( 128–145 ) versus 126 ( 121–128 ) kcal · kg−1 · day−1 ( P regained birth weight faster ( P = 0.001 ) and maintained their z scores for weight and head circumference from birth to 36 weeks ’ postmenstrual age ( both P The median ( interquartile range ) growth velocity was 17.4 ( 16.3–18.6 ) g · kg−1 · day−1 in the intervention group and 13.8 ( 13.2–15.5 ) g · kg−1 · day−1 in the control group ( P improved growth in the intervention group , the proportion of growth-restricted infants was 11 of 23 both at birth and at 36 weeks ’ postmenstrual age , whereas this proportion increased among the controls from 4 of 21 to 13 of 21 ( P = 0.04 ) . Conclusions : Enhanced supply of energy , protein , essential fatty acids , and vitamin A caused postnatal growth along the birth percentiles for both weight and head circumference",
"Objective . To evaluate the developmental outcomes of children who participated in an augmented r and omized clinical trial of supplementing a st and ard infant formula with long-chain polyunsaturated fatty acids . Design . R and omized clinical trial , augmented with a nonr and omized human milk comparison group . There were three r and omized formula groups : st and ard formula , st and ard formula containing docosahexaenoic acid ( DHA ) , and st and ard formula containing DHA and arachidonic acid . Setting . Three clinical sites serving diverse population s : Kansas City , MO ; Portl and , OR ; and Seattle , WA . Participants . A total of 274 healthy full-term infants were enrolled in the infant-feeding protocol ; of these , 197 ( 72 % ) participated in assessment s of developmental outcome . Formula Supplements . In the r and omized trial , one group received a st and ard formula , another group received a formula that had been supplemented with DHA from fish oil , and a third group received a formula supplemented with both DHA and arachidonic acid from an egg phospholipid . Outcome Measures . Mental and Motor Scales of the Bayley Scales of Infant Development at 12 months of age ; vocabulary and gesture communication scores from the MacArthur Communicative Development Inventories at 14 months of age . Results . There were no statistically significant differences for either the Bayley Mental Scale or the Bayley Motor Scale , neither when the analysis was restricted to the three r and omized formula groups nor when the analysis included all four groups . However , the DHA formula group had significantly lower scores on two of the MacArthur scales : the DHA group scored lower than the nonr and omized human milk comparison group on the Vocabulary Comprehension Scale , and the DHA group scored lower than the r and omized control formula group on the Vocabulary Production Scale . Moreover , additional analyses both in the formula groups and in the human milk comparison group found significant negative correlations between DHA levels and vocabulary outcomes . Conclusion . We believe that additional research should be undertaken before the introduction of these supplements into st and ard infant formulas",
"DHA and arachidonic acid ( AA ) are important for neurodevelopment . A traditional neonatal neurological examination and the evaluation of general movement quality are sensitive techniques for assessing neurodevelopment in young infants . Mildly abnormal general movements at 3 months have been associated with a non-optimal current brain condition . We investigated whether supplementation of DHA during pregnancy and lactation influences the infant 's brain development and whether additional AA modulates this effect . Healthy women were r and omly assigned to DHA ( 220 mg/d , n 42 ) , DHA+AA ( 220 mg each/d , n 41 ) or control ( n 36 ) , from about week 17 ( range 14 - 20 weeks ) of pregnancy until 12 weeks postpartum . The control and the DHA+AA groups had approximately comparable dietary DHA/AA ratios . The st and ardised neonatal neurological examination was carried out at 2 weeks . General movement quality was assessed at 2 and 12 weeks . Neither DHA alone nor DHA+AA influenced outcomes in the traditional examination . General movement quality of infants in the DHA group was lower than that of infants in the other two groups , especially at 12 weeks : 61 % of the infants in the DHA group showed mildly abnormal general movements compared with 31 % in the control group ( P = 0.008 ) and 34 % in the DHA+AA group ( P = 0.015 ) . We conclude that general movement quality at 12 weeks is sensitive to the maternal dietary DHA/AA balance",
"OBJECTIVES A r and omized , masked , controlled trial was conducted to assess effects of supplementing premature infant formulas with oils containing the long-chain polyunsaturated fatty acids , arachidonic acid ( AA ; 20:4 n6 ) , and docosahexaenoic acid ( DHA ; 22:6 n3 ) on growth , visual acuity , and multiple indices of development . METHODS Infants ( N = 470 ) with birth weights 750 to 1800 g were assigned within 72 hours of the first enteral feeding to 1 of 3 formula groups with or without long-chain polyunsaturated fatty acids : 1 ) control ( N = 144 ) , 2 ) AA+DHA from fish/fungal oil ( N = 140 ) , and 3 ) AA+DHA from egg-derived triglyceride (egg-TG)/fish oil ( N = 143 ) . Infants were fed human milk and /or Similac Special Care with or without 0.42 % AA and 0.26 % DHA to term corrected age ( CA ) , then fed human milk or NeoSure with or without 0.42 % AA and 0.16 % DHA to 12 months ' CA . Infants fed exclusively human milk to term CA ( EHM-T ; N = 43 ) served as a reference . RESULTS Visual acuity measured by acuity cards at 2 , 4 , and 6 months ' CA was not different among groups . Visual acuity measured by swept-parameter visual-evoked potentials in a subgroup from 3 sites ( 45 control , 50 AA+DHA [ fish/fungal ] ; 39 AA+DHA [ egg-TG/fish ] ; and 23 EHM-T ) was better in both the AA+DHA ( fish/fungal ; least square [ LS ] means [ cycle/degree ] + /- st and ard error [ SE ; octaves ] 11.4 + /- 0.1 ) and AA+DHA ( egg-TG/fish ; 12.5 + /- 0.1 ) than control ( 8.4 + /- 0.1 ) and closer to that of the EHM-T group ( 16.0 + /- 0.2 ) at 6 months ' CA . Visual acuity improved from 4 to 6 months ' CA in all but the control group . Scores on the Fagan test of novelty preference were greater in AA+DHA ( egg-TG/fish ; LS means + /- SE , 59.4 + /- 7.7 ) than AA+DHA ( fish/fungal ; 57.0 + /- 7.5 ) and control ( 57.5 + /- 7.4 ) at 6 months ' CA , but not at 9 months ' CA . There were no differences in the Bayley Mental Development Index at 12 months ' CA . However , the Bayley motor development index was higher for AA+DHA ( fish/fungal ; LS means + /- SE , 90.6 + /- 4.4 ) than control ( 81.8 + /- 4.3 ) for infants Spanish-speaking infants and twins were excluded from the analyses , the MacArthur Communicative Development Inventory revealed that control infants ( LS means + /- SE , 94.1 + /- 2.9 ) had lower vocabulary comprehension at 14 months ' CA than AA+DHA ( fish/fungal ) infants ( 100.6 + /- 2.9 ) or AA+DHA ( egg-TG/fish ) infants ( 102.2 + /- 2.8 ) . There were no consistent differences in weight , length , head circumference , or anthropometric gains . CONCLUSION These results showed a benefit of supplementing formulas for premature infants with AA and DHA from either a fish/fungal or an egg-TG/fish source from the time of first enteral feeding to 12 months ' CA",
"BACKGROUND The range of human milk docosahexaenoic acid ( DHA ) concentrations worldwide is much broader than the range explored in r and omized clinical trials to date . OBJECTIVE The primary objective was to determine the effect of 4 amounts of DHA supplementation on the visual acuity of formula-fed infants at 12 mo of age . Secondary objectives were to evaluate visual acuity maturation , red blood cell fatty acids , tolerance , anthropometric measures , and adverse events . DESIGN This double-masked , r and omized trial was conducted at 2 sites ( Dallas and Kansas City ) . Three hundred forty-three healthy , term , formula-fed infants were enrolled at 1 - 9 d of age and were r and omly assigned to be fed 1 of the following 4 infant formulas containing equivalent nutrient amounts , except for long-chain polyunsaturated fatty acids : control ( 0 % DHA ) , 0.32 % DHA , 0.64 % DHA , or 0.96 % DHA ; DHA-supplemented formulas also provided 0.64 % arachidonic acid . Visual acuity was measured by visual evoked potentials in 244 infants who completed the 12-mo primary outcome examination . RESULTS Infants fed control formula had significantly poorer visual evoked potential visual acuity at 12 mo of age than did infants who received any of the DHA-supplemented formulas ( P visual evoked potential visual acuity between the 3 amounts of DHA supplementation for either site at any age tested . CONCLUSIONS DHA supplementation of infant formula at 0.32 % of total fatty acids improves visual acuity . Higher amounts of DHA supplementation were not associated with additional improvement of visual acuity . This trial was registered at clinical trials.gov as NCT00753818",
"Abstract Objective : To determine whether supplementation of infant formula milk with long chain polyunsaturated fatty acids ( LCPUFAs ) influences blood pressure in later childhood . Design : Follow up of a multicentre , r and omised controlled trial . Setting : Four study centres in Europe . Participants : 147 formula fed children , with a reference group of 88 breastfed children . Intervention : In the original trial newborn infants were r and omised to be fed with a formula supplemented with LCPUFAs ( n=111 ) or a formula without LCPUFAs but otherwise nutritionally similar ( n=126 ) . In the present follow up study the blood pressure of the children at age 6 years was measured . Main outcome measures : Systolic , diastolic , and mean blood pressure . Results : 71 children in the LCPUFA supplementation group ( 64 % of the original group ) and 76 children in the non-supplementation group ( 60 % ) were enrolled into the follow up study . The LCPUFA group had significantly lower mean blood pressure ( mean difference −3.0 mm Hg ( 95 % confidence interval −5.4 mm Hg to −0.5 mm Hg ) ) and diastolic blood pressure ( mean difference −3.6 mm Hg ( −6.5 mm Hg to −0.6 mm Hg ) ) than the non-supplementation group . The diastolic pressure of the breastfed children ( n=88 ( 63 % ) ) was significantly lower than that of the non-supplemented formula group but did not differ from the LCPUFA formula group . Conclusions : Dietary supplementation with LCPUFAs during infancy is associated with lower blood pressure in later childhood . Blood pressure tends to track from childhood into adult life , so early exposure to dietary LCPUFAs may reduce cardiovascular risk in adulthood . What is already known on this topic Breast milk contains long chain polyunsaturated fatty acids , and breastfed children have lower blood pressure than children fed with formula milk Blood pressure differences in childhood are known to carry through into adulthood Dietary omega 3 fatty acid supplementation can lower blood pressure in adults with hypertension What this paper adds Supplementation with long chain polyunsaturated fatty acids in infancy results in lower blood pressure later in",
"Docosahexaenoic acid ( DHA ) is important for infant development . The DHA transfer from maternal diet into human milk has not been investigated in detail . We studied the effects of DHA supplementation on the fatty acid composition of human milk and the secretion of dietary (13)C-labeled fatty acids , including DHA , into human milk . Ten lactating women were r and omized to consume , from 4 to 6 weeks postpartum , an oil rich in DHA ( DHASCO , 200 mg of DHA/day ) ( n = 5 ) or a placebo oil ( n = 5 ) . Dietary intakes were followed by 7-day protocol s. On study day 14 a single dose of [U-(13)C]DHASCO was given orally , milk sample s were collected over 48 h , and milk production was recorded . Milk fatty acid composition was determined by gas-liquid chromatography and isotopic enrichment was determined by gas chromatography- combustion-isotope ratio mass spectrometry ( GC-C-IRMS ) . Milk DHA content did not differ between the supplemented and placebo group at study entry ( 0.29 vs. 0.28 wt% , median ) . After 2 weeks of supplementation the milk DHA content was almost 2-fold higher in the supplemented versus placebo group ( 0.37 vs. 0.21 wt% , P = 0.003 ) . Cumulative recovery of [(13)C]palmitic , [(13)C]oleic , and [(13)C]docosahexaenoic acids in human milk at 48 h was similar between supplemented and placebo groups ( palmitic acid 7.40 vs. 8 . 14 % , oleic acid 9.14 vs. 9.97 % , and docosahexaenoic acid 9.09 vs. 8 . 03 % of dose , respectively ) . Notable lower recovery was observed for [(13)C]myristic acid in both the supplemented and placebo groups , 0 . 62 versus 0.77 % of dose . Dietary DHA supplementation increases the DHA content in human milk . DHA transfer from the diet into human milk is comparable to palmitic and oleic acid transfer",
"BACKGROUND Two factors thought to influence the risk of asthma are the promoting effect of sensitization to house dust mites and the preventive effect of increased omega-3 fatty acids . Although house dust mite allergen avoidance has been used as a preventive strategy in several trials , the effect of omega-3 fatty acid supplementation in the primary prevention of asthma and allergic disease is not known . OBJECTIVE To measure the effects of dietary supplementation with omega-3 fatty acids and house dust mite allergen avoidance in children with a family history of asthma . METHODS A total of 616 children at high risk of asthma were enrolled antenatally in a r and omized controlled trial , and 526 children remained in the trial at age 3 years . The outcomes were symptoms of allergic disease and allergen sensitization . RESULTS There was a significant 10.0 % ( 95 % CI , 3.7 - 16.4 ) reduction in the prevalence of cough in atopic children in the active diet group ( P=.003 ; number needed to treat , 10 ) but a negligible 1.1 % ( 95 % CI , -7.1 to 9.5 ) reduction cough among nonatopic children . There was a 7.2 % ( 95 % CI , 10.11 - 14.3 ) reduction in sensitization to house dust mite in the active allergen avoidance group ( P=.05 ; number needed to treat , 14 ) . No significant differences in wheeze were found with either intervention . CONCLUSION These results suggest that our interventions , design ed to be used in simple public health campaigns , may have a role in preventing the development of allergic sensitization and airways disease in early childhood . This offers the prospect of reducing allergic disease in later life",
"OBJECTIVE To determine whether a formula containing n-6 and n-3 long-chain polyunsaturated fatty acids ( LCP ) from purified phospholipids increases the content of 20:4n-6 and 22:6n-3 of plasma lipids and modifies the plasma antioxidant capacity in low-birth-weight infants . STUDY DESIGN Seventeen infants were fed a conventional formula for low birth-weight infants ( F ) , and 17 a formula containing n-6 and n-3 LCP from purified pig-brain phospholipids ( LCP-F ) . Fourteen infants receiving human milk from a human milk bank were used as a reference ( HM ) . Growth index were measured and blood sample s were taken at entry and after 15 days and 30 days of feeding . RESULTS In infants fed LCP-F the levels of 22:6n-3 in total plasma lipids and in plasma phospholipids and triglycerides were higher than in infants fed F and closer to the levels of HM group throughout the study . Docosahexaenoic acid concentration in total plasma lipids was 3.46+/-0.19 mg/dl in infants fed LCP-F and 2.08+/-0.20 in infants fed F after 15 days of feeding ( P concentration of 20:4n-6 in the LCP-F was significantly higher than in the F group at 15 and 30 days of feeding . Plasma antioxidant capacity did not differ significantly between the study groups . CONCLUSION Feeding low birth-weight infants a formula containing LCP phospholipids results in an increase of n-3 and n-6 LCP in plasma towards that of infants fed human milk",
"The evidence of the effect of the age at introduction of new foods during infancy on the development of asthma and allergic rhinitis is inconsistent and scarce . We set out to study these associations . A prospect i ve birth cohort of infants with increased HLA-DQB1-conferred risk for type 1 diabetes was recruited in 1996 - 2000 . The families completed at home a record on the age at introduction of new foods . Persistent asthma and allergic rhinitis were assessed at the age of 5 years with an International Study of Asthma and Allergies in Childhood-type question naire . The Cox proportional hazards regression analyses were adjusted for parental asthma and allergic diseases , and several perinatal and sociodemographical factors . Out of the 1293 children , 77 ( 6.0 % ) developed persistent asthma ; and out of the 1288 children , 185 ( 14.4 % ) developed allergic rhinitis by the age of 5 years . Early age at introduction of oats was associated with a reduced risk of persistent asthma ( hazard ratio ( HR ; 95 % CI ) for the first and mid-tertiles compared with the latest tertile was 0.36 ( 0.15 , 0.85 ) and 0.37 ( 0.22 , 0.62 ) , respectively , P of fish was dose dependently associated with a decreased risk of allergic rhinitis ( HR ( 95 % CI ) for the first and mid-tertiles compared with the latest tertile was 0.34 ( 0.22 , 0.54 ) and 0.45 ( 0.28 , 0.70 ) , respectively , P oats is inversely and independently associated with development of persistent asthma is novel . We confirmed the earlier observation that the age at introduction of fish is inversely related to the risk of allergic rhinitis . Clinical implication s remain to be determined",
"OBJECTIVE Breast-fed infants receive docosahexaenoic acid ( DHA ) and arachidonic acid ( ARA ) in their diet . Upon weaning , infants lose this dietary source of long-chain polyunsaturates because many commercial formulas do not contain these important constituents for neural membrane biogenesis . We evaluated the benefits of postweaning dietary supplementation of DHA + ARA on visual maturation . STUDY DESIGN Healthy term infants ( n = 61 ) were breast-fed to 4 to 6 months , then were r and omly assigned to commercial formula or formula supplemented with DHA ( 0.36 % ) + ARA ( 0.72 % ) . Measurements of red blood cell ( RBC ) fatty acids , visually evoked potential ( VEP ) acuity , and stereoacuity were done before and after weaning . RESULTS At 1 year of age , RBC-DHA in the commercial formula-fed group was reduced by 50 % from the weaning level , whereas there was a 24 % increase in the DHA + ARA-supplemented group . The primary outcome measure , VEP acuity , was significantly more mature in supplemented infants at 1 year of age . Elevated RBC-DHA levels were associated with more mature VEP acuity . There were no significant diet-related differences in stereoacuity . CONCLUSIONS These data extend through the first year of life the critical period in which a dietary supply of DHA and ARA can contribute in optimizing visual development in term infants",
"ABSTRACT : The objective of this study was to compare circulating lipid docosahexaenoic acid [ 22:6(n-3 ) , DHA ] levels in term infants fed a powdered ( CORN oil ) or liquid ( SOY oil ) infant formula or human milk ( HM ) . Infants whose mothers chose not to breast feed were r and omly assigned to the CORN or SOY formula group . The formula fat differed in linolenic acid [ 18:3(n-3 ) ] content : it was 0.8 % for the CORN and 4.8 % for the SOY . Linoleic acid ( 18:2(n-6 ) ] was 31.5 and 34.2 % fatty acids in the CORN and SOY formula , respectively . The formulas or HM were fed from birth through 8 wk of age , and growth and the plasma and red blood cell ( RBC ) phospholipid fatty acid composition was determined at 3 d , 4 wk , and 8 wk of age . Growth did not differ among groups . The plasma phospholipid and RBC phosphatidylethanolamine DHA was similar in the CORN and SOY formula groups at all ages . Plasma and RBC phosphatidylethanolamine levels of DHA were significantly lower in infants fed the CORN or SOY formula than in infants fed HM during wk 4 and 8 . Plasma and RBC 22:5(n-6 ) was not increased in the formula groups at any age . The formula content of linolenic acid had no effect on the RBC or plasma DHA levels of the infants . The biologic or functional significance of the lower plasma and RBC DHA in infants fed formula rather than HM is unknown . The need for a dietary source of DHA and specificity of plasma or RBC phospholipid DHA as a measure of desaturation and elongation of linolenic acid in developing organs remains uncertain",
"The CNS and the retina are enriched in long chain polyunsaturated ( LCP ) fatty acids , specifically docosahexaenoic acid ( DHA , 22:6n-3 ) and arachidonic acid ( AA , 20:4n-6 ) , which are present in human milk but not in most infant formulas . In the present study of 134 formula-fed and 63 breast-fed infants , we prospect ively evaluated whether providing a source of DHA and AA or DHA alone in formula would increase red blood cell ( RBC ) phospholipid levels of these fatty acids , enhance visual function , or affect growth during the first year . Healthy term infants were r and omized to be fed formulas containing linoleic acid ( ≈10 % kcal ) and α-linolenic acid ( ≈1 % kcal ) plus ( 1 ) no added LCP fatty acids ( control formula ) , ( 2 ) DHA ( 0.12 wt% fatty acids ) and AA ( 0.43 wt% ) from egg yolk phospholipid ( AA + DHA formula ) , or ( 3 ) DHA ( 0.2 wt% ) from fish oil ( DHA formula ) . A breast-fed group was studied concurrently and permitted formula supplementation after 3 mo . Visual acuity was measured using both the acuity card procedure and a visual evoked potential method at 2 , 4 , 6 , 9 , and 12 mo . Infants fed the control formula had 10 - 40 % lower RBC levels of DHA and AA than infants in the breast-fed group . Infants fed the AA+ DHA formula had levels of both LCP within ≈10 % of the values for infants in the breast-fed group , and infants fed the DHA formula had 25 - 55 % higher DHA levels and 15 - 40 % lower AA levels . There were no differences in growth or in visual function during this 12-mo feeding study",
"AIM Long-chain polyunsaturated fatty acid ( LCPUFA ) supplementation of infant formula may have a beneficial effect on cognitive development . This study aim ed to investigate the effect of LCPUFA formula supplementation primarily on cognition and secondarily on behaviour at age 9 years . Special attention was paid to the potentially modifying effect of maternal smoking during pregnancy . METHOD A double-blind , r and omized control study was performed in two groups of healthy infants born at term : one group , constituting the control group , received st and ard formula ( n=169 ) and another group received st and ard formula supplemented with LCPUFAs ( n=146 ) . A breastfed group ( n=159 ) served as an additional reference . At 9 years of age , 72 % of the children ( control group : n=123 ; 71 males , 52 females ; LCPUFA group : n=91 ; 42 males , 49 females ; breastfed group : n=127 , 64 males , 63 females ) underwent extensive cognitive and behavioural testing . RESULTS An interaction between infant nutrition and smoking during pregnancy was found . Among children exposed to smoking during pregnancy , LCPUFA supplementation was associated with higher mean verbal IQ scores ( p=0.007 ) and learning and memory ( p=0.006 ) . Among children not exposed to smoking during pregnancy , LCPUFA supplementation was associated with lower mean verbal memory scores ( p=0.003 ) . Executive function scores were significantly lower in the LCPUFA-supplemented group than in the control group ( p=0.001 ) . Breastfeeding was associated with better performance on IQ ( p=0.005 ) . INTERPRETATION No consistent beneficial effect of LCPUFA formula supplementation on cognitive development in term-born infants was found . The study confirmed that breastfeeding is associated with better cognition",
"We investigated whether the disparity in neural maturation between breastfed and formula-fed term infants could be corrected by the addition of fish oil , a source of docosahexaenoic acid ( DHA , 22:6 omega 3 ) , to infant formula . Healthy , term infants were r and omised at birth to receive either a supplemented or placebo formula if their mothers had chosen to bottle feed . Breastfed term infants were enrolled as a reference group . Infant erythrocyte fatty acids and anthropometry were assessed on day 5 and at 6 , 16 , and 30 weeks of age . Visual evoked potential ( VEP ) acuity was determined at 16 and 30 weeks . VEP acuities of breastfed and supplemented-formula-fed infants were better than those of placebo-formula-fed infants at both 16 and 30 weeks of age ( p Erythrocyte DHA in breastfed and supplemented-formula-fed infants was maintained near birth levels throughout the 30-week study period but fell in placebo-formula-fed infants ( p Erythrocyte DHA was the only fatty acid that consistently correlated with VEP acuity in all infants at both ages tested . A continuous supply of DHA may be required to achieve optimum VEP acuity since infants breastfed for short periods ( of VEP than infants receiving a continuous supply of DHA from either breastmilk or supplemented formula . Erythrocyte arachidonic acid ( 20:4 omega 6 ) in supplemented-formula-fed infants was reduced below that of infants fed breastmilk or placebo formula at 16 and 30 weeks ( p adverse effects were noted , with growth of all infants being similar . DHA seems to be an essential nutrient for the optimum neural maturation of term infants as assessed by VEP acuity . Whether supplementation of formula-fed infants with DHA has long-term benefits remains to be eluci date",
"Background : There is some evidence that the n-6/n-3 long-chain polyunsaturated fatty acids ( LCPUFAs ) ratio in early nutrition , and thus in breast milk , could influence infant body composition . Methods : In an open-label r and omized controlled trial ( RCT ) , 208 healthy pregnant women were allocated to a dietary intervention ( supplementation with 1,200 mg n-3 LCPUFAs per day and instructions to reduce arachidonic acid ( AA ) intake ) from the 15th wk of gestation until 4 mo of lactation or to follow their habitual diet . Breast milk LCPUFAs at 6 wk and 4 mo postpartum were related to infant body composition assessed by skinfold thickness ( SFT ) measurements and ultrasonography during the first year of life . Results : Dietary intervention significantly reduced breast milk n-6/n-3 LCPUFAs ratio . In the whole sample , early breast milk docosahexaenoic acid ( DHA ) , eicosapentaenoic acid ( EPA ) , and n-3 LCPUFAs at 6 wk postpartum were positively related to the sum of four SFT measurements at age 1 . Breast milk AA and n-6 LCPUFAs at 6 wk postpartum were negatively associated with weight , BMI , and lean body mass ( LBM ) up to 4 mo postpartum . Conclusion : Breast milk n-3 LCPUFAs appear to stimulate fat mass growth over the first year of life , whereas AA seems to be involved in the regulation of overall growth , especially in the early postpartum period",
"Our study examined if dietary long-chain polyunsaturated fatty acids ( LCPUFA ) have an impact on oxidative stress in preterm infants . Serum malonyldialdehyde ( MDA ) , total peroxide concentrations , and total antioxidant capacity were determined at mean ( st and ard deviation [ SD ] ) 34.7 ( 10.9 ) days of life in 104 healthy preterm infants ( gestational age , 32.6 [ 2.9 ] weeks ; birthweight ; 1605 [ 285 ] g ) who were r and omly assigned to be fed since birth either a formula containing LCPUFA ( arachidonic and docosahexaenoic ) ( group A , n = 50 ) or a LCPUFA-free formula with identical compositions for other nutrients ( group B , n = 54 ) . Clinical and anthropometric characteristics did not differ significantly between the two groups . Mean ( SD ) serum MDA levels did not differ significantly between groups A ( 0.23 [ 0.04 ] micromol/L ) and B ( 0.22 [ 0.05 ] micromol/L ) . The concentrations of total peroxides were below the detection limits of the assay in 41 of 50 ( 82 % ) infants of group A and 43 of 54 ( 79 % ) infants of group B and not significantly different between the two infant groups . No difference was observed in serum total antioxidant capacity between groups A ( 340.0 [ 46.2 ] micromol/L ) and B ( 354.7 [ 46.5 ] micromol/L ) . We concluded that supplementation of infant formulas with LCPUFA does not affect lipid peroxidation in healthy preterm infants",
"Abstract When term infants are fed st and ard formula that does not contain long-chain polyunsaturated fatty acids ( LC-PUFA ) , they still show lower levels of docosahexaenoic acid ( DHA ) in red blood cell ( RBC ) phospholipids by several weeks or months postnatally . This study was design ed in order to evaluate a potential alternative for supplementing term infant formulas with DHA by adding a high-DHA/low-eicosapentanoic acid fish oil to levels similar to that in human milk ( 0.3 % ) . A total of 37 term infants were included in the study at 3 days of life . DHA concentrations remained stable between inclusion and 4 months of life at around 8 % of the RBC phospholipids in the LC-PUFA enriched formula-fed group whereas it decreased significantly in the st and ard formula-fed group . In the human milk-fed group , RBC DHA concentrations at 4 months of age were significantly lower than that at birth and were significantly correlated with the duration of breast feeding ( r = 0.85 ; P = 0.0002 ) . A significant decrease of arachidonic acid between inclusion and 4 months of age was observed in the enriched formula-fed group and reached a mean value at 4 months , which was significantly lower than that observed in the human milk or st and ard formula-fed groups ( P high-docosahexaenoic acid/low-eicosapentanoic acid fish oil up to 4 months of age is efficient in improving docosahexaenoic acid status , however it increases the risk of impaired n-6 fatty acid status",
"We investigated whether the previously reported preventive effect of maternal ω-3 fatty acid supplementation on IgE-associated allergic disease in infancy may be mediated by facilitating a balanced circulating Th2/Th1 chemokine profile in the infant . Vaccine-induced immune responses at 2 y of age were also evaluated . Pregnant women , at risk of having an allergic infant , were r and omized to daily supplementation with 1.6 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid or placebo from the 25th gestational week through 3.5 mo of breastfeeding . Infant plasma was analyzed for chemokines ( cord blood , 3 , 12 , 24 mo ) and anti-tetanus and anti-diphtheria IgG ( 24 mo ) . High Th2-associated CC-chemokine lig and 17 ( CCL17 ) levels were associated with infant allergic disease ( p lower CCL17/CXC-chemokine lig and 11 ( CXCL11 ) ( Th2/Th1 ) ratios ( p supplementation was linked with higher Th1-associated CXCL11 levels ( p increased IgG titers to diphtheria ( p = 0.01 ) and tetanus ( p = 0.05 ) toxins . Thus , the prospect of balancing the infant immune system toward a less Th2-dominated response , by maternal ω-3 fatty acid supplementation , seems to be influenced by allergic status",
"BACKGROUND The prevalence of asthma has increased in developed countries in the past 2 decades . The effectiveness of intervention measures on the primary prevention of asthma has not been well studied . OBJECTIVE To assess the effectiveness of a multifaceted intervention program in the primary prevention of asthma in high-risk infants ( in this study , infants are defined as persons from birth to the age of 1 year ) . DESIGN Prospect i ve , prenatally r and omized , controlled study with follow-up through the age of 1 year . SETTING University hospital-based setting s at 2 Canadian centers : Vancouver , British Columbia , and Winnipeg , Manitoba . PARTICIPANTS A total of 545 high-risk infants ( at least 1 first-degree relative with asthma or 2 first-degree relatives with other IgE-mediated allergic diseases ) identified before birth . INTERVENTIONS Avoidance of house dust mite and pet allergens and environmental tobacco smoke , encouragement of breastfeeding , and supplementation with a partially hydrolyzed formula . MAIN OUTCOME MEASURES Probable or possible asthma , rhinitis without apparent colds , and a prick skin test result positive for common inhalant allergens . RESULTS Thirty-eight ( 15.1 % ) of the 251 infants available for assessment in the intervention group and 49 ( 20.2 % ) of the 242 infants available for assessment in the control group fulfilled the criteria for possible or probable asthma ( adjusted relative risk , 0.66 ; 90 % confidence interval , 0.44 - 0.98 ) . Also , 16.7 % of the infants in the intervention group and 27.3 % of the infants in the control group developed rhinitis without colds ( adjusted relative risk , 0.51 ; 90 % confidence interval , 0.35 - 0.74 ) . The incidence of positive skin test results to 1 or more inhalant allergens was similar in both groups ( 4.4 % in the intervention group and 4.6 % in the control group ) . CONCLUSIONS Our multifaceted intervention program result ed in a modest but significant ( P= .04 ) reduction in the risk of possible or probable asthma and rhinitis without apparent colds at the age of 12 months in high-risk infants . In the absence of a vali date d definition of asthma at the age of 12 months , follow-up studies are needed to determine the effectiveness of the intervention program in the primary prevention of asthma in high-risk infants",
"AIM To investigate whether the low docosahexaenoic acid ( DHA ) status of malnourished , mostly breast fed , Pakistani children can be improved by fish oil ( FO ) supplementation . METHODS Ten malnourished children ( aged 8–30 months ) received 500 mg FO daily for nine weeks . The supplement contained 62.8 mol% ( 314 mg ) long chain polyunsaturated fatty acids of the ω3 series ( LCPUFAω3 ) and 22.5 mol% ( 112 mg ) DHA . Seven FO unsupplemented children served as controls . Red blood cell ( RBC ) fatty acids were analysed at baseline and at the study end . RESULTS FO supplementation augmented mean ( SD ) RBC DHA from 2.27 ( 0.81 ) to 3.35 ( 0.76 ) mol% , without significantly affecting the concentrations of LCPUFAω6 . Unsupplemented children showed no RBC fatty acid changes . One FO supplemented child with very low initial RBC arachidonic acid showed a remarkable increase from 4.04 to 13.84 mol% , whereas another with high RBC arachidonic acid showed a decrease from 15.64 to 10.46 mol% . CONCLUSION FO supplementation improves the DHA status of malnourished children . The supplement is apparently well absorbed and not exclusively used as a source of energy",
"BACKGROUND Docosahexaenoic acid is present in high concentration in retina and does not influence visual development in preterm infants . It is still under discussion whether docosahexaenoic acid is important for visual development in term infants . METHODS Thirty-seven infants fed formula for a median of 14 days were r and omized at median age of 25 days to three formulas : a ) DHAGF : 0.3 wt% docosahexaenoic acid and 0.5 wt% gamma-linolenic acid ; b ) DHAF 0.3 wt% docosahexaenoic acid ; or c ) STF : st and ard formula without long-chain polyunsaturated fatty acids and 17 breast-fed infants were observed , using blood sample s and anthropometric measurements from 1 to 4 months of age . At 4 months , visual acuity was measured by swept steady-state visual evoked potential . A cross-sectional study on 25 breast-fed infants was carried out as a reference group for the analyses . RESULTS Infants fed the two docosahexaenoic acid-supplemented formula had relative docosahexaenoic acid concentrations in red blood cell phospholipids almost as high as those in breast-fed infants , whereas infants in the st and ard formula group had significantly lower levels . The addition of gamma-linolenic acid to the formula had a positive effect on red blood cell arachidonic acid levels , compared with levels obtained using fish oil only . Visual acuity was significantly different among all feeding groups ( analysis of variance ; p = 0.05 , means + /- st and ard deviation : breast-fed , 0.37+/-0.06 logMAR ; DHAF and DHAGF combined , 0.40+/-0.07 logMAR ; and st and ard formula 0.44+/-0.07 logMAR . However , there was no statistical difference among the formula groups . In a multiple regression analysis including all formula-fed infants , weight at delivery ( p = 0.002 ) , but not type of formula , was significantly associated with visual acuity at 4 months of age . CONCLUSIONS The addition of docosahexaenoic acid result ed in concentrations in red blood cells at similar levels as those in breast-fed infants , whereas the increase in visual acuity did not reach significance . The addition of gamma-linolenic acid result ed in higher arachidonic acid concentrations in red blood cells",
"OBJECTIVES To evaluate safety and benefits of feeding preterm infants formulas containing docosahexaenoic acid ( DHA ) and arachidonic acid ( ARA ) until 92 weeks postmenstrual age ( PMA ) , with follow-up to 118 weeks PMA . STUDY DESIGN This double-blinded study of 361 preterm infants r and omized across three formula groups : ( 1 ) control , no supplementation ; ( 2 ) algal-DHA ( DHA from algal oil , ARA from fungal oil ) ; and ( 3 ) fish-DHA ( DHA from fish oil , ARA from fungal oil ) . Term infants breast-fed > or = 4 months ( n = 105 ) were a reference group . Outcomes included growth , tolerance , adverse events , and Bayley development scores . RESULTS Weight of the algal-DHA group was significantly greater than the control group from 66 to 118 weeks PMA and the fish-DHA group at 118 weeks PMA but did not differ from term infants at 118 weeks PMA . The algal-DHA group was significantly longer than the control group at 48 , 79 , and 92 weeks PMA and the fish-DHA group at 57 , 79 , and 92 weeks PMA but did not differ from term infants from 79 to 118 weeks PMA . Supplemented groups had higher Bayley mental and psychomotor development scores at 118 weeks PMA than did the control group . Supplementation did not increase morbidity or adverse events . CONCLUSIONS Feeding formulas with DHA and ARA from algal and fungal oils result ed in enhanced growth . Both supplemented formulas provided better developmental outcomes than unsupplemented formulas",
"AIM A follow up study of developmental quotient ( DQ ) at 24 months of toddlers whose diets in early infancy differed in fatty acid composition , and in whom an association between diet and DQ was observed at 4 months . METHODS 81 toddlers were distributed among three groups according to early type of diet : st and ard infant formula ( SFo , n = 30 ) ; long chain polyunsaturated fatty acid ( LC-PUFA ) enriched formula ( LCPFo , n = 26 ) ; human milk ( HM , n = 25 ) . DQ at 24 months was assessed by Brunet-Lézine ’s psychomotor developmental test . A subgroup ( n = 20 ; SFo 8 ; LCPFo 6 ; HM 6 ) was tested for erythrocyte phosphatidylcholine and phosphatidylethanolamine . RESULTS No DQ differences were found by analysis of variance . Neither DQ nor erythrocyte docosahexaenoic acid at 4 months were predictors of DQ scores at 24 months . Phosphatidylcholine arachidonic and docosahexaenoic acid correlated positively , and phosphatidylcholine linoleic acid and phosphatidylethanolamine eicosapentaenoic acid negatively , with DQ . Multiple regression analysis including these variables explained 52 % of interindividual DQ variance . A strong association was found between the erythrocyte phosphatidylcholine arachidonic/linoleic acid ratio and DQ ( r= 0.75 ; p = 0.0001 ) . CONCLUSIONS The diet/DQ association found at 4 months was not predictive of DQ scores at 24 months . Irrespective of dietary or genetic factors , there appears to be a strong correlation between the LC-PUFA composition of the red cell membrane and higher neurodevelopmental performance",
"n-3 Long-chain PUFA ( LC-PUFA ) intake during infancy is important for neurodevelopment ; however , previous studies of n-3 LC-PUFA supplementation have been inconclusive possibly due to an insufficient dose and limited methods of assessment . The present study aim ed to evaluate the effects of direct supplementation with high-dose fish oil ( FO ) on infant neurodevelopmental outcomes and language . In the present r and omised , double-blind , placebo-controlled trial , 420 healthy term infants were assigned to receive a DHA-enriched FO supplement ( containing at least 250 mg DHA/d and 60 mg EPA/d ) or a placebo ( olive oil ) from birth to 6 months . Assessment occurred at 18 months via the Bayley Scales of Infant and Toddler Development ( 3rd edition ; BSID-III ) and the Child Behavior Checklist . Language assessment occurred at 12 and 18 months via the Macarthur-Bates Communicative Development Inventory . The FO group had significantly higher erythrocyte DHA ( P = 0·03 ) and plasma phospholipid DHA ( P = 0·01 ) levels at 6 months of age relative to placebo . In a small subset analysis ( about 40 % of the total population ) , children in the FO group had significantly higher percentile ranks of both later developing gestures at 12 and 18 months ( P = 0·007 ; P = 0·002 , respectively ) and the total number of gestures ( P = 0·023 ; P = 0·006 , respectively ) . There was no significant difference between the groups in the st and ard or composite scores of the BSID-III . The results suggest that improved postnatal n-3 LC-PUFA intake in the first 6 months of life using high-dose infant FO supplementation was not beneficial to global infant neurodevelopment . However , some indication of benefits to early communicative development was observed",
"Polyunsaturated n-3 fatty acids ( n-3PUFA ) may improve brain development and prevent cardiovascular disease . Heart rhythm is autonomically controlled and among the affected cardiovascular risk markers in adults . The aim of the study was to examine whether fish oil supplementation in late infancy could modify heart rate ( HR ) and heart rate variability ( HRV ) . In a 2 × 2-intervention , 83 healthy Danish infants were r and omized to ± fish oil ( 3.4 ± 1.1 mL/d ) and cow 's milk or infant formula from 9 to 12 mo of age . In 57 infants , 0.5-h ECG recordings were successfully obtained before and after the intervention and erythrocyte fatty acid composition was determined in 30 of these . Fish oil supplementation raised erythrocyte n-3PUFA content ( p in HR or HRV . However , a fish-oil × gender interaction was observed on mean RR interval ( p = 0.001 ) with a 6 % longer mean RR interval in fish-oil-supplemented boys ( p = 0.007 ) . Irrespective of gender , there was a positive association between the 9- and 12-mo changes in RR interval and erythrocyte n-3PUFA ( p in erythrocyte n-3PUFA , mean RR interval was found to be longer ( p = 0.011 ) in the fish-oil-supplemented groups . The study suggests that fish oil may affect heart rhythm in infants similar to that observed in adults . This may imply low n-3PUFA-status in late infancy and n-3PUFA influence on CNS function",
"Objective : To investigate the impact of maternal diet during breastfeeding on atopic sensitization of infants at risk . Design : Prospect i ve cohort study . Setting : Turku University Central Hospital , Finl and .Subjects and methods : Altogether 114 infants with a family history of atopic disease were followed during their first year of life . The mothers completed a 4 day food record during breastfeeding just before the infants were 3 months old . Atopic sensitization of the infants was determined by a positive skin prick test result at 12 months . Results : Positive skin prick test reactivity to at least one antigen was detected in 27/114 ( 24 % ) infants at 12 months . The energy intake of the mothers was low , mean 8.0 MJ/day ( 95 % CI 7.7–8.3 ) , and the proportion of energy derived from fat was high , mean 36.6 E% ( 95 % CI 35.6–37.6 ) . Atopic mothers had a higher intake of total fat and saturated fat and a lower intake of carbohydrate as a percentage of total energy intake than non-atopic mothers ; P=0.017 , P=0.050 , P=0.004 respectively . Maternal intake of saturated fat during breastfeeding was associated with atopic sensitization of the infant , OR=1.16 ( 95 % CI 1.001–1.36 ) ; P=0.048 irrespective of the maternal atopic status . Conclusions : Our results show that an unbalanced maternal diet during breastfeeding may be a risk factor underlying the later development of atopic sensitization of the infant regardless of maternal atopic disease . The observation thus extends findings implying that early nutrition programmes the subsequent health of the child to the risk of developing atopic disease . Sponsorship : Academy of Finl and and National Technology Agency . European Journal of Clinical Nutrition ( 2000 ) 54 ,",
"Background and Objective : Feeding long-chain polyunsaturated fatty acids ( LCP ) influences immunity in adults ; however , less is known about their effect during development . The aim of the study was to determine the effect of feeding LCP on immunity in healthy infants during the first 4 months of life . Patients and Methods : Formula-fed infants were r and omized at ≤14 days of age to st and ard term formula ( Formula ) or formula containing LCP ( Formula+LCP ) . Infants exclusively fed human milk ( HM ) were included for comparison . At 16 weeks of age , blood was collected and phenotypes , the ability to proliferate and produce cytokines ( interleukin [IL]-2 , IL-4 , IL-6 , IL-10 , IL-12 , interferon [IFN]-γ , tumor necrosis factor [TNF]-α , TGF-β ) after incubation with phytohemaglutinin ( PHA ) , β-lactoglobulin , or soy protein were measured . Results : Feeding LCP result ed in a higher than and more similar proliferation rate to PHA in HM-fed infants , possibly because of a greater TH1 type cytokine response and a higher percentage of antigen mature ( CD45RO+ ) cells ( P The response to β-lactoglobulin did not differ among groups . After incubation with soy protein Formula+LCP , compared with Formula produced less IL-2 and more TNF-α and had a higher percentage of CD8 + and a lower percentage of CD20 + ( CD20+CD54 + ) cells poststimulation ( P produced less IL-2 after PHA , had a lower percentage of CD80 + cells , and a higher percentage of CD54 + cells after incubation with food proteins ( P Formula-fed infants , at low risk for allergy , respond differently to mitogen and food proteins ex vivo than those fed HM . Feeding LCP altered some of these differences in the direction that is hypothesized to confer immune benefits",
"Background The tissue accretion of long-chain polyunsaturated fatty acids is compromised in infants born prematurely . Human milk contains long-chain polyunsaturated fatty acids , but most preterm infant formulas do not . The long-term effects of preterm formula supplemented with arachidonic acid and docosahexaenoic acid , in proportions typical of those in human milk , were therefore investigated . Methods In this double-blind , r and omized study , 288 preterm infants received experimental formula ( n = 77 ) , unsupplemented ( control ) formula ( n = 78 ) , or human milk ( n = 133 ) until 48 weeks postconceptional age ( PCA ) . Term formula , without supplemental long-chain polyunsaturated fatty acids , was administered from 48 to 92 weeks PCA to formula-fed infants and to infants weaned from human milk . Anthropometric and fatty acid data were assessed by using analysis of variance . Results At 92 weeks PCA , no statistically significant anthropometric measurement differences were found except for midarm circumference , which was smaller in human milk – fed infants than in those fed formula . Phospholipid concentrations were similar in the experimental and human milk – fed groups , and docosahexaenoic acid levels were significantly greater than in the control group . The types and incidences of adverse events were similar among the feeding groups . Conclusions The results of this study demonstrate the efficacy and long-term safety of preterm formula supplemented with long-chain polyunsaturated fatty acids",
"The need for a dietary supply of docosahexaenoic acid ( DHA ) and arachidonic aid ( AA ) in term infants was evaluated in a double-masked r and omized clinical trial of the effects of supplementation of term infant formula with DHA ( 0.35 % of total fatty acids ) or with DHA ( 0.36 % ) and AA(0.72 % ) on visual acuity development . One hundred and eight healthy term infants were enrolled in the study ; 79 were exclusively formula-fed from birth ( r and omized group ) and 29 were exclusively breast-fed ( gold st and ard group ) . Infants were evaluated at four time points during the first 12 mo of life for blood fatty acid composition , growth , sweep visual evoked potential(VEP ) acuity , and forced choice preferential looking acuity . Supplementation of term infant formula with DHA or with DHA and AA during the first 4 mo of life yields clear differences in total red blood cell ( RBC ) lipid composition . Supplementation of term infant formula with DHA or with DHA and AA also yields better sweep VEP acuity at 6 , 17 , and 52 wk of age but not at 26 wk of age , when acuity development reaches a plateau . The RBC lipid composition and sweep VEP acuity of supplemented infants was similar to that of human milk-fed infants , whereas the RBC lipid composition and sweep VEP acuity of unsupplemented infants was significantly different from human milk-fed infants . Differences in acuity among diet groups were too subtle to be detected by the forced choice preferential looking protocol . Infants in all diet groups had similar rates of growth and tolerated all diets well . Thus , early dietary intake of preformed DHA and AA appears necessary for optimal development of the brain and eye of the human infant",
"OBJECTIVE To investigate the effect of reducing the n-6/n-3 fatty acid ratio in maternal nutrition on the maternal and cord blood leptin axis and their association with infant body composition up to 2 years . DESIGN AND METHODS 208 healthy pregnant women were r and omized to either a dietary intervention to reduce the n-6/n-3 fatty acid ratio from 15th week of gestation until 4 months postpartum or a control group . Leptin , soluble leptin receptor and free leptin index were determined in maternal and cord plasma and related to infant body composition assessed by skinfold thicknesses up to 2 years . RESULTS The intervention had no effect on either the maternal or fetal leptin axis . Maternal leptin in late pregnancy was inversely related to infant weight and lean body mass ( LBM ) up to 2 years , after multiple adjustments . Cord leptin was positively related to weight , body fat , and LBM at birth , and inversely associated with weight , BMI , fat mass , and LBM at 2 years and weight gain up to 2 years . The contribution of cord leptin to infant outcomes was overall stronger compared with maternal leptin . CONCLUSIONS Both , maternal and fetal leptin were associated with subsequent infant anthropometry with a greater impact of fetal leptin",
"ABSTRACT : A direct influence of dietary long-chain polyunsaturated fatty acids ( LC-PUFA ) on the developmental quotient ( DQ ) of the healthy term infant remains unexplored . To test this hypothesis , we design ed a prospect i ve study of three types of diet . Twentynine infants received a LC-PUFA-supplemented formula , 31 received a st and ard infant formula , and 30 infants were breastfed exclusively . Neurodevelopmental response was measured by the Brunet-Lézine psychomotor development lest at 4 mo . The fatty acid status was also assessed among three diet subgroups ( 59 subjects ) at 4 mo . Formula-fed infants who received LC-PUFA supplementation scored significantly higher ( p Brunet-Lézine scale than infants who received the st and ard formula . Breast-fed infants also performed better than those fed the st and ard formula . Arachidonic acid and docosahexaenoic acid levels in circulating lipids and erythrocyte phospholipids were higher among breast-fed infants and among the group fed the arachidonic- and docosahexaenoic acid-supplemented formula . These findings are suggestive that formula supplementation with one or both of these fatty acids can benefit term infants in neurodevelopmental performance",
"Objective : To assess the effects of dietary long chain polyunsaturated fatty acid ( LCPUFA ) supplementation on auditory brainstem maturation of healthy term newborns during the first 16 weeks of life by measuring brainstem auditory evoked potentials ( BAEPs ) . Design : Throughout the 16 week study period , infants in the formula A group ( n = 28 ) were assigned to be fed exclusively with the same formula supplemented with DHA , and infants in the formula B group ( n = 26 ) were assigned to receive only a DHA unsupplemented but otherwise similar formula . During the study period , the first 26 consecutive infants to be fed exclusively on their mother ’s milk for at least the first 16 weeks of life were chosen as the control group . BAEP measurements were performed twice : at the first and 16th week of age . Results : There were no significant differences among the study and control groups in the BAEP measurements performed at the study entry . At 16 weeks of age , all absolute wave and interpeak latencies in the study and control groups had significantly decreased . The decreases were significantly greater in the formula A and control groups than in the formula B group . Conclusions : Infants fed on human milk or a formula supplemented with LCPUFAs during the first 16 weeks of life show more rapid BAEP maturation than infants fed on a st and ard formula . Although the clinical importance and long term effects of these findings remain to be determined , routine supplementation of formulas with LCPUFAs should be considered",
"OBJECTIVE We tested the hypothesis that balanced addition of long-chain polyunsaturated fatty acid ( LCPUFA ) to preterm formula during the first weeks of life would confer long-term neurodevelopmental advantage in a double-blind , r and omized , controlled trial of preterm formula with and without preformed LCPUFA . METHODS The participants were 195 formula-fed preterm infants ( birth weight Main outcome measures were Bayley Mental Developmental Index ( MDI ) and Psychomotor Developmental Index ( PDI ) at 18 months and Knobloch , Passamanick and Sherrard 's Developmental Screening Inventory at 9 months ' corrected age . Safety outcome measures were anthropometry at 9 and 18 months , tolerance , infection , necrotizing enterocolitis , and death . RESULTS There were no significant differences in developmental scores between r and omized groups , although infants who were fed LCPUFA-supplemented formula showed a nonsignificant 2.6-point ( 0.25 st and ard deviation ) advantage in MDI and PDI at 18 months , with a greater ( nonsignificant ) advantage ( MDI : 4.5 points ; PDI : 5.8 points ) in infants below 30 weeks ' gestation . LCPUFA-supplemented infants were shorter than control infants at 18 months ( difference in length st and ard deviation score : 0.44 ; 95 % confidence interval : 0.08 - 0.8 ) . No other significant short- or long-term differences in safety outcomes were observed . Breastfed infants had significantly higher developmental scores at 9 and 18 months than both formula groups and were significantly heavier and longer at 18 months than LCPUFA-supplemented but not control infants . CONCLUSIONS With the dose , duration , and preparation of LCPUFA used , efficacy was not demonstrated , although an advantage in later neurodevelopment can not be excluded by global tests of development up to 18 months , particularly in infants below 30 weeks ' gestation . The surprising effect of LCPUFA-supplemented formula on growth 18 months beyond the intervention period needs to be confirmed in other studies using similar supplementation strategies . Additional follow-up of this cohort is critical at an age when more specific tests of cognitive function are possible",
"It has been recommended to supplement formulas for preterm infants with n-3 and n-6 long-chain polyunsaturated fatty acids ( LCP ) to improve growth , visual acuity , and neurodevelopmental performance . However , large amounts of LCP may increase lipid peroxidation and oxidative stress in preterm infants . We investigated if , under high supplementation of natural tocopherols , LCP addition to formula can be performed safely without causing tocopherol depletion in cell membranes . Thirty-one healthy preterm infants with gestational ages from 28 to 32 weeks were evaluated in a prospect i ve , r and omized study from birth to day 42 . Nine infants received an n-3 and n-6 LCP-enriched formula ( A ) , eleven infants a st and ard formula ( B ) , and eleven infants breast milk ( control group ) . Alpha- and gamma-tocopherol extracts were added to both formulas , amounting to five times the value in breast milk ( 2.3 mg/dL in both formulas versus 0.45 mg/dL in breast milk ) . Erythrocyte arachidonic acid ( AA ) and docosahexaenoic acid ( DHA ) in the phosphatidylethanolamine fraction were similar in the three groups over the study period , whereas a significant reduction of erythrocyte AA and DHA could be detected in the phosphatidylcholine fraction in all three groups from day 14 onwards , when compared to respective cord blood values , with lowest values in the st and ard formula group . Amazingly , levels of alpha- and gamma-tocopherol were higher in plasma , erythrocytes , platelets , monocytes , and polymorphonuclear leukocytes with LCP supplementation as compared to st and ard formula and breast milk from day 7 onwards , whereas in buccal mucosal cells , this was not the case until day 42 . Gammatocopherol uptake in the LCP-supplemented group was also significantly higher in all cell fractions studied from day 7 onwards . We therefore hypothesize that the LCP supplementation used in formula A improves tocopherol solubility and stability in biological membranes . Under high-dose vitamin E addition to n-3 and n-6 LCP-supplemented formula , no evidence for tocopherol depletion and furthermore , high accumulation of tocopherols , can be detected in healthy preterm infants",
"Because docosahexaenoic acid ( DHA ) may be an essential nutrient for the visual and early cognitive development of preterm infants , DHA enrichment of preterm formulas has been recommended . This r and omized trial was design ed to study the n-6 and n-3 fatty acid status of healthy preterm infants fed a formula enriched with a low eicosapentaenoic-fish oil until 4 mo corrected age compared with that of infants fed a st and ard formula . A reference group of breast-fed infants was studied concurrently . The fatty acid content of red blood cell ( RBC ) phospholipid was assessed at enrollment , hospital discharge , expected term , and 3 and 6 mo postterm . The DHA content of RBC phospholipid was higher in infants fed the enriched versus the st and ard formula at hospital discharge , expected term , and 3 and 6 mo postterm . However , compared with infants fed the st and ard formula , infants fed the enriched formula had also higher RBC phospholipid eicosapentaenoic content ( 0.69 ± 0.15%versus 0.25 ± 0.12 % , p lower RBC phospholipid arachidonic acid content ( 15.1 ± 0.93%versus 18.8 ± 0.89%;p preterm infants with low-eicosapentaenoic fish oil is effective in improving DHA status , but results in worsening of n-6 fatty acid status . We speculate that preterm infants may require a dietary supply of arachidonic acid as well as DHA if the same fatty acid status as that of breast-fed infants is to be achieved",
" The 209 mothers to be , enrolled in a r and omized , prospect i ve , allergy-prevention study from allergy-prone families , totally abstained from cow 's milk and egg from gestational week 28 to delivery . This article presents the development of allergic disease at 5 years of age in their children , compared with the development of allergic disease in the children of the control mothers who took normal food throughout pregnancy . The prevalence of allergic disease could be evaluated in 198 children ( 95 % ) . Allergic disease was monitored with question naires , skin prick testing , serum-IgE determinations , and physical examination . Eczema , allergic rhinoconjunctivitis , and asthma was equally common in the groups . Persistent food intolerance to egg was significantly more common in children of the mothers receiving the diet . This long-term follow-up confirms our previous findings that maternal elimination diet during late pregnancy does not prevent the development of allergic disease in the genetically predisposed child",
"Objective : To evaluate α-linolenic acid ( ALA ) ( 18∶3 n-3 ) and linolenic acid ( LA ) ( 18∶2 n-6 ) in cholesterol esters ( CE ) as markers of ALA and LA dietary intakes in preterm infants . Subjects : Forty-five preterm infants : two groups fed different formulas , the third fed human milk . Design : ALA and LA dietary intakes were precisely recorded in each infant to accurately determine the cumulative amount of ingested ALA and LA during two intervals : ( i ) between the second day after the first significant formula intake ( D0 ) and the fifteenth day ( D15 ) ; and ( ii ) between D0 and the first day of the 37th week of post-conception age ( W37 ) . The corresponding amounts of ingested ALA and LA were related to ALA and LA levels determined by capillary column gas – liquid chromatography in plasma cholesterol esters at D15 and W37 , respectively . Results : ALA in CE was very significantly correlated to D0–D15 and D0–W37 ALA intakes ( 0.66 ; P=0.0001 and 0.70 ; P=0.0001 ) , respectively . LA in CE was weakly correlated to D0–D15 LA intakes ( 0.03 ; P=0.01 ) and whatever the group ( human milk or enriched formula ) the correlation was lost at W37 . Conclusion : In preterm infants , ALA in CE can be considered as representative of ALA dietary intakes , whereas LA in CE appears as a poor marker of LA intakes . European Journal of Clinical Nutrition ( 2000 ) 54 ,",
"Objectives : Long-chain polyunsaturated fatty acid ( LC-PUFA ) enrichment of preterm infant formulas is recommended to meet high dem and s. Dietary LC-PUFA may inhibit endogenous LC-PUFA synthesis , thus limiting their benefit . We investigated effects of different docosahexaenoic acid ( DHA ) intakes on plasma and erythrocyte fatty acids and endogenous LC-PUFA synthesis in preterm infants . Methods : Forty-two preterm infants ( birth weight 1000–2200 g ) were r and omized double-blind to preterm formulas with & ggr;-linolenic acid ( 0.4 % ) and arachidonic acid ( AA , 0.1 % ) but different DHA contents ( A : 0.04 % , B : 0.33 % , C : 0.52 % ) ; 24 received human milk ( HM : 0.51 % AA , 0.38 % DHA , nonr and omized ) . Blood was sample d on study days 0 , 14 , and 28 . Uniformly 13C-labeled linoleic acid ( 2 mg/kg ) and & agr;-linolenic acid ( 1 mg/kg ) were applied orally on day 26 and blood sample s collected 48 hours later . Results : On day 28 , group A had the lowest and group C the highest plasma phospholipid concentrations of eicosapentaenoic acid and DHA . Erythrocyte phospholipid DHA was lowest in group A , but comparable in groups B , C , and HM . Plasma and erythrocyte AA were lower in formula groups than in HM . DHA intake had no effect on DHA synthesis . LC-PUFA synthesis was lower in HM infants . Conclusions : DHA supply dose dependently increased plasma DHA . Formula DHA levels of 0.33 % matched plasma DHA status of infants fed HM . LC-PUFA synthesis was lower in infants fed HM than formulas with different DHA and low AA contents . With the LC-PUFA supplementation used , DHA in formulas did not inhibit AA or DHA synthesis",
"Objective To determine if improvements in cognitive outcome detected at 18 months ’ corrected age ( CA ) in infants born high-docosahexaenoic acid ( DHA ) compared with st and ard-DHA diet were sustained in early childhood . Design Follow-up of a multicentre r and omised controlled trial . R and omisation was stratified for sex , birth weight ( Five Australian tertiary hospitals from 2008 to 2013 . Participants 626 of the 657 participants r and omised between 2001 and 2005 were eligible to participate . Interventions High-DHA ( ≈1 % total fatty acids ) enteral feeds compared with st and ard-DHA ( ≈0.3 % total fatty acids ) from age 2–4 days until term CA . Primary outcome Full Scale IQ of the Wechsler Abbreviated Scale of Intelligence ( WASI ) at 7 years CA . Prespecified subgroup analyses based on the r and omisation strata ( sex , birth weight ) were conducted . Results 604 ( 92 % of the 657 originally r and omised ) consented to participate ( 291 high-DHA , 313 st and ard-DHA ) . To address missing data in the 604 consenting participants ( 22 for primary outcome ) , multiple imputation was performed . The Full Scale IQ was not significantly different between groups ( high-DHA 98.3 , SD 14.0 , st and ard-DHA 98.5 , SD 14.9 ; mean difference adjusted for sex , birthweight strata and hospital −0.3 , 95 % CI −2.9 to 2.2 ; p=0.79 ) . There were no significant differences in any secondary outcomes . In prespecified subgroup analyses , there was a significant sex by treatment interaction on measures of parent-reported executive function and behaviour . Scores were within the normal range but girls receiving the high-DHA diet scored significantly higher ( poorer outcome ) compared with girls receiving the st and ard-DHA diet . Conclusions Supplementing the diets of preterm infants with a DHA dose of approximately 1 % total fatty acids from days 2–4 until term CA showed no evidence of benefit at 7 years ’ CA . Trial registration number Australian New Zeal and Clinical Trials Registry : ACTRN12606000327583",
"Long-chain ( LC ) polyunsaturated fatty acids ( PUFA ) ( LCP ) are considered conditionally essential nutrients for low birth weight infants ( LBWI ) . Therefore , enrichment of LBWI formulae with metabolites both linoleic ( omega-6 ) and alpha-linolenic ( omega-3 ) acids at levels typical for human milk has been recommended . However , previous feeding trials with LCP-enriched formulae evaluated only a dietary supplementation with omega-3 LCP from fish oils alone or with both omega-3 and omega-6 LCP at levels considerably lower than usual human milk contents . We studied the effects of an LBWI formula providing the major omega-3 and omega-6 LCP , docosahexaenoic and arachidonic acids , in amounts similar to those in average human milk . Twenty-seven LBWIs were enrolled in this study when they tolerated full enteral feeding ( > or = 130 ml milk/kg/day ) . Infants either received their own mother 's milk ( n = 8 , birthweight 1218 + /- 146 g , gestational age 30.2 + /- 1.5 weeks , mean + /- SD ) fortified with protein and minerals ( FM-85 , Nestle Ag , Munchen , Germany ; dosage 5 g/100 ml milk ) or were r and omly assigned to blinded batches of an LBWI formula ( Prematil , Milupa AG , Friedrichsdorf , Germany ) without LCP ( n = 10 , 1280 + /- 229 g , 31.1 + /- 3.1 weeks ) or with LCP ( n = 9 , 1253 + /- 334 g , 30.4 + /- 3.3 wks . ) . During the study period of 21 days , the three feeding groups did not differ in growth and feeding tolerances as assessed by occurrence of gastric residuals , spitting , or abdominal distention ; however , firms stools were noted more frequently in the two formula groups . ( ABSTRACT TRUNCATED AT 250 WORDS",
"ABSTRACT : Red blood cell ( RBC ) phospholipids of infants fed human milk compared with formula have more arachidonic acid ( AA ) and docosahexanoic acid ( DHA ) . The addition of low levels of marine oil to infant formula with 0.6 to 2.0 % α-linolenic acid ( LLA , 18:3n-3 ) prevented declines in DHA in formula-fed infants ; however , the feeding trials were short ( 4 to 6 wk ) , LLA concentrations were low compared with current formulas ( 3.0 to 5.0 % LLA ) , and the formulas were unstable . Trials with stable formulas were necessary to determine if dietary DHA could maintain phospholipid DHA after discharge from the hospital and , in fact , if it was necessary with higher intakes of LLA . The results of acute ( 4 wk ) and extended ( to 79 wk postconception ) feeding of such formulas on RBC and plasma phospholipid AA and DHA are reported here . Control formulas were identical to commercially available formulas . Experimental formulas differed only in the addition of small amounts of marine oil . DHA in RBC and plasma phosphatidylethanolamine ( PE ) declined during four weeks of feeding but not if marine oil provided DHA ( 0.2 % or 0.4 % ) and plasma phospholipid AA ( g/100 g ) decreased with time and marine oil feeding . Extended feeding with marine oil accounted for half the DHA in RBC and plasma phosphatidylethanolamine at equilibrium ; however , RBC ( g/100 g ) and plasma AA ( g/100 g ; mg/L plasma ) decreased progressively until late infancy and were depressed further by marine oil . We conclude that 1 ) AA and DHA decline in RBC and plasma phospholipids of preterm infants when only their n-6 and n-3 fatty acid precursors are consumed ; and 2 ) marine oil can maintain cord concentrations of RBC phosphatidylethanolamine DHA but further reduces AA",
"OBJECTIVE : To test the hypothesis that long-chain polyunsaturated fatty acid ( LCPUFA ) supplementation in infancy would improve cognition into later childhood ( after 9 years ) at both general and specific levels . METHODS : A comprehensive cognitive battery was completed by 107 formerly preterm infants ( mean age : 128 months ) . As infants , they had been assigned r and omly to receive LCPUFA-supplemented ( N = 50 ) or control ( N = 57 ) formula , between birth and 9 months ; the docosahexaenoic acid level ( DHA ) in the supplemented formulas was 0.5 % . In addition to r and omized comparisons , we planned supplementary analyses to examine the effects of both gender and feeding group ( those receiving some maternal breast milk versus those receiving none ) . RESULTS : There were no significant differences between r and omized diet groups on any cognitive measure . There was significant interaction between gender and supplementation ; girls only showed beneficial effects of LCPUFAs on literacy . Significant interaction also occurred between feeding group and supplementation ; increases of 0.7 SD in verbal IQ , full-scale IQ , and memory scores were found for the LCPUFA group , but only for infants who received only formula and no maternal breast milk . CONCLUSIONS : The results of this post–9-year cognitive follow-up study in a r and omized trial of LCPUFA-supplemented formula for preterm infants suggest no overall group effects but indicate that gender-specific and diet-specific effects may exist . The data provide some evidence that LCPUFAs are a key factor in the cognitive benefits of breast milk . Caution is advised in data interpretation because of the small groups used",
"OBJECTIVE The purpose of this study was to determine the effect of docosahexaenoic acid supplementation on plasma phospholipid docosahexaenoic acid content and indices of depression and information processing for women who breast-feed . STUDY DESIGN Mothers who planned to breast-feed their infants were assigned r and omly in a double-masked fashion to receive either docosahexaenoic acid ( approximately 200 mg/d ) or placebo for the first 4 months after the delivery . Major outcome variables included plasma phospholipid fatty acid patterns and scores on a self-rating question naire of current depression symptoms . A structured clinical interview of depression , scores on another self-rating question naire of depression symptoms , and a laboratory measure of information processing were obtained in subgroups of the total population . RESULTS Plasma phospholipid contents of docosahexaenoic acid at baseline were 3.15 + /- 0.78 and 3.31 + /- 0.70 ( mg/dL of total fatty acids ) in the docosahexaenoic acid and placebo groups , respectively . After 4 months , the plasma phospholipid docosahexaenoic acid content of the docosahexaenoic acid group was 8 % higher ( 3.40 + /- 0.97 mg/dL ) , whereas that of the placebo group was 31 % lower ( 2.27 + /- 0.87 mg/dL ) . Despite the higher plasma phospholipid docosahexaenoic acid content of the supplemented group after 4 months , there was no difference between groups in either self-rating or diagnostic measures of depression ; information processing scores of the two groups also did not differ . CONCLUSION Docosahexaenoic acid supplementation ( approximately 200 mg/d ) for 4 months after the delivery prevented the usual decline in plasma phospholipid docosahexaenoic acid content of women who breastfeed but did not influence self-ratings of depression , diagnostic measures of depression , or information processing",
"We investigated whether n-3 LCPUFA affected immune function in late infancy and explored effect-modification by single nucleotide polymorphisms ( SNPs ) and links to intestinal microbiota . Infants ( n=105 ) were r and omized to fish oil ( FO , 1.2g/d n-3 LCPUFA ) or sunflower oil (SO)-supplements from age 9 - 18 months . Immune function was assessed by ex vivo cytokine production in stimulated blood and plasma immunoglobulin E ( IgE ) . We genotyped functional SNPs in PPARG2 and COX2 and analyzed fecal microbiota by 16S-rRNA terminal restriction fragment length polymorphism . FO compared to SO reduced Lactobacillus paracasei-stimulated IL-6 at 18 months ( P=0.03 , n=104 ) . This effect was most pronounced among infants wild-type for PPARG2-Pro12Ala and /or COX2-T8473C ( P 18 months IgE in all infants ( P=0.004 ) ( bp100 ) and with IL-6 production among infants weaned before 9 months ( P=0.047 ) ( bp102 ) . Thus , FO reduced IL-6 in a genotype-modified manner . The microbiota was partly linked to IL-6 and IgE , not directly to FO",
"OBJECTIVE To compare the effects of the exogenous supply of long-chain polyunsaturated fatty acids ( LCP ) and cholesterol on the lipid and fatty acid status in full-term , 4-month old infants . METHODS Twenty-three infants received a st and ard infant formula while twenty-one were given a formula enriched with LCP and cholesterol in a prospect i ve , r and omized study . The composition of the two formulas differed only in fat quality . A group of fifteen breastfed infants fed was used as reference . No one was complemented with solid foods before blood sampling at 4 months of life . RESULTS Differences in total-cholesterol and low-density lipoprotein-cholesterol ( LDL-C ) levels between feeding groups were mainly gender-related . Dietary cholesterol tended to increase LDL-C plasma levels . The breastfed and the enriched formula-fed groups had higher levels of circulating LCP than the group that received the st and ard formula . In the erythrocytes of infants fed the st and ard formula , C22:6 n-3 levels were less than 50 % those of the breastfed and the enriched formula-fed ones . Higher C20:4 n-6 levels were found in the erythrocytes of the enriched formula-fed group . CONCLUSIONS Formula-fed , full-term infants maintain a lipid and fatty acid status close to that of breastfed infants when supplied with dietary LCP and cholesterol",
"BACKGROUND The prevalence of atopic dermatitis ( AD ) , a chronic skin disease , has increased substantially in recent decades , and different factors have been implicated in its etiology . Although dietary habits are being investigated , few conclusive findings have been reported . Nevertheless , increased consumption of polyunsaturated fatty acids ( PUFA ) and a diet poor in antioxidants have been related to AD . OBJECTIVES The objectives of this study were to investigate the association between AD , the intake of different foods , and the effect of a Mediterranean diet among Spanish schoolchildren aged 6 to 7 . METHODS We performed a cross-sectional study with 20 106 schoolchildren aged 6 - 7 years from 10 different areas of Spain . The participation rate was 76.50 % . The prevalence of AD was assessed using the International Study of Asthma and Allergies in Childhood question naire and the criteria of the Spanish Academy of Dermatology . To calculate the Mediterranean diet score , we classified food into 2 groups : Mediterranean food , including fruit , seafood , vegetables , pulses , cereals , pasta , rice , and potatoes ; and non-Mediterranean food , including meat , milk , and fast food . RESULTS Milk was negatively associated with AD . Butter and nuts also were negatively associated , although statistical significance was only reached when these foods were consumed 3 or more times a week . CONCLUSIONS We found no association between the Mediterranean diet score and AD and a positive association between AD and obesity",
"n-3 long-chain polyunsaturated fatty acids ( n-3 LCPUFA ) , from fish oil ( FO ) , in rodents have been shown to reduce adipogenesis . Evidence of an effect on adipose tissue mass in humans is limited , and no studies have specifically aim ed to eluci date this in infancy . To explore whether n-3 LCPUFA intake affects adipose tissue growth , we r and omly allocated 154 healthy infants to daily supplementation with FO or sunflower oil ( SO ) from 9 to 18 mo of age and measured z-score changes in various anthropometric assessment s of body size and skinfold thicknesses and plasma adipokine concentrations . Among the 133 completing infants , erythrocyte n-3 PUFA increased more in those receiving FO than in infants receiving SO [ 12.2 ± 0.7 ( mean ± SE ) versus 2.0 ± 0.4 fatty acid percentage ( FA% ) , p n-6 PUFA ( −8.9 ± 0.7 versus −0.9 ± 0.6 FA% , p between FO consumption relative to SO consumption and any of the anthropometric measures related to the size of the fat mass , but infants in the FO group had a lower skinfold ratio ( triceps/subscapular ) at 18 mo than those in SO group ( p = 0.02 ) . Our findings do not support the hypothesis that dietary n-3 LCPUFA is important for infant fat mass , but future studies testing this specifically are warranted",
"One hundred and sixty‐two women with respiratory allergy to animal d and ers and /or pollens were r and omly allocated to a diet consisting of either a very low ingestion of hens ' egg and cows ' milk or a daily ingestion of one hens ' egg and about 11 of cows ' milk during the last 3 months of pregnancy . One hundred and sixty‐three infants were followed prospect ively up to 18 months of age when the cumulated incidence of atopic disease in each child was evaluated blindly . No significant differences in the distribution of atopic disease were found among the infants in relation to the maternal diet during late pregnancy . The numbers of skin‐prick tests positive to ovalbumin , ovomucoid , β‐lactoglobulin and cows ' milk were likewise not influenced by differences in the maternal diet during late pregnancy . Genetic factors rather than maternal diet during the perinatal period probably have a greater effect on the incidence of atopic diseases during early infancy",
"BACKGROUND Early life exposures may be important in the development of asthma and allergic disease . OBJECTIVE To test house dust mite ( HDM ) avoidance and dietary fatty acid modification , implemented throughout the first 5 years of life , as interventions to prevent asthma and allergic disease . METHODS We recruited newborns with a family history of asthma antenatally and r and omized them , separately , to HDM avoidance or control and to dietary modification or control . At age 5 years , they were assessed for asthma and eczema and had skin prick tests for atopy . RESULTS Of 616 children r and omized , 516 ( 84 % ) were evaluated at age 5 years . The HDM avoidance intervention result ed in a 61 % reduction in HDM allergen concentrations ( microg/g dust ) in the child 's bed but no difference in the prevalence of asthma , wheeze , or atopy ( P > .1 ) . The prevalence of eczema was higher in the active HDM avoidance group ( 26 % vs 19 % ; P = .06 ) . The ratio of omega-6 to omega-3 fatty acids in plasma was lower in the active diet group ( 5.8 vs 7.4 ; P prevalence of asthma , wheezing , eczema , or atopy did not differ between the diet groups ( P > .1 ) . CONCLUSION Further research is required to establish whether other interventions can be recommended for the prevention of asthma and allergic disease . CLINICAL IMPLICATION S House dust mite avoidance measures and dietary fatty acid modification , as implemented in this trial during infancy and early childhood , did not prevent the onset of asthma , eczema , or atopy in high-risk children",
"The effect of genetic and environmental factors on the prevalence of allergic disorders in early childhood was determined in a prospect i ve follow‐up study . Information was available on 1174 children at the age of 2 years . Two‐hundred and seventy‐five were considered to have an allergic disorder . The prevalence varied from 3.2 % for rhinitis to 10.9 % , for asthma . At 2 years 60 children reacted positively on skin‐prick test ( SPT ) . Multivariate logistic regression analysis was used to obtain adjusted odds ratios ( 95 % confidence interval ) for each factor . For asthma , positive family history , male sex , low birth‐weight , maternal smoking and season of birth were significant risk factors . For eczema , positive family history was the only significant risk factor . For rhinitis , lower socio‐economic group and autumn birth were significant . Maie sex and low birth‐weight were significant for skin test positivity . Positive family history and low birth‐weight were significant risk factors for any allergy . Low birth‐weight was also a significant risk for skin test reactivity to house dust mite . Genetic and environmental factors have a profound effect on the development of allergic disorders in the first two years of life",
"Background : Extrauterine growth restriction is common among very low birth weight infants ( VLBW , BW . Optimal postnatal nutrient supply is essential to limit growth restriction and ensure adequate growth and neurodevelopment . Objectives : We compared an enhanced postnatal nutrient supply to a st and ard supply and evaluated the effects on growth velocity , head circumference growth and cerebral maturation - the latter by magnetic resonance diffusion tensor imaging ( DTI ) . We hypothesized increased growth velocity , head circumference growth and decreased mean diffusivity ( MD ) in cerebral white matter ( WM ) areas , suggesting improved cerebral maturation among infants on the enhanced nutrient supply . Methods : In this r and omized controlled trial , infants on the enhanced nutrient supply received increased amounts of energy , protein , fat , essential fatty acids and vitamin A until discharge . DTI was performed close to term equivalent age . Outcomes were growth velocity , head circumference growth and WM mean diffusivity . Results : Among the 50 included infants , 14 in the intervention group and 11 controls underwent a successful DTI . Infants on the enhanced diet achieved improved growth velocity ( 16.5 vs. 13.8 g/kg/day , p = 0.01 ) and increased head circumference ( Δz score : 0.24 vs. -0.12 , p = 0.15 ) . A significantly lower MD was seen in a large WM area such as the superior longitudinal fasciculi ( 1.19 × 10 - 3 vs. 1.24 × 10 - 3 mm2/s , p = 0.04 , adjusted for age when scanned ) . Conclusions : Enhanced nutrient supply to VLBW infants is associated with improved growth velocity , increased head circumference growth and decreased regional WM mean diffusivity , suggesting improved maturation of cerebral connective tracts",
"The influence of dietary long chain polyunsaturated fatty acid ( LCP ) supply , and especially of docosahexaenoic acid ( DHA ) , on evoked potential maturation , was studied in 58 healthy preterm infants using flash visual evoked potentials ( VEPs ) , flash electroretinography ( ERG ) , and brainstem acoustic evoked potentials ( BAEPs ) at 52 weeks of postconceptional age . At the same time , the fatty acid composition of red blood cell membranes was examined . The infants were fed on breast milk ( n = 12 ) , a preterm formula supplemented with LCP ( PF-LCP ) ( n = 21 ) , or a traditional preterm formula ( PF ) ( n = 25 ) . In the breast milk and PF-LCP groups the morphology and latencies of the waves that reflect the visual projecting system were similar ; in the PF group the morphology was quite different and the wave latencies were significantly longer . This could mean that the maturation pattern of VEPs in preterm infants who did not receive LCP was slower . Moreover , a higher level of erythrocyte LCP , especially DHA , was found in breast milk and PF-LCP groups compared with the PF group . ERG and BAEP recordings were the same in all three groups . These results suggest that a well balanced LCP supplement in preterm formulas can positively influence the maturation of visual evoked potentials in preterm infants when breast milk is not available",
"In view of the importance of long-chain polyunsaturated fatty acids ( LCP ) for growth and development of fetal and infant neural tissue , the influence of the dietary n-3 and n-6 LCP intake on the LCP status of forty-three preterm infants ( birth weight was studied . Thirty-one formula-fed infants were r and omly assigned to receive a conventional formula lacking LCP ( n 16 ) , or an 22:6n-3- and 20:4n-6-enriched formula ( n 15 ) ; twelve infants received their own mother 's breast milk . Fatty acid compositions of plasma and erythrocyte ( RBC ) phospholipids ( PL ) were determined in umbilical venous blood , in weekly postnatal sample s until day 35 of life and , for the formula-fed infants , at 3 months of corrected age . Both in plasma ( P 22:6n-3 and the 20:4n-6 status of formulated preterm infants to values found for human-milk-fed preterm infants . Additional studies are necessary to evaluate the potentially favourable effects of this combined addition on the neurodevelopmental outcome of preterm infants",
"The nutritional requirements of preterm infants for the long chain polyunsaturated essential fatty acids , arachidonic acid ( AA ) and docosahexaenoic acid ( DHA ) , have not been clearly defined . The present study evaluated preterm infants of less than 2.3 kg birth weight fed a commercial formula ( Preemie SMA ® ) devoid of AA and DHA and compared this control group with similar infant groups fed one of three formulas containing a range of 0.32 to 1.1 % AA and 0.24 to 0.76 % DHA . An analogous group of infants fed their mothers ' breast milk and a breast milk fortifier ( when indicated ) was also studied . Erythrocyte membrane phospholipids were isolated from blood sample s collected at 12 d of age and after a further 4 wk of feeding . Infants fed the formula without AA and DHA showed a reduction in AA level in erythrocyte phosphatidylcholine , and a reduced level of DHA in phosphatidylethanolamine in comparison with infants fed breast milk or infant formula containing AA and DHA . Supplementing infant formula with increasing levels of AA and DHA produced a clear dose response in the levels of AA and DHA found in erythrocyte membrane phospholipids . From comparison of membrane phospholipid fatty acid composition it appears that a formula level of 0.32 - 1.1 % AA and 0.24 - 0.76 % DHA provides sufficient levels of these fatty acids to achieve a similar fatty acid composition to that of infants fed human milk for most of the lipid fractions examined",
"The influence of dietary omega-3 fatty acid supply on visual acuity development was evaluated in very low birth weight ( VLBW ) infants using visual-evoked potential ( VEP ) and forced-choice preferential-looking ( FPL ) procedures at 36 and 57 wk postconception . The VLBW infants born at 27 - 33 wk postconception were r and omized to one of three diet groups : corn oil , which provided solely linoleic acid ; soy oil , which provided linoleic and alpha-linolenic acids ; or soy/marine oil ; which was similar to the soy oil formula but also provided preformed long chain omega-3 fatty acids . The VLBW infants in the soy/marine oil group had higher omega-3 levels in erythrocyte membranes and better VEP and FPL acuities at 36 and 57 wk than infants in the corn oil group . The soy oil group had intermediate omega-3 levels in erythrocyte membranes and significantly poorer VEP acuity at 57 wk compared with the soy/marine oil group . Only the soy/marine oil group had acuities comparable to the \" gold st and ards \" of VLBW infants fed human milk and preterm infants who were born and tested at 35 - 36 wk postconception . In addition , VEP and FPL acuity were poorer in a nonr and omized group of formula-fed full-term infants than in breast-fed full-term infants . The results suggest that dietary omega-3 fatty acid supply may play an important role in early human visual development",
"OBJECTIVE To test the hypothesis that in the premature infant with an enterostomy , early enteral supplementation with Microlipid ( fat supplement ) and fish oil increases enteral fat absorption and decreases the requirement for Intralipid ( intravenous fat emulsion ) . STUDY DESIGN Premature infants ( usual care ( control 18 infants ) or early supplementing enteral fat and fish oil ( treatment 18 infants ) . Intravenous fat emulsion was decreased as enteral fat intake was increased . Daily weight , ostomy output , and nutrition data were recorded . Weekly 24-hour ostomy effluent was collected until bowel reanastomosis , and fecal fat , fecal liquid , and dry feces were measured . Fat absorption ( g/kg/d ) was calculated by subtracting fecal fat from dietary fat . The fecal liquid and dry feces were reported as mg/g wet stool . Date were analyzed by using ANOVA and mixed-effects model . RESULTS The interval from initial postoperative feeding to bowel reanastomosis varied from 2 to 10 weeks . The treatment group received more dietary fat and less intravenous fat emulsion and had higher enteral fat absorption , less fecal liquid , and drier feces than the control group . These effects were greater among infants with a high ostomy compared with those with a low ostomy . Enteral fat intake was significantly correlated with fat absorption . CONCLUSION Early enteral fat supplement and fish oil increases fat absorption and decreases the requirement for intravenous fat emulsion . This approach could be used to promote bowel adaptation and reduce the use of intravenous fat emulsion in the premature infant with an enterostomy",
"BACKGROUND Long-chain polyunsaturated fatty acids ( LCPUFA ) are important for normal visual and brain development . Although present in human milk , LCPUFA have until recently been absent from artificial formulas , and infants may have limited ability to synthesis e LCPUFA . To determine the clinical significance of this relative deficiency of LCPUFA , we undertook a r and omised trial of the relation between LCPUFA supplementation and infant cognitive behaviour . METHODS 44 term infants had been r and omised to a formula supplemented with LCPUFA ( 21 ) or not supplemented with LCPUFA ( 23 ) , which they had taken from birth to age 4 months . Infant cognitive behaviour was assessed at 10 months of age by a means-end problem-solving test -- the intentional execution of a sequence of steps to achieve a goal . The problem required three intermediate steps to achieve the final goal , uncovering and retrieving a hidden toy . FINDINGS Infants who received LCPUFA-supplemented formula had significantly more intentional solutions than infants who received the no-LCPUFA formula ( median 2.0 vs 0 , p=0.021 ) . Intention scores ( median 14.0 vs 11.5 [ maximum 18 ] ) were also increased in this group ( p=0.035 ) . INTERPRETATION These findings suggest that term infants may benefit from LCPUFA supplementation , and that the effects persist beyond the period of supplementation . Since higher problem-solving scores in infancy are related to higher childhood IQ scores , supplementation with LCPUFA may be important for the development of childhood intelligence",
"BACKGROUND Studies investigating cognitive outcomes following docosahexaenoic acid ( DHA ) supplementation of infant formula yield conflicting results , perhaps due to inadequate dietary concentrations . AIM To determine the optimal DHA concentration in term formula to support cognitive maturation . DESIGN This was a double-masked , r and omized , controlled , prospect i ve trial . A total of 181 infants were enrolled at 1 - 9 days of age and assigned r and omly to receive one of four term infant formulas with one of four levels of docosahexaenoic acid : Control ( 0 % DHA ) , 0.32 % DHA , 0.64 % DHA , or 0.96 % DHA . All DHA-supplemented formulas contained 0.64 % arachidonic acid ( ARA ) . Infants were fed the assigned formulas until 12 months of age . One hundred forty-one children completed the 12-month feeding trial and were eligible for this study . Cognitive function was assessed in 131 children at 18 months of age using the Bayley Scales of Infant Development II ( BSID II ) . RESULTS There were no diet group differences on the Mental Development Index ( MDI ) , the Psychomotor Development Index ( PDI ) , or the Behavior Rating Scale ( BRS ) of the BSID II . However , when the scores of children who received any of the three DHA-supplemented formulas were combined and compared to control children , a significant difference emerged : the MDI scores of DHA-supplemented children were higher ( 104.1 v. 98.4 ; p=0.02 ) . CONCLUSIONS These results suggest that dietary supplementation of DHA during the first year of life leads to enhanced cognitive development at 18 months of age . DHA concentration of 0.32 % is adequate to improve cognitive function ; higher concentrations did not confer additional benefit",
"BACKGROUND The effect of long-chain polyunsaturated fatty acid ( LCPUFA ) intake on cognitive development is controversial . Most r and omized trials have assessed cognition at 18 mo , although significant development of cognitive abilities ( early executive function ) emerge later . OBJECTIVE The objective was to evaluate cognition beyond 18 mo and longitudinal cognitive change from 18 mo to 6 y in children who were fed variable amounts of docosahexaenoic acid ( 0.32 % , 0.64 % , and 0.96 % of total fatty acids ) and arachidonic acid ( ARA ; 0.64 % ) compared with children who were not fed LCPUFA as infants . DESIGN Eighty-one children ( 19 placebo , 62 LCPUFA ) who participated in a double-blind , r and omized trial of LCPUFA supplementation as infants were re-enrolled at 18 mo and tested every 6 mo until 6 y on age-appropriate st and ardized and specific cognitive tests . RESULTS LCPUFA supplementation did not influence performance on st and ardized tests of language and performance at 18 mo ; however , significant positive effects were observed from 3 to 5 y on rule-learning and inhibition tasks , the Peabody Picture Vocabulary Test at 5 y , and the Weschler Primary Preschool Scales of Intelligence at 6 y. Effects of LCPUFAs were not found on tasks of spatial memory , simple inhibition , or advanced problem solving . CONCLUSIONS The data from this relatively small trial suggest that , although the effects of LCPUFAs may not always be evident on st and ardized developmental tasks at 18 mo , significant effects may emerge later on more specific or fine-grained tasks . The results imply that studies of nutrition and cognitive development should be powered to continue through early childhood . This parent trial was registered at clinical trials.gov as NCT00266825",
"To determine whether docosahexaenoic acid ( DHA ) supplementation of breast-feeding mothers increases the DHA contents of breast milk and infant plasma phospholipids ( PPs ) , breast-feeding women were r and omly assigned to 3 DHA-supplementation groups ( 170 - 260 mg/d ) or a control group . Group 1 ( n = 6 ) consumed an algae-produced high-DHA triacylglycerol ; group 2 ( n = 6 ) consumed high-DHA eggs ; group 3 ( n = 6 ) consumed a high-DHA , low-eicosapentaenoic acid marine oil ; and group 4 ( n = 6 ) received no supplementation . From before to after supplementation ( 2 and 8 wk postpartum ) , mean ( + /-SD ) maternal PP DHA increased in groups 1 , 2 , and 3 by 1.20 + /- 0.53 , 0.63 + /- 0.82 , and 0.76 + /- 0.35 mol% of fatty acids , respectively ( 23 - 41 % ) , but decreased in group 4 by 0.44 + /- 0.34 mol% ( 15 % ) . Breast-milk DHA of groups 1 , 2 , and 3 increased by 0.21 + /- 0.16 , 0.07 + /- 0.11 , and 0 . 12 + /- 0.07 mol% , respectively ( 32 - 91 % ) but decreased in group 4 by 0.03 + /- 0.04 mol% ( 17 % ) . Mean infant PP DHA in groups 1 , 2 , and 3 increased by 1.63 + /- 0.79 , 0.40 + /- 1.0 , and 0.98 + /- 0.61 mol% , respectively ( 11 - 42 % ) , but only by 0.18 + /- 0.74 mol% ( 5 % ) in group 4 . Correlations between the DHA contents of maternal plasma and breast milk and of milk and infant PPs were significant . Breast-milk and maternal and infant PP 22:5n-6 concentrations were lowest in group 2 . DHA supplementation increases the plasma and breast-milk DHA concentrations of lactating women , result ing in higher PP DHA concentrations in infants",
"The effect of breast-feeding was compared with that of two fat-modified milk formulas in 45 infants ( 15 per group ) studied by assessing body weight gain for 4 months and plasma lipids , lipoprotein profiles , fatty acid profiles of plasma and red blood cells , and plasma tocopherol status 3 months after birth . A saturated fat formula with coconut oil/soybean oil ( COCO/SOY ) had a fatty acid content and polyunsaturated/saturated ratio ( P/S , 0.55 ) comparable with that of human milk fat ( P/S , 0.39 ) and had the same fat energy content ( 50 % kcal ) . The second formula , with corn oil/soybean oil ( CORN/SOY ) , was highly unsaturated ( P/S , 4.6 ) , with only 35 % kcal from fat . Energy intake and body weight gain were similar for all groups . Plasma total cholesterol , triglyceride , and phospholipid levels were significantly lower ( greater than 20 % on average ) in infants fed the CORN/SOY formula than in infants fed either the COCO/SOY formula or human milk . Infants fed the CORN/SOY formula also had lower ( 25 % to 35 % ) plasma low-density lipoprotein cholesterol and apolipoprotein B levels and low-density lipoprotein/high-density lipoprotein and apolipoprotein B/apolipoprotein A-I ratios . Plasma , red blood cell , and cholesteryl ester fatty acids from infants fed COCO/SOY contained less 18:1 and more 18:2 ; cholesterol esters in plasma from breast-fed infants had the highest 20:4n-6 levels . Plasma tocopherol levels were higher in infants consuming formulas . The presence of cholesterol in human milk appeared to exp and the low-density lipoprotein pool and exert an \" unfavorable \" increase in the low-density lipoprotein/high-density lipoprotein ratio . Thus modulation of infant lipoproteins by changing dietary fat and cholesterol is feasible and in keeping with the known response in adults",
"Presently , there is growing interest in long-chain polyunsaturated fatty acids ( LCPUFAs ) , which are considered a major determinant of growth , visual and neural development , and long-term health.1 Two groups of LCPUFAs have received special interest : homologues of linoleic acid ( LA ) of the n-6 series , which are precursors of arachidonic acid ( AA ) , and homologues of α-linolenic acid ( ALA ) of the n-3 series , which are precursors of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) ",
"Background / Aims : The supply of docosahexaenoic acid ( DHA , 22:6ω–3 ) , important for fetal/infant neurodevelopment , depends on the maternal fatty acid ( FA ) status , which may be marginal in central Europe . Therefore , we investigated the effect of a daily vitamin/mineral supplement with and without 200 mg DHA from mid-pregnancy through lactation on the DHA concentrations in maternal and infant red blood cell phospholipids ( RBC% ) , and in breast milk FA ( % ) . Methods : At 21 weeks ’ gestation , 144 women were enrolled into a r and omised , double-blind clinical trial receiving daily : ( 1 ) a basic vitamin-mineral supplement ( Vit/Min group ) , ( 2 ) Vit/Min plus 4.5 g fructo-oligosaccharide ( FOS group ) , or ( 3 ) Vit/Min plus 4.5 g FOS plus 200 mg fish oil-derived DHA ( DHA-FOS group ) . FAs were determined by capillary gas-liquid chromatography . Results : While maternal RBC-DHA% at enrolment was not different , at 37 weeks gestation , and 3 months after delivery RBC-DHA% were significantly higher in the DHA-FOS group . The breast milk DHA% was twice as high in the DHA-FOS group ( 0.50 % ) than in the two others ( 0.25 % ) ( p ) . The RBC-DHA% of the infants in the DHA-FOS group was also significantly higher , and correlated significantly with maternal RBC-DHA% before and 3 months after delivery . Conclusions : In central Europe , a dose of 200 mg/day DHA from mid-pregnancy through lactation seems appropriate to improve the DHA status of mothers and infants ",
"Background / objective : Long chain polyunsaturated fatty acids have beneficial effects in preterm neurophysiological development and are semi-essential . Their levels and variation in plasma and red cells in term and preterms are better known than their intestinal absorption . In this paper the absorption of supplemented arachidonic acid ( AA ) and docosahexaenoic acid ( DHA ) is evaluated in a preterm group . Design : Four newborn r and omized groups were studied . Group T comprised 11 terms on regular formula . Preterms : group P ( n=9 ) was on a classic preterm formula . Intervention : groups PA ( n=9 ) and PB ( n=13 ) were on the same formula but PB contained AA and DHA in similar proportion to breast milk . At 20 days a 3 day metabolic balance was taken for Ca , Pi , Mg , total fat and individual fatty acids ( C8–C24 , saturated unsaturated ) . Results : Calcium absorption was ( mean±s.d . ) 51±13 % in terms . In preterms it was respectively 45±18 , 38±11 and 37±21 % . Total fat absorption was 92.0±8.0 % in terms , and from 95.0±2.0 to 91.0±8.0 % in preterms . Absorption of 8:0 , 10:0 and 12:0 showed a very high and constant rate despite significant intake differences ( 715–33 mg/kg/day ) . Linoleic acid and α-linolenic acid were absorbed in the three groups at around 94 % regardless of a greater LA intake in group P. Details of absorption ( mg/kg/day ) were : for AA , intake 17±7 , fecal excretion 5±4 , net retention 12±5 ( 75.0±18 % ) ; for DHA , intake 10±3 , fecal excretion 3±2 , net retention 6±4 ( 62.3±30 % ) . Conclusion : Intestinal absorption of fatty acids is high and is comparable in terms and preterms as regards the studied acids . Longer acids were less well absorbed . The supplemented amounts of AA and DHA were less well absorbed and probably not impairing calcium absorption . Sponsorship : University of Alicante , University of Miguel Hernández . European Journal of Clinical Nutrition ( 2001 ) 55 ,",
"BACKGROUND & AIMS Protein source , macronutrient composition and content of long chain-polyunsaturated fatty acids ( LC-PUFA ) of infant formulae may influence infant growth . We aim ed to assess the effect of a modified infant formula on growth . METHODS In a r and omized , double-blind trial , 213 healthy term infants consumed isoenergetic study formulae ( intervention formula - IF , control formula - CF ) from the first month of life until the age of 120 days . IF ( 1.89 g protein/100 kcal ) contained α-lactalbumin ( ALAB ) and LC-PUFA , while CF ( 2.30 g protein/100 kcal ) provided st and ard whey and no LC-PUFA . Anthropometry and dietary intake were regularly assessed . A venous blood sample was obtained on day 120 . RESULTS Both formulae were well-accepted without significant differences in health related observations . Weight gain was not statistically different between formula groups ( IF : 30.2 ± 6.3 vs. CF : 28.3 ± 6.5 g/day , mean ± SD , P = 0.06 ) . Length gain was higher in IF ( 0.11 ± 0.02 vs. 0.10 ± 0.02 cm/day , P = 0.02 ) . Energy intake from formula was higher in CF at 90 and 120 days ( IF : 509 ± 117 and 528 ± 123 vs. CF : 569 ± 152 and 617 ± 169 kcal/day , P in CF was significantly higher at each assessment . Growth per energy intake was higher in IF compared to CF for weight ( 6.45 ± 2.01 vs. 5.67 ± 2.21 g/100 kcal , P = 0.02 ) and length ( 0.23 ± 0.08 vs. 0.20 ± 0.08 mm/100 kcal , P = 0.04 ) . CONCLUSIONS The modified infant formula with reduced protein content with added ALAB and LC-PUFA , meets infant requirements of protein for adequate growth . The increased energetic efficiency of the new infant formula might result from improved protein composition by added ALAB . Apparently minor differences in composition can markedly affect energetic efficiency for growth . The study was registered at Clinical Trials.gov ( NCT01094080 )",
"This study examines whether feeding infants formula supplemented with long-chain polyunsaturated fatty acids ( LCPUFA ) improves cognitive function of 9-month-olds . Participants included 229 infants from 3 r and omized controlled trials . Children received either formula supplemented with docosahexaenoic acid and arachidonic acid , or a control formula beginning at 1 - 5 days ( 12-month feeding study ) , or following 6 weeks ( 6-week-weaning study ) or 4 - 6 months of breastfeeding ( 4-to 6-month weaning study ) . Infants were assessed with a 2-step problem solving task . In the 12-month feeding and 6-week weaning studies , supplemented children had more intentional solutions ( successful task completions ) and higher intention scores ( goal -directed behaviors ) than controls . These results suggest that LCPUFA supplementation improves means-end problem solving",
"OBJECTIVE To analyze cytokine responses and the clinical course of septic neonates orally supplemented with docosahexaenoic acid as well as to evaluate fatty acid incorporation into leukocytes . METHODS A quasiexperimental study was conducted in neonates who developed sepsis following a surgical procedure . Selected neonates were r and omly assigned to receive 100 mg docosahexaenoic acid ( G-DHA ) daily or olive oil ( G-OO ) as placebo for 14 d throughout a sepsis episode . At selection ( baseline ) , blood sample s were obtained to determine interleukin-1 (IL-1)β , interleukin-6 ( IL-6 ) , and tumor necrosis factor-α as well as the leucocyte fatty acid profile . Measurements were repeated at 7 ( D7 ) and 14 d ( D14 ) of follow-up . Within- and between-group comparisons were conducted with parametric statistics after logarithmic transformation . Repeated measurement analyses with a general linear model procedure were used , adjusting according to human milk intake , use of anti-inflammatory drugs , and nutritional status . RESULTS Sixty-three neonates were included : 29 in G-DHA group and 34 in G-OO group . Although decreases of cytokines during hospitalization were similar in both groups , there was a greater decrease of IL-1β in the G-DHA group than in the G-OO group after adjusting by confounders ( P = 0.028 ) . Leukocyte docosahexaenoic acid increased from 4.96 ± 2.96 at baseline to 5.52 ± 3.05 and 5.92 ± 2.8 at D7 and D14 , respectively , in the G-DHA group ( P = 0.044 ) . Illness severity was inversely associated with the proportion of docosahexaenoic acid in leukocytes throughout follow-up ( P = 0.034 ) . CONCLUSIONS Oral supplementation with docosahexaenoic acid to neonates attenuates IL-1β response and the clinical course of sepsis . This may be an additional strategy to further benefit ill neonates even if they are not c and i date s for parenteral nutrition",
"Summary .Long-chain polyunsaturated fatty acids ( LCP ) are considered conditionally essential nutrients for the infant born prematurely , and attempts are being made to match fatty acid profiles of formula and breast fed infants . In this double-blind , r and omized study we investigated the effects of a formula enriched with both n-6 and n-3 LCP on plasma fatty acid profiles , antioxidant status and growth of premature infants . 29 infants received either a formula devoid of LCP or a LCP supplemented formula ( 0.5 g/100 g fat linoleic acid metabolites , 0.8 g/100 g fat α-linolenic acid metabolites ) . 17 breast fed infants served as a control group . At study entry as well as two and four weeks later , plasma and urine sample s were collected , growth data obtained and food tolerance was documented . At the end of the four week study period , plasma docosahexaenoic acid ( DHA ) levels of supplemented infants were significantly higher than those of unsupplemented infants and similar to those of infants fed human milk . Plasma n-6 LCP concentrations including arachidonic acid ( AA ) were similar between groups . The plasma α-tocopherol levels of breast fed and supplemented infants were similar and tended to be lower than in infants fed the formula devoid of LCP . Urinary malondialdehyde ( MDA ) excretion of formula fed infants was significantly higher compared to infants fed human milk , but did not differ between the two formula groups . Parameters of growth and milk tolerance did not differ between groups . Our results demonstrate that plasma LCP levels similar to those of breast fed infants can be achieved with the LCP supplemented formula used in this trial , without evidence of adverse effects of the LCP enrichment",
"Objectives : To determine the effect of increasing docosahexaenoic acid ( DHA , 22 : 6 n-3 ) in breast milk on infant fatty acid profiles . A secondary aim was to examine aspects of neural development . Design and Setting Double blind , placebo controlled study of infants recruited from postnatal wards at Flinders Medical Centre . Subjects : Fifty-two healthy term infants who were breast fed for at least 12 weeks and were from middle class families . Intervention : Breast milk with DHA concentrations that ranged from 0.1–1.7 % of total fatty acids . This was achieved by supplementation of the maternal diet for the first 12 weeks post partum . Results : Breast milk DHA was related to infant plasma ( r=0.89 , P phospholipids in a saturable curvilinear manner so that breast milk DHA above 0.8 % of total fatty acids result ed in little further increase in infant plasma or erythrocyte DHA levels . The rise in plasma and erythrocyte DHA was approximated by a fall in total n-6 polyunsaturated fatty acids . We could detect no relationship between visual evoked potential acuity ( measured at 12 and 16 weeks ) of infants by either the dietary grouping or the DHA status of individuals . A stepwise multiple regression showed that infant erythrocyte DHA at 12 weeks and home stimulation were the only independent factors associated with Bayley 's MDI at 1 y ( adjusted model r2=0.18 , P infant plasma and erythrocyte phospholipid DHA . There were no long-term effects of infant DHA status on indices of neurodevelopment . Sponsorship : Financial support was provided by Martek Biosciences , MD , USA and the National Health and Medical Research Council , Australia",
"Objective To test the hypothesis that consumption of infant formulas containing long-chain polyunsaturated fatty acids ( LCPUFAs ) by preterm infants would favourably influence growth , body composition and blood pressure ( BP ) at age 10 years . Methods This was a follow-up study of a preterm cohort ( to unsupplemented or LCPUFA-supplemented formulas to 9 months post term . The setting was a research clinic at Yorkhill Hospital for Sick Children , Glasgow , UK . A total of 107 children aged 9–11 years who participated in the original r and omised controlled trial ( 45 % follow-up ) took part . Main outcome measures were : ( 1 ) anthropometry , ( 2 ) body composition and ( 3 ) BP . Results There were no differences in growth or BP between r and omised groups for the whole cohort . However , girls who had received LCPUFA-supplemented formula were heavier ( 42.20 ( SD 9.61 ) vs 36.94 ( 9.46 ) kg , p=0.05 ) , had greater skin fold thicknesses ( biceps 10.7 ( 3.3 ) vs 8.5 ( 3.6 ) mm , p=0.03 ; suprailiac 16.7 ( 8.2 ) vs 12.0 ( 7.5 ) mm , p=0.03 ) and higher BP ( mean 82.2 ( 8.4 ) vs 78.1 ( 6.2 ) mm Hg , p=0.04 : systolic 111.4 ( 10.1 ) vs 105.9 ( 9.0 ) mm Hg , p=0.04 : diastolic 64.8 ( 8.4 ) vs 61.1 ( 5.4 ) mm Hg , p=0.05 ) . Differences in weight SD score ( 0.85 ( 95 % CI 0.13 to 1.58 ) , p=0.02 ) , Ln sum of skin fold thicknesses ( 0.27 ( 0.02 to 0.52 ) , p=0.04 ) and BP ( mean 4.6 mm Hg ( 0.43 to 8.84 ) , p=0.03 ; systolic 6.1 ( 0.45 to 11.7 ) , p=0.04 ) remained after adjustment for prer and omisation confounders . Differences in BP were not significant following adjustment for current weight . Conclusions Girls born preterm and r and omised to LCPUFA-supplemented formula showed increased weight , adiposity and BP at 9–11 years , which might have adverse consequences for later health . No effects were seen in boys . Long-term follow-up of other LCPUFA supplementation trials is required to further investigate this finding",
"BACKGROUND The Childhood Asthma Prevention Study was a r and omized controlled trial conducted in children with a family history of asthma in whom omega-3 fatty acid supplementation and restriction of dietary omega-6 fatty acids did not prevent asthma , eczema , or atopy at age 5 years . OBJECTIVE We sought to examine the relation of all measures of omega-3 and omega-6 polyunsaturated fatty acids with outcomes at age 5 years in the whole birth cohort , regardless of r and omization group . METHODS Plasma fatty acids were measured at 18 months , 3 years , and 5 years . Compliance with the fatty acid supplements was estimated every 6 months . Dietary intake was assessed at 18 months by means of weighed-food record and at 3 years by means of food-frequency question naire . At age 5 years , 516 children were examined for wheeze and eczema ( question naire ) and atopy ( skin prick tests , n = 488 ) . Multiple logistic regression was used to evaluate associations between exposures and outcomes . RESULTS Plasma levels of omega-3 or omega-6 fatty acids were not associated with wheeze , eczema , or atopy at age 5 years ( P = .11-.96 ) . Overall , fatty acid exposure , measured as plasma levels , dietary intake , and compliance with supplements , was not associated with any respiratory or allergic outcomes ( P = .35-.59 ) . CONCLUSION This observational analysis of the cohort , using the full range of observed variation in omega-3 and omega-6 fatty acid exposure , supports the negative findings of the r and omized controlled trial . CLINICAL IMPLICATION S Modification of dietary polyunsaturated fatty acids in early childhood is not helpful in preventing atopy and asthma ",
"Adiponectin has potent insulin-sensitizing effects , improves lipid metabolism , and potentially protects against the development of metabolic syndrome . Thus , increasing adiponectin levels in preterm infants at risk for developing metabolic syndrome may be of special interest . The aim of this study was to examine the effects of dietary long-chain polyunsaturated fatty acids ( LCPUFA ) on serum adiponectin and lipid concentrations in preterm infants . Adiponectin and lipid levels of 60 healthy preterm infants [ gestational age 32.7 ( 1.9 ) wk ] r and omly assigned to be fed either 1 ) a formula containing LCPUFA [ arachidonic and docosahexanoic ] ( + LCPUFA group ) or 2 ) the same formula without LCPUFA ( −LCPUFA/control group ) , were determined at mean ( SD ) 33.8 ( 11.7 ) d. Adiponectin and HDL-C concentrations were significantly higher in the + LCPUFA group than in controls ( p = 0.002 and p = 0.01 , respectively ) ; whereas , triglyceride levels were lower ( p = 0.06 ) . Adiponectin correlated positively with HDL-C levels and negatively with triglyceride levels in the + LCPUFA group but not in the controls . In conclusion , circulating adiponectin concentrations were higher in preterm infants fed a formula containing LCPUFA than infants fed an LCPUFA-free formula and they correlated with lipidemic profile ",
"OBJECTIVES To determine the effect of alpha-linolenic acid ( ALA ) intake ( or the dietary linoleic acid [LA]/ALA ratio ) on the growth and visual function of term infants . STUDY DESIGN Normal term infants were assigned r and omly and in masked fashion at birth to receive formulas with approximately 16 % of total fatty acids as LA and 0.4 % , 1.0 % , 1.7 % , or 3.2 % of fatty acids as ALA ( LA/ALA ratios of 44 , 18.2 , 9.7 , and 4.8 ) for the first 4 months of life . The fatty acid pattern of plasma phospholipids was determined shortly after birth and at approximately 21 , 60 , and 120 days of age . Anthropometric data were obtained at the same times and also at approximately 240 days of age . Transient visual evoked responses ( VERs ) were measured at approximately 120 and 240 days of age . For comparisons , anthropometric and VER data also were obtained in infants who were exclusively breast-fed for the first 4 months of life . RESULTS Infants who received the formula with 3.2 % ALA ( LA/ALA ratio , 4.8 ) had higher plasma concentrations of phospholipid docosahexaenoic acid ( DHA ) but lower concentrations of arachidonic acid at 21 , 60 , and 120 days of age . Mean weight of this group at 120 days of age was 760 gm less ( p formula with 0.4 % ALA ( LA/ALA ratio , 44 ) . Despite differences in plasma phospholipid DHA contents among groups , neither VER latency nor amplitude differed significantly among formula groups or between any formula group and age-matched , breast-fed infants . CONCLUSIONS The highest versus the lowest ALA intake ( or the lowest vs the highest LA/ALA ratio ) result ed in higher plasma phospholipid DHA content from 21 to 120 days of age but was not associated with improved visual function as assessed by transient VER . Moreover , mean body weight of infants who received the highest versus lowest ALA intake was less at 120 days ( p < 0.05 ) . These data suggest that the lower LA/ALA ratios currently recommended for infant formulas should not be adopted until the effect of such ratios on growth are evaluated more completely",
"The effects of dietary docosahexaenoic acid ( DHA ) supply during infancy on later cognitive development of healthy term infants were evaluated in a r and omized clinical trial of infant formula milk supplemented with 0.35 % DHA or with 0.36 % DHA and 0.72 % arachidonic acid ( AA ) , or control formula which provided no DHA or AA . Fifty-six 18-month-old children ( 26 male , 30 female ) who were enrolled in the trial within the first 5 days of life and fed the assigned diet to 17 weeks of age were tested using the Bayley Scales of Infant Development , 2nd edition ( BSID-II ) ( Bayley 1993 ) at the Retina Foundation of the Southwest , Dallas , TX . These children had also been assessed at 4 months and 12 months of age for blood fatty-acid composition , sweep visual evoked potential ( VEP ) acuity , and forced-choice preferential looking ( FPL ) acuity ( Birch et al. 1998 ) . Supplementation of infant formula with DHA+AA was associated with a mean increase of 7 points on the Mental Development Index ( MDI ) of the BSID-II . Both the cognitive and motor subscales of the MDI showed a significant developmental age advantage for DHA- and DHA+AA-supplemented groups over the control group . While a similar trend was found for the language subscale , it did not reach statistical significance . Neither the Psychomotor Development Index nor the Behavior Rating Scale of the BSID-II showed significant differences among diet groups , consistent with a specific advantage of DHA supplementation on mental development . Significant correlations between plasma and RBC-DHA at 4 months of age but not at 12 months of age and MDI at 18 months of age suggest that early dietary supply of DHA was a major dietary determinant of improved performance on the MDI",
"The adipokine visfatin has been proposed to exert insulin-mimicking effects and to play a role in the development of metabolic syndrome . Preterm infants are at risk for the later development of insulin resistance and , possibly , for other components of metabolic syndrome . Dietary long-chain polyunsaturated fatty acids ( LCPUFAs ) during the perinatal period may reduce the risk of metabolic syndrome . The authors ' objective was to study the circulating concentrations of visfatin in preterm infants and to examine associations of visfatin with anthropometric measurements , metabolic indices , and dietary LCPUFAs . Serum visfatin concentrations were determined by enzyme-linked immunosorbent assay at mean ( SD ) 33.8 ( 11.7 ) days of life in 60 healthy preterm infants ( gestational age , 32.7 [ 1.9 ] weeks ) r and omly assigned to be fed since birth either a formula containing LCPUFA ( arachidonic and docosahexaenoic acid ) ( + LCPUFA group ) or the same formula without LCPUFA ( -LCPUFA group ) . Associations of visfatin with anthropometric parameters , serum glucose , insulin , homeostasis model assessment index of insulin resistance , blood lipids , and adiponectin levels were examined . Serum visfatin levels were significantly higher in the + LCPUFA than in the -LCPUFA group ( P with body weight z score ( β = 0.31 , P = .02 ) , total cholesterol ( β = 0.34 , P = .01 ) , high-density lipoprotein cholesterol ( HDL-C ) ( β = 0.47 , P .001 ) , and adiponectin levels ( β = 0.29 , P = .03 ) , but not with indices of insulin sensitivity . In multiple regression analysis , HDL-C and dietary LCPUFAs correlated independently with serum visfatin levels . Circulating visfatin levels in preterm infants are independently associated with HDL-C levels and dietary LCPUFAs . Whether the higher visfatin levels in the + LCPUFA preterm infant group are beneficial for the later health of these infants remains to be determined",
"OBJECTIVE To test the efficacy and safety of long-chain polyunsaturated fatty acid ( LCPUFA ) supplementation with gamma-linolenic acid , a precursor of arachidonic acid , and docosahexaenoic acid in preterm infants . STUDY DESIGN Preterm ( r and omly assigned to unsupplemented or LCPUFA-supplemented formula to 9 months after term . The main outcome measure was the Bayley Mental and Psychomotor Indexes ( MDI , PDI ) at 18 months after term . Safety outcome measures were anthropometry ( 9 and 18 months ) , feed tolerance , infection , and clinical complications . RESULTS There were no significant differences in neurodevelopment between groups overall . In preplanned subgroup analyses , LCPUFA-supplemented boys had significantly higher Bayley MDI than did control boys ( difference , 5.7 points ; 95 % CI , 0.3 to 11.1 ; P=.04 ) . LCPUFA-supplemented infants showed significantly greater weight gain ( difference , 310 g ; 95 % CI , 30 to 590 g ; P=.03 ) and length gain ( difference , 1.0 cm ; 95 % CI , 0.02 to 1.9 ; P=.05 ) between birth and 9 months , with greater effect in boys ( weight difference at 9 months , 510 g ; 95 % CI , 80 to 930 g ; P=.02 ; length difference at 18 months , 1.8 cm ; 95 % CI , 0.1 to 1.8 ; P=.03 ) . CONCLUSIONS This trial , using the strategy of providing gamma-linolenic acid as a source of arachidonic acid , showed efficacy for growth and for neurodevelopment in boys , with no adverse effects . These data have important implication s for LCPUFA-supplementation strategy in preterm infants",
"STUDY DESIGN The Infant Fish Oil Supplementation Study is a double-blind r and omised controlled trial investigating whether the incidence of allergic disease can be reduced and developmental outcomes enhanced through supplementation with omega-3 fatty acids . Infants at high risk of developing allergic disease will be r and omised to receive either fish oil or olive oil supplements until 6 months of age and followed up at six postnatal clinic visits to assess allergy outcomes and infant neurodevelopment . INTERVENTION Study groups to consist of a treatment group allocated to receive 650 mg of fish oil daily ( 250 - 280 mg docosahexaenoic acid and at least 60 mg eicosapentaenoic acid and a placebo group ( olive oil ) from birth to 6 months of age . OUTCOMES Allergy outcomes will be assessed by clinical history , clinical assessment s and allergen skin prick tests at the 12 , 30 and 60 month visits . Neurodevelopmental assessment s to be conducted at 18 months , and language question naires at 12 , 18 and 30 months . Sample s will be collected from mothers antenatally , from infants at birth , and at clinic visits from 6 months onwards for immunological assessment s. Fatty acid composition to be measured in erythrocytes and plasma ( at birth and after the supplementation period ) to assess the effect of the intervention on fatty acid status . Information on medical history , diet and other lifestyle factors at an antenatal clinic visit and postnatal clinic visits will also be collected . CONCLUSION This study is design ed to examine clinical ly relevant effects of a novel , non-invasive and potentially low cost approach to reduce the incidence of allergic disease and facilitate neurodevelopment during early childhood",
"BACKGROUND The visual and mental development of preterm infants improved after feeding them milk enriched with docosahexaenoic acid ( DHA ) in amounts matching the fetal accretion rate . OBJECTIVE The objective was to evaluate whether feeding preterm infants milk with a higher DHA content than that used in current practice influences language or behavior in early childhood . DESIGN This was a follow-up study in a subgroup of infants enrolled in the DINO ( Docosahexaenoic acid for the Improvement in Neurodevelopmental Outcome ) trial . In a double-blind r and omized controlled trial , infants born at were fed milk containing 1 % of total fatty acids as DHA ( higher-DHA group ) or approximately 0.3 % DHA ( control group ) until reaching full-term equivalent age . The longer-term effects of the intervention on language , behavior , and temperament were measured by using the MacArthur Communicative Development Inventory ( MCDI ) at 26-mo corrected age , the Strengths and Difficulties Question naire ( SDQ ) , and the Short Temperament Scale for Children ( STSC ) between 3- and 5-y corrected age . RESULTS Mean ( + /-SD ) MCDI scores did not differ significantly ( adjusted P = 0.8 ) between the higher-DHA group ( 308 + /- 179 , n = 60 ) and the control group ( 316 + /- 192 , n = 67 ) per the Vocabulary Production subscale . Composite scores on the SDQ and STSC did not differ between the higher-DHA group and the control group [ SDQ Total Difficulties : higher-DHA group ( 10.3 + /- 6.0 , n = 61 ) , control group ( 9.5 + /- 5.5 , n = 64 ) , adjusted P = 0.5 ; STSC score : higher-DHA group ( 3.1 + /- 0.7 , n = 61 ) , control group ( 3.0 + /- 0.7 , n = 64 ) , adjusted P = 0.3 ] . CONCLUSIONS Feeding preterm infants milk containing 3 times the st and ard amount of DHA did not result in any clinical ly meaningful change to language development or behavior when assessed in early childhood . Whether longer-term effects of dietary DHA supplementation can be detected remains to be assessed . This trial was registered with the Australia and New Zeal and Clinical Trial Registry at www.anzctr.org.au as 12606000327583",
"Polyunsaturated fatty acids ( PUFA ) are vital for the normal development of the brain and the eye retina in infancy . Breast milk contains significant amounts of PUFA , and compensates for their low production in infancy . Only recently a few companies with worldwide product distribution have started to enrich infant formula with PUFA . We evaluated the safety and clinical efficacy of a locally made PUFA-enriched infant formula , produced for the first time in Israel . 50 normal , full term infants participated in a prospect i ve , r and omized double-blind study . Half received a regular whey-predominant infant formula ( Materna Plus ) , and the other half a PUFA-enriched formula ( Materna Premium ) , both produced in Israel , for 30 days . Evaluation included physical examination , growth parameters , stool analysis , daily parental question naires regarding infant behavior and defecation , and developmental assessment . There were no significant differences on comparing growth parameters , infant behavior , attacks of restlessness , gas severity , or stool characteristics in the 2 groups . There were no side effects or abnormal stool findings in either group , and no differences in developmental assessment at 3 months of age . We conclude that the locally-produced PUFA-enriched infant formula is safe and clinical ly efficient . We assume that the lack of any effect on developmental indices is due to the relatively short exposure to the PUFA-enriched diet . Nevertheless , based on the recent literature , there is no doubt that PUFA supplementation is vital in improving infant brain and eye development",
"BACKGROUND Docosahexaenoic acid ( DHA ) intake throughout the first year of life is associated with neurodevelopmental and neuropsychological benefits . Few studies have evaluated the role of DHA intakes on age at achievement of gross motor milestones . OBJECTIVE The objective was to assess the effects of DHA supplementation throughout the first year of life on the achievement of four gross motor milestones in healthy infants . DESIGN In this multicenter prospect i ve , r and omized , double-blind , placebo-controlled trial , 1160 healthy neonates were assigned to receive supplementation with either 20 mg liquid DHA ( n = 580 ) or placebo ( n = 580 ) orally once daily throughout the first year of life . The primary endpoint was the time at achievement of 4 gross motor milestones ( sitting without support , h and s- and -knees crawling , st and ing alone , and walking alone ) . All analyses were performed on an intention-to-treat basis . RESULTS The time to achievement of sitting without support was shorter ( P DHA [ median : 26 wk ; interquartile range ( IQR ) : 24 - 29 wk ] than in those who received placebo ( 27 wk ; 26 - 31 wk ) . No significant difference between infants who received DHA or placebo was found for h and s- and -knees crawling [ 39 wk ( 34 - 44 wk ) compared with 40 wk ( 35 - 44 wk ) , respectively ] , st and ing alone [ 49 wk ( 43 - 55 wk ) compared with 49 wk ( 44 - 57 wk ) , respectively ] , and walking alone [ 55 wk ( 50 - 60 wk ) compared with 56 wk ( 52 - 61 wk ) , respectively ] . CONCLUSIONS Despite the 1-wk advance in sitting without support associated with DHA supplementation , no demonstrable persistent effects of DHA supplementation on later motor development milestones were found . Thus , the long-term clinical significance of the 1-wk change in sitting without support , if any , remains unknown . This trial is registered at ( clinical trials.gov ) as NCT00610922",
"BACKGROUND n-3 Fatty acid supplementation in adults results in cardiovascular benefits . However , the cardiovascular effects of n-3 supplementation in early childhood are unknown . OBJECTIVE The objective was to evaluate blood pressure ( BP ) and arterial structure and function in 8-y-old children who had participated in a r and omized controlled trial of dietary n-3 and n-6 modification over the first 5 y of life . DESIGN The children ( n = 616 ; 49 % girls ) were r and omly assigned antenatally to active ( n = 312 ; increase in n-3 intake and decrease in n-6 intake ) or control ( n = 304 ) diet interventions implemented from the time of weaning or introduction of solids until 5 y of age . At age 8.0 + /- 0.1 y , BP , carotid intima-media thickness , carotid artery distensibility , augmentation index , and brachial pulse wave velocity were measured in 405 of these children . Venous blood was collected for measurement of plasma fatty acids , lipoproteins , high-sensitivity C-reactive protein , and asymmetric dimethylarginine . Plasma fatty acid concentrations were also assessed during the intervention . RESULTS Plasma concentrations of n-3 fatty acids were higher and of n-6 were lower in the active than in the control diet group at 18 mo and 3 and 5 y ( P Concentrations of n-3 and n-6 fatty acids were similar at 8 y. At 8 y of age , no significant differences were found in BP , carotid intima-media thickness , carotid artery distensibility , augmentation index , asymmetric dimethylarginine , high-sensitivity C-reactive protein , or lipoproteins between diet groups . CONCLUSION A dietary supplement intervention to increase n-3 and decrease n-6 intakes from infancy until 5 y does not result in significant improvements in arterial structure and function at age 8 y. This trial was registered at the Australian Clinical Trials Registry as ACTRN012605000042640",
"The objective of this study was to assess the relation between observed levels of omega-3 fatty acids in plasma and symptoms of asthma and atopy in children at 18 months of age . A total of 616 women at risk of having a child who would develop asthma because of a family history were recruited from the antenatal clinics of six hospitals in Sydney , Australia . Families were r and omized to either active omega-3 supplemented or control group . The active group received a daily tuna fish oil supplement and omega-3-rich margarines and cooking oils and the control group received a placebo supplement with polyunsaturated margarines and cooking oils . When the children were 18 months of age an assessment of symptoms was carried out by a research nurse blinded to treatment group allocation . Atopy was measured by skin prick tests , blood was collected to determine serum immunoglobulin E ( IgE ) , and plasma fatty acid concentrations . A total of 376 children ( 61.0 % of total recruited ) completed an assessment at 18 months and had blood taken to determine plasma fatty acid concentrations . Omega-3 fatty acid levels were expressed in quintiles of exposure ' as treated ' without reference to treatment group allocation . Wheeze ever , doctor visits for wheeze , bronchodilator use and nocturnal coughing were significantly reduced in children in the higher exposure quintiles . Serum IgE was reduced in the highest quintile but not significantly so . There was no difference in diagnosed asthma or atopy between the exposure quintiles . Although wheeze at this age may not be a good indicator of asthma in later childhood , it is encouraging that some symptoms have been reduced in children with high omega-3 fatty acid concentrations in plasma",
"BACKGROUND Studies investigating the effects of docosahexaenoic acid ( DHA ) in infant formula on language development yield conflicting results . No study to date has investigated the effects of DHA in infant formula on school readiness . AIM To determine the effects of different dietary concentrations of DHA provided during the first 12 months of life on language development and school readiness . DESIGN This was a double-masked , r and omized , controlled , prospect i ve trial . A total of 182 infants were enrolled at 1 - 9 days of age and assigned r and omly to receive infant formula with one of four levels of DHA : control ( 0 % DHA ) , 0.32 % DHA , 0.64 % DHA , or 0.96 % DHA . All formulas with DHA also contained 0.64 % arachidonic acid . One hundred forty-one children completed the 12-month feeding trial and were eligible for this study . Consent was obtained from 131 participants . School readiness was assessed at 2.5 years using the Bracken Basic Concept Scale-Revised ( BBCS-R ) and receptive vocabulary was assessed at 2 and 3.5 years using the Peabody Picture Vocabulary Test-Third Edition ( PPVT-III ) . RESULTS There were no diet group differences on any of the BBCS-R subscales . On the PPVT-III , the control group had higher raw scores and st and ard scores than both the 0.32 % and 0.96 % groups at 2 years of age . These differences were not evident at 3.5 years . CONCLUSIONS Dietary DHA during the first year of life did not enhance school readiness or language development . Children who consumed infant formula with 0.32 % and 0.96 % DHA showed lower receptive vocabulary scores than controls at 2 but not 3.5 years of age",
"We investigated whether supplementation with arachidonic acid ( 20:4 omega 6 ; AA ) , or a combination of AA and docosahexaenoic acid ( 22:6 omega 3 ; DHA ) would affect human milk polyunsaturated fatty acid ( PUFA ) composition . Ten women were daily supplemented with 300 mg AA , eight with 300 mg AA , 110 mg eicosapentaenoic acid ( 20:5 omega 3 ; EPA ) and 400 mg DHA , for one week and eight women served as unsupplemented controls . Milk sample s were collected on days 0 , 1 and 7 . The fatty acid composition of the milk was analyzed by capillary gas chromatography with flame ionisation detection . Supplementation with AA alone had no effect on breastmilk AA , but tended to reduce EPA and DHA levels . Administration of a combination of AA , EPA and DHA tended to increase both milk AA and long chain PUFA (LCPUFA)omega 3 content . A larger simultaneous increase of milk AA , DHA and EPA than observed in the present study can probably be accomplished by the use of a combination of a lower LCPUFA omega 6/LCPUFA omega 3 ratio and higher AA , EPA and DHA dosages",
"BACKGROUND We tested whether addition of n-3 and n-6 long-chain polyunsaturated fatty acids ( LCPUFA ) to infant-formula milk during the first 6 months promotes long-term cognitive and motor development , without adverse consequences . METHODS We did a double-blind , r and omised , controlled , efficacy and safety trial of formula with and without LCPUFAs , with an additional breastfed reference group , in four hospitals in two cities in the UK . The participants were 447 healthy full-term babies . 309 were fed formula ( 155 without LCPUFAs ) and 138 were breastfed for at least 6 weeks . The main outcome measures were : Bayley Mental and Psychomotor Development Indices ( MDI , PDI ) at 18 months ( primary efficacy outcome ) and Knobloch , Passamanick , and Sherrards test at 9 months ( secondary outcome ) . Principal safety outcomes were : infection , atopy , growth , and gastrointestinal tolerance . FINDINGS Babies fed formula with and without LCPUFA did not differ in cognitive or motor development , growth , infection , atopy or tolerance . The mean ( 95 % CI ) MDI was 0.5 ( -2.7 to 3.8 ) units and the PDI 0.6 ( -1.8 to 3.0 ) units higher in the supplementation group . Formula-fed infants had similar developmental scores to the breastfed reference group after adjustment for higher social class and maternal education in the latter . INTERPRETATION There was no evidence of a beneficial or adverse effect on cognitive and motor development or growth up to 18 months . Although no significant differences in safety outcomes were observed , we suggest such data should be collected in future LCPUFA trials . Our trial does not provide support for addition of LCPUFA to st and ard infant formula but we are now doing further follow-up of this cohort",
"This study evaluated preterm infants of less than 2.3 kg birth weight fed commercial formula ( Preemie SMA ® ) devoid of arachidonic acid ( AA ) and docosahexaenoic acid ( DHA ) and compared this control group with similar infant groups fed one of three formulas containing a range of 0.32—1.1 % AA and 0.24—0.75 % DHA in the fat component of the formula . An analogous group of infants fed on their mothers ' breast milk and a breast milk fortifier was also studied . Individual lipoprotein fractions were isolated from blood sample s collected at 12 d of age and after a further 4 wk of feeding . The fatty acid content of individual lipid components , isolated from each lipoprotein fraction was quantitatively determined in order to identify change in marker pools of essential fatty acid . The high density lipoproteins ( HDL ) and low density lipoproteins ( LDL ) phospholipid and cholesterol ester fractions contain most of the AA and DHA found in the lipoprotein fractions ( total of 0.49 % and 0.35 % , respectively ) . Infants fed a formula without AA and DHA showed a reduction in AA level in the phospholipid fraction of all lipoproteins and in the HDL and LDL cholesterol ester fraction . A reduced level of DHA was also observed primarily in the lipoprotein phospholipid fraction in comparison with infants fed breast milk or infant formula containing AA and DHA . Supplementing infant formula with increasing levels of AA and DHA produced a clear dose response in the level of AA found in the HDL and LDL phospholipid fraction . From comparison of the fatty acid levels present in the lipoproteins it appears that a formula level of 0.49 % AA and 0.35 % DHA provides sufficient levels of these fatty acids to achieve a similar fatty acid content to that of infants fed breast milk for the major lipoprotein fractions examined . □ Diet , fatty acid , infant ,",
" Healthy newborn infants were either breast-fed or r and omly design ated to receive a st and ard formula , formula plus cholesterol , or formula plus gamma-linolenic acid at birth . At 0 , 7 , and 30 days of life , the following variables were measured : cholesteryl esters ( cholesteryl arachidonate , cholesteryl oleate , cholesteryl palmitate , and cholesteryl linoleate ) , high-density lipoprotein ( HDL ) cholesterol , apoproteins ( A-I , A-II , B , C-II , C-III , and E ) , and the cholesterol and apoprotein A-I content of the HDL subfractions HDL-2b , HDL-(2a + 3a ) , and HDL-(3b + 3c ) . Breast-fed infants had higher serum levels of cholesterol , cholesteryl oleate , cholesteryl palmitate , cholesteryl arachidonate , and HDL-2b than had formula-fed infants . Addition of gamma-linolenic acid to formula raised cholesteryl-arachidonate levels , and cholesterol and gamma-linolenic acid raised serum HDL-2b levels compared with those produced by unsupplemented formula . Our data suggest that both exogenous cholesterol and gamma-linolenic acid contribute to the maturation of HDL particles associated with human milk consumption in newborn infants . They may also promote adequate delivery of cholesterol and arachidonic acid to the developing brain",
"OBJECTIVES . Arachidonic acid ( 20:4n-6 ) and docosahexaenoic acid ( 22:6n-3 ) are essential for brain growth and cognitive development . We have reported that supplementing pregnant and lactating women with n-3 very-long-chain polyunsaturated fatty acids promotes higher IQ scores at 4 years of age as compared with maternal supplementation with n-6 polyunsaturated fatty acids . In our present study , the children were examined at 7 years of age with the same cognitive tests as at 4 years of age . We also examined the relation between plasma fatty acid pattern and BMI in children , because an association between arachidonic acid and adipose tissue size has been suggested . METHODS . The study was r and omized and double-blinded . The mothers took 10 mL of cod liver oil or corn oil from week 18 of pregnancy until 3 months after delivery . Their children were tested with the Kaufman Assessment Battery for Children at 7 years of age , and their height and weight were measured . RESULTS . We did not find any significant differences in scores on the Kaufman Assessment Battery for Children test at 7 years of age between children whose mothers had taken cod liver oil ( n = 82 ) or corn oil ( n = 61 ) . We observed , however , that maternal plasma phospholipid concentrations of α-linolenic acid ( 18:3n-3 ) and docosahexaenoic acid during pregnancy were correlated to sequential processing at 7 years of age . We observed no correlation between fatty acid status at birth or during the first 3 months of life and BMI at 7 years of age . CONCLUSION . This study suggests that maternal concentration of n-3 very-long-chain polyunsaturated fatty acids during pregnancy might be of importance for later cognitive function , such as sequential processing , although we observed no significant effect of n-3 fatty acid intervention on global IQs . Neonatal fatty acid status had no influence on BMI at 7 years of age",
"Objective : To investigate whether diet influences the composition of the intestinal microbiota in 10-month-old infants . Patients and Methods : Fecal sample s were collected from sixty-five 10-month-old infants participating in a r and omized 2 × 2 intervention study comparing cow 's milk ( CM ) with infant formula ( IF ) with or without fish oil ( FO ) supplement . Infants r and omized to CM received a daily iron supplement . Bacterial DNA was extracted from the feces . Polymerase chain reaction was performed with primers targeting the V3 and V6–8 region of the 16S rRNA gene and analyzed by denaturing gradient gel electrophoresis ( DGGE ) . Cluster analysis of the DGGE gels was performed by use of the Pearson correlation coefficient . Results : Sample s from infants receiving CM clustered differently than did those from the IF group in the V3-based DGGE gels ( P distribution with or without FO in the CM group ( P = 0.001 ) but not in the IF group ( P = 0.39 ) . Repeat analysis with the V6–8-based DGGE gels showed the same pattern , although the V3 gels had 2.5 times as many b and s as the V6–8 gels . Conclusions : Consumption of CM or IF has a decisive influence on the composition of the intestinal microbiota . Supplementation with FO showed an effect on the microbiota only in the CM group . We speculate that these differences could be influenced by the intake of iron and n-3 polyunsaturated fatty acids , respectively",
"Full-field electroretinograms ( ERGs ) were obtained from very-low-birth-weight ( VLBW ) neonates to determine whether omega-3 ( omega-3 ) fatty acids are essential for normal human retinal development . Eighty-one infants born at 30.4 ( st and ard deviation , + /- 1.5 ) wk gestation were , within 10 d of birth , either enrolled to receive mother 's milk ( naturally containing both omega-6 and omega-3 essential fatty acids ) or r and omized to receive one of the infant formulas . Corn oil-based Formula A contained mainly linoleic acid ( 18:2 omega-6 ) and was low in all omega-3 fatty acids . Soy oil-based Formula B contained ample alpha-linolenic acid ( 18:3 omega-3 ) but no long-chain omega-3 . Formula C , supplemented with both alpha-linolenic acid and marine oils , was comparable to human milk in long-chain omega-3 . Full-field ERGs were obtained in the special care nursery from infants aged 36 and 57 wk postconception . Ten healthy preterm infants born at 35 wk gestation were tested at 36 wk postconception . Significant differences were found among groups in rod ERG function . Post hoc comparisons showed that infants fed Formula A had significantly higher rod thresholds than infants receiving long-chain omega-3 ( human milk , Formula C , and intrauterine ) . Infants receiving Formula B had intermediate thresholds that were significantly higher than those of infants receiving intrauterine nutrition . Analysis of the leading edge of the a-wave showed that b-wave differences originated at the photoreceptor level . Differences were not present in infants at 57 wk postconception . No significant differences among groups were found in cone b-waves at 36 or 57 wk postconception . Oscillatory potentials had significantly longer implicit times at 57 wk postconception in infants fed Formula A than in infants receiving human milk . These findings suggest that retinal function varies with the dietary supply of omega-3 fatty acids in VLBW infants",
"Objective : To study the effect of modified polyunsaturated fatty acid ( PUFA ) profiles of complementary food on long-chain ( LC ) PUFA composition in healthy infants . Design : Double blinded , r and omised , controlled intervention trial . Setting : Dortmund , Germany . Patients : Free-living sample of healthy term infants . Methods : Participants were r and omly assigned within the first 2 months of life . During the intervention period from 4 to 10 months , the control group ( n = 53 ) received commercial complementary meals with corn oil ( 3.4 g/meal ) rich in n-6 linoleic acid ( LA ) , the intervention group ( n = 49 ) received the same meals with rapeseed oil ( 1.6 g/meal ) rich in n-3 alpha-linolenic acid ( ALA ) . Fatty acid intake was assessed from dietary records throughout the intervention period . Fatty acid proportions ( % of total fatty acid ) in total plasma were analysed before and after the intervention . Results : Plasma fatty acid profiles did not differ between the intervention and control groups before the intervention . During the intervention , the only difference in fatty acid intake between the intervention and control groups was a higher intake of ALA in the intervention group , 21 % deriving from study food and a lower ratio of LA/ALA ( 10.7 vs 14.8 ) . At the end of the intervention , the plasma proportions of total n-3 fatty acids and of n-3 LC-PUFA , but not of ALA , were higher and the ratios of n-6/n-3 fatty acids were lower in the intervention group . Conclusions : Feasible dietary modifications of the precursor fatty acid profile via n-3 PUFA-rich vegetable oil favoured n-3 LC-PUFA synthesis in the complementary feeding period when LC-PUFA intake from breast milk and formula is decreasing",
"BACKGROUND & AIMS High supply of protein and energy has been introduced to very-low-birth-weight infants to improve growth and cognitive development . The aim of this study was to compare two different feeding strategies on postnatal growth and clinical outcome during neonatal hospitalization . METHODS Fifty very-low-birth-weight infants were r and omized to either an enhanced or a st and ard feeding protocol within 24 h after birth . Chi-square and T-tests were applied . RESULTS First week protein , fat and energy supply was significantly higher in the intervention group compared to the control group ( all P septicemia in the intervention group , 63 % vs. 29 % ( P = 0.02 ) , and no more patients were included . The infants in the intervention group demonstrated improved postnatal growth , but they also disclosed significant electrolyte deviations during the first week of life with hypophosphatemia , hypokalemia and hypercalcemia . First week phosphate nadir was lower in the infants experiencing septicemia ( 1.23 ( 0.50 ) mmol/L ) as compared to the infants without ( 1.61 ( 0.61 ) mmol/L ) ( P = 0.03 ) . CONCLUSION Our study implies that enhanced feeding may induce electrolyte imbalances in VLBW infants , and that deleterious side effects similar to those seen in refeeding syndrome may occur . Clinical Trials.gov , number NCT01103219 and the EudraCT number is 2010 - 020464 - 38",
"A prospect i ve study in healthy infants predefining both diet fatty acid and cholesterol , from birth to age 1 year , compared response of cholesterol fractions in three groups : r and om assignment to 1 ) monounsaturated-(Hi-Mono ) ( n = 20 ) , or 2 ) polyunsaturated-(Hi-Poly ) ( n = 22 ) fatty acid-enriched diets , or 3 ) non-r and omized selection to breast feeding ( Human Milk ) ( n = 25 ) . In each group , design ated weaning foods and supplements maintained fatty acid and cholesterol intake similar to that of each group 's defined formulas , with long-term compliance confirmed by plasma phospholipid fatty acid concentrations . By 12 months , total cholesterol was significantly lower in the Hi-Poly group compared to either of the other groups ( P Low density lipoprotein (LDL)- and high density lipoprotein (HDL)-cholesterol concentrations were significantly lower by 12 months in the Hi-Poly group , compared to the Hi-Mono groups . However , at the earlier 4-month interval , total cholesterol and LDL-cholesterol in both Hi-Mono and Hi-Poly groups were not different from each other , although each was significantly lower than the parallel Human Milk-group ( P total and LDL-cholesterol such that , after 12 months ' feedings , all lipid fractions of this Hi-Mono group were no different from those of the Human Milk group . In independent group comparisons , there were no significant differences in HDL-cholesterol concentrations after 4 and 9 months on these diets . Independent of diet , HDL-cholesterol showed a falling trend as an overall time-effect across all groups ( P polyunsaturated acids in early infancy has a significant cholesterol-lowering effect compared to monounsaturates . These differences in total , LDL- , and HDL-cholesterol plasma concentrations between polyunsaturates and monounsaturates were not significantly evident until feedings had continued for a year",
"OBJECTIVES : Impaired fetal growth is an independent cardiovascular risk factor and is associated with arterial wall thickening in children . No preventive strategy has been identified . We sought to determine whether dietary omega-3 fatty acid supplementation during early childhood prevents the association between impaired fetal growth and carotid arterial wall thickening . METHODS : The Childhood Asthma Prevention Study was a r and omized , controlled single-blind trial in 616 children born at term , recruited antenatally from maternity hospitals in Sydney . Participants were r and omized to either a 500-mg-daily fish oil supplement and canola-based margarines and cooking oil ( omega-3 group ) , or a 500-mg-daily sunflower oil supplement and omega-6 fatty acid – rich margarines and cooking oil ( control group ) , from the start of bottle-feeding or 6 months of age until 5 years of age . Carotid intima-media thickness ( IMT ) , a noninvasive measure of sub clinical atherosclerosis , was the primary endpoint of a cardiovascular sub study ( CardioCAPS ) at age 8 years . We examined the association of fetal growth with carotid IMT in children with birth weight , control group [ n = 176 ] ) . RESULTS : In the control group , fetal growth was inversely associated with carotid IMT , but this was prevented in the omega-3 group ( difference between groups of 0.041 mm [ 95 % confidence interval 0.006 , 0.075 ] per kg birth weight , adjusted for gestational age and gender , Pheterogeneity = .02 ) . CONCLUSIONS : The inverse association of fetal growth with arterial wall thickness in childhood can be prevented by dietary omega-3 fatty acid supplementation over the first 5 years of life",
"AIM To determine the effect of neonatal docosahexaenoic acid ( DHA ) supplementation in preterm infants on later respiratory-related hospitalisations . METHODS We enrolled 657 infants in a multicentre , r and omised , controlled trial design ed to study the long-term efficacy of higher dose dietary DHA in infants born Treatment was with high DHA ( ∼1 % ) compared with st and ard DHA ( ∼0.3 % ) in breast milk or formula , given from the first week of life to term equivalent . Parent-reported hospital admissions to 18 months corrected age were recorded . The proportion of children hospitalised for lower respiratory tract ( LRT ) conditions and the mean number of hospitalisations per infant were determined . RESULTS Twenty-three per cent ( 154/657 ) of infants were hospitalised for LRT conditions . Seventy-three per cent ( 173/238 ) of admissions were for bronchiolitis . There was no significant effect of higher DHA on the proportion of infants admitted for LRT conditions ( high DHA 22 % vs. st and ard DHA 25 % , adjusted relative risk 0.92 , 95 % confidence interval ( CI ) 0.68 - 1.24 , P = 0.57 ) or in the mean number of admissions per infant ( high DHA 0.34 , st and ard DHA 0.38 , adjusted ratio of means 0.91 , 95 % CI 0.63 - 1.32 , P = 0.62 ) . The sexes responded differently to treatment ( interaction P = 0.046 ) , with reduced admissions in boys given high DHA , but this was not statistically significant ( high DHA 19 % , st and ard DHA 28 % , adjusted relative risk 0.69 , 95 % CI 0.46 - 1.04 , P = 0.08 ) . CONCLUSIONS Hospitalisation for LRT problems in the first 18 months for preterm infants was not reduced by neonatal supplementation with 1 % DHA ",
"Preterm infants fed formulas with docosahexaenoic acid ( DHA , 22:6n-3 ) during the interval equivalent to the last intrauterine trimester and beyond have higher circulating DHA and transiently higher visual acuity compared with infants fed formulas containing linolenic acid . In term infants several nonr and omized studies of infants receiving DHA from human milk suggest a relationship between DHA status and acuity , but the evidence for a cause- and -effect relationship is mixed . In the present study , term infants were r and omly assigned to a st and ard term formula ( n = 20 ) or the same formula with egg yolk lecithin to provide DHA ( 0.1 % ) and arachidonic acid(AA , 20:4n-6 , 0.43 % ) ( n = 19 ) at levels reported in milk of American women . A third group of infants was breast fed for ≥3 mo(n = 19 ) . Grating visual acuity ( Teller Acuity Card procedure ) and plasma and red blood cell ( RBC ) phosphatidylcholine ( PC ) and phosphatidylethanolamine ( PE ) DHA and AA were determined at corrected ages of 2 , 4 , 6 , 9 ( acuity only ) , and 12 mo past term = 40 wk postmenstrual age ( PMA ) . At 2 mo breast-fed infants and infants fed the supplemented formula had higher grating acuity than term infants fed st and ard formula . As in preterm infants , the increase was transient . Plasma PC DHA and AA and RBC PE AA increased by 2 mo in supplemented infants , but RBC PE DHA in supplemented infants was not higher than in controls until 4 mo and beyond . Despite normal intrauterine accumulation of DHA and AA , infants fed formula with 2 % linolenic acid and 0.1 % DHA had better 2-mo visual acuity than infants fed formula with 2 % linolenic acid",
"OBJECTIVE To determine if docosahexaenoic acid ( DHA ) and arachidonic acid ( ARA ) supplementation influences growth or visual acuity of formula-fed premature infants . STUDY DESIGN Double-blind , multi-center study of 194 premature infants given preterm formula with no DHA or ARA ( control ) , 0.15 % energy DHA , or 0.14 % DHA + 0.27 % ARA from single-cell triglycerides for at least 28 days and then fed term formula ( no DHA or ARA ) to 57 weeks postmenstrual age ( PMA ) , with 90 breast-fed term infants as reference . RESULTS Infants fed DHA+ARA formula gained weight significantly faster ( post-hoc analysis ) during preterm formula feeding than control infants ( 34.7 vs. 30.7 g/d ) and had weights and weight : length ratios not different from term breast-fed infants at 48 and 57 weeks PMA . Infants fed control or DHA formula had lower body weights than term infants . Red blood cell phosphatidylethanolamine ARA was significantly correlated to weight gain during preterm formula feeding and to weight and length at 40 , 48 , and 57 weeks PMA ( r = 0.19 to 0.24 , P = .004-.02 ) . Providing DHA or DHA+ARA during the preterm period had no effect on subsequent visual acuity or incidence of adverse events . CONCLUSIONS Feeding DHA+ARA from single-cell triglycerides enhances weight gain in formula-fed premature infants with no evidence of adverse effects",
"Abstract We compared growth of infants whose mothers either did or did not receive docosahexaenoic acid ( DHA ) supplements during pregnancy and lactation . At 21 weeks ' gestation , 144 women were enrolled into a r and omized , double-blind clinical trial receiving : ( 1 ) a basic supplement consisting of vitamins and minerals ( BS ) , or ( 2 ) BS plus 4.5 g fructooligosaccharide ( BSF ) , or ( 3 ) BSF plus fish oil DHA ( 200 mg ) until the end of the third month of lactation . Infants ' length , weight and head circumference were measured at birth and at 1 , 3 and 21 months . A total of 51 mothers/infants were lost to follow-up by the third month and 24 at 21 months . The two groups not receiving DHA were combined into a control group . Analysis with mixed models adjusted for confounding factors showed a significant time dependent effect for the DHA group on the development of the body mass index ( BMI ) ( P=0.037 ) , and of weight ( P=0.046 ) , but no effect on the development of length ( P=0.537 ) , or of head circumference ( P=0.267 ) . At 21 months , weight of the DHA group was lower by −601 g ( 95 % CI −171 ; −1030 g ) and BMI was lower by −0.76 kg/m2 ( 95 % CI −0.07 ; −1.46 ) compared to controls . The results indicate that DHA taken by pregnant and lactating mothers may reduce BMI in late infancy",
"BACKGROUND While there is a large body of data on the effects of long-chain polyunsaturated fatty acid supplementation of infant formula on visual and cognitive maturation during infancy , longterm visual and cognitive outcome data from r and omized trials are scarce . AIM To evaluate docosahexaenoic acid ( DHA ) and arachidonic acid (ARA)-supplementation of infant formula on visual and cognitive outcomes at 4 years of age . METHODS Fifty-two of 79 healthy term infants who were enrolled in a single-center , double-blind , r and omized clinical trial of DHA and ARA supplementation of infant formula were available for follow-up at 4 years of age . In addition , 32 breast-fed infants served as a \" gold st and ard \" . Outcome measures were visual acuity and the Wechsler Preschool and Primary Scale of Intelligence -- Revised . RESULTS At 4 years , the control formula group had poorer visual acuity than the breast-fed group ; the DHA- and DHA+ARA-supplemented groups did not differ significantly from the breast-fed group . The control formula and DHA-supplemented groups had Verbal IQ scores poorer than the breast-fed group . CONCLUSION DHA and ARA-supplementation of infant formula supports visual acuity and IQ maturation similar to that of breast-fed infants",
"OBJECTIVE We tested the hypothesis of whether a pharmacologic , orogastric dose of docosahexaenoic acid ( DHA ) administered during the acute phase of sepsis protects the nutritional status of neonates . METHODS A r and omized , placebo-controlled trial was conducted . Neonates who developed sepsis after a surgical procedure were r and omly assigned to receive daily 100 mg of DHA or 100 mg of olive oil as placebo for 14 d. At selection , illness severity was evaluated and a blood sample was obtained to measure erythrocyte fatty acid composition . Energy intake and type of feeding were recorded daily . Body composition was also determined at selection and after 14 d of follow-up with the deuterium dilution technique . Body composition differences between d 14 and baseline were calculated and compared between groups . Confounders were analyzed in a multiple regression model . RESULTS In all , 16 DHA and 11 placebo cases were followed up . Both groups showed an increase in length and head circumference , but length gain tended to be greater in neonates with DHA ( P = 0.07 ) . The DHA group presented increases in body mass ( 50 g , P = 0.03 ) and fat mass ( 70 g , P = 0.03 ) , whereas infants in the placebo group did not show an increase in any body composition components . Gain in fat mass was positively related with the DHA of erythrocytes and whether or not infants received DHA . CONCLUSIONS Orogastric DHA administered in the acute phase of infection likely protects the nutritional status of neonates with sepsis",
"Background In contrast to human milk , current infant formulas in the United States do not contain ω3 and ω6 long-chain polyunsaturated fatty acids . This may lead to suboptimal blood lipid fatty acid profiles and to a measurable diminution of visual function in developing term infants . The need for docosahexaenoic acid and arachidonic acid supplementation in the infant diet was evaluated in a double-blind , r and omized clinical trial . Methods Healthy term infants were r and omized to diets of ( 1 ) commercial formula , ( 2 ) docosahexaenoic acid – enriched formula ( 0.35 % of total fatty acids ) , or ( 3 ) docosahexaenoic acid– ( 0.36 % ) and arachidonic acid– ( 0.72 % ) enriched formula . Eighty-seven infants completed the 17-week nutritional trial , and 58 were observed until 52 weeks of life . A reference group was exclusively breast fed for at least 17 weeks ( n = 29 ) . Outcome measures included electroretinographic responses , visual evoked potentials , and blood fatty acid analysis in infants at birth and at 6 , 17 , and 52 weeks of age . Results Commercial formula-fed infants had 30 % to 50 % lower content of docosahexaenoic acid in total red blood cell lipids during the 17-week feeding trial compared with breast-fed infants . Significant differences persisted at the 1-year follow-up . Arachidonic acid content was consistently reduced in the commercial formula group by 15 % to 20 % . Infants fed long-chain polyunsaturated fatty acid – enriched formulas had docosahexaenoic acid and arachidonic acid blood lipid profiles resembling those of human milk-fed infants . Infants receiving this enriched formula had more mature electroretinographic responses than commercial formula-fed infants at 6 weeks of age . Human milk-fed and docosahexaenoic acid-enriched formula-fed infants had better visual acuity than commercial formula-fed infants at both 17 and 52 weeks of age . Early ( 17-week ) fatty acid profiles in blood lipids were correlated with later ( 52-week ) visual function development in study infants . Conclusions Results from this clinical trial demonstrate that long-chain polyunsaturated fatty acid supplementation of formula in term infants produces blood lipid fatty acid profiles that are similar to those observed in breast-fed infants . This supplementation leads to better visual function later in life ( i.e. , 1 year of age ) than that shown by infants fed commercial formula",
"CONTEXT Uncertainty exists about the benefit of dietary docosahexaenoic acid ( DHA ) on the neurodevelopment of preterm infants . OBJECTIVE To determine the effect of meeting the estimated DHA requirement of preterm infants on neurodevelopment at 18 months ' corrected age . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind controlled trial enrolling infants born at less than 33 weeks ' gestation from April 2001 to October 2005 at 5 Australian tertiary hospitals , with follow-up to 18 months . INTERVENTION High-DHA ( approximately 1 % total fatty acids ) enteral feeds compared with st and ard DHA ( approximately 0.3 % total fatty acids ) from day 2 to 4 of life until term corrected age . MAIN OUTCOME MEASURES Bayley Mental Development Index ( MDI ) at 18 months ' corrected age . A priori subgroup analyses were conducted based on r and omization strata ( sex and birth weight or = 1250 g ) . RESULTS Of the 657 infants enrolled , 93.5 % completed the 18-month follow-up . Bayley MDI scores did not differ between the high- and st and ard-DHA groups ( mean difference , 1.9 ; 95 % confidence interval [ CI ] , -1.0 to 4.7 ) . The MDI among girls fed the high-DHA diet was higher than girls fed st and ard DHA in unadjusted and adjusted analyses ( unadjusted mean difference , 4.7 ; 95 % CI , 0.5 - 8.8 ; adjusted mean difference , 4.5 ; 95 % CI , 0.5 - 8.5 ) . The MDI among boys did not differ between groups . For infants born weighing less than 1250 g , the MDI in the high-DHA group was higher than with st and ard DHA in the unadjusted comparison ( mean difference , 4.7 ; 95 % CI , 0.2 - 9.2 ) but did not reach statistical significance following adjustment for gestational age , sex , maternal education , and birth order ( mean difference , 3.8 ; 95 % CI , -0.5 to 8.0 ) . The MDI among infants born weighing at least 1250 g did not differ between groups . CONCLUSION A DHA dose of approximately 1 % total fatty acids in early life did not increase MDI scores of preterm infants overall born earlier than 33 weeks but did improve the MDI scores of girls . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12606000327583",
"Long-chain PUFA ( LCPUFA ) supplementation of formula can have beneficial effects on neurodevelopmental outcome in early infancy , but uncertainty exists regarding effects after 6 months . The present study is the first to investigate whether consumption by term infants of formula containing LCPUFA for the first 2 months after birth improves neurological condition of these children at 9 years of age . A prospect i ve , double-blind , r and omised control study was performed in two groups of healthy term infants : a control group with st and ard formula ( n 169 ) and a LCPUFA-supplemented group ( LF ; n 146 ) . A breast-fed group ( BF ; n 159 ) served as a reference . At age 9 years , children were neurologically assessed according to Touwen , result ing in a Neurological Optimality Score and information on severity and type of minor neurological dysfunction ( MND ) . Information on potential confounders was collected at enrollment and follow-up . Multivariate analyses were carried out to evaluate the effect of nutrition while adjusting for confounders . Attrition ( 28 % ) was selective : drop-outs in the LF group were more often boys and had a significantly lower mental developmental index at 18 months . Neurological optimality and severity and type of MND at 9 years did not differ between the two formula groups . Children in the BF group showed significantly less often fine manipulative dysfunction than formula-fed children . In conclusion , LCPUFA supplementation of formula during the first 2 postnatal months in healthy term infants does not alter neurological function at school age . The study confirmed that breast-fed infants have a slightly better neurodevelopmental outcome than formula-fed infants",
"The objective of this study was to evaluate the effect of conventional and long-chain polyunsaturated fatty acids (LCP)-enriched preterm formula on prostanoid formation in preterm infants during their first weeks of life . In a prospect i ve , r and omized , double-blind study , healthy infants received either formula enriched with LCP ( n = 10 ) , st and ard preterm formula(n = 10 ) , or ( expressed ) breast milk ( n = 10 ) . Urine was sample d , and anthropometric measurements were taken at study entry and after the study period of 3 wk . In vivo formation of prostagl and in E2 , thromboxane A2 , and prostacyclin was evaluated by measuring the urinary excretion of the respective index metabolites by gas chromatography-mass spectrometry . There were no significant differences in urinary prostanoid excretion and anthropometric data between the groups at the end of the study period . We conclude that neither conventional formula nor supplementation of a preterm formula with LCP for a period of 3 wk substantially influence prostanoid formation in healthy preterm infants",
"OBJECTIVE . The objective of our study was to evaluate the effect of supplementation with docosahexaenoic acid and arachidonic acid for human milk-fed preterm infants . The primary end point was cognitive development at 6 months of age . METHODS . The study was a r and omized , double-blind , placebo-controlled study among 141 infants with birth weights of The intervention with 32 mg of docosahexaenoic acid and 31 mg of arachidonic acid per 100 mL of human milk started 1 week after birth and lasted until discharge from the hospital ( on average , 9 weeks ) . Cognitive development was evaluated at 6 months of age by using the Ages and Stages Question naire and event-related potentials , a measure of brain correlates related to recognition memory . RESULTS . There was no difference in adverse events or growth between the 2 groups . At the 6-month follow-up evaluation , the intervention group performed better on the problem-solving subscore , compared with the control group ( 53.4 vs 49.5 points ) . There was also a nonsignificant higher total score ( 221 vs 215 points ) . The event-related potential data revealed that infants in the intervention group had significantly lower responses after the st and ard image , compared with the control group ( 8.6 vs 13.2 ) . There was no difference in responses to novel images . CONCLUSIONS . Supplementation with docosahexaenoic acid and arachidonic acid for very preterm infants fed human milk in the early neonatal period was associated with better recognition memory and higher problem-solving scores at 6 months",
"INTRODUCTION This intervention examined whether fish-oil-supplementation in late infancy modifies free-play test scores and if this is related to blood pressure ( BP ) and mean RR interval . PATIENTS AND METHODS 83 Danish 9-month-old infants were r and omized to ±fish oil ( FO ) ( 3.4±1.1mL/d ) for 3months and 61 of these completed the free-play-test before and after the intervention . RESULTS Most of the free-play scores changed during the intervention , but the intervention affected only the number of looks away from the toy , which was increased in + FO and decreased in -FO ( p=0.037 ) . The increased numbers of looks away were associated with an increase in erythrocyte eicosapentaenoic acid ( r=0.401 , p=0.017 , n=35 ) and were also associated with a decrease in systolic-BP ( r=-0.511 , p late infancy can influence brain development and that the cognitive and cardiovascular effects may be related"
] |
4116c356-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND AND AIMS Probiotic supplementation seems to provide beneficial effects in the prevention and treatment of radiation-induced diarrhea . We performed a systematic review and meta- analysis to estimate the efficacy of probiotic supplementation for prevention and treatment of radiation-induced diarrhea . METHODS Two review ers independently search ed PubMed , EMBASE , Cochrane Library , Google Scholar and on-line clinical trials registers ( up to January 2009 ) for r and omized controlled trials that evaluated the efficacy of probiotic supplementation for the prevention and treatment of radiation-induced diarrhea . Each clinical trial was separately evaluated for study characteristics , method ologic quality and outcomes . Results of the r and omized controlled trials were pooled in a meta- analysis . RESULTS Four r and omized controlled trials were included . Three clinical trials , with a total of 632 subjects , evaluated the preventive effects of probiotic supplementation and 1 study evaluated the therapeutic role . R and om effects meta- analysis of the preventive trials did not show significant differences between probiotic supplementation and control groups ( odds ratio 0.47 ; 95 % confidence interval : 0.13 - 1.67 ) . However , the few available trials and the presence of significant clinical and statistical heterogeneity limited the analysis . Similarly , the therapeutic clinical trial did not show significant differences between active and placebo groups . No major adverse events owing to probiotic supplementation were reported in any study . CONCLUSIONS Probiotic supplementation showed beneficial effect in the prevention and treatment of radiation-induced diarrhea in experimental animal studies . Encouraging results have been observed in humans ; however , the few available clinical studies do not allow firm conclusions . More well-performed , r and omized placebo-controlled studies are needed
|
[
"PURPOSE To analyze the cause of GI symptoms after pelvic radiotherapy ( RT ) in a consecutive series of patients with symptoms beginning after RT . A striking lack of evidence is available concerning the optimal treatment for the 50 % of patients who develop permanent changes in bowel habits affecting their quality of life after pelvic RT . As a result , in the UK , most such patients are never referred to a gastroenterologist . METHODS AND MATERIAL S All diagnoses were prospect ively recorded from a consecutive series of patients with symptoms that started after RT and who were referred during a 32-month period to a gastroenterology clinic . Patients either underwent direct access flexible sigmoidoscopy or were investigated in a st and ard manner by one gastroenterologist after first being seen in the clinic . RESULTS A total of 265 patients referred from 15 institutions were investigated . They included 90 women ( median age , 61.5 years ; range , 22 - 84 years ) and 175 men ( median age , 70 years ; range , 31 - 85 years ) . RT had been completed a median of 3 years ( range , 0.1 - 34 years ) before the study in the women and 2 years ( range , 0 - 21 years ) before in the men . Of the 265 patients , 171 had primary urologic , 78 gynecologic , and 16 GI tumors . The GI symptoms included rectal bleeding in 171 , urgency in 82 , frequency in 80 , tenesmus , discomfort , or pain in 79 , fecal incontinence in 79 , change in bowel habit in 42 , weight loss in 19 , vomiting without other obstructive symptoms in 18 , steatorrhea in 7 , nocturnal defecation in 8 , obstructive symptoms in 4 , and other in 24 . After investigation , significant neoplasia was found in 12 % . One-third of all diagnoses were unrelated to the previous RT . More than one-half of the patients had at least two diagnoses . Many of the abnormalities diagnosed were readily treatable . The symptoms were generally unhelpful in predicting the diagnosis , with the exception of pain , which was associated with neoplasia ( p pelvic RT , specific GI symptoms were not a reliable measure of the underlying diagnoses , and the evaluation of new GI symptoms is worthwhile . An algorithm for this purpose is proposed",
"Radiotherapy is a cornerstone in the treatment of malignancies in the pelvis . Consequently , there is usually exposure of the intestine and especially the lower colon and rectum , with ensuing disturbances in bowel habits at different times following radiotherapy . The main problem is diarrhoea associated with lactose intolerance , bile salt absorption and fat malabsorption . Bacterial contamination has also been described . In the present study we have evaluated the influence of the active administration of specific bacterial cultures in fermented milk , which inhibit the growth of potentially pathogenic micro-organisms , to 40 consecutive patients with chronic alteration in their bowel habits caused by previous radiotherapy of pelvic malignancies . The results suggest that intake of fermented milk products could be of value in decreasing chronic bowel discomfort following radiotherapy of pelvic malignancies . However , a more extensive study is warranted in order to very the significance of the results and to find the optimal product",
"PURPOSE To determine whether a probiotic drink containing Lactobacillus casei DN-114 001 reduces the incidence of radiation-induced diarrhea in patients with gynecologic cancer . METHODS AND MATERIAL S Patients who were undergoing pelvic radiotherapy ( 45 - 50 Gy , conventional fractionation ) for either cervical carcinoma ( radiotherapy and weekly cisplatin ) or endometrial adenocarcinoma ( postoperative radiotherapy ) were r and omly assigned to a probiotic drink or placebo , in a double-blind fashion . The probiotic drink consisted of liquid yogurt containing L. casei DN-114 001 at 10(8 ) CFU/g . The patients recorded the daily the number of bowel movements and scored the stool consistency using the Bristol scale . Diarrhea was grade d weekly according the Common Toxicity Criteria system . The primary endpoint was to reduce the incidence of diarrhea , defined by a Common Toxicity Criteria Grade of 2 or greater or the need for loperamide . RESULTS A total of 85 patients were enrolled . Grade 2 or greater diarrhea and /or the use of loperamide was observed in 24 of 41 patients in the placebo group and 30 of 44 in the probiotic group ( p = 0.568 ) . No differences were found in the median time to the presentation of the primary endpoint . Probiotic intervention had a significant effect on stool consistency ( p = 0.04 ) . The median time for patients to present with Bristol scale stools of Type 6 or greater was 14 days for patients receiving the probiotic drink vs. 10 days for those receiving placebo . CONCLUSION Nutritional intervention with the probiotic drink containing L. casei DN-114 001 does not reduce the incidence of radiation-induced diarrhea as defined by a Common Toxicity Criteria Grade 2 or greater . However , it had a significant effect on stool consistency as measured by the Bristol scale",
"Background and aims Gastrointestinal toxicity is frequently observed during radiotherapy for malignancies in the abdomen and pelvis . This study was performed to determine the efficacy and tolerability of Lactobacillus rhamnosus ( Antibiophilus ® ) in comparison to placebo in a double-blind trial design . Its aim was to determine any clinical ly relevant difference between Antibiophilus ® and placebo in terms of efficacy in patients suffering from mild to moderate diarrhoea induced by radiation therapy . Methods The study was performed in two radiotherapy units in Hungary ; the results are based on the data for 206 recruited patients . Results Based on statistical analysis , Antibiophilus ® patients showed superiority with respect to the number of bowel movements ( P and faeces consistency ratings by the investigators ( P regard to diarrhoea grade and faeces consistency showed a statistically highly significant treatment-by-time interaction ( P < 0.001 ) which was supported by the evidence of tendencies or P values below the nominal 5 % level in the second half of this study . Conclusions Overall , there was a highly favourable benefit/risk ratio in favour of Antibiophilus ®",
"THE R AND OMIZED controlled trial ( RCT ) , more than any other methodology , can have a powerful and immediate impact on patient care . Ideally , the report of such an evaluation needs to convey to the reader relevant information concerning the design , conduct , analysis , and generalizability of the trial . This information should provide the reader with the ability to make informed judgments regarding the internal and external validity of the trial . Accurate and complete reporting also benefits editors and review ers in their deliberations regarding su bmi tted manuscripts . For RCTs to ultimately benefit patients , the published report should be of the highest possible st and ard",
"Wound-care journals contain abundant reports of trials , but not all report a satisfactory methodology . Systematic review s of wound-care trials have highlighted many areas for improvement , and the National Institute for Clinical Excellence ( NICE ) guidelines recommend that primary research in the field of pressure ulcer prevention should adhere more closely to current method ological st and ards in terms of conduct and reporting . The CONSORT tool was developed to help achieve these improvements in the design and reporting of r and omised controlled trials ( RCTs )",
" Twenty-four female patients suffering from gynaecological malignancies and scheduled for internal and external irradiation of the pelvic area ( pelvic dose 5000 cGy ) were selected for a study on prevention of intestinal side-effects by live Lactobacillus acidophilus cultures . The patients were r and omised into two groups . Both groups received dietary counselling recommending a low-fat and low-residue diet during radiotherapy . The control group received dietary counselling only . The test group received 150 ml of a fermented milk test product supplying them with at least 2 X 10(9 ) live Lactobacillus acidophilus bacteria daily and 6.5 % lactulose as substrate for the bacteria . The results indicated that the test product appeared to prevent radiotherapy-associated diarrhoea . However , flatulence was increased probably due to lactulose ingestion in the test group"
] |
4116c39c-06ff-11f0-808a-c43d1ab1c353
|
Aim or objective The aim of this study is to consoli date studies of physiological measures following sport-related concussion ( SRC ) to determine if a time course of postinjury altered neurobiology can be outlined . This biological time course was considered with respect to clinical ly relevant outcomes such as vulnerability to repeat injury and safe timing of return to physical contact risk . Design Systematic review . Data sources PubMed , CINAHL , Cochrane Central , PsychINFO . Eligibility criteria for selecting studies Studies were included if they reported original research on physiological or neurobiological changes after SRC . Excluded were cases series Results A total of 5834 articles were identified , of which 80 were included for full-text data extraction and review . Relatively few longitudinal studies exist that follow both physiological dysfunction and clinical measures to recovery . Summary / conclusions Modalities of measuring physiological change after SRC were categorised into the following : functional MRI , diffusion tensor imaging , magnetic resonance spectroscopy , cerebral blood flow , electrophysiology , heart rate , exercise , fluid biomarkers and transcranial magnetic stimulation . Due to differences in modalities , time course , study design and outcomes , it is not possible to define a single ‘ physiological time window ’ for SRC recovery . Multiple studies suggest physiological dysfunction may outlast current clinical measures of recovery , supporting a buffer zone of gradually increasing activity before full contact risk . Future studies need to use generalisable population s , longitudinal design s following to physiological and clinical recovery and careful correlation of neurobiological modalities with clinical measures
|
[
"Abstract The biology of post-concussive symptoms is unclear . Symptoms are often increased during activities , and have been linked to decreased cerebrovascular reactivity and perfusion . The aim of this study was to examine cerebral blood flow ( CBF ) in children with different clinical recovery patterns following mild traumatic brain injury ( mTBI ) . This was a prospect i ve controlled cohort study of children with mTBI ( ages 8 to 18 years ) who were symptomatic with post-concussive symptoms at one month post-injury ( symptomatic , n = 27 ) and children who had recovered quickly ( asymptomatic , n = 24 ) . Pseudo continuous arterial spin labeling magnetic resonance imaging ( MRI ) was used to quantify CBF . The mTBI groups were imaged at 40 days post-injury . Global and regional CBF were compared with healthy controls of similar age and sex but without a history of mTBI ( n = 21 ) . Seventy-two participants ( mean age : 14.1 years ) underwent neuroimaging . Significant differences in CBF were found : global CBF was higher in the symptomatic group and lower in the asymptomatic group compared with controls , ( F(2,69 ) 9.734 ; p Post-injury symptom score could be predicted by pre-injury symptoms and CBF in presence of mTBI ( adjusted R2 = 0.424 ; p patterns of cerebral perfusion are seen following mTBI and are associated with the recovery trajectory . Symptomatic children have higher CBF . Children who “ recovered ” quickly , have decreased CBF suggesting that clinical recovery precedes the cerebral recovery . Further longitudinal studies are required to determine if these perfusion patterns continue to change over time",
"Objective : Some patients with postconcussion syndrome ( PCS ) have reduced exercise capacity that may reflect altered central cardiorespiratory control . The purpose of this study was to evaluate control of cerebral blood flow ( CBF ) during exercise in females with PCS . Setting : University Concussion Clinic . Participants : Nine female Division 1 collegiate team athletes with PCS ( 23 ± 6 years ) and a reference group of 13 healthy female recreational aerobic athletes ( 21 ± 3 years ) . Design : A prospect i ve experimental study . All PCS athletes were compared with the reference group at the beginning of the study . Six of the PCS athletes were subsequently measured before and after a subsymptom threshold aerobic exercise treatment program . Main Measures : Exercise treadmill test during which blood pressure ( BP ) , minute ventilation ( E ) , end-tidal CO2 ( PETCO2 ) , and CBF velocity ( CBFV , by transcranial Doppler ) were measured . Results : Participants with PCS had significantly lower E ( by 18 % ) and greater PETCO2 ( 5 % ) and CBFV ( 14 % ) versus the reference group at similar workloads in association with appearance of symptoms and premature exercise cessation . Subthreshold exercise normalized E , PETCO2 , CBFV and exercise tolerance . Before treatment , PCS had low CO2 sensitivity that blunted their exercise ventilation . CO2 sensitivity and ventilation improved after exercise treatment . Conclusion : Some PCS patients have exercise intolerance due to abnormal CBF regulation that may be the result of concussion-induced altered sensitivity to CO2 . Return of normal CBF control and exercise tolerance may be physiological markers of recovery from concussion",
"Aim To investigate incidence of concussion , clinical outcomes and subsequent injury risk following concussion . Methods In a two-season ( 2012/2013 , 2013/2014 ) prospect i ve cohort study , incidence of diagnosed match concussions ( injuries/1000 h ) , median time interval to subsequent injury of any type ( survival time ) and time spent at each stage of the graduated return to play pathway were determined in 810 professional Rugby Union players ( 1176 player seasons ) . Results Match concussion incidence was 8.9/1000 h with over 50 % occurring in the tackle . Subsequent incidence of any injury for players who returned to play in the same season following a diagnosed concussion ( 122/1000 h , 95 % CI 106 to 141 ) was 60 % higher ( IRR 1.6 , 95 % CI 1.4 to 1.8 ) than for those who did not sustain a concussion ( 76/1000 h , 95 % CI 72 to 80 ) . Median time to next injury following return to play was shorter following concussion ( 53 days , 95 % CI 41 to 64 ) than following non-concussive injuries ( 114 days , 95 % CI 85 to 143 ) . 38 % of players reported recurrence of symptoms or failed to match their baseline neurocognitive test during the graduated return to play protocol . Summary and conclusions Players who returned to play in the same season after a diagnosed concussion had a 60 % greater risk of time-loss injury than players without concussion . A substantial proportion of players reported recurrence of symptoms or failed to match baseline neurocognitive test scores during graduated return to play . These data pave the way for trials of more conservative and comprehensive graduated return to play protocol s , with a greater focus on active rehabilitation",
"The arterial pulse wave ( APW ) has a distinct morphology whose contours reflect dynamics in cardiac function and peripheral vascular tone as a result of sympathetic nervous system ( SNS ) control . With a transition from rest to increased metabolic dem and , the expected augmentation of SNS outflow will not only affect arterial blood pressure and heart rate but it will also induce changes to the contours of the APW . Following a sports concussion , a transient state cardiovascular autonomic dysfunction is present . How this state affects the APW has yet to be described . A prospect i ve , parallel-group study on cardiovascular autonomic control ( i.e. , digital electrocardiogram and continuous beat-to-beat blood pressure ) was performed in the seated upright position in 10 athletes with concussion and 7 non-injured control athletes . Changes in APW were compared at rest and during the first 60 s ( F60 ) of an isometric h and grip test ( IHGT ) in concussed athletes and non-injured controls within 48 h and 1 week of injury . The concussion group was further separated by the length of time until they were permitted to return to play ( RTP > 1week ; RTP ≤ 1week ) . SysSlope , an indirect measurement of stroke volume , was significantly lower in the concussion group at rest and during F60 at 48 h and 1week ; a paradoxical decline in SysSlope occurred at each visit during the transition from rest to IHGT F60 . The RTP > 1week group had lower SysSlope ( 405 ± 200 ; 420 ± 88 ; 454 ± 236 mmHg/s , respectively ) at rest 48 h compared to the RTP ≤ 1week and controls . Similarly at 48 h rest , several measurements of arterial stiffness were abnormal in RTP > 1week compared to RTP ≤ 1week and controls : peak-to-notch latency ( 0.12 ± 0.04 ; 0.16 ± 0.02 ; 0.17 ± 0.05 , respectively ) , notch relative amplitude ( 0.70 ± 0.03 ; 0.71 ± 0.04 ; 0.66 ± 0.14 , respectively ) , and stiffness index ( 6.4 ± 0.2 ; 5.7 ± 0.4 ; 5.8 ± 0.5 , respectively ) . Use of APW revealed that concussed athletes have a transient increase in peripheral artery stiffness , which may be a compensatory adaptation to a paradoxical decline of stroke volume during the transition from rest to a state of increased metabolic dem and within 48 h of concussion . This dysfunction of the SNS appeared to be more pronounced among concussed athletes who were removed from participation for > 1 week compared to those who resumed play within 7 days",
"Objective Increased awareness around neurocognitive deficits after mild traumatic brain injury ( mTBI ) has progressed the search for objective , diagnostic , and monitoring tools , yet imaging biomarkers for mTBI and recovery are not established in clinical use . It has been suggested that mTBI impairs cerebrovascular reactivity ( CVR ) to CO2 , which could be related to post-concussive syndrome ( PCS ) . We investigate CVR evolution after mTBI using blood-oxygen-level dependent ( BOLD ) magnetic resonance imaging ( MRI ) and possible correlation with PCS . Methods A prospect i ve cohort of 25 mTBI patients and 18 matched controls underwent BOLD MRI CVR measurements . A subset of 19 mTBI patients underwent follow-up testing . Visits took place at a mean of 63 and 180 days after injury . Symptoms were assessed with the Sport Concussion Assessment Tool 2 ( SCAT2 ) . Symptoms , CVR and brain volume [ gray matter ( GM ) , white matter ( WM ) , and whole brain ( WB ) ] , age , and sex , were examined between groups and longitudinally within traumatic brain injury ( TBI ) patients . Results Traumatic brain injury participants were 72 % males , mean age being 42.7 years . Control participants were 61 % with mean age of 38.7 years . SCAT2 scores tended to improve among those mTBI patients with follow-up visits ( p = 0.07 ) ; however , they did not tend to recover to scores of the healthy controls . Brain volumes were not statistically different between groups at the first visit ( WM p = 0.71 ; GM p = 0.36 ) . In mTBI patients , there was a reduction in GM volume between visits 1 and 2 ( p = 0.0046 ) . Although mean CVR indexes were similar ( WM p = 0.27 ; GM p = 0.36 ; and WB p = 0.35 ) , the correlation between SCAT2 and CVR was negative in controls ( WM-r = −0.59 ; p = 0.010 ; GM-r = −0.56 ; p = 0.016 ; brain-r = −0.58 ; p = 0.012 ) and weaker and positive in mTBI ( brain-r = 0.4 ; p = 0.046 ; GM-r = 0.4 ; p = 0.048 ) . SCAT2 correlated with GM volume ( r = 0.5215 , p = 0.0075 ) in mTBI but not in controls ( r = 0.2945 , p = 0.2355 ) . Conclusion There is a correlation between lower GM CVR indexes and lower performance on SCAT2 in patients with mTBI , which seems to be associated with more symptoms . This correlation seems to persist well beyond 120 days . mTBI may lead to a decrease in GM volume in these patients",
"Background The on-field diagnosis of sports-related concussion ( SRC ) is complicated by the lack of an accurate and objective marker of brain injury . Purpose To compare subject-specific changes in the astroglial protein , S100B , before and after SRC among collegiate and semi-professional contact sport athletes , and compare these changes to differences in S100B before and after non-contact exertion . Study Design Longitudinal cohort study . Methods From 2009–2011 , we performed a prospect i ve study of athletes from Munich , Germany , and Rochester , New York , USA . Serum S100B was measured in all SRC athletes at pre-season baseline , within 3 hours of injury , and at days 2 , 3 and 7 post-SRC . Among a subset of athletes , S100B was measured after non-contact exertion but before injury . All sample s were collected identically and analyzed using an automated electrochemiluminescent assay to quantify serum S100B levels . Results Forty-six athletes ( 30 Munich , 16 Rochester ) underwent baseline testing . Thirty underwent additional post-exertion S100B testing . Twenty-two athletes ( 16 Rochester , 6 Munich ) sustained a SRC , and 17 had S100B testing within 3 hours post-injury . The mean 3-hour post-SRC S100B was significantly higher than pre-season baseline ( 0.099±0.008 µg/L vs. 0.058±0.006 µg/L , p = 0.0002 ) . Mean post-exertion S100B was not significantly different than the preseason baseline . S100B levels at post-injury days 2 , 3 and 7 were significantly lower than the 3-hour level , and not different than baseline . Both the absolute change and proportional increase in S100B 3-hour post-injury were accurate discriminators of SRC from non-contact exertion without SRC ( AUC 0.772 and 0.904 , respectively ) . A 3-hour post-concussion S100B > 0.122 µg/L and a proportional S100B increase of > 45.9 % over baseline were both 96.7 % specific for SRC . Conclusions Relative and absolute increases in serum S100B can accurately distinguish SRC from sports-related exertion , and may be a useful adjunct to the diagnosis of SRC",
"Our aim was to quantify with functional magnetic resonance imaging ( fMRI ) changes in brain activity in concussed athletes and compare the results with those of normal control subjects . Regional brain activations associated with a working memory task were obtained from a group of concussed athletes ( 15 symptomatic , 1 asymptomatic ) and eight matched control subjects , using blood oxygen level dependent ( BOLD ) fMRI . The average percent signal change from baseline to working memory condition in each region of interest was computed . Symptomatic concussed athletes demonstrated task-related activations in some but not all the regions of interest , even when they performed as well as the control subjects . Furthermore , several concussed athletes had additional increases in activity outside the regions of interest , not seen in the control group . Quantitative analysis of BOLD signals within regions of interest revealed that , in general , concussed athletes had different BOLD responses compared to the control subjects . The task-related activation pattern of the one symptom-free athlete was comparable to that of the control group . We also repeated the study in one athlete whose symptoms had resolved . On the first study , when he was still symptomatic , less task-related activations were observed . On follow-up , once his symptoms had disappeared , the task-related activations became comparable to those of the control group . These results demonstrate the potential of fMRI , in conjunction with the working memory task , to identify an underlying pathology in symptomatic concussed individuals with normal structural imaging results",
"Impact-related mild traumatic brain injuries ( mTBI ) are a major public health concern , and remain as one of the most poorly understood injuries in the field of neuroscience . Currently , the diagnosis and management of such injuries are based largely on patient-reported symptoms . An improved underst and ing of the underlying pathophysiology of mTBI is urgently needed in order to develop better diagnostic and management protocol s. Specifically , dynamic post-injury changes to the myelin sheath in the human brain have not been examined , despite ‘ compromised white matter integrity ’ often being described as a consequence of mTBI . In this preliminary cohort study , myelin water imaging was used to prospect ively evaluate changes in myelin water fraction , derived from the T2 decay signal , in two varsity hockey teams ( 45 players ) over one season of athletic competition . 11 players sustained a concussion during competition , and were scanned at 72 hours , 2 weeks , and 2 months post-injury . Results demonstrated a reduction in myelin water fraction at 2 weeks post-injury in several brain areas relative to preseason scans , including the splenium of the corpus callosum , right posterior thalamic radiation , left superior corona radiata , left superior longitudinal fasciculus , and left posterior limb of the internal capsule . Myelin water fraction recovered to pre-season values by 2 months post-injury . These results may indicate transient myelin disruption following a single mTBI , with subsequent remyelination of affected neurons . Myelin disruption was not apparent in the athletes who did not experience a concussion , despite exposure to repetitive subconcussive trauma over a season of collegiate hockey . These findings may help to explain many of the metabolic and neurological deficits observed clinical ly following mTBI",
"OBJECTIVE The relationship between athlete reports of symptoms , neurophysiological activation , and neuropsychological functioning is investigated in a sample of high school athletes . METHODS All athletes were evaluated using functional magnetic resonance imaging ( fMRI ) , a computer-based battery of neurocognitive tests , and a subjective symptom scale . Athletes were evaluated within approximately 1 week of injury and again after clinical recovery using all assessment modalities . RESULTS This study found that abnormal fMRI results during the first week of recovery predicted clinical recovery . As a group , athletes who demonstrated hyperactivation on fMRI scans at the time of their first fMRI scan demonstrated a more prolonged clinical recovery than athletes who did not demonstrate hyperactivation at the time of their first fMRI scan . CONCLUSION These results demonstrate the relationship between neurophysiological , neuropsychological , and subjective symptom data in a relatively large sample composed primarily of concussed high school athletes . fMRI represents an important evolving technology for the underst and ing of brain recovery after concussion and may help shape return-to-play guidelines in the future",
"CONTEXT The known detrimental effects of sport concussions on motor system function include balance problems , slowed motor execution , and abnormal motor cortex excitability . OBJECTIVE To assess whether these concussion-related alterations of motor system function are still evident in collegiate football players who sustained concussions but returned to competition more than 9 months before testing . DESIGN Case-control study . SETTING University laboratory . PATIENTS OR OTHER PARTICIPANTS A group of 21 active , university-level football players who had experienced concussions was compared with 15 university football players who had not sustained concussions . INTERVENTION(S ) A force platform was used to assess center-of-pressure ( COP ) displacement and COP oscillation regularity ( approximate entropy ) as measures of postural stability in the upright position . A rapid alternating-movement task was also used to assess motor execution speed . Transcranial magnetic stimulation over the motor cortex was used to measure long-interval intracortical inhibition and the cortical silent period , presumably reflecting y-aminobutyric acid subtype B receptor-mediated intracortical inhibition . MAIN OUTCOME MEASURE(S ) COP displacement and oscillation regularity , motor execution speed , long-interval intracortical inhibition , cortical silent period . RESULTS Relative to controls , previously concussed athletes showed persistently lower COP oscillation r and omness , normal performance on a rapid alternating-movement task , and more M1 intracortical inhibition that was related to the number of previous concussions . CONCLUSIONS Sport concussions were associated with pervasive changes in postural control and more M1 intracortical inhibition , providing neurophysiologic and behavioral evidence of lasting , sub clinical changes in motor system integrity in concussed athletes",
"Objective To investigate the clinical utility and sensitivity of a portable , automatic , frontal quantitative electroencephalographic ( QEEG ) acquisition device currently in development in detecting abnormal brain electrical activity after sport-related concussion . Design This was a prospect i ve , non-r and omized study of 396 high school and college football players , including cohorts of 28 athletes with concussion and 28 matched controls . All subjects underwent preseason baseline testing on measures of postconcussive symptoms , postural stability , and cognitive functioning , as well as QEEG . Clinical testing and QEEG were repeated on day of injury and days 8 and 45 postinjury for the concussion and control groups . Main Outcomes and Results The injured group reported more significant postconcussive symptoms during the first 3 days postinjury , which resolved by days 5 and 8 . Injured subjects also performed poorer than controls on neurocognitive testing on the day of injury , but no differences were evident on day 8 or day 45 . QEEG studies revealed significant abnormalities in electrical brain activity in the injured group on day of injury and day 8 postinjury , but not on day 45 . Conclusions Results from the current study on clinical recovery after sport-related concussion are consistent with early reports indicating a typical course of full recovery in symptoms and cognitive dysfunction within the first week of injury . QEEG results , however , suggest that the duration of physiological recovery after concussion may extend longer than observed clinical recovery . Further study is required to replicate and extend these findings in a larger clinical sample , and further demonstrate the utility of QEEG as a marker of recovery after sport-related concussion",
"OBJECT Mild traumatic brain injury ( MTBI ) , often referred to as concussion when it occurs in sports , produces persistent cognitive problems in at least 15 % of patients . Unfortunately , conventional neuropsychological tests usually yield results within normal limits in this population . The main objective of this event-related potential ( ERP ) study was to underst and brain functioning during the performance of a working memory ( WM ) task in patients who have sustained an MTBI , mostly due to motor vehicle accident or sports concussion . This study also aim ed for a better underst and ing of the association between brain functioning as measured with ERP , behavioral performance on the WM task , postconcussion symptoms , type of injury ( that is , sports concussion vs other types ) , and time since the injury . METHODS Forty-four patients with MTBI ( 7.6 ± 8.4 months postinjury ) were tested on a visual WM task with simultaneous recording of ERP , and were compared with 40 control volunteers who were their equivalent for age and sex . Amplitude and latency of frontal ( N200 and N350 ) and parietal ( P200 and P300 ) ERP waves were measured and were compared between groups . Correlation analyses were also performed between ERP characteristics , clinical variables , and behavioral performance . RESULTS A significant group difference was found for behavioral performance on the WM task , in which the MTBI group had a lower percentage of correct answers than the control group ( p smaller amplitudes of both frontal N350 and parietal P300 ERP components when compared with control volunteers ( p for latency of ERP components . Smaller ERP amplitudes were associated with slower reaction times and worse accuracy on the WM task among patients with MTBI ( p patients after MTBI or sports concussion , even for those in the nonacute stage after their injury . Current st and ard clinical evaluations most often fail to detect cerebral dysfunction after MTBI , even when patients or athletes report symptoms . Clinicians should be aware that patients with MTBI , including sports concussion , probably have underlying mild but persistent cerebral dysfunctions that require further investigation",
"Objective : To examine functional brain activation patterns before and after postconcussive symptoms ( PCS ) resolution . Design : Prospect i ve serial study with male athletes using functional magnetic resonance imaging ( fMRI ) . Setting : Hospital laboratory and imaging facility . Participants : 9 symptomatic concussed athletes who experienced persisting PCS at least 1 month postinjury and 6 healthy athletes . Interventions : All athletes filled out a PCS checklist and underwent an fMRI session during which they performed a working-memory task . Main outcome measurements : Behavioral outcomes were response speed and accuracy on the working memory tasks performed during the fMRI session . Functional imaging outcomes were blood oxygen level-dependent fMRI activation patterns associated with a working memory task . Results : There was no difference in behavioral performance between the groups . Despite normal structural MRI findings , all symptomatic concussed athletes initially showed atypical brain activation patterns in the dorsolateral prefrontal cortex ( DLPC ) . Compared to the initial postinjury evaluation , those athletes at follow-up with PCS resolved showed significant increases in activation in the left DLPC . Concussed athletes whose PCS status remained unchanged at follow-up continued to show atypical activation in DLPC . Healthy athletes showed remarkably clear and consistent brain activations in DLPC initially as well as in follow-up , highlighting the test-retest reliability of fMRI . Conclusions : The results demonstrate the feasibility of using fMRI to detect an underlying pathology in symptomatic concussed athletes with normal structural imaging results and its potential to document recovery . Such information may be of considerable value for clinical judgment and patient management",
"Objective : To evaluate a grade d treadmill test for retest reliability ( RTR ) and interrater reliability ( IRR ) in the evaluation of the physiologic effects of symptom exacerbation from concussion . Design : Prospect i ve case series ( RTR ) and blinded rater assessment of 10 actors portraying patients with and without symptom exacerbation ( IRR ) . Setting : University Sports Medicine Concussion Clinic . Participants : For RTR , 21 refractory concussed patients ( 11 athletes and 10 nonathletes ) and 10 healthy subjects ; for IRR , 32 raters representing a variety of health care disciplines . Intervention : For RTR , a Balke protocol treadmill test to symptom exacerbation before and after 2 to 3 weeks . For IRR , video recordings of actors during the treadmill test viewed by raters blinded to condition . Main Outcome Measures : For RTR , agreement of the tests for maximal heart rate ( HR ) , systolic blood pressure , diastolic blood pressure , and rating of perceived exertion . For IRR , presence or absence of symptom exacerbation and the symptom exacerbation HR . Results : Raters achieved a sensitivity of 99 % for identifying actors with symptom exacerbation and a specificity of 89 % for ruling out concussion symptoms and agreed on 304 of 320 observations ( accuracy of 95 % ) . The intraclass correlation coefficient for the symptom exacerbation HR was large at 0.90 ( 95 % confidence interval , 0.78 - 0.98 ) . The treadmill test had good RTR for maximum HR ( intraclass correlation coefficient , 0.79 ) but not for systolic blood pressure , diastolic blood pressure , or rating of perceived exertion . Conclusions : The Balke exercise treadmill protocol has very good IRR and sufficient RTR for identifying patients with symptom exacerbation from concussion",
"OBJECT A neuroimaging assessment tool to visualize global and regional impairments in cerebral blood flow ( CBF ) and cerebrovascular responsiveness in individual patients with concussion remains elusive . Here the authors summarize the safety , feasibility , and results of brain CO2 stress testing in adolescents with postconcussion syndrome ( PCS ) and healthy controls . METHODS This study was approved by the Biomedical Research Ethics Board at the University of Manitoba . Fifteen adolescents with PCS and 17 healthy control subjects underwent anatomical MRI , pseudo-continuous arterial spin labeling MRI , and brain stress testing using controlled CO2 challenge and blood oxygen level-dependent ( BOLD ) MRI . Post hoc processing was performed using statistical parametric mapping to determine voxel-by-voxel regional resting CBF and cerebrovascular responsiveness of the brain to the CO2 stimulus ( increase in BOLD signal ) or the inverse ( decrease in BOLD signal ) . Receiver operating characteristic ( ROC ) curves were generated to compare voxel counts categorized by control ( 0 ) or PCS ( 1 ) . RESULTS Studies were well tolerated without any serious adverse events . Anatomical MRI was normal in all study participants . No differences in CO2 stimuli were seen between the 2 participant groups . No group differences in global mean CBF were detected between PCS patients and healthy controls . Patient-specific differences in mean regional CBF and CO2 BOLD responsiveness were observed in all PCS patients . The ROC curve analysis for brain regions manifesting a voxel response greater than and less than the control atlas ( that is , abnormal voxel counts ) produced an area under the curve of 0.87 ( p Adolescent PCS is associated with patient-specific abnormalities in regional mean CBF and BOLD cerebrovascular responsiveness that occur in the setting of normal global resting CBF . Future prospect i ve studies are warranted to examine the utility of brain MRI CO2 stress testing in the longitudinal assessment of acute sports-related concussion and PCS",
"The diagnosis of sports-related concussion is mainly based on subjective clinical symptoms and neuropsychological tests . Therefore , reliable brain injury biomarkers to assess when it is safe to return to play are highly desirable . The overall objective of this study was to evaluate the utility of two newly described tau fragments for diagnosis and prognosis of sports-related concussions . This multi-center prospect i ve cohort study involved all 12 teams of the top professional ice hockey league in Sweden . A total of 288 players consented to participate in the study . Thirty-five players sustained concussions , of whom 28 underwent repeated blood samplings at 1 , 12 , 36 , and 144 h after the trauma , or when the player returned to play ( 7 to > 90 days ) . There was no significant increase in the levels of Tau-A in post-concussion sample s compared with preseason values . However , serum levels of Tau-C were significantly higher in post-concussion sample s compared with preseason . Further , levels of Tau-A correlated with the duration of post-concussive symptoms . Tau-A in serum , which is newly discovered biomarker , could be used to predict when it is safe to return to play after a sports-related concussion",
"IMPORTANCE Lack of objective biomarkers for brain damage hampers acute diagnosis and clinical decision making about return to play after sports-related concussion . OBJECTIVES To determine whether sports-related concussion is associated with elevated levels of blood biochemical markers of injury to the central nervous system and to assess whether plasma levels of these biomarkers predict return to play in professional ice hockey players with sports-related concussion . DESIGN , SETTING , AND PARTICIPANTS Multicenter prospect i ve cohort study involving all 12 teams of the top professional ice hockey league in Sweden , the Swedish Hockey League . Two hundred eighty-eight professional ice hockey players from 12 teams contesting during the 2012 - 2013 season consented to participate . All players underwent clinical preseason baseline testing regarding concussion assessment measures . Forty-seven players from 2 of the 12 ice hockey teams underwent blood sampling prior to the start of the season . Thirty-five players had a concussion from September 13 , 2012 , to January 31 , 2013 ; of these players , 28 underwent repeated blood sampling at 1 , 12 , 36 , and 144 hours and when the players returned to play . MAIN OUTCOMES AND MEASURES Total tau , S-100 calcium-binding protein B , and neuron-specific enolase concentrations in plasma and serum were measured . RESULTS Concussed players had increased levels of the axonal injury biomarker total tau(median , 10.0 pg/mL ; range , 2.0 - 102 pg/mL ) compared with preseason values ( median , 4.5pg/mL ; range , 0.06 - 22.7 pg/mL ) ( P levels of the astroglial injury biomarker S-100 calcium-binding protein B were also increased in players with sports-related concussion(median , 0.075 μg/L ; range , 0.037 - 0.24 μg/L ) compared with preseason values ( median,0.045 μg/L ; range , 0.005 - 0.45 μg/L ) ( P concentrations of total tau and S-100 calcium-binding protein B were measured immediately after a concussion , and they decreased during rehabilitation . No significant changes were detected in the levels of neuron-specific enolase from preseason values ( median , 6.5 μg/L ; range,3.45 - 18.0 μg/L ) to postconcussion values ( median , 6.1 μg/L ; range , 3.6 - 12.8 μg/L ) ( P = .10 ) . CONCLUSIONS AND RELEVANCE Sports-related concussion in professional ice hockey players is associated with acute axonal and astroglial injury . This can be monitored using blood biomarkers , which may be developed into clinical tools to guide sport physicians in the medical counseling of athletes in return-to-play decisions",
"IMPORTANCE Animal models suggest that reduced cerebral blood flow ( CBF ) is one of the most enduring physiological deficits following concussion . Despite this , longitudinal studies documenting serial changes in regional CBF following human concussion have yet to be performed . OBJECTIVE To longitudinally assess the recovery of CBF in a carefully selected sample of collegiate athletes and compare time course of CBF recovery with that of cognitive and behavioral symptoms . DESIGN , SETTING , AND PARTICIPANTS A cohort of collegiate football athletes ( N = 44 ) participated in this mixed longitudinal and cross-sectional study at a private research institute specializing in neuroimaging between March 2012 and December 2013 . Serial imaging occurred approximately 1 day , 1 week , and 1 month postconcussion for a subset of participants ( n = 17 ) . All athletes reported no premorbid mood disorders , anxiety disorders , substance abuse , or alcohol abuse . MAIN OUTCOMES AND MEASURES Arterial spin labeling magnetic resonance imaging was used to collect voxelwise relative CBF at each visit . Neuropsychiatric evaluations and a brief cognitive screen were also performed at all 3 points . Clinicians trained in sports medicine provided an independent measure of real-world concussion outcome ( ie , number of days withheld from competition ) . RESULTS The results indicated both cognitive ( simple reaction time ) and neuropsychiatric symptoms at 1 day postinjury that resolved at either 1 week ( cognitive ; P CBF recovery in the right insular and superior temporal cortex . Importantly , CBF in the dorsal midinsular cortex was both decreased at 1 month postconcussion in slower-to-recover athletes ( t11 = 3.45 ; P = .005 ) and was inversely related to the magnitude of initial psychiatric symptoms ( Hamilton Depression Scale : r = -0.64 , P = .02 ; Hamilton Anxiety Scale : r = -0.56 , P = .046 ) , suggesting a potential prognostic indication for CBF as a biomarker . CONCLUSIONS AND RELEVANCE To our knowledge , these results provide the first prospect i ve evidence of reduced CBF in human concussion and subsequent recovery . The resolution of CBF abnormalities closely mirrors previous reports from the animal literature and show real-world validity for predicting outcome following concussion"
] |
4116c3d8-06ff-11f0-808a-c43d1ab1c353
|
Background Vegetarian diets exclude all animal flesh and are being widely adopted by an increasing number of people ; however , effects on blood lipid concentrations remain unclear . This meta‐ analysis aim ed to quantitatively assess the overall effects of vegetarian diets on blood lipids . Methods and Results We search ed PubMed , Scopus , Embase , ISI Web of Knowledge , and the Cochrane Library through March 2015 . Studies were included if they described the effectiveness of vegetarian diets on blood lipids ( total cholesterol , low‐density lipoprotein cholesterol , high‐density lipoprotein cholesterol , and triglyceride ) . Weighted mean effect sizes were calculated for net changes by using a r and om‐effects model . We performed subgroup and univariate meta‐regression analyses to explore sources of heterogeneity . Eleven trials were included in the meta‐ analysis . Vegetarian diets significantly lowered blood concentrations of total cholesterol , low‐density lipoprotein cholesterol , high‐density lipoprotein cholesterol , and non – high‐density lipoprotein cholesterol , and the pooled estimated changes were −0.36 mmol/L ( 95 % CI −0.55 to −0.17 ; P affect blood triglyceride concentrations , with a pooled estimated mean difference of 0.04 mmol/L ( 95 % CI −0.05 to 0.13 ; P=0.40 ) . Conclusions This systematic review and meta‐ analysis provides evidence that vegetarian diets effectively lower blood concentrations of total cholesterol , low‐density lipoprotein cholesterol , high‐density lipoprotein cholesterol , and non – high‐density lipoprotein cholesterol . Such diets could be a useful nonpharmaceutical means of managing dyslipidemia , especially 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 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",
"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",
"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",
"OBJECTIVE To quantify the degree of disagreement between the two most popular methods for dealing with missing data : intention to treat ( ITT ) and per protocol ( PP ) . STUDY DESIGN AND SETTING We performed a systematic review of r and omized two-armed clinical trials ( CTs ) published between 2001 and 2003 , abstract ed in PubMed and reporting both the ITT and PP analyses on a primary binary endpoint , out of which 74 papers were finally selected . The treatment effect of each CT was measured by the odds ratio , and the disagreement between them was quantified by the Bl and -Altman method . RESULTS On average , the PP estimator provides greater values Log(e)ORPP=1 x 25.Log(e)ORITT , ( 95 % CI : 1.15 , 1.35 ) than the corresponding ITT estimator , although the limits of concordance showed that the ratio between the two estimators varies greatly from 0.39 up to 2.53 . CONCLUSION These results confirm that missing values may cause both systematic and unpredictable bias in CTs . Further efforts should be made to minimize protocol deviations and to use better statistical methods to highlight the drawbacks of missing information . In the presence of protocol deviations , the conclusion of a CT can not rest on the single reporting of either the ITT or the PP approach alone",
"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",
"Although the causal relationships of high serum levels of total cholesterol ( TC ) and low-density lipoprotein cholesterol ( LDL-C ) with coronary artery disease ( CAD ) are well established , there have been few community-based epidemiologic studies of these relations in Japan . Furthermore , even when analysis is restricted to ischemic stroke , the relationship between dyslipidemia and stroke is very weak . Accordingly , it is difficult to perform cohort studies of dyslipidemia and cardiovascular disease . A series of studies , such as the NIPPON DATA ( National Integrated Project for Prospect i ve Observation of Non-communicable Disease and Its Trends in the Aged ) cohort study of a representative sample of Japanese , have greatly increased existing evidence . NIPPON DATA 80 revealed a clear positive relationship between TC and CAD , and indicated that reverse causality between hypocholesterolemia and liver disease may increase all-cause mortality in hypocholesterolemic Japanese . NIPPON DATA 90 showed that serum high-density lipoprotein cholesterol ( HDL-C ) was inversely associated with all-cause mortality , even when HDL-C was very high . NIPPON DATA 80 revealed that low-normal levels of serum albumin and TC are associated with a decline in activity during old age , especially in women . The Suita study —a unique cohort study of urban residents — showed that LDL-C and non – HDL-C were equally accurate in predicting the incidence of myocardial infa rct ion . Further research of this quality is needed to ascertain the public health burden of dyslipidemia in Japan",
"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",
"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",
"In a cross-over experiment the effect of short-term vegetarianism on serum lipids , lipoproteins and apoproteins was studied . The experimental diet was free of animal products , with the exception of skim milk , and consequently low in saturated fat and cholesterol . Fifteen free-living individuals were r and omly assigned to 3-week periods on either the experimental diet or a control diet which closely approximated the usual intake in the U.S.A. Significant reductions in total cholesterol ( 12.5 % ) , low density lipoprotein cholesterol ( 14.7 % ) , and apo B ( 13.2 % ) were observed , accompanied by a non-significant decrease in high density lipoprotein cholesterol ( 10 % ) , apo A-I ( 3 % ) and a non-significant increase in apo-II ( 4 % ) . These data suggest that a fat-modified diet low in total fat , saturated fat and cholesterol , and moderate ( not high ) in polyunsaturated fat may not lower HDL-C or its apoproteins as much as a diet high in polyunsaturated fat , while having similar effects on LDL-C , and would therefore be preferable as the basis for primary prevention of atherosclerosis"
] |
4116c414-06ff-11f0-808a-c43d1ab1c353
|
INTRODUCTION Chromium is an essential trace mineral for carbohydrate and lipid metabolism , which is currently prescribed to control diabetes mellitus . Results of previous systematic review s and meta-analyses of chromium supplementation and metabolic profiles in diabetes have been inconsistent . AIM The objective of this meta- analysis was to assess the effects on metabolic profiles and safety of chromium supplementation in type 2 diabetes mellitus and cholesterol . METHODS Literature search es in PubMed , Scopus and Web of Science were made by use of related terms-keywords and r and omized clinical trials during the period of 2000 - 2014 . RESULTS Thirteen trials fulfilled the inclusion criteria and were included in this systematic review . Total doses of Cr supplementation and brewer 's yeast ranged from 42 to 1,000 μg/day , and duration of supplementation ranged from 30 to 120 days . The analysis indicated that there was a significant effect of chromium supplementation in diabetics on fasting plasma glucose with a weighted average effect size of -29.26 mg/dL , p = 0.01 , CI 95 % = -52.4 to -6.09 ; and on total cholesterol with a weighted average effect size of -6.7 mg/dL , p = 0.01 , CI 95 % = -11.88 to -1.53 . CONCLUSIONS The available evidence suggests favourable effects of chromium supplementation on glycaemic control in patients with diabetes
|
[
"The aim of this study was to determine the effect of chromium (Cr)-enriched yeast on blood glucose and insulin variables , blood lipids , and blood markers of oxidative stress in persons with type 2 diabetes mellitus ( median duration : 3.0 yr ) . Thirty-six subjects ( 9 men , 27 women ; mean age : 61.3 yr ; mean body mass index : 34.33 kg/m2 ) were supplemented with 400 μg Cr/d as Cr-enriched yeast ( n=19 ) or placebo ( n=17 ) for 12 wk in a r and omized , double-blind study . The most interesting results were obtained by comparison of the change in the placebo group to the change in the Cr group . The Cr group showed a significantly greater increase in serum Cr compared to the placebo group ( p decrease in fasting serum glucose compared to placebo ( p ) . Blood markers of oxidative stress glutathione peroxidase activity and levels of reduced glutathione were essentially unchanged in the Cr group after 12 wk , but decreased significantly in the placebo group ( p respectively ) , Serum HbA1c and glycated protein ( fructosamine ) were essentially unchanged in the Cr group , whereas HbA1c tended to increase in the placebo group ( from 6.94 % to 7.11 % ) . Fasting serum insulin decreased in both groups , with a greater tendency in the Cr group ( −16.5 % vs −9.5 % ) . These data suggest that supplementation of well-controlled type 2 diabetics with Cr-enriched yeast is safe and can result in improvements in blood glucose variables and oxidative stress",
"OBJECTIVE —Chromium treatment has been reported to improve glycemic control in patients with type 2 diabetes . However , concern exists about the possible toxic effects of chromium picolinate . The aim of this study was to determine the effect of chromium treatment in the form of chromium yeast on glycemic control in a Western population of patients with type 2 diabetes who were being treated with oral hypoglycemic agents . RESEARCH DESIGN AND METHODS —In this 6-month , double-blind study , patients with moderate glycemic control , being treated with oral hypoglycemic agents , were r and omly assigned to receive either a placebo or treatment with 400 μg of chromium daily in the form of chromium yeast . The primary efficacy parameter was a change in A1C . Secondary end points were changes in lipid profile , BMI , blood pressure , body fat , and insulin resistance . RESULTS —No differences were found for the change in A1C between the intervention and placebo groups , nor were any differences found between the groups for the secondary end points . CONCLUSIONS —There is no evidence that chromium in the form of chromium yeast is effective in improving glycemic control in Western patients with type 2 diabetes who are taking oral hypoglycemic agents",
"PROJECT Chromium is an essential nutrient involved in normal carbohydrate and lipid metabolism . It influences glucose metabolism by potentiating the action as taking part in insulin signal amplification mechanism . A placebo-controlled single blind , prospect i ve study was carried out to investigate the effect of chromium supplementation on blood glucose , HbA(1)C and lipid profile in newly onset patients with type-2 diabetes . PROCEDURE Total 40 newly onset type-2 diabetics were selected and after 1 month stabilization further r and omly divided into two groups viz . study group and placebo group . The study group received 9 g brewer 's yeast ( 42 μg Cr ) daily and the other placebo group received yeast devoid of chromium for 3 months . Subjects were instructed not to change their normal eating and living habits . Fasting blood glucose , HbA(1)C and lipid profile were analyzed at beginning and completion of the study . RESULTS Results revealed that fasting blood glucose level significantly reduced in the subjects consuming yeast supplemented with chromium ( 197.65±6.68 to 103.68±6.64 mg/dL ; p ) . HbA(1)C values improved significantly from 9.51±0.26 % to 6.86±0.28 % ; p better glycaemic control . In experimental group total cholesterol , TG and LDL levels were also significantly reduced from 199.66±3.11 to 189.26±3.01 mg/dL ; p effect of chromium supplementation on glycaemic control and lipid variables in subjects with newly onset type-2 diabetes",
"OBJECTIVE Chromium treatment has been reported to improve glycemic control and insulin sensitivity in specific population s of patients with type 2 diabetes . The aim of this study was to determine the effect of chromium treatment on glycemic control in a Western population of insulin-dependent patients with type 2 diabetes . RESEARCH DESIGN AND METHODS In this 6-month double-blind study , patients with an HbA(1c ) ( A1C ) > 8 % and insulin requirements of > 50 units/day were r and omly assigned to receive treatment with placebo or 500 or 1,000 mug chromium daily in the form of chromium picolinate . The primary efficacy parameter was a change in A1C . Secondary end points were changes in lipid profile , BMI , blood pressure , and insulin requirements . RESULTS In this per- protocol analysis ( n = 46 ) , the decrease in A1C was approximately equal across the three groups ( 0.4 % ) . All patients had a BMI > 25 kg/m(2 ) . No differences were found in the secondary end points . We found a weak relationship between an increasing serum chromium concentration and improvement of the lipid profile . CONCLUSIONS There is no evidence that high-dose chromium treatment is effective in obese Western patients with type 2 diabetes",
"Background : The atherogenic index of plasma ( AIP ) , defined as logarithm [ log ] of the ratio of plasma concentration of triglycerides to high-density lipoprotein ( HDL ) cholesterol , has recently been proposed as a predictive marker for plasma atherogenicity and is positively correlated with cardiovascular disease risk . The nutrient combination of chromium picolinate and biotin ( CPB ) has been previously shown to reduce insulin resistance and hyperglycemia in patients with type 2 diabetes ( T2DM ) . Methods : Thirty-six moderately obese subjects with T2DM and with impaired glycemic control were r and omized to receive CPB or placebo in addition to their oral hyperglycemic agents for 4 weeks . Measurements of blood lipids ( including ratio of triglycerides to HDL cholesterol ) , fructosamine , glucose , and insulin were taken at baseline and after 4 weeks . Results : At the final visit , the active group had a significantly lower AIP compared to the placebo group ( P triglyceride level ( P ratio of low-density lipoprotein ( LDL ) to HDL cholesterol ( P urinary chromium levels were inversely correlated with the change in AIP ( P Urinary chromium levels were significantly increased in the CPB group . In the CPB group , glucose levels decreased at 1 hour and 2 hours and glucose area under the curve and fructosamine level were significantly decreased . Ratios of total to HDL cholesterol , LDL to HDL cholesterol , and non-HDL to HDL cholesterol were significantly decreased between the treatments at final visit . No significant adverse events were observed in the CPB or placebo groups . Conclusions : These results suggest that the combination of chromium picolinate and biotin may be a valuable nutritional adjuvant therapy to reduce AIP and correlated CVD risk factors in people with T2DM",
"BACKGROUND Pre clinical studies have shown that the combination of chromium picolinate and biotin significantly enhances glucose uptake in skeletal muscle cells and enhances glucose disposal . The present pilot study was conducted to determine if supplementation with chromium picolinate and biotin can improve glycemic control in patients with type 2 diabetes mellitus with suboptimal glycemic control despite use of oral antihyperglycemic agents . METHODS Forty-three subjects with impaired glycemic control ( 2-h glucose > 200 mg/dL ; glycated hemoglobin > or=7 % ) , despite treatments with oral antihyperglycemic agents , were r and omized to receive 600 microg of chromium as chromium picolinate and biotin ( 2 mg/day ) ( Diachrome ( , Nutrition 21 , Inc. , Purchase , NY ) in addition to their pre study oral antihyperglycemic agent therapy . Measurements of glycemic control and blood lipids were taken at baseline and after 4 weeks . RESULTS After 4 weeks , there was a significantly greater reduction in the total area under the curve for glucose during the 2-h oral glucose tolerance test for the treatment group ( mean change -9.7 % ) compared with the placebo group ( mean change + 5.1 % , P fructosamine ( P triglycerides ( P triglycerides/ high-density lipoprotein cholesterol ratio ( P adverse events were attributed to chromium picolinate and biotin supplementation . CONCLUSIONS This pilot study demonstrates that supplementation with a combination of chromium picolinate and biotin in poorly controlled patients with diabetes receiving antidiabetic therapy improved glucose management and several lipid measurements . Chromium picolinate/ biotin supplementation may represent an effective adjunctive nutritional therapy to people with poorly controlled diabetes with the potential for improving lipid metabolism",
"Background : Brewer 's yeast may have beneficial effects on insulin receptors because of itsglucose tolerance factor in diabetic patients . This study was conducted to investigate the effects of brewer 's yeast supplementation on glycemic indices in patients with type 2 diabetes mellitus . Methods : In a r and omized double-blind controlled clinical trial , 84 adults ( 21 men and 63 women ) aged 46.3 ± 6.1 years old with type 2 diabetes mellitus were recruited and divided r and omly into two groups : Supplement group receiving brewer 's yeast ( six 300 mg tablets/day , total 1800 mg ) and control group receiving placebo ( six 300 mg tablets/day ) for 12 weeks . Body weight , height , body mass index , food consumption ( based on 24h food record ) , fasting blood sugar ( FBS ) , glycosylated hemoglobin , insulin sensitivity , and insulin resistance were measured before and after the intervention . Data analysis was performed using the Statistical Package for Social Sciences ( version 18.0 ) . Results : The changes in FBS , glycosylated hemoglobin , and insulin sensitivity were significantly different between the two groups during the study ( respectively P difference in FBS , glycosylated hemoglobin , and insulin sensitivity at the end of the study between the two groups after removing the effects of baseline values ( respectively P = 0.002 , P Changes in body mass index , 24h food record , insulin resistance were not significant . Conclusions : Dietary supplementation with brewer›s yeast besides the usual treatment of diabetes can ameliorate blood glucose variables in type 2 diabetes mellitus",
"Chromium supplements are thought to be the second most commonly taken nutritional supplement , used by an estimated 10 million Americans ( 1 ) . Chromium is an essential element in humans , and deficiency is associated with the development of diabetes , which was first noted in patients receiving long-term parenteral nutrition before the advent of routine chromium supplementation ( 2,3 ) . In these patients , diabetes resolved following chromium replacement ( 2–4 ) . The dietary requirement for chromium is controversial , with the recommended daily intake in the U.S. being 0.05–0.20 μg ( 5 ) . Chromium is abundant in the environment ; however , aside from the extreme situation of unsupplemented parenteral nutrition , it has proven difficult to ascertain any clinical effects , due solely to chromium deficiency . Despite these difficulties , chromium supplements are widely promoted in the complementary health industries . There are many studies examining the effects of various forms of chromium supplementation ( rev . in 6,7 ) . These studies utilized a variety of chromium formulations , varying doses , and patients with normal glucose tolerance , diabetes , or gestational diabetes . The outcomes have been inconsistent . Some studies showed no benefit , and other studies have shown inconsistent improvements in glucose , insulin resistance , and /or lipids . The paucity of data has prompted the National Institutes of Health to release a program announcement to address the issue : “ Chromium as an adjuvant therapy",
"SCOPE Chromium and cysteine supplementation have been shown to improve glucose metabolism in animal studies . This study examined the hypothesis that chromium dinicocysteinate ( CDNC ) , a complex of chromium and l-cysteine , is beneficial in lowering oxidative stress , vascular inflammation , and glycemia in type 2 diabetic subjects . METHODS AND RESULTS Type 2 diabetic subjects enrolled in this study were given placebo for 1 month for stabilization and then r and omized into one of three groups : placebo ( P ) , chromium picolinate ( CP ) , or CDNC , after which they received daily oral supplementation for 3 months . Of the 100 patients enrolled in the study , 74 patients completed it . There were 25 patients in the P supplemented group , 25 in the CP supplemented and 24 in the CDNC supplemented group who completed the study . Blood markers of glycemia , vascular inflammation , HOMA insulin resistance , and oxidative stress were determined at r and omization and after 3 months of supplementation with P , CP , or CDNC . There was a significant decrease at 3 months in insulin resistance ( p = 0.02 ) and in the levels of protein oxidation ( p = 0.02 ) and TNF-α ( p = 0.01 ) in the CDNC supplemented cohort compared to baseline . However , there was no statistically significant change in these markers in the CP supplemented group compared to baseline . Insulin levels significantly decreased ( p = 0.01 ) for subjects receiving CDNC but not CP . There was no significant impact of supplementation on HbA(1c ) or glucose levels in either of the groups . CONCLUSION CDNC supplementation lowers insulin resistance by reducing blood levels of TNF-α , insulin , and oxidative stress in type 2 diabetic subjects . Therefore , CDNC supplementation has potential as an adjunct therapy for individuals with type 2 diabetes",
"The aim of this study is to evaluate the effect and safety of chromium-containing milk powder in patients with type 2 diabetes mellitus . A r and omized , double-blind , placebo-controlled trial was conducted in Taiwan . A total of 60 patients with type 2 diabetes mellitus , aged 30 to 75 years , and on a dose of gliclazide sulfonylurea agent ( Their glycosylated hemoglobin ranged from 7.5 % to 12 % , fasting plasma glucose ( FPG ) from 140 to 250 mg/dL , and body mass index from 20 to 35 kg/m(2 ) . The subjects were divided into 2 groups , one group to receive chromium-containing milk powder ( chromium 200 microg/20 g milk powder ) and the other to receive placebo twice a day for 16 weeks . Frequently sample d intravenous glucose tolerance test ( IVGTT ) was performed before and after treatment . The chromium group demonstrated a lower FPG and fasting insulin ( -38.1 + /- 9.2 vs 63 + /- 8 . 5 mg/dL and -1.7 + /- 0.2 vs 1.9 + /- 0.3 microU/mL , respectively ; P Lower glycosylated hemoglobin was observed in chromium-treated male patients ( -1.1 + /- 0 . 5 vs 0.7 + /- 0 . 2 ; P metabolic parameters ( lipid profiles including total cholesterol , triglyceride , low-density lipoprotein cholesterol , and high-density lipoprotein cholesterol ) , except improvement of insulin resistance ( homeostasis model assessment for insulin resistance and insulin sensitivity index from frequently sample d intravenous glucose tolerance test ) observed in male patients ( -2.1 + /- 1.1 vs -0.41 + /- 1.12 and 0.18 + /- 0.11 vs -0.15 + /- 0 . 2 , respectively ; P adverse events in both groups , except for mild complaints in the chromium group on constipation ( 5 % ) and flatulence ( 5 % ) . Intake of milk powder containing 400 microg/d of chromium for 16 weeks in subjects with type 2 diabetes mellitus result ed in lowering of FPG , fasting insulin , and improvement of metabolic control in male patients",
"Objective : To investigate the effect of chromium nicotinate supplementation on insulin sensitivity , glycemic control , and lipid profile in subjects with type 2 diabetes . Material s and Methods : In a double-blind clinical trial , 56 overweight individuals with type 2 diabetes were r and omized into 3 groups : placebo ( NC0 ) , 50 μg ( NC50 ) , and 200 μg ( NC200 ) of chromium as chromium nicotinate . Chromium status , sensitivity to insulin , glycemic control , and lipid profile were assessed at the beginning of the study and 45 days and 90 days after . Results : In the beginning , most subjects showed low concentrations of serum chromium ( 71.88 % ) , regular levels of urinary chromium ( 80.65 % ) , and insulin resistance ( 73.80 % ) . The serum chromium concentrations did not differ among the groups over time ( p = 0.2549 ) . The changes in serum chromium and urine concentrations did not relate to changes in fasting glucose ( p > 0.05 ) . At 90 days of intervention , there was no significant difference between groups in fasting glucose , glycosylated hemoglobin , homeostasis model assessment insulin resistance ( HOMA-IR ) , total cholesterol , and low-density lipoprotein ( LDL ) ; there was increase in homeostasis model assessment β-cell function ( HOMA-β ; p = 0.0349 ) and high-density lipoprotein ( HDL ; p = 0.0425 ) in the NC0 group and a reduction of triglycerides in the NC0 ( p = 0.0177 ) and NC50 ( p = 0.0336 ) groups . Conclusion : Supplementation at 50 and 200 μg of chromium as chromium nicotinate did not promote glycemic control , increase insulin sensitivity , or change the lipid profile of subjects with diabetes"
] |
4116c450-06ff-11f0-808a-c43d1ab1c353
|
PURPOSE In Asian countries , low-dose tamsulosin ( 0.2 mg ) is used widely but this dose has been less popular than 0.4 mg tamsulosin or other types of alpha blockers . The aim of this study was to investigate the efficacy and safety of low-dose tamsulosin by systematic review and meta- analysis . METHODS We conducted a meta- analysis of improvements of lower urinary tract symptoms using International Prostate Symptom Score ( IPSS ) , maximal urinary flow rate ( Qmax ) , post-voided residual volume ( PVR ) , and quality of life ( QOL ) . Relevant studies were found using MEDLINE , Embase , and the Cochrane library . Final inclusion was determined by r and omized controlled trials ( RCT ) and performance of IPSS . RESULTS A total of fourteen studies were included , with a total sample size of 2147 subjects ( 1044 experimental and 1103 controls ) . Study duration s ranged from 4 to 52 weeks . The mean change of IPSS improvement from baseline for tamsulosin was -7.18 ( 95 % CI : -7.83 , -6.54 ) . The mean change of QOL improvement from baseline was -1.34 ( 95 % CI : -1.46 , -1.22 ) . The overall Qmax improvement from baseline was 2.32 ml/sec ( 95 % CI : 1.95 , 2.70 ) . The mean change of PVR improvement from baseline was -11.12 ml ( 95 % CI : -17.61 , -4.64 ) . Regarding safety , four studies did not report any adverse events while others reported that adverse events were all tolerated . CONCLUSIONS Although this study did not consider placebo effect and has high IPSS baseline scores , this study clarifies that low-dose tamsulosin has generally positive effect and safety in treatment of LUTS and could be a suitable option as an initial treatment , especially for patients with low body mass index , as is typical of Asian people
|
[
"PURPOSE We evaluated the long-term ( up to 6 years ) safety and efficacy of the selective alpha 1A-adrenoceptor antagonist tamsulosin in patients with lower urinary tract symptoms associated with benign prostatic hyperplasia . MATERIAL S AND METHODS A total of 609 patients were enrolled in a 4-year multicenter open label extension study . Subjects entered the study after completion of a 1-year open label trial that included patients who previously completed up to 57 weeks of double-blind , placebo controlled studies . Maintenance doses ( 0.4 or 2 x 0.4 mg daily ) established in the 1-year study were continued . Efficacy and safety were assessed every 3 months . Primary efficacy evaluations were changes from baseline maximum urine flow rate and total American Urological Association symptom index , and the responder rates for those 2 end points . Secondary end points were changes in American Urological Association subset scores , Boyarsky symptom scores , average urine flow rate , post-void residual urine volume , quality of life index and investigator global assessment . RESULTS Of the 609 patients who entered the 4-year extension study 159 had a 2-year or greater prior experience with tamsulosin , yielding a potential 6-year experience on the medication . Of this 159 patient subset 109 completed the whole 6 years . Initial rapid improvements from baseline in primary and secondary end points were maintained each year throughout the duration of the study . Tamsulosin was well tolerated , confirming the safety profile demonstrated in earlier studies . Orthostatic hypotension was observed in 1.3 % of the patients . CONCLUSIONS This study demonstrates the sustained efficacy , safety and excellent long-term tolerability of tamsulosin for up to 6 years in patients with lower urinary tract symptoms associated with benign prostatic hyperplasia",
"AIMS To evaluate the efficacy and treatment satisfaction with low-dose ( 0.2 mg ) tamsulosin in patients with symptomatic benign prostatic hyperplasia ( BPH ) , and to investigate individual lower urinary tract symptoms according to treatment satisfaction . METHODS A cross-sectional study was conducted in a total sample of 2574 patients from multiple centres . International Prostate Symptom Score ( IPSS ) , prostate volume , uroflowmetry and combined medications were review ed . Detailed question naires were used to assess treatment satisfaction and IPSS 8 weeks after treatment with low-dose tamsulosin . RESULTS After 8 weeks of treatment with low-dose tamsulosin , IPSS improved significantly . Among the 2574 patients , 1,630 ( 63.42 % ) were satisfied and 940 patients ( 36.50 % ) were dissatisfied with low-dose tamsulosin . The reasons for dissatisfaction included efficacy problems ( 84.66 % ) and side effects ( 3.72 % ) . Treatment satisfaction was affected by symptom duration , baseline IPSS , and prostate size ( p = 0.0441 , IPSS voiding ( IPSS-V ) and IPSS storage ( IPSS-S ) after treatment differed significantly depending on the degree of satisfaction ( p IPSS-V after treatment did not improve in patients who were ' not satisfied ' or ' totally not satisfied ' ( p = 0.170 , 0.240 , respectively ) . All the individual IPSS items except urgency ( p = 0.1436 ) varied significantly with the degree of satisfaction ( p low-dose tamsulosin improved IPSS , but more than one-third of patients were dissatisfied with the treatment . The main reason for dissatisfaction was efficacy problems , and the degree of satisfaction was related to symptom duration , baseline IPSS , and prostate size , and also to IPSS-V. In patients with severe LUTS , the tamsulosin dose should be increased earlier",
"BACKGROUND Tamsulosin hydrochloride can significantly improve benign prostatic hyperplasia ( BPH ) symptoms after the first dose and achieve long-term efficacy in European and American population s ; however , the corresponding studies from China are rarely seen . The purpose of this study was to evaluate the long-term efficacy and safety of tamsulosin hydrochloride 0.2 mg once daily in patients with lower urinary tract symptoms ( LUTS ) suggestive of BPH in China . METHODS Chinese patients with LUTS suggestive of BPH were enrolled in a 4-week placebo run-in period and subsequent 60-week open-label study . Tamsulosin hydrochloride 0.2 mg was administered daily during the period of the study . The efficacy and safety parameters were evaluated at the end of treatment period I ( 0 - 12 weeks ) and period II ( 13 - 60 weeks ) . The BPH patients were divided into tamsulosin monotherapy group and combination therapy group which received concomitant medication of finasteride 5 mg once daily after the evaluation at the end of treatment period I. RESULTS A total of 113 patients were recruited to the study . Eighty-two patients received tamsulosin monotherapy and twenty-nine received combination therapy during the treatment period II . Tamsulosin hydrochloride produced a great improvement in mean maximum urinary flow rate ( Q(max ) ) ( 1.7 ml/s , 3 ml/s ) and a significant decrease in mean international prostate symptom score ( IPSS ) ( 4.1 , 6.4 ) after 12-week and 60-week treatments , respectively . At the end of treatment period II , there were significant improvement in IPSS , quality of life ( QOL ) score , Q(max ) and average flow rate ( Q(ave ) ) for combination therapy group compared with the treatment period I ( all P No serious adverse events ( SAE ) were recorded during the study . CONCLUSION Long-term tamsulosin hydrochloride therapy is a safe , effective and well-tolerated method for the treatment for LUTS suggestive of BPH in China",
"OBJECTIVE To determine whether transrectal ultrasonography ( TRUS ) can predict the clinical response of patients with benign prostatic hypertrophy ( BPH ) to alpha 1-blocker and anti- and rogen therapy . PATIENTS AND METHODS From April 1994 to July 1995 , 128 patients with BPH were r and omized to treatment for 6 months with either tamsulosin ( a long-acting selective alpha 1-blocker ) or allylestrenol ( an anti- and rogen ) , with 64 patients receiving tamsulosin ( 0.2 mg/day ) and 64 receiving allylestrenol ( 50 mg/day ) . The results of TRUS , uroflowmetry and the American Urologic Association ( AUA ) symptom score were compared before and after treatment . TRUS was used to calculate the transition zone ( TZ ) volume , transition zone ratio ( TZ ratio = TZ volume/total prostate volume ) , total prostate volume and prostate-specific antigen density ( PSAD ) . RESULTS Both groups showed a statistically significant improvement in the AUA symptom score , quality -of-life ( QOL ) score and peak urinary flow rate ( Qmax ) at 6 months ( P tamsulosin group , there was a significant negative correlation between the pretreatment PSAD and the percentage change in Qmax ( r = -0.640 , P percentage change in the AUA symptom score ( r = 0.589 , P allylestrenol group showed a significant positive correlation between PSAD and the percentage change in Qmax ( r = 0.397 , P AUA symptom score ( r = -0.313 , P anti- and rogen therapy , while those with a low PSAD responded better to alpha 1-blocker therapy",
"Purpose To compare the efficacy and safety of Sulosin D ( PACIFICPHARMA , Korea ) and Harnal D ( ASTELLAS PHARMA KOREA , Korea ) in treating patients with lower urinary tract symptoms associated with benign prostatic hyperplasia ( BPH ) . Material s and Methods This r and omized , controlled , open-label , multicenter non-inferiority study was conducted at four sites in Korea . We r and omly assigned 123 patients with an International Prostate Symptom Score ( IPSS ) ≥12 to receive either Sulosin D or Harnal D treatment for 8 weeks . The primary outcome was the mean change in IPSS from baseline to endpoint . Secondary outcomes were the mean change from baseline to endpoint in IPSS quality of life subscores , maximum uroflowmetry ( Qmax ) , and post-voiding residuals ( PVR ) . Results In all , 123 patients were r and omly assigned ( 60 Sulosin D and 63 Harnal D ) . The changes in the total IPSS from baseline in the Sulosin D- and Harnal D-treated groups were -4.97 and -4.03 , respectively . There were significant decreases compared with baseline in both groups . The mean difference ( Sulosin D - Harnal D ) was -0.91 ( with a two-sided 90 % confidence interval ) , inferring that Sulosin D was not inferior to Harnal D. The mean changes in the IPSS subscore , Qmax , and PVR from baseline were comparable between the groups ( both p>0.05 ) . During the treatment periods , the incidence of adverse events was 23.33 % and 34.92 % in the Sulosin D and Harnal D groups , respectively ( p=0.1580 ) . Conclusions We demonstrate the non-inferiority of Sulosin D to Harnal D in patients with lower urinary tract symptoms associated with BPH",
"OBJECTIVES To evaluate the long-term efficacy and safety of once-daily tamsulosin ( 0.4 and 0.8 mg ) , a unique selective alpha1A-adrenoceptor antagonist in patients with benign prostatic hyperplasia ( BPH ) . METHODS This trial extended a 13-week , Phase III multicenter placebo-controlled , double-blind outpatient trial for an additional 40 weeks . Of 618 patients , 418 ( 68 % ) continued into the extension phase on the same double-blind medication and dose . The primary efficacy parameters were total American Urological Association ( AUA ) symptom score and maximum urinary flow ( Qmax ) . RESULTS The mean changes in AUA symptom score from baseline to end point were statistically significant in all groups ( P Qmax for both tamsulosin groups but not for the placebo group . The statistically significant improvements from baseline in efficacy parameters observed for each tamsulosin group at the end of the 13-week Phase III trial were maintained during the long-term extension phase . Tamsulosin at both dosages was well tolerated as maintenance therapy . Clinical ly significant orthostatic hypotension was not observed . Vital sign changes in either hypertensive or normotensive patients were not clinical ly significantly different across the three groups . CONCLUSIONS Tamsulosin once-daily at 0.4 or 0.8 mg was shown to be effective , safe , and well tolerated in the target BPH population during long-term use",
"To examine the clinical usefulness of selective and non-selective alpha 1-adrenoceptor antagonists , we compared a selective ( tamsulosin ) and non-selective ( terazosin ) alpha 1-adrenoceptor antagonists in the treatment of Chinese patients with benign prostatic hyperplasia ( BPH ) . The study was a single-blind , r and omized , multicenter design to compare a fixed dose of tamsulosin ( 0.2 mg ) or terazosin ( 2 mg ) given once daily after breakfast for four weeks . A total of 212 patients were enrolled with 201 patients included in the analysis . The primary variables assessed were changes in total International Prostatic Symptom Score ( IPSS ) , maximum urinary flow rate ( Qmax ) , and average urinary flow rate ( AFR ) four weeks after dosing . Adverse events were recorded through the treatment period . Both tamsulosin and terazosin produced significant improvements in total IPSS ( total score of 11.8 + /- 4.5 ; decrease in 45.1 % and total score of 13.3 + /- 5.3 ; decrease in 39.0 % , respectively ) ( p Qmax ( 13.2 + /- 4.1 mL/s , 37.5 % increase and 13.6 + /- 3.6 mL/s , 30.8 % increase , respectively ) ( p AFR ( 7.7 + /- 3.3 mL/s , 37.5 % increase and 7.8 + /- 3.1 mL/s , 25.8 % increase , respectively ) ( p Tamsulosin was superior to terazosin in improvement of total IPSS ( p incidence of adverse events by administration of tamsulosin was less than that by terazosin ( 13 and 50 , respectively ; p dizziness ( p hypotension ( p terazosin were significantly greater than that by tamsulosin . Both systolic and diastolic blood pressure of sitting position decreased significantly in patients treated with terazosin ( p tamsulosin , a selective alpha 1A-adrenoceptor antagonist , was superior to terazosin , a non-selective alpha 1-adrenoceptor antagonist , in efficacy and adverse events in patients with symptomatic BPH",
"This section contains papers from Japan , Austria , the UK , and joint papers from France , Denmark , Switzerl and , Australia and the USA . A wide variety of lower urinary tract topics is covered , from BPH to overactive bladder and urodynamic stress incontinence",
"A prospect i ve r and omized controlled study was performed to compare the clinical effects of naftopidil and tamsulosin . Men complaining of lower urinary tract symptoms due to benign prostatic hyperplasia were r and omized into two groups : one receiving 50 mg naftopidil once daily ( Naf group , n=36 patients ) , and the other receiving 0.2 mg tamsulosin once daily ( Tam group , n=32 patients ) . In the Naf group at 12 weeks , 7 items of the International Prostate Symptom Score ( IPSS ) , storage and voiding symptoms , total IPSS , quality of life ( QOL ) index ( QOLI ) and Qmax were improved significantly . In the Tam group at 12 weeks , 6 items of IPSS except urgency , storage and voiding symptoms , total IPSS , QOLI and Qmax were improved significantly . Improvement of residual urine volume ( PVR ) was insignificant in both groups . In intergroup comparison between the Naf and the Tam groups , variations of 7 items of IPSS , storage and voiding symptoms , total IPSS , QOLI , Qmax and PVR at 4 and 12 weeks after treatment were not statistically significant . There was almost no difference in clinical efficacy between Naf and Tam",
"PURPOSE We assessed the impact of intermittent tamsulosin treatment on abnormal ejaculation . MATERIAL S AND METHODS This prospect i ve study was performed between January 2001 and December 2004 . It included 405 patients who were at least 50 years old with lower urinary tract symptoms . This study was divided into 2 phases . In phase 1 patients received a 0.4 mg tamsulosin capsule daily after breakfast for at least 3 months . The second phase of this study was performed in the 30 patients with abnormal ejaculation . In this phase these patients received 0.4 mg tamsulosin once daily every other day . Patients were assessed at study entry and at study week 6 . RESULTS Abnormal ejaculation was reported as retro grade ejaculation by 18 patients , as decreased volume by 7 and as absent ejaculate by 5 . Ejaculatory function recovered during intermittent tamsulosin treatment in 12 patients with retro grade ejaculation and in 7 with decreased volume or absent ejaculate . As a result , 19 of 30 patients ( 63.3 % ) with abnormal ejaculation recovered . A significant improvement in retro grade ejaculation was found after intermittent tamsulosin treatment ( p = 0.02 ) . Although there were improvements in decreased volume or absent ejaculate at week 6 of intermittent treatment , these differences were not statistically significant ( p = 0.42 and 0.61 , respectively ) . CONCLUSIONS The results of the current study , which to our knowledge is the first report of the effect of intermittent tamsulosin treatment on abnormal ejaculation , show that this treatment modality is well tolerated and provides comparable improvements for abnormal ejaculation",
"OBJECTIVE To compare the efficacy and safety of a fixed dose ( 0.2 mg ) of tamsulosin , a selective alpha 1A-adrenoreceptor antagonist , with an increasing dose ( 1 - 5 mg ) of terazosin , a non-selective antagonist , in the treatment of urinary outflow obstruction associated with benign prostatic hyperplasia ( BPH ) in Korean patients . PATIENTS AND METHODS The study comprised a single-blind and r and omized design with tamsulosin or terazosin taken once daily for 8 weeks . A total of 98 patients was enrolled , with 72 patients included in the analyses after 4 and 8 weeks . The primary variables assessed were changes in the maximum urinary flow rate Qmax and the total International Prostate Symptom Score ( IPSS ) , with the post-void residual urine volume , ' obstructive ' and ' irritative ' questions in the IPSS , and the investigators ' global assessment of efficacy also determined . The number of patients with a clinical ly significant response to treatment with tamsulosin or terazosin was determined and defined as those with > 20 % improvement from the baseline Qmax or > 20 % decrease in total IPSS . Adverse reactions possibly or probably related to study medication were recorded throughout the treatment period . RESULTS Both tamsulosin and terazosin produced similar significant improvements in subjective and objective symptoms of urinary outflow obstruction ( P > 0.05 ) . Systolic and diastolic ( st and ing ) blood pressures decreased significantly in patients treated with terazosin ( P dry mouth and dizziness which were usually mild and transient , were significantly higher in patients on terazosin ( 18 patients , versus one on tamsulosin , P . CONCLUSION Tamsulosin was as effective as terazosin in treating urinary outflow obstruction associated with BPH , but had a markedly better safety profile",
"Objective To compare the efficacy and safety of an incremental‐dose regimen of terazosin ( 1–2 mg daily ) and a fixed‐dose regimen of tamsulosin ( 0.2 mg daily ) , on Japanese patients with symptomatic benign prostatic hyperplasia ( BPH )",
"Introduction : To investigate the incidence of ejaculatory disorders caused by naftopidil and tamsulosin in patients with lower urinary tract symptoms ( LUTS ) suggestive of benign prostatic hyperplasia ( BPH ) . Material s and Methods : Ninety-five patients with LUTS/BPH who had International Prostate Symptom Scores ( IPSS ) of 8 or more were r and omly assigned to receive naftopidil ( 50 mg/day , n = 48 ) or tamsulosin ( 0.2 mg/day , n = 47 ) . Before and 12 weeks after treatment , a question naire was used to evaluate ejaculation . Results : Among men who had sexual activity during the 12 weeks , the proportion who reported an abnormal feeling on ejaculation was higher in the tamsulosin group ( 16.7 % ) than in the naftopidil group ( 7.4 % ) , although the difference was not significant ( p = 0.402 ) . The proportion of men who reported reduced ejaculatory volume after treatment was significantly higher in the tamsulosin group ( 96.0 % ) than in the naftopidil group ( 73.1 % , p = 0.0496 ) . On the other h and , the improvements in IPSS and the quality of life index were significantly higher in the tamsulosin group than in the naftopidil group . Conclusions : Tamsulosin may cause a higher incidence of ejaculatory disorders than naftopidil , although the efficacy of 0.2 mg tamsulosin may be better than that of 50 mg naftopidil",
"OBJECTIVE To evaluate the efficacy and safety of tamsulosin 0.4 mg once daily ( as a modified-release formulation ) compared with placebo in patients with benign prostatic enlargement , lower urinary tract symptoms and prostatic ' obstruction ' ( symptomatic benign prostatic hyperplasia [ BPH ] ) . PATIENTS AND METHODS Of 313 patients with symptomatic BPH enrolled in a 2-week placebo run-in period , 296 were subsequently r and omized to receive either placebo ( 98 patients ) or tamsulosin 0.4 mg once daily ( 198 patients ) for 12 weeks . The primary variables assessed to determine efficacy were maximum urinary flow rate ( Qmax ) from free-flow measurements and the total Boyarsky symptom score . RESULTS Tamsulosin produced greater improvements in Qmax ( 1.4 mL/s , 13.1 % ) than did placebo ( 0.4 mL/s , 3.8 % ) ( P = 0.028 ) and a greater decrease in total symptom score ( 3.4 points , 35.8 % reduction ) than did placebo ( 2.2 points , 23.7 % reduction ) ( P = 0.002 ) . Significantly more tamsulosin-treated patients ( 67 % ) than placebo-treated patients ( 44 % ) had a > or = 25 % decrease in total symptom score after 12 weeks ( P tamsulosin for 12 weeks also produced significant improvements in average urinary flow rate ( P = 0.040 ) , irritative ( P = 0.013 ) and obstructive ( P = 0.014 ) symptom scores and symptoms of nocturia ( P = 0.022 ) and hesitancy ( P = 0.004 ) . Tamsulosin was tolerated well by the patients . The incidence of adverse events emerging during treatment was comparable in the tamsulosin- and placebo-treated groups ( 34 % and 24 % respectively , P = 0.109 ) , as was the incidence of cardiovascular-related adverse events ( 5 % and 7 % respectively ; P = 0.596 ) . There were no significant differences in changes in blood pressure or pulse rates between the tamsulosin- and placebo-treated groups . CONCLUSION Tamsulosin 0.4 mg once daily is safe , well tolerated and clinical ly effective in improving symptoms and urinary flow rate in patients with symptomatic BPH",
" OBJECTIVE : This study compared α-blocker monotherapy with combination therapy involving an α-blocker and a 5-α reductase inhibitor for benign prostatic hyperplasia ( BPH ) , according to baseline prostate volume . METHODS : Korean men diagnosed with BPH were r and omized to 12 months ' treatment with 0.2 mg tamsulosin or 0.2 mg tamsulosin plus 0.5 mg dutasteride . Prostate specific antigen ( PSA ) , prostate volume , transition zone volume ( TZV ) , International Prostate Symptom Score ( IPSS ) , maximal urinary flow rate ( Q max ) , postvoid residual urine volume and sexual function were assessed at baseline and after 12 months ' treatment . Variables were analysed based on baseline prostate volumes of ≤ 35 ml or > 35 ml . RESULTS : In total , 216 men with BPH were included . Combination therapy result ed in significant improvements in prostate volume , TZV , PSA , IPSS and Q max , which were most pronounced in men with a prostate volume > 35 ml . CONCLUSIONS : Tamsulosin monotherapy was sufficient treatment for BPH in Korean men with a prostate volume ≤ 35 ml . Combination tamsulosin and dutasteride therapy provided greater benefits than tamsulosin monotherapy in men with BPH whose prostate volume was > 35 ml",
"PURPOSE To revise the 2003 version of the American Urological Association 's ( AUA ) Guideline on the management of benign prostatic hyperplasia ( BPH ) . MATERIAL S AND METHODS From MEDLINE ® search es of English language publications ( January 1999 through February 2008 ) using relevant MeSH terms , articles concerning the management of the index patient , a male ≥45 years of age who is consulting a healthcare provider for lower urinary tract symptoms ( LUTS ) were identified . Qualitative analysis of the evidence was performed . Selected studies were stratified by design , comparator , follow-up interval , and intensity of intervention , and meta-analyses ( quantitative synthesis ) of outcomes of r and omized controlled trials were planned . Guideline statements were drafted by an appointed expert Panel based on the evidence . RESULTS The studies varied as to patient selection ; r and omization ; blinding mechanism ; run-in periods ; patient demographics , comorbidities , prostate characteristics and symptoms ; drug doses ; other intervention characteristics ; comparators ; rigor and intervals of follow-up ; trial duration and timing ; suspected lack of applicability to current US practice ; and techniques of outcomes measurement . These variations affected the quality of the evidence review ed making formal meta- analysis impractical or futile . Instead , the Panel and extractors review ed the data in a systematic fashion and without statistical rigor . Diagnosis and treatment algorithms were adopted from the 2005 International Consultation of Urologic Diseases . Guideline statements concerning pharmacotherapies , watchful waiting , surgical options and minimally invasive procedures were either up date d or newly drafted , peer review ed and approved by AUA Board of Directors . CONCLUSIONS New pharmacotherapies and technologies have emerged which have impacted treatment algorithms . The management of LUTS/BPH continues to evolve",
"OBJECTIVES To evaluate the clinical efficacy and safety of Naftopidil tablet in treating benign prostatic hyperplasia . METHODS Eighty BPH patients were divided into two groups r and omly by double-blind , double-simulated and active control parallel study trials . Forty patients in treatment group were given Naftopidil tablet 25 mg , p.o . , qn for 42 days , while 40 patients in control group were given Tamsulosin 0.2 mg , p.o . , qn for 42 days . Statistical analysis was given from 77 cases in the groups . Estimation of the efficacy was done by the change of major indexes include international prostate symptom score ( IPSS ) , maximum flowrate ( Qmax ) and secondary indexes such as quality of life ( QOL ) , residual urine ( Ru ) and volume of prostate ( V ) . RESULTS The changes of IPSS , Qmax , QOL had significant difference between two groups before and after treatment(P change of Ru had no significant difference between two groups before and after treatment ( P > 0.05 ) while there was significant difference between two groups after six-week treatment(P change of V had no significant difference ( P > 0.05 ) . The adverse reactions in both groups were mild , and there was no significant difference between two groups(P > 0.05 ) . CONCLUSIONS Naftopidil tablet was safe and effective in treating benign prostatic hyperplasia",
"OBJECTIVES To evaluate the efficacy and safety of two once-daily doses of tamsulosin , the first selective alpha1A-antagonist studied in clinical trials . METHODS Patients with benign prostatic hyperplasia ( BPH ) were r and omized to receive either tamsulosin ( 0.4 and 0.8 mg/day ) or placebo ( n = 756 ) . Primary efficacy parameters were improvement in the total American Urological Association ( AUA ) symptom score and peak urinary flow ( Qmax ) . Secondary efficacy parameters were improvement in measurements at individual double-blind visits corresponding to the primary efficacy parameters ; percentage of patients with a 3-mL/s increase in Qmax ; total AUA irritative , obstructive , and bother scores ; individual AUA symptom scores ; total , irritative , obstructive , and individual Boyarsky symptom scores ; average urinary flow rate and other uroflowmetric parameters ; and investigator 's global assessment . RESULTS Statistically significant improvements in all efficacy parameters were observed in tamsulosin-treated compared with placebo-treated patients . Additionally , the 0.4-mg/day dose demonstrated a rapid onset of action ( 4 to 8 hours ) based on Qmax after the first dose of double-blind medication . A review of the safety parameters demonstrated excellent tolerance at 1 week after the initial 0.4-mg/day dose and continued tolerance during the additional 12 weeks of 0.4- and 0.8-mg/day dosing . The incidence of positive orthostatic test results in the tamsulosin groups was comparable to that observed in the placebo group . Adverse events were comparable in the 0.4-mg/day tamsulosin and placebo groups and were somewhat higher in the 0.8-mg/day tamsulosin group . CONCLUSIONS Tamsulosin was effective , safe , and well tolerated in the target BPH population at both the 0.4- and 0.8-mg/day dose levels , without the blood pressure-lowering effects typical of nonselective alpha-adrenergic antagonists",
"Patients often want considerable information about their conditions , and enhanced patient participation might reduce unwanted practice variation and improve medical decisions . The authors assessed how men with benign prostatic hyperplasia reacted to an educational program design ed to facilitate participation in decisionmaking , and how strongly ratings of their symptom state and the prospect of complications predicted their treatment choice . A prospect i ve cohort study was conducted in three hospital-based urology practice s : two in prepaid group practice s , and one Veterans Administration clinic . Four hundred twenty-one men with symptomatic benign prostatic hyperplasia without prior prostatectomy or benign prostatic hyperplasia complications were enrolled , and 373 provided usable ratings . Subjects participated in an interactive videodisc-based shared decisionmaking program about benign prostatic hyperplasia and its treatment options , prostatectomy , and “ watchful waiting . ” They rated the length , clarity , balance , and value of the program and were followed for 3 months to determine if they underwent surgery . Patients rated the program as generally clear , informative , and balanced . Across all three sites , 77 % of patients were very positive and 16 % were generally positive about the program 's usefulness in making a treatment decision . Logistic models predicting choice of surgical treatment documented the independent importance of negative ratings of the current symptom state ( odds ratio 7.0 , 95 % confidence interval 2.9–16.6 ) , as well as the prospect of postoperative sexual dysfunction ( odds ratio 0.20 , 95 % confidence interval 0.08–0.48 ) in decisionmaking . Patients rated the Shared Decisionmaking Program very positively and made decisions consistent with their assessed preferences . These results suggest that patients can be helped to participate in treatment decisions , and support a r and omized trial of the Shared Decisionmaking Program",
"OBJECTIVE To assess the effect of tamsulosin on the Sexual Health Inventory for Men ( SHIM ) score in men diagnosed with lower urinary tract symptoms ( LUTS ) due to benign prostatic hyperplasia ( BPH ) . PATIENTS AND METHODS Analysis from the national data base of a programme of the Prostate Cancer Educational Council identified 7974 men who completed the American Urologic Association Symptom Score ( AUA-SS ) and SHIM question naires . The patients were divided into three groups ; group 1 , men taking tamsulosin ; group 2 , men on other prescription medications for treating BPH symptoms ; and group 3 , men not currently taking any BPH medications . Linear regression was used to assess the association of tamsulosin and other alpha-blocker prescriptions for treating BPH symptoms with the decline in SHIM score . The interaction terms between AUA and the intake of tamsulosin was also adjusted for in the final analysis . RESULTS The median age of the men was 60 years . In groups 1 , 2 and 3 , ( 234 , 291 and 7449 men , respectively ) the mean ( sd ) AUA-SS was 13.0 ( 7.2 ) , 12.1 ( 7.2 ) and 6.9 ( 5.8 ) , and the mean SHIM scores 11.7 ( 6.8 ) , 12.7 ( 6.5 ) and 15.9 ( 6.0 ) , respectively . Adjusting for the AUA-SS , men in group 1 on tamsulosin had a significantly higher SHIM score with increasing AUA-SS score than men on other medications ( P SHIM ( P higher AUA-SS and lower SHIM score than men in the other two groups , suggesting more severe symptoms in these men . CONCLUSIONS Men taking tamsulosin to treat LUTS appear to be at an advantage over men taking other alpha-blockers when the effect of LUTS on sexual health is considered . Furthermore , this effect was more profound in patients with more severe LUTS than those with mild and moderate symptoms . Future prospect i ve trials are warranted to confirm this effect",
"OBJECTIVE To compare the efficacy of the doxazosin gastrointestinal therapeutic system ( doxazosin-GITS ) 4 mg and tamsulosin 0.2 mg on nocturia in Chinese men with lower urinary tract symptoms ( LUTS ) suggestive of benign prostatic hyperplasia ( BPH ) . METHODS Data were analyzed from a prospect i ve , multicenter , r and omized , open , parallel study of Chinese men aged 50 - 84 years with LUTS/BPH . Two hundred patients were r and omized to receive daily treatment with 4 mg doxazosin-GITS ( n=100 ) or 0.2 mg tamsulosin ( n=100 ) for 8 weeks . Nocturia was assessed by question 7 of the International Prostate Symptom Score ( IPSS- question 7 ) and a frequency-volume chart ( FVC ) at weeks 4 and 8 . Self-reported quality of sleep and quality of life by the last question of the IPSS question naire were also evaluated . RESULTS A total of 189 patients ( 94 receiving doxazosin-GITS , 95 tamsulosin ) completed the study . The reduction from baseline in mean nocturia was greater with doxazosin-GITS than tamsulosin by the FVC ( 1.7 vs 1.3 at week 4 ; 2.1 vs 1.7 at week 8 , both P=.001 ) and by the IPSS- question 7 ( 1.5 vs 1.1 at 4 weeks , P=.001 ; 2.0 vs 1.6 at 8 weeks , P quality of sleep was significantly more with doxazosin-GITS than tamsulosin ( 43.6 % vs 27.4 % at 4 weeks , P=.020 ; 81.9 % vs 67.4 % at 8 weeks , P=.022 ) , and quality of life was better with doxazosin-GITS ( 2.5 vs 2.8 at 4 weeks , P=.001 ; 2.1 vs 2.5 at 8 weeks , P Chinese patients with LUTS/BPH , doxazosin-GITS is slightly better than tamsulosin in reducing the frequency of nocturia"
] |
4116c48c-06ff-11f0-808a-c43d1ab1c353
|
Context Which lipid-lowering policies with statins are cost-effective ? Contribution This modeling exercise found that the Adult Treatment Panel III guidelines , which recommend treatment based on cholesterol level and estimated coronary heart disease risk , are reasonably cost-effective if statins cost about $ 1.50 to $ 2.20 per pill . At costs lower than $ 0.10 per pill , treating all persons with LDL cholesterol levels greater than 3.4 mmol/L ( > 130 mg/dL ) could be a better strategy . Implication Optimum policies for lipid lowering with statins are highly dependent on statin costs . The Editors Coronary heart disease ( CHD ) is the leading cause of death in the United States ( 1 ) . Inhibitors of HMG-CoA reductase , known as statins , lower cholesterol and prevent CHD events and mortality ( 2 , 3 ) . However , statins are expensive and sometimes cause side effects , which makes it difficult for patients , physicians , and policymakers to decide who should receive them . The Third Report of the Expert Panel on Detection , Evaluation , and Treatment of High Blood Cholesterol in Adults ( Adult Treatment Panel III , or ATP III ) , published by the National Cholesterol Education Program in 2001 ( 4 ) and up date d in 2004 ( 3 ) , provides comprehensive recommendations on when and how to treat high cholesterol levels with statins . These guidelines recommend treatment on the basis of a combination of cholesterol level and estimated CHD risk , with more aggressive cholesterol treatment thresholds recommended for patients with higher estimated risk . Adherence to ATP III guidelines is modest ( 5 , 6 ) , and many questions remain about strategy 's cost , complexity , and efficiency ( 6 ) . Previous cost-effectiveness analyses ( 719 ) show that statin therapy is generally cost-effective for secondary prevention and for high-risk primary prevention but do not focus on population -level impact or average cost-effectiveness across the heterogeneous U.S. population , including such subgroups of patients as those with low risk but very high cholesterol levels . Also , it is unclear whether the ATP III approach to risk stratification , in which risk is formally assessed only for patients with 2 or more established risk factors , is the simplest and most cost-effective way of targeting statin therapy . Finally , ATP III bases treatment decisions on both risk and cholesterol level . The 2004 up date to ATP III ( 3 ) notes that treatment of high-risk subgroups may be useful even when cholesterol levels are low , which suggests that a more purely risk-based approach may be simpler and more cost-effective than the ATP III approach . An even simpler algorithm based on patient age might provide similar cost-effectiveness , given that age is the primary driver of CHD risk ( 20 ) . The CHD Policy Model is a mathematical state-transition model of CHD in the United States that can be used to project event rates and costs related to CHD . We used the model to evaluate ATP III primary prevention guidelines and to compare the strategy 's overall impact , cost , and cost-effectiveness with alternative risk- and age-based strategies under varying assumptions about the cost and side effects of statins . Methods Structure of the Model The CHD Policy Model is a computer-simulated , state-transition ( Markov cohort ) model of CHD incidence , prevalence , mortality , and costs among persons older than 35 years in the U.S. population . The demographicepidemiologic submodel predicts CHD incidence and non-CHD mortality among persons without CHD , stratified by age , sex , diastolic blood pressure , smoking status , high-density lipoprotein ( HDL ) cholesterol level , low-density lipoprotein ( LDL ) cholesterol level , diabetes mellitus , and use of statin therapy . After CHD develops , a bridge submodel characterizes the initial CHD event ( cardiac arrest , myocardial infa rct ion , or angina ) and its sequelae over 30 days . A disease history submodel then predicts subsequent CHD events , revascularization procedures , CHD mortality , and non-CHD mortality among patients with CHD , stratified by age , sex , and history of events . Each health state and event has an annual cost and quality -of-life adjustment . All population distributions , risk factor levels , coefficients , event rates , case-fatality rates , costs , and quality -of-life adjustments can be modified for forecasting simulations . More details about the model have been published elsewhere ( 2123 ) and are also in the Appendix . Data Sources We used population size projections for 2000 to 2050 , provided by the 2000 U.S. Census ( 24 ) , and data from the National Health and Nutrition Examination Survey , 1999 to 2004 ( 25 ) , to estimate joint distributions of risk factor values in the U.S. population . We estimated the background prevalence of CHD in 2000 from the National Health Interview Survey , 2000 ( 26 ) . We estimated CHD deaths , prehospital deaths from cardiac arrest , and non-CHD deaths from U.S. Vital Statistics ( 27 ) on the basis of codes from the International Classification of Diseases , 10th revision . We obtained case-fatality and revascularization rates and the number of patients who had myocardial infa rct ions or out-of-hospital cardiac arrests and survived to hospital discharge from the National Hospital Discharge Survey ( NHDS ) ( 28 ) and complementary sources ( Appendix ) . We estimated -coefficients that were conditional on age and sex by using examinations 9 to 13 of the original Framingham cohort and examinations 1 to 6 of the offspring ( 29 ) ( Appendix ) . The LDL cholesterol coefficient decreases in magnitude with increasing age in the model ( LDL cholesterol is a weaker risk factor in older adults ) , as estimated in the Framingham data ( Appendix ) . Statin efficacy was modeled via LDL cholesterollowering . Our model closely replicated the reduction in coronary events with statins ( 30 ) and approximated the cost-effectiveness ratios of individual trials ( 31 , 32 ) when we used their outcomes data ( Appendix ) . We estimated total health care costs from the perspective of the health care system by using national data from the Centers for Medicare & Medicaid Services ( 33 ) . We estimated the CHD cost component by using California data ( 34 ) , deflated by using cost-to-charge ratios ( 35 ) and the ratio of the U.S. national average costs to the California average ( 36 ) and then inflated to 2006 dollars by using the Bureau of Labor Statistics Consumer Price Index for Medical Care Costs ( 37 ) . We based health-related quality -of-life weights on observational data ( 38 ) and discounted costs and quality -adjusted life-years ( QALYs ) at a rate of 3 % per year . Statin Therapy Assumptions We categorized statin drugs and doses that decrease LDL cholesterol level by approximately 27 % ( such as fluvastatin , 40 mg ; lovastatin , 20 mg ; pravastatin , 20 mg ; and simvastatin , 10 mg ) as low intensity and those that decrease it by approximately 55 % ( such as atorvastatin , 80 mg , and rosuvastatin , 40 mg ) as high intensity ( 39 , 40 ) . We estimated direct medication costs for the base-case scenario by averaging the lowest average wholesale price reported in the 2006 National Drug Data File for low-intensity statins ( $ 2.11 per pill ) and high-intensity statins ( $ 2.81 per pill ) . An informal telephone and Web site survey we conducted in 2008 , which examined out-of-pocket costs for a self-insured patient to buy statins of different types in various setting s , showed that costs varied from $ 0.17 per pill ( generic lovastatin at large discount chains ) to $ 5.00 per pill or more ( nongeneric statins at retail pharmacy chains ) . Because of this range , we performed sensitivity analyses that specified the preferred strategy at any given statin pill cost . We held the ratio of pill costs for low- to high-intensity statins ( $ 2.11:$2.81 ) constant in all analyses . We derived side-effect rates from a systematic review of statin trials ( 41 ) and assumed that side effects occurred at twice the rate for high-intensity statins on the basis of data ( 42 ) that indicated that some side effects are dose-related . We based some of our assumptions about extra monitoring requirements for patients receiving statins and for the consequences of myopathy and hepatitis episodes on clinical judgment ( Table 1 ) ( 4345 ) . We derived the costs of hospitalization for acute kidney failure ( for rhabdomyolysis ) and liver failure from the Healthcare Cost and Utilization Project ( 46 ) . For the base-case scenario , we assumed 100 % adherence to therapy and no quality -of-life decrement from the act of taking a statin pill every day ( Table 1 ) . Table 1 . Model Assumptions Comparing Lipid-Lowering Strategies For all analyses , we assumed full adherence to secondary prevention guidelines outlined in the 2004 ATP III up date ( 3 ) , which recommend aggressive lipid-lowering for persons with known CHD or a CHD equivalent , such as diabetes , and for persons with a 10-year CHD risk greater than 20 % . We assumed that a healthy lifestyle would be recommended for all persons and therefore held these factors constant across strategies at current levels . We applied ATP III primary prevention guidelines ( 4 ) by lowering LDL cholesterol levels for prescribed subgroups of the population defined by LDL cholesterol level , number of CHD risk factors , and 10-year CHD risk estimated by using the ATP III point-based algorithm ( Appendix ) . We assumed that persons who were already receiving statins were receiving a low-intensity statin and modeled the cost and efficacy of switching to a higher-intensity statin . On the basis of an analysis of National Health and Nutrition Examination Survey 1999 to 2000 data that showed that 25 % of persons with LDL cholesterol levels greater than 4.1 mmol/L ( > 160 mg/dL ) would have levels greater than 4.9 mmol/L ( > 190 mg/dL ) , we simulated treating 25 % of persons with levels greater than 4.1 mmol/L ( > 160 mg/dL ) with statins according to the ATP III strategy . This assumption ( required because of limitations with the model ) introduces a slight bias in the direction of making ATP III look less cost-effective .
|
[
"BACKGROUND The objective of this study was to assess the cost-effectiveness of pravastatin therapy in survivors of myocardial infa rct ion with average cholesterol levels . METHODS We performed a cost-effectiveness analysis based on actual clinical , cost , and health-related quality -of-life data from the Cholesterol and Recurrent Events ( CARE ) trial . Survival and recurrent coronary heart disease events were modeled from trial data in Markov models , with the use of different assumptions regarding the long-term benefit of therapy . RESULTS Pravastatin therapy increased quality -adjusted life expectancy at an incremental cost of $ 16,000 to $ 32,000 per quality -adjusted life-year gained . In subgroup analyses , the cost-effectiveness of pravastatin therapy was more favorable for patients > 60 years of age and for patients with pretreatment low-density lipoprotein cholesterol levels > 125 mg/dL. Results were sensitive to the cost of pravastatin and to assumptions about long-term survival benefits from pravastatin therapy . CONCLUSIONS The cost-effectiveness of pravastatin therapy in survivors of myocardial infa rct ion with average cholesterol levels compares favorably with other interventions",
"Objectives To evaluate the cost effectiveness of 40 mg simvastatin daily continued for life in people of different ages with differing risks of vascular disease . Design A model developed from a r and omised trial was used to estimate lifetime risks of vascular events and costs of treatment and hospital admissions in the United Kingdom . Setting 69 hospitals in the UK . Participants 20 536 men and women ( aged 40 - 80 ) with coronary disease , other occlusive arterial disease , or diabetes . Interventions 40 mg simvastatin daily versus placebo for an average of 5 years . Main outcome measures Cost effectiveness of 40 mg simvastatin daily expressed as additional cost per life year gained . Major vascular event defined as non-fatal myocardial infa rct ion or death from coronary disease , any stroke , or revascularisation procedure . Results were extrapolated to younger and older age groups at lower risk of vascular disease than were studied directly , as well as to lifetime treatment . Results At the April 2005 UK price of � 4.87 ( € 7 ; $ 9 ) per 28 day pack of generic 40 mg simvastatin , lifetime treatment was cost saving in most age groups and vascular disease risk groups studied directly . Gains in life expectancy and cost savings decreased with increasing age and with decreasing risk of vascular disease . People aged 40 - 49 with 5 year risks of major vascular events of 42 % and 12 % at start of treatment gained 2.49 and 1.67 life years , respectively . Treatment with statins remained cost saving or cost less than � 2500 per life year gained in people as young as 35 years or as old as 85 with 5 year risks of a major vascular event as low as 5 % at the start of treatment . Conclusions Treatment with statins is cost effective in a wider population than is routinely treated at present",
"The Beaver Dam Health Outcomes Study ( BDHOS ) is an ongoing longitudinal cohort study of health status and health-related quality of life for a r and om sample of adults ( age range at interview was 45 to 89 years ; mean = 64.1 , SD = 10.8 ) in a community population . In a face-to-face interview lasting approximately an hour , each participant responds to several batteries of questions . Included are a history of chronic medical conditions , current medi cations , and past surgeries ; the SF-36 ( a general health-status question naire ) ; the Quality of Well-being index ; self-rated health status on a five-point scale from \" excellent \" to \" poor \" ; and evaluation of current health using the method of time tradeoffs . The authors present results from 1,356 interviews on these four principal measures , reporting mean scores by sex , by age , and for persons reporting being affected by various medical conditions . They believe data from the BDHOS will provide research ers and policy makers a reference col lection of vital statistics for health-related quality of life . Additionally , the data provide a way to compare results from studies that utilize different indices from among the four principal measures of the BDHOS . Key words : health status ; quality of life ( health-related ) ; population study ; cohort study . ( Med Decis Making 1993;13:89 - 102",
"CONTEXT Despite improved underst and ing of atherothrombosis , cardiovascular prediction algorithms for women have largely relied on traditional risk factors . OBJECTIVE To develop and vali date cardiovascular risk algorithms for women based on a large panel of traditional and novel risk factors . DESIGN , SETTING , AND PARTICIPANTS Thirty-five factors were assessed among 24 558 initially healthy US women 45 years or older who were followed up for a median of 10.2 years ( through March 2004 ) for incident cardiovascular events ( an adjudicated composite of myocardial infa rct ion , ischemic stroke , coronary revascularization , and cardiovascular death ) . We used data among a r and om two thirds ( derivation cohort , n = 16 400 ) to develop new risk algorithms that were then tested to compare observed and predicted outcomes in the remaining one third of women ( validation cohort , n = 8158 ) . MAIN OUTCOME MEASURE Minimization of the Bayes Information Criterion was used in the derivation cohort to develop the best-fitting parsimonious prediction models . In the validation cohort , we compared predicted vs actual 10-year cardiovascular event rates when the new algorithms were compared with models based on covariates included in the Adult Treatment Panel III risk score . RESULTS In the derivation cohort , a best-fitting model ( model A ) and a clinical ly simplified model ( model B , the Reynolds Risk Score ) had lower Bayes Information Criterion scores than models based on covariates used in Adult Treatment Panel III . In the validation cohort , all measures of fit , discrimination , and calibration were improved when either model A or B was used . For example , among participants without diabetes with estimated 10-year risks according to the Adult Treatment Panel III of 5 % to less than 10 % ( n = 603 ) or 10 % to less than 20 % ( n = 156 ) , model A reclassified 379 ( 50 % ) into higher- or lower-risk categories that in each instance more accurately matched actual event rates . Similar effects were achieved for clinical ly simplified model B limited to age , systolic blood pressure , hemoglobin A(1c ) if diabetic , smoking , total and high-density lipoprotein cholesterol , high-sensitivity C-reactive protein , and parental history of myocardial infa rct ion before age 60 years . Neither new algorithm provided substantive information about women at very low risk based on the published Adult Treatment Panel III score . CONCLUSION We developed , vali date d , and demonstrated highly improved accuracy of 2 clinical algorithms for global cardiovascular risk prediction that reclassified 40 % to 50 % of women at intermediate risk into higher- or lower-risk categories",
"Background —There are few data regarding the determinants of sudden cardiac death ( SCD ) in women , primarily because of their markedly lower rate of SCD compared with men . Nonetheless , existing data , although sparse , suggest possible gender differences in risk factors for SCD . Methods and Results —In this prospect i ve cohort of 121 701 women aged 30 to 55 years at baseline , SCD was defined as death within 1 hour of symptom onset . From 1976 to 1998 , 244 SCDs were identified . Although the risk of SCD increased markedly with age , the percentage of cardiac deaths that were sudden decreased . Most ( 69 % ) women who suffered a SCD had no history of cardiac disease before their death . However , almost all of the women who died suddenly ( 94 % ) had reported at least 1 coronary heart disease risk factor . Smoking , hypertension , and diabetes conferred markedly elevated ( 2.5- to 4.0-fold ) risk of SCD , similar to that conferred by a history of nonfatal myocardial infa rct ion ( relative risk , 4.1 ; 95 % confidence interval , 2.9 to 6.7 ) . Family history of myocardial infa rct ion before age 60 years and obesity were associated with moderate ( 1.6-fold ) elevations in risk . With regard to mechanism , 88 % of SCDs were classified as arrhythmic . In 76 % of these , the first rhythm documented was ventricular tachycardia or ventricular fibrillation . Conclusions —These prospect i ve data suggest that , as in men , coronary heart disease risk factors predict risk of SCD in women and that SCD is usually an arrhythmic death . Therefore , prevention of atherosclerosis or ventricular arrhythmias may reduce the incidence of SCD in women",
"In the United Kingdom , the current recommendation is that lipid-lowering drugs should be prescribed for primary prevention only to subjects with an absolute coronary risk ( AR ) greater than 15 % in 5 years ( i.e. , myocardial infa rct ion or angina ) . However , to achieve greater benefit it may be preferable to direct treatment to those patients showing the greatest absolute risk reduction ( ARR ) . The aim of this study was to compare the characteristics of subjects eligible for lipid-lowering drugs based on the AR criteria or on an ARR of > 4.45 % . A prospect i ve study was carried out over 29 months in primary care in a part of the United Kingdom with a prevalence of coronary disease nearly 20 % above the national average . Risk factors were recorded in men and women aged 30 - 75 years who were being considered by their primary care physician for lipid-lowering drug therapy . Of the 2351 patients included in the study , 2139 ( 91 % ) and 101 ( 4.3 % ) were , respectively , below and above the criteria for treatment by both AR and ARR criteria . In 111 ( 4.7 % ) subjects , treatment was recommended based on only one of the criteria -82 on AR and 29 on ARR . Comparing these two groups , those treated on AR only were older ( mean age 68.1 years [ SD , 4.1 ] vs. 49.1 years [ SD , 4.6 ] ; p total cholesterol ( 260 vs. 288 mg/dL ; p=0.015 ) ; higher high-density lipoprotein cholesterol ( 50 vs. 43 mg/dL ; p=0.003 ) , lower low-density lipoprotein cholesterol ( 160 vs. 184 mg/dL ; p=0.03 ) , a lower total to high-density lipoprotein cholesterol ratio ( 5.4 vs. 7.1 ; p triglycerides ( 258 vs. 435 mg/dL ; p=0.007 ) . The AR group also had a higher mean systolic blood pressure ( 170.9 vs. 158.9 mm Hg ; p=0.013 ) , presumably an attribute of their greater age . Although the AR and ARR groups did not show a difference in the proportion of males or diabetics , there was a significantly greater proportion of smokers in the latter group ( 72 % vs. 35 % ; p=0.001 ) . In conclusion , treatment recommendations based on AR alone would result in nontreatment of young subjects with significant hyperlipidemia and at high relative risk of coronary disease , whereas lipid-lowering drugs would be given preferentially to patients whose main coronary heart disease risk factors are age and hypertension but not hyperlipidemia . By contrast , treatment recommendations based on ARR ensure that lipid-lowering drugs are directed to patients who will derive the most benefit . Furthermore , delaying treatment in younger subjects at high relative risk but not high AR results in their accumulating significant coronary risk in the years before their AR exceeds an arbitrary threshold before lipid-lowering drugs are prescribed",
"Context National guidelines recommend aspirin or statin drugs individually to reduce first coronary heart disease ( CHD ) events , but there are no guidelines about taking both . Contribution The authors used a Markov model to estimate the cost-effectiveness of aspirin , statins , both drugs , or neither in men . In patients with a 10-year risk for CHD of 7.5 % , aspirin alone reduced costs and lengthened life compared with no treatment . Adding a statin cost $ 56200 per additional quality -adjusted life-year at a 7.5 % risk but only $ 42500 at a 10 % risk . Caution s The authors ' analysis was limited to men . Implication s Therapy with aspirin alone is effective and cost-effective in men with an average level of risk for CHD . The addition of a statin is more cost-effective as risk increases . The Editors Aspirin and statin drugs have been shown to be effective for preventing first coronary heart disease ( CHD ) events ( 1 - 3 ) . Systematic review s and meta-analyses suggest that the relative risk reductions with both forms of therapy are similar in magnitude and seem to be independent and relatively constant across the range of underlying risk for CHD ( 2 - 5 ) . The absolute benefit from these treatments seems to be proportional to the patient 's underlying risk for CHD . National treatment guidelines recommend aspirin and statin drugs individually for the primary prevention of cardiovascular events in men who are at increased risk ( 4 , 6 , 7 ) . However , no U.S. guidelines have addressed how these drugs should be used together , and we are unaware of any previous analyses that have reported the cost-effectiveness of these drugs when used in combination for CHD prevention . To help inform clinical and policy decisions about primary CHD prevention , we performed a costutility analysis that examined the use of aspirin therapy , statin therapy , or combination therapy with both drugs in men with various underlying levels of risk for CHD . Methods To examine the cost and utility associated with aspirin and with statin use , we used Microsoft Excel 2002 for Windows ( Microsoft Corp. , Redmond , Washington ) to develop a Markov state-transition model . The model was design ed to simulate cohorts of initially healthy middle-aged men with no history of cardiovascular events and with various levels of 10-year risk for CHD ( Figure 1 ) . Figure 1 . General structure of the Markov model . Base-Case Scenario In our base-case scenario , we compared the effectiveness of 10 years of aspirin therapy , statin therapy , combination therapy with both drugs , and no therapy in 45-year-old men with a 10-year risk for CHD of 7.5 % . After 10 years , both groups adopted the treatment used in the intervention group . Although the differences in therapy were maintained for only 10 years , we examined the effects of these therapies over a lifetime . Model Assumptions All persons were initially healthy and progressed through the model in annual cycles . In each cycle , an individual remained healthy , had an initial cardiovascular event ( angina , myocardial infa rct ion , or stroke ) , experienced adverse effects from therapy ( gastrointestinal bleeding from aspirin or myopathy from statins ) , or died . We assumed that those who had cardiovascular events or adverse events stayed in the subacute state for the remainder of that cycle and then entered a postevent state . Adherence to treatment was assumed to be 100 % in the absence of adverse effects , although the treatment efficacy data were based on the actual rates of adherence in the clinical trials . Persons who had adverse effects from therapy stopped taking the offending medication ; their procession through the model was similar to that of healthy patients after the initial cycle . All costs and outcomes were discounted at 3 % in accordance with current consensus recommendations ( 8) . Model Parameters Model parameters , including base-case values , ranges , and references , are shown in Table 1 ( 1 - 3 , 9 - 29 ) . Table 1 . Base-Case Estimates and Ranges Used in Sensitivity Analyses Noncardiovascular Mortality Age-dependent noncardiovascular mortality rates were estimated from the National Vital Statistics life tables ( 31 ) . Rates were adjusted as the cohort aged over the time horizon of the analysis . Cardiovascular Event Rates Baseline risks for initial cardiovascular events ( myocardial infa rct ion , stroke , angina , and death from CHD ) were drawn from Framingham risk equations by using hypothetical scenarios of nonsmoking , nonhypertensive , nondiabetic men at different levels of risk for CHD ( Appendix Table ) ( 32 ) . Assuming an exponential distribution , we translated these 10-year risks into annual event-related transition probabilities . These probabilities were allowed to change over time to reflect increasing risk for CHD over the time horizon of the analysis . Appendix Table . Sample Baseline Characteristics of 45-Year-Old Men by Risk Level Because we were interested in primary prevention , we did not simulate or examine the details of a patient 's course after a primary , nonfatal event . Instead , we assigned them an increased risk for death , increased costs , and decreased utilities by using data from the literature regarding the average experience of patients after an initial event . The increased relative risk for death after an initial event ( Table 1 ) was drawn from population -based studies in the United Kingdom ( 12 , 16 ) and applied to the general mortality rates from the U.S. life tables to generate the estimated postevent mortality rates . We modified these event rates by assuming that all patients received optimal secondary prevention . Adverse Effects The excess risks for gastrointestinal bleeding with aspirin use and for myopathy with statin use were drawn from systematic review s of r and omized trials and a recent secondary data analysis ( 2 , 26 , 27 ) . Risks for gastrointestinal bleeding and myopathy in untreated patients were assumed to be zero so that only treatment-induced adverse events were counted . Because better data were not available , we estimated the risks for death from aspirin-related gastrointestinal bleeding and statin-induced myopathy and varied them in sensitivity analysis . Patients who had nonfatal adverse effects were not given therapy with alternate agents for primary prevention of CHD . Modeling Stroke Because many r and omized trials of aspirin prophylaxis did not distinguish by stroke type , we had difficulty estimating the precise effect of aspirin on ischemic and hemorrhagic strokes ( 30 ) . To account for this limitation , we used 2 approaches to model the effect of aspirin on stroke . In the base-case analysis , we followed the approach that was used in a recent meta- analysis ( 9 ) by including hemorrhagic stroke and ischemic stroke together in 1 estimate of the effect of aspirin on total stroke ( relative risk for stroke with aspirin , 1.06 ) . In an alternate scenario , we modeled hemorrhagic stroke and ischemic stroke as separate health states . We assumed that aspirin was associated with an excess annual risk of 20 hemorrhagic strokes per 100000 users on the basis of published meta-analyses and that one third of these hemorrhagic strokes would be fatal ( 19 , 30 , 33 ) . We conservatively assumed that aspirin had no effect on ischemic stroke ( 30 ) . The costs and utilities of ischemic stroke and hemorrhagic stroke were also considered separately . Treatment Efficacy We used summary relative risk estimates from existing meta-analyses or relative risks from individual trials to estimate the efficacy of aspirin and statin therapy , either alone or in combination , for preventing CHD events ( 3 , 24 , 29 ) . Where data were limited , we made conservative assumptions . The efficacy of the combined use of aspirin and statins was assumed to be independent on the basis of data from secondary prevention trials ( 5 ) . We did not model the effect of aspirin or statins on initial use of revascularization procedures in the absence of a cardiovascular event . All patients who survived an initial cardiovascular event were assumed to have received secondary preventive therapy with aspirin and a statin or with an alternate agent if they could not tolerate aspirin or statins . The effect of treatments on all-cause mortality was estimated from meta-analyses of secondary prevention trials ( 18 - 20 ) . Costs We conducted our analysis from the perspective of a third-party payer . State costs ( Table 1 ) , which were derived from data from the published literature and several recent national data bases , are expressed in 2003 dollars . To estimate the costs during the year in which an event occurred , we estimated acute care costs by drawing on data regarding hospital charges from the Healthcare Utilization Project data base and by converting these values to costs . To convert hospital charges to costs , we used the 1999 cost-to-charge ratio value of 0.4501 , which was derived from the Medicare Provider Analysis and Review of short-stay hospitals ( 28 ) . We then used the Medical Consumer Price Index to generate an inflation factor of 1.195 , which was applied to the 1999 cost figure to convert 1999 dollars to 2003 dollars ( 17 ) . In addition to the acute care costs , we assumed that each patient who survived an acute event would also incur one half of the estimated ongoing annual costs of care for the first year . Costs for subsequent years were based on ongoing costs of care that were drawn from the medical literature ( 22 - 25 ) . Drug costs were obtained from the 2003 Red Book average wholesale prices ( 21 ) . For our base-case analysis , we set the annual statin cost to $ 730 by averaging the Red Book prices of simvastatin ( $ 922 for 10 mg/d ) and lovastatin ( $ 503 for 10 mg/d ) . The base-case cost of aspirin was based on an annual cost of $ 16 for Bayer aspirin ( Bayer Healthcare LLC , Morristown , New Jersey ) . The annual cost of generic aspirin was estimated at approximately $ 6 ( 21 ) . We varied the costs of each drug over wide ranges in sensitivity analysis . To check our cost estimates , we compared our derived values with other cost estimates",
"OBJECTIVES To determine whether elevated serum cholesterol level is associated with all-cause mortality , mortality from coronary heart disease , or hospitalization for acute myocardial infa rct ion and unstable angina in persons older than 70 years . Also , to evaluate the association between low levels of high-density lipoprotein cholesterol ( HDL-C ) and elevated ratio of serum cholesterol to HDL-C with these outcomes . DESIGN Prospect i ve , community-based cohort study with yearly interviews . PARTICIPANTS A total of 997 subjects who were interviewed in 1988 as part of the New Haven , Conn , cohort of the Established Population for the Epidemiologic Study of the Elderly ( EPESE ) and consented to have blood drawn . MAIN OUTCOME MEASURES The risk factor-adjusted odds ratios of the 4-year incidence of all-cause mortality , mortality from coronary heart disease , and hospitalization for myocardial infa rct ion or unstable angina were calculated for the following : subjects with total serum cholesterol levels greater than or equal to 6.20 mmol/L ( > or = 240 mg/dL ) compared with subjects with cholesterol levels less than 5.20 mmol/L ( Elevated total serum cholesterol level , low HDL-C , and high total serum cholesterol to HDL-C ratio were not associated with a significantly higher rate of all-cause mortality , coronary heart disease mortality , or hospitalization for myocardial infa rct ion or unstable angina after adjustment for cardiovascular risk factors . The risk factor-adjusted odds ratio for all-cause mortality was 0.99 ( 95 % confidence interval [ CI ] , 0.56 to 2.69 ) for the group who had cholesterol levels greater than or equal to 6.20 mmol/L ( > or = 240 mg/dL ) compared with the group that had levels less than 5.20 mmol/L ( total serum cholesterol to HDL-C compared with those in the lowest tertile . CONCLUSIONS Our findings do not support the hypothesis that hypercholesterolemia or low HDL-C are important risk factors for all-cause mortality , coronary heart disease mortality , or hospitalization for myocardial infa rct ion or unstable angina in this cohort of persons older than 70 years",
"OBJECTIVES We sought to describe the incidence , characteristics and survival of out-of-hospital sudden cardiac arrest ( SCA ) in the Maastricht area of The Netherl and s. BACKGROUND Incidence and survival rates of out-of-hospital SCA in different communities are often based on the number of victims resuscitated by the emergency medical services . Our population -based study in the Maastricht area allows information on all victims of witnessed and unwitnessed SCA occurring outside the hospital . METHODS Incidence , patient characteristics and survival rates were determined by prospect ively collecting information on all cases of SCA occurring in the age group 20 to 75 years between January 1 , 1991 and December 31 , 1994 . Survival rates were related to the site of the event ( at home vs. outside the home ) and the presence or absence of a witness and rhythm at the time of the resuscitation attempt in out-of-hospital SCA . RESULTS Five hundred fifteen patients were included ( 72 % men , 28 % women ) . In 44 % of men and 53 % of women , SCA was most likely the first manifestation of heart disease . In patients known to have had a previous myocardial infa rct ion ( MI ) , the mean interval between the MI and SCA was 6.5 years , with > 50 % having a left ventricular ejection fraction > 30 % . The mean yearly incidence of SCA was 1 in 1,000 inhabitants . Of all deaths in the age groups studied , 18.5 % were sudden . Nearly 80 % of SCAs occurred at home . In 60 % of all cases of SCA a witness was present . Cardiac resuscitation , which was attempted in 51 % of all subjects , result ed overall in 32 ( 6 % ) of 515 patients being discharged alive from the hospital . Survival rates for witnessed SCA were 8 % ( 16 of 208 subjects ) at home and 18 % ( 15 of 85 subjects ) outside the home ( 95 % confidence interval 1 % to 18.8 % ) . CONCLUSIONS The majority of victims of SCA can not be identified before the event . Sudden cardiac arrest usually occurs at home , and the survival of those with a witnessed SCA at home was low compared with that outside the home , indicating the necessity of optimizing out-of-hospital resuscitation , especially in the at-home situation",
"To assess the impact of patient age on the use of diagnostic testing in the management of acute myocardial infa rct ion , the authors review ed the hospital charts of 4,109 patients hospitalized for vali date d acute myocardial infa rct ion in the Worcester , Massachusetts , metropolitan area during selected years between 1975 and 1986 . Older patients were more likely to be female and to have a prior history of angina , hypertension , and diabetes mellitus ( p less than 0.001 ) . Acute myocardial infa rct ions among older patients were more likely to be recurrent , anterior in location , non-Q wave , smaller as reflected by peak creatine kinase levels , and complicated by congestive heart failure , cardiogenic shock , and atrial fibrillation ( p less than 0.001 ) . In-hospital mortality was directly related to increasing patient age ( p less than 0.001 ) . Patterns of utilization of the following diagnostic tests were examined : Holter monitoring , radionuclide ventriculography , echocardiography , exercise testing , pulmonary artery catheterization , and coronary arteriography . After adjustment for differences in demographic and clinical characteristics and in-hospital mortality , patients aged 65 years and older were significantly less likely to undergo exercise testing than were patients less than age 55 . Patients older than age 75 were significantly less likely to undergo radionuclide ventriculography , pulmonary artery catheterization , and coronary arteriography than were younger patients . Sex-specific analyses did not produce results substantially different from those for the overall study population . The results of this community-wide study suggest that among patients hospitalized for acute myocardial infa rct ion , chronologic age may be an independent determinant of utilization patterns of diagnostic testing . These findings suggest the need for a prospect i ve evaluation of this issue , with an additional emphasis placed on the contributions of functional status and noncardiovascular illness to decision-making in the clinical management of acute myocardial infa rct ion patients",
"We carried out a systematic overview using individual patient data from the seven r and omised trials that have compared a strategy of initial coronary artery bypass graft ( CABG ) surgery with one of initial medical therapy to assess the effects on mortality in patients with stable coronary heart disease ( stable angina not severe enough to necessitate surgery on grounds of symptoms alone , or myocardial infa rct ion ) . 1324 patients were assigned CABG surgery and 1325 medical management between 1972 and 1984 . The proportion of patients in the medical treatment group who had undergone CABG surgery was 25 % at 5 years , 33 % at 7 years , and 41 % at 10 years : 93.7 % of patients assigned to the surgery group underwent CABG surgery . The CABG group had significantly lower mortality than the medical treatment group at 5 years ( 10.2 vs 15.8 % ; odds ratio 0.61 [ 95 % CI 0.48 - 0.77 ] , p = 0.0001 ) , 7 years ( 15.8 vs 21.7 % ; 0.68 [ 0.56 - 0.83 ] , p risk reduction was greater in patients with left main artery disease than in those with disease in three vessels or one or two vessels ( odds ratios at 5 years 0.32 , 0.58 , and 0.77 , respectively ) . Although relative risk reductions in subgroups defined by other baseline characteristics were similar , the absolute benefits of CABG surgery were most pronounced in patients in the highest risk categories . This effect was most evident when several prognostically important clinical and angiographic risk factors were integrated to stratify patients by risk levels and the extension of survival at 10 years was examined ( change in survival -1.1 [ SE 3.1 ] months in low-risk group , 5.0 [ 4.2 ] months in moderate-risk group , and 8.8 [ 5.4 ] months in high-risk group ; p for trend CABG surgery is associated with lower mortality than one of medical management with delayed surgery if necessary , especially in high-risk and medium-risk patients with stable coronary heart disease . In low-risk patients , the limited data show a non-significant trend towards greater mortality with CABG",
"Abstract Objective : To estimate the economic efficiency of using pravastatin to prevent the transition from health to cardiovascular disease in men with hypercholesterolaemia . Design : Economic benefit analysis based on data from the West of Scotl and coronary prevention study . Treatment specific hazards of developing cardiovascular disease according to various definitions were estimated . Scottish record linkage data provided disease specific survival . Cost estimates were based on extracontractual tariffs and event specific average lengths of stay calculated from the West of Scotl and coronary prevention study . Subjects : Men with hypercholesterolaemia similar to the subjects in the West of Scotl and coronary prevention study . Main outcome : Cost consequences , the number of transitions from health to cardiovascular disease prevented , the number needed to start treatment , and cost per life year gained . Results : If 10 000 of these men started taking pravastatin , 318 of them would not make the transition from health to cardiovascular disease ( number needed to treat , 31.4 ) , at a net discounted cost of £ 20 m over 5 years . These benefits imply an undiscounted gain of 2460 years of life , and thus £ 8121 per life year gained , or £ 20 375 per life year gained if benefits are discounted . Restriction to the 40 % of men at highest risk reduces the number needed to treat to 22.5 ( £ 5601 per life year gained ( undiscounted ) and £ 13 995 per life year gained ( discounted ) ) . Conclusions : In subjects without evidence of prior myocardial infa rct ion but who have hypercholesterolaemia , the use of pravastatin yields substantial health benefits at a cost that is not prohibitive overall and can be quite efficient in selected high risk subgroups . Key messages The West of Scotl and coronary prevention study showed that pravastatin can prevent cardiovascular disease in men with hypercholesterolaemia So far , reports have deemed this prevention unjustified due to adverse economic implication s This analysis , based on data from the West of Scotl and coronary prevention study and extensive data from the Scottish record linkage system , shows that using pravastatin in this way is worth considering because of its substantial clinical benefit at a reasonable cost Practitioners must now consider using pravastatin to prevent cardiovascular disease in men with hypercholesterolaemia Increased economic efficiency may be obtained by restricting prevention to patients with additional risk",
"STUDY OBJECTIVE To determine the epidemiology of unwitnessed out-of-hospital cardiac arrest and the factors associated with survival after resuscitation using the Utstein style data collection . METHODS We conducted a prospect i ve cohort study in a 525,000- population city served by a single EMS system comprising a tiered response with physicians in the field . We studied consecutive unwitnessed out-of-hospital cardiac arrests that occurred between January 1 , 1994 , and December 31 , 1995 . We determined survival from cardiac arrest to discharge from hospital and the factors associated with survival . RESULTS Of the 809 patients for whom resuscitation was considered , 205 ( 25.3 % ) had sustained unwitnessed arrests . Cardiac origin of arrest was verified in 52 % of cases . The most common noncardiac causes of arrest were trauma , intoxication , near-drowning , and hanging . In 150 patients ( 73.2 % ) the presenting rhythm was asystole , in 28 ( 13.6 % ) it was pulseless electrical activity , and in 27 ( 13.2 % ) it was ventricular fibrillation . Resuscitation was attempted in 162 cases , 59 ( 36.4 % ) of whom demonstrated return of spontaneous circulation ; 45 ( 27.8 % ) were hospitalized alive , and 8 ( 4.9 % ) were discharged . The survivors represented 6.7 % of all out-of-hospital cardiac arrest survivors during the study period . Survival was most likely if patients presented with pulseless electrical activity ; none of the patients with asystole of cardiac origin survived . Sex ( P = .032 ) , age ( inverse relationship , P = .0004 ) , scene of collapse ( P = .042 ) , and interval from call receipt to arrival of first responders ( P = .004 ) were associated with survival . In a logistic-regression model , near-drowning remained an independent factor of survival ( odds ratio , 15.5 ; 95 % confidence interval , 1.2 to 200 ) . A routine priority dispatching protocol differentiated cardiac arrest patients with survival potential from those who already had irreversible signs of death . CONCLUSION This survey shows that survival after unwitnessed out-of-hospital cardiac arrest is unlikely with an initial response of basic life support alone . Withdrawal of resuscitation should be considered if an adult victim of unwitnessed cardiac arrest is found in asystole and the arrest is of obvious cardiac origin",
"OBJECTIVE : To determine the positive predictive value of ICD-9-CM coding of acute myocardial infa rct ion and cardiac procedures . METHODS : Using chart- abstract ed data as the st and ard , we examined administrative data from the Veterans Health Administration for a national r and om sample of 5,151 discharges . MAIN RESULTS : The positive predictive value of acute myocardial infa rct ion coding in the primary position was 96.9 % . The sensitivity and specificity of coding were , respectively , 96 % and 99 % for catheterization , 95.7 % and 100 % for coronary artery bypass graft surgery , and 90.3 % and 99.7 % for percutaneous transluminal coronary angioplasty . CONCLUSIONS : The positive predictive value of acute myocardial infa rct ion and related procedure coding is comparable to or better than previously reported observations of administrative data bases",
"BACKGROUND Lowering the blood cholesterol level may reduce the risk of coronary heart disease . This double-blind study was design ed to determine whether the administration of pravastatin to men with hypercholesterolemia and no history of myocardial infa rct ion reduced the combined incidence of nonfatal myocardial infa rct ion and death from coronary heart disease . METHODS We r and omly assigned 6595 men , 45 to 64 years of age , with a mean ( + /- SD ) plasma cholesterol level of 272 + /- 23 mg per deciliter ( 7.0 + /- 0.6 mmol per liter ) to receive pravastatin ( 40 mg each evening ) or placebo . The average follow-up period was 4.9 years . Medical records , electrocardiographic recordings , and the national death registry were used to determine the clinical end points . RESULTS Pravastatin lowered plasma cholesterol levels by 20 percent and low-density-lipoprotein cholesterol levels by 26 percent , whereas there was no change with placebo . There were 248 definite coronary events ( specified as nonfatal myocardial infa rct ion or death from coronary heart disease ) in the placebo group , and 174 in the pravastatin group ( relative reduction in risk with pravastatin , 31 percent ; 95 percent confidence interval , 17 to 43 percent ; P definite nonfatal myocardial infa rct ions ( 31 percent reduction , P death from coronary heart disease ( definite cases alone : 28 percent reduction , P = 0.13 ; definite plus suspected cases : 33 percent reduction , P = 0.042 ) , and death from all cardiovascular causes ( 32 percent reduction , P = 0.033 ) . There was no excess of deaths from noncardiovascular causes in the pravastatin group . We observed a 22 percent reduction in the risk of death from any cause in the pravastatin group ( 95 percent confidence interval , 0 to 40 percent ; P = 0.051 ) . CONCLUSIONS Treatment with pravastatin significantly reduced the incidence of myocardial infa rct ion and death from cardiovascular causes without adversely affecting the risk of death from noncardiovascular causes in men with moderate hypercholesterolemia and no history of myocardial infa rct ion",
"OBJECTIVES We sought to report the first and repeat events and to separate spontaneous and procedure-related events over two years in the Fast Revascularization during InStability in Coronary artery disease ( FRISC-II ) invasive trial . BACKGROUND The FRISC-II invasive trial compared the long-term effects of an early invasive versus noninvasive strategy , in terms of death and myocardial infa rct ion ( MI ) and the need for repeat hospital admissions and late revascularization procedures in patients with coronary artery disease ( UCAD ) . METHODS In the FRISC-II trial , 2,457 patients with UCAD were r and omized to an early invasive or noninvasive strategy . RESULTS At 24 month follow-up , there were reductions in mortality ( n = 45 [ 3.7 % ] vs. 67 [ 5.4 % ] ; risk ratio 0.68 [ 95 % confidence interval ( CI ) 0.47 to 0.98 ] ; p = 0.038 ) , MI ( n = 111 [ 9.2 % ] vs. 156 [ 12.7 % ] ; risk ratio 0.72 [ 95 % CI 0.57 to 0.91 ] ; p = 0.005 ) , and the composite end point of death or MI ( n = 146 [ 12.1 % ] vs. 200 [ 16.3 % ] ; risk ratio 0.74 [ 95 % CI 0.61 to 0.90 ] ; p = 0.003 ) in the invasive compared with the noninvasive group . Procedure-related MIs were two to three times more common , but spontaneous ones were three times less common in the invasive than in the noninvasive group . After the first year , there was no difference in mortality ( n = 20 [ 1.7 % ] ) between the two groups and fewer MIs in the invasive group ( p = 0.031 ) . CONCLUSIONS In UCAD , the early invasive approach leads to a sustained reduction in mortality , cardiac morbidity , and the need for repeat hospital admissions and late revascularization procedures . Although the benefits are greatest during the first months , during the second year , cardiac morbidity is lower and the need for hospital care is less in the invasive group"
] |
4116c4c8-06ff-11f0-808a-c43d1ab1c353
|
Autism Spectrum Disorder ( ASD ) is a neurodevelopmental disease that is specially characterized by impairments in social communication and social skills . ASD has a high prevalence in children , affecting 1 in 160 subjects . Virtual reality ( VR ) has emerged as an effective tool for intervention in the health field . Different recent papers have review ed the VR-based treatments in ASD , but they have an important limitation because they only use clinical data bases and do not include important technical indexes such as the Web of Science index or the Scimago Journal & Country Rank . To our knowledge , this is the first contribution that has carried out an evidence -based systematic review including both clinical and technical data bases about the effectiveness of VR-based intervention in ASD . The initial search identified a total of 450 records . After the exclusion of the papers that are not studies , duplicated articles , and the screening of the abstract and full text , 31 articles met the PICO ( Population , Intervention , Comparison and Outcomes ) criteria and were selected for analysis . The studies examined suggest moderate evidence about the effectiveness of VR-based treatments in ASD . VR can add many advantages to the treatment of ASD symptomatology , but it is necessary to develop consistent validations in future studies to state that VR can effectively complement the traditional treatments
|
[
"PURPOSE Surgical training methods are evolving with the technological advancements , including the application of virtual reality ( VR ) and augmented reality . However , 28 to 40 % of novice residents are not confident in performing a major surgical procedure . VR surgery , an immersive VR ( iVR ) experience , was developed using Oculus Rift and Leap Motion devices ( Leap Motion , Inc , San Francisco , CA ) to address this challenge . Our iVR is a multisensory , holistic surgical training application that demonstrates a maxillofacial surgical technique , the Le Fort I osteotomy . The main objective of the present study was to evaluate the effect of using VR surgery on the self-confidence and knowledge of surgical residents . MATERIAL S AND METHODS A multisite , single-blind , parallel , r and omized controlled trial ( RCT ) was performed . The participants were novice surgical residents with limited experience in performing the Le Fort I osteotomy . The primary outcome measures were the self- assessment scores of trainee confidence using a Likert scale and an objective assessment of the cognitive skills . Ninety-five residents from 7 dental schools were included in the RCT . The participants were r and omly divided into a study group of 51 residents and a control group of 44 . Participants in the study group used the VR surgery application on an Oculus Rift with Leap Motion device . The control group participants used similar content in a st and ard PowerPoint presentation on a laptop . Repeated measures multivariate analysis of variance was applied to the data to assess the overall effect of the intervention on the confidence of the residents . RESULTS The study group participants showed significantly greater perceived self-confidence levels compared with those in the control group ( P = .034 ; α = 0.05 ) . Novices in the first year of their training showed the greatest improvement in their confidence compared with those in their second and third year . CONCLUSIONS iVR experiences improve the knowledge and self-confidence of the surgical residents",
"OBJECTIVE This article review s the available literature about the use of novel methods of rehabilitation using virtual reality interventions for people living with posttraumatic brain injuries . MATERIAL S AND METHODS The MEDLINE , EMBASE , SCOPUS , and Cochrane Library data bases were search ed using the terms \" virtual reality \" OR \" video games \" AND \" traumatic brain injury . \" Included studies investigated therapeutic use of virtual reality in adults with a brain trauma result ing from acquired closed head injury , reported outcomes that included measures of motor or cognitive functionality , and were published in a peer- review ed journal written in English . RESULTS Eighteen articles fulfilled inclusion criteria . Eight were case studies , five studies had a quasi-experimental design with a pre-post comparison , and five were pilot r and omized control trials or comparative studies . The virtual reality systems used were commercial or custom design ed for the study and ranged from expensive , fully immersive systems to cheap online games or videogames . In before-after comparisons , improvements in balance were seen in four case studies and two small r and omized control trials . Between-group comparisons in these r and omized control trials showed no difference between virtual reality and traditional therapy . Post-training improvements were also seen for upper extremity functions ( five small studies ) and for various cognitive function measures ( four case studies and one pilot r and omized control trial ) . Attitudes of participants toward virtual reality interventions was more positive than for traditional therapy ( three studies ) . CONCLUSIONS The evidence that the use of virtual reality in rehabilitation of traumatic brain injury improves motor and cognitive functionality is currently very limited . However , this approach has the potential to provide alternative , possibly more affordable and available rehabilitation therapy for traumatic brain injury in setting s where access to therapy is limited by geographical or financial constraints",
"Anxiety is common in children with autism spectrum disorders ( ASD ) , with specific fears and phobias one of the most frequent subtypes . Specific fears and phobias can have a serious impact on young people with ASD and their families . In this study we developed and evaluated a unique treatment combining cognitive behaviour therapy ( CBT ) with graduated exposure in a virtual reality environment ( VRE ) . Nine verbally fluent boys with an ASD diagnosis and no reported learning disability , aged 7 to 13 years old , were recruited . Each had anxiety around a specific situation ( e.g. crowded buses ) or stimulus ( e.g. pigeons ) . An individualised scene was recreated in our ‘ wrap-around ’ VRE . In the VRE participants were coached by a psychologist in cognitive and behavioural techniques ( e.g. relaxation and breathing exercises ) while the exposure to the phobia/fear stimulus was gradually increased as the child felt ready . Each child received four 20–30 minute sessions . After participating in the study , eight of the nine children were able to tackle their phobia situation . Four of the participants completely overcame their phobia . Treatment effects were maintained at 12 months . These results provide evidence that CBT with VRE can be a highly effective treatment for specific phobia/fear for some young people with ASD . Trial Registration Controlled-Trials.com IS RCT N58483069",
"OBJECTIVES Parkinson 's disease ( PD ) is a progressive neurodegenerative disorder characterized by motor clinical alterations among others . Postural problems have serious consequences for patients , not only limiting their daily life but also increasing some risks , like the risk of fall . Inadequate postural control and postural instability is a major problem in PD patients . A Virtual Motor Rehabilitation System ( VMR ) has been tested in patients with PD in the intervention period . Our purpose was to analyze the evolution of the spatial postural control during the intervention period , to see if there are any changes caused precisely by this intervention . METHODS Ten people with PD carried out 15 virtual rehabilitation sessions . We tested a groundbreaking system based on Virtual Motor Rehabilitation in two periods of time ( baseline evaluation and final evaluation ) . In the training sessions , the participants performed a customizable treatment using a low-cost system , the Active Balance Rehabilitation system ( ABAR ) . We stored the pressure performed by the participants every five hundredths of a second , and we analyzed the patients ' pressure when they maintained their body on the left , on the right , and in the center in sitting position . Our system was able to measure postural control in every patient in each of the virtual rehabilitation sessions . RESULTS There are no significant differences in the performance of postural control in any of the positions evaluated throughout the sessions . Moreover , the results show a trend to an improvement in all positions . This improvement is especially remarkable in the left/right positions , which are the most important positions in order to avoid problems such as the risk of fall . With regard to the suitability of the ABAR system , we have found outst and ing results in enjoyment , success , clarity , and helpfulness . CONCLUSIONS Although PD is a progressive neurodegenerative disorder , the results demonstrate that patients with PD maintain or even improve their postural control in all positions . We think that the main factor influencing these results is that patients use more of their available cognitive processing to improve their postural control . The ABAR system allows us to make this assumption because the system requires the continuous attention of patients , promoting cognitive processing",
"Objective : To investigate the effect of exposure to a virtual reality ( VR ) environment preoperatively on patient-reported outcomes for surgical operations . Background : There is a scarcity of well-developed quality improvement initiatives targeting patient satisfaction . Methods : We performed a r and omized controlled trial of patients undergoing cranial and spinal operations in a tertiary referral center . Patients underwent a 1:1 r and omization to an immersive preoperative VR experience or st and ard preoperative experience stratified on type of operation . The primary outcome measures were the Evaluation du Vecu de l’Anesthesie Generale ( EVAN-G ) score and the Amsterdam Preoperative Anxiety and Information ( APAIS ) score , as markers of the patient 's experience during the surgical encounter . Results : During the study period , a total of 127 patients ( mean age 55.3 years , 41.9 % females ) underwent r and omization . The average EVAN-G score was 84.3 ( st and ard deviation , SD , 6.4 ) after VR , and 64.3 ( SD , 11.7 ) after st and ard preoperative experience ( difference , 20.0 ; 95 % confidence interval , CI , 16.6–23.3 ) . Exposure to an immersive VR experience also led to higher APAIS score ( difference , 29.9 ; 95 % CI , 24.5–35.2 ) . In addition , VR led to lower preoperative VAS stress score ( difference , −41.7 ; 95 % CI , −33.1 to −50.2 ) , and higher preoperative VAS preparedness ( difference , 32.4 ; 95 % CI , 24.9–39.8 ) , and VAS satisfaction ( difference , 33.2 ; 95 % CI , 25.4–41.0 ) scores . No association was identified with VAS stress score ( difference , −1.6 ; 95 % CI , −13.4 to 10.2 ) . Conclusions : In a r and omized controlled trial , we demonstrated that patients exposed to preoperative VR had increased satisfaction during the surgical encounter . Harnessing the power of this technology , hospitals can create an immersive environment that minimizes stress , and enhances the perioperative experience",
"Objectives : Cognitive-behavioral therapies ( CBT ) for fibromyalgia syndrome ( FMS ) are important interventions in the management of this condition . Empirical evidence reports that although the results are promising , further research is needed to respond more appropriately to these patients . This study focuses on exploring the use of Virtual Reality ( VR ) as an adjunct to the activity management component . The aim of this study is to present the results of a small-sized r and omized controlled trial to test the preliminary efficacy and acceptability of this component . Material s and Methods : The final sample was composed of 61 women diagnosed with FMS according to the American College of Rheumatology . The sample was r and omly allocated to 2 conditions : VR treatment and treatment as usual . Results : Participants in the VR condition achieved significant improvements in the primary outcome : disability measured with the FIQ . The improvement was also significant in secondary outcomes , such as perceived quality of life and some of the coping strategies included in the Chronic Pain Coping Inventory : task persistence and exercise . There were no differences in other secondary outcome measures like pain intensity and interference and depression . Participants reported high satisfaction with the VR component . Discussion : The effects were related to the psychological aspects targeted in the treatment . The component was well accepted by FMS patients referred from a public hospital . These findings show that the VR component could be useful in the CBT treatment of FMS and encourage us to continue exploring the use of integrating VR with CBT interventions for the treatment of FMS"
] |
4116c504-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND Benign prostatic hyperplasia ( BPH ) , a non-malignant enlargement of the prostate in aging men , can cause bothersome urinary symptoms ( intermittency , weak stream , straining , urgency , frequency , incomplete emptying ) . Finasteride , a five-alpha reductase inhibitor ( 5ARI ) , blocks the conversion of testosterone to dihydrotestosterone , reduces prostate size , and is commonly used to treat symptoms associated with BPH . OBJECTIVES To compare the clinical effectiveness and harms of finasteride versus placebo and active controls in the treatment of lower urinary tract symptoms ( LUTS ) . SEARCH STRATEGY We search ed The Cochrane Library ( which includes CDSR ( Cochrane Data base of Systematic Review s ) , DARE ( Data base of Abstract s of Review s of Effects ) , HTA ( Heath Technology Assessment s ) , and CENTRAL ( Cochrane Central Register of Controlled Trials , and which includes EMBASE and MEDLINE ) , LILACS ( Latin American and Caribbean Center on Health Sciences Information ) and Google Scholar for r and omized , controlled trials ( RCTs ) . We also h and search ed systematic review s , references , and clinical - practice guidelines . SELECTION CRITERIA R and omized trials in the English language with placebo and /or active arms with a duration of at least 6 months . DATA COLLECTION AND ANALYSIS JT extracted the data , which included patient characteristics , outcomes , and harms . Our primary outcome was change in a vali date d , urinary symptom-scale score , such as the AUA/IPSS . A clinical ly meaningful change was defined as 4 points . We also categorized outcomes by trial lengths of ≤ 1 year ( short term ) and > 1 year ( long term ) . MAIN RESULTS Finasteride consistently improved urinary symptom scores more than placebo in trials of > 1 year duration , and significantly lowered the risk of BPH progression ( acute urinary retention , risk of surgical intervention , ≥ 4 point increase in the AUASI/IPSS ) . In comparison to alpha-blocker monotherapy , finasteride was less effective than either doxazosin or terazosin , but equally effective compared to tamsulosin . Both doxazosin and terazosin were significantly more likely than finasteride to improve peak urine flow and nocturia , versus finasteride . Versus tamsulosin , peak urine flow and QoL improved equally well versus finasteride . However , finasteride was associated with a lower risk of surgical intervention compared to doxazosin , but not to terazosin , while finasteride and doxazosin were no different for risk of acute urinary retention . Two small trials reported no difference in urinary symptom scores between finasteride and tamsulosin . Finasteride + doxazosin and doxazosin monotherapy improved urinary symptoms equally well ( ≥ 4 point improvement).For finasteride , there was an increased risk of ejaculation disorder , impotence , and lowered libido , versus placebo . Versus doxazosin , finasteride had a lower risk of asthenia , dizziness , and postural hypotension , and versus terazosin , finasteride had a significant , lower risk of asthenia , dizziness , and postural hypotension . AUTHORS ' CONCLUSIONS Finasteride improves long-term urinary symptoms versus placebo , but is less effective than doxazosin . Long-term combination therapy with alpha blockers ( doxazosin , terazosin ) improves symptoms significantly better than finasteride monotherapy . Finasteride + doxazosin improves symptoms equally - and clinical ly - to doxazosin alone . In comparison to doxazosin , finasteride + doxazosin appears to improve urinary symptoms only in men with medium ( 25 to 40 mL ) or large prostates ( ≥ 40 mL ) , but not in men with small prostates ( 25 mL).Comparing short to long-term therapy , finasteride does not improve symptoms significantly better than placebo at the short term , but in the long term it does , although the magnitude of differences was very small ( from point to 2.2 points ) . Doxazosin improves symptoms better than finasteride both short and long term , with the magnitude of differences ∼2.0 points and 1.0 point , respectively . Finasteride + doxazosin improves scores versus finasteride alone at both short and long term , with mean differences ∼2.0 points for both time points . Finasteride + doxazosin versus doxazosin improves scores equally for short and long term . Drug-related adverse effects for finasteride are rare ; nevertheless , men taking finasteride are at increased risk for impotence , erectile dysfunction , decreased libido , and ejaculation disorder , versus placebo . Versus doxazosin , which has higher rates of dizziness , postural hypotension , and asthenia , men taking finasteride are at increased risk for impotence , erectile dysfunction , decreased libido , and ejaculation disorder . Finasteride significantly reduces asthenia , postural hypotension , and dizziness versus terazosin . Finasteride significantly lowers the risk of asthenia , dizziness , ejaculation disorder , and postural hypotension , versus finasteride + terazosin
|
[
"BACKGROUND The Early Intervention Study , a placebo-controlled clinical trial , enrolled approximately 200 patients between age 45 - 65 years who had mild symptoms associated with early benign hyperplasia ( BPH ) . Prostate volume was measured by magnetic resonance imaging ( MRI ) and read by the local radiologist , who was blinded to the treatment group but not to the sequence of MRI scans . In order to ascertain whether knowledge of the sequence of the MRI scans by the local radiologist was introducing bias in prostate volume changes , a single radiologist was selected to reread all MRI scans at the end of the study . METHODS Each film was masked as to patient identity , study drug , and date . A new r and omization schedule was prepared to blind the single reader to both sequence and treatment . The two sets of readings were compared . RESULTS Accuracy was dramatically improved when defined as percentage of patients with a 20 % or more decrease in prostate volume , from 14 % to 0 % in placebo patients , and from 38 % to 29 % in finasteride patients . The variability was significantly reduced ( by 50 % ) when read by a single observer [ 1 ] . CONCLUSIONS A single reader , blinded to time sequence as well as to therapy , improves the accuracy and precision of the measurements when compared to multiple readers , blinded only to drug therapy",
"A group of 69 men with bladder outflow obstruction due to benign prostatic hyperplasia ( BPH ) were treated in a double-blind , placebo-controlled study with finasteride ( Proscar , MK-906 ) , a 5-alpha reductase inhibitor , 5 mg or 10 mg/day or placebo for 3 months ; subsequently , 20 patients received finasteride 5 mg/day for a further 9 months in an open extension study . In treated patients dihydrotestosterone declined by over 60 % , remaining unchanged with placebo . Symptom scores fell significantly in all 3 groups . Mean maximum flow rates fell slightly in placebo-treated patients but improved by 1.5 ml/s in the 10 mg group and by 3.3 ml/s in the 5 mg group . After 1 year 's treatment , the reduction in symptom score and increase in flow rate were well maintained ; the mean prostate volume was reduced by 14 % and prostatic specific antigen declined by 28 % . It was concluded that finasteride shows some efficacy in the treatment of BPH , with minimal toxicity , but 12 months of therapy or longer may be necessary to achieve maximal effect",
"The clinical effects of finasteride , a 5 alpha-reductase inhibitor , in patients with benign prostatic hyperplasia ( BPH ) were evaluated in a double-blind , placebo-controlled study . Forty-six patients with symptomatic BPH were r and omly assigned to 2 groups , the finasteride group and the placebo group . The finasteride group received 5 mg of finasteride daily for 6 months . Prostate volume , urinary flow , urinary symptoms , serum prostate-specific antigen ( PSA ) and adverse events were determined before and after treatment . After 6 months of treatment the patients treated with 5 mg of finasteride per day had a 30 % decrease in their total urinary symptom score , a 14 % decrease in prostate volume and a 0.9 ng/dL decrease of PSA . Their maximal urinary flow rate increased by 1.42 mL per second and the mean urinary flow rate increased by 0.64 mL per second . The patients given placebo showed no significant changes in their prostate volume , serum PSA and maximal and mean urinary flow rate . However , the symptom scores in the placebo group also decreased significantly . When compared with the placebo group , those in the finasteride group had significantly lower prostate volume , serum PSA , maximal urinary flow rate and urinary symptoms , but not mean urinary flow rate . The frequency of adverse events was low in both the finasteride and placebo groups . These results show that finasteride may be an effective and safe alternative for the treatment of patients with BPH",
"Objective To test the hypothesis that in patients with benign prostatic hyperplasia ( BPH ) , the outcome of drug therapy with finasteride may be predictable from the baseline prostate volume and that positive clinical effects might be expected only in patients with prostate volumes of > 40 mL , using a subgroup analysis of results from a previously reported clinical trial of finasteride and phytotherapy",
"We assessed the long-term safety and efficacy of finasteride , an orally active 5 alpha-reductase inhibitor , in 2 previously reported groups of patients with symptomatic benign prostatic hyperplasia ( BPH ) . Prostate volume was measured by magnetic resonance imaging , and the maximum urinary flow rate was assessed noninvasively . Symptoms were scored utilizing a patient self-administered symptom score question naire . Total symptom scores ranged from 0 ( or asymptomatic ) to 35 ( severely symptomatic ) . After an initial double-blind period , the patients in study 1 were treated with 10 mg finasteride for 1 year and then switched to 5 mg finasteride for an additional 4 years , whereas patients in study 2 were treated with 5 mg finasteride for the entire 5 years . A total of 190 patients were r and omized in the double-blind studies , 156 entered year 1 of the open extension and 70 patients completed 5 years of finasteride therapy . In both studies prostate volume was reduced from baseline by 30 % , dihydrotestosterone was reduced by 72 % , and the maximum urinary flow rate improved by approximately 1.5 ml/s . Prostate-specific antigen was decreased by approximately 50 % . Finasteride was well tolerated ; approximately 10 % of patients reported sexual adverse experiences during the 5-year study period , which were considered drug related by the investigators . The incidence in reporting sexual adverse experiences did not increase with the increased duration of treatment : findings consistent with previous reports . In summary treatment of BPH with finasteride for 5 years inhibits the progression of the disease with an excellent safety profile and represents a low-risk medical option for the treatment of symptomatic BPH",
"In this multicentre , double-blind study , patients with LUTS/BPH were r and omised to 26 weeks with finasteride 5 mg once daily ( n=204 ) or tamsulosin 0.4 mg once daily ( n=199 ) . Double-blind treatment was continued for another 26 weeks ( total treatment duration : 1 y ) . The primary efficacy parameter was the difference in mean change in total Symptom Problem Index ( SPI ) from baseline to end point at week-26 in the intention-to-treat ( ITT ) and per protocol ( PP ) population s. Tamsulosin induced a greater improvement in total SPI ( −5.2 points or −37 % ) compared to finasteride ( −4.5 points or −31 % ) at week-26 ( P=0.055 in ITT and P=0.032 in PP ) . Tamsulosin improved urinary symptoms ( particularly the more bothersome storage symptoms ) and flow more quickly than finasteride . The difference was statistically significant for the SPI from week-1 ( reduction , respectively , −2.5 vs −1.8 points , P=0.043 ) to week-18 and for Qmax from week-1 ( increase , respectively , 2.3 vs 0.7 ml/s , P=0.0007 ) to week-12 . Both treatments were well tolerated with a comparable incidence of adverse events , including urinary retention",
"We studied the effects of 5 alpha-reductase inhibitor ( finasteride ) in the treatment of benign prostatic hyperplasia ( BPH ) . This study is a r and omized controlled trial . Sixty-two patients were treated with 5 alpha-reductase ( finasteride 5 mg/day ) and 61 patients ( control group ) with placebo for one year . Prostatic volume , maximal urine flow rate , AUA symptom scoring , residual urine volume and prostate-specific antigen ( PSA ) levels were evaluated at 3 , 6 , 9 and 12 months . In the first 6 months prostatic volume decreased rapidly ( 20.5 % ) , in the second 6 months it decreased slowly and reached the maximal rate ( 23.3 % ) . Maximal urine flow rate increased in the second 6 months . AUA symptom scores decreased first at 3 months and were 4.6 points lower at the end of the 12th month . There were no significant changes in residual volume . The 5 alpha-reductase inhibitor caused a 50 % decrease in PSA levels , like in other studies .Becuase of the prolonged use of the drug , treatment with 5 alpha-reductase inhibitor is not tolerated by many patients and being expensive its future in the pharmacotherapy of BPH is unclear",
"The purpose of this paper is to examine effects of finasteride 5 mg across different age groups in an ethnically diverse population of men with symptomatic benign prostatic hyperplasia ( BPH ) seen in community urology and primary care practice s. Data were combined from two previous placebo-controlled r and omised trials of finasteride that evaluated changes in urinary symptoms , blinded global assessment s of urologic status , adverse experiences , and effects on dihydrotestosterone ( DHT ) and prostate-specific antigen ( PSA ) in over 4500 men . Finasteride showed a favourable efficacy and tolerability profile in this large ethnically diverse population and was similarly effective in middle-aged and older men with BPH and prostate gl and enlargement",
"PURPOSE We evaluated the effectiveness of single or combination drug therapy on nocturia in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia . MATERIAL S AND METHODS A total of 3,047 men with lower urinary tract symptoms/benign prostatic hyperplasia enrolled in the Medical Therapy of Prostatic Symptoms trial were r and omly assigned to receive doxazosin alone , finasteride alone , combination therapy or placebo . Treatment effectiveness was assessed according to intent to treat by mean reduction in self-reported nightly nocturia at 1 and 4 years . A subgroup analysis by age ( younger than 70 vs 70 years old or older ) was also performed . RESULTS Of the men 2,583 reported 1 or more episodes of nocturia and finished 12 or more months of the trial . Mean nocturia was similar in all groups at baseline . Mean nocturia was reduced at 1 year by 0.35 , 0.40 , 0.54 and 0.58 in the placebo , finasteride , doxazosin and combination groups , respectively . Reductions with doxazosin and combination therapy were statistically greater than with placebo ( p nocturia was also significantly reduced in patients treated with doxazosin and combination therapy ( p ) . In men older than 70 years ( 495 ) all drugs significantly reduced nocturia at 1 year ( finasteride 0.29 , doxazosin 0.46 and combination 0.42 ) compared to placebo ( 0.11 , p Doxazosin and combination therapy reduced nocturia more than placebo , but the net benefit of active drug compared to placebo was often modest with a net difference of less than 0.20 fewer nightly nocturia episodes at 1 and 4 years . Findings in men 70 years old or older were similar , with an even smaller effect observed for finasteride",
"OBJECTIVES To determine the long-term effects of finasteride treatment on prostate tissue composition ; to relate these effects to clinical outcomes ; and to test the hypothesis that finasteride exerts a selective or preferential action on the transition zone . METHODS Nineteen men with symptomatic benign prostatic hyperplasia ( BPH ) who completed a 6-month double-blind trial of finasteride were enrolled in a 24-month open-label extension study of drug responders . Magnetic resonance imaging and prostate biopsy for morphometric analysis were performed together 70 times : at baseline ( n = 19 ) , after treatment periods of intermediate duration ( 6 to 18 months , n = 32 ) , and after long-term drug treatment ( 24 to 30 months , n = 19 ) . At baseline , prostate volume averaged 51 cc , of which 57 % was transition zone . RESULTS Decreases in symptom score , dihydrotestosterone and prostate-specific antigen levels , and prostate volume occurred at 6 months ( P Prostate epithelium contracted progressively from baseline ( 19.2 % tissue composition ; 6.0-cc volume ; 3.2 stroma/epithelial ratio ) to intermediate ( 12.5 % , 3.3 cc , and 5.6 , respectively ) to long-term treatment ( 6.4 % , 2.0 cc , and 17.4 , respectively , P Percent epithelial contraction was similar in the peripheral and transition zones ( P = NS ) . The transition zone remained a relatively constant proportion ( 53 % to 58 % ) of whole-prostate volume from baseline to long-term observation . CONCLUSIONS Long-term finasteride treatment ( 24 to 30 months ) results in a marked involution of the prostate epithelium , which continues to progress for many months after clinical effects stabilize . The effect on the epithelium is similar in the peripheral and transition zones for both morphometric and volumetric changes . Progressive contraction of the prostate epithelium appears to constitute the underlying mechanism for sustained action of finasteride",
"This study sought to assess the efficacy , tolerability , and effect of finasteride on health-related quality of life ( HRQL ) in a diverse population of men with moderate-to-severe symptomatic benign prostatic hyperplasia ( BPH ) . This double-blind study evaluated finasteride and placebo for 12 months in 2342 men with BPH ( 16.2 % black , 14.5 % Hispanic , 69.3 % Caucasian/other ) in a community-based setting . At 3-month intervals , urinary symptoms were measured by use of the American Urologic Association symptom index . HRQL was assessed by use of the BPH impact index ( BII ) , which evaluated degree of bother , worry , physical discomfort , and restriction in activities as a result of urinary symptoms . Additional questions regarding activities of living were administered , and global assessment s of change in urologic status were performed by both patients and investigators . Compared with placebo , patients treated with finasteride had a statistically significant decrease in symptom scores when first measured at month 3 . Symptom scores continued to improve in finasteride-treated patients throughout the study ; at month 12 , the mean decrease in symptom scores in the finasteride-treated patients was -4.8 compared with -3.4 for placebo patients ( P = 0.0001 ) . Statistically significant differences in favor of finasteride also were noted at month 12 on the BII ( P = 0.0465 ) , and finasteride-treated patients experienced less interference with activities of living ( P = 0.0518 ) . Patient and investigator global assessment s of urologic status showed that significantly more patients in the finasteride group considered themselves improved and were considered improved by investigators at month 12 ( P = 0.000 ) . Finasteride was generally well tolerated . The incidence of drug-related sexual adverse experiences was significantly higher in the finasteride group ( P = 0.000 ) , but led to withdrawal in only 1.5 % of patients . The demonstrated efficacy and tolerability of finasteride in reducing symptoms and improving quality of life confirm observations of previous trials and make finasteride a highly desirable treatment option for many men with symptomatic BPH",
"Urodynamic effects of the 5-alpha-reductase inhibitor , finasteride , were studied in the treatment of patients with bladder outlet obstruction due to benign prostatic hyperplasia ( BPH ) . A total of 36 patients was r and omly assigned in a double-bind manner to receive either 5 mg . finasteride daily ( 19 ) or placebo ( 17 ) for 6 months . The possible relief of bladder outlet obstruction was monitored with uroflowmetry and repeated urodynamics . The mean flow rate , detrusor opening pressure , detrusor pressure at maximum flow and maximum detrusor pressure improved significantly in the patients treated with finasteride . There were no significant differences in the improvement of symptom score or peak flow rate , or in the reduction of residual urine between the finasteride and placebo groups . The treatment result ed in 30 % average decrease in prostatic size and 46 % decrease in prostate specific antigen concentration . The efficacy of finasteride in relief of bladder outlet obstruction caused by BPH seems to be of the same degree as that achieved by chemical castration therapy but without any significant side effects . There were wide variations among BPH patient response to finasteride treatment . Further studies are needed to define the responders who benefit from this treatment",
"PURPOSE We determined the effect of long-term treatment with finasteride on the incidence of acute urinary retention ( AUR ) and benign prostatic hyperplasia ( BPH ) related surgery in men with BPH . MATERIAL S AND METHODS The Proscar ( Merck and Co. , Inc. , Whitehouse Station , New Jersey ) Long-Term Efficacy and Safety Study ( PLESS ) was comprised of 3040 men with enlarged prostates , moderate to severe symptomatic BPH and no clinical evidence of prostate cancer . Patients were r and omized to placebo or 5 mg finasteride daily for 4 years . Of the 3016 r and omized patients with available efficacy data 62 % completed the original 4-year study ( 1006 on finasteride and 891 on placebo ) and 89 % of these ( 908 from the original finasteride arm and 785 from the placebo arm ) continued in a 2-year open extension on finasteride . Followup was attempted in discontinued patients . Complete 6-year outcomes data , including 6-year followup in 770 men who had discontinued treatment during years 1 to 6 , were available for 2463 ( 82 % ) of the 3016 originally r and omized patients . RESULTS For patients on continuous finasteride treatment the decrease in incidence of AUR and /or BPH related surgery in the 4-year base study was sustained during the open extension . In patients who were switched from placebo to finasteride in the extension , the incidence of AUR and /or BPH related surgery was similar to that in the continuous finasteride arm . CONCLUSIONS The 6-year data from PLESS confirmed and further extended the findings from the original 4-year trial , demonstrating that finasteride treatment led to a sustained decrease in the incidence of AUR and /or BPH related surgery in men with BPH and enlarged prostates",
"Endocrine therapy by means of castration for benign prostatic hyperplasia was introduced already in the middle of the 19th century . The technique was never popularized and was ab and oned following the introduction of safe surgical techniques . In the second half of this century , small series of various endocrine treatments have been reported , mainly using progestational agents . The hormone dependency of the prostate is unique , since testosterone itself is not very active on the prostate cells but has to be converted to 5 alpha-dihydrotestosterone , which is almost ten times as effective an and rogen in the prostate cell . By blocking this conversion , highly specific anti and rogenic effect will be obtained in the prostate but not in other organs of the body . The first 5 alpha-reductase inhibitor , finasteride , has proven effective in reducing prostate DHT . In large clinical trials , it has shown to reduce prostate size , improve urinary flow and reduce symptom score , statistically significantly better than placebo . The effect is sustained over at least 3 years . In a double-blind , r and omized , placebo-controlled study over 2 years , patients were similarly improved in the finasteride group , whereas they deteriorated in the placebo group . This indicates that finasteride is able to halt the progression of the natural course of benign prostatic hyperplasia . Benign prostatic hyperplasia , generally believed to be a stromal disease , is potentially dependent on estrogens for its development . By blocking aromatization of testosterone to estrogen in the prostate cells , a hypothetical beneficial effect on the disease process should be gained . Results from phase II- studies have been promising . However , in placebo-controlled studies , aromatase inhibitors did not perform better than placebo . ( ABSTRACT TRUNCATED AT 250 WORDS",
"PURPOSE We evaluated the associations among lower urinary tract symptoms , prostate specific antigen ( PSA ) and erectile dysfunction ( ED ) in men with benign prostatic enlargement enrolled in the Proscar ( Merck , Whitehouse Station , New Jersey ) Long-Term Efficacy and Safety Study . MATERIAL S AND METHODS The Proscar Long-Term Efficacy and Safety Study was a 4-year , r and omized , double-blind , placebo controlled study that enrolled 3,040 men with moderate to severe lower urinary tract symptoms and an enlarged prostate gl and . Two questions assessed ED . A logistic regression model , including the effect of patient age , was used to examine the relationships among quasi-American Urological Association Symptom Score ( AUASS ) , PSA , and ED at baseline . Changes in ED scores from baseline to study closeout were analyzed with ANOVA . RESULTS A total of 2,981 patients had baseline data available for analysis . Mean age was 64 years , mean quasi-AUASS was 15 , mean PSA was 2.8 ng/ml and mean prostate volume was 55 cm . At baseline every 1 point increase in quasi-AUASS was associated with a 2 % increased risk of ED even after controlling for age ( p placebo but not in finasteride treated men a 1-unit decrease in quasi-AUASS was associated with a slight but statistically significant decrease in ED . No association existed between increasing PSA and ED on baseline or longitudinal analysis . CONCLUSIONS We found a moderately strong association between baseline quasi-AUASS and the ED rate in men with an enlarged prostate , a finding that was supported by longitudinal data in the placebo arm . The absence of a relationship between PSA and ED highlights the need for further investigation into the mechanisms of benign prostatic hyperplasia related sexual dysfunction",
"PURPOSE We determined the mechanism of adverse events associated with alpha1-blockers for treating benign prostatic hyperplasia ( BPH ) . MATERIAL S AND METHODS We r and omized 1,229 men with clinical BPH at 31 Veterans Affairs medical centers into equal treatment groups , including those who received placebo , terazosin , finasteride , and combined terazosin and finasteride therapy , respectively . Adverse events were captured at all study visits during our 1-year study . Our current review of adverse events is limited to patients r and omized to the placebo and terazosin groups . We compared the incidence of orthostatic blood pressure change , postural symptoms and orthostatic hypotension in men who were normotensive and hypertensive at baseline , respectively . We also determined the association of changes in systolic blood pressure with the incidence of treatment related adverse events . RESULTS The treatment related rates of dizziness , asthenia , postural hypotension and syncope were 19 % , 6 % , 6 % and 1 % , respectively . Of these adverse events only postural hypotension was associated with orthostatic blood pressure changes . The incidence of asthenia , dizziness and postural hypotension was not significantly greater in patients with a systolic blood pressure decrease of 5 or greater and less than 5 mm . Hg , respectively . CONCLUSIONS Dizziness and asthenia are not associated with changes in blood pressure , suggesting that these treatment related adverse events associated with alpha1-blockers are not related to vascular events . Design ing a subtype selective alpha1 antagonist that has less effect on blood pressure may not result in marked improvement in tolerability over commercially available alpha1-blockers",
"PURPOSE We analyze patterns of prostate growth in men diagnosed with benign prostatic hyperplasia ( BPH ) and treated with placebo during 4 years , and determine which baseline parameters were the strongest predictors of growth . MATERIAL S AND METHODS A total of 3,040 men were enrolled in the 4-year r and omized , placebo controlled Proscar Long-Term Efficacy and Safety study . Of these men a subgroup of 10 % underwent pelvic magnetic resonance imaging prostate volume measurement at baseline and yearly thereafter . Absolute and percent volume changes during 4 years were calculated in the 164 placebo treated men in the subgroup . The ability of age , baseline prostate volume and prostate specific antigen ( PSA ) to predict prostate growth in placebo treated patients was assessed by multiple linear regression analyses , receiver operator characteristics curves , and evaluations of growth stratified by tertiles of baseline serum PSA and decades of life . RESULTS In placebo treated patients a steady increase in mean plus or minus st and ard deviation prostate volume from year to year was noted ( 2.5+/-6.1 , 4.9+/-6.8 , 6.4+/-8.5 and 7.2+/-8.8 ml . at years 1 , 2 , 3 and 4 , respectively ) . Mean volume changes at 4 years ranged from -9 to + 30 ml . Mean percent change from baseline ranged from 12.5 % to 16.6 % for men 50 to 59 years old to those 70 to 79 years old . Baseline serum PSA was a strong predictor of growth with 7.4 % to 22.0 % change at 4 years from the lowest to highest PSA tertiles . Annualized growth rates from baseline were 0.7 ml . per year for PSA 0.2 to 1.3 , 2.1 for PSA 1.4 to 3.2 and 3.3 for PSA 3.3 to 9.9 ng./ml . Multiple linear regression analysis showed that serum PSA was a stronger predictor of prostate growth than age or baseline prostate volume . All but 1 man with baseline serum PSA greater than 2.0 ng./ml . had prostate growth during 4 years , and 32.6 % of men with serum PSA less than 2.0 exhibited a decrease in volume . CONCLUSIONS Serum PSA is a stronger predictor of growth of the prostate in placebo treated patients than age or baseline prostate volume . Since prostate volume is a risk factor for acute urinary retention and the need for BPH related surgery , the ability of PSA to predict prostate growth may be an important factor when considering individual treatment options for BPH . Such use of PSA represents a shift in paradigm away from focusing solely on symptoms of BPH toward a more comprehensive approach with consideration of predicting and preventing risk factors of BPH related outcomes",
"Finasteride is an enzyme inhibitor which blocks the conversion of testosterone by 5 alpha-reductase to dihydrotestosterone , the active and rogenic metabolite in the prostate . In a double-blind , placebo-controlled study , 707 patients with moderately symptomatic BPH were treated for 2 years . The study confirmed that treatment significantly improved symptoms , reduced prostate size and increased urine flow rate . Side effects were usually mild . The authors find that finasteride can reverse the natural progression of BPH",
"The efficacy and safety profiles of finasteride were tested in 1,645 patients with benign prostatic hyperplasia ( BPH ) over a 12-month period . The following effects were observed : ( 1 ) a 60 - 80 % reduction in serum dihydrotestosterone levels ; ( 2 ) a 20 % reduction in prostate volume ; ( 3 ) significant increases in the maximum urinary flow rate compared with placebo ; and ( 4 ) significant improvement in urinary symptoms , particularly obstructive symptoms . All effects were well maintained for the entire duration of the study . Finasteride had a good safety profile and was well tolerated",
"OBJECTIVES To assess the utility of voiding and filling symptom subscores in predicting features of benign prostatic hyperplasia ( BPH ) progression , including acute urinary retention ( AUR ) and prostate surgery . METHODS The Proscar Long-term Efficacy and Safety Study ( PLESS ) was a 4-year study design ed to evaluate the effects of finasteride versus placebo in men with lower urinary tract symptoms ( LUTS ) , clinical evidence of BPH , and no evidence of prostate cancer . A self-administered question naire was employed to quantify LUTS at baseline . Receiver operating characteristics ( ROC ) curves were used to assess baseline characteristics from patients treated with placebo as predictors of outcomes . The characteristics assessed included the overall symptom score ( Quasi-AUA SI ) , separate voiding and filling subscores , prostate volume ( PV ) and serum prostate-specific antigen ( PSA ) levels . RESULTS PV and PSA were superior to the symptom scores at predicting episodes of spontaneous AUR and all types of AUR . The Quasi-AUA SI and the filling and voiding subscores were effective at predicting progression to surgery ; however , PSA was more effective at predicting this outcome . To better evaluate symptoms as predictors of surgery , patients who experienced a preceding episode of AUR were excluded from the surgery analysis . In the absence of preceding AUR , the best predictors of future surgery were the Quasi-AUA SI and the filling subscore . CONCLUSIONS Among men with LUTS , clinical BPH and no history of AUR , the overall symptom score and storage subscore are useful parameters to aid clinicians in identifying patients at risk for future prostate surgery . PV and PSA were the best predictors of AUR , while PSA was the best predictor of prostate surgery ( for all indications )",
"We measured the maximum urinary flow rate monthly for 1 year by uroflowmetry in 1,645 patients in a double-blind , placebo-controlled study of finasteride therapy for benign prostatic hyperplasia . Patients were r and omized to receive placebo ( 555 ) or finasteride ( 1,090 ) . A total of 23,857 flow measurements was obtained . Because of the presence of artifacts on many uroflow curves , we read the maximum urinary flow rate values manually and compared them to the values provided electronically by the uroflowmeter . On average , the manually read values were 1.5 ml . per second lower than the machine read values . Artifacts causing a difference of 2 ml . per second or more between the 2 methods were found in 20 % and of more than 3 ml . per second in 9 % of the tracings . The difference between treatment groups in mean maximum urinary flow rate change at the end of the study was the same with both reading methods . However , confidence intervals were 15 to 25 % larger for the machine read compared to the manually read values . This larger variability in machine read maximum urinary flow rate has a marked negative impact on the power of statistical tests to assess any given difference in maximum urinary flow rate between treatment groups . Furthermore , it increases sample size requirements by 50 % to achieve any given statistical power . We conclude that maximum urinary flow rate artifacts contribute significantly to the variability of maximum urinary flow rate measurement by uroflowmetry . Manual reading of the maximum urinary flow rate eliminates an important fraction of such variability",
"PURPOSE We assess the long-term effects of finasteride on bladder outlet obstruction and symptoms in the treatment of patients with benign prostatic hyperplasia . MATERIAL S AND METHODS Of the original 36 patients assigned to treatment with 5 mg . finasteride daily ( group 1 ) or placebo ( group 2 ) for 6 months 27 completed an open extension study of 5 mg . finasteride for 4 more years . The possible relief of bladder outlet obstruction was monitored with repeated pressure-flow studies at baseline , 6 months and 4.5 years . RESULTS The treatment result ed in a further slight decrease in detrusor pressure at maximum flow rate in group 1 and a significant decrease in group 2 during the 4-year period , whereas improvement in maximum flow rate did not achieve statistical significance . Concomitantly , there was a significant improvement in obstructive and irritative symptoms . CONCLUSIONS Finasteride decreases bladder outlet obstruction moderately and only occasionally relieves it completely . However , the decrease in obstruction achieved in many patients is sufficient to improve the symptoms significantly . The beneficial effect is long-lasting",
"Objectives : We evaluated prostate volume and prostate – specific antigen ( PSA ) as predictors of acute urinary retention ( AUR ) in men with benign prostatic enlargement ( BPE ) . Methods : Data were pooled from 3 identical 2–year , multinational , multicenter , non – US , placebo – controlled finasteride trials in 4,222 men with BPE and no evidence of prostate cancer . Results : The 2–year incidence of spontaneous AUR was higher in placebo patients with enlarged prostates ( 4.2 % in men with prostate volume ≥40 ml vs 1.6 % in the . Finasteride reduced AUR incidence by 61 % in men with larger prostates , by 63 % in men with higher PSA levels , and by 47 % in men with smaller prostates , compared with placebo . Conclusions : BPE patients with larger prostate volumes , higher PSA levels and no evidence of prostate cancer have an increased risk of developing AUR and therefore derive the greatest benefit from the risk reduction seen with finasteride therapy",
"OBJECTIVES The aim of this study was to : ( 1 ) determine effects of finasteride on transition zone ( TZ ) volume , TZ ratio ( TZ volume/total prostate volume ) , and total prostate volume ; ( 2 ) analyze differences in TZ and total volume reduction among patients who improve peak urinary flow rates following finasteride therapy with those who do not ; ( 3 ) investigate which parameters correlate with improvement in peak urinary flow rate and urinary symptom score ; and ( 4 ) establish if there is any predictive value of these parameters for response to therapy . METHODS Twenty-three patients with symptomatic benign prostatic hyperplasia ( BPH ) were treated with finasteride ( 5 mg/d ) for 12 months and underwent transrectal ultrasound ( TRUS ) evaluation of total and TZ volume of prostate and measurement of peak flow rate and modified Boyarsky symptom score at baseline and at 12 months . Statistical analysis was done by unpaired t , Mann-Whitney , and Spearman rank correlation tests among responders ( more than 3 cc/s improvement in peak flow rate ) and nonresponders ( less than 3 cc/s improvement in peak flow rate ) to therapy . RESULTS ( 1 ) Responders had substantial reduction in TZ volume ( 44.8 % versus 16.05 % ; P ratio ( 25 % versus 5 % increase , P TZ volume ( r = 0.50 ; P TZ ratio ( r = 0.60 ; P peak flow rates . No similar correlation was seen with total prostate volume changes . ( 3 ) Pretreatment TZ ratio helped in predicting peak flow improvement following finasteride therapy ( r = 0.52 ; P modified Boyarsky symptom score decreased by 3.1 ( mean ) , but there was no correlation with changes in peak urinary flow rate , total prostate volume , TZ volume , and TZ ratio . TZ ratio did not have significant predictive value for improvement in symptom score . CONCLUSIONS This study provides data that simple measurable parameters are available which may be used prior to therapy to predict uroflow response to finasteride and similar agents",
"OBJECTIVES To summarize the 6-year clinical trial data with finasteride . Benign prostatic hyperplasia is a chronic and progressive disease and therefore assessment of long-term safety and efficacy is important . METHODS The North American and International Phase III Finasteride trials enrolled symptomatic men with enlarged prostate gl and s. The initial 1-year placebo-controlled study was followed by a 5-year open-label extension . In total , 6-year finasteride data were available in 487 patients originally r and omized to finasteride , and 5-year data were available on 238 patients originally r and omized to placebo . RESULTS After 6 years of treatment with finasteride 5 mg , the mean quasi-American Urological Association Symptom Score improved by 4.0 points , the median prostate volume decreased by 24 % , and the mean maximal urinary flow rate increased by 2.9 mL/s ( P finasteride treatment was well tolerated , with a low incidence of drug-related sexual adverse events occurring during the first year and even fewer occurrences during the 5-year open extension . CONCLUSIONS Treatment with finasteride leads to durable improvement in urinary tract symptoms , flow rate , and prostate volume , with no increase in the prevalence of drug-related adverse events over time",
"OBJECTIVES To evaluate the incidence and resolution of sexual adverse experiences ( AEs ) in men with benign prostatic hyperplasia treated with finasteride 5 mg compared with placebo . METHODS The Proscar Long-term Efficacy and Safety Study ( PLESS ) was a 4-year , r and omized , double-blind , placebo-controlled trial assessing the efficacy and safety of finasteride 5 mg in 3040 men , aged 45 to 78 years , with symptomatic benign prostatic hyperplasia , enlarged prostates , and no evidence of prostate cancer . Patients completed a question naire at screening regarding their history of sexual dysfunction . During treatment , spontaneously self-reported sexual AEs were recorded . RESULTS At screening , 46 % of patients in each treatment group reported some history of sexual dysfunction . During year 1 of the study , 15 % of finasteride-treated patients and 7 % of placebo-treated patients had sexual AEs that were considered drug related by the investigator ( P new sexual AEs ( 7 % in each group ) . The drug-related sexual AE profile for finasteride was similar for men with or without a history of sexual dysfunction . Sexual AEs resolved while continuing therapy in 12 % of finasteride patients and 19 % of placebo patients . Only 4 % of finasteride and 2 % of placebo patients discontinued the study because of sexual AEs . In men who discontinued with a sexual AE , 50 % and 41 % experienced resolution of their sexual AE after discontinuing finasteride or placebo therapy , respectively . CONCLUSIONS Compared with placebo , men treated with finasteride experienced new drug-related sexual AEs with an increased incidence only during the first year of therapy",
"OBJECTIVE To study if placebo-induced improvement in men with symptomatic benign prostatic hyperplasia ( BPH ) is maintained over two years , and to study the efficacy and safety from intervention with finasteride 5 mg for 24 months . METHODS This was a multicenter , double-blind , placeba-controlled study involving 707 patients with moderate symptoms of BPH enrolled at 59 centers in five Sc and inavian countries . Following enrollment and a four-week single-blind placebo run-in period , patients were r and omized to receive finasteride 5 mg once daily or placebo for 24 months . Urinary symptoms , urinary flow rate , prostate volume , postvoiding residual urinary volume , and serum concentrations of prostate-specific antigen together with laboratory safety parameters were measured at entry and at months 12 and 24 . Interim physical and laboratory examinations were performed when indicated clinical ly . RESULTS In finasteride-treated patients the total symptom score improved throughout the study , with a significant difference between the two groups at 24 months ( p placebo-treated patients , there was an initial improvement in the symptom score but no change from baseline at 24 months . The maximum urinary flow rate decreased in the placebo group , but improved in the finasteride group , result ing in a between-group difference of 1.8 mL/s at 24 months ( p mean change in prostate volume was + 12 % in the placebo group versus -19 % in the finasteride-treated group ( p%lt;0.01 ) . Finasteride was generally well tolerated throughout the two-year study period . CONCLUSIONS The efficacy of therapy with finasteride 5 mg in improving both symptoms and maximum urinary flow rate and reducing prostate volume has been shown to be maintained during 24 months while patients receiving placebo experienced a return to baseline or deterioration of these parameters during the study . These results demonstrate that finasteride can reverse the natural progression of BPH",
"BACKGROUND Benign prostatic hyperplasia is commonly treated with alpha-adrenergic-receptor antagonists ( alpha-blockers ) or 5alpha-reductase inhibitors . The long-term effect of these drugs , singly or combined , on the risk of clinical progression is unknown . METHODS We conducted a long-term , double-blind trial ( mean follow-up , 4.5 years ) involving 3047 men to compare the effects of placebo , doxazosin , finasteride , and combination therapy on measures of the clinical progression of benign prostatic hyperplasia . RESULTS The risk of overall clinical progression -- defined as an increase above base line of at least 4 points in the American Urological Association symptom score , acute urinary retention , urinary incontinence , renal insufficiency , or recurrent urinary tract infection -- was significantly reduced by doxazosin ( 39 percent risk reduction , P finasteride ( 34 percent risk reduction , P=0.002 ) , as compared with placebo . The reduction in risk associated with combination therapy ( 66 percent for the comparison with placebo , P doxazosin ( P risks of acute urinary retention and the need for invasive therapy were significantly reduced by combination therapy ( P finasteride ( P doxazosin . Doxazosin ( P finasteride ( P=0.001 ) , and combination therapy ( P scores , with combination therapy being superior to both doxazosin ( P=0.006 ) and finasteride ( P doxazosin and finasteride was safe and reduced the risk of overall clinical progression of benign prostatic hyperplasia significantly more than did treatment with either drug alone . Combination therapy and finasteride alone reduced the long-term risk of acute urinary retention and the need for invasive therapy",
"OBJECTIVES To evaluate the efficacy and tolerability of the selective alpha(1)-adrenergic antagonist doxazosin and the 5-alpha-reductase inhibitor finasteride , alone and in combination , for the symptomatic treatment of benign prostatic hyperplasia . METHODS In a prospect i ve , double-blind , placebo-controlled trial , 1095 men aged 50 to 80 years were r and omized to treatment for 52 weeks with doxazosin , finasteride , the combination of doxazosin and finasteride , or placebo . The dose of finasteride ( or its matched placebo ) was 5 mg/day . Doxazosin ( or its matched placebo ) was initiated at 1 mg/day , and titrated up to a maximum of 8 mg/day over approximately 10 weeks according to the response of the maximal urinary flow rate ( Qmax ) and International Prostate Symptom Score ( IPSS ) . The IPSS and Qmax were assessed at baseline and at weeks 10 , 14 , 26 , 39 , and 52 or at the endpoint . RESULTS An intent-to-treat analysis of 1007 men showed doxazosin and doxazosin plus finasteride combination therapy produced statistically significant improvements in total IPSS and Qmax compared with placebo and finasteride alone ( P total IPSS and Qmax . All treatments were generally well tolerated . CONCLUSIONS Doxazosin was effective in improving urinary symptoms and urinary flow rate in men with benign prostatic hyperplasia , and was more effective than finasteride alone or placebo . The addition of finasteride did not provide further benefit to that achieved with doxazosin alone",
"Benign prostatic hyperplasia ( BPH ) is a highly prevalent condition in aging men , which can be progressive and lead to acute urinary retention ( AUR ) and the need for surgery . It is commonly treated with alpha-blockers and 5alpha-reductase inhibitors ( 5ARIs ) , both of which improve the symptoms of BPH . Long-term treatment with 5ARIs can also reduce the risk of developing AUR and the need for surgery . The l and mark Medical Therapy of Prostatic Symptoms ( MTOPS ) trial demonstrated that over 4 years the combination of the type 2-specific 5ARI , finasteride and the alpha-blocker doxazosin was more effective than either agent alone in reducing overall clinical progression . Since the initiation of MTOPS , it has been shown that patients with larger prostates and higher prostate-specific antigen ( PSA ) levels are at greater risk of BPH progression , and are therefore arguably more likely to benefit from combination therapy . The Combination of Avodart and Tamsulosin ( CombAT ) trial is a 4-year , global , multicenter , r and omized , double-blind , parallel-group study design ed to investigate the benefits of combination therapy with the dual 5ARI dutasteride and the alpha-blocker tamsulosin compared with each monotherapy in improving symptoms and long-term outcomes in men with moderate-to-severe symptoms of BPH and prostate enlargement . Symptoms and long-term outcomes ( AUR and surgery ) will be assessed as separate primary endpoints at 2 and 4 years , respectively . Eligible patients were at least 50 years old with prostate volume > or = 30 cm(3 ) and PSA level > or = 1.5 ng/mL. A total of 4838 subjects have been enrolled . This paper describes the rationale , design and baseline data of the CombAT study",
"OBJECTIVES To evaluate prostate cancer detection and prostate-specific antigen ( PSA ) among men with benign prostatic hyperplasia treated with finasteride . METHODS Three thous and forty men 45 to 78 years of age with PSA less than 10 ng/mL and no history of prostate cancer were r and omized in a double-blind , placebo-controlled trial to finasteride ( n = 1524 ) or placebo ( n = 1516 ) for up to 4 years . A prer and omization biopsy negative for prostate cancer was obtained in 98 % of patients with a screening PSA of 4.0 ng/mL or more , and an end-of- study biopsy was requested of all such patients without a recent second negative biopsy or a prostate cancer diagnosis . RESULTS Overall , 644 patients ( 21 % ) underwent biopsy and 201 ( 6.6 % ) underwent transurethral resection of the prostate . Prostate cancer was diagnosed in 4.7 % of men on finasteride and 5.1 % on placebo ( P = 0.7 ) . Elevated PSA prompted diagnosis in 35 % of cases on finasteride and 34 % on placebo . The area under the receiver operating characteristic curve for last PSA was 0.84 on finasteride and 0.79 on placebo ( P = 0.07 ) . Use of an upper limit of normal for last PSA of 2.0 ng/mL for finasteride and 4.0 ng/mL for placebo yielded similar sensitivity ( 66 % versus 70 % , P = 0.6 ) , higher specificity ( 82 % versus 74 % , P likelihood ratio ( 3.6 versus 2.7 , P < 0.05 ) for finasteride than for placebo . CONCLUSIONS In men treated with finasteride , multiplying PSA by 2 and using normal ranges for untreated men preserves the usefulness of PSA for prostate cancer detection",
"Tamsulosin ( 0.2 mg ) and finasteride ( 5 mg ) once daily for 24 weeks were compared in a single-blind , r and omized study as initial treatments for lower urinary tract symptoms associated with benign prostatic hyperplasia ( BPH ) in 205 Korean patients . Symptom and quality of life ( QOL ) assessment by the International Prostatic Symptom Score ( I-PSS ) , maximum urinary flow rate ( Q max ) and adverse events were analysed at 4 weeks and 24 weeks . On intention-to-treat analysis , both drugs showed similar efficacy at endpoint ( decreased I-PSS , increased Q max and improved QOL score ; 34.7 % , 23.9 % and 34.1 % for tamsulosin , and 30.5 % , 22.2 % and 23.1 % for finasteride , respectively ) . However , tamsulosin produced significant improvements in I-PSS and Q max at 4 weeks compared with finasteride ( 17.6 % versus 10.0 % and 10.9 % versus 3.1 % , respectively ) , and a superior QOL score improvement during the study . Adverse events were observed significantly more frequently among finasteride than tamsulosin patients ( 23 versus four ) . Both were equally effective in long-term treatment of urinary outflow obstruction symptoms associated with BPH in Korean patients , but tamsulosin was more effective for short-term treatment , with a better safety profile",
"PURPOSE We evaluate the efficacy of medical therapy on nocturia in men with benign prostatic hyperplasia ( BPH ) . MATERIAL S AND METHODS We performed a secondary analysis of data from the VA Cooperative Study Program Trial in which 1,229 men with BPH 45 to 80 years old were r and omly assigned to receive terazosin , finasteride , combination or placebo . RESULTS The 1,078 men who completed 12 months of the trial are included in this study . Of those men 1,040 ( 96.5 % ) had at least 1 episode of nocturia at baseline and 38 ( 3.5 % ) had less than 1 episode ( baseline nocturia is an average of 2 measures ) . Of those 1,040 men 788 ( 75.8 % ) had 2 or more nocturia episodes . Overall , nocturia decreased from a baseline mean of 2.5 to 1.8 , 2.1 , 2.0 and 2.1 episodes in the terazosin , finasteride , combination and placebo groups , respectively . Of men with 2 or more episodes of nocturia 50 % reduction in nocturia was seen in 39 % , 25 % , 32 % and 22 % in the terazosin , finasteride , combination and placebo groups , respectively . Changes in nocturia were correlated with changes in reported bother from nocturia ( Pearson correlation 0.48 ) , BPH impact index ( 0.32 ) and overall satisfaction with urinary symptoms ( 0.33 ) . CONCLUSIONS Terazosin and combination therapy reduced nocturia in men with BPH , yet the net advantage of terazosin over placebo was a net reduction of 0.3 nocturia episode . For a person to reach a 50 % or greater reduction in nocturia , the advantage of terazosin over placebo was 17 percentage points . Changes in nocturia had a moderate impact on symptom specific quality of life measures",
"OBJECTIVE To evaluate the efficacy and safety of 2 years ' treatment of moderate benign prostatic hyperplasia ( BPH ) with finasteride . DESIGN Double-blind , parallel-group , placebo-controlled , multicentre , prospect i ve r and omized study . SETTING Outpatient care in 28 centres across Canada . PARTICIPANTS Men aged 45 to 80 , in good health , with moderate BPH and no evidence of prostate cancer . A total of 613 men were entered into the study ; 472 completed the 2 years of treatment . INTERVENTION After 1 month of receiving a placebo ( run-in period ) , patients were given either finasteride ( 5 mg/d ) or a placebo for 2 years . OUTCOME MEASURES EFFICACY changes from baseline in BPH symptom scores , maximum urinary flow rates and prostate volume . SAFETY onset , course and resolution of all adverse events during the treatment period . RESULTS In the efficacy analyses the mean BPH symptom scores decreased 2.1 points ( from 15.8 to 13.7 ) in the finasteride group , as compared with a decrease of 0.7 points ( from 16.6 to 15.9 ) in the placebo group ( P maximum urinary flow rate increased by a mean of 1.4 mL/s ( from 11.1 to 12.5 mL/s ) in the finasteride group , as compared with an increase of 0.3 mL/s ( from 10.9 to 11.2 mL/s ) in the placebo group ( p mean prostate volume decreased by 21 % ( from a mean volume of 44.1 cm3 at baseline ) in the treatment group ; it increased by 8.4 % ( from a mean volume of 45.8 cm3 at baseline ) in the placebo group ( p proportion of patients who experienced any adverse event was similar in the two groups ( 81.0 % in the treatment group and 81.2 % in the placebo group ) . However , the incidence of adverse events related to sexual dysfunction were significantly higher in the finasteride group than in the placebo group ( ejaculation disorder 7.7 % v. 1.7 % and impotence 15.8 % v. 6.3 % ; p and effective alternative to watchful waiting in the treatment of moderate BPH",
"OBJECTIVES To assess the long-term effects of finasteride on pressure-flow parameters in men with urodynamically documented bladder outflow obstruction ( BOO ) . METHODS One hundred twenty-one men with benign prostatic enlargement ( BPE ) and lower urinary tract symptoms ( LUTS ) underwent a pressure-flow study ( PFS ) at 1 of 11 clinical centers . The PFS technique was st and ardized , and all tracings were read by a single reader unaware of the treatment group . Patients who were obstructed according to a modified Abrams-Griffiths nomogram were r and omized to 5 mg finasteride ( n = 81 ) or placebo ( n = 40 ) for 12 months ; all patients continuing into an open extension received finasteride during the second 12 months of therapy . Results of the initial 12-month study demonstrated the benefit of finasteride treatment on PFS parameters . To examine the continuing effects over time , an analysis of the data from 54 patients who completed 24 months of treatment with finasteride is provided . RESULTS Detrusor pressure at maximum flow ( PdetQmax ) continued to decrease during the second 12 months of therapy ( decreases of 5.3 and 11.7 cm H2O at months 12 and 24 , respectively ) . The percentage of patients obstructed by Abrams-Griffiths classification decreased from 76.2 % at baseline to 66.7 % at month 12 and 59.6 % at month 24 . An intention-to-treat analysis yielded similar results . CONCLUSIONS Finasteride improves urodynamic measures of obstruction in men with BPE and LUTS , with continued improvement during the second 12 months of therapy",
"PURPOSE In the present analysis we examined data from the MTOPS ( Medical Therapy of Prostatic Symptoms ) trial to determine the effect of long-term finasteride treatment , either alone or in combination with doxazosin , on total prostate volume across the full range of baseline total prostate volume values in men enrolled in this study . MATERIAL S AND METHODS In this trial a total of 3,047 patients with lower urinary tract symptoms were r and omized to placebo , doxazosin ( 4 to 8 mg ) , finasteride ( 5 mg ) or the combination of doxazosin and finasteride ( average length of treatment 4.5 years ) . Total prostate volume was measured by transrectal ultrasound in all patients at baseline , yearly and at study end or at termination of participation . RESULTS Long-term treatment with finasteride led to a consistent reduction of approximately 25 % in total prostate volume compared to placebo in men with a relatively small prostate ( less than 25 to 30 ml ) , as well as in those with a moderate size ( 30 to less than 40 ml ) or enlarged prostate ( 40 ml or greater ) at baseline . CONCLUSIONS In this MTOPS data analysis long-term ( more than 4 years ) treatment with finasteride , either alone or in combination with doxazosin , led to a consistent , clinical ly significant reduction in total prostate volume compared to placebo in patients with lower urinary tract symptoms and benign prostatic hyperplasia whose baseline prostate size ranged from relatively small ( less than 25 to 30 ml ) to enlarged ( 40 ml or greater )",
"This study was design ed to determine the efficacy of the 5 alpha-reductase inhibitor finasteride ( Proscar , MK-906 ) in men with reduced urinary flow rates and symptoms of urinary outflow obstruction secondary to benign prostatic hyperplasia . Forty-five men were r and omized to one of three groups receiving either placebo , 1 mg/day or 5 mg/day finasteride for the first 12 months of the study period . At the end of this period all men received 5 mg/day finasteride for a further 2 years . Efficacy was determined by measurement of prostate volume , maximum urinary flow rate , and symptom score using a modified Boyarsky assessment . Prostate volume reduced by 20 and 27 % , respectively , for those on 1 and 5 mg after the first year . At 3 years the volume had reduced by 43 % . This reduction in prostate volume was associated with an improvement in maximum urinary flow rate by 50 % ( 1 mg ) , and 35 % ( 5 mg ) at 1 year , and 36 % at 3 years . The total , obstructive and non-obstructive symptom scores decreased ( improved ) for patients on 1 and 5 mg finasteride , with the total score reducing by 33 % from baseline at year 3 . The results demonstrate that finasteride causes a modest but significant clinical improvement in men with urinary outflow obstruction secondary to benign prostatic hyperplasia",
"PURPOSE We sought to quantify prostate tissue changes induced by finasteride and to identify a predictor of finasteride response in men with symptomatic benign prostatic hyperplasia ( BPH ) via a r and omized , placebo controlled , double-blind clinical trial . MATERIAL S AND METHODS Men with symptomatic BPH ( 52 to 78 years old ) were r and omly assigned to 6 months of treatment with finasteride ( 26 ) or placebo ( 15 ) . Outcome measures were clinical ( urinary symptom score and flow rate ) , chemical ( serum prostate specific antigen and dihydrotestosterone levels ) , volumetric ( transrectal ultrasound , and magnetic resonance imaging for whole and zonal prostate volumes ) and histological ( morphometry of prostate sextant biopsies , separated into inner and outer gl and segments , to measure the percent epithelium , stroma and gl and ular lumen ) . RESULTS In the finasteride group we found a suggestion of decreasing symptom scores and increasing flow rates ( not significant ) with significant decreases ( p prostate specific antigen ( 48 % ) , dihydrotestosterone ( 74 % ) and prostate volume ( 21 % ) . Finasteride treatment induced a 55 % decrease in inner gl and epithelium ( p stroma or lumina . We also found a linear correlation between pretreatment inner gl and epithelial content and prostate volume decrease induced by the drug ( tau = 0.58 , p = 0.01 ) . CONCLUSIONS Finasteride treatment results in a major suppression of prostate epithelium , which is most pronounced in the inner gl and . Moreover , a finasteride induced prostate volume decrease was predictable by quantification of epithelial tissues of the inner gl and . These data lend additional support to the emerging concept of transition zone primacy in symptomatic BPH",
"BACKGROUND Controversy regarding the relative efficacy of treatments for the relief of the symptoms of benign prostatic hyperplasia ( BPH ) . METHODS This was a 6-month double-blind r and omized equivalence study that compared the effects of a plant extract ( 320 mg Permixon ) with those of a 5 alpha-reductase inhibitor ( 5 mg finasteride ) in 1,098 men with moderate BPH using the International Prostate Symptom Score ( IPSS ) as the primary end-point . RESULTS Both Permixon and finasteride decreased the IPSS ( -37 % and -39 % , respectively ) , improved quality of life ( by 38 and 41 % ) , and increased peak urinary flow rate ( + 25 % and + 30 % , P = 0.035 ) , with no statistical difference in the percent of responders with a 3 ml/sec improvement . Finasteride markedly decreased prostate volume ( -18 % ) and serum PSA levels ( -41 % ) ; Permixon improved symptoms with little effect on volume ( -6 % ) and no change in PSA levels . Permixon fared better than finasteride in a sexual function question naire and gave rise to less complaints of decreased libido and impotence . CONCLUSIONS Both treatments relieve the symptoms of BPH in about two-thirds of patients but , unlike finasteride , Permixon has little effect on so-called and rogen-dependent parameters . This suggests that other pathways might also be involved in the symptomatology of BPH",
"To determine the influence of and rogen deprivation induced by the potent 5 alpha-reductase inhibitor finasteride on the volume of the zones of the prostate , 20 symptomatic men with established BPH were r and omized to one of three groups : placebo , finasteride 1 mg , and finasteride 5 mg/day . The volume of the entire prostate gl and , periurethral zone , and peripheral zone and the seminal vesicles were determined by three dimensional reconstructions of magnetic resonance contoured images of the prostate . There was no significant difference between the results achieved with 1 and 5 mg of finasteride per day ; thus the results in these two groups were combined . In the placebo group there was no significant change in the volume of any structure . Following treatment for 1 year with finasteride there was a significant ( P total gl and size ( 11.5 + /- 3.2 cc ) . Similarly , there was a significant ( P total gl and size ( 11.5 + /- 3.2 cc ) . Similarly , there was a significant ( P size of the periurethral zone of the prostate ( 6.2 + /- 3 cc ) . Although there was also a decrease in the size of the peripheral zone of the prostate ( 2.8 + /- 1.2 cc ) this did not reach statistical significance . There was no significant change in the volume of the seminal vesicles . These findings indicate for the first time that and rogen deprivation induces a significant decrease in the size of the periurethral zone of the prostate in men with established BPH",
"OBJECTIVES To investigate the change in prostate volume and symptoms after discontinuation of 5alpha-reductase inhibitors ( 5ARIs ) in men with moderate to severe symptoms due to benign prostatic hyperplasia ( BPH ) . METHODS A total of 120 patients with BPH were enrolled from December 2004 to May 2008 . The patients were r and omized into 2 groups : group 1 received finasteride 5 mg plus alfuzocin 10 mg or tamsulosin 0.2 mg daily , and group 2 received dutasteride 0.5 mg plus alfuzocin 10 mg or tamsulosin 0.2 mg daily . All the patients received combination therapy for 1 year , followed by 1 year of alpha-blocker monotherapy . The prostate volume , International Prostate Symptom Score , and serum prostate-specific antigen level were determined at baseline and at 12 and 24 months after treatment . RESULTS At 1 year after treatment , the prostate volume was reduced by 24.5 % + /- 10.01 % ( P prostate volume had increased by 20.7 % + /- 14.1 % ( P International Prostate Symptom Score had significantly deteriorated at 1 year after cessation of the 5ARIs in both groups compared with the values at the end of 1 year of combination therapy . CONCLUSIONS Our data demonstrate that the discontinuation of 5ARIs during combination therapy induces prostate regrowth , as well as aggravation of symptoms in men with BPH . This result , therefore , suggests that the life-long use of 5ARIs should be considered for the prevention of BPH progression",
"The effects of urinary symptoms on health-related quality of life ( HRQL ) are important in therapeutic decision making . Few have evaluated the treatment effects on HRQL in men with benign prostatic hyperplasia ( BPH ) , even though increased urinary symptoms are associated with greater worry , bother , and interference with living activities . We report on patient assessment s of such disease-specific measures as well as general HRQL measures from two placebo-controlled clinical trials of finasteride in the treatment of symptomatic BPH . Patients treated with finasteride appeared to have greater improvement than placebo-treated patients in disease-specific measures and in patient global assessment . The treated group appeared to have a greater mean increase in sexual domain scores . As expected , general measures ( health rating , life satisfaction , ladder of life ) changed little . Thus , treatment with finasteride appears to reduce bother , worry , and activity interference due to symptoms but in a small percentage of men may lead to slightly reduced sexual function",
"OBJECTIVES To evaluate the effects of finasteride , a specific type II 5-alpha-reductase inhibitor , on symptoms of benign prostatic hyperplasia , prostate volume , and urinary flow during a 7 to 8-year period . METHODS A total of 190 men with symptomatic benign prostatic hyperplasia and enlarged prostates entered one of two Phase II double-blind 3 to 6-month studies . Of these , 156 patients continued taking open-label finasteride , and more than 70 patients completed 7 to 8 years of treatment . The symptoms were scored using a patient self-administered modified Boyarsky symptom question naire . Prostate volume was measured by magnetic resonance imaging or ultrasonography , and the maximal urinary flow rate was assessed noninvasively . RESULTS Treatment with finasteride for 7 to 8 years led to sustained improvement in symptoms , reduction in prostate volume ( 28 % from baseline ) , and increased urinary flow ( median 2.5 mL/s from baseline ) . Decreases in dihydrotestosterone ( 86 % ) and prostate-specific antigen ( 54 % ) levels were also maintained . Long-term finasteride treatment was safe and generally well tolerated . CONCLUSIONS Long-term treatment with finasteride was well tolerated and result ed in durable symptom relief and improvement in prostate volume and urinary flow",
"OBJECTIVES To evaluate the safety and efficacy of finasteride 5 mg during a 10-year period in men with enlarged prostates from a single center who participated in the double-blind and extension phases of the multicenter , Phase III , North American benign prostatic hyperplasia ( BPH ) trial . It is important that the long-term safety and efficacy of drugs intended for chronic administration in men with BPH be well understood . METHODS The Phase III North American BPH trial involved a 1-year , placebo-controlled , double-blind study , followed by a 5-year open extension with finasteride 5 mg/day . The trial enrolled men with symptomatic BPH , an enlarged prostate on digital rectal examination , and no evidence of prostate cancer . Of the 46 patients originally enrolled from our institution , 43 were r and omized to receive finasteride or placebo , of whom 41 ( 95 % ) completed the double-blind study and entered the 5-year extension . Thirty ( 73 % ) of these 41 patients completed the 5-year extension . Patients continued to be followed up by their physicians for an additional 5 years , for a total follow-up of at least 10 years . RESULTS Twenty-four ( 56 % ) of the original 43 patients r and omized to finasteride or placebo were judged as successfully treated during the 10-year finasteride follow-up ( 17 patients taking finasteride alone at 10 years and 7 patients who were taking finasteride alone when they discontinued during the 10-year follow-up for reasons not related to finasteride treatment ) . Altogether , 22 ( 51 % ) of the original 43 r and omized patients continued finasteride treatment at 10 years ( 17 taking finasteride alone , 4 taking finasteride plus an alpha-blocker , and 1 taking finasteride for treatment of hematuria ) . Finasteride was well tolerated , with no new adverse experiences occurring with increasing duration of exposure to the drug . CONCLUSIONS This long-term follow-up study has demonstrated that appropriately selected patients with symptomatic BPH and enlarged prostates are likely to have a long-term response to taking finasteride 5 mg daily",
"OBJECTIVES To determine the effect of discontinuation of alpha-blockade and continuation of finasteride in men with lower urinary tract symptoms and enlarged prostates receiving combination treatment and to determine whether the alpha-blocker dose influences the ability to discontinue it . METHODS We treated 272 consecutive men with a prostate size greater than 40 g and American Urological Association symptom score greater than 20 with 5 mg finasteride and 2 mg doxazosin daily . Two hundred forty men reported a favorable response to therapy , defined as any reduction in symptom score and toleration of the medications . The dose was maintained at 2 mg doxazosin in 100 men and was titrated to 4 mg doxazosin in 80 patients and to 8 mg doxazosin in an additional 60 patients . We discontinued doxazosin at 3 , 6 , 9 , or 12 months , while continuing finasteride , and then re-evaluated the patients 1 month later to determine whether any worsening of symptoms had result ed . RESULTS In patients discontinuing doxazosin at 3 months , success ( defined as no increase in symptom score and no desire to resume doxazosin ) was reported by 20 % , 15 % , and 13 % of those taking 2 , 4 , and 8 mg , respectively . In patients discontinuing doxazosin at 6 months , success was reported by 48 % , 45 % , and 40 % of those taking 2 , 4 , and 8 mg , respectively . In patients discontinuing doxazosin at 9 months , success was reported by 84 % , 80 % , and 73 % of those taking 2 , 4 , and 8 mg , respectively . In patients discontinuing doxazosin at 12 months , success was reported by 84 % , 85 % , and 87 % of those taking 2 , 4 , and 8 mg , respectively . CONCLUSIONS Patients with lower urinary tract symptoms and moderately enlarged prostates initially receiving combination therapy using finasteride and an alpha-blocker are likely to experience no significant symptom deterioration after discontinuing the alpha-blocker after 9 to 12 months of combination therapy regardless of the dose of alpha-blocker chosen",
"PURPOSE We determine the effect of placebo , finasteride , terazosin and a combination of drugs on bother due to symptoms , quality of life and patient perception of improvement , and identify baseline clinical factors that predict clinical response to medical therapy . MATERIAL S AND METHODS A total of 1,229 subjects with clinical benign prostatic hyperplasia ( BPH ) were r and omized to 1 year of placebo , finasteride , terazosin or drug combination . The primary outcome measures were American Urological Association ( AUA ) symptom score and peak flow rate . Relevant secondary outcome measures were symptom problem score , BPH impact score and global rating of improvement . RESULTS Group mean differences in symptom problem and BPH impact scores between the finasteride versus placebo , and terazosin versus combination groups were not statistically or clinical ly significant . Group mean differences in all outcome measures were highly statistically significant between the terazosin and finasteride , and combination and finasteride groups . The percentage of subjects who rated improvement as marked or moderate with placebo , finasteride , terazosin and combination was 39 , 44 , 61 and 65 % , respectively . In the subsets of men in the placebo , finasteride , terazosin and combination groups with prostates greater than 50 cm.3 group mean decrease from baseline in AUA symptom score was -2.5 , -3.6 , -6 and -7 , group mean increase in peak flow rate was 0.6 , 2.7 , 3.6 and 3.7 ml . per second , group mean decrease in symptom problem score was -2.2 , - 1.9 , -3.1 and -4.5 , and group mean decrease in BPH impact score was -0.6 , -0.3 , -1.1 and -1.5 , respectively . A correlational analysis failed to show a significant relationship between baseline prostate volume and treatment response to finasteride . There was a significant but weak relationship between change in AUA symptom score and peak flow rate in the finasteride and combination groups . The symptom responses with terazosin were independent of baseline peak flow rate . CONCLUSIONS In men with clinical BPH finasteride and placebo are equally effective , while terazosin and combination are significantly more effective . In men with clinical BPH and large prostates the advantage of finasteride over placebo in terms of symptom reduction , impact on bother due to symptoms and quality of life is small at best , while the advantage of terazosin and combination over finasteride and placebo is highly significant . Baseline prostate volume was not a predictor of response to finasteride in the overall study population . On the basis of our results alpha1 blockers , such as terazosin , should be first line medical treatment for BPH",
"The effects of finasteride , a potent 5 alpha-reductase inhibitor , were assessed in patients with benign prostatic hyperplasia . Patients were treated with finasteride or placebo for 24 weeks in a double-blind multicenter study followed by a 12-month open-extension period . After 24 weeks , finasteride-treated patients , when compared to placebo-treated patients , showed a significant reduction in prostate volume ( 22.5 % median decrease ) and prostate significant antigen ( 32.4 % median decrease ) , a significant increase in maximum urinary flow ( 1.6 ml/s mean increase from baseline ) and a significant improvement in their obstructive symptom scores ( two-point decrease from baseline ) . Finasteride was well tolerated , and the improvements in prostate volume , maximum urinary flow rate and obstructive symptom scores observed in the controlled study were maintained throughout the extension study",
"OBJECTIVES To evaluate the influence of two differently acting anti and rogens , finasteride ( FIN ) and cyproterone acetate ( CPA ) , on the natural history of hematuria associated with benign prostatic hyperplasia ( BPH ) in a prospect i ve , r and omized , controlled study . METHODS Forty-two patients with hematuria episodes due to BPH were r and omly allocated to three subgroups of 14 patients each and treated daily with either 5 mg FIN or 100 mg CPA or were placed in a watchful waiting arm . Patients were evaluated at 3-month intervals , and 40 patients had at least 1 year of follow-up . RESULTS Four patients in the FIN group ( 30 % ) and three in the CPA group ( 23 % ) presented with recurrent hematuria . In both groups , the bleeding episodes were treated conservatively and required no hospitalization . In the control group , 8 patients ( 57 % ) presented with recurrent bleeding ; in 4 , the bleeding was severe and required some form of intervention ( catheterization or transurethral prostatectomy ) . When the frequency and severity of the hematuria episodes were analyzed over time , a statistically significant difference for FIN versus control was present at 9 and 12 months ( analysis of variance , P = 0.035 and P = 0.009 , respectively ) . A similar difference was evident for CPA versus control at 9 and 12 months ( P = 0.028 and P = 0.008 , respectively ) . No statistically significant difference was present between the FIN and CPA groups . Interestingly , no statistically significant effect in bleeding recurrence for both CPA and FIN over controls was present at 3 and 6 months of follow-up . CONCLUSIONS Both FIN and CPA seem to exert a comparable control in hematuria recurrence in patients with BPH , thus confirming the rationale behind the use of anti and rogens for such a purpose . Our results support the hypothesis that any anti and rogen , irrespective of the mode of action , would alter the natural history of BPH-associated hematuria . Interestingly , our results indicate that the speed of action of FIN may not be as rapid as previously described",
"In 18 of 55 original patients who completed 5 years of treatment with finasteride , significant reductions in prostate size were noted at 1 year and sustained thereafter . Symptom scores in these same patients were significantly improved or stable over the 5 years while maximal urinary flow rates were unchanged . Data from 15 of 18 other patients who dropped out of the study before 5 years showed changes in prostate size , symptom score and flow rates that were similar to those noted in patients treated for 5 years . No side effects were noted in this study except for sexual dysfunction , which occurred in less than 5 % of the patients . With few exceptions , finasteride appears to arrest the process of BPH over a 5 year period as indicated by sustained reductions in prostate size accompanied by either symptomatic improvement or stability in all other patients",
"OBJECTIVES To evaluate the long-term effects of finasteride on symptoms , acute urinary retention ( AUR ) , and the need for benign prostatic hyperplasia (BPH)-related surgery in relationship to baseline symptom severity . METHODS A total of 3040 men with BPH were treated for 4 years with finasteride or placebo . The changes from baseline in symptoms and the incidence of BPH-related surgery and AUR were determined in men with mild ( less than 8) , low-moderate ( 8 to 12 ) , high-moderate ( 13 to 19 ) , and severe ( greater than 19 ) baseline quasi-American Urological Association symptoms for all patients and for the subgroup with a baseline prostate-specific antigen ( PSA ) level of 1.4 ng/mL or greater . RESULTS In patients who completed the 4-year study , the change in symptom score , stratified by baseline symptom severity , was + 1.4 + /- 0.5 ( mild ) , -0.8 + /- 0.3 ( low-moderate ) , -3.6 + /- 0.3 ( high-moderate ) , and -7.7 + /- 0.5 ( severe ) in finasteride-treated patients and , respectively , + 3.4 + /- 0.5 , + 0.7 + /- 0.3 , -1.4 + /- 0.3 , and -5.3 + /- 0.6 in placebo-treated patients ( between-group P risk of BPH-related surgery increased among placebo patients with increasing baseline symptom severity to a greater extent than the risk of AUR . Finasteride reduced the risk of AUR or the need for BPH-related surgery in all subgroups ( P men with a baseline PSA of 1.4 ng/mL or greater . CONCLUSIONS Compared with placebo , finasteride had a beneficial effect on symptoms , AUR , and BPH-related surgery in all symptom categories . BPH-related surgery , but not AUR , occurred more commonly in placebo-treated men with more severe baseline symptoms . The greatest absolute benefit of finasteride on symptoms and the reduction in risk of AUR and surgery was in men with higher baseline symptom scores and a baseline PSA level of 1.4 ng/mL or greater",
"BACKGROUND Finasteride , a 5 alpha-reductase inhibitor , has been shown to have beneficial effects in the treatment of benign prostatic hyperplasia . The long-term safety and efficacy of finasteride in the treatment of benign prostatic hyperplasia was assessed . METHODS In two multicenter , double-blind , placebo-controlled studies ( North American and international ) , patients with symptomatic benign prostatic hyperplasia were r and omly assigned to receive finasteride , 1 or 5 mg , or placebo for 1 year followed by an open-extension study in which all patients were treated with finasteride , 5 mg , regardless of original therapy . Men aged 40 to 80 years , in good physical and mental health , were eligible to enter the study . All patients were to have a maximum urinary flow rate of 15 mL/s or less with a voided volume of 150 mL or more , an enlarged prostate , and symptoms of urinary obstruction . Patients with a prostate-specific antigen level of 40 mg/mL or more or any finding suggestive of prostate cancer were excluded . RESULTS Two hundred ninety-eight patients received finasteride , 5 mg , continuously for 24 months . At the end of 24 months of finasteride therapy , the median prostate volume was reduced by 25 % , and 60 % of patients had a 20 % or greater reduction in prostate volume . Maximum urinary flow rate was improved by at least 2 mL/s , and symptoms were improved by approximately 3.5 points . Decreased libido and ejaculation disorders were the only drug-related adverse experiences reported in more than 1 % of patients . CONCLUSION These studies support the long-term safety and tolerability of finasteride , while demonstrating its continuing clinical efficacy in the treatment of patients with symptomatic benign prostatic hyperplasia",
"BACKGROUND Men with benign prostatic hyperplasia can be treated with alpha 1-adrenergic-antagonist drugs that relax prostatic smooth muscle or with drugs that inhibit 5 alpha-reductase and therefore reduce tissue and rogen concentrations . However , the effects of the two types of drugs have not been compared . METHODS We compared the safety and efficacy of placebo , terazosin ( 10 mg daily ) , finasteride ( 5 mg daily ) , and the combination of both drugs in 1229 men with benign prostatic hyperplasia . American Urological Association symptom scores and peak urinary-flow rates were determined at base line and periodically for one year . RESULTS The mean changes from base line in the symptom scores in the placebo , finasteride , terazosin , and combination-therapy groups at one year were decreases of 2.6 , 3.2 , 6.1 , and 6.2 points , respectively ( P placebo ) . The mean changes at one year in the peak urinary-flow rates were increases of 1.4 , 1.6 , 2.7 , and 3.2 ml per second , respectively ( P terazosin and combination therapy with finasteride and with placebo ) . Finasteride had no more effect on either measure than placebo . In the placebo group , 1.6 percent of the men discontinued the study because of adverse effects , as did 4.8 to 7.8 percent of the men in the other three groups . CONCLUSIONS In men with benign prostatic hyperplasia , terazosin was effective therapy , whereas finasteride was not , and the combination of terazosin and finasteride was no more effective than terazosin alone",
"OBJECTIVE To assess the long-term safety and efficacy of finasteride in the treatment of symptomatic benign prostatic hyperplasia in patients treated with finasteride 5 mg for thirty-six months . METHODS Two large multicenter studies were used . Patients were r and omly assigned to treatment with finasteride , 1 or 5 mg , or placebo for twelve months . After completing twelve months of therapy , patients were invited to enter an open extension to the study in which all patients received finasteride 5 mg . Urinary symptoms , urinary flow rate , prostate volume , and serum concentrations of prostate-specific antigen and dihydrotestosterone were measured periodically during the study . RESULTS After thirty-six months of treatment with finasteride 5 mg , prostate volume was reduced from baseline by approximately 27 percent , maximum urinary flow rate improved by approximately 2.3 mL/second , and symptom scores improved by 3.6 points . Forty-two percent of patients had a 30 percent or greater decrease in prostate volume , 40 percent of patients showed an increase of 3 mL/second or more in maximum urinary flow rate , and 48 percent of patients experienced a 50 percent or greater improvement in symptom scores . Finasteride was well tolerated and there was no evidence of increased adverse experiences with increased duration of treatment . CONCLUSIONS The excellent safety profile and sustained clinical efficacy , over thirty-six months , of daily treatment with finasteride 5 mg recommend finasteride as a low-risk medical option for the treatment of symptomatic benign prostatic hyperplasia",
"BACKGROUND And rogens are involved in the development of prostate cancer . Finasteride , an inhibitor of 5alpha-reductase , inhibits the conversion of testosterone to dihydrotestosterone , the primary and rogen in the prostate , and may reduce the risk of prostate cancer . METHODS In the Prostate Cancer Prevention Trial , we r and omly assigned 18,882 men 55 years of age or older with a normal digital rectal examination and a prostate-specific antigen ( PSA ) level of 3.0 ng per milliliter or lower to treatment with finasteride ( 5 mg per day ) or placebo for seven years . Prostate biopsy was recommended if the annual PSA level , adjusted for the effect of finasteride , exceeded 4.0 ng per milliliter or if the digital rectal examination was abnormal . It was anticipated that 60 percent of participants would have prostate cancer diagnosed during the study or would undergo biopsy at the end of the study . The primary end point was the prevalence of prostate cancer during the seven years of the study . RESULTS Prostate cancer was detected in 803 of the 4368 men in the finasteride group who had data for the final analysis ( 18.4 percent ) and 1147 of the 4692 men in the placebo group who had such data ( 24.4 percent ) , for a 24.8 percent reduction in prevalence over the seven-year period ( 95 percent confidence interval , 18.6 to 30.6 percent ; P Tumors of Gleason grade 7 , 8 , 9 , or 10 were more common in the finasteride group ( 280 of 757 tumors [ 37.0 percent ] , or 6.4 percent of the 4368 men included in the final analysis ) than in the placebo group ( 237 of 1068 tumors [ 22.2 percent ] , P Sexual side effects were more common in finasteride-treated men , whereas urinary symptoms were more common in men receiving placebo . CONCLUSIONS Finasteride prevents or delays the appearance of prostate cancer , but this possible benefit and a reduced risk of urinary problems must be weighed against sexual side effects and the increased risk of high- grade prostate cancer",
"PURPOSE We assess the effect of finasteride , a 5alpha-reductase inhibitor , on objective voiding parameters in men with lower urinary tract symptoms and benign prostatic enlargement on digital rectal examination ( known as clinical benign prostatic enlargement ) in a double-blind placebo controlled multicenter study using strict st and ard pressure flow study techniques . MATERIAL S AND METHODS A modification of the Abrams-Griffiths nomogram was used by 1 reader to ensure that all patients met objective criteria for bladder outlet obstruction at baseline . After performing a pressure flow study patients with obstruction were r and omized 2:1 to receive 5 mg . finasteride ( 81 ) or placebo ( 40 ) daily . A second pressure flow study was performed at month 12 . At baseline and month 12 free urinary flow studies and transrectal ultrasound were performed , and International Prostate Symptom Score question naires were completed . Patients were treated between May 1994 and July 1996 . RESULTS Finasteride caused a significant decrease ( -8.1 cm . water ) in detrusor pressure at maximum flow ( p maximum flow rate ( p prostate volume ( p Men with prostates larger than 40 cc had greater improvement in detrusor pressure at maximum flow ( between group difference -14.5 cm . water , 95 % confidence interval -26.2 to -2.6 , p = 0.02 ) and maximum flow rate ( mean treatment effect + 1.6 ml . per second , 95 % confidence interval -0.2 to 3.0 , p = 0.02 ) compared to those with prostates 40 cc or less ( between group differences not significant ) . CONCLUSIONS Finasteride treatment result ed in improvements in urodynamic parameters , which were greater in men with large prostates",
"OBJECTIVES To compare the efficacy and safety of finasteride 5 mg in older ( 65 years old or older ) versus younger ( 45 to younger than 65 years old ) men with benign prostatic hyperplasia ( BPH ) . METHODS The Proscar Long-Term Efficacy and Safety Study ( PLESS ) was a 4-year , r and omized , double-blind , placebo-controlled trial assessing the efficacy and safety of finasteride 5 mg in 3040 men 45 to 78 years old with symptomatic BPH , enlarged prostates , and no evidence of prostate cancer . The endpoints included urinary symptoms , prostate volume , occurrence of acute urinary retention and /or BPH-related surgery , and safety . RESULTS In both age cohorts , finasteride treatment led to a 51 % reduction ( P risk for acute urinary retention and /or BPH-related surgery , a significant ( P improvement in symptom score , and a significant ( P reduction in prostate volume . Within each age cohort , no significant differences were found between the placebo and finasteride-treated patients in the incidence of cardiovascular adverse events . Significant differences were evident between the placebo and finasteride groups in the incidence of the typical , known , drug-related adverse events , but no specific differences were associated with age . No drug interactions of clinical importance were observed in the finasteride-treated patients . CONCLUSIONS The present analysis from PLESS demonstrates that in both older ( 65 years old or older ) and younger men with symptomatic BPH and enlarged prostates , finasteride is highly effective in improving symptoms and reducing prostate volume in many men and in reducing the risk of acute urinary retention and BPH-related surgery . In addition , the safety profile of finasteride in both older and younger men is similar and no drug interactions of clinical importance were observed",
"Objectives : Knowledge regarding the incidence and prevalence of acute urinary retention and the ultimate outcome is very limited . The purpose of the present analysis was to document the natural history and outcomes of acute urinary retention ( AUR ) further specified as being either precipitated or spontaneous , and to evaluate the potential benefit of finasteride therapy . Material s and Methods : Three thous and and forty men with moderate to severe symptoms of BPH and enlarged prostate gl and s by digital rectal examination were enrolled into the 4–year placebo – controlled PLESS trial and were evaluated for occurrences of AUR and BPH – related surgery . Men in the study were seen every 4 months ; discontinued patients were followed up 6 months after discontinuation and again at the end of the 4–year trial . Complete 4–year data on outcomes ( occurrence of AUR or BPH – related surgery ) was available for 92 % of the enrolled subjects in each treatment group . An endpoint committee , blinded to treatment group and center , review ed and categorized all study –related documentation relating to retention and surgery . Results : Over the 4–year period , 99 of 1,503 placebo – treated patients ( 6.6 % ) experienced one or more episodes of AUR in comparison with 42 or 1,513 finasteride – treated patients ( 2.8 % ; p episodes of retention were spontaneous and clearly BPH – related , while the other episodes were precipitated by another factor ( PAUR ) . After spontaneous AUR , subsequent surgery was performed in 39 of 52 ( 75 % ) placebo – treated patients versus 8 of 20 ( 40 % ) finasteride – treated patients ( p = 0.01 ) . BPH – related surgery was less common in men who had a prior episode of PAUR ( 26 % in the placebo group and 14 % in the finasteride group ) . Conclusion : There is a continual risk of spontaneous and precipitated acute urinary retention in men with moderate to severe lower urinary tract symptoms and an enlarged prostate gl and . Fewer patients who developed precipitated AUR than spontaneous AUR go on to need subsequent BPH – related surgery . Significantly fewer finasteride – than placebo – treated patients developed AUR , and among those men , fewer ultimately needed BPH – related surgery "
] |
4116c540-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND Overweight or obese individuals with type 2 diabetes are encouraged to lose weight for optimal glucose management , yet many find this difficult . Determining whether alterations in dietary patterns irrespective of weight loss can aid glucose control has not been fully investigated . METHODS We conducted a systematic review and meta- analysis aim ing to determine the effects of a Mediterranean diet compared to other dietary interventions on glycaemic control irrespective of weight loss . Electronic data bases were search ed for controlled trials that included a Mediterranean diet intervention . The interventions included all major components of the Mediterranean diet and were carried out in free-living individuals at high risk or diagnosed with type 2 diabetes . Network meta- analysis compared all interventions with one another at the same time as maintaining r and omisation . Analyses were conducted within a Bayesian framework . RESULTS Eight studies met the inclusion criteria , seven examined fasting blood glucose ( n = 972 ) , six examined fasting insulin ( n = 1330 ) and three examined HbA1c ( n = 487 ) . None of the interventions were significantly better than the others in lowering glucose parameters . The Mediterranean diet reduced HbA1c significantly compared to usual care but not compared to the Palaeolithic diet . CONCLUSIONS The effect of alterations in dietary practice irrespective of weight loss on glycaemic control can not be concluded from the present review . The need for further research in this area is apparent because no firm conclusions about relative effectiveness of interventions could be drawn as a result of the paucity of the evidence
|
[
"BACKGROUND Despite their beneficial effects on weight loss and blood lipids , high-protein ( HP ) diets have been shown to increase insulin resistance and diabetes risk , whereas high-cereal-fiber ( HCF ) diets have shown the opposite effects on these outcomes . OBJECTIVE We compared the effects of isoenergetic HP and HCF diets and a diet with moderate increases in both cereal fibers and dietary protein ( Mix diet ) on insulin sensitivity , as measured by using euglycemic-hyperinsulinemic clamps with infusion of [6,6-(2)H(2)]glucose . DESIGN We r and omly assigned 111 overweight adults with features of the metabolic syndrome to 1 of 4 two-phased , 18-wk isoenergetic diets by group-matching . Per 3-d food protocol s , the percentages of energy derived from protein and carbohydrates and the intake of cereal fiber per day , respectively , were as follows-after 6 wk : 17 % , 52 % , and 14 g ( control ) ; 17 % , 52 % , and 43 g ( HCF ) ; 28 % , 43 % , and 13 g ( HP ) ; 23 % , 44 % , and 26 g ( Mix ) ; after 18 wk : 17 % , 51 % , and 15 g ( control ) ; 17 % , 51 % , and 41 g ( HCF ) ; 26 % , 45 % , and 14 g ( HP ) ; and 22 % , 46 % , and 26 g ( Mix ) . Eighty-four participants completed the study successfully and were included in the final analyses . Adherence was supported by the provision of tailored dietary supplements twice daily in all groups . RESULTS Insulin sensitivity expressed as an M value was 25 % higher after 6 wk of the HCF diet than after 6 wk of the HP diet ( subgroup analysis : 4.61 ± 0.38 compared with 3.71 ± 0.36 mg · kg(-1 ) · min(-1 ) , P = 0.008 ; treatment × time interaction : P = 0.005 ) . Effects were attenuated after 18 wk ( treatment × time interaction : P = 0.054 ) , which was likely explained by lower adherence to the HP diet . HP intake was associated with a tendency to increased protein expression in adipose tissue of the translation initiation factor serine-kinase-6 - 1 , which is known to mediate amino acid-induced insulin resistance . Biomarkers of protein intake indicated interference of cereal fibers with dietary protein absorption . CONCLUSION Greater changes in insulin sensitivity after intake of an isoenergetic HCF than after intake of an HP diet might help to explain the diverse effects of these diets on diabetes risk . This trial is registered at clinical trials.gov as NCT00579657",
"STUDY OBJECTIVE To determine whether long term weight gain and weight loss are associated with subsequent risk of type 2 diabetes in overweight , non-diabetic adults . DESIGN Prospect i ve cohort . Baseline overweight was defined as BMI ⩾27.3 for women and BMI ⩾27.8 for men . Annual weight change ( kg/year ) over 10 years was calculated using measured weight at subjects ' baseline and first follow up examinations . In the 10 years after measurement of weight change , incident cases of diabetes were ascertained by self report , hospital discharge records , and death certificates . SETTING Community . PARTICIPANTS 1929 overweight , non-diabetic adults . MAIN RESULTS Incident diabetes was ascertained in 251 subjects . Age adjusted cumulative incidence increased from 9.6 % for BMI ⩾37 . Annual weight change over 10 years was higher in subjects who become diabetic compared with those who did not for all BMI of weight gained annually over 10 years was associated with a 49 % increase in risk of developing diabetes in the subsequent 10 years . Each kg of weight lost annually over 10 years was associated with a 33 % lower risk of diabetes in the subsequent 10 years . CONCLUSIONS Weight gain was associated with substantially increased risk of diabetes among overweight adults , and even modest weight loss was associated with significantly reduced diabetes risk . Minor weight reductions may have major beneficial effects on subsequent diabetes risk in overweight adults at high risk of developing diabetes",
"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",
"Mediterranean-inspired diets have been shown to decrease cholesterol levels in patients with hypercholesterolaemia , who frequently exhibit endothelial dysfunction . The aims of the present study are to improve endothelial function by dietary intervention in healthy subjects with lipid levels representative of a Western population . Twenty-two healthy subjects ( mean total cholesterol , 5.6 mmol/l ) were given a Mediterranean-inspired diet rich in omega-3 fatty acids and sterol esters , but low in saturated fat , or an ordinary Swedish diet , for 4 weeks in a r and omized cross-over study . The composition of the diets were : in the Swedish diet , 2090 kcal ( where 1 kcal=4.184 kJ ; 48 % of energy from carbohydrate , 15 % from protein and 36 % from fat ) and 19 g of fibre ; in the Mediterranean-inspired diet , 1869 kcal ( 48 % of energy from carbohydrate , 16 % from protein , 34 % from fat ) and 40 g of fibre . After each dietary period , fasting blood lipids , insulin and glucose levels , as well as apo B ( apolipoprotein B ) and LDL ( low-density lipoprotein ) particle size , were analysed . Endothelial-dependent and -independent vasodilation was measured invasively by venous occlusion plethysmography , and arterial distensibility was assessed by echocardiography tracking . Fibrinolytic capacity across the forearm , as well as oxidative stress measured through urinary F(2)-isoprostane , were evaluated . Total , LDL- and apo B-cholesterol and triacylglycerol ( triglyceride ) concentrations were decreased by 17 % , 22 % , 16 % and 17 % respectively , after the Mediterranean-inspired diet compared with the Swedish diet ( P plasma concentrations of insulin and glucose and LDL particle size , endothelial function , arterial distensibility , fibrinolytic capacity or oxidative stress were detected . Treatment for 4 weeks with a Mediterranean-inspired diet decreased blood lipids in healthy individuals with a low-risk profile for cardiovascular disease . This beneficial effect was not mirrored in vascular function or oxidative stress evaluation",
"OBJECTIVE To test the effects of two Mediterranean diet ( MedDiet ) interventions versus a low-fat diet on incidence of diabetes . RESEARCH DESIGN AND METHODS This was a three-arm r and omized trial in 418 nondiabetic subjects aged 55–80 years recruited in one center ( PREDIMED-Reus , northeastern Spain ) of the Prevención con Dieta Mediterránea [ PREDIMED ] study , a large nutrition intervention trial for primary cardiovascular prevention in individuals at high cardiovascular risk . Participants were r and omly assigned to education on a low-fat diet ( control group ) or to one of two MedDiets , supplemented with either free virgin olive oil ( 1 liter/week ) or nuts ( 30 g/day ) . Diets were ad libitum , and no advice on physical activity was given . The main outcome was diabetes incidence diagnosed by the 2009 American Diabetes Association criteria . RESULTS After a median follow-up of 4.0 years , diabetes incidence was 10.1 % ( 95 % CI 5.1–15.1 ) , 11.0 % ( 5.9–16.1 ) , and 17.9 % ( 11.4–24.4 ) in the MedDiet with olive oil group , the MedDiet with nuts group , and the control group , respectively . Multivariable adjusted hazard ratios of diabetes were 0.49 ( 0.25–0.97 ) and 0.48 ( 0.24–0.96 ) in the MedDiet supplemented with olive oil and nuts groups , respectively , compared with the control group . When the two MedDiet groups were pooled and compared with the control group , diabetes incidence was reduced by 52 % ( 27–86 ) . In all study arms , increased adherence to the MedDiet was inversely associated with diabetes incidence . Diabetes risk reduction occurred in the absence of significant changes in body weight or physical activity . CONCLUSIONS MedDiets without calorie restriction seem to be effective in the prevention of diabetes in subjects at high cardiovascular risk",
"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",
"Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed",
"BACKGROUND AND AIMS Diets high in monounsaturated fatty acids ( MUFA ) such as a Mediterranean diet may reduce the risk of cardiovascular diseases by improving insulin sensitivity and serum lipids . Besides being high in MUFA , a Mediterranean diet also contains abundant plant foods , moderate wine and low amounts of meat and dairy products , which may also play a role . We compared the effects of a high MUFA-diet with a diet high in saturated fatty acids ( SFA ) and the additional effect of a Mediterranean diet on insulin sensitivity and serum lipids . METHODS AND RESULTS A r and omized parallel controlled-feeding trial was performed , in 60 non-diabetics ( 40 - 65 y ) with mild abdominal obesity . After a two week run-in diet high in SFA ( 19 energy-% ) , subjects were allocated to a high MUFA-diet ( 20 energy-% ) , a Mediterranean diet ( MUFA 21 energy-% ) , or the high SFA-diet , for eight weeks . The high MUFA and the Mediterranean diet did not affect fasting insulin concentrations . The high MUFA-diet reduced total cholesterol ( -0.41 mmol/L , 95 % CI -0.74 , -0.09 ) and LDL-cholesterol ( -0.38 mmol/L , 95 % CI -0.65 , -0.11 ) compared with the high SFA-diet , but not triglyceride concentrations . The Mediterranean diet increased HDL-cholesterol concentrations ( + 0.09 mmol/L , 95 % CI 0.0 , 0.18 ) and reduced the ratio of total cholesterol/HDL-cholesterol ( -0.39 , 95 % CI -0.62 , -0.16 ) compared with the high MUFA-diet . CONCLUSION Replacing a high SFA-diet with a high MUFA or a Mediterranean diet did not affect insulin sensitivity , but improved serum lipids . The Mediterranean diet was most effective , it reduced total and LDL-cholesterol , and also increased HDL-cholesterol and reduced total cholesterol/HDL-cholesterol ratio",
"Background The ' Hawthorne Effect ' may be an important factor affecting the generalisability of clinical research to routine practice , but has been little studied . Hawthorne Effects have been reported in previous clinical trials in dementia but to our knowledge , no attempt has been made to quantify them . Our aim was to compare minimal follow-up to intensive follow-up in participants in a placebo controlled trial of Ginkgo biloba for treating mild-moderate dementia . Methods Participants in a dementia trial were r and omised to intensive follow-up ( with comprehensive assessment visits at baseline and two , four and six months post r and omisation ) or minimal follow-up ( with an abbreviated assessment at baseline and a full assessment at six months ) . Our primary outcomes were cognitive functioning ( ADAS-Cog ) and participant and carer-rated quality of life ( QOL-AD ) . Results We recruited 176 participants , mainly through general practice s. The main analysis was based on Intention to treat ( ITT ) , with available data . In the ANCOVA model with baseline score as a co-variate , follow-up group had a significant effect on outcome at six months on the ADAS-Cog score ( n = 140 ; mean difference = -2.018 ; 95%CI -3.914 , -0.121 ; p = 0.037 favouring the intensive follow-up group ) , and on participant-rated quality of life score ( n = 142 ; mean difference = -1.382 ; 95%CI -2.642 , -0.122 ; p = 0.032 favouring minimal follow-up group ) . There was no significant difference on carer quality of life . Conclusion We found that more intensive follow-up of individuals in a placebo-controlled clinical trial of Ginkgo biloba for treating mild-moderate dementia result ed in a better outcome than minimal follow-up , as measured by their cognitive functioning . Trial registration Current controlled trials : IS RCT",
"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",
"Dietary intervention is recognized as a key component in prevention and management of type 2 diabetes ( T2DM ) and the debate persists : which dietary strategy is most effective . In the Dietary Intervention R and omized Controlled Trial ( DIRECT ) 322 moderately obese participants were r and omized for 2 years to one of three diet groups : low-fat , Mediterranean and low-carbohydrate . Differential effects were observed in the sub-group of patients with T2DM at 24 months : participants r and omized to the Mediterranean diet , which had the highest intake of dietary fibers and unsaturated to saturated fat ratio , achieved greater significant improvements in fasting plasma glucose and insulin levels . Patients who were r and omized to the low-carbohydrate diet , which had the minimal intake of carbohydrates , achieved a significant reduction of hemoglobin A1C . Although improvements were observed in all groups , the low-fat diet was likely to be less beneficial in terms of glycemic control and lipid metabolism . Interpretation of results from different studies on dietary strategies may be complex since there is often no consistency in diet compositions , calorie restriction , intensity of intervention , dietary assessment or extent of adherence in the trial . Nevertheless , it seems that low fat restricted calorie diets are effective for weight loss and are associated with some metabolic benefits ; however , some recent trials have shown that low carbohydrate diets are as efficient in inducing weight loss and in some metabolic measures such as serum triglycerides and HDL-cholesterol may be even superior to low fat diets . When addressing the issue of diet quality rather than quantity applying the glycemic index may have some added benefits . Furthermore special features of the Mediterranean diet have apparent additional favorable effects for patients with T2DM",
"BACKGROUND Abdominal obesity ( AO ) is associated with increased risk of cardiovascular disease and type 2 diabetes , whereas the Mediterranean diet exerts a cardioprotective effect . OBJECTIVE We examined whether a close adherence to a Mediterranean-style diet improves endothelial function in individuals with AO . DESIGN We recruited 90 subjects with AO without cardiovascular disease or type 2 diabetes . Participants were r and omly assigned to the intervention or control group . Both groups were instructed to follow a Mediterranean-style diet for 2 mo . Subjects in the intervention group additionally had to follow a specific relevant daily and weekly food plan with close supervision by a dietitian and provision of basic foods . Flow-mediated dilatation ( FMD ) , lipids , C-reactive protein ( CRP ) , and insulin resistance with the homeostasis model assessment ( HOMA-IR ) were measured . RESULTS After 2 mo , subjects in the intervention group increased their intake of total fat due to higher consumption of monounsaturated fatty acids as well as intakes of dietary fiber , vitamin C , and alcohol compared with the control group ( all P increased FMD ( 2.05 % ; 95 % CI : 0.97 , 3.13 % ) , whereas no effect was found in the control group ( -0.32 % ; 95 % CI : -1.31 , 0.67 % ) . Changes in lipids and CRP concentrations did not differ between the 2 groups , whereas diastolic blood pressure decreased in the intervention group ( -6.44 mm Hg ; 95 % CI : -8.57 , -4.31 mm Hg ) compared with the control group ( -0.76 mm Hg ; 95 % CI : -2.83 , 1.31 mm Hg ) . Finally , there was a trend for a reduction in HOMA-IR in the intervention group compared with the control group ( P = 0.072 ) . CONCLUSION Close adherence to a Mediterranean-style diet achieved by close dietetic supervision improves endothelial function in subjects with AO",
"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 Mediterranean-style diets improve control of coronary risk factors and hyperglycemia , but few direct comparisons of the diet with other st and ard diets have been done . Contribution In this r and omized clinical trial , patients with newly diagnosed type 2 diabetes who were assigned to a low-carbohydrate , Mediterranean-style diet had better glycemic control and were less likely to need oral antihyperglycemic therapy than patients assigned to a low-fat diet . Caution The trial was unblinded , and dietary intake was self-reported . Implication A low-carbohydrate , Mediterranean-style diet seems to be preferable to a low-fat diet for glycemic control in patients with newly diagnosed type 2 diabetes . The Editors The p and emic of type 2 diabetes is an enormous public health problem , with 380 million cases worldwide projected by 2025 ( 1 , 2 ) . Lifestyle intervention studies ( 3 ) have demonstrated large reductions in risk for type 2 diabetes that remain after lifestyle counseling is stopped ( 4 , 5 ) . Despite this beneficial effect , the American Diabetes Association ( ADA ) recommends that patients with newly diagnosed type 2 diabetes be treated with pharmacotherapy as well as lifestyle changes ( 6 ) . The rationale for combination therapy is presumably that each form of treatment alone is imperfect . Lifestyle changes are often inadequate because patients do not lose weight or regain weight or their diabetes worsens independent of weight ( 6 ) . Pharmacotherapy also often fails with time ( 7 ) , and some drugs have associated cardiovascular and other risks ( 8 , 9 ) . For those reasons , lifestyle changes proven to be more effective than what is typically recommended would be welcome . For example , Mediterranean-style ( MED ) diets with a high proportion of monounsaturated fat provide cardiovascular benefits and increase insulin sensitivity ( 1012 ) , and the ADA recommends low-carbohydrate or low-fat , calorie-restricted diets for weight loss in overweight and obese patients with type 2 diabetes ( 13 ) . However , few direct , long-term comparisons of the 2 diets in patients with diabetes have been done ( 11 ) . We conducted a r and omized trial to compare the effectiveness , durability , and safety of a low-carbohydrate MED diet and a low-fat diet on glycemic control in patients with newly diagnosed type 2 diabetes . Methods We conducted the trial between January 2004 ( first patient enrolled ) and September 2008 ( end of follow-up of the last patient ) at the research center of the Diabetes Clinic of the Azienda Ospedaliera Universitaria , Second University of Naples , Naples , Italy , in accordance with the Declaration of Helsinki and with the institutional review board 's approval . Screening Phase We recruited men and women with newly diagnosed type 2 diabetes by ADA criteria who had never been treated with antihyperglycemic drugs from the clinical practice s of trial investigators and screened them for eligibility . Inclusion criteria were age 30 to 75 years , body mass index ( BMI ) greater than 25 kg/m2 , and hemoglobin A1c ( HbA1c ) level less than 11 % . Participants also had to be sedentary ( To minimize the likelihood of including participants with late-onset type 1 diabetes , we screened c and i date s by testing for antibodies to glutamate decarboxylase and measuring fasting plasma C-peptides . We excluded patients with positive antibodies or C-peptide levels less than 0.25 pmol/L ( We also excluded patients with abnormal laboratory test results , including liver enzyme levels ( alanine aminotransferase , aspartate aminotransferase , and alkaline phosphatase ) greater than 3 times the upper limit of normal and serum creatinine levels greater than 123.8 mol/L ( > 1.4 mg/dL ) . We required that participants successfully self-monitor their diet and physical activity over a 2-week run-in period . We provided dietary education during that time that emphasized the importance of eating a healthy diet and being physically active for both weight loss and improvement of glycemic control . Participants were also taught to prepare their own meals at home . We encouraged all individuals who smoked to quit and provided self-help material s , referral to local programs , or both , as appropriate . R and omization and Blinding After obtaining informed consent , we r and omly assigned patients to 1 of the 2 study diets by using a computer-generated r and om-number sequence ( simple r and omization ) . Allocation was concealed in sealed study folders that were held in a central , secured location until after informed consent was obtained . The nurses who scheduled the study visits did not have access to the r and omization list , and laboratory staff did not know the participants ' group assignments . Staff members involved in the intervention were aware of group assignments , but those who assessed achievement of the primary outcome were blinded to the intervention . Participants received no financial compensation or gifts . Dietary Interventions We r and omly assigned patients to a low-carbohydrate MED diet or to a low-fat diet . The MED diet was rich in vegetables and whole grains and low in red meat , which was replaced with poultry and fish . We restricted energy intake to 1500 kcal/d for women and 1800 kcal/d for men , with the goal of no more than 50 % of calories from complex carbohydrates , based on evidence that , in the context of a MED diet , a carbohydrate content less than 50 % of daily energy is more beneficial than higher content for weight loss and cardiovascular risk reduction ( 14 ) . The diet had no less than 30 % calories from fat . The main source of added fat was 30 to 50 g of olive oil . The low-fat diet was based on American Heart Association guidelines ( 15 ) ; it was rich in whole grains and restricted additional fats , sweets , and high-fat snacks . We restricted energy intake to 1500 kcal/d for women and 1800 kcal/d for men , with the goal of no more than 30 % of calories from fat and no more than 10 % of calories from saturated fat . Nutritionists and dietitians gave dietary advice to participants in both groups in monthly sessions in the first year and bimonthly sessions thereafter . Participants kept diet diaries after being instructed how to record their intake using food models as examples of portion size and using actual weights or amounts in terms of common measures ( such as cups , teaspoons , and dessert spoons ) . We assessed adherence to the diets by session attendance and review of the diaries . Nondietary Interventions Patients in both groups also received guidance on increasing their level of physical activity , mainly walking for a minimum of 30 minutes per day , but also swimming or aerobic ball games . The physical activity program relied heavily on home-based exercise with gradual progression toward a goal of 175 minutes of moderate-intensity physical activity per week . Although walking was encouraged , participants were allowed to choose other types of moderate-intensity physical activity , and programs were tailored on the basis of the results of a baseline physical fitness test and safety concerns . We asked all patients to record occupational , household , and leisure time physical activity . Outcomes We followed patients for 4 years to assess trial outcomes . The primary outcome measure was time to introduction of antihyperglycemic drug therapy . Trial investigators were responsible for initiating drug therapy by the following protocol . As suggested by the ADA for clinical evaluation and management of diabetic patients ( 16 ) , we measured HbA1c at baseline and every 3 months thereafter . Participants who had a HbA1c level greater than 7 % were given an additional 3 months to reinforce dietary guidance and physical activity ; if the HbA1c level remained greater than 7 % , a drug regimen was introduced . Participants with an HbA1c level greater than 7 % at baseline were counted as having experienced the primary outcome if they still had that level at first follow-up . Trial investigators were also responsible for initiating or titrating antihypertensive or lipid-lowering therapy . Secondary outcome measures were changes in weight ( including BMI and waist circumference ) , glycemic control ( HbA1c , glucose , serum insulin , and adiponectin levels and homeostasis model assessment of insulin sensitivity ) , coronary risk factors ( lipid levels and blood pressure ) , and medications and meeting ADA coronary risk factor goals ( HbA1c level weighed without shoes and in lightweight clothing to the nearest 0.1 kg at baseline and every month . Height at baseline ( for calculation of BMI ) was measured to the nearest millimeter with the use of a wall-mounted stadiometer ( Seca , Hamburg , Germany ) . Waist circumference was measured halfway between the last rib and the iliac crest . We measured HbA1c levels with high-pressure liquid chromatography by using the fully automated Glycosylated Hemoglobin Analyzer System ( Bio-Rad , Hercules , California ) traceable to the Diabetes Control and Complications Trial reference method , with a reference range of 4.0 % to 6.0 % . Insulin sensitivity in the fasting state was assessed with homeostasis model assessment and calculated with the following formula , as described by Matthews and colleagues ( 17 ) : fasting plasma glucose (mmol/L)fasting serum insulin (U/mL)/25 . High scores indicate low insulin sensitivity ( insulin resistance ) . We assayed plasma insulin and adiponectin levels by radioimmunoassay , as described elsewhere ( 18 ) . We performed assays for serum",
"This study examined patterns of changes in plasma fatty acids and carotenoids when women were asked to follow a novel , Greek-Mediterranean exchange list diet . A total of 69 healthy , nonobese women ages 25 to 59 years were r and omized either to continue their own usual diet or to follow a modified Mediterranean diet for 6 months . There were no significant changes in blood lipids , triacylglycerol , insulin , glucose , or C-reactive protein . Mean plasma carotenoids increased by 55 % , which is consistent with a large increase in fruit and vegetable consumption . Likewise , changes in fat intakes were reflected in blood fatty acids , with a 25 % increase in mean plasma monounsaturated fatty acids . Principal component analysis was conducted to examine the sources of interindividual variation for changes in carotenoid and fatty acid levels . Changes in the Mediterranean diet were clustered together in 4 components that accounted for 78 % of the variance in plasma levels . Increases in plasma lutein , alpha-carotene , and beta-carotene clustered together in a \" vegetable \" pattern , and increases in carotenoids found in fruit , beta-cryptoxanthin and zeaxanthin also clustered together but accounted for less of the variance . Increases in plasma monounsaturated fatty acids were clustered with a decrease in plasma polyunsaturated fatty acids , consistent with substitution in the type of oils consumed . The only association of fatty acid levels with carotenoids was that of lycopene , which clustered together with an increase in saturated fatty acids . The changes in blood levels indicate the exchange list diet was effective for targeting Mediterranean nutrient intakes using foods available in the United States",
"Aims /hypothesisMost studies of diet in glucose intolerance and type 2 diabetes have focused on intakes of fat , carbohydrate , fibre , fruits and vegetables . Instead , we aim ed to compare diets that were available during human evolution with more recently introduced ones . Methods Twenty-nine patients with ischaemic heart disease plus either glucose intolerance or type 2 diabetes were r and omised to receive ( 1 ) a Palaeolithic ( ‘ Old Stone Age ’ ) diet ( n = 14 ) , based on lean meat , fish , fruits , vegetables , root vegetables , eggs and nuts ; or ( 2 ) a Consensus ( Mediterranean-like ) diet ( n = 15 ) , based on whole grains , low-fat dairy products , vegetables , fruits , fish , oils and margarines . Primary outcome variables were changes in weight , waist circumference and plasma glucose AUC ( AUC Glucose0–120 ) and plasma insulin AUC ( AUC Insulin0–120 ) in OGTTs . Results Over 12 weeks , there was a 26 % decrease of AUC Glucose0–120 ( p = 0.0001 ) in the Palaeolithic group and a 7 % decrease ( p = 0.08 ) in the Consensus group . The larger ( p = 0.001 ) improvement in the Palaeolithic group was independent ( p = 0.0008 ) of change in waist circumference ( −5.6 cm in the Palaeolithic group , −2.9 cm in the Consensus group ; p = 0.03 ) . In the study population as a whole , there was no relationship between change in AUC Glucose0–120 and changes in weight ( r = −0.06 , p = 0.9 ) or waist circumference ( r = 0.01 , p = 1.0 ) . There was a tendency for a larger decrease of AUC Insulin0–120 in the Palaeolithic group , but because of the strong association between change in AUC Insulin0–120 and change in waist circumference ( r = 0.64 , p = 0.0003 ) , this did not remain after multivariate analysis . Conclusions /interpretationA Palaeolithic diet may improve glucose tolerance independently of decreased waist circumference",
"CONTEXT Obesity is an independent risk factor for cardiovascular disease , which may be mediated by increased secretion of proinflammatory cytokines by adipose tissue . OBJECTIVE To determine the effect of a program of changes in lifestyle design ed to obtain a sustained reduction of body weight on markers of systemic vascular inflammation and insulin resistance . DESIGN AND SETTING R and omized single-blind trial conducted from February 1999 to February 2002 at a university hospital in Italy . PATIENTS One hundred twenty premenopausal obese women ( body mass index > or = 30 ) aged 20 to 46 years without diabetes , hypertension , or hyperlipidemia . INTERVENTIONS The 60 women r and omly assigned to the intervention group received detailed advice about how to achieve a reduction of weight of 10 % or more through a low-energy Mediterranean-style diet and increased physical activity . The control group ( n = 60 ) was given general information about healthy food choices and exercise . MAIN OUTCOME MEASURES Lipid and glucose intake ; blood pressure ; homeostatic model assessment of insulin sensitivity ; and circulating levels of interleukin 6 ( IL-6 ) , interleukin 18 ( IL-18 ) , C-reactive protein ( CRP ) , and adiponectin . RESULTS After 2 years , women in the intervention group consumed more foods rich in complex carbohydrates ( 9 % corrected difference ; P energy ( -310 kcal/d ; P saturated fat ( -3.5 % ; P = .007 ) , and cholesterol intake ( -92 mg/d ; P Body mass index decreased more in the intervention group than in controls ( -4.2 ; P serum concentrations of IL-6 ( -1.1 pg/mL ; P = .009 ) , IL-18 ( -57 pg/mL ; P = .02 ) , and CRP ( -1.6 mg/L ; P = .008 ) , while adiponectin levels increased significantly ( 2.2 microg/mL ; P = .01 ) . In multivariate analyses , changes in free fatty acids ( P = .008 ) , IL-6 ( P = .02 ) , and adiponectin ( P = .007 ) levels were independently associated with changes in insulin sensitivity . CONCLUSION In this study , a multidisciplinary program aim ed to reduce body weight in obese women through lifestyle changes was associated with a reduction in markers of vascular inflammation and insulin resistance",
"CONTEXT Limited information exists on the interaction between diet and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) and the interaction 's effect on serum lipid and lipoprotein levels , insulin sensitivity , and circulating antioxidant vitamin and provitamin levels . OBJECTIVE To evaluate the separate and combined effects of diet and simvastatin therapy on serum levels of lipids , lipoproteins , antioxidants , and insulin . DESIGN , SETTING , AND PARTICIPANTS R and omized , controlled crossover trial conducted from August 1997 to June 1998 in 120 previously untreated hypercholesterolemic men aged 35 to 64 years who were recruited from the community in Turku , southwestern Finl and . INTERVENTIONS After a 4- to 6-week placebo run-in period , participants were r and omly allocated to a habitual diet ( n = 60 ) or dietary treatment group ( n = 60 ) , and each of these groups was further r and omized in a double-blind crossover fashion to receive simvastatin ( 20 mg/d ) or placebo , each for 12 weeks ( n = 30 in each group ) . The main goals of the dietary treatment were to reduce energy intake from saturated plus trans-unsaturated fats to no more than 10 % by replacing them partly with monounsaturated and polyunsaturated fats rich in omega-3 fatty acids and to increase intake of fruits , vegetables , and dietary fiber . MAIN OUTCOME MEASURES Changes in levels of total , low-density lipoprotein ( LDL ) , and high-density lipoprotein ( HDL ) cholesterol ; triglycerides ; apolipoprotein B ; insulin ; glucose ; and antioxidants at week 12 of each treatment period , compared among the 4 groups . RESULTS Dietary treatment decreased levels of total cholesterol by 7.6 % ( P LDL cholesterol by 10.8 % ( P HDL cholesterol by 4.9 % ( P = .01 ) , apolipoprotein B by 5.7 % ( P = .003 ) , serum insulin by 14.0 % ( P = .02 ) , and alpha-tocopherol by 3.5 % ( P = .04 ) . Simvastatin decreased levels of total cholesterol by 20.8 % , LDL cholesterol by 29.7 % , triglycerides by 13.6 % , apolipoprotein B by 22.4 % , alpha-tocopherol by 16.2 % , beta-carotene by 19.5 % , and ubiquinol-10 by 22.0 % ( P increased levels of HDL cholesterol by 7.0 % ( P serum insulin by 13.2 % ( P = .005 ) . Glucose levels remained unchanged in all groups . The effects of dietary treatment and simvastatin were independent and additive . CONCLUSIONS A modified Mediterranean-type diet rich in omega-3 fatty acids efficiently potentiated the cholesterol-lowering effect of simvastatin , counteracted the fasting insulin-elevating effect of simvastatin , and , unlike simvastatin , did not decrease serum levels of beta-carotene and ubiquinol-10",
"Whether a Mediterranean-style diet reduces cardiovascular events and mortality more than a low-fat diet is uncertain . The objectives of this study were to actively compare low-fat and Mediterranean-style diets after first myocardial infa rct ion ( MI ) in a r and omized , controlled clinical trial and to compare dietary intervention per se with usual care in a case-control analysis . First MI survivors were r and omized to a low-fat ( n = 50 ) or Mediterranean-style ( n = 51 ) diet . The 2 diets were low in saturated fat ( diet was distinguished by greater omega-3 fat intake ( > 0.75 % kcal ) . Participants received individual dietary counseling sessions , 2 within the first month and again at 3 , 6 , 12 , 18 , and 24 months , along with 6 group sessions . Combined dietary intervention groups ( cases , n = 101 ) were compared with a usual-care group ( controls , n = 101 ) matched for age , gender , MI type and treatment , and status of diabetes mellitus and hypertension . Primary - outcome -free survival ( a composite of all-cause and cardiac deaths , MI , hospital admissions for heart failure , unstable angina pectoris , or stroke ) did not differ between low-fat ( 42 of 50 ) and Mediterranean-style ( 43 of 51 ) diet groups over a median follow-up period of 46 months ( range 18 to 72 ; log-rank p = 0.81 ) . Patients receiving dietary intervention had better primary - outcome -free survival ( 85 of 101 ) than usual-care controls ( 61 of 101 ) ( log-rank p low-fat or a Mediterranean-style diet similarly and significantly benefits overall and cardiovascular-event-free survival after MI",
"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"
] |
4116c57c-06ff-11f0-808a-c43d1ab1c353
|
Homoeopathy is often advocated for fibromyalgia ( FM ) and many FM patients use it . To critically evaluate all r and omised clinical trials ( RCTs ) of homoeopathy as a treatment for FM , six electronic data bases were search ed to identify all relevant studies . Data extraction and the assessment of the method ological quality of all included studies were done by two independent review ers . Four RCTs were found , including two feasibility studies . Three studies were placebo-controlled . None of the trials was without serious flaws . Invariably , their results suggested that homoeopathy was better than the control interventions in alleviating the symptoms of FM . Independent replications are missing . Even though all RCTs suggested results that favour homoeopathy , important caveats exist . Therefore , the effectiveness of homoeopathy as a symptomatic treatment for FM remains unproven
|
[
"OBJECTIVE To assess the efficacy of individualized classical homeopathy in the treatment of fibromyalgia . METHODS This study was a double-blind , r and omized , parallel-group , placebo-controlled trial of homeopathy . Community-recruited persons ( N = 62 ) with physician-confirmed fibromyalgia ( mean age 49 yr , s.d . 10 yr , 94 % women ) were treated in a homeopathic private practice setting . Participants were r and omized to receive oral daily liquid LM ( 1/50,000 ) potencies with an individually chosen homeopathic remedy or an indistinguishable placebo . Homeopathic visits involved joint interviews and concurrence on remedy selection by two experienced homeopaths , at baseline , 2 months and 4 months ( prior to a subsequent optional crossover phase of the study which is reported elsewhere ) . Tender point count and tender point pain on examination by a medical assessor uninvolved in providing care , self-rating scales on fibromyalgia-related quality of life , pain , mood and global health at baseline and 3 months , were the primary clinical outcome measures for this report . RESULTS Fifty-three people completed the treatment protocol . Participants on active treatment showed significantly greater improvements in tender point count and tender point pain , quality of life , global health and a trend toward less depression compared with those on placebo . CONCLUSIONS This study replicates and extends a previous 1-month placebo-controlled crossover study in fibromyalgia that pre-screened for only one homeopathic remedy . Using a broad selection of remedies and the flexible LM dose ( 1/50,000 dilution factor ) series , the present study demonstrated that individualized homeopathy is significantly better than placebo in lessening tender point pain and improving the quality of life and global health of persons with fibromyalgia",
"OBJECTIVES To assess the feasibility of a R and omised Controlled Trial ( RCT ) design of usual care compared with usual care plus adjunctive care by a homeopath for patients with Fibromyalgia syndrome ( FMS ) . METHODS In a pragmatic parallel group RCT design , adults with a diagnosis of FMS ( ACR criteria ) were r and omly allocated to usual care or usual care plus adjunctive care by a homeopath . Adjunctive care consisted of five in depth interviews and individualised homeopathic medicines . The primary outcome measure was the difference in Fibromyalgia Impact Question naire ( FIQ ) total score at 22 weeks . RESULTS 47 patients were recruited . Drop out rate in the usual care group was higher than the homeopath care group ( 8/24 vs 3/23 ) . Adjusted for baseline , there was a significantly greater mean reduction in the FIQ total score ( function ) in the homeopath care group than the usual care group ( -7.62 vs 3.63 ) . There were significantly greater reductions in the homeopath care group in the McGill pain score , FIQ fatigue and tiredness upon waking scores . We found a small effect on pain score ( 0.21 , 95 % CI -1.42 to 1.84 ) ; but a large effect on function ( 0.81 , 95 % CI -8.17 to 9.79 ) . There were no reported adverse events . CONCLUSIONS Given the acceptability of the treatment and the clinical ly relevant effect on function , there is a need for a definitive study to assess the clinical and cost effectiveness of adjunctive healthcare by a homeopath for patients with FMS",
"In this article , we test the hypothesis that r and omized clinical trials of acupuncture for pain with certain design features ( A + B versus B ) are likely to generate false positive results . Based on electronic search es in six data bases , 13 studies were found that met our inclusion criteria . They all suggested that acupuncture is effected ( one only showing a positive trend , all others had significant results ) . We conclude that the ' A + B versus B ' design is prone to false positive results and discuss the design features that might prevent or exacerbate this problem",
"OBJECTIVES To characterize initial central nervous system responses to olfactory administration of homeopathic remedies as biomarkers for subsequently exceptional , simillimum-like clinical outcomes at a systemic level ( i.e. , both locally and globally ) . DESIGN Double-blinded , r and omized , placebo-controlled clinical trial . SETTING A private homeopathic clinic in Phoenix , AZ , and a university laboratory in Tucson , AZ . PATIENTS Sixty-two ( 62 ) persons with physician-confirmed fibromyalgia ( FM ) ( mean age , 49 years ; 94 % women ) enrolled ; 53 completed the 3-month assessment visit . Exceptional responders ( n = 6 , 23 % of active treatment group ; none on placebo ) were those with improvements in the top one-third for both tender point pain and global health ratings after 3 months . INTERVENTION Patients took daily oral doses of treatment solution in LM ( 1/50,000 dilution ) potency ( active group received individualized remedy ; placebo group received plain solvent ) . Dependent measures : Baseline and 3-month difference scores for initial prefrontal electroencephalographic alpha frequency cordance ( EEG-C , a correlate of functional brain activity ) during 16 pairs of r and omized , double-blinded bottle sniffs ( treatment minus control solutions ) . RESULTS Exceptional responders versus other patients exhibited significantly more negative initial EEG-C difference scores at prefrontal sites . Right prefrontal cordance findings correlated with subsequently reduced pain ( r = 0.85 , p = 0.03 ) , better global health ( r = -0.73 , p = 0.10 ) , and trait absorption ( genetically determined ability to focus attention selectively and fully ) ( r = 0.91 , p = 0.012 ) . CONCLUSIONS These observations suggest prefrontal EEG-C as an early biomarker of individualized homeopathic medicine effects in patients with FM who later exhibit exceptional outcomes . Prefrontal cortex controls executive function , including ability to redirect attention . Interactions between executive function , absorption , and the simillimum remedy could facilitate exceptional responses",
"Previous studies have shown that changes in brain function precede clinical response to antidepressant medications . Here we examined quantitative EEG ( QEEG ) absolute and relative power and a new measure , cordance , for detecting regional changes associated with treatment response . Fifty-one adults with unipolar depression completed treatment trials using either fluoxetine or venlafaxine vs. placebo . Data were recorded at baseline and after 48 h and 1 week on drug or placebo . Baseline and change from baseline values were examined for specific brain regions in four subject groups ( medication and placebo responders and nonresponders ) . No regional baseline QEEG differences were found among the groups ; there also were no significant changes in theta power over time . In contrast , medication responders uniquely showed significant decreases in prefrontal cordance at 48 h and 1 week . Clinical differences did not emerge until after four weeks . Subjects with greater changes in cordance had the most complete 8-week responses . These findings implicate the prefrontal region in mediating response to antidepressant medications . Cordance may have clinical applicability as a leading indicator of individual response",
"mens . Several treatments were required for each tumour , and injecting alcohol was often associated with considerable pain , whereas our patients did not report pain . These reports did not mention changes seen on ultrasound scans during or immediately after injection , which we found useful in laser treatment . The most important advantage of the laser is its precision . It is unlikely that it will ever be possible to predict the extent of necrosis around a site at which absolute alcohol has been injected with an accuracy comparable to that already possible with the laser technique . In conclusion , interstitial laser hyperthermia is feasible and seems to be safe . A multiple fibre system makes it feasible to treat tumours of clinical ly relevant size in the centre of solid organs . The real challenge for the future will be to develop diagnostic techniques that disclose exactly how far individual tumours extend in a wider range of organs ( unlike the well defined tumours treated in this pilot study ) and to establish the conditions of laser treatment that give complete tumour ablation with safe healing . This combination of technologies may be valuable for treating otherwise untreatable tumours in a range of solid organs and for the primary treatment of small neoplasms such as tumours of the prostate and adrenal gl and",
"OBJECTIVE To assess individual difference characteristics of subgroups of patients with fibromyalgia ( FM ) patients with respect to the decision to stay in or switch from r and omly-assigned verum or placebo treatment during an optional crossover phase of a double-blinded homeopathy study . DESIGN Double-blinded , r and omized , placebo-controlled , optional crossover clinical trial . PARTICIPANTS Fifty-three ( 53 ) community-recruited patients with FM entered the optional crossover phase . INTERVENTION Two homeopaths jointly selected an individualized homeopathic remedy for all patients . The pharmacy dispensed either verum LM remedy or indistinguishable placebo in accord with r and omized assignment for 4 months and the patient 's optional crossover decision for an additional 2 months . OUTCOME MEASURES Patients completed a battery of baseline state/trait question naires , including mood , childhood neglect and abuse , and trait absorption . They rated global health ( whole person-centered ) and tender point pain on physical examination ( disease-specific ) at baseline , 3 months , and 6 months . RESULTS Rates of optional crossover from verum to placebo or placebo to verum were comparable ( p = 0.6 ; 31 % , and 41 % , respectively ) . The switch subgroups had greater baseline psychologic issues ( emotional neglect in placebo-switch ; depression and anger in verum-switch ) . The verum-stay subgroup scored highest on treatment helpfulness and included all six exceptional responders who fell , prior to crossover , into the top terciles for improvement in both global health and pain . Patients staying in their r and omly assigned groups , active or placebo ( n = 34 ) , scored significantly higher in trait absorption than did those who switched groups ( n = 19 ) . CONCLUSION Individual difference factors may predict better and poorer responders with FM to specific and nonspecific effects of homeopathic and placebo treatment",
"Fibromyalgia ( FM ) patients show evidence of sensitizability in pain pathways and electroencephalographic ( EEG ) alterations . One proposed mechanism for the cl aim ed effects of homeopathy , a form of complementary medicine used for FM , is time-dependent sensitization ( TDS , progressive amplification ) of host responses . This study examined possible sensitization-related changes in EEG relative alpha magnitude during a clinical trial of homeopathy in FM . A 4-month r and omized , placebo-controlled double-blind trial of daily orally administered individualized homeopathy in physician-confirmed FM , with an additional 2-month optional crossover phase , included three laboratory sessions , at baseline , 3 and 6 months ( N = 48 , age 49.2 ± 9.8 years , 94 % women ) . Nineteen leads of EEG relative alpha magnitude at rest and during olfactory administration of treatment and control solutions were evaluated in each session . After 3 months , the active treatment group significantly increased , while the placebo group decreased , in global alpha-1 and alpha-2 during bottle sniffs over sessions . At 6 months , the subset of active patients who stayed on active continued to increase , while the active-switch subgroup reversed direction in alpha magnitude . Groups did not differ in resting alpha . Consistent with the TDS hypothesis , sniff alpha-1 and alpha-2 increases at 6 months versus baseline correlated with total amount of time on active remedy over all subjects ( r = 0.45 , p = .003 ) , not with dose changes or clinical outcomes in the active group . The findings suggest initiation of TDS in relative EEG alpha magnitude by daily oral administration of active homeopathic medicines versus placebo , with laboratory elicitation by temporolimbic olfactory stimulation or sniffing"
] |
4116c5b8-06ff-11f0-808a-c43d1ab1c353
|
OBJECTIVES A systematic review and meta- analysis were performed on the risk and intensity of postoperative sensitivity ( POS ) in posterior resin composite restorations bonded with self-etch ( SE ) and etch- and -rinse ( ER ) adhesives . SOURCE A comprehensive search was performed in the MEDLINE via PubMeb , Scopus , Web of Science , LILACS , BBO and Cochrane Library and SIGLE without restrictions . The abstract s of the annual conference of the IADR ( 1990 - 2014 ) , unpublished and ongoing trials registry were also search ed . Dissertations and theses were search ed using the ProQuest Dissertations and Periodicos Capes Theses data bases . STUDY SELECTION We included r and omized clinical trials that compared the clinical effectiveness of SE and ER used for direct resin composite restorations in permanent dentition of adult patients . The risk/intensity of POS was the primary outcome . The risk of bias tool of the Cochrane Collaboration was used . The meta- analysis was performed on the studies considered ' low ' risk of bias . DATA After duplicates removal , 2600 articles were identified but only 29 remained in the qualitative synthesis . Five were considered to be ' high ' risk of bias and eleven were considered to be ' unclear ' in the key domains , yielding 13 studies for meta- analysis . The overall relative risk of the spontaneous POS was 0.63 ( 95 % CI 0.35 to 1.15 ) , while the stimuli-induced POS was 0.99 ( 95 % CI 0.63 to 1.56 ) . The overall st and ardized mean difference was 0.08 ( 95%CI -0.19 to 0.35 ) . No overall effect was revealed in the meta-analyses , meaning that no influence of the ER or SE strategy on POS . SIGNIFICANCE The type of adhesive strategy ( ER or SE ) for posterior resin composite restorations does not influence the risk and intensity of POS . CRD42014006617
|
[
"The split-mouth design is a popular design in oral health research . In the most common split-mouth study , each of two treatments are r and omly assigned to either the right or left halves of the dentition . The attractiveness of the design is that it removes a lot of inter-individual variability from the estimates of the treatment effect . However , already about 20 years ago the pitfalls of the design have been reported in the oral health literature . Yet , many clinicians are not aware of the potential problems with the split-mouth design . Further , it is our experience that most statisticians are not even aware of the existence of this design . Since most of the critical remarks appeared in the oral health literature , we argue that it is necessary to introduce the split-mouth design to a statistical audience , so that both clinicians and statisticians clearly underst and the advantages , limitations , statistical considerations , and implication s of its use in clinical trials and advise them on its use in practice",
"The clinical performance of packable and conventional hybrid resin composites in Class I restorations for a period of three years was compared using a r and omized controlled double-blind clinical trial with self-matching design . A total of 50 pairs of Class I restorations were placed in 32 adult patients by one dentist in a self-matching prospect i ve clinical trial . The paired teeth were divided into the TPH Spectrum/XenoIII ( TS ) restoration group and the Synergy Compact/One Coat ( SC ) restoration group according to a r and om number table . Application of the material s followed the manufacturer 's instructions . The restorations were evaluated by two independent evaluators using US Public Health Service (USPHS)-Ryge modified criteria . Statistical analysis was performed using the McNemar 's test with Yates ' continuity correction . After three years , 40 pairs of restorations were available for evaluation . Four TS and two SC restorations failed due to fracture . Only one TS-restored tooth showed postoperative sensitivity at baseline and the symptom disappeared one week later . Alpha ratings of TS vs SC restorations were as follows : 95 % vs 98 % for color match , 85 % vs 88 % for marginal integrity , 88 % vs 90 % for anatomical form , 85 % vs 83 % for marginal discoloration , 88 % vs 93 % for occlusal contact . For both material s , Alpha ratings were 88 % for surface texture . The three-year clinical performances of the two restorative material s were satisfactory and not significantly different for each of the parameters evaluated",
"Dentin bonding using the total-etch method has been cl aim ed to be technique-sensitive . The aim of this study is to examine the effect of acid-etch variations on the dentin demineralization and interfacial structure of the adhesive-dentin bond using a differential staining technique . Single Bond adhesive with 35 % phosphoric acid gel was used . The occlusal one-third of the crown was removed from 60 extracted , unerupted human third molars . Smear layers were created by abrading the dentin with 600 grit SiC under water for 30 s. The prepared teeth were r and omly assigned to four groups according to etching time ( Group 1 , 10 s ; Group 2 , 15 s ; Group 3 , 30 s ; Group 4 , 60 s ) . In each group , the etching gel was : ( i ) applied and spread to the dentin surface and left to st and undisturbed ; ( ii ) applied and gently agitated during etching ; ( iii ) applied without using dispensing tips for the syringe and left for the same period as above . After rinsing , the etched dentin was then treated with the adhesive per manufacturers ' instructions . 3 - 5 micro m thin sections of the adhesive/dentin ( a/d ) interface were cut with a microtome and stained with Goldner 's trichrome . Stained , thin sections from each prepared tooth were imaged with light microscopy . The depth and extent of dentin demineralization , and the a/d interdiffusion zone were clearly visible by this differential staining microtechnique . The thickness of the interdiffusion zone increased as a function of etching time . However , the etchant gel application methods have a significant influence on dentin demineralization . Although agitating acid gel facilitates the penetration and etching into dentin , it should not be recommended , especially for longer etching time . These results indicated that the etching technique has a large effect on the profile of both dentin demineralization and interfacial structure",
"The five-year findings of a study to compare the performance of restorations of Occlusin ( ICI Dental , Macclesfield , UK ) in butt-joint and bevel-edged preparations are reported . Ninety-four ( 79 % ) of the restorations originally placed were review ed at five years , 20 restorations ( 17 % ) having failed during the study . Initial analysis of the overall results having failed to reveal any significant differences between the five-year performance of the two types of restorations , the results were combined and analyzed by Chi-square tests and step-wise logistic regression . Chi-square analysis indicated that of the independent variables investigated , size of restoration had the greatest effect on clinical performance . Step-wise logistic regression revealed that only four of the eight dependent variables investigated showed significant predictive relationships with the independent variables , the logistic equation for occlusal marginal adaptation being the most complex . The greatest amount of generalized occlusal surface wear tended to be seen in large-sized Class II restorations in molar teeth , with the main factor influencing wear being found to be the type of restoration ( Class I or Class II ) . It is concluded that the performance of restorations of Occlusin has not been found to differ significantly in butt-joint and bevel-edged preparations after five years in clinical service . Step-wise logistic regression has been found to be a useful tool in the analysis of data obtained during the clinical evaluation of a restorative material",
"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",
"A study was conducted to determine whether the wear resistance of a posterior composite could be improved by maximizing filler particle-to-particle contacts . This was expected to reduce stress concentrations on the resin matrix and thus reduce occlusal wear . A self-curing quartz-filled composite with this design , P-10 , was used to restore 90 Class I and II cavity preparations in adult teeth . Restorations were recalled after baseline at six months , one year , two years , and three years to measure wear by direct and indirect evaluation methods . There was no apparent advantage for this material compared with other previously evaluated posterior composites . The average cumulative wear for P-10 after three years was 145 microns . In addition , the restorations were evaluated for color-matching , interfacial staining , secondary caries , marginal adaptation , surface texture , and postoperative sensitivity . This material was not significantly different in those ways from other posterior composite products except in terms of more rapid color change , because it is self-cured",
"Abstract . This study investigated the clinical performance of two packable composite resins in Class-II restorations . One hundred and four Class-II restorations were placed in 52 patients by five dentists ( four in dental practice s and one in a university clinic ) in a controlled prospect i ve multicentre clinical trial . Each patient received one Definite/Etch & Prime 3.0 ( D-EP ) and one Solitaire/Solid Bond ( S-SB ) restoration , which were examined clinical ly according to modified USPHS- criteria after 1 week ( baseline ) and after 1 year . Statistical analysis was performed using the Wilcoxon rank sum test and the error rates method . The significance level was set to 0.05 . At baseline both material s performed equally according to the evaluated criteria . After 1 year D-EP showed significantly worse marginal adaptation compared to S-SB . Both material s displayed significant deterioration for the criteria marginal adaptation , marginal discolouration , approximal contact , and fracture of restoration after 1 year compared to baseline . With a failure rate of 9.6 % after 1 year , D-EP did not fulfill ADA acceptance criteria for restorative material s. It is proposed that at least 1-year data of clinical testing should be available before a new material is broadly marketed",
"BACKGROUND Self-etching adhesives are believed to prevent postoperative sensitivity when used under posterior resin-based composite restorations . The authors tested a twofold hypothesis : a self-etch , or SE , adhesive would result in less postoperative sensitivity than a total-etch , or TE , adhesive ; an SE adhesive would result in poorer enamel marginal integrity than a TE adhesive . METHODS Patients were selected on the basis of requiring Class I and II restorations in molars and premolars . The authors placed 30 restorations with the SE material ( Clearfil SE Bond , Kuraray America , New York ) and 36 restorations with Prime & Bond NT ( Dentsply Caulk , Milford , Del. ) , which uses 34 percent phosphoric acid to etch enamel and dentin simultaneously . Preparations were of st and ard design , with all margins in enamel without beveling . Upon rubber dam isolation , the authors conditioned the enamel and dentin walls with the self-etching primer ( for Clearfil SE Bond ) or etched with the proprietary 34 percent phosphoric acid ( for Prime & Bond NT ) , followed by application of the corresponding dentin adhesive . Teeth were restored with the proprietary hybrid resin-based composite indicated for posterior restorations : Clearfil AP-X for Clearfil SE Bond or Esthet-X Micro Matrix Restorative for Prime & Bond NT . The restored teeth were evaluated preoperatively and at two weeks , eight weeks and six months postoperatively for sensitivity to cold ( ice ) , air and masticatory forces , as well as for marginal discoloration . RESULTS Analysis of variance revealed no statistically significant differences in postoperative sensitivity between the SE and TE material s at any recall time . Marginal discoloration was rated as \" absent \" for all restorations at six months . Only one tooth displayed sensitivity to occlusal forces at six months . CONCLUSION The SE adhesive did not differ from the TE adhesive in regard to sensitivity and marginal discoloration . CLINICAL IMPLICATION S Postoperative sensitivity may depend on the restorative technique rather than on the type of dentin adhesive used",
"PURPOSE This longitudinal r and omized controlled clinical trial evaluated direct composite restorations for clinical acceptability as posterior restoratives in single- or multi-surface cavities and provides a survey of the 4-year results . MATERIAL S AND METHODS Three dentists placed 46 Quixfil ( Xeno III ) and 50 Tetric Ceram ( Syntac Classic ) composite restorations in stress-bearing Class I and II cavities in first or second molars ( 43 adult patients ) . Clinical evaluation was performed at baseline and after 4 years by 2 other dentists using modified USPHS criteria . At the last recall period , 37 Quixfil and 46 Tetric Ceram restorations were assessed . RESULTS A total of 89.2 % of Quixfil and 97.8 % of Tetric Ceram posterior composites were assessed to be clinical ly excellent or acceptable with predominating alfa scores . Up to the 4-year recall , four Quixfil restorations failed because of bulk fracture , partial tooth fracture ( 2x ) and postoperative symptoms . One Tetric Ceram restoration was lost due to problems with tooth integrity . No significant differences between the two composites could be detected at 4 years for any of the evaluated clinical criteria ( p > 0.05 ) . The comparison of restoration performance with time within both groups yielded a significant increase in marginal discoloration and decrease in marginal integrity for both material s. After 4 years , small restorations exhibited significantly less marginal discoloration than large restorations . CONCLUSION Clinical assessment of stress-bearing Quixfil and Tetric Ceram posterior composite restorations showed good clinical results with predominantly alfa scores for both material",
"OBJECTIVES To analyze the relationship between the cavity depth and liners with postoperative sensitivity of resin composite restorations . METHODS A clinical follow-up was conducted on 319 resin composite restorations made in the final year of an undergraduate program over a 3-year period . Along with the analyses of cavity type , cavity depth , type of pulpal protection and the material s used , the postoperative sensitivity was also examined on each restoration . RESULTS Thirty-nine percent of the restorations had no protective layer ( Group 1 ) . As the depth of the prepared cavities increased , the restorations received one of the three pulpal protection methods ; a calcium hydroxide base ( Group 2 ) , glass ionomer cement ( Group 3 ) , or protection with a calcium hydroxide base in combination with glass ionomer cement ( Group 4 ) . The incidence of postoperative sensitivity showed no significant difference among Groups 1 , 2 and 3 , but was significantly lower in Group 1 than in Group 4 . The restorations made in shallow and medium depth cavities demonstrated significantly less-postoperative sensitivity than those made in deep cavities . The newer generation dentine-bonding agents showed a significantly lower incidence of postoperative sensitivity than the early generation group . CONCLUSIONS Postoperative sensitivity in resin composite restorations was not related to the absence of protective layers but increased with the depth of cavities restored with the resin composite . The type of dentine-bonding agents could also be responsible for postoperative sensitivity",
"Abstract .The purpose of this study was to evaluate the clinical performance of two \" packable \" posterior composites : Prodigy Condensable ( P ) ( Kerr ) and Definite ( D ) ( Degussa ) . Thirty-six patients participated in the study . A total of 78 restorations were made , 40 with D and 38 with P. Each patient received at least two restorations , one of each studied material . The material s were h and led according to the manufacturer 's instructions . The restorations were finished and polished after 1 week . They were evaluated at baseline and after 1 year by two independent evaluators using the United States Public Health Service ( USPHS ) criteria . Colored slides were made of all the restorations . After 1 year , 35 patients and 76 restorations ( 39 with D and 37 with P ) were available for evaluation . All restorations received A criteria except the following ones , which received B criteria : color P ( one restoration ) and D ( one restoration ) , marginal staining P ( three restorations ) and D ( two restorations ) , surface staining P ( nine restorations ) and D ( three restorations ) , anatomic form P ( one restoration ) and D ( three restorations ) , and marginal adaptation P ( one restoration ) and D ( eight restorations ) . The obtained data were tabulated and statistically analyzed using the Fisher and McNemar tests . After 1 year , P showed a significant increase in superficial staining . For D , the marginal adaptation became significantly worse than baseline and P. The studied material s can be considered acceptable during this evaluation period . Further evaluations are necessary for a better clinical performance analysis",
"The purpose of this study was to evaluate the clinical performance of two \" packable \" posterior composites : Prodigy Condensable/Optibond Solo — Kerr ( PC-OS ) and Definite/Etch & Prime — Degussa ( D-EP ) . Thirty-six patients participated in this study . A total of 78 restorations ( 40 with D-EP and 38 with PC-OS ) were made . Each patient received at least two restorations ( one of each studied material ) . The material s were h and led according to the manufacturer 's instructions . The occlusal adjustments were made at the placement visit . The restorations were finished and polished after 1 week . They were evaluated at baseline , and after 1 year and 2 years by two independent evaluators using the USPHS criteria . Colored slides were made of all the restorations . After 2 years , 34 patients and 74 restorations ( 38 with D-EP and 36 with PC-OS ) were available for evaluation . A total of 50 % of PC-OS restorations received A criterion and 50 % received B criterion ( 2.8 % color , 11.1 % marginal staining , 27.8 % superficial staining , 2.8 % anatomic form and 5.6 % marginal adaptation ) . For D-EP , 60.5 % of restorations received A criterion and 39.5 % received B criterion ( 2.6 % color , 5.3 % marginal staining , 10.5 % superficial staining , 7.9 % anatomic form and 13.2 % marginal adaptation ) . The C criterion was observed only for marginal adaptation with D-EP ( 2 restorations—5.3 % ) . The obtained data were tabulated and statistically analyzed using the Fisher , Chi-square and McNemar tests . After 2 years , PC-OS showed a significant increase in superficial and marginal staining . For D-EP the marginal adaptation and superficial staining became significantly worse than baseline",
"PURPOSE The aim of this blinded , r and omized , prospect i ve long-term study was to evaluate the clinical performance of the two-step self-etching adhesive AdheSE ( AS , Ivoclar Vivadent ) compared to the etch- and -rinse adhesive system Excite ( EX , Ivoclar Vivadent ) in combination with the hybrid resin composite Tetric Ceram HB ( Ivoclar Vivadent ) for Class I and II restorations . MATERIAL S AND METHODS In accordance with a split mouth design , 50 patients received 100 restorations in premolars and molars . The restorations were assigned at r and om to the self-etching ( AS ) or the etch- and -rinse ( EX ) group . Each restoration was scored according to the modified Ryge criteria at baseline and after 6 , 12 , 24 and 48 months . Epoxy resin replicas of 60 restorations were made at each observation period for an additional SEM analysis of the occlusal margins . RESULTS After 4 years , 60 of 100 restorations could be evaluated . The cumulative survival rate for group EX was 100 % and for group AS 96.7 % . One restoration in group AS had failed due to marginal gap formation . For the criterion marginal adaption in group AS , significantly more bravo ratings ( 30 % ) were observed after 4 years compared to group EX ( 6.7 % ) ( p SEM margin analysis revealed no significant differences between groups AS and EX ( Mann-Whitney U-test ; p > 0.05 ) . CONCLUSION Both adhesive systems performed satisfactorily over the four-year observation period . A significant deterioration over time was found for the criterion marginal adaption in AdheSE",
"PURPOSE To clinical ly evaluate two different resin-based composites ( Solitaire I and Ariston pHc ) in order to determine the minimum clinical evaluation time needed to detect critical signs of failure . METHODS In a controlled prospect i ve clinical study , 99 cavities ( 30 Class I , 69 Class II ) in 31 patients were restored ( 50 Ariston pHc without enamel etching and rubber dam , 49 Solitaire I restorations with total etching and rubber dam ) and clinical ly investigated at baseline , after 6 , 12 , and 24 months . RESULTS After 2 years of clinical service , 49 restorations ( Ariston pHc : n = 38 , Solitaire : n = 11 ) had to be replaced . The majority of failures occurred after more than 1.5 years . The reasons for replacement were differently distributed in both groups ( Ariston pHc : 28 tooth fractures , 3 gap formations , 5 hypersensitivities , 1 bulk fracture , 1 marginal fracture . Solitaire : 5 gap formations , 1 hypersensitivity , 3 bulk fractures , 1 wear of the restorative material , 1 void in the restoration ) . Forty-four restorations were still in function after 2 years ( overall failure rate after 2 years : 14 % ; Ariston pHc : 17 % ; Solitaire : 7 % ; survival analysis algorithm according to Kaplan/Meier ) . Comparing the material s , no statistical differences were evident except for the criteria \" integrity tooth \" (= tooth fracture or cracks ) and \" hypersensitivity \" ( from the 12-month recall ; Mann-Whitney U-test ; P Ariston pHc did not show considerably cracked enamel . The additional marginal analysis showed statistically significant differences for both material s regarding the criteria \" perfect margin \" ( decrease ) , \" gap formation \" ( increase ) , and \" negative step formation \" ( increase ; P < 0.05 ; Friedman 2-way ANOVA ) between the four recalls . Therefore , a 2-year in vivo evaluation should be recommended prior to marketing a dental restorative material",
"n a multicentre clinical trial consisting of 12 centres , 232 amalgam and 932 composite Class I and Class II restorations were placed in 447 adult patients . At the 4-year review 76 per cent of patients with 71 per cent of the restorations were retrieved . In 8 centres after 4 years and 4 centres after 5 years a total of 12 amalgam and 92 Occlusin restorations had been replaced , having been considered to have failed . The reasons for failure were classified into three types : Type 1 , related to the restoration ( loss of material , recurrent caries and unacceptable marginal adaptation ) ; Type 2 , related to the restorative process ( pulpal involvement , primary caries , tooth fracture and unacceptable contact ) and Type 3 , caused by external factors . A greater proportion of the restorations of Occlusin were replaced than the restorations of amalgam . For the restorations of Occlusin the reasons for failure were : Type 1 , 59 per cent ; Type 2 , 32 per cent and Type 3 , 9 per cent . Loss of material and recurrent caries accounted for the failure of 35 and 13 restorations of Occlusin respectively . The main Type 2 reasons for failure of the restorations of Occlusin were pulpal involvement ( 16 restorations ) and primary caries ( 9 restorations ) . The overall 4-year survival of Occlusin restorations relative to Type 1 and to Type 1 + Type 2 reasons for failure was 96 per cent and 93 per cent respectively . The centre was found to have a significant influence on the survival rate in both analyses",
"OBJECTIVE This longitudinal r and omized controlled clinical trial evaluated direct composite restorations for clinical acceptability of posterior restoratives in single- or multisurface cavities and provided a preliminary survey of the 3- , 6- , and 18-month results . METHOD AND MATERIAL S Three clinicians placed 46 QuiXfil ( Xeno III ; Dentsply DeTrey ) and 50 Tetric Ceram ( Syntac Classic ; Vivadent ) composite restorations in stress-bearing Class 1 and 2 cavities in first or second molars ( 43 adult patients ) . Clinical evaluation was performed at baseline and after 3 , 6 , and 18 months by 2 other clinicians using modified US Public Health Service criteria . At the final recall period , 45 QuiXfil and 49 Tetric Ceram restorations were assessed . RESULTS A total of 97.8 % of QuiXfil and 100 % of Tetric Ceram posterior composites were assessed to be clinical ly excellent or acceptable with predominating Alpha scores . At the 18-month recall , 1 QuiXfil restoration had failed because of bulk fracture . No significant differences between either composite could be detected at 18 months for all evaluated clinical criteria ( P > .05 ) . Small QuiXfil restorations exhibited significantly less marginal discoloration ( P = .003 ) and better restoration integrity ( P = .008 ) than large restorations . The comparison of restoration performance with time within both groups yielded a significant increase in marginal discoloration for QuiXfil ( P = .011 ) and significant deterioration for anatomic form at the marginal step for Tetric Ceram ( P = .011 ) . However , both changes were only effects of scoring shifts from Alpha to Bravo . CONCLUSION Clinical assessment of stress-bearing QuiXfil and Tetric Ceram posterior composite restorations exhibited for both material s good clinical results with predominating Alpha scores",
"PURPOSE To investigate the effect of restoration technique and adhesive system on the post-operative sensitivity and marginal adaptation of Class I occlusal composite resin restorations placed in vivo . MATERIAL S AND METHODS 48 Class I cavities were restored in vivo according to one of three protocol s : ( 1 ) Scotchbond Multi- Purpose /P50 placed in increments ; ( 2 ) Scotchbond Multi- Purpose /P50 placed in bulk , and ( 3 ) Clearfil Liner Bond 2/Clearfil Ray Posterior placed in bulk . Post-operative sensitivity and sensitivity on loading were recorded 5 - 7 weeks after placement of the restorations ; the teeth were cautiously extracted , immersed in a dye solution and sectioned . SEM observations were made from epoxy resin replicas . Microleakage and gap formation was assessed . RESULTS No differences among adhesive systems or restoration procedures were found for microleakage . Post-operative sensitivity was reported in 14 % of all teeth but was absent in the Clearfil Liner Bond 2 group . Sensitivity on loading was experienced by patients in 56 % of the restorations . Group 1 : nine teeth ; Group 2 : 15 teeth ; Group 3 : three teeth . Differences were statistically significant for all three groups . The SEM analysis showed that restorations placed in two layers showed less gaps than restorations placed in bulk ",
"This study evaluated the post-operative sensitivity of posterior restorations restored with a resin-based restorative material and a self-etching primer . Forty-six restorations , 28 Class I and 18 Class II were placed by two clinicians in 25 patients . After cavity preparations were completed under rubber dam isolation , they were restored using a self-etching primer ( Fluorobond , Shofu Inc , Kyoto , Japan ) and a resin-based restorative material ( Beautifil , Shofu Inc , Kyoto , Japan ) . Patients were contacted on days 2 and 7 post-operatively and question ed regarding the presence of sensitivity , the stimuli that created sensitivity , the length of time the sensitivity lasted and its intensity using a rating scale from slight to severe . If sensitivity was experienced on day 7 , patients were also contacted on days 14 , 30 and 90 to assess the degree of sensitivity . All patients were recalled after 6- , 12- and 24-months for further evaluation of any sensitivity experienced . Chi-Square and Fisher 's Exact Test were used for statistical analysis . At day 2 , six restorations were sensitive to cold with no statistical difference ( p > 0.05 ) from the restorations that were not sensitive . At day 7 , only two restorations were sensitive . No sensitivity was present after day 14 , which was also confirmed at the six-month recall . No correlation could be established among the duration of the sensitivity , the degree of pain and the causes that initiated sensitivity ( p > 0.05 ) . At one-year recall , one restoration was replaced due to post-operative sensitivity that started after the six-month recall . No sensitivity was noted at the 24-month recall . No correlation ( p > 0.05 ) was found between sensitive restorations and those with a normal response throughout the study . The study showed that Fluorobond self-etching primer and Beautifil resin-based restorative material , when placed in posterior restorations , do not result in long-term post-operative sensitivity",
"OBJECTIVE To measure 2-week postoperative sensitivity in Class II composite restorations placed with a self-etching adhesive ( Clearfil SE Bond ) or a total-etch adhesive ( Prime&Bond NT ) with or without a flowable composite as cervical increment . METHOD AND MATERIAL S Upon approval by the University of Guarulhos Committee on Human Subjects , 100 restorations were inserted in 46 patients who required Class II restorations in their molars and premolars . Enamel and dentin walls were conditioned with a self-etching primer ( for Clearfil SE Bond ) or etched with 34 % phosphoric acid ( for Prime&Bond NT ) . A 1- to 2-mm-thick increment of a flowable composite ( Filtek Flow ) was used in the proximal box in 50 % of the restorations of each adhesive . Preparations were restored with a packable composite ( Surefil ) . The restorations were evaluated preoperatively and 2 weeks postoperatively for sensitivity to cold , air , and masticatory forces using a visual analog scale . Marginal integrity of the accessible margins was also evaluated . Statistical analysis used a mixed linear model with subject as a r and om effect . RESULTS Ninety-eight teeth from 44 subjects were observed at 2 weeks . The type of adhesive and use of flowable composite had no significant effects or interaction for any of the four outcomes of interest , ie , change from baseline to 2 weeks in sensitivity and response time for the cold or air stimulus . For the air stimulus , the overall average change from baseline was not significant for either sensitivity or response time . For the cold stimulus , the overall average change from baseline was significant for both sensitivity and response time . No case of sensitivity to masticatory forces was observed . CONCLUSION No differences in postoperative sensitivity were observed between a self-etch adhesive and a total-etch adhesive at 2 weeks . The use of flowable composite did not decrease postoperative sensitivity",
"This study investigated the ability of a glass-ionomer cement ( GIC ) lining to reduce postoperative sensitivity in occlusal cavities restored with resin composite . In addition , the effects of a total-etch and self-etch adhesive on postoperative sensitivity were also compared . Patients who had moderate to deep occlusal caries of at least one molar were recruited . Overall , 103 restorations were placed in 70 participants , with an average age of 22.8 + /- 3.8 years . Preoperatively , each tooth was evaluated for cold-stimulated tooth sensitivity using a visual analog scale . If present , tooth sensitivity induced by cold/hot drinks or occlusal function was also noted . Caries was stained with a caries detector dye , then removed using slow-speed burs and h and excavators . The cavity was restored with one of four r and omly allocated restorative procedures : 1 ) bonded with a two-step , total-etch adhesive ( Single Bond 2 ) ; 2 ) lined with a resin-modified GIC liner ( Fuji Lining LC ) , then bonded with total-etch adhesive ; 3 ) bonded with a two-step , self-etch adhesive ( Clearfil SE Bond ) and 4 ) lined with the GIC liner , then bonded with self-etch adhesive . The cavities were incrementally filled with a nanofilled hybrid resin composite . At recall , postoperative sensitivity was evaluated at one week and one month . Overall , postoperative sensitivity in daily function was rare . No significant difference in postoperative sensitivity , either in daily function or in response to a cold stimulus , was observed between the restorative procedures with or without the GIC liner , regardless of the adhesive used ( p > 0.05 ) . In addition , no difference in postoperative sensitivity was noted between use of the self-etch and total-etch adhesive",
"OBJECTIVES Ormocer composites , consisting of a silicon-based polymer , have been developed recently as a tooth-colored restorative material . The purpose of this prospect i ve r and omized clinical trial was to evaluate the performance of two small-particle hybrid ormocer-based restorative systems ( AD , Admira/Admira Bond , VOCO ; DE , Definite/Etch & Prime 3.0 , Dentsply ) and one small-particle hybrid bis-GMA-based composite restorative system ( TC , Tetric-Ceram/Syntac , Ivoclar-Vivadent ) in class II cavities . METHODS From 128 occlusal-proximal restorations ( 44 AD , 43 DE and 41 TC ) placed in 32 adult patients , eventually 77 ( 22 AD , 29 DE and 26 TC ) remained available for evaluation after 5 years . Their clinical performance was scored according to the USPHS criteria and evaluation of bite-wing radiographs . RESULTS After 5 years , eight AD , six DE and seven TC restorations had failed ( p=0.10 , log-rank test ) . The main reason was fracture or marginal gap formation , while secondary caries accounted for four failures . In all restorations the quality of surface , margins and contact point decreased significantly compared to baseline . DE had a significant poorer color match ( p<0.01 ) . Statistical evaluation using the KW test showed that failures were concentrated on specific patients . CONCLUSIONS In a group of class II restorations , there was no significant difference in failures after 5 years between ormocer-based and bis-GMA-based restorative systems",
"PURPOSE To clinical ly evaluate different br and s of resin composites in Class I restorations . MATERIAL S AND METHODS A total of 120 Class I cavities were prepared in permanent molars and restored with four posterior resin composites : Clearfil Photo Posterior , Z100 , Herculite XR , and Heliomolar RO . The restorations were evaluated at baseline , 1 and 2 years using the USPHS criteria . RESULTS After 1 year , Z100 restorations were rated Alfa in all tested criteria . Clearfil PP , Herculite XR and Heliomolar RO showed slight changes in color match , anatomic form , and marginal adaptation . After 2 years , no significant difference was found in the evaluation of cavosurface discoloration for all tested material s. Z100 and Herculite XR were significantly more color stable than Clearfil PP and Heliomolar RO . The anatomic form evaluation showed Z100 with a significantly higher value than other groups . Heliomolar RO revealed the lowest percentage of marginal adaptation",
"The purpose of this controlled prospect i ve clinical study was to compare the clinical performance of the self-etching adhesive system AdheSE and the established total-etch adhesive system Excite in classes I and II cavities for a period of 2 years . Fifty patients participated in this study . Each received two restorations , one with AdheSE , one with Excite by one calibrated , non-blinded operator . The resin composite used to restore the teeth was Tetric Ceram HB . One calibrated , blinded clinician re-evaluated the restorations at baseline , after 6 , 12 and 24 months after placement using the modified Ryge criteria . For this , vitality , post-operative sensitivity , visible marginal irregularity , marginal discolouration , secondary caries , surface texture , anatomic form and filling defect were considered . After 2 years , 67 restorations were review ed in 34 patients . None of the teeth showed signs of secondary caries . Two teeth , one of each group , had to receive endodontic treatment because of pulp inflammation . All other teeth remained vital . Slight marginal discolourations were observed in six AdheSE restorations and three Excite restorations . These restorations were scored as Beta . After 2 years , an overall clinical success rate , summing up all the Alpha and Beta scores , of 97 % was found , viewing both adhesive systems together . Statistic analysis using log-rank test showed no statistic differences in the overall survival rate between the two material s tested within the observation period . It can be concluded that both adhesive systems tested demonstrated very good clinical performance in the restoration of classes I and II cavities at the end of 2 years",
"This r and omized trial evaluated the 12-month clinical performance of nanofill , a nanohybrid , and a microhybrid composite in restorations in occlusal cavities of posterior teeth . This study utilized 41 patients , each of whom had three molars affected by primary caries or the need to replace restorations . All restorations were performed in accordance with the manufacturer 's recommendations and evaluated in accordance with U.S. Public Health Service-modified criteria . Based on the results of the present study , the material investigated demonstrated acceptable clinical performance after 12 months of clinical service . Long-term re-evaluations are necessary for a more detailed analysis of these composites",
"PURPOSE To assess the one-step self-etching adhesive iBond Gluma inside ( 1-SE ) and the two-step etch- and rinse adhesive Gluma Comfort Bond ( 2-ER ) , both used in combination with the fine particle hybrid composite Venus , in a laboratory and in a prospect i ve clinical study . MATERIAL S AND METHODS In the in vitro study , tooth-composite interaction , microleakage , and adhesive failure of 8 Class V restorations per system were evaluated by light and scanning electron microscopy . In the in vivo study , 90 paired Class III/IV restorations were scored over 48 months ( modified USPHS criteria ) . Cumulative failure rates ( CFR ) were calculated . RESULTS In vitro , microleakage and adhesive failure at enamel margins were significantly increased with 1-SE in comparison with 2-ER . With 1-SE , micromechanical interlocking at enamel was reduced and pores within the adhesive layer arose . In vivo , after 48 months with 1-SE , decreased marginal integrity and an increased number of dark marginal color lines were observed . CONCLUSION Because the results of the 4-year clinical study showed lower esthetics and marginal integrity for the 1-SE adhesive , its use should be viewed critically , which is in line with the reduced enamel-adhesive-composite interaction found in vitro",
"OBJECTIVE Packable composites are a comparatively recent addition to the dentist 's armamentarium , Solitaire-2 being an example of this type of material . This paper reports the performance of 100 restorations formed in Solitaire-2 in conjunction with the Gluma Solid Bond system and Gluma One Bond bonding systems , in Class I and II cavity restorations in permanent teeth , placed in the practice s of five members of the Product Research and Evaluation by Practitioners ( PREP ) Panel , a group of United Kingdom-based dental practitioners who are prepared to undertake research projects in their practice s. METHOD AND MATERIAL S Five members of the PREP Panel were each requested to place 20 Solitaire-2 restorations . These restorations were review ed at 1 year by a trained and calibrated evaluator , and the PREP panel member who had placed the restorations . RESULTS A total of 88 restorations ( 33 Class I , 55 Class II ) in 49 patients ( mean age 43 years ) were review ed at 1 year . One Class II restoration ( a large mesio-occlusodistal restoration ) had been replaced at 10 months after a fracture was detected across the distal box . The remaining 87 ( 99 % ) of the restorations were intact with no secondary caries detected . CONCLUSION Ninety-nine percent of the Solitaire-2 restorations , placed in general dental practice conditions in conjunction with the Gluma Solid Bond system and Gluma One Bond bonding systems , were found to be performing satisfactorily at 1 year",
"PURPOSE To test the hypothesis that the prevention of postoperative sensitivity in resin-based composite restorations is better achieved with a self-etching/self-priming ( SE/SP ) dentin bonding system without lining than with an early generation total-etch ( TE ) bonding system . METHODS Over a 4-year period , clinical follow-ups were conducted on patients who had received composite restorations . The depth of each cavity was categorized as being shallow , medium or deep , and an evaluation was made regarding the need for pulpal protection for each restoration . Three different self-etching/self-priming ( SE/SP ) adhesive systems were compared to three different total-etch ( TE ) adhesive systems . The incidences of postoperative sensitivity ( IPS ) were examined by a st and ardized procedure 1 week after placement of the restoration . Patients ' ages varied between 16 - 83 years . RESULTS The total number of restorations placed in vital teeth were 330 for 150 patients in the SE/SP group , and 126 for 70 patients in the TE group . Incidences of IPS in the total number of restorations stratified for depth were 14 % in deep cavities , 6 % in medium depth cavities and 5 % in shallow cavities in the SE/SP group , and 35 % in deep cavities , 16 % in medium and 4 % in shallow cavities in the TE group . Fisher 's exact test showed the incidence of IPS was significantly higher in cases of deep ( P SE/SP adhesive systems , the presence or absence of a protective liner or base made no significant difference in the IPS in medium and shallow cavities , while the use of such protective layers produced a significantly higher IPS ( 21 % ) , compared with no protection ( 0 % ) , in deep cavities ( P postoperative sensitivity in deep cavities , when the SE/SP dentin bonding systems were used",
"Historically , postoperative pain associated with temperature was considered a thermal conduction problem . More recently , pulpal hydrodynamics has been used to explain this sensitivity . Relative to restorations placed with dentin bonding agents that require a separate etching step , agents that include an acidic primer are believed to result in a better seal of the dentinal tubules . This study compared pain associated with a st and ardized cold stimulus in two groups of restorations . One group was placed with a self-priming resin that required a separate etch step , the other with a self-etching , self-priming dentin bonding agent . This was a community-based , r and omized , double-blind clinical trial . Two hundred and nine restorations were placed for 76 participants . All teeth were asymptomatic at the start of the trial . Immediately following application of a st and ardized cold stimulus , participants rated the pain for each restored tooth using a Visual Analog Scale ( VAS ) . For each group of restorations , VAS scores at 13 weeks were compared to preoperative scores . In addition , the preoperative score was subtracted from the 13-week score , and the two groups of restorations were compared . For both groups of restorations , the median scores were significantly reduced at 13 weeks . This decrease in the VAS score reflects a reduction in sensitivity below that which existed preoperatively . There was no significant difference between the two groups of restorations in terms of change in sensitivity at 13 weeks",
"OBJECTIVE To evaluate the clinical performance of a nanofill and a nanohybrid composite in restorations in occlusal cavities of posterior teeth in a r and omised trial over 30 months . METHODS Forty-one adolescents participated in the study . The teeth were restored with a nanofill ( Filtek Z350 , 3 M ESPE ) , a nanohybrid ( Esthet-X , Dentsply ) ; Filtek Z250 ( 3 M ESPE ) was used as a control . After 30 months , the restorations were evaluated in accordance with the US Public Health Service ( USPHS ) modified criteria . The McNemar and Friedman tests were used for statistical analysis , at a level of significance of 5 % . RESULTS There were significant differences in the roughness of Filtek Z250 ( p=0.008 ) and Filtek Z350 ( p marginal adaptation of Filtek Z250 ( p=0.001 ) , Filtek Z350 ( p Esthet-X ( p=0.011 ) . Except for one of each composite restoration , all the modifications ranged from Alpha to Bravo . There were significant differences in the surface roughness ( p=0.005 ) when the three composites were compared after 30 months . CONCLUSIONS The material s investigated showed acceptable clinical performance after 30 months . Long-term re-evaluations are necessary for a more detailed analysis of these composites ( CEP : # 1252 )",
"The purpose of this study was to evaluate a new resin composite/bonding restorative system in clinical trials involving human subjects . Sixty restorations were inserted in Class I and Class II preparations in premolars and molars . The enamel margins of the preparations were etched for 60 seconds with 37 % phosphoric acid gel . The dentinal surfaces of cavity preparations were etched for 40 seconds with 37 % phosphoric acid in glycerine ( K-etchant gel ) and bonding agent ( Clearfil Photo Bond ) applied . A resin composite ( Clearfil Photoposterior ) was placed in three increments with a 20 second light cure of each increment and a 60 second light cure of the final increment . All the restorations were evaluated using the USPHS system and M-L indirect scale . At 36 month recalls , compared to baseline , surface texture for essentially all the restorations was rated Bravo , while all other characteristics were rated Alpha . Secondary caries was reported for one restoration during the third year of clinical use . Wear showed an adjusted mean value of 14.6 microns at 36 months or 4.9 microns per year . No cases of clinical post-operative sensitivity to hot , cold , percussion and foods were reported during the length of the study . Clearfil Photoposterior resin composite system has exhibited remarkable wear resistance and no post-operative sensitivity throughout the length of the study",
"Two composite resins were evaluated for clinical acceptability as restorative material s in Class I and II cavities over a 2-year-period . In addition , dispersed phase alloy was evaluated for comparison . All restorations were assessed for anatomical form , marginal integrity and marginal leakage using modified United States Public Health Service ( USPHS ) criteria . At the 2-year recall , 96 % of the composites and 100 % of the amalgams were rated ' alpha ' or ' bravo ' , using the parameters of assessment defined in this study . However , a significant number of shifts from the baseline , within the level of acceptability , had occurred . The two composites showed the greatest number of shifts for anatomical form and marginal leakage , while there were no differences between the composites and the amalgam for shifts in marginal integrity . Although a very high level of acceptability was determined for all of the material s , the frequency of rating change within categories for the composites was a cause of concern with regard to their long-term clinical use",
"OBJECTIVE The objective of this prospect i ve clinical trial was to evaluate the 4-year clinical performance of an ormocer-based nano-hybrid resin composite ( Ceram X ; Dentsply/DeTrey ) in Class II restorations placed with a one-step self-etch ( Xeno III ; Dentsply/DeTrey ) and two-step etch- and -rinse adhesive ( Ivoclar Vivadent ) . METHODS Seventy-eight participants received at r and om at least two , as similar as possible , Class II restorations of the nano-hybrid resin composite bonded with either a single step self-etch adhesive or a control 2-step etch- and -rinse adhesive . The 165 restorations were evaluated using slightly modified USPHS criteria at baseline and then yearly during 4 years . RESULTS 162 restorations were evaluated at 4 years . Postoperative sensitivity was observed in 6 patients ( 3 Xeno III , 3 Exite ) between 1 and 3 weeks . Eleven failed restorations ( 6.8 % ) were observed during the follow up . Seven in the one-step self-etch adhesive group ( 7.7 % ) and four in the 2-step etch- and -rinse group ( 5.6 % ) . This result ed in non-significant different annual failure rates of 1.9 % and 1.4 % , respectively . Fracture of restoration was the main reason for failure . CONCLUSION The ormocer-based nano-hybrid resin composite showed a good clinical performance in Class II cavities during the 4 year evaluation . No significant difference was seen in overall clinical effectiveness between the two adhesives"
] |
4116c5fe-06ff-11f0-808a-c43d1ab1c353
|
Because there is a possibility that cannabis or cannabis-like molecules might be used as treatments for certain conditions in the future , it becomes important to consider the possible adverse effects of these compounds . In this paper , the authors review the evidence for persisting effects of nonacute cannabis use on the central nervous system , as reflected by alteration in neuropsychological performance . From the 40 articles that met criteria for inclusion in this review , the authors could not detect consistent evidence for persisting neuropsychological deficits in cannabis users ; however , 22 of the 40 studies reported at least some subtle impairments . The inability to reach a firm conclusion results largely from method ological limitations inherent in most studies . These are considered in detail to inform future studies on ( nonacute ) consequences of cannabis consumption on cognitive abilities
|
[
"A preliminary trial of oral delta-9-tetrahydrocannabinol ( THC ) demonstrated an analgesic effect of the drug in patients experiencing cancer pain . Placebo and 5 , 10 , 15 , and 20 mg THC were administered double blind to ten patients . Pain relief significantly superior to placebo was demonstrated at high dose levels ( 15 and 20 mg ) . At these levels , substantial sedation and mental clouding were reported",
"An extended battery of neuropsychological tests was administered to three groups of college seniors ( lysergic acid diethylamide [LSD]/mescaline users ; marihuana/hashish users ; and controls ) who were matched on predrug usage intellectual and personality dimensions . The study was replicated one year later . In the combined-years ' analyses , the three groups showed statistically significant differences only on the Trail Making Test : LSD/mescaline users performed within normal limits but significantly worse than either of the other two groups . Since the three groups also differed significantly in the extent of their alcohol usage , a covariance analysis was carried out that indicated that this variable did not account for the LSD/mescaline group 's performance on the Trail Making Test . Inference about possible organic dysfunction can not be drawn from these findings , but prospect i ve neuropsychological testing might prove useful",
"The evidence for long-term cognitive impairments associated with chronic use of cannabis has been inconclusive . We report the results of a brain event-related potential ( ERP ) study of selective attention in long-term cannabis users in the unintoxicated state . Two ERP measures known to reflect distinct components of attention were found to be affected differentially by duration and frequency of cannabis use . The ability to focus attention and filter out irrelevant information , measured by frontal processing negativity to irrelevant stimuli , was impaired progressively with the number of years of use but was unrelated to frequency of use . The speed of information processing , measured by the latency of parietal P300 , was delayed significantly with increasing frequency of use but was unaffected by duration of use . The results suggest that a chronic buildup of cannabinoids produces both short- and long-term cognitive impairments"
] |
4116c63a-06ff-11f0-808a-c43d1ab1c353
|
Background : In a study aim ed at identifying the items carrying information regarding the global severity of depression , the 6-item Hamilton Depression Rating Scale ( HAM-D6 ) was derived from the original 17-item version of the scale ( HAM-D17 ) . Since then , the HAM-D6 has been used in a wide range of clinical studies . We now provide a systematic review of the clinimetric properties of HAM-D6 in comparison with those of HAM-D17 and the Montgomery Asberg Depression Rating Scale ( MADRS ) . Methods : We conducted a systematic search of the literature in PubMed , PsycInfo , and EMBASE data bases in accordance with the Preferred Reporting Items for Systematic Review s and Meta-Analyses guideline . Studies reporting data on the clinimetric validity of the HAM-D6 and either the HAM-D17 or MADRS in non-psychotic unipolar or bipolar depression were included in the synthesis . Results : The search identified 681 unique records , of which 51 articles met the inclusion criteria . According to the published literature , HAM-D6 has proven to be superior to both HAM-D17 and MADRS in terms of scalability ( each item contains unique information regarding syndrome severity ) , transferability ( scalability is constant over time and irrespective of sex , age , and depressive subtypes ) , and responsiveness ( sensitivity to change in severity during treatment ) . Conclusions : According to the published literature , the clinimetric properties of HAM-D6 are superior to those of both the HAM-D17 and MADRS . Since the validity of HAM-D6 has been demonstrated in both research and clinical practice , using the scale more consistently would facilitate translation of results from one setting to the other
|
[
"Abstract : In this double-blind , multicenter study , bupropion XL , a norepinephrine-dopamine reuptake inhibitor , and venlafaxine XR , a serotonin-norepinephrine reuptake inhibitor , were compared with regard to sexual functioning , efficacy , and tolerability . A total of 348 sexually active adult out patients with depression were r and omized to receive bupropion XL ( titrated to a target dose of 300 - 450 mg/d ) or venlafaxine XR ( titrated to a target dose of 150 - 225 mg/d ) for 12 weeks . Total scores on the primary dependent variable , the Changes in Sexual Functioning Question naire ( self-report ) , increased for subjects receiving bupropion XL and decreased for those treated with venlafaxine XR ; the mean change scores differed significantly between groups from week 2 onward . Among subjects with normal pretreatment sexual functioning , Changes in Sexual Functioning Question naire total scores remained essentially unchanged for the bupropion XL group but were decreased significantly for the venlafaxine XR group ; mean change scores also differed between groups from week 2 onward . Although the therapies result ed in similar change on the 17-item Hamilton Depression Rating Scale , remission rates were significantly higher among those treated with bupropion XL ( 46 % ) versus venlafaxine XR ( 33 % ) ( odds ratio , 1.93 ; 95 % confidence interval , 1.07 - 3.46 ) . Aside from adverse effects of venlafaxine XR on sexual function , both treatments were reasonably well tolerated . In conclusion , in this patient population ( ie , relatively young , sexually active out patients ) , bupropion XL was at least as effective as venlafaxine XR and had a significantly more favorable sexual side effect profile",
"Trazodone Contramid(R ) once-a-day ( TzCOAD ) is a reformulation of trazodone hydrochloride that controls the release of trazodone over 24 hours . A st and ard effect size analysis ( Cohen 's d ) determined which items of the 17-item Hamilton Depression Rating Scale ( HAMD-17 ) and the Montgomery-Asberg Depression Rating Scale ( MADRS ) showed the greatest improvement in patients with major depressive disorder ( MDD ) , following up to 8 weeks of therapy with TzCOAD . An additional insomnia analysis assessed whether the efficacy of TzCOAD is influenced by improvements in insomnia or baseline severity of insomnia . The analyses used data from a r and omized study of 412 patients receiving 150 - 375 mg TzCOAD ( N = 206 ) or placebo ( N = 206 ) . The results of the Cohen 's d analysis on the modified intent-to-treat population ( LOCF ) showed HAMD items with the greatest improvement were insomnia items ( middle ( -0.35 ) , late ( -0.24 ) ) , feelings of guilt ( -0.24 ) , and depressed mood ( -0.23 ) ; for MADRS items they were reduced sleep ( -0.31 ) , inner tension ( -0.22 ) , reported sadness ( -0.21 ) , and suicidal thoughts ( -0.21 ) . An analysis of covariance showed no significant interaction between improvements in the HAMD Bech-6 core symptoms of depression and the baseline MADRS reduced sleep item or early changes in the HAMD-17 sleep disturbance factor . These results suggest that the antidepressant efficacy was independent of the baseline severity of insomnia and of the improvement in insomnia . Overall , the results eluci date the efficacy components and tolerability characteristics previously demonstrated for TzCOAD monotherapy for patients with MDD at the recommended daily dose of 300 mg",
"Antidepressant effects and unintended effects of paroxetine ( 30 mg/day ) and clomipramine ( 150 mg/day ) were compared in a double-blind , r and omized , inpatient , fixed-dose , plasma-level-controlled study . Patients with a DSM-III diagnosis of major depressive disorder participated . After 1 week of single-blind placebo treatment 120 patients fulfilled the criterion of a Hamilton ( 17-item ) score of greater than or equal to 18 and were started on active treatment for 6 weeks . Drop-outs on paroxetine ( n = 12 ) were largely due to lack of effect , and on clomipramine ( n = 19 ) due to lack of effect ( n = 7 ) , adverse reactions or severe side effects ( n = 10 ) and development of mania ( n = 2 ) . According to the protocol , non-responders ( Hamilton total greater than or equal to 16 ) after 4 weeks active treatment were terminated , and this occurred to 23 patients on paroxetine and four patients on clomipramine . Categorical response measures and group averages of rating scores showed a significantly better therapeutic effect of clomipramine from the second week of treatment on . These results are very similar to our earlier results with another selective serotonin reuptake inhibitor ( citalopram ) , but generally at variance with the literature on this class of antidepressants , which , however , mostly deals with outpatient studies",
"In a 6-week double-blind study , 220 patients with major depression ( mostly out patients ) were r and omly assigned to receive a fixed dose of brofaromine 150 mg daily ( n = 111 ) or placebo ( n = 109 ) after a 1-week single-blind placebo washout . Except for the HAM-D sleep items , brofaromine was superior to placebo on measures of depression as determined by the four methods of assessing drug efficacy : ( 1 ) psychiatric symptom rating ( HAM-D 17-item less the three sleep items ) ; ( 2 ) self-rating scale ( Beck Depression Inventory ) ; ( 3 ) Clinical Global Assessment of Efficacy ; and ( 4 ) drop-out rate due to lack of efficacy . Most commonly reported adverse events with brofaromine were : headache , nausea , dizziness and sleep disturbance . Brofaromine was found to be an effective antidepressant , superior to placebo with a good tolerability profile",
"In depression research , symptoms are routinely assessed via rating scales and added to construct sum-scores . These scores are used as a proxy for depression severity in cross-sectional research , and differences in sum-scores over time are taken to reflect changes in an underlying depression construct . To allow for such interpretations , rating scales must ( a ) measure a single construct , and ( b ) measure that construct in the same way across time . These requirements are referred to as unidimensionality and measurement invariance . We investigated these 2 requirements in 2 large prospect i ve studies ( combined n = 3,509 ) in which overall depression levels decrease , examining 4 common depression rating scales ( 1 self-report , 3 clinician-report ) with different time intervals between assessment s ( between 6 weeks and 2 years ) . A consistent pattern of results emerged . For all instruments , neither unidimensionality nor measurement invariance appeared remotely tenable . At least 3 factors were required to describe each scale , and the factor structure changed over time . Typically , the structure became less multifactorial as depression severity decreased ( without however reaching unidimensionality ) . The decrease in the sum-scores was accompanied by an increase in the variances of the sum-scores , and increases in internal consistency . These findings challenge the common interpretation of sum-scores and their changes as reflecting 1 underlying construct . The violations of common measurement requirements are sufficiently severe to suggest alternative interpretations of depression sum-scores as formative instead of reflective measures . We discuss the possible causes of these violations such as response shift bias , restriction of range , and regression to the mean . ( PsycINFO Data base",
"The consistency of the Hamilton Depression Scale ( HDS ) as a measure of the severity of depressive states has been examined when the scale was used weekly during a trial with imipramine . By use of logistic models ( Rasch ) the consistency of the HDS has been considered across patient‐variables as age , sex , plasma levels of imipramine , and diagnosis . The results showed that the original 17‐item HDS was without adequate consistency , i.e. the total score of the sample of items was no one‐dimensional measure of depressive states . However , a melancholia subscale of the HDS contained items the total of which can be used to compare patients quantitatively , although in some part of the analysis one of these items showed ceiling effect . It was concluded that the melancholia sub‐scale ( containing the items depressed mood , guilt , work and interests , retardation , psychic anxiety , and general somatic symptoms ) can form the basis for further improvements in the field of quantitative rating scales for depressive states",
"Background This paper reports day-to-day data for from a one-week intervention phase , part of a 9-weeks r and omised parallel study with patient having major depression ( data from weekly visits have been reported ) . Wake therapy ( sleep deprivation ) has an established antidepressant effect with onset of action within hours . Deterioration on the following night ’s sleep is , however , common , and we used daily light therapy and sleep time stabilisation as a preventive measure . In particular , we evaluated the day-to-day acute effect of and tolerance to sleep deprivation and examined predictors of response . Methods Patients were assessed at psychiatric inpatient wards . In the wake group ( n = 36 ) , patients did three wake therapies in combination with light therapy each morning together with sleep time stabilisation . In the exercise group ( n = 38 ) , patients did daily exercise . Hamilton subscale scores were primary outcome ( not blinded ) , secondary outcome was self- assessment data from the Preskorn scale and sleep . Results Patients in the wake therapy group had an immediate , large , stable , and statistically significant better antidepressant effect than patients in the exercise group with response rates at day5 of 75.0%/25.1 % and remission rates of 58.6%/6.0 % , respectively . The response and remission rates were diminished at day8 with response rates of 41.9%/10.1 % and remission rates of 19.4%/4.7 % , respectively . Patients and ward personnel found the method applicable with few side effects . Positive diurnal variation ( mood better in the evening ) predicted a larger response to wake therapy . In the wake group napping on days after intervention predicted greater deterioration on day8 . Conclusions The intervention induced an acute antidepressant response without relapse between wake nights but with a diminishing effect after intervention . Development is still needed to secure maintenance of response . Avoiding napping in the days after wake therapy is important . Trial Registration Clinical trials.gov",
" A total of 97 patients , who participated in two studies on the relationship between the clinical effect and plasma levels of imipramine and clomipramine , were examined for improvement curves by use of weekly ratings on the Hamilton Depression Scale ( HDS ) . Although we confirmed that our six-item HDS subscale , in contrast to the total 17-item HDS , was a one-dimensional measure of depression , the Rasch analysis showed that the weekly improvement in subscale scores only applied to the individual patient , i.e. an average improvement curve for a group of depressed patients is an abstract ion to which the individual curves can not be transferred . Our results indicate , however , that when the subscale scores are transformed into three clinical categories of depression : no , mild ( minor ) , moderate/-severe ( major ) they could be described by a common improvement curve for all patients . This is illustrated by the percentage of patients who , week to week , changed from major to minor or no depression , or from minor to no depression . We found no specific improvement pattern for imipramine or clomipramine which could be used diagnostically . There is reason to assume that patients completing a controlled trial necessarily will follow a monotonic improvement curve , and the improvement pattern of all patients fulfilling the entry criteria should , therefore , always be reported . The present study thus indicates that calculation of average improvement curves is neither clinical ly nor statistically meaningful , and should be replaced by measures of changes in number of patients in different main severity categories , or by the final rating score . No difference in outcome between imipramine and clomipramine was shown neither on the subscale nor on the 17-item HDS",
"BACKGROUND The 17-item Hamilton Depression Rating Scale ( HDRS ) is used as a semi-gold st and ard in research . In treatment guidelines , the HDRS measurements serve to determine response and remission and guide clinical decision making for nonresponders . However , its use in clinical practice is limited , possibly because the HDRS is time consuming . In addition , the multidimensional HDRS is criticized for not measuring a unidimensional aspect as depression severity . The Maier and the Bech , two 6-item severity subscales extracted from the HDRS , are relatively unknown . This paper investigates whether the measurements obtained with these subscales are comparable with the original HDRS measurements . METHODS Data from 2 r and omized controlled trials in 482 male and female patients , diagnosed with a major depression ( with or without dysthymia ) according to Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition , of whom 219 participated in the trials , were reanalyzed . A st and ardized stepwise psychopharmacological treatment was compared with a combination of pharmacotherapy with Short Psychodynamic Supportive Psychotherapy in a psychiatric outpatient department . Outcome measures were internal consistency and concurrent validity of HDRS , Maier , Bech , Clinical Global Impression scales , and Symptom Checklist depression subscale . Effect sizes of HDRS , Maier , and Bech were used to compare measured treatment effects for the r and omized subjects participating in the trials . Item Response Theory was used to obtain conversion tables for the HDRS , Maier , Bech , and Symptom Checklist depression subscale . RESULTS We found moderate internal consistency ( Cronbach alpha approximately 0.6 - 0.7 ) and high correlations of the Maier and Bech subscales with overall HDRS scores . Overall , there were no clinical ly relevant differences in effect sizes between Maier , Bech , and HDRS , although some differences were statistically significant . Receiver operating characteristic curves showed no difference between Maier and Bech to define remission but showed the Clinical Global Impression ratings to be unreliable . A cutoff < or = 4 corresponded with an HDRS < or = 7 criterion in both subscales . CONCLUSION In clinical practice , both Maier and Bech scales can be used as equivalents of the HDRS , but will be more efficient",
"The 17-item Hamilton Rating Scale for Depression ( HRSD(17 ) ) and the Montgomery Asberg Depression Rating Scale ( MADRS ) are two widely used clinician-rated symptom scales . A 6-item version of the HRSD ( HRSD(6 ) ) was created by Bech to address the psychometric limitations of the HRSD(17 ) . The psychometric properties of these measures were compared using classical test theory ( CTT ) and item response theory ( IRT ) methods . IRT methods were used to equate total scores on any two scales . Data from two distinctly different outpatient studies of nonpsychotic major depression : a 12-month study of highly treatment-resistant patients ( n=233 ) and an 8-week acute phase drug treatment trial ( n=985 ) were used for robustness of results . MADRS and HRSD(6 ) items generally contributed more to the measurement of depression than HRSD(17 ) items as shown by higher item-total correlations and higher IRT slope parameters . The MADRS and HRSD(6 ) were unifactorial while the HRSD(17 ) contained 2 factors . The MADRS showed about twice the precision in estimating depression as either the HRSD(17 ) or HRSD(6 ) for average severity of depression . An HRSD(17 ) of 7 corresponded to an 8 or 9 on the MADRS and 4 on the HRSD(6 ) . The MADRS would be superior to the HRSD(17 ) in the conduct of clinical trials",
"OBJECTIVE To review factors influencing placebo response and clinical trial outcome in depression , and suggest ways to optimize trial success in mood disorders . DATA SOURCES PubMed search es were conducted by cross-referencing the terms depression , depressive with placebo , clinical trial , and clinical trials for studies published in English between 1970 and September 2013 . STUDY SELECTION Relevant abstract s were identified in PubMed , including clinical trials , quantitative studies , and qualitative research . We obtained and review ed relevant articles and utilized their information to synthesize the present review . DATA EXTRACTION Included articles were grouped in the following areas of relevance : ( 1 ) biological validity of illness , ( 2 ) baseline severity of illness , ( 3 ) chronicity of the index episode of depression , ( 4 ) age of participants , ( 5 ) medical and psychiatric comorbidity , ( 6 ) probability of receiving placebo , ( 7 ) use of prospect i ve treatment phases ( lead-in ) ( 8) dosing schedule , ( 9 ) trial duration , ( 10 ) frequency of follow-up assessment s , and ( 11 ) study outcome measure . RESULTS Several key elements emerge as critical to the ultimate success of a clinical trial , including the probability of receiving placebo , study duration , dosing schedule , visit frequency , the use of blinded lead-in phases , the use of central ized raters , illness severity and duration , and comorbid anxiety . CONCLUSIONS Our increasing underst and ing of the placebo response in clinical trials of major depressive disorder lends to a , gradually , more predictable phenomenon and , hopefully , to one that becomes lesser in magnitude and variability . Several elements have emerged that seem to play a critical role in trial success , gradually reshaping the design of clinical , translational , as well as mechanistic studies in depression",
"OBJECTIVE In unipolar depressed patients participating in trials on antidepressants , we investigated if illness characteristics at baseline could predict conversion to bipolar disorder . METHOD A long-term register-based follow-up study of 290 unipolar depressed patients with a mean age of 50.8 years ( SD=11.9 ) participating in three r and omized trials on antidepressants conducted in the period 1985 - 1994 . The independent effects of explanatory variables were examined by applying Cox regression analyses . RESULTS The overall risk of conversion was 20.7 % , with a mean follow-up time of 15.2 years per patient . The risk of conversion was associated with an increasing number of previous depressive episodes at baseline , [ HR 1.18 , 95 % CI ( 1.10 - 1.26 ) ] . No association with gender , age , age at first depressive episode , duration of baseline episode , subtype of depression or any of the investigated HAM-D subscales included was found . LIMITATIONS The patients were followed-up through the Danish Psychiatric Central Research Register , which result ed in inherent limitations such as possible misclassification of outcome . CONCLUSION In a sample of middle-aged hospitalized unipolar depressed patients participating in trials on antidepressants , the risk of conversion was associated with the number of previous depressive episodes . Therefore , this study emphasizes that unipolar depressed patients experiencing a relatively high number of recurrences should be followed more closely , or at least be informed about the possible increased risk of conversion",
"In the efficacy evaluation of antidepressant treatments , the total score of the Hamilton Depression Rating Scale ( HAMD ) is still regarded as the ‘ gold st and ard ’ . We previously had shown that the Inventory of Depressive Symptomatology ( IDS ) was more sensitive to detect depressive symptom changes than the HAMD17 ( Helmreich et al. 2011 ) . Furthermore , studies suggest that the unidimensional subscales of the HAMD , which capture the core depressive symptoms , outperform the full HAMD regarding the detection of antidepressant treatment effects . The aim of the present study was to compare several unidimensional subscales of the HAMD and the IDS regarding their sensitivity to changes in depression symptoms in a sample of patients with mild major , minor or subsyndromal depression ( MIND ) . Biweekly IDS-C28 and HAMD17 data from 287 patients of a 10-week r and omised , placebo-controlled trial comparing the effectiveness of sertraline and cognitive – behavioural group therapy in patients with MIND were converted to subscale scores and analysed during the antidepressant treatment course . We investigated sensitivity to depressive change for all scales from assessment -to- assessment , in relation to depression severity level and placebo – verum differences . The subscales performed similarly during the treatment course , with slight advantages for some subscales in detecting treatment effects depending on the treatment modality and on the items included . Most changes in depressive symptomatology were detected by the IDS short scale , but regarding the effect sizes , it performed worse than most subscales . Unidimensional subscales are a time- and cost-saving option in judging drug therapy outcomes , especially in antidepressant treatment efficacy studies . However , subscales do not cover all facets of depression ( e.g. atypical symptoms , sleep disturbances ) , which might be important for comprehensively underst and ing the nature of the disease depression . Therefore , the cost-to-benefit ratio must be carefully assessed in the decision for using unidimensional subscales",
"We report the results of a double-blind study comparing the efficacy and safety of low-dose ( 10 - 50 mg ) and high-dose ( 20 - 100 mg ) ranges of gepirone-extended release ( ER ) and placebo in 145 out patients with major depressive disorder . At multiple time points and endpoint ( Week 6 ) , statistically significant reductions in Hamilton Rating Scale for Depression ( HAM-D ) scores were recorded for high-dose gepirone-ER compared to placebo . Analysis of the 17-item HAM-D and 28-item HAM-D scores indicated a relatively early onset of antidepressant efficacy with statistically significant results at treatment Weeks 1 , 2 , 4 , and 6 . A rapid response was evident in the high-dose group , beginning at Week 1 ( p adverse experiences were headache , nausea , dizziness , and insomnia . The results indicate that gepirone-ER is clearly superior to placebo in terms of antidepressant efficacy . When used at higher doses , gepirone-ER appears to be efficacious , safe , and well-tolerated in depressed out- patients",
"BACKGROUND The Psychotic Depression Assessment Scale ( PDAS ) is a rating scale dedicated to the measurement of severity in psychotic depression ( PD ) . The aim of this study was to establish the PDAS cut-off for remission of PD as well as PDAS score-ranges for mild , moderate , and severe PD . The secondary aim was to test how remission , as defined by the PDAS , would perform as outcome measure when applied to the data from a large r and omized controlled trial ( RCT ) in PD . METHODS The study was based on data from the Study of Pharmacotherapy in Psychotic Depression ( STOP-PD ) . The cut-off for remission on the PDAS and the severity-ranges for mild , moderate , and severe PD were defined using the Clinical Global Impression - Severity scale ( CGI-S ) as reference by means of pair-wise receiver operating characteristic ( ROC ) analyses . Subsequently , it was tested whether remission on the PDAS could separate the effects of Olanzapine+Sertraline vs. Olanzapine+Placebo through an intention-to-treat , mixed-effects logistic regression of the data from STOP-PD . RESULTS According to the ROC analyses , the ideal cut-off for remission of PD was a PDAS total score 23 respectively . When applying the PDAS total score as outcome on the STOP-PD data , treatment with Olanzapine+Sertraline performed significantly better than Olanzapine+Placebo ( p total score corresponds to remission of PD",
"We report the results from one site of a two-site , double-blind , placebo-controlled comparison study of gepirone extended release ( ER ) and imipramine in the management of major depression . In the study , 123 subjects with DSM-III-R major depression were r and omized to 8 weeks of treatment with gepirone ER ( 10 - 60 mg/day ) , imipramine ( 50 - 300 mg/day ) , or placebo . According to last observation carried forward ( LOCF ) analyses of 120 intent-to-treat subjects , both gepirone ER and imipramine were superior to placebo at Weeks 6 and 8 on the Hamilton Rating Scale for Depression 17- and 28-item ( HAM-D-17 and HAM-D-28 ) instruments , the Clinical Global Impressions ( CGI ) Severity of illness scale , and the total Bech Six-Item Core Depression Cluster score . Gepirone ER was better tolerated than imipramine when judged by dropout rates for adverse events",
"Clinical study results for neurokinin ( NK ) receptor antagonists in the treatment of depression have been mixed , with Phase III studies failing to fulfill the early promise demonstrated in Phase II studies . Casopitant , a selective NK1 antagonist that achieves nearly complete receptor occupancy was studied in 2 r and omized , placebo-controlled , double-blind , Phase II trials in depressed out patients to test the hypothesis that nearly complete NK1 receptor occupancy is required to achieve antidepressant efficacy . Study 092 used an interactive voice response system to recruit depressed patients with baseline Hamilton Depression ( 17-item , HAMD17 ) total scores higher than 24 who were r and omized to fixed-dose casopitant 30 mg/d , 80 mg/d , or placebo for 8 weeks ( n = 356 ) . Study 096 required Carroll Depression Scale-Revised self- assessment scores of higher than 24 for r and omization to casopitant 120 mg/d , paroxetine 30 mg/d ( both reached via forced titration ) , or placebo for 8 weeks ( n = 362 ) . In study 092 , casopitant 80 mg but not 30 mg achieved statistically significant improvement versus placebo on the primary outcome measure , week 8 last observation carried forward change from baseline HAMD17 ( difference = −2.7 ; 95 % confidence interval , −5.1 to −0.4 , P = 0.023 ) . In study 096 , neither casopitant nor paroxetine achieved statistical separation from placebo at end point on HAMD17 ( casopitant difference = −1.7 ; 95 % CI , −3.8 to 0.4 , P = 0.282 ) . Casopitant and paroxetine were generally well tolerated in most patients . These studies suggest that NK1 antagonists that have nearly complete receptor occupancy may be effective in the treatment of depression ",
"OBJECTIVE There have been few placebo-controlled trials of selective serotonin reuptake inhibitors for depressed elderly patients . This placebo-controlled study of sertraline was design ed to confirm the results of non-placebo-controlled trials . METHOD The subjects were out patients age 60 years or older who had a DSM-IV diagnosis of major depressive disorder and a total score on the 17-item Hamilton Depression Rating Scale of 18 or higher . The patients were r and omly assigned to 8 weeks of double-blind treatment with placebo or a flexible daily dose of 50 or 100 mg of sertraline . The primary outcome variables were the Hamilton scale and Clinical Global Impression ( CGI ) scales for severity and improvement . RESULTS A total of 371 patients assigned to sertraline and 376 assigned to placebo took at least one dose . At endpoint , the patients receiving sertraline evidence d significantly greater improvements than those receiving placebo on the Hamilton depression scale and CGI severity and improvement scales . The mean changes from baseline to endpoint in Hamilton score were -7.4 points ( SD=6.3 ) for sertraline and -6.6 points ( SD=6.4 ) for placebo . The rate of CGI-defined response at endpoint was significantly higher for sertraline ( 45 % ) than for placebo ( 35 % ) , and the time to sustained response was significantly shorter for sertraline ( median , 57 versus 61 days ) . There were few discontinuations due to treatment-related adverse events , 8 % for sertraline and 2 % for placebo . CONCLUSIONS Sertraline was effective and well tolerated by older adults with major depression , although the drug-placebo difference was not large in this 8-week trial",
"OBJECTIVE To assess the efficacy and tolerability of the 5-HT(1A ) agonist gepirone in extended-release formulation ( gepirone-ER ) versus placebo in patients with major depressive disorder . METHOD Patients aged 18 to 70 years were eligible if they satisfied DSM-IV criteria for moderate-to-severe major depressive disorder and had a baseline 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) score > or = 20 . After a 4- to 7-day placebo washout period , patients were r and omly assigned to receive either placebo ( N = 106 ) or gepirone-ER ( 20 - 80 mg/day ) ( N = 103 ) for 56 days . Assessment s were done at weeks 1 - 4 , 6 , and 8 . RESULTS Mean change from baseline in HAM-D-17 score within the intent-to-treat group ( gepirone , N = 101 ; placebo , N = 103 ) was significantly greater with gepirone-ER than placebo at weeks 3 ( p = .013 ) and 8 ( p = .018 ) . Significantly ( p gepirone-ER than placebo were HAM-D-17 responders at weeks 3 ( 33.7 % vs. 18.8 % , respectively ) and 4 ( 38.6 % vs. 24.8 % , respectively ) and HAM-D-17 remitters at weeks 6 ( 24.8 % vs. 13.9 % , respectively ) and 8 ( 28.7 % vs. 14.9 % , respectively ) . Mean change from baseline for HAM-D-25 total score was significantly ( p proportion of HAM-D-25 responders was significantly greater ( p Gepirone-ER was well tolerated : 9.8 % of the gepirone-ER group and 2.8 % of the placebo group discontinued due to adverse events . Common adverse events were considered mild and included dizziness , nausea , and insomnia . Gepirone-ER did not differ statistically compared with placebo in weight gain or sedation . Furthermore , preliminary evidence suggested that gepirone-ER may not be associated with sexual dysfunction . No serious adverse events occurred in gepirone-treated patients . CONCLUSION Gepirone-ER is effective for the short-term treatment of major depressive disorder and is well tolerated",
"In a 6-week , r and omized , double-blind , multicenter trial , sertraline 50 mg , 100 mg , or 200 mg , or placebo , was administered once daily to 369 patients with DSM-III-defined major depression . Efficacy variables included changes from baseline scores for total Hamilton Rating Scale for Depression ( HAMD ) , HAMD Bech Depression Cluster , Clinical Global Impressions ( CGI ) Severity , CGI Improvement , and Profile of Mood States Depression/Dejection Factor . For the evaluable- patients analysis , all sertraline groups showed significantly ( p efficacy variables except one when compared with the placebo group . For the all- patients analysis , all efficacy variables in the 50 mg group were statistically significantly ( p placebo . Side effects increased with increasing dosage but were usually mild and well tolerated . The results of this study show that sertraline 50 mg once daily is as effective as higher dosages for the treatment of major depression with fewer side effects and therapy discontinuations",
"Two hundred forty-one out patients with a DSM-III diagnosis of major depressive disorder participated in a six-week double-blind therapeutic trial of alprazolam , diazepam , imipramine hydrochloride , and placebo . Side effects were given as a major reason for attrition by patients taking the three active compounds and ineffectiveness was the reason given by patients taking placebo . Imipramine-treated patients reported the most and placebo patients the least number of adverse effects . Imipramine and alprazolam , but not diazepam , produced significantly more improvement in depressed symptomatology than did placebo . Mean diazepam scores frequently assumed an intermediate position between those of imipramine or alprazolam and placebo . These treatment differences were found to be independent of initial severity levels of anxiety and depression",
"Two hundred hospitalized patients with DSM-III diagnosis of moderate to severe major depressive episode were r and omized to receive mirtazapine or trazodone for 6 weeks in a double-blind trial . The dosages were 24–72 mg/day for mirtazapine and 150–450 mg/day for trazodone . The improvement on all depression rating scales used was generally greater for mirtazapine , wish statistically significant differences over trazodone in the Hamilton Psychiatric Rating Scale for Depression total score and two subscores ( the Bech melancholia factor and retardation factor ) , the Brief Psychiatric Rating Scale total score , the General Psychiatric Impression Global Assessment Scale , the Beck score and responder rates . Mirtazapine was well tolerated , while the trazodone-treated patients experienced somnolence more frequently , particularly during the first 2 weeks of treatment . Furthermore , postural symptoms were a clinical problem in > ' 6 % of the trazodone-treated patients . In this trial , mirtazapine showed significant clinical advantages over trazodone in terms of overall efficacy and tolerability",
"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",
"OBJECTIVE This study evaluated the efficacy and tolerability of desvenlafaxine succinate ( desvenlafaxine ) in the treatment of major depressive disorder ( MDD ) . METHOD In this 8-week , multicenter , r and omized , double-blind , placebo-controlled trial , adult out patients ( aged 18 - 75 years ) with a primary diagnosis of MDD ( DSM-IV criteria ) were r and omly assigned to treatment with desvenlafaxine ( 100 - 200 mg/day ) or placebo . The primary outcome measure was the 17-item Hamilton Rating Scale for Depression ( HAM-D(17 ) ) score at final on-therapy evaluation . The Clinical Global Impressions-Improvement scale ( CGI-I ) was the key secondary measure . Other secondary measures included the Montgomery-Asberg Depression Rating Scale ( MADRS ) , Clinical Global Impressions-Severity of Illness scale , Visual Analog Scale-Pain Intensity ( VAS-PI ) overall and subcomponent scores , and HAM-D(17 ) response and remission rates . The study was conducted from June 2003 to May 2004 . RESULTS Of the 247 patients r and omly assigned to treatment , 234 comprised the intent-to-treat population . Following titration , mean daily desvenlafaxine doses ranged from 179 to 195 mg/day . At endpoint , there were no significant differences in scores between the desvenlafaxine ( N = 120 ) and placebo ( N = 114 ) groups on the HAM-D(17 ) or CGI-I. However , the desvenlafaxine group had significantly greater improvement in MADRS scores ( p = .047 ) and in VAS-PI overall pain ( p = .008 ) , back pain ( p = .006 ) , and arm , leg , or joint pain ( p nausea , dry mouth , constipation , anorexia , somnolence , and nervousness . CONCLUSION Desvenlafaxine was generally safe and well tolerated . In this study , it did not show significantly greater efficacy than placebo on the primary or key secondary efficacy endpoints , but it did demonstrate efficacy on an alternate depression scale and pain measure associated with MDD . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00063206",
"BACKGROUND Approximately 45 % of patients with major depressive disorder ( MDD ) do not remit when treated with biogenic amine antidepressants . Consequently , there is a significant need for antidepressant agents with different mechanisms of action . Early proof of concept ( POC ) studies with such novel agents play a significant role in helping drug developers identify agents and mechanisms of action that merit more intensive research . Studies have demonstrated that high affinity N-methyl-Daspartate ( NMDA ) receptor blockers ( eg , ketamine ) can produce rapid antidepressant effects in patients who have not responded to currently available agents , but treatment with these agents is accompanied by psychotomimetic effects that make their use problematic . This column describes a POC study involving GLYX-13 , an N-methyl-D-aspartate receptor glycine site functional partial agonist . METHOD In this double-blind , r and omized , placebo-controlled study , a single intravenous ( IV ) dose of GLYX-13 ( 1 , 5 , 10 , or 30 mg/kg ) or placebo was administered to 116 subjects with MDD who had not benefitted from a trial of at least one biogenic amine antidepressant during the current episode . The primary outcome measure was score on the Hamilton Depression Rating Scale-17 ( Ham-D17 ) , which was used to rate overall depressive symptoms at baseline and at 24 hours and days 3 , 7 , 14 , and , in some arms , days 21 and 28 after administration . RESULTS GLYX-13 , 5 or 10 mg/kg IV , reduced depressive symptoms as assessed by the Ham-D17 at days 1 through 7 . Onset of action as assessed using the Bech-6 occurred within 2 hours . GLYX-13 did not elicit psychotomimetic or other significant side effects . CONCLUSION In this early POC study , GLYX-13 reduced depressive symptoms within 2 hours and this effect was maintained for 7 days on average in subjects with MDD who had not responded to another antidepressant agent during the current depressive episode . The findings of this study support the hypothesis that modulation of the NMDA receptor is a valid target for the development of antidepressant drugs and the need for additional studies to further evaluate the effects of GLYX-13 . POC studies such as the one described here play a pivotal role in allowing drug research ers to decide whether to move forward with larger and more expensive studies , and they enable them to focus available re sources on those molecules that appear to have the most therapeutic promise . Based on the POC study described here , a multiple dose study has been completed which showed sustained therapeutic benefit with repeated dosing of GLYX-13 for more than 6 weeks . Phase 3 studies are now being planned",
"Objective : To investigate the use of bright light therapy as an adjunct treatment to sertraline in non‐seasonal major depression",
"BACKGROUND This r and omized , open-label , rater-blinded , multicenter study compared treatment outcomes with the serotonin-norepinephrine reuptake inhibitor ( SNRI ) venlafaxine extended release ( ER ) with selective serotonin reuptake inhibitors ( SSRIs ) in primary care patients with major depressive disorder . METHOD Study data were collected from November 29 , 2000 , to March 4 , 2003 . Out patients who met diagnostic criteria for major depressive disorder according to the Mental Health Screener , a computer-administered telephone interview program that screens for the most common mental disorders , and had a total score on the 17-item Hamilton Depression Rating Scale ( HDRS(17 ) ) ≥ 20 were r and omly assigned to receive up to 6 months of open-label venlafaxine ER 75 - 225 mg/d ( n = 688 ) or an SSRI ( n = 697 ) : fluoxetine 20 - 80 mg/d , paroxetine 20 - 50 mg/d , citalopram 20 - 40 mg/d , and sertraline 50 - 200 mg/d . The primary outcome was remission ( HDRS(17 ) score ≤ 7 ) at study end point using the last-observation-carried-forward method to account for early termination . A mixed-effects model for repeated measures ( MMRM ) analysis evaluated secondary outcome measures . RESULTS Fifty-one percent of patients completed the study . Month 6 remission rates did not differ significantly for venlafaxine ER and the SSRIs ( 35.5 % vs 32.0 % , respectively ; P = .195 ) . The MMRM analysis of HDRS(17 ) scores also did not differ significantly ( P = .0538 ) . Significant treatment effects favoring the venlafaxine ER group were observed for remission rates at days 30 , 60 , 90 , and 135 and a survival analysis of time to remission ( P = .006 ) , as well as Clinical Global Impressions-severity of illness scale ( P = .0002 ) ; Hospital Anxiety and Depression Scale-Anxiety subscale ( P = .03 ) ; 6-item Hamilton Depression Rating Scale , Bech version ( P = .009 ) ; and Quick Inventory of Depressive Symptomatology-Self-Report ( P = .0003 ) . CONCLUSIONS Remission rates for patients treated with venlafaxine ER or an SSRI did not differ significantly after 6 months of treatment . Results of most secondary analyses suggested that SNRI treatment had a greater antidepressant effect versus the SSRIs studied",
"OBJECTIVE This study investigated the efficacy , safety , and tolerability of the selegiline transdermal system ( STS ) administered in a dose range of 6 mg/24 hours to 12 mg/24 hours for treating major depressive disorder ( MDD ) . METHOD Patients meeting DSM-IV criteria for MDD ( N = 265 ) were r and omly assigned to blinded treatment with STS or a matching placebo patch for 8 weeks . Patients failing to meet or maintain protocol -defined therapeutic response criteria at predetermined time points had their STS ( or placebo ) dose increased . Assessment s were conducted at weeks 1 , 2 , 3 , 5 , 6 , and 8 . Patients were not required to follow a tyramine-restricted diet . The study ran from September 2001 through August 2002 . RESULTS Selegiline transdermal system treatment result ed in significantly greater improvement ( p placebo treatment on the 3 depression rating scales : the 28-item Hamilton Rating Scale for Depression ( HAM-D28 ) ( primary outcome measure ) , the Montgomery-Asberg Depression Rating Scale , and the Inventory for Depressive Symptomatology-Self Rated . The treatment effect measured by the HAM-D28 was modest , primarily due to insomnia side effects . The antidepressant efficacy of STS was substantiated further by the significantly greater improvement in core depression symptoms ( HAM-D Bech-6 subscale ) . The side effects of highest incidence were application site reactions and insomnia . There were no safety concerns based on routine clinical laboratory and electrocardiogram monitoring , and there were no occurrences of hypertensive crisis . CONCLUSION Results of this double-blind , placebo-controlled , dose titration trial provide evidence of short-term efficacy , safety , and tolerability of STS in the dose range of 6 mg/24 hours to 12 mg/24 hours for treatment of MDD . Selegiline transdermal system has an improved margin of safety compared with oral monoamine oxidase inhibitors and represents a useful addition to the existing array of antidepressants",
"OBJECTIVES To compare the sensitivity of the 6-item Hamilton Rating Scale for Depression ( HRSD6 ) with the more widely used 17-item Hamilton Rating Scale for Depression ( HRSD17 ) in patients suffering from major depressive disorder , with or without melancholia and /or dysthymic disorder . A secondary objective was to compare the sensitivity of the HRSD6 to the Montgomery-Asberg Depression Rating Scale ( MADRS ) . DESIGN Retrospective analysis of 4 clinical trials that tested antidepressant therapies . SETTING Outpatient treatment in a major psychiatric hospital . PARTICIPANTS One hundred and forty-three male and female out patients meeting the criteria of the DSM-III-R or DSM-IV for major depressive disorder . OUTCOME MEASURES HRSD17 , HRSD6 and MADRS . RESULTS The HRSD6 correlated strongly with the HRSD17 , both at baseline and termination of treatment , and for the subgroups of double depression and melancholia . The HRSD6 was also correlated significantly with the MADRS at both measurement times , and for the subgroups . Paired t-tests with the HRSD6 , HRSD17 and MADRS demonstrated equal sensitivity to change over the course of treatment , both in the full sample and in the dysthymic and melancholic subgroups . CONCLUSIONS The HRSD6 appears to be as sensitive to change over treatment as the HRSD17 and the MADRS . A shorter , less time-consuming measure of depression may have utility in clinical practice and research",
"In clinical pharmacology , the evidence proving that a drug has a therapeutic effect in a specific medical condition is based on two major elements : superiority of the drug over placebo in r and omized clinical trials within the medical condition under examination , and a systematic relationship between the dose of the drug and the magnitude of the response it elicits . In their overview of antidepressants versus placebo , Khan and Brown ( 1 ) conclude that “ no clear dose-response relationship has been established to date for most of the new antidepressants ” , while the superiority of the antidepressants over placebo in terms of effect size statistics is approximately 0.30 , a level they find “ less than impressive ” . In their review of double-blind , placebo-controlled trials of antidepressants conducted from 1981 to 2008 , Khan et al ( 2 ) observed that the Hamilton Depression Scale ( HAM-D ) had been used as an outcome scale in most of the trials . However , the HAM-D was actually used in two different versions , the 21-item version ( HAM-D-21 ) and the 17-item version ( HAM-D-17 ) . The HAM-D-21 was used in one third of the trials and the HAM-D-17 in two thirds . Unfortunately , authors who use the HAM-D-21 rarely provide information about the results on the HAM-D-17 . Khan and Brown ( 1 ) highlight now that the antidepressant-placebo difference seems to be higher in HAM-D-21 trials compared to the trials in which the HAM-D-17 has been used as outcome measure . This is a tautological finding in so far as the st and ard deviation of this difference is not available , which is the case for most of the trials review ed by Khan et al ( 2 ) . Among the trials collected by Khan et al ( 2 ) it is possible , however , to identify ten publications in which the six-item HAM-D ( HAM-D-6 ) is compared to both HAM-D-17 and HAM-D-21 , or to HAM-D-28 . The HAM-D-6 covers the core symptoms of depression : depressed mood , work and interests , guilt feelings , psychomotor retardation , psychic anxiety , and general somatic ( fatigability ) . These six items have clinical and psychometric validity ( 3 ) . In two of these ten trials , a dose-response relationship was investigated . Fabre et al ( 4 ) showed that sertraline was significantly superior to placebo at all three doses ( 50 , 100 , 200 mg daily ) when using HAM-D-6 , but only at 50 mg daily when using HAM-D-17 . Liebowitz et al ( 5 ) showed that desvenlafaxine was superior to placebo at both 50 and 100 mg daily when using HAM-D-6 , but only at 50 mg daily when using HAM-D-17 . An analysis of all placebo-controlled trials of desvenlafaxine showed that at doses of 200 or 400 mg daily the effect size was negative during the first week of treatment ( superiority of placebo ) when using HAM-D-17 but not when using the HAM-D-6 , implying that the HAM-D-17 includes symptoms which might be side effects of the drug ( 6 ) . In placebo-controlled trials of fluoxetine , over a dose range from 20 to 60 mg daily , the effect size using HAM-D-17 was approximately 0.30 , but when using HAM-D-6 it was approximately 0.40 ( 3 ) . For escitalopram , a dose of 10 mg daily obtained an effect size of 0.38 mg using HAM-D-6 and a dose of 20 mg daily gave an effect size of 0.61 ( 3 ) . Over the past decade , the goal when evaluating the effect of an antidepressant has been the event of remission rather than response ( 7 ) . Remission in major depression is defined as a minimal level of the core symptoms of depression ( 7 ) . The syndrome reflected by the HAM-D-6 is a unidimensional measure for specific drug targets , and a cut-off score below 5 indicates that the individual symptoms of the scale are only present to a very doubtful degree ( remission ) . Khan and Brown ( 1 ) refer to the Sequenced Treatment Alternatives to Relieve Depression ( STAR*D ) as an example of a poor response to citalopram treatment . Indeed , when using the conventional definition of remission ( HAM-D-17 36 % of the patients achieved remission . However , when using a HAM-D-6 score of remission , approximately 45 % of the patients in that study achieved remission ( p effect of erythropoietin as augmentation in patients with treatment-resistant depression ( 9 ) . By focusing on the HAM-D-6 , fewer patients are needed to reject the None hypothesis . Psychometrically , Khan and Brown ( 1 ) correctly focus on the use of the HAM-D-17 as the major factor for the “ less than impressive ” effect size of 0.30 and the lack of a dose-response relationship . However , their solution to go for a larger HAM-D version ( HAM-D-21 ) is not justified . The solution is to go for the brief , clinical ly and psychometrically valid subscale ( HAM-D-6 ) . The use of the HAM-D-6 as outcome measure in placebo-controlled clinical trials of antidepressants increases the effect size to 0.40 , which is indicative of clinical significance . Using the HAM-D-6 as outcome measure , a dose-response relationship has been established for newer antidepressants such as escitalopram and desvenlafaxine . Moreover , fewer patients are then needed to identify antidepressant effect in controlled trials , which has important ethical implication s ( fewer patients need to receive placebo ) . In my opinion , we need to aim at establishing “ dose-remission ” rather than dose-response relationship in future trials of antidepressants . The HAM-D-6 contains the core symptoms of depression by which to define the event of remission",
"Two recent meta-analyses on second-generation antidepressants versus placebo in mild to moderate forms of major depression , based on data on all r and omized clinical trials using the Hamilton Depression Scale ( HAMD ) su bmi tted to FDA , have shown an effect size of approximately 0.30 in favour of antidepressants in the acute therapy of major depression . The clinical significance of an effect size at this level was found to be so poor that these meta-analyses have subscribed to the myth of an exclusively placebo-like effect of second-generation antidepressants . A re-allocation of HAMD items focusing on those items measuring severity of clinical depression , the HAMD6 , has identified effect sizes of > or=0.40 for second-generation antidepressants in placebo-controlled trials for which even a dose-response relationship can be demonstrated . In the relapse-prevention phase during continuation therapy of patients with major depression , the advantage of second-generation antidepressants over placebo was as significant as in the acute therapy phase . To explore a myth is not to deny the facts but rather to re-allocate them",
"INTRODUCTION This retrospective analysis compared sensitivity to change on the 17-item and 6-item Hamilton Rating Scales For Depression ( HAM-D ( 17 ) and HAM-D ( 6 ) , respectively ) in relation to antidepressant dose and baseline depression severity . METHODS Data were derived from 6 r and omized , double-blind , placebo-controlled , 8-week trials of fixed-dose desvenlafaxine ( 50 , 100 , 200 or 400 mg/d ) for major depressive disorder . HAM-D ( 17 ) and HAM-D ( 6 ) effect sizes were assessed . RESULTS HAM-D ( 17 ) effect sizes were negative ( favoured placebo ) for higher desvenlafaxine doses ( 200 - 400 mg/d ) at week 1 , but were positive for all doses after week 2 , with no clear dose-response pattern . However , HAM-D ( 6 ) effect sizes were positive for all doses at all weeks . Effect sizes were consistently greater for HAM-D ( 6 ) vs. HAM-D ( 17 ) , regardless of time spent under therapy . Effect sizes were greater for HAM-D ( 6 ) vs. HAM-D ( 17 ) for all desvenlafaxine doses among patients with baseline HAM-D ( 17 ) < 25 , but not among patients with baseline HAM-D ( 17 ) ≥ 25 . DISCUSSION The HAM-D ( 6 ) demonstrated greater sensitivity to change and robustness than the HAM-D ( 17 ) , supporting the greater homogeneity of the HAM-D ( 6 )"
] |
4116c676-06ff-11f0-808a-c43d1ab1c353
|
OBJECTIVE To identify which gait deviations are consistently associated with knee osteoarthritis ( KOA ) and how these are influenced by disease severity , the involved compartment , and sex . METHODS Five electronic data bases and reference lists of publications were search ed . Cross-sectional , observational studies comparing temporospatial variables , joint kinematics , and joint moments between individuals with KOA and healthy controls or between KOA subgroups were considered for review . Only publications scoring ≥50 % on a modified methodology quality index were included . Because of the number of gait deviations examined , only biomechanical variables reported by ≥4 publications were further analyzed . Where possible , a meta- analysis was performed using effect sizes ( ES ) calculated from discrete variables . RESULTS In total , 41 publications examining 20 variables were included . The majority of consistent gait deviations associated with KOA were exhibited by those with severe disease in the temporospatial domain . Individuals with severe KOA exhibited greater stride duration than controls ( ES 1.35 [ 95 % confidence interval ( 95 % CI ) 1.03 , 1.67 ] ) and a decrease in cadence ( ES -0.75 [ 95 % CI -1.12 , -0.39 ] ) compared with controls . The evidence for kinematic and joint moment change was primarily limited or conflicting . There was a lack of evidence for alterations in the external knee adduction moment . CONCLUSION Individuals with KOA exhibit a range of gait deviations compared with controls . Despite its common usage in KOA gait studies , we did not find consistent evidence that knee adduction moment differs between those with and without KOA or between disease severity levels . Further research examining the reasons for a lack of difference in many gait variables in those with knee OA is needed
|
[
"OBJECTIVE The purpose of this study was to investigate lower extremity movement and muscle activation patterns in individuals with knee osteoarthritis and healthy age- and gender-matched control subjects . DESIGN This study utilized a non-r and omized case-control design to compare 24 subjects with unilateral symptomatic knee osteoarthritis to 24 age- and gender-matched control subjects without knee osteoarthritis . BACKGROUND It is hypothesized that knee osteoarthritis is associated with altered lower extremity movement and muscle activation patterns . METHODS A gait analysis was performed to determine the lower extremity movement and muscle activation patterns when walking on a level surface at 1.12 to 1.34 m/s and while descending a 20 cm step . Paired t-tests were used to compare the average of five trials between the groups . RESULTS Subjects with knee osteoarthritis demonstrated less excursion of the knee in the sagittal plane from heelstrike to peak flexion before midstance ( i.e. during loading ) . Subjects with knee osteoarthritis also demonstrated reduced peak vertical ground reaction forces relative to body weight . The muscle activity patterns were also different between the groups . The vastus lateralis , medial hamstrings , tibialis anterior and medial gastrocnemius were on approximately 1.5 times longer than the same muscles in the control subjects . Additionally , significant increases in muscle co-activation were also observed in individuals with knee osteoarthritis during walking . Similar findings were observed when the subject descended a 20 cm step",
"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",
"Joint moments are commonly used to characterize gait . Factors like height and weight influence these moments . This study determined which of two commonly used normalization methods , body mass or body weight times height , most reduced the effects of height and weight on peak hip , knee , and ankle external moments during walking . The effectiveness of each normalization method in reducing gender differences was then tested . Gait data from 158 normal subjects were analyzed using unnormalized values , body mass normalized values , and body weight times height normalized values . Without normalization , height or weight accounted for 7 - 82 % of the variance in all 10 peak components of the moments . With normalization , height and weight accounted for at most 6 % of the variance with the exception of the hip adduction moment normalized by body weight times height and the ankle dorsiflexion moment normalized by body mass . For the hip adduction moment normalized by body weight times height , height still accounted for 13 % of the variance ( p dorsiflexion moment normalized by body mass , 22 % of the variance ( p height and weight differences . Even for the two cases where one normalization method was less effective than the other ( hip adduction-body weight times height ; ankle dorsiflexion-body mass ) the normalization process reduced the variance ascribed to height or weight by 48 % and 63 % , respectively , as compared to the unnormalized data",
"This study tested whether the peak external knee adduction moments during walking in subjects with knee osteoarthritis ( OA ) were correlated with the mechanical axis of the leg , radiographic measures of OA severity , toe out angle or clinical assessment s of pain , stiffness or function . Gait analysis was performed on 62 subjects with knee OA and 49 asymptomatic control subjects ( normal subjects ) . The subjects with OA walked with a greater than normal peak adduction moment during early stance ( p = 0.027 ) . In the OA group , the mechanical axis was the best single predictor of the peak adduction moment during both early and late stance ( R = 0.74 , p radiographic measures of OA severity in the medial compartment were also predictive of both peak adduction moments ( R = 0.43 to 0.48 , p WOMAC subscales ( R = -0.33 to -0.31 , p toe out angle was predictive of the peak adduction moment only during late stance ( R = -0.45 , p peak knee adduction moments by 10 18 % . While the mechanical axis was indicative of the peak adduction moments , it only accounted for about 50 % of its variation , emphasizing the need for a dynamic evaluation of the knee joint loading environment . Underst and ing which clinical measures of OA are most closely associated with the dynamic knee joint loads may ultimately result in a better underst and ing of the disease process and the development of therapeutic interventions",
"Elderly subjects with and without knee pain walked at a comfortable pace during gait analysis . Comparison of peak hip and knee internal extensor generalized muscle moments ( GMMs ) during loading response was made between groups . Walking velocity , peak hip internal extensor GMM , and knee range of motion ( ROM ) were significantly less for the group with knee pain than for the group without pain . Peak hip internal extensor GMM was strongly correlated with velocity , but peak knee internal extensor GMM was not . Knee ROM limitations may account for the increased peak knee internal extensor GMM in the knee pain group"
] |
4116c6b2-06ff-11f0-808a-c43d1ab1c353
|
Screen time , but not overall sedentary behaviour , is consistently related to cardiometabolic health in adolescents . Because of the associations screen time has with dietary intake , diet may be an important factor in the screen time and health relationship ; however , evidence has not previously been synthesized . Thus , the aim of this systematic review was to explore whether the associations between various sedentary behaviours and cardiometabolic risk markers are independent of dietary intake in adolescents . Online data bases and personal libraries were search ed for peer- review ed original research articles published in English before March 2014 . Included studies assessed associations between sedentary behaviour and cardiometabolic markers in 12- to 18-year-olds and adjusted for dietary intake . Twenty-five studies met the inclusion criteria . From the 21 studies examining sedentary behaviour and adiposity , the majority found significant positive associations between television viewing , screen time and self-reported overall sedentary behaviour with markers of adiposity , independent of dietary intake . No significant associations between screen time with blood pressure and cholesterol were reported . Sedentary behaviour appears to be associated with adiposity in adolescents , irrespective of dietary intake . However , the variability of dietary variables between studies suggests further work is needed to underst and the role of dietary intake when examining these associations in youth
|
[
"BACKGROUND Video game playing has been linked to obesity in many observational studies . However , the influence of this sedentary activity on food intake is unknown . OBJECTIVE The objective was to examine the acute effects of sedentary video game play on various components of energy balance . DESIGN With the use of a r and omized crossover design , 22 healthy , normal-weight , male adolescents ( mean ± SD age : 16.7 ± 1.1 y ) completed two 1-h experimental conditions , namely video game play and rest in a sitting position , followed by an ad libitum lunch . The endpoints were spontaneous food intake , energy expenditure , stress markers , appetite sensations , and profiles of appetite-related hormones . RESULTS Heart rate , systolic and diastolic blood pressures , sympathetic tone , and mental workload were significantly higher during the video game play condition than during the resting condition ( P Although energy expenditure was significantly higher during video game play than during rest ( mean increase over resting : 89 kJ ; P , ad libitum energy intake after video game play exceeded that measured after rest by 335 kJ ( P A daily energy surplus of 682 kJ ( 163 kcal ) over resting ( P increase in food intake associated with video game play was observed without increased sensations of hunger and was not compensated for during the rest of the day . Finally , the profiles of glucose , insulin , cortisol , and ghrelin did not suggest an up-regulation of appetite during the video game play condition . CONCLUSION A single session of video game play in healthy male adolescents is associated with an increased food intake , regardless of appetite sensations . The trial was registered at clinical trials.gov as NCT01013246",
"BACKGROUND Television watching and playing of video games ( VGs ) are associated with higher energy intakes . Motion-controlled video games ( MC ) may be a healthier alternative to sedentary screen-based activities because of higher energy expenditures , but little is known about the effects of these games on energy intakes . OBJECTIVE Energy intake , expenditure , and surplus ( intake - expenditure ) were compared during sedentary ( television and VG ) and active ( MC ) screen-time use . DESIGN Young adults ( n = 120 ; 60 women ) were r and omly assigned to the following 3 groups : television watching , playing traditional VGs , or playing MCs for 1 h while snacks and beverages were provided . Energy intakes , energy expenditures , and appetites were measured . RESULTS Intakes across these 3 groups showed a trend toward a significant difference ( P = 0.065 ) . The energy expenditure ( P energy surplus ( P = 0.038 ) was lower , in MC than in television or VG groups . All conditions produced a mean ( ±SD ) energy surplus as follows : 638 ± 408 kcal in television , 655 ± 533 kcal in VG , and 376 ± 487 kcal in MC groups . The OR for consuming ≥500 kcal in the television compared with the MC group was 3.2 ( 95 % CI : 1.2 , 8.4 ) . Secondary analyses , in which the 2 sedentary conditions were collapsed , showed an intake that was 178 kcal ( 95 % CI : 8 , 349 kcal ) lower in the MC condition than in the sedentary groups ( television and VG ) . CONCLUSION MCs may be a healthier alternative to sedentary screen time because of a lower energy surplus , but the playing of these games still result ed in a positive energy balance . This trial was registered at clinical trials.gov as NCT01523795",
"Observational longitudinal research is particularly useful for assessing etiology and prognosis and for providing evidence for clinical decision making . However , there are no structured reporting requirements for studies of this design to assist authors , editors , and readers . The authors developed and tested a checklist of criteria related to threats to the internal and external validity of observational longitudinal studies . The checklist criteria concerned recruitment , data collection , biases , and data analysis and descriptive issues relevant to study rationale , study population , and generalizability . Two raters independently assessed 49 r and omly selected articles describing stroke research published from 1999 to 2003 in six journals : American Journal of Epidemiology , Journal of Epidemiology and Community Health , Stroke , Annals of Neurology , Archives of Physical Medicine and Rehabilitation , and American Journal of Physical Medicine and Rehabilitation . On average , 17 of the 33 checklist criteria were reported . Criteria describing the study design were better reported than those related to internal validity . No relation was found between study type ( etiologic or prognostic ) or word count and quality of reporting . A flow diagram for summarizing participant flow through a study was developed . Editors and authors should consider using a checklist and flow diagram when reporting on observational longitudinal research",
"BACKGROUND The rising prevalence of obesity in children has been linked in part to the consumption of sugar-sweetened drinks . Our aim was to examine this relation . METHODS We enrolled 548 ethnically diverse schoolchildren ( age 11.7 years , SD 0.8 ) from public schools in four Massachusetts communities , and studied them prospect ively for 19 months from October , 1995 , to May , 1997 . We examined the association between baseline and change in consumption of sugar-sweetened drinks ( the independent variables ) , and difference in measures of obesity , with linear and logistic regression analyses adjusted for potentially confounding variables and clustering of results within schools . FINDINGS For each additional serving of sugar-sweetened drink consumed , both body mass index ( BMI ) ( mean 0.24 kg/m2 ; 95 % CI 0.10 - 0.39 ; p=0.03 ) and frequency of obesity ( odds ratio 1.60 ; 95 % CI 1.14 - 2.24 ; p=0.02 ) increased after adjustment for anthropometric , demographic , dietary , and lifestyle variables . Baseline consumption of sugar-sweetened drinks was also independently associated with change in BMI ( mean 0.18 kg/m2 for each daily serving ; 95 % CI 0.09 - 0.27 ; p=0.02 ) . INTERPRETATION Consumption of sugar-sweetened drinks is associated with obesity in children",
"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",
"Background The increasing rate of obesity among Kuwaiti adolescents is associated with immediate and long term-risks to their health and well-being . Objective To up date data on the prevalence of overweight and obesity among Kuwaiti adolescents and to examine the relative contribution of selected lifestyle factors to overweight and obesity in this population . Methods The present study is part of the Arab Teens Lifestyle Study ( ATLS ) . A total of 906 adolescents ( 463 boys and 443 girls ) aged between 14 and 19 years were selected from Kuwaiti schools by a multistage stratified r and omization process . A vali date d question naire was used to collect data on physical activity , sedentary lifestyle , and eating habits . The International Obesity Task Force ( IOTF ) cutoff values for adolescents under 18 years of age were used to define overweight and obesity . Total energy expenditure was calculated using metabolic equivalent-minutes per week . A general linear model was used to establish the proportion of the variance ( expressed in partial eta squared ) in excess weight attributable to differences in eating habits and physical activity . Results The prevalence of overweight and obesity was 50.5 % in boys and 46.5 % in girls . Among boys , moderate and vigorous activities were found to be significantly negatively associated with overweight and obesity ( p overweight and obesity ( p Sedentary behaviors , time spent watching television , and time spent working on the computer were not significantly associated with obesity in either sex . Consumption of breakfast , vegetables , and fast foods ( boys and girls ) and potatoes , cakes and doughnuts , and sweets ( girls only ) was significantly associated with overweight and obesity ( p partial eta square explained by physical activity was less than 3.6 % in boys compared with less than 1.0 % in girls , and eating habits explained less than 1.8 % in boys compared with 2.5 % in girls . Conclusions Physical activity explains a greater proportion of variation in body mass index than do eating habits , particularly in boys . Eating habits explain a greater proportion of variation in body mass index than does physical activity in girls . Prospect i ve studies are needed to clarify the relative effects of sedentary behaviors on overweight in adolescents",
"PURPOSE This study aim ed to establish whether time spent in sport-related physical activities and sedentary behaviors ( e.g. , TV viewing , videogame usage , and homework ) was prospect ively associated with change in blood pressure ( BP ) for 5 yr . METHODS Eight hundred and twenty-one students age 6 yr at baseline ( 397 girls and 424 boys ) were examined from 2003 - 2004 to 2009 - 2011 . Children completed detailed activity question naires . BP was measured using a st and ardized protocol . RESULTS After adjusting for age , ethnicity , parental education , parental history of hypertension , baseline height , BP , body mass index ( BMI ) , baseline time spent in corresponding activity behavior , and change in BMI , each hour per day spent in total screen time was associated with a 0.69 and 0.59 mm Hg increase in diastolic BP ( P = 0.01 ) and mean arterial BP ( P = 0.01 ) , respectively . In boys , each hour per day spent in TV viewing was associated with a concurrent 1.42-mm Hg increase in diastolic BP ( P = 0.04 ) during the 5 yr . Children engaging in low sport-related physical activities at baseline but who engaged in high levels of physical activity ( ≥ 60 min · d(-1 ) ) at follow-up ( n = 154 ) compared with those engaging in low sport-related physical activities at both examinations ( n = 305 ) demonstrated significantly lower mean arterial BP , 7.26 versus 9.61 mm Hg ( P = 0.04 ) . CONCLUSIONS Time spent in physical activity and screen time could influence BP measures during childhood",
"OBJECTIVES To explore the association between electronic media exposure ( television viewing time , personal computer/video game use , total screen time ) , and waist circumference and body mass index , and study whether this association is independent of cardiorespiratory fitness , in a representative sample of adolescents from Montería , Colombia . DESIGN Cross-sectional study analyzing data from 546 students aged 11 - 18 years , from fourteen r and omly selected schools . Z-scores for WC and BMI were calculated . METHODS The physical activity module of the Global School Health Survey 2007 was used to determine EME , and the shuttle run test was used to assess CRF . Linear regression models adjusted by age , school location , physical activity level , type of institution ( public or private ) , consumption of sweetened beverages , fast food , and fried food were used . RESULTS Among boys , independently of cardiorespiratory fitness , high television viewing time ( ≥ 2 h/day ) ( β=+0.22 ; p with waist circumference . High total screen time ( > 3h/day ) was positively associated with waist circumference ( β=+0.34 ; p and body mass index ( β=+0.39 ; p girls , sedentary behavior was not associated with adiposity , but cardiorespiratory fitness ( β=-0.04 ; p low cardiorespiratory fitness , and highlight the need for interventions and prevention strategies"
] |
4116c6ee-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND Disability management ( DM ) is a systematic method to ensure job-retention and job-reintegration in competitive employment for individuals with a disability . There is evidence that ' returning to work ' has a positive impact on the individual , the company and on the society . However , a clear overview of the efficacy and efficiency of the DM programs is scarce . OBJECTIVE To systematic ally review the efficacy and efficiency of the disability management programs . Cochrane , PubMed , Google Scholar , and Web of Science were search ed from 1994 to 2015 . METHODS Two review ers independently evaluated the articles on title , abstract , and full text . The data extraction and results are documented according to the study design s. RESULTS Twenty-eight articles were included in the review . These 28 articles consisted of 7 systematic review s , 3 r and omized controlled trials , 9 clinical trials , 4 mixed- method studies and 5 qualitative studies . CONCLUSIONS The DM program has shown to be effective and efficient . A consensus about the DM components is still not reached . Nevertheless , some components are emphasized more than others ; job accommodation , facilitation of transitional duty , communication between all stakeholders , health care provider advice , early intervention , and acceptance , goodwill and trust in the stakeholders , in the organization , and in the disability management process
|
[
"Background Stress-related disorders are widespread and responsible for high societal costs e.g. sick leave payment and reduced productivity . The aim of this study was to evaluate the effect of an intervention program on return to work or labour market . Methods In a controlled interventional study design we compared 72 emotionally distressed patients , who received support during 2006 , with 89 control individuals who had also been sick listed for emotional distress . Intervention was provided by trained psychologists and social workers who were in continuous dialog with the patients , providing counselling e.g. on decisions concerning resumption of work , support to families , participation in meetings with the workplace . Basically , the controls and the intervention group share the same access to welfare benefits . The main outcome was time to return to labour market ( TTR ) . Results The baseline characteristics were similar in the two groups . There were no differences in the rate of resuming work between the two groups . About 80 % in both groups had returned to the labour market after one year . Conclusion An intervention program with psychological stress management and case management did not improve work capability compared to usual care . Work resumption as a single outcome probably is an insensitive parameter of intervention management quality , and should be supplemented by other data on different aspects of treatment",
"BACKGROUND The high costs and the impact of work disability have become a growing concern for workplaces . As a result , workplace disability management approaches have been developed to lower disability costs , protect the employability of workers , and promote early return to work . METHODS A stratified r and om sample of 455 employers in education ( n = 157 ) , hotel/motel ( n = 110 ) , and health care ( n = 188 ) sectors who completed a mailed Organizational Policies and Practice s ( OPP ) question naire is reported . The OPP question naire asked questions about eight workplace disability management practice s. The article examined the multi-dimensionality , internal consistency , and discriminant validity of the OPP and compares disability management practice s across the three sectors . RESULTS The OPP question naire showed good internal consistency ( Cronbach 's alpha = 0.95 ) and discriminant validity . A one-way analysis of variance ( ANOVA ) for each of the eight subscales demonstrated that there were statistically significant differences between the sectors in ergonomic practice s ( F ( 2,452 ) = 15.8 , P disability case management ( F ( 2,452 ) = 4.6 , P return to work ( F ( 2,452 ) = 10.3 , P people-oriented culture ( F ( 2,452 ) = 4.5 , P OPP seems to be a promising instrument that can be used to assess and monitor how employers are managing disability",
"OBJECTIVE The aim of this study was to explore what characterizes patients receiving clinical interventions vs combined clinical and work-related interventions in a cohort of sick-listed subjects with musculoskeletal or mental disorders . Factors associated with return-to-work were also analysed . DESIGN A prospect i ve cohort study . METHODS A total of 699 newly sick-listed patients responded to a question naire on sociodemographics , measures of health , functioning , work ability , self-efficacy , social support , work conditions , and expectations . The 3-month follow-up question naire included patients ' self-reported measures of return-to-work , work ability and type of interventions . The most frequent International Classification of Diseases-10 diagnoses for patients ' musculoskeletal disorders were dorsopathies ( M50 - 54 ) and soft tissue disorders ( M70 - 79 ) , and for patients with mental disorders , depression ( F32 - 39 ) and stress reactions ( F43 ) . RESULTS Patients with mental disorders who received combined interventions returned to work to a higher degree than those who received only clinical intervention . The prevalence of work-related interventions was higher for those who were younger and more highly educated . For patients with musculoskeletal disorders better health , work ability and positive expectations of return-to-work were associated with return-to-work . However , combined interventions did not affect return-to-work in this group . CONCLUSION Receiving combined interventions increased the probability of return-to-work for patients with mental disorders , but not for patients with musculoskeletal disorders . Better health , positive expectations of return-to-work and better work ability were associated with return-to-work for patients with musculoskeletal disorders",
"Background The causes of prolonged disability due to back pain are multiply determined , involving medical , social , and environmental factors . Possible solutions to the problem of prolonged back pain disability have emerged from recent research but few efforts have been made to transfer evidence -based programs to large community setting s. Objective This article describes three phases of the process of transfer of evidence from rehabilitation research to community practice in the province of Quebec . Methods and Results Phase A : Based on literature review and expert knowledge , the Sherbrooke model was developed and assessed through a population -based , r and omized clinical trial . Results at 1-year follow-up showed quicker return to regular work and improvement of quality of life ; the 6-year follow-up showed the cost-effectiveness of the method .Phase B : Based on the Sherbrooke model experience and recent evidence , a new program addressing the disability paradigm was developed and implemented in the province of Quebec ( Canada ) . Results at 1- and 3-year follow-ups showed that only 24 % of workers were not working owing to their musculoskeletal disorder . The program is presently being tested through a population -based , r and omized clinical trial in a population of construction workers . Phase C : To implement the program at a provincial level , a network for management , research and education in work rehabilitation was developed . An external assessment is presently planned to evaluate return to work and economic outcomes and quality of implementation of the program in various setting",
"A multifaceted disability management program was instituted at an automotive manufacturing organization to control rising workers ' compensation costs . A pilot program showed major cost savings over a 9-month period . When total and component disability leave rates were calculated as a percentage of the available workforce and tracked on a weekly basis over the subsequent 3 years , total disability leave rates fell by nearly 50 % . This was largely attributable to an approximately 50 % decrease in the extended ( > 1-year ) disability leave rate and a 75 % decrease in the workers ' compensation leave rate . A novel approach to biostatistical analysis showed a good fit of weekly disability leave rates to a Poisson r and om variable distribution with an identifiable break point at about 1 1/2 years after observation for extended disability leaves and at 2 years for workers ' compensation leaves . This biostatistical approach may prove generalizable to tracking leave rates in other organizations",
"Sickness absenteeism caused by musculoskeletal disorders ( MSDs ) is a persistent and costly occupational health challenge . In a prospect i ve controlled trial , we compared the effects on sickness absenteeism of a more proactive role for insurance case managers as well as workplace ergonomic interventions with that of traditional case management . Patients with physician-diagnosed MSDs were r and omized either to the intervention group or the reference group offered the traditional case management routines . Participants filled out a comprehensive question naire at the initiation of the study and after 6 months . In addition , administrative data were collected at 0 , 6 , and 12 months after the initiation of the project . For the entire 12-month period , the total mean number of sick days for the intervention group was 144.9 ( SEM 11.8 ) days/person as compared to 197.9 ( 14.0 ) days in the reference group ( P complete rehabilitation investigation ( 84 % versus 27 % ) . The time for doing this was reduced by half ( 59.4 ( 5.2 ) days versus 126.8 ( 19.2 ) , P odds ratio for returning to work in the intervention group was 2.5 ( 95 % confidence interval 1.2–5.1 ) as compared with the reference group . The direct cost savings were USD 1195 per case , yielding a direct benefit-to-cost ratio of 6.8 . It is suggested that the management of MSDs should to a greater degree focus on early return to work and building on functional capacity and employee ability . Allowing the case managers a more active role as well as involving an ergonomist in workplace adaptation meetings might also be beneficial",
"Study design . Population -based r and omized controlled trial . Objective . To assess the effectiveness of workplace intervention and grade d activity , separately and combined , for multidisciplinary rehabilitation of low back pain ( LBP ) . Summary of Background Data . Effective components for multidisciplinary rehabilitation of LBP are not yet established . Methods . Participants sick-listed 2 to 6 weeks due to nonspecific LBP were r and omized to workplace intervention ( n = 96 ) or usual care ( n = 100 ) . Workplace intervention consisted of workplace assessment , work modifications , and case management involving all stakeholders . Participants still sick-listed at 8 weeks were r and omized for grade d activity ( n = 55 ) or usual care ( n = 57 ) . Grade d activity comprised biweekly 1-hour exercise sessions based on operant-conditioning principles . Outcomes were lasting return to work , pain intensity and functional status , assessed at baseline , and at 12 , 26 , and 52 weeks after the start of sick leave . Results . Time until return to work for workers with workplace intervention was 77 versus 104 days ( median ) for workers without this intervention ( P = 0.02 ) . Workplace intervention was effective on return to work ( hazard ratio = 1.7 ; 95 % CI , 1.2–2.3 ; P = 0.002 ) . Grade d activity had a negative effect on return to work ( hazard ratio = 0.4 ; 95 % CI , 0.3–0.6 ; P functional status . Combined intervention had no effect . Conclusion . Workplace intervention is advised for multidisciplinary rehabilitation of subacute LBP . Grade d activity or combined intervention is not advised"
] |
4116c72a-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND Balance training may be beneficial for patients with osteoporosis , although current results are inconclusive . The aim of this systematic review and meta- analysis was to explore the effect of balance training on falls in patients with osteoporosis . METHODS PubMed , Embase , Web of Science , EBSCO , and Cochrane Library data bases were systematic ally search ed . R and omized controlled trials ( RCTs ) assessing the effect of balance training vs usual activities on falls in patients with osteoporosis were included . Two investigators independently search ed articles , extracted data , and assessed the quality of included studies . The primary outcome was fall frequency . This meta- analysis was performed using the fixed- or r and om-effect model when appropriate . RESULTS Six RCTs were included in the systematic review and 3 in the meta-analyses . Compared with control groups , a balance training intervention was found to significantly reduce the frequency of falls ( risk ratio = 0.63 ; 95 % confidence interval ( 95 % CI ) 0.42 - 0.95 ; p = 0.03 ) in patients with osteoporosis , but demonstrated no remarkable influence on the results of the Berg Balance Scale ( mean difference -3.66 ; 95 % CI -12.04 - 4.72 ; p = 0.39 ) and Timed Up and Go test ( mean difference -1.79 ; 95 % CI -6.05 - 2.47 ; p = 0.41 ) . CONCLUSION Balance training may significantly reduce the frequency of falls in patients with osteoporosis
|
[
"Poor balance is one of the most common risk factors for falling , a common cause of work-related injury and death . To evaluate the effects of a 10-week intervention program on balance in older adults , 12 participants aged 61–77 years ( age = 70.4 ± 5.4 years ; mean ± SD ) completed an exercise program ( 60 min , 2 days · week−1 for 10 weeks ) performed while laying/sitting on large air-filled exercise balls ( Thera-B and ® ) . Several postural sway composite scores ( determined while st and ing with feet apart and semit and em , eyes open and closed ) improved ( p ≤ 0.05 ) including medial – lateral amplitude and speed of sway ( reduced by ∼9 % ) , and instantaneous speed ( reduced by ∼13 % ) . Reductions in XY area approached ( p = 0.06 ) statistical significance and anterior – posterior amplitude and speed of sway did not change . Functional reach also improved ( 20.3 % ) . These results suggest that challenging the physiological systems involved in balance control while on the nonstable support surface of the exercise balls improves both static and dynamic balance in older adults and may reduce the risk for falling",
"Objective : To investigate the effect of a 12-month sensomotor balance exercise programme on postural control and the frequency of falling in women with established osteoporosis . Design : R and omized controlled trial where the intervention group was assigned the 12-month Balance Training Programme and the control group did not undertake any intervention beyond regular osteoporosis treatment . Subjects : A total of 100 osteoporotic women – at least with one osteoporotic fracture – aged 65 years old and above . Main measures : Balance was assessed in static and dynamic posture both with performance-based measures of balance , such as the Berg Balance Scale and the Timed Up and Go Test , and with a stabilometric computerized platform . Interventions : Patients in the intervention group completed the 12-month sensomotor Balance Training Programme in an outpatient setting , guided by physical therapists , three times a week , for 30 minutes . Results : The Berg Balance Scale and the Timed Up and Go Test showed a statistically significant improvement of balance in the intervention group ( p = 0.001 and p = 0.005 , respectively ) . Balance tests using the stabilometer also showed a statistically significant improvement in static and dynamic postural balance for osteoporotic women after the completion of the Balance Training Programme . As a consequence , the one-year exercise programme significantly decreased the number of falls in the exercise group compared with the control group . Conclusion : The Balance Training Programme significantly improved the balance parameters and reduced the number of falls in postmenopausal women who have already had at least one fracture in the past",
"Abstract Objectives To evaluate postoperative medical complications and the association between these complications and mortality at 30 days and one year after surgery for hip fracture and to examine the association between preoperative comorbidity and the risk of postoperative complications and mortality . Design Prospect i ve observational cohort study . Setting University teaching hospital . Participants 2448 consecutive patients admitted with an acute hip fracture over a four year period . We excluded 358 patients : all those aged Interventions Routine care for hip fractures . Main outcome measures Postoperative complications and mortality at 30 days and one year . Results Mortality was 9.6 % at 30 days and 33 % at one year . The most common postoperative complications were chest infection ( 9 % ) and heart failure ( 5 % ) . In patients who developed postoperative heart failure mortality was 65 % at 30 days ( hazard ratio 16.1 , 95 % confidence interval 12.2 to 21.3 ) . Of these patients , 92 % were dead by one year ( 11.3 , 9.1 to 14.0 ) . In patients who developed a postoperative chest infection mortality at 30 days was 43 % ( 8.5 , 6.6 to 11.1 ) . Significant preoperative variables for increased mortality at 30 days included the presence of three or more comorbidities ( 2.5 , 1.6 to 3.9 ) , respiratory disease ( 1.8 , 1.3 to 2.5 ) , and malignancy ( 1.5 , 1.01 to 2.3 ) . Conclusions In elderly people with hip fracture , the presence of three or more comorbidities is the strongest preoperative risk factor . Chest infection and heart failure are the most common postoperative complications and lead to increased mortality . These groups offer a clear target for specialist medical assessment",
"Background and Purpose : We have developed a 12-week balance training program for older adults shown to improve fall-related concerns , gait speed , balance performance , and physical function . We hypothesized that this balance training would also contribute to higher habitual physical activity ( PA ) levels and improved health-related quality of life ( HRQoL ) . The primary aim was to evaluate short- and long-term effects of the balance training program on objective ly measured habitual PA in older adults with osteoporosis . Secondary aims were to assess the effects of the balance training on HRQoL , and to study whether any effects on PA were associated with changes in HRQoL , gait speed , balance performance , fall-related concerns , and physical function . Methods : A r and omized controlled trial with follow-up at 3 , 9 , and 15 months , including 91 participants with osteoporosis ( 75.6 ± 5.4 years ) , compared a balance training group ( n = 61 ) with a control group ( n = 30 ) . The primary outcome was effect on habitual PA measured as steps/day , dichotomized into less than 5000 or 5000 or more steps/day . Physical activity was assessed with pedometers ( Yamax ) and accelerometers ( Actigraph ) , HRQoL with the Short Form-36 ( SF-36 ) , gait with a GAITRite walkway , balance performance with Modified-Figure-Eight test and one-leg stance , fall-related concerns with Falls Efficacy Scale International , and physical function with the advanced lower extremity subscale of the question naire Late Life Function and Disability Instrument . Statistical methods used were multivariate logistic regression and logistic generalized estimating equation . Results : Sixty-eight participants completed the short-term follow-up at 3 months , and 53 participants completed the long-term follow-up at 15 months . Per- protocol analysis ( n = 68 ) showed that the odds ratio for having a daily step count of 5000 or more at 3 months was 6.17 ( 95 % confidence interval , 1.23 - 30.91 ) , P = .027 , for the intervention group compared with the control group . The longitudinal analysis ( n = 91 ) showed that the odds ratio for having a daily step count of 5000 or more at 15 months was 2.02 ( 95 % confidence interval , 0.88 - 4.64 ) , P = .096 , for the intervention group compared with the control group . The mental component sum of the SF-36 improved significantly from baseline to 3 months in the intervention group , and the physical component sum improved in both groups , but no statistically significant differences were found between groups . No associations were found between PA and changes in covariates . Discussion and Conclusions : The short-term evaluation showed that balance training increased habitual PA in community-dwelling older adults with osteoporosis . A significantly higher proportion of participants in the intervention group reached a level of 5000 or more steps/day , which is important for overall health . This effect was not associated with improvements in HRQoL , gait speed , balance performance , or fall-related concerns , and did not persist through the long-term follow-up . To accomplish a sustained PA change , a prolonged intervention or more support regarding habitual PA may be required , such as reinforcement with personalized behavior change counseling or PA on prescription",
"Introduction The purpose of this study was to investigate the effect of a 12-month Balance Training Program on balance , mobility and falling frequency in women with osteoporosis . Methods Sixty-six consecutive elderly women were selected from the Osteometabolic Disease Outpatient Clinic and r and omized into 2 groups : the ‘ Intervention ’ , su bmi tted for balance training ; and the ‘ Control ’ , without intervention . Balance , mobility and falling frequency were evaluated before and at the end of the trial , using the Berg Balance Scale ( BBS ) , the Clinical Test Sensory Interaction Balance ( CTSIB ) and the Timed “ Up & Go ” Test ( TUGT ) . Intervention used techniques to improve balance consisting of a 1-hour session each week and a home-based exercise program . Results Sixty women completed the study and were analyzed . The BBS difference was significant higher in the Intervention group compared to Control ( 5.5 ± 5.67 vs −0.5 ± 4.88 score , p two conditions of CTSIB compared to Control ( eyes closed and unstable surface condition : 13 vs one patient , p between the TUGT were reduced in the Intervention group compared to Control ( −3.65 ± 3.61 vs 2.27 ± 7.18 seconds , p the number of falls/patient in the Intervention group compared to Control ( −0.77 ± 1.76 vs 0.33 ± 0.96 , p = 0.018 ) . Conclusion This longitudinal prospect i ve study demonstrated that an intervention using balance training is effective in improving functional and static balance , mobility and falling frequency in elderly women with osteoporosis",
"Study design A thematic review . Objectives To evaluate if physical activity enhances muscle strength , improves balance , and reduces the fall frequency and the fracture incidence . Background One of the major medical problems of today is the increasing incidence of fragility fractures . Muscle strength and fall is one of the major determinants of a fracture . If physical activity could increase muscle strength , improve balance and reduce the fall frequency , then training could be recommended as prevention for fractures . Methods The review used Medline ( Pub Med ) and the search words exercise , physical activity , muscle strength , balance , falls , fractures . R and omized controlled trials ( RCT ) were predominantly included , although this not is a systematic review . Results The evidence that physical activity modifies the risk factors for fall is compelling , although RCT with fractures as end point are lacking . Physical activity is associated with improved muscle strength , co-ordination and balance . Physical training increases muscle strength also in octogenarians by up to 200 % , i.e. a much more pronounced effect than the corresponding increase in muscle volume or bone mass . There is also evidence that physical activity decreases the actual number of falls . Observational cohort and case-control studies imply that physical activity is associated with reduced hip fracture risk . If exercise reduces the number of vertebral fractures and other fragility fractures are less evaluated . Conclusions Physical activity in older ages can be recommended to improve muscle strength and balance , to reduce the risk to fall and fractures , although the highest level of evidence – RCT with fracture as endpoint – is lacking",
"OBJECTIVE To determine the short-term effectiveness of a biofeedback-based , computerized intervention that applied the principles of the ecological theory of perception and control of bodily orientation to the rehabilitation of older adults with a history of falling . PARTICIPANTS Forty-five older adults ( X = 78.5 years ) with a history of falls were assigned to either a control ( n = 21 ) or intervention group ( n = 24 ) . DESIGN A 2 x 2 ( Group x Time ) mixed factorial design with repeated measures on the second factor . SETTING A motor control research laboratory in a university setting . MEASUREMENT Impairments in multiple dimensions of balance ( i.e. , dynamic postural control and sensory organization ) were measured before and after an 8-week balance intervention using the 100 % Limits of Stability Test and Sensory Organization Test . More functional limitations in balance and /or mobility were measured using two clinical tests : Berg Balance Scale and Timed Up and Go test . MAIN RESULTS Repeated measures multivariate analyses and follow-up testing indicated significant improvements in the dynamic balance and sensory integration capabilities in the case of the intervention group only ( P clinical measures of balance and mobility evaluated before and after the intervention for the intervention group only . CONCLUSIONS Theory-driven rehabilitation programs that focus on manipulating individual , task , and environmental constraints concurrently can significantly improve the control of bodily orientation of older adults with a previous history of falls in both static and dynamic action environments . Moreover , the significant improvements in functional performance observed for the intervention group suggest that interventions emphasizing task-specific practice are not the only means by which an older adult 's ability to perform daily activities requiring postural control can be improved",
"Abstract : To examine longitudinal change in health- related quality of life ( HRQoL ) following hip fracture in elderly subjects , 32 patients with hip fractures and 29 sex-matched non-fracture control subjects ( mean ± SD age 82 ± 8 and 86 ± 6 years respectively ) were enrolled in a prospect i ve , case – control study . Fracture subjects completed a generic question naire , Short Form 36 ( SF-36 ) , and a disease-targeted measure , the revised Osteoporosis Assessment Question naire ( OPAQ2 ) , on two separate occasions , within 1 week of fracture and 12–15 weeks after fracture . Controls completed both question naires on two occasions 12 weeks apart . SF-36 scores were significantly correlated with OPAQ2 in comparable domains of Physical Function ( r= 0.76 ) , General Health ( r= 0.70 ) and Mental Health/Tension ( r = 0.86 ) . Control subjects had stable scores with the OPAQ2 and SF-36 . At 3 months after fracture there was a significant reduction in HRQoL in the SF-36 domains Physical Function ( –51 % ) , Vitality ( –24 % ) and Social Function ( –26 % ) and in the OPAQ2 domains Physical Function ( –20 % ) , Social Activity ( –49 % ) and General Health ( –24 % ) . Hip fracture patients thus had a lower baseline HRQoL and experienced a significant deterioration in HRQoL after hip fracture on both the SF-36 and OPAQ2 . HRQoL should be part of a comprehensive assessment of the costs of osteoporosis including fracture-associated morbidity",
"Background Although older adults are disproportionately affected by painful musculoskeletal conditions and receive more opioid analgesics than persons in other age groups , insufficient evidence is available regarding opioid harms in this age group . Objective To examine longitudinal relationships between opioid use and falls , clinical fractures , and changes in physical performance . We hypothesized that opioid use would be associated with greater risks of falling and incident clinical fractures and greater declines in physical performance . Design We analyzed data from the Osteoporotic Fractures in Men Study ( MrOS ) , a large prospect i ve longitudinal cohort study . Participants completed baseline visits from 2000 to 2002 and were followed for 9.1 ( SD 4.0 ) years . Participants MrOS enrolled 5994 community-dwelling men ≥ 65 years of age . The present study included 2902 participants with back , hip , or knee pain most or all of the time at baseline . Main Measures The exposure of interest was opioid use , defined at each visit as participant-reported daily or near-daily use of any opioid-containing analgesic . Among patients , 309 ( 13.4 % ) reported opioid use at one or more visits . Participants were queried every 4 months about falls and fractures . Physical performance scores were derived from tests of grip strength , chair st and s , gait speed , and dynamic balance . Key Results In the main analysis , the adjusted risk of falling did not differ significantly between opioid use and non-use groups ( RR 1.10 , 95 % CI 0.99 , 1.24 ) . Similarly , adjusted rates of incident clinical fracture did not differ between groups ( HR 1.13 , 95 % CI 0.94 , 1.36 ) . Physical performance was worse at baseline for the opioid use group , but annualized change in physical performance scores did not differ between groups ( −0.022 , 95 % CI −0.138 , 0.093 ) . Conclusions Additional research is needed to determine whether opioid use is a marker of risk or a cause of falls , fractures , and progressive impairment among older adults with persistent pain",
"BACKGROUND AND PURPOSE Traditionally , rehabilitation programs emphasize training balance under single-task conditions to improve balance and reduce risk for falls . The purpose of this case report is to describe 3 balance training approaches in older adults with impaired balance . CASE DESCRIPTIONS Three patients were r and omly assigned to 1 of 3 interventions : ( 1 ) single-task balance training , ( 2 ) dual-task training under a fixed-priority instructional set , and ( 3 ) dual-task training under a variable-priority instructional set . OUTCOMES The patients who received balance training under dual-task conditions showed dual-task training benefits ; these training benefits were maintained for 3 months . The patient who received variable-priority training showed improvement on novel dual tasks . DISCUSSION Older adults may be able to improve their balance under dual-task conditions only following specific types of balance training . This case report gives insight on how this intervention might be combined with more traditional physical therapy intervention",
"Objective —To test the efficacy of a community based 10 week exercise intervention to reduce fall risk factors in women with osteoporosis . Methods —Static balance was measured by computerised dynamic posturography ( Equitest ) , dynamic balance by timed figure of eight run , and knee extension strength by dynamometry . Subjects were r and omised to exercise intervention ( twice weekly Osteofit classes for 10 weeks ) or control groups . Results —The outcome in 79 participants ( 39 exercise , 40 control ) who were available for measurement 10 weeks after baseline measurement is reported . After confounding factors had been controlled for , the exercise group did not make significant gains compared with their control counterparts , although there were consistent trends toward greater improvement in all three primary outcome measures . Relative to the change in control subjects , the exercise group improved by 2.3 % in static balance , 1.9 % in dynamic balance , and 13.9 % in knee extension strength . Conclusions —A 10 week community based physical activity intervention did not significantly reduce fall risk factors in women with osteoporosis . However , trends toward improvement in key independent risk factors for falling suggest that a study with greater power may show that these variables can be improved to a level that reaches statistical significance",
"Objective : To compare the efficacy of balance training associated with muscle strengthening or stretching , relative to no intervention , in the postural control of elderly women with osteoporosis . Design : A r and omized , controlled trial . Subjects and interventions : Sample consisted of 50 women aged 65 years or older , with osteoporosis , r and omized into one of three groups : strengthening group ( n = 17 ) performed balance training with muscle strengthening ; stretching group ( n = 17 ) performed balance training with stretching ; and control group ( n = 16 ) , no activities . Interventions lasted eight weeks , twice a week , 60 minutes a day . Main measures : Postural control was evaluated by the modified Clinical Test of Sensory Interaction for Balance ( CTSIBm ) and Limits of Stability Test . Strength was assessed by dynamometry and the shortening of the hamstrings by goniometry . Results : Relative to controls , participants in the strengthening group displayed significantly increased dorsiflexion strength and knee flexion strength , as well as centre of pressure velocity , directional control , and oscillation velocity ( CTSIBm test ) . The stretching group had significantly improvements in hamstring length , knee flexion strength , centre of pressure velocity , and amplitude of movements . Relative to the stretching group , the strengthening group yielded better knee extension strength and directional control . Conclusion : The results suggest that both interventions are effective in improving postural control when compared to the control group , and the strengthening group was superior to the stretching group in knee extension strength and in directional control ",
"OBJECTIVE Physical and psychological incapacity , including fear of falling is related to decreased satisfaction with life in osteoporosis ( OP ) . The impact of a balance exercise program on improving the quality of life is not well established . We have , therefore , investigated the effect of 12-month Balance Training Program in quality of life , functional balance and falls in elderly OP women . METHODS Sixty consecutive women with senile OP were r and omized into a Balance Training Group ( BT ) of 30 patients and no intervention control group ( CG ) of 30 patients . The BT program included techniques to improve balance over a period of 12 months ( 1h exercise session/week and home-based exercises ) . The quality of life was evaluated before and at the end of the trial using the Osteoporosis Assessment Question naire ( OPAQ ) , functional balance was evaluated by Berg Balance Scale ( BBS ) . Falls in the preceding year were noted and compared to the period of study . RESULTS The comparison of OPAQ variations ( INITIAL-FINAL ) revealed a significant improvement in quality of life in all parameters for BT compared to CG : well-being ( 1.61+/-1.44 vs. -1.46+/-1.32 , p physical function ( 1.30+/-1.33 vs. -0.36+/-0.82 , p psychological status ( 1.58+/-1.36 vs. -1.02+/-0.83 , p symptoms ( 2.76+/-1.96 vs. -0.63+/-0.87 , p social interaction ( 1.01+/-1.51 vs. 0.35+/-1.08 , p BBS ( -5.5+/-5.67 vs. + 0.5+/-4.88 p of falls in 50 % in BT group vs. 26.6 % for the CG ( RR : 1.88 , p OP women provides a striking overall health quality of life improvement in parallel with improving functional balance and reduced falls",
"Falls are common in elderly people . Possible consequences include serious injuries and the post-fall syndrome , with functional decline and limitation of physical activity . The present r and omized controlled study sought to clarify the benefits of a combined long-term and home-based fall prevention program for elderly Japanese women . The subjects were individuals aged over 73 years , living at home in a western suburb of Tokyo , who had attended a comprehensive geriatric health check . Persons with a marked decline in the basic activities of daily living ( ADL ) , hemiplegia , or those missing baseline data were excluded . Fifty-two subjects who expressed a wish to participate in the trial were r and omized , 28 to an exercise-intervention group and 24 to a control group . Baseline data for age , h and grip force , walking speed , total serum cholesterol , serum albumin , basic ADL , visual and auditory impairments , self-rated health , and experience of falls did not differ significantly between the two groups . Beginning from June 2000 , the intervention group attended a 6-month program of fall-prevention exercise classes aim ed at improving leg strength , balance , and walking ability ; this was supplemented by a home-based exercise program that focused on leg strength . The control group received only a pamphlet and advice on fall prevention . The average rate of attendance at exercise class was 75.3 % ( range , 64 % to 86 % ) . Participants showed significant improvements in t and em walk and functional reach after the intervention program , with enhanced self confidence . At the 8-month follow-up , the proportion of women with falls was 13.6 % ( 3/22 ) in the intervention group and 40.9 % ( 9/22 ) in the control group . At 20 months , the proportion remained unchanged , at 13.6 % in the intervention group , but had increased to 54.5 % ( 12/22 ) in the control group , which showed a statistically significant difference between the two groups ( Fisher ’s exact test ; P = 0.0097 ) . The total number of falls during the 20-month follow-up period was 6 in the intervention group and 17 in the control group . We conclude that a moderate exercise intervention program plus a home-based program significantly decreases the incidence of falls in both the short and the long term , contributing to improved health and quality of life in the elderly"
] |
4116c766-06ff-11f0-808a-c43d1ab1c353
|
Aims The aim of this systematic review was to report the rate of dislocation following the use of dual mobility ( DM ) acetabular components in primary and revision total hip arthroplasty ( THA ) . Material s and Methods A systematic review of the literature according to the Preferred Reporting Items for Systematic Review s and Meta‐analyses guidelines was performed . A comprehensive search of Pubmed / Medline , Cochrane Library and Embase ( Scopus ) was conducted for English articles between January 1974 and March 2016 using various combinations of the keywords “ dual mobility ” , “ dual‐mobility ” , “ tripolar ” , “ double‐mobility ” , “ double mobility ” , “ hip ” , “ cup ” , “ socket ” . The following data were extracted by two investigators independently : demographics , whether the operation was a primary or revision THA , length of follow‐up , the design of the components , diameter of the femoral head , and type of fixation of the acetabular component . Results In all , 59 articles met our inclusion criteria . These included a total of 17 908 THAs which were divided into two groups : studies dealing with DM components in primary THA and those dealing with these components in revision THA . The mean rate of dislocation was 0.9 % in the primary THA group , and 3.0 % in the revision THA group . The mean rate of intraprosthetic dislocation was 0.7 % in primary and 1.3 % in revision THAs . Conclusion Based on the current data , the use of DM acetabular components are effective in minimising the risk of instability after both primary and revision THA . This benefit must be balanced against continuing concerns about the additional modularity , and the new mode of failure of intraprosthetic dislocation . Longer term studies are needed to assess the function of these newer material s compared with previous generations
|
[
"The two senior authors ( PMP , RP ) independently began using an identical enhanced posterior soft tissue repair after total hip replacement through a posterior approach . In the first author 's experience , a dislocation rate of 4 % in 395 patients before using the enhanced closure was reduced to 0 % in 395 patients in whom the enhanced closure was performed . In the second author 's experience , 160 total hip replacements had a dislocation rate of 6.2 % before the enhanced closure whereas 124 total hip replacements had a dislocation rate of 0.8 % after the enhanced closure . These results are highly statistically significant",
"Introduction The causes for revision of primary total hip arthroplasty ( THA ) are various and quite well known . The developing use of dual-mobility THA ( DM-THA ) seems a relevant option to decrease the risk of instability . Due to lack of long-term follow-up , this innovative retentive concept is suspected to increase the risk of polyethylene ( PE ) wear . the aim of the study was to analyse the causes for DM-THA revision and assess whether or not its occurrence is different from that of fixed-st and ard ( FS ) THA , particularly for aseptic loosening or wear and /or osteolysis . Material s and methods The SoFCOT group conducted an observational prospect i ve multicentre study from 1 January 2010 to 31 December 2011 . Inclusion criteria comprised an exhaustive collection of 2044 first-revision THAs with 251 DM-THAs and 1793 FS-THAs . After excluding complications linked to patient factors ( infection and periprosthetic fractures ) , we performed a matched case – control study ( matching ratio 1:1 ) comparing two groups of 133 THAs . Results Revisions for aseptic loosening or osteolysis/wear were as frequent in DM-THA ( 58.7 % ) as in FS-THA ( 57.1 % ) ( p 0.32 ) ; 7.5 % of DM-THA were revised for dislocation versus 19.5 % of FS-THA ( p 0.007 ) . Discussion Revision for osteolysis/wear and aseptic loosening were as frequent in DM-THA as in FS-THA ; revision for dislocation was less frequent in DM-THA . This confirms the efficiency of the DM concept regarding the risk of dislocation . Causes for revision were different between groups , and revisions for dislocation were less frequent in DM-THA . Only prospect i ve comparative studies could provide reliable information that may support broader use of the DM concept",
"The current study aim ed to evaluate the outcome of a continuous and prospect i ve series of 61 revision THAs with AAOS grade III and IV acetabular bone defect reconstruction using a Kerboull cross-plate , structural allograft and cemented dual mobility cup ( Saturne , Amplitude , Valence , France ) . At a 7.5-year mean follow-up , no instability was reported after revision . In addition , no failure of the acetabular reconstruction was observed in 98 % of the patients with complete allograft osseointegration and no evidence of mechanical rupture of the Kerboull cross-plate and /or loosening of the cemented dual mobility cup . In conclusion , such reconstruction technique demonstrated excellent results at mid-term follow-up in terms of prevention of instability after revision , restoration of the acetabular bone stock , and stable cemented fixation of the dual mobility cup",
"BACKGROUND The use of larger femoral heads has been proposed to reduce the risk of dislocation after total hip arthroplasty , but there is a lack of evidence to support this proposal . The aim of this multicenter r and omized controlled trial was to determine whether the incidence of dislocation one year after total hip arthroplasty is significantly lower in association with the use of a 36-mm femoral head articulation as compared with a 28-mm articulation . METHODS Six hundred and forty-four middle-aged and elderly patients undergoing primary or revision arthroplasty were r and omized intraoperatively to receive either a 36 or 28-mm metal femoral head on highly cross-linked polyethylene . Patients who were at high risk of dislocation ( including those with dementia and neuromuscular disease ) and those undergoing revision for the treatment of recurrent hip dislocation or infection were excluded . Patients were stratified according to other potential risk factors for dislocation , including diagnosis and age . Diagnosis of hip dislocation required confirmation by a physician and radiographic evidence of a dislocation . RESULTS Overall , at one year of follow-up , hips with a 36-mm femoral head articulation had a significantly lower incidence of dislocation than did those with a 28-mm articulation ( 1.3 % [ four of 299 ] compared with 5.4 % [ seventeen of 316 ] ; difference , 4.1 % [ 95 % confidence interval , 1.2 % to 7.2 % ] ) when controlling for the type of procedure ( primary or revision ) ( p = 0.012 ) . The incidence of dislocation following primary arthroplasty was also significantly lower for hips with a 36-mm femoral head articulation than for those with a 28-mm articulation ( 0.8 % [ two of 258 ] compared with 4.4 % [ twelve of 275 ] ; difference , 3.6 % [ 95 % confidence interval , 0.9 % to 6.8 % ] ) ( p = 0.024 ) . The incidence of dislocation following revision arthroplasty was 4.9 % ( two of forty-one ) for hips with a 36-mm articulation and 12.2 % ( five of forty-one ) for hips with a 28-mm articulation ; this difference was not significant with the relatively small sample size of the revision group ( difference , 7.3 % [ 95 % confidence interval , -5.9 % to 21.1 % ] ) ( p = 0.273 ) . CONCLUSIONS Compared with a 28-mm femoral head articulation , a larger 36-mm articulation result ed in a significantly decreased incidence of dislocation in the first year following primary total hip arthroplasty . However , before a 36-mm metal-on-highly cross-linked polyethylene articulation is widely recommended , the incidence of late dislocation , wear , periprosthetic osteolysis , and liner fracture should be established",
"Dislocation is a leading cause of revision after total hip arthroplasty ( THA ) . To address this risk , dual-mobility technology was developed , which features a mobile polyethylene liner locked onto a femoral head and articulating in a metallic acetabular shell . This study reports clinical outcome data after implantation of the third-generation POLARCUP Dual-Mobility System ( Smith & Nephew Orthopaedics AG , Rotkreuz , Switzerl and ) . Primary THA procedures were performed in 150 patients . At 7.1 years , cumulative cup survival according to Kaplan-Meier was 97.4 % . The mean Postel-Merle d'Aubigne score improved from 8.9 to 17.1 during the investigation . Two cups were revised at 5.4 and 6.4 years because of aseptic loosening . No dislocations were observed during follow-up . The current results confirm excellent early to midterm clinical outcomes for the POLARCUP Dual-Mobility System",
"Use of a dual-mobility acetabular cup is associated with a lower risk of dislocation compared with conventional hip implants . The seleXys ® DS acetabular cup combines the advantages of Charnley low-friction arthroplasty with those of dual mobility . We performed a non-r and omised , prospect i ve study of patients receiving primary hip arthroplasty , including an uncemented seleXys ® DS dual-mobility acetabular cup with hydroxyapatite coating ( Mathys AG , Bettlach , Switzerl and ) and a cemented femoral component ( Stallion femoral stem Groupe Lepine , Lyon , France ) . The objective of the study was to evaluate longevity of the implant and the risk of dislocation . All operations were performed by a single surgeon using a posterior approach , with patients lying in the lateral decubitus position . The stem had a modular head diameter of 22.2 mm and was cemented in all patients . A total of 53 patients were studied , and the median duration of follow-up was 78.9 months . Implant survival 6 years after surgery was 98.4 % ( n=47 ; 95 % CI : 89.3–99.8 ) . There was one revision for sepsis 29 months after surgery , and one dislocation . The results of this study appear to demonstrate excellent implant survival and a low rate of dislocation using the chosen implants",
"INTRODUCTION Displaced fractures of the femoral neck in the elderly are best treated with arthroplasty . The type of arthroplasty to be used , either hemi- or total hip arthroplasty , remains controversial as total hip replacements potentially have a higher rate of dislocation . HYPOTHESIS Dual mobility cups have a low dislocation rate when used to manage acute fractures of the femoral neck . PATIENTS AND METHODS In a multicenter prospect i ve study conducted in France over an inclusion time of 3 months , all displaced fractures of the femoral neck treated with arthroplasty were operated on with insertion of a dual mobility cup . Patients had clinical and radiological assessment at 3 , 6 , and 9 months postoperative . RESULTS Two hundred and fourteen hips in 214 patients with a mean age of 83 years ( range , 70 - 103 years ) were included . None of the patients was lost to follow-up . The mortality rate after 9 months was 19 % . Two patients ( 1 % ) had early postoperative infection successfully treated with lavage and antibiotics . Three patients ( 1.4 % ) , operated through a posterior approach , presented one postoperative dislocation , all of which were posterior . Reduction was performed through closed external manipulation under general anesthesia . There was no recurrence of dislocation . DISCUSSION This low rate of dislocation after acute total hip replacement using dual mobility design cups favorably compares with hemiarthroplasties . Dual mobility cups might therefore be considered a valuable option to prevent postoperative dislocation when treating displaced intracapsular fractures of the proximal femur in elderly patients if a total hip replacement is recommended . Further study is needed before extending the indications for total hip arthroplasty following a fracture of the femoral neck , to assess the potential cost and complications of a longer procedure with its potential acetabular complication , and weigh them against the potential benefits",
"UNLABELLED The outcome of a single design of dual mobility cup was prospect ively evaluated in a continuous series of 994 revision THAs with respect to dislocation and intra-prosthetic dislocation ( IPD ) . At a 7.3-year mean follow-up , the dislocation rate was 1.5 % and the IPD rate was 0.2 % . The 2 IPD occurred in acetabular-only revisions and were related to a poor head-to-neck ratio with early impingement and wear at the polyethylene mobile component chamfer . Dual mobility cups demonstrated a low dislocation rate in revision THA but did not compensate for potential perioperative technical errors . In addition , IPD did not appear to be a concern with respect to the benefit in term of instability prevention though caution is advised in acetabular-only revision associated with a poor head-to-neck ratio . LEVEL OF EVIDENCE Therapeutic study -Level IV",
"Background Dislocation after revision THA is a common complication . Large heads have the potential to decrease dislocation rate , but it is unclear whether they do so in revision THA . Questions / purpose sWe therefore determined whether a large femoral head ( 36 and 40 mm ) result ed in a decreased dislocation rate compared to a st and ard head ( 32 mm ) . Methods We r and omized 184 patients undergoing revision THA to receive either a 32-mm head ( 92 patients ) or 36- and 40-mm head ( 92 patients ) and stratified patients by surgeon . The two groups had similar baseline demographics . The primary end point was dislocation . Quality -of-life ( QOL ) measures were WOMAC and SF-36 . The mean followup for dislocation was 5 years ( range , 2–7 years ) ; the mean followup for QOL was 2.2 years ( range , 1.6–4 years ) . Results In the 36- and 40-mm head group , the dislocation rate was 1.1 % ( one of 92 ) versus 8.7 % ( eight of 92 ) for the 32-mm head . There was no difference in QOL outcomes between the two groups . Conclusions Our observations confirm a large femoral head ( 36 or 40 mm ) reduces dislocation rates in patients undergoing revision THA at short-term followup . We now routinely use large heads with a highly crosslinked polyethylene acetabular liner in all revision THAs . Level of Evidence Level I , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence",
"Background Isolated acetabular revisions using st and ard cups are at risk of dislocation . The introduction of a nonconstrained dual-mobility cup was design ed to improve prosthetic stability without increasing loosening rates , but it is unclear whether the risk of dislocation is reduced . Questions / purpose sWe therefore determined : ( 1 ) if the rate of dislocation in isolated acetabular revisions is lower with a dual-mobility cup , ( 2 ) implant survival , ( 3 ) patient function , and ( 4 ) radiographic incidence of migration , loosening , and osteolysis . Methods We prospect ively followed 33 selected patients who underwent isolated acetabular revisions with a minimum of 2 years ’ followup ( mean , 3 years ; range , 2–5 years ) . In 24 patients a stainless steel dual-mobility cup was cemented into an antiprotrusio cage , whereas in nine we used a hyaluronan dual-mobility revision cup with a foramen hook and superior and posterior flanges screw fixations . We determined Harris hip ( HHS ) and WOMAC scores and examined radiographs for migration , loosening , and osteolysis . Results There were no dislocations . Survivorship rates of the femoral and acetabular components were 97 % at 5 years ; the rerevision rate for any reason was 3 % . At last followup , the mean HHS increased from 48 points preoperatively to 86 points . No patients had progressive osteolysis , component migration , or loosening on radiographs . Conclusion In this select group of isolated acetabular revisions , our data suggest the use of a dual-mobility cup reduced the risk of dislocation without increasing loosening from 2 to 5 years . Level of Evidence Level IV , therapeutic study . See the Guidelines for Authors for a complete description of levels of evidence",
"Purpose Dislocation is a frequent complication in total hip arthroplasty ( THA ) revision . Cup fixation is the second concern . In order to know outcomes at two years , we prospect ively followed a continuous series of 78 patients to demonstrate that cementless dual-mobility cup ( DMC ) used in revision THA is safe as regards dislocation risk and bone fixation . Method We enrolled 78 consecutive patients ( 79 cases ) in a prospect i ve study . Mean interval between index surgery and revision was 12.9 years . Mean age at revision was 75.5 years . Two types of cementless DMC were used : a st and ard DMC in 68 cases with low- grade bone defect ( Paprosky grade 1 and 2 ) , and a specific design reconstruction DMC in 11 cases with severe bone loss ( Paprosky grade 3 ) . Results At two years of follow-up , 68 patients were review ed ; four were lost to follow-up . , and six patients were deceased . We identified three types of situations at risk : st and ard risk ( 33 cases ) , Paprosky grade 1 or 2 ; medium risk ( 37 cases ) , revision for recurrent instability ( 21 ) , periprosthetic fractures ( 14 ) or severe loosening Paprosky grade 3 without femorotomy ( 2 ) ; high risk ( nine cases ) , revision for severe loosening with a femorotomy . One ( 1.3 % ) patient dislocated her hip at one month without recurrence . Revision rate for dislocation was 0 % ; two ( 2.7 % ) early mechanical failures occurred . Conclusion Considering outcomes of this series , cementless DMC can be suggested in THA revision surgery",
"BACKGROUND The treatment of dislocation following primary total hip arthroplasty usually requires the use of expensive hospital re sources and sometimes requires revision surgery . The hospital costs associated with treating this complication have not been previously analyzed , to our knowledge . The purpose of this study was to assess the financial impact of treating dislocations at our institution . METHODS Between 1997 and 2001 , 3671 patients underwent a total of 4054 consecutive primary total hip arthroplasties at our institution . The patients were prospect ively followed at regular intervals , and their follow-up data were recorded in an institutional total joint registry . Ninety-nine hips ( 2.4 % ) in ninety-nine patients dislocated . The costs to our institution to treat these dislocations were evaluated by determining the cost of each treatment episode required to reestablish hip stability and were expressed as the percent increase in cost compared with that of an uncomplicated primary total hip replacement . RESULTS Of the ninety-nine hips that dislocated , sixty-two ( 63 % ) remained stable after one or more closed reductions and thirty-seven ( 37 % ) ultimately required revision surgery . The hospital cost of each closed reduction episode represented 19 % of the hospital cost of an uncomplicated total hip replacement . When revision surgery was eventually needed , the average hospital costs of one or more closed reductions and the subsequent revisions represented 148 % of the hospital cost of an uncomplicated primary total hip replacement . CONCLUSIONS Dislocation after primary hip replacement continues to be a prevalent and costly complication that diminishes the cost-effectiveness of an otherwise very successful surgical procedure",
"Background The enhanced posterior soft tissue repair has reduced the frequency of dislocation after primary THA performed through the posterolateral approach . However , the long-term integrity of the repair is unknown and could influence surgeon choice regarding surgical technique and THA approach . Questions / Purpose sWe asked : ( 1 ) What is the durability of the enhanced posterior soft tissue repair at a minimum of 49 months using MRI to evaluate soft tissue to bone integrity ? ( 2 ) How does the appearance of the posterior soft tissues change during this time ? ( 3 ) Are there patient characteristics associated with the long-term imaging appearance of the posterior repair ? Methods All patients without a contraindication for MRI who were undergoing unilateral primary uncemented THA through a posterior approach between February and May 2005 were eligible for inclusion . Ninety percent consented to participate ( 36 of 40 patients ) , and 30 patients were followed prospect ively with MRI postoperatively and again at 3 months ; of those , 22 ( 73 % ; 12 men , 10 women ) completed the study by having another MRI study at a minimum of 49 months ( mean , 51 months ; range , 49–59 months ) . Each patient underwent metal-artifact – reduction sequence MRI to evaluate the integrity of the posterior soft tissues , which had been repaired anatomically during primary THA at a minimum of 4 years earlier . The results were compared with those of prior MR images obtained immediately after surgery and at 3 months postoperatively . All patients were given a self-reported modified Harris hip score at the time of the most recent MRI study ( maximum score = 81 ) . Results At latest followup , 21 of 22 ( 96 % ) patients had a posterior capsule in contact with bone , and 21 of 22 ( 96 % ) had an intact quadratus femoris . Twenty-one patients ( 96 % ) had soft tissue or a scar from the piriformis and conjoined tendons in continuity with bone . In these cases , the interface between the piriformis and conjoined tendons and the greater trochanter observed immediately postoperatively and at 3 months postoperatively became filled with hypointense tissue , with signal characteristics similar to tendon . Time from surgery was most associated with changes in native tendon-to-bone distances ( p MRI signal intensity of the repair ( p were healed to bone . In the majority of patients , scar tissue between the piriformis and conjoined tendons and bone matured to achieve orientation and signal intensity resembling native tendon . We believe the enhanced posterior soft tissue repair facilitates this process . Our results provide a plausible explanation for improved postoperative stability observed in patients receiving an enhanced soft tissue repair compared with those in whom a repair is not performed . Level of Evidence Level IV , therapeutic study",
"Two clinical studies , one prospect i ve r and omized and one retrospective , were performed to evaluate the relationship of femoral head size and acetabular component outer diameter to the prevalence of dislocation of the modular total hip replacement . Between October 1995 and April 1996 , 31 primary total hip arthroplasties in 30 patients were r and omized to a femoral head diameter of 22 mm or 28 mm , for two groups of acetabular components of outer diameters of 56 mm or larger and 54 mm or smaller . Head size ( 22 mm ) and acetabular component outer diameter ( ≥ 56 mm ) were found to increase the risk of dislocation . From December 1984 to January 1994 , 308 primary total hip arthroplasties were performed through a posterior approach by one surgeon using a modular 28 mm femoral head and one type of uncemented acetabular component . The rate of dislocation for acetabular components with an outer diameter of 62 mm or larger was increased significantly ( five of 36 hips , 14 % ) compared with those with an outer diameter of 60 mm or smaller ( 11 of 272 hips , 4 % )",
"Hip instability after total hip replacement has been shown to be a critical cause of failure . The use of dual mobility has been classically restricted to patients \" at risk \" , over 70 years of age . The question rises up about extended indications of so-called \" modern \" second generation dual mobility cups . This prospect i ve multicenter study reports on first results at 2 - 5 years of the HA anatomical ADM cup upon two comparative groups of patients under 70 years ( 112 hips ) vs. over 70 years of age ( 325 hips ) . No dislocation , migration , tilting , wear , or intra-prosthetic dislocation was recorded within each of the two cohorts . Survivorship for cup failures at this 4-year period was ideal at 100 % in the younger patients , and 99.7 % in the older group of patients",
"The principle of dual mobility cups , often called \" tripolar \" , has been developed to overcome the problem of instability following primary hip arthroplasty . We prospect ively compared two cohorts which differed only by the type of bearings , i.e. \" mobile bearing hip \" ( MBH ) in a 143- study cohort of ADM cups versus \" fixed bearing hip \" ( FBH ) of 130 Trident PSL cups , at a follow-up at 2 - 6years . The survival rates at 4.13-years , with instability as endpoint was significantly ( P=0.0176 ) in favor of mobile bearings at 100 % with no dislocation reported , versus 94.8 % with fixed bearings . These mobile bearings , matching both \" modern \" dual mobility cups and annealed highly crossed polyethylene , would appear to offer at longer follow-up a valuable solution to clinical outcomes in acetabular arthroplasty"
] |
4116c7a2-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND A variety of antiarrhythmic drugs have been used to prevent recurrence of atrial fibrillation after conversion to sinus rhythm . We performed a systematic review to determine the effect of long-term treatment with those drugs on death , embolisms , adverse effects , and atrial fibrillation recurrence . METHODS We search ed MEDLINE , EMBASE , the Cochrane Library ( all up to May 2005 ) , and the reference lists of retrieved articles . We included r and omized controlled trials that compared any antiarrhythmic against control ( placebo or no treatment ) or another antiarrhythmic , for more than 6 months . Postoperative atrial fibrillation was excluded . Two evaluators independently review ed the retrieved studies and extracted all data . Disagreements were resolved by discussion . All results were calculated at 1 year of follow-up . RESULTS Forty-four trials were included , with a total of 11 322 patients . Several class IA ( disopyramide phosphate , quinidine sulfate ) , class IC ( flecainide acetate , propafenone hydrochloride ) , and class III ( amiodarone , dofetilide , sotalol hydrochloride ) drugs significantly reduced recurrence of atrial fibrillation ( number needed to treat , 2 - 9 ) , but all increased withdrawals due to adverse effects ( number needed to harm [ NNH ] , 9 - 27 ) and all but amiodarone and propafenone increased proarrhythmia ( NNH , 17 - 119 ) . Class IA drugs , pooled , were associated with increased mortality compared with controls ( Peto odds ratio , 2.39 ; 95 % confidence interval , 1.03 - 5.59 ; P = .04 ; NNH , 109 ) . No other antiarrhythmic showed a significant effect on mortality compared with controls . We could not analyze other outcomes because data were lacking . CONCLUSION Class IA , IC , and III drugs are effective in maintaining sinus rhythm but increase adverse effects , and class IA drugs may increase mortality
|
[
"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",
"CONTEXT Treatment with antiarrhythmic drugs and anticoagulation is considered first-line therapy in patients with symptomatic atrial fibrillation ( AF ) . Pulmonary vein isolation ( PVI ) with radiofrequency ablation may cure AF , obviating the need for antiarrhythmic drugs and anticoagulation . OBJECTIVE To determine whether PVI is feasible as first-line therapy for treating patients with symptomatic AF . DESIGN , SETTING , AND PARTICIPANTS A multicenter prospect i ve r and omized study conducted from December 31 , 2001 , to July 1 , 2002 , of 70 patients aged 18 to 75 years who experienced monthly symptomatic AF episodes for at least 3 months and had not been treated with antiarrhythmic drugs . INTERVENTION Patients were r and omized to receive either PVI using radiofrequency ablation ( n=33 ) or antiarrhythmic drug treatment ( n=37 ) , with a 1-year follow-up . MAIN OUTCOME MEASURES Recurrence of AF , hospitalization , and quality of life assessment . RESULTS Two patients in the antiarrhythmic drug treatment group and 1 patient in the PVI group were lost to follow-up . At the end of 1-year follow-up , 22 ( 63 % ) of 35 patients who received antiarrhythmic drugs had at least 1 recurrence of symptomatic AF compared with 4 ( 13 % ) of 32 patients who received PVI ( P Hospitalization during 1-year follow-up occurred in 19 ( 54 % ) of 35 patients in the antiarrhythmic drug group compared with 3 ( 9 % ) of 32 in the PVI group ( P antiarrhythmic drug group , the mean ( SD ) number of AF episodes decreased from 12 ( 7 ) to 6 ( 4 ) , after initiating therapy ( P = .01 ) . At 6-month follow-up , the improvement in quality of life of patients in the PVI group was significantly better than the improvement in the antiarrhythmic drug group in 5 subclasses of the Short-Form 36 health survey . There were no thromboembolic events in either group . Asymptomatic mild or moderate pulmonary vein stenosis was documented in 2 ( 6 % ) of 32 patients in the PVI group . CONCLUSION Pulmonary vein isolation appears to be a feasible first-line approach for treating patients with symptomatic AF . Larger studies are needed to confirm its safety and efficacy",
"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",
"STUDY OBJECTIVES To compare the efficacy and safety of amiodarone and propafenone when used for the prevention of atrial fibrillation ( AF ) and maintenance of normal sinus rhythm in patients with refractory AF . DESIGN Prospect i ve , r and omized , single-blind trial . SETTING Tertiary cardiac referral center . PATIENTS One hundred forty-six consecutive patients ( 72 men ; mean age , 63 + /- 10 years [ + /- SD ] ) with recurrent symptomatic AF . INTERVENTIONS We studied 146 patients after restoration of sinus rhythm ; patients were r and omized to amiodarone , 200 mg/d , or propafenone , 450 mg/d . Follow-up clinical evaluations were conducted at the first , second , fourth , and sixth months , and at 3-month intervals thereafter . The proportion of patients relapsing to AF and /or experiencing side effects was calculated for each group using the Kaplan-Meier method . End point of the study was recurrence of AF or occurrence of side effects necessitating discontinuation of medication . MEASUREMENTS AND RESULTS Of 146 patients , 72 received amiodarone and 74 received propafenone . The two groups were clinical ly similar . Of the 72 patients receiving amiodarone , AF developed in 25 patients , after an average of 9.8 months , compared to 33 of the 74 patients receiving propafenone after an average of 3.8 months . Twelve patients receiving amiodarone and 2 patients receiving propafenone had side effects necessitating withdrawal of medication while still in sinus rhythm . CONCLUSIONS Amiodarone tends to be more effective than propafenone in maintaining sinus rhythm in patients with AF , but this advantage is offset by a higher incidence of side effects",
"BACKGROUND In-hospital administration of flecainide and propafenone in a single oral loading dose has been shown to be effective and superior to placebo in terminating atrial fibrillation . We evaluated the feasibility and the safety of self-administered oral loading of flecainide and propafenone in terminating atrial fibrillation of recent onset outside the hospital . METHODS We administered either flecainide or propafenone orally to restore sinus rhythm in 268 patients with mild heart disease or none who came to the emergency room with atrial fibrillation of recent onset that was hemodynamically well tolerated . Of these patients , 58 ( 22 percent ) were excluded from the study because of treatment failure or side effects . Out-of-hospital self-administration of flecainide or propafenone -- the \" pill-in-the-pocket \" approach -- after the onset of heart palpitations was evaluated in the remaining 210 patients ( mean age [ + /-SD ] , 59+/-11 years ) . RESULTS During a mean follow-up of 15+/-5 months , 165 patients ( 79 percent ) had a total of 618 episodes of arrhythmia ; of those episodes , 569 ( 92 percent ) were treated 36+/-93 minutes after the onset of symptoms . Treatment was successful in 534 episodes ( 94 percent ) ; the time to resolution of symptoms was 113+/-84 minutes . Among the 165 patients with recurrences , the drug was effective during all the arrhythmic episodes in 139 patients ( 84 percent ) . Adverse effects were reported during one or more arrhythmic episodes by 12 patients ( 7 percent ) , including atrial flutter at a rapid ventricular rate in 1 patient and noncardiac side effects in 11 patients . The numbers of monthly visits to the emergency room and hospitalizations were significantly lower during follow-up than during the year before the target episode ( P feasible and safe , with a high rate of compliance by patients , a low rate of adverse events , and a marked reduction in emergency room visits and hospital admissions",
"OBJECTIVE To assess and compare the safety and efficacy of amiodarone and sotalol in the treatment of patients with recurrent symptomatic atrial fibrillation . DESIGN Prospect i ve , r and omised , single blind , placebo controlled study . SETTING Tertiary cardiac referral centre . PATIENTS 186 consecutive patients ( 97 men , 89 women ; mean ( SD ) age , 63 ( 10 ) years ) with recurrent , symptomatic atrial fibrillation . INTERVENTIONS 65 patients were r and omised to amiodarone , 61 to sotalol , and 60 to placebo . Patients receiving amiodarone were maintained at a dose of 200 mg/day after a 30 day loading phase . The sotalol dose was 160 - 480 mg daily , as tolerated . MAIN OUTCOME MEASURES Recurrence of atrial fibrillation or side effects . RESULTS In the amiodarone group , 31 of the 65 patients developed atrial fibrillation after an average of six months , while 15 ( 11 in sinus rhythm and four in atrial fibrillation ) experienced significant side effects after an average of 16 months . In the sotalol group , relapse to atrial fibrillation occurred in 47 of the 61 patients after an average of eight months ; three experienced side effects during the titration phase . In the placebo group , 53 of the 60 patients developed atrial fibrillation after an average of four months ( p amiodarone and sotalol v placebo ; p amiodarone v sotalol ) . CONCLUSIONS Both amiodarone and sotalol can be used for the maintenance of normal sinus rhythm in patients with symptomatic atrial fibrillation . Amiodarone is more effective but causes more side effects",
"This prospect i ve , r and omized , single-blinded , placebo-controlled study compared the efficacy and safety of sotalol and propafenone when used for long-term prevention of atrial fibrillation . For the long-term maintenance of normal sinus rhythm , propafenone seems to be more effective than sotalol",
"The objective of this r and omized , double-blind , placebo-controlled clinical trial was to test the efficacy and safety of a new sustained-release preparation of the antiarrhythmic drug propafenone ( propafenone SR ) in reducing the frequency of symptomatic arrhythmia recurrences in patients with atrial fibrillation ( AF ) . Patients with a history of symptomatic AF who were in sinus rhythm were r and omly assigned to receive placebo or propafenone SR 425 , 325 , or 225 mg , all twice daily . Recurrent symptomatic arrhythmias were documented using transtelephone electrocardiographic monitoring . Electrocardiograms were review ed by an event committee that was blinded to treatment assignment . In the primary efficacy analysis , propafenone SR significantly lengthened the time to first symptomatic atrial arrhythmia recurrence at all 3 doses compared with placebo as assessed by log-rank test : propafenone SR 425 mg twice daily versus placebo twice daily , p placebo twice daily , p placebo twice daily , p = 0.014 . The median time to recurrence was 41 days in the placebo twice daily group , > 300 days in the propafenone SR 425-mg group , 291 days in the 325-mg group , and 112 days in the 225-mg group . Adverse effects leading to withdrawal were higher in the propafenone SR 425-mg twice daily group than in any other group . Thus , propafenone SR has important and statistically significant antiarrhythmic effects in patients with AF",
"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",
"Atrial fibrillation is one of the most common arrhythmias , leading at least in a subset of patients to severe symptoms ( palpitations , weakness , syncope ) , and to hemodynamic impairment especially in the clinical setting of left ventricular dysfunction . Thus , in many cases restauration of sinus rhythm is indicated because of the negative effects of reduced cardiac output . Quinidine has been the first line drug for many years and has been proven to be highly effective especially when combined with Verapamil . But there is growing concern about using quinidine and other class I-anti-arrhythmic agents because of some hints in clinical trials for increased longterm mortality on these drugs . This study was undertaken to test the efficacy of Sotalol , a beta-blocker with additional strong class-III antiarrhythmic action , compared to a fixed combination of Quinidine and Verapamil for conversion of chronic atrial fibrillation and maintenance of sinus rhythm after medical or electrical cardioversion . To avoid early proarrhythmic effects , potassium values in the range of \" high\"-normal values ( > 4.3 mval/L ) were tried to be obtained . 82 patients were r and omly assigned to receive either Sotalol or Quinidine/Verapamil . There was no difference between the groups as far as the underlying heart disease , duration of atrial fibrillation ( mean 219 days ) and other clinical features including echocardiographic parameters were concerned . The dose of the drug was weight-related individually adjusted , and the drug was continued thereafter . If sinus rhythm could not be established at that time , electric cardioversion was performed and the drug was continued in lower dosage thereafter . ( ABSTRACT TRUNCATED AT 250 WORDS",
"AIMS The purpose of the study was to compare the efficacy and safety of sotalol and bisoprolol in the maintenance of sinus rhythm after electrical cardioversion of atrial fibrillation . METHODS Patients ( n=128 ) were r and omized to sotalol ( 80 mg b.i.d . ) or bisoprolol ( 5 mg x day(-1 ) ) . Patients with contraindications to beta-blockers , class III antiarrhythmic drugs or prior treatment with use of study medication for prevention of atrial fibrillation were excluded . Follow-up clinical evaluation was performed 1 day and 1 month after cardioversion and thereafter at 3-month intervals . RESULTS There were no group differences in baseline clinical characteristics . After a follow-up of 12 months , 59 % of all patients were still in sinus rhythm . The fraction remaining in sinus rhythm was calculated for the two groups by Kaplan -- Meier analysis . During follow-up , 41 % of patients on sotalol and 42 % on bisoprolol developed atrial fibrillation ( ns ) . In two patients ( 3.1 % ) on sotalol , life-threatening proarrhythmias ( torsade de pointes tachycardias ) occurred , whereas none were found in the bisoprolol group . Symptomatic bradycardias occurred in two patients on sotalol and three on bisoprolol . CONCLUSION This study demonstrates that sotalol ( 160 mg x day(-1 ) ) and bisoprolol ( 5 mg x day(-1 ) ) are equally effective in maintaining sinus rhythm . Because of the side effects of sotalol , bisoprolol seems to be advantageous for maintenance of sinus rhythm after cardioversion of atrial fibrillation",
"AIMS In patients with persistent atrial fibrillation ( AF ) , the efficacy and safety of two anti-arrhythmic drugs in preventing the recurrence of AF after successful direct current ( DC ) cardioversion was prospect ively assessed in a multi-centre double-blind , placebo-controlled , r and omised trial using daily trans-telephonic monitoring . METHODS AND RESULTS 1182 patients with persistent AF were prospect ively enrolled , 848 patients were successfully cardioverted and then r and omised to either sotalol ( 383 patients ) , quinidine plus verapamil ( 377 patients ) or placebo ( 88 patients ) . The primary outcome parameter was AF recurrence or death . All patients received an event recorder ( Tele-ECG ) and had to record and transmit via telephone at least one ECG per day during follow-up . The mean follow-up period was 266 days . A total of 191,103 Tele-ECGs were recorded and transmitted . The primary outcome parameter ( AF recurrence of any kind or death ) was observed in 572 patients ( 67 % ) in whom at least one episode of AF recurrence was documented during follow-up , in 348 patients ( 41 % ) AF recurrence was persistent . The recurrence rates after one year for any AF were 83 % for placebo , 67 % for sotalol and 65 % for quinidine plus verapamil , the latter being statistically superior to placebo but not different from sotalol . The recurrence rates for the secondary outcome parameter persistent AF were 77 % , 49 % and 38 % , respectively . Quinidine plus verapamil was significantly superior to placebo and to sotalol . About 95 % of all AF recurrences were initially detected in the daily Tele-ECG , about 70 % of all AF recurrences occurred completely asymptomatic . Adverse events on sotalol and quinidine plus verapamil were comparable with the exception that all torsade de pointes tachycardias occurred on sotalol . CONCLUSION Anti-arrhythmic treatment after DC cardioversion of persistent AF significantly decreases the recurrence rates of persistent AF compared to placebo with superiority of quinidine plus verapamil compared to sotalol . Symptoms were not reliable as clinical surrogates to detect episodes of AF",
"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",
"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",
"Background —In patients with left ventricular dysfunction , atrial fibrillation and flutter ( AF and AFl , respectively ) are common arrhythmias associated with increased morbidity and mortality . The present study investigated the potential of dofetilide in AF-AFl patients with left ventricular dysfunction to restore and maintain sinus rhythm , which might reduce mortality and hospitalizations . Methods and Results —In the Danish Investigations of Arrhythmia and Mortality ON Dofetilide ( DIAMOND ) studies , 506 patients were in AF-AFl at baseline . Over the course of study , cardioversion occurred in 148 ( 59 % ) dofetilide- and 86 ( 34 % ) placebo-treated patients . In these patients , the probability of maintaining sinus rhythm for 1 year was 79 % with dofetilide versus 42 % with placebo ( P Dofetilide had no effect on all-cause mortality , but restoration and maintenance of sinus rhythm was associated with significant reduction in mortality ( risk ratio [ RR ] , 0.44 ; 95 % CI , 0.30 to 0.64;P dofetilide therapy was associated with a significantly lower risk ratio versus placebo for either all-cause ( RR , 0.70 ; 95 % CI , 0.56 to 0.89;P ≤0.005 ) or congestive heart failure ( RR , 0.69 ; 95 % CI , 0.51 to 0.93;P ≤0.02 ) rehospitalization . Conclusions —Dofetilide is safe and increases the probability of obtaining and maintaining sinus rhythm in patients with structural heart disease . The present study suggests that restoration of sinus rhythm is associated with improved survival",
"BACKGROUND AND METHODS In the Cardiac Arrhythmia Suppression Trial , design ed to test the hypothesis that suppression of ventricular ectopy after a myocardial infa rct ion reduces the incidence of sudden death , patients in whom ventricular ectopy could be suppressed with encainide , flecainide , or moricizine were r and omly assigned to receive either active drug or placebo . The use of encainide and flecainide was discontinued because of excess mortality . We examined the mortality and morbidity after r and omization to encainide or flecainide or their respective placebo . RESULTS Of 1498 patients , 857 were assigned to receive encainide or its placebo ( 432 to active drug and 425 to placebo ) and 641 were assigned to receive flecainide or its placebo ( 323 to active drug and 318 to placebo ) . After a mean follow-up of 10 months , 89 patients had died : 59 of arrhythmia ( 43 receiving drug vs. 16 receiving placebo ; P = 0.0004 ) , 22 of nonarrhythmic cardiac causes ( 17 receiving drug vs. 5 receiving placebo ; P = 0.01 ) , and 8 of noncardiac causes ( 3 receiving drug vs. 5 receiving placebo ) . Almost all cardiac deaths not due to arrhythmia were attributed to acute myocardial infa rct ion with shock ( 11 patients receiving drug and 3 receiving placebo ) or to chronic congestive heart failure ( 4 receiving drug and 2 receiving placebo ) . There were no differences between the patients receiving active drug and those receiving placebo in the incidence of nonlethal disqualifying ventricular tachycardia , proarrhythmia , syncope , need for a permanent pacemaker , congestive heart failure , recurrent myocardial infa rct ion , angina , or need for coronary-artery bypass grafting or angioplasty . CONCLUSIONS There was an excess of deaths due to arrhythmia and deaths due to shock after acute recurrent myocardial infa rct ion in patients treated with encainide or flecainide . Nonlethal events , however , were equally distributed between the active-drug and placebo groups . The mechanisms underlying the excess mortality during treatment with encainide or flecainide remain unknown",
"AIMS Dronedarone , a benzofurane derivative without iodine substituents , shares the electrophysiologic properties of amiodarone . This study was design ed to determine the most appropriate dose of dronedarone for prevention of atrial fibrillation ( AF ) after cardioversion . METHODS AND RESULTS Patients with persistent AF were r and omly allocated to 800 , 1200 , 1600 mg daily doses of dronedarone or placebo . The main analysis was conducted on 199/270 patients , who entered the maintenance phase following pharmacological cardioversion or , if unsuccessful , DC cardioversion . Within 6-month follow-up , the time to AF relapse increased on dronedarone 800 mg , with a median of 60 days vs 5.3 days in the placebo group ( relative risk reduction 55 % [ 95 % CI , 28 to 72 % ] P=0.001 ) . No significant effect was seen at higher doses . Spontaneous conversion to sinus rhythm on dronedarone occurred in 5.8 to 14.8 % of patients ( P=0.026 ) . There were no proarrhythmic reactions . Drug-induced QT prolongation was only noticed in the 1600 mg group . Premature drug discontinuations affected 22.6 % of subjects given 1600 mg dronedarone versus 3.9 % on 800 mg and were mainly due to gastrointestinal side effects . No evidence of thyroid , ocular or pulmonary toxicity was found . CONCLUSION Dronedarone , at a 800 mg daily dose , appears to be effective and safe for the prevention of AF relapses after cardioversion . The absence of thyroid side effects and of proarrhythmia are important features of the drug . Further studies are needed to better delineate the antiarrhythmic profile of the drug",
"A multicenter , placebo-controlled , r and omized , double-blind trial compared the preventive effect of aprindine and digoxin on the recurrence of atrial fibrillation ( AF ) with placebo , and also compare the effectiveness of these 2 drugs in the prevention of AF . Patients with symptomatic paroxysmal or persistent AF who had converted to sinus rhythm ( SR ) were r and omly assigned aprindine ( 40 mg/day ) , digoxin ( 0.25 mg/day ) or placebo and followed up on an outpatient basis every 2 weeks for 6 months . Of the 141 patients from 36 participating centers , 47 were given aprindine , 47 digoxin , and 47 were on placebo . After the 6-month follow-up , the Kaplan-Meier estimates of the percentage of patients remaining free of recurrent symptomatic AF on aprindine , digoxin and placebo were 33.3 % , 29.2 % and 21.5 % , respectively . In patients remaining in SR for 15 days after from the start of follow-up , freedom from recurrence was significantly more prevalent in the aprindine group than in the placebo group ( p=0.0414 ) , but there was no significant difference between the digoxin and placebo groups . The rate of adverse events was similar in the 3 groups . In conclusion , neither aprindine nor digoxin had a significant effect on preventing relapse of symptomatic AF ; however , recurrence of AF occurred later with aprindine than with placebo or digoxin",
"BACKGROUND Asymptomatic , or \" silent \" atrial fibrillation could increase the risk of stroke . Little is known about the frequency of asymptomatic atrial fibrillation in patients who also have symptomatic atrial fibrillation ; similarly , little is known about the effect of antiarrhythmic drug therapy on asymptomatic atrial fibrillation . METHODS AND RESULTS Patients in sinus rhythm with a history of symptomatic atrial fibrillation or atrial flutter received placebo or azimilide ( 35 to 125 mg ) once daily for 6 or 9 months in 4 similar double-blind trials . The end point was the first recurrence of a symptomatic ECG-documented supraventricular arrhythmia . Routine transtelephonic electrocardiograms , in the absence of symptoms , were recorded for 30 seconds every 2 weeks until patients completed follow-up or documented a symptomatic supraventricular arrhythmia . Of the 1380 patients , 489 received placebo . Among these patients receiving placebo , 303 transmitted at least one routine ECG while asymptomatic . Asymptomatic atrial fibrillation was recorded in 50 ( 17 % ) within 6 months and before recurrence of symptomatic supraventricular arrhythmia . In the 3 trials evaluating azimilide in therapeutic doses ( 100 and 125 mg ) , asymptomatic atrial fibrillation occurred in 49 of 382 ( 13 % ) receiving azimilide and 43 of 233 ( 18 % ) receiving placebo . Although drug effect on time to first asymptomatic event was not statistically significant ( hazard ratio , 0.70 ; P=0.09 ) , there was a 40 % reduction in asymptomatic atrial fibrillation on azimilide compared with placebo ( P=0.03 ) when repeated observations were considered . CONCLUSIONS Asymptomatic atrial fibrillation is common in untreated patients with a history of symptomatic atrial fibrillation ( and is likely underestimated by this analysis ) . Azimilide may reduce the occurrence of this silent arrhythmia",
"In order to compare the efficacy in preventing recurrencies of symptomatic atrial fibrillation of amiodarone ( A. ) and slow release disopyramide ( D.RET . ) , 76 consecutive patients with recent onset atrial fibrillation ( 1 to 24 hrs . ) were enrolled . In 20 ( 26 % ) conversion to sinus rhythm was obtained by electrical cardioversion , and in 56 ( 74 % ) by oral quinidine loading . Forty-one patients ( group A ) were assigned at r and om to treatment with D.RET . ( 250 mg twice daily ) and 35 patients ( group B ) to amiodarone treatment ( 1200 mg daily for 10 days , and subsequently 200 mg daily ) . The two groups were similar as to age , sex and cardiac pathology . Patients were followed as to clinical condition , st and ard and dynamic ECG after one and three months and every three months subsequently for an average of 13.2 months ( group A ) and 14.1 months ( group B ) . Six group A patients ( 14 % ) were excluded from follow-up on account of side effects which arose during the first week of treatment . Crises of symptomatic atrial fibrillation occurred in 20 patients of group A ( 57 % ) and in 11 ( 32 % ) group patients ; this difference is statistically significant ( p less than 0.05 ) . Four ( 10 % ) group A patients stopped taking the drug due to side effects of an anticholinergic type , and three ( 8.5 % ) patients developed hyperthyroidism during follow-up . The authors therefore come to the conclusion that amiodarone is more effective than slow-release disopyramide in preventing recurrencies of atrial fibrillation ; besides untoward side effects are less frequent with amiodarone",
"AIMS The efficacy of cardioversion ( DCCV ) for restoration of sinus rhythm ( SR ) in persistent atrial fibrillation ( AF ) is limited by a high relapse rate . Relapse may be reduced by amiodarone but no placebo-controlled trials of efficacy have been performed and the appropriate duration of therapy is unknown . METHODS AND RESULTS In this double-blind study , 161 subjects with persistent AF were r and omized to one of three groups-placebo ( n=38 ) ; amiodarone 400 mg BD for 2 weeks prior to DCCV and 200 mg daily for 8 weeks followed by placebo for 44 weeks ( n=62 , short-term amiodarone ) ; amiodarone 400 mg BD for 2 weeks then 200 mg daily for 52 weeks ( n=61 , long-term amiodarone ) . Spontaneous reversion to SR occurred before DCCV in 21 % ( 26/123 ) patients on amiodarone and none of the 38 patients on placebo ( absolute difference 21 % , 95 % confidence interval ( CI ) : 10 to 29 % , P=0.002 ) . At 8 weeks following DCCV , 51 % ( 63/123 ) patients on amiodarone remained in SR compared to 16 % ( 6/38 ) taking placebo ( difference-35 % 95 % CI : -48 to -18 % , P amiodarone were in SR compared to 33 % ( 21/62 ) taking short-term amiodarone ( difference-15 % , 95 % CI : -31 to 2 % , P=0.085 ) . There was no difference in adverse event rate or quality of life scores between groups . CONCLUSIONS Amiodarone pre-treatment before electrical DCCV for persistent AF allows chemical conversion in one-fifth of patients without altering the efficacy of subsequent DC conversion . Amiodarone is more effective than placebo in the maintenance of SR when continued for 8 weeks following successful DCCV . More patients taking long-term amiodarone remained in SR at 52 weeks , but more had serious adverse effects requiring discontinuation of therapy . Eight weeks of adjuvant therapy with amiodarone following successful DCCV may be the preferred option",
"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 ",
"New antiarrhythmic class 1C agents have been proposed in the last few years in an attempt to suppress paroxysmal atrial fibrillation at long-term , as the most commonly used class 1A agents such as quinidine gave highly variable results as regards both side-effects and efficacy . The aim of this r and omized prospect i ve study is to evaluate the efficacy and safety of oral propafenone at long term in preventing paroxysmal atrial fibrillation and to compare the results with those obtained using agents such as quinidine . Two hundred patients with recurrent episodes of symptomatic atrial fibrillation were enrolled for this study with entry criteria based upon a history of more than 3 crises in the previous 6 months , with electrocardiographic ( st and ard electrocardiogram or dynamic registration ) documentation . According to a r and omized selection either propafenone at 300 mg twice daily or hydroquinidine retard 250 mg twice daily were administered to the patients ; clinical check-up was carried out every 3 months or if clinical course worsened . The dosages were increased if proved to be inadequate at check-up ( i.e. recurrence of atrial fibrillation ) up to 300 mg 3 times daily for propafenone and 500 mg twice daily for hydroquinidine . The efficacy at the 3rd month was 71 % for propafenone and 60 % for hydroquinidine , at the 6th month 60 % for propafenone and 56 % for hydroquinidine ; this trend lowered progressively as the follow-up continued , to 48 % for propafenone and 42 % for hydroquinidine ( NS ) . More than 70 % of the responder patients assumed 600 mg twice for propafenone or 250 twice for hydroquinidine . Propafenone had a percentage of 10 % side-effects and hydroquinidine 24 % ( p = 0.02 ) . ( ABSTRACT TRUNCATED AT 250 WORDS",
"BACKGROUND Pilsicainide is a newly synthesized antiarrhythmic agent with class Ic properties . Various antiarrhythmic agents have been used to convert atrial fibrillation ( AF ) to sinus rhythm or decrease the rate of relapse of AF . METHODS We r and omly assigned 62 patients with chronic AF to oral treatment of either a placebo ( 10 patients ) or 150 mg/day of pilsicainide ( 52 patients ) for 4 weeks before electrical cardioversion . Before oral administration of pilsicainide , 41 patients underwent transesophageal echocardiography to investigate whether there was thrombus formation in the heart chambers . Patients without pharmacologic defibrillation underwent direct current cardioversion to restore sinus rhythm . After successful cardioversion , all patients continued to receive pilsicainide and were monitored for up to 2 years . RESULTS Before cardioversion , 11 patients in the pilsicainide group ( 21 % ) reverted to sinus rhythm . No patients in the placebo group reverted to sinus rhythm . Direct current cardioversion was performed in 51 patients ; however , 8 patients were not converted to sinus rhythm ( 5 patients receiving pilsicainide , 3 patients receiving placebo ) , and 3 patients needed intracardiac cardioversion to convert to sinus rhythm . Asymptomatic bradyarrhythmias were observed in 5 patients in the pilsicainide group . During the follow-up period , 33 patients ( 71 % ) in the pilsicainide group remained in sinus rhythm at 1 month ; this number decreased to 23 patients ( 49 % ) at 3 months , 20 ( 43 % ) at 6 months , 16 ( 34 % ) at 12 months , 16 ( 34 % ) at 18 months , and 16 ( 34 % ) at 24 months . All patients receiving placebo continued to receive placebo after the cardioversion , and AF recurred a few days after cardioversion in all cases . No independent discriminant variables were identified in the groups between maintenance and nonmaintenance of sinus rhythm . Although no serious side effects regarding pilsicainide have been documented , one patient died of acute myocardial infa rct ion , most likely not related to pilsicainide administration . CONCLUSIONS Pilsicainide is effective in restoring or maintaining sinus rhythm in patients with chronic AF lasting longer than an average duration of 22 months . No major adverse effects were observed",
"Objective — The aim of this study was to investigate the efficacy and safety of propafenone in the prevention of atrial fibrillation ( AF ) relapse after restoration of sinus rhythm . Methods — This study consisted of 110 consecutive patients with recent onset and persistent AF . After restoration of sinus rhythm , patients were r and omized to propafenone ( n : 58 , age : 60 ± 12 years ) or placebo ( n : 52 , age : 62 ± 10 years).There were 11 withdrawals ( 7 in the propafenone and 4 in the placebo group ) during follow-up . Follow-up evalutations were conducted at the first , 3rd and then at an interval of three months during 15 months . The clinical characteristics in both groups were comparable . The AF relapse was analysed by the Kaplan-Meier method . Results — At 15-month follow-up , AF relapsed in 20 ( 39 % ) and 31 ( 65 % ) patients in the propafenone and placebo groups , respectively ( p = 0.015 ) . In subgroup analysis , AF recurrence was significantly lower in the propafenone group than in the placebo group only in the recent onset AF patients with spontaneous conversion ( 21 % vs. 61 % , p = 0.01 ) . However , the AF relapse rates were similar in patients with persistent AF and with recent AF who converted to sinus rhythm pharmacologically or electrically in the propafenone and placebo groups . Four patients on propafenone and one on placebo had adverse effects necessitating discontinuation of the drug ( p = 0.36 ) . Conclusion — At 15 months , propafenone seems to be superior to placebo for maintaining sinus rhythm in patients with recent onset or peristent AF . This superiority originates mainly from patients with recent onset AF in whom sinus rhythm occurred spontaneously . Its adverse effects are similar to placebo . ( Acta Cardiol 2004 ; 59(3 ) : 255 - 261",
"OBJECTIVES The primary objective of the present study was to assess the efficacy of metoprolol CR/XL to reduce the risk of relapse after cardioversion of persistent atrial fibrillation to sinus rhythm . BACKGROUND Indirect data from studies with d , l sotalol provide evidence that the beta-blocking effects of the compound are important in maintaining sinus rhythm after cardioversion of atrial fibrillation . METHODS After successful conversion to sinus rhythm , 394 patients with a history of persistent atrial fibrillation were r and omly assigned to treatment with metoprolol CR/XL or placebo . The two treatment groups were similar with respect to all pretreatment characteristics . Patients were seen on an outpatient basis for recording of resting electrocardiogram ( ECG ) after one week , one , three and six months of follow-up or whenever they felt that they had a relapse into atrial fibrillation or experienced an adverse event . RESULTS In the metoprolol CR/XL group , 96 patients ( 48.7 % ) had a relapse into atrial fibrillation compared with 118 patients ( 59.9 % ) in the placebo group ( p = 0.005 ) . Heart rate in patients after a relapse into atrial fibrillation was significantly lower in the metoprolol group ( 98 + /- 23 beats/min ) than in the placebo group ( 107 + /- 27 beats/min ) . The rate of adverse events reported was similar in both groups when the difference in follow-up time was taken into account . CONCLUSIONS The results of this double-blind , placebo-controlled study in patients after cardioversion of persistent atrial fibrillation showed that metoprolol CR/XL was effective in preventing relapse into atrial fibrillation or flutter",
"In a prospect i ve study 45 patients with paroxysmal atrial fibrillation were r and omly assigned to one of three groups ( of 15 patients each ) : group I received oral digoxin , three times 0.125 mg up to twice 0.25 mg daily ; group II oral digoxin twice 0.125 mg and quinidine hydrogen sulphate 750 - 1000 mg daily ; group III oral digoxin three times 0.125 mg and flecainide 200 - 300 mg daily . During a mean observation period of 11 months digoxin alone was significantly less effective ( P less than 0.05 ) in reducing or suppressing paroxysms of atrial fibrillation than digoxin plus quinidine or flecainide . Flecainide with digoxin was more effective than the drug regimen in groups I and II ( P less than 0.05 ) . Two patients each in groups I and III had side effects , eight in group II . The results suggest that , at the chosen dosage , flecainide produces fewer side effects than quinidine",
"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 ",
"OBJECTIVES Aim of the present study was to assess the efficacy and safety of flecainide ( F ) and sotalol ( S ) for the prevention of recurrences of paroxysmal atrial fibrillation ( PAF ) . METHODS Sixty-six patients with PAF ( > or = 3 episodes of atrial fibrillation in the last year ) in sinus rhythm , were r and omized to pharmacological oral treatment with F ( 20 patients -Group A ) , with S ( 20 patients -Group B ) and placebo ( P ) ( 26 patients -Group C ) . During the follow-up ( one year duration ) were evaluated on I , III , VI and XII months the number and tolerance of the atrial fibrillation recurrences , cardiac and /or noncardiac side effects . The patients with more than two recurrences in the same follow-up interval withdrew from the study . In each patient 14 clinical and laboratory variables were evaluated . RESULTS After 12 months were arrhythmia-free respectively 70 % of Group A patients , 60 % of Group B patients , 27 % of Group C patients . Univariate analysis showed that treatment with F was related to decrease of atrial fibrillation recurrences ( one recurrence 67 % , two recurrences 81 % , three recurrences 81 % ) , treatment with S was related to decrease of recurrences ( two recurrences 59 % ) ; the variable most significantly related to the risk of arrhythmia recurrence is the higher value of basal cardiac rate ( one recurrence t = 2.15 , two t = 2.22 , three t = 2.96 , four t = 2.06 ) . There was not statistically significant difference in maintenance of sinus rhythm at the end of the follow-up between the groups of patients on F and S ( p = 0.163 ) ; treatment efficacy was significantly higher than P ( p = 0.002 ) . Multivariate analysis showed that treatment with F and S decreases the risk of arrhythmia recurrence respectively of 85 % and 76 % versus placebo at the end of the follow-up . The incidence of cardiac and /or noncardiac side effects was not clinical ly significant . CONCLUSION F and S are both effective and safe for prevention of PAF , with 70 % and 60 % respectively of patients arrhythmia-free after 12 months of treatment . Side effects were common , but clinical ly significant adverse events were uncommon . A higher value of basal cardiac rate was predictive of atrial fibrillation recurrences in the patients during treatment",
"BACKGROUND Atrial fibrillation and paroxysmal supraventricular tachycardia are common disorders of the heart rhythm for which antiarrhythmic drug therapy is commonly prescribed . The Atrial Fibrillation Investigation with Bidisomide ( AFIB ) study was a r and omized , placebo-controlled clinical trial design ed to accomplish three goals in a single protocol : ( 1 ) to determine the efficacy of the antiarrhythmic drug bidisomide in the treatment of these two arrhythmias ; ( 2 ) to establish the appropriate dose range for bidisomide ; and ( 3 ) to detect an adverse mortality effect of bidisomide if one were present in patients with atrial fibrillation . METHODS AND RESULTS In this clinical trial , 1227 patients with atrial fibrillation and 187 with paroxysmal supraventricular tachycardia were r and omly assigned to bidisomide ( 200 , 400 , or 600 mg BID ) or placebo ; patient groups with each arrhythmia were analyzed separately . Symptomatic recurrences of atrial fibrillation and paroxysmal supraventricular tachycardia were documented with the use of transtelephonic ECG monitoring . The time to the first symptomatic arrhythmia recurrence was measured in each patient and compared among treatment groups . Among the atrial fibrillation patients , there was no significant difference in the time to first symptomatic recurrence between the placebo group and any of the three bidisomide treatment groups ; the hazard ratios ( placebo : treatment ) were 1.19 , 1.03 , and 1.14 for bidisomide 200 , 400 , and 600 mg BID , respectively . Among paroxysmal supraventricular tachycardia patients , there was a similar lack of a significant treatment effect ; the hazard ratios were 1.30 , 1.93 , and 1.59 for bidisomide 200 , 400 , and 600 mg BID , respectively . In the primary safety analysis of mortality , 3 of 493 patients taking placebo died , compared with 9 of 488 patients taking one of the two higher doses of bidisomide ( P>.10 ) . CONCLUSIONS Bidisomide in the doses tested did not have a clinical ly important antiarrhythmic effect . The AFIB study provided a novel clinical trial design to test antiarrhythmic drugs for both safety and efficacy",
"AIM The indication to treat paroxysmal atrial fibrillation ( PAF ) is controversial . The Suppression of Paroxysmal Atrial Tachyarrhythmias ( SOPAT ) trial was design ed to answer the following questions : ( 1 ) What is the average rate of spontaneous events of symptomatic PAF with and without anti-arrhythmic medication ? ( 2 ) what is the prevalence of severe side-effects ? and ( 3 ) is the fixed combination of Quinidine + Verapamil inferior to the efficacy of sotalol or not ? METHODS AND RESULTS Within 60 months 172 centres in Germany , Pol and , and The Slovak Republic prospect ively enrolled 1033 patients ( mean age 60 years , 62 % male ) with documented frequent episodes of symptomatic PAF . Patients were r and omised to either Quinidine + Verapamil 480/240 mg/d ( high dose ; 263 patients ) , Quinidine + Verapamil 320/160 mg/d ( low dose ; 255 patients ) , Sotalol 320 mg/d ( 264 patients ) or placebo ( 251 patients ) , of which 1012 patients entered the intention-to-treat analysis . The primary endpoint was the time to first recurrence of symptomatic PAF or premature discontinuation . Secondary outcome parameters were the total number of symptomatic episodes and tolerability of the tested drugs . Patients were followed for a period of up to 12 months by daily and symptom-triggered trans-telephonic ECG-monitoring ( Tele-ECG ) . The mean time under treatment was 233 + /- 152 days . Regarding the primary endpoint , all active treatments were superior to placebo and not different from each other . A total of 756 patients reached the primary endpoint within 105.7 + /- 8.7 d ( mean + /- SEM ) in the placebo group , vs. Quinidine + Verapamil ( high dose ) ( 150.4 + /- 10 d , p = 0.0061 ) , vs. Quinidine + Verapamil ( low dose ) ( 148.9 + /- 10.6 d , p = 0.0006 ) , vs. Sotalol ( 145.6 + /- 93 d , p = 0.0007 ) . All three treatments were also effective in the reduction of AF burden ( days with symptomatic AF [ % ] mean + /- SD , p vs. placebo ) : Quinidine + Verapamil ( high dose ) ( 3.4 + /- 12 , p = 0.0001 ) , Quinidine + Verapamil ( low dose ) ( 4.5 + /- 12.3 , p = 0.008 ) and Sotalol ( 2.9 + /- 6.5 , p = 0.026 ) compared to placebo ( 6.1 + /- 13.5 ) . A total of four deaths , 13 syncopes , and one ventricular tachycardia ( VT ) occurred during the active study period , of which one death and one VT were related to Quinidine/Verapamil . CONCLUSION Taken together , anti-arrhythmic therapy with the fixed combination of Quinidine + Verapamil is as effective as Sotalol in the reduction of the recurrence rate of symptomatic PAF with a low but definite risk of severe side-effects",
"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",
"In this multicentre study , 90 patients who left hospital in sinus rhythm after electroconversion of atrial fibrillation were r and omized to double-blind treatment with either disopyramide ( n = 44 ) or placebo ( n = 46 ) . The groups were comparable regarding age and sex distribution , duration of atrial fibrillation , heart volume and NYHA-classification . Life-table analysis was used to estimate the percentage of patients still in sinus rhythm and tolerating treatment at control visits after 1 , 3 , 6 , 9 and 12 months . After 1 month there was already a significant difference ( P less than 0.01 ) between the two groups ( disopyramide 70 % , placebo 39 % ) , a difference that was still remaining after 12 months ( disopyramide 54 % , placebo 30 % ) . Twenty-four patients , all relapsing to atrial fibrillation before six months on placebo , were converted to sinus rhythm once again . They were then treated with disopyramide in an open manner and after 12 months 37 % were still in sinus rhythm . From the results of this study , disopyramide seems to be a useful drug in maintaining sinus rhythm after electroconversion of atrial fibrillation",
"In order to compare the relative efficacy of quinidine , disopyramide and a placebo in the maintenance of sinus rhythm after cardioversion from atrial fibrillation and in order to examine the incidence of side-effects , 82 patients with continuous atrial fibrillation ( duration more than 1 month but less than 3 years ) were r and omized in a double-blind fashion to receive quinidine , disopyramide or placebo . Six months after cardioversion there was no significant difference between any of the three groups as regards the number of patients remaining in sinus rhythm . The greater distortion of the atrial architecture which occurs in patients with rheumatic mitral valve disease may explain the failure of these anti-arrhythmic agents to prolong the duration of sinus rhythm in this study , in which patients with valvular heart disease comprised 76 % of the total group",
"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",
"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",
"BACKGROUND AND OBJECTIVES The relation between cardiac mortality and antiarrhythmic drug administration has not been fully determined . This relation was analyzed in 1,330 patients enrolled in the Stroke Prevention in Atrial Fibrillation Study , a r and omized clinical trial comparing warfarin , aspirin and placebo for the prevention of ischemic stroke or systemic embolism in patients with nonvalvular atrial fibrillation . METHODS Patients who received antiarrhythmic drug therapy for atrial fibrillation in this study were compared with patients not receiving antiarrhythmic agents . The relative risk of cardiac mortality , including arrhythmic death , in patients receiving antiarrhythmic drug therapy was determined and adjusted for other cardiac risk factors . RESULTS In patients receiving antiarrhythmic drug therapy , cardiac mortality was increased 2.5-fold ( p = 0.006 , 95 % confidence interval [ CI ] 1.3 to 4.9 ) and arrhythmic death was increased 2.6-fold ( p = 0.02 , 95 % CI 1.2 to 5.6 ) . Among patients with a history of congestive heart failure , those given antiarrhythmic medications had a relative risk of cardiac death of 4.7 ( p less than 0.001 , 95 % CI 1.9 to 11.6 ) compared with that of patients not so treated ; the relative risk of arrhythmic death in the treated group was 3.7 ( p = 0.01 , 95 % CI 1.3 to 10.4 ) . Patients without a history of congestive heart failure had no increased risk of cardiac mortality ( relative risk 0.70 , 95 % CI 0.2 to 3.1 ) during antiarrhythmic drug therapy . After exclusion of 23 patients with documented ventricular arrhythmias and adjustment for other variables predictive of cardiac death , patients receiving antiarrhythmic drugs were not at increased risk of cardiac death or arrhythmic death . However , in patients with a history of heart failure who received antiarrhythmic drug therapy , the relative risk of cardiac death was 3.3 ( p = 0.05 , 95 % CI 0.99 to 11.1 ) and that of arrhythmic death was 5.8 ( p = 0.009 , 95 % CI 1.5 to 21.7 ) compared with the risk in patients not taking antiarrhythmic medications . CONCLUSIONS Although antiarrhythmic drug therapy was not r and omly determined in this trial , the data suggest that in patients with atrial fibrillation and a history of congestive heart failure , the risk of such therapy may outweigh the potential benefit of maintaining sinus rhythm",
"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",
"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",
"To compare the relative safety of flecainide acetate to propafenone HCl during long-term treatment ( 12 months ) , we conducted a r and omized , open-label , comparative , parallel , multicenter trial in 200 patients with paroxysmal atrial fibrillation ( AF ) and no history of heart disease . Initial daily doses were flecainide 200 mg ( n = 97 ) or propafenone 450 mg ( n = 103 ) . Dose escalations up to a maximum of flecainide 300 mg/day or propafenone 900 mg/day were permitted after > or = 2 attacks of paroxysmal AF . Patients were assessed for safety and drug tolerance at design ated intervals over the 12-month study unless discontinued for adverse experience or inadequate response . Ten patients on flecainide reported 14 cardiac adverse experiences ; 4 discontinued the drug . Seven propafenone patients reported 8 cardiac adverse experiences ; 5 discontinued the drug . Three proarrhythmic events occurred : 1 propafenone patient developed ventricular tachycardia and 2 flecainide patients experienced AF with a rapid ventricular response . An intention-to-treat analysis showed that the probability of safe and effective treatment after 12 months was 77 % for flecainide-treated patients and 75 % for the propafenone-treated patients . There was an acceptable risk-benefit profile in patients with paroxysmal AF and no evidence of clinical ly significant heart disease who were treated with flecainide or propafenone for 12 months . Further , there was no statistically significant difference in safety or efficacy between flecainide and propafenone in this study"
] |
4116c7de-06ff-11f0-808a-c43d1ab1c353
|
Background Mapping is an increasingly common method used to predict instrument-specific preference-based health-state utility values ( HSUVs ) from data obtained from another health-related quality of life ( HRQoL ) measure . There have been several method ological developments in this area since a previous review up to 2007 . Objective To provide an up date d review of all mapping studies that map from HRQoL measures to target generic preference-based measures ( EQ-5D measures , SF-6D , HUI measures , QWB , AQoL measures , 15D/16D/17D , CHU-9D ) published from January 2007 to October 2018 . Data sources A systematic review of English language articles using a variety of approaches : search ing electronic and utilities data bases , citation search ing , targeted journal and website search es . Study selection Full papers of studies that mapped from one health measure to a target preference-based measure using formal statistical regression techniques . Data extraction Undertaken by four authors using predefined data fields including measures , data used , econometric models and assessment of predictive ability . Results There were 180 papers with 233 mapping functions in total . Mapping functions were generated to obtain EQ-5D-3L/EQ-5D-5L-EQ-5D-Y ( n = 147 ) , SF-6D ( n = 45 ) , AQoL-4D/AQoL-8D ( n = 12 ) , HUI2/HUI3 ( n = 13 ) , 15D ( n = 8) CHU-9D ( n = 4 ) and QWB-SA ( n = 4 ) HSUVs . A large number of different regression methods were used with ordinary least squares ( OLS ) still being the most common approach ( used ≥ 75 % times within each preference-based measure ) . The majority of studies assessed the predictive ability of the mapping functions using mean absolute or root mean squared errors ( n = 192 , 82 % ) , but this was lower when considering errors across different categories of severity ( n = 92 , 39 % ) and plots of predictions ( n = 120 , 52 % ) . Conclusions The last 10 years has seen a substantial increase in the number of mapping studies and some evidence of advancement in methods with consideration of models beyond OLS and greater reporting of predictive ability of mapping functions
|
[
"Purpose The Dermatology Life Quality Index ( DLQI ) and the European Quality of Life-5 Dimension ( EQ-5D ) are separate measures that may be used to gather health-related quality of life ( HRQoL ) information from patients . The EQ-5D is a generic measure from which health utility estimates can be derived , whereas the DLQI is a specialty-specific measure to assess HRQoL. To reduce the burden of multiple measures being administered and to enable a more disease-specific calculation of health utility estimates , we explored an established mathematical technique known as ordinal logistic regression ( OLR ) to develop an appropriate model to map DLQI data to EQ-5D-based health utility estimates . Methods Retrospective data from 4010 patients were r and omly divided five times into two groups for the derivation and testing of the mapping model . Split-half cross-validation was utilized result ing in a total of ten ordinal logistic regression models for each of the five EQ-5D dimensions against age , sex , and all ten items of the DLQI . Using Monte Carlo simulation , predicted health utility estimates were derived and compared against those observed . This method was repeated for both OLR and a previously tested mapping methodology based on linear regression . Results The model was shown to be highly predictive and its repeated fitting demonstrated a stable model using OLR as well as linear regression . The mean differences between OLR-predicted health utility estimates and observed health utility estimates ranged from 0.0024 to 0.0239 across the ten modeling exercises , with an average overall difference of 0.0120 ( a 1.6 % underestimate , not of clinical importance ) . Conclusions This modeling framework developed in this study will enable research ers to calculate EQ-5D health utility estimates from a specialty-specific study population , reducing patient and economic burden",
"Purpose It is not always possible to collect utility-based outcome data , like EQ-5D , needed for conducting economic evaluations in population s of older people . Sometimes , information on other non-utility outcome measures may have been collected . This paper examines the possibility of mapping the EQ-5D from a non-utility-based outcome , the Barthel index . Methods Data for 1,189 UK intermediate care patients were used . Ordinary least squares ( OLS ) , censored least absolute deviations ( CLAD ) estimator and multinomial logistic ( ML ) models were used . The mean absolute error ( MAE ) and root-mean-squared error ( RMSE ) were used to estimate the predictive accuracy of eight regression models . Validation of primary models was carried out on r and om sample s of data collected at admission and discharge . Results Models where the EQ-5D was entered as a continuous dependent variable and Barthel dimensions used as explanatory variables performed better . CLAD performed best on MAE and OLS on the RMSE , while the ML performed the worst on both measures . The CLAD predicted EQ-5D scores that matched the observed values more closely than the OLS . Conclusions It is possible to reasonably predict that the EQ-5D from the Barthel using regression methods and the CLAD model ( 4 ) is recommended",
"Background Mapping from health status measures onto generic preference-based measures is becoming a common solution when health state utility values are not directly available for economic evaluation . However the accuracy and reliability of the models employed is largely untested , and there is little evidence of their suitability in patient data sets . This paper examines whether mapping approaches are reliable and accurate in terms of their predictions for a large and varied UK patient data set . Methods SF-36 dimension scores are mapped onto the EQ-5D index using a number of different model specifications . The predicted EQ-5D scores for subsets of the sample are compared across inpatient and outpatient setting s and medical conditions . This paper compares the results to those obtained from existing mapping functions . Results The model including SF-36 dimensions , squared and interaction terms estimated using r and om effects GLS has the most accurate predictions of all models estimated here and existing mapping functions as indicated by MAE ( 0.127 ) and MSE ( 0.030 ) . Mean absolute error in predictions by EQ-5D utility range increases with severity for our models ( 0.085 to 0.34 ) and for existing mapping functions ( 0.123 to 0.272 ) . Conclusion Our results suggest that models mapping the SF-36 onto the EQ-5D have similar predictions across inpatient and outpatient setting and medical conditions . However , the models overpredict for more severe EQ-5D states ; this problem is also present in the existing mapping functions",
"Background The Paediatric Quality of Life Inventory ( PedsQL ™ ) question naire is a widely used , generic instrument design ed for measuring health-related quality of life ( HRQoL ) ; however , it is not preference-based and therefore not suitable for cost – utility analysis . The Child Health Utility Index–9 Dimension ( CHU-9D ) , however , is a preference-based instrument that has been primarily developed to support cost – utility analysis . Objective This paper presents a method for estimating CHU-9D index scores from responses to the PedsQL ™ using data from a r and omised controlled trial of prednisolone therapy for treatment of childhood corticosteroid-sensitive nephrotic syndrome . Methods HRQoL data were collected from children at r and omisation , week 16 , and months 12 , 18 , 24 , 36 and 48 . Observations on children aged 5 years and older were pooled across all data collection timepoints and were then r and omised into an estimation ( n = 279 ) and validation ( n = 284 ) sample . A number of models were developed using the estimation data before internal validation . The best model was chosen using multi-stage selection criteria . Results Most of the models developed accurately predicted the CHU-9D mean index score . The best performing model was a generalised linear model ( mean absolute error = 0.0408 ; mean square error = 0.0035 ) . The proportion of index scores deviating from the observed scores by estimating CHU-9D index scores and for conducting cost – utility analyses within clinical studies that have only collected PedsQL ™ data . It is valid for children aged 5 years or older . Caution should be exercised when using this with children younger than 5 years , older adolescents ( > 13 years ) or patient groups with particularly poor quality of life . IS RCT N Registry",
"Background . SF-6D utility weights are conventionally produced using a st and ard gamble ( SG ) . SG-derived weights consistently demonstrate a floor effect not observed with other elicitation techniques . Recent advances in discrete choice methods have allowed estimation of utility weights . The objective was to produce Australian utility weights for the SF-6D and to explore the application of discrete choice experiment ( DCE ) methods in this context . We hypothesized that weights derived using this method would reflect the largely monotonic construction of the SF-6D . Methods . We design ed an online DCE and administered it to an Australia-representative online panel ( n = 1017 ) . A range of specifications investigating nonlinear preferences with respect to additional life expectancy were estimated using a r and om-effects probit model . The preferred model was then used to estimate a preference index such that full health and death were valued at 1 and 0 , respectively , to provide an algorithm for Australian cost-utility analyses . Results . Physical functioning , pain , mental health , and vitality were the largest drivers of utility weights . Combining levels to remove illogical orderings did not lead to a poorer model fit . Relative to international SG-derived weights , the range of utility weights was larger with 5 % of health states valued below zero . Conclusion s. DCEs can be used to investigate preferences for health profiles and to estimate utility weights for multi-attribute utility instruments . Australian cost-utility analyses can now use domestic SF-6D weights . The comparability of DCE results to those using other elicitation methods for estimating utility weights for quality -adjusted life-year calculations should be further investigated",
"The Health Utilities Index is a generic multiattribute preference-based system for assessing health-related quality of life , devised by Torrance et al. It is being used in cost-effectiveness evaluations in North America and in international multicentre studies but was not available in France . Following adaptation of the HUI3 classification in France , the purpose of the reported investigation was to derive French preference weights . This article provides a reminder of the theoretical foundations used to model the multiattribute utility function . Within this framework , a multiattribute multiplicative aggregate utility function was constructed in accordance with the explicitly decomposed approach . The study took place in June 1999 over a sample of 365 persons from the French general population , aged between 20 and 65 , and not suffering from any chronic or incapacitating illness . The recruitment procedure was based upon a r and om selection of individuals , using the phone book . Interviews took place in the homes of the interviewees . The methods of revelation ( VAS and SG ) were applied by setting the value of the best possible state of the HUI3 a priori at 1 , and leaving a choice between two states ( worst possible state , death ) for 0 . The aggregated individuals ( person-mean and median ) were calculated and the multiplicative utility functions constructed . A comparison of the calculated utilities with the observed ones provides a primary indicator of the validity of the person-mean or median functions constructed . The slight absolute differences obtained between observed and calculated utilities and the low RMSE scores lead us towards a favourable conclusion",
"RATIONALE , AIMS , AND OBJECTIVES Although nonpreference-based disease-specific measures are widely used in clinical studies , they can not generate utilities for economic evaluation . A solution to this problem is to estimate utilities from disease-specific instruments using the mapping function . This study aim ed to develop a transformation model for mapping the pruritus-visual analog scale ( VAS ) to the EuroQol 5-Dimension 3-Level ( EQ-5D-3L ) utility index in pruritus . METHODS A cross-sectional survey was conducted with a sample ( n = 268 ) drawn from the general population of South Korea . Data were r and omly divided into 2 groups , one for estimating and the other for validating mapping models . To select the best model , we developed and compared 3 separate models using demographic information and the pruritus-VAS as independent variables . The predictive performance was assessed using the mean absolute deviation and root mean square error in a separate data set . RESULTS Among the 3 models , model 2 using age , age squared , sex , and the pruritus-VAS as independent variables had the best performance based on the goodness of fit and model simplicity , with a log likelihood of 187.13 . The 3 models had similar precision errors based on mean absolute deviation and root mean square error in the validation data set . No statistically significant difference was observed between the mean observed and predicted values in all models . CONCLUSIONS In conclusion , model 2 was chosen as the preferred mapping model . Outcomes measured as the pruritus-VAS can be transformed into the EQ-5D-3L utility index using this mapping model , which makes an economic evaluation possible when only pruritus-VAS data are available",
"Objective To help facilitate economic evaluations of oncology treatments , we mapped responses on cancer-specific instrument to generic preference-based measures . Methods Cancer patients ( n = 367 ) completed one cancer-specific instrument , the FACT-G , and two preference-based measures , the EQ-5D and SF-6D . Responses were r and omly divided to form development ( n = 184 ) and cross-validation ( n = 183 ) sample s. Relationships between the instruments were estimated using ordinary least squares ( OLS ) , generalized linear models ( GLM ) , and censored least absolute deviations ( CLAD ) regression approaches . The performance of each model was assessed in terms of how well the responses to the cancer-specific instrument predicted EQ-5D and SF-6D utilities using mean absolute error ( MAE ) and root mean squared error ( RMSE ) . Results Physical , functional , and emotional well-being domain scores of the FACT-G best explained the EQ-5D and SF-6D . In terms of accuracy of prediction as measured in RMSE , the CLAD model performed best for the EQ-5D ( RMSE = 0.095 ) whereas the GLM model performed best for the SF-6D ( RMSE = 0.061 ) . The GLM predicted SF-6D scores matched the observed values more closely than the CLAD and OLS . Conclusion Our results demonstrate that the estimation of both EQ-5D and SF-6D utility indices using the FACT-G responses can be achieved . The CLAD model for the EQ-5D and the GLM model for the SF-6D are recommended . Thus , it is possible to estimate quality -adjusted life years for economic evaluation from studies where only cancer-specific instrument have been administered",
"Background Although cancer-specific Health-Related Quality of Life ( HRQOL ) are commonly included in r and omized clinical trials or other prospect i ve non-r and omized clinical studies , it is rare that preference-based instruments are used that allow the calculation of a utility weight suitable for estimating quality -adjusted life-years gained . Objective To develop a mapping algorithm to transform the EORTC QLQ-C30 question naire responses into EQ-5D derived utilities . Study design Retrospective data analysis of a multicentre , multicountry prospect i ve clinical trial in breast cancer patients . Methods Regression analysis of individual pairs of EQ-5D and QLQ-C30 scores . Results A model that explained 80 % of the variance was developed to estimate EQ-5D Utilities from QLQ-C30 scores at individual level . From this reliable group level means and deviations can be derived . Conclusions Mapping from QLQ-C30 scores to EQ-5D-derived utilities when only QLQ-C30 data are available has been shown to be possible with good accuracy . Validation of the proposed algorithm in other external clinical data sets should be encouraged",
"Study Design . Cross-sectional analysis of the Cervical Spine Research Society Outcomes Study , a longitudinal multicenter cohort study . Objective . To provide a statistical model for estimating health utility from the Cervical Spine Outcomes Question naire ( CSOQ ) domain scores . Summary of Background Data . There is consensus among health-policy research ers that the results of economic evaluations of health can be reported in quality -adjusted life-years ( QALY ) . The CSOQ is a condition-specific instrument that assesses individuals across several domains , including neck and arm/shoulder pain and psychological distress . Methods . The CSOQ and 36-Item Short Form Health Survey ( SF-36 ) were prospect ively administered before surgery ( within 4 weeks ) and after surgery ( at 3 , 6 , and 24 months ) to individuals undergoing anterior cervical decompression and fusion for degenerative disc disease of the cervical spine . Using methods reported by Brazier et al , health utility ( SF-6D ) was estimated using the SF-36 . Regression analyses were used on a training data set ( n = 164 ) to compute the SF-6D from the domain scores of the CSOQ . A validation data set ( n = 328 ) was used to estimate the SF-6D for comparison to the calculated health utility from the SF-36 . Results . Domain scores were moderately correlated with health utility ( SF-6D ) ( P utility . In the validation data set , predicted SF-6D was positively correlated with observed SF-6D ( r = 0.680 , P undergoing elective anterior cervical decompression and fusion for cervical degenerative disc disease . The ability to assess health utility , coupled with the psychometric properties of the CSOQ , should increase the clinical utility of this patient-reported outcomes instrument",
"Background Grass allergen immunotherapy ( AIT ) reduces symptom severity in seasonal allergic rhinoconjunctivitis ( ARC ) but its impact on general health-related utility has not been characterised for the purpose s of economic evaluation . The aim of this study was to model the preferred measure of utility , EQ-5D index , from symptom severity and estimate incremental quality adjusted life years ( QALYs ) associated with SQ-st and ardised grass immunotherapy tablet ( GRAZAX ® , 75,000 SQ-T/2,800 BAU , ALK , Denmark ) . Methods Data were analysed from five consecutive pollen seasons in a r and omised placebo controlled trial of GRAZAX ® . Binomial and Gaussian mixed effects modelling related weekly EQ-5D index score to daily symptom and medication scores ( DSS & DMS respectively ) . In turn , daily EQ-5D index was estimated from ARC symptoms and medication use . Results DSS and DMS were the principal predictors of ‘ perfect ’ health ( EQ-5D = 1.000 ; binomial ) and ‘ imperfect ’ health ( EQ-5D in DSS and DMS reduced the odds of ‘ perfect ’ health ( EQ-5D = 1.000 ) by 27 % and 16 % respectively , and reduced ‘ imperfect ’ health by 0.17 and 0.13 , respectively . Gender remained the only other significant main fixed effect ( Male odds ratio [ OR ] = 1.82 ) . Incremental estimated EQ-5D index utility for GRAZAX ® was observed from day -30 to day + 70 of the pooled pollen season ; mean daily utility for GRAZAX ® = 0.938 units ( 95%CI 0.932 - 0.943 ) vs. 0.914 ( 0.907 - 0.921 ) for placebo , an incremental difference of 0.0238 ( p 0.0324 Quality Adjusted Life Years over the five year study period . Conclusions ARC symptoms and medication use are the main predictors of EQ-5D index . The incremental QALYs observed for GRAZAX ® may not fully describe the health benefits of this treatment , suggesting that economic modelling may be conservative",
"ABSTRACT Objective : Deriving preference scores for the Medical Outcomes Study ( MOS ) Sleep Scale would enable its use in cost – utility analyses . The objective of this study was to map scores of the MOS Sleep Scale to a preference-based health-state utility index ( SF‑6D ) scored from the SF‑36 Health Survey ( SF‑36 ) . Research design and methods : Three data sets were used : ( 1 ) the MOS study , a 4-year observational study of chronically ill patients , ( 2 ) a 7-week open-label , non-comparative clinical trial of an osmotic controlled-release oral delivery system ( OROS ) hydromorphone in the treatment of chronic low back pain ( CLBP ) , and ( 3 ) a 6-week open-label r and omized controlled trial of OROS hydromorphone in the treatment of pain associated with chronic osteoarthritis ( OA ) . Various models were tested , where SF‑6D was regressed onto the Sleep Problem Index‑II ( SLP9 ) in 1000 r and om half ( developmental ) sample s of the MOS ( n = 1413 ) . The best fitting model was applied to the other 1000 r and om half ( cross-validation ) sample s of the MOS ( n = 1412 ) , and to the two trial sample s ( n = 199 in the CLBP trial ; n = 124 in the OA trial ) . Results : The best fitting model in the MOS sample s included a quadratic term for the SLP9 which explained 34 % of the variance in SF‑6D in the developmental sample s. Errors in prediction were greatest at higher SLP9 scores . Addition of demographic and clinical variables to the model explained minimal incremental amounts of variance ( in SF‑6D scores . These results were replicated in the cross-validation MOS sample s. In both developmental and cross-validation MOS sample s , mean predicted and observed SF‑6D scores were nearly identical . When the mapping algorithm developed in the MOS was applied to the CLBP sample , mean predicted SF‑6D scores were 0.09 points higher than observed SF‑6D scores at both baseline and final visits , while changes in predicted and observed SF‑6D scores were identical . Conclusion : Results indicate that it is possible to map MOS SLP9 to SF‑6D yielding useable preference-based scores essential for cost – utility analyses . A limitation concerns the interpretation of SF‑6D scores estimated from SLP9 scores above 60 , where the prediction errors increased considerably",
"OBJECTIVES The SF-6D is a preference-based measure of health derived from the SF-36 that can be used for cost-effectiveness analysis using cost-per- quality adjusted life-year analysis . This study seeks to estimate a system weight for the SF-6D for Portugal and to compare the results with the UK system weights . METHODS A sample of 55 health states defined by the SF-6D has been valued by a representative r and om sample of the Portuguese population , stratified by sex and age ( n = 140 ) , using the St and ard Gamble ( SG ) . Several models are estimated at both the individual and aggregate levels for predicting health-state valuations . Models with main effects , with interaction effects and with the constant forced to unity are presented . R and om effects ( RE ) models are estimated using generalized least squares ( GLS ) regressions . Generalized estimation equations ( GEE ) are used to estimate RE models with the constant forced to unity . Estimations at the individual level were performed using 630 health-state valuations . Alternative functional forms are considered to account for the skewed distribution of health-state valuations . RESULTS The models are analyzed in terms of their coefficients , overall fit , and the ability for predicting the SG-values . The RE models estimated using GLS and through GEE produce significant coefficients , which are robust across model specification . However , there are concerns regarding some inconsistent estimates , and so parsimonious consistent models were estimated . There is evidence of under prediction in some states assigned to poor health . The results are consistent with the UK results . CONCLUSION The models estimated provide preference-based quality of life weights for the Portuguese population when health status data have been collected using the SF-36 . Although the sample was r and omly drowned findings should be treated with caution , given the small sample size , even knowing that they have been estimated at the individual level",
"Background Clinical trials and observational studies lacking measures of health-related quality of life ( QoL ) are often inapplicable when conducting cost-effectiveness analyses using quality -adjusted life-years ( QALYs ) . The only solution is to map QoL ex post from additionally collected clinical outcomes and generic QoL instruments . Nonetheless , mapping studies are absent in psoriatic arthritis ( PsA ) . Methods In this 2-year , prospect i ve , multicentre , non-interventional study of PsA patients , EQ-5D and key clinical parameters such as Disease Activity in PsA ( DAPsA ) , clinical DAPsA ( cDAPsA ; DAPsA without C-reactive protein [ CRP ] ) , and Health Assessment Question naire disability index ( HAQ ) were collected . We employed a linear mixed-effect regression model ( ME ) of the longitudinal data set to explore the best predictors of QoL. Results A total of 228 patients were followed over 873 appointments/observations . DAPsA , cDAPsA and HAQ were stable and highly significant predictors of EQ-5D utilities in both cross-sectional and longitudinal analyses . The best prediction was provided using a linear ME with HAQ and cDAPsA or DAPsA. A HAQ increase of 1 point represented a decrease in EQ-5D by −0.204 or −0.203 ( p dropped EQ-5D equally by −0.005 ( p , cDAPsA provides similar results to DAPsA in predicting",
"Abstract Objective : The aims of this study were to measure the real-life health-related quality of life ( HRQoL ) of newly diagnosed prostate cancer ( PCa ) patients , to compare it with that of the general male population and to explore factors affecting HRQoL. Methods : All newly diagnosed PCa patients in the Helsinki University Hospital were asked to fill in 15D and EORTC QLQ-C30 question naires . Clinical background information was collected retrospectively from patient charts . Patients were categorized into three mutually exclusive groups based on the disease stage : Local , Locally advanced and Metastatic groups . Multivariate linear regression analysis was conducted to explore which factors explained variance in 15D scores . A regression model was built to map the EORTC QLQ-C30 to 15D in a r and om sample of 50 % of patients and the model was tested in the other half of the patients . Results : In total , 1050 men with a mean age of 67 years responded to the question naires . The mean ± SD 15D score of patients was slightly lower than that of the age-st and ardized general male population : 0.905 ± 0.089 vs 0.915 ± 0.082 ( p = .057 ) . The mean ± SD 15D utility scores were 0.912 ± 0.084 , 0.897 ± 0.102 and 0.855 ± 0.109 for Local , Locally advanced and Metastatic groups , respectively . The mapping model of EORTC QLQ-C30 to 15D was robust and fitted well ( root mean square error = 0.042 , adjusted R² = .79 ) . Conclusions : The HRQoL of PCa patients entering treatment was similar to that of the general population . HRQoL was most impaired among patients with metastatic disease , whereas the difference between patients with localized PCa and the general population was minor . Mapping indicated that the 15D score aggregates quite accurately the information from the EORTC QLQ-C30",
"BACKGROUND AND AIMS The aim was to derive health state utility scores in ulcerative colitis ( UC ) by establishing the relationship between the physician-rated ulcerative colitis disease activity index ( UCDAI ) and a patient reported EQ-5D by statistically mapping the two instruments . METHODS In a r and omised controlled trial comparing oral plus enema mesalazine treatment with oral mesalazine treatment alone ( PINCE ) , UCDAI and EQ-5D scores were collected in parallel from patients with active UC . From these data , multinomial logistic regression was used to estimate response probabilities to each of the five domains of the EQ-5D index from assessment of UC disease severity using original and abbreviated ( no endoscopy ) versions of the UCDAI . Predicted EQ-5D responses were converted by Monte Carlo simulation to the EQ-5D index for predicting health-related quality of life ( HRQoL ) . The reliability of the algorithm was tested using UCDAI scores from a second mesalazine RCT ( PODIUM ) . RESULTS The abbreviated-UCDAI showed comparable explanatory performance to the full UCDAI . For patients in remission , mean utility was 0.939 , 0.944 , and 0.940U for PINCE(estimated ) , PINCE(observed ) , and PODIUM , respectively . Mild/moderate and relapsing cases showed mean utilities of 0.801 , 0.811 , and 0.775 , respectively ; whilst for those in severe relapse , the mean utilities were 0.630 , 0.700 and 0.660 units , respectively . The mean squared error between actual and predicted utilities from observations in PINCE was 0.019 . CONCLUSION Response mapping of UC activity to EQ-5D domains produced reliable estimates of patient-rated health state utility consistent with UCDAI rated severity . Comparing abbreviated-UCDAI and full UCDAI suggests that inclusion of endoscopy scores has limited predictive value in estimating patient",
"Purpose The EuroQoL ( EQ-5D ) is ideal to compare quality of life across conditions . However , the Parkinson ’s Disease Question naire ( PDQ-39 ) is often the only quality -of-life instrument used in Parkinson ’s disease research . We aim ed to identify associations between PDQ-39 domains and EQ-5D domains , and compare different methods of developing a function to map the PDQ-39 to EQ-5D scores . Methods Adults with Parkinson ’s disease self-completed both instruments . Ordinal regression identified associations between PDQ-39 domain scores and each EQ-5D domain . Modeling ( n = 80 ) and validation sets ( n = 16 ) were r and omly generated . Overall performance of four methods of mapping the PDQ-39 to EQ-5D scores ( using PDQ-39 domains and total score in ordinal and linear regression ) was assessed with the validation set , followed by assessing the equivalence of observed and predicted EQ-5D scores on the full data set controlling for sociodemographic factors . Results Different sets of PDQ-39 domains were associated with each EQ-5D domain . For example , PDQ-39 “ Activities of Daily Living ” and “ Social Support ” were associated with EQ-5D “ Personal Care , ” while PDQ-39 “ Emotional Well-being ” was associated with EQ-5D “ Anxiety/Depression . ” Over one-third ( 37.5 % ) of predictions from ordinal regressions had an error EQ-5D scores predicted with ordinal regression using PDQ-39 domains were similar in distribution and association with sociodemographic factors to the observed EQ-5D scores . Conclusions Of the four methods tested , using PDQ-39 domains in ordinal regression was superior for mapping EQ-5D scores . The function reported here may prove particularly useful for cost-utility analyses comparing Parkinson ’s disease with other conditions",
"OBJECTIVE Treatment in general is mostly directly aim ed at disease activity , and measures such as the DAS28 might therefore present important additional information . Our aim was to develop and vali date a model that uses a combination of disease activity ( DAS28 ) and HAQs to estimate EuroQoL 5-dimension scale ( EQ5D ) utilities . METHODS Longitudinal data from a cohort study in RA patients from the Utrecht Rheumatoid Arthritis Cohort study Group ( Stichting Reumaonderzoek Utrecht ) who started treatment with a biologic drug were used for mapping and validation . All 702 observations , including DAS28 , HAQ and EQ5D assessed at the same time points , were used . The observations were r and omly divided into a subset for development of the model ( n = 428 observations ) and a subset for validation ( n = 274 ) . A stepwise multivariable regression analysis was used to test the association of DAS28 ( components ) and HAQ ( domains ) with EQ5D . Model performance was assessed using the explained variance ( R(2 ) ) and root mean square errors . Observed and predicted utility scores were compared to check for under- or overestimation of the scores . Finally , the performance of the model was compared with published mapping models . RESULTS Lower DAS28 score and HAQ items dressing and grooming , arising , eating , walking and activities were associated with higher EQ5D scores . The final model had an explained variance of 0.35 and a lower root mean square error as compared with other models tested . The agreement between predicted and observed scores was fair . CONCLUSION HAQ components estimate EQ5D better than total HAQ . Adding DAS28 to HAQ components does not result in better utility estimations",
"Background Many intervention-based studies aim ing to improve mental health do not include a multi-attribute utility instrument ( MAUI ) that produces quality -adjusted life-years ( QALYs ) and it limits the applicability of the health economic analyses . This study aims to develop ‘ crosswalk ’ transformation algorithm between a measure for psychological distress General Health Question naire ( GHQ-12 ) and MAUI EuroQoL ( EQ-5D-3L ) . Methods The study is based on a survey question naire sent to a r and om sample in four counties in Sweden in 2012 . The survey included GHQ-12 and EQ-5D instruments , as well as a question about self-rated health . The EQ-5D index was calculated using the UK and the Swedish tariff values . Two OLS models were used to estimate the EQ-5D health state values using the GHQ-12 as exposure , based on the respondents ( n = 17 , 101 ) of two counties . The algorithms were applied to the data from two other counties , ( n = 15 , 447 ) to check the predictive capacity of the models . Results The final models included gender , age , self-rated health and GHQ-12 scores as a quantitative variable . The regression equations explained 40 % ( UK tariff ) and 46 % ( Swedish tariff ) of the variances . The model showed a satisfying predictive capacity between the observed and the predicted EQ-5D index score , with Pearson correlation = 0.65 and 0.69 for the UK and Swedish models , respectively . Conclusion The algorithms developed in this study can be used to determine cost-effectiveness of services or interventions that use GHQ-12 as a primary outcome where the utility measures are not collected",
"Objective To map the 12-item Multiple Sclerosis Walking Scale ( MSWS-12 ) onto the EuroQol 5-dimension ( EQ-5D ) health-utility index in multiple sclerosis ( MS ) patients participating in the North American Research Committee on Multiple Sclerosis ( NARCOMS ) registry . Design Cross-sectional MSWS-12 to EQ-5D cross-walking analysis . Setting NARCOMS registry spring 2010 biannual up date and supplemental survey . Participants North American patients completing both the MSWS-12 and the EQ-5D r and omly split into derivation and validation cohorts . Outcome measures Ordinary least squares regression was performed within the derivation cohort , with participants ’ EQ-5D as the dependent variable . Results of the MSWS-12 were input as independent variable(s ) into six regression models . Model goodness-of-fit was subsequently assessed in the validation cohort using the mean absolute error ( MAE ) , root mean square error ( RMSE ) and the adjusted R2 . The best performing model was refined in the entire cohort and utilised for additional analyses . Results A total of 3505 NARCOMS participants were included . Their mean±SD EQ-5D and MSWS-12 scores were 0.74±0.18 and 50.8±33.5 , respectively , and these assessment s were found to be moderately correlated ( r=–0.553 , p percentage of EQ-5D estimates within 0.05 and 0.10 of the actual value were 30 % and 61 % , respectively . This mapping equation was more precise in patients with moderate mobility impairment ( MAE=0.087±0.061 at patient-determined disease step ( PDDS ) of 3–6 ) and less precise in patients with no ( MAE=0.141±0.128 at PDDS of 0–2 ) or severe mobility impairment ( MAE=0.121±0.049 at PDDS ≥7 ) . Conclusions The EQ-5D scores can be predicted using the MSWS-12 item scores with reasonable precision in North American patients with MS . Prediction estimates were more precise in patients with moderate mobility impairment",
"Background The aim of this study is to examine the associations between health utility ( HU ) , health-related quality of life ( HRQoL ) , and patient characteristics in postmenopausal osteoporotic ( PMO ) women . Methods Baseline data from a sub sample of 1,245 participants of the Multiple Outcomes of Raloxifene Evaluation study , a r and omized , placebo-controlled , multinational clinical trial to evaluate the safety and efficacy of raloxifene , were analyzed . The study cohort included 694 participants from non-European Union ( non-EU ) countries and 551 participants from EU countries . All participants with complete baseline HU and HRQoL assessment s were included in the following analyses : 1 ) HU ( HUI or EQ-5D ) and HRQoL ( QualEFFO or OPAQ and NHP ) associations ; 2 ) HU variability explained by HRQoL domains ; and 3 ) the percentage of HU variability explained by statistically significant ( p HU scores . HU variance was well explained ( 41 % to 61 % ) by 4 to 6 ( p HU variance was well explained by 5 to 7 significant ( p HRQoL and HU scores with an increased number of vertebral and non-vertebral fractures . Conclusions Both disease-targeted and generic HRQoL domains were well correlated with HU . A large percentage ( 48 % to 64 % ) of the HU variance was explained by HRQoL , after adjusting for baseline characteristics . Both disease-targeted and generic HRQoL measures were significant predictors of HU . HRQoL and HU scores decreased with increased vertebral and non-vertebral fractures",
"BACKGROUND CONTEXT The Neck Disability Index ( NDI ) is a commonly used disease-specific instrument for cervical spine disorders with good responsiveness and psychometric properties compared with general health status measures . However , NDI scores are unitless and do not have an intrinsic value that is comparable to other health status measures , and these scores have limited value in cost-utility analysis . The translation of disease-specific measures to Short Form-6 Dimensions ( SF-6D ) utility scores may be useful in cost-utility analysis . PURPOSE The purpose of this study is to present a model for translating the NDI to SF-6D utility scores , permitting the use of NDI scores in the cost-utility analysis of cervical disorders . STUDY DESIGN / SETTING A secondary analysis of a multicenter prospect i ve clinical trial of the Synthes ProDisc-C ( Synthes , West Chester , PA , USA ) was performed . PATIENT SAMPLE Patients included were r and omized to receive either a total disc arthroplasty or anterior cervical discectomy and fusion for treatment of symptomatic cervical disc disease involving one vertebral level between C3 and C7 . All subjects completed NDI and 36-Item Short Form Health Survey ( SF-36 ) self- assessment s at preoperative and postoperative follow-ups of 6 weeks , 3 , 6 , 12 , 18 , and 24 months . OUTCOME MEASURES The NDI is a vali date d and widely used self-reported question naire design ed to assess patient-determined disability result ing from neck pain , including pain level and effects on activities of daily living . The SF-6D is a preference-based health state classification system derived from six health dimensions of the SF-36 self-reported question naire , including the domains of physical functioning , role limitation , social functioning , bodily pain , mental health , and vitality . METHODS The collected data points were divided into two cohorts : one for model formation and one for the assessment of model validity . SF-36 scores were converted to SF-6D utilities via three previously published methods . Correlation analyses and linear regression modeling between SF-6D and NDI created the models for translating scores . For validation , Spearman and Pearson correlations were calculated between the observed and predicted SF-6D utilities , and prediction errors were calculated . RESULTS Four hundred thirty patients with 2,137 time points were used for creation and validation of the model . Pearson and Spearman correlation coefficients between the NDI and the SF-6D derived from each conversion method were found to be between -0.8255 and -0.8504 ( p mean prediction error was less than 0.006 , with st and ard deviation ( SD ) between 0.082 and 0.093 . DISCUSSION Correlations between NDI and SF-6D utility scores are strong and statistically significant . The model has a large R(2 ) and small RMSE . The prediction models produce a small mean prediction error , but the SD of the prediction errors is large . High correlations between NDI and SF-6D permit these models to be used to calculate overall utilities , changes in utilities , and quality -adjusted life-years for large data sample s. However , the relatively large observed prediction error SDs may limit the accuracy of translation of individual data points or small sample sizes",
"UNLABELLED One of the objectives in the treatment of the inflammatory bowel disease ( IBD ) is improving the patient 's quality of life . However , we do not dispose of vali date d criteria to determine the question naire 's scoring threshold that has to be reached in order to be able to assert that the patients ' quality of life has normalized . OBJECTIVE To determine the normality punctuation cutoff in the IBD specific quality of life question naire IBDQ-36 . METHOD Cross-sectional study in a r and om sample of IBD patients , who have completed the question naires IBDQ-36 and EuroQol-5D . The IBDQ-36 normality was calculated according to its equivalence with the EuroQol-5D tariff ≥ 0.90 , which corresponds to the 95 % CI of the average obtained in a Spanish general population . RESULTS 218 patients were included . According to the EuroQol-5D tariff , 70 patients were considered to have a normal quality of life and 148 a quality of life poorer than the general population . The IBDQ-36 scoring was significantly higher in the normal quality of life group ( 222.9 ± 22.8 vs. 171.4 ± 44.8 in the bad quality of life group , p sensitivity and specificity to predict normality of 0.74 and 0.71 respectively . CONCLUSIONS Scores of the IBDQ-36 equal or superior to 209 suggest quality of life comparable to that perceived by the general population . This study allowed to set a threshold of normality in the management of the inflammatory bowel diseases",
"This is a prospect i ve study to establish prediction models that map the refined Scoliosis Research Society 22-item ( SRS-22r ) onto EuroQoL-5 dimension 5-level ( EQ-5D-5L ) utility scores in adolescent idiopathic scoliosis ( AIS ) patients . Comparison of treatment outcomes in AIS can be determined by cost-utility analysis . However , the mainstay spine-specific health-related quality of life outcome measure , the SRS-22r question naire does not provide utility assessment . In this study , AIS patients were prospect ively recruited to complete both the EQ-5D-5L and SRS-22r question naires by trained interviewers . Ordinary least squares regression was undertaken to develop mapping models , which the validity and robustness were assessed by using the 10-fold cross-validation procedure . EQ-5D-5L utility scores were regressed on demographics , Cobb angle , curve types , treatment modalities , and five domains of the SRS-22r question naire . Three models were developed using stepwise selection method . EQ-5D-5L scores were regressed on 1 ) main effects of SRS-22r subscale scores , 2 ) as per 1 plus squared and interaction terms , and 3 ) as per 2 plus demographic and clinical characteristics . Model goodness-of-fit was assessed using R-square , adjusted R-square , and information criteria ; whereas the predictive performance was evaluated using root mean square error ( RMSE ) , mean absolute error ( MAE ) , and the proportion of absolute error within the threshold of 0.05 and 0.10 . A total of 227 AIS patients with mean age of 15.6 years were recruited . The EQ-5D-5L scores were predicted by four domains of SRS-22r ( main effects of ‘ Function ’ , ‘ Pain ’ , ‘ Appearance ’ and ‘ Mental Health ’ , and squared term of ‘ Function ’ and ‘ Pain ’ ) , and Cobb angle in Model 3 with the best goodness-of-fit ( R-square/adjusted R-square : 62.1%/60.9 % ) . Three models demonstrated an acceptance predictive performance in error analysis applying 10-fold cross-validation to three models where RMSE and MAE were between 0.063–0.065 and between 0.039–0.044 , respectively . Model 3 was therefore recommended out of three mapping models established in this paper . To our knowledge , this is the first study to map a spine-specific health-related quality of life measure onto EQ-5D-5L for AIS patients . With the consideration and incorporation of demographic and clinical characteristics , over 60 % variance explained by mapping model 3 enabled the satisfactory prediction of EQ-5D-5L utility scores from existing SRS-22r data for health economic appraisal of different treatment options",
"OBJECTIVE The objective of this study was to develop empirical algorithms that estimate health-state utility values from disease-specific quality -of-life scores in individuals with migraine . METHODS Data from a cross-sectional , multicountry study were used . Individuals with episodic and chronic migraine were r and omly assigned to training or validation sample s. Spearman 's correlation coefficients between paired EuroQol five-dimensional ( EQ-5D ) question naire utility values and both Headache Impact Test ( HIT-6 ) scores and Migraine-Specific Quality -of-Life Question naire version 2.1 ( MSQ ) domain scores ( role restrictive , role preventive , and emotional function ) were examined . Regression models were constructed to estimate EQ-5D question naire utility values from the HIT-6 score or the MSQ domain scores . Preferred algorithms were confirmed in the validation sample s. RESULTS In episodic migraine , the preferred HIT-6 and MSQ algorithms explained 22 % and 25 % of the variance ( R(2 ) ) in the training sample s , respectively , and had similar prediction errors ( root mean square errors of 0.30 ) . In chronic migraine , the preferred HIT-6 and MSQ algorithms explained 36 % and 45 % of the variance in the training sample s , respectively , and had similar prediction errors ( root mean square errors 0.31 and 0.29 ) . In episodic and chronic migraine , no statistically significant differences were observed between the mean observed and the mean estimated EQ-5D question naire utility values for the preferred HIT-6 and MSQ algorithms in the validation sample s. CONCLUSIONS The relationship between the EQ-5D question naire and the HIT-6 or the MSQ is adequate to use regression equations to estimate EQ-5D question naire utility values . The preferred HIT-6 and MSQ algorithms will be useful in estimating health-state utilities in migraine trials in which no preference-based measure is present",
"OBJECTIVE Disease-oriented quality of life ( QoL ) measures that are not preference-based lack legitimacy for direct use in cost-utility analyses . This has prompted the search for other methods for deriving utilities . The QoL Assessment of Growth Hormone Deficiency in Adults question naire ( QoL-AGHDA ) is a disease-oriented measure used to assess impairment in QoL in adults with growth hormone deficiency . The present study was design ed to generate a model for deriving utilities from the QoL-AGHDA . METHODS The EQ-5D , the QoL-AGHDA , and demographic questions were mailed to a r and om sample ( n = 3005 ) of the Swedish population ( response rate 65 % ) . Multiple regression analysis was used to obtain cross-vali date d parameters of QoL-AGHDA-based utilities . Two models were developed ( simple and full versions ) . The simple version used the EQ-5D(index ) ( derived from European values ) as the dependent variable , and age , sex , and QoL-AGHDA score as independent variables in a regression analysis . The full model utilized all available demographic information . The QoL-AGHDA scores were thus transformed into a single score ( 0 - 1 ) , corresponding to the QoL-AGHDA-based utility . RESULTS The simple transformation algorithm was U ( QoL-AGHDA-based utilities ) = 1.05 - 0.0189 x QoL-AGHDA score - 0.00238 x age - 0.0127 x sex ( male = 0 ; female = 1 ) . The mean of the weighted estimate for the population ( n = 1752 ) was 0.85 ( SD 0.10 ) . The estimate for men ( n = 861 ; mean 0.86 ; SD 0.10 ) was higher ( P < 0.001 ) than for women ( n = 891 ; mean 0.84 ; SD 0.10 ) . CONCLUSION For practical reasons , the simple model can be recommended for deriving utilities directly from the QoL-AGHDA for the Swedish population",
"Purpose To establish and compare generalized or “ global ” mapping relationships between QLQ-C30 and SF-6D , applicable across different cancer types . Methods Patients ( N = 671 ) with breast , myeloma , colorectal , lymphoma , bone marrow , prostate , lung and gastroenteric cancer were r and omly split into estimation ( 75 % ) and validation ( 25 % ) data sets . SF-6D was estimated from QLQ-C30 scores via ordinary least squares , generalized linear models and median ( least-absolute deviations ) regression approaches , and with Bayesian additive regression kernels . Predictive ability was assessed with root mean square error , mean absolute error and proportions of predictions with absolute errors > 0.05 and > 0.1 , whereas explanatory power with adjusted R2 or equivalent fit measures . Two external sample s ( breast and colorectal cancer ) were used to further test the models . Results The QLQ-C30 's global health item , the physical , emotional and social functioning scales , and the fatigue , pain and diarrhea symptom scales were significant predictors ( p overpredicted utilities for patients in worst health and underpredicted them for those in better health ( p SF-6D utilities from QLQ-C30 in patients with different cancers . Testing with diverse patient sample s is required to confirm the generalizability ( or not ) of mapping models across cancer conditions",
"Purpose Economic evaluation of health services commonly requires information regarding health-state utilities . Sometimes this information is not available but non-utility measures of quality of life may have been collected from which the required utilities can be estimated . This paper examines the possibility of mapping a non-utility-based outcome , the Sydney Asthma Quality of Life Question naire ( AQLQ-S ) , onto five multi-attribute utility instruments : Assessment of Quality of Life 8 Dimensions ( AQoL-8D ) , EuroQoL 5 Dimensions 5-Level ( EQ-5D-5L ) , Health Utilities Index Mark 3 ( HUI3 ) , 15 Dimensions ( 15D ) , and the Short-Form 6 Dimensions ( SF-6D ) . Methods Data for 856 individuals with asthma were obtained from a large Multi-Instrument Comparison ( MIC ) survey . Four statistical techniques were employed to estimate utilities from the AQLQ-S. The predictive accuracy of 180 regression models was assessed using six criteria : mean absolute error ( MAE ) , root mean squared error ( RMSE ) , correlation , distribution of predicted utilities , distribution of residuals , and proportion of predictions with absolute errors a quadratic term for the AQLQ-S score along with demographic variables . The four statistical techniques predicted models that performed differently when assessed by the six criteria ; however , the best results , for both the estimation and validation sample s , were obtained using a generalised linear model ( GLM estimator ) . Conclusions It is possible to predict valid utilities from the AQLQ-S using regression methods . We recommend GLM models for this exercise",
"Abstract Purpose Quality of life mapping methods such as “ Transfer to Utility ” can be used to translate scores on disease-specific measures to utility values , when traditional utility measurement methods ( e.g. st and ard gamble , time trade-off , preference-based multi-attribute instruments ) have not been used . The aim of this study was to generate preliminary ordinary least squares ( OLS ) regression-based algorithms to transform scores from the Strengths and Difficulties Question naires ( SDQ ) , a widely used measure of mental health in children and adolescents , to utility values obtained using the preference-based Child Health Utility ( CHU9D ) instrument . Methods Two hundred caregivers of children receiving community mental health services completed the SDQ and CHU9D during a telephone interview . Two OLS regressions were run with the CHU9D utility value as the dependent variable and SDQ subscales as predictors . Result ing algorithms were vali date d by comparing predicted and observed group mean utility values in r and omly selected sub sample s. Results Preliminary validation was obtained for two algorithms , utilising five and three subscales of the SDQ , respectively . Root mean square error values ( .124 ) for both models suggested poor fit at an individual level , but both algorithms performed well in predicting mean group observed utility values . Conclusion This research generated algorithms for translating SDQ scores to utility values and providing research ers with an additional tool for conducting health economic evaluations with child and adolescent mental health data",
"OBJECTIVES The Rol and Morris Question naire ( RMQ ) is a widely used health status measure for low back pain ( LBP ) . It is not preference-based , and there are currently no established algorithms for mapping between the RMQ and preference-based health-related quality -of-life measures . Using data from r and omized controlled trials of treatment for LBP , we sought to develop algorithms for mapping between RMQ scores and health utilities derived using either the EuroQol five-dimensional question naire ( EQ-5D ) or the six-dimensional health state short form ( derived from Medical Outcomes Study 36-Item Short-Form Health Survey ) ( SF-6D ) . METHODS This study is based on data from the Back Skills Training Trial in which data were collected from 701 patients at baseline and subsequently at 3 , 6 , and 12 months postr and omization using a range of outcome measures , including the RMQ , the EQ-5D , and the Short Form 12 item Health Survey ( SF-12 ) ( from which SF-6D utilities can be derived ) . We used baseline trial data to estimate models using both direct and response mapping approaches to predict EQ-5D and SF-6D health utilities and dimension responses . A multistage model selection process was used to assess the predictive accuracy of the models . We then explored different techniques and mapping models that made use of repeated follow-up observations in the data . The estimated mapping algorithms were vali date d using external data from the UK Back Pain Exercise and Manipulation trial . RESULTS A number of models were developed that accurately predict health utilities in this context . The best performing model for RMQ to EQ-5D mapping was a beta regression with Bayesian quasi-likelihood estimation that included 24 dummy variables for RMQ responses , age , and sex as covariates ( mean squared error 0.0380 ) based on repeated data . The model selected for RMQ to SF-6D mapping was a finite mixture model that included the overall RMQ score , age , sex , RMQ score squared , age squared , and an interaction term for age and RMQ score as covariates ( mean squared error 0.0114 ) based on repeated data . CONCLUSIONS It is possible to reasonably predict EQ-5D and SF-6D health utilities from RMQ scores and responses using regression methods . Our regression equations provide an empirical basis for estimating health utilities when EQ-5D or SF-6D data are not available . They can be used to inform future economic evaluations of interventions targeting LBP",
"Purpose To investigate the statistical relationship between the OM8 - 30 health-related quality of life measure for children with otitis media with effusion ( OME ) and measures of health utility ( Health Utilities Index [ HUI ] Mark 3 and Mark 2 ) and to develop models to estimate HUI3 and HUI2 health utilities from OM8 - 30 scores . Methods A placebo-controlled , r and omised trial ( GNOME ) evaluating intranasal mometasone in 217 children with OME provided concurrent responses to OM8 - 30 and HUI at three time points . Ordinary least squares ( OLS ) , generalised linear models and two-step regression analyses were used to predict HUI3 and HUI2 utilities based on OM8 - 30 facet and domain scores . Results OLS models including all nine OM8 - 30 facets with or without predicted hearing level ( HL ) produced the best predictions of HUI3 utilities ( mean absolute error : 0.134 with HL and 0.132 without ; R2 : 0.63 with HL and 0.596 without ) . An OLS model predicting HUI3 utilities based on the two OM8 - 30 domain scores , reported hearing difficulties , predicted HL , age and sex also produced accurate predictions . Conclusion Regression equations predicting HUI3 and HUI2 utilities based on OM8 - 30 facet and domain scores have been developed . These provide an empirical basis for estimating quality -adjusted life years ( QALYs ) for interventions in children with OME",
"Study Design . Cross-sectional cohort . Objective . This study aims to provide an algorithm to estimate Short Form-6D ( SF-6D ) utilities using data from the Neck Disability Index ( NDI ) , neck pain , and arm pain scores . Summary of Background Data . Although cost-utility analysis is increasingly used to provide information about the relative value of alternative interventions , health state values or utilities are rarely available from clinical trial data . The Neck Disability Index ( NDI ) and numerical rating scales for neck and arm pain are widely used diseasespecific measures in patients with cervical degenerative disorders . The purpose of this study is to provide an algorithm to allow estimation of SF-6D utilities using data from the NDI , and numerical rating scales for neck and arm pain . Methods . SF-36 , NDI , neck and arm pain rating scale scores were prospect ively collected before surgery , at 12 and 24 months after surgery in 2080 patients undergoing cervical fusion for degenerative disorders . SF-6D utilities were computed , and Spearman correlation coefficients were calculated for paired observations from multiple time points between NDI , neck and arm pain scores , and SF-6D utility scores . SF-6D scores were estimated from the NDI , neck and arm pain scores were estimated using a linear regression model . Using a separate , independent data set of 396 patients in which NDI scores were available , SF-6D was estimated for each subject and compared to their actual SF-6D . Results . The mean age for those in the development sample was 50.4 ± 11.0 years and 33 % were male . In the validation sample , the mean age was 53.1 ± 9.9 years and 35 % were male . Correlations between the SF-6D and the NDI , neck and arm pain scores were statistically significant ( P mean SF-6D ( 0.49 ± 0.08 ) and the estimated mean SF-6D score ( 0.49 ± 0.08 ) , using the NDI regression model . Conclusion . This regression-based algorithm may be a useful tool to predict SF-6D scores in studies of cervical degenerative disease that have collected NDI but not utility scores",
"Introduction : Cancer clinical trials frequently incorporate quality of life ( QoL ) measures but rarely patient utility . Utility information is required for cost utility evaluations of novel cancer therapies . We assessed the feasibility of converting QoL data into utility scores using the European Organization for Research and Treatment of Cancer Quality of Life-Core 30 question naire ( EORTC QLQ-C30 ) and the EQ-5D in patients with non-small cell lung cancer ( NSCLC ) . Methods : Out patients with all different disease states of NSCLC attending a major Canadian cancer center completed the QLQ-C30 and EQ5D on a single visit . Results of the QLQ-C30 summary scores were mapped to predict EQ-5D utility scores using linear regression . Backward variable elimination using the Akaike Information Criterion was used to reduce the full model that included all QLQ-C30 summary scores to examine which QLQ-C30 dimensions best predict a patient 's utility score . To test the predictive power of the model , 10-fold cross-validation was used . Results : A total of 172 patients participated in the study . Median age of the sample was 66 years ( range , 32–85 years ) ; 46.5 % were men . The cross-validation estimate of mean utility score was 0.76 ( SD : 0.20 ) , which was the same as the actual mean utility score . Of the 15 QLQ-C30 dimensions , 4 functional dimensions ( physical , role , emotional , and social ) and the pain symptom dimension were predictive of patient utility scores . Conclusions : Our study demonstrates the feasibility of deriving utility scores from prospect i ve QoL data . Validation of the QLQ-C30 predictors found in this study could further the ability to estimate cost utility of therapies for economic evaluations",
"Purpose The macular degeneration quality of life ( MacDQoL ) instrument is a vali date d condition-specific measure of quality of life in patients with macular degeneration . This paper presents the first mapping algorithm to predict EQ-5D from responses to the MacDQoL instrument . Methods Responses to the MacDQoL and EQ-5D-3L instruments from 482 patients were collected from the IVAN multicentre trial of two alternative drug treatments for neovascular age-related macular degeneration . Regression specifications were estimated using OLS , censored least absolute deviation , Tobit and two-part models . Their predictive performance was assessed using mean squared error . An internal validation sample based on a r and om selection of 25 % of patients was used to assess the performance of the model estimated on the remaining 75 % of patients . Results A two-part model had the best predictive performance on the full sample . The covariates of this model include responses and weighted impact scores for all 23 condition-specific domains of the MacDQoL , and responses to a general MacDQoL quality of life question . The selected models were successful at predicting means and st and ard deviations of target population s , but prediction is weaker at the upper and lower extremes of the EQ-5D-3L distribution . Conclusion The mapping algorithms provide a means of predicting EQ-5D-3L index scores from MacDQoL scores , and could facilitate cost-effectiveness analyses when the latter but not the former are available to research ers . Further validation of the performance of the algorithms using external data would provide a means of establishing the robustness of the algorithms",
"OBJECTIVE To map the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) onto the EuroQol 5 Dimension ( EQ-5D ) utility index in patients with knee osteoarthritis ( OA ) . METHODS A consecutive sample of patients ( n=258 ) diagnosed with knee OA completed both the WOMAC and the EQ-5D . Regression models with the ordinary least squares ( OLS ) or the censored least absolute deviations as the estimator were used to establish the mapping function . The WOMAC was represented as explanatory variables in four ways : 1 ) total score ; 2 ) domain scores ( i.e. , pain , stiffness , and physical function ) ; 3 ) domain scores plus pair-wise interaction terms to account for possible nonlinearities ; and 4 ) individual item scores . Goodness-of-fit criteria included the mean absolute error ( the primary criterion ) and the root mean squared error , and were obtained using an iterative r and om sampling procedure . Prediction precision was evaluated at individual patient level and at the group level . RESULTS The model using the OLS estimator and the WOMAC domain scores as explanatory variables had the best fit and was chosen as the preferred mapping model . The prediction error at the individual level exceeded the maximal tolerance value ( i.e. , the minimally important difference of the EQ-5D ) in about 16 % of the patients . At the group level , the width of the 95 % confidence interval of prediction errors varied from 0.0176 at a sample size of 400 to 0.0359 at a sample size of 100 . CONCLUSIONS EQ-5D scores can be predicted using WOMAC domain scores with an acceptable precision at both individual and group levels in patients with mild to moderate knee OA",
"Abstract Purpose : To develop a mapping algorithm for the estimation of EQ-5D-based utility scores from observed 25-item National Eye Institute Visual Functioning Question naire ( NEI VFQ-25 ) scores , a disease-specific , patient-reported outcome measure used in several retinal disorders to evaluate vision-specific functioning . Methods : The data set comprised 951 paired EQ-5D/NEI VFQ-25 observations from 344 patients in RESTORE , a 12-month , r and omized , double-blind trial in individuals with visual impairment due to diabetic macular edema . EQ-5D index scores ( utilities ) were calculated based on the UK tariff . We evaluated 11 models using predictor sets based on the NEI VFQ-25 subscales to estimate utility as a function of NEI VFQ-25 score , based on four modeling techniques . Model performance was assessed by 10-fold cross-validation comparing root mean squared error ( RMSE ) , mean absolute error ( MAE ) and correlation with EQ-5D score ( Pearson and Spearman correlation coefficients ) . Results : Mapping results were similar across all techniques and predictor sets . The reverse two-part generalized estimating equation model used fewest predictors and had the best predictive performance ( RMSE 0.200 , MAE 0.140 ) . Predicted and original EQ-5D values were not strongly correlated ( squared Spearman correlation coefficient , 0.34 ) . Conclusions : Although mapping disease-specific instruments to EQ-5D utilities is a preferred method by some reimbursement bodies , finding an appropriate mapping equation is not straightforward . In this study , mapping NEI VFQ-25 scores to EQ-5D utilities provided low predictive power , independent of the modeling methodology applied , suggesting an inability of the EQ-5D to discriminate vision-related activities , and highlighting that mapping exercises may lead to inaccurate utility values that do not represent patients ’ preferences",
"OBJECTIVE The main objective of the study was to estimate a preference-based Short Form (SF)-6D index from the SF-36 for Japan and compare it with the UK results . STUDY DESIGN AND SETTING The SF-6D was translated into Japanese . Two hundred and forty-nine health states defined by this version of the SF-6D were then valued by a representative sample of 600 members of the Japanese general population using st and ard gamble ( SG ) . These health-state values were modeled using classical parametric r and om-effect methods with individual-level data and ordinary least squares ( OLS ) on mean health-state values , together with a new nonparametric approach using Bayesian methods of estimation . RESULTS All parametric models estimated on Japanese data were found to perform less well than their UK counterparts in terms of poorer goodness of fit , more inconsistencies , larger prediction errors and bias , and evidence of systematic bias in the predictions . Nonparametric models produce a substantial improvement in out-of- sample predictions . The physical , role , and social dimensions have relatively larger decrements than pain and mental health compared with those in the United Kingdom . CONCLUSION The differences between Japanese and UK valuations of the SF-6D make it important to use the Japanese valuation data set estimated using the nonparametric Bayesian technique presented in this article",
"ABSTRACT Aim : To map health-related quality of life ( Qol ) with clinical parameters BASFI and ASDAS-CRP measure , and other covariates . Methods : Our prospect i ve multicenter non-interventional observation study of ankylosing spondylitis ( AS ) collected data about QoL and clinical outcomes on the initial and four subsequent visits . We employed simple linear regression analysis of a cross-sectional data set , and fixed effect , r and om effect and pooled linear regression of a longitudinal data set . Results : We showed that BASFI and ASDAS-CRP are very strong , robust predictors of EQ-5D utilities in all regression specifications together with sex ( female ) , invalidity , and activity impairment . Additionally , the longitudinal regression analysis showed that a fixed effect model may be a viable alternative to the most commonly used r and om effect model or pooled linear regression due to the nature of our data set . Conclusion : This is one of the first studies using a fixed effect model in longitudinal patient-level data , although , this method has been widely used in economics",
"This paper describes constructing the Assessment of Quality of Life ( AQoL ) instrument ; design ed to measure health-related quality of life ( HRQoL ) , and to be the descriptive system for a multi-attribute utility instrument . Unlike previous utility instruments ' descriptive systems , the AQoL 's has been developed using state-of-the-art psychometric procedures . The result is a descriptive system which emphasizes five different facets of HRQoL and which can cl aim to have construct validity . Based on the WHO 's definition of health a model of HRQoL was developed . Items were written by focus groups of doctors and the research ers . These were administered to a construction sample , comprising hospital patients , and community members chosen at r and om . Final construction was through an iterative process of factor and reliability analyses . The AQoL measures 5 dimensions : illness , independent living , social relationships , physical senses and psychological wellbeing . Each has three items . Exploratory factor analysis showed the dimensions were orthogonal , and each was unidimensional . Internal consistency was α = 0.81 . Structural equation modeling explored its internal structure ; the comparative fit index was 0.90 . These preliminary results indicate the AQoL has the prerequisite qualities for a psychometric HRQoL instrument for evaluation ; replication with a larger sample is needed to verify these findings . Scaling it for economic evaluation using utilities is being undertaken . Respondents have indicated the AQoL is easy to underst and and is quickly completed . Its initial properties suggest it may be widely applicable",
"Background . Mapping disease-specific instruments into generic health outcomes or utility values is an exp and ing field of interest in health economics . This article constructs an algorithm to translate the modified Rankin scale ( mRS ) into EQ-5D utility values . Methods . mRS and EQ-5D information was derived from stroke or transient ischemic attack ( TIA ) patients identified as part of the Oxford Vascular study ( OXVASC ) . Ordinary least squares ( OLS ) regression was used to predict UK EQ-5D tariffs from mRS scores . An alternative method , using multinomial logistic regression with a Monte Carlo simulation approach ( MLogit ) to predict responses to each EQ-5D question , was also explored . The performance of the models was compared according to the magnitude of their predicted-to-actual mean EQ-5D tariff difference , their mean absolute and mean squared errors ( MAE and MSE ) , and associated 95 % confidence intervals ( CIs ) . Out-of- sample validation was carried out in a subset of coronary disease and peripheral vascular disease ( PVD ) patients also identified as part of OXVASC but not used in the original estimation . Results . The OLS and MLogit yielded similar MAE and MSE in the internal and external validation data sets . Both approaches also underestimated the uncertainty around the actual mean EQ-5D tariff producing tighter 95 % CIs in both data sets . Conclusions . The choice of algorithm will be dependent on the study aim . Individuals outside the United Kingdom may find it more useful to use the multinomial results , which can be used with different country-specific tariff valuations . However , these algorithms should not replace prospect i ve collection of utility data",
"Purpose The chronic liver disease question naire ( CLDQ ) is a frequently used liver-specific quality of life instrument , but it does not provide information on preference-adjusted health status , which is essential for cost-utility analysis . We aim ed to develop a mapping function deriving utilities from the CLDQ in primary sclerosing cholangitis ( PSC ) . Methods Short form-6D ( SF-6D ) utilities were calculated from SF-36 data collected in a recent prospect i ve study in which unselected patients with PSC also completed the CLDQ . Ordinary least squares ( OLS ) , generalized linear , median , and kernel regression analyses were employed to devise a mapping function predicting utilities . This was vali date d in three r and om sub sample s of the cohort and in a separate sample of PSC patients following liver transplantation . Adjusted R2 and root-mean-square error ( RMSE ) as well as Pearson ’s r coefficients and mean absolute errors between predicted and observed values were used to determine model performance . Results Decompensated liver disease and fatigue , systemic symptoms , and emotional distress , assessed with the CLDQ , were related to worse SF-6D utilities . The final OLS prediction model explained 66.3 % of the variance in the derivation sample . Predicted and observed utilities were strongly correlated ( r = 0.807 , p mean absolute error ( 0.0604 ) and adjusted RMSE ( 10.6 % ) were of intermediate size . Similar model characteristics were observed after employment of generalized linear and median regression models and at validation . Conclusions A model has been constructed , showing good validity predicting SF-6D utilities from CLDQ scores at the group level in PSC . Further testing is required to externally vali date the model",
"The Health Utilities Index Mark 2 ( HUI:2 ) is a generic multiattribute , preference-based system for assessing health-related quality of life . Health Utilities Index Mark 2 consists of two components : a seven-attribute health status classification system and a scoring formula . The seven attributes are sensation , mobility , emotion , cognition , self-care , pain , and fertility . A r and om sample of general population parents were interviewed to determine cardinal preferences for the health states in the system . The health states were defined as lasting for a 60-year lifetime , starting at age 10 . Values were measured using visual analogue scaling . Utilities were measured using a st and ard gamble technique . A scoring formula is provided , based on a multiplicative multiattribute utility function from the responses of 194 subjects . The utility scores are death-anchored ( death = 0.0 ) and form an interval scale . Health Utilities Index Mark 2 and its utility scores can be useful to other research ers in a wide variety of setting s who wish to document health status and assign preference scores",
"Purpose Many trials do not measure quality -adjusted life years ( QALYs ) . Therefore , decision analysts often map condition-specific outcomes to preference scores . We estimated the relationship between changes in preference scores and commonly reported condition-specific outcomes in patients with urinary incontinence ( UI ) due to neurogenic detrusor overactivity . Methods In 59 patients recruited to a neurogenic UI trial , clinical outcomes ( UI episodes ) , condition-specific quality of life ( Incontinence Quality of Life Instrument ( I-QOL ) ) , and SF-6D preference scores were measured at enrollment and 24 weeks . We used multiple linear regression to estimate the impact on SF-6D scores of 50 ; 50–99 and 100 % reductions in UI episodes and a 10-point improvement in I-QOL . Results By 24 weeks , mean ( 95 % CI ) daily UI episodes fell by 0.85 ( 0.04 , 1.3 ) and mean I-QOL scores improved by 18 ( 12 , 24 ) . SF-6D scores increased by 0.03 ( 0.003 , 0.058 ) , due to improvements in role limitations . A ≥ 50 % reduction in UI episodes was achieved by 49 % of patients and corresponded to a 0.09 ( 0.02 , 0.16 ) SF-6D increase . A ≥ 10-point increase in I-QOL was attained by 65 % of patients and was associated with a 0.05 ( −0.02 , 0.12 ) SF-6D increase . Conclusions These estimates provide preliminary data for decision analysts wishing to map neurogenic UI outcomes to preference scores",
"In contrast to the recent proliferation of studies incorporating ordinal methods to generate health state values from adults , to date relatively few studies have utilised ordinal methods to generate health state values from adolescents . This paper reports upon a study to apply profile case best worst scaling methods to derive a new adolescent specific scoring algorithm for the Child Health Utility 9D ( CHU9D ) , a generic preference based instrument that has been specifically design ed for the estimation of quality adjusted life years for the economic evaluation of health care treatment and preventive programs targeted at young people . A survey was developed for administration in an on-line format in which consenting community based Australian adolescents aged 11 - 17 years ( N = 1982 ) indicated the best and worst features of a series of 10 health states derived from the CHU9D descriptive system . The data were analyzed using latent class conditional logit models to estimate values ( part worth utilities ) for each level of the nine attributes relating to the CHU9D . A marginal utility matrix was then estimated to generate an adolescent-specific scoring algorithm on the full health = 1 and dead = 0 scale required for the calculation of QALYs . It was evident that different decision processes were being used in the best and worst choices . Whilst respondents appeared readily able to choose ' best ' attribute levels for the CHU9D health states , a large amount of r and om variability and indeed different decision rules were evident for the choice of ' worst ' attribute levels , to the extent that the best and worst data should not be pooled from the statistical perspective . The optimal adolescent-specific scoring algorithm was therefore derived using data obtained from the best choices only . The study provides important insights into the use of profile case best worst scaling methods to generate health state values with adolescent population",
"OBJECTIVES To develop a model to predict EuroQol five-dimensional question naire ( EQ-5D ) values from clinical chronic obstructive pulmonary disease ( COPD ) question naire ( CCQ ) scores . METHODS We used data from three clinical trials ( the R and omized Clinical Trial on Effectiveness of Integrated COPD Management in Primary Care [ RECODE ] , the Assessment Of Going Home Under Early Assisted Discharge [ GO-AHEAD ] , and the Health Status Guided COPD Care [ MARCH ] ) . Data were r and omly split into an estimation sample and a validation sample . The conceptual similarity between patient-reported CCQ and preference-based EQ-5D scores was assessed using correlation and principal-component analysis . Different types of models were estimated with increasing complexity . We selected the final models on the basis of mean absolute error and root mean square error when comparing predicted and observed values from the same population ( internal validity ) and from different trial population s ( external validity ) . We also developed models for different country-specific EQ-5D value sets . RESULTS The principal-component analysis showed that the CCQ domains functional state and mental state are associated with four dimensions of the EQ-5D . The EQ-5D dimension pain/discomfort formed a separate construct on which no CCQ item loaded . The mean observed EQ-5D values were not significantly different from the mean predicted EQ-5D values in internal validation sample s but did significantly differ in external validation sample s. The models underestimated EQ-5D values in milder health states and overestimated them in more severe health states . The predictive ability of the models was similar across different EQ-5D value sets . CONCLUSIONS The models can predict mean EQ-5D values that are similar to observed mean values in a similar population . The overestimating/underestimating of the low/high EQ-5D values , however , limits its use in Markov models . Therefore , mapping should be used cautiously",
"Background . The Health Utilities Index Mark 3 ( HUI3 ) is a generic multiattribute preference‐based measure of health status and health‐related quality of life that is widely used as an outcome measure in clinical studies , in population health surveys , in the estimation of quality ‐adjusted life years , and in economic evaluations . HUI3 consists of eight attributes ( or dimensions ) of health status : vision , hearing , speech , ambulation , dexterity , emotion , cognition , and pain with 5 or 6 levels per attribute , varying from highly impaired to normal . Objectives . The objectives are to present a multiattribute utility function and eight single‐attribute utility functions for the HUI3 system based on community preferences . Study Design . Two preference surveys were conducted . One , the modeling survey , collected preference scores for the estimation of the utility functions . The other , the direct survey , provided independent scores to assess the predictive validity of the utility functions . Measures . Preference measures included value scores obtained on the Feeling Thermometer and st and ard gamble utility scores obtained using the Chance Board . Respondents . A r and om sample of the general population ( ≥16 years of age ) in Hamilton , Ontario , Canada . Results . Estimates were obtained for eight single‐attribute utility functions and an overall multiattribute utility function . The intraclass correlation coefficient between directly measured utility scores and scores generated by the multiattribute function for 73 health states was 0.88 . Conclusions . The HUI3 scoring function has strong theoretical and empirical foundations . It performs well in predicting directly measured scores . The HUI3 system provides a practical way to obtain utility scores based on community preferences",
"OBJECTIVES SF-6D is a preference-based measure of health developed to estimate utility values from the SF-36 . The aim of this study was to estimate a weighting system for the SF-6D health states representing the preferences of a sample of the Southern Brazilian general population . METHODS A sample of 248 health states defined by the SF-6D was valued by a sample of the southern Brazilian population using the st and ard gamble . Mean and individual level multivariate regression models were fitted to the st and ard gamble valuation data to estimate preference weights for all SF-6D health states . The models were compared with those estimated in the UK study . RESULTS Five hundred twenty-eight participants were interviewed , but 58 ( 11 % ) were excluded for failing to value the worst state . Data from 469 subjects producing 2696 health states valuations were used in the regression analysis . In contrast to the best performing model for the UK data , the best performing model for the Brazilian data was a r and om effects model using only the main effects variables , highlighting the importance of adopting a country-specific algorithm to derive SF-6D health states values . Inconsistent coefficients were merged to produce the final recommended model , which has all significant coefficients and a mean absolute difference between observed and predicted st and ard gamble values of 0.07 . CONCLUSIONS The results provide the first population -based value set for Brazil for SF-6D health states , making it possible to generate quality -adjusted life years for cost-utility studies using regional data . Besides , utility weights derived using the preferences of a sample from a southern Brazilian population can be derived from existing SF-36 data sets",
"Abstract The aim of this study was to estimate the mapping model for EuroQol-5D ( EQ-5D ) utility values using the health assessment question naire disability index ( HAQ-DI ) , pain visual analog scale ( VAS ) , and disease activity score in 28 joints ( DAS28 ) in a large , nationwide cohort of rheumatoid arthritis ( RA ) patients in Korea . The KORean Observational study Network for Arthritis ( KORONA ) registry data on 3557 patients with RA were used . Data were r and omly divided into a modeling set ( 80 % of the data ) and a validation set ( 20 % of the data ) . The ordinary least squares ( OLS ) , Tobit , and two-part model methods were employed to construct a model to map to the EQ-5D index . Using a combination of HAQ-DI , pain VAS , and DAS28 , four model versions were examined . To evaluate the predictive accuracy of the models , the root-mean-square error ( RMSE ) and mean absolute error ( MAE ) were calculated using the validation data set . A model that included HAQ-DI , pain VAS , and DAS28 produced the highest adjusted R2 as well as the lowest Akaike information criterion , RMSE , and MAE , regardless of the statistical methods used in modeling set . The mapping equation of the OLS method is given as EQ-5D = 0.95−0.21 × HAQ-DI−0.24 × pain VAS/100–0.01 × DAS28 ( adjusted R2 = 57.6 % , RMSE = 0.1654 and MAE = 0.1222 ) . Also in the validation set , the RMSE and MAE were shown to be the smallest . The model with HAQ-DI , pain VAS , and DAS28 showed the best performance , and this mapping model enabled the estimation of an EQ-5D value for RA patients in whom utility values have not been measured",
"Background Economic evaluation normally requires information to be collected on outcome improvement using utility values . This is often not collected during the treatment of substance use disorders making cost-effectiveness evaluations of therapy difficult . One potential solution is the use of mapping to generate utility values from clinical measures . This study develops and evaluates mapping algorithms that could be used to predict the EuroQol-5D ( EQ-5D-5 L ) and the ICEpop CAPability measure for Adults ( ICECAP-A ) from the three commonly used clinical measures ; the CORE-OM , the LDQ and the TOP measures . Methods Models were estimated using pilot trial data of heroin users in opiate substitution treatment . In the trial the EQ-5D-5 L , ICECAP-A , CORE-OM , LDQ and TOP were administered at baseline , three and twelve month time intervals . Mapping was conducted using estimation and validation data sets . The normal estimation data set , which comprised of baseline sample data , used ordinary least squares ( OLS ) and tobit regression methods . Data from the baseline and three month time periods were combined to create a pooled estimation data set . Cluster and mixed regression methods were used to map from this data set . Predictive accuracy of the models was assessed using the root mean square error ( RMSE ) and the mean absolute error ( MAE ) . Algorithms were vali date d using sample data from the follow-up time periods . Results Mapping algorithms can be used to predict the ICECAP-A and the EQ-5D-5 L in the context of opiate dependence . Although both measures can be predicted , the ICECAP-A was better predicted by the clinical measures . There were no advantages of pooling the data . There were 6 chosen mapping algorithms , which had MAE scores ranging from 0.100 to 0.138 and RMSE scores ranging from 0.134 to 0.178 . Conclusion It is possible to predict the scores of the ICECAP-A and the EQ-5D-5 L with the use of mapping . In the context of opiate dependence , these algorithms provide the possibility of generating utility values from clinical measures and thus enabling economic evaluation of alternative therapy options . Trial registration IS RCT N22608399 . Date of registration : 27/04/2012 . Date of first r and omisation : 14/08/2012",
"OBJECTIVES We sought to develop a mapping function from functional assessment of cancer therapy-melanoma ( FACT-M ) quality of life scores to the EuroQol-5D ( EQ-5D ) utility scores . METHODS FACT-M and EQ-5D scores were collected during a prospect i ve study of melanoma-related quality of life at a tertiary cancer care center in the United States . The study sample was divided into development and validation data sets with equal distributions by cancer stage and treatment status . Censored Least Absolute Deviation ( CLAD ) and Ordinary Least Squares ( OLS ) regression analyses were performed using the developmental data set to derive mapping functions , and model performance was examined through comparisons of residuals and measures of fit in the validation data set . Exploratory analyses examined the predictive ability of clinical factors and individual subscales . RESULTS Of 273 patients , 75 were undergoing treatment with 198 in follow-up surveillance . Relatively even distributions were observed by melanoma stage : I/II ( n = 102 ) , III ( n = 100 ) , and IV ( n = 71 ) . OLS regression result ed in a mapping function of EQ-5D = 0.0037*FACT-M+0.2238 with an R(2 ) 0.499 . CLAD regression result ed in a mapping function of EQ-5D = 0.0042*FACT-M+0.1648 with pseudo R(2 ) 0.328 . When applied to the validation data set , correlations between observed and predicted values result ed in identical coefficients ( r = 0.824 , P residuals only for patients whose EQ-5D = 1 . CONCLUSIONS The OLS mapping function demonstrated better predictive ability and will facilitate the derivation of utilities when direct population preference measures are not available",
"OBJECTIVES To develop an algorithm to predict the three-level EuroQol five-dimensional question naire ( EQ-5D-3L ) utility scores from the Dermatology Life Quality Index ( DLQI ) in psoriasis . METHODS This mapping study used data from the British Association of Dermatologists Biologic Interventions Register-a pharmacovigilance register comprising patients with moderate to severe psoriasis on systemic therapies . Conceptual overlap between the EQ-5D-3L and DLQI was assessed using Spearman rank correlation coefficients and exploratory factor analysis . Six regression methods to predict the EQ-5D-3L index ( direct mapping ) and two regression methods to predict EQ-5D-3L domain responses ( response mapping ) were tested . R and om effects models were explored to account for repeated observations from the same individual . Estimated and actual EQ-5D-3L utility scores were compared using 10-fold cross-validation ( in- sample ) to evaluate predictive performance . Final models were selected using root mean squared error , mean absolute error , and mean error . RESULTS The data set comprised 22,085 observations for which DLQI and EQ-5D-3L were recorded on the same day . A moderate correlation was found between the measures ( r = -0.47 ) . Exploratory factor analysis showed that two EQ-5D-3L domains ( pain/discomfort and depression/anxiety ) were associated with all six DLQI domains . The best-performing model used ordinary least squares with DLQI items , age , and sex as explanatory variables ( with squared , cubic , and interaction terms ) . A tool was produced to allow users to map their data to the EQ-5D-3L , and includes algorithms that require fewer variables ( e.g. , total DLQI scores ) . CONCLUSIONS This study produced mapping algorithms that can generate EQ-5D-3L utility scores from DLQI data for economic evaluations of health interventions for patients with psoriasis",
"Purpose The purpose of the study was to compare alternative statistical techniques to find the best approach for converting QLQ-C30 scores onto EQ-5D-5L and SF-6D utilities , and to estimate the mapping algorithms that best predict these health state utilities . Methods 772 cancer patients described their health along the cancer-specific instrument ( QLQ-C30 ) and two generic preference-based instruments ( EQ-5D-5L and SF-6D ) . Seven alternative regression models were applied : ordinary least squares , generalized linear model , extended estimating equations ( EEE ) , fractional regression model , beta binomial ( BB ) regression , logistic quantile regression and censored least absolute deviation . Normalized mean absolute error ( NMAE ) , normalized root mean square error ( NRMSE ) , r-squared ( r2 ) and concordance correlation coefficient ( CCC ) were used as model performance criteria . Cross-validation was conducted by r and omly splitting internal data set into two equally sized groups to test the generalizability of each model . Results In predicting EQ-5D-5L utilities , the BB regression performed best . It gave better predictive accuracy in terms of all criteria in the full sample , as well as in the validation sample . In predicting SF-6D , the EEE performed best . It outperformed in all criteria : NRMSE = 0.1004 , NMAE = 0.0798 , CCC = 0.842 and r2 = 72.7 % in the full sample , and NRMSE = 0.1037 , NMAE = 0.0821 , CCC = 0.8345 and r2 = 71.4 % in cross-validation . Conclusions When only QLQ-C30 data are available , mapping provides an alternative approach to obtain health state utility data for use in cost-effectiveness analyses . Among seven alternative regression models , the BB and the EEE gave the most accurate predictions for EQ-5D-5L and SF-6D , respectively",
"BACKGROUND In addition to theoretical justifications , many statistical methods have been used for selecting covariates to include in algorithms mapping nonutility measures onto utilities . However , it is not clear whether using exploratory factor analysis ( EFA ) as one such method improves the predictive ability of these algorithms . OBJECTIVE This question is addressed within the context of mapping a non-utility-based outcome , the core 23-item Women 's Health Question naire ( WHQ-23 ) , onto two utility instruments : five-level EuroQol five-dimensional question naire ( EQ-5D-5L ) and the six-dimensional health state short form ( derived from short form 36 health survey ) ( SF-6D ) . METHODS Data on all three outcomes were collected from 455 women from the Australian general population participating in a study assessing attitudes toward in vitro fertilization . Statistical methods for selecting covariates included stepwise regression ( SW ) , including all covariates ( Include all ) , multivariable fractional polynomial ( MFP ) , and EFA . The predictive accuracy of 108 regression models was assessed using five criteria : mean absolute error , root mean squared error , correlation , distribution of predicted utilities , and proportion of predictions with absolute errors of less than 0.0.5 . Validation of \" primary \" models was carried out on r and om sample s of the in vitro fertilization study . RESULTS The best results for EQ-5D-5L and SF-6D predictions were obtained from models using SW , \" Include all , \" and MFP covariate- selection approaches . Root mean squared error ( 0.0762 - 0.1434 ) and mean absolute error ( 0.0590 - 0.0924 ) estimates for these models were within the range of published estimates . EFA was outperformed by other covariate- selection methods . CONCLUSIONS It is possible to predict valid utilities from the WHQ-23 using regression methods based on SW , \" Include all , \" and MFP covariate- selection techniques",
"Purpose To derive children and adolescents ’ preferences for health states defined by the Chinese version of Child Health Utility 9D ( CHU9D-CHN ) instrument in China that can be used to estimate quality -adjusted life years ( QALYs ) for economic evaluation . Methods A profile case best – worst scaling ( BWS ) and a time trade-off ( TTO ) method were combined to derive a Chinese-specific tariff for the CHU9D-CHN . The BWS survey recruited students from primary and high schools using a multi-stage r and om sampling method and was administered in a classroom setting , whilst the TTO survey adopted an interviewer-administrated conventional TTO task and was administered to a convenience sample of undergraduate students . A latent class modelling framework was adopted for analysing the BWS data . Results Two independent surveys were conducted in Nanjing , China , including a valid sample of 902 students ( mean age 13 years ) from the BWS survey and a valid sample of 38 students ( mean age 18 years ) from the TTO survey . The poolability of the best and the worst responses was rejected and the optimal result based on the best responses only . The optimal model suggests the existence of two latent classes . The BWS estimates were further re-anchored onto the QALY scale using the TTO generated health state values via a mapping approach . Conclusion This study provides further insights into the use of the BWS method to generate health state values with young people and highlights the potential different decision rules that young people may employ for determining best vs. worst choices in this context",
"OBJECTIVES To develop algorithms for a conversion of disease-specific quality -of-life into health state values for morbidly obese patients before or after bariatric surgery . METHODS A total of 893 patients were enrolled in a prospect i ve cross-sectional multicenter study . In addition to demographic and clinical data , health-related quality -of-life ( HRQoL ) data were collected using the disease-specific Moorehead-Ardelt II question naire ( MA-II ) and two generic question naires , the EuroQoL-5D ( EQ-5D ) and the Short Form-6D ( SF-6D ) . Multiple regression models were constructed to predict EQ-5D- and SF-6D-based utility values from MA-II scores and additional demographic variables . RESULTS The mean body mass index was 39.4 , and 591 patients ( 66 % ) had already undergone surgery . The average EQ-5D and SF-6D scores were 0.830 and 0.699 . The MA-IIwas correlated to both utility measures ( Spearman 's r = 0.677 and 0.741 ) . Goodness-of-fit was highest ( R(2 ) = 0.55 in the validation sample ) for the following item-based transformation algorithm : utility ( MA-II-based ) = 0.4293 + ( 0.0336 x MA1 ) + ( 0.0071 x MA2 ) + ( 0.0053 x MA3 ) + ( 0.0107 x MA4 ) + ( 0.0001 x MA5 ) . This EQ-5D-based mapping algorithm outperformed a similar SF-6D-based algorithm in terms of mean absolute percentage error ( P = 0.045 ) . CONCLUSIONS Because the mapping algorithm estimated utilities with only minor errors , it appears to be a valid method for calculating health state values in cost-utility analyses . The algorithm will help to define the role of bariatric surgery in morbid obesity",
"OBJECTIVES To estimate models , via ordinary least squares regression , for predicting Euro Qol 5D ( EQ-5D ) , Short Form 6D ( SF-6D ) , and 15D utilities from scale scores of the European Organization for Research and Treatment of Cancer Quality of Life Question naire ( EORTC QLQ-C30 ) . METHODS Forty-eight gastric cancer patients , split up into equal subgroups by age , sex , and chemotherapy scheme , were interviewed , and the survey included the QLQ-C30 , SF-36 , EQ-5D , and 15D instruments , along with sociodemographic and clinical data . Model predictive ability and explanatory power were assessed by root mean square error ( RMSE ) and adjusted R(2 ) values , respectively . Pearson 's r between predicted and reported utility indices was compared . Three r and om sub sample s , half in size the initial sample , were created and used for \" external \" validation of the modeling equations . RESULTS Explanatory power was high , with adjusted R(2 ) reaching 0.909 , 0.833 , and 0.611 for 15D , SF-6D , and EQ-5D , respectively . After normalization of RMSE to the range of possible values , the prediction errors were 12.0 , 5.4 , and 5.6 % for EQ-5D , SF-6D , and 15D , respectively . The estimation equations produced a range of utility scores similar to those achievable by the st and ard scoring algorithms . Predicted and reported indices from the validation sample s were comparable thus confirming the previous results . CONCLUSIONS Evidence on the ability of QLQ-C30 scale scores to validly predict 15D and SF-6D utilities , and to a lesser extent , EQ-5D , has been provided . The modeling equations must be tried in future studies with larger and more diverse sample s to confirm their appropriateness for estimating quality -adjusted life-year in cancer-patient trials including only the QLQ-C30",
"Multi-dimensional Bayesian network classifiers ( MBCs ) are probabilistic graphical models recently proposed to deal with multi-dimensional classification problems , where each instance in the data set has to be assigned to more than one class variable . In this paper , we propose a Markov blanket-based approach for learning MBCs from data . Basically , it consists of determining the Markov blanket around each class variable using the HITON algorithm , then specifying the directionality over the MBC subgraphs . Our approach is applied to the prediction problem of the European Quality of Life-5 Dimensions ( EQ-5D ) from the 39-item Parkinson 's Disease Question naire ( PDQ-39 ) in order to estimate the health-related quality of life of Parkinson 's patients . Fivefold cross-validation experiments were carried out on r and omly generated synthetic data sets , Yeast data set , as well as on a real-world Parkinson 's disease data set containing 488 patients . The experimental study , including comparison with additional Bayesian network-based approaches , back propagation for multi-label learning , multi-label k-nearest neighbor , multinomial logistic regression , ordinary least squares , and censored least absolute deviations , shows encouraging results in terms of predictive accuracy as well as the identification of dependence relationships among class and feature variables"
] |
4116c81a-06ff-11f0-808a-c43d1ab1c353
|
PURPOSE There are controversial data regarding the beneficial effects of ascorbic acid ( AA ) supplementation in type 2 diabetes mellitus ( T2DM ) . In this systematic review , we aim ed to criticize the current relevant data from both observational and r and omized controlled trials ( RCTs ) . METHODS All observational and RCTs conducted to assess anti-hyperglycemic effects of AA in diabetics , published before January 2013 , were included . To obtain all related studies Google Scholar , PubMed , Scopus , IranMedex , and Magiran web data bases were search ed . Exclusion criteria were animal studies , and studies conducted in Type 1 DM , children or pregnant women . Main outcome measures were fasting blood sugar ( FBS ) , and glycated hemoglobin ( HbA1c ) . According to degree of heterogeneity , fixed or r and om effect models were employed . Meta-analyses were done using Stats Direct software , version 3.0.97 . The quality of included articles and publication bias were also assessed . RESULTS We selected 38 articles ; 26 observational studies and 12 RCTs . Due to severe method ological heterogeneity in all observational studies and some of RCTs , we could pool data from only 5 RCTs in a meta- analysis . Single intake of AA versus placebo showed a significant effect on FBS ; with the st and ardized mean difference ( SMD ) : -20.59 , 95 % confidence intervals ( 95 % CI ) : -40.77 to -0.4 ( p= 0.04 ) , but non-significant effect on HbA1c ; SMD : -0.46 , 95 % CI : -1.75 to 0.84 ( p= 0.4 ) . Effect of other antioxidants with/without AA supplementation on FBSwere nonsignificant ; SMD : -4.26 ( p= 0.8 ) , and SMD : -12.04 ( p= 0.3 ) , respectively . Also , their effect on HbA1c was non-significant ; SMD : 0.53 ( p= 0.11 ) , and SMD : 0.28 ( p= 0.34 ) , respectively . CONCLUSIONS Our study supports the positive effect of AA in reduction of FBS in diabetics , however , due to insufficient evidence ragarding long term safety of AA supplementation and limited number of RCTs , the long term use of this vitamin for its anti-diabetic properties can not be strongly recommended
|
[
"OBJECTIVE Underst and ing the relationship between multivitamin use and diabetes risk is important given the wide use of multivitamin supplements among U.S. adults . RESEARCH DESIGN AND METHODS We prospect ively examined supplemental use of multivitamins and individual vitamins and minerals assessed in 1995–1996 in relation to self-reported diabetes diagnosed after 2000 among 232,007 participants in the National Institutes of Health – American Association of Retired Persons Diet and Health Study . Multivitamin use was assessed by a food-frequency question naire at baseline . Odds ratios ( ORs ) and 95 % CIs were calculated by logistic regression models , adjusted for potential confounders . In total , 14,130 cases of diabetes diagnosed after 2000 were included in the analysis . RESULTS Frequent use of any multivitamins was not associated with risk of diabetes after adjustment for potential confounders and uses of individual supplements . Compared with nonusers of any multivitamins , the multivariate ORs among users were 1.07 ( 95 % CI 0.94–1.21 ) for taking vitamins less than once per week , 0.97 ( 0.88–1.06 ) for one to three times per week , 0.92 ( 0.84–1.00 ) for four to six times per week , and 1.02 ( 0.98–1.06 ) for seven or more times per week ( P for trend = 0.64 ) . Significantly lower risk of diabetes was associated with the use of vitamin C or calcium supplements . The multivariate ORs comparing daily users with nonusers were 0.91 ( 0.86–0.97 ) for vitamin C supplements and 0.85 ( 0.80–0.90 ) for calcium supplements . Use of vitamin E or other individual vitamin and mineral supplements were not associated with diabetes risk . CONCLUSIONS In this large cohort of U.S. older adults , multivitamin use was not associated with diabetes risk . The findings of lower diabetes risk among frequent users of vitamin C or calcium supplements warrant further evaluations",
"Fifty diabetic patients took part in a four‐month , double‐blind crossover study comparing 500 mg of vitamin C daily with placebo . No significant difference was observed between vitamin C and placebo therapy in fasting whole blood glucose , serum cholesterol , triglycerides , and glycosylated haemoglobin levels",
"BACKGROUND Observational data suggest a protective effect of several antioxidants on fasting plasma glucose ( FPG ) and type 2 diabetes . However , r and omized trials have yielded inconsistent results . OBJECTIVES The first objective was to assess the effect of 7.5 y of antioxidant supplementation on FPG at 7.5 y. The second objective was to examine the epidemiologic association of baseline dietary intakes or plasma antioxidants and FPG ( at baseline and at 7.5 y ) . DESIGN Subjects ( n = 3146 ) from the Supplementation en Vitamines et Minéraux Antioxydants ( SU.VI.MAX ) primary prevention trial in France were r and omly assigned to receive a daily capsule containing 120 mg vitamin C , 30 mg vitamin E , 6 mg beta-carotene , 100 mug Se , and 20 mg Zn or a placebo . RESULTS After 7.5 y , no significant difference was observed between age-adjusted mean FPG in men ( P = 0.78 ) and women ( P = 0.89 ) in either group . Baseline beta-carotene dietary intakes and plasma concentrations were inversely associated with FPG in multivariate mixed models ( P = 0.0045 and P Baseline plasma vitamin C and selenium were negatively ( P = 0.0455 ) and positively ( P antioxidants at nutritional doses for 7.5 y had no effect on FPG in men or women who followed a balanced diet . An inverse association of baseline beta-carotene dietary intake and plasma concentrations with FPG was found , probably because beta-carotene is an indirect marker of fruit and vegetable intakes",
"BACKGROUND Vitamin C acts as a potent antioxidant ; however , it can also be a prooxidant and glycate protein under certain circumstances in vitro . These observations led us to hypothesize that a high intake of vitamin C in diabetic persons might promote atherosclerosis . OBJECTIVE The objective was to examine the relation between vitamin C intake and mortality from cardiovascular disease . DESIGN We studied the relation between vitamin C intake and mortality from total cardiovascular disease ( n = 281 ) , coronary artery disease ( n = 175 ) , and stroke ( n = 57 ) in 1923 postmenopausal women who reported being diabetic at baseline . Diet was assessed with a food-frequency question naire at baseline , and subjects initially free of coronary artery disease were prospect ively followed for 15 y. RESULTS After adjustment for cardiovascular disease risk factors , type of diabetes medication used , duration of diabetes , and intakes of folate , vitamin E , and beta-carotene , the adjusted relative risks of total cardiovascular disease mortality were 1.0 , 0.97 , 1.11 , 1.47 , and 1.84 ( P for trend vitamin C intake from food and supplements . Adjusted relative risks of coronary artery disease were 1.0 , 0.81 , 0.99 , 1.26 , and 1.91 ( P for trend = 0.01 ) and of stroke were 1.0 , 0.52 , 1.23 , 2.22 , and 2.57 ( P for trend vitamin C were analyzed separately , only supplemental vitamin C showed a positive association with mortality endpoints . Vitamin C intake was unrelated to mortality from cardiovascular disease in the nondiabetic subjects at baseline . CONCLUSION A high vitamin C intake from supplements is associated with an increased risk of cardiovascular disease mortality in postmenopausal women with diabetes",
"This study assessed the antioxidant potencies of several widespread dietary flavonoids across a range of concentrations and compared with vitamin C as a positive control . The antioxidant effects of pretreatment with flavonoids and vitamin C , at st and ardized concentrations ( 7.6 , 23.2 , 93 , and 279.4 micromol/L ) , on oxygen radical-generated DNA damage from hydrogen peroxide ( 100 micromol/L ) in human lymphocytes were examined by using the single-cell gel electrophoresis assay ( comet assay ) . Pretreatment with all flavonoids and vitamin C produced dose-dependent reductions in oxidative DNA damage . At a concentration of 279 micromol/L , they were ranked in decreasing order of potency as follows : luteolin ( 9 % of damage from unopposed hydrogen peroxide ) , myricetin ( 10 % ) , quercetin ( 22 % ) , kaempferol ( 32 % ) , quercitrin ( quercetin-3-L-rhamnoside ) ( 45 % ) , apigenin ( 59 % ) , quercetin-3-glucoside ( 62 % ) , rutin ( quercetin-3-beta-D-rutinoside ) ( 82 % ) , and vitamin C ( 78 % ) . The protective effect of vitamin C against DNA damage at this concentration was significantly less than that of all the flavonoids except apigenin , quercetin-3-glucoside , and rutin . The ranking was similar with estimated ED50 ( concentration to produce 50 % protection ) values . The protective effect of quercetin and vitamin C at a concentration of 23.2 micromol/L was found to be additive ( quercetin : 71 % of maximal DNA damage from unopposed hydrogen peroxide ; vitamin C : 83 % ; both in combination : 62 % ) . These data suggest that the free flavonoids are more protective than the conjugated flavonoids ( eg , quercetin compared with its conjugate quercetin-3-glucoside , P antioxidant activity of free flavonoids is related to the number and position of hydroxyl groups",
"Plasma vitamin A , C and E levels and erythrocyte antioxidant enzyme activities were investigated in type I and type II diabetic subjects with and without complications , i.e. , hypertension , coronary artery disease and renal failure . Reverse phase HPLC was used to quantify vitamin A and E levels . We observed that the vitamin C levels were not significantly different between control and diabetic subjects . However , vitamin A and E levels were significantly lower in type I and type II diabetic subjects compared to controls . Superoxide dismutase ( SOD ) activity was significantly lower in type II , but not in type I , diabetic patients compared to controls . Interestingly , glutathione reductase and peroxidase activities were diminished in type I , but not in type II , diabetic subjects as compared to controls . Catalase activity was lower in both types of diabetic patients in comparison with their respective controls . Altogether these results suggest that diabetes mellitus may be associated with altered antioxidant status regardless to various complications",
"BACKGROUND Epidemiologic studies suggest that greater consumption of fruit and vegetables may decrease the risk of diabetes mellitus , but the evidence is limited and inconclusive . Plasma vitamin C level is a good biomarker of fruit and vegetable intake , but , to our knowledge , no prospect i ve studies have examined its association with diabetes risk . This study aims to examine whether fruit and vegetable intake and plasma vitamin C level are associated with the risk of incident type 2 diabetes . METHODS We administered a semiquantitative food frequency question naire to men and women from a population -based prospect i ve cohort ( European Prospect i ve Investigation of Cancer-Norfolk ) study who were aged 40 to 75 years at baseline ( 1993 - 1997 ) when plasma vitamin C level was determined and habitual intake of fruit and vegetables was assessed . During 12 years of follow-up between February 1993 and the end of December 2005 , 735 clinical ly incident cases of diabetes were identified among 21 831 healthy individuals . We report the odds ratios of diabetes associated with sex-specific quintiles of fruit and vegetable intake and of plasma vitamin C levels . RESULTS A strong inverse association was found between plasma vitamin C level and diabetes risk . The odds ratio of diabetes in the top quintile of plasma vitamin C was 0.38 ( 95 % confidence interval , 0.28 - 0.52 ) in a model adjusted for demographic , lifestyle , and anthropometric variables . In a similarly adjusted model , the odds ratio of diabetes in the top quintile of fruit and vegetable consumption was 0.78 ( 95 % confidence interval , 0.60 - 1.00 ) . CONCLUSIONS Higher plasma vitamin C level and , to a lesser degree , fruit and vegetable intake were associated with a substantially decreased risk of diabetes . Our findings highlight a potentially important public health message on the benefits of a diet rich in fruit and vegetables for the prevention of diabetes",
"Context Clinical studies of vitamin C as a potential anticancer agent have produced inconsistent results despite in vitro evidence that high concentrations kill cancer cells . Contribution Pharmacokinetic studies in healthy persons , using a depletion-repletion design , show that intravenous administration can achieve 70-fold higher blood levels of vitamin C than the highest tolerated oral dose . Caution s Although this study provides better underst and ing of the pharmacokinetic issues involved in research on vitamin C , it provides no evidence that vitamin C has any effect on cancer cells and can not be used to support its clinical use for therapeutic purpose s. The Editors Vitamin C in gram doses is taken orally by many people and administered intravenously by complementary and alternative medicine practitioners to treat patients with advanced cancer ( 1 , 2 ) . After oral intake , vitamin C plasma concentrations are tightly controlled at 70 to 85 mol/L for amounts ( as much as 300 mg daily ) that can be obtained from food ( 3 , 4 ) . However , concentrations achieved by higher pharmacologic doses are uncertain . Despite poor rationale , vitamin C in gram doses was proposed as an anticancer agent decades ago ( 5 ) . Unblinded studies with retrospective or nonr and om controls reported clinical benefit from oral and intravenous vitamin C administered to patients with terminal cancer at a dosage of 10 g daily ( 1 , 6 , 7 ) . Placebo-controlled trials in patients with cancer reported no benefit from oral vitamin C at a dosage of 10 g daily ( 8 , 9 ) , and vitamin C treatment was judged ineffective ( 10 ) . However , in vitro evidence showed that vitamin C killed cancer cells at extracellular concentrations higher than 1000 mol/L ( 11 , 12 ) , and its clinical use by some practitioners continues . We recognized that oral or intravenous routes could produce substantially different vitamin C concentrations ( 13 ) . We report here that intravenous doses can produce plasma concentrations 30- to 70-fold higher than the maximum tolerated oral doses . These data suggest that the role of vitamin C in cancer treatment should be reexamined , and insights from vitamin C pharmacokinetics can guide its clinical use . Methods Pharmacokinetic Studies in Healthy Persons The study was approved by the Institutional Review Board of the National Institute of Diabetes and Digestive and Kidney Diseases , National Institutes of Health . After we obtained written informed consent , 17 healthy volunteers ( 7 men , 10 women ; age , 19 to 27 years ) were studied as in patients by using a depletion-repletion study design ( 3 , 4 ) . Participants were hospitalized for 3 to 6 months and consumed a vitamin C-deficient diet containing less than 0.005 g of vitamin C per day . At plasma vitamin C concentrations less than 8 mol/L , persons were depleted without signs of scurvy . Vitamin C , 0.015 g twice daily , was then administered orally until participants achieved a steady state for this dose ( 0.03 g daily ) . Participants received successive oral daily vitamin C doses of 0.03 g , 0.06 g , 0.1 g , 0.2 g , 0.4 g , 1.0 g , and 2.5 g until a steady state was achieved for each dose . Bioavailability sampling was conducted at a steady state for vitamin C doses of 0.015 g , 0.03 g , 0.05 g , 0.1 g , 0.2 g , 0.5 g , and 1.25 g. For each bioavailability sampling , vitamin C was administered in the fasting state . After oral administration , blood sample s were collected at 0 , 15 , and 30 minutes and at 1 , 1.5 , 2 , 2.5 , 3 , 3.5 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 19 , 22 , and 24 hours ( 3 , 4 ) . After intravenous administration at 250 mg/min , blood sample s were collected at 0 , 2.5 , 5 , 10 , 15 , and 30 minutes and at 1 , 1.5 , 2 , 2.5 , 3 , 3.5 , 4 , 5 , 6 , 7 , 8 , 9 , and 10 hours . Data obtained from bioavailability samplings were used to determine peak plasma and urine vitamin C concentrations . Pharmacokinetic Modeling We used data from 7 men to construct a unique 3-compartment vitamin C pharmacokinetic model with parameters describing saturable absorption , tissue distribution , and renal excretion and reabsorption ( 14 ) . This model was used to predict peak plasma and urine vitamin C concentrations attained when pharmacologic doses of the vitamin are administered . For intravenous administration , it was assumed that vitamin C was infused at a rate of 1 g/min , and urine output was 100 mL/h . Vitamin C Assay Vitamin C was measured by using high-performance liquid chromatography with coulometric electrochemical detection ( 3 , 4 , 15 ) . Statistical Analysis We compared plasma vitamin C concentration curves ( against either dose or time ) by repeated- measures analyses of variance ( ANOVA ) . In addition to the repeating factor ( dose or time ) , other factors considered were sex and route of administration . In the comparison of routes of administration at multiple doses , in which sex not only was an important factor itself but also had an important interaction with route , separate ANOVA were determined for men and women to assess the importance of route of administration . Analyses were performed by using Data Desk , version 5 ( 1995 ) ( Data Description , Inc. , Ithaca , New York ) . Role of the Funding Source The funding source had no role in the design , conduct , and reporting of the study or in the decision to su bmi t the manuscript for publication . Results When 1.25 g of vitamin C was given intravenously , plasma concentrations were significantly higher than when the vitamin was given orally ( P plasma concentrations were significantly higher over all doses ( P peak values from intravenous administration were 6.6-fold higher than mean peak values from oral administration . When all doses were considered , peak plasma vitamin C concentrations increased with increasing intravenous doses , whereas peak plasma vitamin C concentrations seemed to plateau with increasing oral doses . Urine vitamin C concentrations were higher for the same dose given intravenously compared with that administered by the oral route . At the highest dose of 1.25 g , peak urine concentrations from intravenous administration were approximately 3.5 times higher than from oral administration ( data not shown ) . Figure 1 . Plasma vitamin C concentrations in healthy volunteers after intravenous or oral administration of vitamin C. Inset : The 3-compartment vitamin C pharmacokinetic model that we developed predicted that a single oral dose of 3 g , the maximum tolerated single dose , produced a peak plasma concentration of 206 mol/L ( Figure 2 , top ) . Peak predicted concentration after a single 1.25-g oral dose was slightly lower at 187 mol/L. For 200 mg , an amount obtained from vitamin C-rich foods , peak predicted concentration was approximately 90 mol/L. Plasma concentrations for all of these amounts returned to steady-state values , approximately 70 to 85 mol/L , after 24 hours . With 3 g given orally every 4 hours , the maximum tolerable ( 6 ) , peak predicted plasma concentration was approximately 220 mol/L ( Figure 2 , top ) . By contrast , after intravenous administration , predicted peak plasma vitamin C concentrations were approximately 1760 mol/L for 3 g , 2870 mol/L for 5 g , 5580 mol/L for 10 g , 13 350 mol/L for 50 g , and 15 380 mol/L for 100 g ( Figure 2 , bottom ) . Doses of 60 g given intravenously are used for cancer treatment by complementary and alternative medicine practitioners ( 2 ) . Predicted peak urine vitamin C concentrations were as much as 140-fold higher after intravenous administration compared with oral administration ( data not shown ) . Figure 2 . Predicted plasma vitamin C concentrations in healthy persons after oral ( top ) or intravenous ( IV ) ( bottom ) administration of vitamin C. Discussion Our data show that vitamin C plasma concentrations are tightly controlled when the vitamin is taken orally , even at the highest tolerated amounts . By contrast , intravenous administration bypasses tight control and results in concentrations as much as 70-fold higher than those achieved by maximum oral consumption . Both findings have clinical relevance . Vitamin C oral supplements are among the most popular sold , and gram doses are promoted for preventing and treating the common cold , managing stress , and enhancing well-being ( 1 ) . Our data show that single supplement gram doses produce transient peak plasma concentrations that at most are 2- to 3-fold higher than those from vitamin C-rich foods ( 200 to 300 mg daily ) . In either case , plasma values return to similar steady-state concentrations in 24 hours . Because differences in plasma concentrations from supplements and from food intake are not large , supplements would be expected to confer little additional benefit , a finding supported by available evidence ( 16 , 17 ) . However , consumption of fruits and vegetables , which contain vitamin C , is beneficial for unknown reasons ( 16 , 17 ) . On the basis of current knowledge and the pharmacokinetics presented here , physicians should advise their patients to consume fruits and vegetables , not vitamin C supplements , to obtain potential benefits . Just as important , our data show that intravenous administration of vitamin C produces substantially higher plasma concentrations than can be achieved with oral administration of vitamin C. This difference was previously unrecognized and may have treatment implication s. Case series published by Cameron , Campbell , and Pauling ( l , 6 , 7 ) have been controversial . In these series , several hundred patients with terminal cancer treated with 10 g of vitamin C intravenously for 10 days and then 10 g orally indefinitely were compared with more than 1000 retrospective and prospect i ve controls . Patients treated with vitamin C survived 150 to 300 days longer than controls ( 1 , 6 , 7 ) . Other research ers reported benefit consisting of increased survival , improved well-being , and reduced pain ( 1 ) . All of these",
"OBJECTIVE To examine the cross-sectional association between plasma vitamin C , self-reported diabetes , and HbA1c . RESEARCH DESIGN AND METHODS Data from a population -based study of diet , cancer , and chronic disease were analyzed . A total of 2,898 men and 3,560 women 45 - 74 years of age who were registered with general practice s in Norfolk , U.K. , were recruited to the European Prospect i ve Investigation Into Cancer-Norfolk study between 1995 and 1998 . RESULTS Mean plasma vitamin C levels were significantly higher in individuals with HbA1c levels or = 7 % ) . An inverse gradient of mean plasma vitamin C was found in both sexes across quintiles of HbA1c distribution prevalent undiagnosed hyperglycemia per 20 micromol/l ( or 1 SD ) increase in plasma vitamin C was 0.70 ( 0.52 - 0.95 ) ( adjusted for sex , age , BMI , waist-to-hip ratio , tertiary education , any use of dietary supplements , vegetarian diet , alcohol consumption , physical activity , dietary vitamin E , dietary fiber , dietary saturated fat , and smoking history ) . The unadjusted change in HbA1c per 20 micromol/l increase in vitamin C estimated by linear regression was -0.12 % ( -0.14 to -0.09 ) in men and -0.09 % ( -0.11 to -0.07 ) in women . After adjusting for the possible confounders , these values were -0.08 % ( -0.11 to -0.04 ) in men and -0.05 % ( -0.07 to -0.03 ) in women . CONCLUSIONS An inverse association was found between plasma vitamin C and HbA1c . Dietary measures to increase plasma vitamin C may be an important public health strategy for reducing the prevalence of diabetes",
"BACKGROUND & OBJECTIVE Diabetes mellitus is one of the most common metabolic disorders that causes micro- and macro-vascular complications . Because of additive effects of hyperglycaemia and hyperlipidaemia for cardiovascular diseases , lipid abnormalities should be evaluated in diabetes . As vitamin C is known for its beneficial effects on serum lipids and glycated haemoglobin ( HbA1c ) , we evaluated the effect of different doses of vitamin C on blood glucose , serum lipids and serum insulin in individuals with type 2 diabetes mellitus . METHODS A total of 84 patients with type 2 diabetes referred to Yazd Diabetes Research Center , Iran , were included in the study . They received r and omly either 500 mg or 1000 mg daily of vitamin C for six weeks . Fasting blood sugar ( FBS ) , triglyceride ( TG ) , total cholesterol ( TC ) , low and high density lipoprotein ( LDL , HDL ) , glycated haemoglobin HbA(Ic ) and serum insulin were measured before and after vitamin C consumption and the results were analyzed . RESULTS A significant decrease in FBS , TG , LDL , HbA1c and serum insulin was seen in the group supplemented with 1000 mg vitamin C. The dose of 500 mg vitamin C , however , did not produce any significant change in any of the parameters studied . INTERPRETATION & CONCLUSION Our results indicate that daily consumption of 1000 mg supplementary vitamin C may be beneficial in decreasing blood glucose and lipids in patients with type 2 diabetes and thus reducing the risk of complications",
"A significantly lower vitamin C concentration has been found in the blood and particularly in the leukocytes of hypercholesterolemic diabetic patients than of healthy blood donors . Ascorbic acid administered in a dose of 500 mg per day for 12 months to metabolically stabilized hypercholesterolemic subjects with maturity-onset diabetes mellitus ( diabetic diet without insulin or diabetic drugs ) brought about a striking decline of cholesterolemia and a moderate decline of triglyceridemia . The serum lipid level in the control group given placebo remained unaltered . A daily administration of 500 mg of ascorbic acid for six months failed to affect the fasting level of serum immunoreactive insulin . It is assumed that the long-term administration of ascorbic acid to maturity-onset diabetics removed the tissue ascorbate deficiency and improved the liver ability to compensate the increased endogenous synthesis of cholesterol by its enhanced transformation to bile acids",
"BACKGROUND Vitamin C , vitamin E , and beta-carotene are major antioxidants and as such may protect against the development of type 2 diabetes via reduction of oxidative stress . OBJECTIVE The purpose of this study was to investigate the long-term effects of supplementation with vitamin C , vitamin E , and beta-carotene for primary prevention of type 2 diabetes . DESIGN In the Women 's Antioxidant Cardiovascular Study , a r and omized trial that occurred between 1995 and 2005 , 8171 female health professionals aged > or = 40 y with either a history of cardiovascular disease ( CVD ) or > or =3 CVD risk factors were r and omly assigned to receive vitamin C ( ascorbic acid , 500 mg every day ) , vitamin E ( RRR-alpha-tocopherol acetate , 600 IU every other day ) , beta-carotene ( 50 mg every other day ) , or their respective placebos . RESULTS During a median follow-up of 9.2 y , a total of 895 incident cases occurred among 6574 women who were free of diabetes at baseline . There was a trend toward a modest reduction in diabetes risk in women assigned to receive vitamin C compared with those assigned to receive placebo [ relative risk ( RR ) : 0.89 ; 95 % CI : 0.78 , 1.02 ; P = 0.09 ] , whereas a trend for a slight elevation in diabetes risk was observed for vitamin E treatment ( RR : 1.13 ; 95 % CI : 0.99 , 1.29 ; P = 0.07 ) . However , neither of these effects reached statistical significance . No significant effect was observed for beta-carotene treatment ( RR : 0.97 ; 95 % CI : 0.85 , 1.11 ; P = 0.68 ) . CONCLUSION Our r and omized trial data showed no significant overall effects of vitamin C , vitamin E , and beta-carotene on risk of developing type 2 diabetes in women at high risk of CVD . This trial was registered at clinical trials.gov as NCT00000541",
"Background : Dietary recommendations for the prevention of type 2 diabetes mellitus include the message to consume 400 g fruit and vegetables per day . Measurement of habitual diet is inherently difficult , yet errors due to self-report can be eliminated by the use of nutritional biomarkers . The aim of this study was to determine plasma vitamin C concentrations as a biomarker for fruit and vegetable intake in individuals identified at high risk of diabetes . Fruit and vegetables may confer benefit via their antioxidant capacity , thus we also measured urinary F2-isoprostanes as a marker for oxidative stress . Subjects/ Methods : Participants recruited from a high-risk population as part of a diabetes prevention trial provided fasting blood sample s and a spot urine sample for the quantification of plasma vitamin C and F2-isoprostanes , respectively . We compared glycaemic parameters by the increments of the st and ard deviation of plasma vitamin C using multiple regression models . Results : Mean plasma vitamin C of participants was 39.3 μmol/l ( s.d . 21.8 ) . In the unadjusted model , 1 s.d . plasma vitamin C was significantly and inversely associated with HbA1c , fasting and 2 h blood glucose ( P⩽0.0001 ) . Relationships remained significant after adjustment for demographic variables and confounding factors . No significant association was observed between plasma vitamin C and urinary F2-isoprostanes . Conclusion : The data adds to the evidence that small lifestyle changes may influence glucose regulation . The role that fruit and vegetables independently have should be investigated further",
"Background Evidence from observational epidemiologic studies has indicated that antioxidants consumed through the diet or as dietary supplements lower the risk of developing atherosclerotic cardiovascular disease . Evidence suggesting that the major mechanism for the protective effect of antioxidants is mediated through decreased oxidation of lipids , particularly low-density lipoprotein ( LDL ) cholesterol is accumulating . Other evidence , however , suggests that antioxidants may influence traditional modifiable cardiovascular risk factors such as the blood pressure and serum lipids favorably . The purpose of this study was to determine the effect of antioxidant vitamin supplementation on modifiable risk factors for atherosclerotic cardiovascular disease . Design A r and omized , placebo-controlled , clinical trial of antioxidant vitamin supplementation , conducted at a single community-based clinical research center . Methods We assigned 297 retired teachers who were members of the Maryl and Retired Teachers Association r and omly to 2 - 4 months of dietary supplementation with placebo or combined antioxidant vitamin capsules providing 400 IU/day vitamin E , 500 mg/day vitamin C , and 6 mg/day β-carotene . The outcome measures were the blood pressure , fasting serum total cholesterol , high-density lipoprotein cholesterol , LDL cholesterol , and fasting glucose . Results After 2 - 4 months of supplementation the combined antioxidant supplement had had no significant effect on the systolic and diastolic blood pressures , fasting serum lipids ( total cholesterol , high-density lipoprotein cholesterol , and LDL cholesterol ) and fasting glucose , with unadjusted and adjusted analyses . Conclusion Data from this trial suggest that the protective effect from antioxidant vitamin supplementation , if there is one , likely results from mechanisms other than modification of traditionally modifiable cardiovascular risk factors",
"The effect of magnesium ( Mg ) and ascorbic acid ( AA ) supplementation on metabolic control was assessed in 56 outpatient diabetics . A 90-day run-in period was followed by two 90-day treatment periods , during which Mg ( 600 mg/day ) and AA ( 2 g/day ) were administered in a r and omized double-blind cross-over fashion . A decrease in systolic and diastolic blood pressure ( 132 + /- 3 vs. 138 + /- 4 and 77 + /- 2 vs. 82 + /- 2 mm Hg ; p insulin-dependent diabetes mellitus subjects during Mg supplementation . No beneficial effect of Mg supplementation was observed on glycemic control , lipids or blood pressure in non-insulin-dependent diabetes mellitus ( NIDDM ) subjects . AA supplementation improved glycemic control among NIDDM subjects and both fasting blood glucose ( 9.1 + /- 0.5 vs. 10.1 + /- 0.6 mmol/l ; p HbA1c ( 8.5 + /- 0.3 vs. 9.3 + /- 0.3 % ; p AA supplementation on cholesterol ( 5.9 + /- 0.2 vs. 6.2 + /- 0.2 mmol/l ; p triglycerides ( 2.2 + /- 0.2 vs. 2.5 + /- 0.2 ; p AA supplementation may have a beneficial effect in NIDDM subjects on both glycemic control and blood lipids",
"Editor 's Note : In order to encourage dissemination of the STROBE Statement , this article is being published simultaneously in Annals of Internal Medicine , Epidemiology , and PLoS Medicine . It is freely accessible on the Annals of Internal Medicine Web site ( www.annals.org ) and will also be published on the Web sites of Epidemiology and PLoS Medicine . The authors jointly hold the copyright of this article . For details on further use , see the STROBE Web site ( www.strobe-statement.org ) . Rational health care practice s require knowledge about the etiology and pathogenesis , diagnosis , prognosis , and treatment of diseases . R and omized trials provide valuable evidence about treatments and other interventions . However , much of clinical or public health knowledge comes from observational research ( 1 ) . About 9 of 10 research papers published in clinical specialty journals describe observational research ( 2 , 3 ) . The STROBE Statement Reporting of observational research is often not detailed and clear enough to assess the strengths and weaknesses of the investigation ( 4 , 5 ) . To improve the reporting of observational research , we developed a checklist of items that should be addressed : the Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) Statement ( Appendix Table ) . Items relate to the title , abstract , introduction , methods , results , and discussion sections of articles . The STROBE Statement has recently been published in several journals ( 6 ) . Our aim is to ensure clear presentation of what was planned , done , and found in an observational study . We stress that the recommendations are not prescriptions for setting up or conducting studies , nor do they dictate methodology or m and ate a uniform presentation . Appendix Table . The Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) Statement : Checklist of Items That Should Be Addressed in Reports of Observational Studies STROBE provides general reporting recommendations for descriptive observational studies and studies that investigate associations between exposures and health outcomes . STROBE addresses the 3 main types of observational studies : cohort , casecontrol , and cross-sectional studies . Authors use diverse terminology to describe these study design s. For instance , follow-up study and longitudinal study are used as synonyms for cohort study , and prevalence study as a synonym for cross-sectional study . We chose the present terminology because it is in common use . Unfortunately , terminology is often used incorrectly ( 7 ) or imprecisely ( 8) . In Box 1 , we describe the hallmarks of the 3 study design s. Box 1 . Main Study Design s Covered by STROBE The Scope of Observational Research Observational studies serve a wide range of purpose s , from reporting a first hint of a potential cause of a disease to verifying the magnitude of previously reported associations . Ideas for studies may arise from clinical observations or from biological insight . Ideas may also arise from informal looks at data that lead to further explorations . Like a clinician who has seen thous and s of patients and notes 1 that strikes her attention , the research er may note something special in the data . Adjusting for multiple looks at the data may not be possible or desirable ( 9 ) , but further studies to confirm or refute initial observations are often needed ( 10 ) . Existing data may be used to examine new ideas about potential causal factors , and may be sufficient for rejection or confirmation . In other instances , studies follow that are specifically design ed to overcome potential problems with previous reports . The latter studies will gather new data and will be planned for that purpose , in contrast to analyses of existing data . This leads to diverse viewpoints , for example , on the merits of looking at subgroups or the importance of a predetermined sample size . STROBE tries to accommo date these diverse uses of observational research from discovery to refutation or confirmation . Where necessary , we will indicate in what circumstances specific recommendations apply . How to Use this Paper This paper is linked to the shorter STROBE paper that introduced the items of the checklist in several journals ( 6 ) , and forms an integral part of the STROBE Statement . Our intention is to explain how to report research well , not how research should be done . We offer a detailed explanation for each checklist item . Each explanation is preceded by an example of what we consider transparent reporting . This does not mean that the study from which the example was taken was uniformly well reported or well done ; nor does it mean that its findings were reliable , in the sense that they were later confirmed by others : It only means that this particular item was well reported in that study . In addition to explanations and examples , we included boxes with supplementary information . These are intended for readers who want to refresh their memories about some theoretical points or be quickly informed about technical background details . A full underst and ing of these points may require study ing the textbooks or method ological papers that are cited . STROBE recommendations do not specifically address topics , such as genetic linkage studies , infectious disease modeling , or case reports and case series ( 11 , 12 ) . As many of the key elements in STROBE apply to these design s , authors who report such studies may nevertheless find our recommendations useful . For authors of observational studies that specifically address diagnostic tests , tumor markers , and genetic associations , STARD ( 13 ) , REMARK ( 14 ) , and STREGA ( 15 ) recommendations may be particularly useful . The Items in the STROBE Checklist We now discuss and explain the 22 items in the STROBE checklist ( Appendix Table ) and give published examples for each item . Some examples have been edited by removing citations or spelling out abbreviations . Eighteen items apply to all 3 study design s , whereas 4 are design -specific . Starred items ( for example , item 8) indicate that the information should be given separately for cases and controls in casecontrol studies , or exposed and unexposed groups in cohort and cross-sectional studies . We advise authors to address all items somewhere in their paper , but we do not prescribe a precise location or order . For instance , we discuss the reporting of results under a number of separate items , while recognizing that authors might address several items within a single section of text or in a table . Title and Abstract 1(a ) Indicate the study 's design with a commonly used term in the title or the abstract . Example Leukaemia incidence among workers in the shoe and boot manufacturing industry : a casecontrol study ( 18 ) . Explanation Readers should be able to easily identify the design that was used from the title or abstract . An explicit , commonly used term for the study design also helps ensure correct indexing of articles in electronic data bases ( 19 , 20 ) . 1(b ) Provide in the abstract an informative and balanced summary of what was done and what was found . Example Background : The expected survival of HIV-infected patients is of major public health interest . Objective : To estimate survival time and age-specific mortality rates of an HIV-infected population compared with that of the general population . Design : Population -based cohort study . Setting : All HIV-infected persons receiving care in Denmark from 1995 to 2005 . Patients : Each member of the nationwide Danish HIV Cohort Study was matched with as many as 99 persons from the general population according to sex , date of birth , and municipality of residence . Measurements : The authors computed KaplanMeier life tables with age as the time scale to estimate survival from age 25 years . Patients with HIV infection and corresponding persons from the general population were observed from the date of the patient 's HIV diagnosis until death , emigration , or 1 May 2005 . Results : 3990 HIV-infected patients and 379 872 persons from the general population were included in the study , yielding 22 744 ( median , 5.8 y/person ) and 2 689 287 ( median , 8.4 y/person ) person-years of observation . Three percent of participants were lost to follow-up . From age 25 years , the median survival was 19.9 years ( 95 % CI , 18.5 to 21.3 ) among patients with HIV infection and 51.1 years ( CI , 50.9 to 51.5 ) among the general population . For HIV-infected patients , survival increased to 32.5 years ( CI , 29.4 to 34.7 ) during the 2000 to 2005 period . In the subgroup that excluded persons with known hepatitis C coinfection ( 16 % ) , median survival was 38.9 years ( CI , 35.4 to 40.1 ) during this same period . The relative mortality rates for patients with HIV infection compared with those for the general population decreased with increasing age , whereas the excess mortality rate increased with increasing age . Limitations : The observed mortality rates are assumed to apply beyond the current maximum observation time of 10 years . Conclusions : The estimated median survival is more than 35 years for a young person diagnosed with HIV infection in the late highly active antiretroviral therapy era . However , an ongoing effort is still needed to further reduce mortality rates for these persons compared with the general population ( 21 ) . Explanation The abstract provides key information that enables readers to underst and a study and decide whether to read the article . Typical components include a statement of the research question , a short description of methods and results , and a conclusion ( 22 ) . Abstract s should summarize key details of studies and should only present information that is provided in the article . We advise presenting key results in a numerical form that includes numbers of participants , estimates of associations , and appropriate measures of variability and uncertainty ( for example , odds ratios with confidence intervals ) . We regard it insufficient to state only that an exposure is or is not significantly associated with an"
] |
4116c856-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND Vitamin K deficiency can cause bleeding in an infant in the first weeks of life . This is known as Hemorrhagic Disease of the Newborn ( HDN ) . HDN is divided into three categories : early , classic and late HDN . Early HDN occurs within 24 hours post partum and falls outside the scope of this review . Classic HDN occurs on days one to seven ; common bleeding sites are gastrointestinal , cutaneous , nasal and from a circumcision . Late HDN occurs from week 2 - 12 ; the most common bleeding sites are intracranial , cutaneous , and gastrointestinal . Vitamin K is commonly given prophylactically after birth for the prevention of HDN , but the preferred route is uncertain . OBJECTIVES To review the evidence from r and omized trials in order to determine the effectiveness of vitamin K prophylaxis in the prevention of classic and late HDN . Main questions are : Is one dose of vitamin K , given after birth , able to significantly reduce the incidence of classic and late HDN ? Is there a significant difference between the oral route and the intramuscular route in preventing classic and late HDN ? Are multiple oral doses of vitamin K , given after birth , able to significantly reduce the incidence of classic and late HDN ? SEARCH STRATEGY The st and ard search strategy of the Cochrane Neonatal Review Group was used . SELECTION CRITERIA All trials using r and om or quasi-r and om patient allocation , in which methods of vitamin K prophylaxis in infants were compared to each other , placebo or no treatment , were included . DATA COLLECTION AND ANALYSIS Data were extracted independently by each author and were analysed with the st and ard methods of the Cochrane Collaboration and its Neonatal Review Group , using relative risk , risk difference and weighted mean difference . MAIN RESULTS Two eligible r and omized trials , each comparing a single dose of intramuscular vitamin K with placebo or nothing , assessed effect on clinical bleeding . One dose of vitamin K reduced clinical bleeding at 1 - 7 days , including bleeding after circumcision , and improved biochemical indices of coagulation status . Eleven additional eligible r and omized trials compared either a single oral dose of vitamin K with placebo or nothing , a single oral with a single intramuscular dose of vitamin K , or three oral doses with a single intramuscular dose . None of these trials assessed clinical bleeding . Oral vitamin K improved biochemical indices of coagulation status at 1 - 7 days . There was no evidence of a difference between the oral and intramuscular route in effects on biochemical indices of coagulation status . A single oral compared with a single intramuscular dose result ed in lower plasma vitamin K levels at two weeks and one month , whereas a 3-dose oral schedule result ed in higher plasma vitamin K levels at two weeks and at two months than did a single intramuscular dose . REVIEW ER 'S CONCLUSIONS A single dose ( 1.0 mg ) of intramuscular vitamin K after birth is effective in the prevention of classic HDN . Either intramuscular or oral ( 1.0 mg ) vitamin K prophylaxis improves biochemical indices of coagulation status at 1 - 7 days . Neither intramuscular nor oral vitamin K has been tested in r and omized trials with respect to effect on late HDN . Oral vitamin K , either single or multiple dose , has not been tested in r and omized trials for its effect on either classic or late HDN
|
[
"Protein induced by vitamin K absence ( PIVKA-II ) has been used for the evaluation of vitamin K deficiency in the newborn . Differing PIVKA-II detection rates in various studies on hemorrhagic disease of the newborn have not been explained satisfactorily . In this study we investigated the PIVKA-II values of 44 healthy breastfed infants , of whom 29 received vitamin K1 either orally ( N = 13 ) or intramuscularly ( n = 16 ) , and the remaining 15 constituted the control group . PIVKA-II was detected in 15.3 percent ( 2/13 ) of the oral and 25 percent of the ( 4/16 ) intramuscular group on the third day of life . The detection rate was 93.3 percent ( 14/15 ) in the control group . However , at the one-month follow-up , there were no PIVKA-II positive infants . In conclusion , PIVKA-II positivity among breastfed Turkish infants on the third day of life was high compared to that in other studies , perhaps due to a delay in enzyme maturation related to racial , environmental and nutritional factors",
"PIVKA-II ( protein induced by vitamin K absence or antagonist-II ) was measured in two groups of newborns , one group being given 5 mg vitamin K at birth and the other untreated . The untreated group had a significantly higher proportion of PIVKA-II positive babies at 3 and 5 days of age than did the treated group . When vitamin K was administered to newborn babies whose normotest levels were less than 30 % , it was found that the higher the pre-treatment PIVKA-II levels the greater the response to vitamin K , as monitored by the normotest . Thus PIVKA-II levels might be more useful than a coagulation test , since the low activity of vitamin K dependent coagulation factors sometimes reflects not vitamin K deficiency but impaired production of these factors because of immaturity . The findings support the view that vitamin K given prophylactically at birth will help to prevent neonatal bleeding",
"Abstract There is consensus that late vitamin K deficiency bleeding ( VKDB ) should be prevented by vitamin K prophylaxis . One single dose of 1 mg vitamin K1 is effective if given i.m . or s.c . , but not if given orally . Repeated oral doses might be as effective as the parenteral dose but the optimal dose regimen remains to be established . Different oral dose schedules are presently used in different countries . In Australia , Germany , The Netherl and s and Switzerl and active surveillance data on late VKDB were collected in a similar manner and failure rates compared . Identical case definitions were used . There were three basic strategies for oral and one for parenteral vitamin K prophylaxis for healthy newborns in the four countries : ( 1 ) daily supplementation of low dose vitamin K ( 25 μg ) for breast-fed infants ( The Netherl and s ) ; ( 2 ) 3 × 1 mg orally [ Australia ( January 1993 – March 1994 ) and Germany ( December 1992 – December 1994 ) ] ; ( 3 ) 1 mg vitamin K i.m . ( Australia since March 1994 ) ; and ( 4 ) 2 × 2 mg vitamin K ( new mixed micellar preparation ) ( Switzerl and ) . The respective failure rates per 100,000 live births ( including cases given all recommended doses and those given incomplete prophylaxis ) were for strategy : ( 1 ) 0.2 ( 0–1.3 ) in The Netherl and s ; ( 2 ) 2.3 ( 95 % CI 1.6–3.4 ) in Germany and 2.5 ( 1.1–4.8 ) in Australia ( oral prophylaxis ) ; ( 3 ) Australia ( i.m . prophylaxis ) 0 ( 0–0.9 ) ; and ( 4 ) 3.6 ( 0.7–10.6 ) in Switzerl and . The failure rates for complete prophylaxis only were : strategy ( 1 ) 0 ( 0–0.7 ) in The Netherl and s ; ( 2 ) 1.8 ( 1.1–2.8 ) in Germany and 1.5 ( 0.5–3.6 ) in Australia ; ( 3 ) Australia ( i.m . ) 0 ( 0–0.9 ) ; and ( 4 ) 1.2 ( 0–6.5 ) in Switzerl and . Conclusions The Australian data confirm that three oral doses of 1 mg vitamin K are less effective than i.m . vitamin K prophylaxis . A daily low oral dose of 25 μg vitamin K1 following an initial oral dose of 1 mg after birth for exclusively breast-fed infants may be as effective as parenteral vitamin K prophylaxis . The effectiveness of the “ mixed-micellar ” preparation of vitamin K1 needs further study",
"OBJECTIVE To compare a new oral preparation of vitamin K1 ( Konakion MM ) containing lecithin and glycocholic acid with a st and ard intramuscular ( IM ) preparation during the first 8 weeks of life in exclusively breast fed infants . METHODS Infants were r and omised at birth to the IM group ( 1 mg vitamin K ) or the oral group ( 2 mg given at birth and repeated at 7 and 30 days of life ) . Prothrombin time ( INR ) , plasma vitamin K1 , and PIVKA II ( undercarboxylated prothrombin ) were monitored at 14 , 30 , and 56 days of age . RESULTS Seventy nine infants were r and omised to the oral group and 77 to the IM group . Sixty seven infants in each group completed eight weeks of the study . Prothrombin times did not differ between the two groups . Mean ( SD ) plasma vitamin K1values ( in ng/ml ) decreased in both groups over time , but were higher in the oral group at 14 and 56 days : 2.0 ( 1.6 ) v 1.3 ( 1.1 ) at 14 days ; 0.5 ( 0.3 ) v 0.5 ( 0.7 ) at 30 days ; and 0.5 ( 0.8 ) v 0.2 ( 0.2 ) at 56 days of life . PIVKA II was raised ( ⩾ 0.1 AU/ml ) in cord blood in 47 % of the infants . By 14 days , only one infant in each group had a raised PIVKA II value and both of these initially had high concentrations of PIVKA II in cord blood . At 30 days , there were no raised PIVKA II values . At 56 days , there were no raised PIVKA II values in the oral group , although three infants in the IM group had raised values . CONCLUSIONS Plasma vitamin K concentrations were at least equal or significantly higher in babies given oral vitamin K supplements compared with IM treated babies at the time points measured . Through the first 8 weeks of life , multiple doses of the new oral preparation maintain haemostasis and vitamin K status in breast fed infants at least equal to that of the intramuscular preparation",
"ABSTRACT . In a r and omized study of 300 infants , the effect of 1 mg of peroral vitamin K given at birth was compared to the same dose given as an intramuscular injection . The combined activity of coagulation factor II + VII + X taken after 48 and before 72 hours after delivery served as the primary endpoint . Prothrombin ( antigen ) and PIVKA II ( acarboxyprothrombin ) were also measured . All infants were observed for events of bleeding until discharge from the hospital , normally on the fifth day . No significant differences between the groups in any of the biochemical markers were observed . The 95 % confidence limits of the differences were very narrow for all factors . No cases of bleeding were observed . We conclude that administration of 1 mg peroral vitamin K is as efficient as intramuscular administration of the same dose in the prevention of classical hemorrhagic disease of the newborn",
"The plasma disposition of a new mixed-micellar preparation ( KONAKION MM , Roche ) of phylloquinone ( vitamin K1 ) has been studied in 25 healthy , fully breast-fed , newborn babies , r and omized to receive a single dose of either 1.5 mg i.m . ( 11 babies ) or 3 mg p.o . ( 14 babies ) . Venous blood sample s were collected at 25 h , 4 days , and 24 days . After p.o . administration , the median plasma phylloquinone concentration increased to 89 ng/ml after 24 h , then decreased to 51 ng/ml after 4 days ; the respective concentrations after i.m . injection were 146 ng/ml and 34 ng/ml . The higher plasma phylloquinone level in the i.m . group after 24 h was not statistically significant compared with that of the p.o . group , but the reversed higher concentration in the p.o . group after 4 days was significant ( p median plasma phylloquinone had decreased to 0.44 ng/ml ( range 0.19 - 1.44 ) and 1.05 ng/ml ( range 0.37 - 1.87 ) in the p.o . and i.m . groups , respectively . There was a significant difference between these plasma concentrations ( p range of plasma concentrations at 24 h and 4 days suggests a greater consistency of absorption from this micellar preparation than from other emulsion-based preparations . Further studies are required to assess the long-term protection of a single oral dose against late hemorrhagic disease of the newborn . Until such time , breast-fed babies given this preparation orally should receive ( an ) additional dose(s )",
"Intramuscular administration of vitamin K for prophylaxis against hemorrhagic disease of the newborn has the disadvantage of increased cost , pain , anxiety to parents and risk of transmission of infection . Oral route is a better alternative . Oral absorption of vitamin K has been shown to be equally good using special oral preparations . However , this preparation is not available in India . A prospect i ve study was carried out on 51 full term , healthy breastfed newborns to evaluate if the injectable water soluble preparation of vitamin K ( menadione sodium bisulphite ) could be as effective . Fourteen babies received 1 mg vitamin K intramuscularly , 24 received 2 mg vitamin K orally while 13 controls did not receive vitamin K at birth . PIVKA-II levels were measured in cord blood and at 72 - 78 hours of age in all babies as a marker of vitamin K deficiency . The overall PIVKA-II prevalence in cord blood was 64.7 % . At 72 - 78 hours , PIVKA-II was present in 50 % of babies in IM group , 58.3 % of babies in oral group and in 76.9 % of babies in ' no vitamin K ' group ( p > 0.05 ) . The PIVKA-II levels decreased or did not change at 72 - 78 hours in 91.6 % of babies in oral group versus 92.8 % of babies in IM group ( p > 0.05 ) . On the other h and , PIVKA-II levels increased in 30.7 % of babies who did not receive vitamin K as against in 7.8 % of babies receiving vitamin K in either form ( p vitamin K prophylaxis is required for all newborns at birth and injectable vitamin K ( menadione sodium bisulphite ) given orally to term healthy babies is effective in preventing vitamin K deficiency state",
"A r and omised clinical trial was conducted to establish the effects of oral and intramuscular administration of vitamin K at birth on plasma concentrations of vitamin K1 , proteins induced by vitamin K absence ( PIVKA-II ) , and clotting factors . Two groups of about 165 healthy breast fed infants who received at r and om 1 mg vitamin K1 orally or intramuscularly after birth were studied at 2 weeks and 1 and 3 months of age . Although vitamin K1 concentrations were statistically significantly higher in the intramuscular group , blood coagulability , activities of factors VII and X and PIVKA-II concentrations did not reveal any difference between the two groups . At 2 weeks of age vitamin K1 concentrations were raised compared with reported unsupplemented concentrations and no PIVKA-II was detectable . At 3 months vitamin K1 concentrations were back at unsupplemented values and PIVKA-II was detectable in 11.5 % of infants . Therefore , a repeated oral prophylaxis will be necessary to completely prevent ( biochemical ) vitamin K deficiency beyond the age of 1 month",
"The study was design ed to know the effect of oral vitamin K ( VK ) treatment , on clotting factors II-VII-IX-X and the protein induced by VK absence from factor II ( PIVCA II ) on full term infants . Seventy healthy newborns were studied and each was r and omly placed in one of two groups : Group A , newborns that received human milk and milk formula ( mixed feeding ) and group B , newborns that were exclusively breast fed . These groups were also divided in two subgroups : I received 2 mg of VK1 orally and II ( control ) did not receive VK . Clotting activity of the coagulation factors and PIVCA II was determined from blood plasma obtained immediately after birth and 48 hours after VK administration . Basal activity of the factors analyzed was similar in all groups with values ranging from 25 % to 40 % . After 48 hours a significant increase in all factors studied and a decrease of PIVKA II was observed in those children who received oral VK . The results suggest that oral VK effectively increases VK dependent factors and prevents the risk of hemorrhagic disease in the newborn , with the advantage of being less traumatic and less risky to the infant than intramuscular VK",
"One hundred term exclusively breast fed babies weighing more than 2.5 kg were evaluated to determine the efficacy of various modes and doses of Vitamin K to prevent hemorrhagic disease of newborn ( HDN ) . The babies were grouped into four categories of 25 each : Group A--1 mg Vitamin K intramuscular ( Menadione sodium disulphite ) at birth ; Group B--0.5 mg Vitamin K intramuscular ; Group C--1 mg Vitamin K orally , and group D -- no Vitamin K. The prothrombin index was estimated in all babies between 36 - 72 hours of age . The results revealed a prothrombin index in Groups A , B , C and D as 94.98 + /- 7.64 % , 95.08 + /- 9.91 % , 92.51 + /- 10.10 % and 80.39 + /- 15.90 % , respectively . The differences between Groups A , B and C were insignificant . However , Group D , prothrombin index was significantly reduced as compared with the other three groups . It is , therefore , concluded that oral Vitamin K is as effective as injectable Vitamin K and its usage is recommended in our country to reduce complications and costs of parenteral therapy",
"Classical hemorrhagic disease of newborn ( HDNB ) was first described in 1894(1 ) . Clinical ly manifest classical HDNB is relatively uncommon with incidence of 1 - 2/1000 live births . Exclusively breastfed babies are predisposed to develop HDNB because of absence of bacterial flora in the gut , lack of stores of vitamin K and low vitamin K levels in breastmilk(2,3 ) . In the absence of vitamin K , its precursor non-carboxylated proteins called Proteins Induced in Vitamin K Absence ( PIVKA ) are elevated . Levels of PIVKA-II ( Precursor Protein of Factor II ) are more specific than Pro-thrombin Time ( PT ) because the former does not get elevated in states of decreased synthesis of coagulation factors as occurs in hepatitis(4 ) . The American Academy of Pediatrics ( AAP ) recommends prophylactic administration of intramuscular ( IM ) vitamin K for all newborn babies at birth(5 ) whereas in India , there is lack of consensus and ( IM ) vitamin K is given only to high risk babies in many centers . Intramuscular vitamin K is associated with the potential risks of transmission of viral infections , lymphoreticular malignancies in later childhood and excessive cost . Oral administration of vitamin K is thus preferable because of safety and cost effectiveness . The present study was conducted to look for sub- clinical evidence of vitamin K deficiency in exclusively breastfed term neonates and evaluate the efficacy of orally and intramuscularly administered water soluble vitamin K in them"
] |
4116c89c-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND The effects of vitamin D on fractures , falls , and bone mineral density are uncertain , particularly for high vitamin D doses . We aim ed to determine the effect of vitamin D supplementation on fractures , falls , and bone density . METHODS In this systematic review , r and om-effects meta- analysis , and trial sequential analysis , we used findings from literature search es in previously published meta-analyses . We up date d these findings by search ing PubMed , Embase , and Cochrane Central on Sept 14 , 2017 , and Feb 26 , 2018 , using the search term " vitamin D " and additional keywords , without any language restrictions . We assessed r and omised controlled trials of adults ( > 18 years ) that compared vitamin D with untreated controls , placebo , or lower-dose vitamin D supplements . Trials with multiple interventions ( eg , co-administered calcium and vitamin D ) were eligible if the study groups differed only by use of vitamin D. We excluded trials of hydroxylated vitamin D analogues . Eligible studies included outcome data for total or hip fractures , falls , or bone mineral density measured at the lumbar spine , total hip , femoral neck , total body , or forearm . We extracted data about participant characteristics , study design , interventions , outcomes , funding sources , and conflicts of interest . The co- primary endpoints were participants with at least one fracture , at least one hip fracture , or at least one fall ; we compared data for fractures and falls using relative risks with an intention-to-treat analysis using all available data . The secondary endpoints were the percentage change in bone mineral density from baseline at lumbar spine , total hip , femoral neck , total body , and forearm . FINDINGS We identified 81 r and omised controlled trials ( n=53 537 participants ) that reported fracture ( n=42 ) , falls ( n=37 ) , or bone mineral density ( n=41 ) . In pooled analyses , vitamin D had no effect on total fracture ( 36 trials ; n=44 790 , relative risk 1·00 , 95 % CI 0·93 - 1·07 ) , hip fracture ( 20 trials ; n=36 655 , 1·11 , 0·97 - 1·26 ) , or falls ( 37 trials ; n=34 144 , 0·97 , 0·93 - 1·02 ) . Results were similar in r and omised controlled trials of high-dose versus low-dose vitamin D and in subgroup analyses of r and omised controlled trials using doses greater than 800 IU per day . In pooled analyses , there were no clinical ly relevant between-group differences in bone mineral density at any site ( range -0·16 % to 0·76 % over 1 - 5 years ) . For total fracture and falls , the effect estimate lay within the futility boundary for relative risks of 15 % , 10 % , 7·5 % , and 5 % ( total fracture only ) , suggesting that vitamin D supplementation does not reduce fractures or falls by these amounts . For hip fracture , at a 15 % relative risk , the effect estimate lay between the futility boundary and the inferior boundary , meaning there is reliable evidence that vitamin D supplementation does not reduce hip fractures by this amount , but uncertainty remains as to whether it might increase hip fractures . The effect estimate lay within the futility boundary at thresholds of 0·5 % for total hip , forearm , and total body bone mineral density , and 1·0 % for lumbar spine and femoral neck , providing reliable evidence that vitamin D does not alter these outcomes by these amounts . INTERPRETATION Our findings suggest that vitamin D supplementation does not prevent fractures or falls , or have clinical ly meaningful effects on bone mineral density . There were no differences between the effects of higher and lower doses of vitamin D. There is little justification to use vitamin D supplements to maintain or improve musculoskeletal health . This conclusion should be reflected in clinical guidelines . FUNDING Health Research Council of New Zeal and
|
[
"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",
"Background In meta-analyses supplementation with vitamin D appears to reduce incidence of fractures , and in cross-sectional studies there is a positive association between serum 25-hydroxyvitamin D ( 25(OH)D ) levels and bone mineral density ( BMD ) . However , the effect of supplementation with high doses of vitamin D on BMD is more uncertain and could in theory have both positive and negative effects . Methods The study was a one year , double blind placebo-controlled intervention trial performed at the University Hospital of North Norway . 421 subjects , 21 - 70 years old , were included and 312 completed the study . The subjects were r and omized to vitamin D3 40.000 IU per week ( DD group ) , vitamin D3 20.000 IU per week ( DP group ) , or placebo ( PP group ) . All subjects were given 500 mg calcium daily . Serum 25(OH)D , osteoprotegrin ( OPG ) , receptoractivator of nuclear factor-kappaB lig and ( RANKL ) , and BMD at the lumbar spine and the hip were measured before and at the end of the study . Results At baseline the mean serum 25(OH)D levels were 58 nmol/L ( all subjects ) and increased to 141 and 100 nmol/L in the DD and DP groups , respectively . After one year , no significant differences were found between the three groups regarding change in BMD , serum OPG or RANKL . Conclusions Supplementation with high doses of vitamin D for one year does not appear to have a negative effect on BMD in healthy subjects . In order to disclose a positive effect , subjects with low BMD and /or low serum 25(OH)D levels need to be studied . Trial registration The trial was registered at Clinical Trials.gov ( NCT00243256 )",
"OBJECTIVES To assess the feasibility of a vitamin D intervention delivered through a Meals-on-Wheels ( MOW ) program to improve 25-hydroxyvitamin D ( 25(OH)D ) concentrations and reduce falls in homebound older adults . DESIGN Single-blind , cluster r and omized trial . SETTING MOW , Forsyth County , North Carolina . PARTICIPANTS Community-dwelling homebound adults aged 65 to 102 ( N = 68 ) . INTERVENTION MOW clients were r and omized to vitamin D3 ( 100,000 IU/month ; n = 38 ) or active placebo ( 400 IU vitamin E/month ; n = 30 ) according to MOW delivery route . MEASUREMENTS Serum 25(OH)D was assessed at baseline and 5-month follow-up ; proportions of participants in 25(OH)D categories were compared using Fisher exact test . Falls were assessed using monthly fall calendars , and rate of falls was estimated using negative binomial generalized estimating equation models . RESULTS Mean ± st and ard deviation 25(OH)D concentrations were 20.9 ± 11.5 ng/mL at baseline , with 57 % having 25(OH)D concentrations less than 20 ng/mL. Retention and adherence were high ( > 90 % ) . After the 5-month intervention , only one of 34 participants r and omized to vitamin D3 had 25(OH)D concentrations less than 20 ng/mL , compared with 18 of 25 participants r and omized to placebo ( P the rate of falls over 5 months was not significantly different according to intervention group ( risk ratio ( RR ) = 0.48 , 95 % confidence interval ( CI ) = 0.19 - 1.19 ) , but after adjustment for sex , race , season of year , baseline 25(OH)D status , and history of falls , participants r and omized to vitamin D3 had a lower rate of falling than those r and omized to placebo ( RR = 0.42 , 95 % CI = 0.21 - 0.87 ) . CONCLUSION A vitamin D intervention delivered through MOW was feasible , result ing in improvements in 25(OH)D concentrations and a lower rate of falls in adjusted analyses . Further research is needed to vali date the reduction in falls from this type of intervention",
"IMPORTANCE Observational studies suggest that vitamin D supplementation is associated with benefits for knee osteoarthritis , but current trial evidence is contradictory . OBJECTIVE To compare the effects of vitamin D supplementation vs placebo on knee pain and knee cartilage volume in patients with symptomatic knee osteoarthritis and low vitamin D levels . DESIGN , SETTING , AND PARTICIPANTS A multicenter r and omized , double-blind , placebo-controlled clinical trial in Tasmania and Victoria , Australia . Participants with symptomatic knee osteoarthritis and low 25-hydroxyvitamin D ( 12.5 - 60 nmol/L ) were enrolled from June 2010 to December 2011 . The trial was completed in December 2013 . INTERVENTIONS Participants were r and omly assigned to receive monthly treatment with oral vitamin D3 ( 50,000 IU ; n = 209 ) or an identical placebo ( n = 204 ) for 2 years . MAIN OUTCOMES AND MEASURES Primary outcomes were change in tibial cartilage volume ( assessed using magnetic resonance imaging [ MRI ] ) and change in the Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) pain score ( 0 [ no pain ] to 500 [ worst pain ] ) from baseline to month 24 . Secondary outcomes were cartilage defects and bone marrow lesions ( assessed using MRI ) . RESULTS Of 413 enrolled participants ( mean age , 63.2 years ; 50 % women ) , 340 ( 82.3 % ) completed the study . The level of 25-hydroxyvitamin D increased more in the vitamin D group ( 40.6 nmol/L ) than in the placebo group ( 6.7 nmol/L ) ( P of tibial cartilage volume or WOMAC pain score . There were no significant differences in change of tibiofemoral cartilage defects or change in tibiofemoral bone marrow lesions . Adverse events ( ≥ 1 per patient ) occurred in 56 participants in the vitamin D group and in 37 participants in the placebo group ( P = .04 ) . [ table : see text ] . CONCLUSIONS AND RELEVANCE Among patients with symptomatic knee osteoarthritis and low serum 25-hydroxyvitamin D levels , vitamin D supplementation , compared with placebo , did not result in significant differences in change in MRI-measured tibial cartilage volume or WOMAC knee pain score over 2 years . These findings do not support the use of vitamin D supplementation for preventing tibial cartilage loss or improving WOMAC knee pain in patients with knee osteoarthritis . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01176344 ; anzctr.org.au Identifier : ACTRN12610000495022",
"IMPORTANCE Vitamin D deficiency has been associated with poor physical performance . OBJECTIVE To determine the effectiveness of high-dose vitamin D in lowering the risk of functional decline . DESIGN , SETTING , AND PARTICIPANTS One-year , double-blind , r and omized clinical trial conducted in Zurich , Switzerl and . The screening phase was December 1 , 2009 , to May 31 , 2010 , and the last study visit was in May 2011 . The date s of our analysis were June 15 , 2012 , to October 10 , 2015 . Participants were 200 community-dwelling men and women 70 years and older with a prior fall . INTERVENTIONS Three study groups with monthly treatments , including a low-dose control group receiving 24,000 IU of vitamin D3 ( 24,000 IU group ) , a group receiving 60,000 IU of vitamin D3 ( 60,000 IU group ) , and a group receiving 24,000 IU of vitamin D3 plus 300 μg of calcifediol ( 24,000 IU plus calcifediol group ) . MAIN OUTCOMES AND MEASURES The primary end point was improving lower extremity function ( on the Short Physical Performance Battery ) and achieving 25-hydroxyvitamin D levels of at least 30 ng/mL at 6 and 12 months . A secondary end point was monthly reported falls . Analyses were adjusted for age , sex , and body mass index . RESULTS The study cohort comprised 200 participants ( men and women ≥ 70 years with a prior fall ) . Their mean age was 78 years , 67.0 % ( 134 of 200 ) were female , and 58.0 % ( 116 of 200 ) were vitamin D deficient ( . Intent-to-treat analyses showed that , while 60,000 IU and 24,000 IU plus calcifediol were more likely than 24,000 IU to result in 25-hydroxyvitamin D levels of at least 30 ng/mL ( P = .001 ) , they were not more effective in improving lower extremity function , which did not differ among the treatment groups ( P = .26 ) . However , over the 12-month follow-up , the incidence of falls differed significantly among the treatment groups , with higher incidences in the 60,000 IU group ( 66.9 % ; 95 % CI , 54.4 % to 77.5 % ) and the 24,000 IU plus calcifediol group ( 66.1 % ; 95 % CI , 53.5%-76.8 % ) group compared with the 24,000 IU group ( 47.9 % ; 95 % CI , 35.8%-60.3 % ) ( P = .048 ) . Consistent with the incidence of falls , the mean number of falls differed marginally by treatment group . The 60,000 IU group ( mean , 1.47 ) and the 24,000 IU plus calcifediol group ( mean , 1.24 ) had higher mean numbers of falls compared with the 24,000 IU group ( mean , 0.94 ) ( P = .09 ) . CONCLUSIONS AND RELEVANCE Although higher monthly doses of vitamin D were effective in reaching a threshold of at least 30 ng/mL of 25-hydroxyvitamin D , they had no benefit on lower extremity function and were associated with increased risk of falls compared with 24,000 IU . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01017354",
"Background : Low bone mineral density ( BMD ) is a significant comorbidity in HIV . However , studies evaluating vitamin D supplementation on bone health in this population are limited . This study investigates changes in bone health parameters after 12 months of supplementation in HIV-infected youth with vitamin D insufficiency . Methods : This is a r and omized , active-control , double-blind trial investigating changes in bone parameters with 3 different vitamin D3 doses [ 18,000 ( st and ard/control dose ) , 60,000 ( moderate dose ) , and 120,000 IU/monthly ( high dose ) ] in HIV-infected youth 8–25 years old with baseline serum 25-hydroxyvitamin D ( 25(OH)D ) concentrations BMD and bone turnover markers were measured at baseline and 12 months . Results : One hundred two subjects enrolled . Over 12 months , serum 25(OH)D concentrations increased with all doses , but the high dose ( ie , 120,000 IU/monthly ) maintained serum 25(OH)D concentrations in an optimal range ( ≥30 or ≥20 ng/mL ) throughout the study period for more subjects ( 85 % and 93 % , respectively ) compared with either the moderate ( 54 % and 88 % , respectively ) or st and ard dose ( 63 % and 80 % , respectively ) . All dosing groups showed some improvement in BMD ; however , only the high-dose arm showed significant decreases in bone turnover markers for both procollagen type 1 aminoterminal propeptide ( −3.7 ng/mL ; P = 0.001 ) and & Bgr;-CrossLaps ( −0.13 ng/mL ; P = 0.0005 ) . Conclusions : High-dose vitamin D supplementation ( 120,000 IU/mo ) given over 12 months decreases bone turnover markers in HIV-infected youth with vitamin D insufficiency , which may represent an early , beneficial effect on bone health . High vitamin D doses are needed to maintain optimal serum 25(OH)D concentrations",
"OBJECTIVES To determine the efficacy and safety of high-dose vitamin D supplementation for prevention of acute respiratory infection ( ARI ) in older long-term care residents . DESIGN R and omized controlled trial investigating high-dose vs st and ard-dose vitamin D from 2010 to 2014 . SETTING Colorado long-term care facilities . PARTICIPANTS Long-term care residents aged 60 and older ( n = 107 ) . INTERVENTION The high-dose group received monthly supplement of vitamin D3 100,000 IU , the st and ard-dose group received a monthly placebo ( for participants taking 400 - 1,000 IU/d as part of usual care ) or a monthly supplement of 12,000 IU of vitamin D3 ( for participants taking incidence of ARI during the 12-month intervention . Secondary outcomes were falls and fractures , 25-hydroxyvitamin D levels , hypercalcemia , and kidney stones . RESULTS Participants ( 55 high dose , 52 st and ard dose ) were r and omized and included in the final analysis . The high-dose group had 0.67 ARIs per person-year and the st and ard-dose group had 1.11 ( incidence rate ratio ( IRR ) = 0.60 , 95 % confidence interval ( CI ) = 0.38 - 0.94 , P = .02 ) . Falls were more common in the high-dose group ( 1.47 per person-year vs 0.63 in st and ard-dose group ; IRR = 2.33 , 95 % CI = 1.49 - 3.63 , P Fractures were uncommon and similar in both groups ( high dose 0.10 vs st and ard dose 0.19 per person-year ; P = .31 ) . Mean trough 25-hydroxyvitamin D levels during the trial were 32 . ng/mL in the high-dose group and 25.1 ng/mL in the st and ard-dose group . There was no hypercalcemia or kidney stones in either group . CONCLUSION Monthly high-dose vitamin D3 supplementation reduced the incidence of ARI in older long-term care residents but was associated with a higher rate of falls without an increase in fractures ",
"We evaluated the improvement of intact parathyroid hormone ( iPTH ) levels and bone parameters by supplementing nutritional vitamin D ( cholecalciferol ) to combined calcimimetic ( cinacalcet ) and active vitamin D analog ( calcitriol ) among severe secondary hyperparathyroidism ( SHPT ) hemodialysis ( HD ) patients . A r and omized , controlled open-label study was undertaken in 60 HD patients with serum iPTH > 1000 pg/mL or persistently high iPTH ≥ 600 pg/mL even after > 3 months of calcitriol ( 3 μg/week ) . The study group received oral cholecalciferol ( 5000 IU/ day ) and the control group received a placebo . All patients received fixed dose cinacalcet ( 30 mg/day , orally ) and calcitriol . Calcitriol was reduced if iPTH ≤ 300 pg/mL and cinacalcet was withdrawn if serum iPTH was persistently low ( iPTH ≤ 300 pg/mL ) for 4 weeks after the reduction of calcitriol . A significantly lower iPTH level was noted from the 20th week in the study group compared to the placebo group , and the target iPTH ≤ 300 pg/mL was achieved at the 24th week in the study group . Most patients achieved serum 25-(OH)D3 ≥ 30 ng/mL in the study group . Nearly 40 % of study patients gained > 10 % improvement in femoral neck ( FN ) bone mineral density ( BMD ) . We conclude that cholecalciferol additively reduced serum iPTH levels , improved 25-(OH)D3 levels and improved FN BMD when used together with cinacalcet/calcitriol in severe SHPT HD patients",
"BACKGROUND Increased vitamin D intake may preserve or increase bone mineral density ( BMD ) in older persons . OBJECTIVE A 2-y double-blind study was undertaken to determine whether weekly administration of 10 000 units of vitamin D(2 ) maintained or increased BMD in younger postmenopausal women more efficiently than did calcium supplements alone . DESIGN One hundred eighty-seven women who were > or= 1 y postmenopausal were r and omly assigned to take either 1000 mg Ca/d after the evening meal or 1000 mg Ca/d plus 10 000 U vitamin D(2)/wk in a double-blind , placebo-controlled format . The BMD of the proximal forearm , lumbar spine , femoral neck , Ward 's triangle , and femoral trochanter was measured at 6-mo intervals by osteodensitometry . RESULTS During the 2-y period , there was no significant difference in the change in BMD at any site between the subjects taking calcium supplements and those taking calcium plus vitamin D(2 ) . Both groups significantly ( P gained BMD in Ward 's triangle and the femoral trochanter but significantly ( P lost bone in the proximal radius . There was no significant change in the lumbar spine or femoral neck BMD . CONCLUSION In younger postmenopausal women ( age : 56 y ) whose average baseline serum 25-hydroxyvitamin D concentration was well within the normal range , the addition of 10 000 U vitamin D(2)/wk to calcium supplementation at 1000 mg/d did not confer benefits on BMD beyond those achieved with calcium supplementation alone",
"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",
"Summary This trial compared the effects of daily treatment with vitamin D or placebo for 1 year on blood tests of vitamin D status . The results demonstrated that daily 4000 IU vitamin D3 is required to achieve blood levels associated with lowest disease risks , and this dose should be tested in future trials for fracture prevention . Introduction The aim of this trial was to assess the effects of daily supplementation with vitamin D3 4000 IU ( 100 μg ) , 2000 IU ( 50 μg ) or placebo for 1 year on biochemical markers of vitamin D status in preparation for a large trial for prevention of fractures and other outcomes . Methods This is a r and omized placebo-controlled trial in 305 community-dwelling people aged 65 years or older in Oxfordshire , UK . Outcomes included biochemical markers of vitamin D status ( plasma 25-hydroxy-vitamin D [ 25[OH]D ] , parathyroid hormone [ PTH ] , calcium and alkaline phosphatase ) , cardiovascular risk factors and tests of physical function . Results Mean ( SD ) plasma 25(OH)D levels were 50 ( 18 ) nmol/L at baseline and increased to 137 ( 39 ) , 102 ( 25 ) and 53 ( 16 ) nmol/L after 12 months in those allocated 4000 IU , 2000 IU or placebo , respectively ( with 88 % , 70 % and 1 % of these groups achieving the pre-specified level of > 90 nmol/L ) . Neither dose of vitamin D3 was associated with significant deviation outside the normal range of PTH or albumin-corrected calcium . The additional effect on 25(OH)D levels of 4000 versus 2000 IU was similar in all subgroups except for body mass index , for which the further increase was smaller in overweight and obese participants compared with normal-weight participants . Supplementation with vitamin D had no significant effects on cardiovascular risk factors or on measures of physical function . Conclusions After accounting for average 70 % compliance in long-term trials , doses of 4000 IU vitamin D3 daily may be required to achieve plasma 25(OH)D levels associated with lowest disease risk in observational studies",
"Multiple sclerosis ( MS ) is a possible cause of secondary osteoporosis . In this phase II trial we assessed whether a weekly dose of 20,000 IU vitamin D3 prevents bone loss in ambulatory persons with MS age 18–50 years . Clinical Trials.gov ID NCT00785473 . All patients managed at the University Hospital of North Norway who fulfilled the main inclusion criteria were invited to participate in this double-blinded trial . Participants were r and omised to receive 20,000 IU vitamin D3 or placebo once a week and 500 mg calcium daily for 96 weeks . The primary outcome was the effect of the intervention on percentage change in bone mineral density ( BMD ) at the hip , the spine , and the ultradistal radius over the study period . Of 71 participants r and omised , 68 completed . Mean serum 25-hydroxyvitamin D [ 25(OH)D ] levels in the intervention group increased from 55 nmol/L at baseline to 123 nmol/L at week 96 . After 96 weeks , percentage change in BMD did not differ between groups at any site . BMD decreased at the hip , by 1.4 % in the placebo group ( 95 % CI −2.3 to −0.4 , SD 2.7 , p = 0.006 ) and by 0.7 % in the treatment group ( −1.6 to 0.2 , 2.7 , p = 0.118 ) , difference 0.7 % ( −1.9 to 0.7 , p = 0.332 ) . Findings were not altered by adjustment for sex or serum 25(OH)D. Supplementation with 20,000 IU vitamin D3 a week did not prevent bone loss in this small population . Larger studies are warranted to assess the effect of vitamin D on bone health in persons with MS",
"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 Ergocalciferol ( vitamin D(2 ) ) supplementation plays a role in fall prevention , but the effect in patients living in the community in sunny climates remains uncertain . We evaluated the effect of ergocalciferol and calcium citrate supplementation compared with calcium alone on the risk of falls in older women at high risk of falling . METHODS A 1-year population -based , double-blind , r and omized controlled trial of 302 community-dwelling ambulant older women aged 70 to 90 years living in Perth , Australia ( latitude , 32 degrees S ) , with a serum 25-hydroxyvitamin D concentration of less than 24.0 ng/mL and a history of falling in the previous year . Participants were r and omized to receive ergocalciferol , 1000 IU/d , or identical placebo ( hereinafter , ergocalciferol and control groups , respectively ) . Both groups received calcium citrate , 1000 mg/d . Fall data were collected every 6 weeks . RESULTS Ergocalciferol therapy reduced the risk of having at least 1 fall over 1 year after adjustment for baseline height , which was significantly different between the 2 groups ( ergocalciferol group , 53.0 % ; control group , 62.9 % ; odds ratio [ OR ] , 0.61 ; 95 % confidence interval [ CI ] , 0.37 - 0.99 ) . When those who fell were grouped by the season of first fall or the number of falls they had , ergocalciferol treatment reduced the risk of having the first fall in winter and spring ( ergocalciferol group , 25.2 % ; control group , 35.8 % ; OR , 0.55 ; 95 % CI , 0.32 - 0.96 ) but not in summer and autumn , and reduced the risk of having 1 fall ( ergocalciferol group , 21.2 % ; control group , 33.8 % ; OR , 0.50 ; 95 % CI , 0.28 - 0.88 ) but not multiple falls . CONCLUSION Patients with a history of falling and vitamin D insufficiency living in sunny climates benefit from ergocalciferol supplementation in addition to calcium , which is associated with a 19 % reduction in the relative risk of falling , mostly in winter",
"Low levels of 25-hydroxyvitamin D ( 25OHD ) are associated with increased bone turnover and risk of fractures . Plasma 25OHD is inversely related to body mass index , and vitamin D deficiency is common in obesity . We aim ed to determine whether vitamin D supplementation affects bone turnover and bone mineral density ( BMD ) in obese subjects . Fifty-two healthy obese men and women aged 18–50 years with plasma 25OHD levels below 50 nmol/L were r and omized to 7,000 IU of cholecalciferol daily or placebo for 26 weeks . We measured plasma levels of 25OHD , parathyroid hormone ( PTH ) , and markers of bone turnover , as well as BMD at the hip , spine , forearm , and whole body . Compared with placebo , treatment with cholecalciferol increased mean plasma 25OHD from 35 to 110 nmol/L ( p significantly decreased PTH ( p 0.05 ) . BMD increased significantly at the forearm by 1.6 ± 0.7 % ( p = 0.03 ) . The bone resorption marker C-terminal telopetide of type 1 collagen ( CTX ) decreased borderline significantly in the cholecalciferol group compared with the placebo group ( p = 0.07 ) . Changes in plasma 25OHD correlated inversely with changes in plasma levels of bone-specific alkaline phosphatase ( r = −0.38 , p = 0.01 ) and CTX ( r = −0.33 , p = 0.03 ) . Changes in CTX correlated inversely with changes in spine BMD ( r = −0.45 , p = 0.04 ) . Increasing circulating 25OHD levels by cholecalciferol treatment is of importance to bone health in young obese subjects as increased levels of 25OHD are associated with a decrease in both PTH and bone turnover and with an increase in BMD at the forearm",
"CONTEXT Low 25-hydroxyvitamin D levels are common in patients with primary hyperparathyroidism ( PHPT ) and associated with higher PTH levels and hungry bone syndrome after parathyroidectomy ( PTX ) . However , concerns have been raised about the safety of vitamin D supplementation in PHPT . OBJECTIVE We aim ed to assess safety and effects on calcium homeostasis and bone metabolism of supplementation with high doses of vitamin D in PHPT patients . DESIGN , SETTING This was an investigator-initiated double-blind , r and omized , placebo-controlled , parallel-group trial from a single center . PATIENTS Forty-six PHPT patients were recruited , with a mean age of 58 ( range 29 - 77 ) years , and 35 ( 76 % ) were women . INTERVENTIONS Intervention included daily supplementation with 70 μg ( 2800 IU ) cholecalciferol or identical placebo for 52 weeks . Treatment was administered 26 weeks before PTX and continued for 26 weeks after PTX . MAIN OUTCOME MEASURES PTH , calcium homeostasis , and bone metabolism were evaluated . RESULTS Preoperatively , 25-hydroxyvitamin D increased from 50 to 94 nmol/L in the treatment group and decreased from 57 to 52 nmol/L in the placebo group ( P ) . Compared with placebo , vitamin D decreased PTH significantly by 17 % before PTX ( P = .01 ) , increased lumbar spine bone mineral density by 2.5 % ( P = .01 ) , and decreased C-terminal β-CrossLaps by 22 % ( P . The trabecular bone score did not change in response to treatment , but improved after PTX . Postoperatively , PTH remained lower in the cholecalciferol group compared with the placebo group ( P = .04 ) . Plasma creatinine and plasma and urinary calcium did not differ between groups . CONCLUSIONS Daily supplementation with a high vitamin D dose safely improves vitamin D status and decreases PTH in PHPT patients . The vitamin D treatment is accompanied by reduced bone resorption and improved bone mineral density before operation",
"The aim was to assess the effects of resistance training and vitamin D supplementation on physical performance of healthy elderly subjects . Ninety-six subjects , aged 70 years or more with 25 OH vitamin D levels of 16 ng/ml or less , were r and omized to a resistance training or control group . Trained and control groups were further r and omized to receive in a double blind fashion , vitamin D 400 IU plus 800 mg of calcium per day or calcium alone . Subjects were followed for nine months . Serum 25 OH vitamin D increased from 12.4+/-2.2 to 25.8+/-6.5 ng/ml among subjects supplemented with vitamin D. Trained subjects had significant improvements in quadriceps muscle strength , the short physical performance test and timed up and go . The latter improved more in trained subjects supplemented with vitamin D. At the end of the follow up , gait speed was higher among subjects supplemented with vitamin ( whether trained or not ) than in non-supplemented subjects ( 838+/-147 and 768+/-127 m/12 min , respectively , p=0.02 ) . Romberg ratio was lower among supplemented controls than non-supplemented trained subjects ( 128+/-40 % and 144+/-37 % , respectively , p=0.05 ) . In conclusion , vitamin D supplementation improved gait speed and body sway , and training improved muscle strength",
"Due to little outdoor activity and low dietary intake of vitamin D ( VD ) , Bangladeshi low-income women are at risk for osteoporosis at an early age . The present study assessed the effect of VD , Ca and multiple micronutrient supplementation on VD and bone status in Bangladeshi young female garment factory workers . This placebo-controlled 1-year intervention r and omly assigned 200 apparently healthy subjects ( aged 16 - 36 years ) to four groups : VD group , daily 10 microg VD ; VD and Ca ( VD-Ca ) group , daily 10 microg VD+600 mg Ca ; multiple micronutrient and Ca ( MMN-Ca ) group , 10 microg VD and other micronutrients+600 mg Ca ; a placebo group . Serum 25-hydroxyvitamin D ( S-25OHD ) , intact parathyroid hormone ( S-iPTH ) , Ca , phosphate and alkaline phosphatase were measured . Bone mineral density and bone mineral content were measured by dual-energy X-ray absorptiometry . All measurements were made at baseline and at 12 months . Significantly ( P S-25OHD concentrations were observed in the supplemented groups than in the placebo group after the intervention . Supplementation had an effect ( P S-iPTH in the VD-Ca and MMN-Ca groups compared with the placebo group . Bone mineral augmentation increased at the femur in the supplemented groups . Supplementation with VD-Ca should be recommended as a strategic option to reduce the risk of osteomalacia and osteoporosis in these subjects . MMN-Ca may have analogous positive health implication s with additional non-skeletal benefits",
"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",
"CONTEXT Effects of long-term calcium , with or without vitamin D , on hip bone mineral density ( BMD ) and bone turnover in sunny climates have not been reported . OBJECTIVE The aim was to evaluate the effect of vitamin D added to calcium supplementation on hip dual-energy x-ray absorptiometry BMD and calcium-related analytes . DESIGN , SETTING , AND PARTICIPANTS The study was a 5-yr r and omized , controlled , double-blind trial of 120 community-dwelling women aged 70 - 80 yr . INTERVENTIONS The interventions were 1200 mg/d calcium with placebo vitamin D ( Ca group ) or with 1000 IU/d vitamin D2 ( CaD group ) , or double placebo ( control ) . MAIN OUTCOME MEASURES Hip BMD , plasma 25-hydroxyvitamin D , biomarkers of bone turnover , PTH , and intestinal calcium absorption were measured . RESULTS Hip BMD was preserved in CaD ( -0.17 % ) and Ca ( 0.19 % ) groups but not controls ( -1.27 % ) at yr 1 and maintained in the CaD group only at yr 3 and 5 . The beneficial effects were mainly in those with baseline 25-hydroxyvitamin D levels below the median ( 68 nmol/liter ) . At yr 1 , compared with controls , the Ca and CaD groups had 6.8 and 11.3 % lower plasma alkaline phosphatase , respectively ( P urinary deoxypyridinoline to creatinine ratio , respectively ( P PTH at 3 and 5 yr cf . controls ( 27.8 and 31.3 % , P PTH levels above the median ( 3.6 pmol/liter ) . Therapy did not affect intestinal calcium absorption at high carrier loads . CONCLUSIONS Addition of vitamin D to calcium has long-term beneficial effects on bone density in elderly women living in a sunny climate , probably mediated by a long-term reduction in bone turnover rate",
"Severe vitamin D deficiency is common among Muslim immigrants . The dose necessary to correct the deficiency and its consequence for bone health are not known for immigrants . The aim was to assess the effect of relatively low dosages of supplemental vitamin D on vitamin D and bone status in Pakistani immigrants . This 1-year-long r and omised double-blinded placebo-controlled intervention with vitamin D3 ( 10 and 20 microg/d ) included girls ( 10.1 - 14.7 years ) , women ( 18.1 - 52.7 years ) and men ( 17.9 - 63.5 years ) of Pakistani origin living in Denmark . The main endpoints were serum 25-hydroxyvitamin D ( S-25OHD ) , parathyroid hormone , bone turnover markers and bone mass . The study showed that supplementation with 10 and 20 microg vitamin D3 per d increased S-25OHD concentrations similarly in vitamin D-deficient Pakistani women ( 4-fold ) , and that 10 microg increased S-25OHD concentrations 2-fold and 20 microg 3-fold in Pakistani men . S-25OHD concentrations increased at 6 months and were stable thereafter . Baseline S-25OHD concentrations tended to be lower in girls and women than in men ; females achieved about 46 nmol/l and men 55 nmol/l after supplementation . Serum intact parathyroid hormone concentrations decreased at 6 months , but there was no significant effect of the intervention on bone turnover markers and dual-energy X-ray absorptiometry measurements of the whole body and lumbar spine",
"CONTEXT Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures ; however , adherence to daily supplementation is typically poor . OBJECTIVE To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture . DESIGN , SETTING , AND PARTICIPANTS A double-blind , placebo-controlled trial of 2256 community-dwelling women , aged 70 years or older , considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were r and omly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years . The study concluded in 2008 . INTERVENTION 500,000 IU of cholecalciferol or placebo . MAIN OUTCOME MEASURES Falls and fractures were ascertained using monthly calendars ; details were confirmed by telephone interview . Fractures were radiologically confirmed . In a sub study , 137 r and omly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels . RESULTS Women in the cholecalciferol ( vitamin D ) group had 171 fractures vs 135 in the placebo group ; 837 women in the vitamin D group fell 2892 times ( rate , 83.4 per 100 person-years ) while 769 women in the placebo group fell 2512 times ( rate , 72.7 per 100 person-years ; incidence rate ratio [ RR ] , 1.15 ; 95 % confidence interval [ CI ] , 1.02 - 1.30 ; P = .03 ) . The incidence RR for fracture in the vitamin D group was 1.26 ( 95 % CI , 1.00 - 1.59 ; P = .047 ) vs the placebo group ( rates per 100 person-years , 4.9 vitamin D vs 3.9 placebo ) . A temporal pattern was observed in a post hoc analysis of falls . The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months ( test for homogeneity ; P = .02 ) . In the sub study , the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3 % of the sub study participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group , 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L , were approximately 90 nmol/L at 3 months , and remained higher than the placebo group 12 months after dosing . CONCLUSION Among older community-dwelling women , annual oral administration of high-dose cholecalciferol result ed in an increased risk of falls and fractures . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12605000658617 ; is rct n.org Identifier : IS RCT N83409867",
"Summary The effects of higher than recommended vitamin D doses on bone mineral density ( BMD ) and quality are not known . In this study , higher intakes , in postmenopausal women undergoing weight control over 1 year , had no effect on areal or volumetric BMD but prevented the deterioration in cortical bone geometry . Introduction Studies examining how bone responds to a st and ard dose of vitamin D supplementation have been inconsistent . In addition , the effects of higher doses on BMD and quality are not known . Postmenopausal women undergoing weight control to improve health outcomes are particularly at risk for bone loss and might benefit from supplemental vitamin D intake above the recommended allowance . Methods This 1-year-long , r and omized , double-blind controlled study addresses whether vitamin D supplementation , in healthy overweight/obese older women , affects BMD and bone structural parameters . In addition , bone turnover and serum total , free , and bioavailable 25-hydroxyvitamin D ( 25OHD ) responses to one of three daily levels of vitamin D3 ( 600 , 2000 , 4000 IU ) with 1.2 Ca g/day during weight control were examined . Results Fifty-eight women ( age , 58 ± 6 years ; body mass index , 30.2 ± 3.8 kg/m2 , serum 25OHD , 27.3 ± 4.4 ng/mL ) were r and omized to treatment . After 1 year , serum 25OHD concentrations increased to 26.5 ± 4.4 , 35.9 ± 4.5 , and 41.5 ± 6.9 ng/mL , in groups 600 , 2000 , and 4000 IU , respectively , and differed between groups ( p ± 4.1 % ) . Cortical ( Ct ) thickness of the tibia changed by −1.5 ± 5.1 % , + 0.6 ± 3.2 % , and + 2.0 ± 4.5 % in groups 600 , 2000 , and 4000 IU , respectively , and each group was significantly different from each other ( p decline in Ct thickness was prevented with higher vitamin D3 supplementation , but there were no other significant changes due to treatment over 1 year . Whether these findings translate to changes in biomechanical properties leading to reduced fracture risk should be addressed in future studies",
"Patients with primary hyperparathyroidism ( PHPT ) have higher bone turnover , lower bone mineral density ( BMD ) , and an increased risk of fractures . They also have a high incidence of low vitamin D levels ( 25-OH-vitamin D effect on the bone . In this double-blinded clinical trial , 150 patients with PHPT were r and omized , after successful parathyroidectomy ( PTX ) , to 1-year daily treatment with either cholecalciferol 1600 IU and calcium carbonate 1000 mg ( D+ ) or calcium carbonate alone ( D- ) . BMD was measured in the lumbar spine , femoral neck , total hip , distal and 33 % radius using dual-energy X-ray absorptiometry ( DXA ) before surgery and after 1 year of study medication . Median age was 60 ( range 30 - 80 ) years and there were 119 ( 79 % ) women and 31 ( 21 % ) men ; 76 % had 25-OH-D % had persistent elevated parathyroid hormone ( PTH ) 6 weeks after PTX . A similar increase in BMD in the lumbar spine , femoral neck , and total hip was observed in both groups ( D+ : 3.6 % , 3.2 % , and 2.7 % , p vitamin D supplementation also increased their BMD in distal radius ( median 2.0 % ; interquartile range , -1.7 % to 5.4 % ; p=0.013 ) . The changes in BMD , especially in the hips , were correlated to the baseline concentrations of PTH , ionized calcium , and bone markers ( p vitamin D substitution was observed among patients with a persistent postoperative PTH elevation , who also improved their BMD at 33 % radius and radius ultradistal ( p improvement of radius BMD , our data show no beneficial effect on BMD or bone turnover markers of vitamin D supplementation after PTX . Preoperative PTH seems to have the strongest association with improvement in BMD",
"BACKGROUND The 2009 KDIGO ( Kidney Disease : Improving Global Outcomes ) chronic kidney disease-mineral and bone disorder clinical practice guideline suggests correcting 25-hydroxyvitamin D3 ( 25[OH]D ) levels patients treated with maintenance hemodialysis , but does not provide a specific treatment protocol . STUDY DESIGN 2-center , double-blind , r and omized , 13-week , controlled trial followed by a 26-week open-label study . SETTING & PARTICIPANTS 55 adult maintenance hemodialysis patients with 25(OH)D levels INTERVENTION Cholecalciferol , 25,000IU , per week orally versus placebo for 13 weeks , then 26 weeks of individualized cholecalciferol prescription based on NKF-KDOQI ( National Kidney Foundation-Kidney Disease Outcomes Quality Initiative ) guidelines . OUTCOMES Primary end point was the percentage of patients with 25(OH)D levels≥30ng/mL at 13 weeks . Secondary outcomes included the percentage of patients with normal calcium , phosphorus , and intact parathyroid hormone ( iPTH ) blood levels . Safety measures included incidence of hypercalcemia and hypervitaminosis D. MEASUREMENTS Blood calcium and phosphate were measured weekly ; iPTH , 25(OH)D , 1,25-dihydroxyvitamin D3 ( 1,25[OH]2D ) , and bone turnover markers , trimonthly ; fetuin A and fibroblast growth factor 23 ( FGF-23 ) serum levels and aortic calcification scores were determined at weeks 0 and 39 . RESULTS The primary end point significantly increased in the treatment group compared with the placebo group ( 61.5 % vs 7.4 % ; P well as 1,25(OH)2D levels ( 22.5 [ IQR , 15 - 26 ] vs 11 [ IQR , 10 - 15]pg/mL ; P proportion of patients achieving the target calcium level ( 76.9 % vs 48.2 % ; P=0.03 ) . Incidence of hypercalcemia and phosphate and iPTH levels were similar between groups . The second 26-week study phase did not significantly modify the prevalence of 25(OH)D level≥30ng/mL in patients issued from the placebo group . LIMITATIONS Small size of the study population . CONCLUSIONS Oral weekly administration of 25,000IU of cholecalciferol for 13 weeks is an effective , safe , inexpensive , and manageable way to increase 25(OH)D and 1,25(OH)2D levels in hemodialysis patients . Further evaluation of clinical end points is suggested",
"Objectives The role vitamin D intake/production plays in sarcoidosis-associated hypercalcaemia is uncertain . However , authoritative review s have recommended avoiding sunlight exposure and vitamin D supplements , which might lead to adverse skeletal outcomes from vitamin D insufficiency . We investigated the effects of vitamin D supplementation on surrogate measures of skeletal health in patients with sarcoidosis and vitamin D insufficiency . Design R and omised , placebo-controlled trial . Setting Clinical research centre . Participants 27 normocalcaemic patients with sarcoidosis and 25-hydroxyvitamin D ( 25OHD ) Intervention 50 000 IU weekly cholecalciferol for 4 weeks , then 50 000 IU monthly for 11 months or placebo . Primary and secondary outcome measures The primary endpoint was the change in serum calcium over 12 months , and secondary endpoints included measurements of calcitropic hormones , bone turnover markers and bone mineral density ( BMD ) . Results The mean age of participants was 57 years and 70 % were women . The mean ( SD ) screening 25OHD was 35 ( 12 ) and 38 ( 9 ) nmol/L in the treatment and control groups , respectively . Vitamin D supplementation increased 25OHD to 94 nmol/L after 4 weeks , 84 nmol/L at 6 months and 78 nmol/L at 12 months , while levels remained stable in the control group . 1,25-Dihydroxy vitamin D levels were significantly different between the groups at 4 weeks , but not at 6 or 12 months . There were no between-groups differences in albumin-adjusted serum calcium , 24 h urine calcium , markers of bone turnover , parathyroid hormone or BMD over the trial . One participant developed significant hypercalcaemia after 6 weeks ( total cholecalciferol dose 250 000 IU ) . Conclusions In patients with sarcoidosis and 25OHD , vitamin D supplements did not alter average serum calcium or urine calcium , but had no benefit on surrogate markers of skeletal health and caused one case of significant hypercalcaemia . Trial registration This trial is registered at the Australian New Zeal and Clinical Trials Registry ( http://www.anzctr.org.au ) . The registration number is ACTRN12607000364471 , date of registration 5/7/2007",
"Abstract Objective : To determine the effect of four monthly vitamin D supplementation on the rate of fractures in men and women aged 65 years and over living in the community . Design : R and omised double blind controlled trial of 100 000 IU oral vitamin D3 ( cholecalciferol ) supplementation or matching placebo every four months over five years . Setting and participants : 2686 people ( 2037 men and 649 women ) aged 65 - 85 years living in the general community , recruited from the British doctors register and a general practice register in Suffolk . Main outcome measures : Fracture incidence and total mortality by cause . Results : After five years 268 men and women had incident fractures , of whom 147 had fractures in common osteoporotic sites ( hip , wrist or forearm , or vertebrae ) . Relative risks in the vitamin D group compared with the placebo group were 0.78 ( 95 % confidence interval 0.61 to 0.99 , P=0.04 ) for any first fracture and 0.67 ( 0.48 to 0.93 , P=0.02 ) for first hip , wrist or forearm , or vertebral fracture . 471 participants died . The relative risk for total mortality in the vitamin D group compared with the placebo group was 0.88 ( 0.74 to 1.06 , P=0.18 ) . Findings were consistent in men and women and in doctors and the general practice population . Conclusion : Four monthly supplementation with 100 000 IU oral vitamin D may prevent fractures without adverse effects in men and women living in the general community . What is already known in this topic Vitamin D and calcium supplements are effective in preventing fractures in elderly women Whether isolated vitamin D supplementation prevents fractures is not clear What this paper adds Four monthly oral supplementation with 100 000 IU vitamin D reduces fractures in men and women aged over 65 living in the general community Total fracture incidence was reduced by 22 % and fractures in major osteoporotic sites by 33",
"Background There remains uncertainty regarding the appropriate therapeutic management of hip fracture patients . The primary aim of our study was to examine whether large loading doses in addition to daily vitamin D offered any advantage over a simple daily low-dose vitamin D regimen for increasing vitamin D levels . Methods In this r and omized controlled study , patients over age 50 with an acute fragility hip fracture were enrolled from two hospital sites in Ontario , Canada . Participants were r and omized to one of three loading dose groups : placebo ; 50,000 IU vitamin D2 ; or 100,000 IU D2 . Following a placebo/loading dose , all patients received a daily tablet of 1,000 IU vitamin D3 for 90 days . Serum 25-hydroxy vitamin D ( 25-OHD ) was measured at baseline , discharge from acute care ( approximately 4-weeks ) , and 3-months . Results Sixty-five patients were enrolled in the study ( 44 % male ) . An immediate rise in 25-OHD occurred in the 100,000 group , however there were no significant differences in 25-OHD between the placebo , 50,000 and 100,000 loading dose groups after 4-weeks ( 69.3 , 84.5 , 75.6 nmol/L , p = 0.15 ) and 3-months ( 86.7 , 84.2 , 73.3 nmol/L , p = 0.09 ) , respectively . At the end of the study , approximately 75 % of the placebo and 50,000 groups had reached the target therapeutic range ( 75 nmol/L ) , and 44 % of the 100,000 group . Conclusions In correcting vitamin D insufficiency/deficiency in elderly patients with hip fracture , our findings suggest that starting with a lower daily dose of Vitamin D3 achieved similar results as providing an additional large loading dose of Vitamin D2 . At the end of the study , all three groups were equally effective in attaining improvement in 25-OHD levels . Given that a daily dose of 1,000 IU vitamin D3 ( with or without a loading dose ) result ed in at least 25 % of patients having suboptimal vitamin D status , patients with acute hip fracture may benefit from a higher daily dose of vitamin D.Trial registration Clinical Trials #",
"Background Improving vitamin D ( 25-OHD ) status may be an important modifiable factor that could reduce disability severity , fall-rates and mortality associated after hip fracture surgery . Providing a loading-dose post-surgery may overcome limitations in adherence to daily supplementation . Method In this r and omized , double-blind , placebo-controlled trial , 218 adults , aged 65-years or older , requiring hip fracture surgery were assigned to receive a single loading-dose of cholecalciferol ( 250,000 IU vitamin-D3 , the REVITAHIP - Replenishment of Vitamin D in Hip Fracture strategy ) or placebo , both receiving daily vitamin-D(800 IU ) and calcium ( 500 mg ) for 26-weeks . Outcome measures were 2.4 m gait-velocity , falls , fractures , death ( Week-4 ) , 25-OHD levels , quality -of-life measure ( EuroQoL ) and mortality at weeks-2 , 4 and 26 . Results Mean age of 218 participants was 83.9(7.2 ) years and 77.1 % were women . Baseline mean 25-OHD was 52.7(23.5)nmol/L , with higher levels at Week-2 ( 73 vs 66 nmol/L ; p = .019 ) and Week-4 ( 83 vs 75 nmol/L ; p = .030 ) in the Active-group , but not at Week-26 . At week-4 , there were no differences in 2.4 m gait-velocity ( 0.42 m/s vs 0.39 m/s , p = .490 ) , fractures ( 2.7 % vs 2.8 % , p = .964 ) but Active participants reported less falls ( 6.3 % vs 21.1 % , χ2 = 4.327 ; p = 0.024 ) , with no significant reduction in deaths at week-4 ( 1 vs 3 , p = 0.295 ) , higher percentage reporting ‘ no pain or discomfort ’ ( 96.4 % vs 88.8 % , p = 0.037 ) , and trended for higher EuroQoL-scores ( p = 0.092 ) at week-26 . One case of hypercalcemia at week-2 normalised by week-4 . Conclusion Among older people after hip fracture surgery , the REVITAHIP strategy is a safe and low cost method of improving vitamin-D levels , reducing falls and pain levels . Trial registration The protocol for this study is registered with the Australian New Zeal and Clinical Trials Registry ANZCTRN ACTRN12610000392066 ( Date of registration : 14/05/2010 )",
"BACKGROUND vitamin D supplementation reduces the incidence of fractures in older adults . This may be partly mediated by effects of vitamin D on neuromuscular function . OBJECTIVE to determine the effects of vitamin D supplementation on aspects of neuromuscular function known to be risk factors for falls and fractures . DESIGN r and omised , double-blind , placebo-controlled study . SETTING falls clinic taking referrals from general practitioners and accident and emergency department . SUBJECTS 139 ambulatory subjects ( > /=65 years ) with a history of falls and 25-hydroxyvitamin D ( 25OHD ) INTERVENTION patients were r and omised to receive a single intramuscular injection of 600,000 i.u . ergocalciferol or placebo . OUTCOME MEASURES assessment s including biochemistry , postural sway , choice reaction time ( CRT ) , aggregate functional performance time ( AFPT ) , and quadriceps strength were carried out at baseline and 6 months post-intervention . RESULTS baseline characteristics were comparable between both groups . 25OHD in the treatment group increased significantly at 6 months . AFPT deteriorated in the control group and improved in the intervention group , representing a significant difference between groups ( + 6.6 s versus -2.0 s , t = 2.80 , P CRT ( -0.06 s versus + 0.41 s , t = -2.52 , P postural sway ( + 0.0025 versus -0.0138 , t = 2.35 , P muscle strength change between groups ( -10 N versus -2 N , t = -1.26 , ns ) . A significant correlation between change in AFPT and change in 25OHD levels was observed ( r = 0.19 , P = 0.03 ) . There was no significant difference in the number of falls ( 0.39 versus 0.24 , t = 1.08 , P = 0.28 ) or fallers ( 14 versus 11 , P = 0.52 ) between two groups . CONCLUSIONS vitamin D supplementation , in fallers with vitamin D insufficiency , has a significant beneficial effect on functional performance , reaction time and balance , but not muscle strength . This suggests that vitamin D supplementation improves neuromuscular or neuroprotective function , which may in part explain the mechanism whereby vitamin D reduces falls and fractures",
"Black women have lower serum 25-hydroxyvitamin D ( 25[OH]D ) levels and higher parathyroid hormone ( PTH ) levels than white peers but lower bone turnover , suggesting skeletal resistance to PTH . Our objective was to determine if vitamin D supplementation ( 1,000 IU/day ) would prevent bone loss and whether vitamin D receptor ( VDR ) polymorphisms modify the response . We performed a 2-year r and omized , controlled , double-blind study of 1,000 IU vitamin D3 vs. placebo in postmenopausal black women with serum 25(OH)D levels Measurements of 25(OH)D , PTH , and bone turnover were evaluated at baseline and 3 , 6 , 12 , 18 , and 24 months . DNA was extracted from peripheral blood leukocytes , and genotyping was conducted using st and ard techniques . Spine and hip bone mineral density ( BMD ) was measured at baseline and every 6 months . Serum 25(OH)D increased 11 ng/mL with vitamin D supplementation ( p Vitamin D supplementation produced a significant decline in PTH at 3 months only , with no differences in bone turnover between placebo and vitamin D at any time point . Two-year changes in BMD were not significantly different between placebo- and vitamin D-treated black women at any skeletal site . Despite similar elevations in 25(OH)D , femoral neck BMD was only responsive to vitamin D supplementation in FF subjects ( n = 47 ) , not Ff/ff subjects ( n = 31 ) . Vitamin D supplementation does not appear to influence bone loss in black women . However , in the FF polymorphism of the VDR gene group , vitamin D supplementation may retard the higher rate of bone loss",
"A double-blind placebo-controlled r and omized phase II trial was performed to determine whether High Dose Vitamin D2 supplementation ( HDD ) in women receiving adjuvant anastrozole improves aromatase inhibitor-induced musculoskeletal symptoms ( AIMS S ) and bone loss . Patients with early breast cancer and AIMS S were stratified according to their baseline 25-hydroxy vitamin D ( 25OHD ) level . Stratum A ( 20–29 ng/ml ) received either HDD 50,000 IU capsules weekly for 8 weeks then monthly for 4 months or placebo . Stratum B ( 10–19 ng/ml ) received either HDD for 16 weeks and then monthly for 2 months , or placebo . AIMS S was assessed by the Brief Pain Inventory-Short Form ( BPI-SF ) , the Fibromyalgia Impact Question naire ( FIQ ) , and the Health Assessment Question naire-Disability Index ( HAQ-DI ) at baseline , 2 , 4 , and 6 months . Bone Mineral Density ( BMD ) was measured at baseline and at 6 months . The primary endpoint of the study was the change-from-baseline musculoskeletal pain . The secondary endpoint was the percent change in BMD at 6 months . Sixty women were enrolled . Baseline characteristics were comparable between the groups . At 2 months , FIQ pain ( P = 0.0045 ) , BPI worst-pain ( P = 0.04 ) , BPI average-pain ( P = 0.0067 ) , BPI pain-severity ( P = 0.04 ) , and BPI interference ( P = 0.034 ) scores were better in the HDD than placebo group . The positive effect of HDD on AIMS S was stronger across all time points in Stratum B than Stratum A ( FIQ pain , P = 0.04 ; BPI average , P = 0.03 ; BPI severity , P = 0.03 ; BPI interference , P = 0.04 ) . BMD at the femoral neck decreased in the placebo and did not change in the HDD group ( P = 0.06 ) . Weekly HDD improves AIMS S and may have a positive effect on bone health . Vitamin D supplementation strategies for breast cancer patients on AI should be further investigated",
"BACKGROUND Care of elderly patients after hip fracture is not well established . METHODS We enrolled 173 patients with acute hip fracture who were 65 years or older ( 79.2 % women ; mean age , 84 years ; 77.4 % living at home ) . Using a factorial design , we r and omly allocated patients to extended physiotherapy ( PT ) ( supervised 60 min/d during acute care plus an unsupervised home program ) vs st and ard PT ( supervised 30 min/d during acute care plus no home program ; single-blinded ) , and to cholecalciferol therapy , 2000 vs 800 IU/d ( double-blinded ) . Primary outcome was rate of falls ; secondary outcome was rate of hospital readmissions during the 12-month follow-up . All analyses included 173 individuals and used multivariate Poisson regression analyses . RESULTS At baseline , 50.9 % of participants had 25-hydroxyvitamin D levels of less than 12 ng/mL and 97.7 % of less than 30 ng/mL. We documented 212 falls and 74 hospital readmissions . Because this was a factorial design trial , all analyses tested the main effect of each treatment while controlling for the other in 173 participants . Extended vs st and ard PT reduced the rate of falls by 25 % ( 95 % confidence interval [ CI ] , -44 % to -1 % ) . Cholecalciferol treatment , 2000 vs 800 IU/d , did not reduce falls ( 28 % ; 95 % CI , -4 % to 68 % ) , but reduced the rate of hospital readmissions by 39 % ( 95 % CI , -62 % to -1 % ) . CONCLUSIONS Extended PT was successful in reducing falls but not hospital readmissions , whereas cholecalciferol treatment , 2000 IU/d , was successful in reducing hospital readmission but not falls . Thus , the 2 strategies may be useful together because they address 2 different and important complications after hip fracture",
"In this prospect i ve study , the authors determined intrinsic risk factors for falls and recurrent falls and constructed a risk profile that indicated the relative contribution of each risk factor and also estimated the probabilities of falls and recurrent falls . In 1992 , over a 28-week period , falls were recorded among 354 elderly subjects aged 70 years or over who were living in homes or apartments for the elderly in Amsterdam and the vicinity . During the study period , 251 falls were reported by 126 subjects ( 36 % ) , and recurrent falls ( > or = 2 falls ) were reported by 57 subjects ( 16 % ) . Associations of falls and recurrent falls with potential risk factors were identified in logistic regression models . Mobility impairment regarding one or more of the tested items ( i.e. , impairment of balance , leg-extension strength , and gait ) was associated with falls ( adjusted odds ratio ( OR ) = 2.6 ) and was strongly associated with recurrent falls ( OR = 5.0 ) . Dizziness upon st and ing was associated with falls ( OR = 2.1 ) and recurrent falls ( OR = 2.1 ) . However , several risk factors were associated with recurrent falls only : history of stroke ( OR = 3.4 ) , poor mental state ( OR = 2.4 ) , and postural hypotension ( OR = 2.0 ) . The authors constructed a risk profile for recurrent falls that included the five risk factors mentioned above . Inclusion of all risk factors in the profile implied an 84 % probability of recurrent falls over a period of 28 weeks , compared with 3 % when no risk factor was present . The probability of recurrent falls ranged only from 11 % to 29 % when predicted by number of falls occurring in the previous year . Physical activity , use of high-risk medication , and the use of vitamin D3 , which was r and omly allocated to the participants , were not strongly related to either falls or recurrent falls . In conclusion , a large range of probabilities of falls , especially of recurrent falls , was estimated by the risk profiles , in which mobility impairment was the major risk factor . Recurrent fallers may therefore be especially amenable to prevention based on mobility improvement",
"Summary Vitamin D is widely used in osteoporosis treatment , although the optimal dose is not known . This 1-year clinical study among 297 women aged 50–80 years old showed that a vitamin D3 dose of 6,500 IU/day was not better than the st and ard dose of 800 IU/day in improving bone mineral density ( BMD ) in the hip and spine . Introduction The purpose of this study was to determine whether a high dose of vitamin D3 was better than the st and ard dose in improving BMD and reducing bone turnover in postmenopausal women with reduced bone mass . Methods The study was a 1-year r and omized double-blind controlled trial comparing high-dose vitamin D3 with the st and ard dose . Postmenopausal women ( n = 297 ) with a BMD T-score ≤ −2.0 in either lumbar spine ( L2–4 ) or total hip were included and r and omized to 6,500 IU vitamin D3/day ( 20,000 IU twice per week + 800 IU/day ) or 800 IU vitamin D3/day ( placebo twice per week + 800 IU/day ) . Both groups were given 1,000 mg elemental calcium/day . The primary endpoint was a change in BMD in total hip and lumbar spine ( L2–4 ) . Results After 1 year , serum 25-hydroxyvitamin D ( 25(OH)D ) increased [ mean ( SD ) ] from 71 ( 23 ) to 185 ( 34 ) nmol/l and from 71 ( 22 ) to 89 ( 17 ) nmol/l in the high- and st and ard-dose vitamin D groups , respectively . BMD at all measurement sites was unchanged or slightly improved with no significant differences between the groups . Although bone turnover was reduced in both groups , the more pronounced reduction in serum levels of the bone formation marker P1NP in the st and ard-dose group may indicate that this treatment was more efficient . Adverse events did not differ between the groups . Conclusions One year treatment with 6,500 IU vitamin D3/day was not better than 800 IU/day regarding BMD in vitamin D-replete postmenopausal women with reduced bone mass and was less efficient in reducing bone turnover",
"Background and aims : Insufficient vitamin D status , commonly found in older people , has been associated with muscle weakness which , in old age , impairs mobility and is a risk factor for falling . In a r and omized , double-blind placebo-controlled trial , we tested the hypothesis that vitamin D + calcium supplementation improves muscle strength and mobility , compared with calcium mono-therapy in vitamin D-insufficient female geriatric patients . Methods : Seventy female geriatric patients > 65 years of age with serum 25-hydroxyvitamin D3 ( 25OHD ) concentrations between 20 and 50 nmol/L , visiting an outpatient geriatric department , were included . Participants received either cholecalciferol 400 IU/day + calcium 500 mg/day ( D/Cal group ) or a placebo + calcium 500 mg/day ( Plac/Cal group ) for 6 months . At baseline and 6 months , muscle strength , power and functional mobility were tested . Results : At baseline , 25OHD was significantly ( p with knee extension strength ( r=0.42 ) , h and grip strength ( r=0.28 ) , leg extension power ( r=0.34 ) , Timed Get Up and Go ( r=−0.31 ) and Modified Cooper test ( r=0.44 ) . At 6 months , a significant difference in 25OHD ( 77.2 vs 41.6 nmol/L , p and 1,25OHD was found between the two groups . Significantly improving vitamin D status in the D/Cal group compared with the Plac/Cal group did not result in a significant difference in strength or functional mobility between the two groups . Conclusions : Daily 400IU vitamin D + 500 mg calcium supplementation is not enough to significantly improve strength or mobility in vitamin D-insufficient female geriatric patients",
"The purpose of the study was to determine the effect of vitamin D supplementation on bone turnover and bone loss in elderly women . Three hundred forty-eight women , ages 70 yr and older , were r and omized to receive 400 IU vitamin D3 per day ( n = 177 ) or placebo ( n = 171 ) , double-blind , for a period of 2 yr . Main outcome measures were bone mineral density of both hips ( femoral neck and trochanter ) and the distal radius , as well as biochemical markers of bone turnover . The effect of vitamin D supplementation was expressed as the difference in mean ( percentage ) change between the placebo group and the vitamin D group . The measurements were repeated in 283 women after 1 yr and in 248 women after 2 yr . Vitamin D supplementation significantly increased serum 25-hydroxyvitamin D ( 250HD ) ( + 35 nmol/L ) and 1,25-dehydroxyvitamin D [ 1,25-(OH)2D ] ( + 7.0 pmol/L ) levels and urinary calcium/creatinine ratios ( + 0.5 % ) and significantly decreased PTH(1 - 84 ) secretion ( -0.74 pmol/L ) after 1 yr . No effect was found for the parameters of bone turnover . The effect on the bone mineral density of the left femoral neck was + 1.8 % in the first yr , + 0.2 % in the second yr , and + 1.9 % during the whole period ( 95 % confidence interval 0.4 , 3.4 % ) . At the right femoral neck the effects were + 1.5 % , + 1.1 % , and + 2.6 % ( confidence interval 1.1 , 4.0 % ) , respectively . No effect was found at the femoral trochanter and the distal radius . Supplementation with 400 IU vitamin D3 daily in elderly women slightly decreases PTH secretion and increases bone mineral density at the femoral neck",
"Abstract : Vitamin D status is known to be an important determinant of bone mineral density ( BMD ) . There is a significant seasonal variation in serum vitamin D , and some studies have reported an associated seasonal variation in BMD . The present study was devised to investigate whether a seasonal variation in BMD could be detected in healthy normal subjects , along with associated variations in serum parathyroid hormone ( PTH ) , intestinal calcium absorption and biochemical markers of bone turnover . A second aim was to investigate whether , if such variations were identified , they could be suppressed by vitamin D supplementation . The subjects were 70 healthy female volunteers ( mean age 47.2 years , range 24–70 years ) recruited into a double-masked crossover study and followed over 2 years . During the first year 35 subjects received a daily oral supplement containing 800 IU ( 20 mg ) cholecalciferol ( group 1 ) and 35 subjects received a placebo preparation ( group 2 ) . During the second year the treatment each group received was reversed . Lumbar spine ( L1–L4 ) , left proximal femur and total body BMD were measured by DXA at 3-month intervals . Serum 25-hydroxyvitamin D ( 25-OHD ) , serum PTH , bone markers ( bone-specific ALP ( BSAP ) and urinary crosslinks ( DYPD/creatinine ) ) and calcium absorption were also measured at each visit . Cholecalciferol treatment increased serum 25-OHD by 25.4 nmol/l ( p serum PTH of 6.6 ng/l ( p = 0.011 ) was seen in subjects in the lowest quartile of baseline serum 25-OHD . The treatment had no significant effect on spine , femur or total body BMD , calcium absorption or bone markers . When Fourier analysis was used to analyze the data for seasonal effect ( defined as twice the amplitude of the 1-year period variation ) a highly significant effect for 25-OHD of 18 nmol/l ( p for BMD , PTH , calcium absorption or bone markers . The analysis set a 95 % confidence limit to the seasonal effect of less than 0.6 % for spine , total hip and total body BMD . It was concluded that in the population of healthy women studied there was no evidence of seasonal variation in spine , femur or total body BMD , serum PTH , calcium absorption or bone markers . Vitamin D supplementation was found to have no effect on BMD ",
"Summary In this post hoc analysis of the VITdAL-ICU study , an RCT in critically ill adults with 25-hydroxyvitamin D levels ≤20 ng/ml , vitamin D3 did not have a significant effect on β-Crosslaps and osteocalcin . Introduction Observational studies have shown accelerated bone loss in ICU survivors . A reversible contributor is vitamin D deficiency . In a post hoc analysis of the VITdAL-ICU study , we evaluated the effect of high-dose vitamin D3 on the bone turnover markers ( BTM ) β-Crosslaps ( CTX ) and osteocalcin ( OC ) . Methods The VITdAL-ICU study was a r and omized , double-blind , placebo-controlled trial in critically ill adults with 25-hydroxyvitamin D levels ≤20 ng/ml who received placebo or high-dose vitamin D3 ( a loading dose of 540,000 IU and starting 1 month after the loading dose five monthly maintenance doses of 90,000 IU ) . In this analysis on 289 survivors ( 209 telephone , 80 personal follow-up visits ) , BTM were analyzed on days 0 , 3 , 7 , 28 , and 180 ; self-reported falls and fractures were assessed . Bone mineral density ( BMD ) was measured after 6 months . Results At baseline , CTX was elevated ; OC was low in both groups — after 6 months , both had returned to normal . There were no differences between groups concerning BTM , BMD , falls , or fractures . In linear mixed effects models , CTX and OC showed a significant change over time ( p between the vitamin D and placebo group ( p = 0.688 and p = 0.972 , respectively ) . Conclusions Vitamin D supplementation did not have a significant effect on BTM . Further studies should assess the effectiveness of vitamin D on musculoskeletal outcomes in ICU survivors",
"Sarcopenia and osteoporosis represent a growing public health problem . We studied the potential benefit of whole-body vibration ( WBV ) training given a conventional or a high dose of daily vitamin D supplementation in improving strength , muscle mass , and bone density in postmenopausal women . In a 2 × 2 factorial- design trial , 113 institutionalized elderly females aged over 70 years ( mean age 79.6 years ) were r and omly assigned either to a WBV or a no-training group , receiving either a conventional dose ( 880 IU/day ) or a high dose ( 1600 IU/day ) of vitamin D(3 ) . The primary aim was to determine the effects of 6 months of WBV and /or vitamin D supplementation on isometric and dynamic strength , leg muscle mass , and hip bone mineral density ( BMD ) . Additionally , the increase in 25-hydroxyvitamin D [ 25(OH)D ] levels between conventional and high-dose supplementation was compared . After 6 months of treatment , dynamic muscle strength , hip BMD , and vitamin D serum levels improved significantly in all groups , whereas isometric strength and muscle mass did not change . When compared with no training , the WBV program did not result in additional improvements . When compared with 880 IU , a high dose of 1600 IU of vitamin D did result in higher serum vitamin D levels but did not result in additional improvements . In institutionalized women older than 70 years , the WBV training protocol tested is not more efficient in enhancing muscle mass , strength , and hip BMD compared with vitamin D supplementation . A higher dose of 1600 IU of vitamin D does not provide additional musculoskeletal benefit in this population compared with conventional doses",
"BACKGROUND The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal . METHODS We recruited 36,282 postmenopausal women , 50 to 79 years of age , who were already enrolled in a Women 's Health Initiative ( WHI ) clinical trial . We r and omly assigned participants to receive 1000 mg of elemental [ corrected ] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo . Fractures were ascertained for an average follow-up period of 7.0 years . Bone density was measured at three WHI centers . RESULTS Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group ( P calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture ( 95 percent confidence interval , 0.72 to 1.08 ) , 0.90 for clinical spine fracture ( 0.74 to 1.10 ) , and 0.96 for total fractures ( 0.91 to 1.02 ) . The risk of renal calculi increased with calcium plus vitamin D ( hazard ratio , 1.17 ; 95 percent confidence interval , 1.02 to 1.34 ) . Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 ( 95 percent confidence interval , 0.52 to 0.97 ) . Effects did not vary significantly according to prer and omization serum vitamin D levels . CONCLUSIONS Among healthy postmenopausal women , calcium with vitamin D supplementation result ed in a small but significant improvement in hip bone density , did not significantly reduce hip fracture , and increased the risk of kidney stones . ( Clinical Trials.gov number , NCT00000611 . )",
"IMPORTANCE Observational data link low 25-hydroxyvitamin D levels to both prevalent blood pressure and incident hypertension . No clinical trial has yet examined the effect of vitamin D supplementation in isolated systolic hypertension , the most common pattern of hypertension in older people . OBJECTIVE To test whether high-dose , intermittent cholecalciferol supplementation lowers blood pressure in older patients with isolated systolic hypertension . DESIGN Parallel group , double-blind , placebo-controlled r and omized trial . SETTING Primary care clinics and hospital clinics . PARTICIPANTS Patients 70 years and older with isolated systolic hypertension ( supine systolic blood pressure > 140 mm Hg and supine diastolic blood pressure INTERVENTIONS A total of 100,000 U of oral cholecalciferol or matching placebo every 3 months for 1 year . MAIN OUTCOMES AND MEASURES Difference in office blood pressure , 24-hour blood pressure , arterial stiffness , endothelial function , cholesterol level , insulin resistance , and b-type natriuretic peptide level during 12 months . RESULTS A total of 159 participants were r and omized ( mean age , 77 years ) . Mean baseline office systolic blood pressure was 163/78 mm Hg . Mean baseline 25-hydroxyvitamin D level was 18 ng/mL. 25-Hydroxyvitamin D levels increased in the treatment group compared with the placebo group ( + 8 ng/mL at 1 year , P ) office blood pressure ( −1 [ −6 to 4]/−2 [ −4 to 1 ] mm Hg at 3 months and 1 [ −2 to 4]/0 [ −2 to 2 ] mm Hg overall treatment effect ) . No significant treatment effect was evident for any of the secondary outcomes ( 24-hour blood pressure , arterial stiffness , endothelial function , cholesterol level , glucose level , and walking distance ) . There was no excess of adverse events in the treatment group , and the total number of falls was nonsignificantly lower in the group receiving vitamin D ( 36 vs 46 , P = .24 ) . CONCLUSIONS AND RELEVANCE Vitamin D supplementation did not improve blood pressure or markers of vascular health in older patients with isolated systolic hypertension . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N92186858",
"Daily vitamin D in addition to calcium supplementation reduces falls and fractures in older women . However , poor adherence to therapy is a common clinical problem . To examine the effects of supervised oral 3-monthly vitamin D therapy on falls , muscle strength , and mobility , we conducted a 9-month r and omized , double-blind , placebo-controlled trial in 686 community-dwelling ambulant women aged over 70 years . Participants received either oral cholecalciferol 150,000 IU every 3 months ( n = 353 ) or an identical placebo ( n = 333 ) . All participants were advised to increase dietary calcium intake . Falls data were collected 3-monthly . At baseline , 3 , 6 , and 9 months , muscle strength was measured by a h and held dynamometer and mobility by the Timed Up and Go ( TUG ) test . Serum 25 hydroxyvitamin D ( 25OHD ) was measured in a subgroup of 40 subjects . Mean age at baseline was 76.7 ± 4.1 years . The average serum 25OHD value at baseline was 65.8 ± 22.7 nmol/L. By 3 , 6 , and 9 months after supplementation , 25OHD levels of the vitamin D group were approximately 15 nmol/L higher than the placebo group . Calcium intake did not change significantly between baseline ( 864 ± 412 mg/day ) and 9 months ( 855 ± 357 mg/day ) . Faller rates in the two groups did not differ : vitamin D group , 102 of 353 ( 29 % ) ; placebo group , 89 of 333 ( 27 % ) . At 9 months , compared to placebo or baseline , muscle strength , and TUG were not altered by vitamin D. In conclusion , oral cholecalciferol 150,000 IU therapy administered 3-monthly had neither beneficial nor adverse effects on falls or physical function . These data together with previous findings confirm that intermittent large doses of vitamin D are ineffective or have a deleterious effect on falls . Thus despite adherence issues with daily vitamin D replacement , an intermittent , high-dose vitamin D regimen can not be supported as a strategy to reduce falls and fractures",
"OBJECTIVES To determine whether vitamin D supplementation reduces the risk of fracture or falls in elderly people in care home accommodation . DESIGN A r and omised controlled trial of cluster design . SETTING AND SUBJECTS 223 Residential units ( mainly identical 30-bedded units ) , within 118 homes for elderly people throughout Britain , with 3,717 participating residents ( 76 % women , average age 85 years ) . The units provided mainly or entirely residential care ( 35 % of residents ) , nursing care ( 42 % ) or care for elderly mentally infirm ( EMI ) residents ( 23 % ) . METHODS Participants were r and omly allocated by residential unit ( cluster design ) to a treated group offered ergocalciferol 2.5 mg every 3 months ( equivalent to a daily dose of 1,100 IU ) , or to a control group . Fractures were reported by staff and confirmed in hospital , and routinely collected data on reported falls were obtained . RESULTS After median follow-up of 10 months ( interquartile range 7 - 14 months ) , 64 ( 3.6 % ) of 1,762 vitamin D-treated residents and 51 ( 2.6 % ) of 1,955 controls had one or more non-vertebral fractures , and 24 ( 1.3 % ) and 20 ( 1.0 % ) , respectively , had a hip fracture . The proportion reporting at least one fall was 44 % in vitamin D-treated and 43 % in control residents . The differences between the vitamin D and control groups were not statistically significant . The incidence of all non-vertebral fractures in the care homes ( 3.2 % per year ) and of hip fractures ( 1.1 % per year ) was low , similar to rates in elderly people in sheltered accommodation , and the pre-treatment serum 25-hydroxy vitamin D concentration was high [ median 47 nmol/l , measured in a 1 % ( n = 18 ) sample ] . CONCLUSIONS We found no evidence that vitamin D prevents fractures or falls in elderly people in care home accommodation",
"OBJECTIVES To determine whether relative vitamin D deficiency during the winter months contributes to age-related bone loss and whether rates of change in hard- and soft-tissue mass vary during the year . DESIGN Double-blind , placebo-controlled , 1-year trial in 249 women in which equal numbers of women were r and omized to either placebo or 400 IU of vitamin D daily . All women received 377 mg/d of supplemental calcium largely as calcium citrate malate . PATIENTS Healthy , ambulatory postmenopausal women with usual intakes of vitamin D of 100 IU/d . MEASUREMENTS Duplicate spine and whole-body scans were done by dual energy x-ray absorptiometry at 6-month intervals that were timed to periods when 25-hydroxyvitamin D levels were highest and lowest . Period 1 was June-July to December-January and period 2 was December-January to the next June-July . Serum parathyroid hormone and plasma 25-hydroxyvitamin D levels were measured during periods 1 and 2 . MAIN RESULTS In the placebo group , spinal bone mineral density increased in period 1 , decreased in period 2 , and sustained no net change . Women treated with vitamin D had a similar spinal increase in period 1 ( 1.46 % compared with 1.40 % in placebo ) , less loss in period 2 ( -0.54 % compared with -1.22 % , CI for the difference , 0.05 % to 1.31 % , P = 0.032 ) and a significant overall benefit ( 0.85 % compared with 0.15 % , CI for the difference , 0.03 % to 1.37 % , P = 0.04 ) . In period 2 , 25-hydroxyvitamin D levels were lower and parathyroid hormone levels were higher in the placebo than in the vitamin D group . Whole-body lean and fat tissue and bone mineral density varied during the year but did not change overall . CONCLUSIONS At latitude 42 degrees , healthy postmenopausal women with vitamin D intakes of 100 IU daily can significantly reduce late wintertime bone loss and improve net bone density of the spine over one year by increasing their intake of vitamin D to 500 IU daily . A long-term benefit of preventing vitamin D insufficiency in the winter seems likely although it remains to be shown . Observed changes in bone as well as in fat and lean tissue appear to be related to season",
"OBJECTIVES To determine whether vitamin D supplementation can reduce the incidence of falls and fractures in older people in residential care who are not classically vitamin D deficient . DESIGN R and omized , placebo-controlled double-blind , trial of 2 years ' duration . SETTING Multicenter study in 60 hostels ( assisted living facilities ) and 89 nursing homes across Australia . PARTICIPANTS Six hundred twenty-five residents ( mean age 83.4 ) with serum 25-hydroxyvitamin D levels between 25 and 90 nmol/L. INTERVENTION Vitamin D supplementation ( ergocalciferol , initially 10,000 IU given once weekly and then 1,000 IU daily ) or placebo for 2 years . All subjects received 600 mg of elemental calcium daily as calcium carbonate . MEASUREMENTS Falls and fractures recorded prospect ively in study diaries by care staff . RESULTS The vitamin D and placebo groups had similar baseline characteristics . In intention-to-treat analysis , the incident rate ratio for falling was 0.73 ( 95 % confidence interval (CI)=0.57 - 0.95 ) . The odds ratio for ever falling was 0.82 ( 95 % CI=0.59 - 1.12 ) and for ever fracturing was 0.69 ( 95 % CI=0.40 - 1.18 ) . An a priori subgroup analysis of subjects who took at least half the prescribed capsules ( n=540 ) , demonstrated an incident rate ratio for falls of 0.63 ( 95 % CI=0.48 - 0.82 ) , an odds ratio ( OR ) for ever falling of 0.70 ( 95 % CI=0.50 - 0.99 ) , and an OR for ever fracturing of 0.68 ( 95 % CI=0.38 - 1.22 ) . CONCLUSION Older people in residential care can reduce their incidence of falls if they take a vitamin D supplement for 2 years even if they are not initially classically vitamin D deficient",
"Specific receptors for vitamin D have been identified in human muscle tissue . Cross-sectional studies show that elderly persons with higher vitamin D serum levels have increased muscle strength and a lower number of falls . We hypothesized that vitamin D and calcium supplementation would improve musculoskeletal function and decrease falls . In a double-blind r and omized controlled trial , we studied 122 elderly women ( mean age , 85.3 years ; range , 63 - 99 years ) in long-stay geriatric care . Participants received 1200 mg calcium plus 800 IU cholecalciferol ( Cal+D-group ; n = 62 ) or 1200 mg calcium ( Cal-group ; n = 60 ) per day over a 12-week treatment period . The number of falls per person ( 0 , 1 , 2 - 5 , 6 - 7 , > 7 falls ) was compared between the treatment groups . In an intention to treat analysis , a Poisson regression model was used to compare falls after controlling for age , number of falls in a 6-week pretreatment period , and baseline 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum concentrations . Among fallers in the treatment period , crude excessive fall rate ( treatment - pretreatment falls ) was compared between treatment groups . Change in musculoskeletal function ( summed score of knee flexor and extensor strength , grip strength , and the timed up&go test ) was measured as a secondary outcome . Among subjects in the Cal+D-group , there were significant increases in median serum 25-hydroxyvitamin D ( + 71 % ) and 1,25-dihydroxyvitamin D ( + 8 % ) . Before treatment , mean observed number of falls per person per week was 0.059 in the Cal+D-group and 0.056 in the Cal-group . In the 12-week treatment period , mean number of falls per person per week was 0.034 in the Cal+D-group and 0.076 in the Cal-group . After adjustment , Cal+D-treatment accounted for a 49 % reduction of falls ( 95 % CI , 14 - 71 % ; p crude average number of excessive falls was significantly higher in the Cal-group ( p = 0.045 ) . Musculoskeletal function improved significantly in the Cal+D-group ( p = 0.0094 ) . A single intervention with vitamin D plus calcium over a 3-month period reduced the risk of falling by 49 % compared with calcium alone . Over this short-term intervention , recurrent fallers seem to benefit most by the treatment . The impact of vitamin D on falls might be explained by the observed improvement in musculoskeletal function",
"Background . New and potent immunosuppressive regimens allow for reduced doses of corticosteroids after renal transplantation . The aims of our study were to investigate whether the use of low-dose corticosteroids is associated with a reduction in posttransplant bone loss and to assess the ability of cholecalciferol supplementation to further decrease bone loss in this setting . Methods . Ninety patients admitted for renal transplantation and scheduled to be treated per protocol with low doses of prednisolone were r and omized to receive either 400 mg daily oral calcium ( Ca group , n=44 ) or the same dose of calcium in association with a monthly dose of 25,000 IU of vitamin D3 ( CaVitD group , n=46 ) . Bone mineral density ( BMD ) was measured by dual energy absorptiometry at baseline and at 1 year . Results . The overall population experienced a moderate but significant −2.3±0.9 % loss of lumbar spine BMD ( P but no bone loss at the femoral neck and shaft during the first posttransplant year . Bone loss tended to be slightly higher in the CaVitD group , but the difference did not reach statistical significance . Patients in the CaVitD group had significantly higher 25(OH ) but not 1,25(OH)2 vitamin D levels . We observed a highly significant negative correlation between 25(OH ) vitamin D and intact parathyroid hormone ( iPTH ) serum levels . Conclusions . Kidney-transplant recipients receiving modern immunosuppressive regimens with low doses of corticosteroids experience only minimal loss of BMD during the first posttransplant year . Cholecalciferol supplementation did not prevent posttransplant bone loss but contributed to the normalization of iPTH levels after renal transplantation",
"Falls are a serious health problem in the aging population . Because low levels of vitamin D have been associated with increased fall rates , many trials have been performed with vitamin D ; two meta-analyses showed either a small effect or no effect of vitamin D on falls . We conducted a study of the effect of vitamin D on serum 25 hydroxyvitamin D ( 25OHD ) and data on falls was collected as a secondary outcome . In a 12-month double blind r and omized placebo trial , elderly women , mean age 66 years , were r and omized to one of seven daily oral doses of vitamin D or placebo . The main inclusion criterion for study was a baseline serum 25OHD history of falls was collected at baseline and fall events were collected every 3 months . Results showed that the effect of vitamin D on falls followed a U-shaped curve whether analyzed by dose or serum 25OHD levels . There was no decrease in falls on low vitamin D doses 400 , 800 IU , a significant decrease on medium doses 1600 , 2400,3200 IU ( p=0.020 ) and no decrease on high doses 4000 , 4800 IU compared to placebo ( p=0.55 ) . When compared to 12-month serum 25OHD quintiles , the faller rate was 60 % in the lowest quintile , fall rates were 68 % on low dose , 27 % on medium doses and 100 % on higher doses . Fall rates on high doses were increased compared to medium doses ( Odds Ratio 5.6.95 % CI : 2.1 - 14.8 ) . In summary , the maximum decrease in falls corresponds to a 12- month serum 25OHD of 32 - 38ng/ml ( 80 - 95nmol/L ) and faller rates increase as serum 25OHD exceed 40 - 45ng/ml ( 100 - 112.5nmol/L ) . The Tolerable upper limit ( TUL ) recently increased in 2010 from 2000 to 4000 IU/day may need to be reduced in elderly women especially in those with a fall history",
"Vitamin D deficiency is common in elderly persons , especially those with hip fracture [ 1 , 2 ] . It is caused by low exposure to sunshine , decreased synthesis of vitamin D3 in the aging skin , and a diet low in vitamin D [ 3 , 4 ] . The mean vitamin D intake in elderly persons in the Netherl and s is about 100 IU/d , half that of elderly persons in the United States [ 5 ] . Most of this vitamin D comes from margarine , which is the only vitamin D-supplemented food in the Netherl and s ( 3 IU/g ) . In vitamin D deficiency , the low serum concentration of 25-hydroxyvitamin D [ 25(OH)D ] leads to a low 1,25-dihydroxyvitamin D [ 1,25(OH)2D ] concentration and then to a higher serum parathyroid hormone concentration , especially in the winter [ 6 - 10 ] . Histologically , the increased parathyroid activity is associated with high bone turnover , leading to cortical bone loss and low density bone [ 5 , 11 ] , which may lead to hip fracture . We previously studied the effects of vitamin D supplementation in residents of a home for the elderly and residents of a nursing home [ 10 ] . Vitamin D3 , 400 IU/d , led to an adequate increase of the serum 25(OH)D concentration , to a small but significant increase of the serum 1,25(OH)2D concentration , and to a decrease of the serum concentration of intact parathyroid hormone . It was recently observed [ 12 , 13 ] that bone mineral density at the hip is positively related to serum 25(OH)D concentration in postmenopausal and elderly women . Therefore , it might be expected that vitamin D supplementation would increase bone mineral density in elderly persons deficient in vitamin D. In line with this expectation , it was shown that vitamin D supplementation prevented bone loss from the spine during the winter in postmenopausal women [ 14 ] . These results suggest that vitamin D supplementation may reduce the incidence of hip fractures , because bone strength shows a strong correlation with bone mineral density [ 15 ] . However , increasing bone mineral density through a therapeutic intervention does not necessarily lead to increased bone strength , as has been shown with sodium fluoride [ 16 ] . Bone structure and bone quality are also determinants of bone strength [ 17 ] , and falls are a risk factor for hip fractures [ 18 ] . Therefore , hip fracture should be the outcome criterion in studies on the effect of vitamin D supplementation . Intervention studies on the prevention of osteoporotic fractures necessitate large numbers of patients , because the outcome has an annual incidence of 0.5 % to 4 % in the elderly population [ 19 ] . We report the results of a large-scale , prospect i ve study on the effect of vitamin D supplementation on the incidence of hip and other osteoporotic fractures . Methods Participants The study included 2578 persons ( 1916 women and 662 men ) 70 years of age and older ( mean age SD , 80 6 years ; range , 70 to 97 years ) . Participants were recruited from general practitioners , from apartment houses for elderly persons , and from homes for elderly persons in Amsterdam and its vicinity . Persons recruited from practitioners were living independently ; those recruited from apartment houses and homes were receiving some care , but less than they would have received in a nursing home . Participants had to be reasonably healthy and able to give informed consent . Persons with a history of hip fracture or total hip arthroplasty , known hypercalcemia , sarcoidosis , or recent urolithiasis ( were not excluded . The spontaneous use of vitamin D supplements and multivitamins was discouraged , but the prescription practice s of the general practitioners were not altered . All vitamin use was carefully documented . The study was approved by the Ethical Review Board of the Vrije Universiteit Hospital , and all participants gave informed consent . Study Design After checking the inclusion and exclusion criteria and obtaining informed consent , the participants were r and omly assigned to receive either active treatment with vitamin D3 or placebo . The study was double-blind , and r and omization was done in blocks of 10 per general practice , apartment house , or home . R and omization lists were made using a computerized r and om-number generator . Lists in sealed envelopes were sent to the hospital pharmacy for assignment . Each participant took either one tablet per day that contained vitamin D3 , 400 IU , or one placebo tablet per day that was identical in appearance and taste to the vitamin tablet . After enrollment , the participants received the first container of tablets ( 210 tablets ) . The container was replaced every 6 months with a full container . All participants were also advised in writing to consume at least three servings of dairy products per day ( for example , 1 glass of milk , 1 cup of yogurt , and 1 slice of cheese ) to ensure a calcium intake of at least 800 to 1000 mg/d . The study was started in August 1988 . The last participant was enrolled in December 1990 , and all participants had stopped using study medication by December 1993 . The follow-up period had been planned to last no more than 3 years , but because the number of hip fractures during the study was lower than expected , a 6-month extension was planned . The study participants thus received medication for 3 to 3.5 years ; those who received it for 3.5 years were those who consented to the 6-month extension . Total follow-up was to a maximum of 4 years . Data collected at baseline included an outdoor activity score ( 1 equals going outdoors less than once a week ; 2 equals going outdoors 1 or 2 times per week ; and 3 equals going outdoors 3 times per week or more ) and a score for sunshine exposure ( when outside : 1 equals in the shade as much as possible ; 2 equals sometimes in sunshine ; 3 equals much exposure to sunshine ) . These scores show a positive relation with serum 25(OH)D concentration [ 3 ] . Mobility was estimated by a walking score that ranged from 1 ( unable to walk ) to 5 ( walks independently a fair distance on any surface ) [ 20 ] . The dietary calcium intake from dairy products was estimated in a subset of 348 women by using a question naire , as described previously [ 21 ] . The participants were evaluated annually with a question naire on hip fractures , other peripheral fractures , outdoor score , sunshine exposure score , use of vitamin supplements , and walking score . Each general practitioner or caretaker was asked to immediately report change of address , hip fracture , or death . Hip fracture and death were verified by the general practitioner . All participants were followed for the maximal period of 4 years if possible , even if they had stopped using the trial medication , had sustained a fracture , or had moved to another city . To investigate possible selection bias , 267 potential participants in a home for the elderly and its adjunct apartments ( all residents of the institution ) were studied for baseline characteristics , including age , sex , sunshine exposure score , outdoor score , walking score , and reasons for nonparticipation . Compliance was checked when the tablet containers were replaced ( every 6 months ) , by question naire ( every year ) , and by measurement of the serum 25(OH)D concentration . Serum 25(OH)D concentration was measured at baseline and after 1 year in 270 persons who participated in a sub study investigating the effect of vitamin D supplementation on bone mineral density and bone turnover variables . This sub study included a nonr and om sample of participants from several apartment houses and homes for the elderly and is described in detail elsewhere [ 21 ] . In the same sub study , dietary calcium intake from diary products was assessed . Serum 25(OH)D concentration was also estimated during the third year of the study in February and March in a r and om sample of 96 participants drawn from the remaining study population . These participants received a letter giving them an appointment within 10 days ; the blood sample s were drawn at home . Serum 25(OH)D concentration was measured by competitive protein binding assay after being purified by gradient high-pressure liquid chromatography . The intra- and interassay coefficients of variation were 5 % and 6 % , respectively [ 22 ] . Statistical Analysis Baseline data of the vitamin D group and the placebo group were compared using t-tests ( age , calcium intake ) , chi-square tests ( sex , residence ) , and Wilcoxon rank-sum tests ( scores ) . The serum 25(OH)D concentrations of both groups were compared using t-tests . Data on fractures and mortality were analyzed by survival analysis using log-rank tests , Cox proportional-hazards regression , and hazard rate ratios [ 23 ] . Hip fractures are presented using the Kaplan-Meier method . All participants were kept in the study as long as possible . The data were analyzed in two ways . The intention-to-treat analysis included all r and omly assigned participants for either the total follow-up period or until fracture , death , or loss to follow-up . The active treatment analysis included the participants as long as they stated that they were using the trial medication . Thus , the participants were included in the active treatment analysis until they stopped using the trial medication , regardless of whether a fracture occurred after they had stopped . Age , sex , and residence were added in both analyses as covariates to the Cox regression model . Because outdoor score , sunshine score , and walking score were interrelated ( correlation coefficients ranging from 0.21 to 0.59 ) and were likely to indicate general health or mobility , they were averaged over the years and added up to a sum score . For this purpose , the walking score was simplified ( 1 , 2 , or 3 equals 1 ; 4 equals 2 ; 5 equals 3 ) , because the lower walking scores applied to a few participants only . The result ing total score , ranging from 3 to 9 , was entered as a covariate in the model . The level of compliance ( weekly intake as reported on",
"The long term effects of hormone replacement therapy ( HRT ) and vitamin D3 ( Vit D ) on bone mineral density ( BMD ) were studied . A total of 464 nonosteoporotic early postmenopausal women from the Kuopio Osteoporosis Study ( n = 13100 ) were r and omized to four groups : 1 ) HRT ( sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate , 2 ) Vit D3 ( 300 and 100 IU/day during the fifth year ) , 3 ) HRT and Vit D combined , and 4 ) placebo . Lumbar ( L2-L4 ) and femoral neck BMD were determined by dual x-ray absorptiometry ( DXA ) at baseline and after 2.5 and 5 yr of treatment . Intention to treat analysis ( n = 464 ) showed that after 5 yr , lumbar BMD remained unchanged in the HRT and HRT plus Vit D groups [ + 0.2 % ( P = 0.658 ) and + 0.9 % ( P = 0.117 ) , respectively ] , whereas lumbar BMD decreased by 4.6 % in the Vit D group and by 4.5 % in the placebo group ( P loss of femoral neck BMD was less in the HRT ( -1.4 % ; P = 0.005 ) and HRT plus Vit D ( -1.3 % ; P = 0.003 ) groups than in the Vit D and placebo groups ( -4.3 % ; P 370 women who complied with the 5-yr treatment , the effect was more pronounced : lumbar BMD had increased by 1.5 % in the HRT ( P = 0.009 ) and by 1.8 % in the HRT plus Vit D group ( P = 0.005 ) , with a plateau after 2.5 yr , whereas lumbar BMD had decreased in both the Vit D and placebo groups ( 4.6 % and 4.7 % ; P Femoral neck BMD decreased again less in the HRT ( -0.4 % ) and HRT plus Vit D ( -0.6 % ) groups than in the Vit D and placebo groups ( -4.4 % in both ) . This study confirms the positive long term effect of HRT on BMD also seen in intention to treat analysis . The data suggest that low dose vitamin D3 supplementation does not prevent bone loss in healthy , nonosteoporotic , early postmenopausal women , and it confers no benefit additional to that of HRT alone ",
"BACKGROUND Vitamin D deficiency is common in older people and may increase risk of falls and fracture . Hospital in patients are at particular risk of falling . Previous studies suggest that vitamin D improves neuromuscular function and reduces falls . OBJECTIVE To determine whether routine supplementation with vitamin D plus calcium reduces numbers of fallers and falls in a cohort of hospital admissions while they are in patients . DESIGN R and omised , double-blind , controlled study . PARTICIPANTS two hundred and five acute admissions > 65 years to a geriatric medical unit . METHODS Patients were r and omised to intervention of daily vitamin D 800 iu plus calcium 1,200 mg or control group of daily calcium 1,200 mg , until discharge or death . RESULTS Baseline characteristics were similar in both groups with a median age 84 years and a median length of stay = 30 days ( IQR 14.75 - 71.00 ) . In a pre-selected sub-group ( 54/205 participants ) , median admission vitamin D level = 22.00 nmol/l ( IQR 15.00 - 30.50 ) . This did not significantly increase in the treatment versus control group . Median study drug adherence = 88 % , with no significant difference between study groups ( Mann-Whitney : P = 0.711 ) . Although there were fewer fallers in the vitamin D cohort , this did not reach statistical significance ( vitamin D : calcium = 36:45 fallers ; RR 0.82 ( CI 0.59 - 1.16 ) . Neither the mean number of falls ( vitamin D : calcium = 1.040:1.155 ; Mann-Whitney P = 0.435 ) or time to first fall ( Log-rank test P = 0.377 ) differed between groups . CONCLUSIONS In a population of geriatric hospital in patients , vitamin D did not reduce the number of fallers . Routine supplementation can not be recommended to reduce falls in this group",
"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",
"OBJECTIVES We investigated the incidence of new non-vertebral fractures during HRT or low-dose vitamin ( Vit ) D3 supplementation in a 5-year prospect i ve trial . METHODS A total of 464 early postmenopausal women , ( a subgroup of the Kuopio Osteoporosis Study , n = 13,100 ) were r and omized to four groups : ( 1 ) HRT , a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate ; ( 2 ) Vit D ( 300 IU/day and 100 IU/day during the fifth years ) ; ( 3 ) HRT + Vit D ; and ( 4 ) placebo . Lumbar ( L2 - 4 ) and femoral neck bone mineral densities ( BMD ) were determined by dual X-ray absorptiometry ( DXA ) at baseline , after 2.5 and 5 years of treatment . All new symptomatic non-vertebral , radiographically defined fractures were recorded . RESULTS Altogether , 368 women ( 79 % ) completed the 5 year treatment . In all , 32 women had 39 non-vertebral fractures during a mean of 4.3 year follow-up ( HRT 4 , Vit D 10 , HRT + Vit D 8 and placebo 17 ) . The reduction in the incidence of new non-vertebral fractures was significant in women with HRT alone ( P = 0.032 ) when adjusted by baseline BMD and previous fractures ; observed also with the intention-to-treat principle ( P = 0.048 ) . When the HRT groups were pooled , HRT showed a significantly lower incidence of new non-vertebral fractures ( P = 0.042 ) than women receiving placebo and also after adjusting as above ( P = 0.016 ) ; both in valid-case and in the intention-to-treat analysis . In the Vit D group , the fracture incidence was non-significantly decreased ( P = 0.229 ) in comparison with the placebo group . The estimated risk of new non-vertebral fractures among women treated with HRT alone was 0.29 ( 95 % CI , 0.10 - 0.90 ) and with Vit D 0.47 ( 95 % CI , 0.20 - 1.14 ) and with HRT + Vit D 0.44 ( 95 % CI , 0.17 - 1.15 ) , in comparison with the placebo group ( adjusted by femoral BMD and previous fractures ) . CONCLUSIONS This study is the first prospect i ve trial confirming the beneficial effect of HRT on prevention of peripheral fractures in non-osteoporotic postmenopausal women . The effect of low-dose Vit D remains to be proved",
"OBJECTIVES To determine the effectiveness of vitamin D supplementation in preventing decline in physical function in older men . DESIGN R and omized , double-blind , placebo-controlled clinical trial . SETTING Single-center study conducted at a Veterans Affairs Healthcare System . PARTICIPANTS Sedentary men aged 65 to 90 ( mean 72.4 ± 6.8 ) with baseline 25-hydroxyvitamin D ( 25(OH)D levels of less than 30 ng/mL and Short Physical Performance Battery ( SPPB ) test scores of 9 or less ( N = 130 ) . INTERVENTION Daily capsule containing cholecalciferol 4,000 IU daily or placebo for 9 months . MEASUREMENTS Main outcomes were SPPB score and gait speed . RESULTS After the intervention , serum 25(OH)D increased from 23.1 ± 5.0 ng/mL to 46.2 ± 12.7 ng/mL in the cholecalciferol group and from 22.5 ± 5.3 ng/mL to 24.0 ± 7.2 ng/mL in the placebo group . At study end , improvements in SPPB score and gait speed were not significantly greater in men receiving cholecalciferol than in those receiving placebo . No differences were found in adverse events or numbers of falls . CONCLUSION Daily cholecalciferol 4,000 IU for 9 months result ed in significant increases in 25(OH)D concentrations , but achieving these higher levels did not result in improvements in SPPB score or gait speed . These data do not support prescribing vitamin D supplements to older sedentary men to prevent physical function decline",
"Summary Vitamin D may affect skeletal muscle function . In a double-blind , r and omised , placebo-controlled trial , we found that vitamin D3 supplementation ( 400 or 1,000 I.U. vs. placebo daily for 1 year with bimonthly study visits ) does not improve grip strength or reduce falls . Introduction This study aim ed to test the supplementation effects of vitamin D3 on physical function and examine associations between overweight/obesity and the biochemical response to treatment . Methods In a parallel group double-blind RCT , healthy postmenopausal women from North East Scotl and ( latitude—57 ° N ) aged 60–70 years ( body mass index ( BMI ) , 18–45 kg/m2 ) were assigned ( computer r and omisation ) to daily vitamin D3 ( 400 I.U. ( n = 102)/1,000 I.U. ( n = 101 ) ) or matching placebo ( n = 102 ) ( 97 , 96 and 100 participants analysed for outcomes , respectively ) from identical coded containers for 1 year . Grip strength ( primary outcome ) , falls , diet , physical activity and ultraviolet B radiation exposure were measured bimonthly , as were serum 25(OH)D , adjusted calcium ( ACa ) and phosphate . Fat/lean mass ( dual energy X-ray absorptiometry ) , anthropometry , 1,25-dihydroxyvitamin D and parathyroid hormone were measured at baseline and 12 months . Participants and research ers were blinded throughout intervention and analysis . Results Treatment had no effect on grip strength ( mean change (SD)/year = −0.5 ( 2.5 ) , −0.9 ( 2.7 ) and −0.4 ( 3.3 ) kg force for 400/1,000 I.U. vitamin D3 and placebo groups , respectively ( P = .10 , ANOVA ) ) or falls ( P = .65 , chi-squared test ) . Biochemical responses were similar across BMI categories ( in serum ACa in overweight compared to non-overweight participants ( P = .01 , ANOVA ; 1,000 I.U. group ) . In the placebo group , 25(OH)D peak concentration change ( winter to summer ) was negatively associated with weight ( r = −.268 ) , BMI ( r = −.198 ) , total ( r = −.278 ) and trunk fat mass ( r = −.251 ) , with total and trunk fat mass predictive of winter to summer 25(OH)D change ( P = .01/.004 respectively , linear regression ) . Conclusion We found no evidence of an improvement in physical function following vitamin D3 supplementation for 1 year",
"BACKGROUND We conducted a r and omized , placebo-controlled , double-blind trial to test the hypothesis that vitamin D(3 ) supplementation would prevent bone loss in calcium-replete , African American postmenopausal women . METHODS Two hundred eight healthy black postmenopausal women , 50 to 75 years of age , were assigned to receive either placebo or 20 microg/d ( 800 IU ) of vitamin D(3 ) . Calcium supplements were provided to ensure a total calcium intake of 1200 to 1500 mg/d . After 2 years , the vitamin D(3 ) dose was increased to 50 microg/d ( 2000 IU ) in the active group , and the study continued for an additional year . Bone mineral density ( BMD ) was measured every 6 months . Markers of bone turnover , vitamin D metabolites , and parathyroid hormone ( PTH ) levels were measured in serum . RESULTS There were no significant differences in BMD between the active and control groups throughout the study . There was also no relationship between serum 25-hydroxyvitamin D levels attained and rates of bone loss . There was an increase in BMD of the total body , hip , and radius at 1 year in both groups . Over the 3 years , BMD declined at these sites by 0.26 % to 0.55 % per year . The BMD of the lumbar spine increased slightly in the placebo and active groups . There were no persistent changes in serum PTH levels or the markers of bone turnover , although there was a transient decline in PTH in both groups at 3 months . No significant adverse events were attributed to vitamin D supplementation . CONCLUSIONS There was no observed effect of vitamin D(3 ) supplementation on bone loss or bone turnover markers in calcium-replete , postmenopausal African American women . Further studies are needed to determine if these findings are applicable to women of other ethnic groups",
"Summary The rationale of this study was to determine the effect of high-dose vitamin D3 supplementation on bone mineral density ( BMD ) . Prediabetic males given vitamin D had significantly less reduction in BMD at the femoral neck compared to the controls . The clinical implication s of our findings require further investigation . Introduction Type 2 diabetes mellitus is associated with increased fracture risk , and recent studies show crosstalk between bone and glucose metabolism . Few studies have investigated the effect of vitamin D supplementation on the bone without additional calcium . In the present study , we aim ed to determine whether a high dose of vitamin D3 could improve bone mass density ( BMD ) in prediabetic subjects . Methods The current study was conducted as a secondary research on a previously performed trial , in which 511 subjects with prediabetes were r and omized to vitamin D3 ( 20,000 IU per week ) versus placebo for 5 years . BMD was measured using dual-energy X-ray absorptiometry ( DEXA ) . Results Two hundred and fifty-six subjects were r and omized to vitamin D and 255 to placebo . Mean baseline serum 25-hydroxyvitamin D ( 25(OH)D ) level was 60 nmol/L. Two hundred and two and 214 in the vitamin D and placebo groups , respectively , completed BMD measurements , whereas one in each group was excluded due to use of bisphosphonates . Males given vitamin D had significantly less reduction in BMD at the femoral neck measurement site compared to the controls ( 0.000 versus − 0.010 g/cm2 , p = 0.008 ) . No significant differences between intervention groups were seen at the total hip measurement site , regarding both males and females . Conclusions Vitamin D3 supplementation alone may be beneficial in males with prediabetes , but confirmatory studies are needed",
"Objective : To evaluate the effect of isolated vitamin D supplementation ( VITD ) on the rate of falls and postural balance in postmenopausal women fallers . Methods : In this double-blind , placebo-controlled trial , 160 Brazilian younger postmenopausal women were r and omized into two groups : VITD group , vitamin D3 supplementation 1,000 IU/day/orally ( n = 80 ) and placebo group ( n = 80 ) . Women with amenorrhea at least 12 months , age 50 to 65 years , and a history of falls ( previous 12 months ) were included . Those with neurological or musculoskeletal disorders , vestibulopathies , drugs use that could affect balance and osteoporosis were excluded . The intervention time was 9 months . Postural balance was assessed by stabilometry ( computerized force platform ) and investigation on the occurrence/recurrence of falls was performed by interviews . The plasma concentration of 25-hydroxyvitamin D [ 25(OH)D ] was measured by high-performance liquid chromatography . Statistical analysis was achieved by intention-to-treat , using analysis of variance , Student 's t test , Tukey test , chi-square , and logistic regression . Results : After 9 months , mean values of 25(OH)D increased from 15.0 ± 7.5 ng/mL to 27.5 ± 10.4 ng/mL ( + 45.4 % ) in the VITD group , and decreased from 16.9 ± 6.7 ng/mL to 13.8 ± 6.0 ng/mL ( −18.5 % ) in the placebo group ( P ) . The occurrence of falls was higher in the placebo group ( + 46.3 % ) with an adjusted risk of 1.95 ( 95 % confidence interval [ CI ] 1.23 - 3.08 ) times more likely to fall and 2.80 ( 95 % CI 1.43 - 5.50 ) times higher for recurrent falls compared to the VITD group ( P There was reduction in body sway by stabilometry , with lower amplitude of antero-posterior ( −35.5 % ) and latero-lateral ( −37.0 % ) oscillation , only in the VITD group ( P Brazilian postmenopausal women fallers , isolated vitamin D supplementation for 9 months result ed in a lower incidence of falls and improvement in postural balance ",
"Summary Sunlight deprivation results in vitamin D deficiency but serum vitamin D levels can be maintained above 50nmol/L when supplemented with 50,000IU at least every alternate month . Introduction Anta rct ic expeditioners are exposed to prolonged sunlight deprivation result ing in vitamin D deficiency . We hypothesised that monthly dosing of 50,000 IU vitamin D ( ~1,600 IU daily ) will increase serum 25-hydroxyvitamin D ( 25(OH)D ) , suppress parathyroid hormone ( PTH ) and improve bone mineral density ( BMD ) , 50,000 IU alternate months ( ~800 IU daily ) will maintain these measures , while a single 50,000 IU dose pre-departure ( ~1,00 IU daily ) will not be protective . Methods This was a r and omised double-blind study involving 110 healthy adults : 91 males , mean age 41 years ( range 24–65 years ) working in Anta rct ica for up to 12 months , who we administered 50,000 IU vitamin D3 monthly , alternate months or a single dose pre-departure . Serum 25(OH)D , PTH , osteocalcin , CTx and calcium were assessed at baseline , mid- and end of expedition . Proximal femur and lumbar spine BMD were assessed pre- and post-expedition . Results Baseline 25(OH)D was 59 ± 14 nmol/L. By mid-expedition , 25(OH)D increased by 7 nmol/L in those supplemented monthly ( p , 25(OH)D decreased by 8 nmol/L ( p PTH increased by 27 % ( p increased by ~22 % in all groups but BMD remained unchanged . If serum 25(OH)D was > 50 nmol/L at baseline , 25(OH)D was maintained above this level with all regimens . If 25(OH)D was 50 nmol/L , the single pre-departure dose was ineffective . Conclusion During sunlight deprivation of up to 12 months , serum 25(OH)D levels can be maintained above 50 nmol/L when expeditioners are provided with 50,000 I U at least every alternate month",
"BACKGROUND Severe vitamin D deficiency causes osteomalacia , yet trials of vitamin D supplementation in the community have not on average demonstrated benefit to bone mineral density ( BMD ) or fracture risk in adults . OBJECTIVE To determine whether monthly high-dose vitamin D supplementation influences BMD in the general population and in those with low 25-hydroxyvitamin D levels . METHODS Two-year sub study of a trial in older community-resident adults . A total of 452 participants were r and omized to receive monthly doses of vitamin D3 100 000 IU , or placebo . The primary end-point was change in lumbar spine BMD . Exploratory analyses to identify thresholds of baseline 25-hydroxyvitamin D for vitamin D effects on BMD were prespecified . RESULTS Intention-to-treat analyses showed no significant treatment effect in the lumbar spine ( between-groups difference 0.0071 g cm-2 , 95%CI : -0.0012 , 0.0154 ) or total body but BMD loss at both hip sites was significantly attenuated by ~1/2 % over 2 years . There was a significant interaction between baseline 25-hydroxyvitamin D and treatment effect ( P = 0.04 ) . With baseline 25-hydroxyvitamin D ≤ 30 nmol L-1 ( n = 46 ) , there were between-groups BMD changes at the spine and femoral sites of ~2 % , significant in the spine and femoral neck , but there was no effect on total body BMD . When baseline 25-hydroxyvitamin D was > 30 nmol L-1 , differences were ~1/2 % and significant only at the total hip . CONCLUSIONS This sub study finds no clinical ly important benefit to BMD from untargeted vitamin D supplementation of older , community-dwelling adults . Exploratory analyses suggest meaningful benefit in those with baseline 25-hydroxyvitamin D ≤ 30 nmol L-1 . This represents a significant step towards a trial-based definition of vitamin D deficiency for bone health in older adults ",
"IMPORTANCE Experts debate optimal 25-hydroxyvitamin D ( 25[OH]D ) levels for musculoskeletal health . OBJECTIVE To compare the effects of placebo , low-dose cholecalciferol , and high-dose cholecalciferol on 1-year changes in total fractional calcium absorption , bone mineral density , Timed Up and Go and five sit-to-st and tests , and muscle mass in postmenopausal women with vitamin D insufficiency . DESIGN , SETTING , AND PARTICIPANTS This r and omized , double-blind , placebo-controlled clinical trial was conducted at a single center in Madison , Wisconsin , from May 1 , 2010 , through July 31 , 2013 , and the final visit was completed on August 8 , 2014 . A total of 230 postmenopausal women 75 years or younger with baseline 25(OH)D levels of 14 through 27 ng/mL and no osteoporosis were studied . INTERVENTIONS Three arms included daily white and twice monthly yellow placebo ( n=76 ) , daily 800 IU vitamin D3 and twice monthly yellow placebo ( n=75 ) , and daily white placebo and twice monthly 50,000 IU vitamin D3 ( n=79 ) . The high-dose vitamin D regimen achieved and maintained 25(OH)D levels≥30 ng/mL. MAIN OUTCOMES AND MEASURES Outcome measures were 1-year change in total fractional calcium absorption using 2 stable isotopes , bone mineral density and muscle mass using dual energy x-ray absorptiometry , Timed Up and Go and five sit-to-st and tests , functional status ( Health Assessment Question naire ) , and physical activity ( Physical Activity Scale for the Elderly ) , with Benjamini-Hochberg correction of P values to control for the false discovery rate . RESULTS After baseline absorption was controlled for , calcium absorption increased 1 % ( 10 mg/d ) in the high-dose arm but decreased 2 % in the low-dose arm ( P = .005 vs high-dose arm ) and 1.3 % in the placebo arm ( P = .03 vs high-dose arm ) . We found no between-arm changes in spine , mean total-hip , mean femoral neck , or total-body bone mineral density , trabecular bone score , muscle mass , and Timed Up and Go or five sit-to-st and test scores . Likewise , we found no between-arm differences for numbers of falls , number of fallers , physical activity , or functional status . CONCLUSIONS AND RELEVANCE High-dose cholecalciferol therapy increased calcium absorption , but the effect was small and did not translate into beneficial effects on bone mineral density , muscle function , muscle mass , or falls . We found no data to support experts ' recommendations to maintain serum 25(OH)D levels of 30 ng/mL or higher in postmenopausal women . Instead , we found that low- and high-dose cholecalciferol were equivalent to placebo in their effects on bone and muscle outcomes in this cohort of postmenopausal women with 25(OH)D levels less than 30 ng/mL. TRIAL REGISTRATION clinical trials.gov Identifier : NCT00933244",
"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",
"R and omized controlled trials have shown that a combination of vitamin D and calcium can prevent fragility fractures in the elderly . Whether this effect is attributed to the combination of vitamin D and calcium or to one of these nutrients alone is not known . We studied if an intervention with 10 microg of vitamin D3 per day could prevent hip fracture and other osteoporotic fractures in a double-blinded r and omized controlled trial . Residents from 51 nursing homes were allocated r and omly to receive 5 ml of ordinary cod liver oil ( n = 569 ) or 5 ml of cod liver oil where vitamin D was removed ( n = 575 ) . During the study period of 2 years , fractures and deaths were registered , and the principal analysis was performed on the intention-to-treat basis . Biochemical markers were measured at baseline and after 1 year in a sub sample . Forty-seven persons in the control group and 50 persons in the vitamin D group suffered a hip fracture . The corresponding figures for all nonvertebral fractures were 76 persons ( control group ) and 69 persons ( vitamin D group ) . There was no difference in the incidence of hip fracture ( p = 0.66 , log-rank test ) , or in the incidence of all nonvertebral fractures ( p = 0.60 , log-rank test ) in the vitamin D group compared with the control group . Compared with the control group , persons in the vitamin D group increased their serum 25-hydroxyvitamin D concentration with 22 nmol/liter ( p = 0.001 ) . In conclusion , we found that an intervention with 10 microg of vitamin D3 alone produced no fracture-preventing effect in a nursing home population of frail elderly people",
"BACKGROUND survivors of hip fracture are at 5- to 10-fold risk of a second hip fracture . There is little consensus about secondary prevention . Many are given calcium and vitamin D , but the evidence supporting this is circumstantial . OBJECTIVE to compare the effects of different calcium and vitamin D supplementation regimens on bone biochemical markers , bone mineral density and rate of falls in elderly women post-hip fracture . DESIGN r and omised controlled trial . SETTING orthogeriatric rehabilitation ward . METHODS 150 previously independent elderly women , recruited following surgery for hip fracture , were assigned to receive a single injection of 300,000 units of vitamin D(2 ) , injected vitamin D(2 ) plus 1 g/day oral calcium , 800 units/day oral vitamin D(3 ) plus 1 g/day calcium , or no treatment . Follow-up was one year , with measurement of 25-hydroxyvitamin D , parathyroid hormone , bone mineral density , and falls . RESULTS mean 25-hydroxyvitamin D increased and mean parathyroid hormone was suppressed in all the actively treated groups , more so in the group receiving combined oral vitamin D and calcium . Twenty per cent of participants injected with vitamin D were deficient in 25-hydroxyvitamin D a year later . Bone mineral density showed small but statistically significant differences of up to 4.6 % between actively treated groups and placebo . Relative risk of falling in the groups supplemented with vitamin D was 0.48 ( 95 % CI 0.26 - 0.90 ) compared with controls . CONCLUSION Vitamin D supplementation , either orally or with injected vitamin D , suppresses parathyroid hormone , increases bone mineral density and reduces falls . Effects may be more marked with calcium co-supplementation . The 300,000 units of injected vitamin D may not last a whole year",
"Background In r and omized trials there may be no overriding reason whether or not to have a placebo control . Purpose We assessed the effects of an open trial design ( no placebo and people know what tablets they are given ) compared with a blinded , placebo-controlled design on recruitment , compliance and retention within a r and omized trial of secondary osteoporotic fracture prevention . Methods We undertook a r and omized controlled comparison nested within a placebo-controlled trial of nutritional supplementation amongst people aged 70 years or over who had previously sustained a fracture , recruited in a UK teaching hospital . R and omization was 2 : 1 in favour of the blinded , placebo-controlled trial design . Results From 180 eligible participants r and omized to receive information based on the open trial design , 134 ( 74.4 % ) consented to take part , compared with 233 ( 65.1 % ) of 358 people r and omized to the blinded , placebo-controlled design ( difference 9.4 % , 95 % confidence interval 1.3–17.4 % ) . Reluctance to take a placebo and the desire to know tablet allocation were reasons given for not taking part in the blinded , placebo-controlled design . There was no significant difference in tablet compliance . Open trial participants were more likely to remain in the trial for one year ( difference 13.9 % , 95 % confidence interval 3.1–24.6 % ) , mainly reflecting the high retention of the open trial no tablet group compared to the open trial tablet group ( difference 23.6 % , 95 % confidence interval 11.9–35.2 % ) . The odds ratio for reporting an adverse event in the open trial compared to the blinded , placebo-controlled design was 0.64 ( 95 % confidence interval 0.28–1.49 ) , and for reporting a fracture was 0.81 ( 0.36–1.85 ) . Conclusions We conclude that using an open trial design may enhance participant recruitment and retention and thus improve generalizability and statistical power , but withdrawal rates may differ between the study allocations and may threaten the internal validity of the trial",
"BACKGROUND Elderly people who have a fracture are at high risk of another . Vitamin D and calcium supplements are often recommended for fracture prevention . We aim ed to assess whether vitamin D3 and calcium , either alone or in combination , were effective in prevention of secondary fractures . METHODS In a factorial- design trial , 5292 people aged 70 years or older ( 4481 [ 85 % ] of whom were women ) who were mobile before developing a low-trauma fracture were r and omly assigned 800 IU daily oral vitamin D3 , 1000 mg calcium , oral vitamin D3 ( 800 IU per day ) combined with calcium ( 1000 mg per day ) , or placebo . Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months . Analysis was by intention-to-treat and the primary outcome was new low-energy fractures . FINDINGS 698 ( 13 % ) of 5292 participants had a new low-trauma fracture , 183 ( 26 % ) of which were of the hip . The incidence of new , low-trauma fractures did not differ significantly between participants allocated calcium and those who were not ( 331 [ 12.6 % ] of 2617 vs 367 [ 13.7 % ] of 2675 ; hazard ratio ( HR ) 0.94 [ 95 % CI 0.81 - 1.09 ] ) ; between participants allocated vitamin D3 and those who were not ( 353 [ 13.3 % ] of 2649 vs 345 [ 13.1 % ] of 2643 ; 1.02 [ 0.88 - 1.19 ] ) ; or between those allocated combination treatment and those assigned placebo ( 165 [ 12.6 % ] of 1306 vs 179 [ 13.4 % ] of 1332 ; HR for interaction term 1.01 [ 0.75 - 1.36 ] ) . The groups did not differ in the incidence of all-new fractures , fractures confirmed by radiography , hip fractures , death , number of falls , or quality of life . By 24 months , 2886 ( 54.5 % ) of 5292 were still taking tablets , 451 ( 8.5 % ) had died , 58 ( 1.1 % ) had withdrawn , and 1897 ( 35.8 % ) had stopped taking tablets but were still providing data for at least the main outcomes . Compliance with tablets containing calcium was significantly lower ( difference : 9.4 % [ 95 % CI 6.6 - 12.2 ] ) , partly because of gastrointestinal symptoms . However , potentially serious adverse events were rare and did not differ between groups . INTERPRETATION The findings do not support routine oral supplementation with calcium and vitamin D3 , either alone or in combination , for the prevention of further fractures in previously mobile elderly people",
"BACKGROUND A suboptimal vitamin D and calcium status has been associated with higher risk of type 2 diabetes in observational studies , but evidence from trials is lacking . OBJECTIVE We determined whether vitamin D supplementation , with or without calcium , improved glucose homeostasis in adults at high risk of diabetes . DESIGN Ninety-two adults were r and omly assigned in a 2-by-2 factorial- design , double-masked , placebo-controlled trial to receive either cholecalciferol ( 2000 IU once daily ) or calcium carbonate ( 400 mg twice daily ) for 16 wk . The primary outcome was the change in pancreatic β cell function as measured by the disposition index after an intravenous-glucose-tolerance test . Other outcomes were acute insulin response , insulin sensitivity , and measures of glycemia . RESULTS Participants had a mean age of 57 y , a body mass index ( BMI ; in kg/m(2 ) ) of 32 , and glycated hemoglobin ( Hb A(1c ) ) of 5.9 % . There was no significant vitamin D × calcium interaction on any outcomes . The disposition index increased in the vitamin D group and decreased in the no-vitamin D group ( adjusted mean change ± SE : 300 ± 130 compared with -126 ± 127 , respectively ; P = 0.011 ) , which was explained by an improvement in insulin secretion ( 62 ± 39 compared with -36 ± 37 mU · L(-1 ) · min , respectively ; P = 0.046 ) . Hb A(1c ) increased less , but nonsignificantly , in the vitamin D group than in the no-vitamin D group ( 0.06 ± 0.03 % compared with 0.14 ± 0.03 % , respectively ; P = 0.081 ) . There was no significant difference in any outcomes with calcium compared with no calcium . CONCLUSION In adults at risk of type 2 diabetes , short-term supplementation with cholecalciferol improved β cell function and had a marginal effect on attenuating the rise in Hb A(1c ) . This trial was registered at clinical trials.gov as NCT00436475",
"BACKGROUND Epidemiologic and pre clinical data suggest that higher intake and serum levels of vitamin D and higher intake of calcium reduce the risk of colorectal neoplasia . To further study the chemopreventive potential of these nutrients , we conducted a r and omized , double-blind , placebo-controlled trial of supplementation with vitamin D , calcium , or both for the prevention of colorectal adenomas . METHODS We recruited patients with recently diagnosed adenomas and no known colorectal polyps remaining after complete colonoscopy . We r and omly assigned 2259 participants to receive daily vitamin D3 ( 1000 IU ) , calcium as carbonate ( 1200 mg ) , both , or neither in a partial 2 × 2 factorial design . Women could elect to receive calcium plus r and om assignment to vitamin D or placebo . Follow-up colonoscopy was anticipated to be performed 3 or 5 years after the baseline examinations , according to the endoscopist 's recommendation . The primary end point was adenomas diagnosed in the interval from r and omization through the anticipated surveillance colonoscopy . RESULTS Participants who were r and omly assigned to receive vitamin D had a mean net increase in serum 25-hydroxyvitamin D levels of 7.83 ng per milliliter , relative to participants given placebo . Overall , 43 % of participants had one or more adenomas diagnosed during follow-up . The adjusted risk ratios for recurrent adenomas were 0.99 ( 95 % confidence interval [ CI ] , 0.89 to 1.09 ) with vitamin D versus no vitamin D , 0.95 ( 95 % CI , 0.85 to 1.06 ) with calcium versus no calcium , and 0.93 ( 95 % CI , 0.80 to 1.08 ) with both agents versus neither agent . The findings for advanced adenomas were similar . There were few serious adverse events . CONCLUSIONS Daily supplementation with vitamin D3 ( 1000 IU ) , calcium ( 1200 mg ) , or both after removal of colorectal adenomas did not significantly reduce the risk of recurrent colorectal adenomas over a period of 3 to 5 years . ( Funded by the National Cancer Institute ; Clinical Trials.gov number , NCT00153816 . )",
"IMPORTANCE While vitamin D supplementation and exercise are recommended for prevention of falls for older people , results regarding these 2 factors are contradictory . OBJECTIVE To determine the effectiveness of targeted exercise training and vitamin D supplementation in reducing falls and injurious falls among older women . DESIGN , SETTING , AND PARTICIPANTS A 2-year r and omized , double-blind , placebo-controlled vitamin D and open exercise trial conducted between April 2010 and March 2013 in Tampere , Finl and . Participants were 409 home-dwelling women 70 to 80 years old . The main inclusion criteria were at least 1 fall during the previous year , no use of vitamin D supplements , and no contraindication to exercise . INTERVENTIONS Four study groups , including placebo without exercise , vitamin D ( 800 IU/d ) without exercise , placebo and exercise , and vitamin D ( 800 IU/d ) and exercise . MAIN OUTCOMES AND MEASURES The primary outcome was monthly reported falls . Injurious falls and the number of fallers and injured fallers were reported as secondary outcomes . In addition , bone density , physical functioning ( muscle strength , balance , and mobility ) , and vitamin D metabolism were assessed . RESULTS Intent-to-treat analyses showed that neither vitamin D nor exercise reduced falls . Fall rates per 100 person-years were 118.2 , 132.1 , 120.7 , and 113.1 in the placebo without exercise , vitamin D without exercise , placebo and exercise , and vitamin D and exercise study groups , respectively ; however , injurious fall rates were 13.2 , 12.9 , 6.5 , and 5.0 , respectively . Hazard ratios for injured fallers were significantly lower among exercisers with vitamin D ( 0.38 ; 95 % CI , 0.17 - 0.83 ) and without vitamin D ( 0.47 ; 95 % CI , 0.23 - 0.99 ) . Vitamin D maintained femoral neck bone mineral density and increased tibial trabecular density slightly . However , only exercise improved muscle strength and balance . Vitamin D did not enhance exercise effects on physical functioning . CONCLUSIONS AND RELEVANCE The rate of injurious falls and injured fallers more than halved with strength and balance training in home-dwelling older women , while neither exercise nor vitamin D affected the rate of falls . Exercise improved physical functioning . Future research is needed to determine the role of vitamin D in the enhancement of strength , balance , and mobility . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00986466",
"Few year-long vitamin D supplementation trials exist that match seasonal changes . The aim of this study was to determine whether daily oral vitamin D3 at 400 IU or 1000 IU compared with placebo affects annual bone mineral density ( BMD ) change in postmenopausal women in a 1-year double-blind placebo controlled trial in Scotl and . White women aged 60 to 70 years ( n = 305 ) were r and omized to one of two doses of vitamin D or placebo . All participants started simultaneously in January/February 2009 , attending visits at bimonthly intervals with 265 ( 87 % ) women attending the final visit and an additional visit 1 month after treatment cessation . BMD ( Lunar iDXA ) and 1,25-dihydroxyvitamin D[1,25(OH)2 D ] , N-terminal propeptide of type 1 collagen [ P1NP ] , C-terminal telopeptide of type I collagen [ CTX ] , and fibroblast growth factor-23 [ FGF23 ] were measured by immunoassay at the start and end of treatment . Circulating PTH , serum Ca , and total 25-hydroxyvitamin D [ 25(OH)D ] ( latter by t and em mass spectrometry ) were measured at each visit . Mean BMD loss at the hip was significantly less for the 1000 IU vitamin D group ( 0.05 % ± 1.46 % ) compared with the 400 IU vitamin D or placebo groups ( 0.57 % ± 1.33 % and 0.60 % ± 1.67 % , respectively ) ( p 0.05 ) . Mean ( ± SD ) baseline 25(OH)D was 33.8 ± 14.6 nmol/L ; comparative 25(OH)D change for the placebo , 400 IU , and 1000 IU vitamin D groups was -4.1 ± 11.5 nmol/L , + 31.6 ± 19.8 nmol/L , and + 42.6 ± 18.9 nmol/L , respectively . Treatment did not change markers of bone metabolism , except for a small reduction in PTH and an increase in serum calcium ( latter with 1000 IU dose only ) . The discordance between the incremental increase in 25(OH)D between the 400 IU and 1000 IU vitamin D and effect on BMD suggests that 25(OH)D may not accurately reflect clinical outcome , nor how much vitamin D is being stored",
"OBJECTIVES To compare the effects of 12 months of vitamin D3 supplementation with that placebo on lean mass , bone mineral density ( BMD ) , and muscle strength in overweight or obese postmenopausal women completing a structured weight-loss program . DESIGN Double-blind , placebo-controlled r and omized clinical trial . SETTING Fred Hutchinson Cancer Research Center , Seattle , Washington . PARTICIPANTS Postmenopausal women aged 50 to 75 with a body mass index ( BMI ) of 25 kg/m(2 ) or greater and a serum 25-hydroxyvitamin D ( 25(OH)D ) concentration between 10.0 and 32.0 ng/mL ( insufficient ) ( N = 218 ) . INTERVENTION Oral vitamin D3 2,000 IU/d or placebo in combination with a lifestyle-based weight loss intervention consisting of a reduction of 500 kcal to 1,000 kcal per day and 225 min/wk of moderate- to vigorous-intensity aerobic exercise . MEASUREMENTS Serum 25(OH)D , body composition , and muscle strength were measured before r and omization ( baseline ) and at 12 months . Mean changes of the groups were compared ( intention to treat ) using generalized estimating equations . RESULTS Change in 25(OH)D was significantly different between the vitamin D and placebo groups at 12 months ( 13.6 ng/mL vs -1.3 ng/mL , P change in lean mass ( -0.8 kg vs -1.1 kg , P = .53 ) or BMD of the spine ( -0.01 g/cm(2 ) vs 0.0 g/cm(2 ) , P = .82 ) or right femoral neck ( both -0.01 g/cm(2 ) , P = .49 ) were detected between the groups . Leg strength decreased in the vitamin D group but not in the placebo group ( -2.6 pounds vs 1.8 pounds , P = .03 ) . In women r and omized to vitamin D , achieving repletion ( 25(OH)D ≥ 32 ng/mL ) did not alter results . CONCLUSION Vitamin D3 supplementation during weight-loss decreased leg strength but did not alter changes in lean mass or BMD in postmenopausal women with vitamin D insufficiency",
"BACKGROUND Adults with low concentrations of 25-hydroxyvitamin D ( 25[OH]D ) in blood have an increased risk of falls and fractures , but r and omised trials of vitamin D supplementation have had inconsistent results . We aim ed to assess the effect of high-dose vitamin D supplementation on fractures and falls . METHODS The Vitamin D Assessment ( ViDA ) Study was a r and omised , double-blind , placebo-controlled trial of healthy volunteers aged 50 - 84 years conducted at one centre in Auckl and , New Zeal and . Participants were r and omly assigned to receive either an initial oral dose of 200 000 IU ( 5·0 mg ) colecalciferol ( vitamin D3 ) followed by monthly 100 000 IU ( 2·5 mg ) colecalciferol or equivalent placebo dosing . The prespecified primary outcome was cardiovascular disease and secondary outcomes were respiratory illness and fractures . Here , we report secondary outcome data for fractures and post-hoc outcome data for falls . Cox proportional hazards models were used to estimate hazard ratios ( HRs ) for time to first fracture or time to first fall in individuals allocated vitamin D compared with placebo . The analysis of fractures included all participants who gave consent and was by intention-to-treat ; the analysis of falls included all individuals who returned one or more question naires . This trial is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12611000402943 . FINDINGS Between April 5 , 2011 , and Nov 6 , 2012 , 5110 participants were recruited and r and omly assigned either colecalciferol ( n=2558 ) or placebo ( n=2552 ) . Two participants allocated placebo withdrew consent after r and omisation ; thus , a total of 5108 individuals were included in the analysis of fractures . The mean age of participants was 65·9 years ( SD 8·3 ) and 2971 ( 58 % ) were men . The mean concentration of 25(OH)D in blood was 63 nmol/L ( SD 24 ) at baseline , with 1534 ( 30 % ) having 25(OH)D concentrations lower than 50 nmol/L. Follow-up was until July 31 , 2015 , with a mean treatment duration of 3·4 years ( SD 0·4 , range 2·5 - 4·2 ) . During follow-up , 2638 participants reported having a fall , 1312 ( 52 % ) of 2539 in the vitamin D group compared with 1326 ( 53 % ) of 2517 in the placebo group . The HR for falls-adjusted for age , sex , ethnic origin , history of recent fall , physical activity , and baseline 25(OH)D-was 0·99 ( 95 % CI 0·92 - 1·07 ; p=0·82 ) for vitamin D compared with placebo . Non-vertebral fractures were reported in 292 individuals , 156 ( 6 % ) of 2558 in the vitamin D group and 136 ( 5 % ) of 2550 in the placebo group . The adjusted HR for fractures was 1·19 ( 95 % CI 0·94 - 1·50 ; p=0·15 ) for vitamin D compared with placebo . 123 ( 2 % ) people died during the trial , 65 assigned vitamin D and 58 allocated placebo ; the difference between treatment groups was not significant . INTERPRETATION High-dose bolus vitamin D supplementation of 100 000 IU colecalciferol monthly over 2·5 - 4·2 years did not prevent falls or fractures in this healthy , ambulatory , adult population . Further research is needed to ascertain the effects of daily vitamin D dosing , with or without calcium . FUNDING Health Research Council of New Zeal and and Accident Compensation Corporation of New Zeal and",
"OBJECTIVE This study aims to investigate the efficacy and safety of oral fixed-dose combination of strontium ranelate 2 g/vitamin D₃ 1000 IU daily vs strontium ranelate 2 g daily for correcting vitamin D insufficiency in osteoporosis . DESIGN A 6-month international , r and omized , double-blind , parallel-group , phase 3 study . METHODS A total of 518 men and postmenopausal women aged ≥50 years with primary osteoporosis ( T-score ≤-2.5 s.d . ) and serum 25-hydroxyvitamin D ( 25(OH)D ) > 22.5 nmol/l were included . Patients were allocated to strontium ranelate 2 g/vitamin D₃ 1000 IU daily ( n=413 ) or strontium ranelate 2 g daily ( n=105 ) . The participants received calcium 1 g daily . The primary endpoint was serum 25(OH)D at last post-baseline evaluation during 3 months . RESULTS Both groups were comparable at baseline . Mean baseline of 25(OH)D was 44.1 ± 14.6 nmol/l . After 3 months , the percentage of patients with 25(OH)D ≥50 nmol/l was higher with strontium ranelate/vitamin D₃ vs strontium ranelate ( 84 vs 44 % , P , 4.2 - 10.9 ) . The efficacy of the fixed-dose combination on 25(OH)D was maintained at 6 months ( 86 vs 40 % , P Mean 25(OH)D was 65.1 and 49.5 nmol/l , respectively , after 3 months and 66.9 and 45.4 nmol/l after 6 months . Physical performance improved in both groups . Falls were 17 and 20 % in the strontium ranelate/vitamin D₃ and strontium ranelate groups respectively . Parathyroid hormone levels were inversely correlated with 25(OH)D. No clinical ly relevant differences in safety were observed . CONCLUSIONS This study confirms the efficacy and safety of fixed-dose combination of strontium ranelate 2 g/vitamin D₃ 1000 IU for correction of vitamin D insufficiency in osteoporotic patients",
"There are few data on the relative effects of calcium supplementation with or without extra vitamin D on BMD in patients selected for low vitamin D status . The aim of this study is to evaluate the relative importance of vitamin D and calcium treatment on BMD and bone-related chemistry in elderly women with vitamin D insufficiency . Three hundred two elderly women ( age , 77.2 + /- 4.6 yr ) with serum 25(OH)D concentrations in a 1-yr r and omized , double-blind , placebo-controlled trial . All subjects received 1000 mg calcium citrate per day with either 1000 IU ergocalciferol ( vitamin D(2 ) ) or identical placebo ( control ) . The effects of time and time treatment interactions were evaluated by repeated- measures ANOVA . At baseline , calcium intake was 1100 mg/d , and 25(OH)D was 44.3 + /- 12.9 nM ; this increased in the vitamin D group by 34 % but not the control group after 1 year ( 59.8 + /- 13.8 versus 45.0 + /- 13.3 nM , p Total hip and total body BMD increased significantly , and procollagen type I intact N-terminal propeptide ( PINP ) decreased during the study with no difference between the treatment groups ( hip BMD change : vitamin D , + 0.5 % ; control , + 0.2 % ; total body BMD change : vitamin D , + 0.4 % ; control , + 0.4 % ; PINP change : vitamin D , -3.9 % ; placebo , -2.8 % ) . Although the fasting plasma and urine calcium increased in both groups equally , there was no detectable change in serum PTH . The increase in 25(OH)D achieved with vitamin D supplementation had no extra effect on active fractional intestinal calcium absorption , which fell equally in both groups ( vitamin D , -17.4 % ; control , -14.8 % ) . In patients with a baseline calcium intake of 1100 mg/d and vitamin D insufficiency , vitamin D(2 ) 1000 IU for 1 year has no extra beneficial effect on bone structure , bone formation markers , or intestinal calcium absorption over an additional 1000 mg of calcium . Vitamin D supplementation adds no extra short-term skeletal benefit to calcium citrate supplementation even in women with vitamin D insufficiency"
] |
4116c8d8-06ff-11f0-808a-c43d1ab1c353
|
OBJECTIVE To develop treatment recommendations for children with juvenile idiopathic arthritis manifesting as non-systemic polyarthritis , sacroiliitis , or enthesitis . METHODS The Patient/ Population , Intervention , Comparison , and Outcomes ( PICO ) questions were developed and refined by members of the guideline development teams . A systematic review was conducted to compile evidence for the benefits and harms associated with treatments for these conditions . GRADE ( Grading of Recommendations Assessment , Development and Evaluation ) methodology was used to rate the quality of evidence . A group consensus process was conducted among the Voting Panel to generate the final recommendations and grade their strength . A Parent and Patient Panel used a similar consensus approach to provide patient/caregiver preferences for key questions . RESULTS Thirty-nine recommendations were developed ( 8 strong and 31 conditional ) . The quality of supporting evidence was very low or low for 90 % of the recommendations . Recommendations are provided for the use of nonsteroidal antiinflammatory drugs , disease-modifying antirheumatic drugs , biologics , and intraarticular and oral glucocorticoids . Recommendations for the use of physical and occupational therapy are also provided . Specific recommendations for polyarthritis address general medication use , initial and subsequent treatment , and adjunctive therapies . Good disease control , with therapeutic escalation to achieve low disease activity , was recommended . The sacroiliitis and enthesitis recommendations primarily address initial therapy and adjunctive therapies . CONCLUSION This guideline provides direction for clinicians , caregivers , and patients making treatment decisions . Clinicians , caregivers , and patients should use a shared decision-making process that accounts for patients ' values , preferences , and comorbidities . These recommendations should not be used to limit or deny access to therapies
|
[
"Objective To evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis ( pcJIA ) . Methods This three-part , r and omised , placebo-controlled , double-blind withdrawal study ( NCT00988221 ) included patients who had active pcJIA for ≥6 months and inadequate responses to methotrexate . During part 1 , patients received open-label tocilizumab every 4 weeks ( 8 or 10 mg/kg for body weight ( BW ) patients with ≥JIA-American College of Rheumatology ( ACR ) 30 improvement entered the 24-week , double-blind part 2 after r and omisation 1:1 to placebo or tocilizumab ( stratified by methotrexate and steroid background therapy ) for evaluation of the primary end point : JIA flare , compared with week 16 . Patients flaring or completing part 2 received open-label tocilizumab . Results In part 1 , 188 patients received tocilizumab ( 2 , 163 patients received tocilizumab ( n=82 ) or placebo ( n=81 ) . JIA flare occurred in 48.1 % of patients on placebo versus 25.6 % continuing tocilizumab ( difference in means adjusted for stratification : −0.21 ; 95 % CI −0.35 to −0.08 ; p=0.0024 ) . At the end of part 2 , 64.6 % and 45.1 % of patients receiving tocilizumab had JIA-ACR70 and JIA-ACR90 responses , respectively . Rates/100 patient-years ( PY ) of adverse events ( AEs ) and serious AEs ( SAEs ) were 480 and 12.5 , respectively ; infections were the most common SAE ( 4.9/100 PY ) . Conclusions Tocilizumab treatment results in significant improvement , maintained over time , of pcJIA signs and symptoms and has a safety profile consistent with that for adults with rheumatoid arthritis . Trial registration number : NCT00988221",
"Objective To investigate the efficacy and safety of etanercept ( ETN ) in paediatric subjects with extended oligoarticular juvenile idiopathic arthritis ( eoJIA ) , enthesitis-related arthritis ( ERA ) , or psoriatic arthritis ( PsA ) . Methods CLIPPER is an ongoing , Phase 3b , open-label , multicentre study ; the 12-week ( Part 1 ) data are reported here . Subjects with eoJIA ( 2–17 years ) , ERA ( 12–17 years ) , or PsA ( 12–17 years ) received ETN 0.8 mg/kg once weekly ( maximum 50 mg ) . Primary endpoint was the percentage of subjects achieving JIA American College of Rheumatology ( ACR ) 30 criteria at week 12 ; secondary outcomes included JIA ACR 50/70/90 and inactive disease . Results 122/127 ( 96.1 % ) subjects completed the study ( mean age 11.7 years ) . JIA ACR 30 ( 95 % CI ) was achieved by 88.6 % ( 81.6 % to 93.6 % ) of subjects overall ; 89.7 % ( 78.8 % to 96.1 % ) with eoJIA , 83.3 % ( 67.2 % to 93.6 % ) with ERA and 93.1 % ( 77.2 % to 99.2 % ) with PsA. For eoJIA , ERA , or PsA categories , the ORs of ETN vs the historical placebo data were 26.2 , 15.1 and 40.7 , respectively . Overall JIA ACR 50 , 70 , 90 and inactive disease were achieved by 81.1 , 61.5 , 29.8 and 12.1 % , respectively . Treatment-emergent adverse events ( AEs ) , infections , and serious AEs , were reported in 45 ( 35.4 % ) , 58 ( 45.7 % ) , and 4 ( 3.1 % ) , subjects , respectively . Serious AEs were one case each of abdominal pain , bronchopneumonia , gastroenteritis and pyelocystitis . One subject reported herpes zoster and another varicella . No differences in safety were observed across the JIA categories . Conclusions ETN treatment for 12 weeks was effective and well tolerated in paediatric subjects with eoJIA , ERA and PsA , with no unexpected safety findings",
"Introduction While adalimumab is licensed for ankylosing spondylitis ( AS ) , open uncontrolled studies suggest therapeutic efficacy of TNF-inhibitors in juvenile onset AS ( JoAS ) . Methods A total of 32 patients aged 12 to 17 years with severe , active and refractory JoAS were enrolled in a multicenter , r and omized , double-blind , placebo-controlled parallel study of 12 weeks , followed by open-label adalimumab until week 24 for all patients . ASAS40 was used as the primary , and ASAS20 , PedACR and single items were used as the secondary outcome measures for the intention to treat population . Results A total of 17 patients were r and omized to receive adalimumab 40 mg/2 weeks and 15 patients received placebo . Two patients ( one of each group ) discontinued prematurely due to insufficient efficacy and were labeled as non-responders . In the double-blind part , more patients on adalimumab achieved an ASAS40 at week 4 ( 41 % ) , week 8 ( 53 % ) and week 12 ( 53 % ) than on placebo ( 20 % , 33 % , 33 % ) , while differences at week 8 only reached borderline significance ( P = 0.05 ) . Also , at 4 , 8 and 12 weeks ASAS20/PedACR30/70 response rates were higher in the adalimumab group ( 53%/53%/29 % ; 59%/76%/41 % ; 53%/65%/53 % ) compared to placebo ( 27%/27%/7 % ; 27%/33%/13 % ; 33%/40%/27 % ) . In the adalimumab group a significant decrease of all disease activity parameters was noted at week 12 and was even more pronounced at week 24 . At week 12 the Bath Ankylosing Spondylitis Disease activity spinal inflammation score decreased by 65 % ( P ) , the back pain score decreased by 50 % ( P ) , the Bath AS Functional Index ( BASFI ) score decreased by 47 % ( P ) , while the Childhood Health Assessment Question naire-Disability Index ( CHAQ-DI ) score improved by 65 % ( P 0.005 ) . ANCOVA analysis demonstrated superiority of adalimumab over placebo for the physician global assessment of disease activity , parents ' global assessment of subject 's overall well-being , active joint count ( all P rate ( ESR ) ( P Injection site reactions were the most common adverse events . There were 17 various infections occurring in the double-blind phase , 8 on placebo , 9 on adalimumab and a further 19 in the open label period . Conclusions Adalimumab was well tolerated and highly effective in a double-blind r and omized trial in patients with JoAS . Treatment effects rapidly occurred and persisted for at least 24 weeks of treatment . Trial registration EudraCT 2007 - 003358 - 27",
"Importance One-third of patients with rheumatoid arthritis show inadequate response to tumor necrosis factor α ( TNF-α ) inhibitors ; little guidance on choosing the next treatment exists . Objective To compare the efficacy of a non-TNF-targeted biologic ( non-TNF ) vs a second anti-TNF drug for patients with insufficient response to a TNF inhibitor . Design , Setting , and Participants A total of 300 patients ( conducted between 2009 - 2012 ) with rheumatoid arthritis , with persistent disease activity ( disease activity score in 28 joints-erythrocyte sedimentation rate [ DAS28-ESR ] ≥ 3.2 [ range , 0 - 9.3 ] ) and an insufficient response to anti-TNF therapy were included in a 52-week multicenter , pragmatic , open-label r and omized clinical trial . The final follow-up date was in August 2013 . Interventions Patients were r and omly assigned ( 1:1 ) to receive a non-TNF-targeted biologic agent or an anti-TNF that differed from their previous treatment . The choice of the biologic prescribed within each r and omized group was left to the treating clinician . Main Outcomes and Measures The primary outcome was the proportion of patients with good or moderate response according to the European League Against Rheumatism ( EULAR ) scale at week 24 . Secondary outcomes included the EULAR response at weeks 12 and 52 ; at weeks 12 , 24 , and 52 ; DAS28ESR , low disease activity ( DAS28 ≤3.2 ) , remission ( DAS28 ≤2.6 ) ; serious adverse events ; and serious infections . Results Of the 300 r and omized patients ( 243 [ 83.2 % ] women ; mean [ SD ] age , 57.1 [ 12.2 ] years ; baseline DAS28-ESR , 5.1 [ 1.1 ] ) , 269 ( 89.7 % ) completed the study . At week 24 , 101 of 146 patients ( 69 % ) in the non-TNF group and 76 ( 52 % ) in the second anti-TNF group achieved a good or moderate EULAR response ( OR , 2.06 ; 95 % CI , 1.27 - 3.37 ; P = .004 , with imputation of missing data ; absolute difference , 17.2 % ; 95 % CI , 6.2 % to 28.2 % ) . The DAS28-ESR was lower in the non-TNF group than in the second anti-TNF group ( mean difference adjusted for baseline differences , -0.43 ; 95 % CI , -0.72 to -0.14 ; P = .004 ) . At weeks 24 and 52 , more patients in the non-TNF group vs the second anti-TNF group showed low disease activity ( 45 % vs 28 % at week 24 ; OR , 2.09 ; 95 % CI , 1.27 to 3.43 ; P = .004 and 41 % vs 23 % at week 52 ; OR , 2.26 ; 95 % CI , 1.33 to 3.86 ; P = .003 ) . Conclusions and Relevance Among patients with rheumatoid arthritis previously treated with anti-TNF drugs but with inadequate primary response , a non-TNF biologic agent was more effective in achieving a good or moderate disease activity response at 24 weeks than was the second anti-TNF medication . Trial Registration clinical trials.gov Identifier : NCT01000441",
"To assess health‐related quality of life ( HRQOL ) in abatacept‐treated children/adolescents with juvenile idiopathic arthritis ( JIA )",
"Objective . The main objective was to determine the 2-year clinical benefit and safety of etanercept ( ETN ) in children with the juvenile idiopathic arthritis ( JIA ) categories of extended oligoarthritis ( eoJIA ) , enthesitis-related arthritis ( ERA ) , or psoriatic arthritis ( PsA ) . Methods . CLIPPER was a 96-week , phase IIIb , open-label , multicenter study . Patients with eoJIA , ERA , or PsA received ETN 0.8 mg/kg once weekly ( 50 mg max ) for up to 96 weeks . The proportions of patients reaching the JIA American College of Rheumatology ( ACR ) 30/50/70/90/100 and inactive disease responses at Week 96 were calculated . Adverse events ( AE ) were collected throughout the study ( intention-to-treat sample ) . Results . There were 127 patients ( eoJIA n = 60 , ERA n = 38 , PsA n = 29 ) who received ≥ 1 dose of ETN . The mean disease duration was 31.6 ( eoJIA ) , 23.0 ( ERA ) , and 21.8 ( PsA ) months . At Week 96 , JIA ACR 30/50/70/90/100/inactive disease responses ( 95 % CI ) were achieved by 84.3 % ( 76.7 , 90.1 ) , 83.5 % ( 75.8 , 89.5 ) , 78.7 % ( 70.6 , 85.5 ) , 55.1 % ( 46.0 , 63.9 ) , 45.7 % ( 36.8 , 54.7 ) , and 27.6 % ( 20.0 , 36.2 ) of patients , respectively . The most common AE ( no. events , events per 100 patient-yrs ) overall were headache ( 23 , 10.7 ) , pyrexia ( 12 , 5.6 ) , and diarrhea ( 10 , 4.6 ) . The most common infections were upper respiratory tract infection ( 83 , 38.6 ) , pharyngitis ( 50 , 23.2 ) , gastroenteritis ( 22 , 10.2 ) , bronchitis ( 19 , 8.8 ) , and rhinitis ( 17 , 7.9 ) . No cases of malignancy , active tuberculosis , demyelinating disorders , or death were reported . Conclusion . Over 96 weeks of therapy , ETN demonstrated sustained efficacy at treating the clinical symptoms of all 3 JIA categories , with no major safety issues",
"OBJECTIVE To investigate the effects of an 8-week , 24-session weight-bearing physical conditioning program on disease signs and symptoms in children with chronic arthritis . METHODS In a within-subjects , repeated measures design , 25 subjects , ages 8 - 17 years , with chronic polyarticular juvenile rheumatoid arthritis ( JRA ) , were assessed at study entry , after an 8-week control period , and after an 8-week exercise period , for 1 ) disease status , based on joint count ( JC ) and articular severity index ( ASI ) ( sum of scores for joint swelling , pain on motion , tenderness , and limitations of motion ) ; 2 ) worst pain during the past week , using a 10-cm visual analog scale ( VAS ) , and 3 ) aerobic endurance , using the 9-minute run-walk test of the Health Related Physical Fitness Test battery . The 60-minute conditioning program included warm-up ( 10 minutes ) , low-impact aerobics ( 25 minutes ) , strengthening ( 15 minutes ) , and cool-down and flexibility exercises ( 10 minutes ) . Subjects exercised twice a week at their rheumatology center and once a week at home , using a commercial exercise video-tape supplied by the investigator . RESULTS Significant improvement was found in the ASI ( Friedman analysis of variance [ ANOVA ] ) , JC , and 9-minute run-walk test ( repeated measures ANOVA ) from the pre- to post-exercise tests . Mean VAS pain scores decreased 16 % from study entry to the post-exercise test . Statistically significant improvement ( reliable change index > 1.96 ) occurred in 80 % of subjects on the ASI and 72 % on the JC . CONCLUSION Children and adolescents with chronic polyarticular JRA can improve their aerobic endurance through participation in weight-bearing physical conditioning programs without disease exacerbation or increased pain , and may achieve decreased joint signs and symptoms through increased physical activity",
"The efficacy and safety of abatacept in patients with juvenile idiopathic arthritis ( JIA ) who experienced an inadequate response to disease‐modifying antirheumatic drugs were previously established in a phase III study that included a 4‐month open‐label lead‐in period , a 6‐month double‐blind withdrawal period , and a long‐term extension ( LTE ) phase . The aim of this study was to present the safety , efficacy , and patient‐reported outcomes of abatacept treatment ( 10 mg/kg every 4 weeks ) during the LTE phase , for up to 7 years of followup",
"OBJECTIVE To compare the efficacy and safety of intra-articular triamcinolone hexacetonide ( TH ) and triamcinolone acetonide ( TA ) in children with oligoarticular juvenile idiopathic arthritis ( JIA ) . METHODS One hundred and thirty joints of 85 patients undergoing intra-articular injections were r and omly treated with either TH or TA depending on the availability of the drug . The efficacy of both treatments was evaluated prospect ively in a blinded fashion . A good response was defined as a decrease in the articular score of > or = 60 % from baseline . Clinical , laboratory and immunological variables were noted in order to examine possible factors , other than treatment , predictive of the result . RESULTS Seventy injections were performed using TH and 60 with TA . The two groups were comparable for clinical , immunological and laboratory characteristics . The rate of response was significantly higher with TH than with TA : 81.4 % vs 53.3 % ( P = 0.001 ) at 6 months , 67.1 vs 43.3 % ( P = 0.006 ) at 12 months , and 60 vs 33.3 % ( P = 0.002 ) at 24 months . CONCLUSION At comparable doses TH appeared to be much more effective than TA for intra-articular use , in both short- and long-term follow-up . This result was not affected by disease duration or degree of local and systemic inflammation",
"Objective To compare the relative bioavailability , safety and tolerability of oral methotrexate ( MTX ) and subcutaneous ( SC ) MTX administered via an auto-injector ( MTXAI ) in patients with rheumatoid arthritis ( RA ) . Methods In this r and omised , multicenter , open-label , three-way crossover study , patients ≥18 years with adult RA undergoing treatment with MTX for ≥3 months were assigned to receive MTX 10 , 15 , 20 and 25 mg weekly in a r and om sequence of three treatments : oral , SC into the abdomen and SC into the thigh . For 24 h after administration of each treatment , blood sample s were collected for pharmacokinetic analysis and injection sites were assessed . Results Forty-seven patients completed the study . Systemic exposure of oral MTX plateaued at doses ≥15 mg/week . In contrast , SC MTX demonstrated a linear increase in systemic exposure that was greater than oral MTX at each dose . No unexpected AEs were noted for either formulation . Conclusions Unlike oral MTX , the systemic exposure of SC MTX did not plateau over the doses studied , particularly at doses ≥15 mg/week . In this study , higher systemic MTX exposure was not associated with increases in AEs . Patients with an inadequate clinical response to oral MTX may benefit from higher drug exposure by switching to SC MTX . Trial registration number NCT01618968",
"Background This study aim ed to assess long-term safety and developmental data on juvenile idiopathic arthritis ( JIA ) patients treated in routine clinical practice with celecoxib or nonselective nonsteroidal anti-inflammatory drugs ( nsNSAIDs ) . Methods Children aged ≥2 to were enrolled into this prospect i ve , observational , multicenter st and ard-of-care registry . Eligible patients were newly or recently prescribed ( ≤6 months ) an nsNSAID or celecoxib . Enrolled patients were followed to the end of the study , whether they remained on the original NSAID , switched , or discontinued therapy altogether . All adverse events ( AEs ) regardless of severity were captured in the data base . Results A total of 274 patients ( nsNSAID , n = 219 ; celecoxib , n = 55 ) were observed for 410 patient-years of observation . Naproxen , meloxicam , and nabumetone were the most frequently used nsNSAIDs . At baseline , the celecoxib group was older , had a numerically longer median time since diagnosis , and a numerically higher proportion of patients with a history of gastrointestinal-related NSAID intolerance . AEs reported were those frequently observed with NSAID treatment and were similar across groups ( nsNSAIDs : 52.0 % ; celecoxib : 52.9 % ) . Twelve unique patients experienced a total of 18 serious AEs ; the most frequent were infections , and none was attributed to NSAID use . Conclusions The safety profile of celecoxib and nsNSAIDs appears similar overall . The results from this registry , ongoing pharmacovigilance , and the phase 3 trial that led to the approval of celecoxib for children with JIA provide evidence that the benefit-risk for celecoxib treatment in JIA remains positive . Trial registration Clinical Trials.gov identifier NCT00688545",
"OBJECTIVE To consider the relevance of the duration of a clinical trial in ankylosing spondylitis : long-term ( i.e. 1 yr ) vs short-term ( i.e. 6 weeks ) assessment of a non-steroidal anti-inflammatory drug (NSAID)-placebo controlled study . METHODS The design was a prospect i ve , multicentre , double-blind , placebo-controlled study of 6 weeks duration with a 12 months double-blind extension . Study drugs were placebo ( n = 121 ) or active NSAID ( n = 352 ) . A decrease of at least 50 % in pain and /or global assessment and /or functional impairment during the study defined the response to treatment . The percentage of patients discontinuing the study drug over time ( life table analysis ) permitted the evaluation of both the efficacy and toxicity . RESULTS Among the 473 recruited patients , the percentage of responders was similar at 1 yr and week 6 with a highly statistically significant difference in favour of the active NSAID groups when compared to placebo ( at 1 yr , 17 % in the placebo group vs 37 , 50 and 43 % in the piroxicam 20 mg , meloxicam 15 mg and meloxicam 22.5 mg , respectively , for the patient 's overall assessment ) without any statistically significant difference between the three active groups . However , evaluation of the patients discontinuing the study drug during the 1 yr of the study permitted the detection of a statistically significant difference between the active NSAID groups . A lower percentage of patients taking meloxicam 22.5 mg had to discontinue the study drug when compared to either meloxicam 15 mg or piroxicam 20 mg ( 37 % vs 53 % and 53 % , respectively , P drug-related upper gastrointestinal adverse events occurred in 13 , 32 , 20 and 18 % in the placebo , piroxicam 20 mg , meloxicam 15 mg and meloxicam 22.5 mg groups , respectively . Some of the adverse events occurred only after week 6 . CONCLUSION This study suggests that a 1 yr trial might be of optimum value compared to a 6 week assessment in order to define better the efficacy and tolerability of NSAIDs in ankylosing spondylitis",
"OBJECTIVE To evaluate the safety and efficacy of up to 8 years of etanercept treatment in patients with polyarticular-course juvenile rheumatoid arthritis ( JRA ) . METHODS Patients with JRA who previously participated in a r and omized controlled trial ( RCT ) of etanercept were eligible to receive etanercept in a long-term open-label extension ( OLE ) trial . Safety end points included the incidences of serious adverse events ( SAEs ) , medically important infections ( MIIs ) , and death . Efficacy end points included the American College of Rheumatology ( ACR ) Pediatric 30 ( Pedi 30 ) , Pedi 50 , Pedi 70 , Pedi 90 , and Pedi 100 criteria for improvement . RESULTS Of the 69 patients originally enrolled in the RCT , 58 ( 84 % ) participated in the OLE , for a total of 318 patient-years of etanercept exposure . A total of 42 of the 58 patients ( 72 % ) entered the fourth year of continuous etanercept treatment , and 26 patients ( 45 % ) entered the eighth year . Sixteen patients ( 23 % of those entering the RCT ) reported 39 SAEs . The overall rate of SAEs ( 0.12 per patient-year ) did not increase with long-term exposure to etanercept . The rate of MIIs ( 0.03 per patient-year ) remained low ; 1 new MII was reported in patients with > or = 5 years of etanercept exposure . No cases of tuberculosis , opportunistic infections , malignancies , lymphomas , lupus , demyelinating disorders , or deaths were reported . An ACR Pedi 70 response or higher was achieved by 100 % of patients with 8 years of data ( 11 of 11 ) and by 61 % of patients according to the last observation carried forward data ( 28 of 46 ) . CONCLUSION These data suggest that the acceptable safety profile of etanercept therapy is maintained for up to 8 years in this population of JRA patients . Improvements in the signs and symptoms of JRA were also maintained for up to 8 years",
"OBJECTIVE This study was undertaken to evaluate the long-term safety and effectiveness of etanercept alone or in combination with methotrexate ( MTX ) in children with selected categories of juvenile idiopathic arthritis ( JIA ) . METHODS Patients ages 2 - 18 years with rheumatoid factor (RF)-positive or RF-negative polyarthritis , systemic JIA , or extended oligoarthritis were eligible for the study . Patients received MTX alone ( > or = 10 mg/m(2)/week [ approximately 0.3 mg/kg/week ] , maximum dosage 1 mg/kg/week ) , etanercept alone ( 0.8 mg/kg/week , maximum dose 50 mg ) , or etanercept plus MTX for 3 years in an open-label , nonr and omized study . Safety was assessed by measuring rates of adverse events , and effectiveness was assessed using the physician 's global assessment of disease activity and the pediatric total joint assessment . RESULTS A total of 197 , 103 , and 294 patients were enrolled in the MTX , etanercept , and etanercept plus MTX groups , respectively . Exposure-adjusted rates of adverse events were similar among the 3 treatment groups ( 18.3 , 18.7 , and 21.6 per 100 patient-years in the MTX , etanercept , and etanercept plus MTX groups , respectively ) . Respective rates per 100 patient-years of serious adverse events ( 4.6 , 7.1 , and 6.0 ) and medically important infections ( 1.3 , 1.8 , and 2.1 ) were also similar among the 3 treatment groups . Scores for physician 's global assessment and total active joints improved from baseline , and improvement was maintained for the duration of the study . CONCLUSION These data confirm the findings of other long-term studies and suggest that etanercept or etanercept plus MTX has an acceptable safety and effectiveness profile in children with selected categories of JIA . Improvement was maintained for 3 years in those continuing to receive medication",
"Background There is a lack of published evidence on the importance of methotrexate ( MTX ) dose and route of administration on both its efficacy and adverse events in children with Juvenile Idiopathic Arthritis ( JIA ) . We aim ed to document our clinical practice based on the treat-to-target approach in order to support the concept that better therapeutic effect achieved with an optimal dose of parenteral MTX is associated with clinical ly acceptable adverse effects comparable to those reported for oral treatment . Methods Study inclusion criteria were indication of new MTX therapy for active arthritis in confirmed JIA patients younger than 18 years . Eligible patients were evaluated prospect ively every 3 months for 1 year using st and ardized instruments for treatment response ( American College of Rheumatology Pediatric ( ACRPedi ) response , Juvenile Arthritis Disease Activity Score ( JADAS ) 71 , Clinical ly Inactive Disease ( CID ) ) and adverse events ( laboratory monitoring , Methotrexate Intolerance Severity Score ( MISS ) ) . MTX responders had to achieve at least ACRPedi 70 response . MTX intolerance was defined by MISS ≥ 6 . Results In 45/55 patients ( 81.8 % ) MTX was started as subcutaneous injection . The initial median weekly dose was 14.4 mg/m2 in parenteral and 11.7 mg/m2 in oral administration . MTX therapy was effective in the level of ACRpedi70 and CID in 50.9 % and 30.9 % of patients at month 6 and in 70.9 % and 56.4 % after 12 months of the treatment , respectively . MTX intolerance at 6 and 12 months was noted in 25.5 % and 30.6 % , respectively . Management of intolerance included change in the dose and /or route of administration , education and councelling . Adverse events led to MTX withdrawal in 5 patients ( 9 % ) due to toxicity ( n = 3 ) and intolerance ( n = 2 ) . We did not find any significant predictive factors for either MTX therapeutic response or intolerance . ConclusionS ubcutaneous MTX weekly dose around 15 mg/m2 is associated not only with a high response rate within the first 12 months of treatment , but also with a relatively low rate of significant adverse effects that would lead to the treatment termination . It allows early recognition of MTX non-responders and addition of biologic therapy . Sustainability of therapeutic effect and longer-term evolution of adverse events will be addressed by an ongoing extension of the study",
"BACKGROUND We compared the safety and efficacy of leflunomide with that of methotrexate in the treatment of polyarticular juvenile rheumatoid arthritis in a multinational , r and omized , controlled trial . METHODS Patients 3 to 17 years of age received leflunomide or methotrexate for 16 weeks in a double-dummy , blinded fashion , followed by a 32-week blinded extension . The rates of American College of Rheumatology Pediatric 30 percent responses ( ACR Pedi 30 ) and the Percent Improvement Index were assessed at baseline and every 4 weeks for 16 weeks and every 8 weeks during the 32-week extension study . RESULTS Of 94 patients r and omized , 86 completed 16 weeks of treatment , 70 of whom entered the extension study . At week 16 , more patients in the methotrexate group than in the leflunomide group had an ACR Pedi 30 response ( 89 percent vs. 68 percent , P=0.02 ) , whereas the values for the Percent Improvement Index did not differ significantly ( -52.87 percent vs. -44.41 percent , P=0.18 ) . In both groups , the improvements achieved at week 16 were maintained at week 48 . The most common adverse events in both groups included gastrointestinal symptoms , headache , and nasopharyngeal symptoms . Aminotransferase elevations were more frequent with methotrexate than with leflunomide during the initial study and the extension study . CONCLUSIONS In patients with polyarticular juvenile rheumatoid arthritis , methotrexate and leflunomide both result ed in high rates of clinical improvement , but the rate was slightly greater for methotrexate . At the doses used in this study , methotrexate was more effective than leflunomide",
"OBJECTIVES Methotrexate ( MTX ) is the cornerstone disease-modifying anti-rheumatic drug ( DMARD ) in juvenile idiopathic arthritis ( JIA ) . In Dutch patients , MTX intolerance occurred frequently and was associated with subcutaneous ( SC ) administration . The aim of this study was to assess the prevalence of MTX intolerance and its association with the route of administration in a German cohort of JIA patients . METHODS A cross-sectional study of JIA patients on MTX was performed . Primary outcome was MTX intolerance , which was determined using the vali date d Methotrexate Intolerance Severity Score ( MISS ) question naire . The prevalence of gastrointestinal adverse effects and MTX intolerance was compared between patients on MTX SC and MTX administered orally ( PO ) . RESULTS Of 179 JIA patients on MTX , 73 ( 40.8 % ) were intolerant . The odds of MTX intolerance were higher in patients using MTX exclusively SC compared to exclusively PO ( adjusted odds ratio 3.37 [ 95 % confidence interval 1.19 - 10.0 ] ) . There was strong evidence that the former experienced more behavioural complaints ( 76.1 % vs. 47.4 % , p=0.001 ) and weak evidence that they experienced more abdominal pain after MTX intake ( 43.5 % vs. 27.4 % , p=0.056 ) . CONCLUSIONS The prevalence of MTX intolerance was high and exclusively SC administration of MTX was associated with MTX intolerance and behavioural adverse effects . The prevalence of gastrointestinal adverse effects was at least as high as in patients on MTX PO . The frequently held assumption that SC causes fewer side effects than PO seems unwarranted . Definite answers about the differences between SC and PO administration with respect to safety and efficacy should be obtained by r and omised trials",
"BACKGROUND The antimetabolite methotrexate has been shown in placebo-controlled trials to be effective in adults with rheumatoid arthritis . Methotrexate may also be effective in children with resistant juvenile rheumatoid arthritis , but the supporting data are from uncontrolled trials . METHODS Centers in the United States and the Soviet Union participated in this r and omized , controlled , double-blind trial design ed to evaluate the effectiveness and safety of orally administered methotrexate . Patients received one of the following treatments each week for six months : 10 mg of methotrexate per square meter of body-surface area ( low dose ) , 5 mg of methotrexate per square meter ( very low dose ) , or placebo . The use of prednisone ( less than or equal to 10 mg per day ) and two nonsteroidal antiinflammatory drugs was also allowed . RESULTS The 127 children ( mean age , 10.1 years ) had a mean duration of disease of 5.1 years ; 114 qualified for the analysis of efficacy . According to a composite index of several response variables , 63 percent of the children who received low-dose methotrexate improved , as compared with 32 percent of those in the very-low-dose group and 36 percent of those in the placebo group ( P = 0.013 ) . As compared with the placebo group , the low-dose group also had significantly larger mean reductions from base line in the number of joints with pain on motion ( -11.0 vs. -7.1 ) , the pain-severity score ( -19 vs. -11.5 ) , the number of joints with limited motion ( -5.4 vs. -0.7 ) , and the erythrocyte sedimentation rate ( -19.0 vs. -6 mm per hour ) . In the methotrexate groups only three children had the drug discontinued because of mild-to-moderate side effects ; none had severe toxicity . CONCLUSIONS Methotrexate given weekly in low doses is an effective treatment for children with resistant juvenile rheumatoid arthritis , and at least in the short term this regimen is safe",
"OBJECTIVES Etanercept , a recombinant TNF receptor fusion protein , has been approved for the treatment of resistant polyarticular course juvenile idiopathic arthritis at a dosage of 0.4 mg/kg twice weekly in children older than 4 years . In adult patients , efficacy and safety of etanercept 25 mg twice weekly was comparable with 50 mg once weekly . Therefore , safety and efficacy of etanercept once weekly 0.8 mg/kg up to 50 mg s.c . was evaluated in a 3 month open label trial . METHODS Twenty patients 4 to 17 years old received 0.8 mg of etanercept per kilogram of body weight subcutaneously once weekly for 3 months in an open multicentre trial . Active polyarticular disease was defined by the presence of five or more active joints with swelling , alternatively with pain or tenderness combined with limitation of motion . Safety assessment s were based on adverse events ( AEs ) reports . Efficacy was assessed using the PedACR30/50/70 criteria . RESULTS At the start of treatment the patients showed high disease activity . A rapid reduction of all disease activity parameters was observed . A PedACR30/50/70 response was reached by 75%/35%/10 % of patients after 4 weeks , 90%/75%/35 % after 8 weeks and 95%/75%/75 % after 12 weeks of treatment . There were 37 AEs , none of them serious , with injection site reactions and minor infections being the most frequent . There was no drop out . Long-term follow-up of the patients will be carried out in the German JIA Registry . CONCLUSION Treatment with etanercept once weekly using a double dosage leads to a significant improvement of disease activity in patients with active polyarticular course juvenile idiopathic arthritis and is well tolerated",
"OBJECTIVE To assess the outcome of adult patients with JIA who received etanercept ( ETA ) during childhood . METHODS JuMBO ( Juvenile arthritis MTX/Biologics long-term Observation ) is an ongoing prospect i ve cohort study . It follows adult JIA patients who were formerly included in the national JIA biologic register . In JuMBO , clinical status , therapy and the occurrence of adverse events are documented every 6 months by physicians ; additionally , patient-derived data are included [ e.g. functional capacity and health-related quality of life ( HRQoL ) ] . Here , data from the last available visit of patients were analysed . RESULTS Until December 2010 , 346 patients with a median age of 21 years were included in JuMBO . The majority of them had polyarthritis . Seventy-eight per cent of them were still on DMARDs , 45 % on ETA . The disease was inactive in about one in five patients . A restricted functional capacity was reported by 51 % of participants and fatigue by 76 % . The patients judged their HRQoL to be lower than a reference group from the general population , but only with regard to physical health . HRQoL correlated with the patient 's perceived fatigue . Most frequently observed comorbidities in the young adults with JIA were disease related and included uveitis , IBDs and psoriasis . During the observation period , 2.1 severe infections and 1.5 new-onset autoimmune events per 100 patient-years were reported in patients on ETA , respectively . CONCLUSION The first data from the JuMBO register indicate an improved long-term outcome of patients with severe JIA treated in the biologic era and an acceptable safety profile of ETA",
"Enthesitis‐related arthritis ( ERA ) is a juvenile idiopathic arthritis ( JIA ) category , primarily affecting entheses and peripheral joints . This study evaluated efficacy , safety , and pharmacokinetics of adalimumab versus placebo in patients with ERA",
"OBJECTIVES To identify contributing factors associated with inactive disease ( ID ) and clinical remission for patients with juvenile idiopathic arthritis ( JIA ) treated with etanercept . METHODS Data of an ongoing , long-term , multicentre , prospect i ve , open-label observational study were analysed . Results . A total of 4898 follow-up forms from 787 JIA patients treated with etanercept were evaluated . Sixty-four per cent of the patients were female , 75 % concomitantly received MTX and 45.9 % received corticosteroids . Until the last observation , 47.6 % of patients reached the criteria for ID and 26.6 % achieved the remission on medication criteria . For both , ID and remission on medication , a significant influence of shorter disease duration ( P dosage of at least 0.8 mg/kg ( P=0.02 ) , lower active joint counts ( P=0.001 ) and lower childhood HAQ score ( P odds ratio ( OR ) for a girl 's chance to reach ID was 0.73 ( P=0.049 ) and for remission on medication was 0.68 ( P=0.04 ) compared with boys . The concomitant administration of MTX raised the relative chance , especially in patients with seronegative polyarthritis ( OR 2.0 ; P=0.03 ) . CONCLUSION Upon treatment with etanercept , many JIA patients reached ID and remission on medication , although they had suffered from long-st and ing , refractory disease . Earlier initiation of treatment , less severe disease , use of at least the recommended weekly dosage of etanercept , and concomitant treatment with MTX seemed to independently increase the chance for reaching remission . These data should be confirmed by controlled prospect i ve studies",
"OBJECTIVE Pharmacokinetic studies have shown that the biological effect of triamcinolone acetonide ( TA ) is equivalent to that of triamcinolone hexacetonide ( TH ) , if used at double the dosage . In this study we compared the efficacy of intra-articular TA at a dose twice that of TH in symmetrically involved joints , in children with juvenile idiopathic arthritis ( JIA ) . METHOD Children with active arthritis and a similar degree of inflammation in two symmetrical joints were enrolled in the study . The symmetry was assessed by both clinical examination and synovial fluid analysis . The dose given was 1 mg/kg up to 40 mg of TH or 2.0 mg/kg up to 80 mg of TA . The identity of injected compound was blinded to the patient and to the physician . RESULTS Thirty-seven patients , 30 female , seven male , with JIA , entered the study . A total of 86 joints were injected . Twenty-one ( 53.8 % ) of the joints injected with TA relapsed first compared with only six ( 15.4 % ) of the joints injected with TH . In three ( 7.7 % ) relapse occurred simultaneously . Nine ( 23 % ) were still in remission after 24-month follow-up . The percentage of joints with lasting remission was higher with TH than with TA ( 80 vs 47.5 % after 12 months and 63.6 vs 32.4 % after 24 months , respectively ; log rank test P = 0.003 ) . CONCLUSION Even when TA is given at higher doses , TH is more effective and should be considered the drug of choice for intra-articular treatment of JIA",
"Objective This report aims to determine the safety , pharmacokinetics ( PK ) and efficacy of subcutaneous golimumab in active polyarticular-course juvenile idiopathic arthritis ( polyJIA ) . Methods In this three-part r and omised double-blinded placebo-controlled withdrawal trial , all patients received open-label golimumab ( 30 mg/m2 of body surface area ; maximum : 50 mg/dose ) every 4 weeks together with weekly methotrexate during Part 1 ( weeks 0–16 ) . Patients with at least 30 % improvement per American College of Rheumatology Criteria for JIA ( JIA ACR30 ) in Part 1 entered the double-blinded Part 2 ( weeks 16–48 ) after 1:1 r and omisation to continue golimumab or start placebo . In Part 3 , golimumab was continued or could be restarted as in Part 1 . The primary outcome was JIA flares in Part 2 ; secondary outcomes included JIA ACR50/70/90 responses , clinical remission , PK and safety . Results Among 173 patients with polyJIA enrolled , 89.0 % ( 154/173 ) had a JIA ACR30 response and 79.2%/65.9%/36.4 % demonstrated JIA ACR50/70/90 responses in Part 1 . At week 48 , the primary endpoint was not met as treatment groups had comparable JIA flare rates ( golimumab vs placebo : 32/78=41 % vs 36/76=47 % ; p=0.41 ) , and rates of clinical remission were comparable ( golimumab vs placebo : 10/78=12.8 % vs 9/76=11.8 % ) . Adverse event and serious adverse event rates were similar in the treatment groups during Part 2 . Injection site reactions occurred with improvement in children with active polyJIA . Golimumab was well tolerated , and no unexpected safety events occurred . Clinical Trial Registration NCT01230827 ; Results",
"OBJECTIVE We previously documented that abatacept was effective and safe in patients with juvenile idiopathic arthritis ( JIA ) who had not previously achieved a satisfactory clinical response with disease-modifying antirheumatic drugs or tumor necrosis factor blockade . Here , we report results from the long-term extension ( LTE ) phase of that study . METHODS This report describes the long-term , open-label extension phase of a double-blind , r and omized , controlled withdrawal trial in 190 patients with JIA ages 6 - 17 years . Children were treated with 10 mg/kg abatacept administered intravenously every 4 weeks , with or without methotrexate . Efficacy results were based on data derived from the 153 patients who entered the open-label LTE phase and reflect > or=21 months ( 589 days ) of treatment . Safety results include all available open-label data as of May 7 , 2008 . RESULTS Of the 190 enrolled patients , 153 entered the LTE . By day 589 , 90 % , 88 % , 75 % , 57 % , and 39 % of patients treated with abatacept during the double-blind and LTE phases achieved responses according to the American College of Rheumatology ( ACR ) Pediatric 30 ( Pedi 30 ) , Pedi 50 , Pedi 70 , Pedi 90 , and Pedi 100 criteria for improvement , respectively . Similar response rates were observed by day 589 among patients previously treated with placebo . Among patients who had not achieved an ACR Pedi 30 response at the end of the open-label lead-in phase and who proceeded directly into the LTE , 73 % , 64 % , 46 % , 18 % , and 5 % achieved ACR Pedi 30 , Pedi 50 , Pedi 70 , Pedi 90 , and Pedi 100 responses , respectively , by day 589 of the LTE . No cases of tuberculosis and no malignancies were reported during the LTE . Pneumonia developed in 3 patients , and multiple sclerosis developed in 1 patient . CONCLUSION Abatacept provided clinical ly significant and durable efficacy in patients with JIA , including those who did not initially achieve an ACR Pedi 30 response during the initial 4-month open-label lead-in phase",
"Objective : We undertook an observational study to obtain a complete overview of the long-term effectiveness and safety of etanercept in patients with different juvenile idiopathic arthritis ( JIA ) subtypes . Methods : At baseline we collected patient and disease characteristics of all Dutch patients with JIA who started treatment with etanercept . Disease activity was evaluated ( at start of the study , after 3 months and then yearly ) according to the JIA core set of the American College of Rheumatology paediatric definition for 30 , 50 and 70 % improvement ( ACR Pedi 30 , 50 and 70 ) . Use of etanercept and concomitant drugs was monitored . Adverse events were recorded . Results : We included 146 patients with JIA with a median follow-up of 2.5 years per patient ( range 0.3–7.3 ) . JIA subtypes represented : 27 % systemic , 8 % polyarticular rheumatoid factor positive , 38 % polyarticular rheumatoid factor negative , 19 % oligoarticular extended , 3 % enthesitis-related and 5 % psoriatica . Most patients ( 77 % ) met the criteria of the ACR Pedi 30 in the first 3 months of treatment . For the majority of patients this improvement was sustained ; 53 ( 36 % ) of all patients met the remission criteria . No other second-line agents were needed in 43 patients . Although patients with systemic JIA responded initially less to etanercept therapy than patients from other subtypes , those who did respond showed equal effectiveness in the long term . Serious adverse events rate was low ( 0.029 per patient year ) . Conclusions : Etanercept is effective and safe in JIA , even for a large proportion of the patients with systemic JIA . The greatest improvement occurred in the first 3 months of treatment , and was sustained for a long time in most patients ( up to 75 months )",
"OBJECTIVE To assess the efficacy , tolerability , and safety of sulfasalazine ( SSZ ) in the treatment of juvenile chronic arthritis ( JCA ) . METHODS We conducted a 24-week r and omized , placebo-controlled , double-blind , multicenter study of patients with active JCA of both oligoarticular and polyarticular onset . Patients were treated with a dosage of 50 mg/kg/day of SSZ ( maximum 2,000 mg/day ) or placebo . The efficacy variables were joint scores , physician 's , parents ' , and patient 's overall assessment s , and laboratory parameters of inflammation . RESULTS Of the 69 patients enrolled , 52 ( 75 % ) completed the trial . Six patients ( 18 % ) withdrew from the placebo group , and 11 ( 31 % ) withdrew from the SSZ group ( P = 0.18 ) . In the intention-to-treat analysis of end point efficacy , between-group differences were significant for the overall articular severity score ( P = 0.02 ) , all global assessment s ( P = 0.01 ) , and the laboratory parameters ( P Adverse events occurred more frequently in the SSZ group and were the main reason for withdrawal ( P placebo-controlled study show that SSZ is effective and safe in the treatment of children with oligoarticular- and polyarticular-onset JCA , although it was not well tolerated in one-third of the patients",
"OBJECTIVE To examine the efficacy and safety of different rituximab doses plus methotrexate ( MTX ) , with or without glucocorticoids , in patients with active rheumatoid arthritis ( RA ) resistant to disease-modifying antirheumatic drugs ( DMARDs ) , including biologic agents . METHODS A total of 465 patients were r and omized into 9 treatment groups : 3 rituximab groups ( placebo [ n = 149 ] , 500 mg [ n = 124 ] , or 1,000 mg [ n = 192 ] on days 1 and 15 ) each also taking either placebo glucocorticoids , intravenous methylprednisolone premedication , or intravenous methylprednisolone premedication plus oral prednisone for 2 weeks . All patients received MTX ( 10 - 25 mg/week ) ; no other DMARDs were permitted . RESULTS Significantly more patients who received 2 500-mg or 2 1,000-mg infusions of rituximab met the American College of Rheumatology 20 % improvement criteria ( achieved an ACR20 response ) at week 24 ( 55 % and 54 % , respectively ) compared with placebo ( 28 % ; P ACR50 responses were achieved by 33 % , 34 % , and 13 % of patients , respectively ( P ACR70 responses were achieved by 13 % , 20 % , and 5 % of patients ( P Changes in the Disease Activity Score in 28 joints ( -1.79 , -2.05 , -0.67 ; P European League Against Rheumatism criteria ( P Glucocorticoids did not contribute significantly to the primary efficacy end point , ACR20 response at 24 weeks . Intravenous glucocorticoid premedication reduced the frequency and intensity of first infusion-associated events ; oral glucocorticoids conferred no additional safety benefit . Rituximab was well tolerated ; the type and severity of infections was similar to those for placebo . CONCLUSION Both rituximab doses were effective and well tolerated when added to MTX therapy in patients with active RA . The primary end point ( ACR20 response ) was independent of glucocorticoids , although intravenous glucocorticoid premedication improved tolerability during the first rituximab infusion",
"Objectives In juvenile idiopathic arthritis ( JIA ) , the efficacy of very early disease-modifying drug therapy , synthetic or biological , is not well known . Three alternative strategies were compared for treating recent‑onset polyarticular JIA . Methods In a 54-week multicentre open-label clinical trial , 60 disease-modifying antirheumatic drug (DMARD)-naive patients aged 4–15 years were r and omly assigned into three treatment arms . The efficacy of infliximab plus methotrexate ( TNF ) was compared to that of two synthetic therapies : methotrexate alone ( MTX ) and DMARD methotrexate , sulphasalazine and hydroxychloroquine in combination ( COMBO ) . Primary endpoint was American College of Rheumatology paediatric 75 % improvement ( ACR Pedi 75 ) . Secondary endpoints were inactive disease and safety . Results In 59 patients , mean ( ±SE ) age at baseline was 9.6±0.4 years , duration of JIA 1.9±0.2 months and number of active joints 18±1 . ACR Pedi 75 was achieved in 100 % ( 19/19 ) of patients receiving TNF , 65 % ( 13/20 ) on COMBO ( 95 % CI 44 % to 86 % ) and 50 % ( 10/20 ) on methotrexate ( 95 % CI 28 % to 72 % ) p achieved inactive disease , whereas eight ( 40 % ; 95 % CI 22 % to 63 % ) on COMBO and five ( 25 % ; 95 % CI 6 % to 44 % ) on methotrexate did ( p=0.002 ) . Patients on TNF spent a mean 26 weeks ( 95 % CI 18 to 34 ) with inactive disease , longer than did those receiving COMBO ( 13 weeks ; 95 % CI 6 to 20 ) , or methotrexate ( 6 weeks ; 95 % CI 2 to 10 ) . Serious adverse events were rare . Conclusion In early polyarticular JIA , targeting to achieve minimally active or inactive disease , infliximab plus methotrexate was superior to synthetic DMARD in combination and strikingly superior to methotrexate alone",
"OBJECTIVE To assess the efficacy , safety , and tolerability of etoricoxib , a cyclooxygenase 2 ( COX-2 ) selective inhibitor , administered continuously over 52 weeks for the treatment of ankylosing spondylitis ( AS ) . METHODS This 2-part , multicenter , double-blind , parallel-group , 52-week study evaluated 2 doses of etoricoxib ( 90 and 120 mg ) compared with naproxen at 1,000 mg . A 6-week , active-comparator- and placebo-controlled period ( part I ) was followed by a 46-week active-comparator-controlled period ( part II ) . The primary outcome measures ( on 100-mm visual analog scales ) were patient 's assessment of spine pain , patient 's global assessment of disease activity , and the Bath Ankylosing Spondylitis Functional Index . RESULTS Of the 387 patients r and omized to receive treatment , 301 ( 77.8 % ) completed part I and 284 ( 75.9 % ) completed part II . Compared with placebo over 6 weeks , those receiving 90 mg etoricoxib , 120 mg etoricoxib , and naproxen demonstrated significantly ( P primary end points ; treatment effects ( expressed as the difference in least squares mean change versus placebo ) were 21 - 29 mm for spine pain , 18 - 25 mm for disease activity , and 11 - 15 mm for function . Compared with patients receiving naproxen , significantly greater improvement in all primary end points was demonstrated in the combined group receiving either 90 mg etoricoxib or 120 mg etoricoxib over 6 weeks , in each individual etoricoxib treatment group over 6 weeks , and in the combined etoricoxib group over 1 year ( all P incidence of overall clinical , drug-related , or serious adverse experiences ( AEs ) and discontinuations due to AEs . Safety observations during part II were generally consistent with those in part I. CONCLUSION Etoricoxib at doses of 90 mg and 120 mg demonstrated superior efficacy compared with placebo over 6 weeks , and compared with naproxen over 1 year . These study results demonstrate that etoricoxib is generally safe , well-tolerated , and efficacious for the treatment of AS",
"OBJECTIVE To identify a core set of outcome variables for the assessment of children with juvenile arthritis ( JA ) , to use the core set to develop a definition of improvement to determine whether individual patients demonstrate clinical ly important improvement , and to promote this definition as a single efficacy measure in JA clinical trials . METHODS A core set of outcome variables was established using a combination of statistical and consensus formation techniques . Variables in the core set consisted of 1 ) physician global assessment of disease activity ; 2 ) parent/patient assessment of overall well-being ; 3 ) functional ability ; 4 ) number of joints with active arthritis ; 5 ) number of joints with limited range of motion ; and 6 ) erythrocyte sedimentation rate . To establish a definition of improvement using this core set , 21 pediatric rheumatologists from 14 countries met , and , using consensus formation techniques , scored each of 72 patient profiles as improved or not improved . Using the physicians ' consensus as the gold st and ard , the chi-square , sensitivity , and specificity were calculated for each of 240 possible definitions of improvement . Definitions with sensitivity or specificity of of improvement with the highest final score was as follows : at least 30 % improvement from baseline in 3 of any 6 variables in the core set , with no more than 1 of the remaining variables worsening by > 30 % . The second highest scoring definition was closely related to the first ; the third highest was similar to the Paulus criteria used in adult rheumatoid arthritis trials , except with different variables . This indicates convergent validity of the process used . CONCLUSION We propose a definition of improvement for JA . Use of a uniform definition will help st and ardize the conduct and reporting of clinical trials , and should help practitioners decide if a child with JA has responded adequately to therapy . We are in the process of prospect ively validating this definition and several others that scored highly",
"Background Treatment of juvenile idiopathic arthritis ( JIA ) has changed dramatically since the introduction of biological agents in 1999 . Objective To evaluate trends in prescription patterns of biological agents and the subsequent outcome of JIA . Methods The Arthritis and Biologics in Children register ( multicentre prospect i ve observational study ) aim ed to include all consecutive patients with JIA in the Netherl and s who had started biological agents since 1999 . Patients were divided according to year of introduction of first biological agent . Patient characteristics at introduction of the first biological agent and its effectiveness were analysed over 12 years . Results 335 patients with non-systemic JIA and 86 patients with systemic JIA started a biological agent between 1999 and 2010 . Etanercept remained the most often prescribed biological agent for non-systemic JIA ; anakinra became first choice for systemic JIA . The use of systemic glucocorticoids and synthetic disease-modifying antirheumatic drugs before biological agents decreased . During these 12 years of observation , biological agents were prescribed earlier in the disease course and to patients with lower baseline JADAS ( Juvenile Arthritis Disease Activity Score ) disease activity . All baseline disease activity parameters were lowered in patients with non-systemic JIA . In systemic JIA , prescription patterns changed towards very early introduction of biological agents ( median 0.4 years of disease duration ) in patients with a low number of joints with active arthritis and high erythrocyte sedimentation rates . These changes for both systemic and non-systemic JIA result ed in more patients with inactive disease after 3 and 15 months of treatment . Conclusions Biological agents are increasingly prescribed , earlier in the disease and in patients with JIA with lower disease activity . These changes are accompanied by better short-term disease outcomes",
"OBJECTIVE To compare the efficacy and safety of methotrexate ( MTX ) after oral and intramuscular administration in children with juvenile chronic arthritis ( JCA ) . METHODS Pediatric rheumatology centers in Italy participated in this short-term , prospect i ve , open trial . Each investigator was allowed to choose the oral or intramuscular route of administration according to his personal preference in everyday clinical practice . Patients enrolled by each center were given MTX through the same method of administration . All patients received 10 mg/m2 of MTX each week for six months . RESULTS A total of 257 patients with JCA ( 127 treated orally and 130 intramuscularly ) were enrolled in the trial by 11 Italian centers . The response rate after 6 months of MTX therapy was 58 % in the oral and 61 % in the intramuscular cohort . The frequency of adverse side effects did not differ significantly between the two treatment groups . CONCLUSION The results of this study suggest that MTX at the conventional dose regimen is equally effective and has a similar safety profile in children with JCA when administered orally or by intramuscular injections",
"OBJECTIVE To evaluate the short-term efficacy of celecoxib , a cyclooxygenase 2-specific inhibitor , in the treatment of ankylosing spondylitis ( AS ) . METHODS The study was a 6-week r and omized , double-blind , placebo-controlled trial with 3 treatment arms : placebo , ketoprofen 100 mg twice daily , and celecoxib 100 mg twice daily . Patients who had AS according to the modified New York criteria , without peripheral synovitis and with active disease ( pain > or = 40 mm on a 100-mm visual analog scale [ VAS ] and an increase in pain of at least 30 % after nonsteroidal antiinflammatory drug withdrawal ) were eligible for study . Primary outcome measures were change in pain intensity ( VAS ) and change in functional impairment ( Bath Ankylosing Spondylitis Functional Index [ BASFI ] ) . RESULTS Of the 246 r and omized patients , 76 were allocated to receive placebo , 90 ketoprofen , and 80 celecoxib . There were no statistically significant differences between treatment groups at study entry . During the 6 weeks of the study , the decrease in pain and functional impairment was greater in the active treatment groups than in the placebo group , with a trend in favor of celecoxib when the 2 active treatments were compared . The mean changes were -13 mm , -21 mm , and -27 mm ( P = 0.006 ) for pain and 1 , -6 , and -12 ( P = 0.0008 ) for BASFI score in the placebo , ketoprofen , and celecoxib groups , respectively . During treatment , the number of patients reporting epigastric pain was 6 ( 8 % ) , 13 ( 14 % ) , and 10 ( 13 % ) in the placebo , ketoprofen , and celecoxib groups , respectively . CONCLUSION The results of this study confirm the clinical ly relevant antiinflammatory effect of celecoxib at a 200-mg daily dosage , with significant improvement of both pain and function in patients with AS",
"OBJECTIVE To analyze patterns of stress , mood , disease symptoms , and activity reduction in children with polyarticular arthritis , using a prospect i ve daily diary method . METHODS For a 2-month period , 51 children with polyarticular arthritis ( mean age 12.4 years , 65 % female ) completed daily diaries that included measures of symptoms of pain , stiffness , and fatigue , as well as stress , mood , and activity reduction . Functional status and disease activity were assessed at the initial and followup evaluations with use of the Childhood Health Assessment Question naire , physician global assessment , joint count , and laboratory testing . RESULTS Children reported having pain , stiffness , and fatigue on > 70 % of days , with significant variability in symptom levels . Results revealed significant same-day relationships between stress , mood , and disease symptoms , after controlling for covariates . Specifically , daily fluctuations in both stress and mood were predictive of increased pain , stiffness , and fatigue . Increases in daily stress , mood , and disease symptoms were also significantly related to decreased participation in social activities on a day-to-day basis . Only mood and stiffness were predictors of a cutback in school attendance . CONCLUSION Stress and mood are important predictors of daily disease symptoms in children with polyarticular arthritis . Moreover , daily fluctuations in stress , mood , and disease symptoms are predictive of aspects of daily function , including participation in school and social activities . Thus , health care providers should solicit daily symptom reports when making decisions regarding clinical management . Nonpharmacologic interventions such as cognitive-behavioral therapy and stress management may be useful adjuvant therapy when treating the disease symptoms of children with polyarticular arthritis",
"Importance Published evidence on the long-term safety of etanercept ( ETA ) and adalimumab ( ADA ) in patients with polyarticular juvenile idiopathic arthritis ( pJIA ) is still limited . Objectives To investigate the rates of serious adverse events ( SAE ) and of events of special interest ( ESI ) under ETA and ADA treatment . Design , setting and participants Patients with pJIA were prospect ively observed in the national JIA biological register , Biologika in der Kinderrheumatologie , and its follow-up register , Juvenile arthritis Methotrexate/Biologics long-term Observation . Main outcomes and measures We calculated the relative risks of SAE and ESI for ETA and ADA compared with methotrexate ( MTX ) . Results Among the 1414 patients treated with ETA ( n=1414 ; 4461 exposure years ( EY ) ) and ADA ( n=320 ; 493 EY ) , significantly more SAE , infections and medically important infections were observed ( ETA : 4.5 , 5.7 , 0.9 ; ADA : 4.7 , 11.4 , 0.4 per 100 EY ) compared with those treated with MTX alone ( n=1455 ; 2.907 EY ; 2.6 , 5.5 , 0.5 per 100 EY ) . The risk for malignancies was not significantly increased for ETA and ADA compared with MTX ( 0.09 , 0.27 and 0.07/100 person-years ) . Patients under ETA monotherapy developed more frequently incident inflammatory bowel disease ( IBD ) and incident uveitis ( 0.5 and 0.8/100 EY ) than patients treated by ETA in combination with MTX ( 0.1 and 0.2/100 EY ) or MTX alone ( 0.03 and 0.1/100 EY ) . Conclusions and relevance Our data confirm the acceptable long-term tolerability of ETA and ADA in pJIA . However , whether the onset of IBD and uveitis during ETA monotherapy is a paradoxical effect or an inadequate response to therapy remains unclear and requires further investigation in this growing cohort",
"OBJECTIVE To evaluate the safety and efficacy of infliximab in the treatment of juvenile rheumatoid arthritis ( JRA ) . METHODS This was an international , multicenter , r and omized , placebo-controlled , double-blind study . One hundred twenty-two children with persistent polyarticular JRA despite prior methotrexate ( MTX ) therapy were r and omized to receive infliximab or placebo for 14 weeks , after which all children received infliximab through week 44 . Patients received MTX plus infliximab 3 mg/kg through week 44 , or MTX plus placebo for 14 weeks followed by MTX plus infliximab 6 mg/kg through week 44 . RESULTS Although a higher proportion of patients in the 3 mg/kg infliximab group than in the placebo group had achieved responses according to the American College of Rheumatology ( ACR ) Pediatric 30 ( Pedi 30 ) criteria for improvement at week 14 ( 63.8 % and 49.2 % , respectively ) , the between-group difference in this primary efficacy end point was not statistically significant ( P = 0.12 ) . By week 16 , after the crossover from placebo to infliximab 6 mg/kg when all patients were receiving infliximab , an ACR Pedi 30 response was achieved in 73.2 % of all patients . By week 52 , ACR Pedi 50 and ACR Pedi 70 responses had been reached in 69.6 % and 51.8 % , respectively , of patients . Infliximab was generally well tolerated , but the safety profile of infliximab 3 mg/kg appeared less favorable than that of infliximab 6 mg/kg , with more frequent occurrences of serious adverse events , infusion reactions , antibodies to infliximab , and newly induced antinuclear antibodies and antibodies to double-str and ed DNA observed with the 3 mg/kg dose . CONCLUSION While infliximab at 3 mg/kg and 6 mg/kg showed durable efficacy at 1 year , achievement of the primary efficacy end point at 3 months did not differ significantly between infliximab-treated and placebo-treated patients . Safety data indicated that the 6-mg/kg dose may provide a more favorable risk/benefit profile . These results warrant further investigation in children with JRA",
"OBJECTIVE To evaluate the long-term efficacy and safety of etanercept in children with juvenile rheumatoid arthritis ( JRA ) participating in an ongoing multicenter , open-label , extended-treatment trial . All patients had been participants in an initial r and omized efficacy and safety trial of etanercept . METHODS Etanercept was administered at a dosage of 0.4 mg/kg ( maximum 25 mg ) subcutaneously twice each week . Safety and efficacy evaluations were performed every 3 - 4 months . The JRA 30 % definition of improvement ( DOI ) was defined as improvement of > or = 30 % in at least 3 of 6 response variables used to assess disease activity , with no more than 1 variable worsening by more than 30 % . RESULTS At the time of analysis , 48 of the 58 patients ( 83 % ) were still enrolled in the study ; 43 of them ( 74 % ) had completed 2 years of treatment . Of these 43 patients , 81 % met the JRA 30 % DOI , 79 % met the JRA 50 % DOI , and 67 % met the JRA 70 % DOI . Ten children started low-dose methotrexate after year 1 . Of the 32 children taking prednisone , the dosage was decreased to serious infections ( varicella with aseptic meningitis in one and complicated sepsis in the other ) . In general , adverse events were of the types seen in a general pediatric patient population . CONCLUSION Children with severe , longst and ing , methotrexate-resistant polyarticular JRA demonstrated sustained clinical improvement with > 2 years of continuous etanercept treatment . Etanercept was generally well-tolerated . There were no increases in the rates of adverse events over time . However , children taking etanercept should be monitored closely for infections",
"OBJECTIVE To evaluate the efficacy and safety of methotrexate ( MTX ) compared with placebo in patients with active ankylosing spondylitis ( AS ) . METHODS This 24 week , double bind , r and omized , placebo controlled trial compared the response between MTX 7.5 mg/week or placebo in patients with active AS . The primary outcome measure was a composite index of improvement in 5 of the following scales : severity of morning stiffness , physical well being , the Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) , the Bath Ankylosing Spondylitis Functional Index ( BASFI ) , the Health Assessment Question naire for Spondyloarthropathies ( HAQ-S ) , and physician and patient global assessment of disease activity . RESULTS Seventeen patients received MTX and 18 placebo . In the intention-to-treat analysis at 24 weeks , 53 % of patients in the MTX group had a treatment response , compared with 17 % in the placebo group ( p = 0.03 ) . We observed significant improvements with MTX in physical well being ( p = 0.009 ) , BASDAI ( p = 0.02 ) , BASFI ( p = 0.02 ) , physician global assessment ( p patient global assessment ( p = 0.03 ) , and HAQ-S ( p = 0.02 ) . In the adjusted analysis only MTX determined the improvement in the primary outcome . At the end of the trial , one patient with MTX withdrew due to a lack of compliance , and one with placebo due to a lack of efficacy . We did not observe significant differences in rates of side effects between the 2 groups . CONCLUSION MTX is safe and effective for patients with AS . Longterm studies are needed to evaluate the permanence of its benefit",
"OBJECTIVE To analyze patterns of daily pain , stiffness , and fatigue related to juvenile arthritis ; to examine the relationships of demographics , disease severity , and psychological adjustment to daily disease symptoms ; and to examine daily disease symptoms as predictors of reduced participation in school and social activity . METHODS For a 2-month period , 41 children with polyarticular juvenile arthritis completed daily diaries that included measures of symptoms and function . Children also underwent an initial evaluation and 4 followup evaluations that included a joint count , laboratory testing , and completion of question naires assessing physical and psychosocial functioning . RESULTS Children reported having pain an average of 73 % of days , with the majority of children ( 76 % ) reporting pain on > 60 % of all days . On average , children described the intensity of their daily pain as being in the mild to moderate range ; however , a significant subgroup ( 31 % ) reported pain in the severe range . Higher physician global assessment ratings , increased functional disability , and increased anxiety were significantly associated with increased daily pain and other daily symptoms . Multilevel r and om-effects analyses indicated that increased daily symptoms of pain , stiffness , and fatigue were significant predictors of reduced participation in school and social activities . CONCLUSION Physicians should consider treating pain more aggressively in children with arthritis , in order to preserve function in school and social domains , as well as physical function . Moreover , optimal pain management in children with arthritis should include therapeutic regimens addressing anxiety as well as st and ard pharmacologic interventions",
"Since the introduction of intra-articular steroid therapy 40 yr ago there have been many changes in the treatment of rheumatoid patients . Previous studies suggest differing times of response for the same agents . This study reports the response , measured by a five-point pain chart , of 300 patients with painful rheumatoid knees . Sixty received hydrocortisone succinate ( HC ) , 150 received triamcinolone acetonide ( TA ) , and 120 triamcinolone hexacetonide ( TH ) . Results demonstrated little effect with HC , but good responses with TA and TH . More patients were rendered painfree for a longer time with TH ; 18 % at 12 weeks , as against 9 % with TA ( chi 2 test P improvement with TH as against 44 % with TA ( chi 2 test P < 0.05 ) . TH is the preferred preparation for injection of the rheumatoid knee",
"Objective To investigate the effects of electromyographic ( EMG ) biofeedback training on pain , quadriceps strength , and functional ability in juvenile rheumatoid arthritis ( JRA ) . Design This is a r and omized controlled study ; 36 children ( 11 boys and 25 girls ) with polyarticular JRA , with ages ranging from 8 to 13 years , were selected and assigned r and omly , using computer-generated r and om numbers , into 2 groups . The control group ( n = 18 ) received the conventional physical therapy program , whereas the study group ( n = 18 ) received the same program as the control group in addition to EMG biofeedback-guided isometric exercises for 3 days a week for 12 weeks . Pain , peak torque of quadriceps strength , and functional ability were evaluated before , after 6 weeks , and at the end of 12 weeks of the treatment program . Results By 6 weeks , significant differences were observed in the study group ( P pain levels , whereas nonsignificant differences were observed in all measured variables in the control group . By 12 weeks , each group demonstrated significant improvements in pain , quadriceps strength , and functional ability ( P reduce pain , improve quadriceps strength , and functional performance in JRA",
"Objective : To examine the potential therapeutic effect of methotrexate 20 mg given weekly as subcutaneous injections to 20 patients with ankylosing spondylitis refractory to non-steriodal antirheumatic drugs . Patients and methods : 20 patients with ankylosing spondylitis , a mean Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) score of 5.6 ( range 4–9.3 ) and predominantly axial manifestations were treated with weekly 15 mg methotrexate subcutaneously for 4 weeks , which was then increased to 20 mg subcutaneously for the next 12 weeks . Clinical outcome assessment s included , among others , BASDAI score physical function , spinal mobility , patients ’ and physicians ’ global assessment ( visual analogue scale ) , peripheral joint assessment , quality of life ( Short Form 36 ) and C reactive protein . The primary end point of the study was a 20 % improvement on the ASsessment s in Ankylosing Spondylitis ( ASAS 20 ) scale . Results : Using an intention-to-treat analysis , ASAS 20 was achieved in only 25 % of patients . An ASAS 40 response was achieved in 10 % of patients , and no patient reached an ASAS 70 response or the ASAS criteria for partial remission . For the mean BASDAI score , no change was observed between baseline and week 16 ( baseline 5.6 v week 16 , 5.6 ) . No improvement was observed in any of the clinical parameters or C reactive protein , except a small but non-significant decrease in the number of swollen joints . Conclusions : In this open study , methotrexate did not show any benefit for axial manifestations in patients with active ankylosing spondylitis beyond the expected placebo response",
"Objective . To compare child self-report and parent/proxy report of health-related quality of life ( HRQOL ) , disability , and fatigue in children with active polyarticular juvenile idiopathic arthritis ( JIA ) to that of children with inactive polyarticular JIA and to previous data from healthy controls . Methods . Cross-sectional survey of children with polyarticular JIA diagnosed and treated between 2000 to 2006 and their parent/proxy . The Childhood Health Assessment Question naire , Pediatric Quality of Life Inventory ( PedsQL ) Generic Core Scales , PedsQL Rheumatology Module , and PedsQL Multidimensional Fatigue Scale were administered . Disease activity data were collected from the physician clinic notes . Comparisons were performed with t tests . Correlations between patient and parent/proxy reports were measured with Pearson correlation coefficients . Results . Sixty children and /or their parents/proxies participated ( 79 % response rate ) . Disease activity status was available for 52 , and 32 met criteria for inactive disease ( 62 % ) . Participants reported lower scores on the PedsQL Generic Core Scales ( range 2.54–9.13 points lower ) and the PedsQL Rheumatology Module ( range 2.46–6.96 points lower ) than those with inactive disease . Participants also reported lower scores on the PedsQL Multidimensional Fatigue Scale than did healthy controls , regardless of disease activity status ( range 0.06–9.2 points lower ) . Conclusion . Although children in this cohort with polyarticular JIA and inactive disease reported HRQOL scores similar to those of healthy controls , children with polyarticular JIA and their parents/proxies tended to report more fatigue than controls , regardless of disease activity . Application of these measures prospect ively to larger cohorts of children with JIA is needed to assess these differences",
"We report long-term safety & efficacy of infliximab (IFX)+ methotrexate ( MTX ) treatment in JRA patients . In an international , multicenter , r and omized , double-blind study , 122 children w/active polyarticular JRA despite prior MTX therapy received MTX plus a 3-dose induction ( wks 0 , 2 , 6 ) of IFX 3 mg/kg through wk 44 , or placebo ( PBO ) for 14 wks followed by IFX 6 mg/kg ( wks 14 , 16 , 20 , & then q8 wks ) through wk 44 . Patients completing treatment through wk 44 were eligible to enter an open-label extension ( OLE ) of IFX 3 mg/kg , beginning at wk 52 & continuing q8 wks through wk 196 . All patients continued with concomitant MTX . Physicians could increase or decrease the IFX dose by ≤1.5 mg/kg/infusion q8 wks , up to 6 mg/kg or down to 3 mg/kg , based on clinical response . Primary endpoint was the proportion of patients meeting ACR-Pedi-30 , defined as improvement of ≥30 % in ≥3 of 6 core variables , & ≤1 of the remaining variables worsened by > 30 % . Remission was defined as 0 joints with active arthritis , normal ESR , & physician 's global assessment ≤10 mm on a 10-cm visual analog scale . 78/122(63.9 % ) children entered the OLE . The mean(SD ) IFX dose at wk 196 was 4.4(1.6)mg/kg . IFX was well-tolerated;14.1 % of patients discontinued due to adverse events ( AE ) from wks 52–204 . The distribution/types of AE were similar to those in the first 52 wks & no new safety issues were reported . Among the 36 study patients by wk 204 , ACR-Pedi-30/50/70/90 responses were 91.7%(33/36 ) , 83.3%(30/36 ) , 69.4%(25/36 ) , & 50%(18/36 ) , respectively . 39%(14/36 ) of patients achieved remission . From wk 52 through wk 216 , 36.6%(26/71 ) of patients were positive for IFXantibodies ; 57.7%(15/26 ) of these had an infusion reaction . Continuous IFX+MTX administered up to 4 yrs was safe & effective in JRA patients , although accompanied by a high rate of patient discontinuation , which included subjects in remission",
"OBJECTIVE To evaluate the clinical relevance of CRP in AS and investigate the treatment effect of NSAIDs/coxibs on CRP . METHODS Data of 851 patients with painful axial AS participating in two r and omized controlled trials evaluating coxibs ( celecoxib ) and NSAIDs ( naproxen/ketoprofen ) were used . The clinical relevance of CRP in AS was studied : the number of patients with abnormal CRP at baseline was expressed as a percentage , and the correlation among CRP , patient ( age and gender ) and disease [ Bath AS Disease Activity Index ( BASDAI ) , Bath AS Functional Index ( BASFI ) ] characteristics was investigated . The st and ardized response mean ( SRM ) over placebo was used to detect the treatment effect of NSAIDs/coxibs on CRP . RESULTS The 851 enrolled patients ( 73 % of whom were men ) had an active disease , as assessed through functional impairment . Mean ( s.d . ) baseline CRP was 14 ( 19 ) ( median 7.2 ) mg/l ; 61 % of patients had an increased CRP . The CRP levels were correlated positively with male sex , BASDAI and BASFI and negatively with age ( multivariate analysis ) . There was a significant difference in the changes of CRP between placebo and NSAIDs/coxibs group ( P = 0.003 ; SRM over placebo : 0.25 ) . Such a treatment effect was of higher magnitude in the subgroup of patients with increased CRP and usually of lower magnitude than the treatment effect of other outcome variables such as BASDAI and BASFI . CONCLUSIONS Increased CRP was frequently observed in patients with painful axial AS and was correlated both with activity and functional severity of the disease . The treatment effect of NSAIDs/coxibs was relevant in the subgroup of patients with increased CRP at baseline",
"OBJECTIVE To determine whether aggressive treatment initiated early in the course of rheumatoid factor (RF)-positive or RF-negative polyarticular juvenile idiopathic arthritis ( JIA ) can induce clinical inactive disease within 6 months . METHODS Between May 2007 and October 2010 , a multicenter , prospect i ve , r and omized , double-blind , placebo-controlled trial of 2 aggressive treatments was conducted in 85 children ages 2 - 16 years with polyarticular JIA of Patients received either methotrexate ( MTX ) 0.5 mg/kg/week ( maximum 40 mg ) subcutaneously , etanercept 0.8 mg/kg/week ( maximum 50 mg ) , and prednisolone 0.5 mg/kg/day ( maximum 60 mg ) tapered to 0 by 17 weeks ( arm 1 ) , or MTX ( same dosage as arm 1 ) , etanercept placebo , and prednisolone placebo ( arm 2 ) . The primary outcome measure was clinical inactive disease at 6 months . An exploratory phase determined the rate of clinical remission on medication ( 6 months of continuous clinical inactive disease ) at 12 months . RESULTS By 6 months , clinical inactive disease had been achieved in 17 ( 40 % ) of 42 patients in arm 1 and 10 ( 23 % ) of 43 patients in arm 2 ( χ(2 ) = 2.91 , P = 0.088 ) . After 12 months , clinical remission on medication was achieved in 9 patients in arm 1 and 3 patients in arm 2 ( P = 0.053 ) . There were no significant interarm differences in adverse events . CONCLUSION Although this study did not meet its primary end point , early aggressive therapy in this cohort of children with recent-onset polyarticular JIA result ed in clinical inactive disease by 6 months and clinical remission on medication within 12 months of treatment in substantial proportions of patients in both arms"
] |
4116c914-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND Work-related musculoskeletal disorders are a group of musculoskeletal disorders that comprise one of the most common disorders related to occupational sick leave worldwide . Musculoskeletal disorders accounted for 21 % to 28 % of work absenteeism days in 2017/2018 in the Netherl and s , Germany and the UK . There are several interventions that may be effective in tackling the high prevalence of work-related musculoskeletal disorders among workers , such as physical , cognitive and organisational interventions . In this review , we will focus on work breaks as a measure of primary prevention , which are a type of organisational intervention . OBJECTIVES To compare the effectiveness of different work-break schedules for preventing work-related musculoskeletal symptoms and disorders in healthy workers , when compared to conventional or alternate work-break schedules . SEARCH METHODS We search ed the Cochrane Central Register of Controlled Trials ( CENTRAL ) , MEDLINE , Embase , CINAHL , PsycINFO , SCOPUS , Web of Science , Clinical Trials.gov and the World Health Organization International Clinical Trials Registry Platform , to April/May 2019 . In addition , we search ed references of the included studies and of relevant literature review s. SELECTION CRITERIA We included r and omised controlled trials ( RCTs ) of work-break interventions for preventing work-related musculoskeletal symptoms and disorders among workers . The studies were eligible for inclusion when intervening on work-break frequency , duration and /or type , compared to conventional or an alternate work-break intervention . We included only those studies in which the investigated population included healthy , adult workers , who were free of musculoskeletal complaints during study enrolment , without restrictions to sex or occupation . The primary outcomes were newly diagnosed musculoskeletal disorders , self-reported musculoskeletal pain , discomfort or fatigue , and productivity or work performance . We considered workload changes as secondary outcomes . DATA COLLECTION AND ANALYSIS Two review authors independently screened titles , abstract s and full texts for study eligibility , extracted data and assessed risk of bias . We contacted authors for additional study data where required . We performed meta-analyses , where possible , and we assessed the overall quality of the evidence for each outcome of each comparison using the five GRADE considerations . MAIN RESULTS We included six studies ( 373 workers ) , four parallel RCTs , one cross-over RCT , and one combined parallel plus cross-over RCT . At least 295 of the employees were female and at least 39 male ; for the remaining 39 employees , the sex was not specified in the study trial . The studies investigated different work-break frequencies ( five studies ) and different work-break types ( two studies ) . None of the studies investigated different work-break duration s. We judged all studies to have a high risk of bias . The quality of the evidence for the primary outcomes of self-reported musculoskeletal pain , discomfort and fatigue was low ; the quality of the evidence for the primary outcomes of productivity and work performance was very low . The studies were executed in Europe or Northern America , with none from low- to middle-income countries . One study could not be included in the data analyses , because no detailed results have been reported . Changes in the frequency of work breaksThere is low- quality evidence that additional work breaks may not have a considerable effect on musculoskeletal pain , discomfort or fatigue , when compared with no additional work breaks ( st and ardised mean difference ( SMD ) -0.08 ; 95 % CI -0.35 to 0.18 ; three studies ; 225 participants ) . Additional breaks may not have a positive effect on productivity or work performance , when compared with no additional work breaks ( SMD -0.07 ; 95 % CI -0.33 to 0.19 ; three studies ; 225 participants ; very low- quality evidence ) .We found low- quality evidence that additional work breaks may not have a considerable effect on participant-reported musculoskeletal pain , discomfort or fatigue ( MD 1.80 on a 100-mm VAS scale ; 95 % CI -41.07 to 64.37 ; one study ; 15 participants ) , when compared to work breaks as needed ( i.e. microbreaks taken at own discretion ) . There is very low- quality evidence that additional work breaks may have a positive effect on productivity or work performance , when compared to work breaks as needed ( MD 542.5 number of words typed per 3-hour recording session ; 95 % CI 177.22 to 907.78 ; one study ; 15 participants ) .Additional higher frequency work breaks may not have a considerable effect on participant-reported musculoskeletal pain , discomfort or fatigue ( MD 11.65 on a 100-mm VAS scale ; 95 % CI -41.07 to 64.37 ; one study ; 10 participants ; low- quality evidence ) , when compared to additional lower frequency work breaks . We found very low- quality evidence that additional higher frequency work breaks may not have a considerable effect on productivity or work performance ( MD -83.00 number of words typed per 3-hour recording session ; 95 % CI -305.27 to 139.27 ; one study ; 10 participants ) , when compared to additional lower frequency work breaks . Changes in the duration of work breaksNo trials were identified that assessed the effect of different duration s of work breaks . Changes in the type of work breakWe found low- quality evidence that active breaks may not have a considerable positive effect on participant-reported musculoskeletal pain , discomfort and fatigue ( MD -0.17 on a 1 - 7 NRS scale ; 95 % CI -0.71 to 0.37 ; one study ; 153 participants ) , when compared to passive work breaks . Relaxation work breaks may not have a considerable effect on participant-reported musculoskeletal pain , discomfort or fatigue , when compared to physical work breaks ( MD 0.20 on a 1 - 7 NRS scale ; 95 % CI -0.43 to 0.82 ; one study ; 97 participants ; low- quality evidence ) . AUTHORS ' CONCLUSIONS We found low- quality evidence that different work-break frequencies may have no effect on participant-reported musculoskeletal pain , discomfort and fatigue . For productivity and work performance , evidence was of very low- quality that different work-break frequencies may have a positive effect . For different types of break , there may be no effect on participant-reported musculoskeletal pain , discomfort and fatigue according to low- quality evidence . Further high- quality studies are needed to determine the effectiveness of frequency , duration and type of work-break interventions among workers , if possible , with much higher sample sizes than the studies included in the current review . Furthermore , work-break interventions should be reconsidered , taking into account worker population s other than office workers , and taking into account the possibility of combining work-break intervention with other interventions such as ergonomic training or counselling , which may may possibly have an effect on musculoskeletal outcomes and work performance
|
[
"BACKGROUND This study exp and ed previous NIOSH-IRS research examining the effects of rest breaks and stretching exercises on symptoms and performance in data -entry workers . METHODS All workers spent 4 weeks with conventional breaks ( two 15 min breaks per day ) and 4 weeks with supplementary breaks ( two 15 min breaks plus four 5 min breaks per day ) . One-half were assigned at r and om to a group instructed to perform brief stretching exercises during breaks . The remainder comprised the \" no stretching \" ( control ) group . RESULTS 51 workers ( stretch group n = 21 ; no stretch group n = 30 ) completed the study symptom question naires . Discomfort and eyestrain were significantly lower with supplementary breaks , and supplementary breaks attenuated accumulation of discomfort and eyestrain during work sessions . Data -entry speed was significantly faster with supplementary breaks so that work output was maintained , despite replacing 20 min of work time with break time . In the stretch group , workers reported stretching during only 25 % of conventional breaks and 39 % of supplementary breaks , and no significant effects of stretching on discomfort or performance were observed . CONCLUSIONS These results provide further converging evidence that supplementary breaks reliably minimize discomfort and eyestrain without impairing productivity . Low compliance in performing stretches prevented valid assessment of stretching effects . Further research on stretching exercises and exercise compliance is warranted",
"Background Intermittent work breaks are common in fields with high workload but not yet for surgeons during operations . We evaluated the effects of intraoperative breaks during complex laparoscopic surgery ( 5 min every half hour ) on the surgeon . Methods Fifty-one operations were r and omized to a scheme with intraoperative breaks and release of the pneumoperitoneum ( intermittent pneumoperitoneum ( IPP ) ) or conventional conduct ( CPP ) . Stress hormones and α-amylase were determined in the surgeon ’s saliva pre- , intra- , and postoperatively . Mental performance and error scores , musculoskeletal strain , and continuous ECG were secondary endpoints . Results Regular intraoperative breaks did not prolong the operation ( IPP vs. CPP group : 176 vs. 180 min , p > 0.05 ) . The surgeon ’s cortisol levels during the operation were reduced by 22 ± 10.3 % in the IPP vs. the CPP group ( p intraoperative events in the IPP vs. the CPP group , which yielded higher α-amylase peaks . The pre- to postoperative increase in the error rates of the bp-concentration test was fourfold reduced in the IPP group ( p = 0.052 ) . The relevant locomotive strain-scores were grossly reduced by IPP ( p reduce psychological stress and preserve performance without prolongation of the operation time compared with the traditional work scheme",
"Background The etiology of de Quervain 's tenosynovitis ( dQ ) has been based on conflicting small case series and cohort studies lacking method ological rigor . A prospect i ve case-control study was conducted to analyze the most common risk factors for dQ. Methods Between January 2003 and May 2011 , 189 patients surgically treated for dQ vs. 198 patients with wrist ganglia ( WG ) ( controls ) were identified in our clinic ’s electronic data base . Sample characteristics , exertional , anatomical , and medical risk factors were compared between groups . Results dQ vs. WG differed by average age ( 52 vs. 43 years ) and gender ratio ( 15/62 vs. 26/39 ) . No significant difference between dQ vs. WG was found after subgrouping professional activities ( manual labor : 18 % vs. 26 % , respectively , p = 0.23 ) . No asymmetric distribution of comorbidities , wrist trauma , forceful or repetitive manual work , or medication was observed . Conclusions Neither heavy manual labor nor trauma could be shown to be predisposing risk factors for",
"There is limited research on the effects of different types of rest-break interventions for visual display unit ( VDU ) operators on neck and shoulder postures . This study examined the effect of rest-break interventions on the neck and shoulder postures of symptomatic VDU operators during prolonged computer work . Thirty subjects were r and omly and equally assigned to breaks with stretching , breaks with dynamic movement and passive breaks . Subjects performed the typing task for 60 min and received 3-min breaks after 20 min of work . The craniovertebral and forward shoulder angles were obtained from a 3D motion analysis system . Results showed that there were no significant differences in the craniovertebral and forward shoulder angles among any types of rest breaks . It can be concluded that the three types of rest-break interventions had positive effects on neck and shoulder posture during prolonged computer terminal work",
"The abbreviated vigilance task can quickly generate vigilance decrements , which has been argued is due to depletion of cognitive re sources needed to sustain performance . Research ers suggest inclusion of rest breaks within vigilance tasks improve overall performance ( Helton & Russell , 2015 ; Ross , Russell , & Helton , 2014 ) , while different types of breaks demonstrate different effects . Some literature suggests exposure to natural movements/stimuli helps restore attention ( Herzog , Black , Fountaine , & Knotts , 1997 ; Kaplan , 1995 ) . Participants were r and omly assigned to one experimental condition : dog video breaks , robot video breaks , countdown breaks or continuous vigilance . We assessed task performance and subjective reports of stress/workload . The continuous group displayed worst performance , suggesting breaks help restore attention . The dog videos did not affect performance , however , decreased reports of distress . These results support the importance of rest breaks and acknowledge the benefit of natural stimuli for promoting wellbeing/stress relief , overall suggesting performance and wellbeing may be independent , which warrants future studies",
"Objective . This study evaluated the effect of different types of activities during rest-break interventions on neck and shoulder muscle activity , muscle discomfort and productivity among symptomatic video display unit ( VDU ) operators performing prolonged computer terminal work . Study design and setting . R and omized controlled trial was used . Thirty symptomatic VDU operators were r and omly assigned to 2 active break groups ( stretching and dynamic movement ) and a reference group . The subjects performed the same typing task for 60 min and received 3-min breaks after each 20 min of work . Root mean square and median frequency were calculated for neck and shoulder muscle activity . Muscle discomfort was measured with Borg ’s CR-10 scale . Productivity was measured by counting words . Results . There were no significant differences between the types of activities during breaks on neck and shoulder muscle activity , muscle discomfort or productivity . However , there was a significant difference in the level of muscle discomfort over time . Conclusions . Three types of activity during breaks showed a favourable effect on neck and shoulder muscle activity and productivity , and a positive effect on muscle discomfort in symptomatic VDU operators",
"This study examined the effects of supplementary rest breaks on musculoskeletal discomfort , eyestrain , mood , and performance in data -entry workers . Two rest break schedules were compared in a within-subjects design . Workers alternated between a ‘ conventional ’ and a ‘ supplementary ’ schedule in 4-week intervals . The conventional schedule contained a 15-min break during the first half of the work shift and a 15-min break during the second half of the shift . The supplementary schedule contained the same two 15-min breaks , and a 5-min break during each hour which otherwise did not contain a break , for a total of 20 extra minutes of break time . Results are based on data from 42 workers . They indicated that discomfort in several areas of the body , and eyestrain , were significantly lower under the supplementary than under the conventional schedule . While symptoms increased from pre- to post-work periods under both schedules , the magnitude of the increases was significantly less under the supplementary schedule . In addition , increases in discomfort of the right forearm , wrist and h and over the course of the work week under the conventional schedule were eliminated under the supplementary schedule . These beneficial effects were obtained without reductions in data -entry performance",
"Background To prolong sustainable healthy working lives of construction workers , a worksite prevention program was developed which aim ed to improve the health and work ability of construction workers . The aim of the current study was to investigate the effectiveness of this program on social support at work , work engagement , physical workload and need for recovery . Methods Fifteen departments from six construction companies participated in this cluster r and omized controlled trial ; 8 departments ( n=171 workers ) were r and omized to an intervention group and 7 departments ( n=122 workers ) to a control group . The intervention consisted of two individual training sessions of a physical therapist to lower the physical workload , a Rest-Break tool to improve the balance between work and recovery , and two empowerment training sessions to increase the influence of the construction workers at the worksite . Data on work engagement , social support at work , physical workload , and need for recovery were collected at baseline , and at three , six and 12 months after the start of the intervention using question naires . Results No differences between the intervention and control group were found for work engagement , social support at work , and need for recovery . At 6 months follow-up , the control group reported a small but statistically significant reduction of physical workload . Conclusion The intervention neither improved social support nor work engagement , nor was it effective in reducing the physical workload and need for recovery among construction workers . Trial registration",
"In direct proportion to current technological developments , both the computer usage in the workplaces is increased and requirement of leaving the desk for an office worker in order to photocopy a document , send or receive an e-mail is decreased . Therefore , office workers stay in the same postures accompanied by long periods of keyboard usage . In recent years , with intent to reduce the incidence of work related musculoskeletal disorders several exercise reminder software programs have been developed . The purpose of this study is to evaluate the effectiveness of the exercise reminder software program on office workers ' perceived pain level , work performance and quality of life . 39 healthy office workers accepted to attend the study . Participants were r and omly split in to two groups , control group ( n = 19 ) and intervention group ( n = 20 ) . Visual Analogue Scale to evaluate the perceived pain was administered all of the participants in the beginning and at the end of the study . The intervention group used the program for 10 weeks . Findings showed that the control group VAS scores remained the same , but the intervention group VAS scores decreased in a statistically significant way ( p exercise reminder software programs may help to reduce perceived pain among office workers . Further long term studies with more subjects are needed to describe the effects of these programs and the mechanism under these effects",
"Workers in physically dem and ing occupations require rest breaks to recover from physiological stress and biomechanical loading . Physiological stress can increase the risk of developing musculoskeletal disorders and repeated loading of the spine may increase the potential for incurring back pain . The aim of the study was to assess the impact of an altered activity-rest schedule on physiological and spinal loading in hospital-based porters . An existing 4-h activity-rest schedule was obtained from observations on eight male porters . This schedule formed the normal trial , which included two 5- and one 15-min breaks . An alternative 4-h schedule was proposed ( experimental condition ) that had two breaks each of 12.5 min . It was hypothesized that the experimental trial is more effective in promoting recovery from physiological strain and spinal shrinkage than the normal trial , due to the 5-min breaks being insufficient to allow physiological variables to return to resting levels or the intervertebral discs to reabsorb fluid . Ten males performed both test conditions and oxygen uptake VO2 , heart rate , minute ventilation VE , perceived exertion and spinal shrinkage were recorded . There were no significant differences in any of the measured variables between the two trials ( p > 0.05 ) . Median heart rates were 78 ( range 71–93 ) and 82 ( 71–90 ) beats.min - 1 for the normal trial and the experimental trial respectively , indicating that the activity was of low intensity . The light intensity was corroborated by the oxygen uptakes ( 0.75 , range 0.65 - 0.94 l.min - 1 . Spinal shrinkage occurred to the same extent in the two trials ( 2.12±3.16 mm and 2.88±2.92 mm in the normal trial and the experimental trial respectively ) . Varying the length and positioning of the rest breaks did not significantly affect the physiological responses or magnitude of spinal shrinkage between the two trials . More physically dem and ing work than the porters ' schedule should induce greater physiological fatigue and spinal shrinkage . The ratio between activity and rest breaks would then become more important",
"Neck and shoulder disorders are a considerable health problem amongst frequent microscope users . We aim ed to investigate the neck and shoulder discomfort experienced during prolonged microscopic activity and to assess the benefits of minibreaks . A prospect i ve crossover study was performed on 17 healthy volunteers sitting still while looking down a bench with and without the Ipswich Microbreak Technique ( IMT ) . We used a subjective measure of time to fatigue and pain in the neck and shoulder regions as well as objective readings from a surface electromyogram ( sEMG ) . The IMT delayed the sensation of pain in the neck and shoulder region while reducing the overall sEMG muscle activation . In conclusion , IMT is a useful strategy in reducing and delaying the pain in neck and shoulder from prolonged working under the microscope . This technique can be incorporated in other activities that involve a sustained stationary position",
"Introduction The 15-minute work break provides an opportunity to promote health , yet few studies have examined this part of the workday . We studied physical activity and sedentary behavior among office workers and compared the results of the Booster Break program with those of a second intervention and a control group to determine whether the Booster Break program improved physical and behavioral health outcomes . Methods We conducted a 3-arm , cluster-r and omized controlled trial at 4 worksites in Texas from 2010 through 2013 to compare a group-based , structured Booster Break program to an individual-based computer-prompt intervention and a usual-break control group ; we analyzed physiologic , behavioral , and employee measures such as work social support , quality of life , and perceived stress . We also identified consistent and inconsistent attendees of the Booster Break sessions . Results We obtained data from 175 participants ( mean age , 43 y ; 67 % racial/ethnic minority ) . Compared with the other groups , the consistent Booster Break attendees had greater weekly pedometer counts ( P sedentary behavior and self-reported leisure-time physical activity ( P in triglyceride concentrations ( P = .02 ) ( levels remained within the normal range ) . Usual-break participants significantly increased their body mass index , whereas Booster Break participants maintained body mass index status during the 6 months . Overall , Booster Break participants were 6.8 and 4.3 times more likely to have decreases in BMI and weekend sedentary time , respectively , than usual-break participants . Conclusion Findings varied among the 3 study groups ; however , results indicate the potential for consistent attendees of the Booster Break intervention to achieve significant , positive changes related to physical activity , sedentary behavior , and body mass index",
"Objectives I-Preventive is a digital preventive tool for musculoskeletal disorders ( MSDs ) in computer workers . We sought to determine its impact on pain in computer workers with upper limb MSDs and visual discomfort . Methods We conducted a pilot cluster r and omised trial in 2 different sites of a tyre factory in France . We r and omised 200 employees to either an intervention group ( I-Preventive ) or control group , each comprising symptomatic and asymptomatic employees . The workers were followed up for 5 months . The main outcome was overall recovery from symptoms following 1 month 's intervention based on Nordic-style and eyestrain question naires . Results We included 185/200 workers : 96 in the intervention group ( mean age 41.8±1.4 years ; 88.5 % males ) and 79 in the control group ( mean age 42.9±12.0 years ; 94.5 % males ) . The most painful areas ( numerical scale ≥2 ) were the neck ( 40.0 % ) , upper back ( 18.8 % ) and shoulders ( 15.7 % ) . For the most painful anatomical area , the Nordic score significantly decreased after 1 month in the intervention group ( p=0.038 ) ; no change was observed in the control group ( p=0.59 ) . After 1 month 's use , the intervention group reported less pain in the painful area and less visual discomfort symptoms ( p=0.02 ) . Adherence to the I-Preventive program was 60 % . Conclusions I-Preventive is effective in the short term on musculoskeletal symptoms and visual discomfort by promoting active breaks and eyestrain treatment . This easy-to-use digital tool allows each worker to focus on areas of their choice via personalised , easy exercises that can be performed in the workplace . Trial registration number NCT02350244 ; Pre- results",
"Background Interventions design ed to increase workplace physical activity may not automatically reduce high volumes of sitting , a behaviour independently linked to chronic diseases such as obesity and type II diabetes . This study compared the impact two different walking strategies had on step counts and reported sitting times . Methods Participants were white-collar university employees ( n = 179 ; age 41.3 ± 10.1 years ; 141 women ) , who volunteered and undertook a st and ardised ten-week intervention at three sites . Pre-intervention step counts ( Yamax SW-200 ) and self-reported sitting times were measured over five consecutive workdays . Using pre-intervention step counts , employees at each site were r and omly allocated to a control group ( n = 60 ; maintain normal behaviour ) , a route-based walking group ( n = 60 ; at least 10 minutes sustained walking each workday ) or an incidental walking group ( n = 59 ; walking in workday tasks ) . Workday step counts and reported sitting times were re-assessed at the beginning , mid- and endpoint of intervention and group mean± SD steps/day and reported sitting times for pre-intervention and intervention measurement points compared using a mixed factorial ANOVA ; paired sample -t-tests were used for follow-up , simple effect analyses . Results A significant interactive effect ( F = 3.5 ; p counts . Daily steps for controls decreased over the intervention period ( -391 steps/day ) and increased for route ( 968 steps/day ; t = 3.9 , p for reported sitting times , but average values did decrease relative to the control ( routes group = 7 minutes/day ; incidental group = 15 minutes/day ) . Reductions were most evident for the incidental group in the first week of intervention , where reported sitting decreased by an average of 21 minutes/day ( t = 1.9 ; p increased physical activity in white-collar employees . Our data suggests that workplace walking , particularly through incidental movement , also has the potential to decrease employee sitting times , but there is a need for on-going research using concurrent and objective measures of sitting , st and ing and walking",
"OBJECTIVES This study evaluated the effects on work-related neck and upper-limb disorders among computer workers stimulated ( by a software program ) to take regular breaks and perform physical exercises . Possible effects on sick leave and productivity were studied as well . A r and omized controlled design was used with cluster r and omization . Altogether 268 computer workers with complaints in the neck or an upper limb from 22 office locations were r and omized into a control group , one intervention group stimulated to take extra breaks and one intervention group stimulated to perform exercises during the extra breaks during an 8-weekperiod . Question naires were administered before and after the intervention , and questions were generated by the software during the intervention period . Computer usage was recorded online . RESULTS The data on self-reported recovery suggested a favorable effect ; more subjects in the intervention groups than in the control group reported recovery ( 55 % versus 34 % ) from their complaints and fewer reported deterioration ( 4 % versus 20 % ) . However , a comparison between the reported pre- and postintervention scores on the severity and frequency of the complaints showed no significant differences in the change among the three groups . No effects on sick leave were observed . The subjects in the intervention groups showed higher productivity . CONCLUSIONS The use of a software program stimulating workers to take regular breaks contributes to perceived recovery from neck or upper-limb complaints . There seems to be no additional effects from performing physical exercises during these breaks",
"Introduction This study aims to investigate the relationship between work-related physical and psychosocial characteristics and complaints of the neck , shoulder and forearm/h and s. Methods Data were used from a prospect i ve Dutch cohort study among computer office workers with a follow-up period of 2 years . The study was conducted among 264 computer users . Physical and psychosocial risk factors were tested to predict the occurrence of neck , shoulder and forearm/h and s complaints . Bivariate and multivariable logistic regression was used to identify the association between risk factors and outcome variables . Results The 2 year follow-up prevalence rates with 95 % CI for neck complaints were 0.31 ( 0.28–0.37 ) , for shoulder complaints 0.33 ( 0.27–0.39 ) and for forearm/h and s complaints 0.21 ( 0.14–0.28 ) . Four main predictors for the occurrence of neck and shoulder complaints were identified : ( 1 ) Irregular head and body posture [ OR : 1.1 ( 1.0–1.2 ) P = 0.04 ] ; ( 2 ) task difficulty ( job dem and s ) [ OR : 1.2 ( 1.0–1.5 ) P = 0.01 ] ; ( 3 ) number of working hours/day with the computer [ OR : 1.20 ( 1.0–1.4 ) P = 0.03 ] ; and ( 4 ) having had a previous history of complaints [ OR : 7.2 ( 3.8–13.2 ) P = 0.01 ] . Two predictors were identified for forearm/h and s complaints : time pressure ( job dem and s ) [ OR : 1.20 ( 1.0–1.4 ) P = 0.03 ] and having had a previous history of complaints [ OR : 7.1 ( 3.5–14.1 ) P = 0.06 ] . Conclusion This longitudinal study suggests that risk factors of upper musculoskeletal complaints in computer workers consist of a mixture of physical and psychosocial characteristics",
"OBJECTIVE This study aim ed to investigate the effectiveness of a prevention program on work ability , health , and sick leave targeted at construction worksites . METHODS A total of 15 departments ( N = 297 workers ) from 6 construction companies participated in this cluster r and omized controlled trial and were r and omly allocated to the intervention ( 8 departments ; N = 171 workers ) or control ( 7 departments ; N = 122 workers ) group . The intervention consisted of two individual training sessions with a physical therapist aim ed at lowering the physical workload , a rest-break tool to improve the balance between work and recovery , and two empowerment training sessions to increase the worker 's influence at the worksite . Data on work ability , physical and mental health status , and musculoskeletal symptoms were collected at baseline , and at 3 , 6 , and 12 months follow-up . Sick leave data were obtained from the companies . RESULTS Overall , no differences in work ability [ β 0.02 , 95 % confidence interval ( 95 % CI ) -0.34 - 0.37 ] or physical and mental health status ( β -0.04 , 95 % CI -1.43 - 1.35 , and β 0.80 95 % CI -0.51 - 2.11 , respectively ) were found between the intervention and control group . The intervention showed an overall decline in musculoskeletal symptoms ( ranging from OR 0.68 , 95 % CI 0.34 - 1.33 , to OR 0.86 , 95 % CI 0.47 - 1.57 ) and long-term sick leave ( OR 0.44 , 95 % CI 0.13 - 1.26 ) among construction workers . Both reductions were not statistically significant . CONCLUSION The prevention program seemed to result in a beneficial but not statistically significant decline in the prevalence of musculoskeletal symptoms and long-term sick leave among construction workers , but showed no effects with regard to work ability , physical health , and mental health",
"BACKGROUND Prolonged sitting is prevalent in the workplace and is associated with adverse health markers . PURPOSE Investigate the effects of point-of-choice ( PoC ) prompting software , on the computer used at work ( PC ) , to reduce long uninterrupted sedentary periods and total sedentary time at work . DESIGN Assessor-blinded , parallel group , active-controlled r and omized trial . SETTING / PARTICIPANTS A convenience sample of office workers from Glasgow , United Kingdom . Data were collected April to June 2010 , and analyzed October 2010 to June 2011 . INTERVENTION The education group ( n=14 ) received a brief education session on the importance of reducing long sitting periods at work . The PoC group ( n=14 ) received the same education along with prompting software on their PC for 5 workdays , which reminded them to st and up every 30 minutes . MAIN OUTCOME MEASURES Sitting time was measured objective ly using the activPAL ™ activity monitor for 5 workdays at baseline and 5 workdays during the intervention . The number and time spent sitting in events > 30 minutes ' duration were the main outcome measures . RESULTS At baseline , participants spent 5.7±1.0 hours/day ( 76%±9 % ) of their time at work sitting . Of that time , 3.3±1.3 hours/day was spent sitting in 3.7±1.4 events > 30 minutes . There was a significant difference between the groups in the change ( intervention to baseline ) of both the number ( ANCOVA ; -6.8 % , p=0.014 ) and duration ( -15.5 % , p=0.007 ) of sitting events > 30 minutes . During the intervention , compared with baseline , the PoC group reduced the number ( paired t-test ; -0.11 events/hour , p=0.045 ) and duration ( -12.2 % , p=0.035 ) of sitting events > 30 minutes . However , there was no significant difference in total sitting time between groups ( -4.4 % , p=0.084 ) . CONCLUSIONS Point-of-choice prompting software on work computers recommending taking a break from sitting plus education is superior to education alone in reducing long uninterrupted sedentary periods at work . TRIAL REGISTRATION This trial was registered at Clinical Trials.govNCT01628861",
"We investigated the effects of active versus passive pauses implemented during computer mouse work on muscle oxygenation and EMG of the forearm extensor carpi radialis muscle , and on wrist position sense . Fifteen healthy female subjects ( age : 19–24 years ) performed a 60-min mouse-operated computer task , divided into three 20 min periods , on two occasions separated by 3–6 days . On one occasion a passive pause ( subjects resting ) was implemented at the end of each 20-min period , and on another occasion an active pause ( subjects performed a number of high intensity extensions of the forearm ) was implemented . Also at the end of each 20-min period , test contractions were conducted and subjective ratings of fatigue and stress were obtained . Another parameter of interest was total haemoglobin calculated as the summation of oxy- and deoxy-haemoglobin , since it reflects blood volume changes . The most interesting findings were an overall increasing trend in total haemoglobin throughout the mouse work ( P increase in oxygen saturation ( P ) . EMG amplitude and median frequency tended to decrease ( P=0.08 and 0.05 , respectively ) during the mouse work but was not different between pause types . Borg ratings of forearm fatigue showed an overall increase during the activity ( P stress did not change . Position sense did not change due to the mouse work for either pause type . While increasing trends were found for both pause types , the present study lends support to the hypothesis of an enhancement in oxygenation and blood volume for computer mouse work implemented with active pauses . However , a presumption of an association between this enhancement and attenuated fatigue during the mouse work was not supported",
"Computer operators at two work sites ( n = 73 , n = 19 ) were prompted to take three 30-s and one 3-min break from computer work each hour in addition to conventional rest breaks . Some operators were asked to perform stretching exercises during the short breaks . Mood state and musculoskeletal discomfort were assessed at each work site over a 2- or 3-week baseline period and a 4- or 6-week treatment period , respectively . Operator productivity measures were obtained from company records . Operators complied with about half of the added breaks but favoured 3-min breaks over 30-s breaks . No improvement in productivity or well-being was found at the larger work site . At the smaller work site , productivity , eye , leg and foot comfort all improved when the short breaks included stretching exercises . These results provide evidence that frequent short breaks from continuous computer-mediated work can benefit worker productivity and well-being when the breaks integrate with task dem and",
"Objective : This prospect i ve experimental study evaluates the effectiveness of micropauses ( MPs ) to prevent muscular fatigue and its deleterious effect on surgeons during prolonged surgical procedures . Background : Operating is a hazard for surgeon 's health . Beyond acute injuries and blood-borne infections , back and neck pain is a poorly recognized factor causing chronic ailment in more than half the surgeons surveyed . MP , a 20-second break every 20 minutes , is an accepted strategy used widely in the workplace . Methods : We design ed a crossover experimental study . Sixteen surgeons were tested 3 times : once in a control situation before any surgery ( CTL ) and twice after a prolonged , reproducible operation ( at least 2 hours ) , 1 of these with formal MP ( WMP ) the other without ( WOMP ) . Muscular fatigue was tested by holding a 2.5-kg weight as long as possible with a stretched arm . Accuracy was evaluated with a device , measuring the mistakes made when following a predetermined path on a board . Finally , discomfort was measured by visual analog scale . Results : We found a statistically and more importantly clinical ly significant difference between the CTL and WOMP groups in all 3 tests . MPs prevented completely or almost completely the effects of fatigue associated with surgery [ accuracy ( No. errors ) CTL : 1.1 , WOMP : 7.7 , WMP : 1.7 ; fatigue ( seconds ) CTL : 137 , WOMP : 92 , WMP : 142 ] . Conclusions : Surgical procedures are associated with significant muscular fatigue that can be measured simply and which has a direct effect on comfort and surgical accuracy . More important , this effect is completely or almost completely prevented by MPs",
"Microbreaks are scheduled rest breaks taken to prevent the onset or progression of cumulative trauma disorders in the computerized workstation environment . The authors examined the benefit of microbreaks by investigating myoelectric signal ( MES ) behavior , perceived discomfort , and worker productivity while individuals performed their usual keying work . Participants were r and omly assigned to one of three experimental groups . Each participant provided data from working sessions where they took no breaks , and from working sessions where they took breaks according to their group assignment : microbreaks at their own discretion ( control ) , microbreaks at 20 min intervals , and microbreaks at 40 min intervals . Four main muscle areas were studied : the cervical extensors , the lumbar erector spinae , the upper trapezius/supraspinatus , and the wrist and finger extensors . The authors have previously shown that when computer workers remained seated at their workstation , the muscles performing sustained postural contractions displayed a cyclic trend in the mean frequency ( MNF ) of the MES ( McLean et al. , J. Electrophysiol . Kinesiol . 10 ( 1 ) ( 2000 ) 33 ) . The data provided evidence ( p microbreak protocol s were associated with a higher frequency of MNF cycling at the wrist extensors , at the neck when microbreaks were taken by the control and 40 min protocol groups , and at the back when breaks were taken by the 20 and 40 min protocol groups . No significant change in the frequency of MNF cycling was noted at the shoulder . It was determined ( p microbreaks had a positive effect on reducing discomfort in all areas studied during computer terminal work , particularly when breaks were taken at 20 min intervals . Finally , microbreaks showed no evidence of a detrimental effect on worker productivity . The underlying cause of MNF cycling , and its relationship to the development of discomfort or cumulative trauma disorders remains to be determined",
"BACKGROUND A major challenge for flight crews is the need to maintain vigilance during long , highly automated nighttime flights . No system currently exists to assist in managing alertness , and countermeasure options are limited . Surveys reveal many pilots use breaks as an in-flight countermeasure , but there have been no controlled studies of their effectiveness . HYPOTHESIS We hypothesized that brief , regular breaks could improve alertness and performance during an overnight flight . METHOD A 6-h , uneventful , nighttime flight in a Boeing 747 - 400 flight simulator was flown by fourteen two-man crews . The 14 subjects in the treatment group received 5 short breaks spaced hourly during cruise ; the 14 subjects in the control group received 1 break in the middle of cruise . Continuous EEG/EOG , subjective sleepiness , and psychomotor vigilance performance data were collected . RESULTS During the latter part of the night , the treatment group showed significant reductions for 15 min post-break in slow eye movements , theta-b and activity , and unintended sleep episodes compared with the control group . The treatment group reported significantly greater subjective alertness for up to 25 min post-break , with strongest effects near the time of the circadian trough . There was no evidence of objective vigilance performance improvement at 15 - 25 min post-break , with expected performance deterioration occurring due to elevated sleep drive and circadian time . CONCLUSIONS The physiological and subjective data indicate the breaks reduced nighttime sleepiness for at least 15 min post-break and may have masked sleepiness for up to 25 min , suggesting the potential usefulness of short- duration breaks as an in-flight fatigue countermeasure",
"Aim : This study was design ed to clarify the effects of active rest , with a focus on the practice of short-time group exercise by workplace units , on personal relationships , mental health , physical activity , and work ability among workers . Methods : Fifty-nine white-collar workers ( 40 males and 19 females ) performed our active rest ( short-time exercise ) program , which consists of warm-up , cognitive functional training , aerobic exercise , resistance training and cool-down for 10 minutes per day , 3 times per week during their lunch breaks for 10 weeks . Participants from a workplace unit were r and omly allocated to the intervention ( five workplaces , n=29 ) or control groups ( six workplaces , n=30 ) . The participants ' anthropometric measurements , and their Profile of Mood States ( POMS ) 2 , Brief Job Stress Question naire ( BJSQ ) , physical activity levels and Work Ability Index were examined at the baseline and after the 10-week intervention . Results : After 10 weeks , physical activity levels , especially the time spent in moderate and vigorous intensity , increased in the intervention group ( p \" vigor-activity \" and \" friendliness \" improved in POMS 2 , while \" vigor , \" \" interpersonal stress , \" \" support from superiors , colleagues , and family/friends , \" and \" job satisfaction \" improved in BJSQ in the intervention group ( p exercise participation was positively correlated with the change in \" vigor-activity \" in POMS 2 ( r=0.467 , p=0.011 ) . Conclusions : These results suggest that the practice of active rest by workplace units is important for improving personal relationships , mental health , and physical activity among workers",
"Objective : The present study was design ed to examine the effects of active rest by workplace units on not only workers ’ individual vigor but also workplace vigor and presenteeism . Methods : A total of 130 workers performed our active rest ( short-time exercise ) program for 10 minutes per day during their lunch breaks , three to four times per week for 8 weeks . Subjects from a workplace unit were r and omly allocated to the intervention ( n = 66 ) or control ( n = 64 ) groups . The participants ’ work engagement and Work Functioning Impairment Scale ( WFun ) were examined at the baseline and after the 8-week intervention period . Results : After 8 weeks , the intervention group showed improved “ vigor ” values in work engagement and WFun ( P active rest program by workplace units provides a viable means for improving workplace vigor and presenteeism",
"Objective : The aim of this study was to investigate the effect of intraoperative targeted stretching micro breaks ( TSMBs ) on the experienced pain and fatigue , physical functions , and mental focus of surgeons . Background : Surgeons are routinely subject to mental and physical stresses through the course of their work in the operating room . One of the factors most contributory to the shortening of a surgeon 's career is work-related pain and its effects on patient safety and personal relationships . Methods : Surgeons and operating room staff from 4 medical centers rated pain/fatigue , physical , and mental performance using vali date d scales during 2 operative days : 1 day without implementing TSMB , the other including st and ardized ( 1.5 to 2 minutes ) guided TSMB at appropriate 20 to 40-minute intervals throughout each case . Case type and duration were recorded as were surgeon pain data before and after each procedure and at the end of the surgical day . Individual body part pre/postdiscomfort difference was modeled , controlling for clinical center . R and om coefficient mixed models accounted for surgeon variability . Results : Sixty-six participants ( 69 % men , 31 % women ; mean 47 years ) completed 193 “ non-TSMB ” and 148 “ TSMB ” procedures . Forty-seven percent of surgeons were concerned that musculoskeletal pain may shorten their career . TSMB improved surgeon postprocedure pain scores in the neck , lower back , shoulders , upper back , wrists/h and s , knees , and ankles . Operative duration did not differ ( P > 0.05 ) . Improved pain scores with TSMB were statistically equivalent ( P > 0.05 ) for laparoscopic and open procedures . Surgeons perceived improvements in physical performance ( 57 % ) and mental focus ( 38 % ) ; 87 % of respondents planned to continue TSMB . Conclusions : Many surgeons are concerned about career-ending or limiting musculoskeletal pain . Intraoperative TSMB may represent a practical , effective means to reduce surgeon pain , enhance performance , and increase mental focus without extending operative time",
"Cluster r and omised trials have diminishing returns in power and precision as cluster size increases . Making the cluster a lot larger while keeping the number of clusters fixed might yield only a very small increase in power and precision , owing to the intracluster correlation . Identifying the point at which observations start making a negligible contribution to the power or precision of the study —which we call the point of diminishing returns — is important for design ing efficient trials . Current methods for identifying this point are potentially useful as rules of thumb but do n’t generally work well . We introduce several practical aids to help research ers design cluster r and omised trials in which all observations make a material contribution to the study . Power curves enable identification of the point at which observations begin to make a negligible contribution to a study for a given target difference . Under this paradigm , the number needed per arm under individual r and omisation gives an upper bound on the cluster size , which should not be exceeded . Corresponding precision curves can be useful for accommodating flexibility in the choice of target difference and show the point at which confidence intervals around the estimated effect size no longer decrease . To design efficient trials , the number of clusters and cluster size should be determined concurrently , not independently . Funders and research ers should be aware of diminishing returns in cluster trials . Research ers should routinely plot power or precision curves when performing sample size calculations so that the implication s of cluster sizes can be transparent . Even when data appear to be “ free , ” in the sense that few re sources are needed to obtain the data , excessive cluster sizes can have important",
"A pilot study examined the effectiveness of a biofeedback mouse in reducing upper extremity pain and discomfort in office workers ; in addition , relative mouse use ( RMU ) , satisfaction and the feasibility of running a r and omised controlled trial ( RCT ) in a workplace setting were evaluated . The mouse would gently vibrate if the h and was idle for more than 12 s. The feedback reminded users to rest the arm in neutral , supported postures . Analysis showed a statistically significant reduction in shoulder pain and discomfort for the intervention group at T2 ( 38.7 % lower than controls ) . Statistically significant differences in RMU time between groups were seen post intervention ( −7 % at T1 and + 15 % at T2 for the intervention group ) . Fifty-five percent of the intervention group was willing to continue using the mouse . It appears feasible to perform an RCT for this type of intervention in a workplace setting . Further study including more participants is suggested . Practitioner Summary : The study findings support the feasibility of conducting r and omised control trials in office setting s to evaluate ergonomics interventions . The intervention result ed in reduced pain and discomfort in the shoulder . The intervention could be a relevant tool in the reduction of upper extremity musculoskeletal disorder . Further research will better explain the study 's preliminary findings",
"Objective The aim of the field study was to objectify physicians ’ vigilance , well-being , and cognitive performance in the course of 24-hr shifts with and without afternoon rest . Subjects , Setting , and Design Eleven residents ( four women , seven men ; age , 33.5 ± 4.7 yrs ) were observed when doing two regular 24-hr shifts at the emergency department ( r and omized crossover design ): one without rest , the other with a period of rest in the early afternoon ( duration , 2:31 ± 1:04 hrs ) and the opportunity of having a nap ( duration , 1:07 ± 0:26 hrs , n = 6 ) . Electroencephalography and psychometric tests were carried out at 8 am and at midnight . Measurements Measurements included subjective perception of workload , stress , and sleeping behavior ; computer-analyzed electroencephalography ; adjective checklist ( Eigenschaftswörterliste 60 S , a self-rating scale ) ; complex reaction time test ; Pauli test ( number of calculations during 3 mins ) ; and numerical memory test . Results Electroencephalographic analyses showed a significant decrease in alpha power and a significant increase in beta power in the evening as compared with the morning on both days . The nocturnal increase observed in delta activity was significantly less pronounced in duties with rest than in duties without rest . Physicians felt deactivated at night . The Eigenschaftswörterliste 60 S indicated deactivation at night and a rest-induced activation in the subgroup that had taken the opportunity to sleep in the afternoon . Psychometric tests did not show any significant differences , neither between performance in the morning and evening nor between results with and without rest . Conclusion As expected , electroencephalographic recordings showed nocturnal deactivation and a vigilance-promoting effect of the afternoon rest . These objective findings were in accordance with the results derived from self-rating scales . On the other h and , in short-lasting psychometric tests , performance was found unchanged after 16 hrs of routine work . In further studies , a discrimination between resting periods with and without sleep will be important",
"A worksite study was conducted to examine whether a 15-min nap during a post-lunch rest period would affect subsequent alertness , performance , and nocturnal sleep in eight factory workers under a 3-week protocol . Subjects were asked to take the nap at 12:30 h on a reclining chair during the nap week , and to remain awake during the no-nap week . The order of these 2 weeks was counterbalanced between the subjects . During the third , follow-up week , each subject determined whether or not she/he would nap . Alertness on the job and nocturnal sleep were assessed using a sleep diary . Wrist activity was also recorded during sleep at night . Choice reaction time task ( RT ) was performed at 10:00 and 15:00 h every day of the nap week and every other day of the no-nap and follow-up weeks . Perceived alertness was significantly higher in the afternoon after nap than after no nap at the end of the week . Similar effects were observed during the follow-up week where almost half of the subjects napped . No significant differences between the three weeks were found for RT performance or nocturnal sleep . Workers ' attitudes toward the nap were favourable . Although further intervention research is required , our results suggest that post-lunch napping may have the potential to promote daytime alertness at work",
" The cluster r and omized trial with a concurrent economic evaluation is considered the gold st and ard evaluative design for the conduct of implementation research evaluating different strategies to promote the transfer of research findings into clinical practice . This has implication s for the planning of such studies , as information is needed on the effects of clustering on both effectiveness and efficiency outcomes . This paper describes the design considerations specific to implementation research studies , focusing particularly on the estimation of sample size requirements and on the need for reliable information on intracluster correlation coefficients for both effectiveness and efficiency outcomes",
"H and cultivation and harvest of agricultural products constitute strenuous physical tasks . Working with labor-management ergonomics committees in agricultural setting s , the UC Agricultural Ergonomics Research Center ( AERC ) tested an experimental rest and recovery protocol for its impact on symptoms and productivity during two types of work tasks . The experimental condition consisted of adding a 5 min rest break to every working hour in which there was no other scheduled break ( e.g. , lunchtime ) . This result ed in an additional 20 min of rest per workday . We tested the intervention in two trials : Trial one compared workers ( n=66 ) r and omly assigned to an experimental or a control group during the harvest of commercial strawberries . Trial two utilized a cross-over design ( n=16 pairs of workers ) to compare experimental and control conditions while workers inserted bud grafts into young 18 ' ' high citrus trees . For both trials , workers under the experimental condition reported significantly less severe symptoms than workers under control conditions . The order in which the intervention was given , however , appeared to result in variations in productivity . We conclude that the introduction of frequent , brief rest breaks may improve symptoms for workers engaged in strenuous work tasks ",
"OBJECTIVES The primary aim of this study was to examine the impact of physical activity ( PA ) in the natural environment ( eg , \" green exercise \" ) on resting autonomic function in the Walks4Work intervention . A secondary aim was to assess the feasibility of Walks4Work in terms of adherence , change in PA levels , and cardiovascular health parameters . METHODS In an 8-week r and omized control trial , 94 office workers in an international company were allocated to one of three groups : control , nature ( NW ) , or built ( BW ) lunchtime walking route . Both walking groups were required to undertake two lunchtime walks each week . The NW route centered around trees , maintained grass , and public footpaths . In contrast , the BW consisted of pavement routes through housing estates and industrial areas . Data were collected at baseline and following the intervention . To investigate the impact of the intervention , mixed- design analysis of variance ( ANOVA ) were performed . RESULTS A total of 73 participants completed the intervention ( drop-out rate of 22 % ) . No difference was observed in resting autonomic function between the groups . Self-reported mental health improved for the NW group only . PA levels increased at the intervention mid-point for all groups combined but adherence to the intervention was low with rates of 42 % and 43 % within the BW and NW groups , respectively . CONCLUSION Accompanying a guideline of two active lunchtimes per week with low facilitator input appears inadequate for increasing the number of active lunchtimes and modifying cardiovascular health parameters in an office population . However , this population fell within normal ranges for cardiovascular measures and future research should consider investigating at-risk population s , particularly hypertensive individuals",
"Background Faster recovery from work may help to prevent work-related ill health . Aims To provide a preliminary assessment of the range and nature of interventions that aim to improve recovery from cognitive and physical work . Methods A scoping review to examine the range and nature of the evidence , to identify gaps in the evidence base and to provide input for systematic review s. We search ed for workplace intervention studies that aim ed at enhancing recovery . We used an iterative method common in qualitative research to obtain an overview of study elements , including intervention content , design , theory , measurements , effects and cost-effectiveness . Results We found 28 studies evaluating seven types of interventions mostly using a r and omized controlled study design . For person-directed interventions , we found relaxation techniques , training of recovery experiences , promotion of physical activity and stress management . For work-directed interventions , there were participatory changes , work-break schedules and task variation . Most interventions were based on the conservation of re sources and affect-regulation theories , none were based on the effort-recovery theory . The need for recovery ( NfR ) and the recovery experiences question naires ( REQ ) were used most often . Study authors reported a beneficial effect of the intervention in 14 of 26 published studies . None of the studies that used the NfR scale found a beneficial effect , whereas studies that used the REQ showed beneficial effects . Three studies indicated that interventions were not cost-effective . Conclusions Feasible and possibly effective interventions are available for improving recovery from cognitive and physical workload . Systematic review s are needed to determine their effectiveness",
"Objective : The aim of this study was to determine whether individuals who participated in an intervention to reduce sitting at work would report changes in arousal , fatigue , and mood . Methods : Inactive females with full-time sedentary occupations ( N = 49 ) were r and omly assigned to take short , frequent breaks ( SBs ) or longer , planned breaks ( LBs ) from sitting each workday for 8 weeks . At baseline and postintervention , participants completed measures of arousal , fatigue , and mood . Within- and between-group changes were examined . Results : SB participants reduced sitting and reported moderate to large improvements in all affective outcomes except calmness ( d = −0.44 to -0.82 ) , whereas effect sizes were small for the LB group ( d = 0.01 to -0.28 ) . Only changes in negative affect differed between groups ( P = 0.045 ) . Conclusion : This study suggests that taking short , frequent breaks from sitting may be an effective strategy for improving affective outcomes among sedentary female employees",
"UNLABELLED Purpose : To perform a systematic review with best evidence synthesis examining the literature on the relationship between occupational loading tasks and knee osteoarthritis ( OA ) . METHODS Two data bases were search ed to identify articles published between 1946 and April , 2011 . Eligible studies were those that ( 1 ) included adults reporting on their employment history ; ( 2 ) measured individuals ' exposure to work-related activities with heavy loading in the knee joint ; and ( 3 ) identified presence of knee OA ( determined by X-ray ) , cartilage defects associated with knee OA ( identified by magnetic resonance imaging ) , or joint replacement surgery . RESULTS A total of 32 articles from 31 studies met the inclusion criteria . We found moderate evidence that combined heavy lifting and kneeling is a risk factor for knee OA , with odds ratios ( OR ) varying from 1.8 to 7.9 , and limited evidence for heavy lifting ( OR=1.4 - 7.3 ) , kneeling ( OR=1.5 - 6.9 ) , stair climbing ( OR=1.6 - 5.1 ) , and occupational groups ( OR=1.4 - 4.7 ) as risk factors . When examined by sex , moderate level evidence of knee OA was found in men ; however , the evidence in women was limited . CONCLUSIONS Further high- quality prospect i ve studies are warranted to provide further evidence on the role of occupational loading tasks in knee OA , particularly in women"
] |
4116c950-06ff-11f0-808a-c43d1ab1c353
|
OBJECTIVE . This systematic review addresses the effectiveness of occupational therapy – related interventions for adults with fibromyalgia . METHOD . We examined the literature published between January 2000 and June 2014 . A total of 322 abstract s from five data bases were review ed . Forty-two Level I studies met the inclusion criteria . Studies were evaluated primarily with regard to the following outcomes : daily activities , pain , depressive symptoms , fatigue , and sleep . RESULTS . Strong evidence was found for interventions categorized for this review as cognitive – behavioral interventions ; relaxation and stress management ; emotional disclosure ; physical activity ; and multidisciplinary interventions for improving daily living , pain , depressive symptoms , and fatigue . There was limited to no evidence for self-management , and few interventions result ed in better sleep . CONCLUSION . Although the evidence supports interventions within the scope of occupational therapy practice for people with fibromyalgia , few interventions were occupation based
|
[
"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",
"Background : The presence and severity of the chronic pain syndrome fibromyalgia ( FM ) is associated with unresolved stress and emotional regulation difficulties . Written emotional disclosure is intended to reduce stress and may improve health of people with FM . Purpose : This study tests the effects of at-home , written emotional disclosure about stressful experiences on the health of people with FM and uses multiple follow-ups to track the time course of effects of disclosure . Methods : Adults with FM ( intention-to-treat , n = 83 ; completers , n = 72 ) were r and omized to write for 4 days at home about either stressful experiences ( disclosure group ) or neutral time management ( control group ) . Group differences in immediate mood effects and changes in health from baseline to 1-month and 3-month follow-ups were examined . Results : Written disclosure led to an immediate increase in negative mood , which did not attenuate across the 4 writing days . Repeated- measures analyses from baseline to each follow-up point were conducted on both intention-to-treat and completer sample s , which showed similar outcomes . At 1 month , disclosure led to few health benefits , but control writing led to less negative affect and more perceived support than did disclosure . At 3-month follow-up , these negative affect and social support effects disappeared , and written disclosure led to a greater reduction in global impact , poor sleep , health care utilization , and ( marginally ) physical disability than did control writing . Interpretation of these apparent benefits needs to be made cautiously , however , because the disclosure group had somewhat poorer health than controls at baseline and the control group showed some minor worsening over time . Conclusions : Written emotional disclosure can be conducted at home , and there is tentative evidence that disclosure benefits the health of people with FM . The benefits , however , may be delayed for several months after writing and may be of limited clinical significance",
"Background The effectiveness of eHealth interventions in terms of reach and outcomes is now well documented . However , there is a need to underst and not only whether eHealth interventions work , but also what kind of functions and mechanisms enhance their effectiveness . The present investigation contributes to tackling these challenges by investigating the role played by functional interactivity on patients ’ knowledge , empowerment , and health outcomes . Objectives To test whether health knowledge and empowerment mediate a possible relationship between the availability of interactive features on an eHealth application and individuals ’ health outcomes . We present an empirical , model-driven evaluation of the effects of functional interactivity implemented in an eHealth application , based on a brief theoretical review of the constructs of interactivity , health knowledge , empowerment , and health outcomes . We merged these constructs into a theoretical model of interactivity effects that we tested on an eHealth application for patients with fibromyalgia syndrome ( FMS ) . Methods This study used a pretest – posttest experimental design . We recruited 165 patients and r and omly assigned them to three study groups , corresponding to different levels of functional interactivity . Eligibility to participate in the study required that patients ( 1 ) be fluent in Italian , ( 2 ) have access to the Internet , ( 3 ) report confidence in how to use a computer , and ( 4 ) have received a diagnosis of FMS from a doctor . We used structural equation modeling techniques to analyze changes between the pretest and the posttest results . Results The main finding was that functional interactivity had no impact on empowerment dimensions , nor direct observable effects on knowledge . However , knowledge positively affected health outcomes ( b = –.12 , P = .02 ) , as did the empowerment dimensions of meaning ( b = –.49 , P and impact ( b = –.25 , P effects of knowledge and empowerment were concerned . The differential effect of interactive functions was by far weaker than expected . The strong impact of knowledge and empowerment on health outcomes suggests that these constructs should be targeted and enhanced by eHealth applications",
"UNLABELLED Altan L , Korkmaz N , Bingol U , Gunay B. Effect of Pilates training on people with fibromyalgia syndrome : a pilot study . OBJECTIVE To investigate the effects of Pilates on pain , functional status , and quality of life in fibromyalgia , which is known to be a chronic musculoskeletal disorder . DESIGN R and omized , prospect i ve , controlled , and single-blind trial . SETTING Physical medicine and rehabilitation department . PARTICIPANTS Women ( N=50 ) who had a diagnosis of fibromyalgia syndrome ( FMS ) according to the American College of Rheumatology criteria . INTERVENTION The participants were r and omly assigned into 2 groups . In group 1 , a Pilates exercise program of 1 hour was given by a certified trainer to 25 participants 3 times a week for 12 weeks . In group 2 , which was design ed as the control group , 25 participants were given a home exercise ( relaxation/stretching ) program . In both groups , pre- ( week 0 ) and posttreatment ( week 12 and week 24 ) evaluation was performed by one of the authors , who was blind to the group allocation . MAIN OUTCOME MEASURES Primary outcome measures were pain ( visual analog scale ) and Fibromyalgia Impact Question naire ( FIQ ) . Exploratory outcome measures were number of tender points , algometric score , chair test , and Nottingham Health Profile . RESULTS Twenty-five Pilates exercise and 24 relaxation/stretching exercise participants completed the study . In group 1 , significant improvement was observed in both pain and FIQ at week 12 but only in FIQ at 24 weeks . In group 2 , no significant improvement was obtained in pain and FIQ at week 12 and week 24 . Comparison of the 2 groups showed significantly superior improvement in pain and FIQ in group 1 at week 12 but no difference between the 2 groups at week 24 . CONCLUSIONS We suggest Pilates as an effective and safe method for people with FMS . Our study is the first clinical study design ed to investigate the role of the Pilates method in FMS treatment . We believe that further research with more participants and longer follow-up periods could help assess the therapeutic value of this popular physical exercise method",
"BACKGROUND AND OBJECTIVE Affect and how it is regulated plays a role in pain perception , maintenance of pain , and its resolution . This r and omized , controlled trial evaluated an innovative affective self-awareness ( ASA ) intervention , which was design ed to reduce pain and improve functioning in individuals with fibromyalgia . PARTICIPANTS AND METHODS Forty-five women with fibromyalgia were r and omized to a manualized ASA intervention ( n = 24 ) or wait-list control ( n = 21 ) . The intervention began with a one-time physician consultation , followed by 3 weekly , 2-h group sessions based upon a mind-body model of pain . Sessions focused on structured written emotional disclosure and emotional awareness exercises . Outcomes in both conditions were measured by a blinded assessor at baseline , post-intervention , and 6-month follow-up . MEASURES The primary outcome was pain severity ( Brief Pain Inventory ) ; secondary outcomes included tender-point threshold and physical function ( SF-36 Physical Component Summary ) . Intent-to-treat analyses compared groups on outcomes using analysis of covariance and on the proportion of patients achieving ≥30 % and ≥50 % pain reduction at 6 months . RESULTS Adjusting for baseline scores , the intervention group had significantly lower pain severity ( p higher self-reported physical function ( p and higher tender-point threshold ( p = 0.02 ) at 6 months compared to the control group . From baseline to 6 months , 45.8 % of the ASA intervention group had ≥30 % reduction in pain severity , compared to none of the controls ( p self-awareness intervention improved pain , tenderness , and self-reported physical function for at least 6 months in women with fibromyalgia compared to wait-list control . This study suggests the value of interventions targeting emotional processes in fibromyalgia , although further studies should evaluate the efficacy of this intervention relative to active controls",
"Introduction The objective of this study was to investigate the effects of moderate-to-high intensity Nordic walking ( NW ) on functional capacity and pain in fibromyalgia ( FM ) . Methods A total of 67 women with FM were recruited to the study and r and omized either to moderate-to-high intensity Nordic Walking ( n = 34 , age 48 ± 7.8 years ) or to a control group engaging in supervised low-intensity walking ( LIW , n = 33 , age 50 ± 7.6 years ) . Primary outcomes were the six-minute walk test ( 6MWT ) and the Fibromyalgia Impact Question naire Pain scale ( FIQ Pain ) . Secondary outcomes were : exercise heart rate in a submaximal ergometer bicycle test , the FIQ Physical ( activity limitations ) and the FIQ total score . Results A total of 58 patients completed the post-test . Significantly greater improvement in the 6MWT was found in the NW group ( P = 0.009 ) , as compared with the LIW group . No between-group difference was found for the FIQ Pain ( P = 0.626 ) . A significantly larger decrease in exercise heart rate ( P = 0.020 ) and significantly improved scores on the FIQ Physical ( P = 0.027 ) were found in the NW group as compared with the LIW group . No between-group difference was found for the change in the FIQ total . The effect sizes were moderate for the above mentioned outcomes . Conclusions Moderate-to-high intensity aerobic exercise by means of Nordic walking twice a week for 15 weeks was found to be a feasible mode of exercise , result ing in improved functional capacity and a decreased level of activity limitations . Pain severity did not change over time during the exercise period . Trial registration Clinical trials.gov identifier NCT00643006",
"Previous research ers have found that 10-form Tai chi yields symptomatic benefit in patients with fibromyalgia ( FM ) . The purpose of this study was to further investigate earlier findings and add a focus on functional mobility . We conducted a parallel-group r and omized controlled trial FM-modified 8-form Yang-style Tai chi program compared to an education control . Participants met in small groups twice weekly for 90 min over 12 weeks . The primary endpoint was symptom reduction and improvement in self-report physical function , as measured by the Fibromyalgia Impact Question naire ( FIQ ) , from baseline to 12 weeks . Secondary endpoints included pain severity and interference ( Brief Pain Inventory ( BPI ) , sleep ( Pittsburg sleep Inventory ) , self-efficacy , and functional mobility . Of the 101 r and omly assigned subjects ( mean age 54 years , 93 % female ) , those in the Tai chi condition compared with the education condition demonstrated clinical ly and statistically significant improvements in FIQ scores ( 16.5 vs. 3.1 , p = 0.0002 ) , BPI pain severity ( 1.2 vs. 0.4 , p = 0.0008 ) , BPI pain interference ( 2.1 vs. 0.6 , p = 0.0000 ) , sleep ( 2.0 vs. −0.03 , p = 0.0003 ) , and self-efficacy for pain control ( 9.2 vs. −1.5 , p = 0.0001 ) . Functional mobility variables including timed get up and go ( −.9 vs. −.3 , p = 0.0001 ) , static balance ( 7.5 vs. −0.3 , p = 0.0001 ) , and dynamic balance ( 1.6 vs. 0.3 , p = 0.0001 ) were significantly improved with Tai chi compared with education control . No adverse events were noted . Twelve weeks of Tai chi , practice twice weekly , provided worthwhile improvement in common FM symptoms including pain and physical function including mobility . Tai chi appears to be a safe and an acceptable exercise modality that may be useful as adjunctive therapy in the management of FM patients . ( Clinical Trials.gov Identifier , NCT01311427",
"Background Self-management programmes ( SMP ) are recommended for patients with fibromyalgia . The purpose of this study was to evaluate effects of a one week multidisciplinary inpatient self-management programme on psychological distress , skills as a consumer of health services , self-efficacy , and functional and symptomatic consequences of fibromyalgia ( FM ) . Methods A r and omised controlled two-armed , assessor-blinded trial with three-week follow-up to evaluate SMP . Primary outcomes were the General Health Question naire ( GHQ-20 ) and the Effective Musculoskeletal Consumer Scale ( EC-17 ) , while secondary outcomes included the Fibromyalgia Impact Question naire ( FIQ ) and Self-efficacy scales for pain , function and symptoms ( ASES ) . Results 150 patients with FM were r and omised to one week one SMP ( n = 75 ) or to a waiting list control group ( n = 75 ) . Of these , 58 participants in the treatment group and 60 in the control group completed the study . At three weeks ’ follow up there was a significant difference in EC-17 ( 0 - 100 ) in favour of the treatment group ( mean difference 4.26 , 95 CI 0.8 to 7.7 , p = 0.02 ) . There were no differences between the groups for any of the other outcomes . Conclusion This study shows that in patients with FM the SMP had no effect on psychological distress , functional and symptomatic consequences and self-efficacy , except for a small short-term effect on skills and behaviour that are important for managing and participating in health care ( EC-17 ) . Clinical Trials.gov I d : NCT01035125.Trial registration Clinical Trials.gov I d :",
"This study aim ed to examine the effectiveness of a multidisciplinary intervention with aftercare ( MD ) compared to aerobic exercise ( AE ) and usual care ( UC ) in recently diagnosed patients with fibromyalgia ( FM ) . In a Zelen-like design , eligible patients from the outpatient rheumatology clinics of three medical centres in the South of the Netherl and s were consecutively recruited and pre-r and omised to MD ( n = 108 ) , AE ( n = 47 ) or UC ( n = 48 ) . MD consisted of a 12-week course of sociotherapy , physiotherapy , psychotherapy and creative arts therapy ( three half days per week ) , followed by five aftercare meetings in 9 months . AE was given twice a week in a 12-week course . UC varied but incorporated at least education and lifestyle advice . Primary outcomes were health-related quality of life ( HR-Qol ) , participation and health care utilisation . Secondary outcome was the Fibromyalgia Impact Question naire ( FIQ ) . Total follow-up duration of the study was 21–24 months . As willingness to participate in AE was limited , this group has been analysed but interpretation of the data is considered arguable . Within the MD group , a statistically significantly improved HR-Qol and a statistically significant reduction in number of hours sick leave , number of contacts with general practitioners and number of contacts with medical specialists was found . Moreover , statistically significant improvements were found on the FIQ , which increased after the intervention . However , no statistically significant between-group differences were found at the endpoint of the study . MD seemed to yield positive effects , but firm conclusions with regard to effectiveness can not be formulated due to small between-group differences and limitations of the study",
"OBJECTIVES To assess the efficacy of a 6-week interdisciplinary treatment that combines coordinated psychological , medical , educational , and physiotherapeutic components ( PSYMEPHY ) over time compared to st and ard pharmacologic care . METHODS R and omised controlled trial with follow-up at 6 months for the PSYMEPHY and control groups and 12 months for the PSYMEPHY group . Participants were 153 out patients with FM recruited from a hospital pain management unit . Patients r and omly allocated to the control group ( CG ) received st and ard pharmacologic therapy . The experimental group ( EG ) received an interdisciplinary treatment ( 12 sessions ) . The main outcome was changes in quality of life , and secondary outcomes were pain , physical function , anxiety , depression , use of pain coping strategies , and satisfaction with treatment as measured by the Fibromyalgia Impact Question naire , the Hospital Anxiety and Depression Scale , the Coping with Chronic Pain Question naire , and a question regarding satisfaction with the treatment . RESULTS Six months after the intervention , significant improvements in quality of life ( p=0.04 ) , physical function ( p=0.01 ) , and pain ( p=0.03 ) were seen in the PSYMEPHY group ( n=54 ) compared with controls ( n=56 ) . Patients receiving the intervention reported greater satisfaction with treatment . Twelve months after the intervention , patients in the PSYMEPHY group ( n=58 ) maintained statistically significant improvements in quality of life , physical functioning , pain , and symptoms of anxiety and depression , and were less likely to use maladaptive passive coping strategies compared to baseline . CONCLUSIONS An interdisciplinary treatment for FM was associated with improvements in quality of life , pain , physical function , anxiety and depression , and pain coping strategies up to 12 months after the intervention",
"Objective Alzheimer ’s disease and related dementias ( ADRD ) affect more than five million Americans and their family caregivers . Caregiving creates challenges , may contribute to decreased caregiver health and is associated with $ 9.7 billion of caregiver health care costs . The purpose of this 12 month r and omized clinical trial ( RCT ) was to examine if the Enhancing Physical Activity Intervention ( EPAI ) , a moderate to vigorous physical activity ( MVPA ) treatment group , versus the Caregiver Skill Building Intervention ( CSBI ) control , would have greater : ( 1 ) MVPA adherence ; and ( 2 ) physical function . Methods Caregivers were r and omly assigned to EPAI or CSBI ( N=211 ) . MVPA was assessed using a self-report measure ; and physical function was objective ly assessed using two measures . Intention-to-treat analyses used descriptive , categorical and generalized estimating equations ( GEE ) , with an exchangeable working correlation matrix and a log link , to examine main effects and interactions in change of MVPA and physical function over time . Results At 12 months , EPAI significantly increased MVPA ( p= number of steps ( p= stable caregiving hours and use of formal services ; while CSBI increased hours of caregiving ( p= more formal services ( p= physical function tests . Conclusion The EPAI had a stronger 12 month effect on caregiver MVPA and physical function , as well as maintaining stability of caregiving hours and formal service use ; while CSBI increased caregiving hours and use of formal services . A study limitation included greater EPAI versus CSBI attrition . Future directions are proposed for dementia family caregiver physical activity research",
"& 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",
"OBJECTIVES This study aim ed to verify whether techniques of yoga with and without the addition of Tui Na might improve pain and the negative impact of fibromyalgia ( FMS ) on patients ' daily life . DESIGN Forty ( 40 ) FMS women were r and omized into two groups , Relaxing Yoga ( RY ) and Relaxing Yoga plus Touch ( RYT ) , for eight weekly sessions of stretching , breathing , and relaxing yogic techniques . RYT patients were further su bmi tted to manipulative techniques of Tui Na . OUTCOME MEASURE Outcome measures comprised the Fibromyalgia Impact Question naire ( FIQ ) , pain threshold at the 18 FMS tender points , and a verbal graduation of pain assessed before treatment and on the followup . The visual analog scale ( VAS ) for pain was assessed before and after each session and on the follow-up . RESULTS Seventeen ( 17 ) RYT and 16 RY patients completed the study . Both RY and RYT groups showed improvement in the FIQ and VAS scores , which decreased on all sessions . The RYT group showed lower VAS and verbal scores for pain on the eighth session , but this difference was not maintained on the follow-up . Conversely , RY VAS and verbal scores were significantly lower just on the follow-up . CONCLUSIONS These study results showed that yogic techniques are valid therapeutic methods for FMS . Touch addition yielded greater improvement during the treatment . Over time , however , RY patients reported less pain than RYT . These results suggest that a passive therapy may possibly decrease control over FMS symptoms",
"Objectives : To evaluate the feasibility of a r and omized-controlled trial and to obtain estimates of the effects of combined cognitive-behavioral therapy ( CBT ) and milnacipran for the treatment of fibromyalgia . Methods : Fifty-eight patients with fibromyalgia were r and omized to 1 of the 3 treatment arms : ( 1 ) combination therapy ( n=20 ) ; ( 2 ) milnacipran+education ( n=19 ) ; and ( 3 ) placebo+CBT ( n=19 ) . Patients received either milnacipran ( 100 mg/d ) or placebo . Patients also received 8 sessions of phone-delivered CBT or educational instructions , but only from baseline to week 9 . Assessment s were conducted at baseline , week 9 , and 21 . The primary endpoints were baseline to week 21 changes in weekly average pain intensity and physical function ( SF-36 physical function scale ) . Results : Compared with milnacipran , combination therapy demonstrated a moderate effect on improving SF-36 physical function ( SE=9.42 [ 5.48 ] , P=0.09 , effect size=0.60 ) and in reducing weekly average pain intensity ( mean difference [SE]=−1.18 [ 0.62 ] , P=0.07 , effect size=0.67 ) . Compared with milnacipran , CBT had a moderate to large effect in improving SF-36 physical function ( mean difference [SE]=11.0 [ 5.66 ] , P=0.06 , effect size=0.70 ) . Despite the presence of concomitant central ly acting therapies , dropout rate was lower than anticipated ( 15 % at week 21 ) . Importantly , at least 6 out of the 8 phone-based therapy sessions were successfully completed by 89 % of the patients ; and adherence to the treatment protocol s was > 95 % . Conclusions : In this pilot study , a therapeutic approach that combines phone-based CBT and milnacipran was feasible and acceptable . Moreover , the preliminary data supports conducting a fully powered r and omized-controlled trial . Clinical Trial Registration : NCT01038323",
"OBJECTIVE The objective of this study was to evaluate resistance training ( RES ) and RES combined with chiropractic treatment ( RES-C ) on fibromyalgia ( FM ) impact and functionality in women with FM . DESIGN The design of the study was a r and omized control trial . SETTING Testing and training were completed at the university and chiropractic treatment was completed at chiropractic clinics . PARTICIPANTS Participants ( 48 + /- 9 years ; mean + /- st and ard deviation ) were r and omly assigned to RES ( n = 10 ) or RES-C ( n = 11 ) . INTERVENTION Both groups completed 16 weeks of RES consisting of 10 exercises performed two times per week . RES-C received RES plus chiropractic treatment two times per week . OUTCOME MEASURES Strength was assessed using one repetition maximum for the chest press and leg extension . FM impact was measured using the FM impact question naire , myalgic score , and the number of active tender points . Functionality was assessed using the 10-item Continuous Scale Physical Functional Performance test . Analyses of variance with repeated measures compared groups before and after the intervention . RESULTS Six ( 6 ) participants discontinued the study : 5 from RES and 1 from RES-C. Adherence to training was significantly higher in RES-C ( 92.0 + /- 7.5 % ) than in RES ( 82.8 + /- 7.5 % ) . Both groups increased ( p upper and lower body strength . There were similar improvements in FM impact in both groups . There were no group interactions for the functionality measures . Both groups improved in the strength domains ; however , only RES-C significantly improved in the pre- to postfunctional domains of flexibility , balance and coordination , and endurance . CONCLUSIONS In women with FM , resistance training improves strength , FM impact , and strength domains of functionality . The addition of chiropractic treatment improved adherence and dropout rates to the resistance training and facilitated greater improvements in the domains of functionality",
"Women diagnosed with fibromyalgia ( N = 72 ) participated in a 10-week r and omized trial to examine the effectiveness of guided imagery on self-efficacy , perceived stress , and selected biobehavioral factors ( FMS symptoms ; immune biomarkers ) . Participants in both guided imagery and usual care control conditions completed measures and donated 3 cc of blood at baseline , 6- and 10-weeks . A mixed effects linear model to test for differences between groups for all behavioral and biologic variables demonstrated that after 10 weeks of daily intervention use , guided imagery participants reported statistically significant increases in self-efficacy and statistically significant decreases in stress , fatigue , pain , and depression . There were no statistically significant changes in biomarker levels , although total group C-reactive protein was elevated at baseline ( 4.7 mg/L ) , indicating an inflammatory process . Subsequent studies should be undertaken to more fully eluci date the biobehavioral aspects of nonpharmacological intervention effectiveness",
"The purpose of this study was to evaluate the efficacy of a multidisciplinary treatment program in patients severely affected by fibromyalgia . Thirty-four fibromyalgia patients were r and omly divided into two groups . The control group : 17 women who continued their medical treatment and participated in four educational sessions and the experimental group that included 17 patients who besides the former medical treatment also underwent a weekly 1-h session program for 8 weeks including massage therapy , ischemic pressure on the 18 tender points , aerobic exercise and thermal therapy . At the beginning of the program , there were no significant differences between the two groups in any of the parameters . At the end of treatment , there was a significant improvement in the experimental group in the following items : vitality , social functioning , grip strength and the 6-min walk test . At 1 month after the end of treatment , the experimental group showed significant differences in overall health perception , social functioning , grip strength and the 6-min walk test . At that time , considering the threshold for clinical efficacy set at an improvement of 30 % or above for the analyzed variables , 25 % of the patients met the requirement for improvement of the following : number of symptoms : Visual Analogic Scale for fatigue , Fibromyalgia Impact Question naire and Beck Anxiety Inventory . In conclusion , patients with severe manifestations of fibromyalgia can obtain improvement with a short-term , low-cost and simple-delivery multidisciplinary program . However , additional studies including higher numbers of patients are needed to confirm the beneficial effect of this treatment program",
"Objectives : Regular exercise is associated with important benefits in patients with fibromyalgia ( FM ) . Unfortunately , long-term maintenance of exercise after a structured program is rare . The present study tested the efficacy of Motivational Interviewing ( MI ) to promote exercise and improve symptoms in patients with FM . Methods : A total of 216 patients with FM were r and omized to 6 MI sessions ( n=107 ) or an equal number of FM self-management lessons ( education control/EC , n=109 ) . Co- primary endpoints were an increase of 30 minutes in moderate-vigorous physical activity and improvement in the Fibromyalgia Impact Question naire (FIQ)-Physical Impairment score , assessed at pretreatment , posttreatment , and 3-month and 6-month follow-up . Secondary outcomes included clinical ly meaningful improvements in FIQ score , pain severity ratings , and a 6-minute walk test . Results : There were no significant treatment group differences in either co- primary endpoint at 6-month follow-up . However , more MI participants than controls exhibited meaningful improvements in FIQ score at 6-month follow-up ( 62.9 % vs. 49.5 % , P=0.06 ) . Compared with EC participants , MI participants also displayed a larger increment in their 6-minute walk test ( 43.9 vs. 24.8 m , P=0.03 ) . In addition , MI was superior to EC in increasing the number of hours of physical activity immediately postintervention and in reducing pain severity both immediately after the intervention and at 3-month follow-up . Conclusions : Despite a lack of benefits on long-term outcome , MI seems to have short-term benefits with respect to self-report physical activity and clinical outcomes . This is the first study in FM that explicitly addresses exercise maintenance as a primary aim . Clinical Trial Registration : NCT00573612",
"OBJECTIVES ( 1 ) To investigate the effects of a 6-week intervention of guided imagery on pain level , functional status , and self-efficacy in persons with fibromyalgia ( FM ) ; and ( 2 ) to explore the dose-response effect of imagery use on outcomes . DESIGN Longitudinal , prospect i ve , two-group , r and omized , controlled clinical trial . SETTING AND SUBJECTS The sample included 48 persons with FM recruited from physicians ' offices and clinics in the mid-Atlantic region . INTERVENTION Participants r and omized to Guided Imagery ( GI ) plus Usual Care intervention group received a set of three audiotaped guided imagery scripts and were instructed to use at least one tape daily for 6 weeks and report weekly frequency of use ( dosage ) . Participants assigned to the Usual Care alone group su bmi tted weekly report forms on usual care . MEASURES All participants completed the Short-Form McGill Pain Question naire ( SF-MPQ ) , Arthritis Self- Efficacy Scale ( ASES ) , and Fibromyalgia Impact Question naire ( FIQ ) , at baseline , 6 , and 10 weeks , and su bmi tted frequency of use report forms . RESULTS FIQ scores decreased over time in the GI group compared to the Usual Care group ( p = 0.03 ) . Ratings of self-efficacy for managing pain ( p = 0.03 ) and other symptoms of FM also increased significantly over time ( p = Pain as measured by the SF-MPQ did not change over time or by group . Imagery dosage was not significant . CONCLUSIONS This study demonstrated the effectiveness of guided imagery in improving functional status and sense of self-efficacy for managing pain and other symptoms of FM . However , participants ' reports of pain did not change . Further studies investigating the effects of mind-body interventions as adjunctive self-care modalities are warranted in the fibromyalgia patient population",
"OBJECTIVE To assess the impact of a long-term exercise programme vs usual care on perceived health status , functional capacity and depression in patients with fibromyalgia . DESIGN R and omized controlled trial . SUBJECTS Forty-two women with fibromyalgia were allocated r and omly to 1 of 2 groups : an experimental group that carried out aerobic , strength and flexibility exercises for 24 weeks and a usual care control group . METHODS Health status and functional capacity were evaluated using the Fibromyalgia Impact Question naire and the Short Form Health Survey 36 . Depression was evaluated with the Beck Depression Inventory . RESULTS Significant improvements were observed in health status and functional capacity for the exercise group over the control group . The magnitude of the effect size of these improvements , expressed as Cohen 's d , was medium . The effect size ( 95 % confidence interval ) for the Fibromyalgia Impact Question naire was 0.58 ( -14.12 , -2.35 ) , for the Short Form Health Survey 36 . global score 0.54 ( 1.28 , 14.52 ) , and in the mental health domain of the Short Form Health Survey 36 . 0.51 ( 1.20 , 16.26 ) . There was a large effect size in vitality . All the aforementioned improvements can be considered as clinical ly important changes . CONCLUSION Results confirm that a long-term combination of aerobic exercise , strengthening and flexibility improves psychological health status and health-related quality of life in patients with fibromyalgia",
"OBJECTIVES To analyse the effect of a 24-week physical training programme in water and on l and on women with fibromyalgia . METHODS A controlled study was conducted from December 2009 to May 2010 . Seventy-two women with fibromyalgia ( age : 51.79±7.87 years ) were assigned to an exercise group ( 3 sessions/week , 2 sessions in water , 1 session on l and ) ( n=42 ) and to a control group ( n=30 ) . The variables analysed were : number of tender points , visual analogue scale ( VAS ) of pain , algometer score , functional capacity ( leg strength , h and -grip dynamometry , flexibility , agility , balance , aerobic endurance , heart response ) , body composition ( body mass index , fat mass index , skeletal muscle mass index and percentage of body fat ) and psychological variables ( Fibromyalgia Impact Question naire [ FIQ ] and Short Form Health Survey 36 [ SF-36 ] ) . RESULTS The exercise group improved in the algometer score ( p positive tender points ( p=0.005 ) , VAS ( p in functional capacity ( leg strength , p=0.001 ; h and -grip dynamometry , p=0.001 ; flexibility , p balance , p=0.006 ; 6-minute walk test , p ; mean heart rate , p=0.031 ; maximum heart rate , p the percentage of body fat ( p=0.040 ) . There was also an improvement in the subscales of the SF-36 ; vitality ( p=0.004 ) , mental health ( p=0.001 ) social role functioning ( p=0.020 ) and general health functioning ( p=0.002 ) . CONCLUSIONS The findings of this study show that a 24-week physical training programme ( 3 sessions/week , of which 2 sessions are in water and 1 session is on l and ) reduces pain and disease impact and improves functional capacity in women with fibromyalgia",
"Summary Strengthening and aerobic exercise had equivalent effects on reducing pain severity in patients with fibromyalgia . Abstract Strength training and aerobic exercise have beneficial effects on pain in adults with fibromyalgia . However , the equivalence of strengthening and aerobic exercise has not been reported . The primary aim of this r and omized equivalence trial involving patients with fibromyalgia admitted to an interdisciplinary pain treatment program was to test the hypothesis that strengthening ( n = 36 ) and aerobic ( n = 36 ) exercise have equivalent effects ( 95 % confidence interval within an equivalence margin ±8 ) on pain , as measured by the pain severity subscale of the Multidimensional Pain Inventory . Secondary aims included determining the effects of strengthening and aerobic exercise on peak Vo2 uptake , leg strength , and pressure pain thresholds . In an intent‐to‐treat analysis , the mean ( ± st and ard deviation ) pain severity scores for the strength and aerobic groups at study completion were 34.4 ± 11.5 and 37.6 ± 11.9 , respectively . The group difference was −3.2 ( 95 % confidence interval , −8.7 to 2.3 ) , which was within the equivalence margin of Δ8 . Significant improvements in pain severity ( P ( P that strength and aerobic exercise had equivalent effects on reducing pain severity among patients with fibromyalgia",
"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",
"Background : In a 12-week r and omized controlled trial of the effects of lifestyle physical activity ( LPA ) on symptoms and function among adults with fibromyalgia , we found that LPA participants increased their average daily step count by 54 % , improved their self-reported functioning by 18 % , and reduced their pain by 35 % . Objectives : The objective of the study was to evaluate the intermediate ( 6 months ) and long-term ( 12 months ) effects of the LPA intervention on outcomes . Methods : Participants completed follow-up assessment s of physical activity , pain , fibromyalgia-related function , fatigue , depression , number of tender points , 6-minute walk test , and perceived improvement at 6 and 12 months after intervention . Results : Of the 73 participants who completed the 12-week trial , 53 ( 73 % ) completed both the 6- and 12-month follow-up . Although the LPA participants reported greater perceived improvement at each follow-up , they did not differ from controls on pain , physical activity , tenderness , fatigue , depression , or the 6-minute walk test . Self-reported functioning declined markedly at follow-up for the LPA participants . Conclusions : Although participants reported greater perceived improvement at each assessment , the beneficial effects of LPA on physical activity , function , and pain found after the 12-week intervention were not sustained over time . This recidivism is seen in studies of activity and exercise in nearly any condition , and innovative methods that may prevent this are a focus of future studies",
"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",
"Background Patients with fibromyalgia ( FM ) experience pain as well as deficits in positive affect and social relations that are not explicitly addressed in most behavioral treatments . Purpose The purpose of this study is to compare the effects of a 12-module online intervention targeting socioemotional regulation via mindful awareness/acceptance ( MSER ) with those of an attention-control treatment , healthy lifestyle tips ( HT ) . Methods Seventy-nine FM patients were r and omly assigned to MSER or HT , with outcomes assessed via online diary reports of pain , coping efficacy , affect , and social relations . Multilevel analyses revealed greater improvements in social functioning , positive affect , and coping efficacy for pain and stress ( all ps self-efficacy for coping with pain and positive engagement in relationships , marginal increases in positive affect , and decreases in relationship stress from an automated online intervention that targets socioemotional regulation skills . Findings highlight the potential utility of widely accessible , low-cost intervention methods for fibromyalgia ( Clinical trials.gov number NCT01748786 )"
] |
4116c98c-06ff-11f0-808a-c43d1ab1c353
|
Introduction Prolonged , uninterrupted periods of sedentary time may be associated with increased risk of Type II diabetes , cardiovascular disease and all-cause mortality even if the minimum recommended levels of daily physical activity are achieved . It is reported that children spend approximately 80 % of their day engaged in sedentary behaviours . Since children spend a large portion of their waking time at school , school-based interventions targeting excessive or interrupted periods of sedentary time have been investigated in a number of studies . However , results of the effectiveness of studies to- date have been inconsistent . Aim To conduct a systematic review to evaluate the effectiveness of school-based interventions design ed to reduce sedentary behaviour on objective ly measured sedentary time in children . Methods Five electronic data bases were search ed to retrieve peer- review ed studies published in English up to and including August 2015 . Studies that reported objective ly measured sedentary time before and after a school-based intervention to reduce sedentary time were included in the review . Risk of bias was assessed using the Cochrane Collaboration method . Results Our search identified eleven papers reporting eight interventions . Studies focused on the physical environment , the curriculum , individual in-class activities , homework activities or a combination of these strategies . Three studies reported decreases in sedentary time following intervention . Study follow-up periods ranged from immediately post-intervention to 12 months . None of the studies were judged to have a low risk of bias . Conclusions Multicomponent interventions which also include the use of st and ing desks may be an effective method for reducing children 's sedentary time in a school-based intervention . However , longer term trials are needed to determine the sustained effectiveness of such interventions on children 's sedentary time
|
[
"Aims This study assessed the efficacy of a school-based healthy lifestyle intervention ( Sport for LIFE ) for increasing physical activity , decreasing sedentary behaviour , reducing screen time behaviour , encouraging healthy attitudes and behaviour to nutrition , and reducing body mass index ( BMI ) in 8–9-year-old primary school children from lower socioeconomic background s in Northern Irel and . Methods A non-r and omised controlled trial of 416 children from 24 schools took part . Schools were r and omly assigned to one of two groups , an intervention or control group with 12 schools in each group . The intervention group received a 12-week school-based programme based on social cognitive theory . At baseline and follow-up , groups completed question naires assessing physical activity , screen time behaviour and dietary patterns . On each occasion anthropometric assessment s of height and weight were taken . Physical activity and sedentary behaviour were measured by accelerometry . Results Significant effects were observed for vigorous , moderate and light activity for the intervention group at follow-up . Sedentary behaviour was significantly reduced for the intervention group but not for the control group . No significant effects of the intervention on BMI , screen time behaviour or attitudes to nutrition , with the exception of non-core foods , were shown . Conclusions The programme was effective in increasing physical activity and reducing sedentary behaviour , however no significant changes in screen time behaviour and attitude to nutrition , with the exception of non-core foods , were observed . Future research ideas are offered for tackling low levels of physical activity in children",
"BakckgroundThe first aim was to examine the effect of the UP4FUN pilot intervention on children ’s total sedentary time . The second aim was to investigate if the intervention had an effect on children ’s physical activity ( PA ) level . Finally , we aim ed to investigate demographic differences ( i.e. age , gender , ethnicity , living status and having siblings ) between children in the intervention group who improved in sedentary time and PA at post-test and children in the intervention group who worsened in sedentary time and PA at post-test . Methods The six weeks UP4FUN intervention was tested in a r and omized controlled trial with pre-test post-test design with five intervention and five control schools in Belgium and included children of the 5th and 6th grade . The children wore accelerometers for seven days at pre- and post-test . Analyses included children with valid accelerometer data for at least two weekdays with minimum 10h-wearing time and one weekend day with 8h-wearing time . Result Final analyses included 372 children ( 60 % girls , mean age = 10.9 ± 0.7 years ) . There were no significant differences in the change in sedentary time or light PA between intervention and control schools for the total sample or for the subgroup analyses by gender . However , children ( specifically girls ) in the intervention group had a higher decrease in moderate-to-vigorous PA than children in the control group . In the intervention group , children who lived with both parents and children with one or more siblings were less likely to reduce sedentary time after exposure to the intervention . Older children , girls and children who lived with both parents were less likely to increase light PA after the intervention . Conclusion The UP4FUN intervention did not result in an effect on children ’s sedentary time . Based on the high amounts of accelerometer-derived sedentary time in this age group , more efforts are needed to develop strategies to reduce children ’s sedentary time",
"Background The optimal targets and strategies for effectively reducing sedentary behavior among young people are unknown . Intervention research that explores changes in mediated effects as well as in outcome behaviors is needed to help inform more effective interventions . Therefore , the purpose of this study was to examine the mid-intervention mediating effects on children ’s objective ly assessed classroom and total weekday sedentary time in the Transform-Us ! intervention . Methods The results are based on 293 children , aged 7- to 9-years-old at baseline , from 20 schools in Melbourne , Australia . Each school was r and omly allocated to one of four groups , which targeted reducing sedentary time in the school and family setting s ( SB ; n = 74 ) , increasing or maintaining moderate- to vigorous-intensity physical activity in the school and family setting s ( PA ; n = 75 ) , combined SB and PA ( SB + PA ; n = 80 ) , or the current practice control ( C ; n = 64 ) . Baseline and mid-intervention data ( 5–9 months ) were collected in 2010 and analyzed in 2012 . Classroom and total weekday sedentary time was objective ly assessed using ActiGraph accelerometers . The hypothesized mediators including , child enjoyment , parent and teacher outcome expectancies , and child perceived access to st and ing opportunities in the classroom environment , were assessed by question naire . Results The SB + PA group spent 13.3 min/day less in weekday sedentary time at mid-intervention compared to the control group . At mid-intervention , children in the SB group had higher enjoyment of st and ing in class ( 0.9 units ; 5-unit scale ) and all intervention groups had more positive perceptions of access to st and ing opportunities in the classroom environment ( 0.3 - 0.4 units ; 3-unit scale ) , compared to the control group . However , none of the hypothesized mediator variables had an effect on sedentary time ; thus , no mediating effects were observed . Conclusions While beneficial intervention effects were observed on some hypothesized mediating variables and total weekday sedentary time at mid-intervention , no significant mediating effects were found . Given the dearth of existing information , future intervention research is needed that explores mediated effects . More work is also needed on the development of reliable mediator measures that are sensitive to change overtime . Trial registration ACTRN12609000715279IS RCT",
"Objective To investigate the effectiveness of a school based intervention to increase physical activity , reduce sedentary behaviour , and increase fruit and vegetable consumption in children . Design Cluster r and omised controlled trial . Setting 60 primary schools in the south west of Engl and . Participants Primary school children who were in school year 4 ( age 8 - 9 years ) at recruitment and baseline assessment , in year 5 during the intervention , and at the end of year 5 ( age 9 - 10 ) at follow-up assessment . Intervention The Active for Life Year 5 ( AFLY5 ) intervention consisted of teacher training , provision of lesson and child-parent interactive homework plans , all material s required for lessons and homework , and written material s for school newsletters and parents . The intervention was delivered when children were in school year 5 ( age 9 - 10 years ) . Schools allocated to control received st and ard teaching . Main outcome measures The pre-specified primary outcomes were accelerometer assessed minutes of moderate to vigorous physical activity per day , accelerometer assessed minutes of sedentary behaviour per day , and reported daily consumption of servings of fruit and vegetables . Results 60 schools with more than 2221 children were recruited ; valid data were available for fruit and vegetable consumption for 2121 children , for accelerometer assessed physical activity and sedentary behaviour for 1252 children , and for secondary outcomes for between 1825 and 2212 children for the main analyses . None of the three primary outcomes differed between children in schools allocated to the AFLY5 intervention and those allocated to the control group . The difference in means comparing the intervention group with the control group was –1.35 ( 95 % confidence interval –5.29 to 2.59 ) minutes per day for moderate to vigorous physical activity , –0.11 ( –9.71 to 9.49 ) minutes per day for sedentary behaviour , and 0.08 ( –0.12 to 0.28 ) servings per day for fruit and vegetable consumption . The intervention was effective for three out of nine of the secondary outcomes after multiple testing was taken into account : self reported time spent in screen viewing at the weekend ( –21 ( –37 to –4 ) minutes per day ) , self reported servings of snacks per day ( –0.22 ( –0.38 to –0.05 ) ) , and servings of high energy drinks per day ( –0.26 ( –0.43 to –0.10 ) ) were all reduced . Results from a series of sensitivity analyses testing different assumptions about missing data and from per protocol analyses produced similar results . Conclusion The findings suggest that the AFLY5 school based intervention is not effective at increasing levels of physical activity , decreasing sedentary behaviour , and increasing fruit and vegetable consumption in primary school children . Change in these activities may require more intensive behavioural interventions with children or upstream interventions at the family and societal level , as well as at the school environment level . These findings have relevance for research ers , policy makers , public health practitioners , and doctors who are involved in health promotion , policy making , and commissioning services . Trial registration Current Controlled Trials IS RCT N50133740",
"Background Decreasing sedentary activities that involve prolonged sitting may be an important strategy to reduce obesity and other physical and psychosocial health problems in children . The first step to underst and ing the effect of sedentary activities on children ’s health is to objective ly assess these activities with a valid measurement tool . Purpose To examine the validity of the ActivPAL monitor in measuring sitting/lying , st and ing , and walking time , transition counts and step counts in children in a laboratory setting . Methods Twenty five healthy elementary school children ( age 9.9 ± 0.3 years ; BMI 18.2 ± 1.9 ; mean ± SD ) were r and omly recruited across the Auckl and region , New Zeal and . Children were fitted with ActivPAL monitors and observed during simulated free-living activities involving sitting/lying , st and ing and walking , followed by treadmill and over-ground activities at various speeds ( slow , normal , fast ) against video observation ( criterion measure ) . The ActivPAL sit-to-st and and st and -to-sit transition counts and steps were also compared with video data . The accuracy of step counts measured by the ActivPAL was also compared against the New Lifestyles NL-2000 and the Yamax Digi-Walker SW-200 pedometers . Results We observed a perfect correlation between the ActivPAL monitor in time spent sitting/lying , st and ing , and walking in simulated free-living activities with direct observation . Correlations between the ActivPAL and video observation in total numbers of sit-to-st and and st and -to-sit transitions were high ( r = 0.99 ± 0.01 ) . Unlike pedometers , the ActivPAL did not misclassify fidgeting as steps taken . Strong correlations ( r = 0.88 - 1.00 ) between ActivPAL step counts and video observation in both treadmill and over-ground slow and normal walking were also observed . During treadmill and over-ground fast walking and running , the correlations were low ( r = 0.21 - 0.46 ) . Conclusion The ActivPAL monitor is a valid measurement tool for assessing time spent sitting/lying , st and ing , and walking , sit-to-st and and st and -to-sit transition counts and step counts in slow and normal walking . The device did not measure accurately steps taken during treadmill and over-ground fast walking and running in children",
"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 The UP4FUN intervention is a family-involved school-based intervention aim ing at reducing and breaking up sitting time at home ( with special emphasis on screen time ) , and breaking up sitting time in school among 10–12 year olds in Europe . The purpose of the present paper was to evaluate its short term effects . Methodology /Principal Findings A total of 3147 pupils from Belgium , Germany , Greece , Hungary and Norway participated in a school-r and omized controlled trial . The intervention included 1–2 school lessons per week for a period of six weeks , along with assignments for the children and their parents . Screen time and breaking up sitting time were registered by self-report and total sedentary time and breaking up sitting time by accelerometry . The effect of the intervention on these behaviors was evaluated by multilevel regression analyses . All analyses were adjusted for baseline values and gender . Significance level was p≤0.01 . No significant intervention effects were observed , neither for self-reported TV/DVD or computer/game console time , nor for accelerometer-assessed total sedentary time and number of breaks in sitting time . The intervention group , however , reported more positive attitudes towards ( β = 0.25 ( 95 % CI 0.11 , 0.38 ) ) and preferences/liking for ( β = 0.20 ( 95 % CI 0.08 , 0.32 ) ) breaking up sitting time than the control group . Conclusions / Significance No significant intervention effect on self-reported screen time or accelerometer-assessed sedentary time or breaks in sitting time was observed , but positive effects on beliefs regarding breaking up sitting time were found in favor of the intervention group . Overall , these results do not warrant wider dissemination of the present UP4FUN intervention . Trial Registration International St and ard R and omized Controlled Trial Number Registry IS RCT",
"Background This pragmatic evaluation investigated the effectiveness of the Children ’s Health , Activity and Nutrition : Get Educated ! ( CHANGE ! ) Project , a cluster r and omised intervention to promote healthy weight using an educational focus on physical activity and healthy eating . Methods Participants ( n = 318 , aged 10–11 years ) from 6 Intervention and 6 Comparison schools took part in the 20 weeks intervention between November 2010 and March/April 2011 . This consisted of a teacher-led curriculum , learning re sources , and homework tasks . Primary outcome measures were waist circumference , body mass index ( BMI ) , and BMI z-scores . Secondary outcomes were objective ly-assessed physical activity and sedentary time , and food intake . Outcomes were assessed at baseline , at post-intervention ( 20 weeks ) , and at follow-up ( 30 weeks ) . Data were analysed using 2-level multi-level modelling ( levels : school , student ) and adjusted for baseline values of the outcomes and potential confounders . Differences in intervention effect by subgroup ( sex , weight status , socio-economic status ) were explored using statistical interaction . Results Significant between-group effects were observed for waist circumference at post-intervention ( β for intervention effect = −1.63 ( 95 % CI = −2.20 , -1.07 ) cm , p for BMI z-score at follow-up ( β=−0.24 ( 95 % CI = −0.48 , -0.003 ) , p=0.04 ) . At follow-up there was also a significant intervention effect for light intensity physical activity ( β=25.97 ( 95 % CI = 8.04 , 43.89 ) min , p=0.01 ) . Interaction analyses revealed that the intervention was most effective for overweight/obese participants ( waist circumference : β=−2.82 ( 95 % CI = −4.06 , -1.58 ) cm , p body size outcomes and light physical activity , and most effectively influenced body size outcomes among overweight and obese children and girls . The findings add support for the effectiveness of combined school-based physical activity and nutrition interventions . Additional work is required to test intervention fidelity and the sustained effectiveness of this intervention in the medium and long term . Trial registration Current Controlled Trials IS RCT N03863885",
"Background There is increasing evidence for the effectiveness of parental support programmes to promote healthy behaviours and prevent obesity in children , but only few studies have been conducted among groups with low socio-economic status . The aim of this study was to develop and evaluate the effectiveness of a parental support programme to promote healthy dietary and physical activity habits and to prevent overweight and obesity in six-year-old children in disadvantaged areas . Methods A cluster-r and omised controlled trial was carried out in disadvantaged areas in Stockholm . Participants were six-year-old children ( n = 378 ) and their parents . Thirty-one school classes from 13 schools were r and omly assigned to intervention ( n = 16 ) and control groups ( n = 15 ) . The intervention lasted for 6 months and included : 1 ) Health information for parents , 2 ) Motivational Interviewing with parents and 3 ) Teacher-led classroom activities with children . Physical activity was measured by accelerometry , dietary intake and screen time with a question naire , body weight and height were measured and BMI st and ard deviation score was calculated . Measurements were conducted at baseline , post-intervention and at 5months follow-up . Group effects were examined using Mixed-effect Regression analyses adjusted for sex , parental education and baseline values . Results Fidelity to all three intervention components was satisfactory . Significant intervention effects were found regarding consumption of unhealthy foods ( p = 0.01 ) and unhealthy drinks ( p = 0.01 ) . At follow-up , the effect on intake of unhealthy foods was sustained for boys ( p = 0.03 ) . There was no intervention effect on physical activity . Further , the intervention had no apparent effect on BMI sds for the whole sample , but a significant difference between groups was detected among children who were obese at baseline ( p = 0.03 ) which was not sustained at follow-up . Conclusions The Healthy School Start study shows that it is possible to influence intake of unhealthy foods and drinks and weight development in obese children by providing individual parental support in a school context . However , the effects were short-lived . Therefore , the programme needs to be prolonged and /or intensified in order to obtain stronger and sustainable effects . This study is an important contribution to the further development of evidence -based parental support programmes to prevent overweight and obesity in children in disadvantaged areas ",
"Background To investigate the interpersonal and physical environment mediators of the Transform-Us ! mid-intervention effects on physical activity ( PA ) during recess and lunchtime . Methods Transform-Us ! is a clustered r and omised school-based intervention with four groups : sedentary behaviour intervention ( SB-I ) , PA intervention ( PA-I ) , combined PA+SB-I and control group . All children in grade 3 from 20 participating primary schools in Melbourne , Australia were eligible to complete annual evaluation assessment s. The outcomes were the proportion of time spent in moderate-to-vigorous PA ( MVPA ) and light PA ( LPA ) during recess and lunchtime assessed by accelerometers . Potential mediators included : perceived social support from teachers ; perceived availability of line markings ; perceived accessibility of sports equipment ; and perceived school play environment . Generalised linear models were used and mediation effects were estimated by product-of-coefficients ( a·b ) approach . Results 268 children ( 8.2 years , 57 % girls at baseline ) provided complete data at both time points . A significant intervention effect on MVPA during recess in the SB-I and PA-I groups compared with the control group ( proportional difference in MVPA time ; 38 % ( 95 % CI 21 % to 57 % ) and 40 % ( 95 % CI 20 % to 62 % ) , respectively ) was found . The perceived school play environment was significantly positively associated with MVPA at recess among girls . An increase in perceived social support from teachers suppressed the PA+SB-I effect on light PA during recess ( a·b= −0.03 , 95 % CI −0.06 to −0.00 ) . No significant mediating effects on PA during recess and lunchtime were observed . Conclusions A positive perception of the school play environment was associated with higher MVPA during recess among girls . Future studies should conduct mediation analyses to explore underlying mechanisms of PA interventions",
"Background : Accurate measurement of physical activity patterns can be used to identify sedentary behaviour and may facilitate interventions aim ed at reducing inactivity . Objective : To evaluate the activPAL physical activity monitor as a measure of posture and motion in everyday activities using observational analysis as the criterion st and ard . Methods : Wearing three activPAL monitors , 10 healthy participants performed a range of r and omly assigned everyday tasks incorporating walking , st and ing and sitting . Each trial was captured on a digital camera and the recordings were synchronised with the activPAL . The time spent in different postures was visually classified and this was compared with the activPAL output . Results : Intraclass correlation coefficients ( ICC 2,1 ) for interdevice reliability ranged from 0.79 to 0.99 . Using the Bl and and Altman method , the mean percentage difference between the activPAL monitor and observation for total time spent sitting was 0.19 % ( limits of agreement −0.68 % to 1.06 % ) and for total time spent upright was −0.27 % ( limits of agreement −1.38 % to 0.84 % ) . The mean difference for total time spent st and ing was 1.4 % ( limits of agreement −6.2 % to 9.1 % ) and for total time spent walking was −2.0 % ( limits of agreement −16.1 % to 12.1 % ) . A second-by-second analysis between observer and monitor found an overall agreement of 95.9 % . Conclusion : The activPAL activity monitor is a valid and reliable measure of posture and motion during everyday physical activities",
"Little is known about the effectiveness of school-based health promotion on physical activity inequalities among children from low-income areas . This study compared the two-year change in physical activity among 10 - 11 year-old children attending schools with and without health promotion programs by activity level , body weight status , and socioeconomic background s to assess whether health promotion programs reduce or exacerbate health inequalities . This was a quasi-experimental trial of a Comprehensive School Health ( CSH ) program implemented in schools located in socioeconomically disadvantaged neighbourhoods in Edmonton , Alberta , Canada . In the spring of 2009 and 2011 , pedometer ( 7 full days ) and demographic data were collected from cross-sectional sample s of grade five children from 10 intervention and 20 comparison schools . Socioeconomic status was determined from parent self-report . Low-active , active , and high-active children were defined according to step-count tertiles . Multilevel linear regression methods adjusted for potential confounders were used to assess the relative inequity in physical activity and were compared between groups and over-time . In 2009 , a greater proportion of students in the intervention schools were overweight ( 38 % vs. 31 % p = 0.03 ) and were less active ( 10,827 vs. 12,265 steps/day p relative difference in step-counts between intervention and comparison schools reduced from -15.5 % to 0 % among low-active students , from -13.4 % to 0 % among active students , and from -15.1 % to -2.7 % among high-active students . The relative difference between intervention and comparison schools reduced from -11.1 % to -1.6 % among normal weight students , from -16.8 % to -1.4 % among overweight students , and was balanced across socioeconomic subgroups . These findings demonstrate that CSH programs implemented in socioeconomically disadvantaged neighbourhoods reduced inequalities in physical activity . Investments in school-based health promotion are a viable , promising , and important approach to improve physical activity and prevent childhood obesity , and may also reduce inequalities in health"
] |
4116c9c8-06ff-11f0-808a-c43d1ab1c353
|
In the present review , we argue that social disconnectedness could and should be included in primary -care screening protocol s for the detection of cardiometabolic disease . Empirical evidence indicates that weak social connectedness represents a serious risk factor for chronic diseases , including cardiovascular disease , diabetes , and various cancers . Weak social connectedness , however , is largely regarded as a second-tier health-risk factor in clinical and research setting s. This may be because the mechanisms by which this factor impacts on physical health are poorly understood . Budding research , however , advances the idea that social connectedness buffers against stress-related allostatic load-a known precursor for cardiovascular disease and cancer . The present paper review s the empirical knowledge on the relationship between everyday stress , social connectedness , and allostatic load . Of 6022 articles retained in the literature search , 20 met predefined inclusion criteria . These studies overwhelmingly support the notion that social connectedness correlates negatively with allostatic load . Several moderators of this relationship were also identified , including gender , social status , and quality of social ties . More research into these factors , however , is warranted to conclusively determine their significance . The current evidence strongly indicates that the more socially connected individuals are , the less likely they are to experience chronic stress and associated allostatic load . The negative association between social connectedness and various chronic diseases can thus , at least partially , be explained by the buffering qualities of social connectedness against allostatic load . We argue that assessing social connectedness in clinical and epidemiological setting s may therefore represent a considerable asset in terms of prevention and intervention
|
[
"CONTEXT The physical health consequences of childhood psychosocial adversities may be as substantial as the mental health consequences , but whether this is the case remains unclear because much prior research has involved unrepresentative sample s and a selective focus on particular adversities or physical outcomes . The association between early-onset mental disorders and subsequent poor physical health in adulthood has not been investigated . OBJECTIVE To investigate whether childhood adversities and early-onset mental disorders are independently associated with increased risk of a range of adult-onset chronic physical conditions in culturally diverse sample s spanning the full adult age range . DESIGN Cross-sectional community surveys of adults in 10 countries . SETTING General population . PARTICIPANTS Adults ( ie , aged ≥18 years ; N = 18 303 ) , with diagnostic assessment and determination of age at onset of DSM-IV mental disorders , assessment of childhood familial adversities , and age of diagnosis or onset of chronic physical conditions . MAIN OUTCOME MEASURES Risk ( ie , hazard ratios ) of adult-onset ( ie , at age > 20 years ) heart disease , asthma , diabetes mellitus , arthritis , chronic spinal pain , and chronic headache as a function of specific childhood adversities and early-onset ( ie , at age years ) DSM-IV depressive and anxiety disorders , with mutual adjustment . RESULTS A history of 3 or more childhood adversities was independently associated with onset of all 6 physical conditions ( hazard ratios , 1.44 to 2.19 ) . Controlling for current mental disorder made little difference to these associations . Early-onset mental disorders were independently associated with onset of 5 physical conditions ( hazard ratios , 1.43 to 1.66 ) . CONCLUSIONS These results are consistent with the hypothesis that childhood adversities and early-onset mental disorders have independent , broad-spectrum effects that increase the risk of diverse chronic physical conditions in later life . They require confirmation in a prospect ively design ed study . The long course of these associations has theoretical and research implication",
"This study was design ed to examine the prospect i ve relations of perceived racial discrimination with allostatic load ( AL ) , along with a possible buffer of the association . A sample of 331 African Americans in the rural South provided assessment s of perceived discrimination from ages 16 to 18 years . When youth were 18 years , caregivers reported parental emotional support and youth assessed peer emotional support . AL and potential confounder variables were assessed when youth were 20 . Latent growth mixture modeling identified two perceived discrimination classes : high and stable , and low and increasing . Adolescents in the high and stable class evinced heightened AL even with confounder variables controlled . The racial discrimination to AL link was not significant for young adults who received high emotional support ",
"This study examined whether highly cynical individuals benefit less from social support during an acute stressor than individuals low in cynicism . College students ( 52 men , 52 women ) performed a stressful speech task alone or in the presence of a supportive confederate . There was an interactive effect of social support and cynicism on cardiovascular reactivity : Low cynicism participants who received support has smaller increases in blood pressure during the speech than low cynicism participants without support and high cynicism participants with or without support . Participants ' psychological stress appeared to mediate the main effects of support on blood pressure reactivity , but not the Support x Cynicism interaction . Results suggest that cynical attitudes may undermine the stress buffering potential of interpersonal support",
"OBJECTIVE Analyses test the hypothesis that aspects of social relationships ( quantity of ties , social support and social strain ) are associated with differences in levels of biological risk across multiple major physiological regulatory systems and consequently overall multi-systems risk ( i.e. , allostatic load [ AL ] ) . METHODS Data are from the Coronary Artery Risk Development in Young Adults ( CARDIA ) study --a bi-ethnic , prospect i ve , multi-center epidemiological study , initiated in 1985 - 1986 to track the development of cardiovascular risk in young adulthood ( N=5115 ) . At the year 15 follow-up when participants were between 32 and 45 years of age , additional social and biological data were collected ; biological data used to assess AL were collected at the Oakl and , CA and Chicago , IL sites ( N=844 ) . RESULTS Social strains were most strongly and positively related to overall AL ( Cohen 's d=.79 for highest vs. lowest quartile ) , and to each of its component biological subsystems , independent of social ties and support as well as sociodemographics and health behaviors . Social ties and emotional support were also negatively related to AL ( Cohen 's d=.33 and d=.44 for lowest vs. highest quartiles of ties and support , respectively ) though controls for social strains reduced these associations to non- significance . Social support and social strain were more strongly related to overall AL than to any of its component subscales while social ties were less strongly related to AL and to its component subscales . There was no evidence that effects differed by sex , age or ethnicity . CONCLUSIONS Findings focus attention on the particularly strong relationship between social strains and profiles of biological risk and support the cumulative impact of social factors on biological risks , showing larger effects for cumulative AL than for any of the individual biological systems",
"Objective To examine the relationship between perceived discrimination and medication adherence among black people with hypertension and the role of stress and depressive symptoms in this relationship . Perceived racial discrimination has been associated with poor health outcomes in blacks ; its relationship to medication adherence among hypertensive patients remains untested . Methods We measured perceived racial discrimination at baseline , stress and depressive symptoms at 6 months , and medication adherence at 12 months among patients enrolled in a 30-site cluster-r and omized controlled trial testing a patient and physician-targeted intervention to improve blood pressure . A mediational method with bootstrapping ( stratified by site ) confidence intervals was used to estimate the indirect association between perceived discrimination and medication adherence through stress and depression . Results Of 1056 patients from 30 sites enrolled in the trial , 463 had complete data on all four measures at 6 and 12 months and were included in the analyses . Adjusting for clustering , perceived discrimination was associated with poor medication adherence ( B = 0.138 , p = .011 ) at 12 months , and with stress ( B = 2.24 , p = .001 ) and depression ( B = 1.47 , p = .001 ) at 6 months . When stress and depression were included in the model , there was a 65 % reduction in the total association of perceived discrimination with medication adherence , and the relationship was no longer significant ( B = 0.049 , p = .35 ) . Conclusions Perceived discrimination is associated with poor medication adherence among hypertensive blacks , and stress and depressive symptoms may account for this relationship . Trial Registration clinical trials.gov Identifier : NCT00233220"
] |
4116ca04-06ff-11f0-808a-c43d1ab1c353
|
Background The health effects of light-intensity physical activity ( PA ) are not well known today . Objective We conducted a systematic review to assess the association of accelerometer-measured light-intensity PA with modifiable health outcomes in adults and older adults . Methods A systematic literature search up to March 2016 was performed in the PubMed , EMBASE , Web of Science and Google Scholar electronic data bases , without language limitations , for studies of modifiable health outcomes in adults and older adults in the National Health and Nutrition Examination Survey accelerometer data set . Results Overall , 37 cross-sectional studies and three longitudinal studies were included in the analysis , with considerable variation observed between the studies with regard to their operationalization of light-intensity PA . Light-intensity PA was found to be beneficially associated with obesity , markers of lipid and glucose metabolism , and mortality . Few data were available on musculoskeletal outcomes and results were mixed . Conclusions Observational evidence that light-intensity PA can confer health benefits is accumulating . Currently inactive or insufficiently active people should be encouraged to engage in PA of any intensity . If longitudinal and intervention studies corroborate our findings , the revision of PA recommendations to include light-intensity activities , at least for currently inactive population s , might be warranted
|
[
"Sedentary adults ( N = 379 ) were r and omly assigned in a 2 x 2 design to walk 30 min per day at a frequency of either 3 - 4 or 5 - 7 days per week , at an intensity of either 45%-55 % or 65%-75 % of maximum heart rate reserve . Analyses of exercise accumulated over 6 months showed greater amounts completed in the higher frequency ( p = .0001 ) and moderate intensity ( p = .021 ) conditions . Analyses of percentage of prescribed exercise completed showed greater adherence in the moderate intensity(p = .02 ) condition . Prescribing a higher frequency increased the accumulation of exercise without a decline in adherence , whereas prescribing a higher intensity decreased adherence and result ed in the completion of less exercise",
"As the world 's population ages , the occurrence of osteoporosis-related fractures is projected to increase . Low areal bone mineral density ( aBMD ) , a well-known risk factor for fractures , may be influenced by physical activity ( PA ) . In this cross-sectional study , we aim ed to investigate potential associations between objective measures of PA and bone properties , in a population -based cohort of 1228 70-year-old men and women . We measured volumetric BMD ( vBMD , mg/cm(3 ) ) together with cross-sectional area ( CSA , mm(2 ) ) by peripheral quantitative computed tomography at sites located 4 % and 66 % in the distal-proximal trajectory at the tibia and radius . We also measured aBMD ( g/cm(2 ) ) by dual energy X-ray absorptiometry at the femoral neck , lumbar spine ( L1-L4 ) and radius . Participants wore triaxial accelerometers for 7 consecutive days to obtain objective estimates of PA . The intensity of the objective PA was divided into light ( 100 - 1951 counts/min [ CPM ] ) , moderate ( 1952 - 5724 cpm ) and vigorous ( ≥ 5725 cpm ) . Maximal accelerations for the anterior-posterior ( z ) , medio-lateral ( x ) , and vertical ( y ) axes were also separately assessed . Associations were investigated using bivariate correlations and multiple linear regression , adjusted for height , weight and sex . Vigorous PA showed the strongest association with femoral neck aBMD ( β=0.09 , p both moderate and vigorous PAs were associated with cortical area and trabecular vBMD in the weight-bearing tibia ( all p Peak vertical accelerations were associated significantly with cortical area ( β=0.09 , p ) and trabecular vBMD ( β=0.09 , p=0.001 ) of the tibia , whereas peak anterior-posterior accelerations showed no correlation with these properties . No positive association was found between objective ly measured PA and bone parameters of the radius . In conclusion , vertical accelerations and moderate to vigorous PA independently predict bone properties , especially in the weight-bearing tibia , in 70-year-old men and women",
"Objectives : We have a limited underst and ing of the epidemiological association between objective ly measured physical activity and depression among older adults . Therefore , the purpose of this study was to examine the association between accelerometer-assessed physical activity and depression symptoms among a nationally representative sample of US older adults . Methods : Data from the 2005–2006 National Health and Nutrition Examination Survey was used . 708 older adults ( 65 + years ) wore an ActiGraph 7164 accelerometer for at least 4 days , and completed data on the study covariates along with depression , as assessed by the Patient Health Question naire-9 . Results : After controlling for age , gender , race-ethnicity , body mass index , marital status , education , comorbidity index , and physical functioning , for every 60-minute increase in light-intensity physical activity , participants were 20 % ( OR = 0.80 ; 95 % CI : 0.67–0.95 ; p = 0.01 ) less likely to be depressed . Moderate-to-vigorous physical activity was also inversely associated with depression ( OR = 0.78 ; 95 % CI : 0.64–0.94 ; p = 0.01 ) . Conclusion : These findings suggest that promoting physical activity , even light-intensity physical activity , may have positive mental health effects among older adults . Future prospect i ve and experimental studies are warranted",
"Physical activity enhances insulin action in obese/overweight individuals . However , the exercise prescription required for the optimal enhancement is not known . The purpose of this study was to test the hypothesis that exercise training consisting of vigorous-intensity activity would enhance insulin sensitivity more substantially than moderate-intensity activity . Sedentary , overweight/obese subjects ( n = 154 ) were r and omly assigned to either control or an exercise group for 6 mo : 1 ) low-volume/moderate-intensity group [ approximately 12 miles walking/wk at 40 - 55 % peak O2 consumption ( Vo2 peak ) ] , 2 ) low-volume/high-intensity group ( approximately 12 miles jogging/wk at 65 - 80 % Vo2 peak ) , and 3 ) high-volume/high-intensity group ( approximately 20 miles jogging/wk at 65 - 80 % Vo2 peak ) . Training volume ( miles/wk ) was achieved by exercising approximately 115 min/wk ( low-volume/high-intensity group ) or approximately 170 min/wk ( low-volume/moderate-intensity and high-volume/high-intensity groups ) . Insulin action was measured with an insulin sensitivity index ( SI ) from an intravenous glucose tolerance test . In the control group , there was a decrement ( P SI . In contrast , all the exercise groups significantly ( P SI ; the relative increment in the low-volume/moderate-intensity and high-volume/high-intensity groups ( approximately 85 % ) were greater than in the low-volume/high-intensity group ( approximately 40 % ) . In conclusion , physical activity encompassing a wide range of intensity and volume minimizes the insulin resistance that develops with a sedentary lifestyle . However , an exercise prescription that incorporated approximately 170 min of exercise/wk improved insulin sensitivity more substantially than a program utilizing approximately 115 min of exercise/wk , regardless of exercise intensity and volume . Total exercise duration should thus be considered when design ing training programs with the intent of improving insulin action",
"UNLABELLED The elevation of postpr and ial plasma triglycerides ( PPTG ) in the blood is an independent risk factor for atherosclerosis . Although acute exercise typically attenuates PPTG , the effect of exercise intensity on PPTG is less well established , particularly in well-controlled conditions for physical activities and diet . PURPOSE We sought to determine the efficacy of exercise at 65 % V˙O2max with an extended sitting time and isoenergetic intermittent walking exercise at a self-selected walking speed ( approximately 25 % V˙O2max ) on PPTG compared with that of a sitting control condition . In a r and omized crossover design , nine healthy young men completed three trials with a > 1-wk interval between trials . After 2 d of activity and diet normalization , participants performed prolonged sitting nonexercise control ( CON ) , prolonged sitting with subsequent 1-h running at 65 % V˙O2max ( MOD ) , or isoenergetic intermittent walking at approximately 25 % V˙O2max ( LOW ) on day 3 . This was followed on day 4 by a 6-h high-fat tolerance test . RESULTS MOD and LOW reduced incremental triglyceride ( TG ) area under the curve ( TG AUCI ) compared with that in CON by 33.6 % ( P also reduced TG AUCI compared with that in LOW by 17.2 % ( P 0.03 ) . The reduced TG AUCI in MOD was accompanied by reduced plasma glucose response and enhanced fat oxidation compared with those in LOW and CON ( for all , P effective in reducing PPTG compared with CON . However , MOD was more effective in reducing PPTG compared with LOW",
"BACKGROUND The health benefits of leisure-time physical activity are well known , but whether less exercise than the recommended 150 min a week can have life expectancy benefits is unclear . We assessed the health benefits of a range of volumes of physical activity in a Taiwanese population . METHODS In this prospect i ve cohort study , 416,175 individuals ( 199,265 men and 216,910 women ) participated in a st and ard medical screening programme in Taiwan between 1996 and 2008 , with an average follow-up of 8·05 years ( SD 4·21 ) . On the basis of the amount of weekly exercise indicated in a self-administered question naire , participants were placed into one of five categories of exercise volumes : inactive , or low , medium , high , or very high activity . We calculated hazard ratios ( HR ) for mortality risks for every group compared with the inactive group , and calculated life expectancy for every group . FINDINGS Compared with individuals in the inactive group , those in the low-volume activity group , who exercised for an average of 92 min per week ( 95 % CI 71 - 112 ) or 15 min a day ( SD 1·8 ) , had a 14 % reduced risk of all-cause mortality ( 0·86 , 0·81 - 0·91 ) , and had a 3 year longer life expectancy . Every additional 15 min of daily exercise beyond the minimum amount of 15 min a day further reduced all-cause mortality by 4 % ( 95 % CI 2·5 - 7·0 ) and all-cancer mortality by 1 % ( 0·3 - 4·5 ) . These benefits were applicable to all age groups and both sexes , and to those with cardiovascular disease risks . Individuals who were inactive had a 17 % ( HR 1·17 , 95 % CI 1·10 - 1·24 ) increased risk of mortality compared with individuals in the low-volume group . INTERPRETATION 15 min a day or 90 min a week of moderate-intensity exercise might be of benefit , even for individuals at risk of cardiovascular disease . FUNDING Taiwan Department of Health Clinical Trial and Research Center of Excellence and National Health Research Institutes",
"BACKGROUND Obesity is a major health problem due , in part , to physical inactivity . The amount of activity needed to prevent weight gain is unknown . OBJECTIVE To determine the effects of different amounts and intensities of exercise training . DESIGN R and omized controlled trial ( February 1999-July 2002 ) . SETTING AND PARTICIPANTS Sedentary , overweight men and women ( aged 40 - 65 years ) with mild to moderate dyslipidemia were recruited from Durham , NC , and surrounding communities . INTERVENTIONS Eight-month exercise program with 3 groups : ( 1 ) high amount/vigorous intensity ( calorically equivalent to approximately 20 miles [ 32.0 km ] of jogging per week at 65%-80 % peak oxygen consumption ) ; ( 2 ) low amount/vigorous intensity ( equivalent to approximately 12 miles [ 19.2 km ] of jogging per week at 65%-80 % ) , and ( 3 ) low amount/moderate intensity ( equivalent to approximately 12 miles [ 19.2 km ] of walking per week at 40%-55 % ) . Subjects were counseled not to change their diet and were encouraged to maintain body weight . MAIN OUTCOME MEASURES Body weight , body composition ( via skinfolds ) , and waist circumference . RESULTS Of 302 subjects screened , 182 met criteria and were r and omized and 120 completed the study . There was a significant ( P amount of exercise and amount of weight loss and fat mass loss . The high-amount/vigorous-intensity group lost significantly more body mass ( in mean [ SD ] kilograms ) and fat mass ( in mean [ SD ] kilograms ) ( -2.9 [ 2.8 ] and -4.8 [ 3.0 ] , respectively ) than the low-amount/moderate-intensity group ( -0.9 [ 1.8 ] and -2.0 [ 2.6 ] , respectively ) , the low-amount/vigorous-intensity group ( -0.6 [ 2.0 ] and -2.5 [ 3.4 ] , respectively ) , and the controls ( + 1.0 [ 2.1 ] and + 0.4 [ 3.0 ] , respectively ) . Both low-amount groups had significantly greater improvements than controls but were not different from each other . Compared with controls , all exercise groups significantly decreased abdominal , minimal waist , and hip circumference measurements . There were no significant changes in dietary intake for any group . CONCLUSIONS In nondieting , overweight subjects , the controls gained weight , both low-amount exercise groups lost weight and fat , and the high-amount group lost more of each in a dose-response manner . These findings strongly suggest that , absent changes in diet , a higher amount of activity is necessary for weight maintenance and that the positive caloric imbalance observed in the overweight controls is small and can be reversed by a modest amount of exercise . Most individuals can accomplish this by walking 30 minutes every day",
"OBJECTIVE To describe the 1 ) lifestyle intervention used in the Finnish Diabetes Prevention Study , 2 ) short- and long-term changes in diet and exercise behavior , and 3 ) effect of the intervention on glucose and lipid metabolism . RESEARCH DESIGN AND METHODS There were 522 middle-aged , overweight subjects with impaired glucose tolerance who were r and omized to either a usual care control group or an intensive lifestyle intervention group . The control group received general dietary and exercise advice at baseline and had an annual physician 's examination . The subjects in the intervention group received additional individualized dietary counseling from a nutritionist . They were also offered circuit-type resistance training sessions and advised to increase overall physical activity . The intervention was the most intensive during the first year , followed by a maintenance period . The intervention goals were to reduce body weight , reduce dietary and saturated fat , and increase physical activity and dietary fiber . RESULTS The intervention group showed significantly greater improvement in each intervention goal . After 1 and 3 years , weight reductions were 4.5 and 3.5 kg in the intervention group and 1.0 and 0.9 kg in the control group , respectively . Measures of glycemia and lipemia improved more in the intervention group . CONCLUSIONS The intensive lifestyle intervention produced long-term beneficial changes in diet , physical activity , and clinical and biochemical parameters and reduced diabetes risk . This type of intervention is a feasible option to prevent type 2 diabetes and should be implemented in the primary health care system",
"Exercise duration and intensity are important parameters in exercise prescription and play a major role in improving insulin sensitivity ( including transient and persistent improvement effects following cessation of training ) in patients with type 2 diabetes mellitus ( T2DM ) . However , whether duration or intensity of exercise is the more important factor has yet to be established . Therefore , we aim ed to determine whether exercise prescriptions differing in duration and intensity differ in their ability to aid T2DM patients to retain insulin sensitivity following the conclusion of a period of training . Sedentary T2DM patients ( age 51.2 ± 1.3 years ) were assigned to either a low-intensity ( 50 % VO(2peak ) , n = 27 ) or a high-intensity exercise group ( 75 % VO(2peak ) , n = 28 ) , and followed a 12-week exercise program of 5 sessions/week and 240 kcal/session . Insulin sensitivity ( oral glucose tolerance test , ISI ) was measured when subjects were sedentary and at 16 - 24 h and 15 days after the final training bout . The low-intensity group spent more training time to training per exercise session than the high-intensity group ( 56.1 ± 3.0 min/session vs. 34.3 ± 2.4 min/session ) ( P the total amount of energy expended was the same . ISI was increased in both groups 16 - 24 h after the final training session , but only the low-intensity group still had elevated ISI 15 days after the cessation of training . These findings suggest that in T2DM patients , the persistent training-induced improvements in insulin sensitivity may be more dependent on exercise duration than exercise intensity in regimens with the same level of energy expenditure",
"Objective : To examine physical activity ( PA ) thresholds affecting glucose , insulin and lipid concentrations and body fat composition in high-risk patients for type 2 diabetes (T2D).Intervention : A total of 113 subjects of both genders having abnormal glucose levels in the oral glucose tolerance test were contacted . A total of 78 subjects with age 58.8±10.4 years and body mass index 31.7±5.3 kg m−2 were r and omly assigned to intervention and control groups . Intervention consisted of a supervised walking ( 60 min three times weekly ) for 3 months . All the subjects received st and ard care for PA and weight reduction and wore an accelerometer during the whole wakeful time . Results : Over 80 % of the daily steps clustered at an acceleration level of 0.3–0.7 g ( 2–3 km h−1 of walking ) and were 5870 in the intervention and 4434 in the control group ( P in fasting and 2-h glucose , body weight or maximal oxygen uptake . In contrast , changes in fasting and 2-h insulin ( −3.4 mU l−1 , P=0.035 and −26.6 , P=0.003 , respectively ) , homeostasis model assessment -estimated insulin resistance ( −1.0 , P=0.036 ) , total cholesterol ( −0.55 mmol l−1 , P=0.041 ) , low-density lipoprotein ( LDL ) cholesterol ( −0.36 mmol l−1 , P=0.008 ) and visceral fat area ( −5.5 cm2 , P=0.030 ) were significantly greater in the intervention than in control subjects . The overall effects of PA were analyzed by quartiles of daily steps of all subjects . There were significant reductions in total and LDL cholesterol and visceral fat area between the highest ( daily steps over 6520 ) and the lowest quartile ( 1780–2810 daily steps ) . The changes associated with PA remained significant after adjustments of baseline , sex , age and body weight change . Conclusion : Habitual and structured PAs with the acceleration levels of 0.3–0.7 g and daily steps over 6520 , equivalent to walking at 2–3 km h−1 for 90 min daily , st and ing for the relative PA intensity of 30–35 % of the maximal oxygen uptake , are clinical ly beneficial for overweight/obese and physically inactive individuals with a high risk for T2D",
"OBJECTIVES To examine associations between objective measures of activity level and mortality risk in older men . DESIGN Prospect i ve cohort study . SETTING Six U.S. sites . PARTICIPANTS Men aged 71 and older followed an average of 4.5 years ( N = 2,918 ) . MEASUREMENTS Time awake spent in sedentary behavior ( metabolic equivalent ( MET ) level ≤1.50 ) , light activity ( MET level 1.51 - 2.99 ) , and at least moderate activity ( MET level ≥3.00 ) measured using an activity monitor worn for 5 days or longer and expressed as quartiles . Deaths were confirmed with death certificates ; cause of death was adjudicated by review of certificates and records . RESULTS During follow-up , 409 ( 14 % ) men died . After multivariable adjustment , comparing Q4 with Q1 , more time spent in sedentary behavior ( Q4 vs Q1 , hazard ratio ( HR ) = 1.51 , 95 % confidence interval ( CI ) = 1.10 - 2.08 ) , less time spent in light activity ( Q1 vs Q4 , HR = 1.54 , 95 % CI = 1.06 - 2.24 ) , and less time spent in at least moderate activity ( Q1 vs Q4 , HR = 1.56 , 95 % CI = 1.09 - 2.25 ) were similarly associated with greater mortality risk primarily due to higher risks of cardiovascular and noncardiovascular , noncancer death . The association between time spent in sedentary behavior and mortality varied according to time spent at higher activity level . More time spent in sedentary behavior was associated with greater risk of death in men spending 1.2 ( median ) h/d or more in at least moderate activity ( Q4 vs Q1 , HR = 2.09 , 95 % CI = 1.26 - 3.49 ) but not in those spending less time ( Q4 vs Q1 , HR = 1.02 , 95 % CI = 0.62 - 1.66 ) ( P = .005 for interaction ) . CONCLUSION In older men exceeding current guidelines on physical activity , more time spent in sedentary behavior is associated with greater mortality risk ",
"BACKGROUND Increased physical activity is related to reduced risk of cardiovascular disease , possibly because it leads to improvement in the lipoprotein profile . However , the amount of exercise training required for optimal benefit is unknown . In a prospect i ve , r and omized study , we investigated the effects of the amount and intensity of exercise on lipoproteins . METHODS A total of 111 sedentary , overweight men and women with mild-to-moderate dyslipidemia were r and omly assigned to participate for six months in a control group or for approximately eight months in one of three exercise groups : high-amount-high-intensity exercise , the caloric equivalent of jogging 20 mi ( 32.0 km ) per week at 65 to 80 percent of peak oxygen consumption ; low-amount-high-intensity exercise , the equivalent of jogging 12 mi ( 19.2 km ) per week at 65 to 80 percent of peak oxygen consumption ; or low-amount-moderate-intensity exercise , the equivalent of walking 12 mi per week at 40 to 55 percent of peak oxygen consumption . Subjects were encouraged to maintain their base-line body weight . The 84 subjects who complied with these guidelines served as the basis for the main analysis . Detailed lipoprotein profiling was performed by nuclear magnetic resonance spectroscopy with verification by measurement of cholesterol in lipoprotein subfractions . RESULTS There was a beneficial effect of exercise on a variety of lipid and lipoprotein variables , seen most clearly with the high amount of high-intensity exercise . The high amount of exercise result ed in greater improvements than did the lower amounts of exercise ( in 10 of 11 lipoprotein variables ) and was always superior to the control condition ( 11 of 11 variables ) . Both lower-amount exercise groups always had better responses than the control group ( 22 of 22 comparisons ) . CONCLUSIONS The highest amount of weekly exercise , with minimal weight change , had widespread beneficial effects on the lipoprotein profile . The improvements were related to the amount of activity and not to the intensity of exercise or improvement in fitness",
"Abstract . The development of rebound hypoglycaemia has been reported after pre-exercise carbohydrate ( CHO ) ingestion in some studies but not in others . Differences in the experimental design and factors such as the exercise intensity are likely to be responsible for the discrepancies between these studies . Exercise intensity might be a crucial factor since it affects both insulinaemia and glucose uptake . Therefore the aim of the present study was to compare the glycaemic and insulinaemic responses to exercise at different intensities after ingestion of a st and ardized pre-exercise CHO load . Eight moderately trained subjects consumed 75 g of glucose 45 min prior to 20 min of exercise at 40 % , 65 % or 80 % maximal power output . Blood sample s were collected before glucose ingestion , at 15 min intervals at rest and 5 min intervals during exercise . During exercise , measurements of heart rate and breath-by-breath analysis of expired gas were performed continuously . The trials were performed at [ mean ( SEM ) ] 55 ( 1 ) , 77 ( 1 ) and 90 ( 1 ) percentages maximal oxygen uptake . At the onset of exercise , plasma glucose concentration returned to pre-ingestion levels , while the insulin concentration was more than three times higher than at rest [ on average 57 ( 7 ) compared to 16 ( 1 ) μU·ml–1 ) . During exercise , plasma glucose concentrations decreased during the first 5 min of exercise and then stabilized in all trials at concentrations that would not be considered to be hypoglycaemic . There were no significant differences in glucose or insulin concentrations between the three trials during exercise . These data suggest that the glycaemic response to ingestion of 75 g of CHO 45 min pre-exercise is similar during exercise of different intensities",
"PURPOSE Women who are unable to return to a healthy weight by 6 months postpartum increase their risk factors for the development of chronic disease ( CD ; including metabolic syndrome , obesity , and cardiovascular disease ) . In a prospect i ve r and omized intervention study , we examined the effect of exercise intensity on risk factors for CD in the postpartum . We hypothesized that women receiving an intervention targeting healthy weight loss would have improved CD risk factors compared with women not receiving the intervention . Further , we hypothesized that nutrition control and moderate-intensity exercise would have the greatest improvement in CD risk factors versus low-intensity exercise . METHODS Women were r and omly assigned to a nutrition plus low-intensity ( 30 % HR reserve ; n = 20 ) or moderate-intensity ( 70 % HR reserve ; n = 20 ) exercise intervention group . The program consisted of supervised walking for 45 min , three to four times per week for 16 wk . All women were screened for CD at the beginning ( 7 - 8 wk postpartum ) and at the end ( 23 - 25 wk postpartum ) of the study . A historical control group of 20 sedentary postpartum women was matched by body mass index , age , and parity . RESULTS The low- and moderate-intensity groups lost more body mass ( -4.2 ± 4.0 and -5.0 ± 2.9 kg , respectively ) compared with the control group ( -0.1 ± 3.3 kg , P was reduced for the low- and moderate-intensity groups ( -0.29 ± 0.21 and -0.28 ± 0.17 mmol · L ) compared with the control group ( 0.03 ± 0.18 mmol · L , P = 0.015 ) . In addition , glucose concentrations were reduced and adiponectin concentrations increased ( P = 0.037 ) , regardless of exercise intensity , although the sedentary controls remained unchanged or at increased risk for CD . CONCLUSIONS Women receiving a postpartum intervention targeting healthy weight loss , regardless of exercise intensity , improved CD risk factors compared with women not receiving the intervention",
"BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin",
"Postpr and ial blood glucose concentration is a risk factor for the development of cardiovascular diseases and diabetes , even at states well below hyperglycemic levels . A previous study has shown that postmeal exercise of moderate intensity blunts the blood glucose increase after carbohydrate intake ( Høstmark et al. Prev . Med . 42(5 ) : 369 - 371 ) . The objective of the present study was to examine whether even postmeal slow walking would have a similar effect . Fourteen healthy women aged > 50 years participated in 3 experiments in a r and om crossover design : after a carbohydrate-rich meal , either they were seated ( control experiment ) or they performed slow postmeal walking for 15 min ( W15 ) or 40 min ( W40 ) . Blood glucose concentration was determined prior to the meal ( fasting ) , and at 11 time points throughout each experiment . The W15 trial lowered the blood glucose values during walking and delayed the peak blood glucose value ( p = 0.003 ) . In W40 , the postmeal blood glucose increase during walking was blunted , the peak glucose value was delayed ( p = 0.001 ) , and the incremental area under the 2-h blood glucose curve ( IAUC ) was reduced ( p = 0.014 ) . There was a negative relationship between IAUC and walking time ( p = 0.016 ) . The individual reducing effect of walking on IAUC correlated strongly with IAUC on the control day ( p the blood glucose response to a carbohydrate-rich meal . The magnitude of this effect seems to be related to the duration of walking and to the magnitude of the postpr and ial blood glucose response when resting after a carbohydrate-rich meal",
"OBJECTIVE We studied whether the quantity and quality of walking necessary to decrease the risk of cardiovascular disease among women differed substantially from that required to improve cardiorespiratory fitness . DESIGN A r and omized , controlled , dose-response clinical trial with a follow-up of 24 weeks . SETTING A private , nonprofit biomedical research facility . PARTICIPANTS One hundred two sedentary premenopausal women , 20 to 40 years of age , were r and omized to one of four treatment groups ; 59 completed the study ( 16 aerobic walkers [ 8.0-km/h group ] , 12 brisk walkers [ 6.4-km/h group ] , 18 strollers [ 4.8-km/h group ] , and 13 sedentary controls ) . Eighty-one percent were white , 17 % black , and 2 % Hispanic . INTERVENTION Intervention groups walked 4.8 km per day , 5 days per week at 8.0 km/h , 6.4 km/h , or 4.8 km/h on a tartan-surfaced , 1.6-km track for 24 weeks . MAIN OUTCOME MEASURES Fitness ( determined by maximal oxygen uptake ) and cardiovascular risk factors ( determined by resting blood pressure and serum lipid and lipoprotein levels ) . RESULTS As compared with controls , maximal oxygen uptake increased significantly ( P less than .0001 ) and in a dose-response manner ( aerobic walkers greater than brisk walkers greater than strollers ) . In contrast , high-density lipoprotein cholesterol concentrations were not dose related and increased significantly ( P less than .05 ) and to the same extent among women who experienced considerable improvements in their physical fitness ( 8.0-km/h group , + 0.08 mmol/L ) and those who had only minimal improvements in fitness ( 4.8-km/h group , + 0.08 mmol/L ) . High-density lipoprotein cholesterol also increased among the 6.4-km/h group , but did not attain statistical significance ( + 0.06 mmol/L ; P = .06 ) . Dietary patterns revealed no significant differences among groups . CONCLUSION Thus , we conclude that vigorous exercise is not necessary for women to obtain meaningful improvements in their lipoprotein profile . Walking at intensities that do not have a major impact on cardiorespiratory fitness may nonetheless produce equally favorable changes in the cardiovascular risk profile",
"OBJECTIVES To explore the effects of breaking up prolonged sitting time with st and ing or light-intensity walking on a range of cardiometabolic risk markers . DESIGN A r and omised three-period , three-treatment acute crossover trial . METHODS Ten non-obese adults took part in three trials : ( 1 ) uninterrupted sitting ; ( 2 ) seated with 2-min bouts of st and ing every 20 min ; and ( 3 ) seated with 2-min bouts of light-intensity walking every 20 min . Two st and ardised test drinks ( total 80.3 carbohydrate , 50 g fat ) were provided after an initial 1-h period of uninterrupted sitting . Plasma glucose and blood pressure were assessed hourly to calculate area under the curve . Total cholesterol , HDL , and triglycerides were assessed at baseline and 5-h . ANOVAs were used to explore between-trial differences . RESULTS Glucose area under the curve was lower in the activity-break condition compared to the uninterrupted sitting and st and ing-break conditions : mean area under the curve 18.5 ( 95 % CI 17 , 20 ) , 22.0 ( 20.5 , 23.5 ) , and 22.2 ( 20.7 , 23.7 ) mmol L/5-h , respectively , p0.05 ) . Systolic and diastolic blood pressure area under the curve did not differ significantly between conditions , nor did responses in lipid parameters ( p>0.05 ) . CONCLUSIONS This study suggests that interrupting sitting time with frequent brief bouts of light-intensity activity , but not st and ing , imparts beneficial postpr and ial responses that may enhance cardiometabolic health . These findings may have importance in the design of effective interventions to reduce cardiometabolic disease risk"
] |
4116ca40-06ff-11f0-808a-c43d1ab1c353
|
PURPOSE The aim of the present study was to investigate the effect of increasing dietary linoleic acid ( LA ) intake on the blood concentrations of inflammatory markers including cytokines , acute phase reactants and adhesion molecules in adults . METHODS We comprehensively search ed PubMed , Embase and Cochrane Library for eligible studies . Overall , 30 r and omized controlled studies involving 1377 subjects were included for meta- analysis . RESULTS No significant effect of higher LA intake was observed for cytokines : tumor necrosis factor ( SMD : -0.01 ; 95 % CI : -0.19 to 0.17 ) , interleukin-6 ( SMD : 0.11 , 95 % CI : -0.07 to 0.29 ) , adiponectin ( SMD : 0.17 , 95 % CI : -0.17 to 0.50 ) and monocyte chemoattractant protein 1 ( SMD : 0.14 , 95 % CI : -0.33 to 0.60 ) . Pooled effect size from 16 studies showed that the C-reactive protein ( CRP ) concentration was not significantly affected by increasing LA intake ( SMD = 0.09 , 95 % CI : -0.05 to 0.24 ) . However , subgroup and meta-regression analysis suggested that in subjects with a more profound increase of dietary LA intake , LA might increase the blood CRP level . Other acute phase reactants including fibrinogen and plasminogen activator inhibitor-1 and adhesion molecules were not significantly changed when LA was increased in diet . No significant heterogeneity or publication bias was observed , although only a limited number of eligible studies were included for some markers . CONCLUSION Our meta- analysis suggested that increasing dietary LA intake does not have a significant effect on the blood concentrations of inflammatory markers . However , the extent of change in dietary LA intake might affect the effect of LA supplementation on CRP
|
[
"PUFA of the n−6 and n−3 series have beneficial effects on key risk factors of coronary heart disease ( CHD ) . Our earlier studies on the intake of FA and on the FA composition of plasma and platelet phospholipids suggested the need to improve the n−3 PUFA nutritional status in the Indian population . The present long-term study was conducted on 80 middle-aged Indian subjects ( 40 men and 40 women ) using the subjects ' own home-prepared diets to evaluate the effects of dietary n−3 PUFA on biochemical indices of CHD risk . Substitution of Blend G ( equal proportions of groundnut and canola oils ) for groundnut oil or substitution of Blend S ( equal proportions of sunflower and canola oils ) for sunflower oil increased α-linolenic acid ( ALNA ) fourfold and decreased the linoleic acid (LA)/ALNA ratio from 35 to 6 and 65 to 9 , respectively . Twelve subjects ( six men and six women ) who received Blend G were switched back to groundnut oil and were administered 0.3 g daily of long-chain ( LC ) n−3 PUFA from fish oil . At the end of the trial period for both blends in both sexes , plasma lipid and apolipoprotein levels had not changed , and ADP-induced aggregation had decreased . In plasma and platelet phospholipids , LA as well as LCn-3 PUFA had increased , suggesting competition between LA and ALNA for metabolism into the respective LC-PUFA . Fish oil supplementation increased LCn-3 PUFA in plasma and platelet phospholipids , decreased ADP-induced platelet aggregation , and increased plasma cholesterol . On the basis of the increased LCn-3 PUFA in plasma phospholipids , it was calculated that 0.75 % energy ( en% ) ( 2.2 g ) ALNA ( from vegetable oils ) may be required to increase LCn-3 PUFA to about the same extent as 0.1 en% ( 0.3 g ) LCn-3 PUFA ( from fish oils ) . Since both n−6 and n−3 PUFA play a critical role in fetal growth and development and in the programming of diet-related chronic diseases in adults , an improvement in the n−3 PUFA nutritional status in cereal-based diets through long-term use of cooking oils containing 25–40 % LA and 4 % ALNA may contribute to the prevention of CHD in Indians",
"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",
"Dietary alpha-linolenic acid ( ALA ) can be converted to long-chain ( n-3 ) PUFA in humans and may potentially reproduce the beneficial effects of eicosapentaenoic ( EPA ) and docosahexaenoic ( DHA ) acids on risk factors for coronary heart disease ( CHD ) . This study compared the effects of increased intakes of ALA with those of dietary EPA and DHA on blood coagulation and fibrinolytic factors in fasting subjects . A placebo-controlled , parallel study was conducted in 150 moderately hyperlipidemic subjects , age 25 - 72 y. Subjects were r and omly assigned to one of five interventions and consumed a total intake of 0.8 or 1.7g/d EPA+DHA , 4.5 or 9.5g/d ALA or control ( linoleic acid ; LA ) for 6 mo . Fatty acids were incorporated into 25 g of fat spread , which replaced the subject 's normal spread and three capsules . Long-term supplementation with either dietary EPA+DHA or estimated biologically equivalent amounts of ALA did not affect factors VIIa , VIIc , VIIag , XIIa , XIIag , fibrinogen concentrations , plasminogen activator inhibitor-1 or tissue plasminogen activator activity compared with the control . ( n-3 ) PUFA of plant or marine origin do not differ from one another or from LA in their effect on a range of blood coagulation and fibrinolytic factors",
"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",
"Excess ectopic fat storage is linked to type 2 diabetes . The importance of dietary fat composition for ectopic fat storage in humans is unknown . We investigated liver fat accumulation and body composition during overfeeding saturated fatty acids ( SFAs ) or polyunsaturated fatty acids ( PUFAs ) . LIPOGAIN was a double-blind , parallel-group , r and omized trial . Thirty-nine young and normal-weight individuals were overfed muffins high in SFAs ( palm oil ) or n-6 PUFAs ( sunflower oil ) for 7 weeks . Liver fat , visceral adipose tissue ( VAT ) , abdominal subcutaneous adipose tissue ( SAT ) , total adipose tissue , pancreatic fat , and lean tissue were assessed by magnetic resonance imaging . Transcriptomics were performed in SAT . Both groups gained similar weight . SFAs , however , markedly increased liver fat compared with PUFAs and caused a twofold larger increase in VAT than PUFAs . Conversely , PUFAs caused a nearly threefold larger increase in lean tissue than SFAs . Increase in liver fat directly correlated with changes in plasma SFAs and inversely with PUFAs . Genes involved in regulating energy dissipation , insulin resistance , body composition , and fat-cell differentiation in SAT were differentially regulated between diets , and associated with increased PUFAs in SAT . In conclusion , overeating SFAs promotes hepatic and visceral fat storage , whereas excess energy from PUFAs may instead promote lean tissue in healthy humans",
"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",
"Objective : To examine the effects of lecithin on serum lipoprotein , plasma fibrinogen and macro molecular protein complex ( MPC ) levels . Subjects and study design : Twenty free living hyperlipidaemic men participated in this double-blind study which controlled for possible indirect effects . The subjects were r and omly assigned to one of three treatments : frozen yoghurt or frozen yoghurt with 20 g soya bean lecithin or frozen yoghurt with 17 g sunflower oil . Sunflower oil was used to control for the increased energy and linoleic acid intake from lecithin . Yoghurt served as the ‘ vehicle ’ for the lecithin and sunflower oil and yoghurt alone was given to one group to control for possible effects due to the yoghurt ‘ vehicle ’ , as well as other environmental influences . Variables were measured with st and ard methods twice at baseline and after 2 and 4 weeks of treatment . Results : Plasma linoleic acid levels increased significantly with lecithin and sunflower oil treatments indicating that compliance to the treatments were obtained . Lecithin treatment did not have significant effects on serum total cholesterol , triglyceride , high density lipoprotein cholesterol , low density lipoprotein cholesterol , apolipoprotein A , apolipoprotein B or lipoprotein ( a ) levels . Plasma fibrinogen and MPC levels were also not affected by lecithin therapy . Sunflower oil treatment result ed in significant increased body weight , serum TC and decreased MPC levels . Conclusion : Lecithin treatment had no independent effects on serum lipoprotein , plasma fibrinogen or MPC levels in hyperlipidaemic men . Sponsorship : Drybean Producers Organisation ( South Africa ) ; Chempure cc ( South Africa ) ; SACCA , Pty . Ltd. ( South Africa )",
"BACKGROUND Dietary linoleic acid ( LA , 18:2n-6 ) lowering in rats reduces n-6 polyunsaturated fatty acid ( PUFA ) plasma concentrations and increases n-3 PUFA ( eicosapentaenoic ( EPA ) and docosahexaenoic acid ( DHA ) ) concentrations . OBJECTIVE To evaluate the extent to which 12 weeks of dietary n-6 PUFA lowering , with or without increased dietary n-3 PUFAs , alters unesterified and esterified plasma n-6 and n-3 PUFA concentrations in subjects with chronic headache . DESIGN Secondary analysis of a r and omized trial . Subjects with chronic headache were r and omized for 12 weeks to ( 1 ) average n-3 , low n-6 ( L6 ) diet ; or ( 2 ) high n-3 , low n-6 LA ( H3-L6 ) diet . Esterified and unesterified plasma fatty acids were quantified at baseline ( 0 weeks ) and after 12 weeks on a diet . RESULTS Compared to baseline , the L6 diet reduced esterified plasma LA and increased esterified n-3 PUFA concentrations ( nmol/ml ) , but did not significantly change plasma arachidonic acid ( AA , 20:4n-6 ) concentration . In addition , unesterified EPA concentration was increased significantly among unesterified fatty acids . The H3-L6 diet decreased esterified LA and AA concentrations , and produced more marked increases in esterified and unesterified n-3 PUFA concentrations . CONCLUSION Dietary n-6 PUFA lowering for 12 weeks significantly reduces LA and increases n-3 PUFA concentrations in plasma , without altering plasma AA concentration . A concurrent increase in dietary n-3 PUFAs for 12 weeks further increases n-3 PUFA plasma concentrations and reduces AA",
"BACKGROUND Blood lipids and inflammatory markers levels have been associated with the development and progression of atherosclerosis . As the association of inflammatory markers with plasma fatty acids has not been extensively evaluated and understood , we sought to investigate the associations between dietary and plasma fatty acids with various inflammation and coagulation markers . METHODS High sensitivity C-reactive protein ( hsCRP ) , interleukin-6 ( IL-6 ) , tumor necrosis factor-alpha ( TNF-alpha ) , fibrinogen , and homocysteine were measured in serum of 374 free-living , healthy men and women , r and omly selected from the ATTICA 's study data base . Total plasma fatty acids were determined by gas chromatography . Dietary fatty acids were assessed through a semi-quantitative FFQ . RESULTS Multi-adjusted regression analyses revealed that plasma n-3 fatty acids were inversely associated with CRP , IL-6 and TNF-alpha ; plasma n-6 fatty acids were inversely associated with CRP , IL-6 and fibrinogen ; monounsaturated fatty acids were inversely associated with CRP and IL-6 ( all p-values n-6/n-3 ratios exhibited the strongest positive correlations with all the markers studied . No associations were observed between dietary fatty acids and the investigated markers . CONCLUSIONS Measurements of total plasma fatty acids could provide insights into the relationships between diet and atherosclerotic disease . Moreover , the n-6/n-3 ratio may constitute a predictor of low- grade inflammation and coagulation",
"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 )",
"BACKGROUND Public health strategies to lower cardiovascular disease ( CVD ) risk involve reducing dietary saturated fatty acid ( SFA ) intake to ≤10 % of total energy ( % TE ) . However , the optimal type of replacement fat is unclear . OBJECTIVE We investigated the substitution of 9.5 - 9.6%TE dietary SFAs with either monounsaturated fatty acids ( MUFAs ) or n-6 ( ω-6 ) polyunsaturated fatty acids ( PUFAs ) on vascular function and other CVD risk factors . DESIGN In a r and omized , controlled , single-blind , parallel-group dietary intervention , 195 men and women aged 21 - 60 y from the United Kingdom with moderate CVD risk ( ≥50 % above the population mean ) followed one of three 16-wk isoenergetic diets ( % TE target compositions , total fat : SFA : MUFA : n-6 PUFA ) that were rich in SFAs ( 36:17:11:4 , n = 65 ) , MUFAs ( 36:9:19:4 , n = 64 ) , or n-6 PUFAs ( 36:9:13:10 , n = 66 ) . The primary outcome measure was flow-mediated dilatation ; secondary outcome measures included fasting serum lipids , microvascular reactivity , arterial stiffness , ambulatory blood pressure , and markers of insulin resistance , inflammation , and endothelial activation . RESULTS Replacing SFAs with MUFAs or n-6 PUFAs did not affect the percentage of flow-mediated dilatation ( primary endpoint ) or other measures of vascular reactivity . Of the secondary outcome measures , substitution of SFAs with MUFAs attenuated the increase in night systolic blood pressure ( -4.9 mm Hg , P = 0.019 ) and reduced E-selectin ( -7.8 % , P = 0.012 ) . Replacement with MUFAs or n-6 PUFAs lowered fasting serum total cholesterol ( -8.4 % and -9.2 % , respectively ) , low-density lipoprotein cholesterol ( -11.3 % and -13.6 % ) , and total cholesterol to high-density lipoprotein cholesterol ratio ( -5.6 % and -8.5 % ) ( P ≤ 0.001 ) . These changes in low-density lipoprotein cholesterol equate to an estimated 17 - 20 % reduction in CVD mortality . CONCLUSIONS Substitution of 9.5 - 9.6%TE dietary SFAs with either MUFAs or n-6 PUFAs did not significantly affect the percentage of flow-mediated dilatation or other measures of vascular function . However , the beneficial effects on serum lipid biomarkers , blood pressure , and E-selectin offer a potential public health strategy for CVD risk reduction . This trial was registered at www . clinical trials.gov as NCT01478958",
"Background : The aim of the study was to investigate the effects of sesame oil on endothelial function and to detect the underlying mechanisms , both in the postpr and ial state and after long-term consumption . Design : We enrolled 30 hypertensive men in a two-phase study . In the first phase , 26 volunteers consumed 35 g of either sesame oil or control oil . Endothelial function , inflammatory activation and nitric oxide syntase ( NOS ) inhibition was assessed after a 12-hour fast and 2 hours after consumption of an oil-containing st and ardized meal . In the second phase , 30 volunteers consumed 35 g of sesame oil or control oil daily for 2 months and the above-mentioned parameters were assessed at baseline , 15 , 30 and 60 days . Methods : Endothelial function was estimated by endothelium-dependent FMD ( flow-mediated dilatation ) of the brachial artery . Results : Flow-mediated dilatation ( FMD ) improved significantly both after acute ( p = 0.001 ) and long-term sesame oil consumption ( p = 0.015 , p = 0.005 and p = 0.011 for 15 , 30 and 60 days respectively ) . Intracellular adhesion molecule ( ICAM ) levels decreased significantly after only 60 days of daily sesame oil intake ( p = 0.014 ) . By contrast , no changes were observed in the control group in either phase of the study . Conclusions : This is the first study to show that sesame oil consumption exerts a beneficial effect on endothelial function and this effect is sustained with long-term daily use",
"BACKGROUND AND AIM Monounsaturated fatty acids ( MUFA ) have been shown to be beneficial . Their haemostatic effects , however , are poorly known . We compared the effects of oleic acid ( OA ) and linoleic acid ( LA ) on variables related with coagulation and fibrinolysis in healthy subjects . METHODS AND RESULTS Thirty-eight healthy volunteers ( 20 women , 18 men ; mean age 27 ) consumed a saturated fat baseline diet for four weeks and were then switched to either a high LA diet ( 11.5 en% ) or a high OA diet ( 18.0 en% ) for another four weeks when nearly all food was provided for the whole day . A control group of 13 subjects consumed their habitual diet throughout the study . No differences between the OA and LA diets were found in the plasma levels of fibrinogen , plasminogen activator inhibitor , antithrombin III , von Willebr and factor antigen or D-dimers . Factor FVII coagulant activity was significantly lower after the OA diet . CONCLUSIONS The results indicate largely similar effects for OA and LA on factors related with coagulation and fibrinolysis in humans . The effects of dietary fatty acid composition on FVII coagulant activity should be further studied",
"BACKGROUND Leukocyte adhesion and transendothelial migration , the critical pathogenic components in the development of atherosclerotic lesions , are largely mediated by cellular adhesion molecules ( CAMs ) . We examined whether dietary supplementation with alpha-linolenic acid ( ALA , 18:3n-3 ) affects the levels of soluble forms of CAMs in dyslipidaemic patients . METHODS We recruited 90 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=60 ) or to 15 ml of safflower oil ( rich in linoleic acid [ LA , 18:2n-6 ] ) per day ( n=30 ) . 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 12 weeks . Blood lipids , soluble intercellular adhesion molecule-1 ( sICAM-1 ) , soluble vascular cell adhesion molecule-1 ( sVCAM-1 ) and soluble E-selectin ( sE-selectin ) were measured . RESULTS Dietary supplementation with ALA significantly decreased sVCAM-1 levels ( median decrease 18.7 % [ 577.5 ng/ml versus 487 ng/ml , P=0.0001 ] ) . In the LA supplemented group , sVCAM-1 was also significantly decreased but to a lesser extent ( median decrease 10.6 % [ 550.5 ng/ml versus 496 ng/ml , P=0.0001 ] ) . After controlling for smoking habits , no significant difference was observed in the reduction of sVCAM-1 levels between the two treatment arms ( P=0.205 ) . The decrease of sVCAM-1 was independent of lipid changes in both groups . CONCLUSIONS Dietary supplementation with ALA for 12 weeks significantly decreases sVCAM-1 levels in dyslipidaemic patients . This effect presents a potential mechanism for the beneficial effect of plant n-3 polyunsaturated fatty acids in the prevention of coronary artery disease . In addition , dietary supplementation with LA significantly decreases sVCAM-1 levels , an effect which requires further investigation",
"Summary . Background : High intake of vegetables and fruits is associated with decreased risk of coronary heart disease . Part of these cardioprotective effects may be mediated via the antithrombotic effects of compounds found in vegetables and fruits , such as flavonoids . Aim of the study : To study the effects of high and low intake of vegetables , berries and apple on platelet function and inflammatory markers . Methods : The study was a r and omised , controlled parallel human dietary intervention with healthy female and male volunteers ( n = 77 , 19–52 y ) . Nineteen healthy volunteers served as controls . The volunteers consumed one of four strictly controlled isocaloric 6-week diets containing either 810 or 196 g/10 MJ of vegetables , berries and apple and rich either in linoleic acid ( 11 % of energy , en% ) or oleic acid ( 12 en% ) . Blood and three 24-hour urine sample s were collected at the beginning and at the end of the study period for analyses of various markers of platelet function and inflammation . Results : No differences between the treatment groups were seen in platelet count or volume , markers of platelet activation ( ex vivo aggregation to ADP and thrombin receptor activating peptide , protein kinase C activity , urinary 2,3-dinor-thromboxane B2 excretion , plasma P-selectin ) , plasma intercellular adhesion molecule-1 , sensitive C-reactive protein , or antiphospholipid antibodies . Conclusions : The results indicate that in healthy volunteers 6-week diets differing markedly in the amounts of vegetables , berries and apple do not differ in their effects on platelets or inflammation ",
"Increased inflammation with aging has been linked to sarcopenia . The purpose of this study was to evaluate the effects of supplementing older adults with alpha-linolenic acid ( ALA ) during a resistance training program , based on the hypothesis that ALA decreases the plasma concentration of the inflammatory cytokine tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 , which in turn would improve muscle size and strength . Fifty-one older adults ( 65.4 + /- 0.8 years ) were r and omized to receive ALA in flax oil ( ~14 g.day-1 ) or placebo for 12 weeks while completing a resistance training program ( 3 days a week ) . Subjects were evaluated at baseline and after 12 weeks for muscle thickness of knee and elbow flexors and extensors ( B-mode ultrasound ) , muscle strength ( 1 repetition maximum ) , body composition ( dual energy X-ray absorptiometry ) , and concentrations of TNF-alpha and IL-6 . Males supplementing with ALA decreased IL-6 concentration over the 12 weeks ( 62 + /- 36 % decrease ; p = 0.003 ) , with no other changes in inflammatory cytokines . Chest and leg press strength , lean tissue mass , muscle thickness , hip bone mineral content and density , and total bone mineral content significantly increased , and percent fat and total body mass decreased with training ( p ALA being a significantly greater increase in knee flexor muscle thickness in males ( p Total-body bone mineral density improved in the placebo group , with no change in the ALA group ( p = 0.05 ) . ALA supplementation lowers the IL-6 concentration in older men but not women , but had minimal effect on muscle mass and strength during resistance training",
"Various studies have already shown that the fatty acid composition of dietary fat has different effects on hemostasis and platelet function . However , knowledge on this topic is incomplete . In the present study , fifty-eight healthy students received either a 4-week rapeseed oil [ high content of monounsaturated fatty acids ( MUFA ) and high n-3/n-6 PUFA ratio ] , an olive oil ( high content of MUFA , low n-3/n-6 PUFA ratio ) or a sunflower oil ( low content of MUFA , low n-3/n-6 PUFA ratio ) diet . In each group , effects on hemostatic parameters were compared with a wash-in diet rich in saturated fatty acids with respect to intermediate-time effects on the hemostatic system and platelet function . With the olive oil diet , a reduction of coagulation factors VIIc , XIIc , XIIa , and Xc was found , whereas sunflower oil led to lower values of coagulation factors XIIc , XIIa , and IXc . In all study groups levels of plasmin-alpha2-antiplasmin were lower in week 4 than at baseline . Lower fibrinogen binding on platelets was found after the sunflower oil diet , whereas expression of CD62 and spontaneous platelet aggregation were slightly higher after the olive oil diet . However , given the major differences in the fatty acid compositions of the diets , the differences between the groups with respect to hemostasis tended to be small . Therefore , the clinical significance of the present findings remains to be evaluated",
"Objective : The impact of dietary polyunsaturated fatty acids ( PUFAs ) of the n-6 and n-3 series on the cardiovascular system is well documented . To directly compare the effects of three dietary oils ( fish , flaxseed and hempseed ) given in concentrations expected to be self-administered in the general population on specific cardiovascular parameters in healthy volunteers . Design : 86 healthy male and female volunteers completed a 12 week double blinded , placebo controlled , clinical trial . They were r and omly assigned to one of the four groups . Subjects were orally supplemented with two 1 gm capsules of placebo , fish oil , flaxseed oil or hempseed oil per day for 12 weeks . Results : Plasma levels of the n-3 fatty acids docosahexanoic acid and eicosapentanoic acid increased after 3 months supplementation with fish oil . Alpha linolenic acid concentrations increased transiently after flaxseed supplementation . However , supplementation with hempseed oil did not significantly alter the concentration of any plasma fatty acid . The lipid parameters ( TC , HDL-C , LDL-C and TG ) did not show any significant differences among the four groups . Oxidative modification of LDL showed no increase in lag time over the 12 wk period . None of the dietary interventions induced any significant change in collagen or thrombin stimulated platelet aggregation and no increase in the level of inflammatory markers was observed . Conclusion : From a consumer 's perspective , ingesting 2 capsules of any of these oils in an attempt to achieve cardiovascular health benefits may not provide the desired or expected result over a 3 month period"
] |
4116ca7c-06ff-11f0-808a-c43d1ab1c353
|
The risk of sarcopenia increases with aging . Malnutrition in the elderly population is an important risk factor for sarcopenia . Calcium ( Ca ) , phosphate ( P ) , vitamin D and protein are key nutrients for the human body and affect muscle mass and quality . Dairy products are rich in these nutrients , which implicates that dairy products might be ideal for elderly population . This systematic review highlights the effects of dairy products on muscle mass , muscle strength and body performance in the elderly population in the perspective of Ca , P , vitamin D and protein
|
[
"To assess age and gender differences in muscle strength , isometric , concentric ( Con ) , and eccentric ( Ecc ) peak torque was measured in the knee extensors at a slow ( 0.52 rad/s ) and fast ( 3.14 rad/s ) velocity in 654 subjects ( 346 men and 308 women , aged 20 - 93 yr ) from the Baltimore Longitudinal Study of Aging . Regression analysis revealed significant ( P Con and Ecc peak torque for men and women at both velocities , but no differences were observed between the gender groups or velocities . Age explained losses in Con better than Ecc peak torque , accounting for 30 % ( Con ) vs. 19 % ( Ecc ) of the variance in men and 28 % ( Con ) vs. 11 % ( Ecc ) in women . To assess age and gender differences in the ability to store and utilize elastic energy , the stretch-shortening cycle was determined in a subset of subjects ( n = 47 ) . The older women ( mean age = 70 yr ) showed a significantly greater enhancement in the stretch-shortening cycle , compared with men of similar age ( P muscle quality for Con peak torque ( P muscle quality ( P Ecc peak torque . Thus both men and women experience age-related losses in isometric , Con , and Ecc knee extensor peak torque ; however , age accounted for less of the variance in Ecc peak torque in women , and women tend to better preserve muscle quality with age for Ecc peak torque . In addition , older women have an enhanced capacity to store and utilize elastic energy compared with similarly aged men as well as with younger women and men",
"Insulin resistance is one of the most common features of polycystic ovary syndrome ( PCOS ) . Some studies suggest that vitamin D deficiency may have a role in insulin resistance ; thus , the aim of the current study was to determine the effect of vitamin D supplementation on insulin resistance in women with PCOS and a vitamin D deficiency . We hypothesized that vitamin D supplementation would lower the glucose level and insulin resistance in women with PCOS and a vitamin D deficiency . The current study was a r and omized , placebo-controlled , double-blinded trial with 50 women with PCOS and a vitamin D deficiency , 20 to 40 years old , assigned to receive 3 oral treatments consisting of 50,000 IU of vitamin D₃ or a placebo ( 1 every 20 days ) for 2 months ( vitamin D , n = 24 ; placebo , n = 26 ) . The fasting blood glucose , insulin , 25-hydroxyvitamin D , and parathyroid hormone levels , as well as the homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were measured at baseline and after treatment . In the vitamin D group , the serum level of 25-hydroxyvitamin D increased ( 6.9 ± 2.8 to 23.4 ± 6.1 ng/mL , P , and the parathyroid hormone level decreased ( 70.02 ± 43.04 to 50.33 ± 21.99 μ IU/mL , P = .02 ) . There were no significant changes in the placebo group . There was a significant increase in insulin secretion in the vitamin D group ( P = .01 ) , but this was not significant compared with the placebo group . The fasting serum insulin and glucose levels and the insulin sensitivity and homeostasis model assessment of insulin resistance did not change significantly by the end of the study . We were not able to demonstrate the effect of vitamin D supplementation on insulin sensitivity and insulin resistance in women with PCOS and vitamin D deficiency",
"Muscle mass decreases with age , leading to \" sarcopenia , \" or low relative muscle mass , in elderly people . Sarcopenia is believed to be associated with metabolic , physiologic , and functional impairments and disability . Methods of estimating the prevalence of sarcopenia and its associated risks in elderly population s are lacking . Data from a population -based survey of 883 elderly Hispanic and non-Hispanic white men and women living in New Mexico ( the New Mexico Elder Health Survey , 1993 - 1995 ) were analyzed to develop a method for estimating the prevalence of sarcopenia . An anthropometric equation for predicting appendicular skeletal muscle mass was developed from a r and om sub sample ( n = 199 ) of participants and was extended to the total sample . Sarcopenia was defined as appendicular skeletal muscle mass (kg)/height2 ( m2 ) being less than two st and ard deviations below the mean of a young reference group . Prevalences increased from 13 - 24 % in persons under 70 years of age to > 50 % in persons over 80 years of age , and were slightly greater in Hispanics than in non-Hispanic whites . Sarcopenia was significantly associated with self-reported physical disability in both men and women , independent of ethnicity , age , morbidity , obesity , income , and health behaviors . This study provides some of the first estimates of the extent of the public health problem posed by sarcopenia",
"BACKGROUND Very limited data suggest that meat consumption by older people may promote skeletal muscle hypertrophy in response to resistance training ( RT ) . OBJECTIVE The objective of this study was to assess whether the consumption of an omnivorous ( meat-containing ) diet would influence RT-induced changes in whole-body composition and skeletal muscle size in older men compared with a lactoovovegetarian ( LOV ) ( meat-free ) diet . DESIGN Nineteen men aged 51 - 69 y participated in the study . During a 12-wk period of RT , 9 men consumed their habitual omnivorous diets , which provided approximately 50 % of total dietary protein from meat sources ( beef , poultry , pork , and fish ) ( mixed-diet group ) . Another 10 men were counseled to self-select an LOV diet ( LOV-diet group ) . RESULTS Maximal strength of the upper- and lower-body muscle groups that were exercised during RT increased by 10 - 38 % ( P changes in whole-body composition and skeletal muscle size differed significantly between the mixed- and LOV-diet groups ( time-by-group interactions , P RT , whole-body density , fat-free mass , and whole-body muscle mass increased in the mixed diet group but decreased in the LOV- diet group . Type II muscle fiber area of the vastus lateralis muscle increased with RT for all men combined ( P Type I fiber area was unchanged with RT in both diet groups . CONCLUSION Consumption of a meat-containing diet contributed to greater gains in fat-free mass and skeletal muscle mass with RT in older men than did an LOV diet",
"Background At present , it is unknown whether the use of nutrient-rich dairy proteins improves the markers of sarcopenia syndrome . Therefore , our proposal was to investigate whether adding 210 g of ricotta cheese daily would improve skeletal muscle mass , h and grip strength , and physical performance in non-sarcopenic older subjects . Subjects and methods This was a single-blind r and omized clinical trial that included two homogeneous , r and omized groups of men and women over 60 years of age . Participants in the intervention group were asked to consume their habitual diet but add 210 g of ricotta cheese ( IG/HD + RCH ) , while the control group was instructed to consume only their habitual diet ( CG/HD ) . Basal and 12-week follow-up measurements included appendicular skeletal muscle mass ( ASMM ) by dual-energy X-ray absorptiometry , h and grip strength by a h and held dynamometer , and physical performance using the short physical performance battery ( SPPB ) and the stair-climb power test ( SCPT ) . The main outcomes were relative changes in ASMM , strength , SPPB , and SCPT . Results ASMM increased in the IG/HD + RCH ( 0.6±3.5 kg ) , but decreased in the CG/HD ( −1.0±2.6 ) . The relative change between groups was statistically significant ( P=0.009 ) . The relative change in strength in both groups was negative , but the loss of muscle strength was more pronounced in CG/HD , though in this regard statistical analysis found only a tendency ( P=0.07 ) . The relative change in the balance-test scores was positive for the IG/HD + RCH , while in the CG/HD it was negative , as those individuals had poorer balance . In this case , the relative change between groups did reach statistical significance . Conclusion The addition of 210 g of ricotta cheese improves ASMM and balance-test scores , while attenuating the loss of muscle strength . These results suggest that adding ricotta cheese to the habitual diet is a promising dietetic strategy that may improve the markers of sarcopenia in subjects without a pronounced loss of ASMM or sarcopenia",
"A 9-wk study of adaptation to marginal protein intakes was conducted in 12 elderly women . Subjects were r and omly assigned to two groups fed a weight-maintenance diet containing either 1.47 ( low ) or 2.94 ( adequate ) g protein.kg body cell mass-1.d-1 ( 0.45 and 0.92 g.kg body wt-1.d-1 , respectively ) . Mean nitrogen balance in the low-protein group remained negative throughout the study . These subjects experienced significant losses in lean tissue , immune response , and muscle function . The adequate-protein group was in nitrogen balance throughout the study , without changes in lean tissue , and with improvements in immune response , serum immunoglobulins , albumin , total protein values , and muscle function . Thus , elderly women fed the low-protein diet accommo date d to the diet by compromising functional capacity , whereas those fed the adequate diet maintained functional capacity",
"Low protein intake can lead to declined lean mass ( LM ) in elderly . We examined the associations of total protein ( TP ) , animal protein ( AP ) and plant protein ( PP ) intakes with LM . The association of TP intake with LM change was further evaluated according to weight change status . This cross-sectional and prospect i ve cohort study included 554 women aged 68 ( sd 1·9 ) years from the Osteoporosis Risk Factor and Prevention – Fracture Prevention Study ( OSTPRE-FPS ) . The intervention group ( n 270 ) received daily cholecalciferol ( 800 IU ; 20 μg ) and Ca ( 1000 mg ) for 3 years while the control group received neither supplementation nor placebo ( n 282 ) . Participants filled out a question naire on lifestyle factors and a 3-d food record in 2002 and underwent dual-energy X-ray absorptiometry for body composition measurements at baseline and 3 years . Multiple linear regressions evaluated the association between protein intake and LM , adjusting for relevant covariates . At the baseline TP and AP intakes were positively associated with LM and trunk LM , TP was associated also with appendicular LM ( aLM ) . Follow-up results showed that in the total population and the intervention group , higher TP and AP were associated with increased LM and aLM ( P ≤ 0·050 ) . No such associations were observed in the control group . PP intake was also associated with aLM change in the total population . Overall , the associations were independent of fat mass . Further , among weight maintainers , TP intake was positively associated with LM , aLM and trunk LM changes ( P ≤ 0·020 ) . In conclusion , dietary TP , especially AP , intake may be a modifiable risk factor for sarcopenia by preserving LM in the elderly",
"BACKGROUND AND OBJECTIVES Higher phosphate is associated with mortality in dialysis patients but few prospect i ve studies assess this in nondialysis patients managed in an outpatient nephrology clinic . This prospect i ve longitudinal study examined whether phosphate level was associated with death in a referred population . DESIGN , SETTING , PARTICIPANTS & MEASUREMENTS Patients ( 1203 ) of nondialysis chronic kidney disease ( CKD ) in the Chronic Renal Insufficiency St and ards Implementation Study were assessed . Survival analyses were performed for quartiles of baseline phosphate relative to GFR , 12-month time-averaged phosphate , and baseline phosphate according to published phosphate targets . RESULTS Mean ( SD ) eGFR was 32 ( 15 ) ml/min per 1.73 m(2 ) , age 64 ( 14 ) years , and phosphate 1.2 ( 0.30 ) mmol/L. Cox multivariate adjusted regression in CKD stages 3 to 4 patients showed an increased risk of all-cause and cardiovascular mortality in the highest quartile compared with that in the lowest quartile of phosphate . No association was found in CKD stage 5 patients . Patients who had values above recommended targets for phosphate control had increased risk of all-cause and cardiovascular death compared with patients below target . The highest quartile compared with the lowest quartile of 12-month time-averaged phosphate was associated with an increased risk of mortality . CONCLUSIONS In CKD stages 3 to 4 patients , higher phosphate was associated with a stepwise increase in mortality . As phosphate levels below published targets ( as opposed to within them ) are associated with better survival , guidelines for phosphate in nondialysis CKD patients should be re-examined . Intervention trials are required to determine whether lowering phosphate will improve survival ",
"BACKGROUND AND OBJECTIVE : We have previously demonstrated an antiobesity effect of dietary Ca ; this is largely mediated by Ca suppression of calcitriol levels , result ing in reduced adipocyte intracellular Ca2 + and , consequently , a coordinated increase in lipid utilization and decrease in lipogenesis . Notably , dairy Ca is markedly more effective than other Ca sources . DESIGN : Obese subjects were placed on balanced deficit ( −500 kcal/day ) diets and r and omized to control ( 400–500 mg Ca/day ; n=16 ) or yogurt ( 1100 mg Ca/day ; n=18 ) treatments for 12 weeks . Dietary macronutrients and fiber were held constant at the US average . MEASUREMENTS : Body weight , body fat and fat distribution ( by dual-energy X-ray absorptiometry ) , blood pressure and circulating lipids were measured at baseline and after 12 weeks of intervention . RESULTS : Fat loss was markedly increased on the yogurt diet ( −4.43±0.47 vs −2.75±0.73 kg in yogurt and control groups ; P ) while lean tissue loss was reduced by 31 % on the yogurt diet . Trunk fat loss was augmented by 81 % on the yogurt vs control diet ( P in waist circumference ( −3.99±0.48 vs −0.58±1.04 cm , P the fraction of fat lost from the trunk was higher on the yogurt diet vs control ( P significantly augments fat loss and reduces central adiposity during energy restriction",
"OBJECTIVES Protein supplementation has been proposed as an effective dietary strategy to increase skeletal muscle mass and improve physical performance in frail elderly people . Our objective was to assess the impact of 24 weeks of dietary protein supplementation on muscle mass , strength , and physical performance in frail elderly people . DESIGN / SETTING / PARTICIPANTS A total of 65 frail elderly subjects were included and r and omly allocated to either daily protein or placebo supplementation ( 15 g protein at breakfast and lunch ) . MEASUREMENTS Skeletal muscle mass ( DXA ) , muscle fiber size ( muscle biopsy ) , strength ( 1-RM ) , and physical performance ( SPPB ) were assessed at baseline , and after 12 and 24 weeks of dietary intervention . RESULTS Skeletal muscle mass did not change in the protein- ( from 45.8 ± 1.7 to 45.8 ± 1.7 kg ) or placebo-supplemented group ( from 46.7 ± 1.7 to 46.6 ± 1.7 kg ) following 24 weeks of intervention ( P > .05 ) . In accordance , type I and II muscle fiber size did not change over time ( P > .05 ) . Muscle strength increased significantly in both groups ( P with leg extension strength tending to increase to a greater extent in the protein ( 57 ± 5 to 68 ± 5 kg ) compared with the placebo group ( 57 ± 5 to 63 ± 5 kg ) ( treatment × time interaction effect : P = .059 ) . Physical performance improved significantly from 8.9 ± 0.6 to 10.0 ± 0.6 points in the protein group and did not change in the placebo group ( from 7.8 ± 0.6 to 7.9 ± 0.6 points ) ( treatment × time interaction effect : P = .02 ) . CONCLUSION Dietary protein supplementation improves physical performance , but does not increase skeletal muscle mass in frail elderly people",
"BACKGROUND The purpose of this double-blind r and omized clinical trial was to compare the relative effectiveness of a higher protein and conventional carbohydrate intake during weight loss on body composition and physical function in older women . METHODS Thirty-one overweight or obese , postmenopausal women ( mean ± SD : age 65.2 ± 4.6 years , body mass index 33.7 ± 4.9 kg/m(2 ) ) were prescribed a reduced calorie diet ( 1,400 kcal/day ; 15 % , 65 % , 30 % energy from protein , carbohydrate , and fat , respectively ) and r and omly assigned to 2 × 25 g/day whey protein ( PRO n = 15 ) or maltodextrin ( CARB n = 16 ) supplementation for 6 months . Lean soft tissue ( LST ) via dual-energy X-ray absorptiometry ; thigh muscle , subcutaneous adipose tissue ( SAT ) , and intermuscular adipose tissue with magnetic resonance imaging ; knee strength with isokinetic dynamometry ; balance and physical function with a battery of performance tests . RESULTS PRO lost more weight than CARB ( -8.0 % ± 6.2 % , -4.1 % ± 3.6 % , p = .059 ; respectively ) . Changes in LST , % LST , and strength , balance , or physical performance measures did not differ between groups ( all p > .05 ) . Weight to leg LST ratio improved more in PRO versus CARB ( -4.6 ± 3.6 % , -1.8 ± 2.6 % , p = .03 ) . PRO lost 4.2 % more muscle ( p = .01 ) , 10.9 % more SAT ( p = .02 ) , and 8.2 % more intermuscular adipose tissue ( p = .03 ) than CARB . Relative to thigh volume changes , PRO gained 5.8 % more muscle ( p = .049 ) and lost 3.8 % greater SAT ( p = .06 ) than CARB . Weight to leg LST ratio ( r(2 ) = .189 , p = .02 ) and SAT ( r(2 ) = .163 , p = .04 ) predicted improved up and go , relative muscle ( r(2 ) = .238 , p = .01 ) and SAT ( r(2 ) = .165 , p = .04 ) predicted improved transfer test , and % LST predicted improved balance ( r(2 ) = .179 , p = .04 ) . CONCLUSIONS A higher protein intake during caloric restriction maintains muscle relative to weight lost , which in turn enhances physical function in older women",
"Background Sarcopenia is strongly associated with an inadequate intake of dietary protein . Dietary protein supplementation boosts muscle-protein synthesis and increases muscle mass in the elderly . This study tested whether adding a protein-rich food , ricotta cheese , to the habitual diet increased total appendicular skeletal muscle mass and strength in elderly people . Methods Participants ( n = 40 ) , were sarcopenic elderly men and women over 60 years of age . Two comparison groups were formed at r and om and followed for 3 months : the intervention group received 210 g/day of ricotta cheese plus the habitual diet , while the control group followed the habitual diet with no additional intervention . Total appendicular skeletal muscle ( TASM ) was assessed by dual-energy X-ray absorptiometry , while strength was measured using a h and held dynamometer at baseline and after the intervention period . The primary outcomes were the percentage of relative change in TASM and strength . Results The percentage of relative change in TASM was not significant between the groups after the intervention period . Muscle strength improved in the intervention group , but showed only a tendency towards significance ( P = 0.06 ) . Secondary analysis showed that the men in the intervention group gained 270 g in TASM compared to those in the control group , and improved their fasting insulin levels ( P = 0.05 ) , muscle strength , lean body mass in the arms , and body weight variables . Conclusion The results of this study indicate that a nutritional intervention using a high- quality protein food , specifically ricotta cheese , in order to increase the amount of protein intake might not be regarded as fully promising in elderly men and women with sarcopenia . However , the gender effects on muscle strength , lean tissue in the arms , homeostatic assessment of insulin resistance , and body weight detected in this study suggest that additional research is needed on elderly male subjects with sarcopenia",
"BACKGROUND Protein may play a role in preventing muscle loss with aging . To our knowledge , there have been no long-term r and omized controlled trials to examine the effects of increased dietary protein intake on muscle health in community-dwelling older women . OBJECTIVE In this study , we evaluated the effects of whey protein supplementation on muscle mass and physical function in community-dwelling older Australian women . METHODS In this 2 y r and omized , double-blind , placebo-controlled trial , women aged 70 - 80 y ( mean 74.3 ± 2.7 y ) were r and omly assigned to either a high protein drink containing 30 g of whey protein ( n = 109 ) or a placebo drink containing 2.1 g protein ( n = 110 ) daily . Dual-energy X-ray absorptiometry appendicular skeletal muscle mass , upper arm and calf ( 38 % tibia ) muscle cross-sectional area , physical function including h and grip strength , lower limb muscle strength and Timed Up and Go test , and 24 h urinary nitrogen were measured at baseline , 1 y , and 2 y. RESULTS A total of 196 women with at least one follow-up measurement were included in this analysis . Baseline mean BMI was 26.7 ± 3.9 kg/m(2 ) and protein intake was 76 ± 17 g/d ( 1.1 ± 0.3 g · kg body weight(-1 ) · d(-1 ) ) . A mean increase in protein intake of ∼ 20 g/d in the protein group was confirmed by the estimates from 24 h urinary nitrogen . Over the 2 y in both groups there was a significant decrease in the upper arm ( mean ± SE : -5.59 ± 0.75 cm(2 ) ) and calf ( -0.77 ± 0.11 cm(2 ) ) muscle area , as well as h and grip strength ( -1.30 ± 0.3 kg ) ( all P but appendicular skeletal muscle mass did not change significantly . There were no significant effects of the protein intervention on any of the muscle mass or physical function measures ( all P > 0.05 ) at 1 and 2 y. CONCLUSION This study showed that in protein-replete , healthy , ambulant , postmenopausal older women , 30 g/d of extra protein did not improve the maintenance of muscle mass or physical function despite evidence of deterioration in muscle measurements in the upper limb . This trial was registered at the Australian New Zeal and Clinical Trials Registry as ACTRN012607000163404",
"Muscle mass declines with aging . Amino acids alone stimulate muscle protein synthesis in the elderly . However , mixed nutritional supplementation failed to improve muscle mass . We hypothesized that the failure of nutritional supplements is due to altered responsiveness of muscle protein anabolism to increased amino acid availability associated with endogenous hyperinsulinemia . We measured muscle protein synthesis and breakdown , and amino acid transport in healthy young ( 30 + /- 3 yr ) and elderly ( 72 + /- 1 yr ) volunteers in the basal postabsorptive state and during the administration of an amino acid-glucose mixture , using L-[ring-(2)H(5)]phenylalanine infusion , femoral artery and vein catheterization , and muscle biopsies . Basal muscle amino acid turnover was similar in young and elderly subjects . The mixture increased phenylalanine leg delivery and transport into the muscle in both groups . Phenylalanine net balance increased in both groups ( young , -27 + /- 8 to 64 + /- 17 ; elderly , -16 + /- 4 to 29 + /- 7 nmol/(min.100 mL ) ; P : Muscle protein synthesis increased in the young , but remained unchanged in the elderly [ young , 61 + /- 17 to 133 + /- 30 ( P : = 0 . 005 ) ; elderly , 62 + /- 9 to 70 + /- 14 nmol/(min.100 mL ) ( P : = NS ) ] . In both groups , protein breakdown decreased ( P : = 0.012 ) and leg glucose uptake increased ( P : = 0.0258 ) with the mixture . We conclude that the response of muscle protein anabolism to hyperaminoacidemia with endogenous hyperinsulinemia is impaired in healthy elderly due to the unresponsiveness of protein synthesis",
"Background : Previous work demonstrated that a soy-dairy protein blend ( PB ) prolongs hyperaminoacidemia and muscle protein synthesis in young adults after resistance exercise . Objective : We investigated the effect of PB in older adults . We hypothesized that PB would prolong hyperaminoacidemia , enhancing mechanistic target of rapamycin complex 1 ( mTORC1 ) signaling and muscle protein anabolism compared with a whey protein isolate ( WPI ) . Methods : This double-blind , r and omized controlled trial studied men 55–75 y of age . Subjects consumed 30 g protein from WPI or PB ( 25 % soy , 25 % whey , and 50 % casein ) 1 h after leg extension exercise ( 8 sets of 10 repetitions at 70 % one-repetition maximum ) . Blood and muscle amino acid concentrations and basal and postexercise muscle protein turnover were measured by using stable isotopic methods . Muscle mTORC1 signaling was assessed by immunoblotting . Results : Both groups increased amino acid concentrations ( P mTORC1 signaling after protein ingestion ( P 0.05 ) . Postexercise fractional synthesis rate ( FSR ; P ≥ 0.05 ) , fractional breakdown rate ( FBR ; P ≥ 0.05 ) , and net balance ( P = 0.08 ) did not differ between groups . WPI increased FSR by 67 % ( mean ± SEM : rest : 0.05 % ± 0.01 % ; postexercise : 0.09 % ± 0.01 % ; P decreased FBR by 46 % ( rest : 0.17 % ± 0.01 % ; postexercise : 0.09 % ± 0.03 % ; P made net balance less negative ( P increase FSR ( rest : 0.07 % ± 0.03 % ; postexercise : 0.09 % ± 0.01 % ; P ≥ 0.05 ) , tended to decrease FBR by 42 % ( rest : 0.25 % ± 0.08 % ; postexercise : 0.15 % ± 0.08 % ; P = 0.08 ) , and made net balance less negative ( P between groups for FSR , FBR , or net balance ( P ≥ 0.05 ) . Conclusions : WPI and PB ingestion after exercise in older men induced similar responses in hyperaminoacidemia , mTORC1 signaling , muscle protein synthesis , and breakdown . These data add new evidence for the use of whey or soy-dairy PBs as targeted nutritional interventions to counteract sarcopenia . This trial was registered at clinical trials.gov as NCT01847261",
"Objectives Assess sex-specific nutritional intake and dietary habits of independently living older adults with normal and slow gait speeds . Design New Mexico Aging Process Study , cross-sectional , secondary data analysis . Setting Albuquerque , New Mexico USA . Participants Three-hundred fifteen adults 60 years and older ( 194 women and 121 men ) . Measurements Gait speed test , 3-day diet records , Mini-Mental State Examination , and body mass index . Results Slow gait speed was associated with lower total calories ( −154 kcal/day ) and zinc ( 1mg/day ) ( .05 less protein ( −4.1g/day ) , calcium ( −140 mg ) , fiber ( -2.8g/day ) and iron ( −2.5mg/day ) ( p less , protein ( −5.5g/day ) , carbohydrate ( −19.1g/day ) , fiber ( −2.7gm/day ) , vitamin C ( −18.4mg/day ) and higher fat intake ( p=0.03 ) . Slower women snacked less , had trouble chewing/biting , and lived alone ( p=.04 ) . Slower men were less likely to snack . Conclusions We found sex-specific nutritional differences associated with gait speed . Those presenting with slow gait speed may need encouragement to increase meat and whole grain breads/cereal . Those with trouble eating should be advised on adapting diet to maintain adequate nutrition and encouraged on regular snacking to achieve higher nutrient intake . Prospect i ve and r and omized controlled studies are needed to confirm these findings and provide further evidence for putting these suggestions into practice",
"Objectives Leucine-rich milk and whey proteins have been suggested for prevention of age related loss of muscle mass and strength i.e. sarcopenia . The effects of milk protein supplementation and low intensity home based physical exercise on body composition and muscle functions were investigated . Design A r and omized double blind crossover trial . Setting Community dwelling members of Helsinki rheumatoid association . Participants Older people ( N = 47 , mean age 69.5 years ) suffering from polymyalgia rheumatica . Intervention Patients performed as many st and ups as possible twice a day after which they ingested a regular ( Control ) or a whey protein enriched dairy product with high leucine content ( Test ) . The 8-week intervention periods were separated by a 4-week wash-out . Measurements Body composition was measured by dual x-ray absorptiometry and muscle functions by h and grip strength , force platform countermovement jump performance , chair st and test , and walking speed . Results The 16-week home-based post-exercise supplementation result ed in a 1.8 % increase ( p = 0.052 ) in lower limb muscle mass . Walking speed ( + 5.3 % , p = 0.007 ) and chair st and test performance ( −12.2 % , p increased jump power ( + 3.0 % , p = 0.084 ) was observed . However , significant and consistent differences were not found in the changes of muscle mass indices or muscle functions between supplements , but the test supplement tended to prevent accumulation of body fat . Conclusion A low intensity home based exercise program combined with post-exercise milk protein supplementation is feasible despite some gastrointestinal complaints and seems effective in improving the muscle mass and functions of older persons with a inflammatory disease . Further studies are needed to establish , whether and to what extent the use of leucine-enriched whey products prevent or treat age-associated sarcopenia and whether they are superior to the present commercial milk products",
"To determine the differences between arm and leg muscle quality ( MQ ) across the adult life span in men and women , concentric ( Con ) and eccentric ( Ecc ) peak torque ( PT ) were measured in 703 subjects ( 364 men and 339 women , age range 19 - 93 yr ) and appendicular skeletal muscle mass ( MM ) was determined in the arm and leg in a subgroup of 502 of these subjects ( 224 men and 278 women ) . Regression analysis showed that MQ , defined as PT per unit of MM , was significantly higher in the arm ( approximately 30 % ) than in the leg across age in both genders ( P Arm and leg MQ declined at a similar rate with age in men , whereas leg MQ declined approximately 20 % more than arm MQ with increasing age in women ( P PT , respectively ) . Moreover , the age-associated decrease in arm MQ was steeper in men than in women whether Con or Ecc PT was used ( both P Arm MQ as determined by Con PT showed a linear age-related decline in men and women ( 28 and 20 % , respectively , P arm MQ as determined by Ecc PT showed a linear age-related decline in men ( 25 % , P quadratic decline in leg MQ as determined by Con PT ( approximately 40 % ) and Ecc PT ( approximately 25 % ; both P MQ is affected by age and gender , but the magnitude of this effect depends on the muscle group studied and the type of muscle action ( Con vs. Ecc ) used to assess strength",
"BACKGROUND Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons . Calcium and vitamin D supplements reduce this secondary hyperparathyroidism , but whether such supplements reduce the risk of hip fractures among elderly people is not known . METHODS We studied the effects of supplementation with vitamin D3 ( cholecalciferol ) and calcium on the frequency of hip fractures and other nonvertebral fractures , identified radiologically , in 3270 healthy ambulatory women ( mean [ + /- SD ] age , 84 + /- 6 years ) . Each day for 18 months , 1634 women received tricalcium phosphate ( containing 1.2 g of elemental calcium ) and 20 micrograms ( 800 IU ) of vitamin D3 , and 1636 women received a double placebo . We measured serial serum parathyroid hormone and 25-hydroxyvitamin D ( 25(OH)D ) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women . RESULTS Among the women who completed the 18-month study , the number of hip fractures was 43 percent lower ( P = 0.043 ) and the total number of nonvertebral fractures was 32 percent lower ( P = 0.015 ) among the women treated with vitamin D3 and calcium than among those who received placebo . The results of analyses according to active treatment and according to intention to treat were similar . In the vitamin D3-calcium group , the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months ( P serum 25(OH)D concentration had increased by 162 percent over the base-line value ( P bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group ( P vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women",
"OBJECTIVES Protein supplementation has been proposed as an effective dietary strategy to augment the skeletal muscle adaptive response to prolonged resistance-type exercise training in elderly people . Our objective was to assess the impact of protein supplementation on muscle mass , strength , and physical performance during prolonged resistance-type exercise training in frail elderly men and women . DESIGN / SETTING / PARTICIPANTS A r and omized , double-blind , placebo-controlled trial with 2 arms in parallel among 62 frail elderly subjects ( 78 ± 1 year ) . These elderly subjects participated in a progressive resistance-type exercise training program ( 2 sessions per week for 24 weeks ) during which they were supplemented twice daily with either protein ( 2 * 15 g ) or a placebo . MEASUREMENTS Lean body mass ( DXA ) , strength ( 1-RM ) , and physical performance ( SPPB ) were assessed at baseline , and after 12 and 24 weeks of intervention . RESULTS Lean body mass increased from 47.2 kg ( 95 % CI , 43.5 - 50.9 ) to 48.5 kg ( 95 % CI , 44.8 - 52.1 ) in the protein group and did not change in the placebo group ( from 45.7 kg , 95 % CI , 42.1 - 49.2 to 45.4 kg , 95 % CI , 41.8 - 48.9 ) following the intervention ( P value for treatment × time interaction = .006 ) . Strength and physical performance improved significantly in both groups ( P = .000 ) with no interaction effect of dietary protein supplementation . CONCLUSIONS Prolonged resistance-type exercise training represents an effective strategy to improve strength and physical performance in frail elderly people . Dietary protein supplementation is required to allow muscle mass gain during exercise training in frail elderly people . TRIAL REGISTRATION clinical trials.gov identifier : NCT01110369",
"Fracture of the proximal femur is the most dramatic clinical sequela of osteoporosis [ 1 , 2 ] . It is associated with a high mortality rate , need for long-term medical care , and prolonged disability [ 3 - 5 ] . Protein malnutrition is often seen in elderly persons and is more severe in patients with hip fracture [ 6 - 11 ] . Protein deficiency may contribute to the occurrence of hip fracture by reducing muscle strength , impairing movement coordination , and diminishing the protective layer of soft tissue padding [ 9 , 10 , 12 - 14 ] It may also be associated with lower bone mineral density at the proximal femur [ 15 ] . Furthermore , malnutrition in general and protein deficiency in particular at admission and during recovery may adversely influence clinical outcome after hip fracture [ 7 , 9 , 10 , 16 - 18 ] . Protein restriction has been shown to reduce plasma levels of insulin-like growth factor-I ( IGF-I ) by inducing resistance to the action of growth hormone in the liver and increasing the metabolic clearance rate of the growth factor [ 19 - 23 ] . Furthermore , evidence shows that protein depletion may blunt the effect of IGF-I on target organs [ 20 ] . Thus , low protein intake in elderly persons may be detrimental to skeletal integrity , muscle strength , and immune response [ 11 , 24 - 27 ] because of decreased production and action of IGF-I , which favorably influences these systems [ 28 - 33 ] . Previous studies [ 16 , 17 ] have shown that a 5-week course of protein supplements can reduce the medical complication rate and duration of hospital stay in patients with recent hip fracture . These findings were independent of energy , calcium , and vitamin D intake [ 17 ] . Whether these observations were related to the restoration of decreased IGF-I levels and whether bone may benefit from long-term protein supplementation are not known . We investigated whether protein supplements in vitamin D-replete patients with a recent hip fracture who were receiving calcium supplements could increase circulating IGF-I levels and favorably influence bone mineral density . Methods Patients Patients were recruited in the orthopedic ward of Geneva University Hospital , the referral center that receives 94.6 % of all patients with hip fracture from an area with a population of approximately 400 000 persons [ 5 ] . The protocol was approved by the ethical committee of the Geneva University Hospital Department of Surgery . Inclusion criteria were age greater than 60 years ; recent hip fracture ( within 2 weeks ) attributable to osteoporosis ( that is , a fracture after a minor trauma , such as a fall from st and ing height ) ; and the ability to give written , informed consent . Exclusion criteria were pathologic fracture ; fracture caused by severe trauma ; history of contralateral hip fracture ; severe mental impairment ; active metabolic bone disease ; renal failure ( plasma creatinine concentration 200 mol/L ) ; acute illness that could interfere with the study protocol ; severe malnutrition ( serum albumin level Using a r and om number table , we assigned patients to receive an oral protein supplement composed of 90 % milk proteins or a placebo made isocaloric by the addition of maltodextrins . Patients took the assigned intervention 5 days a week for 6 months in addition to their regular diet . All patients received one oral dose of vitamin D3 , 200 000 IU ( vitamine D3B.O.N. , Doms-Adrian , Courbevoie , France ) , to correct any possible vitamin D deficiency [ 34 ] . The daily protein supplement ( Meritene , S and oz Nutrition Ltd. , Berne , Switzerl and ) provided 1050 kJ ( 250 kcal ) of energy in the form of 20 g of proteins , 3.1 g of lipids , and 35.7 g of carbohydrates ( 54.4 g in placebo ) . The other constituents of the 65 g powder supplement were vitamin A ( 1000 IU ) , vitamin K1 ( 30 g ) , vitamin C ( 20 mg ) , calcium ( 550 mg ) , magnesium ( 91 mg ) , phosphorus ( 429 mg ) , and sodium ( 228 mg ) . The supplement is design ed to normalize but not overcompensate for the insufficient dietary intake of protein of elderly persons with a recent fracture of the proximal femur [ 16 ] . Compliance was verified by weekly phone calls and by counting the remaining nutritional supplement bags , which were forwarded monthly by mail . Clinical Data Medical history , clinical characteristics , anthropometric data , and performance status according to an Activities of Daily Living score [ 35 ] were evaluated . Dietary intakes were recorded by using a food-frequency question naire [ 36 ] about the week before the fracture . Food intakes were analyzed by using a nutrient software system ( Fruitdor , Astra-Calve , Paris , France ) . Dietary intake of calcium , phosphorus , and protein was calculated from intake of dairy products , meat , fish , and vegetables . Because many patients were unable to st and a few days after hip fracture , their height was determined with a fathom measure while they were recumbent . Body weight was determined with a scale that correlated highly with that provided by measurement of whole body bone , fat , and lean mass as assessed by dual x-ray absorptiometry [ 37 ] . Mid-arm circumference was measured with a tape measure ( coefficient of variation , 2 % ) . Isometric muscle strength of the biceps of the dominant arm was evaluated with a dynamometer ( Lido , Lidoactive Isokinetic System , Loredan Biomedical Inc. , West Sacramento , California ) , which measures the peak torque ( coefficient of variation dynamometer ( Vigorimeter , Martin Medizin-Technik , Tuttlingen , Germany ) [ 38 ] . The mean of three measurements was used for calculation . Biochemical Data Within 120 hours after surgery , we used st and ard methods to analyze venous blood sample s for protein-corrected plasma levels of calcium , phosphate , creatinine , total proteins , albumin , and prealbumin . We also measured levels of IGF-I ( Nichols Institute , San Juan Capistrano , California ) after acid-ethanol extraction and cryoprecipitation [ 39 ] , intact parathyroid hormone ( Immulite , Diagnostic Products , Los Angeles , California ) , calcitriol , calcidiol ( Incstar , Stillwater , Minnesota ) , and osteocalcin ( CIS-BIO International , Gif-sur-Yvette , France ) . Biochemical measurements were repeated 6 and 12 months after the fracture . Serum IGF-I binding proteins were measured by Western lig and blot analysis [ 40 ] . Briefly , 3 L of serum was boiled and separated onto 15 % sodium dodecylsulfate polyacrilamide gel electrophoresis under nonreducing conditions . Proteins were electrically blotted onto a nitrocellulose membrane , and IGF-I binding proteins were detected after incubating the membranes with radioiodinated IGF-I at 4C for 24 hours . Insulin-like growth factor binding proteins were quantified by phosphorimaging ( Molecular Dynamics , Sunnyvale , California ) . The intensity of the b and s corresponding to the appropriate molecular weights [ 40 ] was expressed as the percentage of total bound radioactive IGF-I. Measurements of calcium , phosphate , and creatinine were obtained from the second fasting morning urine . The ratio of hydroxyproline to creatinine in the same sample was taken as a reflection of bone resorption . Markers of bone resorption ( pyridinoline and deoxypyridinoline ) in the first morning spot urine were measured by detecting fluorescence emission after acid hydrolysis and separation with isocratic reverse-phase high-performance liquid chromatography ( BioRad System , Munich , Germany ) , and the values were adjusted to the creatinine concentration . Immunologic Data Concentrations of IgA , IgG , IgM , and isohemagglutinins were measured by using st and ard methods . Cell-mediated immunity was assessed by using a skin-test antigens for cellular hypersensitivity system ( STACH , Institut Merieux , Lyon , France ) , which evaluates the size of the skin reaction to various antigens injected intradermally [ 41 ] . Bone Mass Assessment We measured areal bone mineral density at the lumbar spine ( anteroposterior and lateral views ) , the contralateral proximal femur ( femoral neck and trochanter ) , and the contralateral mid-femoral shaft . We also measured whole-body bone mineral content , fat , and lean mass by using dual x-ray absorptiometry ( Hologic QDR-2000 , Waltham , Massachusetts ) . The coefficients of variation of these measurements are reported elsewhere [ 37 , 42 ] . Vertebral Deformity Two series of lateral radiography of the thoracic and lumbar spine were taken at the start of the study and at 12 months . The films were examined by a single investigator ( who was unaware of treatment group assignment ) according to a 6-point analysis procedure for each vertebral body from T4 to L4 [ 43 , 44 ] ( intra-observer coefficient of variation , 1.8 % to 3.1 % ) . At baseline , fracture was defined by a decrease of 20 % in the ratio of anterior or middle height to posterior height . Patients were considered to have a new vertebral deformity if the anterior , middle , or posterior height decreased by more than 20 % between the two examinations . Statistical Analysis All values are given as the mean SD for baseline measurement and the mean SE for comparisons of outcome results . All analyses were performed by using the SAS procedure ( Cary , North Carolina ) . One-way analysis of variance was used . A two-tailed P value less than 0.05 was considered significant . Role of the Funding Sources This study was supported by grants from S and oz Nutrition Ltd. , Berne , Switzerl and , and the Swiss National Research Science Foundation . The skin-test antigens for cellular hypersensitivity system was supplied by Rhone-Poulenc , Thalwil , Switzerl and . No organization influenced the design , conduct , or reporting of the study . Results Of 842 patients evaluated from April 1992 to February 1994 , 82 were recruited into the r and omized , double-blind , placebo-controlled trial . This low enrollment rate was due to patients ' poor medical or cognitive conditions and reluctance to give informed consent .",
"OBJECTIVE Higher calcium and dairy intakes may be associated with lower body weights , but a mechanism in humans has yet to be eluci date d. We compared the effects of a dairy-based high-calcium diet and a low-calcium diet on macronutrient oxidation . RESEARCH METHODS AND PROCEDURES Subjects ( 10 men and nine women ) consumed a low-dairy ( LD , approximately one serving per day , approximately 500 mg Ca(2+)/d ) or high-dairy ( HD , approximately three to four servings per day , approximately 1400 mg Ca(2+)/d ) energy balance diet for 1 week . Each diet condition was performed twice . On the 7th day , subjects were studied in a room calorimeter under one of four study conditions , applied in a r and omized crossover design . Within each diet condition , subjects were studied under conditions of energy balance and acute energy deficit . The deficit ( -600 kcal/d ) was induced only for the 24 hours that subjects resided in the room and was achieved by a combination of caloric restriction and exercise . RESULTS Under energy balance conditions , there was no effect of diet treatment on respiratory quotient or 24-hour macronutrient oxidation . Under energy deficit conditions , 24-hour fat oxidation was significantly increased on the HD diet ( HD with deficit = 136 + /- 13 g/d , LD with deficit = 106 + /- 7 g/d , p = 0.02 ) . DISCUSSION Consumption of a dairy-based high-calcium diet increased 24-hour fat oxidation under conditions of acute energy deficit . We hypothesize that these effects are due to an increased fat oxidation during exercise",
"OBJECTIVES To describe associations between dietary nutrient intake and progression of sarcopenia , the age-related loss of muscle mass and strength . DESIGN Prospect i ve cohort study of community-dwelling older adults . SETTING Southern Tasmania , Australia . PARTICIPANTS Seven hundred forty noninstitutionalized older adults ( 50 % female ; mean age 62 ± 7 ) r and omly sample d from electoral rolls . MEASUREMENTS Dietary nutrient intake was examined at baseline and follow-up ( 2.6 ± 0.4 years later ) using The Cancer Council Victoria 's Food Frequency Question naire ( FFQ ) . Appendicular lean mass ( aLM ) was assessed using dual X-ray absorptiometry and muscle strength of the knee extensors using a dynamometer . RESULTS Failing to meet the recommended dietary intake for protein was associated with significantly lower aLM at baseline ( -0.81 kg , 95 % confidence interval ( CI ) = -1.54 to -0.08 ) and follow-up ( -0.79 kg , 95%CI = -1.42 to -0.17 ) . Energy-adjusted protein intake was a positive predictor of change in aLM over 2.6 years ( β = 0.10 , P = .003 ) . Energy-adjusted intake of iron ( β = 0.07 , P = .02 ) , magnesium ( β = 0.07 , P=.02 ) , phosphorus ( β = 0.07 , P = .047 ) , and zinc ( β = 0.08 , P = .02 ) were positive predictors of change in aLM , whereas retinol ( β = -0.09 , P = .005 ) was a negative predictor of change in aLM after adjustment for protein intake . No significant associations were observed between nutrient intake and muscle strength . CONCLUSION Protein and several other dietary nutrients are associated with muscle mass and rate of muscle loss ( but not strength ) in older adults , suggesting that multiple dietary components may ameliorate the progression of sarcopenia"
] |
4116cab8-06ff-11f0-808a-c43d1ab1c353
|
Background : Duloxetine hydrochloride ( DUL ) is an antidepressant included in the pharmacological class of serotonin-norepinephrine reuptake inhibitors approved for the treatment of major depressive disorder , generalized anxiety disorder , diabetic peripheral neuropathic pain , fibromyalgia , and chronic musculoskeletal pain . The aim of this review was to eluci date current evidence s on the use of DUL in the treatment of a variety of psychiatric disorders . Methods : This systematic review was conducted according to PRISMA ( Preferred Reporting Items for Systematic Review s and Meta-Analyses ) guidelines . PubMed data base was search ed from January 1 , 2003 , to September 30 , 2018 , using 11 key terms related to psychiatric disorders ( " persistent depressive disorder , " " dysthymic disorder , " " bipolar disorder , " " seasonal affective disorder , " " obsessive-compulsive disorder , " " social phobia , " " panic disorder , " " posttraumatic stress disorder , " " schizophrenia , " " eating disorders , " " sexual disorders , " " personality disorders " ) and one key term related to duloxetine ( " duloxetine hydrochloride " ) . Article titles and abstract s were scanned to determine relevance to the topic . For additional studies , the authors also examined the reference lists of several of the included papers . Results : Duloxetine may be an effective treatment for mood spectrum disorders , panic disorder , several symptom clusters of borderline personality , and as add-on drug in schizophrenia . Modest or conflicting results have been found for the efficacy of duloxetine in obsessive-compulsive disorder , posttraumatic stress disorder , eating , and sexual disorders . Conclusion : Major limitations of the review ed studies were short trial duration , small sample sizes , and the lack of control groups . Defining the potential role of DUL in the treatment of psychiatric disorders other than major depressive disorder and generalized anxiety disorder needs further r and omized , placebo-controlled studies
|
[
"The pharmacokinetics and safety of duloxetine were evaluated in a single-blind , placebo-controlled , escalating multiple-dose study in 12 healthy male subjects . In the treatment group ( n = 8) , duloxetine was administered orally at a starting dose of 20 mg twice daily ( bid ) and escalated at weekly intervals to 30 mg bid , then to 40 mg bid . The observed plasma concentration-time data at all three dose levels were adequately described by a one-compartment model with a first-order absorption rate constant . The mean oral clearance , apparent volume of distribution , and half-life values were 114 L/h ( range : 44 to 218 L/h ) , 1943 L ( range : 803 to 3531 L ) , and 12.5 h ( range : 9.2 to 19.1 h ) , respectively . Somnolence , nausea , and dry mouth were observed following the initial dose , but they resolved with continuing drug administration . Duloxetine was not associated with clinical ly significant changes in blood pressure ( BP ) or heart rate ( HR ) measured in the st and ing position . However , in recumbent position , small increases in systolic ( or = 9 mmHg ) and diastolic ( 5 mmHg ) BP and small decreases in HR ( mean HR ( transient sleep disturbance . No clinical ly important changes in electrocardiograms , cardiac intervals , clinical laboratory tests , and neurological functions were observed . These results indicate that duloxetine exhibits linear pharmacokinetics with respect to dose and duration of treatment and that a multiple oral dose regimen starting at 20 mg bid and gradually escalating up to 40 mg bid was generally well tolerated",
"This pilot aims to better underst and the market for childcare in Saudi Arabia – both the supply and dem and sides – and to design a r and omized controlled experiment to test whether access to affordable day care ( in the form of subsidies , for example ) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired . In addition , the study seeks to underst and the degree to which employment early on in one ’s life impacts employment in later stages . The pilot will provide information on the groups of women the experiment should target , appropriate levels for the childcare subsidy , and the quality and current geographic locations of daycare sites . Expected Impact Determine the effects of facilitating childcare access on Saudi women ’s employment . PRINCIPAL INVESTIGATORS Boston University Patricia Cortes Harvard University Claudia Goldin Swarthmore College Jennifer",
"OBJECTIVE To determine efficacy of continued treatment with the serotonin norepinephrine reuptake inhibitor duloxetine on symptom reduction and functional improvement in out patients with dysthymia . METHOD Fifty out patients with DSM-IV-TR diagnosed dysthymia who had participated in a 10 week double-blind , placebo-controlled study of duloxetine received open treatment for three months . Nineteen duloxetine responders continued duloxetine , 24 patients initially treated with placebo started open duloxetine treatment , and 7 duloxetine non-responders were treated with desvenlafaxine or bupropion , selected by clinician choice . RESULTS Patients continuing duloxetine maintained symptom improvement , 84 % meeting response and 63 % remission criteria at week 22 . Patients initially treated with placebo showed similarly high levels of response ( 83 % ) and remission ( 62 % ) at week 22 , and most duloxetine non-responders subsequently responded to other antidepressants . Duloxetine-continuation patients improved modestly between weeks 10 and 22 on measures of social and cognitive functioning and temperament . Despite this improvement concurrently across several functional domains , 66.7 % of patients continuing duloxetine remained in the impaired range of functioning according to the Social Adjustment Scale ( SAS ) . CONCLUSIONS Continued duloxetine treatment appears to be effective in maintaining symptom response in dysthymic disorder , and has positive effects on social functioning . However , the majority of patients do not show normalization of functioning , even when controlling for remission status . Additional treatments should be considered to target residual impairments in social functioning in mood remitted patients with persistent depressive disorder",
"The objective of this prospect i ve study was to assess the efficacy and tolerability of duloxetine in the treatment of in military veterans with posttraumatic stress disorder (PTSD).Twenty subjects were enrolled in this 12-week , open-label trial . Diagnosis and symptom severity were assessed with the Clinician Administered PTSD Scale ( CAPS ) . Depressive symptoms were assessed the Hamilton Depression Rating Scale . All subjects had a CAPS score of at least 60 at baseline . Subjects with lifetime history of psychotic disorders or bipolar illness were excluded . Fifteen participants completed 12 weeks of treatment , five dropped-out from the trial , 3 due to side effects . For patients who discontinued , missing values were estimated using \" the last observation carried forward \" method . Significant improvements were seen on : CAPS total and all subscales , depression and sleep measures . Most of the improvement was observed by week 2 of treatment . Nine participants ( 45 % ) were classified as responders , defined by 20 % or greater improvement on CAPS total score . The mean daily dose of duloxetine was 81 mg . The most common side effects were constipation ( 20 % ) diarrhea ( 25 % ) and nausea ( 20 % ) . Two subjects developed tachycardia , one withdrew from the trial due to this problem . Duloxetine had a fast onset of action and was effective in about half of the subjects , it was well tolerated in most subjects . These preliminary results in a difficult to treat population warrant the conduction of a double blind , placebo-controlled study of duloxetine in PTSD",
"Panic disorder with or without agoraphobia is a common , often chronic and refractory anxiety disorder . Although a number of pharmacotherapies are now indicated for panic disorder , many patients do not respond to available interventions . We hypothesized that duloxetine , a serotonin‐norepinephrine reuptake inhibitor ( SNRI ) that has greater initial noradrenergic effects than venlafaxine , would have broad efficacy for individuals with panic disorder . Fifteen individuals with panic disorder with or without agoraphobia received 8 weeks of open label duloxetine flexibly dosed from 60 to 120 mg per day . Duloxetine treatment result ed in significant anxiolysis as measured by the primary outcome measure , the Panic Disorder Severity Scale ( PDSS ) ( paired t(df ) = 4.02(14 ) , P= 0.0013 ) , as well as measures of generalized anxiety , depression and quality of life ( all P < 0.05 ) . Although definitive conclusions are limited due to its small open‐label nature , this first prospect i ve study provides preliminary support for the efficacy of duloxetine for panic disorder and suggests larger r and omized controlled study is warranted",
"Objective : Premenstrual dysphoric disorder ( PMDD ) is a complex clinical syndrome that is notoriously difficult to treat . The purpose of the present study was to provide preliminary data on the effectiveness of duloxetine in PMDD . Research design and methods : Fifty-five women with PMDD were treated with a 60 mg/day dosage of duloxetine for two menstrual cycles . Responses were assessed at first and second treatment cycle . Main outcome measures : Outcome measures included a visual analogue scale , the Zung Self-rating Scale for Depression , the Hamilton Depression Rating Scale , the Hamilton Anxiety Rating Scale and the Clinical Global Impressions Scale . Results : Fifty patients completed the trial . All had significant improvement of depression and anxiety and response , defined as a 50 % decrease in daily symptom scores , occurred in 39 ( 78 % ) patients . The effects of active treatment were marked by the first active cycle of menstruation . Conclusions : Duloxetine 60 mg/day was effective in reducing PMDD symptoms and generally well tolerated . Limitations of the study were open-label design and lack of placebo control . However , the results appeared to be strong and consistent across measures . Adverse events ( nausea , insomnia , poor appetite ) were low . Further studies are needed to confirm these results",
"Abstract Aim : Though premature ejaculation ( PE ) has been overshadowed by current attention given to erectile dysfunction , it is the most widespread form of male sexual dysfunction . Delayed or inhibited ejaculation , a known side effect of selective serotonin reuptake inhibitors ( SSRIs ) , has made SSRIs potentially useful in the treatment of this disorder . In the present study , we examined the efficacy of duloxetine , an SSRI , in the treatment of PE . Method : The study included 20 married patients diagnosed with PE . The patients were r and omly assigned to two groups , duloxetine ( group I ) and placebo ( group II ) , each consisting of 10 patients . The effects on the ejaculatory function were estimated by the intravaginal ejaculation latency time . All patients were evaluated by using clinical global impression-improvement Scale ( CGI-I ) . Results : The increase in the intravaginal ejaculation latency time in the duloxetine group was statistically significant than that of placebo group . Of group I patients , four ( 40 % ) were considered as “ very much improved ” and four ( 40 % ) “ much improved ” by CGI-I and only one of group II patients ( 10 % ) showed “ much improved ” . Conclusion : Duloxetine appears to be superior to placebo in the pharmacological treatment of PE when administered on a chronic basis",
"OBJECTIVE The aim of this observational study was to evaluate the effects of duloxetine in the treatment of seasonal affective disorder ( SAD ) . PATIENTS AND METHODS 26 SAD patients were treated with open-label duloxetine 60 - 120 mg per day over 8 weeks . Ratings included the Structured Interview Guide for the Hamilton Depression Rating Scale ( SAD version ; SIGH-SAD ) and the Clinical Global Impression ( CGI ) . To estimate treatment effects on social functioning in SAD we employed the Social Adaptation Self Evaluation Scale ( SASS ) , the Sheehan Disability Scale ( SDS ) , and assessment s of days lost due to illness and days with reduction in productivity . RESULTS Duloxetine led to a significant improvement ( p SIGH-SAD , CGI severity , SASS , and SDS scores . Days lost due to illness and days with reduction in productivity were significantly diminished during treatment ( p duloxetine over 8 weeks yielded a response rate ( SIGH-SAD duloxetine might be effective and able to ameliorate the negative social consequences of SAD",
"Premenstrual dysphoric disorder ( PMDD ) affects 3 - 8 % of women of reproductive age and is characterized by severe mood symptoms that cause important functional impairment . Serotonergic antidepressants appear to be an effective treatment for this disorder . The purpose of this study was to collect evidence on the efficacy and tolerability of duloxetine , a dual reuptake inhibitor of serotonin and norepinephrine , in the treatment of PMDD . We conducted a pilot , single-blind , non-controlled , fixed-dose trial . After two cycles for diagnosis confirmation , including a single-blind placebo cycle , 20 women with PMDD were treated continuously for three menstrual cycles with 60 mg/d duloxetine . The primary measure of the efficacy of treatment with duloxetine was the significant reduction in premenstrual symptoms demonstrated by the comparison between the mean Daily Record of Severity of Problems ( DRSP ) scores at baseline to endpoint ( p=0.0002 ) . Statistically significant symptom reduction was observed in the first treatment cycle and throughout all the treatment phase . Clinical response , defined as a reduction 50 % of baseline premenstrual symptoms , occurred in 65 % of subjects ( intention-to-treat population ) . Significant improvements were demonstrated by secondary measures , including reduction in self-rated functional impairment ( p=0.01 ) and improvement in quality of life ( p=0.04 ) . The main side-effects associated with duloxetine were dry mouth , nausea , drowsiness , insomnia , decreased appetite , decreased libido , and sweating . Duloxetine was effective and generally well tolerated in the treatment of PMDD . Further large-scale , double-blind , placebo-controlled studies are needed to evaluate duloxetine as an additional treatment strategy for the management of PMDD",
"OBJECTIVE Numerous double-blind studies have assessed the efficacy of antidepressants in treating chronic depressive disorder , including dysthymic disorder , low- grade chronic depression . However , there are no double-blind , placebo-controlled studies of serotonin-norepinephrine reuptake inhibitors in chronic depressive disorder . METHOD Out patients with chronic depressive disorder , but without concurrent major depressive disorder ( MDD ) , were r and omly assigned to prospect i ve double-blind duloxetine ( beginning at 30 mg/d , increased to a maximum dose of 120 mg/d ) versus placebo for 10 weeks . Inclusion criteria were current DSM-IV-TR diagnosis of dysthymic disorder or depression not otherwise specified , age 18 - 75 years , and a Hamilton Depression Rating Scale ( HDRS ) score ≥ 12 . Exclusion criteria included current major depression . The study was conducted between August 2006 and December 2011 . HDRS , Cornell Dysthymia Rating Scale ( CDRS ) , Clinical Global Impressions ( CGI ) , Beck Depression Inventory ( BDI ) , Global Assessment of Functioning ( GAF ) , Social Adjustment Scale ( SAS ) , and other assessment s were administered at each visit . We hypothesized that duloxetine would be superior to placebo in ( 1 ) 24-item HDRS total score , ( 2 ) the percentage of subjects classified as responders and remitters , and ( 3 ) secondary measures ( CDRS , BDI , CGI ) . Response was defined as > 50 % decrease in 24-item HDRS and CGI-Improvement scale score of 1 or 2 ( \" very much improved \" or \" much improved \" ) . Remission was defined as HDRS-17 item score ≤ 4 and 0 on item 1 of the HDRS ( depressed mood ) . RESULTS 65 subjects were enrolled , of whom 57 began medication . They ranged in age from 19 to 70 years ( mean ± SD = 41.63 ± 11.22 ) and included 24 women and 33 men . Baseline 24-item HDRS score ( mean ± SD ) for both groups was 20.75 ± 4.92 . After 10 weeks , duloxetine-treated subjects had significantly lower 24-item HDRS scores than placebo-treated subjects ( time-by-drug group effect on analysis of variance : F1,55 = 9.43 , P = .003 ) . Responder and remitter analyses significantly favored duloxetine treatment . The response rate was 65.5 % for duloxetine versus 25.0 % for placebo ( χ(2)(1 ) = 9.43 , P = .003 ) ; and the remitter rate was 55.2 % for duloxetine versus 14.3 % for placebo ( χ(2)(1 ) = 10.46 , P = .002 ) . After 10 weeks , duloxetine-treated subjects did not differ significantly better from placebo-treated subjects on the SAS ( time-by-drug group effect on analysis of variance : F(1,46 ) = 0.35 , P = .555 ) or on the GAF ( time-by-drug group effect on analysis of variance : F(1,51 ) = .01 , P = .922 ) . CONCLUSIONS Results on the 24-item HDRS , CGI , and CDRS suggest that duloxetine is efficacious in acute treatment of chronic nonmajor depressive disorder . Response and remission rates also differed significantly , favoring duloxetine treatment , but BDI , GAF , and social functioning ( Social Adjustment Scale ) did not . Duloxetine appears to be effective in acute treatment of nonmajor chronic depression . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00360724",
"Attempts have been made to find appropriate drug regimens to treat binge eating disorder ( BED ) . Several reports have examined the use of selective serotonin reuptake inhibitors ( SSRIs ) or mood stabilizers ; both serotonin and noradrenalin reuptake inhibitors ( SNRIs ) have been reported to be useful for binge eating , but the available data are limited . We evaluated the efficacy of duloxetine , an SNRI , in 45 obese patients who reported binge eating",
"Abstract Purpose In the current analysis due to the mechanism of effect , we evaluated the treatment benefit of duloxetine 40 mg comparing with paroxetine 20 mg , based on its effects on personal distress and interpersonal difficulty related to ejaculation , perceived control over ejaculation , and satisfaction with sexual intercourse , as well as the patient-reported global impression of change in premature ejaculation ( PE ) and the effect on intravaginal ejaculatory latency times ( IELT ) in men with premature ejaculation . Material s and methods The study included 80 married male patients diagnosed with lifelong PE . A total of 80 patients were r and omly distributed into two groups of 40 patients each . Group 1 patients received 40 mg duloxetine once a day for a month . Group 2 patients received 20 mg paroxetine once a day for a month . International index of erectile function question naire ( IIEF ) and IELT and PE profile were recorded before and after treatment . Results Comparing the groups ’ mean treatment IELT , there was no difference between groups . The IELT increase from baseline to treatment was 117 % in the duloxetine group ( P paroxetine group ( P IELT increase ( P > 0.05 ) . Also , there was no statistically significant difference between two groups at baseline IIEF to treatment IIEF scores . All PEP measures improved significantly with duloxetine and paroxetine groups ( P duloxetine is safe and effective for the treatment for premature ejaculation",
"Guidelines of the American Psychiatric Association for borderline personality disorder ( BPD ) indicate selective serotonin reuptake inhibitors and the serotonin and noradrenaline reuptake inhibitor ( SNRI ) venlafaxine for treating affective dysregulation and impulsive behavioural dyscontrol symptoms . The SNRI duloxetine has been studied in patients with major depression , generalized anxiety disorder and fibromyalgia , showing particular efficacy on somatic complaints . This study investigates duloxetine in the treatment of patients with BPD . Eighteen out patients with a DSM-IV-TR diagnosis of BPD were treated with open-label duloxetine , 60 mg/day , for 12 weeks . Patients were assessed at baseline , week 4 and 12 with the CGI Severity item , the BPRS , the HAM-D , the HAM-A , the SOFAS , the BPD Severity Index ( BPDSI ) and the HSCL-90-Somatization Subscale ( HSCL-90 SOM ) . Adverse effects were evaluated using the Dosage Record Treatment Emergent Symptom Scale . Statistics were performed with the analysis of variance . Significant P values were ≤0.05 . Fourteen patients completed the study . Four patients ( 22.2 % ) discontinued treatment in the first 4 weeks because of non-compliance . A significant change was found for : BPRS , HAM-D , SOFAS , BPDSI total score and items ‘ impulsivity ’ , ‘ outbursts of anger ’ and ‘ affective instability ’ and HSCL-90 SOM . Adverse effects were mild headache and nausea . Initial results suggest that duloxetine is an effective and well-tolerated treatment for BPD , with positive effects on somatic symptoms ",
"Introduction The aim of this study is to evaluate the efficacy of duloxetine augmentation in treatment of resistant obsessive-compulsive disorder ( OCD ) . Methods This augmentation trial was design ed as an 8-week r and omized controlled , double-blind study . Forty-six patients experiencing OCD who had failed to respond to at least 12 weeks of treatment with a selective serotonin reuptake inhibitor ( fluoxetine , citalopram , or fluvoxamine ) were r and omly allocated to receive duloxetine or sertraline plus their current anti-OCD treatment . The Yale-Brown Obsessive Compulsive Scale ( Y-BOCS ) was the primary outcome measure . Treatment response was defined as 25 % or more decrease in scores of Y-BOCS . The mean dosage of duloxetine was 44.4 mg/d ( range , 20–60 mg/d ) , and the mean dosage of sertraline was 123.8 mg/d ( range , 50–200 mg/d ) . Results Forty-six patients ( 24 of 30 in duloxetine group and 22 of 27 in sertraline group ) completed the trial . Both groups showed improvement during the 8-week study period ( mean Y-BOCS total score at week 8 as compared with baseline : P duloxetine plus their initial medications experienced a mean decrease of 33.0 % in Y-BOCS score , and the patients with sertraline added to their initial medication experienced a mean decrease of 34.5 % in Y-BOCS . Discussion Our double-blind controlled clinical trial showed duloxetine to be as effective as sertraline in reducing obsessive and compulsive symptoms in patients with resistant OCD . However , it needs to be noted that our study is preliminary , and larger double-blind placebo-controlled studies are necessary to confirm the results",
"Antidepressant drugs have often been used as an augmentation strategy for those patients who have demonstrated a suboptimal response to clozapine . The present 16-week double-blind , r and omized , placebo-controlled trial study aim ed to explore the efficacy and tolerability of duloxetine add-on pharmacotherapy on clinical symptomatology and executive cognitive functioning in a sample of patients with treatment-resistant schizophrenia receiving clozapine . After clinical and neurocognitive assessment s , the patients were r and omly allocated to receive , in a double-blind design , at a dose of 60 mg per day of duloxetine or a placebo . A final sample of 33 patients completed the study . The results obtained indicate that duloxetine added to stable clozapine treatment showed a beneficial effect on the negative and general psychopathological symptomatology in a sample of treatment-resistant schizophrenic patients . With regard to executive cognitive functions , duloxetine augmentation of clozapine had no significant effects . The findings provide evidence that duloxetine augmentation of clozapine treatment is safe and well tolerated and may be of benefit for patients who are partially responsive to clozapine monotherapy",
"OBJECTIVE To compare the effects of starting doses of duloxetine taken with or without food on tolerability and efficacy in patients with major depressive disorder ( MDD ) . METHOD This double-blind , concurrent-dose-controlled , parallel- design trial contained a variable expected- duration placebo lead-in period and was conducted in adult out patients with DSM-IV-TR-defined MDD at psychiatric outpatient sites between October 2004 and January 2006 . In actuality , patients received placebo for 1 week and then were r and omly assigned to duloxetine 30 mg once daily in the morning ( q.a.m . ) ( N = 219 ) , 30 mg twice daily ( b.i.d . ) ( N = 213 ) , or 60 mg q.a.m . ( N = 215 ) for 1 week along with 1 of 2 instructions about food : take study drug with food or do not take within 1 hour of eating . For the remaining 5 weeks of acute treatment , all patients received 60 mg once daily . The primary objective was to compare incidence of treatment-emergent nausea at 30 mg q.a.m . versus 60 mg q.a.m . using item 112 ( nausea ) of the Association for Methodology and Documentation in Psychiatry adverse event scale ( AMDP-5 ) . Secondary outcome measures included mean change on AMDP-5 item 112 , discontinuations due to adverse events , mean changes in AMDP-5 items and subscales , spontaneously reported treatment-emergent adverse events , and vital signs . Efficacy was evaluated by the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) . RESULTS The primary analysis , which combined data from both food groups , showed no significant difference in the incidence of nausea between starting doses of 30 mg q.a.m . and 60 mg q.a.m . ( 23 % vs. 29 % , respectively ; p = .207 ) . However , mean changes on the AMDP-5 nausea item revealed a significant main effect of food ( p = .010 ) and a significant interaction between food and starting dose ( p = .033 ) . The food-by-dose interaction indicated that the benefit from taking drug with food was greatest in patients started at 60 mg q.a.m . , and the benefit of starting at 30 mg q.a.m . was greatest in patients taking drug without food . In patients who took study drug without food , there was a significant difference across initial-dose groups for discontinuation due to adverse events ( 30 mg q.a.m . = 3.6 % , 30 mg b.i.d . = 14.0 % , 60 mg q.a.m . = 10.2 % ; 30 mg q.a.m . vs. 30 mg b.i.d . , p = .008 ; 30 mg q.a.m . vs. 60 mg q.a.m . , p = .066 ) ; however , in patients who took study drug with food , discontinuations due to adverse events did not significantly differ ( 30 mg q.a.m . = 5.4 % , 30 mg b.i.d . = 7.5 % , 60 mg q.a.m . = 7.4 % ; all p values > .50 ) . Patients who started at 30 mg b.i.d . or 60 mg q.a.m . without food did not differ regarding mean changes ( i.e. , increases ) in the common adverse events score after 1 week of treatment but had significantly greater mean changes than patients who started at 30 mg q.a.m . without food ( 0.87 , 0.82 , and 0 , respectively ; p dulox-etine at 30 mg q.a.m . for 1 week with or without food or starting duloxetine at the therapeutic dose of 60 mg q.a.m . with food can improve the initial tolerability of the medication . Adding this information to existing knowledge of duloxetine will enable the clinician to tailor therapy most appropriately for the individual patient . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT 00191061",
"Background : This study sought to investigate the efficacy of duloxetine for the treatment of obsessive-compulsive disorder ( DSM-IV ) . Methods : Twenty individuals were enrolled in a 17-week , open-label trial of duloxetine at Massachusetts General Hospital . Data were collected between March 2007 and September 2012 . Study measures assessing obsessive-compulsive disorder symptoms , quality of life , depression , and anxiety were administered at baseline and weeks 1 , 5 , 9 , 13 , and 17 . The primary outcome measures were the Yale-Brown Obsessive Compulsive Scale and Clinical Global Improvement scale . Results : For the 12 study completers , pre- and posttreatment analyses revealed significant improvements ( P clinician- and self-rated measures of obsessive-compulsive disorder symptoms and quality of life . Among the 12 completers , more than one-half ( n=7 ) satisfied full medication response criteria . Intention-to-treat analyses ( n=20 ) showed similar improvements ( P patients with obsessive-compulsive disorder . Clinical Trials.gov NCT00464698 ; http:// clinical trials.gov/ct2/show/NCT00464698?term=NCT00464698&rank=1",
"Abstract The present 12-week open-label uncontrolled trial was aim ed to explore the efficacy of reboxetine add-on pharmacotherapy on clinical symptoms and cognitive functioning in 15 patients with schizophrenia with suboptimal response ( mean [ SD ] Brief Psychiatric Rating Scale baseline total score , 32.2 [ 5.4 ] ) despite receiving clozapine monotherapy at the highest tolerated dosage . The results obtained evidence d that reboxetine at a dosage of 4 mg/d mildly reduced only depressive symptoms ( Calgary Depression Scale for Schizophrenia : P = 0.035 , Cohen d = 0.7 ) , whereas worsening of performances on phonemic fluency ( P = 0.012 , Cohen d = 0.5 ) was observed . After Bonferroni correction , changes at the Calgary Depression Scale for Schizophrenia and at the Verbal Fluency Task were not further confirmed . The results obtained indicate that reboxetine seemed to be scarcely effective for reducing clinical symptoms in patients with schizophrenia who have had an incomplete clinical response to clozapine . Regarding cognitive functioning , in our sample , a trend to experience cognitive impairment in the examined domains was observed , as confirmed by a mild worsening of performances on cognitive tasks . Schizophrenia is a heterogeneous disorder with regard to pathophysiology ; therefore , data reflecting the mean response of a sample of patients may fail to reveal therapeutic effects . More research is needed to better identify subgroups of patients with peculiar features , which may account for responsivity to experimental medications and augmentation strategies",
"BACKGROUND Although not as common as major depressive disorder , dysthymia is not rare and is associated with substantial impairment . Antidepressants and some psychotherapies are often effective . We explored the efficacy of the antidepressant duloxetine , a serotonin and norepinephrine reuptake inhibitor . METHOD Between February 2005 and April 2006 , we recruited 24 adults with DSM-IV dysthymia or dysthymia and concurrent major depression ( \" double depression \" ) who had an entry score of > or = 17 on the clinician-rated Inventory for Depressive Symptomatology ( IDS-C ) . We excluded subjects with significant medical illnesses and those requiring other psychotropic agents or undergoing psychotherapy . Subjects received duloxetine 60 mg/day for 6 weeks , increased as tolerated to 120 mg/day for the remainder of the 12-week trial for those with an inadequate treatment response . RESULTS The subjects ' mean + /- SD IDS-C scores decreased significantly from baseline ( 27.3 + /- 6.3 ) to endpoint ( 7.8 + /- 7.4 , Student t = 12.38 , df = 23 , p IDS-C response rate ( intent-to-treat [ ITT ] ) was 83 % ( 20/24 ) ; the remission rate ( ITT ) was 79 % ( 19/24 ) . Among study completers , these rates were 89 % ( 17/19 ) and 84 % ( 16/19 ) . Five subjects ( 21 % ) discontinued for side effects . CONCLUSION Duloxetine appears to be an effective and well-tolerated treatment for dysthymia and double depression . A double-blind , placebo-controlled study is under way . If duloxetine is found to be effective , studies powered to detect potential , clinical ly important differences between duloxetine and other antidepressants will be needed . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00185575",
"Objectives : Multimodal analgesia is widely advocated for the control of perioperative pain in an effort to reduce the use of opioid . Duloxetine is a selective inhibitor of serotonin and norepinephrine reuptake with efficacy for chronic pain conditions . The primary objective of this study was to evaluate the efficacy of two 60 mg oral doses of duloxetine in terms of fentanyl consumption during the postoperative period in patients undergoing elective spine surgery . Material s and Methods : This study was prospect i ve , double-blind , r and omized , and placebo controlled . Patients received either 60 mg duloxetine or an identical placebo 1 hour before surgery and again the following morning . The study participants were allocated into 2 groups : Group C ( control ) participants received the placebo and Group D ( duloxetine ) participants received 60 mg duloxetine . The total consumption of fentanyl 48 hours after surgery was measured . Secondary end points were pain scores and the presence or absence of adverse effects , such as headache , nausea , vomiting , itching , dizziness , and drowsiness . Results : Demographic characteristics did not differ between groups . There was a significant difference in fentanyl consumption in the first 24 hours between Groups C and D ( mean difference , 223.11±39.32 µg ; P also differed between Groups C and D after 48 hours ( mean difference , 179.35±32.55 µg ; P over 48 hours did not significantly differ between groups . The incidence of side-effects was similar in both groups . Discussion : Duloxetine was effective as an adjunct for postoperative analgesia and reduced opioid consumption",
"Objective One of the complications of chemotherapy is peripheral neuropathy . Various studies have shown that potent norepinephrine and serotonin reuptake inhibitors such as gabapentin , venlafaxine and duloxetine have therapeutic effects on neuropathy . The aim of this study was to compare the effects of venlafaxine vs. duloxetine on chemotherapy-induced peripheral neuropathy . Methods In this clinical trial , cancer patients who were suffering from chemotherapy-induced peripheral neuropathy comprised the study population . They were r and omly assigned to three pharmacotherapy groups including venlafaxine , duloxetine and placebo . Cranial , sensory , motor neuropathies as well as neuropathic pain were evaluated on day 1 , week 2 , and week 4 after enrollment . Results Grade of cranial , motor , sensory and neuropathic pain decreased significantly in venlafaxine and duloxetine groups . This reduction was more considerable in duloxetine group compared to venlafaxine group ( P venlafaxine in decreasing the symptoms of chemotherapy-induced peripheral neuropathy . Duloxetine was more effective than venlafaxine in decreasing motor neuropathy and neuropathic pain grade",
"Purpose To compare treatment outcomes in patients with major depressive disorder treated with duloxetine , escitalopram , fluoxetine , paroxetine , or sertraline for up to 6 months . Patients and methods Data were taken from a 6-month prospect i ve , observational study that included 1,549 major depressive disorder patients without sexual dysfunction in 12 countries . We report the overall results and those from Asian countries . Depression severity was measured using the Clinical Global Impression and the 16-item Quick Inventory of Depressive Symptomatology Self-Report ( QIDS-SR16 ) . Clinical and functional remissions were defined as having a QIDS-SR16 Clinical Global Impression rating during follow-up was significantly lower in those patients treated with duloxetine compared with escitalopram ( 0.40 , 95 % CI 0.25 to 0.56 ) ; fluoxetine ( 0.22 , 95 % CI 0.05 to 0.38 ) ; paroxetine ( 0.38 , 95 % CI 0.23 to 0.54 ) ; and sertraline ( 0.32 , 95 % CI 0.16 to 0.49 ) . The QIDS-SR16 of duloxetine-treated patients was significantly lower than those treated with escitalopram ( 1.58 , 95 % CI 1.03 to 2.12 ) ; fluoxetine ( 1.48 , 95 % CI 0.90 to 2.06 ) ; paroxetine ( 1.53 , 95 % CI 1.00 to 2.07 ) ; and sertraline ( 1.19 , 95 % CI 0.61 to 1.78 ) . The probability of clinical remission of the patients treated with escitalopram , fluoxetine , paroxetine , and sertraline was lower than those treated with duloxetine ( OR 0.46 , 95 % CI 0.33 to 0.64 ; OR 0.42 , 95 % CI 0.29 to 0.61 ; OR 0.40 , 95 % CI 0.29 to 0.56 ; OR 0.50 , 95 % CI 0.35 to 0.71 ; respectively ) . The regression analysis of functional remission also showed more favorable results for duloxetine , with OR ranging from 0.43 , 95 % CI 0.31 to 0.60 for paroxetine to 0.49 , 95 % CI 0.35 to 0.70 for sertraline . The results for the Asian countries were generally consistent . Conclusion Duloxetine-treated patients had better 6-month outcomes in terms of depression severity and clinical and functional remission , compared with selective serotonin reuptake inhibitor-treated patients",
"Research ers assessed the effectiveness of prazosin combined with scorpion antivenom in assisting recovery from scorpion sting . An open label r and omised controlled trial study design was used . The control treatment was prazosin alone . The setting was a hospital and research centre in Mahad , a region of India . Participants were patients with grade 2 scorpion envenomation , older than 6 months , and with no cardiorespiratory or central nervous system abnormalities . In total , 70 patients were recruited and allocated to treatment ( 35 to prazosin and scorpion antivenom , and 35 to prazosin alone ) by block r and omisation.1 The primary endpoint was resolution of the clinical syndrome within 10 hours of treatment , as assessed by the research ers . The secondary endpoints included the time needed for complete resolution of the clinical syndrome . The proportion of patients who showed complete resolution of the clinical syndrome within 10 hours of treatment was significantly greater in the prazosin plus antivenom group than in the prazosin alone group ( 91.4 % v 22.9 % ; difference 68.5 % , 95 % confidence interval 51.8 % to 85.2 % ; P The mean time needed for complete resolution of the clinical syndrome was significantly shorter in the antivenom plus prazosin group ( 8 v 17.7 h ; difference −9.7 h , −6.9 to −12.4 ) ; P prazosin compared with prazosin alone . Which of the following statements , if any , are true"
] |
4116cafe-06ff-11f0-808a-c43d1ab1c353
|
OBJECTIVE To provide a basis for making recommendations on the potential to improve use of folic acid supplements in the UK , particularly among low-income and young women . DESIGN Systematic review s of relevant research from 1989 to May 2006 in Europe , the USA , Canada , Australia and New Zeal and . RESULTS Twenty-six systematic review s and /or meta-analyses were identified from the wider public health literature , and eighteen studies on the effectiveness of preconception interventions were included . Ninety studies were identified which were directly relevant to folic acid supplement intake . There were factors that are particularly associated with lower rates of use of folic acid supplements . One of the most important of these is the link with unintended pregnancy , followed by age , socio-economic and ethnic group . Integrated campaigns can increase the use of folic acid supplements to some extent . Research trials indicated that : ( i ) printed re sources and the mass media used in isolation are not effective in the longer term ; and ( ii ) health-care-based initiatives can be effective and are more likely to be successful if they include making supplements easily available . CONCLUSIONS Campaigns and interventions have the potential to exacerbate socio-economic inequalities in folic acid use . One way of addressing this is to include elements that specifically target vulnerable women . To achieve and maintain an effect , they need to be based on good health promotion practice and to be sustained over a long period . However , even high- quality campaigns that increase use result in under half of women in the target group taking supplements
|
[
"Since the publication of r and omised trials showing firm evidence of prevention of neural tube defects with periconceptional folic acid , there have been population health promotion programmes to encourage women to take folic acid supplements , and the introduction of voluntary fortification of some foods with folic acid in Australia . In order to evaluate these two strategies , we collected data by self-administered question naire from a r and om sample of recently pregnant women in Western Australia between September 1997 and March 2000 . Response to health promotion was measured in three ways : ( 1 ) knowledge of the association between periconceptional folate and prevention of spina bifida ( the ' correct message ' ) ; ( 2 ) use of periconceptional vitamin supplements of folic acid daily in the periconceptional period ; and ( 3 ) daily folate intake from fortified foods in the 6 months before pregnancy . We examined the relationship of maternal demographic and behavioural characteristics with these three measures . Overall , 62.3 % of women were aware of the correct message before pregnancy , 28.5 % reported taking 200 microg or more of folic acid from supplements daily in the periconceptional period and 56.6 % of women obtained 100 microg or more of folic acid from fortified foods . Women who first became aware of the correct message during pregnancy or who were unaware of the correct message before or during pregnancy were more likely than women aware before pregnancy to be younger , having their first pregnancy , be single or in a de facto relationship , have no tertiary education , and be a public patient . Similar associations were seen for women taking either no folic acid or folic acid in supplements daily in the periconceptional period . There were no significant associations between these demographic variables and amount of folate obtained from fortified foods . Women who were unaware of the correct message and did not take folic acid supplements were more likely to have smoked , not to have engaged in exercise , and not to have planned their pregnancy , whereas there was no association with these behavioural characteristics and intake of folate from fortified foods . These results indicate that health promotion strategies have not reached all segments of the target population equally , but there is no such disparity with folate-fortified foods , and they suggest that m and atory fortification of a staple food is likely to reach all women regardless of demographic and behavioural characteristics , and hence provide improved opportunity for prevention of neural tube defects in Australia",
"BACKGROUND Pre-conception counselling has the potential to reduce pregnancy complications and congenital disorders . The timing of counselling , before conception , is crucial to maximize the benefit . As many couples are unaware of their risk status and the fact that the first period of pregnancy is crucial , they do not seek information before pregnancy occurs . To reach couples with timely information , it seems that a health care worker needs to take the initiative . In The Netherl and s , the GP is in an ideal position to offer pre-conception counselling . OBJECTIVE The aim of this study was to determine the interest of women aged 18 - 40 in pre-conception counselling if this is offered to them by their own GP . METHOD A cohort of women ( n = 1206 ) received a personal letter from their own GP with an offer of pre-conception counselling . The women were requested to fill in a reply form , indicating if they were interested , might be interested ( if they decided to become pregnant ) or were not interested in an invitation for pre-conception counselling . When interested , they were asked to give an indication as to when they were planning a pregnancy . Women who were not interested were requested to give a reason . RESULTS Almost 70 % of the women returned the reply form . Up to the age of 29 years , at least 80 % of the respondents were interested or might be interested should they decide to have children . Most women , especially the younger women , do not know exactly when they wish to become pregnant . Regardless of age , > 70 % of the respondents were interested . Only 11 % of the respondents indicated specifically that they were not interested in advice . CONCLUSION Women are interested in GP-initiated pre-conception counselling . Further research is needed to assess the effect of programmed and systematic pre-conception counselling , offered by GPs , on pregnancy outcome and the health of the children . A r and omized controlled trial to assess these effects currently is being conducted at the Department of General Practice in Leiden",
"OBJECTIVES To assess women 's concerns when interviewed about the association between folate and neural tube defects ( NTDs ) and to determine how this is affected by time , being folate aware , having seen folate promotional material or being pregnant . DESIGN As part of a community r and omized trial outcomes evaluation , independent cross-sectional follow-up surveys were carried out in 1997 and 2000 . SETTING AND PARTICIPANTS Six local government areas in the state of Victoria , Australia ; 2431 women aged between 15 and 44 years . MAIN VARIABLES STUDIED Whether or not women knew of the association between folate and NTDs ( i.e. were folate aware ) , whether or not women had been concerned by seeing folate/NTD information and if an interview about folate and NTDs had raised any concerns for them . RESULTS In the 1997 survey , 36 % of women said that the interview had raised concerns and this decreased to 26 % in 2000 . Women who were folate aware were significantly less likely to have raised concerns than women who were not folate aware ( OR(adj ) = 0.38 , 95 % CI 0.24 - 0.60 ) . In general , women who had seen promotional material were less likely to feel concern about the interview than those who had not , although this varied with whether or not the promotional material had raised concerns . These effects were greater in women who were pregnant . CONCLUSIONS Women had increased concerns having seen folate promotional material and after being interviewed about it . These results are consistent with the proposition that an initial emotional response to sensitive health information is part of an adaptive response appropriate to the process of health-related behaviour change",
"OBJECTIVE To study the knowledge , attitude and practice of pregnant women regarding periconceptional folic acid ( FA ) intake . DESIGN Question naire-based prospect i ve study . SETTING Antenatal clinic of a District General Hospital . SUBJECTS Three-hundred pregnant women in an antenatal clinic . RESULTS Nearly all ( 298/300 ) had heard of FA . A majority ( 275/300 , 91 % ) knew that FA could prevent neural tube defects , and married women those with higher education those of Social Classes 1 - 3 and women over 30 years of age were more likely to be thus aware . Knowledge about the correct timing of FA intake was seen in 76 % and was more likely in those with higher education married women and women age over 30 years Intake of FA in the periconceptional period was seen in 134/300 ( 44.6 % ) women and was most likely in the married , Social Classes 1 - 3 , women with higher education ( all P knowledge of the correct timing of FA intake was present in only 76 % . Less than half ( 44.6 % ) had taken FA in the periconceptional period , and this was far more common in the more ' privileged ' classes . Low socio-economic status , age less than 30 years , lower educational status and unplanned pregnancy were high risk factors for not taking FA . The challenge to the medical profession for targeting this group can not be over-emphasised",
"OBJECTIVE To estimate folate intake and knowledge in women of childbearing age , in relation to risk of neural tube defects . SUBJECTS/ SETTING One hundred forty-eight women ( aged 18 to 45 years ) in the Vancouver area of British Columbia , Canada . DESIGN Using an interviewer-administered survey , we examined women for folate knowledge and the relation of folate knowledge to intake in a r and om sample . Contribution of folate from food , fortified grain products , and supplements was assessed by vali date d semiquantitative food frequency question naire . STATISTICAL ANALYSIS PERFORMED Descriptive statistics , t tests , Chi;(2 ) , Pearson correlation analysis . RESULTS Mean daily folate intake from food , fortified foods , and supplementation was 812+/-710 Dietary Folate Equivalents (DFE)/day . Fortification of bread and grain products contributed 104+/-68 microg synthetic folic acid (SFA)/day ( equal to 174+/-114 DFE ) , and supplements contributed 205+/-388 microg SFA/day . Although 86 % of women met the Estimated Average Requirement ( 320 DFE/day ) for folate , only 26 % met the recommendation ( 400 microg SFA/day ) for women capable of becoming pregnant . Most ( 95 % ) of the women had heard of folate , but only 25 % knew that it could prevent birth defects . One-fourth of the women had good or very good knowledge of folate-rich foods . However , folate knowledge was not related to its intake . The most common sources of folate information were magazines/newspapers , doctors , and television/radio . Lack of awareness of the importance of folate was the most common reason given for choosing not to use folic acid supplements before pregnancy . However , 78 % of the women indicated that , with knowledge of the benefits of folate , they would use supplemental folic acid daily to reduce the risk of birth defects . APPLICATIONS/ CONCLUSIONS Educational strategies are required to increase folate awareness among women and to promote the benefits of periconceptional folic acid supplementation . Targeting physicians to educate women on the importance of folate could be a potentially successful route .",
"Summary .¶ Objectives : The periconceptional intake of 0.4 mg folic acid is recommended in many countries to prevent neural tube defects . This paper describes the poor implementation of corresponding guidelines in Germany , the effectiveness of an intervention-based on providing adequate information and the problems associated with the implementation.¶ Methods : Two cross sectional studies investigated knowledge , attitude , and behaviour of r and omly sample d gynaecologists ( n = 24/27 ) , pharmacists ( n = 21/21 ) , and women in childbed ( n = 131/118 ) before and after the information campaign.¶ Results : Before the intervention , 3.8 % of the women implemented folic-acid-prophylaxis compared with 9.3 % afterwards ( p = n.s . ) . The awareness of the prophylaxis before pregnancy correlated with socio-economic status and rose from 28 % ( before ) to 42 % after intervention ( p recommended the prophylaxis compared with 74 % ( p<0.05 ) and 43 % ( p = n.s . ) afterwards.¶ Conclusions : The effect of the intervention was small . To improve the situation , fortification of specially selected and labelled food should be considered . An accompanying nation-wide information campaign should focus on women with lower socio-economic status",
"Objectives : To determine the changes since 1996 in knowledge of folate for the prevention of neural tube defects ( NTDs ) among women of child‐bearing age and measure the residual effect of an earlier consumer‐directed information campaign",
"Objective To assess obstetrician-gynecologists ' knowledge of and clinical practice concerning folate . Methods We mailed surveys on nutrition during pregnancy to the 230 ACOG Fellows who are members of the Collaborative Ambulatory Research Network and to a r and om sample of 800 Fellows who are not members of the Network . Our results focus on questions concerning folate . Results We analyzed 488 surveys ( a 47.4 % response rate ) . Approximately two thirds of respondents screen their pregnant patients for folate intake . Fewer ( 53 % ) screen their nonpregnant patients of childbearing age . Those who screened their patients for folate intake were more likely to counsel pregnant patients about diet . They also were more likely to believe that nutritional counseling would improve pregnancy outcomes ( 70.0 % versus 56.5 % ) and overall patient health ( 77.5 % versus 66.5 % ) . Most Fellows were aware that macrocytic anemia was a manifestation of folate deficiency ( 90.4 % ) and that folic acid supplementation during preconception and the early prenatal period helps protect against neural tube defects ( 96.5 % ) . They were aware that alcoholics ( 91.4 % ) , smokers ( 61.3 % ) , and lactating women ( 53.5 % ) are at increased risk of folate deficiency . They were less aware of other consequences of low folate intake , such as increased serum homocysteine ( 20.3 % ) . Respondents who screen their pregnant patients for folate intake correctly answered more of the knowledge questions about folate than physicians who do not screen . Conclusion Obstetrician-gynecologists are generally aware of the link between folate intake and neural tube defects , but are less aware of other aspects of folate metabolism",
"BACKGROUND A preconception care program has the potential to assist women who want to become pregnant by advising these women about risk factors , healthy lifestyles , and assessing readiness for pregnancy . We conducted a r and omized controlled trial to determine whether comprehensive preconception risk assessment at the time of a negative pregnancy test followed by referral to primary care services is effective in initiating treatment for women with preconception risk factors . METHODS One hundred seventy women were offered preconception risk assessment following a negative pregnancy test . Women were assigned r and omly either to a usual care group or an intervention group . Women in the latter group were informed about the risks identified and received an appointment with a primary care clinician who was also informed . Women in the usual care group and their clinicians received no feedback . All charts were review ed and the women were contacted by telephone to determine if interventions to reduce risk were offered by clinicians during the year following the assessment . RESULTS An average of 8.96 risks were identified per woman . The proportion of women having risks in each of 12 risk categories studied ranged from 19 % to 71 % . One hundred women ( 59 % ) made at least one visit during the subsequent year , thus allowing the opportunity for preconception care . The proportion of these women who had a risk addressed ranged from 18 % for psychosocial risks to 48 % for those with fetal exposures ( smoking , alcohol , and drug use ) . There was no difference between groups in the percentage of risks addressed . CONCLUSIONS The notification of women and their clinicians of identified preconception risks did not improve intervention rates . A more organized intervention system including office-based protocol s is needed",
"The objective for this study was to determine whether a brief preconceptional health promotion program for low-income women attending family planning clinics impacts on intendedness of pregnancy . In this prospect i ve study , we examined data on 1378 women presenting for prenatal care at three local health departments . Each of the departments offers a st and ardized preconceptional health promotion program in its family planning clinics . Comparisons were undertaken for 456 women who had been exposed to the family planning preconception program , 309 women who had attended the family planning clinics but had not been exposed to the program , and 613 women who were unknown to the health department before beginning prenatal care . Women exposed to information on preconceptional health during routine family planning visits , the experimental group , had a 51.8 % ( p = 0.064 ) greater likelihood of identifying their pregnancies at intended than a group known to the local health departments ' family planning programs but unexposed to the intervention . Furthermore , the experimental group had a 64.2 % ( p = 0.0009 ) greater likelihood of intendedness than a comparison group not known to the health departments before the initiation of prenatal care . Our study indicates that an introductory program of preconceptional health promotion which is targeted to women not planning a pregnancy in the immediate future is associated with a higher rate of intendedness in subsequent pregnancies . Expansion of similar preconceptional programs in family planning clinics may prove a useful approach for promoting intendedness of pregnancy in low-income women",
"OBJECTIVE Fewer than one third of American women take folic acid daily , although many women report that they would take folic acid if their physicians advised them to do so . This study determined the impact of a physician intervention during routine gynecologic visits on folic acid supplementation . STUDY DESIGN Patients were assigned r and omly to receive brief folic acid counseling , a reminder phone call , and 30 folic acid tablets ( n = 162 women ; intervention group ) or to receive counseling about other preventive health behaviors and a folic acid informational pamphlet ( n = 160 women ; control group ) . Self-reported folic acid use was compared at baseline and at 2 months . RESULTS Of the 279 patients who completed the study , weekly folic acid intake increased in the intervention group by 68 % , compared with 20 % in the control group ( P = .008 ) . No significant differences were found in daily intake . The women who were most influenced by the intervention were black and lower income and not planning pregnancies . CONCLUSION With little effort expended to encourage folic acid use , gynecologists could potentially reduce the risk of folate-preventable birth defects among their patients by as much as 11 %",
"BACKGROUND Evidence for the effectiveness of pre-conception care is growing . GPs are among the possible providers of pre-conception care . OBJECTIVES Our first aim was to investigate current pre-conception care activities of GPs and to determine whether prospect i ve parents would visit the GP in the existing health care system . A further aim was to determine the interest of GPs and prospect i ve parents in the introduction of pre-conception care clinics . METHODS A survey was conducted among 200 GPs and 303 recently married couples ( 606 individuals ) . RESULTS Of the eligible GPs , 52 % ( n = 102 ) participated , as did 70 % ( n = 381 ) of the eligible individuals who are planning a pregnancy . In the current situation , only a few individuals visit their GP pre-conceptionally , and many GPs do not discuss family history or consanguinity with prospect i ve parents . In general , the GPs and prospect i ve parents had a positive attitude towards the introduction of pre-conception care clinics . CONCLUSION Since most GPs and prospect i ve parents favoured the introduction of pre-conception care , future research should focus on the most appropriate way of implementation",
"BACKGROUND R and omized controlled trials have demonstrated that periconceptional folic acid supplementation has a dramatic effect in reducing neural tube defects , one of the most serious congenital anomalies . Unfortunately , supplementation tends to be suboptimal in disadvantaged population s. OBJECTIVE The primary objective was to determine patient factors associated with a lack of use of periconceptional folic acid among Canadian women in a multi-ethnic , urban setting . Our secondary objective was to assess patient knowledge about folic acid tablet supplementation and its link to reduced birth defects . METHODS We undertook a cross-sectional study to survey postpartum Toronto women on their use and knowledge of periconceptional folic acid . RESULTS Of the 383 women surveyed , only 28 % took folic acid or a multivitamin containing folic acid during the periconceptional period . Multivariate analysis revealed that the use of periconceptional folic acid was more common among women of Jewish descent ( adjusted relative risk [ RR ] 0.3 ; 95 % confidence interval [ CI ] , 0.04 - 0.9 ) and those who had 1 or no children ( adjusted RR 0.6 ; 95 % CI , 0.4 - 0.8 ) . Not taking folic acid was associated with unplanned pregnancy ( adjusted RR 1.5 ; 95 % CI , 1.4 - 1.6 ) and a lack of knowledge about when folic acid should be taken ( adjusted RR 1.8 ; 95 % CI , 1.6 - 1.8 ) . CONCLUSION Ethnic background is an independent predictor of periconceptional folic acid use ",
"OBJECTIVE Periconceptional use of folic acid can prevent birth defects , including at least 50 % of neural tube defects . This study used an ongoing surveillance system to explore the association between pregnancy intendedness and women taking periconceptional folic acid . METHODS Oregon Pregnancy Risk Assessment Monitoring System ( PRAMS ) surveys a stratified r and om sample of women after a live birth . In 1998 - 1999 , 1867 women completed the survey ( 64.0 % response rate ) ; responses were weighted for nonresponse . Women were asked whether they took folic acid most days in the month before becoming pregnant . RESULTS Overall , 33.2 % of women took folic acid most days in the month before becoming pregnant , and 39.9 % said that their pregnancy was unintended . Adolescent mothers were less likely to take periconceptional folic acid ( 9.2 % ) and more likely to report unintended pregnancy ( 62.0 % ) than older women . Overall , women who said that their pregnancy was intended were more likely to report that they had taken periconceptional folic acid ( odds ratio : 4.75 ; 95 % confidence interval : 3.16 - 7.14 ) ; after controlling for maternal age and income the odds ratio was 3.70 ( 95 % confidence interval : 2.38 - 5.56 ) . CONCLUSIONS Women whose pregnancies were intended were more likely to have been taking periconceptional folic acid than women whose pregnancies were unintended . The importance of fertile women 's taking daily multivitamins that contain 400 microg ( 0.4 mg ) of folic acid should be stressed among women who are not contemplating pregnancy , especially adolescents and low-income women",
"OBJECTIVE To describe socioeconomic inequalities in the provision and uptake of prenatal care among women in Barcelona ( Spain ) between 1994 and 2003 . METHODS Cross-sectional study of women in Barcelona who delivered a child without birth defects . Information was obtained from hospital medical records and a personal interview with women included in the Barcelona Birth Defects Registry , containing a r and om sample of 2 % of all pregnant women in the city ( n = 2299 ) . DEPENDENT VARIABLES number of obstetric visits , the trimester of the first visit , the number of obstetric ultrasound scans , the fifth-month diagnostic ultrasound scan , invasive procedures , prenatal folic acid intake , pregnancy planning , smoking and smoking cessation . The independent variables were maternal age and social class . Logistic regression models were filted for each dependent variable . RESULTS In social classes with manual occupations , there was a higher proportion of pregnant women who attended less than six obstetric visits and who attended the first obstetric visit after the first trimester . Moreover , these women were less likely to have undergone an invasive procedure , to have taken folic acid supplements , to have planned the pregnancy , to be non-smokers and to stop smoking . In the more privileged classes , there was a higher proportion of women who attended more than 12 obstetric visits and who underwent more than three ultrasound scans . CONCLUSIONS Socioeconomic inequalities were found in the provision and uptake of prenatal care in Barcelona . Uptake was greater in the more advantaged social classes but excessive medicalization was found in all classes . Rationalizing the use of healthcare re sources and reducing excessive medicalization would reduce inequalities in prenatal care in Barcelona",
"OBJECTIVES : To determine the effect of a consumer-directed information campaign to increase knowledge of folate for the prevention of neural tube defects among women of child-bearing age , and to measure women 's recall of sources of information and knowledge about folate . DESIGN : A community r and omized trial . SETTING : Three matched pairs of geographically distinct Local Government Areas in the state of Victoria , Australia . INTERVENTION : Printed information recommending folate intake to decrease the risk of neural tube defects was disseminated to women of child-bearing age in three of the Local Government Areas selected r and omly . MAIN OUTCOME MEASURE : The proportion of women aware of the association between folate and spina bifida . RESULTS : Of 1197 women interviewed prior to the intervention , 12.4 % ( adjusted for the cluster and population sampling unit ) were aware of folate and neural tube defects . After the intervention , there was not only a significant background increase of 3.4 % ( P=0.02 ) in folate awareness since the pre-intervention survey ( n=603 ) , but also a significant additional increase of 4.0 % ( P=0.04 ) owing to the intervention itself ( n=603 ) . Only 70 % of women who were aware of folate knew the correct timing . CONCLUSIONS : The provision of printed educational material can increase folate awareness among women of child-bearing age . A comprehensive , long-term and ongoing health promotion campaign including such material , together with initiatives by relevant health service providers and the food industry , could best address the current low levels of folate awareness among women of child-bearing age",
"OBJECTIVE To assess 1 ) knowledge of neural tube defect ( NTD ) prevention by folic acid , 2 ) frequency of intake of multivitamins and folate- and folic acid-fortified food , and 3 ) factors associated with knowledge and prevention practice s among sexually active minority adolescent and young adult women . METHODS Young minority women were enrolled in a folic acid program at 3 urban Houston , Texas , reproductive health clinics and assessed for NTD knowledge and preventive practice s. A 3-month supply of multivitamins was also dispensed at enrollment . A 3-month program follow-up survey of a r and omly selected sample at 2 sites was conducted . RESULTS Of 387 women ( mean age : 18 + /- 1.9 years ) , 72 % were black and 28 % were Hispanic . At enrollment , clinics were a major source of information of NTD prevention ( 44 % ) ; 52 % had heard of folic acid , 45 % had heard of NTDs , and 50 % had heard of birth defects prevention by multivitamins . Significantly more Hispanic than black young women had heard of NTDs ( 59 % vs 39 % ) . Pregnancy history , regular birth control use , and education level for age were independently associated with knowledge . In young women with low education level for age , regular birth control use was significantly associated with knowledge . At enrollment , daily multivitamin intake was very low ( 9 % ) and folate-rich foods were consumed in inadequate amounts . Adequate folate diet was not associated with knowledge . The program follow-up survey indicated that 88 % to 92 % had knowledge of NTDs and folic acid , and 67 % reported taking a daily multivitamin . CONCLUSIONS Publicly funded clinics may be the only source of information on NTD prevention for many minority young women . Preliminary evidence suggests that a promotion program improves knowledge , and dispensing of multivitamins increases multivitamin use . However , clinicians in such programs need to reinforce daily adherence to multivitamins in young women"
] |
4116cb3a-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND According to the Global Burden of Disease Study 2015 , lower respiratory tract infection is the leading cause of infectious disease death , and the fifth most common cause of death overall . Vitamin C has a role in modulating resistance to infectious agents , therefore vitamin C supplementation may be important in preventing and treating pneumonia . OBJECTIVES To assess the impact of vitamin C supplementation to prevent and treat pneumonia in children and adults . SEARCH METHODS We search ed CENTRAL , MEDLINE , Embase , PubMed , CINAHL , LILACS , Web of Science , and two trials registers to 4 March 2020 . We also checked references to identify additional studies . We did not apply any publication status or language filters . SELECTION CRITERIA We included r and omised controlled trials ( RCTs ) and quasi- RCTs ( studies using allocation methods that are not r and om , e.g. date of birth , medical record number ) assessing the role of vitamin C supplementation in the prevention and treatment of pneumonia in children and adults compared to control or placebo . DATA COLLECTION AND ANALYSIS We used st and ard method ological procedures expected by Cochrane . MAIN RESULTS We included seven studies in the review and identified two ongoing studies . The seven included studies involved a total of 2774 participants ; five studies were RCTs and two were quasi- RCTs . The included studies were conducted in high-income countries ( UK , USA and Chile ) and lower-middle-income countries ( Bangladesh and Pakistan ) . Four studies were conducted in hospital inpatient setting s , two in schools , and one in a military training centre . Three studies included children under five years of age , two school-aged children , one adult participants , and one older participants aged 60 to 90 years . Two studies assessed the effect of vitamin C supplementation for pneumonia prevention ; four studies assessed the effect of vitamin C supplementation as an adjunct to pneumonia treatment ; and one study assessed the role of vitamin C for both prevention and treatment of pneumonia . For pneumonia prevention , the included studies provided supplementation in doses of 500 mg daily for 14 weeks , 2 g daily for 8 weeks , and 2 g daily for 12 weeks . For pneumonia treatment , the included studies provided vitamin C supplementation in doses of 125 mg daily ( until discharge ) , 200 mg for 4 weeks , and 200 mg until discharge , as an adjunct to the pneumonia treatment . We assessed the included studies as at overall either high or unclear risk of bias for r and om sequence generation , allocation concealment , and blinding . We judged the quality of the evidence as very low . Three studies assessed the effect of vitamin C supplementation for pneumonia prevention ; we judged the quality of the evidence as very low . We are uncertain about the effect of vitamin C supplementation on pneumonia incidence ( risk ratio ( RR ) 0.46 , 95 % confidence interval ( CI ) 0.06 to 3.61 ; 2 studies , 736 participants ; I² = 75 % ; very low- quality evidence ) and adverse events ( urticaria ) ( RR 3.11 , 95 % CI 0.13 to 76.03 ; 1 study , 674 participants ; very low- quality evidence ) . No included studies reported our other primary outcomes ( pneumonia prevalence and mortality ) or any of our secondary outcomes . Five studies assessed the effect of vitamin C supplementation as an adjunct to pneumonia treatment ; we judged the quality of the evidence as very low . One study reported a decrease in the duration of illness in the vitamin C supplementation group ( 3.4 days ± 2.54 ) compared to the control group ( 4.5 days ± 2.35 ) , and one study reported a decrease in number of days required for improvement in oxygen saturation ( 1.03 days ± 0.16 versus 1.14 days ± 1.0 ) and respiratory rate ( 3.61 days ± 1.50 versus 4.04 days ± 1.62 ) in the vitamin C supplementation group compared to the control group . We are uncertain of the effect of vitamin C supplementation on mortality due to pneumonia ( RR 0.21 , 95 % CI 0.03 to 1.66 ; 1 study , 57 participants ; very low- quality evidence ) . One study reported that the mean duration of hospital stay was 6.75 days amongst children in the vitamin C supplementation group and 7.75 days in the control group ; another study reported a lower mean duration of hospital stay in the vitamin C supplementation group compared to the control group ( 109.55 hours ± 27.89 versus 130.64 hours ± 41.76 ) . AUTHORS ' CONCLUSIONS Due to the small number of included studies and very low quality of the existing evidence , we are uncertain of the effect of vitamin C supplementation for the prevention and treatment of pneumonia . Further good- quality studies are required to assess the role of vitamin C supplementation in the prevention and treatment of pneumonia
|
[
"A prospect i ve , r and omized , double-blind study was carried out to determine whether vitamin C prophylaxis , 2.0 g/day , vs placebo prophylaxis would reduce the incidence or morbidity of the common cold and other respiratory illnesses in 674 marine recruits during an eight-week period . Whole-blood ascorbic acid levels measured six weeks after initiation of the study were significantly higher in the vitamin C group . There was no difference between the two groups in the incidence or duration of colds . The vitamin C group rated their colds as being less severe , but this was not reflected in different symptom complexes or in fewer sick-call visits or training days lost . This study and the literature do not support the prophylactic use of vitamin C to prevent the common cold",
"Abstract A double-blind study to evaluate vitamin C supplements for respiratory-Infection prophylaxis was conducted among 641 children at a Navajo boarding school over a 14-week period . Supplements",
"A r and omised double-blind trial involving vitamin C/placebo supplementation was conducted on 57 elderly patients admitted to hospital with acute respiratory infections ( bronchitis and bronchopneumonia ) . Patients were assessed clinical ly and biochemically on admission and again at 2 and 4 weeks after admission having received either 200 mg vitamin C per day , or placebo . This relatively modest oral dose led to a significant increase in plasma and white cell vitamin C concentration even in the presence of acute respiratory infection . Using a clinical scoring system based on major symptoms of the respiratory condition , patients supplemented with the vitamin fared significantly better than those on placebo . This was particularly the case for those commencing the trial most severely ill , many of whom had very low plasma and white cell vitamin C concentrations on admission . Various mechanisms by which vitamin C could assist this type of patient are discussed",
"A double-blind placebo trial has been undertaken on 199 elderly patients admitted to an \" acute \" geriatric assessment ward . Clinical and biochemical assessment was made on admission ( 0 ) and at 2 , 4 , 8 , 16 and 24 weeks ( after admission ) . Ninety-four patients were supplemented with vitamin C ( 200 mg per day ) and 105 had placebo tablets . Biochemical assessment included estimations of plasma and leucocyte ( buffy layer ) vitamin C , plasma folate , vitamin B12 , cortisol and total white cell count . Plasma and leucocyte vitamin C levels remained low for several weeks in a substantial proportion of the non-supplemented patients , whereas low levels were virtually eliminated in the supplemented group . The results from this study suggest that the leucocyte vitamin C levels may give some indication of prognosis in this category of patients ( ie . \" acute \" geriatric admissions ) as evidence d by : i ) the significantly higher mortality rate during the trial period of patients who started with low initial leucocyte vitamin C levels compared with those starting with higher levels , despite similar mean initial \" severity of illness scores \" between the two groups . ii ) the marked trend , amongst placebo subjects , for those commencing the study with higher leucocyte vitamin C levels to fare better , in terms of progression to \" well \" , than those starting with low levels . Amongst subjects starting with low leucocyte vitamin C levels , there was a trend for \" vitamin C \" subjects to have fared better by 8 weeks than \" placebo \" subjects . This again occurred despite similar mean initial \" severity scores \" between the two groups . Amongst subjects diagnosed with respiratory infections there was some tendency for supplemented patients to fare better than unsupplemented patients . Low leucocyte vitamin C levels , on admission , appear to be predictive of poor subsequent prognosis in elderly hospitalised patients . Results from this trial suggest that supplementation with a moderate dose of vitamin C may improve this prognosis and larger trials with greater numbers appear to be merited to confirm or deny this hypothesis",
"Background Airway infections are of great importance worldwide and nearly half of the pediatric consultations in industrialized countries are caused by respiratory tract infections ( RTIs ) . Acute respiratory tract infections ( ARTIs ) are among the main causes of morbidity and mortality in children and recurrent infections of the respiratory tract are the most frequent cause of pharmacotherapy in pediatric practice . The aim of this study was to evaluate the efficacy and tolerability of immunotherapy with oral bacterial lysates + vitamin C in the prevention of ARTIs in children . Methods 109 children with ages between 4 and 16 years with frequent respiratory tract infections ( 2–5 infections the previous winter ) were evaluated . Participants were r and omly allocated in 2 groups : 52 patients ( mean age 6.8 ± 2.9 years ; 20 males 32 females ) received no preventive therapy ( NPT group ) and 57 ( mean age 9.0 ± 3.3 years ; males 36 females 21 ) received immunotherapy with oral bacterial lysates + vitamin C ( VC group ) at the recommended dosage . Patients were followed up for 6 months , including the administration period . Primary end points were the type and number of ARTIs . Secondary end points ( after the infection occured ) included : time to clinical cure , severity of infection , absenteeism from school due to an ARTI , number of antibiotic courses or other drugs prescribed , and duration of concomitant drug treatment . Results There were significant differences between groups in the cumulative number of acute infectious episodes : 170 in NPT group ( 141 upper ARTIs , 29 lower ARTI , and 26 otitis episodes ) vs 55 in VC group ( 50 upper ARTIs , 5 lower ARTI and 4 otitis episodes ) . Patients in the NPT group received 127 antibiotic courses compared to 28 in the VC group ( P of absenteeism from school compared to 100 days in the VC group ( P No adverse events related to the trial medications were reported . Conclusions Immunotherapy with oral bacterial lysates and vitamin C appears to be very effective in the prevention of infectious episodes in pediatric patients with frequent respiratory tract infections . Future studies are needed to further explore the role of oral bacteroial lysates in ARTIs prevention",
"Objective : To evaluate the effect of antioxidant Vitamins E and C as adjunct therapy of severe acute lower respiratory infection ( ALRI ) in children . Design : R and omized double-blind placebo-controlled clinical trial . Setting : A large childrens ' hospital serving the urban poor in Kolkata , India . Subjects : Children aged 2–35 months admitted with severe ALRI.Intervention : In total , 174 children were r and omly assigned to receive α-tocopherol 200 mg and ascorbic acid 100 mg twice daily or placebo for 5 days . All children received st and ard treatment for severe ALRI . Outcome measures were : time taken to recover from a very ill status , fever , tachypnoea , and feeding difficulty ; and improvement in oxidative stress and immune response indicated by thiobarbituric acid reacting substances ( TBARS ) and response to skin antigens , respectively . Results : Recovery rate ratios ( 95 % CI ) using proportional hazards model were 0.89 ( 0.64–1.25 ) , 1.01 ( 0.72–1.41 ) , 0.86 ( 0.57–1.29 ) , and 1.12 ( 0.77–1.64 ) for very ill status , feeding difficulty , fever , and tachypnoea , respectively . TBARS values were high and similar in the two groups at admission , discharge , and at 2 weeks follow-up . Serum α-tocopherol significantly increased in treated group at discharge . Immune response to skin antigens were very poor at admission and after 2 weeks , in both groups . Conclusion : Infants with severe ALRI failed to benefit from two antioxidant nutrients as adjunct therapy . Severe ALRI in infants may cause cell-mediated immune dysfunction . We need a better underst and ing of oxidative processes in growing infants to help us better design interventions with antioxidant therapy",
"STUDY OBJECTIVE : To examine the hypothesis that the higher rates of coronary heart disease ( CHD ) in Indians ( South Asians ) compared with Malays and Chinese is partly because of differences in antioxidants ( vitamins A , C , and E , and selenium ) and pro-oxidants ( iron ) . DESIGN : Cross sectional study of the general population . SETTING : Singapore . PARTICIPANTS : R and om sample of 941 persons aged 30 to 69 years . MAIN RESULTS : There were moderate correlations between vitamin A and vitamin E , and between these vitamins and selenium . Mean plasma vitamins A and E were similar by ethnic group . Vitamin A concentration for Indians were ( men 0.66 and women 0.51 mg/l ) , Malays ( men 0.67 and women 0.54 mg/l ) , and Chinese ( men 0.68 and women 0.52 mg/l ) . Vitamin E concentrations for Indians were ( men 12.9 and women 12.8 mg/l ) , Malays ( men 13.6 and women 13.3 mg/l ) , and Chinese ( men 12.6 and women 12.6 mg/l ) . In contrast , mean plasma vitamin C concentrations were lower in Indians ( men 5.7 and women 6.9 mg/l ) and Malays ( men 5.1 and women 6.4 mg/l ) than Chinese ( men 6.3 and women 8.4 mg/l ) . Mean serum selenium was lower in Indians ( men 117 and women 115 micrograms/l ) than Malays ( men 122 and women 122 micrograms/l ) and Chinese ( men 126 and women 119 micrograms/l ) . Mean serum ferritin was much lower in Indians ( men 132 and women 50 micrograms/l ) than Malays ( men 175 and women 85 micrograms/l ) and Chinese ( men 236 and women 92 micrograms/l ) . MAIN CONCLUSIONS : Lower vitamin C and selenium in Indians , particularly in combination , could play a part in their increased risk of CHD . Vitamins A and E , and ferritin ( iron ) have no such role . Lower vitamin C in Indians and Malays is probably because of its destruction by more prolonged cooking . In Indians , lower selenium is probably because of a lower dietary intake and the much lower ferritin to a lower dietary intake of iron and its binding by phytates"
] |
4116cb76-06ff-11f0-808a-c43d1ab1c353
|
Through a rigorous systematic review , this study provides a compendium of MIDs to better interpret the magnitude of treatment effects for PROs relevant to children . CONTEXT : No study has characterized and appraised all anchor-based minimally important differences ( MIDs ) associated with patient-reported outcome ( PRO ) instruments in pediatric studies . OBJECTIVE : To complete a comprehensive systematic survey and appraisal of published anchor-based MIDs associated with PRO instruments used in children . DATA SOURCES : Medline , Embase , and PsycINFO ( 1989 to February 11 , 2015 ) . STUDY SELECTION : Studies reporting empirical ascertainment of anchor-based MIDs among PROs used in pediatric care . DATA EXTRACTION : All pertinent data items related to the characteristics of PRO instruments , anchors , and MIDs . RESULTS : Of 4179 unique citations , 30 studies ( including 32 cohorts ) proved eligible and reported on 28 unique PROs ( 8 generic , 13 disease-specific , 5 symptoms-specific , 2 function-specific ) , with 9 ( 32 % ) classified as patient-reported , 11 ( 39 % ) proxy-reported , and 8 ( 29 % ) both patient- and proxy-reported . Of the 30 studies , we rated 14 ( 44 % ) as providing highly credible estimates of the MID . Most cohorts ( n = 20 , 62 % ) recorded patients ’ direct response to the target PRO and the use of an independent st and ard of comparison ( n = 25 , 78 % ) . Most , however , failed to effectively report measurement properties of the anchor ( n = 24 , 75 % ) . LIMITATIONS : We have not yet addressed the measurement properties of instrument to measure credibility ; our search was restricted to 3 electronic sources , and we used a single data abstract or . CONCLUSIONS : Our study found 28 PROs that have been developed for children , with fewer than half providing credible estimates . Clinicians , clinical trialists , systematic review ers , and guideline developers seeking to effectively summarize and interpret results of studies addressing PROs in child health are likely to find our comprehensive compendium of MIDs of use , both in providing best estimates of MIDs and identifying credible estimates
|
[
"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",
"To provide additional evidence regarding the plausible range of the differences in health-related quality of life ( HRQL ) question naire scores within which the minimal important difference ( MID ) falls , we review ed the results of 32 r and omized controlled trials in individual subjects ( N of 1 RCTs ) with chronic diseases . These trials had been conducted to establish whether a patient was obtaining more good than harm from a medication . Each N of 1 RCT included a series of pairs of treatment periods , one period on active drug , and one on placebo or alternative drug . We examined the relationship between small ( MID ) , medium , and large differences between periods within pairs , as indicated by Global Ratings and differences between these same periods according to HRQL question naires . The results showed a mean difference of 0.29 points per question in HRQL question naire scores corresponded to the MID . Differences of approximately 0.66 points per question corresponded to a moderate difference as ranked by the Global Rating ; difference of about 1.09 points per question represented marked difference",
"OBJECTIVE To test the reliability and validity of specific instructions to classify blinding , when unclearly reported in r and omized trials , as \" probably done \" or \" probably not done . \" STUDY DESIGN AND SETTING We assessed blinding of patients , health care providers , data collectors , outcome adjudicators , and data analysts in 233 r and omized trials in duplicate and independently using detailed instructions . The response options were \" definitely yes , \" \" probably yes , \" \" probably no , \" and \" definitely no. \" We contacted authors for data verification ( 46 % response ) . For each of the five questions , we assessed reliability by calculating the agreement between the two review ers and validity by calculating the agreement between review ers ' consensus and verified data . RESULTS The percentage with unclear blinding status varied between 48.5 % ( patients ) and 84.1 % ( data analysts ) . Reliability was moderate for blinding of outcome adjudicators ( κ=0.52 ) and data analysts ( κ=0.42 ) and substantial for blinding of patients ( κ=0.71 ) , providers ( κ=0.68 ) , and data collectors ( κ=0.65 ) . The raw agreement between the consensus record and the author-verified record varied from 84.1 % ( blinding of data analysts ) to 100 % ( blinding of health care providers ) . CONCLUSION With the possible exception of blinding of data analysts , use of \" probably yes \" and \" probably no \" instead of \" unclear \" may enhance the assessment of blinding in trials",
"BACKGROUND : Self-reported pain scores are used widely in clinical and research setting s , yet little is known about their interpretability in children . In this prospect i ve , observational study we evaluated the relationship between 0 to 10 numerical rating scale ( NRS ) pain scores and other self-reported , clinical ly meaningful outcomes , including perceived need for medicine ( PNM ) , pain relief ( PR ) , and perceived satisfaction ( PS ) with treatment in children postoperatively . METHODS : This study included children ages 7 to 16 years undergoing surgery associated with postoperative pain . One to 4 observations were recorded in each child within the first 24 hours postoperatively . At each assessment , children rated their pain with the NRS , stated their PNM , and rated their satisfaction with pain management . Assessment s were repeated within 1 to 2 hours , and children additionally rated their PR as the same , better , or worse in comparison with the earlier assessment . Receiver operator characteristic curves were developed to examine potential NRS cut-points for PNM and PS , and the minimum clinical ly significant difference ( MCSD ) in pain score associated with PR was calculated . RESULTS : Three hundred ninety-seven observations ( including 189 pairs ) were recorded in 113 children . NRS scores associated with PNM were significantly higher than “ no need ” ( median 6 vs. 3 ; P NRS scores > 4 had good sensitivity ( 0.81 ) and specificity ( 0.70 ) to discriminate PNM , but with a large number of false positives and negatives ( e.g. , 42 % of children with scores > 4 did not need analgesia ) . The MCSD in NRS scores was −1 ( 95 % confidence interval [ CI ] −0.5 to 1 ) or + 1 ( CI 0.5 to 2.7 ) in relation to feel “ a little better ” or “ worse , ” respectively ( P NRS scores > 6 had a sensitivity of 0.82 and specificity of 0.76 in discriminating dissatisfaction with treatment , yet 46 % and 24 % of children with scores > 6 , respectively , were somewhat to very satisfied with their analgesia . CONCLUSIONS : This study provides important information regarding the clinical interpretation of NRS pain scores in children . Data further support the NRS as a valid measure of pain intensity in relation to the child 's PNM , PR , and PS in the acute postoperative setting . However , the variability in scores in relation to other clinical ly meaningful outcomes suggests that application of cut-points for individual treatment decisions is inappropriate",
"OBJECTIVES The objectives of this study were to assess 27-joint Juvenile Arthritis Disease Activity Score ( JADAS-27 ) responsiveness , JADAS-27 changes corresponding to clinical ly important differences and cut-off scores for low and high disease activity in a large prospect i ve JIA cohort . METHODS JADAS-27 responsiveness , using effect size and st and ardized response mean ( SRM ) , and changes in the JADAS-27 corresponding to clinical ly important differences were determined for clinical improvement ( ACRpedi30 ) and worsening ( flare ) . To assess whether various degrees of change in the JADAS-27 could be used to demonstrate improvement or worsening in individual patients , diagnostic parameters were computed for cut-off score changes . Finally , cut-off scores for low and high disease activity and their diagnostic parameters were determined . RESULTS In 228 patients with 529 consecutive visits , ACRpedi30 was detected in 109 and flare in 111 visits . Regarding responsiveness , the effect size was 0.93 and SRM was 1.26 for clinical improvement , while for clinical worsening the effect size was 0.65 and SRM was 0.60 . Changes in the JADAS-27 corresponding to clinical ly important difference were -5.5 for improvement and + 1.7 for worsening . Cut-off score changes in the JADAS-27 had 65 - 90 % sensitivity and 67 - 86 % specificity for improvement , and 31 - 64 % sensitivity and 89 - 97 % specificity for worsening . The JADAS-27 cut-off score for low disease activity was ≤2.7 with 76 % sensitivity and 62 % specificity , and the cut-off score for high disease activity was ≥6 with 77 % sensitivity and 77 % specificity . CONCLUSION The JADAS-27 had moderate to good responsiveness and was changed by clinical ly important differences . The JADAS-27 cut-off scores differentiated between low and high disease activity . These JADAS-27 interpretations could be potentially applicable in clinical care and trials",
"BACKGROUND Limited underst and ing of the interpretability of patient-reported pain scores may impact pain management . The current study assessed the minimal clinical ly significant improvement in pain and pain scores signifying patient-reported need for medication and treatment satisfaction in patients with sickle cell disease ( SCD ) . PROCEDURE Patients , 8 - 18-years-old , with SCD were recruited while receiving treatment for pain . Patients completed initial pain severity ratings using the Visual Analog Scale ( VAS ) and the Numeric Rating Scale ( NRS ) . Serial assessment s of pain severity , pain relief , perceived need for medication , and treatment satisfaction were completed in the emergency department and the hospitalization . Data were used to calculate the minimal clinical ly significant improvement in pain and pain scores associated with perceived need for pain medication and treatment satisfaction . RESULTS Twenty-eight patients completed 305 assessment s during 37 total visits . A decrease in pain severity score of 0.97 cm for the VAS and 0.9 for the NRS was found to be the minimum clinical ly significant improvement in pain . Pain scores > 7.45 cm on the VAS or 7.5 on the NRS were suggestive of patient-reported need for pain medication . Pain scores pain relief , need for pain medication , and treatment satisfaction . Collectively , this study provides data to improve our underst and ing of pain ratings of pediatric patients with SCD",
"OBJECTIVES To determine the clinical ly relevant reference points for the Incontinence Quality of Life ( I-QOL ) question naire scores in women with stress urinary incontinence and compare them with the treatment effects observed with duloxetine and placebo . METHODS Using data from 1133 women with predominant stress urinary incontinence in two r and omized , placebo-controlled duloxetine studies , the within-treatment and between-treatment minimal clinical ly important differences ( MCIDs ) were obtained by anchoring the I-QOL scores to the vali date d Patient Global Impression of Improvement scale ( PGI-I ) . The within-treatment MCID ( mean I-QOL for women rating their condition \" a little better \" with treatment ) and between-treatment MCID ( difference in scores between the group ratings of \" no change \" and \" a little better \" ) were derived . The treatment effects were compared with these MCIDs . Real-time urinary diaries were completed , along with the I-QOL and PGI-I. RESULTS The within-treatment and between-treatment MCID for the I-QOL total score was 6.3 and 2.5 , respectively . The total and subscale scores had almost identical MCIDs . Duloxetine 80 mg significantly improved the I-QOL total and subscale scores . Treatment differences in the I-QOL scores exceeded the between-treatment MCID and the duloxetine I-QOL treatment effect exceeded the within-treatment MCID . The number of patients needed to treat to gain an additional I-QOL responder was 6.8 . CONCLUSIONS Improvements in I-QOL scores should be greater than the within-treatment MCID , and differences between two treatments should be greater than the between-treatment MCIDs , for statistically significant differences to be considered clinical ly meaningful . We propose 2.5 points as a reasonable guide for the I-QOL between-treatment MCID and 6.3 points for the within-treatment MCID",
"Background / Aims Despite documented feasibility , reliability , and validity , the Pediatric Crohn 's Disease Activity Index ( PCDAI ) has yet to be demonstrated to be sensitive to change in the time frame of acute treatment trials . We evaluated short-term responsiveness and determined the minimal change in PCDAI score associated with a clinical ly meaningful improvement in disease activity . Methods St and ardized effect size ( SES ) and st and ardized response mean ( SRM ) were calculated as measures of responsiveness among pediatric patients being treated for acute exacerbations of Crohn disease 1 ) in a regular clinical practice setting and 2 ) as part of a multicenter , r and omized controlled trial ( RCT ) . Receiver operating characteristic ( ROC ) curves were constructed to determine the minimal PCDAI score change associated with significant clinical improvement used as the gold st and ard in 1 ) physician global assessment of change and in 2 ) change in adult Crohn disease activity index ( CDAI ) . Results Among responders , the SES and SRM of the PCDAI were 1.78 and 1.41 ( 95 % CI : 0.89–1.92 ) and 2.10 and 1.95 ( 95 % CI : 1.70–2.20 ) in the clinical practice setting and RCT setting , respectively . The optimal minimal PCDAI change score associated with clinical ly significant change in physician global assessment was determined to be -12.5 ( sensitivity 83.3 % , specificity 92.3 % ) . In the RCT setting a change in PCDAI of –10 corresponded to a change in CDAI of ≱ 70 points . Conclusions The PCDAI is responsive to improvement in disease activity in Crohn disease patients over a short interval . As such , the PCDAI is an appropriate instrument to use in pediatric acute treatment trials",
"STUDY OBJECTIVE We sought to determine the minimum clinical ly significant difference in visual analog scale ( VAS ) pain score for children . METHODS We performed a prospect i ve , single-group , repeated- measures study of children between 8 and 15 years presenting to an urban pediatric emergency department with acute pain . On presentation to the ED , patients marked the level of their pain on a 100-mm nonhatched VAS scale . At 20-minute intervals thereafter , they were asked to give a verbal categoric rating of their pain as \" heaps better , \" \" a bit better , \" \" much the same , \" \" a bit worse , \" or \" heaps worse \" and to mark the level of pain on a VAS scale of the same type as used previously . A maximum of 3 comparisons was recorded for each child . The minimum clinical ly significant difference in VAS pain score was defined as the mean difference between current and preceding scores when the subject reported \" a bit worse \" or \" a bit better \" pain . RESULTS Seventy-three children were enrolled in the study , yielding 103 evaluable comparisons in which pain was rated as \" a bit better \" or \" a bit worse . \" The minimum clinical ly significant difference in VAS score was 10 mm ( 95 % confidence interval 7 to 12 mm ) . CONCLUSION This study found the minimum clinical ly significant difference in VAS pain score for children aged 8 to 15 years ( on a 100-mm VAS scale ) to be 10 mm ( 95 % confidence interval 7 to 12 mm ) . In studies of population s , differences of less than this amount , even if statistically significant , are unlikely to be of clinical significance",
"Abstract Background : The Acne-Specific Quality of Life Question naire ( Acne-QoL ) is a responsive , reliable and valid instrument developed to measure the impact of facial acne across four dimensions of patient QOL . Score changes on this instrument have been used to report statistically significant treatment advantages for a low-dose oral contraceptive ( Estrostep ® ) , containing norethisterone ( norethindrone ) acetate ( NA ) 1 mg and ethinylestradiol ( EE ) [ 20 , 30 , 35 mg ] as compared with placebo in women with moderate acne vulgaris . However , the question remained if these statistically significant results were also clinical ly meaningful . Objectives : To evaluate the statistically significant Acne-QoL benefits observed with NA/EE in terms of their clinical significance , and to compare the three different approaches for defining a minimal clinical ly important difference ( MCID ) for the Acne-QoL instrument . Methods : Since the optimum method for estimating MCIDs has yet to be established , three different published approaches for determining MCIDs were applied and compared using data from two r and omised , double-blind , placebocontrolled studies of the efficacy of NA/EE in the treatment of facial acne . Results : Although the approaches differed substantially , the result ing MCID estimates were comparable . Specifically , the MCID estimates ranged from 0.50–10.3 mean change per item , depending on the domain . The results showed that the statistically significant treatment advantages for NA/EE were also clinical ly significant . Conclusion : When applied to the change scores present , the results showed that the statistically significant treatment advantages for NA/EE were also clinical ly significant",
"This study examined criterion-related validity and clinimetric properties of the pediatric balance scale ( PBS ) in children with cerebral palsy ( CP ) . Forty-five children with CP ( age range : 19 - 77 months ) and their parents participated in this study . At baseline and at follow up , Pearson correlation coefficients were used to determine criterion-related validity by analyzing the correlation between the PBS , including PBS-static , PBS-dynamic , and PBS-total , and criterion measures , including the Gross Motor Function Measure-66 items ( GMFM-66 ) and Functional Independence Measures for Children ( WeeFIM ) . Responsiveness was examined by paired t test and by st and ardized response mean ( SRM ) . The minimal detectable change ( MDC ) was analyzed at the 90 % confidence level , and the minimal clinical ly important differences ( MCID ) was estimated by anchor-based and distribution-based approaches . The PBS with GMFM-66 and WeeFIM showed fair-to-excellent concurrent validity at pretreatment and follow up and predictive validity . The SRM values of all PBS scales were 0.75 . For the PBS-static , PBS-dynamic , and PBS-total , the MDC(90 ) values were 0.79 , 0.96 , and 1.59 , and the MCID ranges were 1.47 - 2.92 , 2.23 - 2.92 , and 3.66 - 5.83 , respectively . Improvement of at least MDC values on the PBS can be considered a true change , not measurement error . A mean change must exceed the MCID range on PBS to be considered clinical ly important change . Therefore , all PBS scales were moderately responsive to change . Clinicians and research ers can use these clinimetric data for PBS to determine if a change score represents a true or clinical ly meaningful effect at posttreatment and follow up",
"OBJECTIVE We compared the minimal important difference ( MID ) values obtained by the receiver operating characteristics ( ROC ) curve approach using different strategies on four outcome measures to guide the optimal use of ROC curve . STUDY DESIGN AND SETTING Studies of two psychometric scales ( Rhinoconjunctivitis Quality -of-Life Question naire [ RQLQ ] and Chronic Respiratory Question naire [ CRQ ] ) and two clinimetric indices ( Pediatric Ulcerative Colitis Activity Index [ PUCAI ] and Pediatric Crohn 's Disease Activity Index [ PCDAI ] ) instruments provided prospect i ve longitudinal data . The MID was calculated from 7- and 15-point global ratings of change dichotomized in multiple ways , using the ROC curve method . Analysis was performed twice : first , using only the two groups adjacent to the dichotomization point ( e.g. , including only patients who had a small vs. moderate change ) ; and second , using the entire cohort split at the same cutoff ( e.g. , including both unchanged subjects with those with small change vs. those who experienced moderate or large change combined ) . RESULTS Using the entire cohort , rather than just those with ratings adjacent to the dichotomization point , yielded more precise and sensible MID estimates . With one exception , high precision was obtained when using the ROC curve method for any cutoff on the rating scale . CONCLUSION When calculating the MID using the ROC curve method , the use of the entire cohort maximizes precision"
] |
4116cbb2-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND Elevated systemic blood pressure results in high intravascular pressure but the main complications , coronary heart disease ( CHD ) , ischaemic strokes and peripheral vascular disease ( PVD ) , are related to thrombosis rather than haemorrhage . Some complications related to elevated blood pressure , heart failure or atrial fibrillation , are themselves associated with stroke and thromboembolism . Therefore it is important to investigate if antithrombotic therapy may be useful in preventing thrombosis-related complications in patients with elevated blood pressure . OBJECTIVES To conduct a systematic review of the role of antiplatelet therapy and anticoagulation in patients with high blood pressure , including those with elevations in both systolic and diastolic blood pressure , isolated elevations of either systolic or diastolic blood pressure , to address the following hypotheses : ( i ) antiplatelet agents reduce total deaths and /or major thrombotic events when compared to placebo or other active treatment ; and ( ii ) oral anticoagulants reduce total deaths and /or major thromboembolic events when compared to placebo or other active treatment . SEARCH METHODS Electronic data bases ( MEDLINE , EMBASE , DARE , CENTRAL , Hypertension Group specialised register ) were search ed up to January 2011 . The reference lists of papers result ing from the electronic search es and abstract s from national and international cardiovascular meetings were h and - search ed to identify missed or unpublished studies . Relevant authors of studies were contacted to obtain further data . SELECTION CRITERIA R and omised controlled trials ( RCTs ) in patients with elevated blood pressure were included if they were of at least 3 months in duration and compared antithrombotic therapy with control or other active treatment . DATA COLLECTION AND ANALYSIS Data were independently collected and verified by two review ers . Data from different trials were pooled where appropriate . MAIN RESULTS Four trials with a combined total of 44,012 patients met the inclusion criteria and are included in this review . Acetylsalicylic acid ( ASA ) did not reduce stroke or ' all cardiovascular events ' compared to placebo in primary prevention patients with elevated blood pressure and no prior cardiovascular disease . In one large trial ASA taken for 5 years reduced myocardial infa rct ion ( ARR 0.5 % , NNT 200 ) , increased major haemorrhage ( ARI 0.7 % , NNT 154 ) , and did not reduce all cause mortality or cardiovascular mortality . In one trial there was no significant difference between ASA and clopidogrel for the composite endpoint of stroke , myocardial infa rct ion or vascular death . In two small trials warfarin alone or in combination with ASA did not reduce stroke or coronary events . The ATC meta- analysis of antiplatelet therapy for secondary prevention in patients with elevated blood pressure reported an absolute reduction in vascular events of 4.1 % as compared to placebo . Data on the 10,600 patients with elevated blood pressure from the 29 individual trials included in the ATC meta- analysis was requested but could not be obtained . AUTHORS ' CONCLUSIONS Antiplatelet therapy with ASA for primary prevention in patients with elevated blood pressure provides a benefit , reduction in myocardial infa rct ion , which is negated by a harm of similar magnitude , increase in major haemorrhage . The benefit of antiplatelet therapy for secondary prevention in patients with elevated blood pressure is many times greater than the harm . Benefit has not been demonstrated for warfarin therapy alone or in combination with aspirin in patients with elevated blood pressure . Ticlopidine , clopidogrel and newer antiplatelet agents such as prasugrel and ticagrelor have not been sufficiently evaluated in patients with high blood pressure . Newer antithrombotic oral drugs such as dabigatran , rivaroxaban , apixaban and endosaban are yet to be tested in patients with high blood pressure . Further trials of antithrombotic therapy including with newer agents and complete documentation of all benefits and harms are required in patients with elevated blood pressure
|
[
"This study determined the effect of nonsteroidal anti-inflammatory drug ( NSAID ) administration on blood pressure in hypertensive patients taking hydrochlorothiazide ( HCTZ ) . Ninety-seven patients with mild essential hypertension and a musculoskeletal indication for NSAID use were studied in a three-phase , multi-center , double-blind , r and omized , parallel study based in 15 academic and community clinics . Patients served as their own controls . Patients with stable hypertension , not taking antihypertensive or NSAID medications , were treated with HCTZ 50 mg/day . After 4 to 5 weeks of treatment and documented stable blood pressure , naproxen 375 mg twice a day or ibuprofen 800 mg three times a day was added . Blood pressure was measured at 2 and 4 weeks of NSAID therapy . The average diastolic blood pressure was 97.5 + /- 2.4 mm Hg and the average of the mean arterial pressure ( MAP ) was 116.8 + /- 6.04 before treatment with HCTZ . Hydrochlorothiazide treatment decreased diastolic blood pressure to 83.1 + /- 5.6 mm Hg , and MAP to 101.1 + /- 6.5 mm Hg . With naproxen or ibuprofen treatments , mean diastolic blood pressure increased less than 3 mm Hg . At 2 weeks , ibuprofen increased diastolic blood pressure by 2.6 mm Hg ( P = .004 ) and naproxen increased diastolic blood pressure 0.7 mm Hg ( P = .40 ) . Both ibuprofen and naproxen significantly increased diastolic pressure at 4 weeks ( 2.1 mm Hg , P = .042 ; and 1.8 mm Hg , P = .043 , respectively ) . There was no correlation between the pre-NSAID blood pressure and the magnitude of change after 2 or 4 weeks of treatment . Changes in MAP reflected a pattern similar to diastolic pressure . ( ABSTRACT TRUNCATED AT 250 WORDS",
"The value of anticoagulant therapy after acute myocardial infa rct ion has been assessed in 1,136 patients admitted to the Bronx Municipal Hospital Center . The treatment reduced the overall mortality in women from 31 % to 15 % , particularly those 55 years of age or over , with moderately severe infa rct ion . The low overall mortality in control men ( 16 % ) was not reduced with treatment , though there was significant reduction of the mortality in a subgroup of men with moderately severe infa rct ion showing Q-wave evolution . Age and sex , as well as the severity of the episode of acute myocardial infa rct ion , are important in determining whether anticoagulant therapy is likely to be beneficial",
"Background The clinical usefulness of intravenous thrombolytic therapy in unstable angina is currently unknown , despite the pathogenetic similarity of this entity to acute myocardial infa rct ion , for which thrombolysis has enjoyed great success . To compare the clinical benefit of intravenous urokinase with that of conventional antithrombotic therapy in preventing the progression of unstable angina to new myocardial infa rct ion , intractable angina , or death within the first 96 hours after hospitalization , 149 patients with unstable angina were r and omized to one of two intravenous thrombolytic strategies . Methods and Results Forty-nine patients received 3 million units urokinase i.v . over 90 minutes plus intravenous heparin ( group A ) ; 47 patients received unblinded 3 million units urokinase i.v . plus 325 mg aspirin p.o . daily ( group B ) ; and 53 patients received placebo thrombolytic infusion plus full-dose heparin ( group C ) . The primary end point of this trial was 96-hour clinical status . There were no significant differences in the baseline characteristics ( age , sex , previous myocardial infa rct ion , hypertension prevalence , diabetes , tobacco use , or previous revascularization ) among the three groups . Despite an excess of minor untoward reactions for the urokinase groups ( chills , 26.5 % and 23.4 % for groups A and B versus 0 % for group C ; p major bleeds ( two , none , and two for groups A , B , and C , respectively;p = NS ) . At 96 hours after presentation , no significant difference emerged in the incidence of new cardiac events : new myocardial infa rct ions developed in 10.2 % of group A , 6.4 % of group B , and 3.8 % of group C ( p = NS ) ; intractable angina occurred in 6.1 % of group A , 10.6 % of group B , and 9.4 % of group C ( p = NS ) . There were no deaths . All three groups encountered a similar incidence of overall cardiac events : 16.31 % , 17.0 % , and 13.2 % for groups A , B , and C , respectively ( p = NS ) . Although trial enrollment was to extend to 600 patients , interim analysis led to early cessation of enrollment due to a negative trend in respect to outcome after thrombolysis . Conclusions High-dose intravenous urokinase followed by either heparin or aspirin can be safely administered to a broad , unselected group of patients with unstable angina . However , this study suggests that no clinical advantage is conferred by urokinase , with either adjunctive antithrombotic therapy over st and ard heparin therapy alone , when given relatively late ( mean , 8.7 hours ) after admission for unstable angina . A possible detrimental effect can not be excluded",
"AIMS To assess the effect of tr and olapril ( 2 mg once daily ) and indomethacin ( 25 mg three times daily ) , alone and in combination , on renal function and renal functional reserve in hypertensive patients ( DBP 95 - 115 mmHg ) requiring regular non-steroidal anti-inflammatory drugs ( NSAIDs ) . METHODS R and omized , double-blind , placebo-controlled , four way crossover design . After 3 weeks treatment renal plasma flow ( RPF ) and glomerular filtration rate ( GFR ) were measured using the p-aminohippurate ( PAH ) and inulin methods . Renal functional reserve was estimated by measuring RPF and GFR at the end of an intravenous infusion of dopamine 2 microg kg(-1 ) and 10 % amino acid solution . RESULTS There was no significant difference in RPF between treatments : -22.79 ml min(-1 ) ( 95 % CI -54.82 , 9.24 ) for placebo and tr and olapril , -10.37 ml min(-1 ) ( 95 % CI -30.7 , 9.96 ) for placebo and indomethacin , -14.78 ml min(-1 ) ( 95 % CI -50.33 , 20.77 ) for placebo and tr and olapril with indomethacin . There was no significant difference in functional reserve RPF between treatments : -34.96 ml min(-1 ) ( 95 % CI -119.8 , 49.88 ) for placebo and tr and olapril , 29.78 ml min(-1 ) , -15.18 , 74.74 ) for placebo and indomethacin , and -25.84 ml min(-1 ) ( 95 % CI -87.62 , 35.94 ) for placebo and tr and olapril with indomethacin . There was no significant difference in GFR between treatments : -1.01 ml min(-1 ) ( 95 % CI -7.45 , 5.42 ) for placebo and tr and olapril , -7.88 ml min(-1 ) ( 95 % CI -15.08 , -0.68 ) for placebo and indomethacin , and -0.36 ml min(-1 ) ( 95 % CI -7.58 , 6.86 ) for placebo and tr and olapril with indomethacin . There was no significant difference in functional reserve GFR between treatments : 5.13 ml min(-1 ) ( 95 % CI -4.97 , 15.23 ) for placebo and tr and olapril , 6.31 ml min(-1 ) ( 95 % CI -1.88 , 14.5 ) for placebo and indomethacin , 7.21 ml min(-1 ) ( 95 % CI 1.26 , 13.16 ) for placebo and tr and olapril with indomethacin . CONCLUSION In hypertensives chronic treatment with NSAIDs or ACEI alone or in combination did not change RPF or GFR and did not change renal functional reserve capacity of RPF or GFR",
"To evaluate the influence of salt sensitivity on the blood pressure response to oral indomethacin treatment , we studied 35 hospitalized essential hypertensive patients ( 24 men and 11 women , aged from 40 to 55 years ) . During a normal NaCl intake ( 120 mmol Na+ per day ) , patients were assigned to receive in a r and omized double-blind fashion either 200 mg indomethacin ( 25 patients ) or placebo ( 10 patients ) for 5 days . Two weeks after the interruption of indomethacin treatment , during which the normal NaCl intake was continued , salt sensitivity was assessed by giving each patient a high ( 220 mmol Na+ per day for 10 days ) and then a low ( 20 mmol Na+ per day for 10 days ) NaCl diet . Blood pressure changes were evaluated , and the measurement taken at the end of the 2 weeks under normal sodium intake was considered baseline blood pressure . Patients were classified as salt sensitive when a diastolic blood pressure change of 10 mm Hg or more occurred after both low and high periods of sodium intake . In salt-resistant patients treated with indomethacin ( n = 12 , nine men and three women , mean age 50.5 + /- 3.7 years ) , neither blood pressure ( systolic blood pressure from 150.8 + /- 11.2 to 154.6 + /- 9.3 mm Hg , NS ; diastolic blood pressure from 99.3 + /- 2.1 to 101.1 + /- 4.4 mm Hg , NS ) nor the urinary Na+ excretion ( from 108.1 + /- 20.9 to 97.9 + /- 9.1 mmol/24 hr , NS ) was significantly affected by the drug . ( ABSTRACT TRUNCATED AT 250 WORDS",
"Twenty four male hypertensive patients suffering also from peripheral obstructive arterial disease were r and omly subdivided in two groups and after a period of farmacological wash-out of one month Group I was treated with Captopril ( C 50 mg bid ) or Ticlopidine ( T 250 mg bid ) for three months and then with the association C plus T for three months again . After placebo administration for one month , patients were further treated with C plus T at low doses ( 25 mg bid and respectively 250 mg daily ) . In the first part of the study , patients of Group II received an inverse sequence of the drugs ( before Ticlopidine 250 mg bid and then Captopril 50 bid ) . In both groups of patients C induced a significant decrease of blood pressure and an increase of PFWD , TWD , and WI . T did not modify blood pressure but slightly increased PFWD , TWD , and WI . The improvement was more evident during administration of C plus T , whereas placebo administration induced a trend toward baseline values . Finally , the chronic administration of C plus T for twelve months induced a further improvement of all considered parameters . In conclusion , chronic administration of C plus T may be useful in the treatment of hypertensive patients suffering from intermittent claudication , improving significantly PFWD and TWD",
"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",
"BACKGROUND When a patient survives thrombolysis for acute myocardial infa rct ion , little information from large studies exists from which to estimate prognosis during follow-up visits . METHODS AND RESULTS Baseline , in-hospital , and later survival data were collected from 41 021 patients enrolled in Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries , a r and omized trial of 4 thrombolytic-heparin regimens with st and ard aspirin and beta-blockade . Cox proportional hazards models were developed to predict 1-year survival in 30-day survivors ( n=37 869 ) from baseline clinical and ECG factors and in-hospital factors ; a combined model then was developed ( C-index 0.800 ) . The model was simplified into a nomogram to predict individual outcomes ( C-index 0.754 ) . Factors reflecting demographics ( advanced age , lighter weight ) , larger infa rct ions ( higher Killip class , lower blood pressure , faster heart rate , longer QRS duration ) , cardiac risk ( smoking , hypertension , prior cerebrovascular disease ) , and arrhythmia were important predictors of death between 30 days and 1 year . Black race was associated with a substantial increase in risk after considering other factors . Revascularization was associated with reduced risk between 30 days and 1 year . CONCLUSIONS When evaluating a patient who has survived acute infa rct ion treated with thrombolysis , clinicians can estimate the likelihood of survival from factors easily measured during admission . Although many risk factors clearly relate to age , left ventricular dysfunction , or clinical instability , black race is an unexplained risk factor requiring further examination",
"Summary In postmyocardial infa rct ion patients longterm aspirin treatment with 1.5 g/day led to a significant increase in systolic and diastolic blood pressure after 6 months . This could not be found in the placebo- and the phenprocoumon-treated patients . After one year the blood pressure behaviour was the same in all three treatment groups . As nonsteroidal antirheumatic drugs can produce hypertension in animals , probably due to inhibition of prostagl and in synthesis , blood pressure control in longterm aspirin treatment is advisable . ZusammenfassungNach 6 Monaten Therapie mit 1,5 g Acetylsalizylsäure täglich wurde bei Postinfarkt-Patienten ein signifikanter Anstieg des systolischen und diastolischen Blutdrucks beobachtet . Ein solches Ansteigen des Blutdrucks konnte bei den mit Placebo oder Phenprocoumon Beh and elten nicht nachgewiesen werden . Ein Jahr nach Therapiebeginn war das Blutdruckverhalten gleich in allen drei Therapiegruppen . Da auch bei Tieren mit nichtsteroidalen Antirheumatika ein Hochdruck erzeugt werden konnte , wahrscheinlich durch Hemmung der Prostagl and insynthese , ist die regelmäßige Blutdruckkontrolle während einer Langzeit-Aspirin-Therapie ratsam",
"Arthritis and hypertension are frequent comorbidities in the elderly hypertensive population . Nonsteroidal anti-inflammatory drugs are often used to relieve pain in arthritic patients but a side effect is sodium retention and consequent elevation of blood pressure ( BP ) . The effect of dihydropyridine calcium blocking drugs is relatively independent of sodium intake , whereas the angiotensin-converting enzyme ( ACE ) inhibitors ' effects can be blunted by a high-sodium diet . This study compared the effects of indomethacin with placebo in elderly patients with essential hypertension who had been controlled with amlodipine or enalapril . Indomethacin 50 mg twice daily or placebo was administered for 3 weeks in a double-blind crossover study to patients controlled with amlodipine or enalapril . The response was assessed by ambulatory BP measurement . Indomethacin raised BP and lowered pulse rates in patients taking enalapril but had little effect in patients receiving amlodipine . The difference caused by indomethacin between the two groups was 10.1/4.9 mm Hg increase in BP and a 5.6 beats/min fall in pulse in people taking enalapril . Addition of indomethacin to patients taking either drug caused a rise in weight and a fall in plasma renin . It is postulated that the effect is due to inhibition of prostagl and in synthesis , which causes sodium retention . In patients taking amlodipine , the fall in plasma renin ameliorates the effect of sodium retention on BP . In patients taking enalapril , plasma renin falls but this is not translated into an effect because of the blockage of converting enzyme . Thus , the full effect of sodium retention on BP is expressed . In patients treated with indomethacin , fewer patients may respond to ACE inhibitors . However , the major problem is the patient who intermittently takes indomethacin or other nonsteroidal anti-inflammatory drugs , which , if a person is treated by an ACE inhibitor causes BP to go out of control . In such patients amlodipine would appear to be a preferred choice to enalapril",
"Background After coronary artery bypass surgery , patients have a high cumulative rate of graft closure and recurrent ischemic events . We sought to determine whether antiplatelet therapy with clopidogrel would be more effective than aspirin , the accepted st and ard , in these patients . Methods and Results The event rates for all-cause mortality , vascular death , myocardial infa rct ion , stroke , and rehospitalization were determined for the 1480 patients with a history of cardiac surgery r and omized to either clopidogrel or aspirin in a trial of 19 185 patients . The event rate per year of vascular death , myocardial infa rct ion , stroke , or rehospitalization was 22.3 % in the 705 patients r and omized to aspirin and 15.9 % in the 775 patients r and omized to clopidogrel ( P = 0.001 ) . A risk reduction was also seen in each of the individual end points examined , including a 42.8 % relative risk reduction in vascular death in patients on clopidogrel versus aspirin ( P = 0.030 ) . In a multivariate model incorporating baseline clinical characteristics , clopidogrel therapy was independently associated with a decrease in vascular death , myocardial infa rct ion , stroke , or rehospitalization in patients with a history of cardiac surgery , with a 31.2 % relative risk reduction ( 95 % CI , 15.8 to 43.8;P = 0.0003 ) . Although clopidogrel therapy was efficacious in the entire Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events ( CAPRIE ) population , multivariate analysis demonstrated that patients with previous cardiac surgery derived particular benefit ( P = 0.015 ) . Conclusion Compared with aspirin , clopidogrel therapy results in a striking reduction in the elevated risk for recurrent ischemic events seen in patients with a history of prior cardiac surgery , along with a decreased risk of bleeding",
"Background — Patients with a non – ST-elevation acute coronary syndrome and prior CABG are at high risk of a recurrent ischemic event despite aspirin therapy . This trial investigated the potential benefit of secondary prevention with warfarin . Methods and Results —In a double-blind r and omized trial , 135 patients with unstable angina or non – ST-segment elevation myocardial infa rct ion , with prior CABG , and who were poor c and i date s for a revascularization procedure received therapy with aspirin and placebo+warfarin , warfarin and placebo+aspirin , or aspirin and warfarin for 12 months . Warfarin was titrated to an international normalized ratio of 2.0 to 2.5 . The primary end point ( death or myocardial infa rct ion or unstable angina requiring hospitalization 1 year after r and omization ) occurred in 14.6 % of the patients in the warfarin-alone group , in 11.5 % of patients in the aspirin-alone group , and in 11.3 % of patients r and omized to the combination therapy ( P = 0.76 ) . Subgroup analyses by risk features provided no indications that warfarin alone or in combination with aspirin could be of benefit over aspirin alone . Bleeding was more frequent in the 2 groups of patients administered warfarin . Conclusions —Moderate-intensity oral anticoagulation alone or combined with low-dose aspirin does not appear to be superior to low-dose aspirin in the prevention of recurrent ischemic events in patients with non – ST-elevation acute coronary syndromes and previous CABG",
"This study investigates the possible effects of acetylsalicylic acid ( ASA ; aspirin ) on systolic ( S ) and diastolic ( D ) blood pressure ( BP ) in healthy and mildly hypertensive subjects receiving ASA at different times according to their rest-activity cycle . A double-blind , r and omized , controlled trial was conducted in 73 healthy young adult volunteers and 18 previously untreated subjects with mild hypertension . The BP of each subject was automatically monitored every 30 minutes for 48h before the trial and at the end of a one-week course of placebo and a one-week course of ASA . Healthy volunteers were r and omly assigned to one of six groups , defined according to the dose of ASA ( either 500 mg/day , the usual commercial dose ; or 100 mg/day ) and timing of ASA and placebo ( within 2h after awakening , Time 1 ; 7h to 9h after awakening , Time 2 ; or within 2h of bedtime , Time 3 ) . Subjects with mild hypertension received the low dose of 100 mg/day ASA , as well as one week of placebo , and were r and omly assigned to one of the same three groups defined above according to the time of treatment . A small ( approximately 2 mmHg in the 24h mean of SBP ) , but statistically significant , BP reduction was found when 500 mg/day ASA was given to healthy volunteers at Time 2 . With 100 mg/day , the effect of ASA in healthy subjects was comparable to the BP reduction found with the higher dose for Time 2 ; there was again no effect on BP at Time 1 , but we found a statistically significant effect at Time 3 ( 2.3 mmHg reduction in the 24h mean of SBP ) , larger than for Time 2 . For hypertensive patients , the BP reduction was again statistically significant for Time 2 and , to a greater extent , for Time 3 ( approximately 4.5 mmHg for both SBP and DBP ) ; all patients in these two groups showed a BP reduction after one week of ASA . The effect was about three times as large as the BP reduction obtained in healthy subjects treated with 100 mg/day ASA . Results indicate a statistically significant time- and dose-dependent effect of ASA on BP . In any meta- analysis of ASA effects , inquiries about the time when subjects took the drug are indicated and may account for discrepancies in the literature . Moreover , the influence of ASA on BP demonstrated here indicates the need to identify and control for ASA effects in patients using ASA before and during their participation in antihypertension medication trials",
"OBJECTIVE Nonsteroidal antiinflammatory drugs ( NSAID ) have been associated with hemodynamically mediated acute renal failure . There appear to be differences among NSAID in producing this effect . We compare renal effects of ibuprofen , sulindac , and nabumetone . METHODS Seventeen women over age 56 receiving hydrochlorothiazide and fosinopril for hypertension who had osteoarthritis requiring NSAID received 3 different NSAID to evaluate potential varying renal effects . In an investigator blinded r and omized study , patients received nabumetone , sulindac , or ibuprofen for 1 month with intervening 2 week control periods . After each period renal function was assessed by inulin and para-aminohippurate clearances and urinary prostagl and ins were measured . RESULTS No overall statistical differences among the NSAID were observed . However , there were clinical ly meaningful differences during ibuprofen therapy : 4 patients developed a clinical ly significant decrease in renal function ; during sulindac therapy one of these also developed a clinical ly significant decrease in renal function . During nabumetone there were 0 episodes of clinical ly significant decrease in renal function . Using Gomez equations , glomerular hydrostatic pressure and afferent and efferent arteriolar resistances were estimated . None changed overall during any intervention . However , the 4 patients who developed decreased renal function while taking ibuprofen were analyzed separately . Glomerular hydrostatic pressure decreased 15 % ; afferent arteriolar resistance increased 85 % . These changes were associated with marked decreases in vasodilatory prostagl and ins compared to patients receiving ibuprofen who did not develop decreases in renal function . CONCLUSION There are differences in effect on renal function among NSAID . These can be correlated with specific alterations in suppression of the cyclooxygenase system cascade and related to changes in the hemodynamic control of glomerular filtration",
"BACKGROUND Nonsteroidal anti-inflammatory drugs may attenuate the antihypertensive effects of diuretics , beta-blockers , angiotensin-converting enzyme inhibitors , central alpha-agonists , and other vasodilators . Their effects on the antihypertensive efficacy of calcium channel blockers are inadequately studied in small numbers of patients but appear to be minimal . METHODS A three-phase , r and omized , double-blind , placebo-controlled multicenter study included 162 patients aged 18 to 75 years with essential hypertension . After diastolic blood pressure was controlled to 90 mm Hg or less with once-daily verapamil hydrochloride , patients received ibuprofen , naproxen , or placebo matching capsules for 3 weeks , and blood pressure , heart rate , weight , and adverse effects were evaluated . A general linear model with 95 % confidence intervals was used to compare each nonsteroidal anti-inflammatory drug treatment group with the placebo group . RESULTS No significant differences in sitting , st and ing , or supine blood pressure were noted with naproxen or ibuprofen compared with placebo . The percentages of patients in each treatment group with increases of 10 mm Hg or more in either systolic or diastolic blood pressure were similar . Statistically significant increases in weight were seen with both nonsteroidal anti-inflammatory drug therapies . Changes in pulse rate were not significant . The incidence of adverse effects was similar across all three treatment groups . CONCLUSIONS The addition of naproxen or ibuprofen to the treatment of hypertensive patients in whom blood pressure is controlled by once-daily verapamil does not cause an increase in blood pressure . Verapamil may therefore offer considerable advantages in maintaining control of blood pressure in patients who regularly receive nonsteroidal anti-inflammatory drug therapy",
"1 . The effects of non-steroidal anti-inflammatory drugs ( NSAID ) on prostacyclin and thromboxane bio synthesis and on blood pressure were determined in 46 patients with mild essential hypertension . Patients who had abstained from antihypertensive therapy for 2 weeks before study were treated with either aspirin , ibuprofen , sulindac or placebo for 7 days . 2 . Excretion rates of 2,3-dinor-6-oxo-prostagl and in ( PG ) F1 alpha , 6-oxo-PGF1 alpha , 2,3-dinorthromboxane ( TX ) B2 and TXB2 were measured as indices of prostacyclin and TXA2 bio synthesis . Sample s were assayed using immunoaffinity chromatography and gas chromatography/electron capture chemical ionisation mass spectrometry . 3 . Aspirin and ibuprofen reduced urinary excretion of all prostacyclin- and thromboxane-derived products . Sulindac inhibited excretion of 2,3-dinor-6-oxo-PGF1 alpha , 6-oxo-PGF1 alpha and 2,3-dinor-TXB2 , but had no significant effect on TXB2 . 4 . Systolic blood pressure increased in the ibuprofen-treated group when compared with the placebo group . There were no other significant changes in systolic or diastolic pressure in any of the treatment groups . Among the patients as a whole , there was a significant negative correlation between change in blood pressure and change in excretion of the prostacyclin-derived but not of the thromboxane-derived products . 5 . We conclude that , in patients with mild essential hypertension , neither sulindac nor aspirin ( in the doses used ) selectively spares prostacyclin bio synthesis by the kidney . The significant relationship between increase in blood pressure and reduction in prostacyclin bio synthesis favours the possibility that in individuals who become hypertensive , prostacyclin bio synthesis determines , in part , the severity of the hypertensive state",
"BACKGROUND An inverse association between moderate alcohol consumption and coronary heart disease ( CHD ) has been observed in several epidemiological studies . To assess whether a similar association exists among diabetics , we examined the relation between light to moderate alcohol consumption and CHD in men with and without diabetes mellitus in a prospect i ve cohort study . METHODS AND RESULTS A total of 87 938 US physicians ( 2790 with diagnosed diabetes mellitus ) who were invited to participate in the Physicians ' Health Study and were free of myocardial infa rct ion , stroke , cancer , or liver disease at baseline were followed for an average of 5.5 years for death with CHD as the underlying cause . During 480 876 person-years of follow-up , 850 deaths caused by CHD were documented : 717 deaths among nondiabetic men and 133 deaths among diabetic men . Among men without diabetes at baseline , the relative risk estimates for those reporting rarely/never , monthly , weekly , and daily alcohol consumption were 1.00 ( referent ) , 1.02 , 0 . 82 , and 0.61 ( 95 % CI 0.49 to 0.78 ; P for trend Among men with diabetes at baseline , the relative risk estimates were 1.00 ( referent ) , 1.11 , 0.67 , and 0.42 ( 95 % CI 0.23 to 0.77 ; P for trend=0.0019 ) . CONCLUSIONS These results suggest that light to moderate alcohol consumption is associated with similar risk reductions in CHD among diabetic and nondiabetic men",
"The benefit of aspirin therapy among women with coronary artery disease ( CAD ) is not well established . Previous studies have shown conflicting results among women . Data from 2,418 women with CAD screened for participation in the ongoing Bezafibrate Infa rct ion Prevention ( BIP ) study were analyzed : 45 % reported aspirin therapy . Baseline characteristics were similar in both groups . Cardiovascular mortality at 3.1 + /- 0.9 years of follow-up was 2.7 % in the aspirin treated group versus 5.1 % in the non-aspirin-treated women ( p = 0.002 ) . All cause mortality was 5.1 % and 9.1 % , respectively ( p = 0.0001 ) . Treatment with aspirin emerged as an independent predictor of reduced cardiovascular ( RR = 0.61 , 95 % confidence interval [ CI ] 0.38 to 0.97 ) and all cause ( RR = 0.66 , 95 % CI 0.47 to 0.93 ) mortality after multiple adjustment for possible confounders such as age , history of myocardial infa rct ion , systemic hypertension , diabetes mellitus , peripheral vascular disease , current smoking , New York Heart Association classification , and concomitant treatment with digitalis . Women who benefited the most from aspirin therapy were older , diabetic , symptomatic , or had a previous myocardial infa rct ion . Thus , treatment with aspirin was associated with reduced mortality among women with CAD . This study suggests that women with CAD should be treated with aspirin , unless specific contraindications exist",
"Objective The objective of this study was to provide a comprehensive comparison of the long term safety and tolerability of clopidogrel , a new adenosine diphosphate ( ADP ) receptor antagonist that inhibits platelet activation induced by ADP , and aspirin ( acetylsalicylic acid ) . Patients and Methods The study population comprised 19 185 patients with symptomatic atherosclerosis manifested as recent ischaemic stroke , recent myocardial infa rct ion or symptomatic peripheral arterial disease . Patients were r and omised to receive clopidogrel 75 mg/day or aspirin 325 mg/day for a minimum of 1 year and a maximum of 3 years . Results Compared with aspirin , clopidogrel reduced the combined risk of ischaemic stroke , myocardial infa rct ion or vascular death by 8.7 % ( p = 0.043 ) . The incidence of early permanent discontinuations of the study drug due to adverse events was almost identical in both treatment groups ( 11.94 % for clopidogrel vs 11.92 % for aspirin ) . Reported neutropenia was similar in the clopidogrel and aspirin groups ( 0.10 vs 0.17 % , respectively ) with corresponding rates ( 0.05 vs 0.04 % , respectively ) for severe neutropenia . Thrombocytopenia was identical in the clopidogrel and aspirin groups ( 0.26 % ) , with the rates of severe thrombocytopenia being 0.19 vs 0.10 % , respectively . None of these observed differences was statistically significant . The overall incidence of haemorrhagic events did not differ statistically significantly between treatment groups ( 9.27 % for clopidogrel vs 9.28 % for aspirin ; p = 0.98 ) . There was a trend towards a lower incidence of intracranial haemorrhage in the clopidogrel group ( 0.31 % ) compared with the aspirin group ( 0.42 % ) . Any reported gastrointestinal haemorrhage was significantly less frequent with clopidogrel ( 1.99 % ) than with aspirin ( 2.66 % ) [ p severe gastrointestinal bleeding were 0.49 vs 0.71 % ; p gastrointestinal adverse events with clopidogrel than with aspirin ( 27.1 vs 29.8 % ; p abdominal pain , dyspepsia , constipation , or peptic , gastric , or duodenal ulceration with clopidogrel . Diarrhoea was significantly more common in the clopidogrel group ( 4.46 vs 3.36 % ; p severe diarrhoea ( 0.23 vs 0.11 % ) was low and was not significantly different between groups . There were significantly more patients with rash in the clopidogrel group ( 6.0 % ) compared with the aspirin group ( 4.6 % ) [ p clopidogrel represents a clinical ly important advance in the treatment of patients with manifest atherosclerotic disease",
"Nonsteroidal antiinflammatory drugs ( NSAID ) are frequently reported to interfere with the blood pressure lowering actions of various antihypertensive medications . We studied 17 women with arthritis and hypertension who were receiving fosinopril and HCTZ , and administered sequentially in r and om order ibuprofen , sulindac , and nabumetone for 1 month each , with an intervening 2-week washout period between each treatment period . During the washout period , subjects received acetaminophen . Blood pressure at the end of 2 weeks of acetaminophen was compared with blood pressure after 1 month of treatment with each of the NSAID . Mean blood pressure was unchanged before and after all NSAID : 108 + /- 7 v 107 + /- 9 for nabumetone , 108 + /-9 v 108 + /- 9 for sulindac , and 108 + /- 8 v 107 + /- 9 for ibuprofen . The 24-h urinary sodium excretion was not significantly different . We conclude that the three NSAID did not neutralize the antihypertensive effect of the combination of fosinopril and HCTZ , and hence the blood pressure lowering action of the combination may not be prostagl and in dependent",
"Aspirin is only modestly effective in the secondary prevention after cerebral ischemia . Studies in other vascular disorders suggest that anticoagulant drugs in patients with cerebral ischemia of presumed arterial ( noncardiac ) origin might be more effective . The aim of the Stroke Prevention in Reversible Ischemia Trial ( SPIRIT ) therefore was to compare the efficacy and safety of 30 mg aspirin daily and oral anticoagulation ( international normalized ratio [ INR ] 3.0–4.5 ) . Patients referred to a neurologist in one of 58 collaborating centers because of a transient ischemic attack or minor ischemic stroke ( Rankin grade $ 3 ) were eligible . R and omization was concealed , treatment assignment was open , and assessment of outcome events was masked . The primary measure of outcome was the composite event “ death from all vascular causes , nonfatal stroke , nonfatal myocardial infa rct ion , or nonfatal major bleeding complication . ” The trial was stopped at the first interim analysis . A total of 1,316 patients participated ; their mean follow‐up was 14 months . There was an excess of the primary outcome event in the anticoagulated group ( 81 of 651 ) versus 36 of 665 in the aspirin group ( hazard ratio , 2.3 ; 95 % confidence interval [ CI ] , 1.6–3.5 ) . This excess could be attributed to 53 major bleeding complications ( 27 intracranial ; 17 fatal ) during anticoagulant therapy versus 6 on aspirin ( 3 intracranial ; 1 fatal ) . The bleeding incidence increased by a factor of 1.43 ( 95 % CI , 0.96–2.13 ) for each 0.5 unit increase of the achieved INR . Anticoagulant therapy with an INR range of 3.0 to 4.5 in patients after cerebral ischemia of presumed arterial origin is not safe . The efficacy of a lower intensity anticoagulation regimen remains to be determined",
" From 1979 - 85 , 2435 patients with a transient ischaemic attack or minor ischaemic stroke were r and omly allocated to receive long term \" blind \" treatment with aspirin 600 mg twice daily ( n = 815 ) , aspirin 300 mg once daily ( n = 806 ) or placebo ( n = 814 ) . No patient was lost to follow up . The \" intention to treat \" comparison included all the serious vascular events and deaths which occurred before the end of the follow up period on 30 September 1986 . There was no difference in efficacy between the 300 mg and 1200 mg daily doses of aspirin , but the lower dose was undoubtedly less gastrotoxic . Also , there was no definite difference in the response of males and females to aspirin . The odds of suffering a major stroke , myocardial infa rct ion or vascular death were 15 % less in the combined aspirin groups compared with the placebo group ( 95 % confidence interval 29 % reduction to 3 % increase in odds ) which is compatible with the continuing overview of all the similar trials of antiplatelet drugs where the relative reduction in odds was 25 % . There was no statistically significant reduction in the likelihood of either disabling major stroke and vascular death or vascular death occurring",
"Effect of non-steroidal anti-inflammatory drug ( NSAID ) on blood pressure ( BP ) control was evaluated in elderly hypertensive patients treated with calcium antagonist . The study was based on a r and omized , crossover design to compare the effect of an NSAID , sulindac , with that of another NSAID , diclofenac sodium , in the hypertension treatment . The study was completed in six elderly female subjects ( the average age : 66 + /- 3 year ) whose systolic BP and diastolic BP were more than 160 mmHg and more than 95 mmHg , respectively . When BP was controlled by nifedipine ( 20 mg x 2 per day in slow releasing form ) within normal limits , sulindac ( 100 mg x 3 per day ) or diclofenac sodium ( 25 mg x 3 per day ) was administered for a week . After one week-washout period , the other NSAID was substituted . Plasma and urinary variables were measured on the final day of each study period . The average systolic BP and diastolic BP and the entry of study were 167 + /- 5 mmHg and 93 + /- 5 mmHg , respectively . Nifedipine significantly decreased the systolic BP to 140 + /- 4 mmHg ( p less than 0.02 ) and the diastolic BP to 84 + /- 4 mmHg ( p less than 0.05 ) . Addition of either sulindac or diclofenac sodium did not affect BP , whereas urinary PGE2 excretion and plasma renin activity were significantly inhibited . Plasma creatinine and electrolyte concentration were not changed by the NSAIDs . The results indicate that either sulindac or diclofenac sodium does not interfere with control of hypertension by a calcium antagonist , nifedipine in in elderly hypertensive patients . ( ABSTRACT TRUNCATED AT 250 WORDS",
"BACKGROUND In a retrospective study , antiplatelet therapy has been shown to be associated with a decreased incidence of erythropoietin-induced hypertension . In order to ascertain the role of antiplatelet drugs in the haemodynamic response to the correction of anaemia by rHuEpo , 18 patients on chronic haemodialysis who started rHuEpo therapy were prospect ively studied . METHODS The subjects were r and omly assigned to receive or not , one of the following antiplatelet drugs : ditazole ( 3 patients ) , ticlopidine ( 3 patients ) or aspirin plus dipyridamole ( 3 patients ) . Cardiac index ( CI ) by echo-Doppler , total peripheral resistance ( TPR ) and mean arterial pressure ( MAP ) were determined at baseline 10 and 20 weeks following the initiation of rHuEpo therapy . rHuEpo therapy was administered subcutaneously at the same dose ( 40 U/kg thrice weekly ) during the first 10 weeks . Ten uraemic patients on haemodialysis who had never received rHuEpo therapy served as the control group . RESULTS One patient in the group without antiplatelet drugs discontinued the study due to the development of severe hypertension after 12 weeks on rHuEpo therapy . There were no significant differences in the haemodynamic parameters at baseline . At 10 weeks , MAP was higher in patients without than with antiplatelet drugs or controls untreated with rHuEpo ( 128.5 + /- 28 versus 100.6 + /- 13.5 versus 98.7 + /- 14 mmHg respectively , P = 0.0047 ) , TPR was also higher in patients without antiplatelet drugs than in the 2 other groups ( 1919 + /- 433 versus 1576 + /- 359 versus 1418 + /- 324 din.seg.cm-5m2 respectively , P = 0.0231 ) , but CI did not differ among the three groups . At 20 weeks , MAP was still higher in patients without antiplatelet drugs than in patients with antiplatelet drugs or controls not on rHuEpo therapy respectively ( 112.9 + /- 24.6 versus 91.0 + /- 9.0 versus 101.7 + /- 14.1 mmHg respectively , P = 0.075 ) , but at this stage TPR and Cl did not differ among the three groups . CONCLUSIONS These data reinforce the previous observation that antiplatelet therapy may prevent the development of rHuEpo-induced hypertension",
"The Coumadin Aspirin Reinfa rct ion Study demonstrated that combination treatment with fixed dose warfarin ( 1 or 3 mg ) + aspirin 80 mg was not superior to aspirin 160 mg alone after myocardial infa rct ion for reducing nonfatal reinfa rct ion , nonfatal stroke , and cardiovascular death . In this analysis , we examined the importance of aspirin dose in the protection against the secondary end point of ischemic stroke . The comparison arms for this analysis were warfarin 1 mg + aspirin 80 mg versus aspirin 160 mg . In the Coumadin Aspirin Reinfa rct ion Study , 2,028 patients were r and omized to aspirin 80 mg plus warfarin 1 mg , and 3,393 were r and omized to aspirin 160 mg alone . A predictive model for ischemic stroke was developed using the Cox proportional-hazards model . A reduced Cox proportional-hazards model was developed to test for the effect of aspirin dose on ischemic stroke in predefined subgroups . The incidence of ischemic stroke was lower in patients treated with aspirin 160 mg than in patients treated with aspirin 80 mg + warfarin 1 mg ( 0.6 % vs 1.1 % ; p = 0.0534 ) . Age , previous stroke or transient ischemic attack , and aspirin dose were independent predictors of ischemic stroke . In addition , the highest risk patients , those with Q-wave myocardial infa rct ion and male patients , appeared to receive greater benefit from aspirin 160 mg than from aspirin 80 mg + warfarin 1 mg . The results of this secondary analysis suggest that aspirin 160 mg is more effective than aspirin 80 mg + warfarin 1 mg in preventing ischemic stroke in post-myocardial infa rct ion patients",
"To determine whether endothelin-1 ( ET-1 ) contributes to hypertension associated with non-steroidal anti-inflammatory drug ( NSAID ) usage in healthy , elderly , normotensive individuals a r and omised , double-blind , placebo-controlled , crossover trial of indomethacin was undertaken in 41 healthy , elderly individuals with stable normotension or controlled hypertension ( blood pressure ( BP ) The main outcome measures were systolic and diastolic BP , heart rate , cardiac output , weight , creatinine clearance , plasma renin activity , aldosterone , endothelin-1 and arginine vasopressin concentrations and 24 h urinary endothelin-1 and 6 keto prostagl and in F1 alpha outputs . Analysis of covariance was used to evaluate the effect of indomethacin on BP and related parameters . Indomethacin treatment for 1 month increased systolic ( + /- s.e.m . : 4.1 + /- 2.2 mm Hg ; 95 % confidence interval 0 to 8.3 mm Hg ) and diastolic BP ( 2.7 + /- 1.1 mm Hg ; 0.4 to 4.9 mm Hg ) without altering cardiac output ( P = 0.59 ) , implying an increase in total peripheral resistance . Indomethacin treatment produced a small increase in weight ( 1.4 + /- 0.4 kg ; 0.6 to 2.2 kg ) , a small reduction in renal function ( creatinine clearance : 6.8 + /- 1.8 mis/min ; 3.3 to 10.3 mis/min ) but a significant ( 83 % ) increase in daily urinary endothelin-1 production ( 13.1 + /- 3.4 ng/ml ; 6.4 to 19.8 ng/ml ) without altering plasma ET-1 concentration , suggesting increased renal synthesis . In conclusion , renal paracrine effects of ET-1 may contribute to NSAID-induced blood pressure elevation in humans",
"Objective : To assess the relationship between chronic intake of nonsteroidal anti-inflammatory drugs ( NSAID ) and outcome , in particular ( gastrointestinal ) bleeding and to investigate whether the effect of chronic NSAID intake was similar in untreated and treated elderly hypertensives . Methods : Eligible patients ( ⩾60 years , with systolic blood pressure 160–219 mm Hg and diastolic blood pressure were r and omised to active treatment or placebo . Active treatment consisted of nitrendipine , with the possible addition of enalapril , hydrochlorothiazide , or both , titrated or combined to reduce the sitting systolic blood pressure by at least 20 mm Hg to below 150 mm Hg . Patients never taking NSAIDs ( n = 2882 ) were compared with patients on chronic NSAID intake ( n= 861 ) , defined as reporting NSAID intake on at least 50 % of the patient forms . Results : There was a tendency towards lower mortality ( relative hazard rate ( 95 % confidence interval ( CI ) , 0.77 ( 0.56–1.06 ) ) and higher incidence of bleeding ( 1.13 ( 0.63–2.05 ) with chronic NSAID intake . Although there was no significant interaction between calcium-channel blocker (CCB)-based treatment and chronic NSAID intake for any of the end points , chronic NSAID intake tended to be associated with a lower incidence of bleeding on active treatment as compared to placebo ( P-value of the interaction term = 0.07 ) . Conclusion : The effect of chronic NSAID intake on outcome was similar in patients on active treatment based on a dihydropyridine CCB or on placebo . However , chronic NSAID intake might have a less deleterious effect on bleeding on active treatment as compared to placebo",
"BACKGROUND When administered intravenously at the time of percutaneous coronary revascularization , glycoprotein IIb/IIIa receptor antagonists decrease the incidence of death and nonfatal myocardial infa rct ion and the need for urgent revascularization . We hypothesized that long-term administration of oral glycoprotein IIb/IIIa antagonists , which block the aggregation of platelets , might stabilize intravascular plaque and prevent additional ischemic cardiac events . METHODS We conducted a prospect i ve , double-blind trial in which 7232 patients were r and omly assigned to receive 20 mg of oral xemilofiban or placebo 30 to 90 minutes before undergoing percutaneous coronary revascularization , with maintenance doses of 10 or 20 mg of xemilofiban or placebo administered three times daily for up to 182 days . There were two primary composite end points : one was death , nonfatal myocardial infa rct ion , or urgent revascularization at 182 days , and the other was death or nonfatal myocardial infa rct ion at 182 days . RESULTS Death , myocardial infa rct ion , or urgent revascularization occurred within 182 days in 324 patients who received placebo ( Kaplan-Meier cumulative event rate , 13.5 percent ) , 332 who received 10 mg of xemilofiban ( 13.9 percent , P=0.82 for the comparison with placebo ) , and 306 who received 20 mg of xemilofiban ( 12.7 percent , P=0.36 for the comparison with placebo ) . The incidence of death or myocardial infa rct ion was also similar in all three groups . Clinical ly significant hemorrhagic complications and thrombocytopenia were infrequent . CONCLUSIONS The administration of the glycoprotein IIb/IIIa antagonist xemilofiban before percutaneous coronary revascularization and for up to six months thereafter does not significantly reduce the incidence of important clinical end points",
"OBJECTIVE To evaluate in hypertensive patients whether or not the sodium-retaining effects of indomethacin can explain the indomethacin-induced attenuation of enalapril antihypertensive effects . DESIGN R and omized , single-blinded , placebo controlled study with a placebo phase ( 2 weeks ) followed by enalapril 20 mg/d ( 4 weeks , once daily ) and enalapril 20 mg + indomethacin 75 mg/d ( 1 week ) . Enalapril dose increased up to 40 mg/d if inadequate response to 20 mg . PATIENTS Twenty-four patients with mild-moderated hypertension , showing an adequate response to enalapril ( 20 - 40 mg/d ) . METHODS Blood pressure evaluated by \" casual \" methods and by 24-hour ambulatory blood pressure monitoring , measurement of 24-hour urinary sodium excretion and fractional excretion of sodium : at the end of placebo , enalapril and enalapril + indomethacin treatments . Determination of the correlations between the changes induced by indomethacin ( when added to enalapril ) on the blood pressure and on sodium excretion effects of enalapril . RESULTS Enalapril significantly reduced casual blood pressure ( systolic/diastolic ) by 33/18 mmHg and 24-hour blood pressure by 20/9 mmHg . When added to enalapril , indomethacin attenuated ( by 50 % ) the antihypertensive effects of enalapril and significantly decreased the 24-hour ( from 120 + /- 11 mmol to 106 + /- 10 mmol ) and fractional excretion of sodium ( from 1.11 + /- 0.09 % to 0.75 + /- 0.06 % ) . However , the indomethacin-induced attenuation of enalapril hypotensive effects did not correlate with indomethacin-induced changes of sodium excretion . CONCLUSIONS When indomethacin is administrated to hypertensive patients that are well controlled with enalapril , it produces a marked attenuation of enalapril hypotensive effects and produces sodium retention . However , the amount of the attenuation of the hypotensive effects of enalapril by indomethacin are completely independent of the amount of the indomethacin-induced sodium retention . These results suggest that the mechanisms involved in interaction between both drugs at the blood pressure domain are probably localized at an extra-renal level",
"To determine the renovascular effects of nonprescription ibuprofen in the maximum labeled over-the-counter ( OTC ) dosage for 7 days , and to compare these effects with those of two other available OTC analgesics , aspirin and acetaminophen , we evaluated 25 elderly patients with mild thiazide-treated hypertension and mild renal insufficiency . Under double-blind conditions , patients were r and omly allocated to one of three treatment groups : ibuprofen 400 mg 3 times/day , aspirin 650 mg 3 times/day , or acetaminophen 650 mg 3 times/day . Blood pressure and indexes of renal function ( blood urea nitrogen , creatinine clearance , serum electrolytes ) were measured over 7 days in a clinical research center . None of the treatments had a clinical ly significant effect on blood pressure . Renal function indexes also remained unchanged during all three treatments . We conclude that elderly patients with mild thiazide-treated hypertension and mild renal insufficiency seem not to be at risk of developing additional renal compromise or of having their hypertension control diminished by treatment with these OTC analgesics for 7 days",
"OBJECTIVE To determine whether a regimen of methotrexate , cyclosporin A , and corticosteroids introduced at onset in poor-prognosis rheumatoid arthritis ( RA ) can produce a significant improvement in outcome compared with st and ard monotherapy with sulfasalazine ( SSZ ) . METHODS Eighty-two consecutive patients presenting with new , untreated RA of less than 12 months ' duration who fulfilled criteria for poor long-term outcome were r and omized to receive either combination therapy ( n = 40 ) or SSZ alone ( n = 42 ) . The primary outcome measures were remission and American College of Rheumatology ( ACR ) criteria for 20 % improvement at 48 weeks . RESULTS After 48 weeks , the numbers of patients who met the ACR criteria for 20 % improvement were not significantly different between the two groups ( combination 58 % versus SSZ 45 % ) , and similar numbers of patients had persisting clinical remission ( approximately 10 % both groups ) . During the first 3 months , there were significantly greater reductions in parameters of disease activity in the combination group . By 24 weeks , the swollen and tender joint counts , C-reactive protein levels , and erythrocyte sedimentation rates had fallen significantly in both groups , with a greater improvement in the swollen and tender joint count in the combination group . At 48 weeks , the radiographic damage score had increased by a median of 1 ( range 0 - 42.5 ) in the combination group and 1.25 ( range 0 - 72.5 ) in the SSZ group ( P = 0.28 ; although there were significant differences in the scores for the right h and ) . There were significantly fewer withdrawals due to lack of efficacy in the combination group than in the SSZ group ( 1 of 40 versus 10 of 42 ; P = 0.007 ) . In the combination group , dose reduction was needed in 22.5 % because of hypertension and in 22.5 % because of elevated creatinine levels . Over 48 weeks , serum creatinine increased in both groups , but particularly in the combination arm . CONCLUSION In poor-prognosis RA patients , \" aggressive \" combination therapy led to more rapid disease suppression but did not result in significantly better ACR response or remission rates . This suggests that in poor-prognosis disease , an approach based on identifying patients with poor treatment responses before extra therapy is added ( \" step-up \" approach ) may be more appropriate than the use of combination therapy in all patients from the outset",
"We performed a subgroup analysis of the first European Stroke Prevention Study including 1,306 patients recruited in a single center , Kuopio , Finl and , to investigate whether or not antiplatelet therapy is effective in the secondary prevention of stroke in hypertensive patients with transient ischemic attack ( TIA ) or stroke . The patients were treated with aspirin , 990 mg/day , plus dipyridamole , 225 mg/day , or placebo for 2 years . The patients with high systolic blood pressure ( > or = 140 mm Hg ; n = 1.105 ) or high diastolic blood pressure ( > or = 85 mm Hg ; n = 1,120 ) at entry , were classified into subgroups by blood pressure level . The effect of treatment was statistically significant in all subgroups with high systolic ( end-point reduction , 55.2 - 68.2 % ) and diastolic blood pressure ( end-point reduction , 47.3 - 82.1 % ) . Risk reduction was , however , greatest in patients with the highest diastolic blood pressure . One possible explanation is that platelets are more activated in these patients , and this can be effectively prevented by antiplatelet therapy . Further studies are needed to confirm this hypothesis",
"Patients who had survived a stroke or transient ischaemic attacks ( TIA ) were admitted to a trial of low-dose aspirin ( 50 mg ) alone , sustained release dipyridamole ( 400 mg/day ) alone , or a combination of the two agents , and results compared with a placebo over 24 months . This low-dose aspirin regimen produced in pairwise comparisons a significant risk reduction of 18 % for stroke , 13 % for stroke and /or death but no reduction in all cause mortality . The sustained release dipyridamole produced a significant risk reduction of 16 % for stroke , 15 % for stroke and /or death but no significant reduction of mortality . In combination , aspirin and dipyridamole produced a risk reduction of 37 % in stroke , 24 % in stroke and /or death , and no reduction in mortality . Similar findings were found in TIA , which was a secondary endpoint . These results are highly significant in comparison with placebo . As expected , there were enhanced reports of alimentary side-effects in the aspirin groups and also enhanced bleeding . Dipyridamole was associated with a slight increase in headache , which resolved in most patients if therapy was continued . The conclusions are that 50 mg/day of aspirin alone or 400 mg/day of sustained release dipyridamole alone are equally effective in stroke and TIA prevention . When used in combination the effects were additive and were significantly more effective than the single agents",
"Objective : To evaluate the influence of non-steroidal anti-inflammatory drugs ( NSAIDs ; aspirin and indomethacin ) on the renal and antihypertensive effects of enalapril and nifedipine gastrointestinal therapeutic system ( GITS ) in patients with essential hypertension . Design and methods : In a crossover study , 18 patients on an unrestricted-salt diet were r and omly assigned to receive either enalapril ( 20 - 40 mg/day ) or nifedipine-GITS ( 30 - 60mg/day ) for 4 - 8 weeks , followed by aspirin ( 100 mg/day for 2 weeks ) and then indomethacin ( 75 mg/day for 1 week ) . Blood pressure was measured by 24 h ambulatory monitoring . Results : Enalapril and nifedipine-GITS significantly reduced blood pressure compared with placebo . Aspirin did not alter the antihypertensive effect of either drug . Indomethacin attenuated ( by 45 % ) the antihypertensive effect of enalapril throughout the 24 h period of evaluation , but did not interfere with the effect of nifedipine . Furthermore , indomethacin significantly reduced the fractional excretion of sodium and plasma levels of prostagl and ins in a similar way when added to either the enalapril or the nifedipine regimen . Conclusions : Vasodilatory prostagl and ins are probably involved in the antihypertensive effects of enalapril but not of nifedipine , and this interaction seems to be independent of any indomethacin-induced decrease in renal sodium excretion . Nifedipine may be an appropriate drug to treat hypertensive patients requiring concomitant therapy with NSAID",
"BACKGROUND Despite treatment , there is often a higher incidence of cardiovascular complications in patients with hypertension than in normotensive individuals . Inadequate reduction of their blood pressure is a likely cause , but the optimum target blood pressure is not known . The impact of acetylsalicylic acid ( aspirin ) has never been investigated in patients with hypertension . We aim ed to assess the optimum target diastolic blood pressure and the potential benefit of a low dose of acetylsalicylic acid in the treatment of hypertension . METHODS 18790 patients , from 26 countries , aged 50 - 80 years ( mean 61.5 years ) with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg ( mean 105 mm Hg ) were r and omly assigned a target diastolic blood pressure . 6264 patients were allocated to the target pressure Felodipine was given as baseline therapy with the addition of other agents , according to a five-step regimen . In addition , 9399 patients were r and omly assigned 75 mg/day acetylsalicylic acid ( Bamycor , Astra ) and 9391 patients were assigned placebo . FINDINGS Diastolic blood pressure was reduced by 20.3 mm Hg , 22.3 mm Hg , and 24.3 mm Hg , in the major cardiovascular events occurred at a mean achieved diastolic blood pressure of 82.6 mm Hg ; the lowest risk of cardiovascular mortality occurred at 86.5 mm Hg . Further reduction below these blood pressures was safe . In patients with diabetes mellitus there was a 51 % reduction in major cardiovascular events in target group Acetylsalicylic acid reduced major cardiovascular events by 15 % ( p=0.03 ) and all myocardial infa rct ion by 36 % ( p=0.002 ) , with no effect on stroke . There were seven fatal bleeds in the acetylsalicylic acid group and eight in the placebo group , and 129 versus 70 non-fatal major bleeds in the two groups , respectively ( p patients with hypertension was associated with a low rate of cardiovascular events . The HOT Study shows the benefits of lowering the diastolic blood pressure down to 82.6 mm Hg . Acetylsalicylic acid significantly reduced major cardiovascular events with the greatest benefit seen in all myocardial infa rct ion . There was no effect on the incidence of stroke or fatal bleeds , but non-fatal major bleeds were twice as common",
"BACKGROUND Many trials in patients with acute myocardial infa rct ion have demonstrated that thrombolytic therapy is not associated with an excessive risk of stroke , as compared with conventional treatment . However , the incidence of various forms of stroke in patients treated with different thrombolytic and antithrombotic regimens and the associated effect of risk factors for stroke are largely unknown . METHODS Strokes occurring in patients hospitalized with acute myocardial infa rct ion who were enrolled in either of two large trials were analyzed . The patients were r and omly assigned to receive streptokinase ( 1.5 million units ) or recombinant tissue plasminogen activator ( t-PA ) ( 100 mg ) and also r and omly assigned to receive subcutaneous heparin or no heparin . Ninety-one percent of the patients also received aspirin . RESULTS Complete data were available on 20,768 patients . A total of 236 ( 1.14 percent ) had strokes in the hospital ; 0.36 percent had hemorrhagic strokes , 0.48 percent ischemic strokes , and 0.30 percent strokes of undefined cause . Patients treated with t-PA had a small but significant excess of stroke as compared with those who received streptokinase ( 1.33 vs. 0.94 percent ; adjusted odds ratio , 1.42 ; 95 percent confidence interval , 1.09 to 1.84 ) . The administration of subcutaneous heparin in addition to a thrombolytic agent did not increase the risk of stroke ( risk with heparin , 1.13 percent ; without heparin , 1.14 percent ) . Older age , a higher Killip class , and the occurrence of anterior infa rct ion significantly increased the risk of stroke , whereas a higher body-mass index or a history of hypertension , diabetes , or smoking did not . CONCLUSIONS Patients with acute myocardial infa rct ion who receive thrombolytic therapy have a small risk of stroke . Treatment with t-PA as compared with streptokinase result ed in a small but significant excess of stroke . Subcutaneous heparin , given together with t-PA or streptokinase and aspirin , did not result in an increased risk of stroke",
"The effects of dihydropyridine calcium antagonists on blood pressure and platelets , and the effects of aspirin on the circadian antihypertensive efficacy of dihydropyridines and on the 24-h platelet-activity profile , were the focus of a double-blind study . Patients with essential hypertension were treated for 8 weeks with either isradipine focus of double-blind study . Patients with essential hypertension were treated for 8 weeks with either isradipine ( 2.5 mg/day ) or nitrendipine ( 10 mg/day ) . Aspirin ( 100 mg/day ) was added to both treatment groups for a further 8 weeks . Measurements were taken after 4 weeks of placebo , after 8 weeks of dihydropyridine treatment , and after 8 weeks of treatment combined with aspirin . Plasma levels of beta-thromboglobulin ( beta-TG ) and platelet aggregation induced by serotonin were measured six times during 24 h. Both dihydropyridines significantly lowered systolic and diastolic blood pressure . The addition of aspirin to dihydropyridine treatment had no significant effects on systolic or diastolic blood pressure . Dihydropyridine treatment lowered the increased 24-h plasma beta-TG profile and inhibited platelet aggregability . Aspirin added to nitrendipine led to a further significant decrease in beta-TG levels whereas its addition to isradipine was accompanied by a partial increase in plasma beta-TG . It is concluded that increases in platelet activity in hypertensive patients can be prevented with either isradipine alone or nitrendipine plus aspirin . Aspirin in a daily dose of 100 mg does not affect the antihypertensive efficacy of calcium antagonists",
"BACKGROUND Nonsteroidal antiinflammatory drugs ( NSAIDs ) may alter blood pressure through their inhibitory effects on prostagl and in bio synthesis . Such potential hypertensive effects of NSAIDs have not been adequately examined in the elderly , who are the largest group of NSAID users . METHODS We performed a r and omized , double-blind , two-period crossover trial of ibuprofen ( 1800 mg per day ) vs placebo treatment in patients older than 60 years of age with hypertension controlled with hydrochlorothiazide . While continuing their usual thiazide dosage , subjects were r and omized to a 4-week treatment period ( ibuprofen or placebo ) followed by a 2-week placebo wash-out period and a second 4-week treatment period with the alternative therapy . Supine and st and ing systolic and diastolic blood pressures were measured weekly . RESULTS Of 25 r and omized subjects , 22 completed the study protocol ( mean age = 73 + /- 6.7 years ) . Supine systolic blood pressure and st and ing systolic blood pressure were increased significantly with ibuprofen treatment , compared with placebo . Mean supine systolic blood pressures were 143.8 + /- 21.0 and 139.6 + /- 15.9 mmHg on ibuprofen and placebo , respectively ( p = .004 ) . Mean st and ing systolic blood pressures were 148.1 + /- 19.9 and 143.4 + /- 17.9 mmHg on ibuprofen and placebo , respectively ( p = .002 ) . CONCLUSION We conclude that 1800 mg per day of ibuprofen does induce a significant increase in systolic blood pressure in older hypertensive patients treated with hydrochlorothiazide . NSAID therapy may negatively impact the control of hypertension in elderly patients",
"The ability of angiotensin converting enzyme ( ACE ) inhibitors to lower blood pressure may in part be due to the formation of vasodilatory prostagl and ins . Inhibition of prostagl and in synthesis with aspirin may therefore theoretically attenuate the antihypertensive effect of ACE inhibitors . This trial studied the interaction between aspirin ( ASA ) and enalapril , an ACE inhibitor , and ASA and losartan , an angiotensin subtype 1 receptor antagonist . Seventeen essential hypertensive patients were studied , maintained on a stable dose of either enalapril ( n = 7 ) or losartan ( n = 10 ) monotherapy for > or = 12 weeks before and throughout the study . Each patient received a 2-week course of placebo , 81 mg/day ASA , and 325 mg/day ASA , each treatment separated by a 2-week washout period . Blood pressure ( BP ) and serum thromboxane B2 ( TXB2 ) sample s were obtained at the end of each treatment period . Placebo was compared with each dose of ASA for each group . In both the enalapril and losartan groups , mean , systolic , and diastolic BP were unchanged with the addition of ASA . Concentrations of TXB2 were suppressed to ASA . This study demonstrates that 81 to 325 mg/day ASA exerts no significant effect on BP in essential hypertensives taking enalapril or losartan",
"BACKGROUND After angioplasty , major complications and ischemic events occur more frequently in diabetic than nondiabetic patients . To determine whether treatment with abciximab is effective in reducing these events in diabetics , we analyzed characteristics and outcomes of diabetic patients enrolled in a large multicenter study ( EPILOG ) . METHODS AND RESULTS Of 2792 patients enrolled , 638 ( 23 % ) were diabetic . Diabetic patients were older , shorter , and heavier ; more likely to be female and have three-vessel disease , prior coronary artery bypass graft surgery , a history of hypertension , or a recent myocardial infa rct ion ; and less likely to be current smokers than their nondiabetic counterparts . During hospitalization , death , myocardial infa rct ion , or urgent revascularization occurred in 7.1 % of diabetics and 7.5 % of nondiabetics . By 6 months , the composite of death and myocardial infa rct ion had occurred in 8.8 % of diabetic patients and 7.4 % of nondiabetics , whereas death , myocardial infa rct ion , or revascularization had occurred in 27.2 % and 22.6 % , respectively . Abciximab treatment reduced death or myocardial infa rct ion among diabetic and nondiabetic patients ( hazard ratios , 0.28 [ 95 % confidence interval ( CI ) , 0.13 to 0.57 ] and 0.47 [ 95 % CI , 0.33 to 0.70 ] at 30 days for diabetics and nondiabetics , respectively , and 0.36 [ 95 % CI , 0.21 to 0.61 ] and 0.60 [ 95 % CI , 0.44 to 0.82 ] at 6 months for diabetics and nondiabetics , respectively ) . Abciximab reduced target vessel revascularization among nondiabetic patients ( hazard ratio , 0.78 [ 95 % CI , 0.63 to 0.96 ] ) but not among diabetics ( hazard ratio , 1.4 [ 95 % CI , 0.94 to 2.08 ] ) . When st and ard- and low-dose heparin adjuncts were compared , diabetics receiving abciximab with st and ard-dose heparin had marginally greater reductions in the composite of death and myocardial infa rct ion and in target vessel revascularization than diabetics assigned to abciximab with low-dose heparin . CONCLUSIONS Abciximab treatment in diabetic patients led to a reduction in the composite of death and myocardial infa rct ion , which was at least as great as that seen in nondiabetic patients . However , target vessel revascularization was reduced in nondiabetic but not diabetic patients . This effect may be associated in part with lower doses of heparin . These differences may be related to differences in the platelet and coagulation systems between diabetics and nondiabetics , the greater extent of coronary artery disease in diabetics , or patient selection and management factors",
"240 patients were admitted to a double-blind study to determine the effect of long-term treatment with platelet-function inhibiting agents on occlusive arterial disease in the lower extremities . Patients were r and omised into 1 of 3 treatment groups : aspirin 330 mg ; dipyridamole 75 mg and aspirin 330 mg ; or matching placebo 3 times daily . The duration of treatment was 2 years . Arteriography was carried out at the beginning of the study and 2 years later or before if deterioration was observed . 199 patients completed the study according to the trial protocol . The serial arteriograms were assessed in pairs qualitatively , by means of simple comparative viewing , and semiquantitatively with Bollinger 's score system . Progression of the disease was most pronounced in the placebo-treated group , less so in the aspirin-treated group , and least of all in the dipyridamole- and -aspirin group . Patients who smoke and those with hypertension may benefit most from treatment with the 2 preparations under investigation",
"A six year r and omised trial was conducted among 5139 apparently healthy male doctors to see whether 500 mg aspirin daily would reduce the incidence of and mortality from stroke , myocardial infa rct ion , or other vascular conditions . Though total mortality was 10 % lower in the treated than control group , this difference was not statistically significant and chiefly involved diseases other than stroke or myocardial infa rct ion . Likewise , there was no significant difference in the incidence of non-fatal myocardial infa rct ion or stroke — indeed , disabling strokes were somewhat commoner among those allocated aspirin . The lower confidence limit for the effect of aspirin on non-fatal stroke or myocardial infa rct ion , however , was a substantial 25 % reduction . Migraine and certain types of musculoskeletal pain were reported significantly less often in the treated than control group , but as the control group was not given a placebo the relevance of these findings was difficult to assess . There was no apparent reduction in the incidence of cataract in the treated group . The lack of any apparent reduction in disabling stroke or vascular death contrasts with the established value of antiplatelet treatment after occlusive vascular disease",
"The associations of diastolic blood pressure ( DBP ) with stroke and with coronary heart disease ( CHD ) were investigated in nine major prospect i ve observational studies : total 420,000 individuals , 843 strokes , and 4856 CHD events , 6 - 25 ( mean 10 ) years of follow-up . The combined results demonstrate positive , continuous , and apparently independent associations , with no significant heterogeneity of effect among different studies . Within the range of DBP studied ( about 70 - 110 mm Hg ) , there was no evidence of any \" threshold \" below which lower levels of DBP were not associated with lower risks of stroke and of CHD . Previous analyses have described the uncorrected associations of DBP measured just at \" baseline \" with subsequent disease rates . But , because of the diluting effects of r and om fluctuations in DBP , these substantially underestimate the true associations of the usual DBP ( ie , an individual 's long-term average DBP ) with disease . After correction for this \" regression dilution \" bias , prolonged differences in usual DBP of 5 , 7.5 , and 10 mm Hg were respectively associated with at least 34 % , 46 % , and 56 % less stroke and at least 21 % , 29 % , and 37 % less CHD . These associations are about 60 % greater than in previous uncorrected analyses . ( This regression dilution bias is quite general , so analogous corrections to the relations of cholesterol to CHD or of various other risk factors to CHD or to other diseases would likewise increase their estimated strengths . ) The DBP results suggest that for the large majority of individuals , whether conventionally \" hypertensive \" or \" normotensive \" , a lower blood pressure should eventually confer a lower risk of vascular disease",
"BACKGROUND Clopidogrel is a new antiplatelet agent that offers increased protection over aspirin in preventing vascular ischaemic events in patients with symptomatic atherosclerosis . In a large , r and omized , international study of clopidogrel and aspirin ( n = 19,185 patients ) clopidogrel was associated with a lower incidence of gastrointestinal adverse events , including gastrointestinal haemorrhage and hospitalizations because of gastrointestinal haemorrhage . The aim of the study was to determine whether macroscopic differences in the gastric mucosa between aspirin- and clopidogrel-treated subjects could be detected by gastroscopy after short-term treatment . METHODS Thirty-six healthy volunteers were r and omized in a double-blind , double-dummy , parallel design , to 75 mg/day of clopidogrel or 325 mg/day of aspirin for 8 days . Gastroscopy was performed at base line before administration of study drug and directly after treatment completion . Gastroduodenal effects were measured in accordance with a modified Lanza scale . RESULTS At base line no difference between the groups was detected ( median Lanza score , 0.0 in both groups ) . At the end of treatment the aspirin group showed a median score of 7.5 , and the clopidogrel group showed an unchanged median score of 0.0 ( P adverse events versus 8 individuals and 13 adverse events for clopidogrel , with approximately half of the adverse events being gastrointestinal in each group . No serious adverse events were reported . CONCLUSION In contrast to aspirin , short-term treatment with clopidogrel does not induce macroscopic changes in the gastroduodenal mucosa . The study results show that in patients without gastroduodenal disease clopidogrel , but not aspirin , does not induce any gastroscopically evident erosions during short-term treatment",
"OBJECTIVE A secondary subgroup analysis of the European Stroke Prevention Study of the effect of antiplatelet medication on the risk of myocardial infa rct ion . DESIGN AND SETTING A r and omized , double-blind placebo-controlled study with two parallel treatment groups ( dipyridamole plus aspirin and placebo ) . Sixteen centers from six countries participated in the study . PATIENTS A total of 2500 patients who had had one or more transient ischemic attacks or cerebral infa rct ions participated . INTERVENTION Combination therapy with dipyridamole ( 75 mg three times a day ) and aspirin ( 330 mg three times a day ) was compared with placebo during 24 months ' follow-up . OUTCOME MEASURES Prevention of fatal and nonfatal myocardial infa rct ion . RESULTS A total of 105 myocardial infa rct ions occurred in the intention-to-treat analysis and 76 occurred in the explanatory analysis . The overall risk reduction of myocardial infa rct ion with the study drugs was approximately 40 % in both statistical analyses , but the result was statistically significant only in the intention-to-treat analysis . Therapeutic efficacy was better among male patients , patients younger than 65 years , and patients with hypertension . CONCLUSION Combination therapy with dipyridamole and aspirin reduces not only the risk of cerebrovascular ischemic events but also the risk of myocardial infa rct ion",
"Abstract Objective : To determine which groups of patients may derive particular benefit or experience harm from the use of low dose aspirin for the primary prevention of coronary heart disease . Design : R and omised controlled trial . Setting : 108 group practice s in the Medical Research Council 's general practice research framework who were taking part in the thrombosis prevention trial . Participants : 5499 men aged between 45 and 69 years at entry who were at increased risk of coronary heart disease . Main outcome measures : Myocardial infa rct ion , coronary death , and stroke . Results : Aspirin reduced coronary events by 20 % . This benefit , mainly for non-fatal events , was significantly greater the lower the systolic blood pressure at entry ( interaction P=0.0015 ) , the relative risk at pressures 130 mm Hg being 0.55 compared with 0.94 at pressures > 145 mm Hg . Aspirin also reduced strokes at low but not high pressures , the relative risks being 0.41 and 1.42 ( P=0.006 ) respectively . The relative risk of all major cardiovascular events — that is , the sum of coronary heart disease and stroke — was 0.59 at pressures 145 mm Hg ( P=0.0001 ) . Conclusion : Even with the limitations of subgroup analyses the evidence suggests that the benefit of low dose aspirin in primary prevention may occur mainly in those with lower systolic blood pressures , although it is not clear even in these men that the benefit outweighs the potential hazards . Men with higher pressures may be exposed to the risks of bleeding while deriving no benefit through reductions in coronary heart disease and stroke",
"Nonsteroidal antiinflammatory drugs ( NSAIDs ) are known to attenuate the antihypertensive effects of a variety of antihypertensive agents including diuretics , beta-blockers , and vasodilators . Because of their unique mechanisms of actions , calcium channel blockers may not be subject to this interaction . This multicenter , double-blind , r and omized , placebo-controlled study was design ed to assess the effect of NSAID therapy on blood pressure control in stable hypertensive patients treated with a calcium channel blocker . One hundred patients with stable blood pressure control on 30 mg nicardipine three times a day were treated with 375 mg naproxen twice a day or placebo for 4 weeks . The mean diastolic blood pressures and estimated mean arterial pressures in both groups changed Body weight in the placebo-treated patients did not change significantly whereas body weight in the naproxen-treated patients increased significantly , from 90.3 + /- 3.2 kg to 91.0 + /- 3.2 kg ( mean = 0.7 , P = .0003 ) . At 4 weeks there was a mean loss of 0.1 kg in the placebo group and a mean gain of 0.4 kg in the naproxen group compared to baseline weights , neither of which was statistically significant ( P = .60 and P = .071 , respectively ) . These results indicate that despite a significant increase in body weight , the antihypertensive action of the calcium channel blocker nicardipine is not significantly affected by cotreatment with naproxen",
"Objective To test the hypothesis that an imbalance in intrarenal prostagl and ins plays a role in cyclosporin-induced nephrotoxicity . Methods and results Indomethacin was given in combination with cyclosporin to healthy volunteers . Cyclosporin alone ( 10mg/kg twice a day ) for 4 days had no effect on effective renal plasma flow ( ERPF ) and glomerular filtration rate but 4 days of therapy with cyclosporin ( 10mg/kg twice a day ) and indomethacin ( 50 mg twice a day ) in combination result ed in a 37 % fall in glomerular filtration rate and a 32 % fall in ERPF . This suggests that autoregulatory mechanisms , possibly involving renal prostagl and ins , may participate in counteracting the tendency for cyclosporin-induced renal vasoconstriction in humans . Cyclosporin increased systemic blood pressure acutely , and this was not influenced by indomethacin even though indomethacin on its own caused sodium retention . This suggests that , in contrast to the renal vasculature , the systemic vascular response to cyclosporin is neither augmented nor buffered by prostagl and ins . Conclusion The reduction in intrarenal prostagl and ins clearly played a key role in the development of cyclosporin-induced renal vasoconstriction , but we could not demonstrate a role for prostagl and ins or for sodium retention in the initiation of cyclosporin-induced hypertension",
"Sixteen hypertensive male out- patients ( 33 - 54 y ) , whose blood pressure ( BP ) had been normalized ( diastolic BP atenolol ( CAS 29122 - 68 - 7 ) , participated in this double-blind , placebo-controlled , parallel group study , which investigated the possible influence of the non-steroidal anti-inflammatory drug tenoxicam ( CAS 59804 - 37 - 4 ) on the control of BP by atenolol . After a run-in of 10 days , to assess the stability of BP control by atenolol , and to determine baseline parameters , 8 patients in group A received 20 mg tenoxicam ( 2 x 20 mg on days 1 and 2 ) , and 8 patients in group B received placebo , daily over 15 days ( days 0 - 14 ) , concomitantly with their atenolol regimen . BP was measured under st and ardized conditions on several days . Heart rate ( EHR ) after 5 min of exercise by bicycle ergometry ( constant 75W ) , and parameters of renal function were assessed before ( baseline ) and during concomitant dosing of atenolol and tenoxicam . On day 14 the mean changes ( delta A , delta B ) from baseline of pre-dose BP ( mmHg ) and EHR ( beats/min ) in groups A and B , and the one-sided 95 % confidence regions ( R ) for delta A , respectively , were ( delta A , delta B , R ) : 4.4 , 1.6 , sitting systolic BP , 2.8 , -0.3 , sitting diastolic BP , -0.3 , -0.6 , st and ing systolic BP , -0.6 , -1.9 , st and ing diastolic BP , 0.4 , -7.5 , < 0.4 for EHR at pre-dose , 3.1 , 0.6 , < 7.8 for EHR at 3.5 h post-dose . ( ABSTRACT TRUNCATED AT 250 WORDS",
"The effects of aspirin ( 1950 mg/day orally ) or indomethacin ( 75 mg/day orally ) on blood pressure were investigated in normotensive volunteers and hypertensive patients receiving antihypertensive medication . Aspirin ( 1950 mg/day ) did not change blood pressure or body weight in normotensive or treated hypertensive subjects . No significant change in plasma renin concentration was seen with aspirin ( 1950 mg/day ) in treated hypertensive subjects . Indomethacin ( 75 mg/day ) significantly increased blood pressure in normotensive subjects and treated hypertensive subjects . Body weight increased significantly in the treated hypertensive subjects but not normotensive subjects . In treated hypertensive subjects indomethacin ( 75 mg/day ) did not change plasma volume , but significantly decreased plasma renin concentration",
"This study tested the hypothesis that treatment with a nonsteroidal anti-inflammatory drug will not alter the hypotensive effect of a dihydropyridine calcium channel antagonist . Fifteen essential hypertensives ( ages 58 - 80 years ) had a supine diastolic blood pressure ( DBP ) nitrendipine 5 - 20 mg twice daily . They entered a double-blind r and omised crossover study in which the addition of indomethacin 25 mg three times daily was compared with placebo in treatment phases each of 4 weeks duration . Subjects were seen weekly and measurements in the last 2 weeks of each phase were compared . Supine blood pressure ( mean + /- SE ) was higher in the indomethacin phase ( 158 + /- 4/80 + /- 2 ) than in the placebo phase ( 154 + /- 4/76 + /- 3 ) ( p supine diastolic blood pressure with indomethacin was > 5 mmHg . Plasma urea was also increased in the indomethacin phase : 7.6 + /- 0.6 mmol/l compared with placebo : 6.3 + /- 0.5 mmol/l ( p indomethacin impairs the blood pressure lowering effect of the dihydropyridine calcium channel antagonist nitrendipine . This increase in blood pressure with indomethacin in subjects treated with nitrendipine may represent either an independent pressor effect of indomethacin or a reduced vasodilator prostanoid contribution to the hypotensive effect of nitrendipine . This blood pressure increase may be sufficient to interfere significantly with clinical blood pressure control in some subjects",
"BACKGROUND Despite the use of antiplatelet agents , usually aspirin , in patients who have had an ischemic stroke , there is still a substantial rate of recurrence . Therefore , we investigated whether warfarin , which is effective and superior to aspirin in the prevention of cardiogenic embolism , would also prove superior in the prevention of recurrent ischemic stroke in patients with a prior noncardioembolic ischemic stroke . METHODS In a multicenter , double-blind , r and omized trial , we compared the effect of warfarin ( at a dose adjusted to produce an international normalized ratio of 1.4 to 2.8 ) and that of aspirin ( 325 mg per day ) on the combined primary end point of recurrent ischemic stroke or death from any cause within two years . RESULTS The two r and omized study groups were similar with respect to base-line risk factors . In the intention-to-treat analysis , no significant differences were found between the treatment groups in any of the outcomes measured . The primary end point of death or recurrent ischemic stroke was reached by 196 of 1103 patients assigned to warfarin ( 17.8 percent ) and 176 of 1103 assigned to aspirin ( 16.0 percent ; P=0.25 ; hazard ratio comparing warfarin with aspirin , 1.13 ; 95 percent confidence interval , 0.92 to 1.38 ) . The rates of major hemorrhage were low ( 2.22 per 100 patient-years in the warfarin group and 1.49 per 100 patient-years in the aspirin group ) . Also , there were no significant treatment-related differences in the frequency of or time to the primary end point or major hemorrhage according to the cause of the initial stroke ( 1237 patients had had previous small-vessel or lacunar infa rcts , 576 had had cryptogenic infa rcts , and 259 had had infa rcts design ated as due to severe stenosis or occlusion of a large artery ) . CONCLUSIONS Over two years , we found no difference between aspirin and warfarin in the prevention of recurrent ischemic stroke or death or in the rate of major hemorrhage . Consequently , we regard both warfarin and aspirin as reasonable therapeutic alternatives",
"BACKGROUND The incidence of stroke in patients with acute coronary syndromes has not been clearly defined because few trials in this patient population have been large enough to provide stable estimates of stroke rates . METHODS AND RESULTS We studied the 10 948 patients with acute coronary syndromes without persistent ST-segment elevation who were r and omly assigned to placebo or the platelet glycoprotein IIb/IIIa receptor inhibitor eptifibatide in the Platelet Glycoprotein IIb/IIIa in Unstable Angina : Receptor Suppression Using Integrilin Therapy ( PURSUIT ) trial to determine stroke rates , stroke types , clinical outcomes in patients with stroke , and independent baseline clinical predictors for nonhemorrhagic stroke . Stroke occurred in 79 ( 0.7 % ) patients , with 66 ( 0.6 % ) nonhemorrhagic , 6 intracranial hemorrhages , 3 cerebral infa rct ions with hemorrhagic conversion , and 4 of uncertain cause . There were no differences in stroke rates between patients who received placebo and those assigned high-dose eptifibatide ( odds ratios and 95 % confidence intervals 0.82 [ 0.59 , 1.14 ] and 0.70 [ 0.49 , 0.99 ] , respectively ) . Of the 79 patients with stroke , 17 ( 22 % ) died within 30 days , and another 26 ( 32 % ) were disabled by hospital discharge or 30 days , whichever came first . Higher heart rate was the most important baseline clinical predictor of nonhemorrhagic stroke , followed by older age , prior anterior myocardial infa rct ion , prior stroke or transient ischemic attack , and diabetes mellitus . These factors were used to develop a simple scoring nomogram that can predict the risk of nonhemorrhagic stroke . CONCLUSIONS Stroke was an uncommon event in patients with acute coronary syndromes in the PURSUIT trial . These strokes are , however , associated with substantial morbidity and mortality rates . The majority of strokes were of nonhemorrhagic causes . Eptifibatide was not associated with an increase in intracranial hemorrhage , and no significant effect on nonhemorrhagic stroke was observed . We developed a useful nomogram for assigning baseline nonhemorrhagic stroke risk in this patient population",
"The safety and pharmacodynamic compatibility of clopidogrel with medications commonly used in patients with atherosclerosis , such as , a beta-adrenergic receptor antagonist ( atenolol ) and a calcium uptake inhibitor ( nifedipine ) were assessed . Atenolol and nifedipine interactions with clopidogrel were studied in patients with peripheral arterial obstructive disease taking a well-established regimen of nifedipine ( N group of 6 patients ) and in patients with coronary artery disease taking a well-established regimen of either atenolol ( A group of 8 patients ) or of atenolol and nifedipine ( AN group of 8 patients ) . The study was conducted as a double-blind , r and omized , crossover comparison of clopidogrel , 75 mg once daily , and placebo treatment for 7 days , with a 14-day washout between treatments . Pharmacodynamic interactions between atenolol and nifedipine , either alone or in combination , and clopidogrel were assessed primarily on the clinical control of angina or hypertension and , secondarily , by comparing the extent of inhibition of ADP ( 5 microM)-induced platelet aggregation achieved between the 3 groups . The mean number of anginal episodes per patient during the placebo week was 1.50 , 9.0 and 11.5 in the A , N and AN groups , respectively ; during the week of clopidogrel treatment , it was 1.39 , 7.3 and 9.0 , respectively , indicating no change in occurrence . Likewise , review of the use of nitrates ( long or short acting ) did not suggest any major change in usage during any period of the study . ECGs did not change between the three recording times ( at screening and at the end of each treatment period ) . Vital signs were also unchanged throughout . Percent inhibition of platelet aggregation on day 7 was 31 % in the N group , 39 % in the A group , 28 % in the AN group , and 33 % overall . In conclusion , the coadministration of clopidogrel did not interfere with the clinical control of hypertension or angina established with atenolol or nifedipine , or both . Clopidogrel retained its full antiplatelet effect , and there were no safety problems caused by the coadministration",
" Patients ( 303 ) who had had carotid territory transient ischemic attacks were r and omly assigned to aspirin or placebo treatments . Patients with amaurosis fugax responded as well to aspirin as those with hemisphere events . Patients with lesions of the appropriate carotid artery responded better to aspirin therapy than patients with no lesion or an occlusion . The aspirin effect was the same across all risk-factor groups . Smoking had no effect on clinical outcome",
"1 . The haemodynamic effects of calcium antagonists could depend at least in part on the activity of vasoactive prostanoids . 2 . We set out to study the effect of the cyclo-oxygenase inhibitor ibuprofen , 400 mg three times daily for 3 days , by a r and omised cross-over study vs placebo in 12 mild to moderate essential hypertensive patients who had been treated for 1 month with amlodipine . 3 . Blood pressure , heart rate and vascular resistances in the upper limb ( Doppler ultrasound ) were measured . Plasma renin activity and urinary aldosterone , as well as indices of renal function , were evaluated . Urinary 2,3-dinor-6-keto-PGF1 alpha and 2,3-dinor-TXB2 , as well as 6-keto-PGF1 alpha and TXB2 , were measured as indices of systemic and renal PGI2 and TXA2 synthesis . 4 . Amlodipine normalised blood pressure and reduced upper limb vascular resistances ; it did not affect urinary prostanoid excretion . Short-term combined administration of ibuprofen result ed in , by comparison with placebo , inhibition of systemic PGI2 ( -80.5 ng 24 h-1 , 95 % CI -99.2 , -61.4 ; P TXA2 ( -216.1 ng 24 h-1 , 95 % CI -276.5 , -155.8 ; P systolic ( + 7.8 mm Hg , 95 % CI + 3.1 , + 12.3 ; P diastolic ( + 3.9 mm Hg , 95 % CI + 1.2 , + 6.6 ; P blood pressure ; it had no significant effect on regional vascular resistances ( + 4.7 mm Hg ml-1 s , 95 % CI -5.6 , + 15.0 ) . Effects of ibuprofen on renal prostanoid synthesis were less marked , and there was no change in indices of renal function or hydro-electrolytic balance . ( ABSTRACT TRUNCATED AT 250 WORDS",
"Objective Differences in renal synthesis between prostagl and ins I2 and E2 , and the relationships of the amounts synthesized to renin release were investigated in patients with essential hypertension . Methods Of 12 in patients , six had low to normal plasma renin activity and six had high renin activity . Before and 30 min after intravenous injection of aspirin D , L-lysine ( 18 mg/kg ) , abdominal aortic and renal venous plasma was sample d and assayed for renin activity , 6-keto-prostagl and in F1α ( as an index of prostagl and in I2 ) , and prostagl and in E2 . Results In patients with low to normal renin activity , mean ± SD plasma levels of 6-keto-prostagl and in F1α were lower in the right and left renal veins ( 3.6 ± 1.4 and 4.1 ± 1.5 pg/ml , respectively ) than in the aorta ( 5.5 ± 2.0 pg/ml ) , but in the other patients , the levels in these veins ( 7.0 ± 2.4 and 6.5 ± 1.5 pg/ml ) were higher than in the aorta ( 5.4 ± 0.9 pg/ml ) . Plasma prostagl and in E2 levels in both veins were higher than in the aorta in both groups and , at each site , the levels were similar in the two groups . Aspirin suppressed renin release in the patients with high renin activity . Conclusions In patients with essential hypertension with low to normal renin activity , either less prostagl and in I2 than prostagl and in E2 is produced in the kidney or else more is metabolized there , and in such patients with high renin activity , the renal synthesis of prostagl and in I2 , more than that of prostagl and in E2 , seems to be related to the increased renin release",
"BACKGROUND Repeat hospitalizations of patients with atherosclerosis represent a considerable burden on the health care system . We sought to determine whether clopidogrel compared with aspirin decreases the need for rehospitalization for ischemia and bleeding . METHODS AND RESULTS The Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events ( CAPRIE ) trial was a r and omized , blinded , multicenter , trial of 19,185 patients with atherosclerotic disease manifested as recent ischemic stroke or myocardial infa rct ion or symptomatic peripheral arterial disease . Without any double-counting of events , the number of rehospitalizations for ischemic events ( defined as angina , transient ischemic attack , or limb ischemia ) or bleeding events was determined for the entire cohort . There was a significant reduction in the total number of rehospitalizations for ischemic events or bleeding with clopidogrel use compared with aspirin ( 1502 vs 1673 ; P = .010 ) over an average of 1.6 years of treatment . This reduction in rehospitalization was consistent across individual outcomes of angina , transient ischemic attack , limb ischemia , and bleeding . Compared with aspirin , clopidogrel also result ed in a 7.9 % relative risk reduction in a combined end point of vascular death , stroke , myocardial infa rct ion , or rehospitalization for ischemic events or bleeding ( 15.1 % to 13.7 % at 1 year ; P = .011 ) . Adjusting for baseline prognostic variables , clopidogrel therapy was an independent predictor for reduction of vascular death , stroke , myocardial infa rct ion , or rehospitalization for ischemic events or bleeding ( P = .009 ) . CONCLUSIONS Treatment with clopidogrel results in a significant decrease in the need for rehospitalization for ischemic events or bleeding compared with aspirin . This meaningful end point tracks well with other , more traditional measures of outcome and has incremental value beyond such end points",
"Some of the antihypertensive effects of angiotensin-converting enzyme ( ACE ) inhibitors occur through nonangiotensin II-mediated mechanisms . One of these is through decreased kinin degradation , leading to enhanced production of vasodilator arachidonic acid metabolites . It was reasoned that if ACE inhibition also leads to an increase in the production of the potent vasoconstrictor thromboxane A2 , then maneuvers that selectively inhibit thromboxane production without reducing prostagl and ins ( PG ) E2 + PGI2 might enhance the antihypertensive effect of ACE inhibition . This double-blinded , r and omized , crossover study was therefore undertaken to determine : ( 1 ) if captopril increases platelet and /or renal thromboxane production ; and ( 2 ) if low-dose aspirin enhances the antihypertensive effect of captopril . Patients with mild essential hypertension and no other significant medical problems were studied . In a double-blinded , r and om order , patients took captopril alone ( 25 mg every 12 h ) for 2 wk and captopril plus aspirin ( 75 mg/day ) for another 2 wk . Active treatment periods were preceded by 2 wk of single-blind placebo . Fifteen patients with a mean age of 53 yr and an average mean arterial pressure ( MAP ) of 114 + /- 8 ( + /- SD ) mm Hg were studied . Serum thromboxane B2 was higher ( P captopril/placebo ( 600 + /- 46 ( + /- SE ) pg/mL ) than during the two washout periods combined ( 420 + /- 57 and 553 + /- 78 ) and was lowest ( P captopril/aspirin ( 302 + /- 36 ) . Captopril treatment significantly increased the urinary excretion of PGE2 ( P = 0.038 ) . Captopril/placebo significantly lowered MAP ( P captopril caused no additional lowering of MAP ( 105.2 + /- 2.8 mm Hg ) . It was concluded that treatment with captopril does increase platelet thromboxane production . However , lowering platelet thromboxane with low doses of aspirin may not enhance the antihypertensive effect of captopril",
"The effects of non-steroidal anti-inflammatory drugs ( NSAIDs ) on the blood pressure and renal function of essential hypertensive patients depend on the specific type of NSAID and antihypertensive drug administered . Twelve patients with essential hypertension , aged 35 to 59 years , stabilized ( blood pressure less than 140/90 mmHg ) with captopril , received ketoprofen ( 100 mg bid for 7 days ) or matching placebo in a r and omized double-blind cross-over fashion . A 3-week wash-out period was included between treatment periods . Blood pressure on the first and last days of the placebo treatment period ( 137 + /- 7 (SD)/80 + /- 8 and 139 + /- 11/81 + /- 9 mmHg ) was similar to respective values during ketoprofen therapy ( 136 + /- 10/79 + /- 7 and 143 + /- 10/81 + /- 9 mmHg ) . The mean differences in systolic and diastolic blood pressures , at the end of the treatment periods , between ketoprofen and placebo were 4 ( 95 % confidence intervals -5 , + 13 ) and 0 (-8 , + 8) mmHg , respectively . Ketoprofen had no effect on 24-h urinary sodium excretion ( 160 + /- 33 and 147 + /- 39 mmol/24 h for ketoprofen and placebo , respectively ) . Ketoprofen was without effect on glomerular filtration rate , renal plasma flow and filtration fraction . In conclusion , our data suggest that ketoprofen is a safe choice when short-term treatment with a NSAID is indicated in an essential hypertensive patient treated with a converting enzyme inhibitor such as captopril",
"A double-blind study was established to evaluate the platelet aggregation inhibiting effect of ticlopidine on the course of ocular vein occlusions . 35 patients with recent central retinal vein occlusions and 54 patients with retinal branch vein occlusions were treated for 6 months . Various ophthalmological and clinical -chemical parameters , including fluorescence angiography , were assessed . Compared with placebo therapy a significant improvement in visual acuity was observed with ticlopidine for branch vein occlusions ; the same trend was seen for the central retinal vein occlusions . Increased ADP-induced platelet aggregation was frequently found : in 72 % of the central retinal vein occlusions and 70 % of the branch vein occlusions . For the Wu and Hoak test , these numbers were respectively 74 % and 67 % . Hypertension was seen in 55 % of all occlusions , hyperlipaemia in 33 % , and diabetes in 29 % . The effect of ticlopidine was most pronounced in patients with increased platelet aggregation and least obvious in hyperlipaemia . Hypertension and diabetes did not apparently influence Ticlopidine 's effects . It is concluded that the platelet aggregation inhibitor ticlopidine is effective in the treatment of recent ocular vein occlusions",
"The use of cyclooxygenase inhibitors has been seen to reduce the efficacy of many antihypertensive drugs . However , cyclooxygenase inhibitors are normally non-selective because they affect both vascular tissue , where the endothelial prostanoids exert principally a vasodilatory action , and the kidneys , where they also play an important role in regulating hydroelectrolytic metabolism by redistribution of intraparenchymal flow . To evaluate the relative importance of vascular district in the hypertensive patient , we administered ibuprofen - a drug acting with only a minimal antagonist activity . A group of 20 male hypertensives were r and omly allocated , according to a single-blind protocol , to treatment with amlodipine ( A , 10 mg/day ) or lisinopril ( L , 20 mg/day ) . Blood pressure was significantly reduced after 30 days , with a mean difference of -21.75 mmHg for systolic blood pressure ( SBP ) ( 95 % confidence interval ( Cl ) : -27.46 to -16.04 ; P diastolic blood pressure ( DBP ) ( 95 % Cl : -17.13 to -11.17 ; P Brachial artery compliance showed a mean increase of 1.657 x 10(-7 ) dyn-1 cm(4 ) ( 95 % Cl : 1.188 to 2.126 ; P forearm resistances showed a mean decrease of -41.973 mmHg ml(-1)s ( 95 % Cl : -75.479 to -8.467 ; P = 0.017 ) . Changes in compliance were significantly related to those in SBP ( r= -0.546 ; P= 0.013 ) . The administration of ibuprofen ( 400 mg , three times a day for 3 days ) was accompanied by a slight but significant increase in SBP , but not in brachial artery compliance or forearm resistances . Only SBP was affected , showing a mean increase of 4.25 mmHg ( 95 % Cl : 1.26 to 7.24 ; P = 0.008 ) . There was also reduced urinary excretion of PGI(2 ) and TXA(2 ) metabolites . The mean change in 6-keto-PGF(1 alpha ) and 2,3-dinor-6-keto-PGF(1 alpha ) was 45.71 ng per g urinary creatinine ( uCr ) ( 95 % Cl : -0.16 to-91.25 ; P= 0.049 ) and -73.17 ng ( g uCr)(-1 ) ( 95 % Cl : -38.81 to -107.53 ; P mean decrease in TXA(2 ) catabolites was highly significant : -39.2 ng ( g uCr)(-1 ) ( 95 % Cl : -18.17 to-60.22 ; P changes in blood pressure and those in urinary 2,3-dinor-6-keto-PGF(1alpha ) excretion , irrespective of antihypertensive regimen . This suggests that , in the hypertensive patient treated with NSAIDs , inhibition of vascular prostanoid synthesis may play an important role in countering the efficacy of an important vascular tone regulatory mechanism",
"Aspirin at low doses is used as an inhibitor of platelet aggregation and is frequently administered to essential hypertensive patients with arterial thrombotic complications . However , it is unknown whether aspirin can modify blood pressure values either in treated or untreated hypertensive patients , as described for other non steroidal anti-inflammatory drugs . Thus 30 patients . 10 with mild uncomplicated and untreated essential hypertension , 10 with essential hypertension under chronic treatment with captopril , 50 mg bid , and 10 with essential hypertension under chronic treatment with atenolol , 100 mg oid , received aspirin , 100 mg oid , and the corresponding placebo for one month , according to a double blind r and omized cross-over design . At the end of each treatment , blood pressure , heart rate , generated serum thromboxane B2 and urinary excretion of thromboxane B2 and 6 keto prostagl and in F1 alpha and plasma renin activity were measured . Both in treated and untreated essential hypertensive patients , aspirin administration did not affect blood pressure , heart rate and urinary 6 keto prostagl and in F1 alpha , while it significantly reduced serum and urinary excretion of thromboxane B2 and plasma renin activity . In conclusion , while the present data confirm that low doses of aspirin selectively inhibit thromboxane B2 synthesis , they indicate that aspirin at 100 mg oid can be administered to treated and untreated essential hypertensive patients without any harmful effect on blood pressure values",
"Background Arthritis and hypertension are common comorbid conditions affecting elderly adults . Use of nonsteroidal anti-inflammatory drugs in patients treated with antihypertensive medication can lead to destabilization of blood pressure control and other cardiorenal events . The potential for similar interactions with cyclooxygenase-2–specific inhibitors has not been fully explored . The authors evaluated the cardiorenal safety of two new cyclooxygenase-2–specific inhibitors , celecoxib and rofecoxib . Methods This study was a 6-week , r and omized , parallel-group , double-blind trial in patients with osteoarthritis who were ≥65 years of age and were taking antihypertensive agents . Patients received once-daily celecoxib 200 mg or rofecoxib 25 mg . The primary endpoints were the development of edema , changes in systolic blood pressure , and changes in diastolic blood pressure as measured at any time point in the study . Measurements occurred at baseline and after 1 , 2 , and 6 weeks of treatment . Findings Eight hundred ten patients received study medication ( celecoxib , n = 411 ; rofecoxib , n = 399 ) . Nearly twice as many rofecoxib-compared with celecoxib-treated patients experienced edema ( 9.5 % vs. 4.9 % , P = 0.014 ) . Systolic blood pressure increased significantly in 17 % of rofecoxib-compared with 11 % of celecoxib-treated patients ( P = 0.032 ) at any study time point . Diastolic blood pressure increased in 2.3 % of rofecoxib-compared with 1.5 % of celecoxib-treated patients ( P = 0.44 ) . At week 6 , the change from baseline in mean systolic blood pressure was + 2.6 mmHg for rofecoxib compared with −0.5 mmHg for celecoxib ( P = 0.007 ) . Conclusions Patients taking antihypertensive therapy and receiving cyclooxygenase-2–specific inhibitors should be monitored for the development of cardiorenal events . Patients receiving celecoxib experienced less edema and less destabilization of blood pressure control compared with those receiving rofecoxib ",
"There are conflicting reports on the interaction of aspirin with angiotensin-converting enzyme inhibitors in heart failure and systemic hypertension . A post hoc analysis of the Captopril and Thrombolysis Study ( CATS ) study was conducted . At r and omization , 94 patients ( 31.5 % ) took aspirin . In patients who took aspirin , the cumulative alpha-hydroxy butyrate dehydrogenase release was 1,151 + /- 132 IU/L in patients r and omized to captopril compared with 1,401 + /- 136 IU/L in patients r and omized to placebo ( difference -250 + /- 189 [ 95 % confidence interval ( CI ) -620 to 120 ] ) . This difference was comparable to the difference in patients who did not use aspirin ( -199 + /- 147 [ 95 % CI -488 to 897 ] ) . One year after acute myocardial infa rct ion , an increase in left ventricular end-diastolic volume index of 2.2 + /- 3.0 ml/m2 in captopril-treated and 1.9 + /- 2.9 ml/m2 in placebo-treated patients was observed in patients who took aspirin ( difference 0.4 + /- 4.2 [ 95 % CI -8.2 to 8.9 ] ) . This difference was also comparable to the difference in patients who did not take aspirin ( 2.2 + /- 3.8 [ 95 % CI -5.2 to 9.7 ] ) . One year after acute myocardial infa rct ion , patients who did take aspirin had a mean change in LV end-diastolic volume index of 2.1 + /- 2.1 ml/m2 compared with 8.4 + /- 1.9 ml/m2 in patients who did not use aspirin ( p = 0.02 ) . Thus , aspirin does not attenuate the acute and long-term effects of angiotensin-converting enzyme inhibition after acute myocardial infa rct ion , but independently reduces LV dilation after myocardial infa rct ion",
"Thirty-seven patients affected by polycythaemia rubra vera ( PRV ) and with at least one additional thrombotic risk factor ( overt vascular disease , diabetes mellitus , treated hypertension , smoking habit , plasma hyperviscosity , hyperfibrinogenemia ) were enrolled in a double-blind r and omized placebo-controlled study , and 18 were given ticlopidine 250 mg , b.i.d . , for 60 days . All the patients had previously been su bmi tted to cytoreduction , and PRV was under control in all cases at the start of the study . During the study , the haematological parameters were controlled every 15 days , and venesection was performed if haematocrit was greater than 46 % . Whole blood viscosity , at low and high shear rates , plasma viscosity , and fibrinogen were measured on days 0 and 60 . In the ticlopidine group , we recorded a significant 13.14 % reduction of the mean fibrinogen level after treatment ( 390 + /- 63 vs. 449 + /- 97 mg/dl , p less than 0.01 ) . All the other haemorheological parameters were not significantly modified by ticlopidine treatment , nor were there significant modifications recorded in the placebo group . Our study shows that ticlopidine may reduce a probable thrombotic risk factor ( hyperfibrinogenemia ) in PRV patients",
"A comparative study of the prevention of recurrences of cerebral transient ischemic attacks during a 6-month observation period was conducted in 73 patients treated with a combination of acetylsalicylic acid and dipyridamole ( ASAD , 1,050 mg + 150 mg/day ) and in 65 patients treated with pentoxifylline ( PTX 1,200 mg/day , Trental 400 t.d.s . ) . The patients were r and omly assigned to the treatments . Risk factor analysis showed high prevalence of arterial hypertension , hyperlipidemia and smoking in these patients . The two groups were matched in terms of age , sex , blood pressure and site of TIA origin ( carotid 63 % in the ASAD , 65 % in the PTX group ) . 23 ASAD patients and 9 PTX patients suffered a recurrence . There were 4 nonfatal stroke events with ASAD and 2 with PTX . 80 recurrent TIAs were recorded in 19 ASAD patients compared with 19 such episodes in 9 PTX subjects . The morbidity rates ( life table analysis ) were significantly lower ( p less than 0.05 ) in the PTX group . The results of the study point to a preventive effect of PTX in terms of the reduction in TIA recurrences"
] |
4116cbee-06ff-11f0-808a-c43d1ab1c353
|
Objectives Sarcopenia , defined as an age-associated loss of skeletal muscle function and muscle mass , occurs in approximately 6 - 22 % of older adults . This paper presents evidence -based clinical practice guidelines for screening , diagnosis and management of sarcopenia from the task force of the International Conference on Sarcopenia and Frailty Research ( ICSFR ) . Methods To develop the guidelines , we drew upon the best available evidence from two systematic review s paired with consensus statements by international working groups on sarcopenia . Eight topics were selected for the recommendations : ( i ) defining sarcopenia ; ( ii ) screening and diagnosis ; ( iii ) physical activity prescription ; ( iv ) protein supplementation ; ( v ) vitamin D supplementation ; ( vi ) anabolic hormone prescription ; ( vii ) medications under development ; and ( viii ) research . The ICSFR task force evaluated the evidence behind each topic including the quality of evidence , the benefitharm balance of treatment , patient preferences/values , and cost-effectiveness . Recommendations were grade d as either strong or conditional ( weak ) as per the GRADE ( Grading of Recommendations Assessment , Development and Evaluation ) approach . Consensus was achieved via one face-to-face workshop and a modified Delphi process . Recommendations We make a conditional recommendation for the use of an internationally accepted measurement tool for the diagnosis of sarcopenia including the EWGSOP and FNIH definitions , and advocate for rapid screening using gait speed or the SARC-F. To treat sarcopenia , we strongly recommend the prescription of resistance-based physical activity , and conditionally recommend protein supplementation/a protein-rich diet . No recommendation is given for Vitamin D supplementation or for anabolic hormone prescription . There is a lack of robust evidence to assess the strength of other treatment options
|
[
"BACKGROUND Cancer-induced muscle wasting begins early in the course of a patient 's malignant disease , result ing in declining physical function and other detrimental clinical consequences . This r and omised , double-blind , placebo-controlled phase 2 trial assessed the efficacy and safety of enobosarm , a selective and rogen receptor modulator , in patients with cancer . METHODS We enrolled male ( > 45 years ) and female ( postmenopausal ) patients with cancer who were not obese and who had at least 2 % weight loss in the previous 6 months . Participants were r and omly assigned ( 1:1:1 ratio , by computer generated list , block size three , stratified by cancer type ) to receive once-daily oral enobosarm 1 mg , 3 mg , or placebo for up to 113 days at US and Argentinian oncology clinics . The sponsor , study personnel , and participants were masked to assignment . The primary endpoint was change in total lean body mass from baseline , assessed by dual-energy x-ray absorptiometry . Efficacy analyses were done only in patients who had a baseline and an on-treatment assessment in the protocol -specified window of within 10 days before baseline or first study drug , and within 10 days of day 113 or end of study ( evaluable efficacy population ) . Adverse events and other safety measurements were assessed in the intention-to-treat ( safety ) population . This trial is registered with Clinical Trials.gov , number NCT00467844 . FINDINGS Enrolment started on July 3 , 2007 , and the last patient completed the trial on Aug 1 , 2008 . 159 patients were analysed for safety ( placebo , n=52 ; enobosarm 1 mg , n=53 ; enobosarm 3 mg , n=54 ) . The evaluable efficacy population included 100 participants ( placebo , n=34 ; enobosarm 1 mg , n=32 ; enobosarm 3 mg , n=34 ) . Compared with baseline , significant increases in total lean body mass by day 113 or end of study were noted in both enobosarm groups ( enobosarm 1 mg median 1·5 kg , range -2·1 to 12·6 , p=0·0012 ; enodosarm 3 mg 1·0 kg , -4·8 to 11·5 , p=0·046 ) . Change in total lean body mass within the placebo group ( median 0·02 kg , range -5·8 to 6·7 ) was not significant ( p=0·88 ) . The most common serious adverse events were malignant neoplasm progression ( eight of 52 [ 15 % ] with placebo vs five of 53 [ 9 % ] with enobosarm 1 mg vs seven of 54 [ 13 % ] with enobosarm 3 mg ) , pneumonia ( two [ 4 % ] vs two [ 4 % ] vs three [ 6 % ] ) , and febrile neutropenia ( three [ 6%vs one [ 2 % ] vs none ) . None of these events were deemed related to study drug . INTERPRETATION Cancer cachexia is an unmet medical need and our data suggest that use of enobosarm might lead to improvements in lean body mass , without the toxic effects associated with and rogens and progestational agents . FUNDING GTx",
"BACKGROUND Age-related losses of muscle mass , strength , and function ( sarcopenia ) pose significant threats to physical performance , independence , and quality of life . Nutritional supplementation could positively influence aspects of sarcopenia and thereby prevent mobility disability . OBJECTIVE To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of sarcopenia . DESIGN A multicenter , r and omized , controlled , double-blind , 2 parallel-group trial among 380 sarcopenic primarily independent-living older adults with Short Physical Performance Battery ( SPPB ; 0 - 12 ) scores between 4 and 9 , and a low skeletal muscle mass index . The active group ( n = 184 ) received a vitamin D and leucine-enriched whey protein nutritional supplement to consume twice daily for 13 weeks . The control group ( n = 196 ) received an iso-caloric control product to consume twice daily for 13 weeks . Primary outcomes of h and grip strength and SPPB score , and secondary outcomes of chair-st and test , gait speed , balance score , and appendicular muscle mass ( by DXA ) were measured at baseline , week 7 , and week 13 of the intervention . RESULTS H and grip strength and SPPB improved in both groups without significant between-group differences . The active group improved more in the chair-st and test compared with the control group , between-group effect ( 95 % confidence interval ) : -1.01 seconds ( -1.77 to -0.19 ) , P = .018 . The active group gained more appendicular muscle mass than the control group , between-group effect : 0.17 kg ( 0.004 - 0.338 ) , P = .045 . CONCLUSIONS This 13-week intervention of a vitamin D and leucine-enriched whey protein oral nutritional supplement result ed in improvements in muscle mass and lower-extremity function among sarcopenic older adults . This study shows proof-of-principle that specific nutritional supplementation alone might benefit geriatric patients , especially relevant for those who are unable to exercise . These results warrant further investigations into the role of a specific nutritional supplement as part of a multimodal approach to prevent adverse outcomes among older adults at risk for disability",
"OBJECTIVES To investigate the effects of exercise and /or nutritional supplementation on body composition , blood components , and physical function in community-dwelling elderly Japanese women with sarcopenic obesity . DESIGN R and omized controlled trial . SETTING Urban community in Tokyo , Japan . PARTICIPANTS Among 1213 community-dwelling elderly women over 70 years of age , 307 were defined with sarcopenic obesity , and 139 women participated in the study . INTERVENTION Participants were r and omly assigned to one of four intervention groups . The exercise and nutrition ( Ex + N ) and exercise only ( Ex ) groups attended 60-minute exercise classes twice a week for 3 months . The Ex + N and nutrition only ( N ) groups were provided with essential amino acid supplementation and tea fortified with catechins to be taken daily for 3 months . Health education classes were provided to the control ( HE ) group every 2 weeks . MEASUREMENTS Bioelectric impedance analysis was used to measure body composition . Skeletal muscle mass index was calculated using measures of muscle mass and height . Physical function measures included grip strength , knee extension strength , usual walking speed , and walking parameters ( stride , step length , width , walking angles ) . Blood sample s were obtained to analyze levels of albumin , triglycerides , cholesterol , hemoglobin A1c , leptin , cystatin C , vitamin D , interleukin-6 , and high-sensitivity C-reactive protein . RESULTS Significant between-group × time interactions were observed in usual walking speed ( P = .012 ) , stride ( P = .004 ) , right step length ( P = .003 ) , average number of steps ( P = .029 ) , and vitamin D ( P decreased total body fat mass ( P = .036 ) and increased stride ( P = .038 ) and vitamin D ( P reductions in trunk fat were observed in the Ex group compared with HE ( P = .014 ) . The Ex + N and Ex interventions were over four times as likely ( odds ratio [ 95 % confidence interval ] ) to reduce body fat mass than the HE group ( 4.42 [ 1.21 - 16.19 ] ; 4.50 [ 1.13 - 17.9 ] , respectively ) . Significant odds ratios of the Ex + N intervention improving walking speed ( 3.05 [ 1.01 - 9.19 ] ) , vitamin D ( 14.22 [ 1.64 - 123.02 ] ) , and leptin ( 3.86 [ 1.19 - 12.47 ] ) were also observed . CONCLUSION Although exercise and nutrition have beneficial effects on individual variables of body composition , blood components , and physical function , improvements in muscle mass and variable combinations such as percent fat + skeletal muscle mass index or percent fat + physical functions were not observed in this population . Further large-scale and long-term investigation is necessary",
"Objective : To study activin signaling and its blockade in sporadic inclusion body myositis ( sIBM ) through translational studies and a r and omized controlled trial . Methods : We measured transforming growth factor β signaling by SMAD2/3 phosphorylation in muscle biopsies of 50 patients with neuromuscular disease ( 17 with sIBM ) . We tested inhibition of activin receptors IIA and IIB ( ActRII ) in 14 patients with sIBM using one dose of bimagrumab ( n = 11 ) or placebo ( n = 3 ) . The primary outcome was the change in right thigh muscle volume by MRI at 8 weeks . Lean body mass , strength , and function were secondary outcomes . Twelve of the patients ( 10 bimagrumab , 2 placebo ) participated in a subsequent 16-week observation phase . Results : Muscle SMAD2/3 phosphorylation was higher in sIBM than in other muscle diseases studied ( p = 0.003 ) . Eight weeks after dosing , the bimagrumab-treated patients increased thigh muscle volume ( right leg + 6.5 % compared with placebo , p = 0.024 ; left leg + 7.6 % , p = 0.009 ) and lean body mass ( + 5.7 % compared with placebo , p = 0.014 ) . Subsequently , bimagrumab-treated patients had improved 6-minute walking distance , which peaked at 16 weeks ( + 14.6 % , p = 0.008 ) compared with placebo . There were no serious adverse events ; the main adverse events with bimagrumab were mild acne and transient involuntary muscle contractions . Conclusions : Transforming growth factor β superfamily signaling , at least through ActRII , is implicated in the pathophysiology of sIBM . Inhibition of ActRII increased muscle mass and function in this pilot trial , offering a potential novel treatment of sIBM . Classification of evidence : This study provides Class I evidence that for patients with inclusion body myositis , bimagrumab increases thigh muscle volume at 8 weeks",
"Protein supplementation in combination with resistance training may increase muscle mass and muscle strength in elderly subjects . The objective of this study was to assess the influence of post-exercise protein supplementation with collagen peptides v. placebo on muscle mass and muscle function following resistance training in elderly subjects with sarcopenia . A total of fifty-three male subjects ( 72·2 ( sd 4·68 ) years ) with sarcopenia ( class I or II ) completed this r and omised double-blind placebo-controlled study . All the participants underwent a 12-week guided resistance training programme ( three sessions per week ) and were supplemented with either collagen peptides ( treatment group ( TG ) ) ( 15 g/d ) or silica as placebo ( placebo group ( PG ) ) . Fat-free mass ( FFM ) , fat mass ( FM ) and bone mass ( BM ) were measured before and after the intervention using dual-energy X-ray absorptiometry . Isokinetic quadriceps strength ( IQS ) of the right leg was determined and sensory motor control ( SMC ) was investigated by a st and ardised one-leg stabilisation test . Following the training programme , all the subjects showed significantly higher ( P . The effect was significantly more pronounced in subjects receiving collagen peptides : FFM ( TG + 4·2 ( sd 2·31 ) kg/PG + 2·9 ( sd 1·84 ) kg ; P ) ; IQS ( TG + 16·5 ( sd 12·9 ) Nm/PG + 7·3 ( sd 13·2 ) Nm ; P ) ; and FM ( TG –5·4 ( sd 3·17 ) kg/PG –3·5 ( sd 2·16 ) kg ; P compared with placebo , collagen peptide supplementation in combination with resistance training further improved body composition by increasing FFM , muscle strength and the loss in FM",
"BACKGROUND Cancer anorexia-cachexia syndrome is associated with increased morbidity and mortality . Anamorelin is an oral ghrelin-receptor agonist with appetite-enhancing and anabolic activity . We assessed the effects of anamorelin on body composition , strength , quality of life , biochemical markers , and safety in patients with cancer anorexia-cachexia . METHODS Data were pooled , a priori , from two completed phase 2 , multicentre , placebo-controlled , double-blind trials in patients with advanced or incurable cancer and weight loss of 5 % or more . Patients were stratified by weight loss severity ( 5 - 15 % , > 15 % ) and r and omly allocated ( 1:1 ) with a computer-generated r and omisation schedule to anamorelin hydrochloride 50 mg or placebo once-daily for 12 weeks . Primary outcome was lean body mass by dual-energy x-ray absorptiometry over the 12 week treatment period in eligible patients who had at least one dose of study drug and post-treatment efficacy assessment . We assessed safety in all patients who received at least one dose of study drug . The trials are registered with Clinical Trials.gov , numbers NCT00219817 and NCT00267358 . FINDINGS Between June 29 , 2005 , and Oct 26 , 2006 , we enrolled 44 patients in the anamorelin group and 38 patients in the placebo group . 74 patients were eligible for the efficacy analyses . Over 12 weeks , lean body mass increased in 38 patients in the anamorelin group by a least-squares mean of 1.89 kg ( 95 % CI 0.84 to 2.95 ) compared with a decrease of a least-squares mean of -0.20 kg ( -1.23 to 0.83 ) for 36 patients in the placebo group ( difference 2.09 kg [ 0.94 - 3.25 ] ; p=0.0006 ) . 42 ( 95 % ) of 44 patients treated with anamorelin and 33 ( 87 % ) of 38 patients treated with placebo had adverse events . The most common grade 3 - 4 adverse events ( treatment-related or not ) in the anamorelin group were fatigue , asthenia , atrial fibrillation , and dyspnoea ( two [ 5 % ] each ) ; in the placebo group , such events were pneumonia ( three [ 8 % ] ) and anaemia , thrombocytopenia , abdominal pain , anxiety , and dyspnoea ( two [ 5 % ] each ) . INTERPRETATION Anamorelin treatment for 12 weeks had a favourable clinical response profile in patients with cancer anorexia-cachexia syndrome . These findings support further investigation in this setting . FUNDING Helsinn Therapeutics ( US ) , Helsinn Healthcare SA",
"BACKGROUND Recent evidence suggests that nutritional interventions may improve muscle outcomes in malnutrition and sarcopenia . OBJECTIVES We evaluated the effects of 2 high- quality oral nutritional supplements ( ONS ) differing in amount and type of key nutrients in older adult men and women . DESIGN A multicenter , r and omized , double-blinded , controlled clinical trial . PARTICIPANTS Malnourished and sarcopenic men and women , 65 years and older ( n = 330 ) . INTERVENTION A 24-week intervention period with 2 energy-rich ( 330 kcal ) ONS treatment groups : Control ONS ( CONS , 14 g protein ; 147 IU vitamin D3 ) versus Experimental ONS ( EONS , 20 g protein ; 499 IU vitamin D3 ; 1.5 g CaHMB ) taken twice daily . Both ONS also contained other vitamins , minerals , and nutrients in varying amounts . MEASUREMENTS Isokinetic peak torque ( PT , Nm ) leg strength , grip strength ( kg ) , and gait speed ( m·s-1 ) were assessed at baseline and 12 and 24 weeks . Left and right leg muscle mass ( LMM , kg ) were assessed by dual-energy x-ray absorptiometry ( DXA ) . Muscle quality ( MQ ) was leg strength expressed relative to the tested LMM ( Nm·kg-1 ) . Subgroup analyses were performed : severe sarcopenia ( low skeletal mass index , low grip strength [ Both ONS groups ( EONS and CONS ) improved PT , MQ , grip strength , and gait speed from baseline with no treatment differences . Those with severe sarcopenia ( 44 % ) exhibited lower baseline PT and MQ , with no differences in strength improvements between treatments . However , participants with mild-moderate sarcopenia exhibited higher baseline PT and MQ , with differences in strength improvements at 12 weeks ( EONS > CONS , P = .032 ) in those with normal grip strength . There were no treatment differences based on sarcopenic severity for either grip strength or gait speed . CONCLUSION ONS improved strength outcomes in malnourished older adults with sarcopenia . In those with mild-moderate sarcopenia , but not severe sarcopenia , consumption of the EONS improved leg muscle strength and quality compared with the st and ard CONS",
"Myostatin is an endogenous negative regulator of muscle growth and a novel target for muscle diseases . We conducted a safety trial of a neutralizing antibody to myostatin , MYO‐029 , in adult muscular dystrophies ( Becker muscular dystrophy , facioscapulohumeral dystrophy , and limb‐girdle muscular dystrophy )",
"BACKGROUND Progressive resistance exercise training ( PRT ) has been shown to increase muscle strength and fat-free mass ( FFM ) in elderly persons . Limited information is available regarding the effects of PRT on lean and fat mass in frail elderly persons . METHODS Ninety-one community-dwelling sedentary men and women , 78 years and older with physical frailty ( defined using st and ardized objective criteria ) were enrolled in a 9-month trial of exercise training ( ET ) . Physical frailty was defined as having 2 of the 3 following criteria : modified Physical Performance Test score between 18 and 32 , peak aerobic power between 10 and 18 ml/kg/min , or self-report of difficulty or assistance with two instrumental activities of daily living or one basic activity of daily living . Participants were r and omly assigned to either a control ( CTL ) group that performed a low intensity home exercise program or a supervised ET group that performed 3 months of low intensity exercise and 3 months of PRT . RESULTS After completion of PRT , ET participants had greater improvements than did CTL participants in maximal voluntary force production for knee extension ( mean Delta + 5.3 + /- 13 ft/lb vs + 1.1 + /- 11 ft/lb , p = .05 ) , measured using isokinetic dynamometry . Total body FFM ( measured using dual energy x-ray absorptiometry ) increased in the ET group , but not in the CTL group ( mean Delta + 0.84 + /- 1.4 kg vs + 0.01 + /- 1.5 kg , p = .005 ) . Total , trunk , intra-abdominal , and subcutaneous fat mass ( measured using dual energy x-ray absorptiometry and (1)H-magnetic resonance imaging ) did not change in response to PRT . CONCLUSIONS Three months of supervised PRT induced improvements in maximal voluntary thigh muscle strength and whole body FFM in frail , community-dwelling elderly women and men . This supervised exercise program may not be sufficient to reduce whole-body or intra-abdominal fat area in this population",
"INTRODUCTION ACE-031 is a soluble form of activin receptor type IIB ( ActRIIB ) . ACE-031 promotes muscle growth by binding to myostatin and other negative regulators of muscle mass . METHODS This double-blind , placebo-controlled study evaluated the safety , pharmacokinetics , and pharmacodynamics of ACE-031 in 48 healthy , postmenopausal women r and omized to receive 1 dose of ACE-031 ( 0.02 - 3 mg/kg s.c . ) or placebo ( 3:1 ) . RESULTS ACE-031 was generally well-tolerated . Adverse events included injection site erythema . Mean ACE-031 AUC(0-∞ ) and C(max ) increased linearly with dose ; mean T(½ ) was 10 - 15 days . Statistically significant increases in mean total body lean mass ( 3.3 % ; P = 0.03 , by DXA ) and thigh muscle volume ( 5.1 % ; P = 0.03 , by MRI ) were observed at day 29 in the 3 mg/kg group . Statistically significant changes in serum biomarkers suggest ACE-031 also improved bone and fat metabolism . CONCLUSIONS Single-dose ACE-031 treatment was generally well-tolerated and result ed in increases in muscle mass in healthy postmenopausal women",
"OBJECTIVES The aim of this study was to evaluate the association between serum levels of 25(OH ) vitamin D3 with midupper arm muscle circumference ( MUAMC ) , h and grip strength and length of hospital stay ( LOS ) after hip fracture . METHODS In total , 102 consecutive patients with hip fracture over the age of 65 were admitted to the orthopedic unit and prospect ively evaluated . All of the patients were treated according to specific protocol s depending on the type of fracture . Anthropometric measurements and h and grip strength were performed , and blood sample s were taken for serum biochemistry and 25(OH ) vitamin D3 analysis within the first 72 h of admission . All of the patients were followed during their hospital stay , and the length of stay was recorded . RESULTS Of the patients , two were excluded because of pathologic fractures . In total , 100 patients with a mean age of 80 ± 7 y were included in the analysis . Among these patients , 73 % were female , and 37 % had vitamin D deficiency . The median LOS was 7 ( 5 - 11 ) d. Patients with vitamin D deficiency had lower h and grip strength in univariate analysis . In the multiple linear regression analysis with robust st and ard error , serum vitamin D levels adjusted by age and sex were associated with h and grip strength but not with MUAMC and LOS after hip fracture . CONCLUSIONS In conclusion , vitamin D serum levels were associated with h and grip strength but not with muscle mass or length of hospital stay after hip fracture",
"BACKGROUND AND AIMS sarcopenia has been indicated as a reliable marker of frailty and poor prognosis among the oldest individuals . We evaluated the impact of sarcopenia on the risk of all-cause death in a population of frail older persons living in community . METHODS we analysed data from the Aging and Longevity Study , a prospect i ve cohort study that collected data on all subjects aged 80 years and older residing in the Sirente geographic area ( n = 364 ) . The present analysis was conducted among those subjects who were between 80 and 85 years of age at the time of the baseline assessment ( n = 197 ) . The main outcome measure was all-cause mortality over 7-year follow-up . According to the European Working Group on Sarcopenia in Older People ( EWGSOP ) criteria , the diagnosis of sarcopenia required the documentation of low muscle mass and the documentation of either low muscle strength or low physical performance . Cox proportional regression models were used to estimate crude and adjusted hazard ratios and 95 % confidence intervals of death by the presence of sarcopenia . RESULTS using the EWGSOP-suggested criteria , 43 subjects with sarcopenia ( 21.8 % ) were identified . During the 7-year follow-up , 29 ( 67.4 % ) participants died among subjects with sarcopenia compared with 63 subjects ( 41.2 % ) without sarcopenia ( P activities of daily living ( ADL ) impairment , body mass index , hypertension , congestive heart failure , chronic obstructive pulmonary disease , number of diseases , TNF-α , participants with sarcopenia had a higher risk of death for all causes compared with non-sarcopenic subjects ( HR : 2.32 , 95 % CI : 1.01 - 5.43 ) . CONCLUSIONS our results obtained from a representative sample of very old and frail subjects show that sarcopenia is associated with mortality , independently of age and other clinical and functional variables",
"BACKGROUND / OBJECTIVE : We aim ed to examine the accuracy of segmental multi-frequency bioelectrical impedance analysis ( SMF-BIA ) for the assessment of whole-body and appendicular fat mass ( FM ) and lean soft tissue mass ( LM ) in frail older women , using dual-energy X-ray absorptiometry ( DXA ) as a reference method .SUBJECTS/ METHODS : All 129 community-dwelling Japanese frail older women with a mean age of 80.9 years ( range , 75–89 years ) from the Frailty Intervention Trial were recruited . The agreements between SMF-BIA and DXA for whole-body and appendicular body composition were assessed using simple linear regression and Bl and –Altman analysis . RESULTS : High coefficients of determination ( R2 ) for whole-body FM ( R2=0.94 , s.e . of estimate (SEE)=1.2 kg ) , whole-body LM ( R2=0.85 , SEE=1.4 kg ) , and appendicular FM ( R2=0.82 , SEE=1.1 kg ) were observed between SMF-BIA and DXA . The R2 coefficient for appendicular LM was moderate ( R2=0.76 , SEE=0.8 kg ) . Bl and –Altman plots demonstrated that there was systematic ( constant ) bias ( that is , DXA minus SMF-BIA ) with overestimation of whole-body FM ( bias=−1.2 kg , 95 % confidence interval (CI)=−1.5 to −0.1 ) and underestimation of whole-body LM ( bias=2.1 kg , 95 % CI=1.8–2.3 ) by SMF-BIA . Similar , the appendicular measurements also demonstrated systematic bias with overestimation of appendicular FM ( bias=−0.3 kg , 95 % CI=−0.5 to −0.1 ) and underestimation of whole-body LM ( bias=1.5 kg , 95 % CI=1.4–1.7 ) by SMF-BIA . In addition , the individual level accuracy demonstrated a non-proportional bias for whole-body LM ( r=0.08 , P=0.338 ) and appendicular FM ( r=0.07 , P=0.413 ) . CONCLUSIONS : SMF-BIA had acceptable accuracy for the estimation of whole-body and appendicular FM and LM in frail older women , although SMF-BIA underestimated LM and overestimated FM relative to DXA",
"CONTEXT Myostatin is a negative regulator of muscle growth . And rogen deprivation ( ADT ) is associated with muscle loss and increased body fat , and currently available therapies have limited efficacy to treat this complication . The antimyostatin peptibody ( AMG 745/Mu-S ) markedly attenuated muscle loss and decreased fat accumulation in orchiectomized mice . OBJECTIVE The objective of the study was to evaluate the safety , pharmacokinetics , and muscle efficacy of AMG 745 in men undergoing ADT for nonmetastatic prostate cancer . METHODS This was a r and omized , blinded , placebo-controlled , multiple-dose , phase 1 study of AMG 745 given for 28 days . The end point of percentage change from baseline in lean body mass ( LBM ) as assessed by dual x-ray absorptiometry was prespecified . RESULTS Rates of adverse events ( AMG 745 vs placebo ) were the following : diarrhea ( 13 % vs 9 % ) , fatigue ( 13 % vs 4 % ) , contusion ( 10 % vs 0 % ) , and injection site bruising ( 6 % vs 4 % ) . Exposure increased linearly from 0.3 mg/kg to 3 mg/kg . AMG 745 significantly increased LBM in the 3 mg/kg vs the placebo groups on day 29 by 2.2 % ( ±0.8 % SE , P = 0.008 ) ; in exploratory fat mass analysis , a decrease of -2.5 % ( ±1.0 % SE , P = 0.021 ) was observed . Pharmacodynamic changes in muscle and fat were maintained at follow-up , 1 month after day 29 . CONCLUSION Four weekly s.c . doses of AMG 745 were well tolerated and were associated with increased LBM and decreased fat in the men receiving ADT for nonmetastatic prostate cancer . RESULTS support further investigation of AMG 745 in clinical setting s with muscle loss and atrophy",
"OBJECTIVES To evaluate the effectiveness of exercise and amino acid supplementation in enhancing muscle mass and strength in community-dwelling elderly sarcopenic women . DESIGN R and omized controlled trial . SETTING Urban community in Tokyo , Japan . PARTICIPANTS One hundred fifty-five women aged 75 and older were defined as sarcopenic and r and omly assigned to one of four groups : exercise and amino acid supplementation ( exercise + AAS ; n = 38 ) , exercise ( n = 39 ) , amino acid supplementation ( AAS ; n = 39 ) , or health education ( HE ; n = 39 ) . INTERVENTION The exercise group attended a 60-minute comprehensive training program twice a week , and the AAS group ingested 3 g of a leucine-rich essential amino acid mixture twice a day for 3 months . MEASUREMENTS Body composition was determined using bioelectrical impedance analysis . Data from interviews and functional fitness parameters such as muscle strength and walking ability were collected at baseline and after the 3-month intervention . RESULTS A significant group × time interaction was seen in leg muscle mass ( P = .007 ) , usual walking speed ( P = .007 ) , and knee extension strength ( P = .017 ) . The within-group analysis showed that walking speed significantly increased in all three intervention groups , leg muscle mass in the exercise + AAS and exercise groups , and knee extension strength only in the exercise + AAS group ( 9.3 % increase , P = .01 ) . The odds ratio for leg muscle mass and knee extension strength improvement was more than four times as great in the exercise + AAS group ( odds ratio = 4.89 , 95 % confidence interval = 1.89 - 11.27 ) as in the HE group . CONCLUSION The data suggest that exercise and AAS together may be effective in enhancing not only muscle strength , but also combined variables of muscle mass and walking speed and of muscle mass and strength in sarcopenic women",
"OBJECTIVES Using data from the Hong Kong Mr and Ms Os study , we vali date d the SARC-F against 3 consensus definitions of sarcopenia from Europe , Asia , and an international group , and compared the ability of all 4 measures to predict 4-year physical limitation , walking speed , and repeated chair st and s. DESIGN Prospect i ve cohort study . SETTING Hong Kong community . PARTICIPANTS Four thous and men and women living in the community . MEASUREMENTS A question naire regarding ability to carry a heavy load , walking , rising from a chair , climbing stairs , and falls frequency was administered . These questions were used to calculate the SARC-F score . Measurements , including appendicular muscle mass , were taken using dual-energy X-ray , grip strength using a dynamometer , 6-m gait speed , and time taken for repeated chair st and . Classification using the SARC-F score was compared using consensus panel criteria from international , European , and Asian sarcopenia working groups . The performance of all 4 methods was compared by examining the predictive ability for 4-year outcomes using ROC curve . RESULTS The SARC-F has excellent specificity but poor sensitivity for sarcopenia classification ; however , all 4 methods have comparable but modest predictive power for 4-year physical limitation . CONCLUSION The SARC-F may be considered a suitable tool for community screening for sarcopenia",
"CONTEXT Hormone administration to elderly individuals can increase lean body mass ( LBM ) and decrease fat , but interactive effects of growth hormone ( GH ) and sex steroids and their influence on strength and endurance are unknown . OBJECTIVE To evaluate the effects of recombinant human GH and /or sex steroids on body composition , strength , endurance , and adverse outcomes in aged persons . DESIGN , SETTING , AND PARTICIPANTS A 26-week r and omized , double-blind , placebo-controlled parallel-group trial in healthy , ambulatory , community-dwelling US women ( n = 57 ) and men ( n = 74 ) aged 65 to 88 years recruited between June 1992 and July 1998 . INTERVENTIONS Participants were r and omized to receive GH ( starting dose , 30 micro g/kg , reduced to 20 micro g/kg , subcutaneously 3 times/wk ) + sex steroids ( women : transdermal estradiol , 100 micro g/d , plus oral medroxyprogesterone acetate , 10 mg/d , during the last 10 days of each 28-day cycle [ HRT ] ; men : testosterone enanthate , biweekly intramuscular injections of 100 mg ) ( n = 35 ) ; GH + placebo sex steroid ( n = 30 ) ; sex steroid + placebo GH ( n = 35 ) ; or placebo GH + placebo sex steroid ( n = 31 ) in a 2 x 2 factorial design . MAIN OUTCOME MEASURES Lean body mass , fat mass , muscle strength , maximum oxygen uptake ( VO(2)max ) during treadmill test , and adverse effects . RESULTS In women , LBM increased by 0.4 kg with placebo , 1.2 kg with HRT ( P = .09 ) , 1.0 kg with GH ( P = .001 ) , and 2.1 kg with GH + HRT ( P Fat mass decreased significantly in the GH and GH + HRT groups . In men , LBM increased by 0.1 kg with placebo , 1.4 kg with testosterone ( P = .06 ) , 3.1 kg with GH ( P Fat mass decreased significantly with GH and GH + testosterone . Women 's strength decreased in the placebo group and increased nonsignificantly with HRT ( P = .09 ) , GH ( P = .29 ) , and GH + HRT ( P = .14 ) . Men 's strength also did not increase significantly except for a marginally significant increase of 13.5 kg with GH + testosterone ( P = .05 ) . Women 's VO(2)max declined by 0.4 mL/min/kg in the placebo and HRT groups but increased with GH ( P = .07 ) and GH + HRT ( P = .06 ) . Men 's VO(2)max declined by 1.2 mL/min/kg with placebo and by 0.4 mL/min/kg with testosterone ( P = .49 ) but increased with GH ( P = .11 ) and with GH + testosterone ( P strength ( r = 0.355 ; P VO(2)max ( r = 0.320 ; P = .002 ) were directly related to changes in LBM . Edema was significantly more common in women taking GH ( 39 % vs 0 % ) and GH + HRT ( 38 % vs 0 % ) . Carpal tunnel symptoms were more common in men taking GH + testosterone ( 32 % vs 0 % ) and arthralgias were more common in men taking GH ( 41 % vs 0 % ) . Diabetes or glucose intolerance occurred in 18 GH-treated men vs 7 not receiving GH ( P = .006 ) . CONCLUSIONS In this study , GH with or without sex steroids in healthy , aged women and men increased LBM and decreased fat mass . Sex steroid + GH increased muscle strength marginally and VO ( 2)max in men , but women had no significant change in strength or cardiovascular endurance . Because adverse effects were frequent ( importantly , diabetes and glucose intolerance ) , GH interventions in the elderly should be confined to controlled studies",
"AIM To investigate the effects of exercise and /or tea catechin supplementation on muscle mass , strength and walking ability in elderly Japanese women with sarcopenia . METHODS A total of 128 women aged over 75 years were defined as sarcopenic and r and omly assigned into four groups : exercise and tea catechin supplementation ( n = 32 ) , exercise ( n = 32 ) , tea catechin supplementation ( n = 32 ) or health education ( n = 32 ) . The exercise group attended a 60-min comprehensive training program twice a week and the tea catechin supplementation group ingested 350 mL of a tea beverage fortified with catechin daily for 3 months . Body composition was determined by bioelectrical impedance analysis . Interview data and functional fitness measurements , such as muscle strength , balance and walking ability , were collected at baseline and after the 3-month intervention . RESULTS There were significant group × time interactions observed in timed up & go ( P usual walking speed ( P = 0.007 ) and maximum walking speed ( P + catechin group showed a significant effect ( odds ratio 3.61 , 95 % confidence interval 1.05 - 13.66 ) for changes in the combined variables of leg muscle mass and usual walking speed compared with the health education group . CONCLUSIONS The combination of exercise and tea catechin supplementation had a beneficial effect on physical function measured by walking ability and muscle mass",
"Background Sarcopenia , the age-related loss of muscle mass [ defined as appendicular LBM/Height2 ( aLBM/ht2 ) below peak value by>1SD ] , strength and function , is a major contributing factor to frailty in the elderly . MK-0773 is a selective and rogen receptor modulator design ed to improve muscle function while minimizing effects on other tissues . Objectives The primary objective of this study was to demonstrate an improvement in muscle strength and lean body mass ( LBM ) in sarcopenic frail elderly women treated with MK-0773 relative to placebo . Design This was a r and omized , double-blind , parallel-arm , placebo-controlled , multicenter , 6-month study . Participants were r and omized in a 1:1 ratio to receive either MK-0773 50 mg b.i.d . or placebo ; all participants received Vitamin D and protein supplementation . Setting General community . Participants 170 Women aged ≥65 with sarcopenia and moderate physical dysfunction . Measurements Dual energy X-ray absorptiometry , muscle strength and power , physical performance measures . Results Participants receiving MK-0773 showed a statistically significant increase in LBM from baseline at Month 6 vs. placebo ( p receiving both MK-0773 and placebo showed a statistically significant increase in strength from baseline to Month 6 , but the mean difference between the two groups was not significant ( p=0.269 ) . Both groups showed significant improvement from baseline at Month 6 in physical performance measures , but there were no statistically significant differences between participants receiving MK-0773 and placebo . A greater number of participants experienced elevated transaminases in the MK-0773 group vs. placebo , which resolved after discontinuation of study therapy . MK-0773 was generally well-tolerated with no evidence of and rogenization . Conclusions The MK-0773-induced increase in LBM did not translate to improvement in strength or function vs. placebo . The improvement of strength and physical function in the placebo group could be at least partly attributed to protein and vitamin D supplementation",
"Objective : To compare the effects of 12 weeks of high‐speed resistance training on functional performance and quality of life in elderly women when using either a traditional‐set ( TS ) or a cluster‐set ( CS ) configuration for inter‐set rest . Methods : Three groups of subjects were formed by block‐ design r and omization as follows : ( i ) control group ( CG , n = 17 ; age , 66.5 ± 5.4 years ) ; ( ii ) 12‐week high‐speed resistance training group under a CS configuration ( CSG , n = 15 ; age , 67.6 ± 5.4 years ) ; and ( iii ) 12‐week high‐speed resistance training group under a TS configuration ( TSG , n = 20 ; age , 68.0 ± 5.3 years ) . Training was undertaken three times per week , including high‐speed resistance training exercises . The main difference between the training groups was the recovery set structure . In the TSG , women rested for 150 s after each set of eight repetitions , whereas the CSG used an interest rest redistribution , such that after two consecutive repetitions , a 30‐s rest was allowed . Results : Group × test interactions were observed for a 10‐m walking speed test , an 8‐foot up‐ and ‐go test , a sit‐to‐st and test , and physical quality of life ( p improve functional performance and quality of life , however , the CS configuration induced significantly greater improvements in functional performance and quality of life than the TS configuration . Conclusion : These results should be considered when design ing appropriate and better resistance training programs for older adults . HighlightsFunctional performance and quality of life may be hindered during aging . High‐speed resistance‐training may increase functional performance and quality of life . High‐speed resistance‐training may be particularly effective using a cluster training sets configuration",
"IMPORTANCE In older adults reduced mobility is common and is an independent risk factor for morbidity , hospitalization , disability , and mortality . Limited evidence suggests that physical activity may help prevent mobility disability ; however , there are no definitive clinical trials examining whether physical activity prevents or delays mobility disability . OBJECTIVE To test the hypothesis that a long-term structured physical activity program is more effective than a health education program ( also referred to as a successful aging program ) in reducing the risk of major mobility disability . DESIGN , SETTING , AND PARTICIPANTS The Lifestyle Interventions and Independence for Elders ( LIFE ) study was a multicenter , r and omized trial that enrolled participants between February 2010 and December 2011 , who participated for an average of 2.6 years . Follow-up ended in December 2013 . Outcome assessors were blinded to the intervention assignment . Participants were recruited from urban , suburban , and rural communities at 8 centers throughout the United States . We r and omized a volunteer sample of 1635 sedentary men and women aged 70 to 89 years who had physical limitations , defined as a score on the Short Physical Performance Battery of 9 or below , but were able to walk 400 m. INTERVENTIONS Participants were r and omized to a structured , moderate-intensity physical activity program ( n = 818 ) conducted in a center ( twice/wk ) and at home ( 3 - 4 times/wk ) that included aerobic , resistance , and flexibility training activities or to a health education program ( n = 817 ) consisting of workshops on topics relevant to older adults and upper extremity stretching exercises . MAIN OUTCOMES AND MEASURES The primary outcome was major mobility disability objective ly defined by loss of ability to walk 400 m. RESULTS Incident major mobility disability occurred in 30.1 % ( 246 participants ) of the physical activity group and 35.5 % ( 290 participants ) of the health education group ( hazard ratio [ HR ] , 0.82 [ 95 % CI , 0.69 - 0.98 ] , P = .03).Persistent mobility disability was experienced by 120 participants ( 14.7 % ) in the physical activity group and 162 participants ( 19.8 % ) in the health education group ( HR , 0.72 [ 95 % CI , 0.57 - 0.91 ] ; P = .006 ) . Serious adverse events were reported by 404 participants ( 49.4 % ) in the physical activity group and 373 participants ( 45.7 % ) in the health education group ( risk ratio , 1.08 [ 95 % CI , 0.98 - 1.20 ] ) . CONCLUSIONS AND RELEVANCE A structured , moderate-intensity physical activity program compared with a health education program reduced major mobility disability over 2.6 years among older adults at risk for disability . These findings suggest mobility benefit from such a program in vulnerable older adults . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01072500",
"OBJECTIVES To cross-culturally adapt and vali date the Spanish- language version of the SARC-F in Mexican community-dwelling older adults . DESIGN Cross-sectional analysis of a prospect i ve cohort . SETTING The FraDySMex study , a 2-round evaluation of community-dwelling adults from 2 municipalities in Mexico City . PARTICIPANTS Participants were 487 men and women older than 60 years , living in the design ated area in Mexico City . MEASUREMENTS Information from question naires regarding demographic characteristics , comorbidities , mental status , nutritional status , dependence in activities of daily living , frailty , and quality of life . Objective measurements of muscle mass , strength and function were as follows : skeletal muscle mass index ( SMI ) was taken using dual-energy x-ray , grip strength using a h and dynamometer , 6-meter gait speed using a GAIT Rite instrumented walkway , peak torque and power for knee extension using a isokinetic dynamometer , lower extremity functioning measured by the Short Physical Performance Battery ( SPPB ) , and balance using evaluation on a foam surface , with closed eyes , in the Modified Clinical Test of Sensory Integration . The SARC-F scale translated to Spanish and the consensus panels ' criteria from European , international , and Asian sarcopenia working groups were applied to evaluate sarcopenia . RESULTS The Spanish language version of the SARC-F scale showed reliability ( Cronbach alfa = 0.641 . All items in the scale correlated to the scale 's total score , rho = 0.43 to 0.76 ) , temporal consistency evaluated by test-retest ( CCI = 0.80 ) , criterion validity when compared to the consensus panels ' criteria ( high specificity and negative predictive values ) . The scale was also correlated to other measures related to sarcopenia ( such as age , quality of life , self-rated health status , cognition , dependence in activities of daily living , nutritional status , depression , gait speed , grip strength , peak torque and power for knee extension , SPPB , balance , SMI , and frailty ) . CONCLUSION The SARC-F scale was successfully adapted to Spanish language and vali date d in community-dwelling Mexican older adults"
] |
4116cc34-06ff-11f0-808a-c43d1ab1c353
|
Supporting positive change in lifestyle behaviours is a priority in tackling the health inequalities experienced by adults with intellectual disabilities . In this systematic review , we examine the evidence on the definition , measurement and epidemiology of sedentary behaviour of adults with intellectual disabilities . A systematic literature search of PUBMED , EMBASE , MEDLINE and Google Scholar was performed to identify studies published from 1990 up to October 2015 . Nineteen papers met the criteria for inclusion in the systematic review . Many research ers do not distinguish between insufficient physical activity and sedentary behaviour . None of the studies reported the reliability and validity of the methods used to measure sedentary behaviour . Sedentary time , assessed objective ly , ranged from 522 to 643min/day : higher than in adults without intellectual disabilities . This first-ever review of sedentary behaviour and intellectual disabilities found that at present the evidence base is weak . Studies calibrating accelerometer data with criterion measures for sedentary behaviour are needed to determine specific cut-off points to measure sedentary behaviour in adults with intellectual disabilities . Research ers should also examine the reliability and validity of using proxy-report question naires to measure sedentary behaviour in this group . A better underst and ing of sedentary behaviour will inform the design of novel interventions to change lifestyle behaviours of adults with intellectual disabilities
|
[
"Background Walking interventions have been shown to have a positive impact on physical activity ( PA ) levels , health and wellbeing for adult and older adult population s. There has been very little work carried out to explore the effectiveness of walking interventions for adults with intellectual disabilities . This paper will provide details of the Walk Well intervention , design ed for adults with intellectual disabilities , and a r and omised controlled trial ( RCT ) to test its effectiveness . Methods / design This study will adopt a RCT design , with participants allocated to the walking intervention group or a waiting list control group . The intervention consists of three PA consultations ( baseline , six weeks and 12 weeks ) and an individualised 12 week walking programme . A range of measures will be completed by participants at baseline , post intervention ( three months from baseline ) and at follow up ( three months post intervention and six months from baseline ) . All outcome measures will be collected by a research er who will be blinded to the study groups . The primary outcome will be steps walked per day , measured using accelerometers . Secondary outcome measures will include time spent in PA per day ( across various intensity levels ) , time spent in sedentary behaviour per day , quality of life , self-efficacy and anthropometric measures to monitor weight change . Discussion Since there are currently no published RCTs of walking interventions for adults with intellectual disabilities , this RCT will examine if a walking intervention can successfully increase PA , health and wellbeing of adults with intellectual disabilities . Trial registration IS RCT N : IS RCT",
"Background Programs to change health behaviours have been identified as one way to reduce health inequalities experienced by disadvantaged groups . The objective of this study was to examine the effectiveness of a behaviour change programme to increase walking and reduce sedentary behaviour of adults with intellectual disabilities . Methods We used a cluster r and omised controlled design and recruited participants over 18 years old and not regularly involved in physical activity from intellectual disabilities community-based organisations . Assessment s were carried out blind to allocation . Clusters of participants were r and omly allocated to the Walk Well program or a 12-week waiting list control . Walk Well consisted of three face-to-face physical activity consultations incorporating behaviour change techniques , written re sources for participants and carers , and an individualised , structured walking programme . The primary outcome measured with accelerometers was change in mean step count per day between baseline and 12 weeks . Secondary outcomes included percentage time per day sedentary and in moderate-vigorous physical activity ( MVPA ) , body mass index ( BMI ) , and subjective well being . Results One hundred two participants in 50 clusters were r and omised . 82 ( 80.4 % ) participants completed the primary outcome . 66.7 % of participants lived in the most deprived quintile on the Scottish Index of Multiple Deprivation . At baseline , participants walked 4780 ( st and ard deviation 2432 ) steps per day , spent 65.5 % ( st and ard deviation 10.9 ) of time sedentary and 59 % percent had a body mass in the obesity range . After the walking programme , the difference between mean counts of the Walk Well and control group was 69.5 steps per day [ 95 % confidence interval ( CI ) -1054 to 1193.3 ] . There were no significant between group differences in percentage time sedentary 1.6 % ( 95 % CI −2.984 to 6.102 ) , percentage time in MVPA 0.3 % ( 95 % CI −0.7 to 1.3 ) , BMI −0.2 kg/m2 ( 95 % CI −0.8 to 0.4 ) or subjective well-being 0.3 ( 95 % CI −0.9 to 1.5 ) . Conclusions This is the first published trial of a walking program for adults with intellectual disabilities . Positively changing physical activity and sedentary behaviours may require more intensive programmes or upstream approaches to address the multiple social disadvantages experienced by adults with intellectual disabilities . Since participants spent the majority of their time sedentary , home-based programmes to reduce sitting time may be a viable health improvement approach . Trial registration Current Controlled Trials IS RCT",
"Background The prevalence of obesity in adults with intellectual disabilities has consistently been reported to be higher than the general population . Despite the negative impact of obesity on health , there is little evidence of the effectiveness of weight management interventions for adults with intellectual disabilities and obesity . Preliminary results from a single-str and ed feasibility study of a multi-component weight management intervention specifically design ed for adults with intellectual disabilities and obesity ( TAKE 5 ) and that satisfied clinical recommendations reported that it was acceptable to adults with intellectual disabilities and their carers . This study aims to determine the feasibility of a full-scale clinical trial of TAKE 5 . Methods This study will follow a pilot r and omised trial design . Sixty-six obese participants ( body mass index ( BMI ) ≥30 kg/m2 ) will be r and omly allocated to the TAKE 5 multi-component weight management intervention or a health education ‘ active ’ control intervention ( Waist Winners Too ( WWToo ) ) . Both interventions will be delivered over a 12-month period . Participants ’ anthropometric measures ( body weight , BMI , waist circumference , percentage body fat ) ; indicators of activity ( levels of physical activity and sedentary behaviour ) and well-being will be measured at three time points : baseline , 6 and 12 months . The research er collecting outcome measures will be blind to study group allocation . Conclusions The data from this study will generate pilot data on the acceptability of r and omisation , attrition rates and the estimates of patient-centred outcomes of TAKE 5 , which will help inform future research and the development of a full-scale r and omised clinical trial . Trial registration IS RCT N52903778",
"Background Adults with intellectual disability ( ID ) are physically very inactive . This study will compare two approaches to increasing physical activity in adults with ID : a lifestyle physical activity ( light-moderate intensity ) approach and a structured exercise ( moderate-vigorous intensity ) approach . The trial will compare the short-term ( 3-month ) and long-term ( 9-month ) outcomes and sustainability of each approach with a usual-care control group . Methods / Design A three-arm r and omised controlled trial ( RCT ) will be conducted . Ninety adults with ID aged 18 - 55 will be r and omly assigned to one of three groups : 1 ) a lifestyle physical activity group ( n = 30 ) , 2 ) a structured exercise group ( n = 30 ) , or 3 ) a usual care control group ( n = 30 ) . Participants in both groups will receive a 12-week intervention delivered by exercise specialists in the community with disability service staff , after which intervention will continue for 6 months , delivered by disability service staff only . Primary outcomes are aerobic fitness , 12-hour energy expenditure , and proxy-reported everyday physical activity . Secondary outcomes include objective ly assessed physical activity and sedentary behaviour , intervention compliance , functional walking capacity , participation in domestic activities , muscle strength , body composition , psychosocial outcomes , quality of life and health care costs . Discussion The trial results will determine the effectiveness and sustainability of two approaches to increasing physical activity and exercise among adults with ID.Trial registration IS RCT N77889248 ( 18 April 2012 )",
"Objective : Although there are evaluation and effectiveness studies of health promotion interventions for adults with intellectual disabilities ( ID ) , r and omized efficacy trials of such interventions are lacking . Design : A r and omized active control intervention trial . Setting : The participants attended the health promotion classes in local disability agency service facilities . Method : We enrolled 443 individuals and r and omly assigned them to one of two eight-week participatory classes . The ‘ Steps to Your Health ’ ( STYH ) classes emphasized moderate to vigorous physical activity ( MVPA ) , healthy eating and body mass index ( BMI ) reduction . The control intervention focused on hygiene and safety . Results : We did not find a statistically significant difference in mean MVPA or BMI change between completers of the STYH group compared to the control group one year after the intervention was completed . We did find that participation in STYH classes had a non-significant association with odds of reduction in BMI ( odds ratio [ OR ] 2.87 , 95 % confidence interval [ CI ] 0.91–9.11 ) and completers who lived in group homes were more likely than their counterparts who lived with families or in apartments to decrease their BMI ( OR 4.61 ; 95 % CI 1.14–18.64 ) . Conclusions : This trial did not demonstrate a significant effect of STYH participation on change in mean minutes of MVPA or mean BMI 12 months after classes ended , although there was a non-significant association with odds of reduction of BMI ( p = 0.07 ) . This study has implication s for design of intervention studies in people with intellectual disability ( ID )",
"AIMS To describe and compare population -level aspects of diabetes and diabetes primary care among people with and without intellectual and developmental disabilities . METHODS Administrative health data accessed from the Institute for Clinical Evaluative Sciences was used to identify a cohort of Ontarians with and without intellectual and developmental disabilities between the ages of 30 and 69 years ( n = 28 567 ) . These people were compared with a r and om sample of people without intellectual and developmental disabilities ( n = 2 261 919 ) according to diabetes prevalence , incidence , age , sex , rurality , neighbourhood income and morbidity . To measure diabetes primary care , we also studied hospitalizations for diabetes-related ambulatory care-sensitive conditions . RESULTS Adults with intellectual and developmental disabilities had a consistently higher prevalence and incidence of diabetes than those without intellectual and developmental disabilities . Disparities in prevalence between those with and without intellectual and developmental disabilities were most notable among women , younger adults and those residing in rural or high income neighbourhoods . In terms of hospitalizations for diabetes-related ambulatory care-sensitive conditions , people with intellectual and developmental disabilities were 2.6 times more likely to be hospitalized . CONCLUSIONS Adults with intellectual and developmental disabilities are at high risk of developing and being hospitalized for diabetes . The findings of the present study have a number of important implication s related to the early detection , prevention and proper management of diabetes among adults with intellectual and developmental disabilities",
"PURPOSE Whilst the health benefits associated with regular physical activity are well known , little objective evidence exists regarding the activity profiles of adults with mild and moderate learning disabilities . The aims of the present study were to establish 7 day physical activity profiles for 24 adults with mild and moderate learning disabilities and to compare them with the general population and current Department of Health recommendations for physical activity . METHOD A descriptive study was used , based on interviews with 24 adults with learning disabilities ( mean age 34 years ) triangulated by daytime and residential care workers . Participants volunteered from two residential homes and one social education centre ( SEC ) in a city in the North of Engl and . RESULTS The physical activity profiles show that the participants led sedentary lifestyles that were more exaggerated than those of the general population . Twenty-two participants ( 93 % ) performed significantly less than the minimum daily levels of physical activity recommended by the Department of Health . CONCLUSIONS Few adults with learning disabilities can choose to walk to work , go for a run or visit the local swimming pool without adequate support . This study suggests that there may not be enough moderate or vigorous physical activity choices available in day and residential care setting s to empower adults with mild and moderate learning disabilities to meet the minimum recommendations of the Department of Health . Hence some people with learning disabilities have no alternatives to a sedentary lifestyle and the health risks associated with physical inactivity"
] |
4116cc70-06ff-11f0-808a-c43d1ab1c353
|
OBJECTIVE To review the existing human controlled intervention studies of vitamin D as adjunctive therapy in setting s of infection and provide recommendations for design and implementation of future studies in this field on the basis of the evidence review ed . METHODS We conducted a systematic review of r and omized controlled clinical trials that studied vitamin D for treatment or prevention of infectious diseases in humans . Studies from 1948 through 2009 were identified through search terms in PubMed and Ovid MEDLINE . RESULTS Thirteen published controlled trials were identified by our search criteria . Ten trials were placebo controlled , and 9 of the 10 were conducted in a rigorous double-blind design . The selected clinical trials demonstrated substantial heterogeneity in baseline patient demographics , sample size , and vitamin D intervention strategies . Serious adverse events attributable to vitamin D supplementation were rare across all studies . On the basis of studies review ed to date , the strongest evidence supports further research into adjunctive vitamin D therapy for tuberculosis , influenza , and viral upper respiratory tract illnesses . In the selected studies , certain aspects of study design are highlighted to help guide future clinical research in the field . CONCLUSION More rigorously design ed clinical trials are needed for further evaluation of the relationship between vitamin D status and the immune response to infection as well as for delineation of necessary changes in clinical practice and medical care of patients with vitamin D deficiency in infectious disease setting
|
[
"RATIONALE Vitamin D has been shown to be involved in the host immune response toward Mycobacterium tuberculosis . OBJECTIVES To test whether vitamin D supplementation of patients with tuberculosis ( TB ) improved clinical outcome and reduced mortality . METHODS We conducted a r and omized , double-blind , placebo-controlled trial in TB clinics at a demographic surveillance site in Guinea-Bissau . We included 365 adult patients with TB starting antituberculosis treatment ; 281 completed the 12-month follow-up . The intervention was 100,000 IU of cholecalciferol or placebo at inclusion and again 5 and 8 months after the start of treatment . MEASUREMENTS AND MAIN RESULTS The primary outcome was reduction in a clinical severity score ( TBscore ) for all patients with pulmonary TB . The secondary outcome was 12-month mortality . No serious adverse effects were reported ; mild hypercalcemia was rare and present in both arms . Reduction in TBscore and sputum smear conversion rates did not differ among patients treated with vitamin D or placebo . Overall mortality was 15 % ( 54 of 365 ) at 1 year of follow-up and similar in both arms ( 30 of 187 for vitamin D treated and 24 of 178 for placebo ; relative risk , 1.19 [ 0.58 - 1.95 ] ) . HIV infection was seen in 36 % ( 131 of 359 ) : 21 % ( 76 of 359 ) HIV-1 , 10 % ( 36 of 359 ) HIV-2 , and 5 % ( 19 of 357 ) HIV-1 + 2 . CONCLUSIONS Vitamin D does not improve clinical outcome among patients with TB and the trial showed no overall effect on mortality in patients with TB ; it is possible that the dose used was insufficient . Clinical trial registered with www.controlled-trials.com/is rct n ( IS RCT N35212132 )",
"RATIONALE Vitamin D was used to treat tuberculosis ( TB ) in the preantibiotic era . Prospect i ve studies to evaluate the effect of vitamin D supplementation on antimycobacterial immunity have not previously been performed . OBJECTIVES To determine the effect of vitamin D supplementation on antimycobacterial immunity and vitamin D status . METHODS A double-blind r and omized controlled trial was conducted in 192 healthy adult TB contacts in London , United Kingdom . Participants were r and omized to receive a single oral dose of 2.5 mg vitamin D or placebo and followed up at 6 weeks . MEASUREMENTS AND MAIN RESULTS The primary outcome measure was assessed with a functional whole blood assay ( BCG-lux assay ) , which measures the ability of whole blood to restrict luminescence , and thus growth , of recombinant reporter mycobacteria in vitro ; the readout is expressed as a luminescence ratio ( luminescence postinfection/baseline luminescence ) . IFN-gamma responses to the Mycobacterium tuberculosis antigens early secretory antigenic target-6 and culture filtrate protein 10 were determined with a second whole blood assay . Vitamin D supplementation significantly enhanced the ability of participants ' whole blood to restrict BCG-lux luminescence in vitro compared with placebo ( mean luminescence ratio at follow-up , 0.57 , vs. 0.71 , respectively ; 95 % confidence interval for difference , 0.01 - 0.25 ; p=0.03 ) but did not affect antigen-stimulated IFN-gamma secretion . CONCLUSIONS A single oral dose of 2.5 mg vitamin D significantly enhanced the ability of participants ' whole blood to restrict BCG-lux luminescence in vitro without affecting antigen-stimulated IFN-gamma responses . Clinical trials should be performed to determine whether vitamin D supplementation prevents reactivation of latent TB infection . Clinical trial registered with www . clinical trials.gov ( NCT 00157066 )",
"AIM to compare the vitamin D group of pulmonary tuberculosis patients with a placebo group in terms of clinical improvement , nutritional status , sputum conversion , and radiological improvement . METHODS sixty seven tuberculosis patient visiting the Pulmonary Clinic , of Cipto Mangunkusumo Hospital , Jakarta , from January 1st to August 31st , 2001 were included in this study . The subjects were r and omised to receive vitamin D ( 0.25 mg/day ) or placebo in a double blind method , during the 6th initial week of Tb treatment . The rate of sputum conversion , complete blood counts , blood chemistry as well as radiologic examination were evaluated . RESULTS there were more male patients than females ( 39:28 ) , 78.7 % were in the productive age group , 71.6 % had low nutritional status , 62.4 % with low education level , and 67.2 % with low income . One hundred percent of the vitamin D group and only 76.7 % of the placebo group had sputum conversion . This difference is statistically significant ( p=0.002 ) . CONCLUSION the sputum conversion had no correlation with the hemoglobin level , blood clotting time , calcium level , lymphocyte count , age , sex , and nutritional status . There were more subjects with radiological improvement in the vitamin D group",
"Malnutrition is common in pulmonary tuberculosis ( TB ) , and may impair survival . The objective of this study was to assess effects of multi-vitamin/mineral ( MVM ) and zinc ( Zn ) supplementation during TB treatment on mortality . Patients diagnosed with sputum-positive pulmonary TB in Mwanza , Tanzania , were r and omised , using a two-by-two factorial design , to Zn ( 45 mg ) or placebo , and MVM ( vitamins A , B , C , D , E , and selenium and copper ) or placebo . Survival status was ascertained at the end of the 8-month TB treatment and supplementation period . Of 499 TB patients , 213 ( 43 % ) had HIV . The mean weight gain at 7 months was 6.88 kg ( 95 % CI 6.36 , 7.41 ) . Zn and MVM combined , but neither alone ( interaction , P=0.03 ) , increased weight gain by 2.37 kg ( 95 % CI 0.91 , 3.83 ) , irrespective of HIV status . Survival status at 8 months was determined for 422 patients ( 84.6 % ) , of which fifty-two ( 12.3 % ) had died . Among fifty-two deaths , there were no effects of MVM ( relative risk ( RR ) 0.73 ; 95 % CI 0.43 , 1.23 ) and Zn ( RR 0.76 ; 95 % CI 0.46 , 1.28 ) . However , among HIV co-infected patients , marginally significant effects of both MVM ( RR 0.60 ; 95 % CI 0.34 , 1.05 ) and Zn ( RR 0.63 , 95 % CI 0.37 , 1.08 ) were seen , and MVM and Zn combined reduced mortality ( RR 0.29 ; 95 % CI 0.10 , 0.80 ; interaction ratio 0.52 ) . In conclusion , supplementation with MVM , including Zn , during treatment of pulmonary TB may reduce mortality in those co-infected with HIV . A r and omised trial of the effect of the combined intervention used in this study should be conducted in a different setting to confirm the finding",
"BACKGROUND Tuberculosis ( TB ) often coincides with nutritional deficiencies . The effects of micronutrient supplementation on TB treatment outcomes , clinical complications , and mortality are uncertain . METHODS We conducted a r and omized , double-blind , placebo-controlled trial of micronutrients ( vitamins A , B complex , C , and E , as well as selenium ) in Dar es Salaam , Tanzania . We enrolled 471 human immunodeficiency virus (HIV)-infected and 416 HIV-negative adults with pulmonary TB at the time of initiating chemotherapy and monitored them for a median of 43 months . RESULTS Micronutrients decreased the risk ofTB recurrence by 45 % overall ( 95 % confidence interval [ CI ] , 7 % to 67 % ; P = .02 ) and by 63 % in HIV-infected patients ( 95 % CI , 8 % to 85 % ; P = .02 ) . There were no significant effects on mortality overall ; however , we noted a marginally significant 64 % reduction of deaths in HIV-negative subjects ( 95 % CI , -14 % to 88 % ; P = .08 ) . Supplementation increased CD3 + and CD4 + cell counts and decreased the incidence of extrapulmonary TB and genital ulcers in HIV-negative patients . Micronutrients reduced the incidence of peripheral neuropathy by 57 % ( 95 % CI , 41 % to 69 % ; P weight gain , body composition , anemia , or HIV load . CONCLUSIONS Micronutrient supplementation could improve the outcome in patients undergoing TB chemotherapy in Tanzania",
"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 . )",
"Abstract Objective : Parasitic infestations are known to elicit T-helper lymphocyte type 2 ( Th-2 ) reactions , characterized by a pronounced eosinophila and high IgE levels . In humans both elevated specific IgE levels and eosinophil counts are associated with resistance to reinfection with schistosomiasis . This study aim ed to establish whether the Th-2 reaction could be enhanced with calcitriol ( vitamin D3 ) . Calcitriol has been shown to cause a shift from Th-1 to Th-2 type reactions when applied locally to the skin . Methods : Fifty-nine patients with Schistostomahaematobium infection were r and omized to one of four treatment modalities , i.e. ( a ) praziquantel ( PZQ ) 60 mg · kg−1orally on day 1 , ( b ) PZQ 60 mg · kg−1 on day 1 plus calcitriol 1 μg per day orally for 5 consecutive days , ( c ) calcitriol 1 μg per day for 5 consecutive days or ( d ) placebo . Blood for differential counts , eosinophil cationic protein ( ECP ) , specific IgE and IgG to whole-worm antigen , as well as urine sample s for egg counts , were collected on days 0 and 21 . Results : Baseline values did not differ significantly between the groups . Calcitriol alone result ed in significant increases in circulating lymphocytes ( median increase of 5.5 % ) and the percentage of eosinophil vacuolization ( mean increase 28 % ) . It , however , significantly decreased ECP levels ( mean decrease 46 % ) . PZQ in combination with calcitriol significantly enhanced production of specific IgE ( mean increase 213 % ) and IgG ( mean increase of 170 % ) and tended to increase eosinophil vacuolization ( mean increase 22 % ) . All these changes also differed significantly from those in the placebo group . The specific IgE and IgG levels were also significantly higher than the already increased levels seen with PZQ treatment only . ECP levels were , however , not significantly affected by combination therapy , whereas PZQ alone significantly enhanced ECP production ( mean increase 93 % ) . Conclusions : The increases in specific IgE responses and percentage of eosinophil vacuolization favour a Th-2 type of reaction . The ECP values viewed in isolation may , paradoxically , indicate a Th-1 response ; this could , however , have been an artefact due to the method of ECP detection ex vivo . Finally , it would seem that calcitriol does cause some immune augmentation when combined with PZQ therapy in patients with schistosomiasis . However , long-term follow-up is needed to prove that these findings would translate into resistance against reinfection",
"Our study was done to assess the value of administration of vitamin D to tuberculous children . The study included twenty four newly diagnosed tuberculous children ; eleven males and thirteen females . Their age ranged from one and half to thirteen years . Thirteen patients were extra thoracic type of T.B. , while only seven were intrathoracic and the rest were mixed . They were r and omly divided into two Groups according to the treatment administered : Group A patients were given Rifampicin , Isoniazid and Streptomycin . Group B received in addition vitamin D. After eight weeks therapy , the patients of each group were evaluated regarding clinical , laboratory , and radiological improvement . Vitamin D level is raised after treatment in both Groups A and B , but this rise is not significant . It also showed insignificant difference between the two groups . Vitamin D level showed very high significant decrease in tuberculous children than matched healthy controls ( non tuberculous children ) . Calcium was significantly elevated after treatment in Group A whereas no significant change was detected in Group B. Phosphorous was highly significantly elevated after treatment in Group A , whereas in Group B it is just significantly elevated . Alkaline phosphatase level in both groups A and B were slightly decreased after treatment . However , this decrease was not significant . Clinical improvement was more evident in Group B patients ( those taking vitamin D ) as compared to Group A patients . The same was noted with X-ray and Sonographic findings . We concluded that vitamin D therapy may be of great value in addition to antituberculous drugs in the treatment of tuberculous children , and its use is highly recommended",
"Hepatitis B remains a significant risk to patients receiving chronic hemodialysis , but no certain method of prevention has been identified . We tested two vaccines , plasma-derived vaccine ( 40-micrograms dose ) and recombinant-derived vaccine ( 40-micrograms and 20-micrograms doses ) , in 61 patients with chronic renal failure who were not yet dependent on dialysis . Patients were followed up clinical ly and with laboratory tests of kidney function and hepatitis B virus serology for one year . Significantly more recipients of plasma-derived vaccine responded to vaccination ; they also achieved a higher titer of antibody to hepatitis B virus than did recipients of recombinant-derived vaccine when evaluated at 6 , 7 , 9 , and 12 mo after vaccination . No serious side effects were observed with any vaccine preparation , nor were excessive adverse effects observed in any group . Compared with the dialysis patients previously studied , patients with renal failure who were not yet dependent on dialysis responded more favorably to the hepatitis B virus vaccine ",
"BACKGROUND We conducted a r and omized , placebo-controlled , double-blind trial to test the hypothesis that vitamin D(3 ) supplementation would prevent bone loss in calcium-replete , African American postmenopausal women . METHODS Two hundred eight healthy black postmenopausal women , 50 to 75 years of age , were assigned to receive either placebo or 20 microg/d ( 800 IU ) of vitamin D(3 ) . Calcium supplements were provided to ensure a total calcium intake of 1200 to 1500 mg/d . After 2 years , the vitamin D(3 ) dose was increased to 50 microg/d ( 2000 IU ) in the active group , and the study continued for an additional year . Bone mineral density ( BMD ) was measured every 6 months . Markers of bone turnover , vitamin D metabolites , and parathyroid hormone ( PTH ) levels were measured in serum . RESULTS There were no significant differences in BMD between the active and control groups throughout the study . There was also no relationship between serum 25-hydroxyvitamin D levels attained and rates of bone loss . There was an increase in BMD of the total body , hip , and radius at 1 year in both groups . Over the 3 years , BMD declined at these sites by 0.26 % to 0.55 % per year . The BMD of the lumbar spine increased slightly in the placebo and active groups . There were no persistent changes in serum PTH levels or the markers of bone turnover , although there was a transient decline in PTH in both groups at 3 months . No significant adverse events were attributed to vitamin D supplementation . CONCLUSIONS There was no observed effect of vitamin D(3 ) supplementation on bone loss or bone turnover markers in calcium-replete , postmenopausal African American women . Further studies are needed to determine if these findings are applicable to women of other ethnic groups",
"Vitamin D has been shown to be an important immune system regulator . Vitamin D insufficiency during winter may cause increased susceptibility to upper respiratory tract infections ( URIs ) . To determine whether vitamin D supplementation during the winter season prevents or decreases URI symptoms , 162 adults were r and omized to receive 50 microg vitamin D3 ( 2000 IU ) daily or matching placebo for 12 weeks . A bi-weekly question naire was used to record the incidence and severity of URI symptoms . There was no difference in the incidence of URIs between the vitamin D and placebo groups ( 48 URIs vs. 50 URIs , respectively , P=0.57 ) . There was no difference in the duration or severity of URI symptoms between the vitamin D and placebo groups [ 5.4+/-4.8 days vs. 5.3+/-3.1 days , respectively , P=0.86 ( 95 % CI for the difference in duration -1.8 to 2.1 ) ] . The mean 25-hydroxyvitamin D level at baseline was similar in both groups ( 64.3+/-25.4 nmol/l in the vitamin D group ; 63.0+/-25.8 nmol/l in the placebo group ; n.s . ) . After 12 weeks , 25-hydroxyvitamin D levels increased significantly to 88.5+/-23.2 nmol/l in the vitamin D group , whereas there was no change in vitamin D levels in the placebo group . There was no benefit of vitamin D3 supplementation in decreasing the incidence or severity of symptomatic URIs during winter . Further studies are needed to determine the role of vitamin D in infection",
"OBJECTIVE . Vitamin D insufficiency occurs commonly in HIV-infected youth in the United States . In light of the importance of vitamin D for skeletal and nonskeletal health , including innate immunity , developing methods for improving vitamin D status in HIV-infected children and adolescents is an important area of clinical research . The objective of this study was to evaluate the effect of administration of oral cholecalciferol , 100000 IU every 2 months , and 1 g/day calcium on serum 25-hydroxyvitamin D concentrations , serum and urine calcium , and HIV disease progression during a 12-month period . METHODS . HIV-infected children and adolescents who were aged 6 to 16 years were r and omly assigned to receive vitamin D ( 100000 IU bimonthly ) and calcium ( 1 g/day ; n = 29 ) or double placebo ( n = 27 ) . Serum 25-hydroxyvitamin D concentrations as measured by radioimmunoassay , albumin-corrected calcium concentrations , and spot urinary calcium-creatinine ratios were determined monthly . RESULTS . No abnormalities in serum calcium concentration were observed . One participant who received placebo developed hypercalciuria . No group differences were seen in the change in CD4 count or CD4 % or viral load during 12 months . The overall mean monthly serum 25-hydroxyvitamin D concentrations were higher in the group that received vitamin D and calcium than in the placebo group , as was the monthly serum 25-hydroxyvitamin D area under the curve . After completing 12 months of study , 2 ( 6.7 % ) participants in the group that received vitamin D and calcium had a trough serum 25-hydroxyvitamin D concentration the placebo group . Twelve ( 44.4 % ) in the group that received vitamin D and calcium had a trough serum 25-hydroxyvitamin D concentration of ≥30 ng/mL compared with 3 ( 11.1 % ) in the placebo group . CONCLUSIONS . Administration of oral cholecalciferol to HIV-infected children and adolescents at a dosage of 100000 IU every 2 months , together with 1 g/day calcium , is safe and results in significant increases in serum 25-hydroxyvitamin D concentrations",
"Calcitriol , also known as 1,25-dihydroxy-vitamin D3 , is a steroid hormone that has been shown to have effects on cytokine production and lymphocyte proliferation . Coadministration of calcitriol with trivalent influenza vaccine in mice enhanced both mucosal and systemic antibody responses . We studied the effects of calcitriol coadministered with a commercially available influenza vaccine in 175 human volunteers in this double-blind , placebo controlled clinical trial . Subjects that received calcitriol experienced more pain at the injection site compared with placebo recipients . No significant differences in hemagglutination inhibition titers against H1N1 , H3N2 , or influenza B antigens were detected at 1 or 3 months postvaccination . We conclude that coadministration of 1.0 microg of calcitriol at a site adjacent to influenza vaccination does not enhance humoral immunity in human volunteers",
"Calcitriol has shown a benefit in various small uncontrolled studies of ex vivo immune function . We hypothesized that paricalcitol , a new vitamin D derivative , will have a positive effect on the immune system with minimal adverse effects on calcium homeostasis . Thirty-one hemodialysis patients not administered vitamin D because of low intact parathyroid hormone ( PTH ) levels were r and omized to placebo or 4 microg of paricalcitol intravenously with the hemodialysis session three times weekly for 12 weeks . Effects on in vivo and ex vivo assessment s of immune function were evaluated . All patients achieved the target dose of paricalcitol . Twenty patients were anergic at the start of the study ; 4 of 11 patients in the paricalcitol group and 0 of 9 patients in the placebo group converted to reactive ( P = 0.09 ) . The in vivo response to st and ard hepatitis B booster vaccine and in vitro proliferation and release of interleukin-2 ( IL-2 ) , IL-6 , tumor necrosis factor-alpha , and interferon-gamma from stimulated lymphocytes were not different between the groups . In contrast to clinical immune effects , paricalcitol increased serum calcium levels and decreased PTH and bone alkaline phosphatase levels ( all P hypercalcemia was infrequent . In vitro experiments showed that paricalcitol led to greater dose-dependent thymidine uptake than calcitriol in lymphocytes isolated from either dialysis patients or control subjects . Paricalcitol has a tendency toward improving delayed hypersensitivity reactions , but did not have other proimmune effects . However , as expected , paricalcitol had significant effects on calcium homeostasis compared with placebo . Thus , patients with low PTH levels are unlikely to experience the proimmune effects of vitamin D therapy without more profound and potentially adverse oversuppression of PTH",
"BACKGROUND Elderly people who have a fracture are at high risk of another . Vitamin D and calcium supplements are often recommended for fracture prevention . We aim ed to assess whether vitamin D3 and calcium , either alone or in combination , were effective in prevention of secondary fractures . METHODS In a factorial- design trial , 5292 people aged 70 years or older ( 4481 [ 85 % ] of whom were women ) who were mobile before developing a low-trauma fracture were r and omly assigned 800 IU daily oral vitamin D3 , 1000 mg calcium , oral vitamin D3 ( 800 IU per day ) combined with calcium ( 1000 mg per day ) , or placebo . Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months . Analysis was by intention-to-treat and the primary outcome was new low-energy fractures . FINDINGS 698 ( 13 % ) of 5292 participants had a new low-trauma fracture , 183 ( 26 % ) of which were of the hip . The incidence of new , low-trauma fractures did not differ significantly between participants allocated calcium and those who were not ( 331 [ 12.6 % ] of 2617 vs 367 [ 13.7 % ] of 2675 ; hazard ratio ( HR ) 0.94 [ 95 % CI 0.81 - 1.09 ] ) ; between participants allocated vitamin D3 and those who were not ( 353 [ 13.3 % ] of 2649 vs 345 [ 13.1 % ] of 2643 ; 1.02 [ 0.88 - 1.19 ] ) ; or between those allocated combination treatment and those assigned placebo ( 165 [ 12.6 % ] of 1306 vs 179 [ 13.4 % ] of 1332 ; HR for interaction term 1.01 [ 0.75 - 1.36 ] ) . The groups did not differ in the incidence of all-new fractures , fractures confirmed by radiography , hip fractures , death , number of falls , or quality of life . By 24 months , 2886 ( 54.5 % ) of 5292 were still taking tablets , 451 ( 8.5 % ) had died , 58 ( 1.1 % ) had withdrawn , and 1897 ( 35.8 % ) had stopped taking tablets but were still providing data for at least the main outcomes . Compliance with tablets containing calcium was significantly lower ( difference : 9.4 % [ 95 % CI 6.6 - 12.2 ] ) , partly because of gastrointestinal symptoms . However , potentially serious adverse events were rare and did not differ between groups . INTERPRETATION The findings do not support routine oral supplementation with calcium and vitamin D3 , either alone or in combination , for the prevention of further fractures in previously mobile elderly people"
] |
4116ccac-06ff-11f0-808a-c43d1ab1c353
|
Background Corruption is the abuse or complicity in abuse , of public or private position , power or authority to benefit oneself , a group , an organisation or others close to oneself ; where the benefits may be financial , material or non- material . It is wide-spread in the health sector and represents a major problem . Objectives Our primary objective was to systematic ally summarise empirical evidence of the effects of strategies to reduce corruption in the health sector . Our secondary objective was to describe the range of strategies that have been tried and to guide future evaluations of promising strategies for which there is insufficient evidence . Search methods We search ed 14 electronic data bases up to January 2014 , including : CENTRAL ; MEDLINE ; EMBASE ; sociological , economic , political and other health data bases ; Human Re sources Abstract s up to November 2010 ; Euroethics up to August 2015 ; and PubMed alerts from January 2014 to June 2016 . We search ed another 23 websites and online data bases for grey literature up to August 2015 , including the World Bank , the International Monetary Fund , the U4 Anti-Corruption Re source Centre , Transparency International , healthcare anti-fraud association websites and trial registries . We conducted citation search es in Science Citation Index and Google Scholar , and search ed PubMed for related articles up to August 2015 . We contacted corruption research ers in December 2015 , and screened reference lists of articles up to May 2016 . Selection criteria For the primary analysis , we included r and omised trials , non-r and omised trials , interrupted time series studies and controlled before-after studies that evaluated the effects of an intervention to reduce corruption in the health sector . For the secondary analysis , we included case studies that clearly described an intervention to reduce corruption in the health sector , addressed either our primary or secondary objective , and stated the methods that the study authors used to collect and analyse data . Data collection and analysis One review author extracted data from the included studies and a second review author checked the extracted data against the reports of the included studies . We undertook a structured synthesis of the findings . We constructed a results table and ' Summaries of findings ' tables . We used the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) approach to assess the certainty of the evidence . Main results No studies met the inclusion criteria of the primary analysis . We included nine studies that met the inclusion criteria for the secondary analysis . One study found that a package of interventions coordinated by the US Department of Health and Human Services and Department of Justice recovered a large amount of money and result ed in hundreds of new cases and convictions each year ( high certainty of the evidence ) . Another study from the USA found that establishment of an independent agency to investigate and enforce efforts against overbilling might lead to a small reduction in overbilling , but the certainty of this evidence was very low . A third study from India suggested that the impacts of coordinated efforts to reduce corruption through increased detection and enforcement are dependent on continued political support and that they can be limited by a dysfunctional judicial system ( very low certainty of the evidence ) . One study in South Korea and two in the USA evaluated increased efforts to investigate and punish corruption in clinics and hospitals without establishing an independent agency to coordinate these efforts . It is unclear whether these were effective because the evidence is of very low certainty . One study from Kyrgyzstan suggested that increased transparency and accountability for co-payments together with reduction of incentives for dem and ing informal payments may reduce informal payments ( low certainty of the evidence ) . One study from Germany suggested that guidelines that prohibit hospital doctors from accepting any form of benefits from the pharmaceutical industry may improve doctors ' attitudes about the influence of pharmaceutical companies on their choice of medicines ( low certainty of the evidence ) . A study in the USA , evaluated the effects of introducing a law that required pharmaceutical companies to report the gifts they gave to healthcare workers . Another study in the USA evaluated the effects of a variety of internal control mechanisms used by community health centres to stop corruption . The effects of these strategies is unclear because the evidence was of very low certainty . Authors ' conclusions There is a paucity of evidence regarding how best to reduce corruption . Promising interventions include improvements in the detection and punishment of corruption , especially efforts that are coordinated by an independent agency . Other promising interventions include guidelines that prohibit doctors from accepting benefits from the pharmaceutical industry , internal control practice s in community health centres , and increased transparency and accountability for co-payments combined with reduced incentives for informal payments . The extent to which increased transparency alone reduces corruption is uncertain . There is a need to monitor and evaluate the impacts of all interventions to reduce corruption , including their potential adverse effects . Interventions to reduce corruption in the health sector What is the aim of this review ? The aim of this Cochrane review is to assess the effectiveness of strategies to reduce corruption in the health sector . Cochrane research ers search ed for all potentially relevant studies , and found nine studies that met their criteria . Key messages The review suggests that some strategies to fight corruption in the health sector can have an effect on corruption . These strategies include the use of independent agencies to investigate and punish corruption , telling healthcare workers that they are not allowed to accept payments from pharmaceutical companies , ensuring that information about healthcare prices is clear and accessible to the public together with increasing healthcare worker salaries . However , the certainty of this evidence varies . We need more high- quality studies that assess the effects of these and other strategies . What was studied in the review ? Corruption can occur in any area of the health sector , and happens when people abuse their own position to benefit themselves , their organisation , or other people close to them . It can take many forms , including bribes , theft , or giving incorrect or inaccurate information deliberately . Healthcare officials , for instance , may steal healthcare funds , hospital administrators may change patient records to increase hospital payments , doctors may accept bribes from pharmaceutical companies in exchange for using their products , and patients may try to bribe hospital staff to avoid treatment queues . Corruption affects the health sector in many ways . It can take money away from healthcare , lead to poorer quality care and make access to healthcare unfair , and often affects poor people the hardest . What are the main results of the review ? The review authors included nine relevant studies that used different strategies to stop corruption . • In a study from the USA , efforts to investigate and punish corruption in the health sector were also increased . An independent agency at the national level coordinated these efforts , which led to convictions and the recovery of large amounts of money ( high certainty evidence ) . These efforts may also have led to substantial savings to the government ( low certainty evidence ) . In another study from the USA establishment of an independent agency to investigate and enforce efforts against overbilling was established , but the effects of these efforts are unclear because the evidence was of very low certainty . In India , there were efforts to stop corruption through the appointment of an ombudsman in one state . However , the effect of this strategy is unclear because the evidence was of very low certainty . • In one study in South Korea and two in the USA , efforts to investigate and punish corruption in clinics and hospitals were increased , without establishing an independent agency . However , it is unclear whether these were effective because the evidence is of very low certainty . • In a study in Kyrgyzstan , the government carried out a number of strategies , including giving patients and the public information about how much they should be paying , and increasing healthcare workers ' salaries . This study shows that these strategies may have led to fewer patients giving their doctors informal payments ( low certainty evidence ) . • In a study in Germany , hospital doctors were given guidelines telling them that they were not allowed to accept money or gifts from pharmaceutical companies . The study suggests that this may have changed doctors ' attitudes about the influence of pharmaceutical companies on their choice of medicines ( low certainty evidence ) . • In one study in the USA , the authorities introduced a law that required pharmaceutical companies to report the gifts they gave to healthcare workers . In another USA-based study , community health centres attempted to stop corruption using a variety of internal control mechanisms . However , the effect of these strategies is unclear because the evidence was of very low certainty . We do n't know what the effects of these strategies have on healthcare or people 's health , or if these strategies had any harmful effects . This is because the studies only assessed the effects of the strategies on corruption and the use of re sources , or because the evidence was of very low certainty . How up to date is this review ? The review authors search ed for studies that had been published up to 06 June 2016
|
[
"Aims To assess the association of social determinants on the performance of health systems around the world . Methods A transnational ecological study was conducted with an observation level focused on the country . In order to research on the strength of the association between the annual maternal and child mortality in 154 countries and social determinants : corruption , democratization , income ine quality and cultural fragmentation , we used a mixed linear regression model for repeated measures with r and om intercepts and a conglomerate-based geographical analysis , between 2000 and 2010 . Results Health determinants with a significant association on child mortality( ) : higher access to water ( βa Quartile 4(Q4 ) vs Quartile 1(Q1 ) = -6,14 ; 95%CI : -11,63 to -0,73 ) , sanitation systems , ( Q4 vs Q1 = -25,58 ; 95%CI : -31,91 to -19,25 ) , % measles vaccination coverage ( Q4 vs Q1 = -7.35 ; 95%CI : -10,18 to -4,52 ) , % of births attended by a healthcare professional ( Q4 vs Q1 = -7,91 ; 95%CI : -11,36 to -4,52 ) and a % of the total health expenditure ( Q3 vs Q1 = -2,85 ; 95%CI : -4,93 to -0,7 ) . Ethnic fragmentation ( Q4 vs Q1 = 9,93 ; 95%CI : -0.03 to 19.89 ) had a marginal effect . For child mortality years , an association was found for these variables and democratization ( not free vs free = 11,23 ; 95%CI : -0,82 to 23,29 ) , out-of-pocket expenditure ( Q1 vs Q4 = 17,71 ; 95%CI : 5,86 to 29,56 ) . For MMR ( Maternal mortality ratio ) , % of access to water for all the quartiles , % of access to sanitation systems , ( Q3 vs Q1 = -171,15 ; 95%CI : -281,29 to -61 ) , birth attention by a healthcare professional ( Q4 vs Q1 = -231,23 ; 95%CI : -349,32 to -113,15 ) , and having corrupt government ( Q3 vs Q1 = 83,05 ; 95%CI : 33,10 to 133 ) . Conclusions Improving access to water and sanitation systems , decreasing corruption in the health sector must become priorities in health systems . The ethno-linguistic cultural fragmentation and the detriment of democracy turn out to be two factors related to health results",
"OBJECTIVES There is often substantial uncertainty about the impacts of health system and policy interventions . Despite that , r and omized controlled trials ( RCTs ) are uncommon in this field , partly because experiments can be difficult to carry out . An alternative method for impact evaluation is the interrupted time-series ( ITS ) design . Little is known , however , about how results from the two methods compare . Our aim was to explore whether ITS studies yield results that differ from those of r and omized trials . STUDY DESIGN AND SETTING We conducted single-arm ITS analyses ( segmented regression ) based on data from the intervention arm of cluster r and omized trials ( C- RCTs ) , that is , discarding control arm data . Secondarily , we included the control group data in the analyses , by subtracting control group data points from intervention group data points , thereby constructing a time series representing the difference between the intervention and control groups . We compared the results from the single-arm and controlled ITS analyses with results based on conventional aggregated analyses of trial data . RESULTS The findings were largely concordant , yielding effect estimates with overlapping 95 % confidence intervals ( CI ) across different analytical methods . However , our analyses revealed the importance of a concurrent control group and of taking baseline and follow-up trends into account in the analysis of C- RCTs . CONCLUSION The ITS design is valuable for evaluation of health systems interventions , both when RCTs are not feasible and in the analysis and interpretation of data from C- RCTs",
"BACKGROUND Artificially influencing the case mix of hospitals may have several deleterious consequences for the hospital care system . One distinguishes over-evaluation ( up-coding ) and under-evaluation ( under-coding ) of the case mix . Apart from its financial consequences , miscoding may cause a fracture in epidemiological time series and , by increasing artificially the severity of illness , may affect the assessment of the quality of hospital care , based on administrative data . METHODS Fixed effects models were used to assess deviant coding behavior at the hospital level . To do so , we examined the linear evolution over time of characteristics such as length of stay and of 21 \" triggering \" conditions susceptible to increase the case mix of a stay . In case of deviant coding , these triggering conditions were checked to direct the audit towards fraud-suspected discharge abstract s. Hereto , a method consisting in comparing a single hospital 's linear evolution over time with the national linear evolution over time was developed , using an interaction term between linear evolution over time and hospitals . To test this methodology , fraud-directed audits were carried out in addition to the usual , at r and om audits . RESULTS Important inter-hospital differences in the linear evolution over time of several characteristics of Belgian hospitals were identified , as well as evidence not only of improving coding practice s , but also of up-coding , fraudulent under-coding and of numerous coding errors without financial impact . The coding errors , ascertained in the at r and om audit , result ed in a wrongful gain for the faulty hospitals of 28.23 days in 258 stays , whereas in case of fraud-directed audits these figures amounted up to 642.68 days in 334 stays . CONCLUSION Fraud-directed audit may constitute a valuable tool in the quality assurance of administrative data bases , improving their use in epidemiology and assessment of the quality of care",
"Objective : The authors sought to determine the effect of an educational seminar on interactions with pharmaceutical representatives on residents ’ attitudes and behavior . Method : A controlled trial of an educational intervention was conducted . Residents at a university-affiliated residency program ( N=32 ) were divided into two groups : one group ( N=18 ) received a 1-hour educational intervention , while the other group ( N= 14 ) served as a control . Both groups completed a 33-item survey before the intervention and 2 months after the intervention . Results : Residents interacted substantially with pharmaceutical representatives . The majority of residents found the interactions and gifts useful and believed their prescribing practice s were not influenced . Compared to the comparison group , the intervention group significantly decreased the reported number of office supplies and noneducational gifts , but showed no change in attitude toward pharmaceutical representatives and their gifts . Conclusion : One-time educational interventions may have significant impact on psychiatric residents ’ targeted gift-accepting behavior but little effect on attitudes",
"BACKGROUND Inappropriate use of hospital services , in the form of unjustified hospital stay days ( HSD ) , constitutes a major burden on a health budget . Reduction of unjustified HSD was achieved in a medical ward in a previous intervention study . METHODS A controlled intervention aim ed at reducing unjustified hospital stay was performed on 155 paediatric in patients and 248 controls , by applying pre-set criteria for hospitalization and comparing to results in previous studies . RESULTS Unjustified stay was decreased from 32.6 % to 14.8 % on the study ward , and from 25.7 % to 19.3 % on the control ward . The children on both wards did not differ significantly in rates of subsequent out of hospital mortality , re-admission , and the subjective evaluation of health by their parents one month following discharge . CONCLUSIONS This study demonstrates that despite the fact that the per cent of unjustified HSD on a paediatric wars is much lower than on medicine or surgery , a significant reduction in unjustified stay can be achieved by intervention programme",
"Background : Authentication processes based on mass serialization technology may help to make the drug supply more secure for patients . Objective : To analyze the AegateProtect service , a new drug authentication service implemented in Belgian and Greek community pharmacies . Methods : A prospect i ve analysis conducted via a mystery shopper audit assessed the reliability of the authentication service in a sample of Belgian community pharmacies . A retrospective analysis evaluated the effectiveness of the authentication service in Belgian and Greek community pharmacies in terms of the number of scans relating to authentic , recalled , expired , and suspicious products . Also , the costs of providing an authentication service in a hypothetical country were weighed against the benefits in terms of preventing the dispensing of subst and ard drugs . Results : The authentication service attained a sample reliability of 100 % ( 95 % CI 99.8 to 100 ) in Belgium . The 220,751 scans tested in Belgium during June – August 2008 consisted of authentic products ( 96.13 % of scans ) , recalled products ( 0.74 % ) , products that may be recalled ( 3.00 % ) , and expired products ( 0.13 % ) . No suspicious products were identified . Similar results were observed in Greece . For a hypothetical country , a modeling exercise showed that an authentication service would become cost-neutral in a scenario in which 0.47 % of products per year are identified as recalled or expired . Conclusions : A drug authentication process such as the AegateProtect service is reliable and effective in identifying recalled , expired , and suspicious drugs in community pharmacies at the point of dispensing . The proportion of products identified as recalled , expired , or suspicious in a given country determines the level of cost benefits of an authentication service",
"This paper identifies which types of patients and hospitals have abusive Medicare billings that are responsive to law enforcement . For a 20 % r and om sample of elderly Medicare beneficiaries hospitalized from 1994 to 1998 with one or more of six illnesses that are prone to abuse , we obtain longitudinal cl aims data linked with social security death records , hospital characteristics , and state/year-level anti-fraud enforcement efforts . We show that increased enforcement leads certain types of types of patients and hospitals to have lower billings , without adverse consequences for patients ' health outcomes",
"Medicare ’s Physician Quality Reporting System ( PQRS ) is the largest quality -reporting system in the U.S. health care system and a basis for the new value-based modifier system for physician payment . The PQRS allows health care providers to report measures of quality of care that include both the process of care and physiological outcomes . Using a multivariate difference-in-differences model , we examine the relationship of PQRS participation to three cl aims -computable measures of inappropriate utilization of health care services and risk-adjusted per capita Medicare expenditures . The data are a national r and om sample of PQRS-participating providers matched to nonparticipating providers by zip code and caseload . We found few significant relationships in the overall analysis . However , the magnitude and statistical significance of the desirable associations increased in subgroups of providers and beneficiaries more prone to overutilization ( e.g. , males , older beneficiaries , beneficiaries treated in larger medical practice s or by nonphysicians , and practice s in rural areas ) , and among beneficiaries with heart conditions , diabetes , and eye problems"
] |
4116cce8-06ff-11f0-808a-c43d1ab1c353
|
Although the regular consumption of resveratrol has been known to improve glucose homeostasis and reverse insulin resistance in type 2 diabetes mellitus ( T2DM ) , the reported results are inconsistent . Thus , we aim ed to assess the effects of resveratrol on glycemic control and insulin sensitivity among patients with T2DM . We search ed for relevant articles published until June 2017 on PubMed - Medline , Embase , Cochrane Library , and Web of Science . R and omized controlled trials in T2DM patients administered with resveratrol as intervention were included . After study selection , quality assessment and data extraction were performed independently by two authors , and STATA and RevMan software were used for statistical analysis . Nine r and omized controlled trials involving 283 participants were included . Meta- analysis showed that resveratrol significantly improved the fasting plasma glucose ( −0.29 mmol/l , 95 % CI : −0.51 , −0.06 , p 0.01 ) and insulin levels ( −0.64 U/mL , 95 % CI : −0.95 , −0.32 , p also reduced homeostasis model assessment of insulin resistance ( HOMA-IR ) index , systolic blood pressure , and diastolic blood pressure among participants with T2DM . The changes in hemoglobin A1c ( HbA1c ) , low-density lipoprotein cholesterol , and high-density lipoprotein cholesterol were negligible . Subgroup analysis comparing the resveratrol supplementation doses of in fasting plasma glucose . In particular , the latter dose presented more favorable results . This meta- analysis provides evidence that supplementation of resveratrol may benefit management of T2DM
|
[
"Although resveratrol has widely been studied for its potential health benefits , little is known about its metabolic effects in humans . Our aims were to determine whether the polyphenol resveratrol improves insulin sensitivity in type 2 diabetic patients and to gain some insight into the mechanism of its action . After an initial general examination ( including blood chemistry ) , nineteen patients enrolled in the 4-week-long double-blind study were r and omly assigned into two groups : a resveratrol group receiving oral 2 × 5 mg resveratrol and a control group receiving placebo . Before and after the second and fourth weeks of the trial , insulin resistance/sensitivity , creatinine-normalised ortho-tyrosine level in urine sample s ( as a measure of oxidative stress ) , incretin levels and phosphorylated protein kinase B (pAkt):protein kinase B ( Akt ) ratio in platelets were assessed and statistically analysed . After the fourth week , resveratrol significantly decreased insulin resistance ( homeostasis model of assessment for insulin resistance ) and urinary ortho-tyrosine excretion , while it increased the pAkt : Akt ratio in platelets . On the other h and , it had no effect on parameters that relate to β-cell function ( i.e. homeostasis model of assessment of β-cell function ) . The present study shows for the first time that resveratrol improves insulin sensitivity in humans , which might be due to a resveratrol-induced decrease in oxidative stress that leads to a more efficient insulin signalling via the Akt pathway",
"Non-alcoholic fatty liver ( NAFL ) disease ( NAFLD ) affects 30 % of overweight adolescents and increases the risk of type 2 diabetes mellitus ( T2D ) . Resveratrol is a naturally occurring compound with potential to reverse NAFL and its associated insulin resistance in adults . The use of resveratrol to reduce risk for T2D through its effect on NAFL has not been examined to date in youth . This paper provides a literature review and protocol for a 30 day proof of principle trial of resveratrol in a population of adolescents at risk for T2D . This r and omized double-blind controlled trial is design ed with the primary objective of evaluating a twice daily supplementation of 75 mg of resveratrol for safety and tolerability in overweight and obese adolescent subjects ( 13 to Secondary objectives are to determine the effect size of the intervention on hepatic steatosis and whole body insulin sensitivity . Adolescents in the intervention arm ( n = 10 ) will receive oral supplementation of resveratrol 75 mg twice daily ( with breakfast and dinner ) for a total daily dose of 150 mg for the duration of 30 days . The comparison group ( n = 10 ) will receive a placebo twice daily for 30 days . Both cases and controls will receive a st and ardized lifestyle intervention program . Subjects in both groups will be followed for an additional 30 days post intervention for total study duration of approximately 60 days . Primary outcome measures include a primary side effect profile determined by participant interview , a side effect profile determined by serum biochemistry and vital signs . Secondary outcome measures include an oral glucose tolerance test , liver and cardiac fat content measured by magnetic resonance spectroscopy , anthropometric measures of overweight/obesity , inflammatory markers , and cardiac function and morphology measured with ultrasonography . Additional outcome measures include serum concentrations of resveratrol , compliance to protocol , physical activity , and nutritional assessment . This study will determine the safety and tolerability of resveratrol in an overweight adolescent population and inform the design of a larger r and omized controlled trial",
"Resveratrol is a naturally occurring polyphenolic compound . Numerous animal studies have been reported on its wide-ranging beneficial effects in the biological system including diabetes mellitus ( DM ) . We hypothesized , therefore , that oral supplementation of resveratrol would improve the glycemic control and the associated risk factors in patients with type 2 diabetes mellitus ( T2DM ) . The present clinical study was therefore carried out to test the hypothesis . Sixty-two patients with T2DM were enrolled from Government Headquarters Hospital , Ootacamund , India , in a prospect i ve , open-label , r and omized , controlled trial . Patients were r and omized into control and intervention groups . The control group received only oral hypoglycemic agents , whereas the intervention group received resveratrol ( 250 mg/d ) along with their oral hypoglycemic agents for a period of 3 months . Hemoglobin A(1c ) , lipid profile , urea nitrogen , creatinine , and protein were measured at the baseline and at the end of 3 months . The results reveal that supplementation of resveratrol for 3 months significantly improves the mean hemoglobin A(1c ) ( means ± SD , 9.99 ± 1.50 vs 9.65 ± 1.54 ; P ( mean ± SD , 139.71 ± 16.10 vs 127.92 ± 15.37 ; P ( mean ± SD , 4.70 ± 0.90 vs 4.33 ± 0.76 ; P ( mean ± SD , 75.6 ± 4.6 vs 72.3 ± 6.2 ; P No significant changes in body weight and high-density lipoprotein and low-density lipoprotein cholesterols were observed . Oral supplementation of resveratrol is thus found to be effective in improving glycemic control and may possibly provide a potential adjuvant for the treatment and management of diabetes",
"Objective . The effect of a proprietary formulation of trans-resveratrol ( t-RSV ) on manifestations of diabetic foot syndrome ( DFS ) was studied in type 2 diabetic patients with newly diagnosed diabetic foot ulcers . Method . Placebo-controlled , examiner-blinded , parallel-group r and omized controlled pilot clinical trial ( ACTRN Clinical Trial Registry number 12610000629033 ) involving 24 patients with DFS ( 15 males and 9 females , average age of 56.4 ± 9.1 years ) divided into the placebo and RSV-treatment groups was performed . 50 mg of t-RSV or placebo capsules was given to each patient twice a day over a 60-day time period . Results . Reduction in the parameters reflecting diabetic ulcer size was more profound in the RSV group as compared to placebo . RSV-treated patients also had a marginally improved performance in the foot pressure test . A statistically significant decline in the plasma fibrinogen level , but not CRP , was also found in the RSV-treated patients . Some improvement in the plasma lipid profile and fasting glucose levels were not related to RSV-treatment , since they have been seen on both the RSV and placebo groups , revealing the effectiveness of medical supervision and education in the newly diagnosed patients with DFS . Conclusion . t-RSV supplementation promotes reduction of the foot ulcer size and reduces plasma fibrinogen level in type 2 diabetic patients",
"The objective of this study was to examine the effectiveness of resveratrol in lowering blood glucose in the presence of st and ard antidiabetic treatment in patients with type 2 diabetes , in a r and omized placebo-controlled double-blinded parallel clinical trial . A total of 66 subjects with type 2 diabetes were enrolled in this study and r and omly assigned to intervention group which was supplemented with resveratrol at a dose 1 g/day for 45 days and control group which received placebo tablets . Body weight , blood pressure , fasting blood glucose , haemoglobin A1c , insulin , homeostatic assessment s for insulin resistance , triglycerides , total cholesterol , low density lipoprotein , high density lipoprotein , and markers of liver and kidney damage were measured at baseline and after 45 days of resveratrol or placebo supplementation . Resveratrol treatment significantly decreased systolic blood pressure , fasting blood glucose , haemoglobin A1c , insulin , and insulin resistance , while HDL was significantly increased , when compared to their baseline levels . On the other h and , the placebo group had slightly increased fasting glucose and LDL when compared to their baseline levels . Liver and kidney function markers were unchanged in the intervention group . Overall , this study showed that resveratrol supplementation exerted strong antidiabetic effects in patients with type 2 diabetes",
"The polyphenol resveratrol is considered to exert many beneficial actions , such as antioxidant , anti-inflammatory , insulin-sensitizer and anticancer effects . Its benefits in patients with type 2 diabetes mellitus ( T2DM ) are controversial . Our aims were to determine whether resveratrol supplementation at two different dosages ( 500 and 40mg/day ) for 6 months i ) reduced the concentrations of C-reactive-protein ( CRP ) and ii ) ameliorated the metabolic pattern of T2DM patients . In the present double-blind , r and omized , placebo-controlled trial , 192 T2DM patients were r and omized to receive resveratrol 500mg/day ( Resv500arm ) , resveratrol 40mg/day ( Resv40arm ) or placebo for 6-months . At baseline and at the trial end , CRP values , anthropometric , metabolic and liver parameters were determined . No serious adverse event occurred . A dose-dependent , though not significant , CRP decrease of 5.6 % ( Resv40arm ) and 15.9 % ( Resv500arm ) was observed vs placebo . We failed to detect significant differences in weight , BMI , waist circumference , and values of arterial blood pressure , fasting glucose , glycated hemoglobin , insulin , C-peptide , free fatty acids , liver transaminases , uric acid , adiponectin , interleukin-6 , in both the Resv500 and Resv40 arms vs placebo . Total cholesterol and triglycerides slightly increased in the Resv500arm . Subgroup analyses revealed that lower diabetes duration ( in both Resv500 and Resv40arms ) , and , in the Resv500arm , younger age , aspirin use and being a smoker were associated with a significantly higher CRP reduction vs placebo . The supplementations with 40mg/day or 500mg/day resveratrol did neither reduce CRP concentrations , nor improve the metabolic pattern of T2DM patients",
"BACKGROUND Resveratrol has been reported to lower glycemia in rodent models of type 2 diabetes associated with the stimulation of glucagon-like peptide 1 ( GLP-1 ) , which is known to slow gastric emptying , stimulate insulin secretion , and suppress glucagon secretion and energy intake . OBJECTIVE We evaluated the effects of 5 wk of resveratrol treatment on GLP-1 secretion , gastric emptying , and glycemic control in type 2 diabetes . DESIGN Fourteen patients with diet-controlled type-2 diabetes [ mean ± SEM glycated hemoglobin ( HbA1c ) : 6.4 ± 0.2 % ( 46.4 ± 2.2 mmol/mol ) ] received resveratrol ( 500 mg twice daily ) or a placebo over two 5-wk intervention periods with a 5-wk washout period in between in a double-blind , r and omized , crossover design . Before and after each intervention period ( 4 visits ) , body weight and HbA1c were measured , and patients were evaluated after an overnight fast with a st and ardized mashed-potato meal labeled with 100 μg (13)C-octanoic acid to measure blood glucose and plasma GLP-1 concentrations and gastric emptying ( breath test ) over 240 min . Daily energy intake was estimated from 3-d food diaries during the week before each visit . RESULTS Fasting and postpr and ial blood glucose and plasma total GLP-1 as well as gastric emptying were similar at each assessment , and the change in each variable from weeks 0 to 5 did not differ between resveratrol and placebo groups . Similarly , changes in HbA1c , daily energy intake , and body weight after 5 wk did not differ between the 2 treatments . CONCLUSIONS In patients with diet-controlled type 2 diabetes , 5 wk of twice-daily 500 mg-resveratrol supplementation had no effect on GLP-1 secretion , glycemic control , gastric emptying , body weight , or energy intake . Our observations do not support the use of resveratrol for improving glycemic control . This trial was registered at www.anzctr.org.au as ACTRN12613000717752",
"OBJECTIVE To determine whether resveratrol supplementation can improve insulin sensitivity and promote overall metabolic health on top of st and ard diabetes care . RESEARCH DESIGN AND METHODS Seventeen subjects with well-controlled type 2 diabetes ( T2D ) were treated with placebo and 150 mg/day resveratrol ( resVida ) in a r and omized double-blind crossover study for 30 days . The main outcome measure was insulin sensitivity by the hyperinsulinemic-euglycemic clamp technique . RESULTS Hepatic and peripheral insulin sensitivity were not affected by resveratrol treatment . Intrahepatic lipid content also remained unaffected by resveratrol ; however , the change in intrahepatic lipid content correlated negatively with plasma resveratrol levels ( R = −0.68 , P = 0.03 ) . Intramyocellular lipid content increased in type 2 muscle fibers ( P = 0.03 ) , and systolic blood pressure tended to decrease ( P = 0.09 ) upon resveratrol treatment . In addition , resveratrol significantly improved ex vivo mitochondrial function ( state 3 and state U respiration upon malate with octanoyl-carnitine , P between plasma levels of a metabolite of resveratrol ( dihydroresveratrol ) and the metformin dose used by the patients ( R = 0.66 , P = 0.005 ) , suggesting an interaction between metformin and resveratrol . It could be speculated that the lack of a resveratrol-induced insulin-sensitizing effect is caused by this interaction . CONCLUSIONS Resveratrol supplementation does not improve hepatic or peripheral insulin sensitivity . Our results question the generalized value of resveratrol as an add-on therapy in the treatment of T2D and emphasize the need to perform studies in drug-naive patients with T2D or subjects with prediabetes",
"Non-alcoholic fatty liver disease ( NAFLD ) is usually associated with insulin resistance , central obesity , reduced glucose tolerance , type 2 diabetes mellitus and hypertriacylglycerolaemia . The beneficial effects of resveratrol on metabolic disorders have been shown previously . The aim of this study was to evaluate the effects of resveratrol supplementation on cardiovascular risk factors in patients with NAFLD . In this r and omised double-blinded placebo-controlled clinical trial , fifty NAFLD patients were supplemented with either a 500-mg resveratrol capsule or a placebo capsule for 12 weeks . Both groups were advised to follow an energy-balanced diet and physical activity recommendations . resveratrol supplementation reduced alanine aminotransferase ( ALT ) and hepatic steatosis significantly more than placebo ( P0·05 ) . There were no significant changes in blood pressure , insulin resistance markers and TAG in either group ( P>0·05 ) . Our data have shown that 12-week supplementation of 500 mg resveratrol does not have any beneficial effect on anthropometric measurements , insulin resistance markers , lipid profile and blood pressure ; however , it reduced ALT and hepatic steatosis in patients with NAFLD",
"The aim of this study was to investigate the impact of resveratrol supplementation along with non-surgical periodontal treatment on blood glucose , insulin , insulin resistance , triglyceride ( TG ) , and periodontal markers in patients with type 2 diabetes with periodontal disease . In this double-blind clinical trial study , 43 patients with diabetes with chronic periodontitis were participated . Subjects were r and omly allocated to intervention and control groups . The intervention and control groups received either 480 mg/day of resveratrol or placebo capsules ( two pills ) for 4 weeks . Fasting blood glucose , insulin , insulin resistance ( homeostasis model assessment of insulin resistance ) , TGs , and pocket depth were measured in all subjects ' pre-intervention and post-intervention . The mean serum levels of fasting insulin and insulin resistance ( homeostasis model assessment of insulin resistance ) were significantly lower in the intervention group compared with control group ( 10.42 ± 0.28 and 10.92 ± 0.9 ; 3.66 ± 0.97 and 4.49 ± 1.56 , respectively ) . There was a significant difference in the mean pocket depth between intervention and control groups ( 2.35 ± 0.6 and 3.38 ± 0.5 , respectively ) following intervention . No significant differences were observed in the mean levels of fasting blood glucose and TGs between two groups ' post-intervention . It is recommended that resveratrol supplementation may be beneficial as adjuvant therapy along with non-surgical periodontal treatment in insulin resistance and improving periodontal status among patients with diabetes with periodontal disease . Copyright © 2016 John Wiley & Sons ,",
"Numerous studies have shown that resveratrol ( RES ) exerts anti-inflammatory effects but human trials evidencing these effects in vivo are limited . Furthermore , the molecular mechanisms triggered in humans following the oral intake of RES are not yet understood . Therefore , the purpose of this study was to investigate the molecular changes in peripheral blood mononuclear cells ( P BMC s ) associated to the one-year daily intake of a RES enriched ( 8 mg ) grape extract ( GE-RES ) in hypertensive male patients with type 2 diabetes mellitus ( T2DM ) . We used microarrays and RT-PCR to analyze expression changes in genes and microRNAs ( miRs ) involved in the inflammatory response modulated by the consumption of GE-RES in comparison to a placebo and GE lacking RES . We also examined the changes in several serobiochemical variables , inflammatory and fibrinolytic markers . Our results showed that supplementation with GE or GE-RES did not affect body weight , blood pressure , glucose , HbA1c or lipids , beyond the values regulated by gold st and ard medication in these patients . We did not find either any significant change on serum inflammatory markers except for a significant reduction of ALP and IL-6 levels . The expression of the pro-inflammatory cytokines CCL3 , IL-1β and TNF-α was significantly reduced and that of the transcriptional repressor LRRFIP-1 increased in P BMC s from patients taking the GE-RES extract . Also , a group of miRs involved in the regulation of the inflammatory response : miR-21 , miR-181b , miR-663 , miR-30c2 , miR-155 and miR-34a were found to be highly correlated and altered in the group consuming the GE-RES for 12 months . Our results provide preliminary evidence that long-term supplementation with a grape extract containing RES downregulates the expression of key pro-inflammatory cytokines with the involvement of inflammation-related miRs in circulating immune cells of T2DM hypertensive medicated patients and support a beneficial immunomodulatory effect in these patients",
"OBJECTIVES The primary aims of the study were to examine the effect of resveratrol on skeletal muscle SIRT1 expression and energy expenditure in subjects with Type 2 diabetes mellitus ( T2DM ) . BACKGROUND Animal and in vivo studies indicate that resveratrol increases SIRT1 expression that stimulates PGC1α activity . Subsequent upregulation of AMPK and GLUT4 expression are associated with improved insulin sensitivity in peripheral tissues . METHODS Ten subjects with T2DM were r and omized in a double-blind fashion to receive 3 g resveratrol or placebo daily for 12 weeks . Secondary outcomes include measures of AMPK , p-AMPK and GLUT4 expression levels , energy expenditure , physical activity levels , distribution of abdominal adipose tissue and skeletal muscle fiber type composition , body weight , HbA1c , plasma lipid subfraction , adiponectin levels , and insulin sensitivity . RESULTS There was a significant increase in both SIRT1 expression ( 2.01 vs. 0.86 arbitrary units [ AU ] , p = .016 ) and p-AMPK to AMPK expression ratio ( 2.04 vs. 0.79 AU , p = .032 ) in the resveratrol group compared with the placebo group . Although the percentage of absolute change ( 8.6 vs. -13.9 % , p = .033 ) and percentage of predicted resting metabolic rate ( RMR ; 7.8 vs. -13.9 % , p = .013 ) were increased following resveratrol , there was a significant reduction in average daily activity ( -38 vs. 43.2 % , p = .028 ) and step counts ( -39.5 vs. 11.8 % , p = .047 ) when compared with placebo . CONCLUSIONS In patients with T2DM , treatment with resveratrol regulates energy expenditure through increased skeletal muscle SIRT1 and AMPK expression . These findings indicate that resveratrol may have beneficial exercise-mimetic effects in patients with T2DM"
] |
4116cd24-06ff-11f0-808a-c43d1ab1c353
|
Abstract Introduction : Numerous eHealth tools for pain assessment and management have been developed and evaluated with promising results regarding psychometric properties , efficacy , and effectiveness . Although considerable re sources are spent on developing and evaluating these tools with the aim of increasing access to care , current evidence suggests they are not made available to end users , reducing their impact and creating potential research waste . Methods : This study consisted of 2 components : ( 1 ) a systematic review of eHealth tools for pediatric pain assessment and /or management published in the past 10 years , and ( 2 ) an online survey , completed by the authors of identified tools , of tool availability , perceived barriers or facilitators to availability , grant funding used , and a vali date d measure of user-centeredness of the design process ( UCD-11 ) . Results : Ninety articles ( 0.86 % of citations screened ) describing 53 tools met inclusion criteria . Twenty-six survey responses were completed ( 49.06 % ) , 13 of which ( 50.00 % ) described available tools . Commonly endorsed facilitators of tool availability included research ers ' beliefs in tool benefits to the target population and research community ; barriers included lack of infrastructure and time . The average cost of each unavailable tool was $ 314,425.31 USD ( $ 3,144,253.06 USD total , n = 10 ) . Authors of available tools were more likely to have followed user-centered design principles and reported higher total funding . Conclusion : Systemic changes to academic and funding structures could better support eHealth tool availability and may reduce potential for research waste . User-centered design and implementation science methods could improve the availability of eHealth tools and should be further explored in future studies
|
[
"Sleep disturbances are commonly reported in youth with chronic pain . We examined whether online cognitive-behavioral therapy ( CBT ) for pain management would impact youth 's sleep . Subjective sleep quality and actigraphic sleep were evaluated in 33 youth ( M = 14.8 years ; 70 % female ) with chronic pain participating in a larger r and omized controlled trial of online-CBT . The Internet treatment condition ( n = 17 ) received 8–10 weeks of online-CBT + st and ard care , and the wait-list control condition ( n = 16 ) continued with st and ard care . Although pain improved with online-CBT , no changes were observed in sleep outcomes . Shorter pretreatment sleep duration was associated with less improvement in posttreatment functioning . Findings underscore the need for further development in psychological therapies to more intensively target sleep loss in youth with chronic pain",
"Abstract Although pain and function improve at immediate posttreatment for youth receiving cognitive behavioral therapy for chronic pain , limited data are available to underst and changes that youth make during psychological treatment . We sought to characterize distinct trajectory patterns of change in pain and function to underst and the temporal association of these changes during internet-delivered cognitive behavioral therapy ( CBT ) . Weekly repeated assessment s of pain and function were conducted during 8 weeks of treatment among 135 adolescents , aged 11 to 17 years , with chronic pain who were r and omized to the cognitive behavioral intervention arm of an ongoing trial of internet-delivered CBT ( Web-based management of adolescent pain ; Web-MAP2 ) . Using r and om-effects growth mixture models , we characterized pain and functional disability trajectories finding distinct trajectory groups indicating patterns of both linear and quadratic effects . Trajectories of change showed that some patients ' pain and functional disability were improving , others worsened or changed minimally . Paired t tests compared the within-subject relative change rate in pain and function demonstrating similar change range for pain and function during the treatment period . There was no support for improvements in either pain or function to precede changes in the other domain . Findings may be useful in informing future studies of psychosocial treatments for pediatric chronic pain to consider how to target treatment strategies to distinct patient response profiles . This may lead to the development of intervention strategies that can both more effectively target children 's pain and function during treatment and lead to sustained changes after treatment",
"BACKGROUND Pain in adolescents with cancer ( 12 - 18 years ) is common and negatively impacts health-related quality of life ( HRQL ) . The Pain Squad+ smartphone app , which provides adolescents with real-time pain self-management support , was developed to address this issue . This study evaluated the implementation of the app to inform a future r and omized controlled trial ( RCT ) and obtain treatment effect estimates for pain intensity , pain interference , HRQL , and self-efficacy . PROCEDURE A one-group baseline/post study design with 40 adolescents recruited from two pediatric tertiary care centers was used . Baseline question naires were completed and adolescents used the app at least twice daily for 28 days , receiving algorithm-informed self-management advice depending on their reported pain . A nurse received alerts in response to sustained pain and contacted adolescents to assist in pain care . Post study question naires were completed . Descriptive analyses , with exploratory inferential testing conducted on health outcome data , were used to address study aims . RESULTS Most ( 40/52 ; 77 % ) eligible adolescents participated . Two participants withdrew participation . Intervention fidelity was impacted by technical difficulties ( occurring for 15 % of participants ) and a prolonged time for nurse contact in the event of sustained pain . Adherence to pain reporting was 68.8 ± 38.1 % . Outcome measure completion rates were high and the intervention was acceptable to participants . Trends in improvements in pain intensity , pain interference , and HRQL were significant , with effect sizes of 0.23 - 0.67 . CONCLUSIONS Implementation of Pain Squad+ is feasible and the app appears to improve pain-related outcomes for adolescents with cancer . A multicenter RCT will be undertaken to examine app effectiveness",
"Background Many promising technological innovations in health and social care are characterized by nonadoption or ab and onment by individuals or by failed attempts to scale up locally , spread distantly , or sustain the innovation long term at the organization or system level . Objective Our objective was to produce an evidence -based , theory-informed , and pragmatic framework to help predict and evaluate the success of a technology-supported health or social care program . Methods The study had 2 parallel components : ( 1 ) secondary research ( hermeneutic systematic review ) to identify key domains , and ( 2 ) empirical case studies of technology implementation to explore , test , and refine these domains . We studied 6 technology-supported programs — video outpatient consultations , global positioning system tracking for cognitive impairment , pendant alarm services , remote biomarker monitoring for heart failure , care organizing software , and integrated case management via data sharing — using longitudinal ethnography and action research for up to 3 years across more than 20 organizations . Data were collected at micro level ( individual technology users ) , meso level ( organizational processes and systems ) , and macro level ( national policy and wider context ) . Analysis and synthesis was aided by sociotechnically informed theories of individual , organizational , and system change . The draft framework was shared with colleagues who were introducing or evaluating other technology-supported health or care programs and refined in response to feedback . Results The literature review identified 28 previous technology implementation frameworks , of which 14 had taken a dynamic systems approach ( including 2 integrative review s of previous work ) . Our empirical data set consisted of over 400 hours of ethnographic observation , 165 semistructured interviews , and 200 documents . The final nonadoption , ab and onment , scale-up , spread , and sustainability ( NASSS ) framework included questions in 7 domains : the condition or illness , the technology , the value proposition , the adopter system ( comprising professional staff , patient , and lay caregivers ) , the organization(s ) , the wider ( institutional and societal ) context , and the interaction and mutual adaptation between all these domains over time . Our empirical case studies raised a variety of challenges across all 7 domains , each classified as simple ( straightforward , predictable , few components ) , complicated ( multiple interacting components or issues ) , or complex ( dynamic , unpredictable , not easily disaggregated into constituent components ) . Programs characterized by complicatedness proved difficult but not impossible to implement . Those characterized by complexity in multiple NASSS domains rarely , if ever , became mainstreamed . The framework showed promise when applied ( both prospect ively and retrospectively ) to other programs . Conclusions Subject to further empirical testing , NASSS could be applied across a range of technological innovations in health and social care . It has several potential uses : ( 1 ) to inform the design of a new technology ; ( 2 ) to identify technological solutions that ( perhaps despite policy or industry enthusiasm ) have a limited chance of achieving large-scale , sustained adoption ; ( 3 ) to plan the implementation , scale-up , or rollout of a technology program ; and ( 4 ) to explain and learn from program failures ",
"BACKGROUND The use of non-pharmacological pain management remains adhoc within acute paediatric burns pain management protocol s despite ongoing acknowledgement of its role . Advancements in adult based pain services including the integration of virtual reality has been adapted to meet the needs of children in pain , as exemplified by the development of multi-modal distraction ( MMD ) . This easy to use , h and held interactive device uses customized programs design ed to inform the child about the procedure he/she is about to experience and to distract the child during dressing changes . AIM ( 1 ) To investigate if either MMD procedural preparation ( MMD-PP ) or distraction ( MMD-D ) has a greater impact on child pain reduction compared to st and ard distraction ( SD ) or h and held video game distraction ( VG ) , ( 2 ) to underst and the impact of MMD-PP and MMD-D on clinic efficiency by measuring length of treatment across groups , and lastly , ( 3 ) to assess the efficacy of distraction techniques over three dressing change procedures . METHODS A prospect i ve r and omised control trial was completed in a paediatric tertiary hospital Burns Outpatient Clinic . Eighty participants were recruited and studied over their first three dressing changes . Pain was assessed using vali date d child report , caregiver report , nursing observation and physiological measures . RESULTS MMD-D and MMD-PP were both shown to significantly relieve reported pain ( p time taken for dressings ( p MMD-D and MMD-PP were sustained with subsequent dressing changes . CONCLUSIONS The use of MMD as a preparatory or a distraction tool in an outpatient burns clinic offered superior pain reduction across three dressing changes to children when compared to st and ard practice s or h and held video games . This device has the potential to improve clinic efficiency with reductions in treatment lengths",
"Abstract Adolescents with chronic pain are often socially isolated , having never met others with chronic pain , and often feel misunderstood by healthy peers . Adolescence is a sensitive period for developing one 's sense of self and autonomy , which often occurs in the context of peer relationships . This developmental process is disrupted in adolescents when their chronic pain interferes with their social interactions . Peer mentoring is proposed as a developmentally timely intervention . The aim of this study is to develop and test the feasibility , acceptability , and impact of the iPeer2Peer program . The iPeer2Peer program is a tailored peer mentorship program that provides modeling and reinforcement by peers ( trained young adults with chronic pain aged 18 - 25 years who have learned to successfully manage their pain ) . This program aim ed to enhance self-management of chronic pain in adolescents through 10 Skype video calls over the course of 8 weeks . A pilot r and omized controlled trial design using waitlist controls was used in an adolescent chronic pain sample . Twenty-eight adolescents aged 14.8 ± 1.6 years ( 93 % female ) completed the trial ( intervention : n = 12 ; control n = 16 ) . Three adolescents completed the intervention after completing their participation in the control arm . The iPeer2Peer program was feasible and acceptable , provided the adolescents were given more time to complete all 10 calls . When compared with controls , adolescents who completed the iPeer2Peer program had significant improvement in self-management skills and their coping efforts were more successful . The iPeer2Peer program is a promising peer mentoring intervention that complements st and ard care for adolescents with chronic pain",
"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",
"ABSTRACT Cognitive – behavioral therapy ( CBT ) interventions show promise for decreasing chronic pain in youth . However , the availability of CBT is limited by many factors including distance to major treatment centers and expense . This study evaluates a more accessible treatment approach for chronic pediatric pain using an Internet‐delivered family CBT intervention . Participants included 48 children , aged 11–17 years , with chronic headache , abdominal , or musculoskeletal pain and associated functional disability , and their parents . Children were r and omly assigned to a wait‐list control group or an Internet treatment group . Primary treatment outcomes were pain intensity ratings ( 0–10 NRS ) and activity limitations on the Child Activity Limitations Interview , both completed via an online daily diary . In addition to their medical care , the Internet treatment group completed 8 weeks of online modules including relaxation training , cognitive strategies , parent operant techniques , communication strategies , and sleep and activity interventions . Youth r and omized to the wait‐list control group continued with the current medical care only . Findings demonstrated significantly greater reduction in activity limitations and pain intensity at post‐treatment for the Internet treatment group and these effects were maintained at the three‐month follow‐up . Rate of clinical ly significant improvement in pain was also greater for the Internet treatment group than for the wait‐list control group . There were no significant group differences in parental protectiveness or child depressive symptoms post‐treatment . Internet treatment was rated as acceptable by all children and parents . Findings support the efficacy and acceptability of Internet delivery of family CBT for reducing pain and improving function among children and adolescents with chronic pain",
"In children , the pain and anxiety associated with acute burn dressing changes can be severe , with drug treatment alone frequently proving to be inadequate . Virtual reality ( VR ) systems have been successfully trialled in limited numbers of adult and paediatric burn patients . Augmented reality ( AR ) differs from VR in that it overlays virtual images onto the physical world , instead of creating a complete virtual world . This prospect i ve r and omised controlled trial investigated the use of AR as an adjunct to analgesia and sedation in children with acute burns . Forty-two children ( 30 male and 12 female ) , with an age range of 3 - 14 years ( median age 9 years ) and a total burn surface area ranging from 1 to 16 % were r and omised into a treatment ( AR ) arm and a control ( basic cognitive therapy ) arm after administration of analgesia and /or sedation . Pain scores , pulse rates ( PR ) , respiratory rates ( RR ) and oxygen saturations ( SaO2 ) were recorded pre-procedurally , at 10 min intervals and post-procedurally . Parents were also asked to grade their child 's overall pain score for the dressing change . Mean pain scores were significantly lower ( p=0.0060 ) in the AR group compared to the control group , as were parental pain assessment scores ( p=0.015 ) . Respiratory and pulse rates showed significant changes over time within groups , however , these were not significantly different between the two study groups . Oxygen saturation did not differ significantly over time or between the two study groups . This trial shows that augmented reality is a useful adjunct to pharmacological analgesia",
"OBJECTIVE To examine a computerized parent training program , \" Bear Essentials , \" to improve parents ' knowledge and coaching to help relieve preschoolers ' immunization distress . METHOD In a r and omized controlled trial , 90 parent-child dyads received Bear Essentials parent training plus distraction , distraction only , or control . Outcomes were parent knowledge , parent and child behavior , and child pain . RESULTS Bear Essentials result ed in improved knowledge of the effects of parents ' reassurance , provision of information , and apologizing on children 's procedural distress . Trained parents also engaged in less reassurance and more distraction and encouragement of deep breathing . Children in Bear Essentials engaged in more distraction and deep breathing than children in other groups . There were no effects on measures of child distress or pain . CONCLUSIONS Results suggest that the interactive computer training program impacted parent knowledge , parent behavior , and child behavior as hypothesized , but modifications will be necessary to have more robust outcomes on child procedural distress",
"Objective . To determine the feasibility of a 12-week Internet-based self-management program of disease-specific information , self-management strategies , and social support with telephone support for youth with juvenile idiopathic arthritis ( JIA ) and their parents , aim ed at reducing physical and emotional symptoms and improving health-related quality of life ( HRQOL ) . Methods . A nonblind pilot r and omized controlled trial ( NCT01011179 ) was conducted to test the feasibility of the “ Teens Taking Charge : Managing Arthritis Online ” Internet intervention across 4 tertiary-level centers in Canada . Participants were 46 adolescents with JIA , ages 12 to 18 years , and 1 parent for each participant , who were r and omized to the control arm ( n = 24 ) or the Internet intervention ( n = 22 ) . Results . The 2 groups were comparable on demographic and disease-related variables and treatment expectation at baseline . Attrition rates were 18.1 % and 20.8 % , respectively , from experimental and control groups . Ninety-one percent of participants r and omized to the experimental group completed all 12 online modules and weekly phone calls with a coach in an average of 14.7 weeks ( SD 2.1 ) . The control group completed 90 % of weekly attention-control phone calls . The Internet treatment was rated as acceptable by all youth and their parents . In posttreatment the experimental group had significantly higher knowledge ( p lower average weekly pain intensity ( p = 0.03 , effect size 0.78 ) . There were no significant group differences in HRQOL , self-efficacy , adherence , and stress posttreatment . Conclusion . Findings support the feasibility ( acceptability , compliance , and user satisfaction ) and initial efficacy of Internet delivery of a self-management program for improving disease-specific knowledge and reducing pain in youth with JIA",
"Background Childhood obesity is a growing health concern known to adversely affect quality of life in children and adolescents . The Patient Reported Outcomes Measurement Information System ( PROMIS ) pediatric measures were developed to capture child self-reports across a variety of health conditions experienced by children and adolescents . The purpose of this study is to begin the process of validation of the PROMIS pediatric measures in children and adolescents affected by obesity . Methods The pediatric PROMIS instruments were administered to 138 children and adolescents in a cross-sectional study of patient reported outcomes in children aged 8–17 years with age-adjusted body mass index ( BMI ) greater than the 85th percentile in a design to establish known-group validity . The children completed the depressive symptoms , anxiety , anger , peer relationships , pain interference , fatigue , upper extremity , and mobility PROMIS domains utilizing a computer interface . PROMIS domains and individual items were administered in r and om order and included a total of 95 items . Patient responses were compared between patients with BMI 85 to 136 participants were recruited and had all necessary clinical data for analysis . Of the 136 participants , 5 % ended the survey early result ing in missing domain scores at the end of survey administration . In multivariate analysis , patients with BMI ≥ 99th percentile had worse scores for depressive symptoms , anger , fatigue , and mobility ( p for depressive symptoms , anxiety , and fatigue ( p Children and adolescents ranging from overweight to severely obese can complete multiple PROMIS pediatric measures using a computer interface in the outpatient setting . In the 5 % with missing domain scores , the missing scores were consistently found in the domains administered last , suggesting the length of the assessment is important . The differences in domain scores found in this study are consistent with previous reports investigating the quality of life in children and adolescents with obesity . We show that the PROMIS instrument represents a feasible and potentially valuable instrument for the future study of the effect of pediatric obesity on quality of life",
"OBJECTIVE To evaluate the efficacy of a distance treatment delivered through Internet and telephone for pediatric recurrent pain . METHODS Forty-seven participants ( 9 - 16 years of age ) were r and omly assigned to either an Internet-based treatment or a st and ard medical care waitlist . Treatment employed a Web-based manual for children and parents with weekly therapist contact by telephone or e-mail . At 1- and 3-month follow-ups , participants were assessed on the outcome variables of pain and quality of life . A 50 % reduction in diary pain scores was considered clinical ly significant . RESULTS Significant between-group differences were found : 71 and 72 % of the treatment group achieved clinical ly significant improvement at the 1- and 3-month follow-ups , respectively , whereas only 19 and 14 % of the control group achieved the criterion . No significant differences were found on the quality of life variable . CONCLUSIONS Distance methods have considerable potential for making effective treatments more accessible with lower associated costs",
"Background Adolescents with Juvenile Idiopathic Arthritis ( JIA ) are at risk for physical , emotional , social and role challenges that negatively impact quality of life . Peer mentoring has been shown to improve positive health behaviours in adolescents with chronic disease while simultaneously providing social support . The objectives of this paper are to examine the feasibility and acceptability of an online peer mentoring program ( iPeer2Peer Program ) for adolescents with JIA . Methods The iPeer2Peer program was examined using a waitlist pilot r and omized control trial ( RCT ) . Participants were r and omly allocated to the intervention or wait-list control group via a secure , web-based r and omization service . Health care providers and investigators were blinded to participant group allocation . Trained peer mentors ( 16–25 years ; successfully managing their JIA ) were matched to participants ( 12–18 years ; diagnosed with JIA ) r and omized to the intervention group to provide peer support and education for effective self-management of JIA . Participant-mentor pairings connected ten times over 8 weeks using Skype video calls . Primary outcomes focused on implementation ( i.e. measures of feasibility and acceptability ) . Secondary outcomes focused on effectiveness ( i.e. measures of self-management , self-efficacy , pain , social support and quality of life ) . Results Thirty adolescents ( mean age 14.3 ± 1.7 years , 97 % female ) completed the RCT ( intervention n = 16 , control n = 14 ) . Primary outcomes : One third ( 32 % ) of adolescents approached agreed to participate , completed baseline measures and were r and omized . Half of pairings completed ten calls within 8 weeks . Average call length was twice the required amount with call lengths of 44.72 ± 15.76 min . Participants reported satisfaction with the program and all reported that they would recommend it to their peers . Participants ’ mean engagement level with the program was 8.53/10 ( range = 7–10 ) . Secondary outcomes : Participants who completed the iPeer2Peer Program demonstrated improvements in their perceived ability to manage JIA ( p No adverse events were reported . Conclusion The iPeer2Peer Program is a promising intervention that improves acceptability of self-management and peer support treatments for adolescents with JIA . By using the Internet to connect mentors to adolescents with JIA it may also improve accessibility to these re sources . Findings will be used to adapt the program and refine the methodology for a full-scale RCT .Trial registration Clinical Trials.gov Identifier : NCT01986400 . Registered November 11 , 2013",
"OBJECTIVE Little is known about how participation in internet-based behavioral interventions influences outcomes in youth with health conditions . This study describes participation in an online behavioral pain management intervention for families of adolescents with chronic pain . METHODS 26 adolescent-parent dyads were r and omized to the intervention arm of a controlled trial evaluating a cognitive-behavioral pain intervention . Participation was measured by the number of logins , messages , completion of interactive fields , and behavioral assignments . Associations between content of messages from participants and treatment outcomes were evaluated . RESULTS Most participants ( 92.3 % ) logged in and completed assignments . Over half of participants initiated messages to the online coach . A greater number of messages sent by adolescents containing rapport or treatment content predicted positive treatment outcomes . CONCLUSIONS Most families actively participated in the intervention . Interaction with an online coach may increase the benefit of this Internet behavioral pain management treatment program for adolescents",
"PURPOSE To evaluate use of a h and held electronic wireless device to implement a pain management protocol for participants with sickle cell disease ( SCD ) . METHODS Participants were 19 patients with SCD aged 9 - 20 who experienced vaso-occlusive pain . A single-session training on the use of cognitive-behavioral coping skills was followed by instruction on how to practice these skills and monitor daily pain experience using the device . Daily pain experience and practice of coping skills were collected for the 8-week intervention period using wireless technology . RESULTS High rates of participation , daily diary completion and consumer satisfaction support the use of h and held wireless devices to implement this protocol . A comparison of the rates of self and device-recorded skills practice provides important information about the use of electronic monitoring for behavioral interventions . CONCLUSION Wireless data transfer technology has significant potential to become a practical method to improve symptom monitoring and communication between patients and providers",
"The difficulty in assessing pain during the neonatal period is one of the main obstacles for appropriate analgesia in intensive care units . The aim of this study was to develop and vali date computer software to monitor neonatal facial movements of pain in real time",
"Aim The aim of this article was to develop and apply an Internet-based headache diary ( i-diary ) for adolescents and compare it with a paper-diary ( p-diary ) regarding adherence , user acceptability and recorded headache activity . Methods In a cross-sectional school-based study , a representative sample of 488 adolescents aged 12–18 years were r and omly allocated by cluster sampling to record for three weeks in i-diaries or p-diaries their headache intensity , disability , and use of acute medication . Results A significantly ( p = 0.008 ) higher proportion of adolescents in the i-diary group used the diary at least once during the 21-day period ( 86 % vs 76 % for the p-diary ) . However , the p-diary group completed a significantly ( p number of diary days ( 20.8 vs 15.0 days for the i-diary ) . The response rate for the i-diary-group was largely evenly distributed over the study period ; conversely , approximately two-thirds of the adolescents using the p-diary responded on all 21 days , whereas one-fourth did not respond at all . The two diary types were rated as equal in easiness to remember ( p = 0.25 ) , but the i-diaries were more bothersome to use ( p = 0.029 ) . Conclusion Although p-diary users completed a higher proportion of diary days , i-diaries provided more reliable and credible estimates of headache parameters because of better real-time assessment",
"Abstract Internet-delivered interventions are emerging as a strategy to address barriers to care for individuals with chronic pain . This is the first large multicenter r and omized controlled trial of Internet-delivered cognitive-behavioral therapy ( CBT ) for pediatric chronic pain . Participants included were 273 adolescents ( 205 females and 68 males ) , aged 11 to 17 years with mixed chronic pain conditions and their parents , who were r and omly assigned in a parallel-group design to Internet-delivered CBT ( n = 138 ) or Internet-delivered Education ( n = 135 ) . Assessment s were completed before treatment , immediately after treatment , and at 6-month follow-up . All data collection and procedures took place online . The primary analysis used linear growth models . Results demonstrated significantly greater reduction on the primary outcome of activity limitations from baseline to 6-month follow-up for Internet CBT compared with Internet education ( b = −1.13 , P = 0.03 ) . On secondary outcomes , significant beneficial effects of Internet CBT were found on sleep quality ( b = 0.14 , P = 0.04 ) , on reducing parent miscarried helping ( b = −2.66 , P = 0.007 ) and protective behaviors ( b = −0.19 , P = 0.001 ) , and on treatment satisfaction ( P values Internet CBT were found for parent-perceived impact ( ie , reductions in depression , anxiety , self-blame about their adolescent 's pain , and improvement in parent behavioral responses to pain ) . In conclusion , our Internet-delivered CBT intervention produced a number of beneficial effects on adolescent and parent outcomes , and could ultimately lead to wide dissemination of evidence -based psychological pain treatment for youth and their families",
"Aim The aim of this article is to compare 90-day and 30-day recall of Pediatric Migraine Disability Assessment ( PedMIDAS ) elements and headache frequency against daily entries from an Internet headache diary among pediatric patients and their parents . Methods In a prospect i ve cohort study , patients aged 10–18 years with episodic migraine or probable migraine completed a 90-day Internet-based headache diary that incorporated PedMIDAS questions . Following the 90-day diary period , patients and parents completed modified PedMIDAS instruments to assess 90-day and 30-day recall . Intraclass correlation coefficients ( ICC ) were calculated to measure recall reliability . The Kruskal-Wallis and Jonckheere-Terpstra tests were used to explore recall accuracy as it relates to each participant ’s self-reported confidence in recall and to patient age . Results Fifty-two subjects completed 90 consecutive diary entries . Comparing 30-day to 90-day recall of PedMIDAS elements , ICC scores improved by 26.2 % ( patients ) and 17.5 % ( parents ) . Patients had better recall than their parents for all study measures . Self-reported confidence in recall and patient age had limited and inconsistent effects on recall accuracy . Conclusion The optimal recall interval to assess migraine disability must balance recall accuracy with generalizability across a range of headache frequencies . When compared to daily diary entries , recall accuracy of PedMIDAS elements and headache frequency improves at 30 days compared to 90 days . Parent report of migraine disability should not be used as a replacement for patient report",
"BACKGROUND Variables that are thought to precipitate migraine or tension-type headache episodes in children hitherto have only been studied using retrospective reports . As such , there is little empirical evidence to support the actual predictive association between presumed headache triggers and actual headache occurrence in children . OBJECTIVE The present study sought to determine if fluctuations in weather , a commonly reported headache trigger in children , predict increased likelihood of headache occurrence when evaluated using rigorous prospect i ve methodology ( \" electronic momentary assessment \") . METHODS Twenty-five children ( 21 girls , 4 boys ) between the ages of 8 - 17 years attending a new patient neurology clinic appointment and having a diagnosis of chronic migraine , chronic tension-type , or episodic migraine headache ( with or without aura ) participated in the study . Children completed baseline measures on headache characteristics , presumed headache triggers , and mood and subsequently were trained in the use of electronic diaries to record information on headaches . Children then completed thrice daily diaries on h and held computers for a 2-week time period ( 42 assessment s per child ) while data on weather variables ( temperature , dew point temperature , barometric pressure , humidity , precipitation , and sunlight ) in the child 's geographic location were recorded each time a diary was completed . Data were analyzed using multilevel models . RESULTS Of the weather variables , relative humidity and presence of precipitation were significantly predictive of new headache onset , with nearly a 3-fold increase in probability of headache occurrence during times of precipitation or elevated humidity in the child 's area , b = 0.38 , t(821 ) = 2.10 , P = .04 , and b = 0.02 , t(821 ) = 2.81 , P = .01 , respectively . These associations remained after accounting for fluctuations in mood , and associations were not significantly stronger in children who at baseline thought that weather was a headache trigger for them . Changes in temperature , dew point temperature , barometric pressure , and sunlight were not significantly predictive of new headache episode occurrence in this sample . CONCLUSIONS Results of the present study lend some support to the belief commonly held by children with recurrent headaches that weather changes may contribute to headache onset . Although electronic momentary assessment methodology was found to be feasible in this population and to have the potential to identify specific headache triggers for children , it remains to be determined how best ( or even whether ) to incorporate this information into treatment recommendations",
"Objectives Intravenous ( IV ) cannulation is commonly performed in pediatric emergency departments ( EDs ) . The busy ED environment is often not conducive to conventional nonpharmacological pain management . This study assessed the use of Ditto ( Diversionary Therapy Technologies , Brisbane , Australia ) , a h and held electronic device which provides procedural preparation and distraction , as a means of managing pain and distress during IV cannulation performed in the pediatric ED . Methods A r and omized controlled trial with 98 participants , aged 3 to 12 years , was conducted in a pediatric ED . Participants were recruited and r and omized into 5 intervention groups as follows : ( 1 ) St and ard Distraction , ( 2 ) PlayStation Portable Distraction , ( 3 ) Ditto Distraction , ( 4 ) Ditto Procedural Preparation , and ( 5 ) Ditto Preparation and Distraction . Children 's pain and distress levels were assessed via self-reports and observational reports by caregivers and nursing staff across the following 3 time points : ( 1 ) before , ( 2 ) during , and ( 3 ) after IV cannulation . Results Caregivers and nursing staff reported significantly reduced pain and distress levels in children accessing the combined preparation and distraction Ditto protocol , as compared to st and ard distraction ( P ⩽ 0.01 ) . This intervention also saw the greatest reduction in pain and distress as reported by the child . Conclusions Caregiver reports indicate that using the combined Ditto protocol was most effective in reducing children 's pain experiences while undergoing IV cannulation in the ED . The use of Ditto offers a promising opportunity to negotiate barriers to the provision of nonpharmacological approaches encountered in the busy ED environment , and provide nonpharmacological pain-management interventions in pediatric EDs",
"OBJECTIVES This study evaluates the usability and feasibility of a Web-based intervention ( Web-MAP ) to deliver cognitive behavioral therapy ( CBT ) to adolescents with chronic pain and their parents . METHODS The Web site was evaluated in two stages . In stage one , recovered adolescents and parents ( n = 5 dyads ) , who had completed office-based CBT through a pediatric pain management clinic , completed ratings of Web site content , usability , appearance , and theme . In stage two , treatment-seeking adolescents and their parents ( n = 6 dyads ) completed the full-length Web program . Program usage data were obtained to assess interaction with the Web site . RESULTS Participants rated moderate to strong acceptability of the program . Usage data indicated that participants interacted with the site and used communication features . CONCLUSIONS Feedback from usability testing provided important information in the process of design ing a feasible Web-based treatment for adolescents with chronic pain for use in a r and omized controlled trial",
"Objectives : We examined the outcomes of a cognitive-behavioral therapy ( CBT ) intervention for pain in pediatric sickle cell disease ( SCD ) using smartphones as a novel delivery method . Material s and Methods : Forty-six children with SCD received CBT coping skills training using a r and omized , waitlist control design . The intervention involved a single session of CBT training and home-based practice using smartphones for 8 weeks . Pre-post question naires between the r and omized groups were used to evaluate changes in active psychological coping and negative thinking using the Coping Strategies Question naire . Daily diaries completed by the full sample during the treatment period were used to assess whether CBT skill use was related to reductions in next-day pain intensity and increases in same-day functional activity . Results : The pre-post group comparison suggested that the youth increased active psychological coping attempts with the intervention . Daily diary data indicated that when children used CBT skills on days with higher pain , there were reductions in next-day pain intensity . There was no such association between skill use and functional activity . Discussion : CBT coping skills training supported using smartphones can increase coping and reduce pain intensity for children with SCD ; however , additions to the study protocol s are recommended in future studies . Advantages and caveats of using smartphones are also discussed",
"BACKGROUND The relationships between pain , stress and anxiety , and their effect on burn wound re-epithelialization have not been well explored to- date . The aim of this study was to investigate the effect of the Ditto ™ ( a h and -held electronic medical device providing procedural preparation and distraction ) intervention on re-epithelialization rates in acute pediatric burns . METHODS / DESIGN From August 2011 to August 2012 , children ( 4 - 12 years ) with an acute burn presenting to the Royal Children 's Hospital , Brisbane , Australia fulfilled the study requirements and were r and omized to [ 1 ] Ditto ™ intervention or [ 2 ] st and ard practice . Burn re-epithelialization , pain intensity , anxiety and stress measures were obtained at every dressing change until complete wound re-epithelialization . RESULTS One hundred and seventeen children were r and omized and 75 children were analyzed ( n=40 st and ard group ; n=35 Ditto ™ group ) . Inability to predict wound management result ed in 42 participants no longer meeting the eligibility criteria . Wounds in the Ditto ™ intervention group re-epithelialized faster than the st and ard practice group ( -2.14 days ( CI : -4.38 to 0.10 ) , p-value=0.061 ) , and significantly faster when analyses were adjusted for mean burn depth ( -2.26 days ( CI : -4.48 to -0.04 ) , p-value=0.046 ) . Following procedural preparation at the first change of dressing , the Ditto ™ group reported lower pain intensity scores ( -0.64 ( CI : -1.28 , 0.01 ) p=0.052 ) and lower anxiety ratings ( -1.79 ( CI : -3.59 , 0.01 ) p=0.051 ) . At the second and third dressing removals average pain ( FPS-R and FLACC ) and anxiety scores ( VAS-A ) were at least one point lower when Ditto ™ intervention was received . CONCLUSIONS The Ditto ™ procedural preparation and distraction device is a useful tool alongside pharmacological intervention to improve the rate of burn re-epithelialization and manage pain and anxiety during burn wound care procedures",
"BACKGROUND Non-pharmacological approaches to supporting young children through painful medical procedures are an essential component of burn pain management protocol s. New technology developed from collaborations between healthcare professionals and IT teams can enhance the preparation and distraction approaches used with children . This study follows on from previous studies using such technology , and aim to determine whether levels of pain and distress using a combined preparation and distraction content can be further reduced , and offer more efficient clinical outcomes . METHODS Forty children ( 3 - 10 years ) undergoing acute burn care procedures were r and omized to two groups : ( 1 ) St and ard Distraction ( SD ) Group and ( 2 ) Multi Modal Distraction ( MMD ) Group ( combined protocol of procedural preparation and distraction ) . Pain intensity and child distress were measured prior to and during the procedure . Clinical utility end points were also included ; length of treatment , days to healing and adverse pain events . RESULTS A combined MMD protocol significantly reduced pain intensity ( p distress scores ( p Length of treatment ( p days to healing and the number of pain adverse events were also reduced ( p MMD protocol . CONCLUSIONS A combined MMD protocol reduces the pain experiences for young children during burn care procedures . When compared with a previous MMD trial , outcomes reiterated the use of procedural preparation as an essential component of non-pharmacological approaches . In addition to minimizing pain and distress , this innovative technology reduced treatment length and pain adverse events , and may have an impact on reducing days to healing , providing evidence of clinical efficacy and utility",
"Objectives : Few treatments have been able to effectively manage pediatric irritable bowel syndrome ( IBS ) . Internet-delivered cognitive behavior therapy ( Internet-CBT ) based on exposure for abdominal symptoms is effective for adult IBS . The objective of this study was to evaluate the efficacy of Internet-CBT based on behavioral exposure for adolescents with IBS . Methods : Adolescents with IBS fulfilling the Rome III criteria were r and omized to either Internet-CBT or a wait-list control . The Internet-CBT was a 10-week intervention where the main component was exposure to IBS symptoms by reduction of avoidance of abdominal symptoms and instead stepwise provocation of symptoms . The primary outcome was total score on Gastrointestinal Symptoms Rating Scale for IBS ( GSRS-IBS ) . Secondary outcomes included adolescent- and parent-rated quality of life and parent-rated gastrointestinal symptoms . Difference between groups was assessed from pretreatment to posttreatment and the Internet-CBT group was also evaluated at 6 months after treatment completion . Results : A total of 101 adolescents with IBS ( 13–17 years of age ) were included in this study . Dropout rates were low ( 6 % ) and all r and omized patients were included in intent-to-treat analyses based on mixed effects models . Analyses showed a significant larger pretreatment to posttreatment change on the primary outcome GSRS-IBS ( B=−6.42 , P=0.006 , effect size Cohen ’s d=0.45 , 95 % confidence interval ( 0.12 , 0.77 ) ) and on almost all secondary outcomes for the Internet-CBT group compared with the control group . After 6 months , the results were stable or significantly improved . Conclusions : Internet-CBT based on exposure exercises for adolescents with IBS can effectively improve gastrointestinal symptoms and quality of life",
"Objectives : To evaluate clinical feasibility of the Pain-QuILT ( previously known as the Iconic Pain Assessment Tool ) from the perspective of adolescents with chronic pain and members of their interdisciplinary health team . The Pain-QuILT ( PQ ) , a web-based tool that records the visual self-report of sensory pain in the form of time-stamped records , was directly compared with st and ard interview questions that were transformed to a paper-based tool . Methods : Qualitative , semi-structured interviews were used to refine the PQ . Adolescents with chronic pain aged 12 to 18 years used the PQ and comparator tool ( r and omized order ) to self-report pain before a scheduled clinic appointment , and then took part in a semi-structured interview . The health team used these pain reports ( PQ and comparator ) during patient appointments , and later participated in focus group interviews . Interview audio recordings were transcribed verbatim and underwent a simple line-by-line content analysis to identify key concepts . Results : A total of 17 adolescents and 9 health team members completed the study . All adolescents felt that the PQ was easy to use and underst and . The median time required for completion of the PQ and comparator tool was 3.3 and 3.6 minutes , respectively . Overall , 15/17 ( 88 % ) of adolescents preferred the PQ to self-report their pain versus the comparator . The health team indicated that the PQ was a clinical ly useful tool and identified minor barriers to implementation . Discussion : Consultations with adolescents and their health team indicate that the PQ is a clinical ly feasible tool for eliciting detailed self-report records of the sensory experience of chronic pain",
"BACKGROUND Over 12,000 children are diagnosed with cancer every year in the United States . In addition to symptoms associated with their disease , children undergoing chemotherapy frequently experience significant pain , which is unfortunately often undertreated . The field of m-Health offers an innovative avenue for pain assessment and intervention in the home setting . The current study describes the development and initial evaluation of a tablet-based program , Pain Buddy , aim ed to enhance pain management and foster improved quality of life in children ages 8 - 18 years undergoing cancer treatment . METHODS An animated avatar-based tablet application was developed using state-of-the-art software . Key aspects of Pain Buddy include daily pain and symptom diaries completed by children , remote monitoring of symptoms by uploading patient 's data through internet to a cloud server , cognitive and behavioral skills training , interactive three-dimensional avatars that guide children through the program , and an incentive system to motivate engagement . Twelve children between the ages of 8 and 18 participated in a pilot study of Pain Buddy . RESULTS Children were highly satisfied with the program . Pain and appetite disturbances were most frequently endorsed . Symptom trigger alerts to outside providers were largely related to clinical ly significant pain . Children infrequently used analgesics , and reported using some non-pharmacological pain management strategies . CONCLUSION Pain Buddy appears to be a promising tool to improve pain and symptom management in children undergoing cancer treatment . Results from the current study will inform future improvements to Pain Buddy , in preparation for a r and omized controlled trial to assess the efficacy of this innovative treatment"
] |
4116cd60-06ff-11f0-808a-c43d1ab1c353
|
Purpose Physical exercise has been shown to be an effective , safe , and quite inexpensive method to reduce cardiovascular and metabolic risk factors and is currently in the process of establishing its relevance for cancer specific morbidity and mortality . The aim of this systematic review was to focus on specific effects of resistance exercise ( RE ) in the adjuvant therapy and rehabilitation of prostate cancer patients ( PCaPs ) receiving or having received and rogen deprivation therapy ( ADT ) . Methods A systematic literature search focusing on relevant and peer- review ed studies published between 1966 and September 2014 , using PubMed , EMBASE , MEDLINE , SCOPUS , and Cochrane Library data bases , was conducted . Results The majority of studies demonstrated RE as an effective and safe intervention to improve muscular strength and performance , fatigue and quality of life ( QoL ) in PCaPs , while there is inconclusive evidence concerning cardiovascular performance , body composition , blood lipids , bone mineral density ( BMD ) , and immune response . Conclusion Existing evidence leads to the conclusion that RE seems to be a safe intervention in PCaPs with beneficial effects on physical performance capacity and QoL. Nevertheless , further research in this field is urgently needed to increase underst and ing of exercise interventions in PCaPs
|
[
"OBJECTIVE To examine the changes from a combined exercise intervention after radical prostatectomy ( RP ) in elderly patients with prostate cancer , because r and omized controlled trials addressing exercise intervention after RP have been lacking . METHODS From May 2009 to May 2010 , all patients who underwent laparoscopic RP were assessed for eligibility . A total of 66 patients were r and omized to an exercise or a control group . The exercise group received a combined exercise intervention ( resistance , flexibility , and Kegel exercises ) twice a week for 12 weeks , and the control group received only Kegel exercises . The primary outcome was physical function , and the secondary outcomes were continence status and quality of life after the exercise intervention . RESULTS A total of 49 patients completed follow-up to the end of study . After the 12-week exercise intervention , except for grip strength , all physical functions were better in the exercise group than in the control group . The 24-hour pad test results ( 12.2 g in the exercise group , 46.2 g in the control group ) and continence rate ( 73.1 % in exercise group , 43.5 % in the control group ) recovered more promptly in the exercise group . On a question naire study using the International Consultation on Incontinence question naire , Beck Depression Inventory , and Medical Outcomes Study 36-item short-form health survey , only the exercise group showed improvement at the last follow-up visit . CONCLUSION A 12-week combined exercise intervention after RP results in improvement of physical function , continence rate , and quality of life . These results could help with prompt recovery of daily activities",
"INTRODUCTION And rogen deprivation therapy ( ADT ) is an important component of modern prostate cancer treatment . Survival benefits from neo-adjuvant and adjuvant hormones may take years to manifest , and balancing this with potential morbidity of therapy can be challenging . This study aim ed to assess whether education and short-term combined aerobic and resistance exercises could help to ameliorate the adverse side effects of ADT . METHODS Eight hundred fifty-nine patients with relapsed or metastatic prostate cancer on leuprorelin acetate were allocated to three interventional streams based on patient preference and medical fitness : supervised group ( Face-to-Face ) exercise sessions , home-based ( At Home ) exercise or a support programme for those incapable of exercising ( Support ) . Patients enrolled onto Face to Face underwent measurement of body composition and cardiorespiratory fitness variables at baseline and programme completion . Patients in the exercise streams were surveyed to determine the programme 's impact on physical fitness and well-being . RESULTS Statistically significant improvements ( p measured cardiorespiratory fitness and strength variables . Programme attrition rates were low ( 75/859 ; 8.7 % ) , the primary reason for withdrawal being discontinuation of hormones ( 70 % ) . Programme satisfaction was high , with 98 % of surveyed patients reporting a positive impact on fitness and 97 % planning to continue exercising after programme completion . At 6 months , improved physical and emotional well-being was reported by 93 and 79 % of patients , respectively . CONCLUSIONS A short-term structured exercise intervention results in high compliance and significant improvements in muscle strength and cardiorespiratory fitness in prostate cancer patients on ADT",
"Summary Our r and omized controlled trial in prematurely menopausal breast cancer survivors showed that impact + resistance training prevented increases in percentage of body fat compared with controls and also improved BMD at the hip and prevented BMD loss at the spine among exercise-trained women who were menopausal for > 1 year . Introduction Cancer treatment-related menopause worsens bone health and body composition in breast cancer survivors ( BCS ) . We investigated whether impact + resistance training could improve bone mineral density ( BMD ) , reduce bone turnover , build muscle , and decrease fat mass in BCS with premature menopause . Methods We conducted a r and omized controlled trial in 71 BCS ( mean age , 46.5 years ) within 5 years of treatment-related menopause . Women were r and omly assigned to one of two groups : ( 1 ) impact + resistance training ( prevent osteoporosis with impact + resistance ( POWIR ) ) or ( 2 ) exercise placebo ( FLEX ) 3 × /week for 1 year . Outcomes were hip and spine BMD ( in grams per square centimeter ) and body composition ( percent body fat ( % BF ) and lean and fat mass ( in kilograms ) ) by DXA and bone turnover markers ( serum osteocalcin ( in nanograms per milliliter ) and urinary deoxypryrodinoline ( in nanomoles per milliliter ) . Results There were no significant group × time interactions for bone outcomes when using an intent-to-treat approach on the full sample . In analyses restricted to BCS who were menopausal for ≥1 year , POWIR increased BMD at the hip and slowed BMD loss at the spine compared with FLEX ( femoral neck — POWIR , 0.004 ± 0.093 g/cm2 vs. FLEX , −0.010 ± 0.089 g/cm2 ; p prevented increases in % BF ( POWIR , 0.01 % vs. FLEX , 1.3 % ; p improvements in % BF than women attending less often ( p Conclusion Impact + resistance training may effectively combat bone loss and worsening body composition from premature menopause in BCS",
"Background : Healthy lifestyle behaviors could have a role in ameliorating some of the adverse effects of and rogen suppression therapy ( AST ) in men with prostate cancer . The primary aim of this study was to assess the feasibility of a tapered supervised exercise program in combination with dietary advice in men with advanced prostate cancer receiving AST . Methods : Advanced prostate cancer patients receiving AST for a minimum of 6 months were r and omized to a 12-week lifestyle program comprising aerobic and resistance exercise , plus dietary advice ( n = 25 ) , or st and ard care ( n = 25 ) . Exercise behavior , dietary macronutrient intake , quality of life , fatigue , functional fitness , and biomarkers associated with disease progression were assessed at baseline , after the intervention , and at 6 months . Results : The lifestyle group showed improvements in exercise behavior ( P dietary fat intake ( P = 0.001 ) , total energy intake ( P = 0.005 ) , fatigue ( P = 0.002 ) , aerobic exercise tolerance ( P and muscle strength ( P = 0.033 ) compared with st and ard care controls . Although a high rate of attrition ( 44 % ) was observed at 6 months , the improvements in key health outcomes were sustained . No effects on clinical prostate cancer disease markers were observed . Conclusions : This preliminary evidence suggests that pragmatic lifestyle interventions have potential to evoke improvements in exercise and dietary behavior , in addition to other important health outcomes in men with advanced prostate cancer receiving AST . Impact : This study shows for the first time that pragmatic lifestyle interventions are feasible and could have a positive impact on health behaviors and other key outcomes in men with advanced prostate cancer receiving AST . Cancer Epidemiol Biomarkers Prev ; 20(4 ) ; 647–57 . © 2011 AACR",
"PURPOSE To examine the effect of progressive resistance training on muscle function , functional performance , balance , body composition , and muscle thickness in men receiving and rogen deprivation for prostate cancer . METHODS Ten men aged 59 - 82 yr on and rogen deprivation for localized prostate cancer undertook progressive resistance training for 20 wk at 6- to 12-repetition maximum ( RM ) for 12 upper- and lower-body exercises in a university exercise rehabilitation clinic . Outcome measures included muscle strength and muscle endurance for the upper and lower body , functional performance ( repeated chair rise , usual and fast 6-m walk , 6-m backwards walk , stair climb , and 400-m walk time ) , and balance by sensory organization test . Body composition was measured by dual-energy x-ray absorptiometry and muscle thickness at four anatomical sites by B-mode ultrasound . Blood sample s were assessed for prostate specific antigen ( PSA ) , testosterone , growth hormone ( GH ) , cortisol , and hemoglobin . RESULTS Muscle strength ( chest press , 40.5 % ; seated row , 41.9 % ; leg press , 96.3 % ; P muscle endurance ( chest press , 114.9 % ; leg press , 167.1 % ; P 6-m usual walk ( 14.1 % ) , 6-m backwards walk ( 22.3 % ) , chair rise ( 26.8 % ) , stair climbing ( 10.4 % ) , 400-m walk ( 7.4 % ) , and balance ( 7.8 % ) . Muscle thickness increased ( P Whole-body lean mass was preserved with no change in fat mass . There were no significant changes in PSA , testosterone , GH , cortisol , or hemoglobin . CONCLUSIONS Progressive resistance exercise has beneficial effects on muscle strength , functional performance and balance in older men receiving and rogen deprivation for prostate cancer and should be considered to preserve body composition and reduce treatment side effects",
"Sex steroids are known to modulate serum lipoproteins . Studies have suggested that serum testosterone levels are associated with a beneficial lipid profile . And rogen deprivation therapy ( ADT ) is employed in the treatment of recurrent and metastatic prostate cancer ( PCa ) , result ing in profound hypogonadism . As male hypogonadism unfavorably influences lipid profile and men with PCa have high cardiovascular mortality , we evaluated the effects of long-term ADT on fasting lipids . This Cross-sectional study was conducted in a university-based research institution . We evaluated 44 men , 16 undergoing ADT for at least 12 months before the study ( ADT group ) , 14 age-matched eugonadal men with non-metastatic PCa who were status post prostatectomy and /or radiotherapy and not on ADT ( non-ADT group ) and 14 age-matched eugonadal controls ( Control group ) . None of the men had known history of diabetes or dyslipidemia . Mean age was similar in the three groups ( P=0.37 ) . Serum total ( P free ( P ) testosterone levels were lower in the ADT group compared to the other groups . Men on ADT had higher body mass index ( BMI ) compared to the other groups ( P ADT group had significantly higher levels of total cholesterol compared to the other two groups ( P=0.03 ) . After adjustment for BMI , men on ADT continued to have significantly higher fasting levels of total cholesterol ( P=0.02 ) , LDL cholesterol ( P=0.04 ) and non-HDL cholesterol ( P=0.03 ) compared to the control group . No significant differences were seen in the levels of other lipoproteins between the three groups . These data show that men undergoing long-term ADT have higher total and LDL cholesterol than age-matched controls . Long-term prospect i ve studies are needed to determine the time of onset of changes in these lipoproteins while on ADT and the influence of these changes on cardiovascular mortality",
"This study examined the effects of and rogen suppression therapy ( AST ) on upper and lower body muscle strength and a range of direct measures of physical performance using a cross-sectional design with 118 men ( 48 men undertaking AST for prostate cancer and 70 healthy aged-matched controls ) from a single tertiary center . Primary end points included muscle strength for the upper- and lower-body ; functional performance — repeated chair rise , usual and fast 6-m walk , 6-m backwards walk and 400-m walk time ; and dual-energy X-ray absorptiometry assessment —whole body , regional soft tissue composition and bone mineral density ( BMD ) . Men on AST had significantly reduced muscle strength for the upper- and lower-body and impaired functional performance compared to controls ( P AST patients had significantly lower whole-body and hip BMD and higher percent of body fat than controls ( P lower whole-body lean mass ( −2.3 kg , P=0.077 ) . Appendicular skeletal muscle was positively associated with upper-body ( r=0.400–0.606 , P ( r=0.549–0.588 , P was related to functional performance . Men undertaking AST were consistently impaired across a broad range of physical and functional musculoskeletal performance assessment s compared with their age-matched normal controls . These findings are relevant for those patients considering AST for sub clinical disease management , but whose physical reserve is marginal . Strategies to counter these adverse effects of AST need to be initiated so that independent living and quality of life can be maintained",
"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",
"Hanson , ED , Srivatsan , SR , Agrawal , S , Menon , KS , Delmonico , MJ , Wang , MQ , and Hurley , BF . Effects of strength training on physical function : influence of power , strength , and body composition . J Strength Cond Res 23(9 ) : 2627 - 2637 , 2009-The purpose of this study was to determine ( a ) the effects of strength training ( ST ) on physical function and ( b ) the influence of strength , power , muscle volume ( MV ) , and body composition on physical function . Healthy , inactive adults ( n = 50 ) aged 65 years and older underwent strength , power , total body composition ( % fat and fat free mass [ FFM ] ) , and physical function testing before and after 22 weeks of ST . Physical function testing consisted of tasks design ed to mimic common physical activities of daily living ( ADL ) . To improve internal validity of the assessment of mid-thigh intermuscular fat , subcutaneous fat , and knee extensors MV , a 10-week unilateral ST program using the untrained leg as an internal control preceded 12 weeks of whole-body ST . Strength , power , and FFM increased significantly with ST ( all p rapid walk , 5 chair st and s , and get up and go time decreased significantly with ST in the overall group ( all p Women improved significantly in both walking test times ( both p stair climb test , whereas men improved in the stair climb test ( p walking test times . Multiple regression analysis revealed the highest R2 ( 0.28 ) for the change in chair st and s time , followed by stair climb and usual walk at 0.27 and 0.21 , respectively . ST improves performance in functional tasks important for ADLs . Changes in strength , power , and FFM are predictors of ST-induced improvements in these tasks",
"BACKGROUND Active for Life After Cancer is a r and omized trial evaluating the efficacy of a 6-month group-based lifestyle physical activity program ( Lifestyle ) for prostate cancer patients to improve quality of life ( QOL ) including physical and emotional functioning compared to a group-based Educational Support Program and a St and ard Care Program ( no group ) . METHOD A total of 134 prostate cancer patients receiving continuous and rogen-ablation were r and omly assigned to one of the three study conditions . RESULTS Results indicated no significant improvements in QOL at 6 or 12 months . Both group-based programs were positively received and yielded good attendance and retention . Lifestyle participants demonstrated significant improvements in most theoretical mediators proposed by the Transtheoretical Model and Social Cognitive Theory to affect physical activity . Despite these improvements , no significant changes were found for most physical activity measures . CONCLUSIONS Results suggest a lifestyle program focusing on cognitive-behavioral skills training alone is insufficient for promoting routine physical activity in these patients",
"Insulin resistance and changes in body composition are side effects of and rogen deprivation therapy ( ADT ) given to prostate cancer patients . The present study investigated whether endurance training improves insulin sensitivity and body composition in ADT-treated prostate cancer patients . Nine men undergoing ADT for prostate cancer and ten healthy men with normal testosterone levels underwent 12 weeks of endurance training . Primary endpoints were insulin sensitivity ( euglycemic-hyperinsulinemic clamps with concomitant glucose-tracer infusion ) and body composition ( dual-energy X-ray absorptiometry and magnetic resonance imaging ) . The secondary endpoint was systemic inflammation . Statistical analysis was carried out using two-way ANOVA . Endurance training increased VO2max ( ml(O2)/min per kg ) by 11 and 13 % in the patients and controls respectively ( P in peripheral tissue insulin sensitivity of 14 and 11 % respectively ( P hepatic insulin sensitivity ( P=0.32 ) . Muscle protein content of GLUT4 ( SLC2A4 ) and total AKT ( AKT1 ) was also increased in response to the training ( P Body weight ( P whole-body fat mass ( FM ) ( P lean body mass ( P=0.99 ) was unchanged . Additionally , reductions were observed in abdominal ( P , subcutaneous ( P and visceral ( P FM amounts . The concentrations of plasma markers of systemic inflammation were unchanged in response to the training . No group × time interactions were observed , except for thigh intermuscular adipose tissue ( IMAT ) ( P=0.01 ) , reflecting a significant reduction in the amount of IMAT in the controls ( P training , ADT-treated prostate cancer patients exhibited improved insulin sensitivity and body composition to a similar degree as eugonadal men",
"OBJECTIVE To examine predictors of adherence in a r and omized controlled trial of resistance exercise training ( RET ) in prostate cancer survivors receiving and rogen deprivation therapy . STUDY DESIGN AND SETTING A r and omized controlled trial conducted at fitness centers in Ottawa and Edmonton , Canada . Prostate cancer survivors ( n=155 ) completed measures of social cognitive variables , quality of life ( QOL ) , behavior , and fitness before being r and omized to either an exercise ( n=82 ) or control ( n=73 ) group . The exercise group was asked to perform supervised RET three times per week for 12 weeks . RESULTS The exercise group attended 28.2 of the 36 ( 78.3 % ) RET sessions . Univariate analyses revealed eight different significant ( Ps exercise adherence including exercise stage of change , intention , age , QOL , fatigue , subjective norm , leg-press test , and perceived behavioral control . A multivariate analysis indicated that there were three independent predictors of adherence that explained 20.4 % of the variance : exercise stage of change ( beta=0.26 ; P=.013 ) , age ( beta=-0.22 ; P=.037 ) , and intention ( beta=0.19 ; P=.073 ) . CONCLUSION Exercise adherence in the trial was very good but not optimal . Adherence was predicted by variables from many different categories including social cognitive , QOL , behavioral , fitness , and demographic . These findings may have important implication s for maximizing adherence during clinical trials of exercise in prostate cancer survivors",
"Background : Previous research has shown exercise to be an effective method to mitigate many adverse treatment-related effects of and rogen suppression therapy ( AST ) but the potential impact of exercise on sexual activity remains unknown . The purpose of this investigation was to report the effect of a 12-week exercise program on sexual activity in prostate cancer patients undergoing AST . Methods : Fifty-seven prostate cancer patients undergoing AST were r and omly assigned to an exercise program ( resistance and aerobic modes ; n=29 ) or usual care control ( n=28 ) . Sexual activity was assessed by the European Organization for Research and Treatment of Cancer prostate cancer-specific quality of life question naire ( QLQ-PR25 ) . Results : QLQ-PR25 data were log transformed and analysis of covariance was used to compare sexual activity between groups following the intervention adjusted for baseline activity . No differences in sexual activity were observed between the exercise and control groups before the intervention . There was a significant ( P=0.045 ) adjusted group difference in sexual activity following the 12-week intervention . Patients undergoing usual care decreased sexual activity while patients in the exercise program maintained their level of sexual activity . At baseline , 20.6 and 22.2 % of participants in the exercise and control groups reported a major interest in sex ( that is , high libido ) . Following the intervention , the exercise group had a significantly higher percentage of participants reporting a major interest in sex ( exercise=17.2 % vs control=0 % ; P=0.024 ) . Conclusions : Participation in a short-term exercise program result ed in the maintenance of sexual activity in prostate cancer patients undergoing AST",
"PURPOSE And rogen deprivation therapy is a common treatment in men with prostate cancer that may cause fatigue , functional decline , increased body fatness , and loss of lean body tissue . These physical changes can negatively affect health-related quality of life . Resistance exercise may help to counter some of these side effects by reducing fatigue , elevating mood , building muscle mass , and reducing body fat . METHODS In a two-site study , 155 men with prostate cancer who were scheduled to receive and rogen deprivation therapy for at least 3 months after recruitment were r and omly assigned to an intervention group that participated in a resistance exercise program three times per week for 12 weeks ( 82 men ) or to a waiting list control group ( 73 men ) . The primary outcomes were fatigue and disease-specific quality of life as assessed by self-reported question naires after 12 weeks . Secondary outcomes were muscular fitness and body composition . RESULTS Men assigned to resistance exercise had less interference from fatigue on activities of daily living ( P = .002 ) and higher quality of life ( P = .001 ) than men in the control group . Men in the intervention group demonstrated higher levels of upper body ( P = .009 ) and lower body ( P muscular fitness than men in the control group . The 12-week resistance exercise intervention did not improve body composition as measured by changes in body weight , body mass index , waist circumference , or subcutaneous skinfolds . CONCLUSION Resistance exercise reduces fatigue and improves quality of life and muscular fitness in men with prostate cancer receiving and rogen deprivation therapy . This form of exercise can be an important component of supportive care for these patients",
"BACKGROUND And rogen deprivation therapy ( ADT ) has significant deleterious effects on body composition that may be accompanied by unfavourable changes in adipokine levels . While exercise has been shown to improve a number of side effects associated with ADT for prostate cancer , no studies have assessed the effect of exercise on adiponectin and leptin levels , which have been shown to alter the mitogenic environment . METHODS Twenty-six men with prostate cancer treated with ADT were r and omized to home-based aerobic exercise training or resistance exercise training for 24 weeks . Adiponectin , leptin , insulin-like growth factor 1 ( IGF-1 ) , insulin-like growth factor binding protein 3 ( IGFBP-3 ) were analyzed by ELISA ( enzyme-linked immunosorbent assay ) , in addition to physical activity volume , peak aerobic capacity , and anthropometric measurements , at baseline , 3 months and 6 months . RESULTS Resistance exercise significantly reduced IGF-1 after 3 months ( p = 0.019 ) ; however , this change was not maintained at 6 months . At 6 months , IGFBP-3 was significantly increased compared to baseline for the resistance training group ( p = 0.044 ) . In an exploratory analysis of all exercisers , favourable changes in body composition and aerobic fitness were correlated with favourable levels of leptin , and favourable leptin : adiponectin and IGF-1:IGFBP-3 ratios at 3 and 6 months . CONCLUSIONS Home-based exercise is correlated with positive changes in adipokine levels and the IGF-axis that may be related to healthy changes in physical fitness and body composition . While the improvements of adipokine markers appear to be more apparent with resistance training compared to aerobic exercise , these findings must be considered cautiously and require replication from larger r and omized controlled trials to clarify the role of exercise on adipokines and IGF-axis proteins for men with prostate cancer",
"Purpose The purpose of this study is to examine the effects of age ( ≤65 years or > 65 years ) and and rogen-deprivation therapy ( ADT , presence or absence ) as factors that may predict changes in body composition and fitness following a 24-week exercise program in prostate cancer patients . Methods One hundred twenty-one men were r and omly allocated to either : ( 1 ) aerobic exercise ( AE ) , ( 2 ) resistance exercise ( RE ) , or ( 3 ) usual care ( UC ) . Body composition was assessed by DXA . Aerobic fitness was assessed through a maximal treadmill test . Muscular strength was assessed by leg extension and bench press using the eight-repetition maximum test . Responses were compared between younger ( ≤65 years ) and older ( > 65 years ) patients with or without ADT . Results There did not appear to be an interaction between age and ADT on body composition or fitness , nor were there any significant changes in body composition for participants ≤65 years . In participants aged > 65 years , lean mass decreased in AE ( p = 0.013 ) and UC ( p = 0.006 ) , but was preserved in RE . In participants receiving ADT , there was a decrease in lean mass in AE ( p = 0.003 ) and UC ( p non-ADT group did not show any changes in body composition but did show improvements in muscular fitness following resistance training ( p body composition and physical fitness following a 24-week exercise program in men with prostate cancer are not influenced by age and /or ADT . Resistance training appears to attenuate the age-related decrease in lean mass and increase in body fat in older patients with prostate cancer and those receiving ADT ",
"OBJECTIVES Gonadotropin-releasing hormone agonists increase fat mass , decrease insulin sensitivity , and increase serum triglycerides . To better characterize the metabolic effects of gonadotropin-releasing hormone agonist treatment , we prospect ively evaluated the changes in body composition , insulin sensitivity , and levels of adiponectin , resistin , C-reactive protein ( CRP ) , and plasminogen activator inhibitor type 1 ( PAI-1 ) . We also assessed the relationships among changes in adipocytokines , body composition , and insulin sensitivity . METHODS In this prospect i ve , 12-week study , 25 nondiabetic men with locally advanced or recurrent prostate cancer and no radiographic evidence of metastases were treated with leuprolide depot and bicalutamide . The outcomes studied included changes from baseline to week 12 in body composition , insulin sensitivity , and levels of adiponectin , resistin , CRP , and PAI-1 . RESULTS The mean + /- st and ard error percentage of fat body mass increased by 4.3 % + /- 1.3 % from baseline to week 12 ( P = 0.002 ) . The insulin sensitivity index decreased by 12.9 % + /- 7.6 % ( P = 0.02 ) . The serum adiponectin levels increased by 37.4 % + /- 7.2 % from baseline to week 12 ( P resistin , CRP , and PAI-1 levels did not change significantly . Changes in body composition tended to be associated with changes in adiponectin , but not insulin sensitivity . CONCLUSIONS Combined and rogen blockade with leuprolide and bicalutamide significantly increased fat mass and adiponectin levels and decreased insulin sensitivity but did not alter the resistin , CRP , or PAI-1 levels . This pattern of metabolic changes appears distinct from the classic metabolic syndrome",
"The role of and rogens in cardiovascular disease is uncertain . We aim ed to determine the vascular effects of and rogen suppression in men with prostate cancer . Arterial stiffness ( or ' compliance ' ) was measured in 16 men ( 71+/-9 years , mean+/-S.D. ) prior to , and 3 months after , complete and rogen suppression with gonadotrophin-releasing hormone analogues as treatment for prostate cancer . Fifteen control men ( 70+/-7 years ) also had arterial stiffness studies at baseline and 3 months later . Two measures of arterial stiffness were employed : systemic arterial compliance ( SAC ) was measured by simultaneous recording of aortic flow and carotid artery pressure ( ' area method ' ) , and pulse wave velocities ( PWVs ) were recorded with the ' Complior ' system . The 16 cases underwent glucose-tolerance and fasting-lipids tests on both visits . After 3 months of testosterone suppression , there was a significant fall in SAC , which was not seen in the controls [ mean change+/-S.E.M. , -0.26+/-0.09 a.c.u . ( arbitrary compliance unit ) in the cases versus + 0.06+/-0.11 in the controls ; P = 0.03 ) . Central , but not peripheral , PWVs tended to increase in the cases ( mean change+/-S.E.M. for aorto-femoral PWV , + 0.5+/-0.4 m/s for cases versus -0.3+/-0.3 m/s for controls ; P = 0.08 ) . After testosterone suppression , fasting insulin levels increased from 6.89+/-4.84 m-units/l to 11.34+/-8.16 m-units/l ( mean+/-S.D. ) , total cholesterol increased from 5.32+/-0.77 mmol/l to 5.71+/-0.82 mmol/l and high-density lipoprotein cholesterol increased from 1.05+/-0.24 mmol/l to 1.26+/-0.36 mmol/l ; P body-mass index , serum glucose , low-density lipoprotein cholesterol or triacylglycerol ( triglyceride ) levels . Our results indicate that loss of and rogens in men leads to an increase in aortic stiffness and serum insulin levels , and may therefore adversely affect cardiovascular risk",
"OBJECTIVES To investigate whether functionally based resistance exercise could improve strength , physical function , and disability among prostate cancer survivors ( PCS ) on and rogen deprivation therapy ( ADT ) ; and to explore potential mediators of changes in outcomes from exercise . DESIGN R and omized controlled trial . SETTING Academic medical center . PARTICIPANTS PCS ( N=51 ; mean age , 70.2y ) on ADT . INTERVENTION PCS were r and omized to moderate to vigorous intensity resistance training or stretching ( placebo control ) for 1 year . MAIN OUTCOME MEASURES Maximal leg press and bench press strength , objective and self-reported physical function , and self-reported disability . Hierarchical linear modeling was used to test for significant group × time differences adjusting for covariates . RESULTS Retention in the study was 84 % , and median attendance to supervised classes was 84 % in the resistance group . No study -related injuries occurred . Maximal leg strength ( P=.032 ) and bench press strength ( P=.027 ) were improved after 1 year of resistance training , whereas little change occurred from stretching . Self-reported physical function improved with resistance training , whereas decreases occurred from stretching ( P=.016 ) . Disability lessened more with resistance training than stretching ( P=.018 ) . One-year change in leg press strength mediated the relation between groups ( resistance or stretching ) and 1-year change in self-reported disability ( P resistance training improved muscle strength in and rogen-deprived PCS . Strengthening muscles using functional movement patterns may be an important feature of exercise programs design ed to improve perceptions of physical function and disability . Findings from this study contribute to the mounting evidence that exercise should become a routine part of clinical care in older men with advanced prostate cancer",
"INTRODUCTION And rogen deprivation therapy ( ADT ) is associated with significant bone loss and an increase in fracture risk among prostate cancer survivors ( PCS ) . We investigated whether impact + resistance training could stop ADT-related declines in bone mineral density ( BMD ) among PCS on ADT . METHODS We r and omized 51 PCS ( mean age , 70.2 yr ) currently prescribed ADT to participate in 1 yr of impact + resistance training ( Prevent Osteoporosis with Impact + Resistance ( POWIR ) ) or in an exercise placebo program of stretching exercise ( FLEX ) . Outcomes were proximal femur ( total hip , femoral neck , and greater trochanter ) and spine ( L1-L4 ) BMD ( g·cm ) and bone turnover markers ( serum osteocalcin ( ng·mL ) and urinary deoxypyrodinoline cross-links ( nmol·mmol Cr ) ) . RESULTS Retention in the 1-yr study was 84 % and median attendance to supervised classes was 84 % in POWIR and 74 % in FLEX . No study -related injuries were reported . There were no significant differences between groups for average L1-L4 BMD or for BMD at any hip site . When examining individual vertebrae , POWIR has a significant effect on preservation of BMD ( -0.4 % ) at the L4 vertebrae compared with losses ( -3.1 % ) in FLEX ( P = 0.03 ) . CONCLUSION Impact + resistance training was a safe and acceptable form of exercise for older PCS on ADT . Among our limited sample , POWIR did not appear to have a clinical ly meaningful effect on hip or spine BMD , but some evidence of skeletal adaptation to resistance + impact training in an and rogen-deprived state was apparent . Future studies need to be conducted on a larger sample of patients and should consider modifications to POWIR that could further enhance loading across the spine and at the hip to preserve BMD at these clinical ly relevant sites",
"And rogen-deprivation therapy ( ADT ) for prostate cancer ( PCa ) has side effects that significantly impair health-related quality of life ( HRQOL ) . Exercise ameliorates many side effects of ADT , but different modalities , particularly in the home-based setting , have not been well studied . In this study the authors r and omly assigned 66 PCa survivors receiving ADT to 6 mo of home-based aerobic or resistance training . Psychosocial well-being and physical fitness were measured at baseline , 3 and 6 mo , and then 6 mo postintervention . Intention-to-treat analyses showed that fatigue and HRQOL were not significantly different between groups ; however , in a per- protocol analysis the resistance-exercise training group demonstrated clinical ly significant improvements in HRQOL . Differential within-group effects on physical fitness were also observed at various time points . At all time points , the aerobic-training group engaged in significantly more physical activity than the resistance-training group , a finding that should be further examined given evidence -based guidelines for activity volume in cancer survivors",
"Sound rigorous methods are needed by research ers and providers to address practical questions about risks , benefits , and costs of interventions as they occur in routine clinical practice such as : Are treatments used in daily practice associated with intended outcomes ? For whom does an intervention work best ? With limited clinical re sources , what are the best interventions to use for specific types of patients ? Answers to such questions can help clinicians , patients , research ers , and health care administrators learn from , and improve , real-world everyday clinical practice . In this article , we describe existing research design s to demonstrate clinical usefulness and comparative effectiveness of rehabilitation treatments . We compare r and omized controlled trials and observational cohort studies of various types , including those that use instrumental variables or propensity scores to control for potential patient or treatment selection effects . We argue that practice -based evidence ( PBE ) study design s include features that address limitations inherent in both r and omized trials and traditional observational studies , and also reduce the need for instrumental variables and propensity scores methods . We give examples of how PBE design s have been used in various rehabilitation areas to determine better treatments for specific types of patients",
"PURPOSE Radiotherapy for prostate cancer ( PCa ) may cause unfavorable changes in fatigue , quality of life ( QOL ) , and physical fitness . We report results from the Prostate Cancer Radiotherapy and Exercise Versus Normal Treatment study examining the effects of 24 weeks of resistance or aerobic training versus usual care on fatigue , QOL , physical fitness , body composition , prostate-specific antigen , testosterone , hemoglobin , and lipid levels in men with PCa receiving radiotherapy . PATIENTS AND METHODS Between 2003 and 2006 , we conducted a r and omized controlled trial in Ottawa , Canada , where 121 PCa patients initiating radiotherapy with or without and rogen deprivation therapy were r and omly assigned to usual care ( n = 41 ) , resistance ( n = 40 ) , or aerobic exercise ( n = 40 ) for 24 weeks . Our primary end point was fatigue assessed by the Functional Assessment of Cancer Therapy-Fatigue scale . RESULTS The follow-up assessment rate for our primary end point of fatigue was 92.6 % . Median adherence to prescribed exercise was 85.5 % . Mixed-model repeated measures analyses indicated both resistance ( P = .010 ) and aerobic exercise ( P = .004 ) mitigated fatigue over the short term . Resistance exercise also produced longer-term improvements ( P = .002 ) . Compared with usual care , resistance training improved QOL ( P = .015 ) , aerobic fitness ( P = .041 ) , upper- ( P lower-body ( P ( P = .036 ) , while preventing an increase in body fat ( P = .049 ) . Aerobic training also improved fitness ( P = .052 ) . One serious adverse event occurred in the group that performed aerobic exercise . CONCLUSION In the short term , both resistance and aerobic exercise mitigated fatigue in men with PCa receiving radiotherapy . Resistance exercise generated longer-term improvements and additional benefits for QOL , strength , triglycerides , and body fat",
"BACKGROUND Prostate cancer is a key driver of cancer-related global disability-adjusted life-years . And rogen-deprivation therapy ( ADT ) for advanced disease is linked to fatigue , reduced physical function , and quality of life ( QoL ) . OBJECTIVE To evaluate the effect of a lifestyle intervention on disease-specific QoL , diastolic blood pressure , and cancer-related fatigue in sedentary men receiving long-term ADT for advanced prostate cancer . DESIGN , SETTING , AND PARTICIPANTS A total of 100 hundred sedentary men with locally advanced or metastatic prostate cancer on long-term ADT were r and omised to an intervention or usual care group . INTERVENTION A 12-wk lifestyle intervention consisting of aerobic and resistance exercise with parallel dietary advice . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Disease-specific QoL was measured using the Functional Assessment of Cancer Therapy-Prostate ( FACT-P ) and Functional Assessment of Cancer Therapy-Fatigue ( FACT-F ) question naires at 12 wk postintervention and at 6 mo following withdrawal of support . Analysis of covariance and mixed regression were conducted . RESULTS AND LIMITATIONS Clinical ly relevant improvements in FACT-P were seen at 12 wk in the intervention group compared with controls ( mean difference : 8.9 points ; 95 % confidence interval [ CI ] , 3.7 - 14.2 ; adjusted p=0.001 ) . No difference was apparent at 6 mo ( mean difference : 3.3 points ; 95 % CI , -2.6 to 9.3 ; adjusted p=0.27 ) . No difference in diastolic blood pressure was seen at either follow-up ( all p > 0.05 ) . Clinical ly relevant improvements in FACT-F were seen at 12 wk ( mean difference : 5.3 points ; 95 % CI , 2.7 - 7.9 ; adjusted p in exercise tolerance and behaviour were maintained at 6 mo ( adjusted p disease-specific QoL that was not maintained postintervention . No effect on blood pressure occurred . Durability of response was seen in fatigue and exercise behaviour . Further evaluation of support structures is essential . TRIAL REGISTRATION IS RCT N88605738",
"BACKGROUND Long-term prostate cancer ( PCa ) survivors are at increased risk for comorbidities and physical deconditioning . OBJECTIVE To determine the effectiveness of a year-long r and omised controlled trial of exercise training in PCa survivors > 5 yr postdiagnosis on physical functioning . DESIGN , SETTING , AND PARTICIPANTS Between 2010 and 2011 , 100 long-term PCa survivors from Trans-Tasman Radiation Oncology Group 03.04 R and omised And rogen Deprivation and Radiotherapy previously treated with and rogen-deprivation therapy and radiation therapy were r and omly assigned to 6 mo of supervised exercise followed by 6 mo of a home-based maintenance programme ( n=50 ) or printed educational material about physical activity ( n=50 ) for 12 mo across 13 university-affiliated exercise clinics in Australia and New Zeal and . INTERVENTION Supervised resistance and aerobic exercise or printed educational material about physical activity . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary end point was a 400-m walk as a measure of cardiovascular fitness . Secondary end points were physical function , patient-reported outcomes , muscle strength , body composition , and biomarkers . Analysis of covariance was used to compare outcomes for groups at 6 and 12 mo adjusted for baseline values . RESULTS AND LIMITATIONS Participants undergoing supervised exercise showed improvement in cardiorespiratory fitness performance at 6 mo ( -19 s [ p=0.029 ] ) and 12 mo ( -13 s [ p=0.028 ] ) and better lower-body physical function across the 12-mo period ( p Supervised exercise also improved self-reported physical functioning at 6 ( p=.006 ) and 12 mo ( p=0.002 ) , appendicular skeletal muscle at 6 mo ( p=0.019 ) , and objective measures of muscle strength at 6 and 12 mo ( p Supervised exercise training in long-term PCa survivors is more effective than physical activity educational material for increasing cardiorespiratory fitness , physical function , muscle strength , and self-reported physical functioning at 6 mo . Importantly , these benefits were maintained in the long term with a home-based programme with follow-up at 12 mo . CLINICAL TRIAL REGISTRY The effect of an exercise intervention on cardiovascular and metabolic risk factors in prostate cancer patients from the RADAR study , ACTRN : ACTRN12609000729224"
] |
4116cda6-06ff-11f0-808a-c43d1ab1c353
|
BACKGROUND The aim of this systematic review was to quantify the effectiveness of progressive resistance strength training ( PRT ) to reduce physical disability in older people . METHODS R and omized controlled trials were identified from search es of relevant data bases and study reference lists and contacts with research ers . Two review ers independently screened the trials for eligibility , rated their quality , and extracted data . Only r and omized controlled trials utilizing PRT as the primary intervention in participants , whose group mean age was 60 years or older , were included . Data were pooled using fixed or r and om effect models to produce weighted mean differences ( WMD ) and 95 % confidence intervals ( CI ) . St and ardized mean differences ( SMD ) were calculated when different units of measurement were used for the outcome of interest . RESULTS 62 trials ( n = 3674 ) compared PRT with a control group . 14 trials had data available to allow pooling of disability outcomes . Most trials were of poor quality . PRT showed a strong positive effect on strength , although there was significant heterogeneity ( 41 trials [ n = 1955 ] , SMD 0.68 ; 95 % confidence interval [ CI ] 0.52 , 0.84 ) . A modest effect was found on some measures of functional limitations such as gait speed ( 14 trials [ n = 798 ] , WMD 0.07 meters per second ; 95 % CI 0.04 , 0.09 ) . No evidence of an effect was found for physical disability ( 10 trials [ n = 722 ] , SMD 0.01 ; 95 % CI -0.14 , 0.16 ) . Adverse events were poorly investigated , but occurred in most studies where they were defined and prospect ively monitored . CONCLUSIONS PRT results in improvements to muscle strength and some aspects of functional limitation , such as gait speed , in older adults . However , based on current data , the effect of PRT on physical disability remains unclear . Further , due to the poor reporting of adverse events in trials , it is difficult to evaluate the risks associated with PRT
|
[
"OBJECTIVE To test the efficacy of high-velocity training in healthy older persons . DESIGN A 12-week r and omized trial , with subjects blocked for gender and residence , comparing high-velocity resistance training with a self-paced walking program . SETTING Retirement community . PARTICIPANTS Forty-three volunteers over the age of 70 years . INTERVENTION Power group : high-velocity leg exercises 3 times weekly with weekly increases in resistance combined with 45 minutes of moderate , nonresistance exercise weekly . Walking group : moderate intensity exercise 30 minutes daily , 6 days weekly . MAIN OUTCOME MEASURES Variables measured included leg press peak power and leg extensor strength . Functional performance outcomes included : 6-minute walk distance , Short Physical Performance Battery , Physical Performance Test , and Medical Outcomes Study Short-Form Health Survey . RESULTS Peak power improved 22 % ( p = .004 ) in the power group ( 3.7 + /- 1.0 W/kg to 4.5 + /- 1.4 W/kg ) but did not change in the walking group ( 3.99 + /-.76 W/kg to 3.65 + /-.94 W/kg ) . Leg extensor power at resistance of 50 % , 60 % , and 70 % of body weight increased 50 % , 77 % , and 141 % , respectively , in the power group ( p Strength improved 22 % in the power-trained individuals and 12 % in the walkers ( p functional task performance in either group . One subject developed a radiculopathy during training . CONCLUSIONS Resistance training focusing on speed of movement improved leg power and maximal strength substantially , but did not improve functional performance in healthy high-functioning older volunteers",
"Changes in strength , speed and size of the quadriceps muscle have been investigated in elderly men and women after 6 months of isometric strength training . We have also indirectly investigated the role of metabolites as a stimulus for muscle hypertrophy by study ing two training protocol s. One thigh was trained using short , intermittent contractions ( IC ) , while the other trained using long , continuous contractions ( CC ) . This meant that there should be a greater metabolite change in the muscle performing CC , as the blood flow is occluded for longer . Nine subjects [ eight women , mean ( SE ) age , 71.8 ( 2.9 ) years ] were measured for contractile properties and strength before and after training , and compared to nine age-matched controls [ 71.5 ( 2.1 ) years ] . The training group increased quadriceps strength by 48.7 (9.1)% ( P muscle strength in the controls . Both muscles showed significant slowing after training as measured by the relaxation times and the force-frequency ratio . There were non-significant decreases in muscle fatigability after training . The control group also showed some significant decreases in fatigability and muscle speed . The training group showed significant increases in muscle ( and bone ) cross-sectional area of 4.0 (1.7)% and 4.9 (1.3)% following the CC and IC protocol s , respectively . These increases were significantly different from the decrease observed in the control group . These findings suggest that people over the age of 55 still have the capacity to increase muscle strength and size , and that the training causes slowing of the muscle . Muscle hypertrophy does not seem to be strongly influenced by metabolite changes in this age group , as there were no differences in measurements observed between protocol",
"OBJECTIVE To use two different exercise programs over a 2-year period to reduce falls and their sequelae among residents of two long-term care facilities . DESIGN R and omized , controlled trial . SETTING The study took place at two long-term care facilities with services ranging from independent living to skilled nursing . PARTICIPANTS One hundred and ten participants whose average age was 84 and who were capable of ambulating with or without assistive devices and could follow simple directions . INTERVENTION Participants were r and omized to one of two exercise groups ( resistance/endurance plus basic enhanced programming or tai chi plus basic enhanced programming ) or to a control group ( basic enhanced programming only ) . Exercise classes were held three times per week throughout the study . MEASUREMENTS Participants were evaluated for cognitive and physical functioning at baseline and 6 , 12 , and 24 months . Falls were determined from incident reports filed by the nursing staffs at the facilities . RESULTS Time to first fall , time to death , number of days hospitalized , and incidence of falls did not differ among the treatment and control groups ( P>.05 ) . Among all participants , those who fell had significantly lower baseline Folstein Mini-Mental State Examination and instrumental activities of daily living scores and experienced significantly greater declines in these measures over the 2-year program . CONCLUSION There were no significant differences in falls among the two exercise groups and the control group . Lack of treatment differences and low adherence rates suggest that residents of long-term care facilities may require individualized exercise interventions that can be adapted to their changing needs",
"OBJECTIVE To determine the effect of frequency of resistive training on gain in muscle strength and neuromuscular performance in healthy older adults . DESIGN A r and omized controlled trial with subjects assigned either to high-intensity resistance training 1 ( EX1 ) , 2 ( EX2 ) , or 3 ( EX3 ) days per week for 24 weeks or to a control group ( CO ) . SETTING An exercise facility at an academic medical center . SUBJECTS Forty-six community-dwelling healthy men ( n = 29 ) and women ( n = 17 ) aged 65 to 79 years . INTERVENTION Progressive resistance training consisting of three sets of eight exercises targeting major muscle groups of the upper and lower body , at 80 % of one-repetition maximum ( 1-RM ) for eight repetitions , either 1 , 2 , or 3 days per week . MEASURES Dynamic muscle strength ( 1-RM ) using isotonic equipment every 4 weeks , bone mineral density and body composition by dual energy X-ray absorptiometry ( DXA ) , and neuromuscular performance by timed chair rise and 6-meter backward t and em walk . RESULTS For each of the eight exercises , muscle strength increased in the exercise groups relative to CO ( P change averaged 3.9 + /- 2.4 ( CO ) , 37.0 + /- 15.2 ( EX1 ) , 41.9 + /- 18.2 ( EX2 ) , and 39.7 + /- 9.8 ( EX3 ) . The time to rise successfully from the chair 5 times decreased significantly ( P 6-meter backward t and em walk approached significance ( P = .10 ) in the three exercise groups compared with CO . Changes in chair rise ability were correlated to percent changes in quadriceps strength ( r = -0.40 , P lean mass ( r = -0.40 , P resistance exercise achieves muscle strength gains similar to 3 days per week training in older adults and is associated with improved neuromuscular performance . Such improvement could potentially reduce the risk of falls and fracture in older adults",
"BACKGROUND In patients with intermittent claudication , a supervised walking exercise program increases peak exercise performance and community-based functional status . Patients with peripheral arterial disease also have muscle weakness in the affected extremity that may contribute to the walking impairment . However , the potential benefits of training modalities other than walking exercise , such as strength training , have not been critically evaluated in this patient population . The present study tested the hypothesis that a strength training program would be as effective as treadmill walking exercise and that combinations of strengthening and walking exercise would be more effective than either alone in improving exercise performance . METHODS AND RESULTS Twenty-nine patients with disabling claudication were r and omized to 12 weeks of supervised walking exercise on a treadmill ( 3 h/wk at a work intensity sufficient to produce claudication ) , strength training ( 3 h/wk of resistive training of five muscle groups of each leg ) , or a nonexercising control group . Grade d treadmill testing was performed to maximally tolerated claudication pain to define changes in peak exercise performance . After 12 weeks , patients in the treadmill training program had a 74 + /- 58 % increase in peak walking time as well as improvements in peak oxygen consumption ( VO2 ) and the onset of claudication pain . Patients in the strength-trained group had a 36 + /- 48 % increase in peak walking time but no change in peak VO2 or claudication onset time . Control subjects had no changes in any of these measures over the 12-week period . After the first 12 weeks , patients in the initial walking exercise group continued for 12 more weeks of supervised treadmill training . This result ed in an additional 49 + /- 53 % increase in peak walking time ( total of 128 + /- 99 % increase over the 24 weeks ) . After the initial 12 weeks , patients in the strength-trained group began 12 weeks of supervised treadmill training , and patients in the control group participated in a 12-week combined program of strengthening and treadmill walking exercise . The combined strength and treadmill training program and treadmill training after 12 weeks of strength training result ed in increases in peak exercise performance similar to those observed with 12 weeks of treadmill training alone . CONCLUSIONS A supervised treadmill walking exercise program is an effective means to improve exercise performance in patients with intermittent claudication , with continued improvement over 24 weeks of training . In contrast , 12 weeks of strength training was less effective than 12 weeks of supervised treadmill walking exercise . Finally , strength training , whether sequential or concomitant , did not augment the response to a walking exercise program",
"OBJECTIVE We evaluated the effects of exercise on neurobehavioral function in healthy older people more than 75 years of age . DESIGN A r and omized controlled trial with 6-month follow-up was conducted . SETTING The study was performed in the rural town of Kahoku , Japan , the population of which is considered representative of the older population of Japan . PARTICIPANTS We studied 42 healthy volunteers ( 18 men and 24 women ; mean age , 79 years ( range 75 to 87 years ) ) who were r and omly assigned to one of two groups , exercise or control . INTERVENTION Subjects assigned to the exercise group were instructed to exercise for 60 minutes twice a week for 6 months . Subjects in the control group were not instructed to engage in an specific exercise regimen . MEASUREMENTS The following measurements were recorded for both groups at baseline and at 6-month follow-up : ( 1 ) Neurobehavioral function as determined by the following tests : Mini-Mental State Exam ( MMSE ) , Hasegawa Dementia Scale Revised ( HDSR ) , Visuospatial Cognitive Performance Test ( VCP-test ) , Button score , Up & Go test , and Functional Reach ; and ( 2 ) Body mass index and blood pressure . RESULTS The effects of exercise were shown in the Up & Go test , and Functional Reach ( ANOVA with repeated measures ) . CONCLUSION This study demonstrates the acceptability and effectiveness of exercise on neurobehavioral function , even in older people more than 75 years of age",
"OBJECTIVES This r and omized controlled trial studied the effects of a low- to moderate-intensity group exercise program on strength , endurance , mobility , and fall rates in fall-prone elderly men with chronic impairments . METHODS Fifty-nine community-living men ( mean age = 74 years ) with specific fall risk factors ( i.e. , leg weakness , impaired gait or balance , previous falls ) were r and omly assigned to a control group ( n = 28 ) or to a 12-week group exercise program ( n = 31 ) . Exercise sessions ( 90 minutes , three times per week ) focused on increasing strength and endurance and improving mobility and balance . Outcome measures included isokinetic strength and endurance , five physical performance measures , and self-reported physical functioning , health perception , activity level , and falls . RESULTS Exercisers showed significant improvement in measures of endurance and gait . Isokinetic endurance increased 21 % for right knee flexion and 26 % for extension . Exercisers had a 10 % increase ( p distance walked in six minutes , and improved ( p observational gait scale . Isokinetic strength improved only for right knee flexion . Exercise achieved no significant effect on hip or ankle strength , balance , self-reported physical functioning , or number of falls . Activity level increased within the exercise group . When fall rates were adjusted for activity level , the exercisers had a lower 3-month fall rate than controls ( 6 falls/1000 hours of activity vs 16.2 falls/1000 hours , p exercise can improve endurance , strength , gait , and function in chronically impaired , fall-prone elderly persons . In addition , increased physical activity was associated with reduced fall rates when adjusted for level of activity",
"OBJECTIVE To determine the effects of 12 weeks of progressive resistance strength training on the isometric strength , explosive power , and selected functional abilities of healthy women aged 75 and over . DESIGN Subjects were matched for age and habitual physical activity and then r and omly assigned into either a control or an exercise group . SETTING The Muscle Function Laboratory , Royal Free Hospital School of Medicine , London . PARTICIPANTS Fifty-two healthy women were recruited through local and national newspapers . Five dropped out before and seven ( 4 exercisers and 3 controls ) during the study . Pre- and posttraining measurements were obtained from 20 exercisers ( median age 79.5 , range 76 to 93 years ) and 20 controls ( median age 79.5 , range 75 to 90 years ) . INTERVENTIONS Training comprised one supervised session ( 1 hour ) at the Medical School and two unsupervised home sessions ( supported by an exercise tape and booklet ) per week for 12 weeks . The training stimulus was three sets of four to eight repetitions of each exercise , using rice bags ( 1 - 1.5 kg ) or elastic tubing for resistance . The exercises were intended specifically to strengthen the muscles considered relevant for the functional tasks , but were not to mimic the functional measurements . No intervention was prescribed for the controls . MEASUREMENTS Pre- and posttraining measurements were made for isometric knee extensor strength ( IKES ) , isometric elbow flexor strength ( IEFS ) , h and grip strength ( HGS ) , leg extensor power ( LEP ) , and anthropometric indices ( Body impedance analysis , arm muscle circumference , and body weight ) . Functional ability tests were chair rise , kneel rise , rise from lying on the floor , 118-m self-paced corridor walk , stair climbing , functional reach , stepping up , stepping down , and lifting weights onto a shelf . Pre- and posttraining comparisons were made using analysis of variance or analysis of covariance ( using weight as a covariate ) for normally distributed continuous data and one-sided Fishers exact test ( 2 x 2 table ) for discontinuous data . RESULTS Improvements in IKES ( mean change 27 % , P = .03 ) , IEFS ( 22 % , P = .05 ) , HGS ( 4 % , P = .05 ) , LEP/kg ( 18 % , P = .05 ) were associated with training , but the improvement in LEP ( 18 % , P = .11 ) did not reach statistical significance . There was an association between training and a reduction in normal pace kneel rise time ( median change 21 % , P = .02 ) and a small improvement in step up height ( median 5 % , P = .005 ) . The other functional tests did not improve . CONCLUSIONS Progressive resistance exercise can produce substantial increases in muscle strength and in power st and ardized for body weight in healthy , very old women . However , isolated increases in strength and LEP/kg may confer only limited functional benefit in healthy , independent , very old women",
"OBJECTIVE To determine the effects of stopping and restarting two types of exercise programs in older adults . DESIGN A controlled , longitudinal study that utilized r and om assignment of volunteers . Treatments were exercise programs design ed to improve cardiovascular or neuromuscular fitness . MEASUREMENTS Dependent variables measured before and after implementation of treatments were : maximum oxygen consumption , oxygen pulse , treadmill and cycle training workloads , quadriceps isokinetic peak torque , quadriceps isokinetic total work , and quadriceps training workload . MAIN RESULTS Exercise training was highly effective in improving cardiovascular endurance or muscular strength . Ten weeks of exercise detraining result ed in small losses in newly gained cardiovascular capacity but more noticeable losses in muscular strength . Exercise retraining was accomplished easily using cardiovascular or resistive exercises . The functional benefits of restarting a cardiovascular exercise program appeared additive despite a 10-week intervening period of exercise detraining . In this age group , cardiovascular exercise produced limited improvements in muscular strength , and resistive exercise training positively influenced cardiovascular exercise performance . CONCLUSIONS Older adults are fairly resilient to 10 weeks of cardiovascular detraining and retain newly gained muscular strength for at least 5 weeks , despite an interruption of formal exercise . An occasional missed exercise session or temporary cessation of habitual exercise should not be a cause for distress in exercising older adults . Instead , they should realize the case with which they may restart their exercise program and also appreciate the generalized fitness benefits that can be ascribed to becoming more active",
"BACKGROUND The purpose of this study was to evaluate how weight training or nursing-based rehabilitative care programs in nursing homes impact on resident performance of Activities of Daily Living ( ADL ) and objectives tests of physical performance . METHODS This study involved a quasi-experimental control , longitudinal comparison of functional status over a 10-month period , where baseline status was adjusted through a weighting procedure based on functional status , cognitive status , and age . All residents from six residential care nursing home facilities were eligible except those with a terminal prognosis , a projected stay of less than 90 days , or with health complications that prohibited contact . Homes were placed into matched triplets based on patient characteristics : two members of each triplet were r and omly design ated to be experimental sites , the third became the control site . Baseline data were available for 468 subjects , follow-up for 392 . ADL self-performance measures derived from the Minimum Data Set , including indicators of early loss ADL , locomotion , and late loss ADL ; a number of objective functional tests ( including measures of balance , power , and endurance ) ; and mood state as measured by the Geriatric Depression Scale . RESULTS Mean ADL values in the two experimental groups declined at a significantly lower rate than did rates for the controls . Functional decline was also lower in more specific measures : locomotion , early loss ADL , and late loss ADL . CONCLUSIONS With both interventions , facilities were able to implement a broad-based intervention that result ed in a significant reduction in ADL decline rates . A facility-wide nursing rehabilitation program can play a useful role in reversing functional decline , helping residents to maintain their involvement in a broad spectrum of ADL activities",
"A r and omized controlled trial examined the growth and form of multidimensional self-esteem over a 12-month period ( 6-month exercise intervention and 6-month follow-up ) in 174 older adults engaged in either a walking or stretching/toning program . The extent to which changes in physical fitness parameters and physical self-efficacy were related to changes in perceptions of attractive body , strength , physical conditioning , and physical self-worth was also determined . Latent growth curve analyses showed a curvilinear pattern of growth in esteem with significant increases at all levels of self-esteem upon completion of the intervention followed by significant declines at 6 months poistintervention in both groups . Frequency of activity and changes in physical fitness , body fat , and self-efficacy were related to improvements in esteem perceptions relative to attractive body , strength , and physical condition . Model fitting procedures suggested that the best fit of the data was to a model in which the influence of changes in efficacy and physical parameters on physical self-worth were mediated by perceptions of attractive body and physical conditions",
"Physical exercise is expected to improve and maintain physical function in older people , thus promoting health and preventing or postponing the onset of disability in later life . The Sendai Silver Center Trial ( SSCT ) was a r and omized controlled trial design ed to evaluate the efficacy of exercise training among healthy free-living older people . Sixty-five eligible participants , aged from 60 to 81 years , were r and omly allocated to an exercise group or a control group . The subjects in the exercise group were asked to attend training classes at the Sendai Silver Center , a municipal health and welfare facility in the center of Sendai City , at least twice a week for 25 weeks . Each training class , lasting two hours , started with a warm-up session , followed by an endurance session with a bicycle ergometer , and a resistance exercise training session using rubber films , and ended with a cool-down session . The subjects in the control group were asked to attend recreational classes at the Center twice a month . There were no drop-outs or accidents during the intervention . Comparison of maximum oxygen consumption ( VO2max ) before and after the 25-week intervention revealed a significant increase in the exercise group ( 2.1 ml/kg/min ) but no significant change in the control group . Our result is equivalent to the participants becoming younger in aerobic capacity by five years after six months of exercise training",
"BACKGROUND Physical activity programs in nursing homes typically consist of seated , range of motion ( ROM ) exercises , regardless of resident abilities . The Functional Fitness for Long-Term Care ( FFLTC ) Program was design ed not only to maintain ROM , but also to improve strength , balance , flexibility , mobility , and function . In addition , it was tailored to meet the needs of both high and low mobility residents . METHODS The feasibility and efficacy of the FFLTC Program were evaluated with 68 residents ( mean age 80 ) from five institutions . Persons were classified as low or high mobility and r and omized into either the FFLTC program or a seated ROM program . Classes were conducted in groups of 4 to 10 residents by trained facility staff for 45 minutes , three times per week . Assessment s at baseline and 4 months consisted of mobility , balance , gait , flexibility , functional capacity , and several upper and lower extremity strength measures . RESULTS Attendance averaged 86 % for the FFLTC and 79 % for the ROM classes . Four months of exercise led to significant improvements in mobility ( 16 % ) , balance ( 9 % ) , flexibility ( 36 % ) , knee ( 55 % ) , and hip ( 12 % ) strength for the FFLTC group . Shoulder strength was the only improvement found for the ROM group . The ROM group significantly deteriorated in some areas , particularly hip strength , mobility , and functional ability . CONCLUSIONS Institutionalized seniors , even those who are physically frail , incontinent and /or have mild dementia , can respond positively to a challenging exercise program . The FFLTC program demonstrated clear benefits over typical , seated ROM exercises . Moreover , with minimal training , the program can be safely delivered at low cost by institutional staff and volunteers",
"BACKGROUND To study the effects of resistance training on muscle strength and size in older people , we enrolled 8 men and 17 women ( mean age 68.2 + /- 1 SEM ) into a one-year exercise trial . METHODS Subjects were r and omly assigned to exercise or control groups . Muscle biopsies were obtained from 11 subjects ( 8 exercisers/3 controls ) at baseline and after 15 weeks ; exercisers underwent another biopsy at 30 weeks . After testing maximum strength using the 1-RM method , the exercisers began a 12-exercise circuit ( 3 sets of 8 repetitions at 75 % of 1-RM ) , 3 times a week . The controls repeated the strength testing every 15 weeks . They were asked to continue usual activities and not to start any exercise program . RESULTS With exercise , muscle strength increased , average increases ranging from 30 % ( hip extensors ) to 97 % ( hip flexors ) . Strength increased rapidly over 3 months , then plateaued for the duration of the experiment . No strength changes were observed in sedentary controls . Cross-sectional area of type 1 muscle fibers increased in exercisers by 15 weeks ( 29.4 + /- 1 % , p Type 2 fiber area did not change at 15 weeks , but increased by 30 weeks of training ( 66.6 + /- 9.5 % , p moderate to high intensity resistance training may be carried out by healthy older adults with reasonable compliance , and that such training leads to sustained increases in muscle strength . These improvements are rapidly achieved and are accompanied by hypertrophy of both type 1 and type 2 muscle fibers",
"BACKGROUND PATIENTS : with chronic airflow obstruction are often limited by muscle fatigue and weakness . As exercise rehabilitation programmes have produced modest improvements at best a study was design ed to determine whether specific muscle training techniques are helpful . METHODS : Thirty four patients with chronic airflow limitation ( forced expiratory volume in one second ( FEV1 ) 38 % of predicted values ) were stratified for FEV1 to vital capacity ( VC ) ratio less than 40 % and arterial oxygen desaturation during exercise and r and omised to a control or weightlifting training group . In the experimental group training was prescribed for upper and lower limb muscles as a percentage of the maximum weight that could be lifted once only . It was carried out three times a week for eight weeks . RESULTS : Three subjects dropped out of each group ; results in the remaining 14 patients in each group were analysed . Adherence in the training group was 90 % . In the trained subjects muscle strength and endurance time during cycling at 80 % of maximum power output increased by 73 % from 518 ( SE69 ) to 898 ( 95 ) s , with control subjects showing no change ( 506 ( 86 ) s before training and 479 ( 89 ) s after training ) . No significant changes in maximum cycle ergometer exercise capacity or distance walked in six minutes were found in either group . Responses to a chronic respiratory question naire showed significant improvements in dyspnoea and mastery of daily living activities in the trained group . CONCLUSIONS : Weightlifting training may be successfully used in patients with chronic airflow limitation , with benefits in muscle strength , exercise endurance , and subjective responses to some of the dem and s of daily living",
"This study determined the cellular energetic and structural adaptations of elderly muscle to exercise training . Forty male and female subjects ( 69.2 + /- 0.6 yr ) were assigned to a control group or 6 mo of endurance ( ET ) or resistance training ( RT ) . We used magnetic resonance spectroscopy and imaging to characterize energetic properties and size of the quadriceps femoris muscle . The phosphocreatine and pH changes during exercise yielded the muscle oxidative properties , glycolytic ATP synthesis , and contractile ATP dem and . Muscle biopsies taken from the same site as the magnetic resonance measurements were used to determine myosin heavy chain isoforms , metabolite concentrations , and mitochondrial volume densities . The ET group showed changes in all energetic pathways : oxidative capacity ( + 31 % ) , contractile ATP dem and ( -21 % ) , and glycolytic ATP supply ( -56 % ) . The RT group had a large increase in oxidative capacity ( 57 % ) . Only the RT group exhibited change in structural properties : a rise in mitochondrial volume density ( 31 % ) and muscle size ( 10 % ) . These results demonstrate large energetic , but smaller structural , adaptations by elderly muscle with exercise training . The rise in oxidative properties with both ET and RT suggests that the aerobic pathway is particularly sensitive to exercise training in elderly muscle . Thus elderly muscle remains adaptable to chronic exercise , with large energetic changes accompanying both ET and RT",
"Objective : Comparison of two flooring types – carpet and vinyl – in the bed areas , and two modes of physiotherapy – conventional therapy and additional leg strengthening exercises – in avoiding falls . Design : R and omized 2 × 2 controlled trial . Setting : Elderly care rehabilitation ward in a community hospital . Subjects : Fifty-four consecutive patients referred for rehabilitation . Outcome measures : The incidence of falls , and the change in strength . Results : There were 10 falls on carpet , and only a single fall on vinyl floor covering ( relative risk 8.3 , 95 % confidence interval 0.95–73 , p = 0.05 ) . There were four falls in those receiving additional exercise , and seven falls in those receiving only conventional physiotherapy ( relative risk 0.21 , 95 % confidence interval 0.04–1.2 , p = 0.12 ) . Fifty-nine per cent of patients were able to complete strength measurements on admission and discharge . In these , h and grip strength improved more in those given additional exercise than conventional physiotherapy ( 2.1 kg versus – 0.3 kg , p preventing falls on a rehabilitation ward , but within this low-powered study , there was a strong trend towards vinyl being superior ",
"OBJECTIVE To evaluate the effects of isokinetic exercise versus a program of patient education on pain and function in older persons with knee osteoarthritis . DESIGN A r and omized , comparative clinical trial , with interventions lasting 8 weeks and evaluations of 12 weeks . SETTING An outpatient Veterans Affairs Medical Center clinic and an affiliated university hospital . PATIENTS One hundred thirteen men and women between 50 and 80 years old with diagnosed osteoarthritis of the knee ; 98 completed the entire assigned treatment . INTERVENTION Patients received either a regimen of isokinetic exercise of the quadriceps muscle three times weekly over 8 weeks or a series of 4 discussion s and lectures led by health care professionals . MAIN OUTCOME MEASURES Variables studied for change were isokinetic and isometric quadriceps strength , pain and function determined by categorical and visual analog scales , and overall status using physician and patient global evaluations by the Arthritis Impact Scale , version 2 , Western Ontario McMaster 's Arthritis Index , and Medical Outcome Study Short Form 36 . RESULTS Both treatment groups showed significant strength gains ( p pain scores for more of the variables measured than those receiving education . Both groups had positive functional outcomes and slightly improved measures of overall status . CONCLUSIONS Isokinetic exercise is an effective and well-tolerated treatment for knee osteoarthritis , but a much less costly education program also showed some benefits",
"To evaluate the effects of 26 wk of aerobic and resistance training on the incidence of injury and program adherence in 70- to 79-yr-old men and women , 57 healthy volunteers ( 25 males , 32 females ) were r and omly assigned to a walk/jog ( W/J , N = 21 ) , strength ( STREN , N = 23 ) , or control ( CONT , N = 13 ) group . Walk/jog training was for 30 - 45 min , 3 d.wk-1 with intensity equal to 40 - 70 % heart rate max reserve ( HRmax reserve ) during the first 13 wk , and 75 - 85 % HRmax reserve for weeks 14 - 26 . STREN training consisted of one set ( 10 - 12 repetitions ) each of 10 variable resistance exercises performed to volitional fatigue . Forty-nine of the original participants completed the training program . Walk/jog training increased VO2max from 22.5 to 27.1 ml.kg-1.min-1 ( P less than or equal to 0.05 ) while STREN and CONT showed no change . STREN improved significantly in chest press and leg extension strength ( P less than or equal to 0.05 ) while W/J and CONT showed no change . Adherence to training was 20/23 ( 87 % ) and 17/21 ( 81 % ) in STREN and W/J , respectively . One repetition maximum ( 1-RM ) strength testing result ed in 11 injuries in the 57 subjects ( 19.3 % ) while STREN training result ed in only two injuries in 23 subjects ( 8.7 % ) . Walk training during weeks 1 - 13 result ed in one injury in 21 subjects ( 4.8 % ) . Eight of 14 subjects ( 57 % ) who began jogging intervals at week 14 incurred an injury : two of eight ( 25 % ) of the men and all of the women ( 6 of 6 ) . All W/J training injuries were to the lower extremity . ( ABSTRACT TRUNCATED AT 250 WORDS",
"Regular exercise has been recommended to improve balance , strength , and coordination in older persons . In this study , 44 persons , aged 50 to 75 years ( mean 62.4 yrs ) underwent assessment s of quadriceps strength , reaction time , neuromuscular control , and body sway on two occasions before beginning a 10-week exercise program . The subjects were retested for the same measures at the end of the program . The mean number of classes attended for the 40 subjects who were retested was 16.2 ( range 11 to 19 ) . On completion of the program , the subjects showed improved performance in the tests of quadriceps strength , reaction time , body sway on a firm surface with the eyes closed , and a compliant surface with the eyes open and closed . In contrast , a group of nonexercisers showed no improvements in any of the test measures . These results suggest that exercise may play a role in improving a number of sensorimotor systems that contribute to stability in older persons",
"PURPOSE To determine whether isokinetic training can improve the strength of the hemiparetic knee musculature , functional mobility , and physical activity and to evaluate its effect on spasticity in long-term stroke survivors . DESIGN Nonr and omized self-controlled trial . SUBJECTS A volunteer sample of 15 community-dwelling stroke survivors of at least 6 months . INTERVENTION A 6-week ( 3 days/week , 40 minutes/day ) program consisting of warm-up , stretches , reciprocal knee extension and flexion isokinetic strengthening , and cool-down for the paretic limb . MAIN OUTCOME MEASURES Peak isokinetic hamstring and quadriceps torque , quadriceps spasticity , gait velocity , timed Up and Go , timed stair climb , and the Human Activity Profile ( HAP ) scores were recorded at baseline , after training , and 4 weeks after training cessation ( follow-up ) . RESULTS Paretic muscle strength improved after training ( p tone remained consistent ( p > .87 ) . Gait velocity increased after training ( p in stair climbing and timed Up and Go were not significant ( p > .37 ; p > .91 ) , although subjects perceived gains in their physical abilities at follow-up ( p strength and gait velocity without concomitant increases in muscle tone are possible after a short-term strengthening program for stroke survivors . The psychological benefit associated with physical activity is significant",
"Abstract . There is evidence that high intensity resistance training promotes bone maintenance in older women , however , the effect of high intensity free weight training has not been investigated in older men or women . Furthermore , little is known about the chronic effect of weight training on serum insulin growth factor-I ( IGF-I ) in this population . We compared the effects of a moderate intensity seated resistance-training program with a high intensity st and ing free weight exercise program on bone mass and serum levels of IGF-I and IGFBP3 in healthy older men and women . Twenty-eight men ( 54.6 ± 3.2 years ) and 26 nonestrogen-replaced women ( 52.8 ± 3.3 years ) served as their own controls for 12 weeks , then were r and omly assigned to a moderate or high intensity training group and trained three times/week for 24 weeks . Prior to and after the control period and at the end of training , bone mass and body composition were assessed by dual energy X-ray absorptiometry ( DXA ) , muscle strength by isokinetic dynamometry , muscular power by Wingate Anaerobic Power Test , and IGF-I by radioimmunoassay ( RIA ) . A repeated measures analysis of covariance ( ANCOVA ) revealed that high intensity training result ed in a gain in spine BMD in men ( 1.9 % ) , P increases in trochanteric BMD ( 1.3 % and 2.0 % , respectively ) and a decrease in femoral BMD ( −1.8 % ) . Neither circulating serum IGF-I nor IGFBP3 were altered by either training regimen , but both training programs result ed in improvements in total body strength ( 37.62 % ) and lean mass ( males 4.1 % , females 3.1 % ) . We conclude that although resistance training of moderate to high intensity produced similar muscle changes in older adults , a higher magnitude is necessary to stimulate osteogenesis at the spine . However , at the spine , intensity was not sufficient to offset low levels of estrogen in early postmenopausal women . Furthermore , bone changes were not accompanied by changes in circulating serum levels of IGF-I or IGFBP3",
" Eighty-six elderly people with limited mobility and dependence in at least one activity of daily living were recruited to a home exercise study . The subjects ( mean age 82 years ) were allocated at r and om to either a strength exercise group , a mobility exercise group or a health education group . Subjects were visited for 30 minutes every 3 - 4 weeks by a physiotherapist who gave both verbal and written instruction . Sixty-nine of the original 86 completed the 6-month study , with five drop-outs from the strength group , ten drop-outs from the mobility group , and two drop-outs from the health education group . By the end of the study , there were no significant differences between the groups with regard to changes in outcome variables . The results showed a trend towards improvement in both the exercise groups in both Sit to St and and Timed Get Up and Go tests , but this failed to attain statistical significance . Further work is required to identify the optimal exercise intervention for this subgroup of the elderly population",
"OBJECTIVE To test the effects of a high intensity home-based progressive strength training program on the clinical signs and symptoms of osteoarthritis ( OA ) of the knee . METHODS Forty-six community dwelling patients , aged 55 years or older with knee pain and radiographic evidence of knee OA , were r and omized to a 4 month home based progressive strength training program or a nutrition education program ( attention control ) . Thirty-eight patients completed the trial with an adherence of 84 % to the intervention and 65 % to the attention control . The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis ( WOMAC ) index pain and physical function subscales . Secondary outcomes included clinical knee examination , muscle strength , physical performance measures , and question naires to measure quality of life variables . RESULTS Patients in the strength training group who completed the trial had a 71 % improvement in knee extension strength in the leg reported as most painful versus a 3 % improvement in the control group ( p self-reported pain improved by 36 % and physical function by 38 % in the strength training group versus 11 and 21 % , respectively , in the control group ( p = 0.01 for between group comparison ) . In addition , those patients in the strength training group who completed the trial had a 43 % mean reduction in pain ( p = 0.01 vs controls ) , a 44 % mean improvement in self-reported physical function ( p physical performance , quality of life , and self-efficacy when compared to the control group . CONCLUSION High intensity , home based strength training can produce substantial improvements in strength , pain , physical function and quality of life in patients with knee OA",
"BACKGROUND This study was undertaken to determine ( a ) whether a program of regular exercise can improve gait patterns in older women , and ( b ) whether any such improvement in gait is mediated by increased lower limb muscle strength . METHOD A 22-week r and omized controlled trial of exercise was conducted as part of the R and wick Falls and Fractures Study in Sydney , Australia . Subjects were 160 women aged 60 - 83 years ( Mean age 71.1 , SD = 5.2 ) who were r and omly recruited from the community . Exercise and control subjects were tested prior to and at the end of the trial . At initial testing , exercisers and controls performed similarly in the strength and gait parameters . They were well matched in terms of age and a number of health and life-style characteristics . RESULTS At the end of the trial , the exercise subjects showed improved strength in five lower limb muscle groups , increased walking speed , cadence , stride length , and shorter stride times as indicated by both reduced swing and stance duration . There were no significant improvements in any of the strength or gait parameters in the controls . Within the exercise group , increased cadence was associated with improved ankle dorsiflexion strength , and increased stride length was associated with improved hip extension strength . Exercise subjects with initial slow walking speed showed greater changes in velocity , stride length , cadence , and stance duration than those with initial fast walking speed . CONCLUSION These findings show that exercise can increase gait velocity and related parameters in older persons , and that part of this increase may be mediated by improved lower limb muscle strength",
"The objectives of this study were to evaluate ( 1 ) the effect of spinal muscle strengthening by loading exercises on the bone mineral density ( BMD ) of the spine , and ( 2 ) the effect of upper extremity loading exercises on the BMD of the midradius and femur in healthy , premenopausal women . The study design was a r and omized , controlled trial of 3 years ' duration . Ninety-six healthy , premenopausal , white women aged 30 - 40 years participated ; 67 completed the study . All subjects were in good health ( normal menses ) and were active , but not athletic ( that is , not involved in a regular sport activity ) . Subjects were r and omized to an exercise or control group . The exercise group performed a supervised , non-strenuous , weight-lifting exercise program . Exercise performance was supervised once a week at the medical facility . In addition , the subjects performed the exercises twice a week on their own . Dietary calcium intake was to be maintained at 1,500 mg/day in both groups . Bone density was measured at the lumbar spine and hip with dual-energy X-ray absorptiometry at 0 , 1 , and 3 years . BMD of the midradius was measured with single photon absorptiometry . Measurements of muscle strength were obtained at baseline and every 3 months for 3 years . Maximal oxygen uptake was measured , and the level of physical activity was recorded . Compliance with the exercise program was excellent during the first year of the study , but decreased thereafter . At the end of 3 years , subject withdrawal was about 34 % from the exercise group and about 22 % from the control group ( total subject withdrawal was about 30 % ) . Muscle strength in the exercise group increased significantly at all involved skeletal sites ( p values all BMD of Ward 's triangle with spinal flexor strength ( r = 0.32 , p = 0.008 ) and with grip strength ( r = 0.38 , p = 0.001 ) . Comparing study groups , we found no significant effect of the loading and nonstrenuous strengthening exercises in the exercise group or free physical activity group ( our control group ) on BMD at the spine , hip , or midradius measurement sites . In active , but not athletic premenopausal women , additional moderate weight-lifting exercises showed no significant effect on BMD",
"Abstract : A r and omised controlled trial was conducted to determine whether a 12–month program of group exercise had beneficial effects on physiological and cognitive functioning and mood in 187 older community – dwelling women . The exercisers ( n= 94 ) and controls ( n= 93 ) were well matched in terms of the test measures and a number of health and life – style assessment s. The mean number of classes attended by the 71 exercise subjects who completed the program was 59.0 ( range 26 to 82 ) . At the end of the trial , the exercisers showed significant improvements in reaction time , strength , memory span and measures of wellbeing when compared with the controls . There was also an indication that anxiety had been reduced in the exercisers . Within the exercise group , improvements in memory span were associated with concomitant improvements in both reaction time and muscle strength . Also , within this group , initial mood measures were significantly inversely associated with improvements at retest , which suggests that the program may have normalised mood states in subjects who had high initial depression , anxiety and stress levels , rather than inducing improvements in all subjects . These findings suggest that group exercise has beneficial effects on physiological and cognitive functioning and wellbeing in older people",
"PURPOSE This investigation examined the effect of 6 months of high- or low-intensity resistance exercise ( REX ) on bone mineral density ( BMD ) and biochemical markers of bone turnover in adults aged 60 - 83 yr . METHODS Sixty-two men and women ( 68.4 + /- 6 yr ) were stratified for strength and r and omly assigned to a control ( CON , N = 16 ) , low-intensity ( LEX , N = 24 ) , or high-intensity ( HEX , N = 22 ) group . Subjects participated in 6 months of progressive REX training . Subjects trained at either 50 % of their one repetition maximum ( 1-RM ) for 13 repetitions ( LEX ) or 80 % of 1-RM for 8 repetitions ( HEX ) 3 times x wk(-1 ) for 24 wk . One set each of 12 exercises was performed . 1-RM was measured for eight exercises . BMD was measured for total body , femoral neck , and lumbar spine by dual energy x-ray absorptiometry ( DXA ) . Serum levels of bone-specific alkaline phosphatase ( BAP ) , osteocalcin ( OC ) , and pyridinoline cross-links ( PYD ) were measured . RESULTS 1-RM significantly increased for all exercises tested for both the HEX and LEX groups ( P increases in total strength ( sum of all eight 1-RMs ) were 17.2 % and 17.8 % for the LEX and HEX groups , respectively . Bone mineral density ( BMD ) of the femoral neck significantly ( P BMD were found . OC increased by 25.1 % and 39.0 % for the LEX and HEX groups , respectively ( P BAP significantly ( P REX training was successful for improving BMD of the femoral neck in healthy elderly subjects . Also , these data suggest REX increased bone turnover , which over time may lead to further changes in BMD",
"PURPOSE This study investigated effects of an 8-wk , low-frequency and low-volume , supervised , progressive strength training program emphasizing free weight , multijoint movements on the muscular power , strength , endurance , and flexibility of African American women 44 to 68 yr of age . METHODS Nineteen sedentary African American women were r and omly assigned to a strength training ( ST ) only group ( N = 12 ; mean age , 51 yr ) or a nonexercise control ( C ) group ( N = 7 ; mean age , 52 yr ) . Maximal power , strength , absolute endurance , and flexibility were assessed before and after training . Subjects trained 2 d x wk(-1 ) using free weight ( barbells and dumbbells ) and machine ( plate loaded ) exercises for two to three sets of 8 to 10 repetitions on both primary and assistance exercises . RESULTS Upper body power ( medicine ball put distance ) significantly increased statistically ( P = 0.002 ) , but gains possibly lacked practical significance because of measurement variation . Lower body power ( peak watts on bicycle ) experienced a small , nonsignificant increase in the ST group . Significant increases ( P = 0.000 ) in 1RM muscle strength occurred in the ST group ( leg press , + 99.8 % ; bench press , + 34.4 % ) . Absolute endurance significantly increased ( P = 0.000 ) in the ST group ( leg press repetitions to failure at 70 % pretest 1RM , + 221 % ; bench press repetitions to failure at 50 % pretest 1RM , + 112 % ) . Significant flexibility gains occurred in the ST group ( sit- and -reach test , + 8.2 % ; P = 0.017 ) . No significant changes occurred in power , strength , absolute endurance , or flexibility in the C group . CONCLUSION This study demonstrates that 8 wk of low-frequency , supervised , progressive strength training emphasizing free weight , multijoint movements can safely cause significant gains in muscle strength , absolute endurance , and flexibility in older African American women",
"Sullivan DH , Wall PT , Bariola JR , Bopp MM , Frost YM : Progressive resistance muscle strength training of hospitalized frail elderly . Am J Phys Med Rehabil 2001;80:503–509 . Objective To determine whether frail elderly patients recuperating from acute illnesses could safely participate in and gain appreciable improvement in muscle strength from progressive resistance muscle strength training . Design Muscle strength ( one repetition maximum ) , functional abilities ( sit-to-st and maneuver and 20-sec maximal safe gait speed ) , and body composition were measured before and at the conclusion of a 10-wk program of lower limb progressive resistance muscle strength training . The nonr and omized study was conducted in a 30-bed geriatric rehabilitation unit of a university-affiliated Veterans Affairs hospital and a 28-bed transitional care unit of a community nursing home . Participants included 19 recuperating elderly subjects ( 14 male , 5 female ; 13 ambulatory , 6 nonambulatory ) > 64 yr ( mean age , 82.8 ± 7.9 yr ) . Results The one repetition maximum increased an average of 74 % ± 49 % ( median , 70 % ; interquartile range , 38%–95 % , and an average of 20 ± 13 kg ( P = 0.0001 ) . Sit-to-st and maneuver times improved in 15 of 19 cases ( 79 % ) . Maximum safe gait speeds improved in 10 of 19 cases ( 53 % ) . Four of the six nonambulatory subjects progressed to ambulatory status . No subject experienced a complication . Conclusions A carefully monitored program of progressive resistance muscle strength training to regain muscle strength is a safe and possibly effective method for frail elderly recuperating from acute illnesses . A r and omized control study is needed to examine the degree to which progressive resistance muscle strength training offers advantages , if any , over routine posthospital care that includes traditional low-intensity physical therapy",
"Chronic heart failure ( CHF ) is characterized by a skeletal muscle myopathy not optimally addressed by current treatment paradigms or aerobic exercise . Sixteen older women with CHF were compared with 80 age-matched peers without CHF and r and omized to progressive resistance training or control stretching exercises for 10 wk . Women with CHF had significantly lower muscle strength ( P aerobic capacity to women without CHF . Exercise training was well tolerated and result ed in no changes in resting cardiac indexes in CHF patients . Strength improved by an average of 43.4 + /- 8.8 % in resistance trainers vs. -1.7 + /- 2.8 % in controls ( P = 0.001 ) , muscle endurance by 299 + /- 66 % vs. 1 + /- 3 % ( P = 0.001 ) , and 6-min walk distance by 49 + /- 14 m ( 13 % ) vs. -3 + /- 19 m ( -3 % ) ( P = 0.03 ) . Increases in type I fiber area ( 9.5 + /- 16 % ) and citrate synthase activity ( 35 + /- 21 % ) in skeletal muscle were independently predictive of improved 6-min walk distance ( r2 = 0.78 ; P = 0.0024 ) . High-intensity progressive resistance training improves impaired skeletal muscle characteristics and overall exercise performance in older women with CHF . These gains are largely explained by skeletal muscle and not resting cardiac adaptations",
"Women aged 67 - 84 yr were r and omly assigned to either resistance exercise ( RE , n = 15 ) or control group ( C , n = 14 ) . RE group completed 10 wk of resistance training , whereas C group maintained normal activity . Blood sample s were obtained from the RE group ( at the same time points as for resting C ) at rest , immediately after resistance exercise , and 2 h after exercise before ( week 0 ) and after ( week 10 ) training . Mononuclear cell ( CD3 + , CD3+CD4 + , CD3+CD8 + , CD19 + , and CD3-CD16+CD56 + ) number , lymphocyte proliferative ( LP ) response to mitogen , natural cell-mediated cytotoxicity ( NCMC ) , and serum cortisol levels were determined . Strength increased significantly in RE subjects ( % change 8-repetition maximum = 148 % ) . No significant group , exercise time , or training effects were found for CD3 + , CD3+CD4 + , or CD3+CD8 + cells , but there was a significant exercise time effect for CD3-CD16+CD56 + cells . LP response was not different between groups , across exercise time , or after training . NCMC was increased immediately after exercise for RE subjects at week 0 and for RE and C groups at week 10 . The week 0 and week 10 NCMC values were above baseline for both RE and C groups 2 h after exercise . In conclusion , acute resistance exercise did not result in postexercise suppression of NCMC or LP , and 10 wk of resistance training did not influence resting immune measures in women aged 67 - 84 yr",
"BACKGROUND Muscle size and strength decrease with aging , and the result ant muscle weakness has been implicated in increased risk of falls in older adults . These falls have large economic and functional costs . METHODS The purpose of this r and omized , controlled study was to determine if an 8-week , 3-day per week intense ( 77.8 + /- 3.4 % of 1-repetition maximum [ 1RM ] ) strength training program could improve functional ability related to the risk of falling in subjects aged 61 - -87 years ( mean 72 , SD 6.3 ) . Twelve strength-training-naive subjects performed two sets of 10 repetitions for six lower body exercises while 12 subjects served as nonintervention controls . Subjects were tested pre- , mid- , and postintervention for strength gain and on three tests of functional ability . RESULTS Postintervention strength was significantly better ( p injuries were reported as a result of either training or 1RM testing . After controlling for preintervention differences , repeated measure analysis of covariance ( ANCOVA ) found a significant difference between experimental and nonintervention control subjects for postintervention maximal walking speed [ F(1,19 ) = 5.03 , p 1-leg blind balance time or 5-repetition sit-to-st and performance [ F(1,19 ) = .082 ; F(1,19 ) = .068 , respectively , p > .05 ] . CONCLUSIONS These findings suggest that strength training alone does not appear to enhance st and ing balance or sit-to-st and performance in active , community-dwelling older adults but that it may improve maximal walking speed . The relationship between strength gain and risk of falls remains unclear . The data do reinforce the notion that intense strength training is a safe and effective way to increase muscle strength in this population",
"BACKGROUND Past studies suggest multidisciplinary interventions that include physical therapy ( PT ) can improve function of nursing home residents . This trial specifically evaluates effects of PT for frail long-stay nursing home residents . DESIGN R and omized , controlled trial . SETTING One academic nursing home and eight community nursing homes . PATIENTS A total of 194 elderly nursing home residents dependent in at least two activities of daily living residing in the nursing home for at least 3 months . INTERVENTIONS Patients were r and omized to individually tailored one-on-one PT sessions or friendly visits ( FVs ) three times a week for 4 months . Physical therapy included range-of-motion , strength , balance , transfer , and mobility exercises . MAIN OUTCOME MEASURES Performance-based physical function assessed by the Physical Disability Index ; self-perceived health status assessed with the Sickness Impact Profile ; observer-reported activities of daily living ; and falls . RESULTS Eighty-nine percent and 92 % of PT and FV sessions , respectively , were attended ; 5 % and 9 % of subjects dropped out in the PT group and FV group , respectively . Compared with the FV group , the PT group experienced no significant improvements in overall Physical Disability Index , Sickness Impact Profile , or activities of daily living scores . A 15.5 % improvement in the mobility subscale of the Physical Disability Index was seen ( 95 % confidence interval [ CI ] , 6.4 % to 24.7 % ) ; no benefits in range-of-motion , strength , or balance subscales were found . Compared with the FV group , the PT group used assistive devices for bed mobility tasks less often ( P = .06 ) and were less likely to use assistive devices and wheelchairs for locomotion ( P group vs 60 falls in the FV group ( P = .11 ) . Charge for the 4-month PT program was $ 1220 per subject ( 95 % CI , $ 412 to $ 1832 ) . CONCLUSION This st and ardized physical therapy program provided modest mobility benefits for very frail long-stay nursing home residents with physical disability due to multiple comorbid conditions",
"OBJECTIVE To determine the safety and efficacy of 3 months of resistive training of multiple lower extremity muscle groups compared with balance training in persons over 75 years . DESIGN R and omized 3-month clinical trial . Subjects ( n = 110 , mean age 80 ) were r and omized to 4 groups in a 2 x 2 design ( control , resistive , balance , combined resistive/balance ) . INTERVENTIONS Resistive training involved knee extension and flexion , hip abduction and extension , and plantar and dorsiflexion using simple resistive machines and s and bags . Balance training consisted of exercises to improve postural control . The control group attended 5 health-related discussion sessions . MEASUREMENTS Summed isokinetic moments ( N m ) of 8 leg movements : hip , knee and ankle flexion/extension , and hip abduction/adduction . Secondary outcomes were gait velocity and chair rise time . MAIN RESULTS Summed peak moment increased in both resistive exercise-trained groups ( 13 % increase in the resistive group and 21 % in the combined training group , P resistance training was significant ( MANOVA F = 21.1 , P strength , and there was no interaction ( positive or negative ) between balance and resistive training . Maximal gait velocity and chair rise time did not improve . Eleven subjects ( 20 % ) had musculoskeletal complaints related to resistive training , but all were able to complete the program with modifications . CONCLUSION Resistive training using simple equipment is an effective and acceptable method to increase overall leg strength in older persons . Resistive or balance training did not improve maximal gait velocity or chair rise time in this sample of relatively healthy older persons",
"OBJECTIVE To determine how multiple risk factors for osteoporotic fractures could be modified by high-intensity strength training exercises in postmenopausal women . DESIGN R and omized controlled trial of 1-year duration . SETTING Exercise laboratory at Tufts University , Boston , Mass. POPULATION Forty postmenopausal white women , 50 to 70 years of age , participated in the study ; 39 women completed the study . The subjects were sedentary and estrogen-deplete . INTERVENTIONS High-intensity strength training exercises 2 days per week using five different exercises ( n = 20 ) vs untreated controls ( n = 19 ) . MAIN OUTCOME MEASURES Dual energy x-ray absorptiometry for bone status , one repetition maximum for muscle strength , 24-hour urinary creatinine for muscle mass , and backward t and em walk for dynamic balance . RESULTS Femoral neck bone mineral density and lumbar spine bone mineral density increased by 0.005 + /- 0.039 g/cm2 ( 0.9 % + /- 4.5 % ) ( mean + /- SD ) and 0.009 + /- 0.033 g/cm2 ( 1.0 % + /- 3.6 % ) , respectively , in the strength-trained women and decreased by -0.022 + /- 0.035 g/cm2 ( -2.5 % + /- 3.8 % ) and -0.019 + /- 0.035 g/cm2 ( -1.8 % + /- 3.5 % ) , respectively , in the controls ( P = .02 and .04 ) . Total body bone mineral content was preserved in the strength-trained women ( + 2.0 + /- 68 g ; 0.0 % + /- 3.0 % ) and tended to decrease in the controls ( -33 + 77 g ; -1.2 % + /- 3.4 % , P = .12 ) . Muscle mass , muscle strength , and dynamic balance increased in the strength-trained women and decreased in the controls ( P = .03 to High-intensity strength training exercises are an effective and feasible means to preserve bone density while improving muscle mass , strength , and balance in postmenopausal women",
"Abstract Objective : To assess the effectiveness of a home exercise programme of strength and balance retraining exercises in reducing falls and injuries in elderly women . Design : R and omised controlled trial of an individually tailored programme of physical therapy in the home ( exercise group , n=116 ) compared with the usual care and an equal number of social visits ( control group , n=117 ) . Setting : 17 general practice s in Dunedin , New Zeal and . Subjects : Women aged 80 years and older living in the community and registered with a general practice in Dunedin . Main outcome measures : Number of falls and injuries related to falls and time between falls during one year of follow up ; changes in muscle strength and balance measures after six months . Results : After one year there were 152 falls in the control group and 88 falls in the exercise group . The mean ( SD ) rate of falls was lower in the exercise than the control group ( 0.87 ( 1.29 ) v 1.34 ( 1.93 ) falls per year respectively ; difference 0.47 ; 95 % confidence interval 0.04 to 0.90 ) . The relative hazard for the first four falls in the exercise group compared with the control group was 0.68 ( 0.52 to 0.90 ) . The relative hazard for a first fall with injury in the exercise group compared with the control group was 0.61 ( 0.39 to 0.97 ) . After six months , balance had improved in the exercise group ( difference between groups in change in balance score 0.43 ( 0.21 to 0.65 ) . Conclusions : An individual programme of strength and balance retraining exercises improved physical function and was effective in reducing falls and injuries in women 80 years and older . Key messages Modifiable risk factors for falls in elderly people have been well defined ; they include loss of muscle strength and impaired balance A programme to improve strength and balance in women aged 80 years and older can be set up safely with four home visits from a physiotherapist This programme reduced falls and moderate injuries appreciably over the subsequent year in Dunedin , New Zeal and The benefit was most noticeable in elderly people who fell",
"Exercise is known to preserve many physiological responses in the healthy elderly , yet those with physical impairments are often discouraged from exercising . The authors studied the effects of a closely supervised exercise program design ed specifically for elders with health problems and functional limitations . Tests , selected for their relevance to clinical patient management , included the Self Evaluation of Life Function question naire , treadmill performance , and tests of autonomic nervous system and neuromotor functions . Ambulatory volunteers , aged 64 to 83 years , with noncardiac health problems , were r and omly assigned to a control group ( CG ; n = 17 ) or a 16-week exercise group ( EG ; 3 hr/wk , n = 18 ) . Nine of the control and 13 of the exercise subjects completed the study . All EG dropouts were due to illness . EG attendance averaged 87 % , and subjects trained at a heart rate ( HR ) of 103 + /- 5 beats/min ( SD ) ( 98 % of prescription HR ) . Though EG test responses showed a tendency to improve , none reached statistical significance . This result was affected by the small number completing the study and the variability inherent in such a sample . Though these impaired elderly subjects enthusiastically and safely participated with high attendance and at an exercise intensity adequate to expect benefit , measurable training effects were not demonstrated",
"OBJECTIVE This 8 week r and omized , double blind clinical trial compared the effect of a combined home based progressive exercise program and treatment with the nonsteroidal medication oxaprozin to treatment with oxaprozin alone on pain and physical functioning in older community dwelling patients with unilateral knee osteoarthritis ( OA ) . METHODS Efficacy variables measured before and after 8 weeks included ( 1 ) pain using the Western Ontario McMaster ( WOMAC ) pain , physical disability , and stiffness subscales and a 10 point visual analog scale ( VAS ) before and after self-paced walking ( SPW ) and stepping ( SPS ) functional tasks ; ( 2 ) physical function using the time to complete a self-paced 40 m walk ( SPW ) and 20 cycles of 2 steps ( SPS ) : ( 3 ) physical activity level using the Physical Activity Scale for Elderly ( PASE ) ; ( 4 ) clinical measures of knee functioning ( range of motion ) . One hundred seventy-nine men and women ( mean age 74 + /- 6 yrs ) with radiographic evidence of mild/moderate medial compartment OA were r and omized to either a progressive home based knee exercise program ( n = 88 ) or a control program ( n = 89 ) . All patients were given oxaprozin 1,200 mg per os daily . RESULTS We observed significant reduction from baseline in activity related pain ( VAS ) ; and improvement in SPW and SPS test time , passive range of motion , and PASE after 8 weeks in both groups . These changes were significantly greater ( p progressive exercise program to nonsteroidal antiinflammatory therapy in patients with knee OA can improve measures of activity and activity related pain more than medication alone",
"OBJECTIVE To determine the short- and long-term effects of resistance training on muscle strength , psychological well-being , control-beliefs , cognitive speed and memory in normally active elderly people . METHODS 46 elderly people ( mean age 73.2 years ; 18 women and 28 men ) , were r and omly assigned to training and control groups ( n=23 each ) . Pre- and post-tests were administered 1 week before and 1 week after the 8-week training intervention . The training sessions , performed once a week , consisted of a 10 min warm-up phase and eight resistance exercises on machines . RESULTS There was a significant increase in maximum dynamic strength in the training group . This training effect was associated with a significant decrease in self-attentiveness , which is known to enhance psychological well-being . No significant changes could be observed in control-beliefs . Modest effects on cognitive functioning occurred with the training procedure : although there were no changes in cognitive speed , significant pre/post-changes could be shown in free recall and recognition in the experimental group . A post-test comparison between the experimental group and control group showed a weak effect for recognition but no significant differences in free recall . Significant long-term effects were found in the training group for muscular strength and memory performance ( free recall ) 1 year later . CONCLUSION An 8-week programme of resistance training lessens anxiety and self-attentiveness and improves muscle strength",
"The effect of 12 weeks of resistance and balance training on strength and gait measures in older persons was tested in a r and omized control trial . Thirty-one residents of two life-care communities volunteered ( mean age , 82.1 years ) . The exercise group ( E ) trained three times per week , performing resistance training to fatigue for knee extension , hip abduction , ankle dorsiflexion , hip extension , and knee flexion , and postural control exercises . The control group ( C ) met weekly for flexibility exercises performed sitting in a chair . The exercise group achieved significant improvements in muscle strength and gait velocity ( p Knee extension one maximum repetition increased 32 % ( 24 % to 40 % , 95 % confidence interval [ CI ] ) , from 55 + /- to 72 + /- 4N.m . Isokinetic knee extension torque increased 25 % ( 3 % to 47 % ) from 40 + /- 5 to 50 + /- 5N.m at 120 degrees s-1 . Usual gait velocity increased 8 % ( 3 % to 13 % ) in E from 1.04 + /- .07 to 1.12 + /- .06 m/s . There was a trend of improvement in maximal gait speed 4 % ( 0 to 8 % ) from 1.43 + /- 0.1 to 1.49 + /- 0.1 m/s , p = 0.054 . Gait and strength measures in C were unchanged . A short-term exercise program that trained strength and balance achieved a clinical ly significant improvement in gait velocity",
"Resistance training ( RT ) has gained popularity as an effective form of exercise for older adults . However , the effects of RT on left ventricular ( LV ) morphology and systolic function in older persons is not well known . The purpose of this study was to assess the effects of 16 weeks of RT on LV morphology and systolic function in healthy older men . Subjects were r and omly assigned into a RT group ( n = 10 ; mean+/- SD age , 68 + /- 3 years ) or a nonexercise control group ( n = 10 ; age 68 + /- 4 years ) . RT was performed 3 times per week for 16 weeks at a mean intensity between 60 % and 80 % of 1 repetition maximum . Leg and bench press 1 repetition maximum and 2-dimensional echocardiography were performed at baseline and after 4 , 8 , 12 , and 16 weeks of training in the RT group . Sixteen weeks of RT was associated with an increase in leg press maximal strength ( baseline , 285 + /- 48 kg ; after 16 weeks , 367 + /- 47 kg ; p bench press maximal strength ( baseline , 59 + /- 11 kg ; after 16 weeks , 69 + /- 11 kg ; p leg press maximal strength ( baseline , 291 + /- 59 kg ; after 16 weeks , 290 + /- 53 kg ; p > 0.05 ) or bench press maximal strength ( baseline , 60 + /- 9 kg ; after 16 weeks , 61 + /- 13 kg ; p > .05 ) was found in control subjects during the same time . RT was not associated with changes in LV cavity size , wall thickness , mass , or systolic function after 4 , 8 , 12 , and 16 weeks of exercise . Thus , 16 weeks of RT was sufficient to increase leg press and bench press maximal strength but did not alter the size or systolic function of the senescent left ventricle",
"Regular exercise is widely advocated for the young and middle-aged , but less is heard about its relevance to elderly people . This study reports the findings of a controlled trial of seated exercise in residents of local authority homes for the elderly . Forty-nine residents aged 64 - 91 years volunteered for the 7-month project , and participated in either twice-weekly exercise or reminiscence sessions . Primary outcome measures were postural sway , flexibility of the spine and knees , h and -grip strength and functional capacity . The average ( range of ) attendance at the exercise sessions was 91 % ( 64 - 100 % ) , and at the reminiscence sessions was 86 % ( 46 - 100 % ) . By the end of the project , the change observed in the exercise group was significantly different from that of the reminiscence group in terms of grip strength ( p spinal flexion ( p chair-to-st and time ( p activities of daily living ( p self-rating of depression ( p very elderly residents of old peoples homes can benefit from participation in regular seated exercise and improve their functional capacity",
"The purpose of this study was to evaluate whether strength training is a useful addition to aerobic training in patients with chronic obstructive pulmonary disease ( COPD ) . Forty-five patients with moderate to severe COPD were r and omized to 12 wk of aerobic training alone ( AERO ) or combined with strength training ( AERO + ST ) . The AERO regimen consisted of three weekly 30-min exercise sessions on a calibrated ergocycle , and the ST regimen included three series of eight to 10 repetitions of four weight lifting exercises . Measurements of peripheral muscle strength , thigh muscle cross-sectional area ( MCSA ) by computed tomographic scanning , maximal exercise capacity , 6-min walking distance ( 6MWD ) , and quality of life with the chronic respiratory question naire were obtained at baseline and after training . Thirty-six patients completed the program and constituted the study group . The strength of the quadriceps femoris increased significantly in both groups ( p thigh MCSA and strength of the pectoralis major muscle increased in the AERO + ST group by 8 + /- 13 % and 15 + /- 9 % , respectively ( p 0.05 ) . These changes were significantly different in the two study groups ( p increase in strength of the latissimus dorsi muscle after training was modest and of similar magnitude for both groups . The changes in peak exercise work rate , 6MWD , and quality of life were comparable in the two groups . In conclusion , the addition of strength training to aerobic training in patients with COPD is associated with significantly greater increases in muscle strength and mass , but does not provide additional improvement in exercise capacity or quality of life",
"The short- and long-term effects of heavy-resistance training ( 85 % of one-repetition maximum ( RM ) ) on elbow flexion and knee extension dynamic and isokinetic strength and on morphology in the biceps brachii and vastus lateralis muscles were evaluated during 1 year in 35 Sc and inavian men and women , aged 70 - 77 years , 12 of whom formed a control group . After the first 11 weeks of training ( n = 23 ; 3 times/week ) elbow flexion and knee extension dynamic strength ( 1 RM ) had increased [ mean + /- SD ] 49 % + /- 16 and 163 % + /- 75 , respectively , with no significant difference between men and women . For the following 27 weeks , strength was maintained with one training session per week ( n = 12 ) but dropped without training ( n = 11 ) . After the final 11 weeks of training ( n = 11 ; 3 times/week ) , strength had further increased 32 % + /- 16 in both the arm and the leg . Isokinetic strength measurements ( Cybex II ; 30 degrees/s ) revealed similar but smaller gains than for dynamic strength . Muscle biopsies ( n = 20 ) taken at the start and after the first 11 weeks of training showed a significant increase in the area of both type 1 and type 2 fibers in the biceps brachii muscle and a positive significant correlation between the percentage increase in the proportional area of type 2 fibers in the vastus lateralis muscle and the percentage increase in knee extension dynamic muscle strength . In conclusion , older Sc and inavian men and women have a high capacity both to improve and to maintain muscle strength , some of which is mediated through an adaptation in the muscle fiber type population",
"OBJECTIVE The purpose s of this pilot study were to determine if a combined dietary and exercise intervention would result in significant weight loss in older obese adults with knee osteoarthritis , and to compare the effects of exercise plus dietary therapy with exercise alone on gait , strength , knee pain , biomarkers of cartilage degradation , and physical function . DESIGN Single-blind , two-arm , r and omized clinical trial conducted for 24 weeks . SETTING A university health and exercise science center . PARTICIPANTS Twenty-four community-dwelling obese older adults aged > or = 60 years , body mass index > or = 28 , knee pain , radiographic evidence of knee osteoarthritis , and self-reported physical disability . INTERVENTION R and omization into two groups : exercise and diet ( E&D ) and exercise alone ( E ) . Exercise consisted of a combined weight training and walking program for 1 hour three times per week . The dietary intervention included weekly sessions with a nutritionist utilizing cognitive-behavior modification to change dietary habits to reach a group goal of an average weight loss of 15 lb ( 6.8 kg ) over 6 months . MEASUREMENTS All measurements were conducted at baseline and 3 and 6 months , except for synovial fluid analysis , which was obtained only at baseline and 6 months . In addition , weight was measured weekly in the E&D group . Physical disability and knee pain were measured by self-report and physical performance was measured using the 6-minute walk and stair climb tasks . Biomechanical testing included kinetic and kinematic analysis of gait and isokinetic strength testing . Synovial fluid was analyzed for levels of total proteoglycan , keratan sulfate , and interleukin-1 beta . RESULTS Twenty-one of the 24 participants completed the study , with one dropout in the E&D group and two in the E group . The E&D group lost a mean of 18.8 lb ( 8.5 kg ) at 6 months compared with 4.0 lb ( 1.8 kg ) in the E group ( P = .01 ) . Significant improvements were noted in both groups in self-reported disability and knee pain intensity and frequency as well as in physical performance measures . However , no statistical differences were found between the two groups at 6 months in knee pain scores or self-reported performance measures of physical function . There was no difference in knee strength between the groups , with both groups showing modest improvements from baseline to 6 months . At 6 months , the E&D group had a significantly greater loading rate ( P = .03 ) and maximum braking force ( P = .01 ) during gait . There were no significant between-group differences in the other biomechanical measures . Synovial fluid sample s were obtainable at both baseline and 6 months in eight participants ( four per group ) . The level of keratan sulfate decreased similarly in both groups from an average baseline of 96.8 + /- 37.1 to 71.5 + /- 23 ng/microg total proteoglycan . The level of IL-1 decreased from 25.3 + /- 9.8 at baseline to 8.3 + /- 6.1 pg/mL. The decrease in IL-1 correlated with the change in pain frequency ( r = -0.77 , P = .043 ) . CONCLUSIONS Weight loss can be achieved and sustained over a 6-month period in a cohort of older obese persons with osteoarthritis of the knee through a dietary and exercise intervention . Both exercise and combined weight loss and exercise regimens lead to improvements in pain , disability , and performance . Moreover , the trends in the biomechanical data suggest that exercise combined with diet may have an additional benefit in improved gait compared with exercise alone . A larger study is indicated to determine if weight loss provides additional benefits to exercise alone in this patient population",
"Both aerobic training ( AT ) and resistance training ( RT ) may increase aerobic power ( VO2peak ) in the older population ; however , the role of changes in the capillary supply in this response has not been evaluated . Twenty healthy men ( age 65 - 74 yr ) engaged in either 9 wk of lower body RT followed by 9 wk of AT on a cycle ergometer ( RT-->AT group ) or 18 wk of AT on a cycle ergometer ( AT-->AT group ) . RT was performed three times per week and consisted of three sets of four exercises at 6 - 12 repetitions maximum . AT was performed three times per week for 30 min at 60 - 70 % heart rate reserve . VO2peak was increased after both RT and AT ( P number of capillaries per fiber perimeter length was increased after both AT and RT ( P VO2peak , whereas capillary density was increased only after AT ( P change in capillary supply and VO2peak ( r = 0.52 ) , suggest the possibility that similar mechanisms may be involved in the increase of VO2peak after high-intensity RT and AT in the older population",
"OBJECTIVE To determine the effects of structured exercise programs on self-reported disability in older adults with knee osteoarthritis . SETTING AND DESIGN A r and omized , single-blind clinical trial lasting 18 months conducted at 2 academic medical centers . PARTICIPANTS A total of 439 community-dwelling adults , aged 60 years or older , with radiographically evident knee osteoarthritis , pain , and self-reported physical disability . INTERVENTIONS An aerobic exercise program , a resistance exercise program , and a health education program . MAIN OUTCOME MEASURES The primary outcome was self-reported disability score ( range , 1 - 5 ) . The secondary outcomes were knee pain score ( range , 1 - 6 ) , performance measures of physical function , x-ray score , aerobic capacity , and knee muscle strength . RESULTS A total of 365 ( 83 % ) participants completed the trial . Overall compliance with the exercise prescription was 68 % in the aerobic training group and 70 % in the resistance training group . Postr and omization , participants in the aerobic exercise group had a 10 % lower adjusted mean ( + /- SE ) score on the physical disability question naire ( 1.71 + /- 0.03 vs 1.90 + /- 0.04 units ; P knee pain question naire ( 2.1 + /- 0.05 vs 2.4 + /- 0.05 units ; P=.001 ) , and performed better ( mean [ + /- SE ] ) on the 6-minute walk test ( 1507 + /- 16 vs 1349 + /- 16 ft ; P time to climb and descend stairs ( 12.7 + /- 0.4 vs 13.9 + /- 0.4 seconds ; P=.05 ) , time to lift and carry 10 pounds ( 9.1 + /- 0.2 vs 10.0 + /- 0.1 seconds ; P time to get in and out of a car ( 8.7 + /- 0.3 vs 10.6 + /- 0.3 seconds ; P resistance exercise group had an 8 % lower score on the physical disability question naire ( 1.74 + /- 0.04 vs 1.90 + /- 0.03 units ; P=.003 ) , 8 % lower pain score ( 2.2 + /- 0.06 vs 2.4 + /- 0.05 units ; P=.02 ) , greater distance on the 6-minute walk ( 1406 + /- 17 vs 1349 + /- 16 ft ; P=.02 ) , faster times on the lifting and carrying task ( 9.3 + /- 0.1 vs 10.0 + /- 0.16 seconds ; P=.001 ) , and the car task ( 9.0 + /- 0.3 vs 10.6 + /- 0.3 seconds ; P=.003 ) than the health education group . There were no differences in x-ray scores between either exercise group and the health education group . CONCLUSIONS Older disabled persons with osteoarthritis of the knee had modest improvements in measures of disability , physical performance , and pain from participating in either an aerobic or a resistance exercise program . These data suggest that exercise should be prescribed as part of the treatment for knee osteoarthritis",
"OBJECTIVE To determine whether a 12-month program of regular exercise can improve balance , reaction time , neuromuscular control , and muscle strength and reduce the rate of falling in older women . DESIGN A r and omized , controlled trial of 12 months duration . SETTING Conducted as part of the R and wick Falls and Fractures Study in Sydney , Australia . PARTICIPANTS One hundred ninety-seven women aged 60 to 85 years ( mean age 71.6 , SD = 5.4 ) who were r and omly recruited from the community . OUTCOME MEASURES Accidental falls , postural sway , reaction time , neuromuscular control , and lower limb muscle strength . MAIN RESULTS Exercise and control subjects were tested before , midway through , and at the end of the trial . At initial testing , exercisers and controls performed similarly in all tests and were well matched in relevant health and lifestyle factors . The mean number of classes attended for the 75 exercise subjects who completed the program was 60.0 ( range 26 - 82 ) . At the end of the trial , the exercise subjects showed improved performance in all five strength measures , in reaction time , neuromuscular control , body sway on a firm surface with the eyes open , and body sway on a compliant surface with the eyes open and closed . In contrast , there were no significant improvements in any of the test measures in the controls . In one test measure , hip flexion strength , the exercisers showed continued improvement throughout the study year . There was no significant difference in the proportion of fallers between the exercise and control subjects . Interesting trends were evident , however , between falls frequency and adherence to the exercise program . CONCLUSIONS These findings show that exercise can produce long-term benefits with regard to improving sensorimotor function in older persons . The findings also suggest that high compliance to an exercise program may reduce falls frequency , although further studies are required to conclusively demonstrate that exercise offers an effective means of preventing falls",
"BACKGROUND Depression in elderly people may be contributed to by the multiple losses of aging . Exercise has the potential to positively impact many of these losses simultaneously . We tested the hypothesis that progressive resistance training ( PRT ) would reduce depression while improving physiologic capacity , quality of life , morale , function and self-efficacy without adverse events in an older , significantly depressed population . METHODS We conducted a 10-week r and omized controlled trial of volunteers aged 60 and above with major or minor depression or dysthymia . Subjects were r and omized for 10 weeks to either a supervised PRT program three times a week or an attention-control group . RESULTS A total of 32 subjects aged 60 - 84 , mean age 71.3 + /- 1.2 yr , were r and omized and completed the study . No significant adverse events occurred . Median compliance was 95 % . PRT significantly reduced all depression measures ( Beck Depression Inventory in exercisers 21.3 + /- 1.8 to 9.8 + /- 2.4 versus controls 18.4 + /- 1.7 to 13.8 + /- 2 , p = .002 ; Hamilton Rating Scale of Depression in exercisers 12.3 + /- 0.9 to 5.3 + /- 1.3 versus controls 11.4 + /- 1.0 to 8.9 + /- 1.3 , p = .008 ) . Quality of life subscales of bodily pain ( p = .001 ) , vitality ( p = .002 ) , social functioning ( p = .008 ) , and role emotional ( p = .02 ) were all significantly improved by exercise compared to controls . Strength increased a mean of 33 % + /- 4 % in exercisers and decreased 2 % + /- 2 % in controls ( p depression scores ( r2 = .617 , p = .0002 ) . CONCLUSIONS PRT is an effective antidepressant in depressed elders , while also improving strength , morale , and quality of life",
"BACKGROUND Beneficial training outcomes have been reported in sedentary patients with chronic heart failure ( CHF ) after exercise training . However , data on training effects in previously trained patients , as well as comparisons of different exercise modes , are lacking . The aim of this study is to compare exercise training on a cycle ergometer ( major muscle mass ) and aerobic knee-extensor training ( minor muscle mass ) in previously trained patients with CHF . METHODS AND RESULTS Twenty-four men and women ( age , 63 + /- 10 years [ mean + /- SD ] ) with stable , moderate CHF ( left ventricular ejection fraction , 30 % + /- 11 % ) who had completed their first exercise training period more than 1 year ago were allocated to either the exercise or control group . After stratification for sex , age , ejection fraction , and cardiac output response , the training group was further r and omized to either cycle ergometer or knee-extensor training for 8 weeks . The control and training patients did not differ at baseline , and the measured variables did not change in the control group during the 8 weeks . Citrate synthase activity in skeletal muscle increased after cycle training ( 23 % ; P knee-extensor training ( 45 % ; P blood lactate concentration at submaximal intensities decreased ( P knee-extensor training did the peak oxygen uptake increase ( 19 % ; P sympathetic nervous system activity , measured as plasma norepinephrine concentration at rest ( P Minnesota Living with Heart Failure question naire scores also showed improvement in the health-related quality of life ( P knee-extensor training . CONCLUSION Physical training is beneficial in previously trained patients with CHF . Aerobic training involving a minor muscle mass shows greater efficiency than training involving a major muscle mass",
"We evaluated the effect of a strength-training program on the ability of persons with essential tremor to exert steady forces with the index finger . Thirteen subjects with a diagnosis of essential tremor were assigned to three different groups : one group trained with heavy loads , one with light loads , and one did not perform any training . Subjects attempted to generate steady contractions during both postural and constant-force tasks . Steadiness was quantified by the root mean square amplitude of acceleration during postural tasks and the st and ard deviation and coefficient of variation of force during the constant-force tasks . Subjects who performed the training program with heavy loads experienced an increase in steadiness around the target force during the constant-force tasks . Subjects in the other two groups did not exhibit any changes . These findings suggest that strength training can decrease the magnitude of tremor . However , we did not observe any associated improvements in functional abilities",
"We investigated if long-term resistance training would increase insulin-like growth factor-1 ( IGF-1 ) bioavailabilty at rest in older women ( 68+/-1 years ) with low bone mineral density . IGF-1 levels were significantly lower ( P insulin-like growth factor binding proteins -1 and -3 ( IGFBP-1 and IGFBP-3 ) significantly higher than an age-matched healthy normal group . Resistance training result ed in significant ( P repetition maximums across all exercises ( range 41 - 78 % ) . Resting IGF-1 levels were significantly ( P resistance training whereas no significant changes occurred in IGFBP-1 and IGFBP-3 levels . IGFBP-1/IGF-1 and IGFBP-3/IGF-1 ratios were significantly decreased ( approximately - 50 % ) as a result of resistance training ( P IGF-1 bioavailability was increased as a result of resistance training induced increases in IGF-1 levels in older women with low bone mineral density . These alterations in the IGF-1 system may be contributing to the significant strength gain observed with the resistance training in this population",
"Cardiac rehabilitation programs have not consistently been shown to improve the psychological well being of their patients . In our study of 38 cardiac patients ( 29 men and 9 women ) , a variety of quality -of-life parameters were assessed before and after they completed either 12 weeks of high-intensity strength training or flexibility training added to their outpatient cardiac rehabilitation aerobic exercise program . The strength-trained patients increased their self-efficacy scores for lifting ( 29 % vs 4 % , p Mood States dimensions : total mood disturbance ( 123 % vs 18 % , p depression/dejection ( 73 % vs 15 % , p fatigue/inertia ( 42 % vs 3 % p Medical Outcome Survey Short Form 36 role emotional health domain scores were significantly improved in the strength group when compared with the flexibility group ( 64 % vs 0 % , p role limitation scores improved in both groups . Increases in strength were associated with enhanced self efficacy and improved mood and well-being scores ( n = 34 , r = 0.30 to 0.53 , p High-intensity strength training added to a cardiac rehabilitation program of selected patients leads to improvements in quality -of-life parameters . These data , in conjunction with improvements in strength , strongly support the value of adding high-intensity strength training to cardiac rehabilitation programs",
"Physical exercise is often recommended as a therapeutic tool to combat pre- and postmenopausal loss of bone density . However , the relationship between training dosage ( intensity , duration , frequency ) and the effect on bone density still is undergoing discussion . Furthermore , the exercise quantification programs are often described so inadequately that they are neither quantitatively nor qualitatively reproducible . The aim of this investigation was to determine whether a clearly defined training of muscle strength , under defined safety aspects , performed only twice weekly , can counteract bone density loss in women with postmenopausal osteopenia . Data from 16 women in the training group ( age , 63.6 + /- 6.2 yr ) and 15 women in the control group ( age , 67.4 + /-9.7 yr ) , of comparable height and weight , were evaluated . Strength training was performed for 6 mo as continually adapted strength training , providing an intensity of about 70 % of each test person 's one repetition maximum . Bone mineral density of lumbar vertebrae 2 to 4 and the femoral neck was measured by dual-energy x-ray absorptiometry . Maximum performance in watts and parameters of hemodynamics were controlled with a bicycle ergometer test to maximal effort . In addition , metabolic data were assessed . In the lumbar spine and femoral neck , the training group showed no significant changes , whereas the control group demonstrated a significant loss of bone mineral density , especially in the femoral neck ( P strength increase was highly significant in all exercised muscle groups , rising to about 70 % above the pretraining status ( P Heart rate and blood pressure data indicated a slight economization , metabolism was not significantly influenced . Based on these findings , we conclude that continually adapted strength training is an effective , safe , reproducible , and adaptable method of therapeutic strength training , following only two exercise sessions per week",
"BACKGROUND Cardiovascular benefits of resistance training in cardiac patients have been suggested but not studied in a r and omized , controlled trial of circuit weight training ( CWT ) without an aerobic exercise component . The purpose of the current study was to examine the effects of 10 weeks of CWT on muscular strength , peak oxygen consumption ( peak VO2 ) , and myocardial oxygen dem and ( mVO2 ) in men after coronary artery bypass surgery . METHODS Twenty-six , post-coronary bypass male subjects ( mean 19 months after bypass ) , aged 60 + /- 8.5 years , were r and omly allocated to 10 weeks of CWT at 40 to 60 % of maximum voluntary contraction ( n = 12 ) or to a control group ( n = 14 ) . Muscular strength was assessed using a modified one repetition maximum technique . Peak VO2 was recorded during symptom-limited treadmill exercise . Rate pressure product , as an indirect measure of mVO2 , was measured during isometric , isodynamic , and dynamic exercise . RESULTS No ischemic symptoms nor electrocardiographic changes were recorded during testing or training . Strength increased by 18 % ( P peak VO2 . Rate pressure product during isometric and isodynamic exercise decreased from pre- to post-testing ( P Moderate intensity CWT is safe and can improve strength in selected low-risk patients after coronary artery bypass surgery . However , it does not significantly increase peak VO2 nor reduce mVO2 during isometric , isodynamic , and dynamic exercise",
"BACKGROUND Although inactivity is an important contributor to impaired functioning and disability with age , little is known concerning how improvements in physical functioning and well-being in older adults vary with the type of physical activity undertaken . METHODS One hundred three adults age 65 years and older , recruited via population -based methods , were r and omized to 12 months of community-based , moderate-intensity endurance and strengthening exercises ( Fit & Firm ) or stretching and flexibility exercises ( Stretch & Flex ) . A combination of class- and home-based exercise formats was used . Measured and self-rated physical performance along with perceived functioning and well-being were assessed pre- and postintervention . RESULTS Fit & Firm subjects showed greater 12-month improvements in both measured and self-rated endurance and strength compared to Stretch & Flex subjects . Stretch & Flex subjects reported greater improvements in bodily pain , and Stretch & Flex men evidence d greater improvements in flexibility relative to Fit & Firm subjects . Although overall exercise adherence was high in both exercise conditions ( approximately 80 % ) , subjects in both conditions showed better adherence to the home- versus class-based portions of their exercise prescriptions . CONCLUSIONS Community-based programs focusing on moderate-intensity endurance and strengthening exercises or flexibility exercises can be delivered through a combination of formats that result in improvement in important functional and well-being outcomes . This represents one of the first studies to report significant improvements in an important quality of life outcome -bodily pain-with a regular regimen of stretching and flexibility exercises in a community-based sample of older adults",
"We conducted a 12-wk resistance training program in elderly women [ mean age 69 + /- 1.0 ( SE ) yr ] to determine whether increases in muscle strength are associated with changes in cross-sectional fiber area of the vastus lateralis muscle . Twenty-seven healthy women were r and omly assigned to either a control or exercise group . The program was satisfactorily completed and adequate biopsy material obtained from 6 controls and 13 exercisers . After initial testing of baseline maximal strength , exercisers began a training regimen consisting of seven exercises that stressed primary muscle groups of the lower extremities . No active intervention was prescribed for the controls . Increases in muscle strength of the exercising subjects were significant compared with baseline values ( 28 - 115 % ) in all muscle groups . No significant strength changes were observed in the controls . Cross-sectional area of type II muscle fibers significantly increased in the exercisers ( 20.1 + /- 6.8 % , P = 0.02 ) compared with baseline . In contrast , no significant change in type II fiber area was observed in the controls . No significant changes in type I fiber area were found in either group . We conclude that a program of resistance exercise can be safely carried out by elderly women , such a program significantly increases muscle strength , and such gains are due , at least in part , to muscle hypertrophy",
"Forty-seven elderly women ( 63 to 88 years of age , mean = 71 years ) were studied to determine the effect of a 25-week light resistance and aerobic exercise program upon arm and leg strength . Three groups were formed : nonexercising controls ( C , n = 12 ) , exercise ( EN , n = 18 ) and exercise with light weights on on the wrists and ankles ( EW , n = 17 ) . Exercise was performed for one hour , three times/week . Subjects were pretested and posttested for maximal isokinetic muscle strength ( angular velocity 60 degrees/sec ) for elbow flexion and extension , shoulder internal and external rotation , and knee flexion and extension . Dunn planned contrasts were used to compare C vs exercise groups combined ( EN + EW ) and EN vs EW . No significant differences were found among groups at baseline . EN + EW improved significantly ( p less than 0.05 ) more than C in elbow extension ( 17 % ) , shoulder internal rotation ( 14 % ) , shoulder external rotation ( 9 % ) , and knee flexion ( 20 % ) . No significant differences were found between EN and EW . These data indicate that elderly women can achieve substantial gains in the strength of arm and leg musculature as a result of regular light resistance and aerobic exercise , but that the use of light weights on the wrists and ankles for added resistance did not enhance this effect",
"BACKGROUND Beneficial training outcomes have been reported in patients with chronic heart failure ( CHF ) following leg exercise training . However , data from more comprehensive training programs are limited . The aim of this study was to test the hypothesis that exercise training applying the concept of comprehensive local muscle training can improve aerobic and functional working capacity as well as quality of life in patients with CHF . METHODS Twenty-four men and women [ age 63+/-9 years ( mean+/-S.D. ) ] with stable , moderate chronic heart failure ( left ventricular ejection fraction 30+/-10 % ) , were investigated in a r and omized controlled study with a training group of 16 patients and a control group of 8 patients . The training was performed as an aerobic resistance training by activating all the main muscle groups , one at a time . The patients exercised for 1 h , three times per week for 8 weeks . RESULTS Patient groups did not differ at baseline . Peak oxygen uptake ( 8 % , P distance walked in a 6-min walking test ( 11 % , P health-related quality of life ( P plasma norepinephrine levels at rest ( 32 % , P peak oxygen uptake ( P quality of life scores ( P comprehensive physical training activating a minor muscle mass at a time markedly improves exercise capacity and quality of life and reduces catecholamine levels , it can be recommended for the rehabilitation of patients with CHF under supervision of a physical therapist",
"The purpose of this study was to determine whether a moderate to high intensity strengthening and aerobic exercise program can improve the strength , exercise capacity , gait and balance of deconditioned male nursing home residents . Ambulatory subjects who scored 30 or less on the modified Tinetti gait and balance assessment scale , who demonstrated less than 80 % of age-matched lower extremity strength on isokinetic muscle testing and who gave informed consent were enrolled . Subjects were r and omized to either an exercise ( n = 8) or a control ( n = 6 ) group . All participants underwent an exercise test to determine maximal oxygen uptake ( Vo2max ) and received quantitative gait and balance measurements . The subjects assigned to the exercise group then completed a 12-wk program of weight training for the lower extremities and stationary cycling . Both the exercise and control groups were then retested . Ten outcome variables were assessed : Tinetti mobility scores , Vo2max , isokinetic-tested lower extremity strength and endurance , stride length , gait velocity , stance time , gait duration , cadence and balance . The exercise group , after completion of the program , demonstrated significant improvements in Tinetti mobility scores ( P combined right and left quadricep muscle strength ( P right and left lower extremity muscular endurance ( P left stride length and gait velocity ( P control group revealed no changes of significance with the exception of improvement of the combined right and left hamstring muscle strength ( P < 0.05 ) . Nevertheless , for those outcome variables that had improved significantly in the exercise group , the changes amounted to only a 5 to 10 % increase over the baseline measurements . These findings showed that an appropriately design ed high intensity exercise program can result in significant although limited improvements for clinical mobility scores , strength , muscular endurance and certain gait parameters",
"BACKGROUND Resistance-training intervention studies have demonstrated meaningful health benefits in older adults ; however , most have used exercises performed at specific intensities on expensive equipment , which limit their widespread applicability . We tested whether two self-paced , less expensive exercise protocol s could be effective and safe for modifying neuromotor performance and functional capacity in community-dwelling adults 65 - 95 years of age . METHODS One hundred and thirty-one subjects were r and omized to a novel resistance training , walking , or control group . Subjects determined their level of resistance or walking intensity ( self-paced ) on a session-by-session basis . Muscle strength , balance , reaction time , stair climbing speed , and a timed pen pickup task were measured before and after the intervention period . Exercisers met three times per week for 10 months . RESULTS Significant improvements in t and em stance and single-legged stance with eyes open times and stair climbing speed were seen in both exercise groups . In addition , resistance trainers improved their muscle strength and ability to pick up an object from the floor and reduced the number of missteps taken during t and em walking , and walkers reduced t and em walking time . Controls showed no significant improvement in any variable . CONCLUSIONS The two self-paced exercise protocol s were effective at improving neuromotor performance and functional capacity in the study sample and show promise as a safe , effective , cost-efficient , acceptable exercise model for primary and secondary prevention in the general population of community-dwelling older adults",
"BACKGROUND AND PURPOSE This prospect i ve clinical investigation examined the effects of a multidimensional exercise program on balance , mobility , and risk for falls in community-dwelling older adults with a history of falling . Factors used to predict adherence and a successful response to exercise were identified . SUBJECTS A total of 105 community-dwelling older adults ( > or = 65 years of age ) with a history of two or more falls in the previous 6 months ( no neurologic diagnosis ) participated . They were classified into ( 1 ) a control group of fallers ( n = 21 ) , ( 2 ) a fully adherent exercise group ( n = 52 ) , and ( 3 ) a partially adherent exercise group ( n = 32 ) . METHODS Following evaluation , each patient received an individualized exercise program addressing the impairments and functional disabilities identified during the assessment . The control group received no intervention . Changes in performance on five clinical tests of balance and mobility and fall risk were compared among groups . RESULTS Both exercise groups scored better than the control group on all measures of balance and mobility . Although both exercise groups showed a reduction in fall risk compared with the control group , the greatest reduction was found in the fully adherent exercise group . Factors associated with successful response to exercise included degree of adherence to exercise program and pretest score on the Tinetti Mobility Assessment . CONCLUSION AND DISCUSSION Exercise can improve balance and mobility function and reduce the likelihood for falls among community-dwelling older adults with a history of falling . The amount of exercise needed to achieve these results , however , could not be determined from this study",
"OBJECTIVE To assess the effects of 12 months ' dynamic strength training on muscle strength and bone mineral density ( BMD ) at the lumbar spine and femoral neck in patients with early rheumatoid arthritis ( RA ) . METHODS Thirty-two subjects in the training group ( EG ) and 33 in the control group ( CG ) completed the study . EG carried out strength training 2 times a week with moderate loads of 50 - 70 % of repetition maximum . They were also encouraged to do recreational physical activities . CG performed recreational physical activities and range of motion exercises . Maximal strength of the knee extensors , trunk extensors and flexors , and grip strength were recorded with dynamometers . BMD was measured using dual x-ray absorptiometry . Modified Disease Activity Score , erythrocyte sedimentation rate , and pain were used for the estimation of disease activity , and Stanford Health Assessment Question naire to measure functional disability . RESULTS The 12 month resistance training in EG led to statistically significant mean increases of 22 - 35 % in all muscle groups examined . CG patients were also able to increase their strength to some degree ( 3 - 24 % ) , but at the end of the study strengths in CG were significantly lower than in EG . By the end of the study lumbar spine BMD had changed by + 0.19 % ( 4.24 ) in EG and by -1.14 % ( 4.36 ) in CG . The corresponding changes of femoral BMD were + 1.10 % ( 3.71 ) and -0.03 % ( 3.58 ) . The changes in BMD were minor and statistically not significant in both groups . However , femoral BMD was found to be decreased among those patients treated periodically with oral glucocorticoids ( n = 15 , 3 subjects from EG and 12 from CG ) compared with changes in BMD among those not treated with systemic glucocorticoids ( n = 50 ) . CONCLUSION Minimally supervised strength training result ed in significant improvements in muscle strength without detrimental effects on disease activity . The detected annual changes in central BMD were minor and statistically insignificant in both groups . Special attention should be focused on those patients with RA with high disease activity and concomitant glucocorticoid treatment",
"Chronic renal insufficiency , regardless of cause , generally progresses to end-stage renal disease ( 1 ) . Malnutrition and muscle wasting in chronic uremia often parallel the progression of renal failure ( 2 ) . They also contribute to excess morbidity and mortality in patients with renal disease ( 3 ) . Protein-restricted diets delay the progression of renal disease ( 4 , 5 ) and alleviate uremic symptoms ( 6 ) . Although nutritional status , as assessed by biochemical and anthropometric indicators , may be maintained during protein restriction ( 6 , 7 ) , studies have shown that deterioration of nutritional status is associated with low energy and protein intake in patients with chronic renal insufficiency ( 8) . Resistance training increases nitrogen retention ( 9 ) , protein synthesis ( 10 ) , and expression of insulin-like growth factor I in skeletal muscle ( 11 ) ; ameliorates losses of muscle mass and function ; and enhances quality of life ( 12 ) in both healthy and unwell persons . The anabolic potential of resistance training counteracts the catabolism of HIV infection ( 13 ) and myopathy secondary to corticosteroid use in cardiac transplantation ( 14 ) , the loss of lean tissue during energy restriction for obesity ( 15 ) , and the interleukin-mediated myopathy of chronic heart failure ( 16 ) . However , its utility as an adjunctive treatment off setting the catabolism of a low-protein diet in uremic patients is not known ( 17 ) . We conducted a r and omized , controlled trial to determine whether resistance training would preserve lean body mass , nutritional status , and muscle function through alterations in protein turnover ( synthesis and oxidation ) in patients with moderate chronic renal insufficiency who were consuming a low-protein diet to slow the progression of renal failure . Methods Study Design Patients older than 50 years of age with chronic renal insufficiency were r and omly assigned to a low-protein diet plus resistance training or a low-protein diet plus sham exercises ( referred to as low-protein diet alone ) . Patients were asked to follow a low-protein diet ( 0.6 g/kg of body weight per day ) for 2 to 8 weeks ( run-in period ) before r and omization . They continued the low-protein diet for an additional 12 weeks after r and omization ( intervention period ) ( Figure 1 ) . The Human Investigation Review Committee at Tufts University , Boston , Massachusetts , and collaborating hospitals approved the study , and written informed consent was obtained from all patients . Figure 1 . Flow of patients through the study . * The post office returned letters because addresses were incorrect or persons had relocated . No patients withdrew , experienced ineffective interventions , or were lost to follow-up . One patient in each group had incomplete postintervention measures because of health-related reasons . HNRCA = Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging . Study Sample Patients were recruited from the nephrology clinic at New Engl and Medical Center , Saint Elizabeth 's and Newton Wellesley Hospitals , and the Lahey Hitchcock Clinic , all in Boston , Massachusetts . Screening procedures took place at the Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging ( HNRCA ) at Tufts University . These procedures included sociodemographic and health history question naires ; physical examination ; electrocardiography ; blood hematology , chemistry , and urine analyses ; and a treadmill stress test . Eligibility criteria included serum creatinine concentrations between 133 and 442 mol/L ( 1.5 and 5.0 mg/dL ) and physician approval to follow a low-protein diet . A nephrologist confirmed renal diagnosis by review ing renal biochemistry results and clinical records . Exclusion criteria were myocardial infa rct ion ( within the past 6 months ) , any unstable chronic condition , dementia , alcoholism , dialysis or previous renal transplantation , current resistance training , recent involuntary weight change ( 2 kg ) , albumin level less than 30 g/L , proteinuria greater than 10 g/d , or abnormal stress test results at screening ( 18 ) . Reasons for early withdrawal from the study included loss of more than 25 % of initial body weight ; need for dialysis or transplantation ; development of any serious condition requiring hospitalization or precluding exercise ; and signs of malnutrition , such as a decrease in serum transferrin levels to less than 1.5 g/L or a 15 % decrease in hemoglobin or leukocyte count to below baseline levels . Diet Dietary intake of macronutrients and micronutrients and adherence to the low-protein diet were monitored twice per week during the run-in period and weekly during the intervention period by 3-day assisted dietary records ( including week and weekend days ) and regular meetings with the study dietitian , who was not blinded to group assignment . Dietary data were coded and analyzed by using Nutritionist-IV software ( N-Squared Computing , San Bruno , California ) . Patients collected one 24-hour urine specimen for every 3-day dietary record . Protein intake was also estimated by urea nitrogen levels ( 19 ) calculated from urine collection s and was used to assess adherence , which was defined as intake within 15 % of the prescribed low-protein intake ( 0.6 g/kg per day ) . Patients were counseled to reduce their habitual protein intake by eating food sources with less protein or by reducing portion sizes of higher-protein foods . Behavior modification strategies , including tips , recipes , food models , and self-monitoring tools for protein counts , were provided . These strategies were adapted from the Modification of Diet in Renal Disease Study ( 20 ) . Exercise Muscle strength was determined twice before r and omization and once after 12 weeks by measuring one repetition maximum ( 1 RM ) ( 21 ) using Keiser resistance training equipment ( Keiser Sports Health Equipment , Inc. , Fresno , California ) . One repetition maximum is the heaviest load that can be lifted once in good form through the full range of motion . Five machines ( chest and leg press , latissimus pull-down , knee extension , and knee flexion ) were used to include functionally large muscle groups . The better of the two baseline measurements of 1 RM was used in analyses and to set initial training loads for patients r and omly assigned to resistance training . All exercise sessions were performed at the HNRCA three times per week under the supervision of an exercise physiologist . Vital signs and body weight were recorded before each session . Patients who performed resistance training had monthly 1 RM testing on each machine . Workload during training was adjusted to reflect 80 % of the most recent 1 RM . In addition , patients ' workloads were progressively increased as appropriate according to the trainer 's objective perception of patients ' difficulty with workloads at each session . Patients performed three sets of eight repetitions on each machine per session , which lasted about 45 minutes ( 21 ) . Patients assigned to the low-protein diet alone performed five to eight sham exercises ( gentle movements while st and ing , sitting , and bending ) for the upper and lower body . These were design ed not to have a physiologic impact but to provide trainer contact time similar to that of the resistance training group . Study Measures All measures were taken before ( week 0 ) and 12 weeks after r and omization . Observers were blinded to study group assignment at all times , except during assessment s of postintervention muscle strength . Main Outcome Measures Total body potassium is the best single measure of body cell mass closely linked to functional status ( 22 ) , prognosis , and survival ( 23 ) . Body cell mass ( muscle and viscera ) comprises the metabolically active tissues where protein is targeted ( 24 ) . Potassium-40 represents approximately 0.0118 % of total body potassium . Loss of total body potassium occurs in patients following low-protein diets ( 25 ) and in patients with renal disease ( 26 ) , as well as in patients with many other wasting syndromes . Total body potassium was determined in the body composition laboratory at HNRCA , with a coefficient of variation of 5 % ( 24 ) . Regional body composition of the area involving the mid-thigh muscle was determined by computerized tomography of the nondominant thigh . A Siemens DR3 CT Scanner ( Somatom-Siemens , Erlangen , Germany ) was used to obtain an 8-mm scan at the midpoint between the inguinal crease and the proximal pole of the patella . Images were digitized and analyzed to the nearest 0.01 cm2 , as described elsewhere ( coefficient of variation , 0.5 % to 1.5 % ) ( 21 ) . Type I and type II muscle-fiber cross-sectional areas were determined from vastus lateralis muscle biopsies of the nondominant thigh , performed with a 5-mm Bergstrom needle ( 27 ) . Sections were stained with adenosine triphosphatase ( pH , 4.3 ) to visualize type I and type II fibers . A slide preparation was made for each biopsy specimen , and 50 to 150 fibers per patient were analyzed by light microscopy ( coefficient of variation , 3 % ) ( 11 , 27 ) . Anthropometry Body weights were measured to the nearest 0.1 kg on a Toledo Weight-Plate ( Bay State Scale & Systems , Inc. , Burlington , Massachusetts ) . Height was measured once to the nearest 0.25 cm , without shoes , by using a wall-mounted stadiometer . Body mass index was determined from body weight and height as kg/m2 . Biochemical Measures All measurements were collected in the fasting state in a blinded fashion at the nutrition evaluation laboratory at HNRCA ( coefficient of variation , 5 % to 10 % ) . Urea nitrogen and creatinine concentrations in serum and urine and levels of plasma insulin-like growth factor I were determined , as described elsewhere ( 25 , 27 ) . In addition , blood cell count ; hematocrit ; and levels of serum albumin , transferrin , and prealbumin were measured monthly to evaluate nutritional status . Glomerular Filtration Rate Glomerular filtration rate was measured as the renal clearance of 125I-iothalamate ( Glofil , Cypros Pharmaceutical Corp. , Carlsbad , California ) , with a coefficient of",
"OBJECTIVE To determine the effect of a low load resistance exercise training program on muscle strength , functional outcome , and cardiovascular endurance . METHODS Forty-nine patients , 37 women and 12 men between the ages of 35 - 76 yrs ( mean 60.5 yrs ) , with definite rheumatoid arthritis ( RA ) functional class II and III ( mean disease duration of 10.5 yrs ) were r and omly assigned to exercise and control groups for a 12 wk resistive muscle training program . A circuit weight bearing form of training was incorporated using light loads with high repetitions . A video tape demonstrating the exercises was given to all exercising participants to enable them to continue the program at home at least 3 times per wk with a biweekly self-report evaluation . Baseline and post-intervention evaluations included joint activity , muscle strength , endurance , functional outcome , and self-report . Cardiovascular fitness measured by treadmill time , anaerobic threshold and peak oxygen consumption ( VO2 ) in this group were assessed at baseline and 12 wks . RESULTS A significant improvement at 12 wks was noted in the exercise group for self-reported joint count ( p = 0.02 ) , number of painful joints ( p = 0.004 ) , HAQ ( p = 0.012 ) , sit-to-st and time ( p = 0.02 ) , grip strength ( p = 0.05 ) knee extension 60 degrees ( p = 0.03 ) , Arthritis Impact Measurement Scales dexterity ( p = 0.02 ) , and time to anaerobic threshold ( p = 0.03 ) . Significant improvement in the exercise group compared to the control group was noted for self-reported joint count ( p = 0.02 ) , night time pain ( p = 0.05 ) , and sit-to-st and time ( p = 0.02 ) . Increase in treadmill time was not statistically significant nor was a change in peak oxygen consumption ( VO2 ) noted . Abnormalities on initial treadmill screening were detected in 2 of 49 asymptomatic patients . They were excluded from the study and subsequent workup revealed significant coronary artery disease . CONCLUSION Low load resistive muscle training increased functional capacity as reported by patients and is a clinical ly safe form of exercise in functional class II and III RA . Screening this population for dormant coronary artery disease is recommended",
"Experimental evidence indicates that a lower synthesis rate of muscle contractile protein myosin heavy chain ( MHC ) occurs in age-related muscle wasting and weakness . To determine the molecular mechanism of this lower synthesis of MHC , we measured transcript levels of isoforms of MHC ( MHCI , MHCIIa , and MHCIIx ) in muscle biopsy sample s of 7 young ( 20 - 27 yr ) , 12 middle-aged ( 47 - 60 yr ) , and 14 older ( > 65 yr ) people . We further determined the effect of 3 mo of resistance exercise training ( exercise ) vs. nonintervention ( control ) on transcript levels of MHC isoforms on these subjects and the fractional synthesis rate ( FSR ) of MHC in 39 people aged 46 - 79 yr . MHCI mRNA levels did not significantly change with age , but MHCIIa decreased 38 % ( P MHCIIx decreased 84 % ( P FSR of MHC by 47 % ( P muscle protein by 56 % ( P Exercise training results in an increase ( 85 % ) in transcript levels of MHCI and a decrease in the transcript levels of MHCIIa and MHCIIx . In conclusion , an age-related lowering of the transcript levels of MHCIIa and MHCIIx is not reversed by exercise , whereas exercise results in a higher synthesis rate of MHC in association with an increase in MHCI isoform transcript levels",
"The effects of 52 weeks resistance training at one of two exercise intensities on thigh muscle strength , fiber cross-sectional area ( CSA ) , and tissue composition were studied in healthy 65 - 79-year-old women . Subjects were assigned to either a control ( CO ) , high-intensity ( HI ) or low-intensity ( LO ) training group . Exercise regimens consisted of three sets of leg press , knee extension , and knee flexion exercises , 3 days/week , at either 80 % of one-repetition maximum ( 1-RM ) for seven repetitions ( HI ) or 40 % of 1-RM for 14 repetitions ( LO ) . Dynamic muscle strength was evaluated by 1-RM , thigh lean tissue mass ( LTM ) , fat mass , and bone mineral density ( BMD , g/cm2 ) by dual energy X-ray absorptiometry , and fiber CSA of vastus lateralis m. by histomorphometry . Muscle strength increased , on average ( + /- SEM ) , by 59.4 + /- 7.9 % and 41.5 + /- 7.9 % for HI and LO , respectively , compared to 1.3 + /- 4.8 % in CO ( P = 0.0001 ) . Type I fiber CSA increased over time ( P type II area ( HI , P = 0.06 ; LO , P = 0.11 ) . There was no significant effect of either exercise program on thigh tissue composition , except for BMD at the 1/3 site ( middle third of the femur ) , where LO and CO groups experienced a decline ( P thigh muscle strength , which were associated with fiber hypertrophy , although these did not translate into appreciable alterations in thigh tissue composition",
" Twelve middle-aged men and 12 middle-aged women in the 50-year-old age group ( M50 ; range 44 - 57 years ; W50 ; 43 - 57 ) , and 12 elderly men and 12 elderly women in the 70-year-old age group ( M70 ; 59 - 75 ; W70 ; 62 - 75 ) volunteered as subjects in order to examine effects of 12-week progressive heavy resistance strength training on electromyographic activity ( EMG ) , muscle cross-sectional area ( CSA ) of the quadriceps femoris and maximal concentric force in a one repetition maximum ( 1 RM ) test of the knee extensor muscles . One half of the subjects in each group performed the knee extension ( and flexion ) exercises only bilaterally ( BIL ) , while another half performed the exercises only unilaterally ( UNIL ) . None of the subject groups demonstrated statistically significant changes in any of the 1 RM values during the 2 week control period with no training ( between week -2 and 0 ) preceding the actual experimental training . However , the 12-week training result ed in increases ( P RM values in each group so that the average relative increase of 19 + /- 12 % ( P bilateral 1 RM in all BIL trained subjects was greater ( P relative increases of 17 + /- 11 % ( P 14 + /- 14 % ( P ) in unilateral 1 RM values of the right and left leg in all UNIL trained subjects were greater ( P relative average increase of 19 + /- 19 % ( P in the maximum averaged IEMG of both legs during the bilateral actions in all BIL trained subjects was greater ( P relative increases of 14 + /- 12 % ( P + /- 6 % ( P CSA in all BIL and UNIL trained subjects did not differ significantly from each others . The present findings suggest that progressive heavy resistance strength training leads to great increases in maximal dynamic strength of the trained subjects accompanied by both considerable neural adaptations and muscular hypertrophy not only in middle-aged but also in elderly men and women . Both bilateral and unilateral exercises are effective to produce functional and structural adaptations in the neuromuscular system , although the magnitude of functional strength increase seems to be specific to the type of exercise used , further supporting the principle of specificity in the design of strength programmes",
" Abstract The effects of a short-term strength training programme on resting lymphocyte subsets and stress hormone concentrations were analysed in 32 elderly sedentary subjects . Out of these 32 subjects , 8 women and 8 men [ mean age 70.1 ( SEM 1.0 ) years ] were r and omly assigned to a 8-week strength training programme which consisted of three sets of eight repetitions at 80 % of one repetition maximum , for leg press , bilateral leg extension and seated chest press , 3 days a week . The remaining 8 women and 8 men [ mean age 70.5 ( SEM 0.9 ) years ] served as controls . Absolute counts of lymphocyte subsets ( CD20 + , CD3 + , CD3+CD4 + , CD3+CD8 + , CD3−CD56+CD16 + ) were measured with a new technique combining fluorescent microspheres and flow cytometry . In the trained subjects , substantial increases in strength took place in one repetition maximum during the 8-week training period for leg press [ from means of 20.7 ( SEM 1.0 ) to 23.6 ( SEM 1.0 ) N · kg−1LBM ( lean body mass ) ] , chest press [ from means of 5.4 ( SEM 0.3 ) to 6.2 ( SEM 0.3 ) N · kg−1LBM ] and bilateral leg extension [ from means of 6.3 ( SEM 0.2 ) to 7.4 ( SEM 0.3 ) N · kg−1LBM ] movements . Baseline cortisol concentration ( P 0.01 ) , CD20 + cell count ( P 0.05 ) , CD3 + cell count ( P ) , and CD4 + cell count ( P strength training on resting adrenaline , noradrenaline and cortisol concentrations or distributions of lymphocyte subsets at rest was observed . The main finding of this study was to demonstrate that 8-week is too short a duration for a strength training programme to modify counts of lymphocyte subsets at rest in elderly sedentary adults",
"Strength measurements were administered to 52 men ranging in age from 42 to 83 years , who were then r and omly assigned within their respective age group to either the Isometric-training Group ( ITG ) or to the Control-exercise Group ( CEG ) . At the conclusion of a six-week training program all initial measurements were again administered . No significant differences were found in ( 1 ) strength trainability by age group , and ( 2 ) in strength trainability by muscle group when the upper-extremity-strength ratios were compared with the lower-extremity-strength ratios . When the initial and final strength scores of the ITG were subjected to a t test for correlated sample s , the findings included : ( 1 ) the four age groups of the ITG experienced statistically significant gains in strength for six of the eight strength measurements , and ( 2 ) as age increased , strength trainability appeared to decrease",
"OBJECTIVE To assess how dietary change affects gain in strength and muscle mass during heavy resistance training of elderly men . DESIGN R and omized controlled trial . INTERVENTION During 12 weeks of resistance training of knee extensors and flexors , a daily supplement of 560 + /- 16 kcal/day ( 17 % energy from protein , 43 % from carbohydrate , 40 % from fat ) was r and omly assigned to six men ( S ) while five men ( U ) received no supplement . Food intake , strength , whole body composition , and midthigh composition by CT scan were assessed before training and at 6 and 12 weeks . SETTING The men were out patients but lived in a Metabolic Research Unit during the three assessment s. PARTICIPANTS Eleven healthy men aged 61 to 72 years . RESULTS Densitometry showed no change over time in fat or fat-free mass . However , the S men increased ( P less than 0.05 ) weight , skinfold thickness at six sites , subcutaneous midthigh fat , and creatinine excretion ; in all men , changes in these values and in midthigh muscle were proportional to changes in reported energy intake ( P less than 0.05 ) . There was midthigh muscle hypertrophy in both groups , but it was greater in S than U ( P less than 0.01 ) . Both groups gained strength ( P less than 0.001 ) with no effect of diet . CONCLUSIONS During physical rehabilitation of the elderly , dietary intake may influence the increase in lean as well as adipose tissue without altering strength gain . These preliminary findings should be confirmed by a larger study with sedentary controls",
"Knee extension strength , walking speed , quadriceps muscle mass and composition of the muscle compartment were studied in 66 to 85-year-old female athletes and controls . Maximal voluntary knee extension force , force/body mass , extension torque , torque/body mass and walking speed were higher for the athletes than the controls . A muscle index indicating intramuscular fat and connective tissue measured using ultrasonography was lower for the athletes than the controls . There were no differences between the study groups in knee extension force related either to cross-sectional area ( CSA ) or lean tissue area ( CSAL ) of the quadriceps . Within the subgroups , there was no significant correlation between knee extension torque and CSA or CSAL of the same muscle . In the athletes high knee extension torque/body mass was related to a low muscle index and high walking speed to a low relative proportion of fat in the muscle . The muscle index was lower the more kilometers trained during the preceding year . In the controls high knee extension torque/body mass and high walking speed were related to a low relative proportion of fat . Knee extension torque and walking speed were higher the more kilometers walked during the preceding year . The results indicate that elderly female athletes have superior muscle performance compared to their age-peers . Performance in a maximal isometric strength test in elderly women is not clearly related to muscle mass . However , to some extent it is related to the composition of the same muscle , especially the degree to which fat is infiltrated into the muscle",
"OBJECTIVE To determine the effects of resistance training on muscular strength , body composition ( percent fat and lean tissue mass ) , and program adherence in active women over 60 years of age . DESIGN This study was design ed as a stratified , r and omized , non-blinded trial . Subjects were stratified into rank-ordered pairs by level of physical activity according to the Blair Seven-Day Recall , then r and omly assigned into either a weight-training ( WT , n = 18 ) or control ( CON , n = 18 ) group . PARTICIPANTS AND SETTING Thirty-six women over the age of 60 ( 67.1 + /- 1.5 , chi + /- SE ) were recruited from the San Diego community . All subjects had to be engaging in some form of aerobic exercise at least 3 days each week for a minimum of 6 months . MEASUREMENTS AND INTERVENTION : Subjects engaged in isotonic training 3 days/week on Polaris machines at a target intensity of 80 % of the 1 repetition maximum ( 1 RM ) for three sets of seven exercises selected to train major muscle groups of the trunk and upper and lower body . The 1 RM was re-tested every 6 weeks in WT and the workload adjusted to maintain target intensity . The 1 RM was tested at 0 , 12 , and 24 weeks in CON . Body fatness and lean tissue mass , excluding skeletal mass , were assessed at 0 and 24 weeks by dual energy radiography using a total body scan . RESULTS Increases in muscle strength of the weight trainers were significant for all seven exercises ( 5%-65 % ) , with the greatest gains in the shoulder and trunk muscles . Percent body fat of weight trainers decreased significantly ( from 38.8 % to 37.9 % , P lean tissue mass increased by 1.5 kg ( P body composition were observed in control subjects . Overall program adherence was 83 % ( 15 weight trainers and 15 control women completed the study ) . Monthly attendance averaged 86.8 + /- 3.3 % , with no incidence of injury during the training sessions . CONCLUSIONS These data indicate that heavy-resistance weight training is safe and enjoyable for older women and that meaningful gains in muscular strength and body composition can be made even in women who are already highly active",
"BACKGROUND AND PURPOSE Loss of lower-extremity strength increases the risk of falls in older persons . The purpose of this study was to test the hypothesis that a vigorous program of lower-extremity strengthening , walking , and postural control exercises would improve the single-stance balance of healthy older women and lower their risk of falls and fall-associated injuries . SUBJECTS From a total of 38 respondents , 21 women were r and omly assigned to either a treatment group ( combined training , n = 12 ) or a control group ( flexibility training , n = 9 ) . The subjects ranged in age from 62 to 75 years ( mean = 68 , SD = 3.5 ) . METHODS A r and omized control trial compared the effects of two exercise programs on static balance . The combined training group exercised three times per week on knee extension and sitting leg press machines , walked briskly for 20 minutes , and performed postural control exercises , which included simple tai chi movements . The flexibility training group performed postural control exercises weekly . Measurements of balance were obtained on a force platform in double and single stance , at baseline and following 6 months of exercise training . RESULTS Double-stance measurements were unchanged after training . The mean displacement of the center of pressure in single stance improved 17 % in the combined training group and did not change in the flexibility training group . A repeated- measures analysis of variance revealed that the difference in improvement between the combined training and flexibility training groups was not significant . DISCUSSION AND CONCLUSION This is the first intervention trial to demonstrate improvements in single-stance postural sway in older women with exercise training . Additional studies with more subjects will be needed to determine whether a combined training program of resistance training , walking , and postural exercises can improve balance more than a program of postural control exercises alone",
"The quadriceps strength of a group of residents homes for the elderly ( mean age 83 years ) was assessed in a r and omized controlled trial of seated group exercise versus group reminiscence therapy . Fifty-five of 65 volunteers completed the 6-month study , with 4 dropouts from the exercise group , and 6 dropouts from the reminiscence group . There were no adverse effects . Average of attendance at the exercise sessions was 72 % ( range , 18 % to 98 % ) and 62 % ( range , 29 % to 100 % ) at the reminiscence sessions . The reminiscence sessions comprised group interaction and discussion prompted by the use of reminiscence aids . By the end of the study , the change observed in the exercise group was significantly different from the reminiscence group in terms of quadriceps strength ( p ability to climb up steps , but neither cognitive function ( Mini-Mental State Examination ) nor reaction time altered significantly ",
"BACKGROUND Age-related loss in physiologic capacities contributes to the decline in physical function in the elderly population . Despite the beneficial effects of exercise interventions on maximal physiologic capacity measures , the functional benefits have not been shown in independently living older adults . The objective of this study was to evaluate exercise in independent older adults for significant and meaningful improvements in physical function , not detected by commonly used measures of physical function . METHODS In a r and omized controlled study , 49 independently living men and women were assigned to either a nonexercise control group ( Control ; n = 26 ) or an exercise training group ( Exercise ; n = 23 ) . Participants ( age = 76+/-4 ) in good general health were recruited from retirement communities or apartments . The combined endurance and strength training was performed at 75 % to 80 % intensity ; the groups met 3 times/week for 6 months of supervised sessions . Outcome measures included physical capacity , health status , and physical function using a newly developed performance test -- the Continuous Scale-Physical Functional Performance test ( CS-PFP ) . RESULTS Compared to the Control group , the Exercise group showed significant increases in maximal oxygen consumption ( 11 % ) and muscle strength ( 33 % ) . No significant differences were found between groups for changes in the Sickness Impact Profile , SF-36 scales , or the 6-minute walk . However , the CS-PFP score improved significantly in the Exercise group ( 14 % , effect size 0.80 ) . CONCLUSIONS Independent older adults gain meaningful functional benefits from several months of exercise training . The public health importance of physical activity may relate not just to its role in preventing decline , but also to its role in enhancing physical function",
"OBJECTIVE Reduced muscle mass and strength are characteristic findings of growth hormone deficiency ( GHD ) and aging . We evaluated measures of muscle strength , muscle fiber type , and cross sectional area in response to treatment with recombinant human growth hormone ( rhGH ) with or without a structured resistance exercise program in frail older subjects . DESIGN Placebo-controlled , r and omized , double blind trial . SETTING Outpatient clinical research center at an urban university-affiliated teaching hospital . PARTICIPANTS Thirty-one consenting older subjects ( mean age 71.3 + /- 4.5 years ) recruited as a subset of a larger project evaluating rhGH and exercise in older people , who underwent 62 quadricep-muscle biopsies . INTERVENTION R and om assignment to a 6-month course of one of four protocol s : rhGH administered subcutaneously daily at bedtime , rhGH and a structured resistance exercise program , structured resistance exercise with placebo injections , or placebo injections only . MEASUREMENTS Muscle biopsy specimens were obtained from the vastus lateralis muscle . Isokinetic dynamometry strength tests were used to monitor individual progress and to adjust the weights used in the exercise program . Serum insulin-like growth factor-I ( IGF-I ) was measured and body composition was measured using a Hologic QDR 1000W dual X-ray densitometer . RESULTS The administration of rhGH result ed in significant increase in circulating IGF-I levels in the individuals receiving rhGH treatment . Muscle strength increased significantly in both the rhGH/exercise ( + 55.6 % , P = .0004 ) as well as the exercise alone ( + 47.8 % , P = .0005 ) groups . There was a significant increase in the proportion of type 2 fibers between baseline and six months in the combined rhGH treated subjects versus those not receiving rhGH ( P = .027 ) . CONCLUSIONS Our results are encouraging in that they suggest an effect of growth hormone on a specific aging-correlated deficit . IGF-I was increased by administrating rhGH and muscle strength was increased by exercise . The administration of rhGH to frail older individuals in this study result ed in significant changes in the proportions of fiber types . Whether changes in fiber cross-sectional area or absolute number occur with long-term growth hormone administration requires further study",
"The purpose of this study was to investigate the effects of a progressive resistance training program on myosin heavy chain isoform expression , fiber type , and capillarization in patients with symptomatic peripheral arterial disease . Patients were r and omized to either a training group ( n = 11 , mean + /- SD , 70 + /- 6 years , 4 men , 7 women ) or a control group ( n = 9 , 66 + /- 6 years , 5 men , 4 women ) . The training sessions were completed 3 times/week , using 2 sets of various exercises , each performed for 8 - 15 repetitions . Muscle biopsies were obtained before and after 24 weeks from the medial gastrocnemius . Following the 24-week training program , the training group had significantly decreased the percentage of myosin heavy chain type IIB . The proportion of type IIB/AB fibers as measured by using myosin adenosine triphosphatase histochemistry decreased significantly in the training group . There were significant increases in type I and type II fiber areas , and capillary density also increased significantly in the training group . There were significant increases in 10 repetition maximum leg press and calf press strengths in the trained subjects . There were no significant changes in any of the measurements in the control group . It is concluded that progressive resistance training results in significant increases in muscle strength and alters skeletal muscle composition of subjects with peripheral arterial disease",
"OBJECTIVE Resistance and endurance training result in gains in fitness in the aged . It is unclear whether the debilitated elderly can perform moderate-intensity training and whether such training results in short-term improvements in strength , endurance , and function in this population . DESIGN R and omized , controlled trial . SETTING S AND PATIENTS Subjects were from a Veterans Affairs nursing home and rehabilitation unit and a community nursing home . They were older than 60 yrs with impairment in at least one physical activity of daily living . Seventy-eight subjects volunteered and 58 ( mean age , 75 yrs ; 9 women , 49 men ) completed the intervention and initial posttest . Only one subject withdrew because of injury or disinterest . INTERVENTION Thrice-weekly resistance training ( using an isokinetic dynamometer ) and twice-weekly endurance training for 4 to 8 weeks . MAIN OUTCOMES Isometric strength in dominant arm and leg , heart rate response to timed endurance test , and activities of daily living score . RESULTS The mean change in isometric strength across the muscle movements tested was 32.8 % in the training group and 10.2 % in the control group ( difference , 22.6 % ; 95 % confidence interval , 6.2 % to 39.0 % ) . No change in heart rate during exercise was seen in the training group . Trained subjects tended to have a greater improvement in functional activity than control subjects , which was statistically significant ( p = .04 ) for those subjects who at enrollment were most dysfunctional ( i.e. , activities of daily living score less than 13 [ maximum score 26 ] ) . CONCLUSION This group of debilitated elderly patients effectively performed resistance training and increased their strength , with the most impaired gaining the most function . Few in the group could effectively perform endurance training",
"Previous studies concerning psychological benefits of exercise among the elderly has focused predominantly on the effects of aerobic exercise . In the present study , psychological and behavioral adaptations in response to 12-weeks of strength training were examined in medically healthy but sedentary 42 older adults ( mean age = 68 years ) . The purpose of this study was to evaluate the effects of high and low intensity resistance training intensity on a ) muscular fitness , b ) psychological affect , and c ) neurocognitive functioning . Subjects were r and omly assigned to high intensity/low volume ( EXH : 2 sets of 8 to 10 repetitions for 75 to 85 % of 1 RM ) , low intensity/high volume ( EXL : 2 sets of 14 to 16 repetitions for 55 to 65 % of 1 RM ) , or no exercise control programs . Prior to and following the 12-week program , subjects underwent comprehensive physiological and psychological evaluations . Physiological assessment included measurements of blood pressure , heart rate , arm and leg muscle strength , body composition , and oxygen consumption ( VO2max ) . Psychological measures included evaluations of mood , anxiety , and physical self-efficacy as well as cognitive functioning . The results of this study indicated that both high and low intensity strength programs were associated with marked improvements in physiological fitness and psychological functioning . Specifically , subjects in the strength training programs increased overall muscle strength by 38.6 % and reduced percent body fat by 3.0 % . Favorable psychological changes in the strength-trained subjects included improvements in positive and negative mood , trait anxiety , and perceived confidence for physical capability . The treatment effects of neurocognitive functioning were not significant . In summary , this study demonstrated that participation in 12-weeks of high or low intensity strength training can improve overall physical fitness , mood , and physical self-efficacy in older adults while cognitive functioning remains constant",
"Underst and ing the stress/strain relationship between exercise and bone is critical to underst and ing the potential benefit of exercise in preventing postmenopausal bone loss . This study examined the effect of a 2-year exercise intervention and calcium supplementation ( 600 mg ) on bone mineral density ( BMD ) in 126 postmenopausal women ( mean age , 60 + /- 5 years ) . Assignment was by block r and omization to one of three groups : strength ( S ) , fitness ( F ) , or nonexercise control ( C ) . The two exercise groups completed three sets of the same nine exercises , three times a week . The S group increased the loading , while the F group had additional stationary bicycle riding with minimal increase in loading . Retention at 2 years was 71 % ( 59 % in the S group , 69 % in the F group , and 83 % in the C group ) , while the exercise compliance did not differ between the exercise groups ( S group , 74 + /- 13 % ; F group , 77 + /- 14 % ) . BMD was measured at the hip , lumbar spine , and forearm sites every 6 months using a Hologic 4500 . Whole body BMD also was measured every 6 months on a Hologic 2000 . There was no difference between the groups at the forearm , lumbar spine , or whole body sites . There was a significant effect of the strength program at the total ( 0.9 + /- 2.6 % ; p intertrochanter hip site ( 1.1 + /- 3.0 % ; p strength program in increasing bone density at the clinical ly important hip site . We concluded that a strength program could be recommended as an adjunct lifestyle approach to osteoporosis treatment or used in combination with other therapies",
"OBJECTIVE To study the effect of a home program of physical therapy . DESIGN Nonr and omized control trial . SETTING Home based . PATIENTS Subjects had total hip arthroplasty ( THA ) for hip osteoarthritis ( hip-OA ) without THA failure , or cardiopulmonary , neurological , or cognitive problems . Twenty-three subjects ( mean age 63.4 years ; mean post-THA period 793 days , 6 to 48 months ) were divided into 3 groups matching with age , gender , and postoperative periods . INTERVENTION The 6-week home program included range of motion ( ROM ) exercises , and low resistance isometric and eccentric exercises of hip abductors . Physical therapists prescribed ROM and isometric exercises for group A , all programs for group B , and no programs for the control group . The programs were modified every 2 weeks as necessary . MAIN OUTCOME MEASURE Hip ROM , maximum isometric hip abduction torque measured by Cybex II , gait speed , and cadence were evaluated . RESULTS The practice ratio of the program was about 70 % for both groups . Maximum isometric torque improved in the THA side of group A ( p Gait speed and cadence also improved significantly . No correlation coefficient existed between practice days and the improvement ratio of the maximum torque . CONCLUSION The home program was effective in long-term post-THA",
"The effects of a 16-wk strength-training program on total and regional body composition were assessed by dual-energy X-ray absorptiometry ( DEXA ) , magnetic resonance imaging ( MRI ) , and hydrodensitometry in 13 untrained healthy men [ 60 + /- 4 ( SD ) yr ] . Nine additional men ( 62 + /- 6 yr ) served as inactive controls . The strength-training program result ed in substantial increases in both upper ( 39 + /- 8 % ; P lower ( 42 + /- 14 % ; P body strength . Total fat-free mass ( FFM ) increased by 2 kg ( 62.0 + /- 7.1 to 64.0 + /- 7.2 kg ; P total fat mass decreased by the same amount ( 23.8 + /- 6.7 to 21.8 + /- 6.0 kg ; P FFM ( 61.3 + /- 7.8 to 63.0 + /- 7.6 kg ; P fat mass ( 23.8 + /- 7.9 to 22.1 + /- 7.7 kg ; P FFM was increased in the arms ( 6.045 + /- 0.860 to 6.418 + /- 0.803 kg ; P fat mass was reduced in the arms ( 2.383 + /- 0.830 to 2.128 + /- 0.714 kg ; P < 0.01 ) , legs ( 7.583 + /- 1.675 to 6.945 + /- 1.551 kg ; P < 0.001 ) , and trunk ( 12.216 + /- 4.143 to 11.281 + /- 3.653 kg ; P < 0.01 ) as a result of training . ( ABSTRACT TRUNCATED AT 250 WORDS",
"BACKGROUND Since falling is associated with serious morbidity among elderly people , we investigated whether the risk of falling could be reduced by modifying known risk factors . METHODS We studied 301 men and women living in the community who were at least 70 years of age and who had at least one of the following risk factors for falling : postural hypotension ; use of sedatives ; use of at least four prescription medications ; and impairment in arm or leg strength or range of motion , balance , ability to move safely from bed to chair or to the bathtub or toilet ( transfer skills ) , or gait . These subjects were given either a combination of adjustment in their medications , behavioral instructions , and exercise programs aim ed at modifying their risk factors ( intervention group , 153 subjects ) or usual health care plus social visits ( control group , 148 subjects ) . RESULTS During one year of follow-up , 35 percent of the intervention group fell , as compared with 47 percent of the control group ( P = 0.04 ) . The adjusted incidence-rate ratio for falling in the intervention group as compared with the control group was 0.69 ( 95 percent confidence interval , 0.52 to 0.90 ) . Among the subjects who had a particular risk factor at base line , a smaller percentage of those in the intervention group than of those in the control group still had the risk factor at the time of re assessment , as follows : at least four prescription medications , 63 percent versus 86 percent , P = 0.009 ; balance impairment , 21 percent versus 46 percent , P = 0.001 ; impairment in toilet-transfer skills , 49 percent versus 65 percent , P = 0.05 ; and gait impairment , 45 percent versus 62 percent , P = 0.07 . CONCLUSIONS The multiple-risk-factor intervention strategy result ed in a significant reduction in the risk of falling among elderly persons in the community . In addition , the proportion of persons who had the targeted risk factors for falling was reduced in the intervention group , as compared with the control group . Thus , risk-factor modification may partially explain the reduction in the risk of falling",
"This study was design ed to assess the effects of 18 months of resistance exercise on regional and total bone mineral density ( BMD ) and soft tissue lean mass ( STL ) in premenopausal women aged 28 - 39 r and omly assigned to an exercise or control group . Twenty-two exercise and 34 control subjects completed the 18-month training study . All subjects were previously inactive and untrained women . Initial , 5- , 12- and 18-month assessment s were made of total and regional BMD and total and regional STL using dual energy X-ray absorptiometry . All subjects consumed a 500 mg/day elemental calcium supplement throughout the study . Initial Ca intake without supplement averaged 1,023 mg/day in total sample . Serum levels of bone osteocalcin and dietary assessment s using 12 r and omly assigned days of diet records were also completed . Muscular strength was assessed from both 1 repetition maximum ( RM ) testing of 10 weightlifting exercises and by peak torque for hip abduction/adduction and knee extension/flexion . Training increased strength by 58.1 % based on 1 RM testing and by 33.8 % based on isokinetic testing at 18 months versus baseline . BMD increased significantly above baseline at the lumbar spine for the exercise group at 5 months ( 2.8 % ) , 12 months ( 2.3 % ) , and 18 months ( 1.9 % ) as compared with controls . Femur trochanter BMD increased significantly ( p total BMD , arm BMD , or leg BMD were found . There was a 20 % increase in BGP in the exercise group as compared with controls at 5 months and this difference was maintained throughout the study . For STL , significant increases for total , arm , and leg were found at 5 , 12 , and 18 months for the exercise group versus control ranging from 1 - 6 % over baseline . These results support the use of strength training for increasing STL and muscular strength with smaller but significant regional increases in BMD in the premenopausal population",
"The present study was design ed to identify prospect ively the individual chronic characteristics associated with falling among elderly persons and to test the hypothesis that risk of falling increases as the number of chronic disabilities increases . Seventy-nine consecutive admissions to three intermediate care facilities were evaluated . Twenty-five of the subjects became recurrent fallers . The nine risk factors included in the fall risk index were mobility score , morale score , mental status score , distant vision , hearing , postural blood pressure , results of back examination , postadmission medications , and admission activities of daily living score . A subject 's fall risk score was the number of index factors present . The proportions of recurrent fallers increased from 0 percent ( 0 of 30 ) in those with 0 to three risk factors , to 31 percent ( 11 of 35 ) in those with four to six factors , to 100 percent ( 14 of 14 ) in those with seven or more factors . Falling , at least among some elderly persons , appears to result from the accumulated effect of multiple specific disabilities . Some of these disabilities may be remediable . The mobility test , the best single predictor of recurrent falling , may be useful clinical ly because it is simple , recreates fall situations , and provides a dynamic , integrated assessment of mobility",
"Objectives —There is a paucity of long term studies on exercise training in elderly women . The purpose of this study was to investigate the effects of one year of progressive resistance exercise ( PRE ) on dynamic muscular strength and the relations to bone mineral density ( BMD ) in elderly women . Methods —Forty four healthy sedentary women ( mean age 68.8 years ) volunteered for this study and were r and omly assigned to either an exercise group or a control group . The exercise group were involved in three one hour sessions a week for 52 weeks of supervised PRE to strengthen the large muscle groups of the body , while the control group were instructed to continue their normal lifestyle . The exercise circuit included three sets of eight repetitions at 75 % of one repetition maximum focused on the large muscle groups . BMD was measured by dual energy x ray absoptiometry ( Lunar DPX ) at the lumbar spine and at three sites in the proximal femur . Other selected parameters of physical fitness were also measured . Results —Statistical analyses ( analysis of covariance ) showed significant strength gains ( p bilateral bench press ( > 29 % ) , bilateral leg press ( > 19 % ) , and unilateral biceps curl ( > 20 % ) . No significant difference between groups was evident in body weight , grip strength , flexibility , waist to hip ratio , or the sum of eight skinfolds . Significant relations ( p dynamic leg strength and the BMD of the femoral neck , Ward 's triangle , and the lumbar spine . Conclusions —Significant strength changes , after one year of PRE , were evident in elderly women , and the muscle increases may parallel changes in BMD ; however , correlation coefficients were moderate",
"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",
"It is considered that skeletal mass in humans may respond to loading or the number of loading cycles . The aim of this study was to examine the effect of a 1 year progressive resistance training program on the bone mass of 56 postmenopausal women . Assignment was by block r and omization to one of two resistance training groups : a strength trained group ( 3 x 8 repetition maximum ) or an endurance group ( 3 x 20 repetition maximum ) . The resistance exercises were selected to stress the ipsilateral forearm and hip region . The exercising side was r and omly assigned with one side exercised while the alternate side acted as the nonexercise control . Bone mineral density ( BMD ) was measured every 3 months at the radial forearm and four hip sites using the Hologic QDR 2000 bone densitometer . A linear regression function was fitted for each individual 's bone density results , and the slope was compared for the exercise and control side using paired t-tests . The bone mass increase with the strength regimen was significantly greater at the trochanteric hip site ( control -0.6 + /- 2.2 % , exercise 1.7 + /- 4.1 % , p increase in BMD with the endurance regimen except at the radius midsite ( control -1.0 + /- 2.3 % , exercise 0.1 + /- 1.4 % , p muscle strength , tested by a one-repetition maximum ( 1RM ) test , increased significantly for all 10 exercises ( p change in BMD and the percentage increase in strength as follows : trochanter with leg press ; intertrochanter with leg press ( p resistance exercise in that although the trochanter and intertrochanter bone density was elevated by the resistance exercises undertaken , there was no effect on the femoral neck value . Postmenopausal bone mass can be significantly increased by a strength regimen that uses high-load low repetitions but not by an endurance regimen that uses low-load high repetitions . We conclude that the peak load is more important than the number of loading cycles in increasing bone mass in early postmenopausal women",
"OBJECTIVES This investigation determined whether an in-home resistance training program achieved health benefits in older adults with disabilities . METHODS A r and omized controlled trial compared the effects of assigning 215 older persons to either a home-based resistance exercise training group or a waiting list control group . Assessment s were conducted at baseline and at 3 and 6 months following r and omization . The program consisted of videotaped exercise routines performed with elastic b and s of varying thickness . RESULTS High rates of exercise adherence were achieved , with 89 % of the recommended exercise sessions performed over 6 months . Relative to controls , subjects who participated in the program achieved statistically significant lower extremity strength improvements of 6 % to 12 % , a 20 % improvement in t and em gait , and a 15 % to 18 % reduction in physical and overall disability at the 6-month follow-up . No adverse health effects were encountered . CONCLUSIONS These findings provide important evidence that home-based resistance exercise programs design ed for older persons with disabilities hold promise as an effective public health strategy",
"Most studies that assess the effects of exercise in the elderly involve subjects who are in good health . The objective of this prospect i ve longitudinal study was to examine the impact of exercise on cardiovascular fitness , flexibility , and strength in an elderly population that included chronically ill individuals . Patients were recruited initially from a population of veterans over 64 years of age who use a VA outpatient clinic as their regular source of care . The exercise intervention consisted of 90 minutes of exercise 3 days per week at 70 % of the patient 's maximal capacity . Activities included stationary cycling , stretching , weight training , and walking . Of 69 patients who began the program , 49 ( 71 % ) reached 4-month follow-up . Most patients completing follow-up ( 76 % ) had at least one chronic disease , such as arthritis , hypertension , or heart disease . Patients who dropped out were more likely to have multiple chronic illnesses than those who remained in the program . Average weekly attendance was 65 % and was stable over time . Improvements in cardiovascular fitness at 4-month follow-up were significant : Metabolic equivalents increased from 7.1 + /- 2.3 to 8.3 + /- 2.6 ( P less than .001 ) , treadmill time increased from 8.5 + /- 3.8 to 11.2 + /- 4.2 minutes ( P less than .001 ) , submaximal heart rate decreased from 123.7 + /- 18.8 to 118.8 + /- 19.4 beats per minute ( P less than .001 ) and resting heart rate decreased from 68.1 + /- 10.6 to 63.3 + /- 11.6 beats per minute ( P = .005 ) . ( ABSTRACT TRUNCATED AT 250 WORDS",
"Skeletal muscle adaptations to high intensity knee extensor strength and /or endurance training in patients with chronic heart failure were investigated . Eleven patients with chronic heart failure were r and omized into two groups and exercised the m. quadriceps femoris 3 days/week for 8 weeks . After training , the maximal exercise intensity tolerated on the ergometer cycle was raised from 99 ( 32 ) to 114 ( 40 ) watts ( W , P Peak dynamic knee extensor work rate showed the greatest increase after endurance training ( 40 % , P Maximal dynamic and isometric strength were elevated by 40 - 45 % ( P strength training . The cross-sectional area of m. quadriceps femoris was increased in the strength-trained legs ( 9 % , P capillary per fibre ratio of m. vastus lateralis was raised by 47 and 58 % in the endurance-trained legs ( P oxidative enzyme activity in m. vastus lateralis was significantly raised above 50 % after endurance training , whereas glycolytic enzyme activity was unaltered . The peripheral skeletal musculature in patients with chronic heart failure adapts fairly quickly to high intensity knee extensor training . This results in a marked rise in local , and a small rise in total work capacity , indicating maintained plasticity of skeletal muscle in chronic heart failure patients",
"OBJECTIVES This paper describes a videotaped , home-based , strength training program , titled Strong-for-Life and reports on its effectiveness in improving muscle strength , psychological well-being , and health status in a sample of older persons . DESIGN AND SETTING We enrolled 102 nondisabled , community-dwelling older people aged 66 to 87 , identified from the Medicare beneficiary list , into a r and omized , controlled trial . MEASUREMENTS Effectiveness was based on change in isokinetic upper and lower extremity muscle strength , psychologic well-being , and health status . RESULTS Results revealed several statistically significant short-term benefits after 12 to 15 weeks of exercise , especially for men . Younger older adults demonstrated a 10 % improvement in knee extensor strength relative to control subjects . Older male exercisers achieved significant differences relative to controls in perceived anger , tension , and overall social functioning . Male exercisers , in general , achieved significant improvement in perceived vigor . Women did not report psychological benefits following participation in the program . CONCLUSION Study results reveal that the Strong for Life program , design ed to be widely disseminated to the nondisabled older population , has many short-term positive benefits",
"Decreases in muscular strength , endurance , and angular velocity have previously been demonstrated in the elderly . Osteoarthritis ( OA ) , especially of the knee , may cause further reductions in these parameters and lead to functional limitations . This study measured the effects of a quantitative progressive exercise muscle rehabilitation program ( QPE ) that was added to a physical therapy ( PT ) program . Forty subjects ( 20 men and 20 women ) with OA of the knees were r and omly selected from a group of volunteers ( N = 437 ) for the 3-month program . Measurements of strength , endurance , angular velocity , and the Jette Functional Status Index were determined before and after 1 , 2 , and 3 months of the program . The QPE program was composed of isometric , isotonic , isotonic with resistance , endurance , and speed contractions prescribed in a progressive sequence . Muscle strength ( 14 % and 29 % ) and endurance ( 38 % and 43 % ) increased significantly ( p walking time and the difficulty and pain experienced during functional activities",
"The effects of 12 wk of progressive resistance strength training on in vivo and in vitro immune parameters were evaluated in a controlled study of eight subjects with rheumatoid arthritis ( RA ) , eight healthy young ( 22 - 30 yr ) , and eight healthy elderly ( 65 - 80 yr ) individuals . Six healthy elderly ( 65 - 80 yr ) nontraining control subjects were also evaluated to account for seasonal and psychosocial effects . Training subjects exercised at 80 % of their one-repetition maximum and performed eight repetitions per set , three sets per session on a twice weekly basis . Peripheral blood mononuclear cell ( P BMC ) sub population s , cytokine and prostagl and in ( PG ) E2 production , proliferative response , and delayed type hypersensitivity ( DTH ) skin response were measured before and after 12 wk of training . Training did not induce changes in P BMC subsets , interleukin (IL)-1 beta , tumor necrosis factor-alpha ( TNF ) , IL-6 , IL-2 , or PGE2 production , lymphocyte proliferation , or DTH response in any of the training groups , compared with control subjects . These data suggest that 12 wk of high-intensity progressive resistance strength training does not affect immune function in young or elderly healthy individuals or subjects with RA",
"OBJECTIVE To determine the effects of heavy resistance strength training ( ST ) on resting blood pressure ( BP ) in older men and women . DESIGN Prospect i ve intervention study . SETTING University of Maryl and Exercise Science Laboratory . PARTICIPANTS Twenty-one sedentary , healthy older men ( 69 + /- 1 year , n = 11 ) and women ( 68 + /- 1 year , n = 10 ) served as subjects for the study . INTERVENTION Six months of progressive whole body ST performed 3 days per week using Keiser K-300 air-powered resistance machines . MEASUREMENTS One-repetition maximum ( 1 RM ) strength was measured for seven different exercises before and after the ST program . Resting BP was measured on six separate occasions before and after ST for each subject . RESULTS Substantial increases in 1 RM strength were observed for upper body ( UB ) and lower body ( LB ) muscle groups for men ( UB : 215 vs 265 kg ; LB : 694 vs 838 kg ; P ST program led to reductions in both systolic ( 131 + /- 2 vs 126 + /- 2 mm Hg , P diastolic ( 79 + /- 2 vs 75 + /- 1 mm Hg , P BP . Systolic BP was reduced significantly in men ( 134 + /- 3 vs 127 + /- 2 mm Hg , P diastolic BP was reduced following training in both men ( 81 + /- 3 vs 77 + /- 1 , mm Hg , P = .054 ) and women ( 78 + /- 2 vs 74 + /- 2 mm Hg , P = .055 ) . CONCLUSIONS Six months of heavy resistance ST may reduce resting BP in older persons . According to the latest guidelines from the Joint National Committee for the Detection , Evaluation , and Treatment of Hypertension , the changes in resting BP noted in the present study represent a shift from the high normal to the normal category",
"OBJECTIVE Muscle strength training is one of the most common therapy methods in physical therapy programs , and the usual goal of this treatment is to improve muscle strength . Little attention has been paid , however , to the effects of strength training on the other components of motor performance . This study examined the effects of a 10-week strength training program on the motor performance of the h and , including reaction time , speed of movement , tapping speed , and coordination in normal healthy volunteers . DESIGN Before-after trial . SUBJECTS AND SETTING Sixteen healthy women volunteers aged 25 to 45 years participated . INTERVENTION Subjects accomplished a 10-week muscle strength training program of the upper extremities . MAIN OUTCOME MEASURES Reaction time , speed of movement , tapping speed , and coordination were measured three times on consecutive days , and muscle strength and electromyographic values of the right upper extremity were recorded once before the training period . After the training period , the same measurements were made as before the training . RESULTS The 10-week strength training decreased choice reaction time by 6 % ( p tapping speed by 3 % ( p coordination by 5 % ( p Speed of movement increased , but this change was not statistically significant . All the measured isometric muscle strengths and electromyographic activations upon maximum isometric contraction increased . CONCLUSIONS A 10-week strength training of the upper extremities increased muscle strength and some motor performance functions of the h and , including choice reaction time , tapping speed , and coordination",
"Tests of vision , vestibular function , peripheral sensation , strength , reaction time , balance and gait were administered to 183 community-dwelling women aged 22 - 99 years . Walking speed , stride length and cadence declined with age with corresponding increases in stance duration and percentage of the stride in the stance phase . Visual acuity and contrast sensitivity , tactile and vibration sense in the lower limb , vestibular function ( as assessed by the vestibular X Writing Test ) , quadriceps and ankle dorsiflexion strength and reaction time were significantly associated with all five gait parameters . Postural sway measures were associated with walking speed , stride length and percentage of the stride in the stance phase . Multiple regression analyses revealed seven sensori-motor measures as significant predictors for one or more of the gait parameters : low contrast visual acuity , tactile sensitivity , vibration sense , vestibular X-test writing performance , quadriceps strength , reaction time and sway . Quadriceps strength was included as a predictor variable for every gait parameter and in each case had the strongest beta weight . Women who fell on two or more occasions in a one-year prospect i ve period had significantly reduced and more variable cadence and significantly increased stance duration ( measured in absolute terms and as a percentage of stride ) than those who did not fall or fell on one occasion only . The study findings eluci date the relative importance of specific physiological systems in the maintenance of normal gait and identify temporal gait measures that are associated with falling in older people ",
"A pilot controlled trial was conducted to determine the feasibility of testing an exercise program as a means of improving balance in aged women . A r and om sample of 50 women more than 65 years old was recruited from two apartment buildings . The buildings were r and omized to serve as exercise and control sites . The 24 exercisers did not differ significantly from the 26 controls except that they were better educated and had better vision . The median compliance was 85 % of requested sessions attended by the exercisers . Follow-up measures were obtained in 92 % and 81 % of the exercise and control groups , respectively . The outcome variables studied were changes in sway ( areas and velocity of the center of force as measured using a biomechanics platform ) in four stances with eyes open or closed , on two feet , or on one foot . After 16 weeks , in stances on one foot , exercisers had smaller areas compared to controls with eyes open , but larger areas with eyes closed . Subgroup analysis indicated that compliance with the exercise program was a determinant of degree of change in the area measures . The inconsistent effect of exercise on area measures of sway in this study may be due to ( a ) lack of statistical power to detect between-group differences , ( b ) inadequate compliance with the exercise program , ( c ) baseline differences between the two groups at r and omization , and ( d ) ineffective or inadequate duration of the exercise program . We conclude that controlled clinical trials to study the effect of exercise on balance measures in community-dwelling elderly women are feasible . ( ABSTRACT TRUNCATED AT 250 WORDS",
"OBJECTIVE To examine the effects of a 3-month low-intensity exercise program on physical frailty . DESIGN R and omized clinical trial . SETTING Regional tertiary-care hospital and academic medical center with an outpatient rehabilitation fitness center . PARTICIPANTS Eighty-four physically frail older adults ( mean age , 83 + /- 4 yrs ) . INTERVENTION Three-month low-intensity supervised exercise ( n = 48 ) versus unsupervised home-based flexibility activities ( n = 36 ) . MAIN OUTCOME MEASURES Physical performance test , measures of balance , strength , flexibility , coordination , speed of reaction , peripheral sensation . RESULTS Significant improvement was made by the exercise group on our primary indicator of frailty , a physical performance test ( PPT ) ( 29 + /- 4 vs 31 + /- 4 out of a possible 36 points ) , as well as many of the risk factors previously identified as contributors to frailty ; eg , reductions in flexibility , strength , gait speed , and poor balance . Although the home exercise control group showed increases in range of motion , the improvements in flexibility did not translate into improvements in physical performance capacity as assessed by the PPT . CONCLUSIONS Our results suggest that physical frailty is modifiable with a program of modest activities that can be performed by virtually all older adults . They also indicate that exercise programs consisting primarily of flexibility activities are not likely to reverse or attenuate physical frailty . Although results suggest that frailty is modifiable , it is not likely to be eliminated with exercise , and efforts should be directed toward preventing the condition",
"OBJECTIVES The objectives of this study were to determine the effects of a strength-training program on walking speed and relative muscular stress , as measured by normalized integrated electromyographic ( nIEMG ) activity , while carrying a box of groceries and st and ing from a chair . DESIGN Prospect i ve intervention study . SETTING Volunteer subjects from the community of Birmingham , Alabama . PARTICIPANTS Fourteen healthy women aged 60 to 77 years . INTERVENTION Sixteen weeks of total body strength conditioning . MEASUREMENTS Before and after 16 weeks of strength conditioning , the following variables were evaluated for all subjects : ( 1 ) strength , six isotonic tests and two isometric tests ; ( 2 ) walking velocity ; ( 3 ) nIEMG of the biceps while carrying a box of groceries ; and ( 4 ) nIEMG of the rectus femoris while st and ing from a chair . MAIN RESULTS After the strength training program , subjects ' isotonic strength increased significantly , an average of 52 % on the isotonic tests and 31 % on the isometric tests . Walking velocity also increased significantly ( 18 % ) . nIEMG of the biceps decreased 36 % while carrying a box of groceries . Rectus femoris nIEMG decreased 40 % while st and ing and 47 % while sitting . CONCLUSIONS After strength conditioning , healthy older women showed not only substantially increased strength but also improvements in walking velocity and the ability to carry out daily tasks such as rising from a chair and carrying a box of groceries",
"PURPOSE This r and omized controlled study assessed whether adding a program of high-intensity strength training ( 80 % of maximum ) to an outpatient cardiac rehabilitation program would be a safe and effective means of improving muscle strength and body composition . METHODS Thirty-eight cardiac patient volunteers ( 29 men and 9 women ) were r and omized to either high-intensity strength training or flexibility training added concurrently to a 12-week outpatient cardiac rehabilitation aerobic exercise program . Muscle strength , local muscle endurance , joint flexibility , maximum treadmill tolerance time , and body composition were measured before and after completion of the training . RESULTS The strength-trained patients ( n = 18 ) had greater increases in mean strength ( 90 + /- 19 % versus 9 + /- 4 % , P local muscle endurance ( 20 versus 6 times , P mean perceived exertion for lifting the initial one repetition maximum load ( 11 + /- 1 versus 15 + /- 1 , P body fat ( 2.8 + /- 2.0 versus 1.3 + /- 2.0 kg , P gain more lean tissue ( 1.5 + /- 2.3 versus 0.5 + /- 1.2 kg , P improvements in treadmill time ( 2.3 + /- 1.3 versus 1.2 + /- 1.0 minute , P joint flexibility were similar for each group . None of the subjects had evidence of cardiac ischemia or arrhythmia during the training sessions . CONCLUSIONS Medically supervised high-intensity strength training is well tolerated when added to the aerobic training of cardiac rehabilitation programs and allows patients to aggressively gain the strength and endurance they will need to complete daily living tasks at lower perceived efforts . Strength training also reduces cardiac risk factors by improving body composition and maximum treadmill exercise time",
"OBJECTIVE --To determine the effectiveness of group- vs home-based exercise training of higher and lower intensities among healthy , sedentary older adults . DESIGN --Year-long r and omized , controlled trial comparing ( 1 ) higher-intensity group-based exercise training ; ( 2 ) higher-intensity home-based exercise training ; ( 3 ) lower-intensity home-based exercise training ; or ( 4 ) assessment -only control . SETTING --General community located in northern California . PARTICIPANTS --One hundred sixty women and 197 men 50 to 65 years of age who were sedentary and free of cardiovascular disease . One out of nine persons contacted through a community r and om-digit-dial telephone survey and citywide promotion were r and omized . INTERVENTIONS --For higher-intensity exercise training , three 40-minute endurance training sessions per week were prescribed at 73 % to 88 % of peak treadmill heart rate . For lower-intensity exercise training , five 30-minute endurance training sessions per week were prescribed at 60 % to 73 % of peak treadmill heart rate . MAIN OUTCOME MEASURES --Treadmill exercise test performance , exercise participation rates , and heart disease risk factors . RESULTS --Compared with controls , subjects in all three exercise training conditions showed significant improvements in treadmill exercise test performance at 6 and 12 months ( P less than .03 ) . Lower-intensity exercise training achieved changes comparable with those of higher-intensity exercise training . Twelve-month exercise adherence rates were better for the two home-based exercise training conditions relative to the group-based exercise training condition ( P less than .0005 ) . There were no significant training-induced changes in lipid levels , weight , or blood pressure . CONCLUSIONS --We conclude that ( 1 ) this community-based exercise training program improved fitness but not heart disease risk factors among sedentary , healthy older adults ; ( 2 ) home-based exercise was as effective as group exercise in producing these changes ; ( 3 ) lower-intensity exercise training was as effective as higher-intensity exercise training in the home setting ; and ( 4 ) the exercise programs were relatively safe",
"The purpose of this study was to examine the effects of a 14-week resistance training program on the anile strength training intensity , postural control , and gait velocity of older adults . Forty-two older adults ( mean age = 72 ) , 21 in the resistance and control groups , completed the 14-week project . The resistance training group participated in 14 weeks of resistance training three times per week using elastic b and s ( Therab and ) for resistance . Isokinetic ankle strength , training intensity , postural stability , and gait velocity were measured prior to and following the 14-week intervention . Following the training , the resistance group exhibited improved ankle dorsiflexion , training resistances , and gait velocity , but showed no change in plantar flexion or postural control . The control group also exhibited improvements in dorsiflexion , but these gains were approximately one-half of the gains observed in the resistance training group . Finally , when adjusted for baseline differences , subjects in the resistance training group demonstrated no changes in the dependent measures over the control group",
"OBJECTIVE To assess the effect of a home based exercise programme , design ed to improve quadriceps strength , on knee pain and disability . Methods —191 men and women with knee pain aged 40–80 were recruited from the community and r and omised to exercise ( n=113 ) or no intervention ( n=78 ) . The exercise group performed strengthening exercises daily for six months . The primary outcome measure was change in knee pain ( Western Ontario McMaster Osteoarthritis index ( WOMAC ) ) . Secondary measures included visual analogue scales ( VAS ) for pain on stairs and walking and WOMAC physical function scores . Results —WOMAC pain score reduced by 22.5 % in the exercise group and by 6.2 % in the control group ( between group difference p scores for pain also reduced in the exercise group compared with the control group ( p Physical function scores reduced by 17.4 % in the exercise group and were unchanged in controls ( p home quadriceps exercises can significantly improve self reported knee pain and function",
"OBJECTIVE To determine the effect of a home exercise program on strength , postural control , and mobility following hip fracture . DESIGN R and omized controlled trial of 1 month 's duration . SETTING Daily exercise carried out within the subjects ' home environments . PARTICIPANTS Forty-two people 64 to 94 years of age , 35 of whom were living independently in the community and 7 of whom were residing in institutional care . Subjects were recruited on average 7 months after a fall-related hip fracture and r and omly allocated to either the intervention or the control group ( n = 21 each ) . The groups were well matched in terms of medical conditions , medication use , disability , and activity levels . INTERVENTION A \" home-based \" program of weight-bearing exercise established at a visit by a physiotherapist . MAIN OUTCOME MEASURES Quadriceps strength , postural sway , functional reach , weight-bearing ability , walking velocity , and self-rated fall risk . The subjects undertook these assessment s at the beginning and end of the trial . RESULTS At pretest , exercisers and controls performed similarly in all tests . At the end of the trial , the intervention group showed significantly greater quadriceps strength in the affected ( hip-fractured ) leg and increased walking velocity . The intervention subjects also improved their weight-bearing ability and reported reduced subjective falls risk . In contrast , there were no significant improvements in any of the test measures in the controls . Within the intervention group , improvements in quadriceps strength were significantly associated with improved performances in the weight-bearing test measures and with increased walking velocity . CONCLUSIONS This exercise program improved strength and mobility following hip fracture . Further research is needed to ascertain whether the extent of this improvement in these fall risk factors is sufficient to prevent falls",
"BACKGROUND Strength loss is strongly associated with functional decline and is reversible with exercise . The effect of increased strength on function has not been clearly established . The purpose of this study was to determine whether strength gain is associated with improvement in physical performance and disability . METHODS One hundred functionally impaired community-dwelling men and women ( 77.6 + /- 7.6 yrs ) were tested at baseline and outcome for lower extremity strength , physical performance , and disability . After r and om group assignment , exercise participants received strengthening exercises in their homes three times a week for 10 weeks while control subjects continued their normal activities . Using multiple regression techniques , the relationship between strength gain and improvement in physical performance and disability was assessed , controlling for age , depression , and baseline strength . RESULTS A significant impact of strength gain on mobility skills ( p = .0009 ) was found . The impact of strength gain on chair rise performance was significant in participants who were more impaired ( p = .04 ) . Strength gain was associated with gain in gait speed ( p = .02 ) and in falls efficacy ( p = .05 ) , but not with other balance , endurance , or disability measures . CONCLUSIONS Lower extremity strength gain is associated with gains in chair rise performance , gait speed , and in mobility tasks such as gait , transfers , stooping , and stair climbing , but not with improved endurance , balance , or disability . Strength gain is also associated with improvement in confidence in mobility . Factors that may influence the ability of strength gain to affect function are initial level of frailty and specificity of exercise . These results support the idea that strength training is an intervention that can potentially improve physical health status in many frail elders",
"To investigate the effects of cessation and subsequent resumption of training on muscle strength in elderly men , 11 men ( aged 65 - 77 years ) , just completing a 24-week r and omized controlled trial of recombinant human growth hormone ( rhGH ) and resistance exercise ( rhGH , n = 6 ; placebo , n = 5 ) , detrained for 12 weeks and subsequently retrained for 8 weeks . During the detraining and retraining phase , subjects did not receive rhGH . The resistance programme included three sets of eight repetitions at 75 % of one-repetition maximum ( 1-RM ) , three times per week , for 10 upper and lower body exercises . Dynamic muscle strength was assessed by the 1-RM method every 2 weeks for 44 weeks . Needle biopsies of vastus lateralis muscle were obtained from seven men . Muscle strength increased during initial training by 40.4 + /- 5.5 % ( mean + /- SEM ) , ranging from 26.0 + /- 5.0 to 83.9 + /- 15.6 % , depending on muscle group . Increased strength was accompanied by hypertrophy ( P strength gains , only 29.9 + /- 5.2 % was lost with detraining . However , type I and II fibre cross-sectional area reverted to pretraining values . After 8 weeks of retraining , muscle strength returned to trained values , but without a significant change in fibre morphology . The results indicate that elderly men lose some muscle strength following short-term detraining , but that only a brief period of retraining suffices to regain maximal strength . Reversal of fibre cross-sectional area with detraining , and only modest improvement with retraining , suggests that much of the retention in strength with detraining and reacquisition of lost strength with retraining reflects neural adaptation",
"PURPOSE This study examined the effects of 24 wk of high intensity strength training or low intensity walking on lumbar bone mineral density ( BMD ) , muscular strength , and calcium turnover in Australian women either taking hormone replacement therapy ( HRT ) or not taking HRT . METHODS A subject pool of 64 women between 45 - 65 yr and r and omly allocated into weights ( N = 21 ) , walking ( N = 20 ) , weightsHRT ( N = 14 ) , and walkingHRT ( N = 9 ) groups completed this study . All subjects trained twice weekly in either a 50-min walking or weight-training program ( 60 - 90 % IRM ) . Measurements included maximal isometric knee strength , IRM bench press , IRM squat , isokinetic back strength , lumbar ( L2-L4 ) BMD , serum osteocalcin , and urinary deoxypyridinoline crosslinks ( Dpd ) . RESULTS No significant group differences in BMD were evident at the completion of training . However , a significant ( P BMD decreased 1.3 % below baseline testing . Osteocalcin levels increased significantly ( P Maximal bench press and squat strength improved significantly ( P isokinetic back strength ( 22.2 % ) . CONCLUSION It was concluded that short-term high intensity resistance training provides an effective means for increasing muscular strength in women between 45 and 65 yr . The training effects on lumbar BMD were not apparent in the present study",
"Knowledge of the effects of exercise on bone mass in postmenopausal women is limited and controversial . Animal studies have shown that the response of bone to bending strain is an alteration of bone geometry . We studied 250 postmenopausal women , aged 52 - 72 years , willing to participate in a 6-month exercise program . The first 125 started the program immediately and the remaining 125 served as controls . The training program included exercises design ed to maximize the stress on the wrist . One hundred and eighteen of the active group and 116 of the control group completed the study and were reassessed 6 months later . Bone mineral density ( BMD ) of the femoral neck , lumbar spine , ultradistal and proximal radius was measured by dual-energy X-ray absorptiometry ( DXA ) both before and at the end of the exercise program . The forearm was also evaluated by peripheral quantitative computed tomography , which measures the area , bone mineral content ( BMC ) , and volumetric density for both the cortical and the trabecular component . The results showed that the DXA measurements at the femoral neck , lumbar spine , ultradistal and proximal radius were similar between the two groups . No significant difference was detected after the exercise program at the proximal radius . At the ultradistal radius , the cross-sectional area of cortical bone rose by 2.8 + /- 15.0 % ( SD , p apposition and corticalization of the trabecular tissue . The volumetric density of cortical bone rose by 2 . 2 + /- 15.8 % ( p trabecular bone decreased by 2.6 + /- 10.7 % ( p bone volume and density in the exercise group were associated with marked increase in cortical BMC ( 3.1 + /- 10.7 % , p trabecular BMC ( -3.4 + /- 14.2 % , p bone mass . However , it appears that some exercises may reshape the bone segment under stress by increasing both the cross-sectional area and the density of the cortical component . These structural changes are theoretically associated with increases in the bending strength",
"This study was design ed to determine whether an 8-week isokinetic muscle-strength-training program improved the functional health status of patients with osteoarthritis of the knee joint . Twenty volunteers with osteoarthritis of the knee joint were r and omly assigned to either an experimental ( n=10 ) or control ( n=10 ) group . The experimental group completed six sets of five maximal contractions three times per week for 8 weeks on a Cybex II dynamometer at 90 degrees per second . Both groups were pre- and posttest for extension and flexion strength of the right and left legs , the 50-foot walk time , range of motion at the knee joint , the Osteoarthritis Screening Index ( OASI ) , and the Arthritis Impact Measurement Scale ( AIMS ) . There was a significant decrease in pain and stiffness , and a significant increase in mobility . There was also a significant decline in arthritis activity in the experimental group as measured by the OASI and AIMS . The experimental group significantly increased in all strength measures , while the control group increased in only right leg flexion and left leg extension across the training period",
"BACKGROUND Although disuse of skeletal muscle and undernutrition are often cited as potentially reversible causes of frailty in elderly people , the efficacy of interventions targeted specifically at these deficits has not been carefully studied . METHODS We conducted a r and omized , placebo-controlled trial comparing progressive resistance exercise training , multinutrient supplementation , both interventions , and neither in 100 frail nursing home residents over a 10-week period . RESULTS The mean ( + /- SE ) age of the 63 women and 37 men enrolled in the study was 87.1 + /- 0.6 years ( range , 72 to 98 ) ; 94 percent of the subjects completed the study . Muscle strength increased by 113 + /- 8 percent in the subjects who underwent exercise training , as compared with 3 + /- 9 percent in the nonexercising subjects ( P Gait velocity increased by 11.8 + /- 3.8 percent in the exercisers but declined by 1.0 + /- 3.8 percent in the nonexercisers ( P = 0.02 ) . Stair-climbing power also improved in the exercisers as compared with the nonexercisers ( by 28.4 + /- 6.6 percent vs. 3.6 + /- 6.7 percent , P = 0.01 ) , as did the level of spontaneous physical activity . Cross-sectional thigh-muscle area increased by 2.7 + /- 1.8 percent in the exercisers but declined by 1.8 + /- 2.0 percent in the nonexercisers ( P = 0.11 ) . The nutritional supplement had no effect on any primary outcome measure . Total energy intake was significantly increased only in the exercising subjects who also received nutritional supplementation . CONCLUSIONS High-intensity resistance exercise training is a feasible and effective means of counteracting muscle weakness and physical frailty in very elderly people . In contrast , multi-nutrient supplementation without concomitant exercise does not reduce muscle weakness or physical frailty",
"We examined the effects of 42 weeks of progressive weight-lifting training on dynamic muscle strength , peak power output in cycle ergometry , symptom limited endurance during progressive treadmill walking and stair climbing , knee extensor cross-sectional areas , and bone mineral density and content in healthy males and females aged 60 - 80 years , currently enrolled in a 2-year resistance training program . Subjects were r and omized into either exercise ( EX ) or control ( CON ) groups ( 60 - 70 years : 38 males and 36 females ; 70 - 80 years : 25 males and 43 females ) . EX trained several muscle groups twice per week for 42 weeks at intensities ranging from 50 - 80 % of the load that they could lift once only ( 1 RM ) ; CON did usual daily activities . After the 10 months there was no change in 1 RM strength in CON , but significant gains ( mean increases up to 65 % ) in EX ( no independent age or gender effects ) ; 30 % and 47 % of the increase in 1 RM had occurred by 6 and 12 weeks , respectively . In EX , the 7.1 % increase in peak cycling power output was significantly greater than in CON ( + 1.1 % ) . The 17.8 % improvement in symptom limited treadmill walking endurance was also greater than in CON ( + 3.4 % ) , but the difference between groups during stair climbing was not significant ( EX + 57 % , CON + 33 % ) . The cross-sectional areas of the knee extensors increased significantly by 5.5 % in EX but were unchanged in CON . There were no changes in bone mineral density or content in either group . We conclude that long-term resistance training in older people is feasible and results in increases in dynamic muscle strength , muscle size , and functional capacity",
"The aim of the present study was to evaluate the effects of a 16-week progressive high-intensity strength training ( HIST ) program on peripheral markers of bone turnover ( bone Gla protein , BGP ; bone alkaline phosphatase , B-AP ; N-terminal propeptide of type I procollagen , PINP ; C-terminal cross-linked telopeptide of type I collagen , ICTP ) in healthy , elderly men over 65 yr of age . Thirty healthy men ( aged 65–81 yr ) , performing light to moderate daily physical activity , were r and omly divided into two groups . Group 1 ( no.=16 ) followed a supervised 16-week progressive HIST program , while subjects of group 2 ( no.=14 ) , used as controls , were requested to maintain their habitual level of physical activity for 16 weeks . HIST program consisted of 6 different sets of exercise ( 2 involving the major muscle groups of the lower limb and 4 involving those of the upper limb ) . Three sessions/week , during which 10 repetitions of each exercise set were completed , were performed . Lower limb exercises shifted from 50 to 80 % of the one maximal repetition ( 1MR ) during the first month of the protocol and were thereafter maintained at an intensity of 80 % 1MR throughout the training . Upper limb exercises shifted from 40 to 65 % of 1MR with a similar pattern . All sessions were preceded by 15 min of cycloergometer exercise at 50 % of maximal oxygen uptake and by a warm-up of 15 repetitions at 20 % of 1MR of each exercise set . The HIST program did not significantly change BGP ( mean±SE , before : 15.6±1.2 μg/l vs after : 16.0±1.2 μg/l , NS ) and PINP levels ( before : 44.6±6.7 μg/l vs after : 43.1±6.0 μg/l , NS ) . On the contrary , serum B-AP significantly increased ( before : 50.2±6.1 IU/l vs after : 62.3±7.0 IU/l , p ( before : 4.0±0.3 μg/l vs after : 3.8±0.3 μg/l , p , a significant improvement in this ratio was found in all subjects of group 1 ( before : 12.9±1.3 IU/μg vs after : 17.3±1.5 IU/μg , p 2 . No significant changes of IGF-I levels were observed after the HIST program ( before : 94.9±9.4 μg/l vs after : 89.9±9.7 μg/l ) . No significant changes of BGP , PINP , B-AP , ICTP , B-APICTP ratio and IGF-I levels were observed in controls ( group 2 ) during the 16 weeks of observation . Although the positive effects of a progressive HIST program on B-AP levels and B-AP-ICTP ratio seem promising , the support of bone mass measurement and the determination of other bone markers are requested to better identify exercise protocol ( duration , intensity ) for elderly people",
"PURPOSE The recommendations for exercise training and physical activity for older adults include cardiovascular and resistance training components ( CVT and RT , respectively ) . The purpose of the present investigation was to compare the fitness benefits of concurrent CVT and RT with those attained through an equivalent duration of CVT or RT alone . METHODS Thirty-six participants ( ages 60 - 84 ) were assigned to a control group or to one of three exercise treatment groups . The treatment groups exercised three times per week for 12 wk using RT ( N = 11 ) , CVT ( N = 10 ) , or CVT and RT ( BOTH , N = 9 ) . Pre- and post-training , participants performed a submaximal exercise test ( GXT ) , five repetition-maximum strength tests ( 5RM ) , and the AAHPERD functional fitness test for older adults . RESULTS All exercise treatment groups revealed lower resting heart rate and rate-pressure product ; lower exercise diastolic blood pressure and rating of perceived exertion ; increased GXT duration ; increased leg , back , and shoulder 5RM scores ; and improved AAHPERD flexibility , coordination , and cardiovascular endurance scores . The exercise treatment groups responded differently on the following : RT and BOTH enhanced arm and chest strength more than CVT ; and BOTH enhanced AAHPERD strength and agility scores more than CVT or RT . CONCLUSIONS Concurrent CVT and RT is as effective in eliciting improvements in cardiovascular fitness and 5RM performance as CVT or RT , respectively . Moreover , incorporating both CVT and RT in exercise programs for older adults may be more effective in optimizing aspects of functional fitness than programs that involve only one component",
"This study tested whether a 12-week dynamic resistance strength training program can change gait velocity and improve measures of balance among adults age 65 and older . Fifty-five community-dwelling adults ( mean age = 71.1 ) were r and omized into an exercise ( n = 25 ) or control ( n = 30 ) group . The exercisers were requested to complete three bouts of strength training per week for 12 weeks using elastic tubing . At posttest the exercisers demonstrated slower gait velocity , enhanced balance , and an improved ability to walk backward , although none of these posttest measures was significantly different from the control group",
"Fifty female subjects , aged 72 - 92 ( mean 82 ) years , were enrolled in a 12-week ( 36 classes ) exercise program aim ed at increasing postural stability . Subjects were residents of sheltered apartments , rest homes or nursing homes , well enough and mobile enough to participate in the classes . The subjects were r and omized into an exercise or a control group . Their postural sway , st and ing at rest on a force platform , was measured with eyes open and eyes closed . The groups were well matched in all respects . The results showed no improvement in the postural sway as a result of the exercise program . We hypothesize that increasing postural sway in the elderly represents a deterioration in , for the most part , the nervous system and may at this extreme of life indicate an irreversible loss of function . For this reason no improvement in postural sway may be possible",
"Twenty active elderly subjects ( mean age = 66.4 years , range 51 - 81 ) participated in a 12-week weight-training program to determine the possibility of increasing muscular strength and lean body weight . The training utilized variable resistance weight machines which trained the major muscle groups . The male subjects ( n = 11 ) experienced an average increase of 66.1 % ( SD = 19.39 , p total maximum weight lifted while the females ( n = 9 ) showed an average increase of 72.2 % ( SD = 33.44 , p Lean body weight , which was calculated by skinfold measurements for each group did increase , but was not statistically significant ( males p weight-training regimen can have on an elderly population",
"Left ventricular function and hemodynamic alterations at rest were measured echocardiographically following running or isometric training in 40 healthy elderly . They were r and omly assigned into two groups . Twenty ( 67 + /- 4 years ) were engaged in running and 20 ( 67.8 + /- 3.8 years ) in isometric training programs . All subjects underwent a 12-week program , 3 times a week 30 min each session . The running exercise ( REX ) group had an aerobic exercise conditioning program at 70 % of their VO2max . The program for the isometric exercise ( IEX ) group included weight lifting utilizing large muscle mass at 30 % of their maximal voluntary contraction . After training , the REX group increased significantly ( p less than 0.05 ) their VO2max from 2.08 + /- 0.37 to 2.36 + /- 0.41 liter/min and ejection fraction 56 + /- 5.9 to 62 + /- 6.1 % . They decreased significantly their heart rate , from 73 + /- 7 to 65 + /- 7 beats/min . No change occurred in the IEX group in left ventricular function and hemodynamic parameters . These data suggest that left ventricular responses at rest differ between the two groups following a short-term training with a favorable response after REX training . In addition , this study demonstrated that a controlled aerobic training program is a better way to improve physical capacity than is a weight lifting program for trained healthy elderly"
] |
4116cde2-06ff-11f0-808a-c43d1ab1c353
|
Background The increasing prevalence of type 2 diabetes mellitus ( T2DM ) can have a substantial impact in low- and middle-income countries ( LMICs ) . Community-based programs addressing diet , physical activity , and health behaviors have shown significant benefits on the prevention and management of T2DM , mainly in high-income countries . However , their effects on preventing T2DM in the at-risk population of LMICs have not been thoroughly evaluated . Methods The Cochrane Library ( CENTRAL ) , MEDLINE , EMBASE and two clinical trial registries were search ed to identify eligible studies . We applied a 10 years limit ( from 01 Jan 2008 to 06 Mar 2018 ) on English language literature . We included r and omized controlled trials ( RCTs ) with programs focused on lifestyle changes such as weight loss and /or physical activity increase , without pharmacological treatments , which aim ed to alter incidence of diabetes or one of the T2DM risk factors , of at least 6 months duration based on follow-up , conducted in LMICs . Results Six RCTs r and omizing 2574 people were included . The risk of developing diabetes in the intervention groups reduced more than 40 % , RR ( 0.57 [ 0.30 , 1.06 ] ) , for 1921 participants ( moderate quality evidence ) , though it was not statistically significant . Significant differences were observed in weight , body mass index , and waist circumference change in favor of community-based programs from baseline , ( MD [ 95 % CI ] ; − 2.30 [ − 3.40 , − 1.19 ] , p significant reduction in fasting blood glucose and HbA1C measurements in favor of the intervention ( MD [ 95 % CI ] ; − 4.94 [ − 8.33 , − 1.55 ] , p respectively . No significant difference was observed in 2-h blood glucose values , systolic or diastolic blood pressure change between the two groups . Conclusion Based on available literature , evidence suggests that community-based interventions may reduce the incidence rate of T2DM and may positively affect anthropometric indices and HbA1C . Due to the heterogeneity observed between trials we recommend more well- design ed RCTs with longer follow-up duration s be executed , to confirm whether community-based interventions lead to reduced T2DM events in the at-risk population of LMIC setting
|
[
"The purpose of the present study was to evaluate the impact of a lifestyle intervention programme , combined with a daily low-glycaemic index meal replacement , on body-weight and glycaemic control in subjects with impaired glucose regulation ( IGR ) . Subjects with IGR were r and omly assigned to an intervention group ( n 46 ) and a control group ( n 42 ) . Both groups received health counselling at baseline . The intervention group also received a daily meal replacement and intensive lifestyle intervention to promote healthy eating habits during the first 3 months of the study , and follow-up visits performed monthly until the end of the 1-year study . Outcome measurements included changes in plasma glucose , glycated Hb ( HbA1c ) , plasma lipids , body weight , blood pressure and body composition ( such as body fat mass and visceral fat area ) . The results showed that body-weight loss after 1 year was significant in the intervention group compared with the control group ( -1·8 ( SEM 0·35 ) v. -0·6 ( SEM 0·40 ) 2·5 kg , P decreased 1·24 mmol/l in the intervention group and increased 0·85 mmol/l in the control group ( P 5 kg body-weight loss at 1 year was associated with a decrease of 1·49 mmol/l in 2 h plasma glucose ( P . The incidence of normal glucose regulation ( NGR ) in the two groups was significantly different ( P=0·001 ) . In conclusion , the combination of regular contact , lifestyle advice and meal replacement is beneficial in promoting IGR to NGR",
"Although evidence suggests that lifestyle interventions can reduce blood pressure ( BP ) and glucose levels , there is little information about the feasibility of such interventions when implemented in community setting s. This study evaluated the effectiveness of a community-based lifestyle intervention on BP and glucose in the middle-aged and older Chinese population . By using a cluster r and omisation approach , 474 participants from two communities were assigned to the intervention group which received intensive health education and behavioural intervention , or the control group which received conventional education . Linear mixed models were used to compare between-group differences on change in BP and fasting glucose after 6 , 12 and 24 months . At the 12-month follow-up , the intervention group experienced significantly reductions in systolic BP ( −4.9 vs. 2.4 mmHg ; mean difference [ MD ] −7.3 mmHg ; p ( −1.9 vs. 1.9 mmHg ; MD −3.8 mmHg ; p ( −0.59 vs. 0.08 mmol/L ; MD −0.67 mmol/L ; p only two communities , it was not possible to adjust for potential clustering by site . This approach of lifestyle interventions conducted through primary care services may be a potential solution for combating hypertension and diabetes in a re source -limited country context in China",
"BACKGROUND The Diabetes Prevention Program ( DPP ) found that an intensive lifestyle intervention can reduce the development of diabetes by more than half in adults with prediabetes , but there is little information about the feasibility of offering such an intervention in community setting s. This study evaluated the delivery of a group-based DPP lifestyle intervention in partnership with the YMCA . METHODS This pilot cluster-r and omized trial was design ed to compare group-based DPP lifestyle intervention delivery by the YMCA to brief counseling alone ( control ) in adults who attended a diabetes risk-screening event at one of two semi-urban YMCA facilities and who had a BMI > or=24 kg/m2 , > or=2 diabetes risk factors , and a r and om capillary blood glucose of 110 - 199 mg/dL. Multivariate regression was used to compare between-group differences in changes in body weight , blood pressures , HbA1c , total cholesterol , and HDL-cholesterol after 6 and 12 months . RESULTS Among 92 participants , controls were more often women ( 61 % vs 50 % ) and of nonwhite race ( 29 % vs 7 % ) . After 6 months , body weight decreased by 6.0 % ( 95 % CI=4.7 , 7.3 ) in intervention participants and 2.0 % ( 95 % CI=0.6 , 3.3 ) in controls ( p total cholesterol ( -22 mg/dL vs + 6 mg/dL controls ; p YMCA sites , it was not possible to adjust for potential clustering by site . CONCLUSIONS The YMCA may be a promising channel for wide-scale dissemination of a low-cost approach to lifestyle diabetes prevention",
"AIM To determine the efficacy of delivering short-message service ( SMS ) to provide diabetes-related information in reducing the risk of developing diabetes in Chinese professional drivers with pre-diabetes . METHODS A pilot single-blinded r and omized controlled trial was conducted in Hong Kong between 05/2009 and 04/2012 . Professional drivers with impaired glucose tolerance ( IGT ) were r and omly allocated to either a SMS group receiving messages comprising knowledge and lifestyle modification on diabetes or to a control group with usual care . Primary outcomes were the incidence rate of diabetes mellitus over 12 and 24 months period . RESULTS Fifty-four , out of 104 professional drivers recruited , were r and omly allocated to intervention group . Fewer subjects developed diabetes at 12 months in intervention group ( 5.56 % ) compared to control group ( 16.00 % ) . Relative risk ( RR ) of diabetes onset was 0.35 ( 95%CI : 0.10–1.24 ) and the number needed to treat ( NNT ) for preventing one diabetes was 9.57 . At 24 months , RR increased to 0.62 ( 95%CI : 0.24–1.61 ) with a NNT of 10.58 . Logistic regression showed a significant odds ratio of 0.04 ( P = 0.021 ) for intervention group compared to control group at 12-month follow-up for completers and a non-significant odds ratio of 0.34 ( P = 0.303 ) at 24-month follow-up . CONCLUSIONS The SMS program proved to have potential to reduce the risk of developing diabetes at 12 months but additional measures should be integrated to prevent or delay disease progression",
"AIMS To investigate a virtual assistance-based lifestyle intervention to reduce risk factors for Type 2 diabetes in young employees in the information technology industry in India . METHODS LIMIT ( Lifestyle Modification in Information Technology ) was a parallel-group , partially blinded , r and omized controlled trial . Employees in the information technology industry with ≥3 risk factors ( family history of cardiometabolic disease , overweight/obesity , high blood pressure , impaired fasting glucose , hypertriglyceridaemia , high LDL cholesterol and low HDL cholesterol ) from two industries were r and omized to a control or an intervention ( 1:1 ) group . After initial lifestyle advice , the intervention group additionally received reinforcement through mobile phone messages ( three per week ) and e-mails ( two per week ) for 1 year . The primary outcome was change in prevalence of overweight/obesity , analysed by intention to treat . RESULTS Of 437 employees screened ( mean age 36.2 ± 9.3 years ; 74.8 % men ) , 265 ( 61.0 % ) were eligible and r and omized into control ( n=132 ) or intervention ( n=133 ) group . After 1 year , the prevalence of overweight/obesity reduced by 6.0 % in the intervention group and increased by 6.8 % in the control group ( risk difference 11.2 % ; 95 % CI 1.2 - 21.1 ; P=0.042 ) . There were also significant improvements in lifestyle measurements , waist circumference , and total and LDL cholesterol in the intervention group . The number-needed-to-treat to prevent one case of overweight/obesity in 1 year was 9 ( 95 % CI 5 - 82 ) , with an incremental cost of INR10665 ( £ 112.30 ) per case treated/prevented . A total of 98 % of participants found the intervention acceptable . CONCLUSIONS A virtual assistance-based lifestyle intervention was effective , cost-effective and acceptable in reducing risk factors for diabetes in young employees in the information technology industry , and is potentially scalable",
"Objective : The objective of this study was to evaluate the effectiveness of a synthetic intervention model aim ed at preventing type 2 diabetes and controlling plasma glucose , body weight and waist circumference in elderly individuals with prediabetes in rural China . Methods : We r and omly assigned 434 ( 180 men and 254 women ; mean age , 69 years ; mean body mass index , 23.6 kg/m2 ) with prediabetes to either the intervention group or the control group . Each participant in the intervention group received synthetic intervention for 1 year . Results : The incidence of diabetes was 4.2 % in the intervention group , versus 19.7 % in the control group at the end of 1 year ( p in fasting glucose ( −3.9 vs. 2.2 mg/dL , p 0.001 ) , body weight ( −3.2 vs. 1.7 kg , p ( −2.4 vs. 1.0 cm , p ( −9.1 vs. −4.6 mg/dL. p = 0.014 ) and HbA1c ( −1.0 vs. 0.1 mg % , p = 0.002 ) at the end of 1 year . Conclusions : The incidence of diabetes of the control group was higher than that of the intervention group . Besides , the synthetic intervention contributes to weight loss and glucose decrease , and may be effective in reducing the risk of diabetes among elderly individuals with prediabetes in rural China",
"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 )",
"Introduction This study investigated the outcomes and identified influencing factors of intensive integrated intervention over 2 years in Chinese patients with impaired glucose regulation ( IGR ) . Methods Adults in Beijing , China , were screened for IGR using the 75 g oral glucose tolerance test . Participants with IGR received lifestyle and health education ; those who still had IGR after 1 year were r and omly assigned to either a routine care group or to an intensive integrated intervention group . Results Of 2344 adults screened , 463 had IGR . Of these , 210 adults had IGR after 1 year and were therefore recruited and r and omized to an intensive integrated intervention group ( n=106 ) or a control group ( n=104 ) . The percentage of patients who reached the set targets of plasma glucose , blood pressure , body mass index , or triglycerides was significantly higher in the intensive integrated intervention group . None of the patients within the intensive integrated intervention group progressed to diabetes , whereas eight ( 9.3 % ) cases of the control group developed type 2 diabetes mellitus ( T2DM ) . Logistic regression analysis showed that both an increase in waist circumference and systolic blood pressure ( SBP ) were positively correlated with the development of T2DM , whereas improvement in islet beta cell function was negatively correlated with the development of T2DM . Conclusions Intensive integrated intervention may significantly decrease the conversion rate of IGR to T2DM , and increase the conversion ratio to normal glucose tolerance . The increase of waist circumference or SBP and the deterioration of islet beta cell function may be important risk factors for progression from prediabetes to diabetes",
"Background Diabetes is now a global epidemic , but most cases are now in low- and middle-income countries . Diabetes self-management education ( DSME ) is key to enabling patients to manage their chronic condition and can reduce the occurrence of costly and devastating complications . However , there is limited evidence on the effectiveness of different DSME programmes in re source limited setting s. Methods We conducted an unblinded , parallel-group , individually-r and omised controlled trial at the University of Calabar Teaching Hospital ( Nigeria ) to evaluate whether an intensive and systematic DSME programme , using structured guidelines , improved glycaemic control compared to the existing ad hoc patient education ( clinical practice was unchanged ) . Eligible patients ( ≥18 years , HbA1c > 8.5 % and physically able to participate ) were r and omly allocated by permuted block r and omisation to participate for six months in either an intensive or conventional education group . The primary outcome was HbA1c ( % ) at six-months . Results We r and omised 59 participants to each group and obtained six-month HbA1c outcomes from 53 and 51 participants in the intensive and conventional education groups , respectively . Intensive group participants had a mean six-month HbA1c ( % ) of 8.4 ( 95 % CI : 8 to 8.9 ) , while participants in the conventional education group had a mean six-month HbA1c ( % ) of 10.2 ( 95 % CI : 9.8 to 10.7 ) . The difference was statistically ( P having HbA1c outcomes on average -1.8 ( 95 % CI : -2.4 to -1.2 ) percentage points lower than conventional group participants . Results were robust to adjustment for a range of covariates and multiple imputation of missing outcome data . Conclusions This study demonstrates the effectiveness of a structured , guideline -based DSME intervention in a LMIC setting versus a pragmatic comparator . The intervention is potentially replicable at other levels of the Nigerian healthcare system and in other LMICs , where nurses/diabetes educators can run the programme . Trial Registration Pan African Clinical Trial Registry",
"Background . Patients with prediabetes are at high risk for diabetes and cardiovascular disease ( CVD ) . No study has explored whether intervention could revert prediabetes to normal glycemic status as the primary outcome . Beijing Prediabetes Reversion Program ( BPRP ) would evaluate whether intensive lifestyle modification and /or pioglitazone could revert prediabetic state to normoglycemia and improve the risk factors of CVD as well . Methods . BPRP is a r and omized , multicenter , 2 × 2 factorial design study . Participants diagnosed as prediabetes were r and omized into four groups ( conventional/intensive lifestyle intervention and 30 mg pioglitazone/placebo ) with a three-year follow-up . The primary endpoint was conversion into normal glucose tolerance . The trial would recruit 2000 participants ( 500 in each arm ) . Results . Between March 2007 and March 2011 , 1945 participants were r and omized . At baseline , the individuals were 53 ± 10 years old , with median BMI 26.0 ( 23.9 , 28.2 ) kg/m2 and HbA1c 5.8 ( 5.6 , 6.1)% . 85 % of the participants had IGT and 15 % had IFG . Parameters relevant to glucose , lipids , blood pressure , lifestyle , and other metabolic markers were similar between conventional and intensive lifestyle intervention group at baseline . Conclusion . BPRP was the first study to determine if lifestyle modification and /or pioglitazone could revert prediabetic state to normoglycemia in Chinese population . Major baseline parameters were balanced between two lifestyle intervention groups . This trial is registered with www.chictr.org.cn : ChiCTR-PRC-06000005",
"BACKGROUND Type 2 diabetes can often be prevented by lifestyle modification ; however , successful lifestyle intervention programmes are labour intensive . Mobile phone messaging is an inexpensive alternative way to deliver educational and motivational advice about lifestyle modification . We aim ed to assess whether mobile phone messaging that encouraged lifestyle change could reduce incident type 2 diabetes in Indian Asian men with impaired glucose tolerance . METHODS We did a prospect i ve , parallel-group , r and omised controlled trial between Aug 10 , 2009 , and Nov 30 , 2012 , at ten sites in southeast India . Working Indian men ( aged 35 - 55 years ) with impaired glucose tolerance were r and omly assigned ( 1:1 ) with a computer-generated r and omisation sequence to a mobile phone messaging intervention or st and ard care ( control group ) . Participants in the intervention group received frequent mobile phone messages compared with controls who received st and ard lifestyle modification advice at baseline only . Field staff and participants were , by necessity , not masked to study group assignment , but allocation was concealed from laboratory personnel as well as principal and co-investigators . The primary outcome was incidence of type 2 diabetes , analysed by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00819455 . RESULTS We assessed 8741 participants for eligibility . 537 patients were r and omly assigned to either the mobile phone messaging intervention ( n=271 ) or st and ard care ( n=266 ) . The cumulative incidence of type 2 diabetes was lower in those who received mobile phone messages than in controls : 50 ( 18 % ) participants in the intervention group developed type 2 diabetes compared with 73 ( 27 % ) in the control group ( hazard ratio 0·64 , 95 % CI 0·45 - 0·92 ; p=0·015 ) . The number needed to treat to prevent one case of type 2 diabetes was 11 ( 95 % CI 6 - 55 ) . One patient in the control group died suddenly at the end of the first year . We recorded no other serious adverse events . INTERPRETATION Mobile phone messaging is an effective and acceptable method to deliver advice and support towards lifestyle modification to prevent type 2 diabetes in men at high risk . FUNDING The UK India Education and Research Initiative , the World Diabetes Foundation",
"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",
"Aims /hypothesisLifestyle modification helps in the primary prevention of diabetes in multiethnic American , Finnish and Chinese population s. In a prospect i ve community-based study , we tested whether the progression to diabetes could be influenced by interventions in native Asian Indians with IGT who were younger , leaner and more insulin resistant than the above population s. Methods We r and omised 531 ( 421 men 110 women ) subjects with IGT ( mean age 45.9±5.7 years , BMI 25.8±3.5 kg/m2 ) into four groups . Group 1 was the control , Group 2 was given advice on lifestyle modification ( LSM ) , Group 3 was treated with metformin ( MET ) and Group 4 was given LSM plus MET . The primary outcome measure was type 2 diabetes as diagnosed using World Health Organization criteria . Results The median follow-up period was 30 months , and the 3-year cumulative incidences of diabetes were 55.0 % , 39.3 % , 40.5 % and 39.5 % in Groups 1–4 , respectively . The relative risk reduction was 28.5 % with LSM ( 95 % CI 20.5–37.3 , p=0.018 ) , 26.4 % with MET ( 95 % CI 19.1–35.1 , p=0.029 ) and 28.2 % with LSM + MET ( 95 % CI 20.3–37.0 , p=0.022 ) , as compared with the control group . The number needed to treat to prevent one incident case of diabetes was 6.4 for LSM , 6.9 for MET and 6.5 for LSM + MET . Conclusions /interpretationProgression of IGT to diabetes is high in native Asian Indians . Both LSM and MET significantly reduced the incidence of diabetes in Asian Indians with IGT ; there was no added benefit from combining them",
"OBJECTIVE To investigate if a six-year intensive lifestyle intervention in people with pre-diabetes lead to reduction of cardiovascular events and cardiovascular disease ( CVD ) mortality in subsequent 23 years . METHODS Five hundreds and nineteen subjects with normal glucose tolerance ( NGT ) and 577 subjects with impaired glucose tolerance ( IGT ) in Da Qing city were recruited in the study in 1986 . The IGT subjects r and omly assigned to either the no-intervention group or one of three lifestyle intervention groups ( diet , exercise , or diet plus exercise ) to receive a 6-year lifestyle intervention . In 2009 , the participants were followed up to assess the primary outcomes of cardiovascular events and CVD mortality by a question naire and medical records . RESULTS Subjects in IGT no-intervention group had the highest incidences of cardiovascular events ( 44.44 % ) and CVD mortality ( 20.00 % ) , while those in NGT group had the lowest incidences of cardiovascular events ( 29.59 % ) and CVD mortality ( 7.52 % ) after 23-year follow-up . The incidences of cardiovascular events and CVD mortality in IGT intervention subjects were 37.84 % and 12.53 % , respectively . The multivariable analyses showed that , after controlling of age , gender , BMI smoking , blood pressure and cardiovascular event at baseline , the CVD mortality and incidence of cardiovascular events in IGT no-intervention group was 1.89 ( HR = 1.89 , 95%CI 1.11 - 3.22 , P = 0.02 ) and 1.38 ( HR = 1.38 , 95%CI 1.01 - 1.90 , P = 0.04 ) times of those in NGT group . However , the CVD mortality and incidence of cardiovascular events were not different in the IGT intervention group compared with those in the NGT group ( HR = 1.39 , 95%CI 0.89 - 2.18 , P = 0.15 and HR = 1.25 , 95%CI 0.98 - 1.59 , P = 0.07 , respectively ) . CONCLUSIONS Subjects with IGT were at high risk for cardiovascular events and mortality . A six-year lifestyle intervention in this population can reduce both the incidence of cardiovascular event and CVD mortality",
"OBJECTIVE The purpose of this study was to describe the process of implementing a diabetes prevention program provided by homecare nurses to residents of public housing communities . DESIGN AND SAMPLE A cluster r and omization pilot study was conducted comparing enhanced st and ard care ( 2 interactive classes on diabetes prevention ) to a diabetes prevention program ( 7 interactive classes and behavioral support ) . The sample ( n = 67 ) was primarily female ( 79 % ) , nonwhite ( 76 % ) , unpartnered ( 83 % ) , with a mean age of 40 years , and an average of 3 children . Mixed methods were used to evaluate the implementation process . MEASURES Data were collected on attendance , attrition , and protocol implementation . Interviews were conducted with nurses and community health workers who assisted with program implementation . RESULTS Homecare nurses were able to implement a diabetes prevention program in public housing communities , with a protocol implementation of 83 % across classes and groups . Attendance was suboptimal with 60 % for the enhanced st and ard care group and 54 % for the diabetes prevention group . Nurses and community health workers were re source ful and positive about program implementation . CONCLUSION Linking existing re sources , such as a homecare agency with a public housing community , is one approach to disseminate diabetes prevention programs",
"BACKGROUND Lifestyle interventions can prevent the deterioration of impaired glucose tolerance to manifest type 2 diabetes , at least as long as the intervention continues . In the extended follow-up of the Finnish Diabetes Prevention Study , we assessed the extent to which the originally-achieved lifestyle changes and risk reduction remain after discontinuation of active counselling . METHODS Overweight , middle-aged men ( n=172 ) and women ( n=350 ) with impaired glucose tolerance were r and omly assigned to intensive lifestyle intervention or control group . After a median of 4 years of active intervention period , participants who were still free of diabetes were further followed up for a median of 3 years , with median total follow-up of 7 years . Diabetes incidence , bodyweight , physical activity , and dietary intakes of fat , saturated fat , and fibre were measured . FINDINGS During the total follow-up , the incidence of type 2 diabetes was 4.3 and 7.4 per 100 person-years in the intervention and control group , respectively ( log-rank test p=0.0001 ) , indicating 43 % reduction in relative risk . The risk reduction was related to the success in achieving the intervention goals of weight loss , reduced intake of total and saturated fat and increased intake of dietary fibre , and increased physical activity . Beneficial lifestyle changes achieved by participants in the intervention group were maintained after the discontinuation of the intervention , and the corresponding incidence rates during the post-intervention follow-up were 4.6 and 7.2 ( p=0.0401 ) , indicating 36 % reduction in relative risk . INTERPRETATION Lifestyle intervention in people at high risk for type 2 diabetes result ed in sustained lifestyle changes and a reduction in diabetes incidence , which remained after the individual lifestyle counselling was stopped",
"The aim of this study was to evaluate the effects of a nutrition education program ( NEP ) on anthropometric , dietetic , and metabolic parameters in high-risk subjects for type 2 diabetes mellitus . Fifty-one participants , both sexes , were r and omly assigned to either the control ( 58.8 % ) or the intervention ( NEP ) group . The intervention group received frequent individual and group nutritional counseling from a team of nutritionists . Participants were assessed at baseline ( M0 ) and after 12 months ( M1 ) for anthropometric , dietetic , and metabolic parameters . The hypothesis was that high-risk subjects for type 2 diabetes mellitus participating in NEP would show an improvement in these parameters . At M1 , the intervention group showed a significant decline in body weight ( -3.4 % ) , body mass index ( -5.7 % ) , cholesterol intake ( -49.5 % ) , fasting glycemia ( -14.0 % ) , fasting insulin ( -9.0 % ) , postpr and ial glycemia ( -21.0 % ) , postpr and ial insulin ( -71.0 % ) , total serum cholesterol ( -23.0 % ) , and glycated hemoglobin ( -24.0 % ) . A decrease in energy intake ( 5 % , P = .06 ) and low-density lipoprotein cholesterol ( 25 % , P = .07 ) was observed in the interventional group , although it did not reach statistical significance . In contrast , the control group presented a significantly higher energy intake ( 19 % , P = .04 ) and a nonsignificant increase in consumption of all macronutrients . The long-term NEP was found to improve anthropometric , dietary , and metabolic parameters in high-risk subjects for type 2 diabetes mellitus ",
"OBJECTIVE Individuals with impaired glucose tolerance ( IGT ) have a high risk of developing NIDDM . The purpose of this study was to determine whether diet and exercise interventions in those with IGT may delay the development of NIDDM , i.e. , reduce the incidence of NIDDM , and thereby reduce the overall incidence of diabetic complications , such as cardiovascular , renal , and retinal disease , and the excess mortality attributable to these complications . RESEARCH DESIGN AND METHODS In 1986 , 110,660 men and women from 33 health care clinics in the city of Da Qing , China , were screened for IGT and NIDDM . Of these individuals , 577 were classified ( using World Health Organization criteria ) as having IGT . Subjects were r and omized by clinic into a clinical trial , either to a control group or to one of three active treatment groups : diet only , exercise only , or diet plus exercise . Follow-up evaluation examinations were conducted at 2-year intervals over a 6-year period to identify subjects who developed NIDDM . Cox 's proportional hazard analysis was used to determine if the incidence of NIDDM varied by treatment assignment . RESULTS The cumulative incidence of diabetes at 6 years was 67.7 % ( 95 % CI , 59.8–75.2 ) in the control group compared with 43.8 % ( 95 % CI , 35.5–52.3 ) in the diet group , 41.1 % ( 95 % CI , 33.4–49.4 ) in the exercise group , and 46.0 % ( 95 % CI , 37.3–54.7 ) in the diet-plus-exercise group ( P relative decrease in rate of development of diabetes in the active treatment groups was similar when subjects were stratified as lean or overweight ( BMI baseline BMI and fasting glucose , the diet , exercise , and diet-plus-exercise interventions were associated with 31 % ( P risk of developing diabetes , respectively . CONCLUSIONS Diet and /or exercise interventions led to a significant decrease in the incidence of diabetes over a 6-year period among those with IGT",
"The purpose of this study was to create and test a prevention model for diabetes mellitus in a primary care unit in Thail and . This study used a three-stage approach : a situational analysis was conducted by a focus group discussion , a model was developed in a brainstorming session with stakeholders , and the model was tested by community participation . Qualitative and quantitative methods were used to collect and analyze the data . The focus group discussion found that co-operation between health volunteers and primary care unit personnel in relation to diabetes screening , as well as defining the role of nurse practitioners who provide diabetic treatment , was important . The proactive model that was used for preventing diabetes mellitus was a health promotion program . It was trialed with 160 persons with prediabetes for 3 months . After the intervention , the mean score for exercise activity among the persons with prediabetes was significantly higher , while the mean score of the Body Mass Index , waist circumference , and systolic blood pressure were significantly lower than before the intervention . This meant that community participation provided proactive services to Thai persons with prediabetes",
"OBJECTIVES We tested the efficacy of a 6-session , evidence -based health promotion intervention aim ed at reducing noncommunicable disease ( NCD ) risk behaviors . METHODS Two hundred male and female factory workers in Ulaanbaatar , Mongolia were r and omly assigned to groups receiving either the health promotion intervention or a time-matched financial literacy control intervention . RESULTS The health promotion intervention increased daily fruit and vegetable intake and physical activity , increased readiness for NCD risk behavior reduction and health promotion knowledge , and reduced the number of daily alcoholic drinks and diabetes symptoms 3 months after the intervention . CONCLUSIONS The findings support the efficacy of the intervention to reduce risk behaviors associated with NCDs . Dissemination of the intervention may improve productivity , reduce costs of health services , and better the quality of life for Mongolians",
"Background : Practicing a health-promoting lifestyle is believed to be effective for delaying or preventing the onset of diabetes . However , although empowerment interventions have proven effective for encouraging the adoption of a health-promoting lifestyle in people with diabetes , these interventions are rarely promoted to people with prediabetes . Purpose : The aims of this study were to develop an empowerment program for people with prediabetes and to examine its efficacy in terms of the adoption of a health-promoting lifestyle and improvements in blood sugar , body mass index , and self-efficacy . Methods : A r and omized controlled trial was conducted between May and December 2013 . A convenience sample of people with a fasting blood sugar level of 100–125 mg/dl during the previous 3 months was recruited from the health examination center of a hospital in Kaohsiung , Taiwan . Participants were assigned to either the experimental group or the control group using block r and omization with a block size of 8 . The experimental group ( n = 38 ) participated in a 4-month empowerment program ( the ABC empowerment program ) , which encouraged participants to practice a health-promoting lifestyle in three phases : awareness raising , behavior building , and results checking . The control group ( n = 40 ) received routine clinical care . Statistical analyses included descriptive statistics , independent t test , paired t test , and generalized estimated equations . Results : After controlling for the differences at baseline and considering the interaction between group and time from baseline to 1 week and 3 months after completing the intervention , the generalized estimating equation showed significantly larger improvements in a health-promoting lifestyle , blood sugar , and self-efficacy in the experimental group than in the control group ( p reduction in body mass index than the control group at 3 months after completing the intervention ( p = .001 ) . Conclusions / Implication s for Practice : The empowerment program was shown to have short-term , positive effects on behavioral , physical , and psychosocial outcomes in a Taiwan population with prediabetes . The results of this study provide a useful reference not only for healthcare personnel when implementing empowerment interventions in people with prediabetes but also for nursing educators and healthcare policymakers",
"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",
"AIMS The Diabetes Community Lifestyle Improvement Program ( D-CLIP ) aims to implement and evaluate in a controlled , r and omized trial the effectiveness , cost-effectiveness , and sustainability of a culturally appropriate , low-cost , and sustainable lifestyle intervention for the prevention of type 2 diabetes mellitus in India . METHODS D-CLIP , a translational research project adapted from the methods and curriculum developed and tested for efficacy in the Diabetes Prevention Program , utilizes innovated methods ( a step-wise model of diabetes prevention with lifestyle and metformin added when needed ; inclusion of individuals with isolated glucose tolerance , impaired fasting glucose , and both ; classes team-taught by professionals and trained community educators ) with the goals of increasing diabetes prevention , community acceptability , and long-term dissemination and sustainability of the program . The study outcomes are : diabetes incidence ( primary measure of effectiveness ) , cost-effectiveness , changes in anthropometric measures , plasma lipids , blood pressure , blood glucose , and HbA(1c , ) Program acceptability and sustainability will be assessed using a mixed methods approach . CONCLUSION D-CLIP , a low-cost , community-based , research program , addresses the key components of translational research and can be used as a model for prevention of chronic diseases in other low and middle-income country setting ",
"BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin",
"The purpose of this study was to investigate the effect of a dietary modification intervention programme by applying the Stages of Change Model in 2 h postpr and ial capillary glucose reduction among Thai population . A r and omized control trial was conducted for people at risk of type 2 diabetes for a period of 8 weeks . The intervention programme consisted of evaluating an individual 's stage of change after being provided dietary information regarding kind of food and portions , discussion with a role model , and keeping a food diary record . By the end of the intervention programme , most participants in the experimental group were in the action stage ( n = 36 ) , whereas those in the control group were in the preparation stage ( n = 32 ) . Body mass index , blood pressure , food consumption behaviour and the 2 h postpr and ial blood glucose ( PPG ) in the experimental group had improved ( P dietary modification programme among people at risk of type 2 diabetes",
"Latinas with type 2 diabetes are in need of culturally sensitive interventions to make recommended long-term lifestyle changes and reduce heart disease risk . To test the longer-term ( 24-month ) effects of a previously successful , culturally adapted , multiple-health-behavior-change program , ¡ Viva Bien ! , 280 Latinas were r and omly assigned to usual care or ¡ Viva Bien!. Treatment included group meetings to promote a culturally adapted Mediterranean diet , physical activity , supportive re sources , problem solving , stress-management practice s , and smoking cessation . ¡ Viva Bien ! participants achieved and maintained some lifestyle improvements from baseline through 24 months , including significant improvements for psychosocial outcomes , fat intake , social – environmental support , body mass index , and hemoglobin A1c . Effects tended to diminish over time . The ¡ Viva Bien ! multiple-behavior program was effective in improving and maintaining some psychosocial , behavioral , and biological outcomes related to heart health across 24 months for Latinas with type 2 diabetes , a high-risk , underserved population ( Clinical Trials.gov number , NCT00233259 )",
"BACKGROUND Lifestyle interventions among people with impaired glucose tolerance reduce the incidence of diabetes , but their effect on all-cause and cardiovascular disease mortality is unclear . We assessed the long-term effect of lifestyle intervention on long-term outcomes among adults with impaired glucose tolerance who participated in the Da Qing Diabetes Prevention Study . METHODS The study was a cluster r and omised trial in which 33 clinics in Da Qing , China-serving 577 adults with impaired glucose tolerance-were r and omised ( 1:1:1:1 ) to a control group or lifestyle intervention groups ( diet or exercise or both ) . Patients were enrolled in 1986 and the intervention phase lasted for 6 years . In 2009 , we followed up participants to assess the primary outcomes of cardiovascular mortality , all-cause mortality , and incidence of diabetes in the intention-to-treat population . FINDINGS Of the 577 patients , 439 were assigned to the intervention group and 138 were assigned to the control group ( one refused baseline examination ) . 542 ( 94 % ) of 576 participants had complete data for mortality and 568 ( 99 % ) contributed data to the analysis . 174 participants died during the 23 years of follow-up ( 121 in the intervention group vs 53 in the control group ) . Cumulative incidence of cardiovascular disease mortality was 11.9 % ( 95 % CI 8.8 - 15.0 ) in the intervention group versus 19.6 % ( 12.9 - 26.3 ) in the control group ( hazard ratio [ HR ] 0.59 , 95 % CI 0.36 - 0.96 ; p=0.033 ) . All-cause mortality was 28.1 % ( 95 % CI 23.9 - 32.4 ) versus 38.4 % ( 30.3 - 46.5 ; HR 0.71 , 95 % CI 0.51 - 0.99 ; p=0.049 ) . Incidence of diabetes was 72.6 % ( 68.4 - 76.8 ) versus 89.9 % ( 84.9 - 94.9 ; HR 0.55 , 95 % CI 0.40 - 0.76 ; p=0.001 ) . INTERPRETATION A 6-year lifestyle intervention programme for Chinese people with impaired glucose tolerance can reduce incidence of cardiovascular and all-cause mortality and diabetes . These findings emphasise the long-term clinical benefits of lifestyle intervention for patients with impaired glucose tolerance and provide further justification for adoption of lifestyle interventions as public health measures to control the consequences of diabetes . FUNDING Centers for Disease Control and Prevention , WHO , the China-Japan Friendship Hospital , Da Qing First Hospital ",
"The study aim ed to assess whether aerobic exercise ( AEx ) training and a fibre-enriched diet can reduce hepatic fat content ( HFC ) and increase glycaemic control in pre-diabetic patients with non-alcoholic fatty liver disease ( NAFLD ) . Six-hundred- and -three patients from seven clinics in Yangpu district , Shanghai , China were recruited . Of them 115 individuals aged 50–65-year fulfilled the inclusion criteria ( NAFLD with impaired fasting glucose or impaired glucose tolerance ) and were r and omly assigned into exercise ( AEx n = 29 ) , diet ( Diet n = 28 ) , exercise plus diet ( AED n = 29 ) , or no-intervention ( NI n = 29 ) groups . Progressive supervised AEx training ( 60–75 % VO2max intensity ) was given 2 - 3 times/week in 30–60 min/sessions , and the diet intervention was provided as lunch with 38 % carbohydrate and diet fibre of 12 g/day for 8.6-month . HFC was assessed by 1H MRS . We found that HFC was significantly reduced in the AEx ( −24.4 % ) , diet ( −23.2 % ) , and AED ( −47.9 % ) groups by contrast to the 20.9 % increase in the NI group ( p = 0.001 for all ) after intervention . However , only AED group significantly decreased HbA1c ( −4.4 % , p = 0.01 ) compared with the NI group ( −0.6 % ) . Aerobic exercise training combined with fibre-enriched diet can reduce HFC more effectively than either exercise or increased fibre-intake alone in pre-diabetic patients with NAFLD"
] |
4116ce1e-06ff-11f0-808a-c43d1ab1c353
|
PURPOSE To provide recommendations on appropriate use of breast tumor biomarker assay results to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer . METHODS A literature search and prospect ively defined study selection sought systematic review s , meta-analyses , r and omized controlled trials , prospect ive-retrospective studies , and prospect i ve comparative observational studies published from 2006 through 2014 . Outcomes of interest included overall survival and disease-free or recurrence-free survival . Expert panel members used informal consensus to develop evidence -based guideline recommendations . RESULTS The literature search identified 50 relevant studies . One r and omized clinical trial and 18 prospect ive-retrospective studies were found to have evaluated the clinical utility , as defined by the guideline , of specific biomarkers for guiding decisions on the need for adjuvant systemic therapy . No studies that met guideline criteria for clinical utility were found to guide choice of specific treatments or regimens . RECOMMENDATIONS In addition to estrogen and progesterone receptors and human epidermal growth factor receptor 2 , the panel found sufficient evidence of clinical utility for the biomarker assays Oncotype DX , EndoPredict , PAM50 , Breast Cancer Index , and urokinase plasminogen activator and plasminogen activator inhibitor type 1 in specific subgroups of breast cancer . No biomarker except for estrogen receptor , progesterone receptor , and human epidermal growth factor receptor 2 was found to guide choices of specific treatment regimens . Treatment decisions should also consider disease stage , comorbidities , and patient preferences
|
[
"BACKGROUND The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor-positive tumors is poorly defined by clinical and histopathological measures . METHODS We tested whether the results of a reverse-transcriptase-polymerase-chain-reaction ( RT-PCR ) assay of 21 prospect ively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative , tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14 . The levels of expression of 16 cancer-related genes and 5 reference genes were used in a prospect ively defined algorithm to calculate a recurrence score and to determine a risk group ( low , intermediate , or high ) for each patient . RESULTS Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks . The proportions of patients categorized as having a low , intermediate , or high risk by the RT-PCR assay were 51 , 22 , and 27 percent , respectively . The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk , intermediate-risk , and high-risk groups were 6.8 percent ( 95 percent confidence interval , 4.0 to 9.6 ) , 14.3 percent ( 95 percent confidence interval , 8.3 to 20.3 ) , and 30.5 percent ( 95 percent confidence interval , 23.6 to 37.4 ) . The rate in the low-risk group was significantly lower than that in the high-risk group ( P overall survival ( P distant recurrence in individual patients . CONCLUSIONS The recurrence score has been vali date d as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative , estrogen-receptor-positive breast cancer",
"BACKGROUND PAM50 is a 50-gene test that is design ed to identify intrinsic breast cancer subtypes and generate a Risk of Recurrence ( ROR ) score . It has been developed to be carried out in qualified routine hospital pathology laboratories . PATIENTS AND METHODS One thous and four hundred seventy-eight postmenopausal women with estrogen receptor (ER)+ early breast cancer ( EBC ) treated with tamoxifen or tamoxifen followed by anastrozole from the prospect i ve r and omized ABCSG-8 trial were entered into this study . Patients did not receive adjuvant chemotherapy . RNA was extracted from paraffin blocks and analyzed using the PAM50 test . Both intrinsic subtype ( luminal A/B , HER2-enriched , basal-like ) and ROR score were calculated . The primary analysis was design ed to test whether the continuous ROR score adds prognostic value in predicting distant recurrence ( DR ) over and above st and ard clinical variables . RESULTS In all tested subgroups , ROR score significantly adds prognostic information to the clinical predictor ( P ROR at 10 years compared with Luminal B ( P low- and high-risk groups occurred also within all tested subgroups . CONCLUSION ( S ) The results of the primary analysis , in combination with recently published results from the ATAC trial , constitute Level 1 evidence for clinical validity of the PAM50 test for predicting the risk of DR in postmenopausal women with ER+ EBC . A 10-year metastasis risk of < 3.5 % in the ROR low category makes it unlikely that additional chemotherapy would improve this outcome -this finding could help to avoid unwarranted overtreatment . CLINICAL TRIAL NUMBER ABCSG 8 : NCT00291759",
"HER2 amplification , TOP2A aberrations , and absence of tissue inhibitor of metalloproteinase ( TIMP-1 ) expression in breast carcinomas have been shown to be associated with incremental benefit from anthracycline-containing adjuvant chemotherapy , and this study was undertaken to vali date these findings in a similar , but independent , r and omized clinical trial . TIMP-1 was examined by immunohistochemistry in archival tumor tissue from 403 of 716 premenopausal high-risk patients with known HER2 and TOP2A status who were r and omized to cyclophosphamide , epirubicin , and fluorouracil ( CEF ) or cyclophosphamide , methotrexate , and fluorouracil ( CMF ) in the MA.5 trial . Ninety-eight ( 24 % ) patients had no TIMP-1 staining of tumor cells , 27 % were HER2 amplified , and 18 % were TOP2A aberrant . Forty-four percentage was classified as HT responsive ( HER2 amplified and /or TIMP-1 negative ) and 37 % as 2 T responsive ( TOP2A aberrant and /or TIMP-1 negative ) . There was no heterogeneity in treatment effect of CEF versus CMF according to TIMP-1 . In HT-responsive patients , CEF was superior to CMF with an improved RFS ( adjusted HR , 0.64 ; 95 % CI , 0.42–0.97 ) , but this was not significant for OS ( adjusted HR , 0.66 ; 95 % CI , 0.42–1.04 ) . A significant HT profile versus treatment interaction was detected for OS ( P = 0.03 ) . In 2T-responsive patients , CEF seemed to improve RFS compared to CMF ( adjusted HR , 0.67 ; 95 % CI , 0.43–1.03 ) and improved OS ( adjusted HR , 0.58 ; 95 % CI , 0.36–0.93 ) . A significant 2 T profile versus treatment interaction was detected for OS ( P = 0.01 ) . With this study , we vali date a more substantial reduction in mortality by CEF compared to CMF in patients with an HT- or 2T-responsive profile ; however , we could not show a similarly significant reduction in RFS events , where a benefit of CEF over CMF was found irrespective of TIMP-1 status . Further studies are necessary before the HT and 2 T profiles may be used to direct the use of anthracyclines ",
"PURPOSE We assessed Tau protein expression in primary breast cancer specimens of patients included in the National Surgical Breast and Bowel Project ( NSABP ) -B 28 clinical trial . Expression levels were correlated with disease-free survival ( DFS ) and overall survival ( OS ) . Interaction between this marker and paclitaxel efficacy was also examined . METHODS Tissue microarrays were available for 1,942 patients ( 63 % of all trial participants ) who were r and omly assigned to receive either four courses of doxorubicin and cyclophosphamide ( AC ) or AC followed by four courses of adjuvant paclitaxel chemotherapy . All patients who were hormone receptor positive received adjuvant endocrine therapy . Immunohistochemistry was used to measure Tau expression at M. D. And erson Cancer Center blinded to clinical outcome . Correlation between Tau and OS and DFS was performed by the NSABP Biostatistical Center . RESULTS Forty-three percent of patients were Tau positive . Tau positivity correlated with estrogen receptor ( ER ) -positive status ( P Tau- and ER-positive status were both associated with better DFS and OS ( P worse DFS and OS ( P Tau expression and benefit from paclitaxel in the total population or among ER-positive or -negative patients . CONCLUSION High Tau protein expression is associated with better prognosis in patients treated with adjuvant anthracycline and paclitaxel chemotherapy and endocrine therapy , but there was no significant interaction between Tau expression and paclitaxel benefit",
"Overexpression of topoisomerase II protein ( topo 2α ) is postulated to be more closely associated with responsiveness to anthracycline-containing chemotherapy than human epidermal growth factor receptor type 2 ( HER2 ) gene amplification or alterations in the topoisomerase II alpha gene ( TOP2A ) . The authors used tissue microarrays from 477 of 710 premenopausal women with node-positive breast cancer r and omized to CEF or CMF adjuvant chemotherapy in the NCIC Clinical Trials Group Mammary 5 ( MA.5 ) trial . No significant interaction was found between treatment and continuous topo 2α level in either relapse-free ( RFS ) or overall survival ( OS ) . In 136 patients ( 28.5 % ) whose tumors showed topo 2α overexpression by immunohistochemistry based on a cut-off of 13 % , CEF was superior to CMF for RFS ( adjusted HR 0.45 ; 95 % CI 0.25–0.82 ; P = 0.009 ) and OS ( adjusted HR 0.50 ; 95 % CI 0.26–0.96 ; P = 0.04 ) . When tumors lacked topo 2α overexpression , CEF was not superior for RFS ( adjusted HR 0.88 ; 95 % CI 0.64–1.22 ; P = 0.46 ) or OS ( adjusted HR 0.95 ; 95 % CI 0.66–1.38 ; P = 0.80 ) . Interaction between topo 2α and treatment was borderline significant for RFS ( P = 0.04 ) and OS ( P = 0.05 ) and not substantially more significant than between TOP2A gene alteration ( Pinteraction = 0.09 for RFS and 0.02 for OS ) or HER2 overexpression ( Pinteraction = 0.002 for RFS and 0.009 for OS ) . Topo 2α protein overexpression based on the cut-off identified in this study , TOP2A gene alterations and HER2 protein overexpression were each associated with responsiveness to anthracycline-containing chemotherapy . The topo 2α protein analysis was exploratory and will require further validation",
"Introduction EndoPredict ( EP ) is an RNA-based multigene test that predicts the likelihood of distant recurrence in patients with estrogen receptor-positive ( ER+ ) , human epidermal growth factor receptor 2–negative ( HER2− ) breast cancer ( BC ) who are being treated with adjuvant endocrine therapy . Herein we report the prospect ive-retrospective clinical validation of EP in the node-positive , chemotherapy-treated , ER+/HER2− BC patients in the GEICAM 9906 trial . Methods The patients ( N = 1,246 ) were treated either with six cycles of fluorouracil , epirubicin and cyclophosphamide ( FEC ) or with four cycles of FEC followed by eight weekly courses of paclitaxel ( FEC-P ) , as well as with endocrine therapy if they had hormone receptor – positive disease . The patients were assigned to EP risk categories ( low or high ) according to prespecified cutoff levels . The primary endpoint in the clinical validation of EP was distant metastasis-free survival ( MFS ) . Metastasis rates were estimated using the Kaplan-Meier method , and multivariate analysis was performed using Cox regression . Results The molecular EP score and the combined molecular and clinical EPclin score were successfully determined in 555 ER+/HER2− tumors from the 800 available sample s in the GEICAM 9906 trial . On the basis of the EP , 25 % of patients ( n = 141 ) were classified as low risk . MFS was 93 % in the low-risk group and 70 % in the high-risk group ( absolute risk reduction = 23 % , hazard ratio ( HR ) = 4.8 , 95 % confidence interval ( CI ) = 2.5 to 9.5 ; P , EP results are an independent prognostic parameter after adjustment for age , grade , lymph node status , tumor size , treatment arm , ER and progesterone receptor ( PR ) status and proliferation index ( Ki67 ) . Using the predefined EPclin score , 13 % of patients ( n = 74 ) were assigned to the low-risk group , who had excellent outcomes and no distant recurrence events ( absolute risk reduction vs high-risk group = 28 % ; P EP was prognostic in premenopausal patients ( HR = 6.7 , 95 % CI = 2.4 to 18.3 ; P = 0.0002 ) and postmenopausal patients ( HR = 3.3 , 95 % CI = 1.3 to 8.5 ; P = 0.0109 ) . There were no statistically significant differences in MFS between treatment arms ( FEC vs FEC-P ) in either the high- or low-risk groups . The interaction test results between the chemotherapy arm and the EP score were not significant . Conclusions EP is an independent prognostic parameter in node-positive , ER+/HER2− BC patients treated with adjuvant chemotherapy followed by hormone therapy . EP did not predict a greater efficacy of FEC-P compared to FEC alone",
"Predictive biomarkers to guide therapy for cancer patients are a cornerstone of precision medicine . Discussed herein are considerations regarding the design and interpretation of such predictive biomarker studies . These considerations are important for both planning and interpreting prospect i ve studies and for using specimens collected from completed r and omized clinical trials . Specific issues addressed are differentiation between qualitative and quantitative predictive effects , challenges due to sample size requirements for predictive biomarker assessment , and consideration of additional factors relevant to clinical utility assessment , such as toxicity and cost of new therapies as well as costs and potential morbidities associated with routine use of biomarker-based tests",
"PURPOSE To develop a guideline to improve the accuracy of immunohistochemical ( IHC ) estrogen receptor ( ER ) and progesterone receptor ( PgR ) testing in breast cancer and the utility of these receptors as predictive markers . METHODS The American Society of Clinical Oncology and the College of American Pathologists convened an international Expert Panel that conducted a systematic review and evaluation of the literature in partnership with Cancer Care Ontario and developed recommendations for optimal IHC ER/PgR testing performance . RESULTS Up to 20 % of current IHC determinations of ER and PgR testing worldwide may be inaccurate ( false negative or false positive ) . Most of the issues with testing have occurred because of variation in preanalytic variables , thresholds for positivity , and interpretation criteria . RECOMMENDATIONS The Panel recommends that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences . A testing algorithm that relies on accurate , reproducible assay performance is proposed . Elements to reliably reduce assay variation are specified . It is recommended that ER and PgR assays be considered positive if there are at least 1 % positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal ( normal epithelial elements ) and external controls . The absence of benefit from endocrine therapy for women with ER-negative invasive breast cancers has been confirmed in large overviews of r and omized clinical trials",
"The development of tumor biomarkers ready for clinical use is complex . We propose a refined system for biomarker study design , conduct , analysis , and evaluation that incorporates a hierarchal level of evidence scale for tumor marker studies , including those using archived specimens . Although fully prospect i ve r and omized clinical trials to evaluate the medical utility of a prognostic or predictive biomarker are the gold st and ard , such trials are costly , so we discuss more efficient indirect \" prospect ive-retrospective \" design s using archived specimens . In particular , we propose new guidelines that stipulate that 1 ) adequate amounts of archived tissue must be available from enough patients from a prospect i ve trial ( which for predictive factors should generally be a r and omized design ) for analyses to have adequate statistical power and for the patients included in the evaluation to be clearly representative of the patients in the trial ; 2 ) the test should be analytically and preanalytically vali date d for use with archived tissue ; 3 ) the plan for biomarker evaluation should be completely specified in writing before the performance of biomarker assays on archived tissue and should be focused on evaluation of a single completely defined classifier ; and 4 ) the results from archived specimens should be vali date d using specimens from one or more similar , but separate , studies",
"Purpose : To test the association between risk stratification and outcome in a prospect ively design ed , blinded retrospective study using tissue arrays of available paraffin blocks from the estrogen receptor – expressing , node-negative sample s from the National Surgical Adjuvant Breast and Bowel Project B14 and B20 tamoxifen and chemotherapy trials . Experimental Design : Tissue arrays were stained by immunohistochemistry targeting p53 , NDRG1 , SLC7A5 , CEACAM5 , and HTF9C . Risk stratification was done using predefined scoring rules , algorithm for combining scores , and cutoff points for low-risk , moderate-risk , and high-risk patient strata . Results : In a univariate Cox model , this test was significantly associated with recurrence-free interval [ HR , 1.3 ( 95 % confidence interval , 1.1 - 1.6 ) ; P = 0.006 ] . In a multivariate model it contributed information independent of age , tumor size , and menopausal status ( P = 0.007 ) . The Kaplan-Meier estimates of the proportion of recurrence-free after 10 years were 73 % , 86 % , and 85 % for the high-risk , moderate-risk , and low-risk groups ( P = 0.001 ) . The Kaplan-Meier estimates of the breast-cancer-specific-death rate were 23 % , 10 % , and 9 % ( P patients ≥60 years old showed Kaplan-Meier estimates of the proportion of recurrence-free of 78 % , 89 % , and 92 % . Both high-risk and low-risk groups showed significant improvement on treatment with cytotoxic chemotherapy . Conclusions : Immunohistochemistry using five monoclonal antibodies assigns breast cancer patients to a risk index that was significantly associated with clinical outcome among the estrogen receptor – expressing , node-negative tamoxifen-treated patients . It seems that the test may be able to identify patients who have greater absolute benefit from adjuvant chemotherapy compared with unstratified patient population s. Exploratory analysis suggests that this test will be most useful in clinical decision making for postmenopausal patients",
"BACKGROUND Adjuvant tamoxifen therapy is effective for postmenopausal women with endocrine-responsive breast cancer . Cytochrome P450 2D6 ( CYP2D6 ) enzyme metabolizes tamoxifen to clinical ly active metabolites , and CYP2D6 polymorphisms may adversely affect tamoxifen efficacy . In this study , we investigated the clinical relevance of CYP2D6 polymorphisms . METHODS We obtained tumor tissues and isolated DNA from 4861 of 8010 postmenopausal women with hormone receptor-positive breast cancer who enrolled in the r and omized , phase III double-blind Breast International Group ( BIG ) 1 - 98 trial between March 1998 and May 2003 and received tamoxifen and /or letrozole treatment . Extracted DNA was used for genotyping nine CYP2D6 single-nucleotide polymorphisms using polymerase chain reaction-based methods . Genotype combinations were used to categorize CYP2D6 metabolism phenotypes as poor , intermediate , and extensive metabolizers ( PM , IM , and EM , respectively ; n = 4393 patients ) . Associations of CYP2D6 metabolism phenotypes with breast cancer-free interval ( referred to as recurrence ) and treatment-induced hot flushes according to r and omized endocrine treatment and previous chemotherapy were assessed . Cox proportional hazards models were used to calculate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) . All statistical tests were two-sided . RESULTS No association between CYP2D6 metabolism phenotypes and breast cancer-free interval was observed among patients who received tamoxifen monotherapy without previous chemotherapy ( P = .35 ) . PM or IM phenotype had a non-statistically significantly reduced risk of breast cancer recurrence compared with EM phenotype ( PM or IM vs EM , HR of recurrence = 0.86 , 95 % CI = 0.60 to 1.24 ) . CYP2D6 metabolism phenotype was associated with tamoxifen-induced hot flushes ( P = .020 ) . Both PM and IM phenotypes had an increased risk of tamoxifen-induced hot flushes compared with EM phenotype ( PM vs EM , HR of hot flushes = 1.24 , 95 % CI = 0.96 to 1.59 ; IM vs EM , HR of hot flushes = 1.23 , 95 % CI = 1.05 to 1.43 ) . CONCLUSIONS CYP2D6 phenotypes of reduced enzyme activity were not associated with worse disease control but were associated with increased hot flushes , contrary to the hypothesis . The results of this study do not support using the presence or absence of hot flushes or the pharmacogenetic testing of CYP2D6 to determine whether to treat postmenopausal breast cancer patients with tamoxifen",
"Purpose : According to current guidelines , molecular tests predicting the outcome of breast cancer patients can be used to assist in making treatment decisions after consideration of conventional markers . We developed and vali date d a gene expression signature predicting the likelihood of distant recurrence in patients with estrogen receptor (ER)–positive , HER2-negative breast cancer treated with adjuvant endocrine therapy . Experimental Design : RNA levels assessed by quantitative reverse transcriptase PCR in formalin-fixed , paraffin-embedded tumor tissue were used to calculate a risk score ( Endopredict , EP ) consisting of eight cancer-related and three reference genes . EP was combined with nodal status and tumor size into a comprehensive risk score , EPclin . Both prespecified risk scores including cutoff values to determine a risk group for each patient ( low and high ) were vali date d independently in patients from two large r and omized phase III trials [ Austrian Breast and Colorectal Cancer Study Group (ABCSG)-6 : n = 378 , ABCSG-8 : n = 1,324 ] . Results : In both validation cohorts , continuous EP was an independent predictor of distant recurrence in multivariate analysis ( ABCSG-6 : P = 0.010 , ABCSG-8 : P quantitative ER , Ki67 , and treatment with EP yielded a prognostic power significantly superior to the clinicopathologic factors alone [ c-indices : 0.764 vs. 0.750 , P = 0.024 ( ABCSG-6 ) and 0.726 vs. 0.701 , P = 0.003 ( ABCSG-8 ) ] . EPclin had c-indices of 0.788 and 0.732 and result ed in 10-year distant recurrence rates of 4 % and 4 % in EPclin low-risk and 28 % and 22 % in EPclin high-risk patients in ABCSG-6 ( P breast cancer patients , independent from clinicopathologic parameters . The EPclin score outperformed all conventional clinicopathologic risk factors . Clin Cancer Res ; 17(18 ) ; 6012–20 . © 2011 AACR",
"BACKGROUND The purpose of this study was to determine the predictive value of breast cancer molecular subclassification regarding the benefit of adjuvant anthracycline-based chemotherapy . PATIENTS AND METHODS Tumor sample s from 823 patients included in two r and omized trials that compared an anthracycline-based chemotherapy with no treatment were used to construct a tissue array . Estrogen receptor ( ER ) , Her2 , epidermal growth factor receptor , cytokeratine 5/6 expressions were determined by immunohistochemistry ( IHC ) . The potential predictive factors of treatment effect on disease-free survival ( DFS ) were assessed by interaction tests and multivariate analysis . RESULTS Sixty-four ( 8 % ) , 98 ( 12 % ) , 109 ( 14 % ) and 527 ( 66 % ) patients presented a Her2+/ER- , basal-like , Her2-/ER-/nonbasal and luminal-like breast cancer . ER expression , when assessed by IHC , was an independent predictive factor for the benefit of chemotherapy on DFS ( test for interaction , P = 0.0015 ) . The molecular subclassification significantly predicted the efficacy of chemotherapy ( test for interaction , P = 0.01 ) , but had no significant added value ( P = 0.32 ) as compared to the ER by treatment interaction . Adjuvant chemotherapy was associated with an adjusted hazard ratio for relapse or death of 0.42 [ 95 % confidence interval ( CI ) : 0.17 - 1.05 ] , 0.54 ( 95 % CI : 0.27 - 1.08 ) , 0.35 ( 95 % CI : 0.18 - 0.68 ) , 1.07 ( 95 % CI : 0.81 - 1.41 ) for patients with Her2+/ER- , basal-like , Her2-/ER-/nonbasal and luminal-like tumors , respectively . CONCLUSION The breast cancer molecular subclassification was predictive for chemotherapy efficacy in adjuvant setting , but did not provide significant additional information to ER",
"Benefit from chemotherapy treatment in breast cancer patients is determined by the molecular make-up of the tumour . In a retrospective analysis , we determined the molecular subtypes of breast cancer originally defined by expression microarrays by immunohistochemistry in tumours of patients who took part in a r and omised study of adjuvant high-dose chemotherapy in breast cancer . In addition , the topoisomerase IIα ( TOP2A ) amplification status was determined by fluorescence in situ hybridisation and chromogenic in situ hybridisation . 411 of the 753 tumours ( 55 % ) were classified as luminal-like , 137 ( 18 % ) as basal-like and 205 ( 27 % ) as human epithelial receptor type 2 ( HER2 ) amplified . The basal-like tumours were defined as having no expression of ER and HER2 ; 98 of them did express epidermal growth factor receptor and /or cytokeratin 5/6 . The luminal-like tumours had a significantly better recurrence free and overall survival than the other two groups . From the 194 HER2-positive tumours , 47 ( 24 % ) were shown to harbour an amplification of TOP2A . Patients with an HER2-amplified tumour r and omised to the high-dose therapy arm did worse than those in the conventional treatment arm , possibly caused by the lower cumulative anthracycline dose in the high-dose arm . The tumours with a TOP2A amplification contributed hardly to this difference , suggesting that TOP2A amplification is not the cause of the steep dose – response curve for anthracyclines in breast cancer . Possibly , the difference of the cumulative dose of only 25 % between the treatment arms was insufficient to yield a survival difference",
"Purpose : p53 as a prognostic and predictive factor in early-stage breast cancer has had mixed results . We studied p53 protein expression , by immunohistochemistry , in a r and omized clinical trial of stage II patients treated with adjuvant doxorubicin and cyclophosphamide with or without paclitaxel [ Cancer and Leukemia Group B ( CALGB ) 9344 , INT0148 ] . Patients and Methods : Epithelial p53 expression was evaluated using two immunohistochemical antibodies ( DO7 and 1801 ) in formalin-fixed , paraffin-embedded tissue from patients with node-positive breast cancer who were r and omized to four cycles of cyclophosphamide and one of three doses of doxorubicin ( 60 , 75 , or 90 mg/m2 ; AC ) and to receive four subsequent cycles of paclitaxel ( T ) or not . Prognostic and predictive value of p53 protein expression was assessed , independent of treatment assignment , for escalating doses of doxorubicin or addition of T with endpoints of relapse-free ( RFS ) and overall survival ( OS ) . Results : Of 3,121 patients , 1,887 patient specimens treated on C9344 were obtained , passed quality control , and evaluated for p53 expression . Expression was 23 % and 27 % for mAbs 1801 and D07 , respectively , with 92 % concordance . In univariate analysis , p53 positivity was associated with worse OS with either antibody , but only p53 staining with monoclonal antibody 1801 had significantly worse RFS . In multivariate analysis , p53 was not predictive of RFS or OS from either doxorubicin dose escalation or addition of paclitaxel regardless of the antibody . Conclusion : Nuclear staining of p53 by immunohistochemistry is associated with worse prognosis in node-positive patients treated with adjuvant doxorubicin-based chemotherapy but is not a useful predictor of benefit from doxorubicin dose escalation or the addition of paclitaxel . Clin Cancer Res ; 17(15 ) ; 5170–8 . © 2011 AACR",
"BACKGROUND We have previously shown the prognostic importance of tumor-infiltrating lymphocytes ( TILs ) in newly diagnosed triple-negative breast cancer ( TNBC ) using tumor sample s from a large clinical trial cohort . In this study , we aim ed to vali date these findings and also investigate associations with trastuzumab benefit in HER2-overexpressing disease ( HER2 + ) . PATIENTS AND METHODS A prospect ive-retrospective study was conducted using sample s from the FinHER adjuvant , phase III trial that enrolled 1010 early-stage BC patients , 778 of whom were HER2-nonamplified . Those with HER2 + disease ( n = 232 ) were r and omized to 9 weeks of trastuzumab or no trastuzumab in addition to chemotherapy . Two pathologists independently quantified stromal TILs in 935 ( 92.6 % ) available slides . The primary end point of distant disease-free survival ( DDFS ) and interactions with trastuzumab were studied in Cox regression models . RESULTS Confirming our previous findings , in TNBC ( n = 134 ) each 10 % increase in TILs was significantly associated with decreased distant recurrence in TNBC ; for DDFS the hazard ratio adjusted for clinicopathological factors : 0.77 ; 95 % confidence interval ( CI ) 0.61 - 0.98 , P = 0.02 . In HER2 + BC ( n = 209 ) , each 10 % increase in lymphocytic infiltration was significantly associated with decreased distant recurrence in patients r and omized to the trastuzumab arm ( DDFS P interaction = 0.025 ) . CONCLUSIONS Higher levels of TILs present at diagnosis were significantly associated with decreased distant recurrence rates in primary TNBC . These results confirm our previous data and further support that TILs should be considered as a robust prognostic factor in this BC subtype . We also report for the first time an association between higher levels of TILs and increased trastuzumab benefit in HER2 + disease . Further research into why some TN and HER2 + BCs can or can not generate a host antitumor immune response and how trastuzumab can favorably alter the immune microenvironment is warranted",
"Background : A dichotomous index combining two gene expression assays , HOXB13 : IL17BR ( H : I ) and molecular grade index ( MGI ) , was developed to assess risk of recurrence in breast cancer patients . The study objective was to demonstrate the prognostic utility of the combined index in early-stage breast cancer . Methods : In a blinded retrospective analysis of 588 ER-positive tamoxifen-treated and untreated breast cancer patients from the r and omised prospect i ve Stockholm trial , H : I and MGI were measured using real-time RT – PCR . Association with patient outcome was evaluated by Kaplan – Meier analysis and Cox proportional hazard regression . A continuous risk index was developed using Cox modelling . Results : The dichotomous H : I+MGI was significantly associated with distant recurrence and breast cancer death . The > 50 % of tamoxifen-treated patients categorised as low-risk had 10-year distant recurrence risk . A continuous risk model ( Breast Cancer Index ( BCI ) ) was developed with the tamoxifen-treated group and the prognostic performance tested in the untreated group was 53 % of patients categorised as low risk with an 8.3 % 10-year distant recurrence risk . Conclusion : Retrospective analysis of this r and omised , prospect i ve trial cohort vali date d the prognostic utility of H : I+MGI and was used to develop and test a continuous risk model that enables prediction of distant recurrence risk at the patient level",
"Clinical biomarker tests that aid in making treatment decisions will play an important role in achieving personalized medicine for cancer patients . Definitive evaluation of the clinical utility of these biomarkers requires conducting large r and omized clinical trials ( RCTs ) . Efficient RCT design is therefore crucial for timely introduction of these medical advances into clinical practice , and a variety of design s have been proposed for this purpose . To guide design and interpretation of RCTs evaluating biomarkers , we present an in-depth comparison of advantages and disadvantages of the commonly used design s. Key aspects of the discussion include efficiency comparisons and special interim monitoring issues that arise because of the complexity of these RCTs . Important ongoing and completed trials are used as examples . We conclude that , in most setting s , r and omized biomarker-stratified design s ( ie , design s that use the biomarker to guide analysis but not treatment assignment ) should be used to obtain a rigorous assessment of biomarker clinical utility",
"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 Predictive markers of response to chemotherapy are lacking in breast cancer patients . Forkhead Box Protein 3 ( FOXP3 ) is an anti-oncogene whose absence in cancer cells could confer resistance to DNA damaging agent . So we made the hypothesis that FOXP3 expression predicts the response to anthracyclines in breast cancer patients and that adjuvant chemotherapy adding taxanes to anthracyclines confers an overall survival ( OS ) benefit over anthracyclines alone , in patients with FOXP3-negative tumors . PATIENTS AND METHODS Expression of FOXP3 in cancer cells was evaluated by immunohistochemistry in tumor sample s from 1097 patients who participated in the PACS01 r and omized trial that evaluated in adjuvant setting the adjunction of docetaxel ( Taxotere ) to anthracyclines in patients with localized breast cancer . Kaplan-Meier analysis and Cox regression model were used to assess OS according to the presence or absence of FOXP3 expression in tumor cells . RESULTS Four hundred and five tumors were found to express FOXP3 ( 37 % ) . FOXP3 expression in breast cancer cells was associated with better OS ( P = 0.003 ) . Uni- and multivariate survival analyses according to treatment arm revealed that FOXP3 expression in breast cancer cells is independently associated with improved OS in patients treated with anthracycline-based adjuvant chemotherapy , but not in patients treated with sequential anthracycline-taxane . Moreover , in vitro experiments showed that FOXP3 induction in breast cancer cell lines using histone deacetylase inhibitor enhances anthracyclines efficacy . CONCLUSION FOXP3 expression in tumor cells may be an accurate predictive biomarker of anthracycline efficacy in breast cancer",
"HER2 gene amplification and topoisomerase IIα gene ( TOP2A ) alteration have been associated with increased benefit from anthracycline compared to non-anthracycline containing adjuvant breast cancer chemotherapy in some but not other studies . Chromosome 17 centromere ( CEP17 ) duplication was measured on TMAs from formalin-fixed paraffin-embedded specimens obtained from 639 of 716 premenopausal women with node positive breast cancer who received cyclophosphamide , epirubicin and fluorouracil ( CEF ) or cyclophosphamide , methotrexate and fluorouracil ( CMF ) in the r and omized controlled mammary 5 ( MA.5 ) adjuvant trial . The prognostic impact of CEP17 duplication and its interactions with treatment were studied for relapse-free survival ( RFS ) and overall survival ( OS ) . Overall , CEP17 duplication was not significantly associated with RFS or OS in multivariate analysis . For patients whose tumours had normal CEP17 copy number there were no apparent benefits for CEF compared to CMF for RFS ( HR 0.98 ; 95 % CI 0.68–1.42 ) or OS ( HR 1.10 ; 95 % CI 0.72–1.69 ) . For patients whose tumours had CEP17 duplication , there was significant benefit for CEF compared to CMF for RFS ( HR 0.54 ; CI 0.33–0.89 ) and a trend towards significance for OS ( HR 0.64 ; CI 0.37–1.09 ) . The adjusted P values for interaction between treatment and CEP17 duplication were 0.09 for RFS and 0.13 for OS . This study suggests that CEP17 duplication has a borderline association with clinical responsiveness to anthracycline containing chemotherapy similar to previous results seen with HER2 amplification and TOP2A alteration in MA.5 . An appropriately powered meta- analysis is required to discriminate the predictive value of these three c and i date markers",
"Purpose : Residual risk of relapse remains a substantial concern for patients with hormone receptor – positive breast cancer , with approximately half of all disease recurrences occurring after five years of adjuvant antiestrogen therapy . Experimental Design : The objective of this study was to examine the prognostic performance of an optimized model of Breast Cancer Index ( BCI ) , an algorithmic gene expression – based signature , for prediction of early ( 0–5 years ) and late ( > 5 years ) risk of distant recurrence in patients with estrogen receptor – positive ( ER+ ) , lymph node – negative ( LN− ) tumors . The BCI model was vali date d by retrospective analyses of tumor sample s from tamoxifen-treated patients from a r and omized prospect i ve trial ( Stockholm TAM , n = 317 ) and a multi-institutional cohort ( n = 358 ) . Results : Within the Stockholm TAM cohort , BCI risk groups stratified the majority ( ∼65 % ) of patients as low risk with less than 3 % distant recurrence rate for 0 to 5 years and 5 to 10 years . In the multi-institutional cohort , which had larger tumors , 55 % of patients were classified as BCI low risk with less than 5 % distant recurrence rate for 0 to 5 years and 5 to 10 years . For both cohorts , continuous BCI was the most significant prognostic factor beyond st and ard clinicopathologic factors for 0 to 5 years and more than five years . Conclusions : The prognostic sustainability of BCI to assess early- and late-distant recurrence risk at diagnosis has clinical use for decisions of chemotherapy at diagnosis and for decisions for extended adjuvant endocrine therapy beyond five years . Clin Cancer Res ; 19(15 ) ; 4196–205 . © 2013 AACR",
"The cell-cycle regulating protein p27(Kip1 ) ( p27 ) has dual roles by acting as both a cdk inhibitor and as an assembly factor for different cdk complexes . Loss of p27 has been linked to malignant features in tumours ; however , the exact role of p27 deregulation in breast cancer regarding prognostic and treatment predictive information has not been fully clarified . We have evaluated p27 expression in 328 primary , Stage II breast cancers from premenopausal patients who had been r and omised to either tamoxifen treatment or no adjuvant treatment after surgery . p27 was associated with the oestrogen receptor and cyclin D1 , and p27 downregulation was associated with high proliferation . There was no association between recurrence-free survival ( RFS ) and p27 ( HR = 0.800 , 95 % CI 0.523 - 1.222 , p = 0.300 ) , indicating that p27 is not a prognostic marker . The predictive value of p27 was analysed by comparing RFS in tamoxifen-treated and untreated patients in subgroups of low and high p27 expression ( HR = 0.747 , 95 % CI 0.335 - 1.664 , p = 0.474 and HR = 0.401 , 95 % CI 0.240 - 0.670 , p p27-high tumours benefited from tamoxifen ( multivariate interaction analysis p = 0.034 ) . Our study suggests that p27 downregulation is associated with tamoxifen resistance in premenopausal breast cancer but is not linked to impaired prognosis",
"Treatment selection markers , sometimes called predictive markers , are factors that help clinicians select therapies that maximize good outcomes and minimize adverse outcomes for patients . Existing statistical methods for evaluating a treatment selection marker include assessing its prognostic value , evaluating treatment effects in patients with a restricted range of marker values , and testing for a statistical interaction between marker value and treatment . These methods are inadequate , because they give misleading measures of performance that do not answer key clinical questions about how the marker might help patients choose treatment , how treatment decisions should be made on the basis of a continuous marker measurement , what effect using the marker to select treatment would have on the population , or what proportion of patients would have treatment changes on the basis of marker measurement . Marker-by-treatment predictiveness curves are proposed as a more useful aid to answering these clinical ly relevant questions , because they illustrate treatment effects as a function of marker value , outcomes when using or not using the marker to select treatment , and the proportion of patients for whom treatment recommendations change after marker measurement . R and omized therapeutic clinical trials , in which entry criteria and treatment regimens are not restricted by the marker , are also proposed as the basis for constructing the curves and evaluating and comparing markers",
"BACKGROUND In breast cancer , immunohistochemical assessment of proliferation using the marker Ki67 has potential use in both research and clinical management . However , lack of consistency across laboratories has limited Ki67 's value . A working group was assembled to devise a strategy to harmonize Ki67 analysis and increase scoring concordance . Toward that goal , we conducted a Ki67 reproducibility study . METHODS Eight laboratories received 100 breast cancer cases arranged into 1-mm core tissue microarrays-one set stained by the participating laboratory and one set stained by the central laboratory , both using antibody MIB-1 . Each laboratory scored Ki67 as percentage of positively stained invasive tumor cells using its own method . Six laboratories repeated scoring of 50 locally stained cases on 3 different days . Sources of variation were analyzed using r and om effects models with log2-transformed measurements . Reproducibility was quantified by intraclass correlation coefficient ( ICC ) , and the approximate two-sided 95 % confidence intervals ( CIs ) for the true intraclass correlation coefficients in these experiments were provided . RESULTS Intralaboratory reproducibility was high ( ICC = 0.94 ; 95 % CI = 0.93 to 0.97 ) . Interlaboratory reproducibility was only moderate ( central staining : ICC = 0.71 , 95 % CI = 0.47 to 0.78 ; local staining : ICC = 0.59 , 95 % CI = 0.37 to 0.68 ) . Geometric mean of Ki67 values for each laboratory across the 100 cases ranged 7.1 % to 23.9 % with central staining and 6.1 % to 30.1 % with local staining . Factors contributing to interlaboratory discordance included tumor region selection , counting method , and subjective assessment of staining positivity . Formal counting methods gave more consistent results than visual estimation . CONCLUSIONS Substantial variability in Ki67 scoring was observed among some of the world 's most experienced laboratories . Ki67 values and cutoffs for clinical decision-making can not be transferred between laboratories without st and ardizing scoring methodology because analytical validity is limited",
"PURPOSE Previous pre clinical and clinical data suggest that the immune system influences prognosis and response to chemotherapy ( CT ) ; however , clinical relevance has yet to be established in breast cancer ( BC ) . We hypothesized that increased lymphocytic infiltration would be associated with good prognosis and benefit from immunogenic CT-in this case , anthracycline-only CT-in selected BC subtypes . PATIENTS AND METHODS We investigated the relationship between quantity and location of lymphocytic infiltrate at diagnosis with clinical outcome in 2009 node-positive BC sample s from the BIG 02 - 98 adjuvant phase III trial comparing anthracycline-only CT ( doxorubicin followed by cyclophosphamide , methotrexate , and fluorouracil [ CMF ] or doxorubicin plus cyclophosphamide followed by CMF ) versus CT combining doxorubicin and docetaxel ( doxorubicin plus docetaxel followed by CMF or doxorubicin followed by docetaxel followed by CMF ) . Readings were independently performed by two pathologists . Disease-free survival ( DFS ) , overall survival ( OS ) , and interaction with type of CT associations were studied . Median follow-up was 8 years . RESULTS There was no significant prognostic association in the global nor estrogen receptor ( ER ) -positive/human epidermal growth factor receptor 2 ( HER2 ) -negative population . However , each 10 % increase in intratumoral and stromal lymphocytic infiltrations was associated with 17 % and 15 % reduced risk of relapse ( adjusted P = .1 and P = .025 ) , respectively , and 27 % and 17 % reduced risk of death in ER-negative/HER2-negative BC regardless of CT type ( adjusted P = .035 and P = .023 ) , respectively . In HER2-positive BC , there was a significant interaction between increasing stromal lymphocytic infiltration ( 10 % increments ) and benefit with anthracycline-only CT ( DFS , interaction P = .042 ; OS , P = .018 ) . CONCLUSION In node-positive , ER-negative/HER2-negative BC , increasing lymphocytic infiltration was associated with excellent prognosis . Further validation of the clinical utility of tumor-infiltrating lymphocytes in this context is warranted . Our data also support the evaluation of immunotherapeutic approaches in selected BC subtypes",
"PURPOSE The 21-gene recurrence score ( RS ) assay quantifies the likelihood of distant recurrence in women with estrogen receptor-positive , lymph node-negative breast cancer treated with adjuvant tamoxifen . The relationship between the RS and chemotherapy benefit is not known . METHODS The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy-treated patients in the National Surgical Adjuvant Breast and Bowel Project ( NSABP ) B20 trial . Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS . RESULTS A total of 651 patients were assessable ( 227 r and omly assigned to tamoxifen and 424 r and omly assigned to tamoxifen plus chemotherapy ) . The test for interaction between chemotherapy treatment and RS was statistically significant ( P = .038 ) . Patients with high-RS ( > or = 31 ) tumors ( ie , high risk of recurrence ) had a large benefit from chemotherapy ( relative risk , 0.26 ; 95 % CI , 0.13 to 0.53 ; absolute decrease in 10-year distant recurrence rate : mean , 27.6 % ; SE , 8.0 % ) . Patients with low-RS ( chemotherapy treatment ( relative risk , 1.31 ; 95 % CI , 0.46 to 3.78 ; absolute decrease in distant recurrence rate at 10 years : mean , -1.1 % ; SE , 2.2 % ) . Patients with intermediate-RS tumors did not appear to have a large benefit , but the uncertainty in the estimate can not exclude a clinical ly important benefit . CONCLUSION The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative , estrogen receptor-positive breast cancer , but also predicts the magnitude of chemotherapy benefit ",
"PURPOSE To evaluate the prognostic and predictive value of Ki-67 labeling index ( LI ) in a trial comparing letrozole ( Let ) with tamoxifen ( Tam ) as adjuvant therapy in postmenopausal women with early breast cancer . PATIENTS AND METHODS Breast International Group ( BIG ) trial 1 - 98 r and omly assigned 8,010 patients to four treatment arms comparing Let and Tam with sequences of each agent . Of 4,922 patients r and omly assigned to receive 5 years of monotherapy with either agent , 2,685 had primary tumor material available for central pathology assessment of Ki-67 LI by immunohistochemistry and had tumors confirmed to express estrogen receptors after central review . The prognostic and predictive value of central ly measured Ki-67 LI on disease-free survival ( DFS ) were assessed among these patients using proportional hazards modeling , with Ki-67 LI values dichotomized at the median value of 11 % . RESULTS Higher values of Ki-67 LI were associated with adverse prognostic factors and with worse DFS ( hazard ratio [ HR ; high : low ] = 1.8 ; 95 % CI , 1.4 to 2.3 ) . The magnitude of the treatment benefit for Let versus Tam was greater among patients with high tumor Ki-67 LI ( HR [ Let : Tam ] = 0.53 ; 95 % CI , 0.39 to 0.72 ) than among patients with low tumor Ki-67 LI ( HR [ Let : Tam ] = 0.81 ; 95 % CI , 0.57 to 1.15 ; interaction P = .09 ) . CONCLUSION Ki-67 LI is confirmed as a prognostic factor in this study . High Ki-67 LI levels may identify a patient group that particularly benefits from initial Let adjuvant therapy",
"BACKGROUND Adjuvant tamoxifen therapy substantially decreases the risk of recurrence and mortality in women with hormone ( estrogen and /or progesterone ) receptor-positive breast cancer . Previous studies have suggested that metabolic conversion of tamoxifen to endoxifen by cytochrome P450 2D6 ( CYP2D6 ) is required for patient benefit from tamoxifen therapy . METHODS Tumor specimens from a subset of postmenopausal patients with hormone receptor-positive early-stage ( stages I , II , and IIIA ) breast cancer , who were enrolled in the r and omized double-blind Arimidex , Tamoxifen , Alone or in Combination ( ATAC ) clinical trial , were genotyped for variants in CYP2D6 ( N = 1203 patients : anastrozole [ trade name : Arimidex ] group , n = 615 patients ; tamoxifen group , n = 588 patients ) and UDP-glucuronosyltransferase-2B7 ( UGT2B7 ) , whose gene product inactivates endoxifen ( N = 1209 patients ; anastrozole group , n = 606 patients ; tamoxifen group , n = 603 patients ) . Genotyping was performed using polymerase chain reaction-based TaqMan assays . Based on the genotypes for CYP2D6 , patients were classified as poor metabolizer ( PM ) , intermediate metabolizer ( IM ) , or extensive metabolizer ( EM ) phenotypes . We evaluated the association of CYP2D6 and UGT2B7 genotype with distant recurrence ( primary endpoint ) and any recurrence ( secondary endpoint ) by estimating the hazard ratios ( HRs ) and corresponding 95 % confidence intervals ( CIs ) using Cox proportional hazards models . All statistical tests were two-sided . RESULTS After a median follow-up of 10 years , no statistically significant associations were observed between CYP2D6 genotype and recurrence in tamoxifen-treated patients ( PM vs EM : HR for distant recurrence = 1.25 , 95 % CI = 0.55 to 3.15 , P = .64 ; HR for any recurrence = 0.99 , 95 % CI = 0.48 to 2.08 , P = .99 ) . A near-None association was observed between UGT2B7 genotype and recurrence in tamoxifen-treated patients . No associations were observed between CYP2D6 and UGT2B7 genotypes and recurrence in anastrozole-treated patients . CONCLUSION The results do not support the hypothesis that CYP2D6 genotype predicts clinical benefit of adjuvant tamoxifen treatment among postmenopausal breast cancer patients",
"Background . Previous analyses of TOP2A and HER2 in the Danish Breast Cancer Coopererative Group ( DBCG ) trial 89D suggested that TOP2A amplifications and possible also deletions are predictive markers for the effect of adjuvant epirubicin in patients with primary breast cancer . We present an up date d and extended statistical analysis , requested for IVD-labeling of TOP2A testing . Material and methods . In the DBCG trial 89D 980 Danish patients were r and omly assigned to nine cycles of intravenous CMF ( cyclophosphamide , methotrexate , and fluorouracil ) or CEF ( cyclophosphamide , epirubicin , and fluorouracil ) . Archival tumor tissue was collected retrospectively from 806 of these patients in a prospect ively design ed , biological sub- study , and was successfully analyzed for TOP2A aberrations and HER2 status in 773 sample s ( 96 % ) . Recurrence-free survival ( RFS ) was the primary endpoint . Results . TOP2A aberrations ( amplifications and deletions ) were significantly associated with shorter RFS ( p overall survival ( OS ) ( p worse prognosis than amplified cases . In a Cox proportional hazard model TOP2A was an independent prognostic marker for RFS and OS . Patients with amplifications had a 61 % reduction in the risk of an event ( p=0.002 ) and a 51 % reduction in the risk of death ( p=0.01 ) if allocated to CEF compared to 6 % and 10 % in TOP2A normal patients . A similar but non-significant trend ( p=0.08 ) was shown in patients with TOP2A deletions . Clear statistical evidence of a differential benefit , favoring CEF among patients with TOP2A aberrations was found for RFS ( p=0.02 for interaction ) but not for OS ( p=0.14 for interaction ) . Conclusion . In conclusion , this up date d analysis of TOP2A aberrations in DBCG trial 89D suggests a differential benefit of adjuvant chemotherapy in patients with primary breast cancer , favoring treatment with epirubicin in patients with TOP2A amplifications , and perhaps deletions . Additional studies are needed to clarify the exact importance of TOP2A deletions on outcome , but deletions have proven to be associated with a very poor prognosis",
"BACKGROUND Biomarkers to improve the risk-benefit of extended adjuvant endocrine therapy for late recurrence in patients with oestrogen-receptor-positive breast cancer would be clinical ly valuable . We compared the prognostic ability of the breast-cancer index ( BCI ) assay , 21-gene recurrence score ( Oncotype DX ) , and an immunohistochemical prognostic model ( IHC4 ) for both early and late recurrence in patients with oestrogen-receptor-positive , node-negative ( N0 ) disease who took part in the Arimidex , Tamoxifen , Alone or in Combination ( ATAC ) clinical trial . METHODS In this prospect i ve comparison study , we obtained archival tumour blocks from the TransATAC tissue bank from all postmenopausal patients with oestrogen-receptor-positive breast cancer from whom the 21-gene recurrence score and IHC4 values had already been derived . We did BCI analysis in matched sample s with sufficient residual RNA using two BCI models-cubic ( BCI-C ) and linear (BCI-L)-using previously vali date d cutoffs . We assessed prognostic ability of BCI for distant recurrence over 10 years ( the primary endpoint ) and compared it with that of the 21-gene recurrence score and IHC4 . We also tested the ability of the assays to predict early ( 0 - 5 years ) and late ( 5 - 10 years ) distant recurrence . To assess the ability of the biomarkers to predict recurrence beyond st and ard clinicopathological variables , we calculated the change in the likelihood-ratio χ(2 ) ( LR-Δχ(2 ) ) from Cox proportional hazards models . FINDINGS Suitable tissue was available from 665 patients with oestrogen-receptor-positive , N0 breast cancer for BCI analysis . The primary analysis showed significant differences in risk of distant recurrence over 10 years in the categorical BCI-C risk groups ( p for overall ( 0 - 10 year ) distant recurrence compared with BCI-C ( interquartile HR 2·30 [ 95 % CI 1·62 - 3·27 ] ; LR-Δχ(2)=22·69 ; p ) . When compared with BCI-L , the 21-gene recurrence score was less predictive ( HR 1·48 [ 95 % CI 1·22 - 1·78 ] ; LR-Δχ(2)=13·68 ; p=0·0002 ) and IHC4 was similar ( HR 1·69 [ 95 % CI 1·51 - 2·56 ] ; LR-Δχ(2)=22·83 ; p ) . All further analyses were done with the BCI-L model . In a multivariable analysis , all assays had significant prognostic ability for early distant recurrence ( BCI-L HR 2·77 [ 95 % CI 1·63 - 4·70 ] , LR-Δχ(2)=15·42 , p ; 21-gene recurrence score HR 1·80 [ 1·42 - 2·29 ] , LR-Δχ(2)=18·48 , p IHC4 HR 2·90 [ 2·01 - 4·18 ] , LR-Δχ(2)=29·14 , p significant for late distant recurrence ( BCI-L HR 1·95 [ 95 % CI 1·22 - 3·14 ] , LR-Δχ(2)=7·97 , p=0·0048 ; 21-gene recurrence score HR 1·13 [ 0·82 - 1·56 ] , LR-Δχ(2)=0·48 , p=0·47 ; IHC4 HR 1·30 [ 0·88 - 1·94 ] , LR-Δχ(2)=1·59 , p=0·20 ) . INTERPRETATION BCI-L was the only significant prognostic test for risk of both early and late distant recurrence and identified two risk population s for each timeframe . It could help to identify patients at high risk for late distant recurrence who might benefit from extended endocrine or other therapy . FUNDING Avon Foundation , National Institutes of Health , Breast Cancer Foundation , US Department of Defense Breast Cancer Research Program , Susan G Komen for the Cure , Breakthrough Breast Cancer through the Mary-Jean Mitchell Green Foundation , AstraZeneca , Cancer Research UK , and the National Institute for Health Research Biomedical Research Centre at the Royal Marsden ( London , UK )",
"PURPOSE It has been suggested that PTEN , a negative regulator of PI3K/AKT signaling , is involved in tumor sensitivity to trastuzumab . We investigated the association between tumor PTEN protein expression and disease-free survival ( DFS ) of patients r and omly assigned to receive chemotherapy alone ( arm A ) or chemotherapy with sequential ( arm B ) or concurrent trastuzumab ( arm C ) in the phase III early-stage human epidermal growth factor receptor 2 ( HER2 ) -positive trial-North Central Cancer Treatment Group ( NCCTG ) N9831 . PATIENTS AND METHODS The intensity and percentage of invasive cells with cytoplasmic PTEN staining were determined in tissue microarray sections containing three cores per block ( n = 1,286 ) or in whole tissue sections ( WS ; n = 516 ) by using st and ard immunohistochemistry ( 138G6 monoclonal antibody ) . Tumors were considered positive for PTEN ( PTEN-positive ) if any core or WS had any invasive cells with ≥ 1 + staining . Median follow-up was 6.0 years . RESULTS Of 1,802 patients included in this analysis ( of 3,505 patients registered to N9831 ) , 1,342 ( 74 % ) had PTEN-positive tumors . PTEN positivity was associated with hormone receptor negativity ( χ(2 ) P nodal positivity ( χ(2 ) P = .04 ) . PTEN did not have an impact on DFS within the various arms . Comparing DFS of arm C to arm A , patients with PTEN-positive and PTEN-negative tumors had hazard ratios ( HRs ) of 0.65 ( P = .003 ) and 0.47 ( P = .005 ) , respectively ( interaction P = .16 ) . For arm B versus arm A , patients with PTEN-positive and PTEN-negative tumors had HRs of 0.70 ( P = .009 ) and 0.85 ( P = .44 ) , respectively ( interaction P = .47 ) . CONCLUSION In contrast to selected pre clinical and limited clinical studies suggesting a decrease in trastuzumab sensitivity in patients with PTEN-negative tumors , our data show benefit of adjuvant trastuzumab for patients with HER2-positive breast cancer , independent of tumor PTEN status"
] |
4116ce5a-06ff-11f0-808a-c43d1ab1c353
|
OBJECTIVE To make a survey of the principal anxiety instruments available for children , when they appeared , the type of methods used , verifying which countries have the highest number of children anxiety instruments and also how is the Brazilian reality on this matter . METHODS A systematic review on electronic data bases -- Psychoinfo ( 1940 - -May 2002 ) , Psyclit ( 1887 - -May 2002 ) , Medline ( 1966 - -May 2002 ) e Eric ( 1966 - -May 2002 ) . Information collected on personal communications and books chapters . The inclusion criterion utilized : studies realized with children , where the anxiety were evaluated with some psychometric instrument . The exclusion criterion : adolescents , adults and animal research articles , articles utilizing projective instruments or studies without any reference of assessment instruments . The indexed articles found in 2 or more data bases were considered only once . RESULTS This review pointed out 1911 studies used at least one assessment instrument to identify the presence of anxiety and 118 instruments were used for this purpose . CONCLUSIONS There are a large number of children anxiety instruments available , however , in Brazil , the only one available in the market is n't up date d and the modern ones are found only in clinic academic centers
|
[
"OBJECTIVE To evaluate course and outcome of DSM-III-R anxiety disorders prospect ively in clinical ly referred children . METHOD Children were blindly and repeatedly assessed with a structured diagnostic interview over a 3- to 4-year period to determine recovery from anxiety disorder and development of new psychiatric disorders . Both psychopathological ( attention-deficit hyperactivity disorder , n = 50 ) and never psychiatrically ill ( NPI , n = 83 ) controls served as comparison groups for children with anxiety disorders ( n = 84 ) . RESULTS The majority of children ( 82 % ) were free from their intake anxiety disorders by the end of the follow-up . Relapse of these anxiety disorders after remission was rare ( 8 % ) . During follow-up , anxious children were more likely to develop new psychiatric disorders ( 30 % ) , primarily new anxiety disorders ( 16 % ) , than were NPI children ( 11 % and 2 % , respectively ) , but not psychopathological controls ( 42 % and 10 % , respectively ) . CONCLUSIONS Overall , results suggest a favorable outcome with respect to diagnostic status for clinical ly referred children with anxiety disorders . However , these children may be at risk for new psychiatric disorders over time",
"The Queensl and Early Intervention and Prevention of Anxiety Project evaluated a child- and family-focused group intervention for preventing anxiety problems in children . This article reports on 12- and 24-month follow-up data to previously reported outcomes at posttreatment and at 6-month follow-up . A total of 1,786 7- to 14-year-olds were screened for anxiety problems using teacher nominations and children 's self-report . After diagnostic interviews , 128 children were selected and assigned to either a 10-week school-based child- and parent-focused psychosocial intervention or a monitoring group . Both groups showed improvements immediately at postintervention and at 6-month follow-up ; the improvement was maintained in the intervention group only reducing the rate of existing anxiety disorder and preventing the onset of new anxiety disorders . At 12 months , the groups converged , but the superiority of the intervention group was evident again at 2-year follow-up . Severity of pretreatment diagnoses , gender , and parental anxiety predicted poor initial response to intervention , whereas pretreatment severity was the only predictor of chronicity at 24 months . Overall , follow-up results show that a brief school-based intervention for children can produce durable reductions in anxiety problems",
"The author describes and emphasizes the value of a symptom and behavior rating checklist for teachers ' use in drug studies with children . Factor analysis of the scale produced five factors that gave reliable subscales over a one-month period . A treatment study of dextroamphetamine with a group of children having learning and /or behavior disorders showed significant changes in all factors compared with a placebo group in a double-blind study",
"OBJECTIVE This study investigated the correlates of a childhood history of anxiety disorders in adult patients participating in a longitudinal study of panic disorder . The authors hypothesized that a history of anxiety during childhood would be associated with higher rates of comorbid anxiety and depressive disorders , greater likelihood of anxiety disorders in family members , and greater chronicity , as reflected by decreased time spent in remission . METHOD The presence of a childhood history of anxiety disorders was assessed by structured interview , and its association with comorbid anxiety and depressive disorders , family history , and select anxiety severity variables was examined in a replication sample of 94 patients . The influence of childhood anxiety on the prospect ively ascertained course of disorder was assessed in a full group of 194 patients . RESULTS Over half ( 54 % ) of the patients experienced anxiety disorders during childhood . These patients experienced higher rates of comorbid anxiety and depression , family history of anxiety , and increased levels of agoraphobia , panic frequency , and global severity of illness at baseline evaluation . Childhood anxiety disorders were not independently associated with the number of months in remission or the severity of illness over time , although a modest effect for this variable was evident when degree of avoidance and anxiety sensitivity at baseline were statistically controlled . CONCLUSIONS Adult panic patients with a history of anxiety disorders in childhood have elevated rates of comorbid anxiety and depressive disorders and a tendency toward increased avoidance , but there was not strong evidence that these patients respond differently to treatment over time",
"Abstract A Fear Survey Schedule for Children ( FSS-FC ) was developed . This scale and the Children 's Manifest Anxiety Scale ( CMAS ) were administered to fifty-nine boys and forty girls ages 9 through 12 . A factor analysis was performed on each scale yielding factored subscales intended for use in clinical assessment and research in children 's fears . A comparison was made between the fear and anxiety scales and an overall correlation of 0.49 between the FSS-FC and CMAS was similar to that obtained in adult studies"
] |
4116ce96-06ff-11f0-808a-c43d1ab1c353
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.